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3 March 2000
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area, immature kidneys, and n human medicine, neonates and infants have long been recognized to re-
higher respiratory rate leading quire monitoring and treatment that are specific to their unique biochemical
to greater fluid losses. and physiologic systems. Although some data on critical care of neonates in
veterinary medicine are available,1 data for pediatric patients are still lacking.
■ Several factors, including greater In veterinary medicine, the term pediatric refers to animals younger than 6
surface area:body weight ratio months of age. The information presented here is limited to dogs and cats 0 to
and lower amounts of body fat, 12 weeks of age and focuses on the neonatal age range (0 to 2 weeks). The dif-
contribute to differences in ferences between adult and pediatric physiology are discussed; and the effects of
pharmacologic effectiveness. these differences on the results of physical examination, interpretation of diag-
nostic tests, treatment principles, and pharmacology are described.
■ Predicting a neonate’s response
to cardiovascular drugs is nearly NUTRITION AND ENVIRONMENT
impossible. Neonates should have a strong suckle reflex and begin to show rooting behav-
ior (opening and closing the lips and moving the head in search for milk) shortly
after birth; they should nurse and sleep constantly during the first 2 to 3 weeks
of life. If the amount of milk being ingested is questionable, the neonate can be
weighed on a gram scale before and after nursing. In general, neonates that are
ingesting sufficient quantities of milk appear sleepy or nap consistently between
feedings. Constant crying, failure to gain weight, and reluctance to nurse indi-
cate inadequate intake. A healthy, vaccinated adult foster dog or cat is ideal for a
neonate that cannot ingest milk from the dam. Other alternatives include bottle-
Compendium March 2000 Small Animal/Exotics
unique. The greater surface area:body weight ratio; autonomic nervous system can cause fluctuations in the
lower amount of body fat, total protein, and albumin effectiveness of autonomic and cardiac drugs.
(the protein to which most drugs preferentially bind); The route of drug delivery in puppies and kittens
and reduced renal excretion caused by immature renal must also be taken into account. In general, intestinal
tubules all contribute to variations in pharmacologic ef- flora is still developing and is very susceptible to dis-
fectiveness. Clearance of drugs is decreased, and the ruption by oral antimicrobials. Oral drug absorption is
half-life of drugs excreted through the kidneys (primar- much higher in the first 24 to 72 hours of life because
ily water-soluble drugs) is decreased because of low of greater permeability of the gastrointestinal tract. Par-
glomerular filtration rate and renal blood flow in enteral routes seem to be the most predictable, with IV
neonates. Hepatic enzyme systems, both phase I (oxida- routes preferred over subcutaneous or intramuscular
tion) and phase II (glucuronidation), are not fully func- routes.13
tional, and adult levels may not be attained until the To our knowledge, studies have not been done on the
animal is 4.5 months of age.13,18,19 This results in higher ideal dose level or interval in neonates for the drugs dis-
plasma levels for most drugs requiring hepatic metab- cussed. We suggest that when decreasing the dose, it
olism for excretion. should be reduced by approximately 30% to 50%;
Drugs that require hepatic metabolism for activation when widening the interval, it should be increased by 2
have lower concentrations in plasma because of the im- to 4 hours (e.g., from every 8 hours to every 12 hours).
maturity of the hepatic enzyme systems. In addition,
oral drugs that undergo first-pass metabolism may ac- Antimicrobials to Avoid in Neonates
cumulate at toxic levels in plasma if given at the adult The adverse effects of chloramphenicol on the
dose. The greater permeability of the blood–brain bar- hematopoietic system include risk for polychromasia,
rier (a protective function that allows oxidizable sub- anisocytosis, target cells, and basophilic granulation of
strates, such as lactate, to be used for energy in emer- leukocytes.13,20 Gentocin was initially believed to be safe
gency situations) in neonates can cause wide variations for neonates because elevations in BUN or creatinine
in drug distribution.13 Differences in maturity of the levels had not been reported, even when very high doses
(10 mg/kg/day) were administered. However, histologic
analysis of kidneys from neonatal puppies that had re-
ceived gentocin at 5 mg/kg/day for 7 days showed sig-
Raise the Standard of Practice at Your Hospital with nificant drug accumulation and pathologic damage to
the renal cortex.21 Neonates have low levels of BUN
STANDARDS of CARE
ENDIU
MP
and creatinine and are isosthenuric for the first few
M
CO
’S •
I
•
CA
DA
N
R D S of
I STANDARDS of CARE
C O M P E N D I U M ’ S
and discoloration of the deciduous teeth. Quinolones,
M
CO
’S •
RE
S TA
CA
DA
N
R D S of
H
epatic lipidosis (HL) is the most common cause of jaundice in cats
in North America. It develops primarily in obese cats that have
recently been anorectic. By definition, HL occurs when >50% of
• Poikilocytosis (i.e., irregular
RBC shapes) is common.
• A mild nonregenerative anemia
accompanies primary
Expert help fast in a portant in large-breed dogs.13
hepatocytes accumulate excessive triglycerides (TGs), resulting in severe cell
■ Step-by-step tips
Subscribe today! present.) The prolonged half-life of these drugs in
Standards of Care: Emergency neonates warrants administering a decreased dose or in-
Call 800-426-9119. and Critical Care Medicine. creasing the dosing interval.13 Metronidazole is the drug
Only $69 for 11 Concise. Authoritative. Cur-
information-packed issues.* rent. No general practice should
of choice for giardiasis and anaerobic infections in
*November/December is a combined issue.
be without it. neonates. It has a decreased clearance and longer half-
life in these animals, and the dose should be decreased
or the dosing interval increased to avoid central ner-
vous system toxicity.13 β-Lactam antibiotics, such as nosis and successful treatment of disease syndromes.
first-generation cephalosporins, seem to be safe in Meticulous attention to detail is the only hope for mak-
neonates; however, an increased dose interval (i.e., ev- ing advances in this area.
ery 12 hours instead of every 8 hours) is suggested be-
cause of a prolonged half-life. REFERENCES
1. Hoskins JD: Veterinary Pediatrics: Dogs and Cats from Birth
to Six Months. Philadelphia, WB Saunders Co, 1990.
Anticonvulsants, Sedatives, and Analgesics 2. Hoskins JD: Pediatric health care and management. Vet Clin
Neonates are particularly dependent on high respira- North Am Small Anim Pract 29:837–852, 1999.
tory rates to prevent hypoxia. High airway resistance 3. Murtaugh RJ, Kaplan PM: Veterinary Emergency and Criti-
coupled with high oxygen demand results in a respira- cal Care Medicine. St Louis, Mosby, 1992, p 464.
4. Johnson CA, Grace JA: Care of newborn puppies and kit-
tory rate that is two to three times faster than that of tens. Kal Kan Forum 6:9, 1987.
adults. Because of decreased myocardial contractility, 5. Averill DR: The neurologic examination. Vet Clin North Am
neonates depend on a relatively fast heart rate to main- Small Anim Pract 11:511, 1981.
tain cardiac output.22 Drugs that significantly depress 6. Earl FL, Melveger BE, Wilson RL: The hemogram and bone
the heart or respiratory rate should be avoided in neo- marrow profile of normal neonatal and weanling beagle
nates. If agents that cause respiratory depression are used, dogs. Lab Anim Sci 23:690–695, 1973.
7. Meyers-Wallen VN, Haskins ME, Patterson DF: Hemato-
ventilation must be controlled. logic values in healthy neonatal, weanling, and juvenile kit-
Renal excretion of diazepam is decreased, which in- tens. Am J Vet Res 45:1322, 1984.
creases the half-life.13 Thus a dose reduction is recom- 8. Massicotte P, Mitchell L, Andrew M: A comparative study
mended. Thiopental can cause an exaggerated response of coagulation systems in newborn animals. Pediatr Res
in young animals because the decreased body fat and 20:961–965, 1986.
9. Center SA, Hornbuckle WE, Hoskins JD: The liver and
decreased hepatic clearance result in higher blood lev- pancreas, in Hoskins JD (ed): Veterinary Pediatrics: Dogs and
els; a dose reduction is recommended for barbiturates.3 Cats from Birth to Six Months. Philadelphia, WB Saunders
Opioids (e.g., fentanyl, butorphanol) are a good choice Co, 1990, pp 189–222.
because they are reversible; however, they can depress 10. Magrini F: Haemodynamic determinants of the arterial blood
heart and respiratory rates and thus should be moni- pressure rise during growth in conscious puppies. Cardiol Res
12:422–428, 1978.
tored carefully and titrated to effect. 11. Tidwell AS, Solano M, Schelling SH: Pediatric neuroimag-
ing. Semin Vet Med Surg (Small Anim) 9:68–85, 1994.
Cardiovascular Drugs 12. Partington BP: Diagnostic imaging techniques, in Hoskins
Cardiovascular drugs pose a unique problem in the JD (ed): Veterinary Pediatrics: Dogs and Cats from Birth to
pediatric population. Because of individual variations Six Months. Philadelphia, WB Saunders Co, 1995, p 11.
13. Boothe DM, Tannert K: Special considerations for drug and
in maturation of α- and β-receptors, predicting re-
fluid therapy in the pediatric patient. Compend Contin Educ
sponse to these drugs is almost impossible. In critically Pract Vet 14(3):313–329, 1992.
ill neonates, exogenous catecholamines are used to in- 14. Mosier JE: Canine pediatrics—The neonate. AAHA Sci Pre-
crease contractility, heart rate, and blood pressure. Re- sent 48:339–347, 1981.
sponse to treatment and monitoring of hemodynamic 15. Poffenbarger EM, Olsen PN, Ralston SL, Chandler ML: Ca-
variables are essential when using these drugs in nine neonatology. Part II. Disorders of the neonate. Com-
pend Contin Educ Pract Vet 13(1):25–37, 1991.
neonates. In general, elevations in the heart rate after 16. Otto CM, Kaufman GM, Crowe DT. Intraosseous infusion
administration of dopamine, dobutamine, or isopro- of fluids and therapeutics. Compend Contin Educ Pract Vet
terenol are unpredictable until 9 to 10 weeks of age in 11(4):421–430, 1989.
puppies.23 Response to atropine and lidocaine24,25 and 17. Fiser DH: Intraosseous infusion. N Engl J Med 322:1579–
renal excretion of digoxin are diminished.13 1581, 1990.
18. Short CR: Drug disposition in neonatal animals. JAVMA 184:
1161–1163, 1984.
CONCLUSION 19. Peters EL, Farber TM, Heider A, Ritter DL: The develop-
Neonates pose significant challenges because of their ment of drug metabolizing enzymes in the young dog. Fed
unique anatomic and physiologic characteristics. Adult Proc Am Soc Biol 30:560, 1971.
physical examination parameters, drug doses, and mon- 20. Plumb DC: Veterinary Drug Handbook. White Bear Lake,
MN, Pharma Vet Publishing, 1991, pp 531–532.
itoring parameters may not be suitable for this age
21. Cowan RH, Jukkola AF, Arant BS: Pathophysiologic evi-
group. Veterinary medicine lacks published physiologic dence of gentamicin nephrotoxicity in neonatal puppies.
values for neonates and pediatric patients. Kittens and Pediatr Res 14:1204–1211, 1980.
puppies are not simply little cats and dogs and should 22. Teitel DF, Hoffman JIE: Ventricular function, in Gluckman
not be treated as such. An awareness of their unique PD, Heyman MA (eds): Pediatrics and Perinatology: The Sci-
homeostasis and response to disease can aid in the diag- entific Basis, ed 2. London, Arnold, 1996, pp 737–748.