Journal of Veterinary Emergency and Critical Care 00(0) 2017, pp 1–11

Clinical Practice Review doi: 10.1111/vec.12603

A review of associated controversies

surrounding glucocorticoid use in veterinary
emergency and critical care
Maya A. Aharon, DVM; Jennifer E. Prittie, DVM, DACVECC and Kate Buriko, DVM, DACVECC

Abstract

Objective – To review the literature in human and veterinary medicine regarding the indications for, efficacy
of, and controversies surrounding glucocorticoid (GC) administration in the emergency and critical care (ECC)
setting, and to provide an overview of the most commonly used synthetic GC formulations.
Medications – Synthetic GCs vary in GC and mineralocorticoid potency, hypothalamic pituitary axis suppres-
sion, duration of action, route of administration, and clinical indication for use. Some of the GC compounds
commonly used in human and veterinary ECC include hydrocortisone, prednisone, methylprednisolone, and
dexamethasone.
Indications for Use – GCs are used in human and veterinary ECC for a variety of disorders including anaphy-
laxis, acute lung injury/acute respiratory distress syndrome, septic shock, and spinal cord injury. Evidence for
morbidity or mortality benefit with administration of GC within these populations exists; however, data are
sparse and often conflicting.
Adverse Effects and Contraindications – Routine use of GC in some conditions such as trauma, hemorrhagic
shock, and traumatic brain injury is likely contraindicated. GC use has been associated with hyperglycemia,
pneumonia, urinary tract infection, gastrointestinal ulceration, or increased mortality in some populations.

(J Vet Emerg Crit Care 2017; 00(0): 1–11) doi: 10.1111/vec.12603

Keywords: acute lung injury, canine, feline, septic shock, steroid, traumatic brain injury

TBI traumatic brain injury

Abbreviations
ALI acute lung injury
ARDS acute respiratory distress syndrome Introduction
ASCI acute spinal cord injury Glucocorticoid (GC) hormones produced in the adrenal
CIRCI critical illness-related corticosteroid insuffi- cortex of most mammals are essential to almost every as-
ciency pect of homeostasis, in that they help regulate glucose,
CRI continuous rate infusion protein, and fat metabolism.1–5 They are also a central
ER emergency room component of the neurohormonal adaptive responses
GC glucocorticoid during disease, enabling the body to react promptly and
HPA hypothalamic pituitary adrenal appropriately to acute stress that would otherwise be
IL interleukin detrimental to survival.1–5 Deficiency in GCs, whether
IVDD intervertebral disc disease naturally occurring or iatrogenically induced, leads to
MC mineralocorticoid dysregulation of glucose, water, and the cardiovascu-
MPSS methylprednisolone sodium succinate lar system, potentially culminating in cardiovascular
NASCIS National Acute Spinal Cord Injury Study collapse.1–5
GCs are frequently administered in both human and
From the Department of Emergency and Critical Care, Animal Medical veterinary emergency and critical care (ECC) settings.
Center, New York, NY 10065.
They may also be administered to aid in the diagnosis
The authors declare no conflicts of interest. of specific adrenal and pituitary diseases. In cases of
Address correspondence and reprint requests to Dr. Maya Aharon, Depart- immune mediated disease, GCs are a cornerstone of stan-
ment of Emergency and Critical Care, Animal Medical Center, 510 East 62nd
Street, New York, NY 10065, USA. Email: Maya_Anne77@yahoo.com dard therapy. However, for certain conditions like sepsis,
Submitted December 10, 2014; Accepted June 30, 2016.


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M.A. Aharon et al.
Table 1: Glucocorticoid free bases comparison
Relative GC and
Relative MC anti-inflammatory
Compound activity potency
Short acting
Cortisol 1 1
Hydrocortisone 0.8 1 20
Cortisone 0.8 0.8
Intermediate acting
Prednisone 1 4
Prednisolone 1 4
Methylprednisolone 0 5
Triamcinolone 0 5
Long acting
Dexamethasone 0 30
Betamethasone 0 30
GC, glucocorticoid; HPA, hypothalamic pituitary adrenal axis; MC, mineralocorticoid.
anaphylaxis, acute respiratory distress, polytrauma,
hemorrhagic shock, and neurologic trauma, contra-
dictory literature exists regarding the usefulness of
GCs. Definitive conclusions are difficult to draw due to
differences in study design, specific GC and formulation
used, dose, timing, route of administration, length of
treatment, and study end points. Questionable efficacy
and meaningful deleterious effects render GC admin-
istration controversial in many cases. Given the limited
evidentiary support for the use of GCs in critically ill
patients, determining the need and specific plan for
steroid therapy in such cases can be challenging.
The purposes of this review are to present the hu-
man and, when available, veterinary data regarding the
use of GCs in the emergency room (ER) and the ICU,
and to discuss the controversies surrounding their use.
GC use in critical illness-related corticosteroid insuffi-
ciency (CIRCI) will not be addressed here and the reader
is referred to a recent review on this topic for more
information.6 The different pharmacologic compounds
most commonly used in the veterinary ICU and ER will
also be discussed.
Exogenous Glucocorticoid Agents
Cholesterol is the common precursor for all adrenocorti-
cal hormones, and contains a 21-carbon ring skeleton that
is the basic structure of both aldosterone and cortisol.1,3–5
This structure is the basis for development of synthetic
steroids. In general, compared to endogenous cortisol,
synthetic GCs have less mineralocorticoid (MC) and
more anti-inflammatory activity; are less avidly bound
to cortisol binding protein (also called transcortin) in
the plasma; undergo less hepatic metabolism; and have
a higher affinity for GC receptors leading to greater
potency and longer duration of action.1,3–5 Potency of
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Equivalent Plasma Biologic half-life/
pharmacologic half-life HPA axis
dose (mg) dog (h) suppression (h)
20 1–1.5 8–12
1 8–12
25 ? 8–12
5 ? 12–36
5 1–3 12–36
4 1.5 12–36
4 ? 24–48
0.75 2 35–54
0.6 ? >48
synthetic GCs is gauged by their anti-inflammatory ac-
tivity in relation to that of cortisol.1,3–5 GCs are metabo-
lized primarily by the liver, but also in the kidney, gas-
trointestinal tract, and other tissues.1,3–5
Each synthetic GC falls into 1 of 3 categories based
on its biologic half-life, which is the time for the
biologic effects to abate by 50%, and the relative
time it suppresses the hypothalamic pituitary adrenal
(HPA) axis: short-acting (<12 hours); intermediate acting
(12–36 hours); and long acting (>48 hours). GC activity
can also be divided into physiologic, anti-inflammatory,
and immunosuppressive, which occur at increasing
dosages, respectively.1,3–5 Equipotent amounts of differ-
ent synthetic GCs exert similar effects, such that a higher
dose of a less potent GC results in similar activity as a
lower dose of a more potent GC (Table 1).1,3–5
Onset and duration of action can be modified by
changing the chemical form of the compound from a
free alcohol to a chemically bound product (as ester or
salt).1,3–5 The free alcohol synthetic GCs are water insol-
uble and are commonly formulated in tablets for oral
administration. Esterification of the alcohol determines
the water/lipid solubility ratio and also influences the
duration of action following subcutaneous or intramus-
cular administration.1,3–5 Thus, the base steroid can be
formulated for enteral or parenteral administration. The
injectable formulation can be modified to have a rapid
absorption and onset of action or a slow absorption and
onset of action.1,3–5
While a detailed description of every synthetic GC
used in veterinary medicine is beyond the scope of this
review, a brief overview of the GCs most commonly used
in the ER and ICU is provided. The reader is referred
elsewhere for more information.3
Hydrocortisone is structurally identical to cortisol,
which is the primary endogenous GC in most species.

Hydrocortisone thus shares cortisol’s GC and MC activ-
ity characteristics.1,3–5 It is rapidly absorbed, short acting,
and eliminated by the liver, gastrointestinal tract, and
kidneys.7 Oral, injectable, and topical formulations are
available.3 In the veterinary emergency and critical care
setting, it is commonly used for GC replacement therapy
in animals with CIRCI.6
Prednisone and prednisolone are intermediate acting
synthetic steroids that are approximately 4 times as po-
tent as cortisol in regards to their anti-inflammatory ac-
tivity and have 0.8 times the MC activity of cortisol.1,3–5
Prednisone and prednisolone are often considered inter-
changeable; however, this is not pharmacologically ac-
curate. Prednisone is biologically inactive, and requires
conversion to prednisolone in the liver in order to exert
its biologic effects.1,3–5 Although hepatic conversion is
rapid in dogs and cats, the oral bioavailability of pred-
nisolone is greater than that of prednisone.8,9 Specifi-
cally, cats require 3–5 times as much prednisone com-
pared to prednisolone to achieve equivalent biologic
effects.10 There is some evidence that impaired liver
function may affect the metabolism of prednisone to
prednisolone in people, although this was not shown
across all studies.11–14 It may be prudent to consider pred-
nisolone therapy rather than prednisone in cats and in
animals with liver disease. Prednisone is available in oral
form, while prednisolone is available in oral, injectable,
and topical preparations.3
Methylprednisolone is an intermediate acting steroid
that is 5 times as potent as cortisol in GC activity and
half as potent as cortisol in MC activity.1,3–5 Laboratory
investigations suggest that methylprednisolone may at-
tenuate secondary injury to tissues after trauma by in-
hibiting lipid peroxidation of cell membranes.15,16 The
water-soluble ester, methylprednisolone sodium succi-
nate (MPSS), can be administered IV or IM and has been
used in veterinary medicine in the treatment of neuro-
logic trauma. Oral, injectable, and topical methylpred-
nisolone compounds are available.3
Dexamethasone is a long-acting steroid with a rel-
ative GC potency of 25–30 compared to cortisol and
virtually no MC activity.1,3–5,17 It is available in oral,
injectable, and topical formulations. The 2 most com-
monly used injectable preparations are dexamethasone
as a free alcohol and the water-soluble ester dexa-
methasone sodium phosphate. The free steroid alcohol
is prepared in an approximately 40% polyethylene gly-
col solution and may be administered IV or IM. It is
absorbed from the site of injection within minutes and
has a rapid onset of action.1,3–5,17 Intravenous adminis-
tration of polyethylene glycol may result in hemolysis,
hypotension, collapse, and CNS depression, coma, or
seizures; therefore, low volumes and slow infusion rate
are recommended.1 The water-soluble ester is suitable

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Glucocorticoid use in emergency and critical care
for IV or IM administration.1,3 The fact that these drugs
are both absorbed and have onset action within minutes
make them ideal for treatment of urgent conditions.1
Indications for Glucocorticoid Use in the
Emergency and Critical Care Setting
Factors such as pain, infection, or trauma stimulate a 10-
fold increase in endogenous GC release into circulation,
where these hormones help ensure delivery of glucose
to the glucose-dependent organs such as the heart and
brain, act synergistically with catecholamines to main-
tain and augment cardiovascular function, modulate re-
nal sodium and water reabsorption and effective circu-
lating volume, and regulate the inflammatory response
to prevent excessive tissue damage.1–5 In the CNS, GCs
also help to maintain cerebral blood flow and electrolyte
concentrations for cerebral function.3–5 In the airways,
GCs induce bronchodilation by increasing ␤2 receptor
expression.3,5 GCs help to limit capillary permeability
and maintain vascular tone because they enhance vascu-
lar responsiveness to vasoactive substances (eg, norep-
inephrine, angiotensin II) in vascular smooth muscle
cells and suppress production of vasodilators (eg, prosta-
cyclin, nitric oxide) in endothelial cells.18,19 This wide
variety of supportive physiologic effects has led to
long-standing interest in GC use in the veterinary ECC
setting.
Hypersensitivity and Anaphylaxis
Immune-mediated type I hypersensitivity reactions
are common in the ER. Animals present with allergic
signs ranging in severity from pruritus, urticaria,
and angioedema to anaphylactic shock. Anaphylaxis
is an acute systemic hypersensitivity reaction that
can be life threatening.20–22 Type I hypersensitivity is
associated with mast cell activation and degranulation
and the release of preformed inflammatory mediators
including histamine, heparin, and proteases into the
systemic circulation.20–22 Activation of the arachidonic
acid cascade results in the release of leukotrienes,
prostaglandins, thromboxane, and platelet activating
factor.20–22 Synthesis and release of cytokines and
chemokines constitutes the late-phase inflammatory
response. Increased vascular permeability, vasodilation,
hypovolemia, impaired cardiac function, and respira-
tory compromise ensue, which results in circulatory
collapse.20–22
It has been proposed that GCs may be of benefit
in the treatment of hypersensitivity reactions and ana-
phylaxis because they may counteract the inflamma-
tory cascade activated in these conditions. GCs inhibit
3
M.A. Aharon et al.
transcription factors and cofactors such as nuclear factor-
␬B, which results in decreased production of many
pro-inflammatory cytokines such as tumor necrosis fac-
tor ␣, interleukin (IL) 1␤, IL-2, IL-6, and granulocyte-
macrophage colony stimulating factor.23–25 GCs suppress
the transcription of inducible nitric oxide synthase and of
cyclooxygenase-2, the inducible form of cyclooxygenase
that converts arachidonic acid to prostaglandins, throm-
boxanes, and prostacyclins.23–25 Some anti-inflammatory
cytokines, such as IL-10, are increased through GC
activity.25 GCs also inhibit the release of inflammatory
mediators from activated macrophages, and the release
of platelet-activating factor from leukocytes and mast
cells.26 Histamine and serotonin release is inhibited from
mast cells and platelets. GCs also inhibit fibroblast pro-
liferation and collagen deposition.26
While use of synthetic GCs for acute hypersensitivity
is widespread in both human and veterinary medicine,
there are few human and no veterinary clinical stud-
ies evaluating the efficacy of GCs in acute allergic
responses or anaphylaxis, and little evidence exists to
support benefit.20,27–30 GC actions such as membrane sta-
bilization, potentiation of vasoconstritive substances,
and maintenance of vascular tone occur within min-
utes of GC administration, which suggests they could
be helpful in animals in anaphylactic shock.18,31 How-
ever, the majority of anti-inflammatory effects produced
by GCs require nuclear transcription and creation of
new molecules, a process that requires 2–24 hours; this
delay exceeds the window of opportunity to treat life-
threatening anaphylaxis.31,32 Improvement in airway in-
flammation, edema, and bronchoconstriction may not
occur for 2–6 hours after administration.33
Another potential benefit of GCs in acute hypersensi-
tivity is attenuation of delayed inflammation. A bipha-
sic anaphylactic response has been documented in 1%–
20% of human cases.34–36 In these cases, initial improve-
ment is followed by recurrence of clinical signs up to
72 hours later. While some reports suggest that GC ther-
apy may reduce the likelihood and severity of this bipha-
sic response, other studies did not show a GC protective
effect.27,29,30,35,37–40 To the authors’ knowledge, a biphasic
anaplylactic response has not been reported in veterinary
medicine.
While it is unclear whether GCs are indicated for
the treatment of acute hypersensitivity, several different
treatment recommendations exist for the use of GCs in
anaphylaxis in dogs and cats.20–22 Following appropri-
ate intravenous fluid resuscitation and treatment with
epinephrine as needed for anaphylactic shock, the clin-
icians may consider using an immunosuppressive dose
of dexamethasone (0.1–0.5 mg/kg IV or IM) or MPSS
(30 mg/kg IV).20–22,41 Continued therapy follow-
ing hospital discharge may include 2–3 days of
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anti-inflammatory doses of prednisone (0.5–1 mg/kg per
day PO) tapered over an additional 2–3 days (Table 2).
Acute Lung Injury and Acute Respiratory Distress
Syndrome
Acute lung injury (ALI) and acute respiratory dis-
tress syndrome (ARDS) are clinical syndromes in
which severe pulmonary inflammation and edema re-
sult in acute respiratory failure.42–45 The early exuda-
tive phase is characterized by increased pulmonary
capillary permeability and protein-rich interstitial and
alveolar edema.44,46 Proteolytic enzymes, reactive oxy-
gen species, pro-inflammatory cytokines (tumor necro-
sis factor ␣, IL-1␤), arachidonic acid metabolites, CXC
chemokine ligand-8 (also known as IL-8), transform-
ing growth factor-␤, and platelet-activating factor per-
petuate lung injury.44,46–48 During the fibroproliferative
phase, reparative processes and fibrosis result in nar-
rowed airspaces and capillaries, which in conjunction
with bronchoconstriction and hypoxemic vasoconstric-
tion, lead to pulmonary hypertension and may result in
secondary cor pulmonale if pulmonary hypertension is
sustained.44,46–48
There are few published reports of ALI or ARDS
in veterinary medicine, and reports of survival are
rare.44,45,49–51 The effects of GCs in the treatment of ALI or
ARDS have not been studied in dogs and cats, and only
isolated reports exist in which GCs were incorporated
in the therapy of ALI or ARDS in veterinary species.50,51
No conclusions can be drawn from these reports.
Mortality rates as high as 40%–60% have been reported
in people with ALI or ARDS.46–48 Prolonged inflamma-
tion and increased fibrosis are associated with a poor
prognosis.52,53 Reported beneficial effects of GCs in these
syndromes include attenuation of proinflammatory cy-
tokine production, phospholipase A2, cyclooxygenase,
and inducible nitric oxide synthase, and modulation of
anti-inflammatory cytokines.52 GCs may help prevent
progression to the fibroproliferative stage of ALI and
ARDS through the inhibition of fibroblast proliferation
and collagen deposition; stimulation of T cell, eosinophil,
and monocyte apoptosis; and inhibition of neutrophil
activation.52 MPSS was the most commonly evaluated
GC, and has been shown to have a larger volume of
distribution, higher concentrations in bronchoalveolar
lavage fluid, and longer plasma half-life compared to
other GCs.54,55
There is general agreement that in people at risk for
ARDS, and in people with early ARDS, high doses of
GCs (MPSS 30 mg/kg every 6 hours) for short periods
(1–4 days) do not appear protective.52,53,56,57 Fur-
thermore, increased incidence of ARDS, infection,
hyperglycemia, and mortality were seen in these
 Glucocorticoid use in emergency and critical care

Table 2: Summary of glucocorticoid protocols

Are GC recom- Are GC con- Possible indications for

Pathology mended traindicated GC Possible protocols for GC

Hypersensitivity No No Dexamethasone 1–2 mg/kg IV/IM or MPSS

and anaphylaxis 30 mg/kg IV
Possibly followed by: Prednisone 0.5–1
mg/kg/d PO × 3 days tapered over an
additional 2- to 3-day period

ALI/ARDS No No Early stage, <14 days from Loading dose of 1 mg/kg MPSS
diagnosis followed by infusion of 1 mg/kg/d for days
1–14,
0.5 mg/kg/d, days 15–21,
0.25 g/kg/day, days 22–25,
0.125 mg/kg/d, days 26–28

Trauma/ No No Failure to achieve Insufficient data

hemorrhagic hemodynamic stability
shock despite adequate
resuscitation and
vasopressor use;
or
adrenal insufficiency

ASCI Debatable No Within 8 hours of injury MPSS 30 mg/kg initial bolus,

Followed by: MPSS CRI of 5.4 mg/kg/h for 24
hours or 15 mg/kg q6 hours for 2 doses

TBI No Yes Documented evidence of HPA For adult human patient (estimated 70 kg):
axis suppression (low Hydrocortisone 200 mg/day infusion with
plasma ACTH and cortisol fludrocortisone 50 ␮g PO once per day
levels) as per Corti-TC × 7 days
study Taper: 100 mg on days 8 and 9, 50 mg on
day 10
May taper sooner if patient responds to 250
␮g corticotropin test

ALI, acute lung injury; ARDS, acute respiratory distress syndrome; ASCI, acute spinal cord injury; CRI, continuous rate infusion; GC, glucocorticoid; HPA,
hypothalamic-pituitary-adrenal; MPSS, methylprednisolone sodium succinate; TBI, traumatic brain injury.

patients.52,53,56,57 In contrast, prolonged (3 days–4
weeks), lower doses of GCs (MPSS 0.5–4 mg/kg every
6 hours) may be of benefit in ALI or ARDS in people.56
Improved oxygenation, decreased lung injury score, de-
creased plasma and bronchoalveolar levels of proinflam-
matory mediators, and increased survival were noted in
GC-treated patients.56,58–61
Results of 2 recent human trials, the ARDS Network
Trial and MPSS Infusion in early Severe ARDS, suggest
that early initiation of prolonged low doses of MPSS
may yield a clinical benefit.62,63 Trends in improved oxy-
genation, respiratory compliance, and blood pressure,
as well as increased number of ventilator and shock free
days, improved lung injury, and multiorgan dysfunction
scores are reported.62,63
Differing underlying etiologies of human and veteri-
nary ALI and ARDS may prevent the direct extrapo-
lation of recommendations for people to dogs and cats.
However, based on the findings in people, high-dose GC
therapy should probably be avoided in veterinary ARDS.
While there is no compelling evidence for a survival ben-
efit with use of GC in early ALI or ARDS, low dose
prolonged therapy using MPSS following a protocol
by Meduri et al63 may be considered in severely affected
patients (Table 2).
Acute Spinal Cord Injury
Acute spinal cord injury (ASCI) initially occurs due to
mechanical damage that causes contusion, compression,
shearing, laceration, or distension of the spinal cord
parenchyma and vasculature. This primary injury ini-
tiates a cascade of events beginning within minutes and
lasting days after the inciting trauma, resulting in sec-
ondary spinal cord injury.64–69 Ischemia, excitotoxicity,


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M.A. Aharon et al.
cytotoxic (cellular) edema, mitochondrial dysfunction,
and increased activation and production of nitric oxide,
eicosanoids, and caspases all propagate neuronal necro-
sis and apoptosis. Reactive oxygen species produced
secondary to neuronal ischemia, hemorrhage, or inflam-
mation induce membrane lipid peroxidation that prop-
agates neuronal death.64–69
Experimental data in dogs and cats
GCs are thought to confer spinal cord protection from
ongoing inflammatory and ischemic injury that occur
secondary to the initial insult by mechanisms unrelated
to their anti-inflammatory activity.64,70–72 Administration
of 30 mg/kg of MPSS, IV, 30 minutes following ASCI,
followed by 15 mg/kg doses at hours 2 and 6, and a
continuous rate infusion (CRI) of 2.5 mg/kg/h for 48
hours attenuated membrane lipid peroxidation, post-
traumatic spinal cord ischemia, intracellular calcium ac-
cumulation, neurofilament degradation, and eicosanoid
production in experimental studies of ASCI in cats.64,70–72
MPSS supported aerobic energy metabolism, maintained
vascular blood flow, and exhibited antioxidant and free
radical scavenger properties in these studies.64,70–72 It
was also associated with improved neurologic function
and decreased posttraumatic spinal cord tissue loss on
histopathologic examination.73 Dexamethasone has not
been found to improve neurologic outcome in experi-
mental cat and rat models of ASCI.74–76 While dexam-
ethasone is approximately 5 times as potent as MPSS
in GC receptor affinity and anti-inflammatory potency,
MPSS appears to have superior antioxidant and lipid
peroxidation inhibition properties.4,16,64,74,77,78
Experimental evidence in dogs is sparse. Methylpred-
nisolone was not found to enhance neurologic recov-
ery after simulated spinal cord trauma in 1 experi-
mental study.79 A trend for better neurologic outcome
was noted in experimental spinal cord injury in bea-
gles treated with surgical decompression and MPSS
(30 mg/kg followed by 5.4 mg/kg/h for 23 hours) com-
pared to the group treated with surgical decompression
alone, but GC treatment benefit did not reach statistical
significance.80 Other studies have shown that GCs may
contribute to excitotoxic neuronal death, exacerbate ox-
idative injury through inhibition of membrane phospho-
lipase A2, and increase accumulation of lactate within
the spinal cord parenchyma.64,71,81–83
Clinical data
GC use in ASCI is controversial in veterinary and hu-
man medicine. Despite the proposed treatment benefits
of GCs in ASCI, improved morbidity, mortality, mean-
ingful functionality, or quality of life have not been uni-
versally documented and adverse effects from GCs have
been reported.
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The National Acute Spinal Cord Injury Study
(NASCIS) I,84 NASCIS II,85 and NASCIS III86 trials re-
ported small but meaningful improvements in sensory
and motor function in people with ASCI receiving high-
dose MPSS within 3–8 hours after injury. Based on
these studies, people treated with MPSS within 3 hours
of injury are continued on the treatment regimen for
24 hours, while patients administered MPSS between 3
and 8 hours following injury are continued on steroid
therapy for 48 hours. In people, initiation of MPSS is not
recommended once more than 8 hours have passed since
the injury.64,86,87 Despite the improved sensory and mo-
tor scores in people treated with MPSS using this pro-
tocol, a statistically significant difference in Functional
Independence Measure was not found.86
In the 2012 Cochrane review of steroids for ASCI, the
authors concluded that MPSS enhances neurologic re-
covery, however unless the initial deficits are minimal,
it is unlikely to bring a return to normal.88 This group
recommends initiation of MPSS therapy within 8 hours
of injury starting with an initial bolus of 30 mg/kg by
IV followed by a CRI of 5.4 mg/kg/h for 24 hours. In
contrast, the most recent American Association of Neu-
rological Surgeons and Congress of Neurological Sur-
geons Joint Guidelines Committee published in 2013,
states that MPSS is not recommended for the treatment
of ASCI.89
There are few data regarding the efficacy of GCs in
ASCI in clinical dog and cat patients. The majority of
data are retrospective, pertaining to intervertebral disc
disease (IVDD) and the potential benefits and compli-
cations seen with GC use in the treatment of IVDD. A
favorable neurologic outcome remains questionable and
significant side effects such as GI ulceration and colonic
perforation have been reported.90 Two retrospective
studies did not find a significant difference in ambulation
recovery rates or in lengths of time till ambulation was
achieved, between dogs that received perioperative GCs
compared to those patients that did not regardless of the
GC administration protocol used.91,92 In a retrospective
study of 105 dogs with neurological injury treated with
high-dose prednisolone sodium succinate (30 mg/kg
IV q 6 h for 36 hours), 35% developed complications
including diarrhea, melena, vomiting, hematochezia,
hematemesis, anorexia, or a combination thereof.93 All
animals that developed complications responded to
conservative management and prolonged hospitaliza-
tion secondary to complications was not noted. Gas-
tric mucosal lesions were detected endoscopically in
76% of dogs treated perioperatively with dexamethasone
(2 mg/kg IV on admission followed by a tapering dose
of oral prednisolone) regardless of concurrent antiulcer
treatment.94 Dachshunds with surgically treated acute
IVDD receiving MPSS (initial dose of 30 mg/kg in the

majority of dogs [range 15–50 mg/kg]; median of 3
doses) had a higher incidence of postoperative GI com-
plications, increased use of gastroprotectives, and in-
creased cost of hospitalization when compared to dogs
receiving other GCs (most commonly dexamethasone
0.08–2 mg/kg single administration and a combination
of dexamethasone with oral prednisone).95 There was no
significant difference in neurologic outcome between the
different GCs in this study.95 Dexamethasone adminis-
tration ranging from 1 to 30 mg/kg in dogs with acute
thoracolumbar IVDD herniation was associated with a
3.4-times increase in the likelihood of complications com-
pared to dogs who received other GCs (MPSS, pred-
nisone) or placebo.96 An 11.4-fold increase in the like-
lihood of a urinary tract infection and 3.5-fold increase
in the likelihood of developing diarrhea were noted in
dogs receiving dexamethasone. Neurologic function at
discharge or at recheck did not differ between groups.96
In two other retrospective studies, GCs were not asso-
ciated with successful medical management (defined as
improved neurologic function without reported relapse
of clinical signs) or improved quality of life in dogs with
presumptive cervical IVDD and were associated with
a lower quality of life and decreased odds for success-
ful outcome in dogs with presumptive thoracolumbar
IVDD.96,97
There are few data regarding the efficacy of GCs
in ASCI in the clinical veterinary setting. The major-
ity of data are retrospective and pertains to the use of
GCs in the management of IVDD in dogs. There is not
strong evidence for a treatment benefit of GCs in this
setting.92,98–100 Meanwhile, significant adverse effects
such as diarrhea, melena, vomiting, hematochezia, he-
matemesis, anorexia, gastrointestinal ulceration, colonic
perforation, and urinary tract infections have been re-
ported, more frequently with dexamethasone than with
MPSS.99–103
Due to the paucity of information and the variable
results of the few experimental, veterinary clinical, and
human studies reported, a recommendation advocating
or discouraging the use of GC in ASCI cannot be made.
If the decision is made to use steroids in ASCI, MPSS
appears to be the GC of choice. Based on available litera-
ture, administration within 8 hours of injury is advisable,
using a protocol of 30 mg/kg MPSS as an initial bolus
followed by either a CRI of 5.4 mg/kg/h for 24 hours
or 2 subsequent injections of MPSS 15 mg/kg at 2 and
6 hours (Table 2).
Adverse Effects of and Contraindications for
Glucocorticoid Use in ECC
Excessive circulating endogenous or exogenous GCs can
lead to abnormal organ function. Synthetic GCs have

C Veterinary Emergency and Critical Care Society 2017, doi: 10.1111/vec.12603
Glucocorticoid use in emergency and critical care
similar effects to endogenous cortisol, and thus they have
multisystemic pharmacologic effects and they suppress
the HPA axis.1–5 Excessive circulating GCs contribute
to blood stasis and hypercoagulability, and can lead to
thromboembolism.104 Additionally, susceptibility to in-
fections is increased. Hyperlipidemia, muscle atrophy,
weakness, insulin resistance, and hyperglycemia, and
possibly development of diabetes mellitus can be seen
with chronic GC excess.1–5 Antidiuretic hormone release
is inhibited by GCs, which may also directly decrease
the permeability of the distal renal tubules to water, re-
sulting in free water loss with subsequent polyuria and
polydipsia.1–5 Glucocorticoids contribute to reduction in
total body calcium stores; inhibit bone, cartilage, and
tissue healing; and may increase susceptibility of the
gastrointestinal tract to ulceration.1–5 Anaphylaxis sec-
ondary to GC administration is a rare yet potentially
fatal adverse effect, and has been reported in both the
human and veterinary literature.20,105 These adverse ef-
fects may contribute to the lack of improvement and
sometimes detrimental outcomes seen with GC use in
certain populations of critically ill patients.
Glucocorticoids in Trauma and Hemorrhagic Shock
In trauma and hemorrhage, the HPA axis, hormonal,
inflammatory, metabolic, and coagulation responses are
activated in an attempt to restore homeostasis and repair
injured tissue.106,107 Stimulation of the HPA axis results
in increased circulating cortisol, which in turn increases
glucose availability to the brain, potentiates epinephrine
in maintaining vascular tone and reactivity, and attenu-
ates the inflammatory response. Local inflammatory me-
diators such as cytokines, arachidonic acid metabolites,
and histamine are released from endothelium and WBCs
at the site of injury.107 The inflammatory response is also
triggered by the ischemia-reperfusion injury associated
with trauma, hemorrhage, and hypotension.
Most experimental and clinical trials evaluating the
use of GCs in the treatment of hemorrhage and traumatic
shock were performed several decades ago using vary-
ing protocols of MPSS or dexamethasone administra-
tion. Potential benefits reported by some investigators
included increased cardiac output, decreased systemic
and pulmonary vascular resistance, increased tissue per-
fusion, decreased incidence of pulmonary thromboem-
bolism, and disseminated intravascular coagulation, as
well as stabilization of lysosomal enzymes and cellular
membranes.108–113 Other trials have failed to show these
benefits or a survival advantage associated with GC
administration.114–118 GC-mediated adverse effects in
traumatic shock include eosinophil granulocyte depres-
sion, sodium retention, hyperglycemia, gastrointestinal
7
M.A. Aharon et al.
ulceration, increased blood urea nitrogen, and increased
risk of pneumonia.119
There is a subset of patients with traumatic shock
that may benefit from exogenous steroid administration.
CIRCI may be present in as many as 40%–90% of peo-
ple suffering from trauma and hemorrhagic or hypo-
volemic shock.120–123 While there is increasing evidence
for the presence of CIRCI and the potential benefits of
GCs in septic veterinary patients, conclusive evidence of
CIRCI is lacking in veterinary trauma and hemorrhagic
or hypovolemic shock patients.124 Hydrocortisone has
been associated with improved survival in trauma pa-
tients with CIRCI requiring vasopressors and mechan-
ical ventilation.125 In the multicenter randomized HY-
POLYTE trial, administration of hydrocortisone as a CRI
(200 mg/24 h for 5 days, followed by 100 mg on day 6
and 50 mg on day 7) in intubated trauma patients was as-
sociated with a significantly reduced risk of developing
pneumonia and a decrease in the duration of mechanical
ventilation, although a survival benefit was not found.126
Significant heterogeneity among studies prevents con-
fident recommendation regarding GC therapy in pa-
tients with trauma and hemorrhagic or hypovolemic
shock. Given the lack of evidence supporting improved
outcome, as well as potential adverse effects, routine
use of GCs cannot be recommended in this setting. GCs
may be considered in patients not responding to medi-
cal management that remain hypotensive despite fluid
resuscitation and vasopressor support (Table 2).
Traumatic Brain Injury
Traumatic brain injury (TBI) results in primary and sec-
ondary injury similar to that seen in ASCI and shares
many of the pathophysiologic sequelae seen in ASCI.
One of the most deleterious consequences of TBI is the
development of cerebral edema and increased intracra-
nial pressure. Because steroids reduce tumor-associated
vasogenic edema,127 are anti-inflammatory, and have
shown some benefit in people with ASCI, they have been
evaluated for use in people with TBI. Despite theoretical
benefits, GCs have not shown a definitive advantage in
the treatment of TBI.128 While it is unclear why GCs do
not help and in fact may harm patients with TBI, the
presence of cytotoxic rather than vasogenic edema in
TBI may in part explain it.129–132 One study reported
an increased risk of posttraumatic seizures in people
treated with GCs within 24 hours of injury.133 Addition-
ally, GCs promote hyperglycemia and insulin resistance.
Early hyperglycemia has been associated with worsened
outcome in TBI patients.134 Hyperglycemia is thought to
exacerbate secondary brain injury through several mech-
anisms including promoting hyperosmolality, lactic acid
production, alterations in neuronal pH, and increases in
8 
C Veterinary Emergency and Critical Care Society 2017, doi: 10.1111/vec.12603
excitatory amino acids.134 The 2007 Brain Trauma Foun-
dation Guidelines state that the majority of evidence in-
dicates that GCs do not lower intracranial pressure or
improve outcome in severe TBI, and that they may have
deleterious effects.135 Furthermore, GCs were associated
with an increased risk of death in the corticosteroid ran-
domization after significant head injury trial.136 GC use
is therefore not recommended for TBI.135,137
Although high-dose GC therapy is not advocated
in TBI patients, physiologic and stress dose GCs may
be considered in TBI patients that also have CIRCI.138
Furthermore, TBI patients may develop a specific
form of CIRCI called acute secondary adrenal insuf-
ficiency subsequent to direct trauma to the pituitary
and hypothalamus.139,140 Such trauma results in acute
and chronic posttraumatic hypopituitarism character-
ized by deficiency in various pituitary hormones (eg,
growth hormone, thyroid stimulating hormone, ACTH,
vasopressin). Foley et al documented a generalized
hypothalamic-pituitary dysfunction or panhypopitu-
itarism in a dog following TBI.141 Clinical signs of
acute secondary adrenal insufficiency, including hypo-
glycemia and hypotension, were alleviated by supple-
mentation of physiologic doses of GCs.141
The use of GC for TBI in small animals has not been
investigated. However, in light of results from human
trials, routine use of GCs in animals with TBI is not rec-
ommended. In cases of trauma induced hypopituitarism
and CIRCI, supplementation of the deficient hormone is
appropriate (Table 2).
Summary
GCs’ physiologic effects are integral to health, affecting
most aspects of cellular and organ function. Their phar-
macologic, anti-inflammatory, and immunosuppressive
properties have proven beneficial in a multitude of dis-
ease processes and provide the rationale for GC use in
some of the conditions encountered in the ECC setting.
However, clinical data pertaining to the efficacy of GC
therapy in this field are inconsistent and often lacking
in both human and veterinary medicine. Adverse effects
may increase morbidity and mortality in these patient
populations. Although definitive recommendations can-
not be made at this time, GC administration may be
considered in anaphylaxis, the early stages of ALI or
ARDS, and in ASCI. In trauma and hemorrhagic shock,
GC may have a role in cases in which CIRCI is suspected
or documented and GCs are contraindicated in TBI in
the absence of documented HPA axis suppression. Ad-
ditional high-quality clinical trials are needed to further
elucidate the role of GCs in both human and veterinary
emergency and critical care.

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