American Journal of Emergency Medicine (2009) 27, 11171124

www.elsevier.com/locate/ajem

Review

Carbamate poisoning: treatment recommendations in the

setting of a mass casualties event
Yossi Rosman MD a,, Igor Makarovsky MSc a , Yedidia Bentur MD b , Shai Shrot MD a ,
Tsvika Dushnistky MD a , Amir Krivoy MD a
a

CBRN Medicine Branch, Medical Corps, Israel Defense Forces, Tel-Hashomer, Israel
Israel Poison Information Center, Rambam Health Care Campus, The Rappaport Faculty of Medicine,
Technion-Israel Institute of Technology, Haifa, Israel
b

Received 24 August 2008; revised 26 January 2009; accepted 27 January 2009

Abstract The threat of using chemical compounds by terrorists as weapons of mass casualties has been a
rising concern in recent years. Carbamates, a group of reversible acetylcholinesterase inhibitors, could
be potentially involved in such toxic mass casualty events because they can cause cholinergic crisis that
could lead to fatality, similar to that of organophosphate poisoning. The medical management of
carbamate poisoning consists of supportive measures and specific antidotal treatment, that is, the
anticholinergic compound atropine. The administration of oximes, acetylcholinesterase reactivators, in
carbamate poisoning is controversial because of the potential toxicity of oximes in conjunction with
carbamate especially in the case of the carbamatecarbaryl poisoning. However, recent data suggest
that this concern may be unwarranted. In this article, we review the current data regarding the pros and
cons of using oximes against carbamates poisoning in a mass casualties event scenario. We also propose
a new decision-making algorithm for the medical first responders in a mass casualties event suspected to
be caused by a cholinergic substance (organophosphate or carbamate). According to this algorithm,
treatment should consist of atropine and oxime regardless of the exact toxic compound involved. We
speculate that in a mass casualties event, the benefits of using oximes outweigh the low level of
potential risk.
2009 Elsevier Inc. All rights reserved.

1. Introduction
In recent years, the potential of using chemical compounds by terrorists as a weapon of mass casualties has been
a rising concern worldwide (eg, the Sarin gas attack in the
Tokyo subway in 1995) [1,2]. Moreover, the use of chemical
compounds in concert with conventional explosives would
further increase the risk for casualties. This threat has led to
Corresponding author. 4b Alonim St. Givat-Shmuel, Israel 54044.
Tel.: +972 3 7373109; fax: +972 3 7376111.
E-mail address: rosmanyossi@gmail.com (Y. Rosman).
0735-6757/$ see front matter 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.ajem.2009.01.035

an increase in the preparedness and awareness of health and

security agencies around the world and has focused the
efforts of emergency medical teams in managing these
complex events in an efficient manner. The first responder in
such an event is faced with several challenges that are
different from those of a mass casualties event inflicted by
conventional explosives or of a military mass casualty event.
One of these challenges is the recognition of toxicologic
involvement in a mass casualty event, manifesting with
various signs and symptoms not related to a conventional
event [3]. Another challenge is the identification of the
clinical toxidrome, on scene, from which the treatment

1118

Y. Rosman et al.

protocol is derived. The cholinergic toxidrome has been

given much attention in recent years as representing
organophosphate (OP) poisoning, hence leading to the
standard treatment protocol with atropine and oximes [4].
Carbamate insecticide poisoning manifests as a cholinergic
crisis clinically indistinguishable from OP poisoning.
However, concerns have been raised about the safety of
using oximes in the setting of carbamate insecticide
poisoning. Table 1 summarizes the main carbamate insecticides, classified according to their relative toxicity. In this
review, we will discuss the nature of carbamate insecticide
poisoning and the controversies regarding the treatment
protocolspecifically the use of oximes. Data were
collected through extensive search on PUBMED and other
Web-based toxicology resources, using the keywords
carbamates, oximes, and the names of specific carbamates. It has to be mentioned that human and animal data
were sparse and included only a few of the carbamates, of
them, pyridostigmine and physiostigmine, which are both
unlikely to be used in a terrorist attack. We have also
developed a simple algorithm to be used by medical first
responders on scene for decision making and medical
management of such an event. Although this article focuses
on managing mass casualties event involving carbamate
poisoning, this information might have bearing on agricultural/industrial mishaps involving a few patients and suicidal
ingestions involving a single patient as well. The recommendations presented in this article are general and do not
address a specific oxime. The discussion is on the principle
of oximes' augmentation in management of carbamates'
poisoning in a mass casualties event.

2. Carbamates' mechanism of toxicity

Similar to OP agents that phosphorylate the acetylcholinesterase (AChE) enzyme, carbamates carbamylate this

Table 1

enzyme. The hydroxyl moiety of the serine that resides

inside the catalytic pocket of the enzyme usually nucleophilically attacks a molecule of acethylcholine and hydrolyzes
it. The enzyme is then restored via a subsequent nucleophilic
attack by a neighboring aspartate. Organophosphates and
carbamates mimic the action of acetylcholine (ACh) and
enter the enzyme instead of ACh. The hydroxyl attacks the
phosphoryl or the carbonyl moiety of the OP or the
carbamate, respectively. Although the normal acetylated
serine is rapidly hydrolyzed and the enzyme is ready for
another reaction, the carbamylated or the phosphorylated
enzyme cannot readily undergo hydrolysis and is not
reactivated because of steric hindrance or some other
electronic factors.
The carbamate-AChE bond is much less stable than the
one formed after a reaction with an OP agent, and
spontaneous decarbamylation (via slow hydrolysis) occurs
after a while, resulting in the reactivation of AChE. In
addition, the enzyme-inhibitor complex does not undergo
the process of aging as occurs with OP agents. Nonetheless,
the transient inhibition of AChE by a carbamate enables
ACh to accumulate at the muscarinic and nicotinic synapses
in the sympathetic and parasympathetic systems and at
neuromuscular junctions of both striated and smooth
muscles, which will eventually result in a clinical cholinergic
crisis [5].

3. Clinical manifestations of
carbamate poisoning
The onset of clinical effects subsequent to carbamate
exposure depends on the dose, route of exposure, type of
carbamate involved, use of protective gear, and the
premorbid state of the victim. Ingestion or inhalation of
carbamates results in a more rapid onset of clinical effects as
compared with dermal exposure. Clinical manifestations

The main carbamate insecticides in use and their relative toxic potency (estimated human values) [5]

High toxicity (LD50 b50 mg/kg)

Moderate toxicity (LD50 = 50-200 mg/kg)

Low toxicity (LD50 N200 mg/kg)

Aldicarb (Temik)
Aldoxycarb (Standak)
Aminocarb (Metacil)
Bendiocarb (Ficam)
Carbofuran (Furadan)
Dimetan (Dimetan)
Dimetilan (Snip)
Dioxacarb (Eleocron, Famid)
Formetanate (Carzol)
Methiocarb (Mesurol)
Methomyl (Lannate, Nudrin)
Oxamyl (Vydate)
Propoxur (Baygon)

Bufencarb (Bux)
Carbosulfan
Pirimicarb (Pirimor)
Promecarb
Thiodicarb (Larvin)
Trimethacarb (Broot)

BPMC (Fenocarb)
Carbaryl (Sevin)
Isoprocarb (Etrofolan)
MPMC (Meobal)
MTMC (Metacrate, Tsumacide)
XMC (Cosban)

Management of carbamate poisoning in a mass casualities event

Table 2 Clinical manifestations of carbamate vs OP
poisoning

Muscarinic
signs

Nicotinic signs

Central nervous
system signs

Carbamate
intoxication

OP intoxication

Miosis, salivation,
sweating, lacrimation,
rhinorrhea, abdominal
cramping, vomiting,
diarrhea, urinary
incontinence,
bronchospasm,
dyspnea, hypoxemia,
bradycardia, bronchial
secretions, pulmonary
edema and
respiratory failure
Less frequent;
muscular twitching,
fasciculations, muscle
weakens including the
respiratory muscles,
paralysis, tachycardia,
hypertension
Rare

As in carbamate
poisoning

Laboratory
findings

AChE inhibition
noticed hours after
intoxication

Delayed
symptoms

Rare

Pediatric
population

Miosis less
prominent; frequent
nicotinic and
CNS signs

Common; as in
carbamate
poisoning

1119

in neurobehavioral testing rarely appear in carbamate

poisoning, although it was documented in a few case reports
[8-12]. The differences between OP and carbamate intoxication are summarized in Table 2.

4. Managing carbamate poisoning

The basic principles of managing carbamate poisoning,
on scene and in hospital, are based on removal from the
source of exposure, supportive measures, decontamination,
seizure control, and antidotes administration.
Supportive measures include oxygenation, airway control, breathing support, intravenous fluids, and vasopressors,
as required. Seizures are usually treated with benzodiazepines (eg, diazepam, midazolam).

5. Antidotes of carbamate intoxication

5.1. Atropine
Common;
agitation,
confusion,
seizures, coma,
respiratory arrest
AChE inhibition
may be prominent
weeks after
intoxication
Intermediate
syndrome, delayed
neuropathy or
neuropsychiatric
effects are common

result from accumulation of ACh in the synapses and

overstimulation of muscarinic and nicotinic receptors
throughout target organs.
Table 2 summarizes the main clinical manifestations of
the cholinergic toxidrome [5]. Unlike OP poisoning,
carbamate poisoning usually begins to resolve within several
hours and disappears within 24 hours, generally without any
permanent sequel. However, deterioration, chronic damage,
delayed neurologic toxicity, and even death may ensue [6].
Carbamates generally do not cross the blood-brain barrier as
easily as OPs; thus, brain effects occur less frequently and
generally with lower severity than with OPs [6,7]. Unlike OP
intoxication, polyneuropathy, subacute neurotoxicity,
delayed neuropathy, intermediate syndrome, or a deficiency

Atropine acts as a competitive muscarinic anticholinergic

agent, thus counteracting the muscarinic cholinergic overstimulation caused by carbamates. There is a consensus on
the importance of atropine therapy in carbamate poisoning.
As shown in Table 3, atropine administration without oximes
results in a relatively high protective ratio (ie, the ratio
between LD50 [lethal dose 50%] with no treatment and LD50
with treatment) of 5.14 to 9.3 in various animal models
poisoned with different carbamates. It is noteworthy that
atropine (the sulfate formation) poorly penetrates the brain in
therapeutic doses. Moreover, it does not affect nicotinic
receptors and acts with low affinity on cholinergic receptors
in the brain. Thus, atropine therapy will not alleviate central
nervous system (CNS) cholinergic signs directly. Nevertheless, atropine may indirectly minimize CNS toxicity by
lowering the associated hypoxia as a result of bronchial
secretions drying.
The standard protocol of atropine therapy in carbamate
toxicity is the same as with OP intoxication (initial dose for
adult, 1-5 mg; pediatric dose, 0.05 mg/kg) [13]. However,
given the reversibility of carbamate binding to AChE (unlike
OP poisoning), the duration of atropine therapy in carbamate
poisoning is expected to be shorter and involves smaller total
amounts of atropine [5].

6. Oxime therapy in carbamate poisoning

Oximes are a group of drugs, developed about 60 years
ago, that have the capacity to reactivate inhibited AChE. The
main oximes that are clinically used include 2-PAM
(pyridine-2-aldoxime methochloride, pralidoxime), P2S

Summary of animal studies applying treatment protocols for carbamates poisoning [23-28]

Type of
carbamate

Author

Carbaryl

Sanderson et al (1961) Rat

Oxime
Natoff et al (1972)
Rat
Oxime
Rat
Oxime
Sterri et al (1979)
Mice
Oxime
Harris et al (1988)
Guinea pigs Oxime
Lieske et al (1992)
Mice
Oxime
Mice
Oxime
Natoff et al (1972)
Rat
Combined oxime and atropine

Aldicarb

Physostigmine

Animal
model

Treatment

Route of Full treatment protocol

exposure

PR a/outcome

PO
IP/SC
IP/SC
PO/SC
IP
PO
PO
IP/SC

Increased mortality
0.25
0.43
0.5
0.6
0.14
0.48
1.8

Natoff et al (1972)

Rat

Harris et al (1988)

Guinea pigs Combined oxime and atropine IP

Lieske et al (1992)

Mice

Natoff et al (1972)
Harris et al (1988)
Lieske et al (1992)
Natoff et al (1972)
Natoff et al (1972)
Sterri et al (1979)
Natoff et al (1972)

Rat
Atropine
Guinea pigs Atropine
Mice
Atropine
Rat
Oxime
Rat
Oxime
Mice
Oxime
Rat
Combined oxime and atropine

Natoff et al (1972)

Rat

Combined oxime and atropine IP/SC

Natoff et al (1972)
Natoff et al (1972)
Sterri et al (1979)
Natoff et al (1972)

Rat
Rat
Rat
Mice
Rat

Atropine
Oxime
Oxime
Oxime
Combined oxime and atropine

Natoff et al (1972)

Rat

Combined oxime and atropine IP/SC

Harris et al (1988)

Guinea pigs Combined oxime and atropine IP

Combined oxime and atropine IP/SC

Combined oxime and atropine PO

Rat
Atropine
Guinea pigs Atropine
Mice
Oxime
Rat
Oxime

Protective ratio (ie, the ratio between LD50 with no treatment and LD50 with treatment).

IP/SC
IP
PO
IP/SC
IP/SC
PO/SC
IP/SC

IP/SC
IP/SC
IP/SC
PO/SC
IP/SC

IP/SC
IP
PO/SC
PO

2-PAM, 100 mg/kg IP, immediately after poisoning

Obidoxime, 90 mg/kg SC, at the onset of intoxication signs
P2S, 50 mg/kg SC, at the onset of intoxication signs
Obidoxime, 80 mg/kg IP, 15 min before poisoning
2-PAM, 22 mg/kg IP, 1 min after intoxication
2-PAM, 25.1 mg/kg IP 5 min after poisoning
TMB-4, 12.6 mg/kg IP, 5 min after poisoning
Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
P2S, 50 mg/kg, and atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
2-PAM, 22 mg/kg, and atropine, 8 mg/kg IV, 1 min
after intoxication
2-PAM, 25.1 mg/kg, and atropine, 11.2 mg/kg IV, 5 min
after poisoning
Atropine 17.4 mg/kg SC, at the onset of intoxication signs
Atropine, 8 mg/kg IV, 1 min after intoxication
Atropine, 11.2 mg/kg IV, 5 min after poisoning
Obidoxime, 90 mg/kg SC, at the onset of intoxication signs
P2S, 50 mg/kg SC, at the onset of intoxication signs
Obidoxime, 80 mg/kg IP, 15 min before poisoning
Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
P2S, 50 mg/kg, and, atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
Atropine, 17.4 mg/kg SC, at the onset of intoxication signs
Obidoxime, 90 mg/kg SC, at the onset of intoxication signs
P2S, 50 mg/kg SC, at the onset of intoxication signs
Obidoxime, 80 mg/kg IP, 15 min before poisoning
Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
P2S, 50 mg/kg, and atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
2-PAM, 22 mg/kg IP, and atropine, 8 mg/kg IV, 1 min
after intoxication
Atropine, at the onset of intoxication signs
Atropine, 8 mg/kg IV, 1 min after intoxication
Obidoxime, 80 mg/kg IP, 15 min before poisoning
2-PAM, 100 mg/kg IP, immediately after poisoning

6.07
3.5
0.98
6.48
6.6
N1.4
2.34
1.54
1.78
6.4
N6.85
5.14
3.37
3
2
N18.86
17.47
8.8
9.3
7.2
3.12
Decreased mortality

Y. Rosman et al.

Natoff et al
Harris et al (1988)
Pyridostigmine Sterri et al (1979)
Isolan
Sanderson et al (1961)
a

1120

Table 3

Management of carbamate poisoning in a mass casualities event

(the methanesulfonate salt of pralidoxime, which is available
in the UK), HI-6 (1-[[[(4-aminocarbonyl)pyridinio]methoxy]
methyl]-2-[(hydroxyimino)methyl]pyridinium dichloride),
and obidoxime 1,1-[oxybis(methylene)]bis{4-[(E)-(hydroxyimino)methyl] pyridinium} (obidoxime; Toxogonin).

6.1. Mechanism of action

The mechanism of action of oximes is related to
reactivation of carbamylated or phosphorylated AChE. The
positively charged aromatic nitrogen of the oxime is attracted
to the anionic site of AChE, allowing the reactive oxime
portion of the molecule to position itself over the
carbamylated or the phosphorylated active site of the
enzyme. Subsequently, a nucleophilic attack of the oxamate
anion takes place on the phosphorylated or the carbamylated
enzyme. As a result, a new adduct is formed (a coupling
product between the phosphorylic/carbamic residue and the
oxime); thus, the enzyme is free to hydrolyze a new ACh
molecule (Fig. 1) [14].

7. Clinical use of oximes in

carbamate poisoning
The administration of AChE reactivators (ie, oximes) in
carbamate intoxication has received considerable attention in
the literature and is considered controversial in several
clinical guidelines [5,13,15-18]. Farago [19] questioned the
role of 2-PAM in a case report of a fatal suicidal ingestion of
carbaryl (1-naphthyl-N-methyl-carbamate). Although it was
implicated that 2-PAM contributed to this patients' toxicity, it
is important to note that according to that description, the
patient was inadequately atropinized. Multiple conflicting
case reports have been documented thereafter [20-22].

7.1. Animal data

Table 3 summarizes the various animal studies done in
the previous years [23-28]. As shown in Table 3, all the
studies showed that in carbaryl poisoning, treatment with an
oxime resulted in a protective ratio of less than 1 (ie, worse
than no treatment at all). The combination of atropine and
oxime, or treatment with atropine alone, resulted in a good
protection ratio. Administration of oximes in animals

Fig. 1

1121

poisoned with carbamates other than carbaryl resulted in

a good protection ratio and an even better protection ratio
when the oxime was combined with atropine. It was
concluded from these studies that in the case of carbamate
intoxication, the best treatment is atropine, and the addition
of oximes may be synergistic or at least ineffective, with
the exception of carbaryl poisoning, in which oxime treatment was concluded to be contraindicated. These studies
were criticized because of usage of inappropriate antidotal
dosing and treatment protocol that are not correlated to
clinical practice.
The alleged detrimental effect of oxime therapy in
carbamate poisoning, especially carbaryl, has sprouted several
theories that might explain this finding. Sanderson et al [24]
suggested that the combination of atropine and oxime might
affect the absorption rate of the carbamate from the gut after
oral administration, partly by reducing pyloric peristalsis,
resulting in a better and faster systemic absorption of the
poison. However, this theory does not explain the increased
toxicity observed in animals poisoned via the parenteral route
[25,26]. Sterri et al [27] suggested that formation of a
carbamylated oxime is the cause for the increased toxicity.
This compound might be a more potent AChE inhibitor than
carbaryl itself. However, Lieske et al [28] and Clark et al [29]
could not isolate the so-called carbamylated oxime and thus
concluded it was not responsible for the enhanced toxicity of
oxime-treated carbaryl poisoning. They proposed a third
theory in which several oximes may act as allosteric
modulators of AChE in carbaryl poisoning. Harris et al [25]
proposed that 2-PAM might reduce the rate of spontaneous
decarbamylation of the inhibited AChE in carbaryl intoxication. Dawson et al [30-32] suggested the opposite, that is, 2PAM increases the rate of carbamylation of AChE. In both
hypotheses, the outcome is similaran increased fraction of
inhibited AChE enzyme.
Conversely, different results suggesting oxime efficacy in
carbamate intoxication were reported by Mercurio-Zappala
et al [33] (Table 4).
They found that 25 mg/kg 2-PAM administered solely or
with atropine was as beneficial as atropine in carbaryl (5 mg/
kg1 LD50 SC) poisoned mice (as compared to no
treatment; P = .025, P = .017, and P b .01, respectively).
High-dose 2-PAM (100 mg/kg), even when combined with
atropine, resulted in increased mortality compared to
atropine alone [33]. Antidotal treatment was initiated
10 minutes after intoxication via the peritoneal route.

Schematic illustration of the reactivation of carbamylated enzyme by 2-PAM.

1122
Table 4

Fatality
rate

Y. Rosman et al.
Fatality from carbaryl (1 LD50, SC) in poisoned mice with different antidotal treatment protocols [33]
Control

Atropine

2-PAM
100 mg/kg

2-PAM
50 mg/kg

2-PAM
25 mg/kg

Atropine + 2-PAM
100 mg/kg

Atropine + 2-PAM
50 mg/kg

Atropine + 2-PAM
25 mg/kg

60%
(n = 20)

15%
(n = 20)

80%
(n = 10)

60%
(n = 10

15%
(n = 20)

66%
(n = 9)

10%
(n = 10)

10%
(n = 10)

The studies suggesting increased carbaryl toxicity after

oxime therapy [23-28] were criticized for using extremely
high doses of oxime (eg, 0.71 LD50 of 2-PAM [24]), using
treatment protocols that are different from clinical practice
(such as pretreatment and oxime treatment with no atropine)
and lack of control group treated with oxime only, without
being exposed to carbamates.

7.2. Human data

It is important to note that beside the single historical case
report of Farago [19] from 1969, who reported a drunk
patient who ingested 0.5 L of 80% carbaryl in a suicide
attempt, there were no other human reports suggesting
deleterious effects of oxime therapy in carbamate poisoning.
The patient described by Farago developed pulmonary
edema and was treated with atropine (intravenously and
intramuscularly at 30-minute intervals, a total dose of 6 mg,
without achieving full atropinization) followed by 2-PAM
(250 mg, 3 hours after ingestion). Thereafter, pulmonary
edema progressed rapidly, and the patient died 6 hours later.
Conversely, several other reports demonstrated the successful use of oximes in patients intoxicated with various
carbamates. Nelson et al [22] reported a case series in which
pralidoxime treatment was beneficial in aldicarb poisoning.
Burgess et al [20] described a case of a 43-year-old man
presenting with coma, cyanosis, incontinence, excessive
lacrimation, and salivation after accidentally ingesting
aldicarb. Despite adequate doses of intravenous atropine
and parlidoxime, the patient's condition deteriorated and he
was in need for ventilatory support. Only when a continuous
intravenous drip of parlidoxime was administered, a clinical
improvement was noted, and the patient was subsequently
discharged with no sequel [20]. Ekins et al [21] described the
case of a 52-year-old patient who accidentally swallowed the
carbamate methomyl. On presentation to the emergency
department, the patient was stuporous and in acute
respiratory distress. His skin was wet, his pupils were 1
mm in diameter, and pink, frothy secretions were present in
the oropharynx. The patient also demonstrated bowel
incontinence. Treatment included nasotracheal intubation
and mechanical ventilation.
Atropine sulfate, 6 mg, was administered intravenously in
the first 10 minutes, leading to less secretions in the lungs.
Pralidoxime, 1 g, was administered intravenously 5 minutes
after the last dose of atropine. Not surprisingly, fasciculations
did not stop after the atropine but did stop after pralidoxime

administration, only to resume 30 minutes later. A second

dose of pralidoxime, 1 g given intravenously, again clearly
stopped the fasciculations. A regimen of atropine, 3 mg/h,
and pralidoxime, 500 mg/h, was begun in a continuous
infusion. After the administration of atropine and pralidoxime, rapid and pronounced clinical improvement occurred.
Within an hour, the patient's lungs were clear to auscultation.
By 3 hours, he was able to write appropriate answers to
questions. The atropine infusion was discontinued 4 hours
after presentation. Pralidoxime therapy was discontinued
after 28 hours. A total of 18 mg of atropine and 16 g of
pralidoxime were given. After 48 hours, his neurologic status
improved markedly, and he was discharged after 9 days with
no symptoms whatsoever [21].
There also seems to be a consensus in clinical practice that
when a poisoned patient presents with a cholinergic crisis,
and the poison is unknown, it is necessary to treat with a
combination of atropine and oximes [5,13,15-18]. However,
if the poison is known to be a carbamate, the use of oximes in
clinical practice is still controversial [5,13,15-18].

8. Discussion
The use of oxime therapy in carbamate intoxication is
controversial. There are those who claim that oxime therapy
is not warranted because carbamate insecticides do not
permanently inhibit AChE, and therefore, toxicity is usually
moderate, reversible, and responds well to atropine and
supportive measures without need for further treatment
[5,15-18,34]. Moreover, some data show that oxime therapy
might actually exacerbate toxicity associated with certain
carbamate exposures, especially with carbaryl [23-28]. On
the other hand, those who advocate oxime therapy in
carbamate poisoning argue that the animal data regarding
oxime toxicity in the case of carbaryl poisoning are not
relevant because of the usage of toxic oxime doses and
treatment protocols that are not in line with current common
clinical practice [33]. Moreover, there are accumulating data
concerning the potential beneficial effects of oximes in
poisoning with most of the carbamate compounds in animal
studies [24-28] and in human case reports [20-22].
Even if oxime monotherapy is harmful in carbaryl
intoxication, the combination of oxime and atropine (as
currently used in common clinical practice) was shown to be
beneficial [25-28]. Furthermore, Lima and Reis [6] reviewed

Management of carbamate poisoning in a mass casualities event

Fig. 2

1123

Decision-making algorithm for medical first responders, on scene, in a mass casualties event.

189 cases of carbamate poisoning that were treated with

antidotal atropine therapy only and found a fairly high
fatality rate of 4% despite adequate doses of atropine. We
speculate that the addition of oxime therapy in these patients
might have reduced this mortality rate.
A mass casualties event involving toxic substances is
characterized by many casualties, with varying clinical
manifestations and severity that challenge health care
providers, especially the medical first responders. Krivoy
et al [3] described 2 dilemmas that first responders in toxic
mass casualties events are faced with. The first dilemma is the
recognition, on scene, that there is a mass casualties event
involving a toxic substance. If the answer to the first dilemma
is affirmative, then the first medical responders face a second
dilemma, which is whether the toxic substance used has
readily available antidotes. In other words, is it an OP
intoxication or not, or as they termed it: OP or not OP [3]. We
propose to refine the second dilemma into cholinergic
syndrome vs noncholinergic syndrome and suggest the
following treatment algorithm for the medical first responder
on scene (Fig. 2). On site, it is practically impossible to
distinguish between OP and carbamate poisonings based on
clinical manifestations only (ie, no chemical identification of
the poison). If medical first responders recognize that they are
facing a mass casualty event, where casualties are presenting
with the cholinergic syndrome, and there is no knowledge of
the specific toxicant, it is advisable to initiate treatment with
atropine and oxime (the concept of on-scene treatment with
atropine and oxime is well known from nerve agents antidote
autoinjectors, such as the US MARK 1 kit [35]). Moreover,
based on the data showed above, even when carbamate
intoxication is present with high certainty (with no information regarding the specific type of carbamate), as previously

pointed out, it is still advised to use atropine in conjunction

with oxime therapy. As previously mentioned, the only
carbamate with which there is some evidence that oxime
therapy might be hazardous is carbaryl. However, carbaryl is
a carbamate with a very low toxicity; hence, its potential to be
used as a chemical compound in a mass casualties event is
very low, in accordance. Even if carbaryl is used as a chemical
weapon, using oxime in combination of atropine will
probably be beneficial, as previously mentioned.
Therefore, it is unreasonable to avoid oxime therapy in a
mass casualty event because of the concern regarding
carbaryl poisoning. If first responders would be instructed
to avoid oxime therapy in this scenario, there is the
dangerous potential that casualties may not receive necessary
oxime therapy when it is indicated (as in OP or other
carbamates intoxication).

9. Conclusions
There are sufficient data to support oximes therapy, in
conjunction with atropine, in mass casualty event, involving
a cholinergic substance, with no need to differentiate on
scene between OP and carbamate intoxication.

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