PHARM D NOTES

Examples of positive inotropic agents include:

 Digoxin
 Amiodarone
 Berberine
 Calcium
 Calcium sensitisers
 Levosimendan
 Catecholamines
 Dopamine
 Dobutamine
 Dopexamine
 Epinephrine (adrenaline)
 Isoprenaline (isoproterenol)
 Norepinephrine (noradrenaline)
 Angiotensin II
 Eicosanoids
 Prostaglandins[10]
 Phosphodiesterase inhibitors
 Enoximone
 Milrinone
 Amrinone
 Theophylline
 Glucagon
 Insulin

Dobutamine — Dobutamine (Dobutrex) is not a vasopressor but rather is an inotrope that

causes vasodilation. Dobutamine's predominant beta-1 adrenergic receptor effect increases
inotropy and chronotropy and reduces left ventricular filling pressure. In patients with heart
failure this results in a reduction in cardiac sympathetic activity.
DRUGS MOA USES S.E.
Propofol Propofol causes Propofol has a wide
global CNS array of benefits including Cardiovascular:
depression, anxiolysis, anticonvulsant activity, Hypotension
presumably through anti-emesis (adults: 3% to
agonism of GABAA and an ability to reduce intracranial
26%; children:
receptors and pressure
perhaps reduced 17%)
glutamatergic activity
through NMDA Central nervous
receptor blockade. system:
Involuntary body
Propofol is a short- movements
acting, lipophilic (children: 17%;
intravenous general adults: 3% to
anesthetic 10%)
For intubated,
Local: Burning
mechanically
ventilated adult sensation at
patients, propofol injection site
should be initiated (adults: ≤18%;
slowly with a children: ≤10%),
continuous infusion pain at injection
in order to titrate to
site (includes
desired clinical effect
and stinging; adults:
minimize ≤18%; children:
hypotension. The ≤10%)
infusion rate should
begin at 5 μg/kg/min Respiratory:
(0.3 mg/kg/h) Apnea (30 to 60
and increased by
seconds duration:
increments of 5 to 10
μg/kg/min (0.3 to 0.6 adults: 24%,
mg/kg/h) until the children: 10%;
desired level of >60 seconds
sedation is achieved. duration: adults:
12%, children:
5%)

MIDAZOLAM
(BZDS) Binds to Anesthesia: IV: Induction of >10%:
stereospecific general anesthesia before Respiratory:
benzodiazepine administration of other Bradypnea,
receptors on the anesthetic agents; decreased tidal
postsynaptic GABA maintenance of anesthesia as volume
neuron at several a component of balanced
sites within the anesthesia. 1% to 10%:
central nervous
system, including the Sedation/anxiolysis/amnesia Cardiovascular:
(preoperative/procedural): Hypotension
limbic system, (children: 3%)
reticular formation. IM: Preoperative
Enhancement of the sedation, anxiolysis, and Central nervous
inhibitory effect of amnesia. system:
GABA on neuronal Drowsiness (1%),
excitability results by IV: Sedation, anxiolysis, headache (1%),
increased neuronal and amnesia prior to or seizure-like
membrane during diagnostic, activity (children:
permeability to therapeutic, or 1%), drug
chloride ions. This endoscopic procedures, dependence
shift in chloride ions or prior to surgery. (physical and
results in psychological
Oral: Sedation, anxiolysis, dependence with
hyperpolarization (a
and amnesia in children prolonged use),
less excitable state)
prior to diagnostic, myoclonus
and stabilization.
therapeutic or endoscopic (preterm infants),
Benzodiazepine
procedures or before severe sedation
receptors and effects
induction of anesthesia.
appear to be linked
Gastrointestinal:
to the GABA-A Sedation for mechanically- Hiccups (adults:
receptors. ventilated patients: IV: 4%; children: 1%),
Benzodiazepines do Sedation of intubated and nausea (3%),
not bind to GABA-B mechanically-ventilated vomiting (3%)
receptors patients as a component of
Midazolam is most anesthesia or during treatment Local: Injection
commonly in a critical care setting by site reaction (IM:
administered via a continuous IV infusion. ≤4%, IV: ≤5%;
continuous infusion severity less than
titrated between Use: Off-Label diazepam), pain at
0.25 and 1.0 Seizures (children/adolescents); injection site (IM:
μg/kg/min. Status epilepticus ≤4%, IV: ≤5%;
(children/adolescents/adults); severity less than
Status epilepticus, refractory diazepam)
(adults); Status epilepticus, Ophthalmic:
refractory (children/adolescents); Nystagmus
Palliative sedation (children: 1%)

Respiratory:
 Apnea (children:
3%), cough (1%)

LORAZEPAM
Binds to Anxiety (oral): Management Hypotension
stereospecific of anxiety disorders, short-
benzodiazepine term (≤4 months) relief of
receptors on the anxiety symptoms, or anxiety
postsynaptic GABA associated with depressive
neuron at several symptoms, or anxiety/stress-
sites within the associated insomnia.
central nervous
system, including the Anesthesia premedication
limbic system, (parenteral): Anesthesia
reticular formation. premedication in adults to
Enhancement of the relieve anxiety or to produce
inhibitory effect of amnesia (diminish recall) or
GABA on neuronal sedation.
excitability results by Anesthesia premedication
increased neuronal (sublingual) [Canadian
membrane product]: Anesthesia
permeability to premedication to relieve
chloride ions. This anxiety prior to surgical
shift in chloride ions procedures.
results in
hyperpolarization (a Status epilepticus
less excitable state) (parenteral): Treatment of
and stabilization. status epilepticus.
Benzodiazepine
receptors and effects
Use: Off-Label
appear to be linked Agitation in the ICU patient;
to the GABA-A Alcohol withdrawal delirium;
receptors. Alcohol withdrawal syndrome;
Benzodiazepines do Chemotherapy-associated nausea
not bind to GABA-B and vomiting (adjunct or
receptors. breakthrough) (adults);
For sedation, 0.25– Chemotherapy-associated nausea
0.5 mg IV every 2–4 and vomiting (adjunct or
h is commonly breakthrough)
sufficient, and 1–2 (children/adolescents);
mg IV
Chemotherapy-associated nausea
 and vomiting (anticipatory)
bolus will provide (children/adolescents);
moderately deep Psychogenic catatonia; Rapid
sedation for 4–8 h. tranquilization of the agitated
patient; Status epilepticus (infants,
children, and adolescents)

AMPHOTERICIN B DEOXYCHOLATE

Pharmacokinetics — Despite over 40 years of clinical use, relatively little is known about the
pharmacokinetics of amphotericin B [7]. The pharmacokinetic profiles of the lipid-based
formulations of amphotericin B differ from those of amphotericin B deoxycholate and from each
other. (See 'Lipid-based amphotericin B formulations' below.)

Absorption — The drug is poorly absorbed (less than 5 percent) after oral administration. As a
result, treatment of invasive mycoses requires intravenous administration. An oral suspension
(no longer commercially available in the United States) is useful only in the treatment of
oropharyngeal candidiasis and is generally reserved for those infections that are refractory to
other agents. Systemic absorption following aerosol administration is also thought to be
minimal.

Distribution — Serum concentrations following intravenous infusions of 30 to 50 mg of

amphotericin B deoxycholate have ranged from 1 to 2 mcg/mL. The drug is highly protein bound
(up to 95 percent), primarily to lipoproteins. It is extensively distributed throughout the body, with
a volume of distribution of approximately 4 L/kg.

Amphotericin B concentrations can be measured in various body tissues and fluids, including
liver, spleen, pleural fluid, peritoneal fluid, joint, vitreous body, and aqueous humor. Poor
penetration into inflamed and uninflamed meninges has been reported, despite demonstrated
clinical efficacy in central nervous system (CNS) fungal infections, such as cryptococcal
meningitis and other fungal infections [2].
Metabolism/elimination — No metabolites have been identified. Drug elimination is biphasic,
with a terminal half-life of up to 15 days. The primary route of elimination of amphotericin B is
not known; urine and biliary excretion account for less than 5 percent of the administered dose.
Serum levels are not influenced by hepatic or renal function or by hemodialysis or peritoneal
dialysis.

Dosing — Doses of intravenous (IV) amphotericin B deoxycholate range from 0.1 to 1.5 mg/kg
per day. Doses of 0.1 mg/kg per day of amphotericin B deoxycholate have been investigated as
prophylaxis in high-risk patients [8,9]. However, this practice has largely been replaced by
alternative agents with less toxicity. The usual dose for most invasive mycoses is 0.5 to 1.0
mg/kg per day. Doses exceeding 1.0 mg/kg per day are generally reserved for treatment of
mucormycosis and azole-refractory invasive coccidioidomycosis (such as meningitis). Daily
doses of 1.5 mg/kg per day should not be exceeded. Pathogen- and disease-specific dosing
recommendations have been published by the Infectious Diseases Society of America (IDSA)
for many invasive mycoses. The IDSA clinical practice guidelines can be accessed at the
IDSA's website [10]. The recommended dosing of amphotericin B for each fungal disease and
infection site is discussed in detail separately. (See relevant topic reviews.)

The dose of amphotericin B does not need to be adjusted for renal dysfunction. In the setting of
renal dysfunction, alternate-day therapy of twice the daily dose has been described. However,
with the advent of lipid-based formulations, such a dosing strategy is rarely employed in current
practice.

The dosing of lipid-based formulations of amphotericin B is discussed below. (See 'Dosing'

below.)

Method of administration — Amphotericin B is most commonly administered intravenously,

but direct or local instillation of amphotericin B has been used in several clinical circumstances.

Intravenous — Intravenous infusions are prepared by combining amphotericin B with 5 percent

dextrose in water (D5W) at a final concentration of 0.1 mg/mL. Although the incidence of acute
hypersensitivity reactions from amphotericin B is rare, a test dose of 1 mg has been
recommended. The test dose can be given as an aliquot of the initial infusion, followed by the
remainder of the dose if there is no apparent reaction within 30 minutes. However, tolerance of
the test dose does not exclude other amphotericin B toxicities.

Infusion times are traditionally four to six hours. Amphotericin B has been given over shorter
time periods (eg, 45 to 60 minutes), but infusion-related reactions (such as fever) may be more
frequent, and this method is not recommended [11]. The practice of titrating the daily dose to
the target dose over several days has not been proven to lessen adverse reactions and may
delay optimal therapy.

Intravenous administration of the total daily dose of amphotericin B given as a continuous

infusion over 24 hours has been associated with less nephrotoxicity compared with
administration over four hours [12]. However, the efficacy of this administration schedule for
patients with established infections has not been proven. Furthermore, amphotericin B exhibits
concentration-dependent pharmacodynamics that may be compromised by continuous infusion.
Continuous infusion of amphotericin B is not US Food and Drug Administration (FDA)-approved
and is not recommended.

Administration of premedications to patients receiving amphotericin B should be considered to

prevent infusion-related reactions and nephrotoxicity. (See 'Adverse effects' below.)

Bladder irrigation — Irrigation of the bladder with amphotericin B has been used in the
treatment of candiduria. There have been several non-blinded randomized trials comparing
amphotericin B bladder irrigation with oral fluconazole [13,14]. Although the use of amphotericin
B bladder irrigation resulted in clearing of candiduria in many patients, relapses were routinely
observed after several weeks. Traditionally, 50 mg of amphotericin B has been added to 1000
mL sterile water for irrigation and given as a continuous bladder irrigation daily for a period of
five days. However, this regimen requires the presence of an indwelling bladder catheter, which
itself is a risk factor for candiduria. Shorter treatment courses (one day) or reduced doses (as
low as 5 mg/day) have been recommended by some authors [15,16].

Current published guidelines on the treatment of candiduria do not recommend the routine use
of amphotericin B bladder irrigation, except in exceptional circumstances, such as treatment of
adult nonneutropenic patients with symptomatic cystitis due to fluconazole-resistant species (C.
glabrata, C. krusei) [17]. (See "Candida infections of the bladder and kidneys", section on
'Fluconazole-resistant Candida'.)

Intraperitoneal — Local instillation of amphotericin B has also been reported in the treatment of
fungal peritonitis (alone or in combination with intravenous therapy). This practice is
discouraged because it causes abdominal pain and can contribute to adhesion formation and
loss of the peritoneum as a dialyzing membrane. Patients with fungal peritonitis should be
treated with catheter removal and systemic antifungal therapy [17]. (See "Fungal peritonitis in
peritoneal dialysis", section on 'Treatment'.)

Intrathecal — Intrathecal administration of amphotericin B deoxycholate in the lumbar

subarachnoid space has been used primarily for the treatment of coccidioidal meningitis. Target
doses generally range from 0.1 to 1.5 mg at intervals ranging from daily to weekly [18]; lower
doses (ie, 0.01 mg) can be started and increased slowly until target doses are reached or the
patient shows signs of intolerance [19]. Adverse effects resulting from intrathecal administration
are frequent and include, but are not limited to, nausea and vomiting, headache, back and/or leg
pain, loss of bowel and/or bladder control, and nerve palsies. The development of arachnoiditis
is a serious complication of this form of therapy.

Intrathecal amphotericin B deoxycholate can also be given through a ventricular Ommaya or

Rickham reservoir. The target dose range is the same as for intrathecal administration in the
lumbar subarachnoid space (0.1 to 1.5 mg daily to weekly). Severe vomiting, headache, and
prostration can occur, and bacterial infection of the reservoir has been reported.

Cisternal administration of amphotericin B deoxycholate, either through a reservoir or by direct

injection, is used in some cases of coccidioidal meningitis in order to attain drug levels in the
basilar meninges, where the infection is localized [18]. The dose range is the same as for
intrathecal and intraventricular administration noted above. Severe headache, vomiting,
prostration, and even death have been reported following intracisternal injection of amphotericin
B [18,20]. Only experts at cisternal injections should undertake this form of therapy. (See
"Coccidioidal meningitis", section on 'Antifungal therapy'.)

Intravitreal — Intravitreal and intracameral (into the aqueous humor) injection of amphotericin B
has been used to treat fungal endophthalmitis. (See "Treatment of endogenous endophthalmitis
due to Candida species" and "Treatment of endophthalmitis due to molds".)

Aerosolized/nebulized — Administration of aerosolized (nebulized) amphotericin B (notably

amphotericin B deoxycholate, amphotericin B lipid complex, and liposomal amphotericin B) has
been reported as a potential strategy in the prevention of invasive fungal infections in select
patient populations, such as patients with hematologic malignancies and lung transplant
recipients [21]. (See "Prophylaxis of invasive fungal infections in adults with hematologic
malignancies", section on 'Amphotericin B' and "Fungal infections following lung
transplantation", section on 'Nebulized amphotericin B'.)

Less frequently, aerosolized (nebulized) formulations of amphotericin B have been used as

adjunctive therapy (in combination with systemic antifungal therapy) in the treatment of invasive
fungal infections of the lung that are refractory to standard therapy or in patients intolerant of
standard therapy [22-24].

Adverse effects
Infusion-related reactions — Infusion-related reactions, particularly nausea, vomiting, chills,
and rigors, are common with IV amphotericin B deoxycholate administration, usually occurring
either during infusion (within 15 minutes to 3 hours following initiation) or immediately following
administration of the dose. Treatment of amphotericin B–related nausea and vomiting (as well
as prevention of subsequent reactions) may require the use of a phenothiazine, such as
promethazine (usual adult dose 12.5 to 25 mg every four to six hours by mouth, intramuscularly
[IM], IV, or per rectum [PR]), prochlorperazine (usual adult dose 10 mg IM or IV or 25 mg PR
every four to six hours), or ondansetron.

Phlebitis is a complication that primarily occurs in patients receiving infusions via a small
peripheral vein. The addition of hydrocortisone (usual adult dose 25 mg) or heparin (usual final
concentration 500 to 1000 U/L) to the infusion may lessen infusion-related thrombophlebitis, but
trials to establish their efficacy are lacking and these adjuncts are not recommended [2].

Other ways to minimize amphotericin B–induced thrombophlebitis include:

●Infusion of the drug using a central line

●Use of alternating infusion sites

●Avoidance of final amphotericin B infusion concentrations exceeding 0.1 mg/mL

●Avoidance of infusion times of less than four hours

Drug-induced fever, chills, and headache can also be seen. These symptoms can be minimized
or prevented by premedication with acetaminophen (usual adult dose 650 to 1000 mg by mouth)
and/or diphenhydramine (usual adult dose 25 to 50 mg by mouth or IV). Nonsteroidal anti-
inflammatory agents may also be useful in this setting. In a double-blind, placebo-controlled
trial, ibuprofen administered 30 minutes prior to amphotericin B deoxycholate reduced the rate
of occurrence of chills from 87 percent to 49 percent [25]. Meperidine (usual adult dose 25 to 50
mg IM or IV) may reduce amphotericin B–induced chills and rigors. However, meperidine is not
routinely recommended for premedication due to its potential side effects.

Nephrotoxicity — Intravenous amphotericin B administration may result in nephrotoxicity. With

amphotericin B deoxycholate, a reversible and often transient decline in glomerular filtration rate
(GFR) has been described in 5 to 80 percent of patients. The net effect is an elevation (above
baseline) in the serum creatinine concentration. Severe renal failure due to amphotericin B
deoxycholate alone is less common, but the risks of such reactions increase with diuretic-
induced volume depletion or the concurrent administration of another nephrotoxin (such as an
aminoglycoside, cyclosporine, nephrotoxic cancer chemotherapy, or foscarnet). Amphotericin B
deoxycholate is substantially more nephrotoxic than the lipid-based formulations of amphotericin
B. This is discussed in greater detail separately. (See "Amphotericin B nephrotoxicity".)

Even though adequately controlled human clinical data to support such a practice is limited,
volume expansion with intravenous sodium chloride (a practice commonly known as "sodium
loading") may ameliorate the decline in GFR. In the absence of contraindications, a total of 500
mL of 0.9 percent sodium chloride is typically given immediately prior to the amphotericin B
infusion or divided before and after amphotericin B administration. (See "Amphotericin B
nephrotoxicity", section on 'Salt loading'.)

Electrolyte abnormalities — Hypokalemia, hypomagnesemia, and hyperchloremic acidosis

are reflections of an increase in distal tubular membrane permeability following intravenous
administration of amphotericin B. Many patients require significant amounts of potassium and/or
magnesium supplementation during therapy. Correction of hypokalemia may be difficult in
patients with persistent hypomagnesemia. (See "Clinical manifestations of magnesium
depletion" and "Amphotericin B nephrotoxicity", section on 'Electrolyte disorders'.)

Other reactions — A reversible, normochromic, normocytic anemia occurs in most patients

receiving IV amphotericin B, but the onset may be delayed for as long as 10 weeks after the
initiation of therapy [11]. Other hematologic side effects have also been described, including
severe leukopenia [26]. Transfusions are infrequently required. Elevations in liver function tests
have been associated with amphotericin B administration infrequently.

Severe allergic reactions (including anaphylaxis) are extremely rare but have been reported.

Patient monitoring — Patients receiving amphotericin B intravenously should be monitored

clinically for infusion-related reactions during and following each administration. Measurements
of renal function should be performed daily during initiation of therapy (up to two weeks) and at
least weekly thereafter, if stable. Some experts recommend that amphotericin B administration
be held or a lipid-based formulation substituted if the plasma creatinine concentration exceeds
2.5 mg/dL (265 micromol/L).

Serum electrolytes (particularly potassium and magnesium) should be assessed at baseline and
at least twice weekly throughout therapy. More frequent monitoring is recommended for patients
experiencing hypokalemia and hypomagnesemia as a result of amphotericin B administration.
Complete blood counts should be measured weekly throughout therapy. Monitoring of liver
function tests is usually not necessary unless the patient has clinical signs or symptoms
suggesting hepatic toxicity.
LIPID-BASED AMPHOTERICIN B FORMULATIONS — Lipid-based formulations of
amphotericin B have been introduced in an attempt to reduce the toxicities associated with
amphotericin B deoxycholate [27,28]. Based on animal models and clinical studies, these
formulations reduce the risk of amphotericin B–related nephrotoxicity. However, in a meta-
analysis, the efficacy of amphotericin B deoxycholate and lipid-based formulations was similar
[29]. The nephrotoxicity of amphotericin B is discussed in greater detail separately. (See
"Amphotericin B nephrotoxicity".)

The available lipid-based formulations are amphotericin B lipid complex (ABLC, Abelcet) and
liposomal amphotericin B (AmBisome) [30,31]. Amphotericin B cholesteryl sulfate complex
(amphotericin B colloidal dispersion, ABCD, Amphotec) is no longer available in the United
States.

Safety and efficacy — Few randomized, comparative studies are available that directly
compare the safety and efficacy of these formulations to amphotericin B deoxycholate
intravenously. Controlled studies establishing the treatment efficacy of these agents are
somewhat limited and often involve patients previously treated with amphotericin B
deoxycholate [32].

●In a meta-analysis of randomized trials, the incidence of nephrotoxicity was significantly

lower with liposomal amphotericin B compared with amphotericin B deoxycholate (15
versus 33 percent) [33]. A lower incidence of nephrotoxicity was also observed with
compounded lipid emulsion/amphotericin B deoxycholate combination preparations
compared with amphotericin B deoxycholate (12 versus 31 percent), although we
generally avoid such preparations given incomplete and conflicting data regarding their
safety, efficacy, and stability. (See "Amphotericin B nephrotoxicity", section on 'Lipid-
based formulations' and 'Amphotericin B plus fat emulsions' below.)

●A randomized trial compared ABCD with amphotericin B deoxycholate in 174 patients

with invasive aspergillosis [34]. Response rates were similar in both groups (52 and 51
percent, respectively). ABCD was less likely to cause nephrotoxicity than amphotericin B
deoxycholate (25 versus 49 percent) but was associated with more infusion-related
toxicity (chills in 53 versus 30 percent).

●In a randomized trial comparing the efficacy of liposomal amphotericin B with

amphotericin B deoxycholate for the treatment of severe disseminated histoplasmosis in
81 AIDS patients, the liposomal formulation resulted in a higher rate of clinical success
(88 versus 64 percent) and lower mortality (2 versus 13 percent) [35].
 ●A trial comparing liposomal amphotericin B to amphotericin B deoxycholate for empiric
therapy in patients with persistent fever and neutropenia found no difference in
composite rates of successful treatment and patient outcomes [36]. However,
significantly fewer patients given liposomal amphotericin B had breakthrough fungal
infections, infusion-related fever, chills or rigors, or nephrotoxicity. This was the first trial
to note a reduction in infusion-related reactions associated with the liposomal
formulation of amphotericin B.

●A study comparing ABLC (5 mg/kg per day) and liposomal amphotericin B (3 or 5

mg/kg per day) as empiric therapy in patients with febrile neutropenia persisting after 72
hours of antibacterial treatment reported equivalent clinical outcome but reduced toxicity
in the liposomal amphotericin B group at both doses compared with ABLC [37]. Fever,
chills and rigors, nephrotoxicity, and toxicity-related discontinuation of therapy were all
reduced in the liposomal amphotericin B group, although all of the infusion reactions
except chills and rigors decreased after the first day in the ABLC-treated patients.

●Other open studies have reported successful use of these products in the treatment of
invasive candidiasis, aspergillosis, coccidioidomycosis, cryptococcosis, and
leishmaniasis [30,38].

●A randomized, double-blind trial in patients with invasive candidiasis compared

liposomal amphotericin B 3 mg/kg per day with micafungin and concluded that
micafungin was as effective and better tolerated [39].

Liposomal amphotericin B has a lower incidence of infusion-related reactions than amphotericin

B deoxycholate. However, there is a unique group of infusion reactions that can occur with
liposomal amphotericin B. These include chest pain, dyspnea, hypoxia, abdominal pain,
flushing, and urticaria and generally respond to therapy with diphenhydramine [40]. Infusion-
related intolerance to one formulation may not predict similar reactions to other formulations. As
an example, ABLC administration was uneventful in 34 of 40 patients (85 percent) who had
previous severe reactions to liposomal amphotericin B in one retrospective study [41].
Premedication with acetaminophen, hydrocortisone, and/or diphenhydramine was used in many
patients.

Electrolyte abnormalities, such as hypokalemia, hypomagnesemia, and hyperchloremic

acidosis, may occur following the administration of both lipid-based and deoxycholate
formulations of amphotericin B (see 'Electrolyte abnormalities' above). False elevations of
serum phosphate may occur when samples from patients receiving AmBisome are analyzed
using the PHOSm assay used in Beckman Coulter analyzers, including the Synchron LX20 [42].

Pharmacokinetics — Lipid-based formulations of amphotericin B differ significantly in

pharmacokinetic profile from amphotericin B deoxycholate and from each other [27]. As an
example, ABLC appears to be taken up rapidly by the reticuloendothelial system and
demonstrates high tissue distribution, lower serum concentrations, and a prolonged elimination
half-life when compared with liposomal amphotericin B. By contrast, liposomal amphotericin B
demonstrates a significantly lower volume of distribution, which results in high serum
concentrations, and a shorter elimination half-life than does ABLC or amphotericin B
deoxycholate. Although lipid formulations of amphotericin B reach detectable concentrations in
pleural fluid, these concentrations are often below the minimum inhibitory concentration required
for some yeasts and dimorphic fungi [43].

Dosing — Doses of ABLC are generally 5 mg/kg per day. The dose of liposomal amphotericin
B ranges from 3 to 5 mg/kg per day (depending upon the indication). Studies of liposomal
amphotericin B in children indicate that comparable weight-based dosing can be used in this
population [44].

A randomized trial examining the impact of escalating the doses of liposomal amphotericin B to
10 mg/kg per day for the first two weeks of therapy in patients with invasive mold infections
(mostly invasive aspergillosis) demonstrated increases in treatment-related nephrotoxicity
without increased efficacy compared with standard dosing of 3 mg/kg per day [45].

The recommended dosing of lipid-based formulations of amphotericin B for the treatment of

each fungal disease is discussed in detail separately. (See relevant topic reviews.)

Optimal doses and administration frequency for the prevention of invasive fungal infections are
uncertain. For example, once-weekly high-dose (ie, 10 mg/kg) liposomal amphotericin B has
been studied in the prevention of invasive fungal infections [46,47]. However, others have
reported an increase in the incidence of invasive fungal infections with such dosing [48].
Therefore, it should not be routinely used in such a manner.

Availability and cost — A report of the availability of amphotericin B deoxycholate worldwide

reported that the drug was not licensed or available in 22 of 155 (14.2 percent) and 42 of 155
(27.1 percent) of the countries surveyed, respectively [49]. In this report, the daily cost of
amphotericin B deoxycholate amphotericin B ranged from (USD) <$1 to $171.
The drug acquisition cost of a lipid-based formulation of amphotericin B is significantly higher
than that of amphotericin B deoxycholate and may exceed $200 per day (depending upon the
formulation and contract pricing). Pharmacoeconomic analyses have been performed to assess
whether or not this increase in cost compared with amphotericin B deoxycholate can be offset
by reductions in toxicity and the costs associated with adverse reactions. A multicenter trial of
414 patients with febrile neutropenia showed that hospital costs were significantly higher for the
group receiving liposomal amphotericin B compared with amphotericin B deoxycholate as first-
line empiric therapy ($48,962 versus $43,184) based upon the cost of the drug [50]. However,
when the cost of the study drug was excluded, hospital costs were lower for the liposomal
amphotericin B group, which was probably due to the increased cost of the management of the
nephrotoxicity associated with amphotericin B deoxycholate. The authors concluded that both
drug cost and risks for nephrotoxicity impact the cost-effectiveness of liposomal amphotericin B.

Amphotericin B plus fat emulsions — It has been suggested that mixing amphotericin B
deoxycholate with fat emulsions may reduce renal dysfunction [33] and infusion-related
reactions. However, incomplete and conflicting data exist regarding the safety, efficacy, and
stability of these mixtures [51]. Thus, their use should be considered investigational and is
discouraged.

DRUG INTERACTIONS — The following interactions are of particular concern with the use of
amphotericin B:

●Amphotericin B should not be given concurrently or sequentially with other nephrotoxic

agents, if possible. (See "Amphotericin B nephrotoxicity".)

●Patients receiving digoxin or skeletal muscle relaxants may be predisposed to toxicity

or enhanced effect of these agents following amphotericin B–induced hypokalemia. (See
"Cardiac arrhythmias due to digoxin toxicity".)

●There are data linking amphotericin B and acute pulmonary reactions in patients
receiving concomitant leukocyte transfusions, but these reactions also can occur without
administering leukocyte transfusions. Infusions of amphotericin B should be separated
as far apart as possible from leukocyte transfusions whenever possible [2].
 GASTRIC LAVAGE
TECHNIQUE
 Perform in an appropriately staffed and equipped resuscitation area
 Do not perform in any patient with an impaired level of consciousness unless the
airway is protected by a cuffed endotracheal tube
 Position the patient in the left decubitus position with 20° head down
 Measure the length of tube required to reach the stomach externally before
beginning the procedure
 Pass a large bore 36-40 G lubricated lavage tube extremely gently down the
oesophagus. Stop if any resistance occurs
 Confirm tube position by aspirating gastric contents and auscultating for
insufflated air at the stomach; consider CXR for confirmation of position
 Administer a 200 mL aliquot of warm tap water or normal saline into the stomach
via the funnel and lavage tube
 Drain the administered fluid into a dependent bucket held adjacent to the bed
 Repeat administration and drainage of fluid aliquots until the effluent is clear
 Activated charcoal 50 g may be administered via the tube once lavage complete.

INTRODUCTION — Gastrointestinal decontamination refers to the practice of functionally

removing an ingested toxin from the gastrointestinal (GI) tract in order to decrease its
absorption.

APPROACH TO GASTROINTESTINAL DECONTAMINATION

The decision to perform GI decontamination is based upon the specific poison(s) ingested, the
time from ingestion to presentation, presenting symptoms, and the predicted severity of
poisoning. GI decontamination is most likely to benefit patients who:

●Present for care soon after ingestion (usually within one to two hours)

●Have ingested a poison and amount suspected to cause toxicity

●Do not have clinical factors (eg, somnolence) that make decontamination dangerous

GI decontamination should not be performed if the agent and amount ingested are clearly
nontoxic, if the agent is considered fully absorbed due to delayed presentation, or if the toxin is
not amenable to decontamination.

METHODS OF DECONTAMINATION

Activated charcoal — Activated charcoal (AC) is a highly adsorbent powder made from
superheated, high surface area, porous particles produced by pyrolysis of organic material. Its
extensive surface area is covered with a carbon-based network that also includes functional
groups (eg, carbonyl, hydroxyl) that adsorb chemicals within minutes of contact, preventing
gastrointestinal absorption and subsequent toxicity.

Indications — AC is most likely to benefit patients when administered while toxin remains in the
stomach. Traditionally, this period is thought to be within one hour of poison ingestion, but the
potential for benefit when administered later cannot be excluded.

Contraindications — Contraindications to the administration of a single-dose of activated

charcoal (SDAC) include:

●Depressed mental status without airway protection (risk of aspiration)

The decision to intubate a poisoned patient is often complicated, but it should be made
independently of the decision to give AC. In particular, tracheal intubation should not
be performed for the sole purpose of giving AC.

●Late presentation (ie, no toxin is likely to remain in the stomach)

●Increased risk and severity of aspiration associated with AC use (eg, hydrocarbon
ingestion)

●Need for endoscopy (eg, significant caustic ingestion) – AC is likely to impair visibility
during endoscopy

●Toxins poorly adsorbed by AC (eg, metals including iron and lithium, alkali, mineral
acids, alcohols)

●Presence of intestinal obstruction (absolute contraindication) or concern for decreased

peristalsis (relative contraindication)

Dose
●Children up to one year of age: 10 to 25 g, or 0.5 to 1.0 g/kg

●Children 1 to 12 years of age: 25 to 50 g, or 0.5 to 1.0 g/kg (maximum dose 50 g)

●Adolescents and adults: 25 to 100 g (with 50 g representing the usual adult dose)

Administration — AC is available as a powder that is mixed with water to form a slurry. The
slurry is gritty and poorly palatable, making administration to children particularly difficult.
Flavoring the slurry with juice, chocolate milk, or ice cream may improve compliance but
potentially decreases the adsorptive capacity of AC [5]. AC is also commercially available as a
suspension with thickening agents, such as sorbitol, which may help improve palatability and
additionally act as a cathartic(laxative) [6,7].

Because sorbitol with AC may cause electrolyte imbalances, it is not recommended in children.
However, if sorbitol-containing AC is the only formulation available, it may be given but only for
one dose.

Complications — The overall rate of AC-associated complications reported in the literature is

low [1]. Gastrointestinal side effects including fullness, abdominal pain, nausea, vomiting,
constipation, and diarrhea have been reported, with higher rates occurring if AC is used in
combination with sorbitol [1]. Treatment with sorbitol-containing AC should be avoided in
children unless there is no alternative, and if that is the case it must never be used for more
than one dose.

Evidence of efficacy and adverse effects

Activated charcoal: Adverse effects — Aspiration is the concern most often cited when
clinicians choose not to administer activated charcoal (AC). In their joint position paper on
single-use AC, the American Academy of Clinical Toxicology and the European Association of
Poison Centres and Clinical Toxicologists state that charcoal itself is not responsible for
aspiration, but rather administering it improperly (ie, to a patient with an inadequately protected
airway; in association with lavage; or instilling it directly into the lung via an improperly placed
nasogastric tube) [1]. In addition, when aspiration does occur, poor outcomes cannot clearly be
attributed to the charcoal itself rather than the aspiration of acidic gastric contents.

A retrospective chart review of 4562 overdose patients looking for predictors of aspiration found
that age, male gender, GCS <15, emesis, seizure, tricyclic antidepressant overdose, and an
elapsed time of more than 24 hours between ingestion and presentation were all predictors of
aspiration pneumonia, whereas AC administration itself was not [26]. Another retrospective
chart review of patients who received AC after intubation found that 2 out of 50, or 4 percent,
developed an infiltrate not present prior to intubation [27]; however, the two cases of aspiration
pneumonia could not clearly be attributed to charcoal administration.

Other less important gastrointestinal side effects have been reported. In a volunteer study,
constipation and abdominal fullness occurred at a rate of 46 percent, nausea at 18 percent, and
vomiting at 8 percent [19]. Constipation occurred in 60 percent of subjects in another volunteer
study [13].

Multidose activated charcoal — In some instances, patients may benefit from the repeated
administration of activated charcoal (MDAC). Three distinct mechanisms are thought to account
for such benefit:

●Interruption of enterohepatic recirculation

●Facilitation of transluminal diffusion from the body into the bowel lumen (“gut dialysis”),
followed by excretion

●Reduced absorption of extended or delayed release formulations

Indications — MDAC may be helpful in life-threatening ingestions of the following medications,

but evidence is limited and opinions among toxicologists vary [2]:

●Carbamazepine (see "Carbamazepine poisoning")

●Dapsone

●Phenobarbital

●Quinine

●Theophylline (see "Theophylline poisoning")

●Acetylsalicylic acid (aspirin) (see "Salicylate (aspirin) poisoning in adults")

●Phenytoin (see "Phenytoin poisoning")

Volunteer and animal data suggest that MDAC increases elimination of several toxins (eg,
amitriptyline, digoxin, disopyramide, nadolol, piroxicam), but clinical data are currently
insufficient to support the routine use of MDAC in these exposures [2].

Contraindications — Contraindications to the use of MDAC are similar to those of SDAC, but
also include:

●Presence of intestinal obstruction (absolute) or concern for decreased peristalsis

(relative)

Dose — An optimal dosing regimen for MDAC has not been established. In general, after the
initial dose, AC should be administered at a rate of at least 12.5 g/hour, or the equivalent, given
as divided doses. Examples of acceptable regimens include 50 g administered every four hours,
or 25 g every two hours. A volunteer study found no difference in effectiveness of larger doses
spread out over time compared to smaller, more frequent doses [28].

Administration — Administration is similar to that of AC, but the concurrent use of a cathartic,
such as sorbitol is not recommended. This is of particular importance with young children, in
whom the development of diarrhea may lead to dangerous fluid shifts and electrolyte imbalance
[2].

Complications — In addition to the complications associated with single-dose AC, constipation

and bowel obstruction have been reported.

Evidence of efficacy and adverse effects — Volunteer trials of MDAC have found significant
decreases in the elimination half life of several drugs, including phenytoin, nortriptyline,
aminophylline, phenobarbital, carbamazepine, phenylbutazone, digoxin, and dapsone
[13,15,28-32]. However, a randomized controlled trial of 4629 poisoned patients comparing the
routine use of MDAC to single-dose AC or no intervention found no difference in rates of
intubation, toxin-specific clinical effects, or mortality among groups [33]. The trial was limited by
the prolonged time to treatment for many patients and lower than expected mortality in the
control group.

Additional concerns specific to the repeated administration of AC include the development of an

ileus or obstruction. There are published reports of patients developing a bowel obstruction
requiring surgical intervention and even bowel perforation following repeated administration of
AC [35-37]. However, the large randomized trial described above did not report any such
complications [33].

Whole bowel irrigation — Whole bowel irrigation (WBI) refers to the administration of
osmotically balanced polyethylene glycol electrolyte solution (PEG-ES) to induce liquid stool
and mechanically flush pills, tablets, or drug packets from the GI tract.

Indications — WBI is not routinely recommended, but it may be helpful in the following settings
[38]:

●Potentially toxic ingestions of sustained-release or enteric coated pill formulations

●Significant ingestions of toxins not adsorbed by activated charcoal (eg, iron tablets,
lead-containing foreign bodies)
 ●Ingestion of illicit drug packets (see "Internal concealment of drugs of abuse (body
packing)")

Contraindications — Contraindications to WBI include:

●Ileus, bowel obstruction, or intestinal perforation

●Clinically significant GI hemorrhage

●Hemodynamic instability (concern for sequestration of bowel and worsening of shock)

●Intractable emesis

Dose — There are no dose-response studies for WBI, but a consensus recommendation
regarding dosing is as follows [3]:

●Children 9 months to 6 years: 500 mL/hr

●Children 6 to 12 years: 1000 mL/hr

●Adolescents and adults: 1500 to 2000 mL/hr

WBI is continued until the rectal effluent is clear. Radiographic studies may be useful in some
circumstances (eg, iron ingestion, body packing) to confirm the absence of residual toxin.

Administration — Most patients tolerate poorly the large volume of fluid that must be taken
orally to effectively perform WBI. In many cases, nasogastric tube placement is necessary for
PEG-ES administration.

Complications — There is a paucity of published data regarding complications associated with

WBI. GI complaints including nausea, vomiting, cramping, and bloating are relatively common
[3,38]. Patients with vomiting and an unprotected airway are at risk of aspiration, but this has not
been reported as a direct result of WBI.

Evidence of efficacy and adverse effects — Whole bowel irrigation (WBI) may be useful for
patients who have ingested extended-release or enteric-coated tablets, particularly when
patients present more than two hours after ingestion and therefore are not likely to benefit from
charcoal administration. Volunteer data suggest that WBI is effective in some cases, but may
interfere with activated charcoal (AC) when administered concurrently [14].

Gastric lavage — Gastric lavage (GL) refers to the passage of a large bore orogastric tube
followed by repetitive instillation and aspiration of small aliquots of fluid in an attempt to aspirate
pill fragments or other toxins from within the stomach. Referred to as “stomach pumping” by the
lay public, this formerly widespread modality has been largely abandoned due to unclear benefit
(particularly when compared with other readily available and less invasive techniques) and the
risk of serious complications.

Indications — The American Association of Poison Centers (AAPC) and the European
Association of Poisons Centres and Clinical Toxicologists (EAPCCT) have issued a joint
statement that gastric lavage should not be employed routinely, if ever, in the management of
poisoned patients [42]. However, there are rare cases (eg, recent and potentially lethal
ingestion) where the procedure may be considered after carefully weighing the well-documented
risks against the unclear benefits.

Contraindications — GL is contraindicated in the following cases:

●Unprotected airway

●Caustic ingestion (due to risk of exacerbating any esophageal or gastric injury)

●Hydrocarbon ingestion (due to high aspiration risk)

●Patients at risk of GI hemorrhage or perforation (recent surgery, underlying anatomic

abnormality or pathology, coagulopathy)

Complications — Complications associated with GL are significant and include the following:
aspiration pneumonia, esophageal or gastric perforation, laryngospasm, hypoxia, dysrhythmia,
and fluid or electrolyte imbalance [42]. GL may also propel toxins that were to be removed past
the pylorus, potentially facilitating systemic absorption and decreasing the effectiveness of
activated charcoal [43].

Evidence of efficacy and adverse effects — Gastric lavage (GL), once a mainstay of
emergency decontamination of poisoned patients, has been largely abandoned due to the
effectiveness of activated charcoal (AC).

When compared directly to AC or when used in conjunction with AC, GL generally does not
provide added benefit according to the results of volunteer and clinical trials.

These results notwithstanding, there is evidence that a small subset of patients presenting early
(within one hour of ingestion) may benefit from GL. In a randomized controlled trial comparing
gastric emptying techniques (syrup of ipecac and GL) with AC, no significant differences were
found between groups with respect to clinical deterioration or admission. However, subgroup
analysis revealed that patients presenting within one hour of ingestion and treated with GL had
a higher rate of clinical improvement than those receiving AC [47]. A second trial using the
same protocol produced similar results, but the group treated with gastric emptying included
more severe overdoses and when the authors controlled for this difference GL appeared to be
of less benefit [48].

Gastric lavage carries significant risks, which, given its questionable clinical benefit, usually
outweigh arguments in favor of its use. In a randomized trial, patients treated with GL had
higher rates of aspiration (9 versus 0 percent) and intubation compared to controls receiving AC
[20]. These findings are consistent with numerous published case reports [42]. Esophageal and
gastric perforation represents another, albeit less common, risk of GL [42,47].

Endoscopy/surgery — Endoscopic or surgical removal of poisons may be indicated when a

life-threatening toxin has been ingested and cannot be effectively removed by less invasive
means. Examples include lethal amounts of heavy metals or pharmacobezoars refractory to
whole bowel irrigation. Surgical removal is indicated in patients exhibiting toxicity following
ingestion of large cocaine packets (“body packers”). In most cases, endoscopy is not
recommended for the removal of illicit drug packets due to the risk of packet rupture during
extraction attempts [49]. (See "Internal concealment of drugs of abuse (body packing)".)

Outdated treatments — The following modalities of GI decontamination have been used in the
past but are no longer routinely recommended:

Syrup of Ipecac — Previously a mainstay of prehospital and emergency department

management of toxic ingestions, Syrup of Ipecac (SoI)-facilitated gastric emptying is no longer
recommended by the American Academy of Clinical Toxicology (AACT), the European
Association of Poisons Centres and Clinical Toxicologists (EAPCCT), or the American
Association of Pediatrics (AAP) [50,51]. A review of volunteer and clinical studies suggests that
SoI is less effective at decreasing systemic absorption than activated charcoal (AC) [12,52],
yields unpredictable and inconsistent results [44,53,54], and has an increased risk of adverse
effects including delayed administration of more effective decontamination measures [24] and
higher rates of aspiration [55].

Cathartics — Cathartics (eg, magnesium citrate, magnesium sulfate, sorbitol, mannitol) are
intended to decrease poison absorption by enhancing rectal evacuation of toxins or the poison-
AC complex. The AACT and EAPCCT advise against the use of cathartics as single agent
therapy. The combination of a cathartic and AC (eg, sorbitol and AC) should be used sparingly
in adults, if at all, and should not be used in children. If the only available formulation of AC
contains sorbitol, it may be necessary to give it to a child, but treatment must be limited to a
single dose in such cases [56]. (See 'Activated charcoal' above.)

Adverse effects associated with cathartic use include increased abdominal pain, nausea,
vomiting, excessive diarrhea, dehydration, and electrolyte abnormalities.

Dilution — Dilution was historically recommended following the ingestion of acidic or alkaline
corrosives to decrease the concentration and, thus, the tissue damage from the ingestion. This
approach is problematic and we recommend that it not be performed
 Burn management

INTRODUCTION — In spite of major advances in therapeutic strategies for the management of

patients with severe burns, including improved resuscitation, enhanced wound coverage,
infection control, and management of inhalation injuries, the consequences of a severe burn are
profound and result in complex metabolic changes that can adversely affect every organ system
[1-3]. Management of a patient with a severe burn injury is a long-term process that addresses
the local burn wound as well as the systemic, psychologic, and social consequences of the
injury.

In situations where resources are limited (mass casualty, natural disaster), triage, stabilization,
and transfer provide optimal outcomes. Outcomes for severely burned patients, particularly
children or older individuals, who cannot be transferred for burn care are poor.

An overview of the initial care and subsequent management of patients with severe (major) burn
injuries is presented here. The initial care and management of minor burns are discussed
separately. (See "Treatment of minor thermal burns".)

The management of associated traumatic injuries and other mechanisms of injury is reviewed
separately. (See "Initial management of trauma in adults" and "Overview of inpatient
management of the adult trauma patient", section on 'Consider other potential injuries' and
"Inhalation injury from heat, smoke, or chemical irritants" and "Topical chemical burns: Initial
assessment and management" and "Environmental and weapon-related electrical injuries".)

SEVERE BURN INJURY — A severe burn is one that is complicated by major trauma or
inhalation injury, a chemical burn (table 1), high-voltage electrical burn, and, in general for
adults, any burn encompassing >20 percent of the total body surface area (TBSA), excluding
superficial burns (epidermal; first-degree burns) (table 2). For older adults and young children, a
burn encompassing less than 20 percent of the TBSA may be considered severe.

EMERGENCY BURN CARE — Emergency care of the burn patient and triage criteria for
referral to a burn center are discussed in detail separately. (See "Emergency care of moderate
and severe thermal burns in adults" and "Emergency care of moderate and severe thermal
burns in children" and "Overview of inpatient management of the adult trauma patient", section
on 'Introduction'.)

Emergency care of the severely burned patient can be provided in an emergency department or
in an intensive care unit (ICU), depending upon the protocol of the institution. In both scenarios,
emergency care follows the principles of the Advanced Trauma Life Support guidelines for
assessment and stabilization of airway, breathing, circulation, disability, exposure, and
environment control [40]. Primary and secondary assessments for the severity (partial or full
thickness) and extent (total body surface area [TBSA]) of the burn, and an evaluation for
associated life-threatening injuries, are promptly performed. Ambient room temperature should
be increased to prevent hypothermia and reduce the patient's stress response [2,41].

Triage and transfer — If the patient does not present initially to a designated burn center,
patients with any of the criteria given in the table (table 3)

should be transferred as soon as stabilized [1,42]. If transportation is not feasible, or if no burn

center is available, the patient should be admitted to an intensive care unit for interim
management, until transfer can be arranged.

Mass casualty events — Approximately 25 to 30 percent of those injured in a casualty event

(mass disaster, terrorist) will sustain a moderate-to-severe burn injury [21]. Generally, a limited
number of individuals are impacted in typical civilian accidents that result in burn injury (eg,
house fires). By contrast, the magnitude and impact of burns associated with a mass disaster
can be devastating, affecting many individuals simultaneously and often exceeding the capacity
(beds, surgeons, nurses, operating rooms, equipment, supplies) of available local burn centers
to provide optimal burn care [17-24,43,44]. With a disaster plan in place, a well-equipped burn
center can typically handle a surge capacity that is up to 50 percent above the normal maximum
capacity.
Guidelines for triage of burn patients in mass disasters recommend that adults and children with
>20 percent TBSA burn should be transferred to a burn center [13,17,21]. The care of severely
burned patients is generally best provided in dedicated burn centers that can provide surgical
grafting support, ICU care, and rehabilitative care. In the United States, the American Burn
Association (ABA) can assist with planning transfer to regional burn facilities [21,45].

Burns less than 20 percent TBSA can be managed at hospitals without a dedicated burn care
center, including those who would otherwise have met the standard criteria for burn center
referral (eg, specific anatomic sites, age, comorbid conditions) (table 3).

In addition to percentage TBSA burned, in mass disasters, the presence of inhalation injury,
other severe injuries, and extremes in age should be incorporated into triage and patient
dispositions (figure 1) [19,21]. (See 'Palliative care' below.)

With mass disasters, triage may require the use of a medical facility leapfrogging process. Burn
victims may be first triaged to the closest hospital. After initial resuscitation, those meeting
criteria should be transferred to a burn center. Transfer should occur between 24 and 72 hours
after initial fluid resuscitation [19]. It might also be necessary to redirect or redistribute patients if
burn centers reach surge capacity [25].

Combined burn/trauma — For combined burn/trauma patients, an understanding of the

independent temporal changes of each injury (eg, penetrating, blunt, burn) (figure 2) and how
they interact with each other allows the clinician to devise the optimal management strategy.
The highest priority (after airway, breathing, and intravenous access) in the setting of combined
burn/trauma is the assessment and treatment of immediately life-threatening injuries, whether
penetrating or blunt, then the management of the burn [46]. The key to the initial management
of a combined burn/trauma patient is that the presence of burn wounds should not interfere with
the basic resuscitation and stabilization. As an example, the presence of burned skin should not
preclude attempts at intravenous access, control of hemorrhaging sites, coverage of open
fractures and wounds, and fixation of closed fractures. (See "Initial management of trauma in
adults" and "Emergency care of moderate and severe thermal burns in adults" and "Emergency
care of moderate and severe thermal burns in children".)

Criteria for intensive care — Burn patients who require mechanical ventilation (eg, inhalation
injury, massive fluid resuscitation), require cardiac or other hemodynamic monitoring to guide
fluid therapy or monitoring for other reasons, or have risk factors for multisystem organ failure
should be managed in an intensive care setting. (See "Predictive scoring systems in the
intensive care unit".)
Palliative care — Although mortality rates related to burn injury have steadily declined, some
patients with severe burns have such a poor chance for survival that they (or their health care
proxy) may elect to withhold treatment. (See "Advance care planning and advance directives"
and "Ethical issues in palliative care" and "Ethical considerations in effective pain management
at the end of life".)

Patients with very large burns and inhalation injury, particularly in the setting of other significant
medical comorbidities, are at increased risk for death. A patient with a Baux score (age + TBSA,
which correlates with mortality) or a revised Baux score (age + TBSA + 17 [presence of
inhalation injury]) [47] of more than 140 to 150 (little to no hope for survival) may elect to forego
any specific burn treatment [48]. Patients can also present with "Do not resuscitate/Do not
intubate" or other advanced directives that are upheld by their surrogates that prohibit heroic
efforts at resuscitation or other life-prolonging measures. In these patients, pain and anxiety are
controlled. Patients can receive such palliative care without being transferred to a burn center,
but many centers prefer to send these patients under the premise that transfer to a specialized
center may provide hope for any chance of survival.

In regions where dedicated burn centers are not available (or have been destroyed), the survival
rate for ≥50 percent TBSA burns is low [21]. The ABA categories and expected outcomes for
burn patients involved in a mass casualty event based upon age and percentage TBSA burn are
given in the table (figure 1) [21]. Although difficult, placing a patient in the expectant category
(ie, anticipated death) helps to save the greatest numbers of lives. However, doing so does not
mean abandoning the patient. It is important to ensure that personnel are present to provide
liberal use of medications to control pain and anxiety, as needed.