Carbamate poisoning: treatment recommendations in the setting of a mass casualties event
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
aCBRN Medicine Branch, Medical Corps, Israel Defense Forces, Tel-Hashomer, Israel
bIsrael Poison Information Center, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
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 carbamate-“carbaryl” 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.
(C) 2009
Introduction
In recent years, the potential of using chemical com- pounds 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: [email protected] (Y. Rosman).
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
0735-6757/$ - see front matter (C) 2009 doi:10.1016/j.ajem.2009.01.035
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 insecti- cides, classified according to their relative toxicity. In this review, we will discuss the nature of carbamate insecticide poisoning and the controversies regarding the treatment protocol-specifically 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 carba- mates. 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 agricul- tural/industrial mishaps involving a few patients and suicidal ingestions involving a single patient as well. The recom- mendations 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.
Carbamates’ mechanism of toxicity
Similar to OP agents that phosphorylate the acetylcholi- nesterase (AChE) enzyme, carbamates carbamylate this
Table 1 The main carbamate insecticides in use and their relative toxic potency (estimated human values) [5]
enzyme. The hydroxyl moiety of the serine that resides inside the catalytic pocket of the enzyme usually nucleophi- lically 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].
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
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 intoxica- tion are summarized in Table 2.
Pediatric Miosis less population prominent; frequent
nicotinic and CNS signs
Common; agitation, confusion, seizures, coma, respiratory arrest AChE inhibition may be prominent weeks after intoxication intermediate syndrome, delayed neuropathy or neuropsychiatric effects are common
Rare
Delayed symptoms
AChE inhibition noticed hours after intoxication
Laboratory findings
Central nervous system signs
Common; as in carbamate poisoning
Nicotinic signs
As in carbamate poisoning
Muscarinic signs
OP intoxication
Carbamate 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
Table 2 Clinical manifestations of carbamate vs OP poisoning
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 con- trol, breathing support, intravenous fluids, and vasopressors, as required. Seizures are usually treated with benzodiaze- pines (eg, diazepam, midazolam).
Antidotes of carbamate intoxication
Atropine
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 over- stimulation 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. Never- theless, 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].
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
Table 3 Summary of animal studies applying Treatment protocols for carbamates poisoning [23-28]
Type of carbamate
Author Animal
model
Treatment Route of
exposure
Full treatment protocol PR a/outcome
Carbaryl Sanderson et al (1961) Rat Oxime PO 2-PAM, 100 mg/kg IP, immediately after poisoning Increased mortality Natoff et al (1972) Rat Oxime IP/SC Obidoxime, 90 mg/kg SC, at the onset of intoxication signs 0.25
Rat Oxime IP/SC P2S, 50 mg/kg SC, at the onset of intoxication signs 0.43
Sterri et al (1979) Mice Oxime PO/SC Obidoxime, 80 mg/kg IP, 15 min before poisoning 0.5
Harris et al (1988) Guinea pigs Oxime IP 2-PAM, 22 mg/kg IP, 1 min after intoxication 0.6
Lieske et al (1992) Mice Oxime PO 2-PAM, 25.1 mg/kg IP 5 min after poisoning 0.14
Mice Oxime PO TMB-4, 12.6 mg/kg IP, 5 min after poisoning 0.48
Natoff et al (1972) Rat Combined oxime and atropine IP/SC Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
Natoff et al (1972) Rat Combined oxime and atropine IP/SC P2S, 50 mg/kg, and atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
Harris et al (1988) Guinea pigs Combined oxime and atropine IP 2-PAM, 22 mg/kg, and atropine, 8 mg/kg IV, 1 min
after intoxication
Lieske et al (1992) Mice Combined oxime and atropine PO 2-PAM, 25.1 mg/kg, and atropine, 11.2 mg/kg IV, 5 min
after poisoning
1.8
6.07
3.5
0.98
Natoff et al (1972) Rat Atropine IP/SC Atropine 17.4 mg/kg SC, at the onset of intoxication signs 6.48 Harris et al (1988) Guinea pigs Atropine IP Atropine, 8 mg/kg IV, 1 min after intoxication 6.6
Lieske et al (1992) Mice Atropine PO Atropine, 11.2 mg/kg IV, 5 min after poisoning N1.4 Aldicarb Natoff et al (1972) Rat Oxime IP/SC Obidoxime, 90 mg/kg SC, at the onset of intoxication signs 2.34
Natoff et al (1972) Rat Oxime IP/SC P2S, 50 mg/kg SC, at the onset of intoxication signs 1.54
Sterri et al (1979) Mice Oxime PO/SC Obidoxime, 80 mg/kg IP, 15 min before poisoning 1.78
Natoff et al (1972) Rat Combined oxime and atropine IP/SC Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
Natoff et al (1972) Rat Combined oxime and atropine IP/SC P2S, 50 mg/kg, and, atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
6.4
N6.85
Natoff et al (1972) Rat Atropine IP/SC Atropine, 17.4 mg/kg SC, at the onset of intoxication signs 5.14 Physostigmine Natoff et al (1972) Rat Oxime IP/SC Obidoxime, 90 mg/kg SC, at the onset of intoxication signs 3.37
Rat Oxime IP/SC P2S, 50 mg/kg SC, at the onset of intoxication signs 3
Sterri et al (1979) Mice Oxime PO/SC Obidoxime, 80 mg/kg IP, 15 min before poisoning 2
Natoff et al (1972) Rat Combined oxime and atropine IP/SC Obidoxime, 90 mg/kg, and atropine, 17.4 mg/kg SC, at the
onset of intoxication signs
Natoff et al (1972) Rat Combined oxime and atropine IP/SC P2S, 50 mg/kg, and atropine, 17.4 mg/kg SC, at the onset of
intoxication signs
Harris et al (1988) Guinea pigs Combined oxime and atropine IP 2-PAM, 22 mg/kg IP, and atropine, 8 mg/kg IV, 1 min
after intoxication
N18.86 17.47
8.8
Natoff et al Rat Atropine IP/SC Atropine…, at the onset of intoxication signs 9.3
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Y. Rosman et al.
Harris et al (1988) Guinea pigs Atropine IP Atropine, 8 mg/kg IV, 1 min after intoxication 7.2
Pyridostigmine Sterri et al (1979) Mice Oxime PO/SC Obidoxime, 80 mg/kg IP, 15 min before poisoning 3.12
Isolan Sanderson et al (1961) Rat Oxime PO 2-PAM, 100 mg/kg IP, immediately after poisoning Decreased mortality
a Protective ratio (ie, the ratio between LD50 with no treatment and LD50 with treatment).
(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)-(hydro- xyimino)methyl] pyridinium} (obidoxime; Toxogonin).
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].
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].
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
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 treat- ment 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 intoxica- tion. Dawson et al [30-32] suggested the opposite, that is, 2- PAM increases the rate of carbamylation of AChE. In both hypotheses, the outcome is similar-an 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/ kg-1 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.
Fig. 1 Schematic illustration of the reactivation of carbamylated enzyme by 2-PAM.
|
human data“>Table 4 Fatality from carbaryl (1x 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 |
|
|
Fatality |
60% |
15% |
80% |
60% |
15% |
66% |
10% |
10% |
|
rate |
(n = 20) |
(n = 20) |
(n = 10) |
(n = 10 |
(n = 20) |
(n = 9) |
(n = 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.
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 success- ful 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 pralidox- ime, 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].
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
Fig. 2 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 informa- tion 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).
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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