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var title_f0_33_528="Etiologies of angioedema in referral populations";

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" Etiologies of angioedema in referral populations",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Data from: Zingale LC, Beltrami L, Zanichelli A, et al. Angioedema without
urticaria: a large clinical survey. CMAJ 2006; 175:1065.",
" </div>",
" </div>",
" </div>",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Multiple distal metatarsal shaft fractures are evident in this patient who
suffered a severe crush injury (thin arrows). There is widening of the space
between the first and second metatarsal. This is usually caused by a tarso-
metatarsal fracture dislocation (Lisfranc injury), but in this case is due to
fracture of the cuneiform (thick arrow).",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Eiff, MP, Hatch, RL, Calmbach, W (Eds).
Fracture Management for Primary Care, 2nd Edition, W.B. Saunders Company,
Philadelphia 2002. Copyright &copy; 2002 Elsevier.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
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var outline_f0_33_529=null;
var title_f0_33_530="Traction-countertraction with axillary pressure";
var content_f0_33_530=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic2\" style=\"width: 1040px;\">",
" <div class=\"videoplayer\"
h264=\"./images/EM/60981/Traction_countertraction.mp4?title=Traction-
countertraction+with+axillary+pressure\" style=\"width:448px;height:352px\">",
" </div>",
" <div class=\"figure\" style=\"width: 470px\">",
" <div class=\"ttl\">",
" Traction-countertraction technique for shoulder reduction",
" </div>",
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" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced from: Simon and Sherman, Emergency Orthopedics, 6th edition. DVD
&copy; Scott Sherman. All rights reserved.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_33_530=[""].join("\n");
var outline_f0_33_530=null;
var title_f0_33_531="Hemi-uterus1";
var content_f0_33_531=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
" <div id=\"graphicsLinks\">",
" <a href=\"?imageKey=OBGYN
%2F67507&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=OBGYN
%2F67507&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 524px\">",
" <div class=\"ttl\">",
" Laparoscopic view of left hemiuterus communicating with single cervix as
demonstrated by flow of blue dye injected through the cervix \"freely spilling\"
from left fallopian tube",
" </div>",
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" </div>",
" <div class=\"lgnd\">",
" Right hemiuterus does not communicate with the cervix and should be removed
laparoscopically.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from:&nbsp;Laufer MR. Structural abnormalities of
the female reproductive tract. In: Pediatric and adolescent gynecology, 6th ed,
Emans SJ, Laufer MR, Goldstein DP (Eds), Lippincott Williams &amp; Wilkins,
Philadelphia 2012. Copyright &copy; 2012 Lippincott Williams &amp; Wilkins.",
" </div>",
" <div class=\"contractual\">",
" <br/>",
" <a href=\"file://www.lww.com\">",
" file://www.lww.com",
" </a>",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_33_531=[""].join("\n");
var outline_f0_33_531=null;
var title_f0_33_532="Mitomycin (ophthalmic): Drug information";
var content_f0_33_532=[" <noscript>",
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JavaScript is required in order for our site to behave correctly. Please enable
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" <div id=\"printHeader\">",
" <div id=\"printHeaderLogo\">",
" <img alt=\"UpToDate\" src=\"./../images/UTD2_masthead.myextg\">",
" <img align=\"right\" alt=\"Wolters Kluwer Health\" height=\"40\"
src=\"./../images/logoWKH.myextg\" width=\"175\">",
" <br>",
" <div id=\"printHeaderText\">",
" Official reprint from UpToDate",
" <sup>",
" &reg;",
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" www.uptodate.com",
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here to print\">",
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" Back",
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" </div>",
" </div>",
" <!-- TC:TOPIC_PAGE -->",
" <div id=\"topicContent\">",
" <div id=\"drugTitle\">",
" Mitomycin (ophthalmic): Drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" (For additional information",
" <a class=\"drug drug_patient\" href=\"UTD.htm?13/62/14307?source=see_link\">",
" see \"Mitomycin (ophthalmic): Patient drug information\"",
" </a>",
" )",
" <br/>",
" For abbreviations and symbols that may be used in Lexicomp (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
" show table",
" </a>",
" )",
" <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F14624261\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: U.S.",
" </span>",
" <ul>",
" <li>",
" Mitosol&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F13895841\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacologic Category",
" </span>",
" <ul>",
" <li>",
" Antineoplastic Agent, Antibiotic;",
" </li>",
" <li>",
" Ophthalmic Agent, Miscellaneous",
" </li>",
" </ul>",
" </div>",
" <div class=\"block doa drugH1Div\" id=\"F13895913\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Adult",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" <b>",
" Glaucoma surgery, adjunctive therapy:",
" </b>",
" Topical ophthalmic: 0.2 mg solution is aseptically applied via saturated
sponges to surgical site of glaucoma filtration surgery for 2 minutes",
" </p>",
" </div>",
" <div class=\"block doe drugH1Div\" id=\"F13895914\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosing: Geriatric",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Refer to adult dosing.",
" </p>",
" </div>",
" <div class=\"block foc drugH1Div\" id=\"F13897433\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Dosage Forms: U.S.",
" </span>",
" <p style=\"text-indent:0em;text-align:justify;display:inline\">",
" Excipient information presented when available (limited, particularly for
generics); consult specific product labeling.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" Powder for solution, ophthalmic [kit]:",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" Mitosol&reg;: 0.2 mg [supplied with diluent]",
" </p>",
" </div>",
" <div class=\"block geq drugH1Div\" id=\"F13895840\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Generic Equivalent Available: U.S.",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" No",
" </p>",
" </div>",
" <div class=\"block adm drugH1Div\" id=\"F13895915\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Administration",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" The inner tray and the contents of the kit are sterile and should only be
handled, opened and assembled by a sterile surgical scrub technician. Use within 1
hour of reconstitution. Technician should fully saturate sponges provided in the
kit with the entire reconstituted solution (0.2 mg). Allow saturated sponges to
remain undisturbed in kit for 60 seconds. Saturated sponges should be applied
aseptically with the use of surgical forceps in a single layer to a treatment area
~10 mm x 6 mm (&plusmn; 2 mm); sponges should be removed from the treatment area
after 2 minutes. Following removal of sponges from eye, the surgical site should
be copiously irrigated. Saturated sponges should be returned to the provided tray
for ultimate disposal into chemotherapy waste bag. Consult product labeling for
additional details. Solution is",
" <b>",
" not",
" </b>",
" intended for intraocular administration.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" Hazardous agent; use appropriate precautions for handling and disposal",
" <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
target=\"_blank\">",
" (NIOSH, 2012)",
" </a>",
" .",
" </p>",
" </div>",
" <div class=\"block use drugH1Div\" id=\"F13895843\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Use",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Adjunct to",
" <i>",
" ab externo",
" </i>",
" glaucoma surgery",
" </p>",
" </div>",
" <div class=\"block mst drugH1Div\" id=\"F13895838\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Medication Safety Issues",
" </span>",
" <div class=\"collapsible\">",
" <span class=\"collapsible-title\">",
" Sound-alike/look-alike issues:",
" </span>",
" <div class=\"collapsible-wrap\">",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" MitoMYcin (Ophthalmic) may be confused with MitoMYcin (Systemic), mitotane,
mitoXANtrone",
" </p>",
" </div>",
" </div>",
" <div class=\"collapsible\">",
" <span class=\"collapsible-title\">",
" High alert medication:",
" </span>",
" <div class=\"collapsible-wrap\">",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" This medication is in a class the Institute for Safe Medication Practices
(ISMP) includes among its list of drug classes which have a heightened risk of
causing significant patient harm when used in error.",
" </p>",
" </div>",
" </div>",
" <div class=\"collapsible\">",
" <span class=\"collapsible-title\">",
" Administration issues:",
" </span>",
" <div class=\"collapsible-wrap\">",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Mitosol&reg; is not intended for intraocular administration; intraocular
administration may result in cell death and lead to corneal and retinal infarction,
and ciliary body atrophy.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;\">",
" Mitosol&reg; is only intended for topical application to the surgical site
of glaucoma filtration surgery.",
" </p>",
" </div>",
" </div>",
" </div>",
" <div class=\"block ars drugH1Div\" id=\"F13895897\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Adverse Reactions Significant",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Frequency not defined: Ocular: Astigmatism induced, bleb
(encapsulated/cystic/thin-walled), bleb leak (chronic), bleb ulceration, bleb-
related infection, blebitis, capsule opacification, capsular constriction,
capsulotomy rupture, cataract development, cataract progression, choroidal
detachment, choroidal effusion, ciliary block, conjunctival necrosis, corneal
endothelial damage, corneal vascularization, cystic conjunctival degeneration,
Descemet&rsquo;s detachment, disk hemorrhage, disk swelling, endophthalmitis,
epithelial defect, fibrin reaction, glaucoma (malignant), hemiretinal vein
occlusion, hyphema, hypotony, hypotony maculopathy, implants dislocated,
intraocular lens capture, iritis, lacrimal drainage system obstruction, loss of
vision (severe), macular edema, retinal detachment (serious and rhegatogenous),
retinal hemorrhage, retinal pigment epithelial tear, retinal vein occlusion, sclera
thinning/ulceration, subconjunctival hemorrhage, superficial punctuate keratitis,
suprachoroidal effusion (including hypoechogenic), suprachoroidal hemorrhage,
supraciliochoroidal fluid present, synechiae (anterior and posterior), upper eyelid
retraction, visual acuity decreased, vitreal hemorrhage/clot, wound dehiscence
(associated with blebitis and scleritis)",
" </p>",
" </div>",
" <div class=\"block coi drugH1Div\" id=\"F13895848\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Contraindications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Hypersensitivity to mitomycin or any component of the formulation;
pregnancy",
" </p>",
" </div>",
" <div class=\"block war drugH1Div\" id=\"F13895849\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warnings/Precautions",
" </span>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Concerns related to adverse effects:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Cataract formation: Increased incidence of lenticular change and
cataract formation has been correlated with use in phakic patients.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Corneal/scleral damage: Inadvertent corneal and/or scleral damage,
including thinning or perforation, may occur with use of mitomycin solution in
concentrations &gt;0.2 mg/mL or for time periods &gt;2 minutes. In addition, direct
contact of the solution with the corneal endothelium will cause cell death.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Hypotony: Increased incidence of postoperative hypotony has been
observed with use.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Special handling:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Hazardous agent: Use appropriate precautions for handling and
disposal",
" <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
target=\"_blank\">",
" (NIOSH, 2012)",
" </a>",
" .",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
" <b>",
" <i>",
" Other warnings/precautions:",
" </i>",
" </b>",
" </p>",
" <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
" &bull; Inappropriate administration: Solution should",
" <b>",
" not",
" </b>",
" be administered intraocularly; intraocular administration may result in cell
death, potentially causing corneal and retinal infarction, and ciliary body
atrophy. Therapy is only intended for topical application to the surgical site of
glaucoma filtration surgery.",
" </p>",
" </div>",
" <div class=\"block cyt drugH1Div\" id=\"F14276343\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Metabolism/Transport Effects",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" None known.",
" </p>",
" </div>",
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xmlns=\"file://www.w3.org/1999/xhtml\">",
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" <br/>",
" <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
" (For additional information:",
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" Launch Lexi-Interact&trade; Drug Interactions Program",
" </a>",
" )",
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src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
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" <div class=\"clear\">",
" </div>",
" <p style=\"text-indent:0em;display:inline\">",
" There are no known significant interactions.",
" </p>",
" </div>",
" <div class=\"block prf drugH1Div\" id=\"F13895844\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
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" Pregnancy Risk Factor",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" X (",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
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" </p>",
" </div>",
" <div class=\"block pri drugH1Div\" id=\"F13895845\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
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" Pregnancy Implications",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Teratogenic effects have been observed in animal reproduction studies
following parenteral administration. Reproduction studies using topical mitomycin
have not been conducted. Use is contraindicated in pregnant women or women who may
become pregnant during therapy.",
" </p>",
" </div>",
" <div class=\"block lac drugH1Div\" id=\"F13895846\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
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" Lactation",
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" <p style=\"text-indent:0em;display:inline\">",
" Excretion unknown/not recommended",
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" Breast-Feeding Considerations",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" It is not known if mitomycin can be detected in breast milk following topical
application. Due to the potential for serious adverse reactions in a nursing
infant, breast feeding is not recommended.",
" </p>",
" </div>",
" <div class=\"block pha drugH1Div\" id=\"F13895906\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
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" Mechanism of Action",
" </span>",
" <p style=\"text-indent:0em;display:inline\">",
" Acts like an alkylating agent and produces DNA cross-linking (primarily with
guanine and cytosine pairs); cell-cycle nonspecific; inhibits DNA and RNA
synthesis; degrades preformed DNA, causes nuclear lysis and formation of giant
cells. While not phase-specific per se, mitomycin has its maximum effect against
cells in late G and early S phases.",
" </p>",
" <p style=\"text-indent:0em;margin-top:2em;\">",
" During use in trabeculectomy (filtration surgery) for glaucoma, mitomycin
topical application is believed to alter conjunctival vascular endothelium and
inhibit fibroblast proliferation.",
" </p>",
" </div>",
" <div class=\"block phk drugH1Div\" id=\"F13895908\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Pharmacodynamics/Kinetics",
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" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Absorption: Systemic absorption following ocular administration is unknown;
however, systemic concentrations are expected to be of multiple orders of magnitude
lower than concentrations produced following parenteral administration.",
" </p>",
" <p style=\"text-indent:-2em;margin-left:2em;\">",
" Metabolism: Cleared from ophthalmic tissue following topical administration
and irrigation; systemic metabolism primarily occurs in the liver",
" </p>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <div class=\"reference\">",
" Bindlish R, Condon GP, Schlosser JD, et al, &ldquo;Efficacy and Safety of
Mitomycin-C in Primary Trabeculectomy: Five-Year Follow Up,&rdquo;",
" <i>",
" Ophthalmology",
" </i>",
" , 2002, 109(7):1336-42.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/33/532/abstract-text/12093659/pubmed\" id=\"12093659\"
target=\"_blank\">",
" 12093659",
" </a>",
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" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" National Institute for Occupational Safety and Health (NIOSH), \"NIOSH List
of Antineoplastic and Other Hazardous Drugs in Healthcare Settings 2012.\"
Available at",
" <a href=\"file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf\"
target=\"_blank\">",
" file://www.cdc.gov/niosh/docs/2012-150/pdfs/2012-150.pdf",
" </a>",
" . Accessed January 21, 2013.",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Palanca-Capistrano AM, Hall J, Cantor LB, et al, &ldquo;Long-Term Outcomes
of Intraoperative 5-Fluorouracil versus Intraoperative Mitomycin C in Primary
Trabeculectomy Surgery,&rdquo;",
" <i>",
" Ophthalmology",
" </i>",
" , 2009, 116(2):185-90.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/33/532/abstract-text/18930550/pubmed\" id=\"18930550\"
target=\"_blank\">",
" 18930550",
" </a>",
" ]",
" </span>",
" </div>",
" </li>",
" <li>",
" <div class=\"reference\">",
" Razeghinejad MR, Tania Tai TY, Fudemberg SJ, et al, &ldquo;Pregnancy and
Glaucoma,&rdquo;",
" <i>",
" Surv Ophthalmol",
" </i>",
" , 2011, 56(4):324-35.",
" <span class=\"pubmed-id\">",
" [PubMed",
" <a href=\"UTD.htm?0/33/532/abstract-text/21620430/pubmed\" id=\"21620430\"
target=\"_blank\">",
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" <h1>",
" RELATED TOPICS",
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" <li class=\"plainItem\">",
" <a class=\"drug drug_patient\" href=\"UTD.htm?13/62/14307?
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" </div>",
" <div class=\"lgnd\">",
" Infiltrative or morpheaform basal cell carcinomas can present as indented,
scar-like lesions.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: www.visualdx.com. Copyright Logical Images,
Inc.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_33_533=[""].join("\n");
var outline_f0_33_533=null;
var title_f0_33_534="Methyldopa and hydrochlorothiazide: Patient drug information";
var content_f0_33_534=[" <noscript>",
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" The content on the UpToDate website is not intended nor recommended as a
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"for medical advice, diagnosis, or treatment. Always seek the advice of your own
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"other qualified health care professional regarding any medical questions or
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"use of this website is governed by the",
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" &copy;2013 UpToDate, Inc.",
" </div>",
" <div id=\"drugTitle\">",
" Methyldopa and hydrochlorothiazide: Patient drug information",
" </div>",
" <div id=\"lexiTitleImg\">",
" <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
width=\"71\"/>",
" </div>",
" <div class=\"clear\">",
" </div>",
" <div id=\"drugCopy\">",
" Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
" </div>",
" <div id=\"topicText\">",
" <p>",
" (For additional information",
" <a class=\"drug drug_general\" href=\"UTD.htm?13/52/14150?source=see_link\">",
" see \"Methyldopa and hydrochlorothiazide: Drug information\"",
" </a>",
" )",
" </p>",
" <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F195117\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Brand Names: Canada",
" </span>",
" <ul>",
" <li>",
" Apo-Methazide&reg;",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt war-os drugH1Div\" id=\"F10029942\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" Warning",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2700810",
" </span>",
" </span>",
" <span class=\"content\">",
" Only use this drug when you are not being helped by some other blood
pressure drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2700602",
" </span>",
" </span>",
" <span class=\"content\">",
" Sometimes drugs are not safe when you take them with certain other drugs.
Taking them together can cause bad side effects. This is one of those drugs. Be
sure to talk to your doctor about all the drugs you take.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yya-os drugH1Div\" id=\"F10029944\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What is this drug used for?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2691888",
" </span>",
" </span>",
" <span class=\"content\">",
" It is used to treat high blood pressure.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt coi-os drugH1Div\" id=\"F10029943\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I need to tell my doctor before I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2702507",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have an allergy to methyldopa, hydrochlorothiazide, or any other
part of this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2705171",
" </span>",
" </span>",
" <span class=\"content\">",
" If you are allergic to any drugs, foods, or other substances. Tell your
doctor about the allergy and what signs you had, like rash; hives; itching;
shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or
any other signs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2701385",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have a sulfa (sulfonamide) allergy, talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2703777",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have kidney disease.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2703780",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have liver disease or if this drug caused liver problems before.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2703859",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have taken certain drugs used for low mood (depression) like
isocarboxazid, phenelzine, or tranylcypromine or drugs used for Parkinson's disease
like selegiline or rasagiline in the last 14 days. Taking this drug within 14 days
of those drugs can cause very bad high blood pressure. Talk with your doctor.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yye-os drugH1Div\" id=\"F10029948\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some things I need to know or do while I take this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697780",
" </span>",
" </span>",
" <span class=\"content\">",
" Wear disease medical alert ID (identification).",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696820",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not run out of this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697204",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have high blood sugar (diabetes), talk with your doctor. This drug
may raise blood sugar.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698416",
" </span>",
" </span>",
" <span class=\"content\">",
" Have your blood pressure and heart rate checked often. Talk with your
doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698463",
" </span>",
" </span>",
" <span class=\"content\">",
" Have your blood work checked often. Talk with your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696717",
" </span>",
" </span>",
" <span class=\"content\">",
" Check all drugs you are taking with your doctor. This drug may not mix well
with some other drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697627",
" </span>",
" </span>",
" <span class=\"content\">",
" Talk with your doctor before using OTC products that may raise blood
pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or
like products, and some natural products or aids.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696882",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not take iron products within 2 hours of this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696611",
" </span>",
" </span>",
" <span class=\"content\">",
" Avoid beer, wine, mixed drinks, or other drugs and natural products that
slow your actions.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697633",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell dentists, surgeons, and other doctors that you use this drug.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697788",
" </span>",
" </span>",
" <span class=\"content\">",
" You may get sunburned more easily. Avoid sun, sunlamps, and tanning beds.
Use sunscreen and wear clothing and eyewear that protects you from the sun.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696701",
" </span>",
" </span>",
" <span class=\"content\">",
" Be careful in hot weather. Drink lots of fluids to stop fluid loss.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697779",
" </span>",
" </span>",
" <span class=\"content\">",
" Watch for gout attacks.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697641",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you are pregnant or plan on getting pregnant. You will
need to talk about the benefits and risks of using this drug while you are
pregnant.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697636",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you are breast-feeding. You will need to talk about any
risks to your baby.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyf-os drugH1Div\" id=\"F10029949\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects of this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698060",
" </span>",
" </span>",
" <span class=\"content\">",
" Feeling lightheaded, sleepy, having blurred eyesight, or a change in
thinking clearly. Avoid driving and doing other tasks or actions that call for you
to be alert or have clear eyesight until you see how this drug affects you.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698051",
" </span>",
" </span>",
" <span class=\"content\">",
" Feeling dizzy. Rise slowly over a few minutes when sitting or lying down.
Be careful climbing.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698217",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of low potassium levels like muscle pain or weakness, muscle cramps,
or a heartbeat that does not feel normal.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698119",
" </span>",
" </span>",
" <span class=\"content\">",
" Headache.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698279",
" </span>",
" </span>",
" <span class=\"content\">",
" Nervous and excitable.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698272",
" </span>",
" </span>",
" <span class=\"content\">",
" Upset stomach or throwing up. Many small meals, good mouth care, sucking
hard, sugar-free candy, or chewing sugar-free gum may help.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698027",
" </span>",
" </span>",
" <span class=\"content\">",
" Dry mouth. Good mouth care, sucking hard, sugar-free candy, or chewing
sugar-free gum may help. See a dentist often.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697963",
" </span>",
" </span>",
" <span class=\"content\">",
" Change in sex ability.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2697869",
" </span>",
" </span>",
" <span class=\"content\">",
" Anemia may rarely happen.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyh-os drugH1Div\" id=\"F10029951\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What are some side effects that I need to call my doctor about right away?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698721",
" </span>",
" </span>",
" <span class=\"content\">",
" If you think there has been an overdose, call 1-800-222-1222 (the American
Association of Poison Control Centers), your local poison control center
(file://www.aapcc.org), or emergency room (ER) right away.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699066",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of an allergic reaction, like rash; hives; itching; red, swollen,
blistered, or peeling skin with or without fever; wheezing; tightness in the chest
or throat; trouble breathing or talking; unusual hoarseness; or swelling of the
mouth, face, lips, tongue, or throat.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699075",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of low mood (depression), thoughts of killing yourself, nervousness,
emotional ups and downs, thinking that is not normal, anxiety, or lack of interest
in life.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698650",
" </span>",
" </span>",
" <span class=\"content\">",
" Tell your doctor if you have too much sweat, fluid loss, throwing up, or
loose stools. This may lead to low blood pressure.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699072",
" </span>",
" </span>",
" <span class=\"content\">",
" Signs of low potassium.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699023",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad dizziness or passing out.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699050",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad swelling or pain of hands or feet.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698634",
" </span>",
" </span>",
" <span class=\"content\">",
" Dark urine or yellow skin or eyes.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699031",
" </span>",
" </span>",
" <span class=\"content\">",
" Very bad headache.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698658",
" </span>",
" </span>",
" <span class=\"content\">",
" Feeling very tired or weak.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699105",
" </span>",
" </span>",
" <span class=\"content\">",
" Any bruising or bleeding.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699104",
" </span>",
" </span>",
" <span class=\"content\">",
" Not able to pass urine.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699086",
" </span>",
" </span>",
" <span class=\"content\">",
" Sudden change in eyesight, eye pain, or irritation.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698603",
" </span>",
" </span>",
" <span class=\"content\">",
" Any rash.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2698977",
" </span>",
" </span>",
" <span class=\"content\">",
" Side effect or health problem is not better or you are feeling worse.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyc-os drugH1Div\" id=\"F10029946\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How is this drug best taken?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695786",
" </span>",
" </span>",
" <span class=\"content\">",
" Take as you have been told, even if you feel well.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695914",
" </span>",
" </span>",
" <span class=\"content\">",
" Take with or without food. Take with food if it causes an upset stomach.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2695872",
" </span>",
" </span>",
" <span class=\"content\">",
" This drug may cause you to pass urine more often. To keep from having sleep
problems, try to take before 6 pm.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2694865",
" </span>",
" </span>",
" <span class=\"content\">",
" Follow the diet and workout plan that your doctor told you about.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyd-os drugH1Div\" id=\"F10029947\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" What do I do if I miss a dose?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696563",
" </span>",
" </span>",
" <span class=\"content\">",
" Take a missed dose as soon as you think about it.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696496",
" </span>",
" </span>",
" <span class=\"content\">",
" If it is close to the time for your next dose, skip the missed dose and go
back to your normal time.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696475",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not take 2 doses at the same time or extra doses.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2696457",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not change the dose or stop this drug. Talk with the doctor.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyi-os drugH1Div\" id=\"F10029952\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" How do I store and/or throw out this drug?",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699336",
" </span>",
" </span>",
" <span class=\"content\">",
" Store at room temperature.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b498:s2699266",
" </span>",
" </span>",
" <span class=\"content\">",
" Store in a dry place. Do not store in a bathroom.",
" </span>",
" </li>",
" </ul>",
" </div>",
" <div class=\"ord-stmt yyj-os drugH1Div\" id=\"F10029953\"
xmlns=\"file://www.w3.org/1999/xhtml\">",
" <span class=\"drugH1\">",
" General drug facts",
" </span>",
" <ul class=\"statements\" style=\"list-style-type:none;\">",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699675",
" </span>",
" </span>",
" <span class=\"content\">",
" If your symptoms or health problems do not get better or if they become
worse, call your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699673",
" </span>",
" </span>",
" <span class=\"content\">",
" Do not share your drugs with others and do not take anyone else's drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699678",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep all drugs out of the reach of children and pets.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699709",
" </span>",
" </span>",
" <span class=\"content\">",
" If you have any questions about this drug, please talk with your doctor,
pharmacist, or other health care provider.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s3302581",
" </span>",
" </span>",
" <span class=\"content\">",
" In Canada, take any unused drugs to the pharmacy. Also, visit
file://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/disposal-defaire-eng.php#th to learn about
the right way to get rid of unused drugs.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699677",
" </span>",
" </span>",
" <span class=\"content\">",
" Keep a list of all your drugs (prescription, natural products, vitamins,
OTC) with you. Give this list to your doctor.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699671",
" </span>",
" </span>",
" <span class=\"content\">",
" These are not all of the side effects that may occur. If you have questions
about side effects, call your doctor. Call your doctor for medical advice about
side effects.",
" </span>",
" </li>",
" <li class=\"statement\">",
" <span class=\"attributes\" style=\"display:none;\">",
" <span class=\"entity\">",
" &bull;",
" </span>",
" <span class=\"link\">",
" urn:lims:b259:s2699683",
" </span>",
" </span>",
" <span class=\"content\">",
" Talk with the doctor before starting any new drug, including prescription
or OTC, natural products, or vitamins.",
" </span>",
" </li>",
" </ul>",
" </div>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 10848 Version 36.0",
" </div>",
" </div>",
" <div id=\"footer\">",
" <div id=\"supportFooter\">",
" <span class=\"sfInfo\">",
" &copy; 2013 UpToDate, Inc. All rights reserved.",
" </span>",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
" Subscription and License Agreement",
" </a>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Release: 21.6- C21.56",
" </span>",
" <br/>",
" <span class=\"sfInfo\">",
" Licensed to:",
" <span class=\"emphasis\">",
" AsanBook Dig. Med. Lib.",
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" </span>",
" <span class=\"sfInfo\">",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" Support Tag: [1004-122.72.76.133-47BF19C4B0-S244013.14]",
" <br/>",
" </span>",
" </div>",
" </div>",
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" <h1>",
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" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F195117\">",
" Brand Names: Canada",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029942\">",
" Warning",
" </a>",
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" </li>",
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" <a class=\"outlineLink\" href=\"#F10029948\">",
" What are some things I need to know or do while I take this drug?",
" </a>",
" </li>",
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" <a class=\"outlineLink\" href=\"#F10029949\">",
" What are some side effects of this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029951\">",
" What are some side effects that I need to call my doctor about right away?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029946\">",
" How is this drug best taken?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029947\">",
" What do I do if I miss a dose?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029952\">",
" How do I store and/or throw out this drug?",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#F10029953\">",
" General drug facts",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"drug drug_general\" href=\"UTD.htm?13/52/14150?
source=related_link\">",
" Methyldopa and hydrochlorothiazide: Drug information",
" </a>",
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" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Reproduced with permission from: Nancy Bresich, PhD and Albert Greene, PhD.",
" </div>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_33_535=[""].join("\n");
var outline_f0_33_535=null;
var title_f0_33_536="Mosquito early life stages";
var content_f0_33_536=[" <div id=\"graphicsToolbar\">",
" <div id=\"graphicsCopy\">",
" &copy;2013 UpToDate",
" <sup>",
" &reg;",
" </sup>",
" </div>",
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" <a href=\"?imageKey=ID
%2F53881&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
" <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=ID
%2F53881&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
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" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\" style=\"width: 568px\">",
" <div class=\"ttl\">",
" Egg, larva, and pupa stages of Anopheline and Culicine mosquitoes",
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" </div>",
" <div class=\"lgnd\">",
" A. Culex mosquitoes lay their eggs in groups (\"rafts\") while Aedes and
Anopheline mosquitoes lay their eggs individually. In addition, Anopheline eggs
have characteristic \"floats.\"",
" <br>",
" B. Culicine larvae maintain a position vertical to the water surface and
breathe via siphon tubes extending to the water surface; the Culex siphon is longer
than the Aedes siphon. In contrast, Anopheles larvae lie in a horizontal position
parallel to the water surface and do not have a siphon.",
" <br>",
" C. In the pupa stage the head and thorax are fused to form a comma-shaped
cephalothorax; during this stage there are no distinguishing characteristics
between the genera.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Modified from figures courtesy of Cheryl Whitehorn, MSc.",
" </div>",
" </br>",
" </br>",
" </div>",
" </div>",
" </div>",
"</div>"].join("\n");
var script_f0_33_536=[""].join("\n");
var outline_f0_33_536=null;
var title_f0_33_537="Intraperitoneal chemotherapy for treatment of ovarian cancer";
var content_f0_33_537=[" <noscript>",
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" Intraperitoneal chemotherapy for treatment of ovarian cancer",
" </div>",
" <div id=\"topicContributors\">",
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" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/537/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/537/contributors\">",
" Joan L Walker, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/537/contributors\">",
" Maurie Markman, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/537/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/537/contributors\">",
" Barbara Goff, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/537/contributors\">",
" Deputy Editor",
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" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/537/contributors\">",
" Sandy J Falk, MD",
" </a>",
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" Literature review current through:",
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" Oct 2013.",
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" This topic last updated:",
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" Jun 14, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;The most common route of ovarian cancer spread is within
the peritoneal cavity. The benefit of administering chemotherapy directly into the
peritoneal cavity is supported by preclinical and pharmacokinetic data. Compared to
intravenous (IV) treatment, intraperitoneal (IP) administration permits a several-
fold increase in drug concentration to be achieved within the abdominal cavity [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/1\">",
" 1",
" </a>",
" ].",
" </p>",
" <p>",
" There is now a growing body of evidence showing a survival advantage for IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" as compared to IV administration of platinum along with intravenous taxane-
based chemotherapy in women with optimally cytoreduced (to &lt;1.0 cm) stage III
epithelial ovarian cancer. The publication of results from the most recent of these
trials, Gynecologic Oncology Group (GOG) trial 172 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" 2",
" </a>",
" ], led the US National Cancer Institute to issue a Clinical Alert in January
of 2006, strongly encouraging the use of IP chemotherapy in this subset of patients
[",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/3\">",
" 3",
" </a>",
" ]. However, while the use of IP chemotherapy is gaining acceptance, it is not
universal, largely due to the greater toxicity associated with this approach. The
data supporting IP chemotherapy as an alternative to IV chemotherapy and the
controversy surrounding its use are presented elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/11/21689?
source=see_link&amp;anchor=H250842013#H250842013\">",
" \"First-line chemotherapy for advanced (stage III or IV) epithelial ovarian,
fallopian tubal, and peritoneal cancer\", section on 'Intraperitoneal
chemotherapy'",
" </a>",
" .)",
" </p>",
" <p>",
" The management of women receiving IP chemotherapy for ovarian cancer,
including issues relating to placement of intraperitoneal catheters, will be
reviewed here. Surgical therapy and initial chemotherapy for advanced ovarian
cancer are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/48/36618?
source=see_link\">",
" \"Epithelial ovarian cancer: Initial surgical management\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/11/21689?
source=see_link\">",
" \"First-line chemotherapy for advanced (stage III or IV) epithelial ovarian,
fallopian tubal, and peritoneal cancer\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H1133978303\">",
" <span class=\"h1\">",
" RATIONALE",
" </span>",
" &nbsp;&mdash;&nbsp;Epithelial ovarian cancer is a disease of the ovarian
surface epithelium. In the vast majority of patients, the disease is confined to
the peritoneal cavity at initial diagnosis and in recurrence [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/4\">",
" 4",
" </a>",
" ]. Because of this natural history, ovarian cancer is an ideal target for
intraperitoneal (IP) therapy. Subsequent studies demonstrated that IP
administration of chemotherapy results in high peritoneal to plasma ratios for peak
concentration, including for",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" ,",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/61/38873?source=see_link\">",
" carboplatin",
" </a>",
" , and",
" <a class=\"drug drug_general\" href=\"UTD.htm?40/59/41913?source=see_link\">",
" docetaxel",
" </a>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/5\">",
" 5",
" </a>",
" ]. Of these agents, cisplatin has been the most extensively studied and
clinical studies have confirmed its activity in the front-line treatment of ovarian
cancer. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/11/21689?
source=see_link&amp;anchor=H250842013#H250842013\">",
" \"First-line chemotherapy for advanced (stage III or IV) epithelial ovarian,
fallopian tubal, and peritoneal cancer\", section on 'Intraperitoneal
chemotherapy'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" IMPORTANCE OF INITIAL SURGICAL CYTOREDUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Despite the regional advantage of IP chemotherapy,
penetration into tumor tissue is limited to a few millimeters of tumor on the
peritoneal surface layers and these approaches are best suited to patients with
minimal residual disease after surgical cytoreduction. A significant obstacle to
realizing the survival benefit from IP chemotherapy is the wide variation in the
proportion of women who undergo optimal cytoreductive surgery. As an example, in a
meta-analysis of 6685 women treated in the platinum era, optimal surgical resection
was only carried out in 42 percent of cases [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/6\">",
" 6",
" </a>",
" ]. Although rates of optimal cytoreduction are significantly higher when
trained gynecologic oncologists perform the surgery (75 percent or higher),
patterns of care studies suggest that only about 50 percent of patients being
treated for ovarian cancer are treated by gynecologic oncologists [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/7,8\">",
" 7,8",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/48/36618?
source=see_link&amp;anchor=H8#H8\">",
" \"Epithelial ovarian cancer: Initial surgical management\", section on
'Optimal cytoreduction'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" INDICATIONS AND CONTRAINDICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;IP chemotherapy is indicated for women with optimally
debulked (to &le;1.0 cm) stage III epithelial ovarian cancer. The benefit of IP
chemotherapy is uncertain in the setting of early stage disease, stage IV (distant
metastatic, (",
" <a class=\"graphic graphic_table graphicRef51205 \" href=\"UTD.htm?
14/43/15038\">",
" table 1",
" </a>",
" ) disease), and in patients who have residual tumor greater than 1 cm in
diameter. Tumor cells more than a few millimeters beneath the surface of the tumor
are not exposed to IP chemotherapy (at least during the first cycle) since
penetration of the drug into tumor tissue is limited to a few surface layers. Some
experts consider that the tumor will be smaller on subsequent cycles, and that as a
result, deeper penetration can be expected in future cycles. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Importance of initial surgical cytoreduction'",
" </a>",
" above.)",
" </p>",
" <p>",
" The use of IP chemotherapy for women with resected early stage disease (stage
I and II, (",
" <a class=\"graphic graphic_table graphicRef51205 \" href=\"UTD.htm?
14/43/15038\">",
" table 1",
" </a>",
" )) is a logical application of this approach. However, there is no clinical
validation that the benefits outweigh the risks in this population, and it is not
yet considered a standard approach. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/48/36618?
source=see_link\">",
" \"Epithelial ovarian cancer: Initial surgical management\"",
" </a>",
" .)",
" </p>",
" <p>",
" Contraindications to IP port placement include patients at poor surgical risk,
active peritonitis or sepsis, and the presence of extensive intraabdominal
adhesions, which prevent adequate distribution of instilled chemotherapeutic
agents.",
" </p>",
" <p>",
" Older age is not necessarily a contraindication to IP chemotherapy, although
women 70 years of age and older may tolerate fewer cycles of IP chemotherapy than
their younger counterparts [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/9\">",
" 9",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" IP CATHETER AND PORT",
" </span>",
" &nbsp;&mdash;&nbsp;We recommend the use of a single lumen implanted port with
a silicone peritoneal catheter (14.3 Fr, Bardport reorder number 0603006) or a
fully implantable port attached to a single lumen venous silicone catheter of large
size (9.6 French [Fr] or higher- reorder number 0602870) so that it does not kink
and obstruct flow (",
" <a class=\"graphic graphic_picture graphicRef52603 \" href=\"UTD.htm?
7/14/7392\">",
" picture 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" 10",
" </a>",
" ]. These catheters are not associated with increased risks of complications or
a higher rate of treatment discontinuation [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/11,12\">",
" 11,12",
" </a>",
" ]. This may be secondary to the material not causing a tissue reaction.",
" </p>",
" <p>",
" Peritoneal catheters designed for dialysis have been associated with bowel
complications when used in ovarian cancer patients for chemotherapy. The catheter
is only needed for infusion; withdrawal of fluid is not needed after chemotherapy.
Furthermore, the Dacron cuff on Tenckhoff dialysis catheters may erode into the
peritoneal cavity and be associated with bowel obstructions. There appear to be
some catheter materials which may encourage the formation of fibrous sheaths and
bowel adhesions, which can make them difficult to remove at the end of therapy.",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Timing",
" </span>",
" &nbsp;&mdash;&nbsp;The optimal timing of IP",
" <span class=\"nowrap\">",
" catheter/port",
" </span>",
" placement has not been established. The IP access device can be placed at the
time of initial laparotomy performed for diagnosis, staging, and cytoreduction, as
long as a thorough discussion with the patient about the potential benefits and
toxicities associated with this approach has taken place prior to surgery.
Alternatively, it could be placed laparoscopically or by mini-laparotomy within a
few weeks, although this necessitates a second surgical procedure. Many patients
are reluctant to have a second operation for placement. Therefore, when the
diagnosis is expected, and optimal surgical resection can be accomplished, it is
ideal to have the chemotherapy delivery devices already in place.",
" </p>",
" <p>",
" Delayed catheter insertion, despite the potential for postoperative adhesion
formation (and limitation of free flow of the IP fluid to some tumor locations),
was not associated with an increased probability of failing to complete IP
chemotherapy in GOG 172 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" 13",
" </a>",
" ]. The entire course of therapy was completed by 41 percent of patients who
had catheters placed at the time of initial surgery versus 35 percent of those with
delayed catheter insertion.",
" </p>",
" <p>",
" Uncomplicated bowel resection during initial surgery does not necessitate
delayed catheter placement. In GOG 172, although patients who required resection of
the rectosigmoid or left colon were at significantly greater risk of not initiating
IP therapy (16 versus 5 percent of those who did not have a left colon or
rectosigmoid resection), the number of completed chemotherapy cycles was similar.
On the other hand, the risk of complications, presumably due to fecal
contamination, appears to be higher when bowel resection is performed as part of
the debulking procedure [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/14\">",
" 14",
" </a>",
" ]. Therefore, delayed insertion of an IP access device should be considered if
the peritoneal cavity is grossly contaminated [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" 13",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h3\">",
" Summary",
" </span>",
" &nbsp;&mdash;&nbsp;In general, it is easier to place an IP port and then
remove it if not needed than to place the device at a second surgery. Thus, in most
cases, it is appropriate to insert IP catheters concurrently with the initial
surgical procedure. However, delayed insertion is preferable if there is diagnostic
uncertainty, intraoperative issues which preclude safe placement at initial
surgery, or if the primary cytoreductive procedure includes a left colon resection
with gross fecal contamination of the peritoneal cavity.",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Location",
" </span>",
" &nbsp;&mdash;&nbsp;While there have been no studies comparing different IP
chemotherapy port locations, the most commonly recommended site is two to three
fingerbreadths above the right or left costal margin in the midclavicular line.
This location permits the port reservoir to be trapped against a fixed underlying
structure (the ribs) while it is being accessed. This prevents internal rotation of
the reservoir and difficulty with insertion of the Huber needle into the port,
which can be a problem if the device is placed in the right or left lower
quadrant.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h1\">",
" SURGICAL PROCEDURE",
" </span>",
" &nbsp;&mdash;&nbsp;We have observed that leaving the cervix in situ helps to
prevent vaginal leakage of the IP infusate; therefore, we try to perform the
procedure with the vaginal cuff intact or after a supracervical hysterectomy. The
removal of all cancer is the highest priority and if entry into the vagina is
required or if a total hysterectomy is performed, then the vaginal cuff should be
closed with delayed absorbable suture to create a water-tight seal [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" 10",
" </a>",
" ]. Careful attention to abdominal wall closure with a water-tight closure to
prevent leaking of ascites or IP chemotherapy is also very important. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/48/36618?
source=see_link\">",
" \"Epithelial ovarian cancer: Initial surgical management\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Placement during initial laparotomy",
" </span>",
" &nbsp;&mdash;&nbsp;The choice of location for the IP catheter depends on the
surgical field. Areas where the peritoneum has been stripped should be avoided. If
a rectosigmoid resection and mobilization of the splenic flexure has been
performed, then the right side should be chosen. If the terminal ileum and right
colon has been resected, then the left side should be chosen. It is important to
remember to expect the transverse colon to be adherent to the anterior abdominal
wall after the complete omentectomy procedure. For this reason, the entry into the
abdominal cavity should be at or below the umbilicus, via a minilap, avoiding the
midline incision.",
" </p>",
" <p>",
" Upon completion of the staging and cytoreduction surgery, a 3 to 4 cm incision
is made in the skin over the lower left or right costal margin at the midclavicular
line and this incision is carried down to the fascia [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/15\">",
" 15",
" </a>",
" ]. A small area under the subcutaneous tissue and over the ribs is dissected
to create a pocket, slightly larger than the diameter of the port, to accommodate
the device. The port needs to be easily palpable and not placed under too much
adipose tissue, which could impede access with the Huber needle.",
" </p>",
" <p>",
" Next, an intraabdominal site is chosen where the catheter will pass through
the peritoneum; this site should be ipsilateral to the IP port incision, and about
6 cm lateral to the umbilicus. The peritoneal cavity is identified and care must be
taken to avoid injury to underlying bowel. Using a tunneling device (available in
the catheter kit, or if unavailable, a long tonsil clamp can be used), a
subcutaneous tunnel is made under the adipose tissue, and overlying the fascia,
from the port pocket to the site of desired entry into the peritoneal cavity.",
" </p>",
" <p>",
" IP catheters are available preattached to the port, or unattached, and the
surgeon can choose his or her preference. The catheter is drawn from the port
through the tunnel and then plunged through fascia and peritoneum using the
smallest perforation possible to minimize retrograde leakage of IP chemotherapy. A
chromic suture can be used to purse string the peritoneum around the catheter when
the peritoneal window is too large. The four corners of the IP port are sutured to
the fascia overlying the rib cage with permanent suture (eg, prolene). The use of
prolene in four corners prevents rotation and flipping of the port, thus avoiding
potential access problems.",
" </p>",
" <p>",
" The system is flushed with 10 mL of",
" <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?source=see_link\">",
" heparin",
" </a>",
" 100",
" <span class=\"nowrap\">",
" units/mL",
" </span>",
" of saline to ensure that there is free flow without leaks, and then the distal
end of the catheter is placed in the pelvis at the desired infusion site. At least
10 cm of catheter should be contained within the peritoneal cavity. The catheter
should be placed where the formation of adhesions is least likely to occur, keeping
in mind what tissues were removed and where peritoneal stripping was required. For
instance, the transverse colon becomes adherent to the upper half of the anterior
abdominal wall after a complete omentectomy. All of the incisions are then closed
with consideration of adhesion prevention strategies and with peritoneal
approximation, if possible, to create an optimum barrier for preventing leakage of
instilled fluid.",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h2\">",
" Delayed insertion",
" </span>",
" &nbsp;&mdash;&nbsp;Alternatively, the catheter and port can be placed during a
subsequent interval surgical procedure, either laparoscopically or by
minilaparotomy [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10,16\">",
" 10,16",
" </a>",
" ]. As was indicated above, the site of the port placement depends on the
surgery previously performed. Following omentectomy, there is usually adherence of
the transverse colon to the anterior abdominal wall. If a rectosigmoid resection
and mobilization of the splenic flexure has occurred, then the right side should be
chosen. If the terminal ileum, and right colon has been resected, then the left
side should be chosen.",
" </p>",
" <p>",
" The site for the IP port is prepared and a tunnel created as described above.
The peritoneal site where the catheter is to penetrate the peritoneum is identified
under direct vision via mini-laparotomy or observed laparoscopically. It is
important to enter the peritoneal cavity under direct vision because a previous
staging laparotomy for ovarian cancer is likely to have resulted in adhesion
formation, particularly between bowel and anterior abdominal wall. The catheter
perforation site through the peritoneum must be separate from other incisions. The
mini-laparotomy should be closed in all layers, with care to be watertight and not
to kink the catheter.",
" </p>",
" <p>",
" There have been reports of tumor growing in the IP catheter tract or port
pocket after laparoscopic placement. This is theorized to be due to tumor
infiltration under the pressure of the carbon dioxide gas or retrograde flow of
ascites into the catheter tract or port pocket. The risk of this complication may
be less if the catheter is not brought through a trocar site that is too large for
the catheter, or if the catheter is pulled through the peritoneum with a tunneler
or pushed through a pull away sheath. It is also important that chemotherapy be
delivered soon after laparoscopy, since nodules in trocar sites can be seen within
two weeks of the procedure; a similar phenomenon occurs at paracentesis sites.",
" </p>",
" <p>",
" Because of this risk, we prefer mini-laparotomy over laparoscopic placement of
the IP port and catheter. The mini-laparotomy incision must be made with the
details of the previous surgery in mind. The transverse colon can be avoided by
making the incision 6 cm lateral to the umbilicus, generally on the right, if the
cecum was not removed. If a rectosigmoid resection and end to end anastomoses was
performed, the left side should be avoided to avoid encountering adhesions.",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h2\">",
" Procedure for chemotherapy administration",
" </span>",
" &nbsp;&mdash;&nbsp;IP chemotherapy infusions have been given in the operating
room or as early as 24 hours postoperatively. The fluid shifts which surround
aggressive surgical debulking make renal toxicity a major concern. During GOG 172,
the average delay of chemotherapy from date of surgery was 21 days [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" 2",
" </a>",
" ]. We and others [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/17\">",
" 17",
" </a>",
" ] suggest waiting until the patient has resumed normal bowel function (ie,
postoperative ileus has resolved) and has recovered enough to be sure there are no
signs of perioperative complications. Treatment may begin 24 hours after an IP
catheter has been placed.",
" </p>",
" <p>",
" Although there is controversy regarding the optimal regimen for IP therapy,
most experts recommend the regimen utilized on the experimental arm of GOG 172 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" 2",
" </a>",
" ]. This consists of six 21-day courses of intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" (135",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" </span>",
" over 24 hours on day 1) with IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" (100",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" </span>",
" in two liters of warmed normal saline) on day 2 and IP paclitaxel (60",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" )",
" </span>",
" on day 8 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" 2",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/11/21689?
source=see_link&amp;anchor=H250842013#H250842013\">",
" \"First-line chemotherapy for advanced (stage III or IV) epithelial ovarian,
fallopian tubal, and peritoneal cancer\", section on 'Intraperitoneal
chemotherapy'",
" </a>",
" .)",
" </p>",
" <p>",
" The technique of IP chemotherapy administration is as follows:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Premedication should include decadron,",
" <a class=\"drug drug_general\" href=\"UTD.htm?21/2/21544?
source=see_link\">",
" ondansetron",
" </a>",
" or equivalent, and usually",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/28/33222?
source=see_link\">",
" aprepitant",
" </a>",
" . (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/18/39210?
source=see_link\">",
" \"Prevention and treatment of chemotherapy-induced nausea and vomiting\"",
" </a>",
" .)",
" </li>",
" <li>",
" Prior to chemotherapy administration, a topical anesthetic, such as
liposomal",
" <a class=\"drug drug_general\" href=\"UTD.htm?34/34/35360?
source=see_link\">",
" lidocaine",
" </a>",
" (applied 30 minutes prior to the procedure) or Emla cream (applied 60
minutes prior to the procedure) is applied to the skin over the IP port site and
covered with an occlusive dressing.",
" </li>",
" <li>",
" IV prehydration with a liter of normal saline to ensure adequate urine
output of 100 mL per hour before administration of the IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?
source=see_link\">",
" cisplatin",
" </a>",
" to prevent renal toxicity. This is not necessary prior to the day 8 IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?
source=see_link\">",
" paclitaxel",
" </a>",
" .",
" </li>",
" <li>",
" After removal of the dressing using sterile technique, chemotherapy is
administered into the IP port using a 19 or 20 gauge right-angled needle (eg, Huber
needle). The chemotherapy (both",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?
source=see_link\">",
" cisplatin",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?
source=see_link\">",
" paclitaxel",
" </a>",
" ) is administered in 1 liter of warmed (37 degrees C) normal saline infused
under gravitational flow alone as rapidly as possible. A second liter of warmed
saline is then infused to help distribute the drug but can be stopped if the
patient becomes too uncomfortable.",
" <br/>",
" <br/>",
" During infusion, the patient is placed supine or in semi-Fowler's position
with her head no higher than 30 degrees above the bed, both for comfort and to
prevent dislocation of the needle. After the infusion (and during the second liter
of hydration), she is repositioned from side to side every 15 minutes for one hour
to help disperse the infusate. Ninety percent of the administered chemotherapeutic
agents are absorbed within four hours.",
" </li>",
" <li>",
" After administration of chemotherapy, the port and catheter are flushed with
at least 10 mL of",
" <a class=\"drug drug_general\" href=\"UTD.htm?39/34/40489?
source=see_link\">",
" heparin",
" </a>",
" 100",
" <span class=\"nowrap\">",
" units/mL.",
" </span>",
" The needle is then removed and the site occluded with a pressure dressing to
prevent leakage of the infusate from the port. The dressing can be removed after 12
hours.",
" </li>",
" <li>",
" Following IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?
source=see_link\">",
" cisplatin",
" </a>",
" , posthydration with another liter of normal saline IV is recommended to
prevent renal toxicity, maintaining urine output of 100 cc per hour.",
" <a class=\"drug drug_general\" href=\"UTD.htm?27/52/28488?
source=see_link\">",
" Furosemide",
" </a>",
" or",
" <a class=\"drug drug_general\" href=\"UTD.htm?3/42/3752?source=see_link\">",
" mannitol",
" </a>",
" can be utilized if the appropriate balance of input and output is concerning
and the patient is not dehydrated. It must be emphasized that IP saline is not
adequate hydration to prevent renal toxicity. Some patients with heart disease need
output to be closely monitored after receiving IV and IP fluid. It is important to
give adequate home nausea medication (",
" <a class=\"drug drug_general\" href=\"UTD.htm?21/2/21544?
source=see_link\">",
" ondansetron",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/28/33222?
source=see_link\">",
" aprepitant",
" </a>",
" ) to prevent delayed",
" <span class=\"nowrap\">",
" nausea/vomiting",
" </span>",
" and dehydration.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Other helpful information for health professionals on administration of IP
chemotherapy is available online from both the GOG and the National Cancer
Institute [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/3,18\">",
" 3,18",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h2\">",
" Catheter removal",
" </span>",
" &nbsp;&mdash;&nbsp;The catheter should be removed as soon as all of the
courses of chemotherapy have been completed, or within one year, given the high
rate of complications [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13,19\">",
" 13,19",
" </a>",
" ]. Removal can be performed as an office procedure under local anesthesia. The
incision is opened, the capsule of scar surrounding the port is cut with a scalpel,
and the four sutures are identified, cut and removed. The port and catheter are
pulled out, usually without difficulty, as they do not typically form adhesions to
bowel or intraperitoneal structures unless a Dacron cuff was utilized.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h1\">",
" COMPLICATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Patients undergoing IP chemotherapy should be regularly
assessed for abdominal pain, catheter-related problems, and signs of infection,
neurotoxicity, renal toxicity, and myelosuppression. We do not routinely administer
growth factor support during the first cycle.",
" </p>",
" <p>",
" In general, there are three main categories of complications for which IP
chemotherapy is discontinued prematurely: abdominal pain with infusions;
intolerance to the higher dose",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" ; and problems related to the access device. Some potentially avoidable issues
include accessing the Huber needle into the port, kinking of the catheter,
retrograde flow of infusate, vaginal leakage of fluid, bowel injuries, and port
infections. They can be minimized by following the surgical techniques outlined
above. When catheters fail, attempts to replace them often fail unless the specific
problem is easily remedied (eg, a rotated port).",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h2\">",
" Prevention and management of complications related to chemotherapy",
" </span>",
" &nbsp;&mdash;&nbsp;Patients administered either IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" or",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" should receive the same supportive care drugs used with IV administration of
these agents. Delayed nausea is common following IP administration of cisplatin.
The nausea and vomiting associated with cisplatin will increase the chance of renal
toxicity if not adequately prevented.",
" </p>",
" <p>",
" The specific antiemetic regimen should be chosen to maximize control of both
acute and delayed emesis (ie, three days of",
" <a class=\"drug drug_general\" href=\"UTD.htm?32/28/33222?source=see_link\">",
" aprepitant",
" </a>",
" in combination with a long-acting serotonin receptor antagonist plus three to
four days of oral corticosteroids). (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/18/39210?
source=see_link&amp;anchor=H7#H7\">",
" \"Prevention and treatment of chemotherapy-induced nausea and vomiting\",
section on 'Neurokinin-1 receptor antagonists'",
" </a>",
" .)",
" </p>",
" <p>",
" In addition, routine premedications, including antihistamines and",
" <a class=\"drug drug_general\" href=\"UTD.htm?33/4/33856?source=see_link\">",
" dexamethasone",
" </a>",
" , should be given before",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" administration to prevent hypersensitivity reactions. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/57/43930?
source=see_link&amp;anchor=H32#H32\">",
" \"Infusion reactions to systemic chemotherapy\", section on 'Taxanes'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h3\">",
" Nephrotoxicity",
" </span>",
" &nbsp;&mdash;&nbsp;The avoidance of",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" -related nephrotoxicity requires that the clinician pay close attention to
hydration status and emesis prophylaxis, particularly with the first cycle of IP
chemotherapy administration. The first cycle is usually the most challenging. This
is because many women are undernourished, with a low albumin level, peripheral
edema, and ascites. Third spacing is associated with poor intravascular volume.
Avoiding dehydration through close attention to volume status and adequate
antiemetic therapy will help to prevent renal toxicity. Within two to three weeks,
the nutritional condition of the patient will likely be markedly improved, and
third spacing will resolve.",
" </p>",
" <p>",
" As noted previously, IV prehydration with a liter of normal saline and a urine
output of at least 100 mL per hour should be achieved before administration of the
IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" . A second liter of IV hydration is given following the IP cisplatin, and two
hours of urine output of greater than 100 cc per hour should be observed prior to
sending the patient home.",
" </p>",
" <p>",
" If renal insufficiency develops, treatment should be withheld until renal
function improves [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/17\">",
" 17",
" </a>",
" ]. In GOG trial 172, if the serum creatinine rose to &ge;2",
" <span class=\"nowrap\">",
" mg/dL,",
" </span>",
" creatinine clearance was measured. Subsequent treatment was held if the
creatinine clearance was less than 50",
" <span class=\"nowrap\">",
" mL/min",
" </span>",
" and only resumed when it rose above 50",
" <span class=\"nowrap\">",
" mL/min.",
" </span>",
" The tolerability of the regimen may be substantially improved by reducing the
IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" dose to 75 or 80",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" </span>",
" [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" The alternative is to give intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/61/38873?source=see_link\">",
" carboplatin",
" </a>",
" . Until further data become available, the substitution of IP carboplatin for
IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" is considered investigational and reserved for clinical trials [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/17,20\">",
" 17,20",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H16\">",
" <span class=\"h3\">",
" Abdominal pain",
" </span>",
" &nbsp;&mdash;&nbsp;Abdominal pain, which may be worse after IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" than after IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" , is thought to be related to stretching and distention of bowel-to-bowel
adhesions. The symptom of pain suggests that free flow of infusate is not occurring
and that drug distribution is likely to be suboptimal. Some patients experience
discomfort related to sensing abdominal distention or from intercostal nerve
irritation [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/21\">",
" 21",
" </a>",
" ]. Abdominal distention may also result in the perception of being short of
breath.",
" </p>",
" <p>",
" If pain is encountered, the second liter of IP normal saline after drug
infusion may be reduced in volume or eliminated, or the rate of flow can be
reduced. GOG trial 172 mandated dose reduction for patients reporting grade 2
abdominal pain (",
" <a class=\"graphic graphic_table graphicRef58287 \" href=\"UTD.htm?
5/59/6075\">",
" table 2",
" </a>",
" ), and changeover to IV chemotherapy for those with grade 3 abdominal pain or
recurrent grade 2 abdominal pain despite dose reduction. Low-grade abdominal pain
can usually be treated with non-opioids [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/22\">",
" 22",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H17\">",
" <span class=\"h3\">",
" Neurotoxicity",
" </span>",
" &nbsp;&mdash;&nbsp;The combination of",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" and",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" is associated with a significant potential for neurotoxicity. Dose reduction
(to 75 or 80",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" )",
" </span>",
" when symptoms are first observed may permit more cycles of IP cisplatin to be
administered. Alternatives include substituting intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?37/61/38873?source=see_link\">",
" carboplatin",
" </a>",
" for cisplatin, and",
" <a class=\"drug drug_general\" href=\"UTD.htm?40/59/41913?source=see_link\">",
" docetaxel",
" </a>",
" for paclitaxel. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/32/43530?
source=see_link\">",
" \"Neurologic complications of non-platinum cancer chemotherapy\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/23/37242?
source=see_link\">",
" \"Neurologic complications of platinum-based chemotherapy\"",
" </a>",
" .)&nbsp;",
" <a class=\"drug drug_general\" href=\"UTD.htm?0/42/678?source=see_link\">",
" Amifostine",
" </a>",
" is another option for these patients.",
" </p>",
" <p class=\"headingAnchor\" id=\"H18\">",
" <span class=\"h2\">",
" Catheter-related complications",
" </span>",
" &nbsp;&mdash;&nbsp;Catheter-related problems are frequent and may necessitate
premature discontinuation of IP chemotherapy.",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In GOG 172 trial, catheter-related problems were the primary reason for
discontinuing IP chemotherapy in 40 of the 119 patients who did not complete the
entire six courses of IP therapy arm and a contributing cause in another ten [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" 13",
" </a>",
" ]. These problems included catheter-related infection (n = 25), a blocked
catheter (n = 10), leakage around the port or into the subcutaneous tissues (n =
5), access problems (n = 8), and vaginal leakage of infusion fluid (n = 2). Similar
complication and completion rates were seen in a single institution review [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/22\">",
" 22",
" </a>",
" ].",
" </li>",
" <li>",
" In a review of data from four trials totaling almost 900 patients, the
frequency of complications were: port complications in 10 to 20 percent, inflow
obstruction in 2 to 9 percent, infection in 4 to 10 percent, and bowel injury in 0
to 2 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" 13",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H19\">",
" <span class=\"h3\">",
" Inability to access port or infuse the drug",
" </span>",
" &nbsp;&mdash;&nbsp;Inability to access the port or infuse the drug into the
peritoneal cavity is best evaluated using fluoroscopy. Once the Huber needle is
directed through the diaphragm of the port into the reservoir, contrast can be
injected. The patient is then observed with fluoroscopy to ensure the integrity and
patency of the catheter and to see whether contrast flows into the peritoneal
cavity. This procedure may also demonstrate adhesions, retrograde flow of dye along
the catheter into the port pocket, and dye entering the gastrointestinal tract.",
" </p>",
" <p>",
" Management depends on the specific problem that is identified:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Rotational problems can usually be corrected in an outpatient surgery suite
by making a small incision over the port under local anesthesia and suturing it in
the correct position.",
" </li>",
" <li>",
" A kinked catheter can be repaired, although in general, this problem is far
more common with 6 Fr catheters (which are not recommended for this reason) than
they are with the sturdier 9.6 or 14.3 Fr silicone catheters",
" </li>",
" <li>",
" If the catheter has been cut by the Huber needle during failed attempts to
access a port, the hole in the catheter can be surgically corrected, allowing IP
chemotherapy to resume.",
" </li>",
" <li>",
" A blocked catheter or the demonstration of retrograde flow at the port or
where the catheter perforates the peritoneum is often caused by adhesions blocking
free flow into the peritoneal cavity. Such problems usually required removal of the
catheter as most blockages are due to adhesions or a fibrous capsule around the
catheter and are not correctable without choosing a new peritoneal infusion site.",
" </li>",
" </ul>",
" </p>",
" <p>",
" Overall, replacing a malfunctioning port allows approximately 50 percent of
patients to complete their planned IP therapy, but requires a committed patient and
surgeon. When access problems are encountered, chemotherapy can be given
intravenously, at least temporarily, to prevent delay of treatment.
Contraindications to replacement include peritonitis, an infected port,
intraabdominal abscess, bowel injury, or fistula.",
" </p>",
" <p class=\"headingAnchor\" id=\"H20\">",
" <span class=\"h3\">",
" Leakage of infusate",
" </span>",
" &nbsp;&mdash;&nbsp;Leakage of infusate through the vaginal and abdominal
surgical wounds may cease when these wounds heal; IP infusion may need to be
delayed in such patients. In such cases, chemotherapy can be given intravenously,
at least temporarily, to prevent delay of treatment.",
" </p>",
" <p class=\"headingAnchor\" id=\"H21\">",
" <span class=\"h3\">",
" Peritonitis, abscess, bowel injury",
" </span>",
" &nbsp;&mdash;&nbsp;Abdominal pain is a common complaint during therapy, and is
usually related to the infusion and distention of the abdomen (see",
" <a class=\"local\" href=\"#H14\">",
" 'Prevention and management of complications related to chemotherapy'",
" </a>",
" above). The possibility of peritonitis or gastrointestinal injury should be
considered if there is rebound, guarding, nausea, vomiting, diarrhea, fever, or an
elevated white blood cell count.",
" </p>",
" <p>",
" Bowel injury (fistulas, accidental perforation by the catheter) and other
complications such as intestinal obstruction can occur, but are uncommon (3 to 5
percent of cases) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" 13",
" </a>",
" ]. In one series, intestinal obstruction developed in 34 percent of patients
after IP chemotherapy commenced, but the majority were related to progression of
malignant intraabdominal disease [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/23\">",
" 23",
" </a>",
" ]. Only 4 percent of patients had intestinal obstruction that was related to
adhesions from IP treatment.",
" </p>",
" <p>",
" Gastrointestinal necrosis and perforation have been associated with
postoperative administration of",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" , both IV and IP [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/24,25\">",
" 24,25",
" </a>",
" ]. It is possibly related to subclinical surgical complications or impaired
host defense and repair mechanisms, which may be unmasked in the first few weeks of
IP therapy.",
" </p>",
" <p>",
" The possibility of these complications can be evaluated by irrigating the
catheter with 50 mL of normal saline, aspirating, and sending the specimen for cell
count and culture [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" 10",
" </a>",
" ]. An upright abdominal x-ray is useful for looking for free air related to
perforated bowel; however, it is possible to cause free air by inadvertent IP
administration of air that is present in the infusion line. Injecting the port with
renografin contrast agent can demonstrate flow into the gastrointestinal tract
(implying bowel injury) on rare occasions.",
" </p>",
" <p>",
" If an intraabdominal infection develops, the port and catheter should be
removed. Initially, broad spectrum antibiotic therapy with coverage for both skin
and gastrointestinal flora is indicated with tailoring of the regimen to cover
subsequently identified pathogens [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" 10",
" </a>",
" ].",
" </p>",
" <p>",
" Early recognition, timely diagnosis, and appropriate treatment of
gastrointestinal tract perforation improves outcome. If free air is identified
under the diaphragm, evaluation includes urgent CT scan or immediate surgical
intervention. A catheter in the lumen of the bowel does not necessarily imply the
need for laparotomy to repair the bowel, as long as peritonitis is absent. Sealing
of the bowel can occur spontaneously, and this situation has been successfully
treated with removal of the catheter alone. However, management of this
complication must be individualized.",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Beyond the Basics topics (see",
" <a class=\"medical medical_patient\" href=\"UTD.htm?10/63/11252?
source=see_link\">",
" \"Patient information: Ovarian cancer diagnosis and staging (Beyond the
Basics)\"",
" </a>",
" and",
" <a class=\"medical medical_patient\" href=\"UTD.htm?40/34/41507?
source=see_link\">",
" \"Patient information: First-line medical treatment of epithelial ovarian
cancer (Beyond the Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H23\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;There is a growing body of evidence showing a survival
advantage for intraperitoneal (IP) administration of platinum and taxane-based
chemotherapy in women with optimally cytoreduced (to &lt;1.0 cm) stage III
epithelial ovarian cancer. This approach is best suited to patients who have
minimal residual disease. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Importance of initial surgical cytoreduction'",
" </a>",
" above.)",
" </p>",
" <p>",
" The following recommendations are geared toward women who are treated with IP
chemotherapy as per the experimental arm of GOG trial 172: six 21-day courses, each
consisting of intravenous",
" <a class=\"drug drug_general\" href=\"UTD.htm?16/58/17320?source=see_link\">",
" paclitaxel",
" </a>",
" (135",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" </span>",
" over 24 hours) on day 1, IP",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?source=see_link\">",
" cisplatin",
" </a>",
" (100",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" </span>",
" in two liters of warmed normal saline) on day 2, and IP paclitaxel (60",
" <span class=\"nowrap\">",
" mg/m",
" <sup>",
" 2",
" </sup>",
" )",
" </span>",
" on day 8 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" 2",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Procedure for chemotherapy administration'",
" </a>",
" above.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" In most cases, the IP port and catheter can be placed at the time of initial
surgery, although delayed placement is preferred if there is diagnostic
uncertainty, intraoperative issues which preclude safe placement at initial
surgery, or if the primary cytoreductive procedure includes a left colon resection
with gross fecal contamination of the peritoneal cavity. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Timing'",
" </a>",
" above.)",
" </li>",
" <li>",
" We recommend the use of a single lumen implanted port with a 14.3 French
(Fr) silicone peritoneal catheter or a fully implantable port attached to a single
lumen venous silicone catheter of large size (9.6 Fr or higher) so that it does not
kink and obstruct flow. We recommend avoiding the dacron cuff which can migrate
into the peritoneal cavity and cause bowel adhesions.",
" <br/>",
" <br/>",
" The port is placed subcutaneously over the lower portion of the rib cage and
connected to a catheter that perforates the peritoneum lateral to the umbilicus.
(See",
" <a class=\"local\" href=\"#H4\">",
" 'IP Catheter and port'",
" </a>",
" above.)",
" </li>",
" <li>",
" Intraperitoneal",
" <a class=\"drug drug_general\" href=\"UTD.htm?20/51/21305?
source=see_link\">",
" cisplatin",
" </a>",
" is administered in 1 liter of warmed infusate, which is dripped through a
large bore Huber needle into the port by gravity and followed by a second liter of
warmed normal saline. The importance of intravenous hydration both before and after
IP cisplatin as well as optimal antiemetic control help to prevent dehydration and
renal toxicity cannot be overstated. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Procedure for chemotherapy administration'",
" </a>",
" above.)",
" </li>",
" <li>",
" Treatment-related complications, including abdominal discomfort, infection,
obstruction, leakage, access problems, and bowel injury, occur in 10 to 35 percent
of patients, but IP therapy can be completed in many. (See",
" <a class=\"local\" href=\"#H13\">",
" 'Complications'",
" </a>",
" above.)",
" <br/>",
" <br/>",
" Replacement of a malfunctioning port will allow approximately 50 percent of
patients to complete their planned IP therapy. Among the indications for removal of
the port and catheter are intraabdominal infection, bowel injury, and nonremediable
catheter blockage (such as retrograde flow of dye into the port pocket or at the
point where the catheter perforates the peritoneum). (See",
" <a class=\"local\" href=\"#H18\">",
" 'Catheter-related complications'",
" </a>",
" above.)",
" </li>",
" <li>",
" We recommend removing the catheter at the completion of chemotherapy or
within one year of placement. (See",
" <a class=\"local\" href=\"#H12\">",
" 'Catheter removal'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
" <ol id=\"reference\">",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/1\">",
" Markman M. Intraperitoneal chemotherapy. Semin Oncol 1991; 18:248.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/2\">",
" Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin and
paclitaxel in ovarian cancer. N Engl J Med 2006; 354:34.",
" </a>",
" </li>",
" <li>",
" NCI Clinical Alert available online at
www.nlm.nih.gov/databases/alerts/ovarian_ip_chemo.html (Accessed on April 27,
2011).",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/4\">",
" Helm CW. The role of hyperthermic intraperitoneal chemotherapy (HIPEC) in
ovarian cancer. Oncologist 2009; 14:683.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/5\">",
" Markman M. Intraperitoneal chemotherapy in the management of malignant
disease. Expert Rev Anticancer Ther 2001; 1:142.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/6\">",
" Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal
cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a
meta-analysis. J Clin Oncol 2002; 20:1248.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/7\">",
" Carney ME, Lancaster JM, Ford C, et al. A population-based study of patterns
of care for ovarian cancer: who is seen by a gynecologic oncologist and who is not?
Gynecol Oncol 2002; 84:36.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/8\">",
" Bristow RE, Zahurak ML, del Carmen MG, et al. Ovarian cancer surgery in
Maryland: volume-based access to care. Gynecol Oncol 2004; 93:353.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/9\">",
" Kothari R, Nagel C, Koopmeiners JS, et al. The effect of age on the
tolerability of intraperitoneal chemotherapy, complication rate, and survival in
patients with ovarian cancer. Gynecol Oncol 2010; 119:491.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/10\">",
" Markman M, Walker JL. Intraperitoneal chemotherapy of ovarian cancer: a
review, with a focus on practical aspects of treatment. J Clin Oncol 2006;
24:988.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/11\">",
" Black D, Levine DA, Nicoll L, et al. Low risk of complications associated
with the fenestrated peritoneal catheter used for intraperitoneal chemotherapy in
ovarian cancer. Gynecol Oncol 2008; 109:39.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/12\">",
" Ivy JJ, Geller M, Pierson SM, et al. Outcomes associated with different
intraperitoneal chemotherapy delivery systems in advanced ovarian carcinoma: a
single institution's experience. Gynecol Oncol 2009; 114:420.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/13\">",
" Walker JL, Armstrong DK, Huang HQ, et al. Intraperitoneal catheter outcomes
in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal
stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group
Study. Gynecol Oncol 2006; 100:27.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/14\">",
" Makhija S, Leitao M, Sabbatini P, et al. Complications associated with
intraperitoneal chemotherapy catheters. Gynecol Oncol 2001; 81:77.",
" </a>",
" </li>",
" <li>",
" Whitney CW. Gynecologic Oncology Group Surgical Procedures Manual. July
2005.",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/16\">",
" Liou WS, Teng NN, Chan JK. A modified technique for insertion of
intraperitoneal port for chemotherapy. J Surg Oncol 2005; 90:247.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/17\">",
" Marth C, Walker JL, Barakat RR, et al. Results of the 2006 Innsbruck
International Consensus Conference on intraperitoneal chemotherapy in patients with
ovarian cancer. Cancer 2007; 109:645.",
" </a>",
" </li>",
" <li>",
" Information on IP chemotherapy from the Gynecologic Oncology Group (GOG)
available online. www.gog.org/IPChemoEd/ipchemoed.html (Accessed on April 26,
2012).",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/19\">",
" Sakuragi N, Nakajima A, Nomura E, et al. Complications relating to
intraperitoneal administration of cisplatin or carboplatin for ovarian carcinoma.
Gynecol Oncol 2000; 79:420.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/20\">",
" Fujiwara K. Can carboplatin replace cisplatin for intraperitoneal use? Int J
Gynecol Cancer 2008; 18 Suppl 1:29.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/21\">",
" Topuz E, Salihoglu Y, Aydiner A, et al. Celsite port and catheter as an
intraperitoneal access device in the treatment of ovarian cancer. J Surg Oncol
2000; 74:223.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/22\">",
" Landrum LM, Gold MA, Moore KN, et al. Intraperitoneal chemotherapy for
patients with advanced epithelial ovarian cancer: a review of complications and
completion rates. Gynecol Oncol 2008; 108:342.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/23\">",
" Kehoe SM, Williams NL, Yakubu R, et al. Incidence of intestinal obstruction
following intraperitoneal chemotherapy for ovarian tubal and peritoneal
malignancies. Gynecol Oncol 2009; 113:228.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/24\">",
" Seewaldt VL, Cain JM, Goff BA, et al. A retrospective review of paclitaxel-
associated gastrointestinal necrosis in patients with epithelial ovarian cancer.
Gynecol Oncol 1997; 67:137.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/537/abstract/25\">",
" Rose PG, Piver MS. Intestinal perforation secondary to paclitaxel. Gynecol
Oncol 1995; 57:270.",
" </a>",
" </li>",
" </ol>",
" </div>",
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" SUMMARY &amp; RECOMMENDATIONS",
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" INTRODUCTION",
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" RATIONALE",
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" IMPORTANCE OF INITIAL SURGICAL CYTOREDUCTION",
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" INDICATIONS AND CONTRAINDICATIONS",
" </a>",
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" <a class=\"outlineLink\" href=\"#H4\">",
" IP CATHETER AND PORT",
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" <a class=\"outlineLink\" href=\"#H5\">",
" Timing",
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" Placement during initial laparotomy",
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" Delayed insertion",
" </a>",
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" Procedure for chemotherapy administration",
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" Catheter removal",
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" COMPLICATIONS",
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" Prevention and management of complications related to chemotherapy",
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" - Nephrotoxicity",
" </a>",
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" <a class=\"outlineLink\" href=\"#H16\">",
" - Abdominal pain",
" </a>",
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" - Neurotoxicity",
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" - Inability to access port or infuse the drug",
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" - Leakage of infusate",
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" - Peritonitis, abscess, bowel injury",
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" INFORMATION FOR PATIENTS",
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" SUMMARY AND RECOMMENDATIONS",
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" <a href=\"#references\">",
" REFERENCES",
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" </li>",
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" <h1>",
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" GRAPHICS",
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title=\"picture 1\">",
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1\">",
" Staging ovarian peritoneal carcinoma",
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" <a class=\"graphic graphic_table\" href=\"UTD.htm?5/59/6075\" title=\"table
2\">",
" NCI CTCAE grading scale for pain",
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" </li>",
" </ul>",
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" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?35/48/36618?
source=related_link\">",
" Epithelial ovarian cancer: Initial surgical management",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?21/11/21689?
source=related_link\">",
" First-line chemotherapy for advanced (stage III or IV) epithelial ovarian,
fallopian tubal, and peritoneal cancer",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/57/43930?
source=related_link\">",
" Infusion reactions to systemic chemotherapy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?42/32/43530?
source=related_link\">",
" Neurologic complications of non-platinum cancer chemotherapy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/23/37242?
source=related_link\">",
" Neurologic complications of platinum-based chemotherapy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?40/34/41507?
source=related_link\">",
" Patient information: First-line medical treatment of epithelial ovarian
cancer (Beyond the Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_patient\" href=\"UTD.htm?10/63/11252?
source=related_link\">",
" Patient information: Ovarian cancer diagnosis and staging (Beyond the
Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/18/39210?
source=related_link\">",
" Prevention and treatment of chemotherapy-induced nausea and vomiting",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_33_538="Clinical manifestations, diagnosis, and management of diabetic
infections of the lower extremities";
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" <a id=\"authors\">",
" </a>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/538/contributors\">",
" Authors",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/538/contributors\">",
" Amy C Weintrob, MD",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/538/contributors\">",
" Daniel J Sexton, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/538/contributors\">",
" Section Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/538/contributors\">",
" Stephen B Calderwood, MD",
" </a>",
" <br/>",
" </div>",
" <div>",
" <a class=\"contributor contributor_credentials contributorType\"
href=\"UTD.htm?0/33/538/contributors\">",
" Deputy Editor",
" </a>",
" <br/>",
" <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
0/33/538/contributors\">",
" Elinor L Baron, MD, DTMH",
" </a>",
" <br/>",
" </div>",
" </div>",
" <div id=\"disclosures\">",
" <a href=\"UTD.htm?0/33/538/contributor-disclosure\" target=\"_blank\">",
" Disclosures",
" </a>",
" </div>",
" <div id=\"reviewProcess\">",
" <span>",
" All topics are updated as new evidence becomes available and our",
" </span>",
" <a href=\"/home/editorial-policy\" target=\"_blank\">",
" peer review process",
" </a>",
" <span>",
" is complete.",
" </span>",
" </div>",
" <div id=\"literatureReviewDate\">",
" <span class=\"emphasis\">",
" Literature review current through:",
" </span>",
" Oct 2013.",
" <span class=\"pipeSpace\">",
" |",
" </span>",
" <span class=\"emphasis\">",
" This topic last updated:",
" </span>",
" Sep 27, 2012.",
" </div>",
" <div id=\"topicText\">",
" <p class=\"headingAnchor\" id=\"H1\">",
" <span class=\"h1\">",
" INTRODUCTION",
" </span>",
" &nbsp;&mdash;&nbsp;Diabetic foot infections are associated with substantial
morbidity and mortality [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/1\">",
" 1",
" </a>",
" ]. Important risk factors for development of diabetic foot infections include
neuropathy, peripheral vascular disease, and poor glycemic control. In the setting
of sensory neuropathy, there is diminished perception of pain and temperature;
thus, many patients are slow to recognize the presence of an injury to their feet.
Autonomic neuropathy can cause diminished sweat secretion resulting in dry, cracked
skin that facilitates the entry of microorganisms to the deeper skin structures. In
addition, motor neuropathy can lead to foot deformities, which lead to pressure-
induced soft tissue damage. Peripheral artery disease can impair blood flow
necessary for healing of ulcers and infections. Hyperglycemia impairs neutrophil
function and reduces host defenses. Trauma in patients with one or more of these
risk factors precipitates development of wounds that can be slow to heal and
predispose to secondary infection.",
" </p>",
" <p>",
" The microbiology, clinical evaluation, diagnosis, and management of diabetic
foot infections will be reviewed here. The general evaluation of the diabetic foot
and management of uninfected diabetic foot lesions are discussed separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/12/11464?
source=see_link\">",
" \"Evaluation of the diabetic foot\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link\">",
" \"Management of diabetic foot lesions\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H905751\">",
" <span class=\"h1\">",
" OVERVIEW OF APPROACH TO THE PATIENT",
" </span>",
" &nbsp;&mdash;&nbsp;In 2012, the Infectious Disease Society of America updated
guidelines on the diagnosis and management of diabetic foot infections, which were
originally published in 2004 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2\">",
" 2",
" </a>",
" ]. Practical guidelines are also published regularly by the International
Working Group on the Diabetic Foot [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/3\">",
" 3",
" </a>",
" ]. The information reviewed in this topic is largely consistent with these
guidelines.",
" </p>",
" <p>",
" The evaluation of a patient with a diabetic foot infection involves three key
steps: 1) determining the extent and severity of infection, 2) identifying
underlying factors that predispose to and promote infection, and 3) assessing the
microbial etiology.",
" </p>",
" <p>",
" The clinical history should focus on the details related to recent trauma, the
duration of the current lesion(s), associated systemic symptoms, and prior
treatment, if any. Mechanical factors that may predispose to the formation of an
ulcer should be noted, and the history of blood glucose control should be assessed.
Evidence of systemic toxicity should also be carefully noted.",
" </p>",
" <p>",
" Clinical examination should note the location of the lesions, extent of
infection (eg, involving skin, subcutaneous tissue, muscles, tendons",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" bone) and whether bone is grossly visible or palpable by probing. Although
osteomyelitis is highly likely if bone is visible, it may be present in the absence
of such findings. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Diagnosis of underlying osteomyelitis'",
" </a>",
" below.)",
" </p>",
" <p>",
" Clinical examination should also include a neurologic evaluation that
documents the extent of sensory loss as well as a vascular evaluation of the
presence and severity of arterial",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" venous insufficiency. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/12/11464?
source=see_link\">",
" \"Evaluation of the diabetic foot\"",
" </a>",
" .)",
" </p>",
" <p>",
" Laboratory evaluation should include complete blood count as well as
measurement of blood glucose, electrolytes, and renal function. Baseline and
subsequent inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-
reactive protein (CRP) can be useful for monitoring response to therapy [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4\">",
" 4",
" </a>",
" ]. Some [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/5,6\">",
" 5,6",
" </a>",
" ] but not all studies [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/7\">",
" 7",
" </a>",
" ] have suggested that procalcitonin (PCT), a novel inflammatory marker, may
also be useful if laboratory facilities that test this substance are locally
available; further investigation is needed to determine the clinical utility of
this assay. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Diagnosis of underlying osteomyelitis'",
" </a>",
" below.)",
" </p>",
" <p>",
" Initial evaluation should include conventional radiographs to evaluate for
bony deformity, foreign bodies, and gas in the soft tissue. In select cases,
magnetic resonance imaging (MRI) can be performed to better evaluate for soft
tissue abnormalities and osteomyelitis. (See",
" <a class=\"local\" href=\"#H12048040\">",
" 'Osteomyelitis'",
" </a>",
" below and",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12071?
source=see_link\">",
" \"Approach to imaging modalities in the setting of suspected
osteomyelitis\"",
" </a>",
" .)",
" </p>",
" <p>",
" Aerobic and anaerobic cultures of deep tissue or bone biopsies should be
obtained at the time of debridement if deep tissue infection or osteomyelitis is
suspected. (See",
" <a class=\"local\" href=\"#H906271\">",
" 'Obtaining samples for culture'",
" </a>",
" below.)",
" </p>",
" <p>",
" If surgical intervention is warranted for management of infection, formal
neurological",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" vascular evaluation is important for determining the extent of surgical
intervention. (See",
" <a class=\"local\" href=\"#H8\">",
" 'Surgery'",
" </a>",
" below and",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/12/11464?
source=see_link\">",
" \"Evaluation of the diabetic foot\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H2\">",
" <span class=\"h1\">",
" MICROBIOLOGY",
" </span>",
" &nbsp;&mdash;&nbsp;Most diabetic foot infections are polymicrobial, with up to
five to seven different specific organisms often involved. The microbiology of
diabetic foot wounds is variable depending on the extent of involvement [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4,8-10\">",
" 4,8-10",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Superficial diabetic foot infections (including cellulitis and infected
ulcers in antibiotic-na&iuml;ve individuals) are likely due to aerobic gram-
positive cocci (including S. aureus, S. agalactiae, S. pyogenes, and coagulase-
negative staphylococci).",
" </li>",
" <li>",
" Ulcers that are deep, chronically infected,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" previously treated with antibiotics are more likely to be polymicrobial.
Such wounds may involve the above organisms in addition to enterococci,
Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes.",
" </li>",
" <li>",
" Wounds with extensive local inflammation, necrosis, malodorous drainage, or
gangrene with signs of systemic toxicity should be presumed to have anaerobic
organisms in addition to the above pathogens. Potential pathogens include anaerobic
streptococci, Bacteroides species, and Clostridium species [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/11-15\">",
" 11-15",
" </a>",
" ].",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H4124489\">",
" <span class=\"h2\">",
" Risk of specific organisms",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H4124497\">",
" <span class=\"h3\">",
" Resistant Staphylococcus aureus",
" </span>",
" &nbsp;&mdash;&nbsp;Methicillin-resistant S. aureus (MRSA) is a common pathogen
in diabetic foot infections, particularly in those who have had previous MRSA
infections or known colonization. Other risk factors for MRSA infection include
prior antibiotic use, previous hospitalization, and residence in a long-term care
facility. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/53/8026?
source=see_link&amp;anchor=H8#H8\">",
" \"Epidemiology of methicillin-resistant Staphylococcus aureus infection in
adults\", section on 'Risk factors'",
" </a>",
" .)",
" </p>",
" <p>",
" It is also important to note that diabetic patients with chronic foot wounds
who receive repeated and prolonged courses of antibiotics represent an important
risk group for development of vancomycin-intermediate Staphylococcus aureus
infections. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/2/16425?
source=see_link\">",
" \"Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus
infections\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4124514\">",
" <span class=\"h3\">",
" Pseudomonas aeruginosa",
" </span>",
" &nbsp;&mdash;&nbsp;P. aeruginosa is a particularly prevalent organism in
diabetic foot infections reported from regions with warm climates. As an example,
in a study of 434 patients with infected diabetic foot ulcers in Northern India, P.
aeruginosa was the most common isolate, found in 20 percent of initial cultures [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/16\">",
" 16",
" </a>",
" ]. Macerated ulcers, foot soaking, and other exposure to water or moist
environments also likely increases the risk of involvement with P. aeruginosa.
However, in temperate climates and in the absence of the preceding findings and
exposures, P. aeruginosa is not a particularly common pathogen. Furthermore, its
role as a pathogen in routine clinical practice is often hard to assess. As an
example, when P. aeruginosa was isolated from participants of clinical studies of
diabetic foot infections, most patients improved on antibiotic regimens that did
not cover Pseudomonas, suggesting that it was not the primary pathogenic organism
[",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/17,18\">",
" 17,18",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H4124592\">",
" <span class=\"h3\">",
" Resistant enteric gram-negative rods",
" </span>",
" &nbsp;&mdash;&nbsp;Gram-negative bacilli that express an extended-spectrum
beta-lactamase (ESBL) are increasing in prevalence worldwide. These pathogens are
more common in patients with prolonged hospital stays, prolonged catheterization,
prior antibiotic use, or residence in a long-term care facility (see",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/53/30553?
source=see_link&amp;anchor=H11#H11\">",
" \"Extended-spectrum beta-lactamases\", section on 'Epidemiology'",
" </a>",
" ). The involvement of ESBL-producing organisms in diabetic foot infections in
particular is also increasingly reported [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/19,20\">",
" 19,20",
" </a>",
" ]. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H3\">",
" <span class=\"h1\">",
" CLINICAL MANIFESTATIONS",
" </span>",
" &nbsp;&mdash;&nbsp;Diabetic foot infections can develop as a result of
neuropathic or ischemic ulcers, traumatic wounds, skin cracks or fissures, or other
defects in the skin of the foot or nail beds (paronychia) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,21\">",
" 2,21",
" </a>",
" ]. Thus, infection can present as localized superficial skin involvement at
the site of a preexisting lesion or as infection of the skin or deeper skin
structures that has spread beyond the site of local trauma. Such infections can
subsequently extend to joints, bones, and the systemic circulation.",
" </p>",
" <p>",
" Diabetic foot infections are often accompanied by the cardinal manifestations
of inflammation (erythema, warmth, swelling, and tenderness)",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" the presence of pus in an ulcer or sinus tract [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/8\">",
" 8",
" </a>",
" ]. However, these local signs of infection may not be evident in certain
cases. Infections may not manifest with warmth and erythema in the setting of
severe ischemia. Diabetics with sensory neuropathy may have diminished sensation in
the involved area and therefore may not complain of tenderness nor, in some cases,
even realize that infection is present. In such instances, infection may progress
to involve deeper tissues before the patient seeks clinical attention.",
" </p>",
" <p>",
" Other local signs that may be present in diabetic foot infections but are
nonspecific include nonpurulent drainage, friable or discolored granulation tissue,
and undermining of wound edges [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2\">",
" 2",
" </a>",
" ].",
" </p>",
" <p>",
" Cutaneous bullae, soft tissue gas, skin discoloration, or a foul odor may
occur in necrotizing infections. Findings of gangrene, severe ischemia, or tissue
necrosis may denote the presence of a limb-threatening infection. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/31/30201?
source=see_link\">",
" \"Clinical features, diagnosis, and natural history of lower extremity
peripheral artery disease\"",
" </a>",
" .)",
" </p>",
" <p>",
" Systemic signs such as fever, chills, hypotension, and tachycardia may
accompany local signs of infection, and their presence indicates an increased
severity of infection. (See",
" <a class=\"local\" href=\"#H12048338\">",
" 'Determining severity of infection'",
" </a>",
" below.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12048040\">",
" <span class=\"h2\">",
" Osteomyelitis",
" </span>",
" &nbsp;&mdash;&nbsp;Osteomyelitis can occur in the setting of a diabetic foot
wound with or without evidence of local soft tissue infection. Several clinical
features are associated with the presence of underlying osteomyelitis in patients
with diabetic foot ulcers, including ulcer size &gt;2 cm",
" <sup>",
" 2",
" </sup>",
" and depth allowing visibly exposed bone or ability to probe to bone [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/22-25\">",
" 22-25",
" </a>",
" ]. The presence of a &ldquo;sausage&rdquo; toe, with erythema and nonpitting
edema that obliterates the normal contour of the digit, has been associated with
underlying osteomyelitis in diabetic patients, but the frequency of this finding is
not known [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/26\">",
" 26",
" </a>",
" ].",
" </p>",
" <p>",
" Many patients with underlying osteomyelitis also have elevated inflammatory
markers, specifically the erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/24\">",
" 24",
" </a>",
" ]. &nbsp;",
" </p>",
" <p>",
" On plain radiographs, findings characteristic of osteomyelitis include
cortical erosion, periosteal reaction, mixed lucency, and sclerosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,24\">",
" 2,24",
" </a>",
" ]. There is often also evidence of soft tissue swelling. However, radiographs
may be normal or have only subtle non-specific findings early in infection.
Magnetic resonance imaging (MRI) findings of osteomyelitis include cortical
destruction, bone marrow edema, and soft tissue inflammation. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12071?
source=see_link&amp;anchor=H3#H3\">",
" \"Approach to imaging modalities in the setting of suspected osteomyelitis\",
section on 'Radiographs'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12071?
source=see_link&amp;anchor=H4#H4\">",
" \"Approach to imaging modalities in the setting of suspected osteomyelitis\",
section on 'Magnetic resonance imaging (MRI)'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4\">",
" <span class=\"h1\">",
" DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;The diagnosis of a diabetic foot infection is primarily
based on suggestive clinical manifestations. The presence of two or more features
of inflammation (erythema, warmth, tenderness, swelling, induration and purulent
secretions) can establish the diagnosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H3\">",
" 'Clinical manifestations'",
" </a>",
" above.)",
" </p>",
" <p>",
" As many diabetic foot wounds are colonized by bacteria, the presence of
microbial growth from a wound culture in the absence of supportive clinical
findings is not sufficient to make the diagnosis of infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H5\">",
" <span class=\"h2\">",
" Diagnosis of underlying osteomyelitis",
" </span>",
" &nbsp;&mdash;&nbsp;The possibility of osteomyelitis should be considered in
diabetic patients with foot wounds associated with signs of infection in the deeper
soft tissues and in patients with chronic ulcers, particularly those overlying bony
prominences that do not heal after several weeks of wound care and off-loading. The
diagnosis of osteomyelitis is definitively made through isolation of bacteria from
a sterilely obtained bone biopsy sample with histologic evidence of inflammation
and osteonecrosis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ]. However, bone biopsy is not always routinely available or practical. In
such instances, the presumptive diagnosis is based on clinical and radiographic
assessment.",
" </p>",
" <p>",
" Certain clinical findings can support the diagnosis of osteomyelitis. In two
systematic reviews that evaluated the diagnostic accuracy of exam findings in the
setting of diabetic foot ulcers, the following factors increase the likelihood of
osteomyelitis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/24,25\">",
" 24,25",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Grossly visible bone or ability to probe to bone",
" </li>",
" <li>",
" Ulcer size larger than 2 cm",
" <sup>",
" 2",
" </sup>",
" </li>",
" <li>",
" Ulcer duration longer than one to two weeks",
" </li>",
" <li>",
" Erythrocyte sedimentation rate (ESR) &gt;70",
" <span class=\"nowrap\">",
" mm/h",
" </span>",
" </li>",
" </ul>",
" </p>",
" <p>",
" If bone is grossly visible, supportive radiographic findings may not be
necessary to make a diagnosis of osteomyelitis. However, for diabetic patients with
one or more of the other above factors, a conventional radiograph with consistent
changes can be helpful in making the diagnosis of osteomyelitis and providing a
baseline image useful for subsequent management decisions. If the radiograph is
indeterminate or normal and the diagnosis remains uncertain, such patients should
undergo magnetic resonance imaging (MRI), which is highly sensitive and specific
for osteomyelitis and superior to radiographs, three-phase bone scans, and white
blood cell scans [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,24,25,27,28\">",
" 2,24,25,27,28",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H12048040\">",
" 'Osteomyelitis'",
" </a>",
" above.)",
" </p>",
" <p>",
" In cases of diagnostic uncertainty based on clinical or radiographic features,
failure of empiric antibiotic therapy, planned hardware placement in potentially
infected bone, and mid- or hindfoot lesions that could lead to high-level
amputations if inadequately treated, obtaining a bone sample to establish diagnosis
is recommended [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2\">",
" 2",
" </a>",
" ]. Culture of such bone biopsy specimens is also important for identifying the
causative organisms and their susceptibilities in order to guide antimicrobial
therapy.",
" </p>",
" <p>",
" A detailed approach to the diagnosis of osteomyelitis in general is outlined
separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=see_link\">",
" \"Overview of osteomyelitis in adults\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12071?
source=see_link\">",
" \"Approach to imaging modalities in the setting of suspected
osteomyelitis\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H4123997\">",
" <span class=\"h1\">",
" DIFFERENTIAL DIAGNOSIS",
" </span>",
" &nbsp;&mdash;&nbsp;Other processes that lead to inflammatory changes in the
skin of the lower extremities can mimic an infection. These include trauma,
crystal-associated arthritis, acute Charcot arthropathy, fracture, thrombosis, and
venous stasis. Usually, infection can be distinguished from these based on history,
exam, and imaging findings. However, infection may co-exist with other inflammatory
processes, and empiric antimicrobial therapy may be warranted in some cases when
the diagnosis is unclear. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/49/4890?
source=see_link\">",
" \"Clinical manifestations and diagnosis of gout\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/38/39527?
source=see_link\">",
" \"Diabetic neuropathic arthropathy\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/30/35305?
source=see_link\">",
" \"Approach to the diagnosis and therapy of lower extremity deep vein
thrombosis\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/17/13592?
source=see_link\">",
" \"Clinical evaluation of lower extremity chronic venous disease\"",
" </a>",
" .).",
" </p>",
" <p class=\"headingAnchor\" id=\"H12048338\">",
" <span class=\"h1\">",
" DETERMINING SEVERITY OF INFECTION",
" </span>",
" &nbsp;&mdash;&nbsp;Assessment of the severity of diabetic foot infections is
important for prognosis and to assist with management decisions (eg, need for
hospitalization, surgical evaluation, or parenteral versus oral antibiotic
therapy). In its 2004 guidelines on the diagnosis and treatment of diabetic foot
infections, the Infectious Diseases Society of America (IDSA) first outlined a
clinical classification scheme to define levels of severity (",
" <a class=\"graphic graphic_table graphicRef55551 \" href=\"UTD.htm?
31/1/31771\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4\">",
" 4",
" </a>",
" ]. Briefly, it classifies diabetic foot changes as uninfected, mild, moderate,
and severe based on the extent of inflammatory findings, the tissue depth involved,
and the presence of signs of systemic toxicity. The International Working Group on
the Diabetic Foot published a nearly identical classification system in 2012 [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/27\">",
" 27",
" </a>",
" ].",
" </p>",
" <p>",
" The prognostic value of such classification schema was assessed in a
longitudinal study of 1666 persons with diabetes; there was a trend toward
increased amputation risk among patients with more severe infections [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/29\">",
" 29",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H6\">",
" <span class=\"h1\">",
" MANAGEMENT",
" </span>",
" &nbsp;&mdash;&nbsp;Management of diabetic foot infections requires attentive
wound management, good nutrition, appropriate antimicrobial therapy, glycemic
control, and fluid and electrolyte balance.",
" </p>",
" <p>",
" Several studies have reported improved outcomes with a multidisciplinary
approach to diabetic foot infections. This includes involvement of specialists in
wound care, infectious diseases, endocrinology, and surgery [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,30-32\">",
" 2,30-32",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H7\">",
" <span class=\"h2\">",
" Wound management",
" </span>",
" &nbsp;&mdash;&nbsp;Local wound care for diabetic foot infections typically
includes debridement of callus and necrotic tissue, wound cleansing, and relief of
pressure on the ulcer [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ].",
" </p>",
" <p>",
" Sharp debridement, with the use of a scalpel or scissors to shear off necrotic
tissue, is the preferred method to remove callus and nonviable tissue. Such
debridement promotes wound healing and removes pathogens that are present in
nonviable tissues [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2\">",
" 2",
" </a>",
" ]. However, enzymatic debridement may be preferable in patients with
significant vascular compromise that might impede the ability to heal new wounds
created by sharp debridement [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/33\">",
" 33",
" </a>",
" ]. As a general rule, surgical intervention is needed for patients with
extensive infection of subcutaneous or deeper structures. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link&amp;anchor=H5#H5\">",
" \"Management of diabetic foot lesions\", section on 'Method of debridement'",
" </a>",
" and",
" <a class=\"local\" href=\"#H8\">",
" 'Surgery'",
" </a>",
" below.)",
" </p>",
" <p>",
" The purpose of wound dressing is to absorb exudate and create a moist
environment to promote healing. A wide array of dressing and wound healing products
for ulcer management has been developed. These products include enzymes, gels,
hydrocolloids, honey and antiseptics containing iodine or silver salts. However,
the efficacy of these agents has not been evaluated or compared in carefully
designed studies [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/21,34\">",
" 21,34",
" </a>",
" ]. Avoidance of weight bearing is generally more important than the specific
type of wound dressing or ointment applied. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link&amp;anchor=H7#H7\">",
" \"Management of diabetic foot lesions\", section on 'Local wound care'",
" </a>",
" .)",
" </p>",
" <p>",
" Off-loading the pressure on the diabetic foot wound is essential to wound
care. Various devices to relieve pressure on the foot are available, including
casts and special shoes. The choice of device should be based on the wound
location, the severity of infection, and the presence of peripheral arterial
disease. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link&amp;anchor=H8#H8\">",
" \"Management of diabetic foot lesions\", section on 'Mechanical off-
loading'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H906271\">",
" <span class=\"h3\">",
" Obtaining samples for culture",
" </span>",
" &nbsp;&mdash;&nbsp;Because microorganisms often colonize lower extremity
wounds regardless of the presence of a true infection, cultures should be performed
only in selected patients. If the clinical suspicion for infection is low, samples
from the wound should not be submitted for culture. In patients with mild infection
(",
" <a class=\"graphic graphic_table graphicRef55551 \" href=\"UTD.htm?
31/1/31771\">",
" table 1",
" </a>",
" ) in whom there is low suspicion for resistant organisms (eg, no recent
antibiotic course), wound culture is often not necessary. However, wound culture is
often helpful in cases of moderate or severe infection (",
" <a class=\"graphic graphic_table graphicRef55551 \" href=\"UTD.htm?
31/1/31771\">",
" table 1",
" </a>",
" ) and when the concern for multidrug-resistant organisms is high. Ideally,
samples for culture should be obtained prior to the initiation of empiric
antibiotics. However, in cases of systemic toxicity or limb-threatening infections,
antibiotic therapy should not be withheld before surgical cultures are obtained.",
" </p>",
" <p>",
" The preferred clinical specimens for reliable culture include aspirate from an
abscess or curettage from the ulcer base following superficial debridement of
necrotic tissue. Organisms cultured from superficial swabs are not reliable for
predicting the pathogens responsible for deeper infection [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/35-38\">",
" 35-38",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=see_link\">",
" \"Overview of osteomyelitis in adults\"",
" </a>",
" .)",
" </p>",
" <p>",
" In the setting of osteomyelitis, bone biopsy is the preferred method of sample
collection for culture. If performed percutaneously, sampling through uninvolved
tissue under radiographic guidance is preferred. Although sinus tract cultures may
be of some use for prediction of osteomyelitis if Staphylococcus aureus or
Salmonella species are identified, in general, such cultures are not worthwhile [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/39,40\">",
" 39,40",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H5\">",
" 'Diagnosis of underlying osteomyelitis'",
" </a>",
" above and",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=see_link&amp;anchor=H8#H8\">",
" \"Overview of osteomyelitis in adults\", section on 'Bone biopsy'",
" </a>",
" .)",
" </p>",
" <p>",
" Samples should be sent for both aerobic and anaerobic bacterial cultures.",
" </p>",
" <p class=\"headingAnchor\" id=\"H8\">",
" <span class=\"h3\">",
" Surgery",
" </span>",
" &nbsp;&mdash;&nbsp;Consultation with a surgeon with experience in diabetic
foot infections is important for cases of severe infections and in most cases of
moderate infections. Surgical debridement is required for cure of infections
complicated by abscess, extensive bone or joint involvement, crepitus, necrosis,
gangrene or necrotizing fasciitis and is important for source control in patients
with severe sepsis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,41,42\">",
" 2,41,42",
" </a>",
" ]. The utility of early surgical debridement was illustrated in a
retrospective review of 112 diabetic patients with severe foot infections [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/41\">",
" 41",
" </a>",
" ]. Those patients who underwent surgical intervention at the time of
presentation had a significantly lower rate of above-ankle amputation than those
who received three days of intravenous antimicrobial therapy prior to surgery.",
" </p>",
" <p>",
" In addition to surgical debridement, revascularization (via angioplasty or
bypass grafting)",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" amputation may be necessary. Determination of the extent of surgical
intervention required should be guided by vascular evaluation [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,21\">",
" 2,21",
" </a>",
" ]. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link&amp;anchor=H19#H19\">",
" \"Management of diabetic foot lesions\", section on 'Revascularization'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/38/8810?
source=see_link&amp;anchor=H1576671063#H1576671063\">",
" \"Lower extremity amputation\", section on 'Indications for amputation'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/43/23225?
source=see_link\">",
" \"Techniques for lower extremity amputation\"",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H9\">",
" <span class=\"h2\">",
" Antimicrobial therapy",
" </span>",
" &nbsp;&mdash;&nbsp;Empiric antibiotic therapy should be selected based on the
severity of infection and the likelihood of involvement of resistant organisms.
(See",
" <a class=\"local\" href=\"#H12048338\">",
" 'Determining severity of infection'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H2\">",
" 'Microbiology'",
" </a>",
" above.).",
" </p>",
" <p>",
" Subsequent antibiotic therapy should be tailored to culture and susceptibility
results. However, it is not always necessary to cover all microorganisms isolated
from cultures [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" Patients with ulcerations that are not infected should not receive antibiotic
therapy [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/43,44\">",
" 43,44",
" </a>",
" ]. However, such patients often benefit from local wound care and measures
that reduce the pressure at the site of ulceration.",
" </p>",
" <p>",
" Our treatment approach outlined below is consistent with the Infectious
Diseases Society of America (IDSA) guidelines on the diagnosis and treatment of
diabetic foot infections and is based on their classification scheme for severity
of infection (",
" <a class=\"graphic graphic_table graphicRef55551 \" href=\"UTD.htm?
31/1/31771\">",
" table 1",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,4\">",
" 2,4",
" </a>",
" ]. (See",
" <a class=\"local\" href=\"#H12048338\">",
" 'Determining severity of infection'",
" </a>",
" above.)",
" </p>",
" <p>",
" In general, the limited data on antibiotic therapy of diabetic foot infections
do not allow comparison of outcomes of different regimens [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ]. On the basis of the available observational studies and randomized trials,
no single drug or combination appears to be superior to others [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/45\">",
" 45",
" </a>",
" ]. In a systematic review of 12 studies comparing antibiotic regimens for
lower extremity skin and soft-tissue infections in diabetic patients, reported
clinical cure rates ranged from 48 to 90 percent [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/46\">",
" 46",
" </a>",
" ]. None of the studies demonstrated a significant benefit for any specific
antibiotic agent. &nbsp;",
" </p>",
" <p class=\"headingAnchor\" id=\"H48099014\">",
" <span class=\"h3\">",
" Empiric therapy",
" </span>",
" </p>",
" <p class=\"headingAnchor\" id=\"H10\">",
" <span class=\"h4\">",
" Mild infection",
" </span>",
" &nbsp;&mdash;&nbsp;Mild diabetic foot infections can be treated with
outpatient oral antimicrobial therapy. Empiric therapy of patients with mild
infections should include activity against skin flora including streptococci and
Staphylococcus aureus. Agents with activity against methicillin-resistant
Staphylococcus aureus (MRSA) should be used in patients with purulent infections
and those at risk for MRSA infection (see",
" <a class=\"local\" href=\"#H4124497\">",
" 'Resistant Staphylococcus aureus'",
" </a>",
" above). Appropriate agents are outlined in the table (",
" <a class=\"graphic graphic_table graphicRef69671 \" href=\"UTD.htm?
17/35/17981\">",
" table 2",
" </a>",
" ).",
" </p>",
" <p>",
" Patients who fail to respond to treatment with agents active against
streptococci and methicillin-susceptible S. aureus should receive extended
antimicrobial coverage to include activity against MRSA, aerobic gram-negative
bacilli, and anaerobes (",
" <a class=\"graphic graphic_table graphicRef69671 \" href=\"UTD.htm?
17/35/17981\">",
" table 2",
" </a>",
" ).",
" </p>",
" <p class=\"headingAnchor\" id=\"H11\">",
" <span class=\"h4\">",
" Moderate infection",
" </span>",
" &nbsp;&mdash;&nbsp;Empiric therapy of deep ulcers with extension to fascia
should include activity against streptococci, Staphylococcus aureus (and MRSA if
risk factors are present), aerobic gram-negative bacilli and anaerobes and can be
administered orally in many cases. Appropriate regimens are outlined in the table
(",
" <a class=\"graphic graphic_table graphicRef69671 \" href=\"UTD.htm?
17/35/17981\">",
" table 2",
" </a>",
" ). Patients presenting with extensive infections that involve deep tissues
should receive empiric parenteral therapy with activity against the above pathogens
(",
" <a class=\"graphic graphic_table graphicRef82495 \" href=\"UTD.htm?
25/29/26077\">",
" table 3",
" </a>",
" ). Empiric coverage for Pseudomonas aeruginosa may not always be necessary
unless the patient has particular risk for involvement with this organism, such as
a macerated wound or one with significant water exposure. (See",
" <a class=\"local\" href=\"#H4124514\">",
" 'Pseudomonas aeruginosa'",
" </a>",
" above.)",
" </p>",
" <p class=\"headingAnchor\" id=\"H12\">",
" <span class=\"h4\">",
" Severe infection",
" </span>",
" &nbsp;&mdash;&nbsp;Limb-threatening diabetic foot infections and those that
are associated with systemic toxicity should be treated with broad-spectrum
parenteral antibiotic therapy. In most cases, surgical debridement is also
necessary. Empiric therapy should include activity against streptococci, MRSA,
aerobic gram-negative bacilli, and anaerobes. Appropriate regimens are outlined in
the table (",
" <a class=\"graphic graphic_table graphicRef82495 \" href=\"UTD.htm?
25/29/26077\">",
" table 3",
" </a>",
" ) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/47\">",
" 47",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H48099075\">",
" <span class=\"h3\">",
" Targeted therapy",
" </span>",
" &nbsp;&mdash;&nbsp;If appropriate wound cultures were submitted, antimicrobial
therapy should be tailored to culture and susceptibility results when available.
However, it is not always necessary to cover all microorganisms isolated from
cultures [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ]. Virulent species such as S. aureus and streptococci (group A or B) should
always be covered, but in polymicrobial infections, less virulent organisms (such
as coagulase negative staphylococci and enterococci) may be less important.
Furthermore, if isolates are resistant to an empiric regimen to which the patient
is clearly responding well, broadening the spectrum to include those isolates may
not be necessary. On the other hand, if the patient is not responding, expanding
therapy to target all isolated organisms may be warranted.",
" </p>",
" <p>",
" For those patients who were initiated on parenteral therapy, a switch to an
oral regimen is reasonable following clinical improvement.",
" </p>",
" <p class=\"headingAnchor\" id=\"H13\">",
" <span class=\"h3\">",
" Duration of therapy",
" </span>",
" &nbsp;&mdash;&nbsp;The duration of antibiotic therapy should be tailored to
individual clinical circumstances. Patients with mild infection should receive oral
antibiotic therapy in conjunction with attentive wound care until there is evidence
that the infection has resolved (usually about one to two weeks). Antibiotics need
not be administered for the entire duration that the wound remains open [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ].",
" </p>",
" <p>",
" Patients with infection also requiring surgical debridement should receive
intravenous antibiotic therapy perioperatively. In the absence of osteomyelitis,
antibiotic therapy should be administered in conjunction with attentive wound care
until signs of infection appear to have resolved (two to four weeks of therapy is
usually sufficient). If there is a good response to parenteral therapy, oral agents
can be used to complete the course of treatment [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/48\">",
" 48",
" </a>",
" ].",
" </p>",
" <p>",
" Patients requiring amputation of the involved limb should receive intravenous
antibiotic therapy perioperatively. If the entire area of infection is fully
resected, a brief course of oral antibiotic therapy (about a week) following
surgery is usually sufficient [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/48\">",
" 48",
" </a>",
" ].",
" </p>",
" <p class=\"headingAnchor\" id=\"H906110\">",
" <span class=\"h2\">",
" Osteomyelitis",
" </span>",
" &nbsp;&mdash;&nbsp;Similar to other types of diabetic foot infections, no data
support the superiority of specific antimicrobial agents for osteomyelitis [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/46\">",
" 46",
" </a>",
" ]. Appropriate regimens for empiric therapy are similar to that for moderate
to severe diabetic foot infections (",
" <a class=\"graphic graphic_table graphicRef82495 \" href=\"UTD.htm?
25/29/26077\">",
" table 3",
" </a>",
" ).",
" </p>",
" <p>",
" Targeted antimicrobial therapy should be tailored to culture and sensitivity
results, ideally from bone biopsy. In one retrospective study of diabetic patients
with osteomyelitis of the toe or metatarsal head, remission (absence of signs of
infection and no need for surgery after one year) was more likely in the 22
patients treated with regimens guided by bone biopsy data compared with the 28
treated based on swab culture data (82 versus 50 percent) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/49\">",
" 49",
" </a>",
" ]. Of note, those who had bone culture were also more likely to be treated
with a rifampicin-containing regimen, which likely was a confounding variable and
limits the interpretation of this finding.",
" </p>",
" <p>",
" For those patients who were initiated on parenteral therapy, a switch to an
oral regimen is reasonable following clinical improvement. Antibiotic therapy for
osteomyelitis is discussed in detail elsewhere. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=see_link&amp;anchor=H16#H16\">",
" \"Overview of osteomyelitis in adults\", section on 'Antibiotic selection'",
" </a>",
" .)",
" </p>",
" <p>",
" Many patients with osteomyelitis of the foot benefit from surgical resection.
In a systematic review of studies evaluating treatment of diabetic foot
osteomyelitis, there was no study that directly compared surgical intervention to
nonsurgical management [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/50\">",
" 50",
" </a>",
" ]. However, studies of prolonged antibiotic therapy without resection reported
success rates comparable to those reported with surgery, about 60 to 90 percent.
Furthermore, partial amputations of the foot (eg, ray or transmetatarsal
amputations) may adversely alter the biomechanics of the foot, increasing the risk
of future ulceration. Thus, in certain cases, limited surgical debridement combined
with prolonged antibiotic therapy may be appropriate [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2,27\">",
" 2,27",
" </a>",
" ]. However, extensive surgical debridement or resection is preferable in the
following clinical circumstances [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/2\">",
" 2",
" </a>",
" ]:",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Persistent sepsis without an alternate source",
" </li>",
" <li>",
" Inability to receive or tolerate appropriate antibiotic therapy",
" </li>",
" <li>",
" Progressive bone deterioration despite appropriate antibiotic therapy",
" </li>",
" <li>",
" Mechanics of the foot are compromised by extensive bony destruction
requiring correction",
" </li>",
" <li>",
" Surgery is needed to achieve soft tissue wound or primary closure &nbsp;",
" </li>",
" </ul>",
" </p>",
" <p>",
" The duration of antibiotic therapy of osteomyelitis depends on the extent of
residual affected tissue. If all infected and necrotic bone and soft tissue has
been resected (eg, amputation), then a brief course (ie, about a week) of
antibiotics is likely adequate. Otherwise, the optimal duration is uncertain. Four
to six weeks is an appropriate course if there is residual infected bone following
debridement of necrotic bone. However, if necrotic bone remains, clinical cure may
require several months of antibiotic therapy. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=see_link&amp;anchor=H17#H17\">",
" \"Overview of osteomyelitis in adults\", section on 'Duration of therapy'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H14\">",
" <span class=\"h2\">",
" Adjunctive therapies",
" </span>",
" &nbsp;&mdash;&nbsp;Adjunctive therapies for treatment of diabetic foot
infections include vacuum-assisted wound closure, hyperbaric oxygen and",
" <a class=\"drug drug_general\" href=\"UTD.htm?23/13/23767?source=see_link\">",
" granulocyte colony-stimulating factor",
" </a>",
" (G-CSF) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/51-53\">",
" 51-53",
" </a>",
" ].",
" </p>",
" <p>",
" Of these, vacuum-assisted wound closure is used most frequently. In a
randomized trial evaluating vacuum-assisted wound closure including 342 patients
with diabetic foot ulcers, complete ulcer closure was achieved more often among
those who used vacuum-assisted closure than those who did not (43 versus 29
percent, respectively) [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/51\">",
" 51",
" </a>",
" ]. Vacuum-assisted closure and hyperbaric oxygen therapy are discussed in
detail separately. (See",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=see_link\">",
" \"Management of diabetic foot lesions\"",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/20/5448?
source=see_link&amp;anchor=H15#H15\">",
" \"Hyperbaric oxygen therapy\", section on 'Infection'",
" </a>",
" and",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/20/5448?
source=see_link&amp;anchor=H16#H16\">",
" \"Hyperbaric oxygen therapy\", section on 'Nonhealing ulcers, skin grafts,
and wound healing'",
" </a>",
" .)",
" </p>",
" <p class=\"headingAnchor\" id=\"H48099278\">",
" <span class=\"h2\">",
" Follow-up",
" </span>",
" &nbsp;&mdash;&nbsp;Close follow-up is important to ensure continued
improvement and to evaluate the need for modification of antimicrobial therapy,
further imaging, or additional surgical intervention. Wound healing and a decrease
in previously elevated inflammatory markers can be signs of clinical resolution,
and may be particularly helpful in cases of osteomyelitis. If clinical evidence of
infection persists beyond the expected duration, issues of patient adherence to
therapy, development of antibiotic resistance, an undiagnosed deeper infection (eg,
abscess or osteomyelitis), or ischemia should be evaluated [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4\">",
" 4",
" </a>",
" ].",
" </p>",
" <p>",
" If infection in a clinically stable patient fails to respond to more than one
antibiotic course, some favor discontinuing antimicrobial therapy to optimize the
yield of culture specimens obtained a few days later [",
" <a class=\"abstract\" href=\"UTD.htm?0/33/538/abstract/4\">",
" 4",
" </a>",
" ]. In general, this is a safe and reasonable approach, although deep cultures
are often positive even if therapy is continued up to the time of debridement.",
" </p>",
" <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
" <span class=\"h1\">",
" INFORMATION FOR PATIENTS",
" </span>",
" &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
&ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
education pieces are written in plain language, at the 5",
" <sup>",
" th",
" </sup>",
" to 6",
" <sup>",
" th",
" </sup>",
" grade reading level, and they answer the four or five key questions a patient
might have about a given condition. These articles are best for patients who want a
general overview and who prefer short, easy-to-read materials. Beyond the Basics
patient education pieces are longer, more sophisticated, and more detailed. These
articles are written at the 10",
" <sup>",
" th",
" </sup>",
" to 12",
" <sup>",
" th",
" </sup>",
" grade reading level and are best for patients who want in-depth information
and are comfortable with some medical jargon.",
" </p>",
" <p>",
" Here are the patient education articles that are relevant to this topic. We
encourage you to print or e-mail these topics to your patients. (You can also
locate patient education articles on a variety of subjects by searching on
&ldquo;patient info&rdquo; and the keyword(s) of interest.)",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Basics topics (see",
" <a class=\"medical medical_basics\" href=\"UTD.htm?19/52/20292?
source=see_link\">",
" \"Patient information: Diabetes and infections (The Basics)\"",
" </a>",
" )",
" </li>",
" </ul>",
" </p>",
" <p class=\"headingAnchor\" id=\"H15\">",
" <span class=\"h1\">",
" SUMMARY AND RECOMMENDATIONS",
" </span>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Hyperglycemia, sensory and autonomic neuropathy, and peripheral arterial
disease all contribute to the pathogenesis of lower extremity infections in
diabetic patients. These infections are associated with substantial morbidity and
mortality. (See",
" <a class=\"local\" href=\"#H1\">",
" 'Introduction'",
" </a>",
" above.)",
" </li>",
" <li>",
" Evaluation of a patient with a diabetic foot infection involves determining
the extent and severity of infection through clinical and radiographic assessment,
identifying and addressing underlying factors that predispose to and promote
infection, assessing the microbial etiology, and determining the need for surgical
intervention. (See",
" <a class=\"local\" href=\"#H905751\">",
" 'Overview of approach to the patient'",
" </a>",
" above.)",
" </li>",
" <li>",
" Laboratory testing should include blood work to evaluate for leukocytosis as
well as blood glucose, electrolytes, and renal function values so that glycemic
control and acid base status can be evaluated and monitored. Baseline and
subsequent inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-
reactive protein (CRP) can be useful for monitoring response to therapy.
Conventional radiographs should be done to evaluate for bony and soft tissue
deformity or abnormalities. Formal vascular evaluation is warranted in cases where
peripheral arterial insufficiency is suspected. (See",
" <a class=\"local\" href=\"#H905751\">",
" 'Overview of approach to the patient'",
" </a>",
" above.)",
" </li>",
" <li>",
" The presence of two or more features of inflammation (erythema, warmth,
tenderness, swelling, induration, or purulent secretions) can establish the
diagnosis of a diabetic foot infection. The definitive diagnosis of osteomyelitis
is made through histologic and microbiologic evaluation of a bone biopsy sample.
However, certain clinical factors can support the presumptive diagnosis of
osteomyelitis in the absence of biopsy:",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" Grossly visible bone or ability to probe to bone",
" </li>",
" <li>",
" Ulcer size larger than 2 cm",
" <sup>",
" 2",
" </sup>",
" </li>",
" <li>",
" Ulcer duration longer than one to two weeks",
" </li>",
" <li>",
" Erythrocyte sedimentation rate (ESR) &gt;70",
" <span class=\"nowrap\">",
" mm/h",
" <br/>",
" <br/>",
" Those",
" </span>",
" with one or more of the above factors whose radiographs are normal or
indeterminate for osteomyelitis should undergo magnetic resonance imaging (MRI).
(See",
" <a class=\"local\" href=\"#H4\">",
" 'Diagnosis'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Management of diabetic foot infections requires attentive wound management,
good nutrition, antimicrobial therapy, glycemic control, and fluid and electrolyte
balance. Wound management includes attentive local wound care including debridement
of callus and necrotic tissue, wound cleansing, and relief of pressure on the
ulcer. Consultation with a surgeon with experience in diabetic foot infection is
important for cases of severe infections and most cases of moderate infections.
Prompt surgical debridement is critical for cure of infections complicated by
abscess, extensive bone or joint involvement, crepitus, necrosis, gangrene or
necrotizing fasciitis and is important for source control in patients with severe
sepsis. (See",
" <a class=\"local\" href=\"#H7\">",
" 'Wound management'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H8\">",
" 'Surgery'",
" </a>",
" above.)",
" </li>",
" <li>",
" The microbiology of diabetic foot wounds varies with the severity and extent
of involvement (",
" <a class=\"graphic graphic_table graphicRef55551 \" href=\"UTD.htm?
31/1/31771\">",
" table 1",
" </a>",
" ). Superficial infections are likely due to aerobic gram-positive cocci
whereas deep, chronically infected,",
" <span class=\"nowrap\">",
" and/or",
" </span>",
" previously treated ulcers are more likely to be polymicrobial. Anaerobic
organisms may also be involved in wounds with extensive local inflammation,
necrosis, or gangrene. When there is concern for multidrug-resistant organisms or
in cases of moderate or severe infection (including deep infections and
osteomyelitis), aerobic and anaerobic cultures of deep tissue or bone biopsies
should be obtained at the time of debridement. Organisms cultured from superficial
swabs are not reliable for predicting the pathogens responsible for deeper
infection. (See",
" <a class=\"local\" href=\"#H2\">",
" 'Microbiology'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H906271\">",
" 'Obtaining samples for culture'",
" </a>",
" above.)",
" </li>",
" <li>",
" Empiric antibiotic therapy should be selected based upon the severity of
infection and the likelihood of involvement of resistant organisms:",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"hyphen-block\">",
" <li>",
" For patients with mild infections, we suggest an empiric antimicrobial
regimen (",
" <a class=\"graphic graphic_table graphicRef69671 \" href=\"UTD.htm?
17/35/17981\">",
" table 2",
" </a>",
" ) with activity against skin flora including streptococci and Staphylococcus
aureus (including methicillin-resistant Staphylococcus aureus [MRSA] if risk
factors are present) (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H10\">",
" 'Mild infection'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients with deep ulcers, we suggest an empiric antimicrobial regimen
with activity against streptococci, staphylococci (and MRSA if risk factors are
present), aerobic gram-negative bacilli and anaerobes (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). Oral antibiotics (",
" <a class=\"graphic graphic_table graphicRef69671 \" href=\"UTD.htm?
17/35/17981\">",
" table 2",
" </a>",
" ) may be appropriate for ulcers that extend to the fascia, whereas
parenteral regimens (",
" <a class=\"graphic graphic_table graphicRef82495 \" href=\"UTD.htm?
25/29/26077\">",
" table 3",
" </a>",
" ) should be used for deeper infections. (See",
" <a class=\"local\" href=\"#H11\">",
" 'Moderate infection'",
" </a>",
" above.)",
" </li>",
" <li>",
" For patients with limb-threatening diabetic foot infections or evidence of
systemic toxicity, we suggest treatment with a broad-spectrum parenteral antibiotic
regimen (",
" <a class=\"graphic graphic_table graphicRef82495 \" href=\"UTD.htm?
25/29/26077\">",
" table 3",
" </a>",
" ) with activity against streptococci, MRSA, aerobic gram-negative bacilli,
and anaerobes (",
" <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
" Grade 2C",
" </a>",
" ). (See",
" <a class=\"local\" href=\"#H12\">",
" 'Severe infection'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bulletCompact-block\">",
" <li>",
" Antimicrobial therapy should be tailored to culture and susceptibility
results when available, and a switch to an oral from parenteral regimen is
reasonable following clinical improvement. Antibiotics need not be administered for
the entire duration that the wound remains open. Close follow-up is important to
ensure continued improvement and to evaluate the need for modification of
antimicrobial therapy, further imaging, or additional surgical intervention. (See",
" <a class=\"local\" href=\"#H48099075\">",
" 'Targeted therapy'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H13\">",
" 'Duration of therapy'",
" </a>",
" above and",
" <a class=\"local\" href=\"#H48099278\">",
" 'Follow-up'",
" </a>",
" above.)",
" </li>",
" </ul>",
" </p>",
" <p>",
" <ul class=\"bullet-block\">",
" <li>",
" Many patients with osteomyelitis of the foot benefit from surgical
resection. However, in certain cases, limited surgical debridement combined with
prolonged antibiotic therapy may be appropriate. The duration of antibiotic therapy
of osteomyelitis depends on the extent of residual affected tissue. (See",
" <a class=\"local\" href=\"#H906110\">",
" 'Osteomyelitis'",
" </a>",
" above.) &nbsp;",
" </li>",
" </ul>",
" </p>",
" </div>",
" <div id=\"topicAgreement\">",
" Use of UpToDate is subject to the",
" <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
target=\"_blank\">",
" Subscription and License Agreement",
" </a>",
" .",
" </div>",
" <div class=\"headingAnchor\" id=\"references\">",
" <h1>",
" REFERENCES",
" </h1>",
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" Tan JS, Friedman NM, Hazelton-Miller C, et al. Can aggressive treatment of
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" </a>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/42\">",
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" </a>",
" </li>",
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" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/43\">",
" Chantelau E, Tanudjaja T, Altenh&ouml;fer F, et al. Antibiotic treatment for
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" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/46\">",
" Peters EJ, Lipsky BA, Berendt AR, et al. A systematic review of the
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Diabetes Metab Res Rev 2012; 28 Suppl 1:142.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/47\">",
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" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/48\">",
" Lipsky BA, Baker PD, Landon GC, Fernau R. Antibiotic therapy for diabetic
foot infections: comparison of two parenteral-to-oral regimens. Clin Infect Dis
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" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/49\">",
" Senneville E, Lombart A, Beltrand E, et al. Outcome of diabetic foot
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" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/50\">",
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progress report on diagnosis and a systematic review of treatment. Diabetes Metab
Res Rev 2008; 24 Suppl 1:S145.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/51\">",
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treatment of diabetic foot ulcers: a multicenter randomized controlled trial.
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" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/52\">",
" Cruciani M, Lipsky BA, Mengoli C, de Lalla F. Are granulocyte colony-
stimulating factors beneficial in treating diabetic foot infections?: A meta-
analysis. Diabetes Care 2005; 28:454.",
" </a>",
" </li>",
" <li>",
" <a class=\"nounderline abstract\" href=\"UTD.htm?0/33/538/abstract/53\">",
" Gough A, Clapperton M, Rolando N, et al. Randomised placebo-controlled trial
of granulocyte-colony stimulating factor in diabetic foot infection. Lancet 1997;
350:855.",
" </a>",
" </li>",
" </ol>",
" </div>",
" <div id=\"topicVersionRevision\">",
" Topic 7651 Version 17.0",
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" </div>",
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" <a href=\"#\" title=\"Collapse Topic Outline\">",
" <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
" </a>",
" </div>",
" <div id=\"innerOutline\">",
" <h1>",
" TOPIC OUTLINE",
" </h1>",
" <div id=\"outline\">",
" <ul>",
" <li>",
" <a class=\"sr_button\" href=\"#H15\" id=\"summRecButton\">",
" <span>",
" SUMMARY &amp; RECOMMENDATIONS",
" </span>",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H1\">",
" INTRODUCTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H905751\">",
" OVERVIEW OF APPROACH TO THE PATIENT",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H2\">",
" MICROBIOLOGY",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H4124489\">",
" Risk of specific organisms",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4124497\">",
" - Resistant Staphylococcus aureus",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4124514\">",
" - Pseudomonas aeruginosa",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H4124592\">",
" - Resistant enteric gram-negative rods",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H3\">",
" CLINICAL MANIFESTATIONS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H12048040\">",
" Osteomyelitis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H4\">",
" DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H5\">",
" Diagnosis of underlying osteomyelitis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H4123997\">",
" DIFFERENTIAL DIAGNOSIS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H12048338\">",
" DETERMINING SEVERITY OF INFECTION",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H6\">",
" MANAGEMENT",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H7\">",
" Wound management",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H906271\">",
" - Obtaining samples for culture",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H8\">",
" - Surgery",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H9\">",
" Antimicrobial therapy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H48099014\">",
" - Empiric therapy",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" <a class=\"outlineLink\" href=\"#H10\">",
" Mild infection",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" <a class=\"outlineLink\" href=\"#H11\">",
" Moderate infection",
" </a>",
" </li>",
" <li class=\"bulletItem2\">",
" <a class=\"outlineLink\" href=\"#H12\">",
" Severe infection",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H48099075\">",
" - Targeted therapy",
" </a>",
" </li>",
" <li class=\"dashItem\">",
" <a class=\"outlineLink\" href=\"#H13\">",
" - Duration of therapy",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H906110\">",
" Osteomyelitis",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H14\">",
" Adjunctive therapies",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"outlineLink\" href=\"#H48099278\">",
" Follow-up",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
" INFORMATION FOR PATIENTS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"outlineLink\" href=\"#H15\">",
" SUMMARY AND RECOMMENDATIONS",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a href=\"#references\">",
" REFERENCES",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" <div class=\"openRelatedGraphics\" id=\"ID/7651\" rel=\"outline_link\">",
" GRAPHICS",
" <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
" View All",
" </a>",
" </div>",
" </h1>",
" <div id=\"relatedGraphics\">",
" <ul>",
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" <a href=\"#\" title=\"TABLES\">",
" TABLES",
" </a>",
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" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?31/1/31771\" title=\"table
1\">",
" Clin classif DM foot infx",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?17/35/17981\" title=\"table
2\">",
" Oral agents for mild to moderate diabetic foot infections",
" </a>",
" </li>",
" <li class=\"bulletItem\">",
" <a class=\"graphic graphic_table\" href=\"UTD.htm?25/29/26077\" title=\"table
3\">",
" Parenteral agents for moderate to severe foot infection",
" </a>",
" </li>",
" </ul>",
" </div>",
" <h1>",
" RELATED TOPICS",
" </h1>",
" <div id=\"relatedTopics\">",
" <ul>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/50/12071?
source=related_link\">",
" Approach to imaging modalities in the setting of suspected osteomyelitis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?34/30/35305?
source=related_link\">",
" Approach to the diagnosis and therapy of lower extremity deep vein
thrombosis",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?13/17/13592?
source=related_link\">",
" Clinical evaluation of lower extremity chronic venous disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/31/30201?
source=related_link\">",
" Clinical features, diagnosis, and natural history of lower extremity
peripheral artery disease",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/49/4890?
source=related_link\">",
" Clinical manifestations and diagnosis of gout",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?38/38/39527?
source=related_link\">",
" Diabetic neuropathic arthropathy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?7/53/8026?
source=related_link\">",
" Epidemiology of methicillin-resistant Staphylococcus aureus infection in
adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?11/12/11464?
source=related_link\">",
" Evaluation of the diabetic foot",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?29/53/30553?
source=related_link\">",
" Extended-spectrum beta-lactamases",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?5/20/5448?
source=related_link\">",
" Hyperbaric oxygen therapy",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?8/38/8810?
source=related_link\">",
" Lower extremity amputation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?36/28/37321?
source=related_link\">",
" Management of diabetic foot lesions",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?4/34/4649?
source=related_link\">",
" Overview of osteomyelitis in adults",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_basics\" href=\"UTD.htm?19/52/20292?
source=related_link\">",
" Patient information: Diabetes and infections (The Basics)",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?22/43/23225?
source=related_link\">",
" Techniques for lower extremity amputation",
" </a>",
" </li>",
" <li class=\"plainItem\">",
" <a class=\"medical medical_review\" href=\"UTD.htm?16/2/16425?
source=related_link\">",
" Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus
infections",
" </a>",
" </li>",
" </ul>",
" </div>",
" </div>"].join("\n");
var title_f0_33_539="Probability of pregnancy after unprotected intercourse";
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" &copy;2013 UpToDate",
" <sup>",
" &reg;",
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" Email",
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" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Probability of pregnancy after unprotected intercourse by timing of coitus",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tr>",
" <td class=\"subtitle1_left\">",
" 3 days before ovulation",
" </td>",
" <td>",
" 15 percent",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\">",
" 1 or 2 days before ovulation",
" </td>",
" <td>",
" 30 percent",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\">",
" day of ovulation",
" </td>",
" <td>",
" 12 percent",
" </td>",
" </tr>",
" <tr>",
" <td class=\"subtitle1_left\">",
" 1 or 2 days after ovulation",
" </td>",
" <td>",
" near zero",
" </td>",
" </tr>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Adapted from: Trusell, J, et al. Contraception 1998; 57:363.",
" </div>",
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var title_f0_33_540="Foods better tolerated";
var content_f0_33_540=[" <div id=\"graphicsToolbar\">",
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" <sup>",
" &reg;",
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title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=GAST
%2F82005&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=4\" onclick=\"\"
title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
" </div>",
" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Foods and beverages that are better tolerated by irritable bowel syndrome
(IBS) patients",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td>",
" Water, ginger ale, Sprite&reg;, and Gatorade&reg;",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Soy milk or rice milk",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Soy or rice based products",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Plain pasta, plain noodles, white rice. No sauces or gravies.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Potato: boiled or baked. No French Fries.",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Breads: French, Italian, whole white, English muffins, and white rolls",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Plain fish, plain chicken, plain turkey, or plain ham",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Eggs: soft-boiled, poached",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cereals: plain cornflakes, Rice Krispies&reg;, Corn or Rice Chex&reg;,
Cheerios&reg;; dry or with soymilk or rice milk",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Salads: lettuce, hard-boiled egg slices, oil and vinegar dressing",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Cooked peas, carrots (avoid raw vegetables)",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Margarine, jams, jellies, peanut butter",
" </td>",
" </tr>",
" <tr>",
" <td>",
" In small amounts: applesauce, cantaloupe, watermelon, honeydew melon",
" </td>",
" </tr>",
" <tr>",
" <td>",
" In small amounts: fruit cocktail, peaches, pears (canned, nondietetic)",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" Substitutes and alternatives are available for the foods and beverages that
induce gastrointestinal symptoms. Listed above are examples of some of the foods
and beverages that IBS patents have found to be well tolerated. It is important to
use daily vitamins (multivitamin, calcium with vitamin D, folic acid, vitamin B
complex, and vitamin C) when on a restricted diet.",
" <div class=\"footnotes\">",
" </div>",
" <div class=\"reference\">",
" Data from: MacDermott RP. Treatment of irritable bowel syndrome in
outpatients with inflammatory bowel disease using a food and beverage intolerance,
food and beverage avoidance diet. Inflamm Bowel Dis 2007; 13:91.",
" </div>",
" </div>",
" </div>",
" </div>",
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var title_f0_33_541="Nutrition labs IBD";
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" <a href=\"?imageKey=PEDS
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title=\"Print this page\"/>",
" </a>",
" <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
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title=\"Print this page\">",
" Print",
" </a>",
" <a class=\"etacLink\" href=\"#\">",
" <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
title=\"Email graphic(s)\"/>",
" </a>",
" <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
" Email",
" </a>",
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" </div>",
" <div class=\"graphic\">",
" <div class=\"figure\">",
" <div class=\"ttl\">",
" Suggested laboratory tests for monitoring nutrition in patients with
inflammatory bowel disease",
" </div>",
" <div class=\"cntnt\">",
" <table cellspacing=\"0\">",
" <tbody>",
" <tr>",
" <td class=\"subtitle1\">",
" &nbsp;",
" </td>",
" <td class=\"subtitle1\">",
" Ulcerative colitis",
" </td>",
" <td class=\"subtitle1\">",
" Crohn disease or indeterminate colitis",
" </td>",
" <td class=\"subtitle1\">",
" Conditional testing*",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Complete blood count",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Albumin",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" </tr>",
" <tr>",
" <td>",
" 25-OH vitamin D",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Vitamin B12",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Folate",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Calcium",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Phosphorus",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Magnesium",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Vitamin A",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Vitamin E",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Prothrombin time",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" Zinc",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" <tr>",
" <td>",
" DXA scanning&bull;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td>",
" &nbsp;",
" </td>",
" <td class=\"centered\">",
" x",
" </td>",
" </tr>",
" </tbody>",
" </table>",
" </div>",
" <div class=\"lgnd\">",
" The above tests and frequencies reflect the author's practice, and may vary
among providers. We perform these tests at least every 12 to 24 months in patients
with quiescent disease, and more frequently in patients with active disease or
known deficiency, or in growing children.",
" <div class=\"footnotes\">",
" DXA: dual energy x-ray absorptiometry; 25-OH vitamin D: 25-hydroxy vitamin
D",
" <br>",
" * These tests are performed in the case of malnutrition, malabsorption,
symptoms of deficiency, or specific risk factors (eg, total parenteral or enteral
nutrition).",
" <br>",
" &bull; DXA scanning is recommended in adults with risk factors for bone
disease, including prolonged cortiocosteroid use or low trauma fracture (See topic
review on Metabolic bone disease in inflammatory bowel disease). There are no
generally accepted standards for frequency of DXA scanning in children with IBD.",
" </br>",
" </br>",
" </div>",
" <div class=\"reference\">",
" Courtesy of: Jonathan E Teitelbaum, MD.",
" </div>",
" </div>",
" </div>",
" </div>",
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" Dermatitis",
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" Atopic dermatitis",
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dermatitis (eczema)",
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" </li>",
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" Dermatitis of the vulva",
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" Overview of dermatitis",
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" Prurigo nodularis",
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" Seborrheic dermatitis in adolescents and adults",
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" Pediatric orthopedics",
" </h1>",
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" <strong>",
" Ankle",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?30/20/31050\">",
" Clinical features and management of ankle pain in the young athlete",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/23/14711\">",
" Evaluation of foot and ankle pain in the young athlete",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Back",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/45/19162\">",
" Back pain in children and adolescents: Overview of causes",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?32/62/33770\">",
" Clinical features; evaluation; and diagnosis of adolescent idiopathic
scoliosis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?2/39/2679\">",
" Evaluation of the child with back pain",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?36/12/37065\">",
" Treatment and prognosis of adolescent idiopathic scoliosis",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Child abuse",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?11/23/11641\">",
" Differential diagnosis of the orthopedic manifestations of child
abuse",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/30/13802\">",
" Orthopedic aspects of child abuse",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Elbow",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?22/25/22937\">",
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" </a>",
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" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/37/13913\">",
" Clinical manifestations and diagnosis of osteochondritis dissecans
(OCD)",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?13/46/14057\">",
" Evaluation of the child with joint pain or swelling",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?20/26/20902\">",
" Growing pains",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?18/36/19014\">",
" Management of osteochondritis dissecans (OCD)",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/60/24522\">",
" Overview of benign bone tumors in children and adolescents",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/9/23706\">",
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" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/54/15208\">",
" Splinting of musculoskeletal injuries",
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related disorders",
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" <a class=\"tocItem\" href=\"UTD.htm?41/17/42264\">",
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" </a>",
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" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?30/6/30823\">",
" Approach to the child with out-toeing",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?28/6/28775\">",
" Clinical features and management of heel pain in the young athlete",
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" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/23/14711\">",
" Evaluation of foot and ankle pain in the young athlete",
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" <strong>",
" Hip",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?41/17/42264\">",
" Approach to the child with in-toeing",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?26/30/27113\">",
" Clinical features and diagnosis of developmental dysplasia of the hip",
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" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?0/12/199\">",
" Epidemiology and pathogenesis of developmental dysplasia of the hip",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?16/21/16729\">",
" Overview of hip pain in childhood",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?24/32/25097\">",
" Radiologic evaluation of the hip in infants, children, and
adolescents",
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" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?22/42/23209\">",
" Slipped capital femoral epiphysis (SCFE)",
" </a>",
" </li>",
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" <a class=\"tocItem\" href=\"UTD.htm?20/48/21254\">",
" Treatment and outcome of developmental dysplasia of the hip",
" </a>",
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" </ul>",
" <strong>",
" Knee",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?26/55/27511\">",
" Approach to the child with bow-legs",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?6/3/6199\">",
" Approach to the child with knock-knees",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?5/9/5273\">",
" Approach to the young athlete with acute knee pain or injury",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?28/34/29223\">",
" Approach to the young athlete with chronic knee pain or injury",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?12/6/12392\">",
" Osgood-Schlatter disease (tibial tuberosity avulsion)",
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" <a class=\"tocItem\" href=\"UTD.htm?24/0/24581\">",
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" <a class=\"tocItem\" href=\"UTD.htm?1/45/1752\">",
" Plica syndrome",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?27/50/28455\">",
" Traumatic causes of acute knee pain and injury in the young athlete",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?3/61/4056\">",
" Treatment of knee injuries in the young athlete",
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" <strong>",
" Neck",
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" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?8/26/8616\">",
" Acquired torticollis in children",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?40/25/41368\">",
" Approach to the young athlete with neck pain or injury",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?42/49/43798\">",
" Congenital muscular torticollis",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?15/28/15815\">",
" Field care and evaluation of the young athlete with acute neck injury",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?23/8/23689\">",
" Overview of cervical spinal cord and cervical peripheral nerve injuries
in the young athlete",
" </a>",
" </li>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?10/49/11033\">",
" Overview of musculoskeletal neck injuries in the young athlete",
" </a>",
" </li>",
" </ul>",
" <strong>",
" Osteoarticular infections",
" </strong>",
" <ul>",
" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?14/30/14826\">",
" Bacterial arthritis: Clinical features and diagnosis in infants and
children",
" </a>",
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" <a class=\"tocItem\" href=\"UTD.htm?39/30/40423\">",
" Bacterial arthritis: Epidemiology, pathogenesis, and microbiology in
infants and children",
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" <a class=\"tocItem\" href=\"UTD.htm?27/33/28186\">",
" Bacterial arthritis: Treatment and outcome in infants and children",
" </a>",
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" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?19/39/20087\">",
" Clinical features of hematogenous osteomyelitis in children",
" </a>",
" </li>",
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" <a class=\"tocItem\" href=\"UTD.htm?17/0/17416\">",
" Epidemiology, pathogenesis, and microbiology of hematogenous
osteomyelitis in children",
" </a>",
" </li>",
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" <a class=\"tocItem\" href=\"UTD.htm?32/32/33289\">",
" Evaluation and diagnosis of hematogenous osteomyelitis in children",
" </a>",
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" <li>",
" <a class=\"tocItem\" href=\"UTD.htm?24/9/24730\">",
" Treatment of hematogenous osteomyelitis in children",
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