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Case report
Challenges of managing snakebite envenomation in a deployed setting Christopher Johnson,1,2 J Rimmer,3 G Mount,4 I Gurney,5 E D Nicol6,7 1
School of Anaesthetics and Intensive Care Medicine, Northern Deanery, Newcastle upon Tyne, UK 2 201 (Northern) Field Hospital (V), Royal Army Medical Corps, Newcastle upon Tyne, UK 3 Gastroenterology Department, Southwest Peninsular Deanery, Derriford Hospital, Plymouth, UK 4 US Army Medical Corps, Internist, 10th Combat Support Hospital, Bastion Role 3, Helmand Province, Afghanistan 5 Emergency Medicine Department, Frimley Park Hospital, , Camberley, UK 6 Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK 7 Faculty of Medicine, Imperial College, London, UK Correspondence to Dr E D Nicol, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; [email protected] Received 19 February 2013 Accepted 28 February 2013 Published Online First 30 May 2013
To cite: Johnson C, Rimmer J, Mount G, et al. J R Army Med Corps 2013;159:307–311.
ABSTRACT Snake bite envenomation causes a significant health burden globally, especially in austere or resource poor settings. This case series describes envenomation in two adults and two children presenting to the Role 3 Medical Treatment Facility in Camp Bastion, Afghanistan. Each case has similarities with respect to the coagulopathy of envenomation but differs in terms of time delay to presentation and response to treatment, including reactions to antivenom. We discuss the challenges and ethical dilemmas in delayed-presentation snakebite, the diagnosis and treatment of coagulopathy and the role of antivenom and surgical debridement.
INTRODUCTION Treatment of snakebite envenomation in an austere deployed setting is recognised in the military medical literature as a potentially complex and serious medical challenge.1 While there is recent guidance on the management of acute snakebite envenomation outlined in the Clinical Guidelines for Operations (CGOs)2 which are currently under revision, delayed presentation following envenomation is unusual in regions where access to healthcare facilities is readily available3 and this kind of guidance may not cover the clinical scenarios faced in a deployed setting. There are estimated to be about 5 million episodes of snakebite envenomation annually leading to approximately 125 000 deaths.4 The most affected are healthy individuals such as children and farming populations in resource poor settings and away from healthcare centres in low-income countries. We present a case series of probable viper envenomation presenting to the emergency department (ED) at the Role 3 Medical Treatment Facility (R3MTF) at Camp Bastion, Afghanistan, during 2012. They occurred in the Southern Helmand area in Afghanistan National Army (ANA) troops and civilian children, so CGOs and Defence Instructions and Notices may not directly apply to this population. These cases highlight the clinical and ethical challenges involved in both the delayed presentation of viper envenomation, as well as the treatment of refractory coagulopathy and tissue damage following envenomation in adults and children. In resource-poor settings with limited access to medical facilities late presentation following envenomation may be more common due to the distance to healthcare facilities and this series adds to the literature for the management of these cases in remote and isolated environments.
DELAYED PRESENTATION OF SNAKEBITE ENVENOMATION Case 1 An Afghan child, estimated to be 5-years-old, presented to the R3MTF about 9 h after a snakebite to
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
his right hand. On arrival, the child was drowsy (Glasgow Coma Scale (GCS) 13) with facial swelling and bleeding from mucus membranes. The patient was electively intubated in the ED and transferred to the intensive treatment unit (ITU). Full blood count and clotting were measured before and after treatment with Pakistani polyvalent snake antivenom diluted in 250 ml of normal saline over 2 h. Liver function tests were mildly deranged (2000 NA NA +ve NA
11.4 155 29.5 * 0.3 >2000 NA NA
13.9 40 20.8 20.9 * NA 3118 6.4 +ve +ve
11.4 129 18.1 18.9 2.38
9.1 136 22.6 40.7 * >4000 92 NA +ve
NA NA 17.0 18.7 0.67 >4000
16.9 60 * * * Positive 1361 NA
12.4 857 19 24.4 1.24 Positive 527 NA
5800 1.1 −ve −ve
NA −ve
Normal range 13.5–17.5 g/dl 150–430 109/l 11.5–15.5 s 25–38 s 1.5–4 g/dl >8.0 ug/ml=+ 55–170 U/l
+ve
*Not measurable. Hb, haemoglobin; Plt, platelets; PT, prothombin time; aPTT, activated partial thromboplastin time; CK, creatanine kinase; WBCT, whole blood clotting time; ROTEM, rotational thromboelastometry; NA, not applicable.
experience with this type of presentation among the deployed staff, and there was a debate regarding the most appropriate management of the right arm, for which the working diagnosis was of compartment syndrome; intracompartmental pressure monitoring was not available. While some felt fasciotomy was most appropriate, others felt the risk of subsequent acute renal failure, which could be fatal without available haemo-filtration, outweighed the benefit of a minimal surgical approach and advocated amputation. The physicians ultimately decided that a fasciotomy would be the most appropriate first line approach as maintaining a functional dominant hand was felt to be worth the potential risk of complications. The patient was transferred to the operating theatre and given prophylactic hydrocortisone, chlorpheniramine and ranitidine prior to the administration of 10 vials of Pakistani polyvalent antivenom diluted in 250 ml of normal saline over 2 h. While the coagulopathy was not fully reversed, a WBCT prior to skin incision was negative. A further pool of platelets, one unit of FFP and one unit of packed red cells were administered during surgery in an attempt to normalise the residual coagulopathy. Following fasciotomy to the hand, forearm and arm, the underlying tissue improved in colour and circulation returned (Figure 4), with Doppler ultrasound demonstrating arterial flow to the wrist. The patient remained haemodynamically stable throughout the operation and was transferred to ITU postoperatively. Renal function, electrolytes and creatine kinase (CK) were monitored overnight due to the risk of rhabdomyolysis after reperfusion of the arm; the CK peaked at 5800, coagulation normalised and a WBCT repeated 20 h after admission was negative. The patient was extubated on Day 2 and transferred to the ward before returning to theatre the following day for partial closure of the fasciotomy wounds and skin grafting. He was subsequently discharged to a local Afghan healthcare facility for continuation of his care.
Case 3 A 21-year-old ANA soldier presented to the R3MTF approximately 4 days after suffering envenomation to the right big toe. He had been evaluated by a Special Forces medic at the time of the bite and reportedly given a dose of antivenom, the type and amount of which was unknown. The patient subsequently developed oedema and ecchymosis of the right foot extending 308
proximally to involve the right calf. By the time of presentation to the R3MTF, he also had diffuse oedema and bruising of the right upper extremity, apparently related to the infusion of antivenom at this site. Clinical history and examination failed to reveal subjective weakness or other neurological features. He was not distressed or dyspnoeic and denied chest pain, fever, rigors or other infectious symptoms. He was slightly hypertensive and afebrile. He had an oedematous right upper arm with intact sensation and radial pulses, his left arm had diffuse bruising, but no oedema. The right leg had mild to moderate diffuse oedema from the foot to the mid-thigh, with concomitant bruising. Distal pulses and sensation were intact in both lower limbs. His initial blood results are shown in column E of Table 1 and his remaining blood results, including renal and liver function, were normal. Although he presented 96 h after envenomation, he remained coagulopathic and because of his risk of continued bleeding and bruising with an already established anaemia and thrombocytopenia, a course of antivenom was given (five vials of Pakistani equine polyvalent snake antivenom diluted in 250 ml of normal saline administered over 2 h). Unfortunately, despite pretreatment with a corticosteroid and an antihistamine, the patient developed a delayed allergic reaction to the infusion with notable tachycardia, tachypnoea, a mild wheeze and rigors. The infusion was discontinued after 200 ml and his symptoms resolved with a single dose of adrenaline. The following day, the patient’s coagulation studies had nearly returned to normal (PT=17.8 s, aPTT=18.7 s), his fibrinogen was detectable at 0.669 g/dl and his WBCT was negative. He was discharged to the Afghan military healthcare system without additional issues or concerns.
REFRACTORY COAGULOPATHY FOLLOWING ENVENOMATION Case 4 A 25-year-old ANA soldier presented approximately 3 h after envenomation to his left leg. On presentation, he was haemodynamically stable and complaining only of mild pain and numbness in the area of the bite. Initially laboratory studies (Table 1 column G) were notable for a significant coagulopathy, with PT and aPTT beyond the limits of measurement, a significantly depressed fibrinogen and a positive WBCT. Antivenom therapy with Pakistani polyvalent antivenom diluted in 250 ml of normal
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
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Case report
Figure 1 (A) ROTEM analysis from a 5-year-old child with presumed viper envenomation. (B) Normal ROTEM analysis (http://www.rotem.de/site/ index.php?option=com_content&view=article&id=2&Itemid=8&lang=en accessed 20 Sept 2012).
saline over 2 h was administered. The PT remained elevated at 26.2 s and he was treated with an additional five vials of antivenom 2 h after the initial dose. This treatment resulted in an improved, although not normalised, PTof 19 s. He was discharged to the local ANA clinic from the ward 36 h after admission. He returned 3 days later with continued bleeding at the snakebite site and significant left leg bruising. The haemoglobin had fallen to 7.7 g/dl and his coagulopathy had also worsened with PT and aPTT again beyond the measurable limit. Despite a second course of 10 vials of antivenom in the ED, his coagulopathy continued and he received a further 10 vials on arrival to the ward. This provided only minor improvement, so further antivenom therapy was continued—a further three standard courses of five vials and three further courses of two vials were required to overcome his coagulopathy. In total, 51 vials of antivenom were required. He tolerated this treatment without
obvious adverse effects and was discharged to the ANA medical system for continued care.
SNAKE SPECIES It is unknown which species of snake was responsible for each of the envenomations described above. The snakes found in Afghanistan are known to be the saw scaled viper (Echis carinatus multisquamatus), snub-nosed viper (Macrovipera lebetina), McMahon’s viper (Eristicophis macmahonii) and false horned viper (Pseudocerasates persicus).1 The clinical presentation and response to treatment suggest that the bites were caused by the bite of E carinatus multisquamatus. (Figure 5) with the exception of the last case, which was likely caused by a species not covered by the Pakistani antivenom, which in this part of the world is likely to be E macmahonii.1
DISCUSSION The treatment of snakebite envenomation in the deployed military setting provides several significant management challenges. Envenomation often affects children and may present outside the usual timeframe usually seen in Western countries. The signs
Figure 2 Necrotic right hand with multiple bulla and poor capillary refill.
Figure 3
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
Necrosis extending from the forearm to the distal elbow. 309
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Case report
Figure 5 Saw scaled viper Echis carinatus multisquamatus (http:// www.latoxan.com/VENOM/SNAKE/Echis-carinatus-multisquamatus.php accessed 18 Feb 2013).
Figure 4 Fasciotomy to the hand and forearm and up to the shoulder. and symptoms following snakebite envenomation also vary according to the type of snake encountered. Typically, viperidae (vipers) envenomates with a haemotoxin causing coagulopathy and muscle breakdown, while elapids envenomate with a neurotoxin. However, these are not exclusive, the venom from elapids can have a haemotoxic effect and that of the viperidae can be neurotoxic. Initial management focuses on obtaining a complete history and physical examination, assessing a patient’s airway, breathing, and circulation and measuring set of vital signs. Thereafter, management focuses on the three major manifestations of snakebite envenomation: local tissue effects, coagulopathy related to venom haemotoxin and systemic effects of envenomation such as neurotoxicity, cardiovascular toxicity and angioedema3 and is aided by basic laboratory blood tests including the measurement of coagulation. The US Department for Defense Armed Forces Pest Management Board describes the symptoms of viper envenomation simply as ‘usually causing sharp pain at site, followed by edema & necrosis. Patients may develop blood-filled blisters at bite site. Heart rate & blood pressure usually increase’.5 The coagulopathy typically caused by viper envenomation is not fully understood6 but is thought to be due to the release of procoagulant enzymes that stimulate the clotting cascade, overwhelming the stored clotting factors resulting in non-coagulable blood; fibrin is formed but broken down by fibrinolysis and a consumptive coagulopathy ensues. In addition to the disseminated intravascular coagulopathy, digestive hydrolases and proteolytic enzymes increase permeability and cause tissue swelling.
Box 1 The whole blood clotting time ▸ An unsophisticated measure of coagulopathy often used where more sophisticated haematological testing is not available. ▸ Approximately 2 ml of whole blood is placed in a plain test tube or universal container and left at room temperature. ▸ A negative result is blood which has clotted at or before 20 min has elapsed. A positive result is unclotted blood at 20 min: this shows the presence of a coagulopathy but does not provide any further information as to the cause. 310
Patients present with pain and swelling around the envenomation site, bleeding, especially from mucus membranes and venepuncture sites, and often a petechial rash. In addition to routine measurement of PT and aPTT, a fibrinogen level and measurement of whole blood clotting time can aid in the assessment of haematological clotting function.7 An alternative assessment tool, thromboelastography (TEG), has been explored in association with snakebite envenomation in an effort to triage paediatric snakebite patients and may be a more accurate predictor of disease severity than the internationalised normalised ratio.8 In our deployed military environment, the use of thromboelastometry (ROTEM), a comparable test with TEG, is well established 9 and understood due to its extensive use in trauma, and thus it was used as a more familiar marker of coagulopathy than the WBCT. We appreciate that the relative complexity and equipment needed make TEG/ROTEM inappropriate for use in all settings where snake envenomation occurs. Several scoring systems and algorithms have been proposed to aid in the decision making process regarding the use of antivenom10 and recently, an evidence-informed, consensus-driven unified treatment algorithm for the management of pit viper snakebites in the USA has been developed.3 While the algorithm is a useful starting point, we appreciate that it deals with a different population of snakes and available antivenom; however, some recommendations are probably transferable. For example, according to this algorithm, snakebite patients with evidence of coagulopathy, neurotoxicity or significant systemic effects from envenomation should receive treatment with antivenom. The dose of the antivenom is region-specific and in the case of Afghanistan the initial dose of the Pakistani polyvalent antivenom recommended (by CGOs and local standard operating procedures) is 10 vials2 with further therapy titrated to clinical response, which include improvements in haematological disturbances, halting local tissue effects, and resolution of systemic and neurological effects.8 The dose for adults and children is the same. However, its use is still controversial11 and major adverse side effects of antivenom are related to its immunogenic potential and may include severe systemic reactions, anaphylaxis and serum sickness.12 There is emerging literature showing that antivenom appears to be safe in a paediatric population;13 a recent randomised controlled trial from Sri Lanka14 investigated the use of adrenaline, promethiazine and hydrocortisone prior to the administration of antivenom and suggested that low dose of subcutaneous adrenaline was the only treatment to exhibit an effect in reducing reaction rate to antivenom and that using hydrocortisone
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
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Case report alongside the adrenaline negated this effect. While this is only a single trial, it is something which should be considered in situations where the quality of the antivenom is poor and the likelihood of an adverse reaction is high. The use of steroids and antihistamines is an established practice prior to the administration of antivenom and we used these ourselves with varying success in cases 2 and 3. This case series provides a few additional discussion points. The use of antivenom remains a potent treatment option, even when there is a significant delay from the time of the snakebite to initial care. In a similar fashion to an acute presentation, clinicians faced with a delayed presentation of snakebite envenomation should rely on a complete history, examination and basic laboratory testing to direct treatment. The treatment of refractory coagulopathy in snakebite envenomation is not well described in the current literature. The US algorithm for the management of snakebite envenomation notes that failure to achieve treatment goals following the administration of two course of antivenom is uncommon.3 It is noted, however, that the clinical effects of envenomation are dynamic and recurrence or delayed-onset of significant clinical effects may be seen in up to 50% of cases.3 Serial examinations and laboratory testing are required, and it should be noted that certain clinical effects, such as coagulopathy, may be less responsive to continued antivenom administration as shown in our case series. The role of surgery in snakebite envenomation is controversial and published studies are usually from single centres. There appears to be a role for serial wound debridement, followed by skin grafting;15 however, amputation does not appear to be supported in the literature. There are a few published cases of compartment syndrome16 17 such as case 2, and although in those sporadic cases a minimal approach with fasciotomies appears to result in a good functional outcome,16 the approach remains controversial with little evidence to support its routine practice.17 In our case, the basis of the discussion in the ED was whether we could get away with a less drastic approach than amputation to try and ensure the child was left with a functioning right hand. While the appearances are graphic we would argue that the outcome was less devastating than an amputation. Although the coagulopathy was not fully resolved prior to taking the child to theatre, the WBCT was negative and the antivenom had been given along with platelets and FFP prior to surgery. It was felt that the surgery resulted in an excellent outcome with almost immediate restoration of circulation to large parts of the arm.
antivenom appears to continue to be effective several days after initial envenomation. When assessing the severity of coagulopathy, ROTEM may be quicker than, and as effective as, WBCT and other standard measures of the coagulation cascade when it is readily available. Surgical intervention should be as minimal as possible, with serial debridement and skin grafting the mainstay of surgical management, but consideration should be given to escharotomy if a suspicion of compartment syndrome exists. Contributors CJ: data collection, writing, editing, submitting. JR and GM: data collection. IG: specialist advice. EN: writing, editing, overall responsibility, senior author, corresponding author. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
2 3
4 5 6 7 8
9 10 11 12
13
14
15
SUMMARY In a military environment snakebite envenomation is likely to continue to be a challenging presentation both in children and adults. Our cases suggest that, despite the risk of side effects,
16 17
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
Lamb L, Ross DA, Lalloo DG, et al. Management of venomous bites and stings in British military personnel deployed in Iraq, Afghanistan and Cyprus. J R Army Med Corps 2008;154(4 Suppl):2–40. Clinical Guidelines for Operations. Joint Doctrine Publication 4–03.1 ( JDP 4–03.1). 2008. Lavonas EJ, Ruha AM, Banner W, et al. Rocky mountain poison and drug center, Denver Health and Hospital Authority. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med 2011;11:2–15. Girish KS, Kemparaju K. Overlooked issues of snakebite management: time for strategic approach. Current Topics Med Chem 2011;11:2494–508. http://www.afpmb.org/content/venomous-animals-g (accessed 22 Oct 2012). Lavonas EJ. Coagulopathy: the most important thing we still don’t know about snakebite. West J Emerg Med 2012;13:75–6. Punguyire D, Iserson KV, Stolz U, et al. Bedside whole-blood clotting times: validity after snakebites. J Emerg Med 2013;44:663–7. Hadley GP, McGarr P, Mars M. The role of thromboelastography in the management of children with snake bite in Southern Africa. Trans R So Trop Med Hyg 1999;93:177–9. Doughty HA, Woolley T, Thomas GOR. Massive transfusion. J R Army Med Corps 2011;157(3 Suppl 1):277–83. Spiller HA, Bosse GM, Ryan ML. Use of antivenom for snakebites reported to United States poison centers. Am J Emerg Med 2010;28:780–5. Lavonas EJ. Antivenoms for snakebite: design, function, and controversies. Current Pharmacol Biotechnol 2012;13:1980–6. Schaeffer TH, Khatri V, Reifler LM, et al. Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis. Acad Emerg Med 2012; 19:121–31. Farrar HC, Grayham T, Bolden B, et al. The use and tolerability of crotalidae polyvalent immune FAB (ovine) in pediatric envenomations. Current Topics Med Chem 2011;11:2494–508. De Silva HA, Pathmeswaran A, Ranasinha CD, et al. Low-Dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Med 2010;8:e1000435. doi:10.1371/journal.pmed.1000435 Laohawiriyakamol S, Sangkhat S, Chiengkriwate P, et al. Surgery in management of snake envenomation in children. World J Pediatr 2011;7:361–4. Roberts RS, Csencsitz TA, Heard CW Jr. Upper extremity compartment syndromes following pit viper envenomation. Clin Pediatr 2012;51:945–9. Cumpston KL. Is there a role for fasciotomy in Crotalinae envenomations in North America? Clinical Toxicology 2011;49:351–65.
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Challenges of managing snakebite envenomation in a deployed setting Christopher Johnson, J Rimmer, G Mount, I Gurney and E D Nicol J R Army Med Corps 2013 159: 307-311 originally published online May 29, 2013
doi: 10.1136/jramc-2013-000047 Updated information and services can be found at: http://jramc.bmj.com/content/159/4/307
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Case report
Challenges of managing snakebite envenomation in a deployed setting Christopher Johnson,1,2 J Rimmer,3 G Mount,4 I Gurney,5 E D Nicol6,7 1
School of Anaesthetics and Intensive Care Medicine, Northern Deanery, Newcastle upon Tyne, UK 2 201 (Northern) Field Hospital (V), Royal Army Medical Corps, Newcastle upon Tyne, UK 3 Gastroenterology Department, Southwest Peninsular Deanery, Derriford Hospital, Plymouth, UK 4 US Army Medical Corps, Internist, 10th Combat Support Hospital, Bastion Role 3, Helmand Province, Afghanistan 5 Emergency Medicine Department, Frimley Park Hospital, , Camberley, UK 6 Department of Military Medicine, Royal Centre for Defence Medicine, Birmingham, UK 7 Faculty of Medicine, Imperial College, London, UK Correspondence to Dr E D Nicol, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK; [email protected] Received 19 February 2013 Accepted 28 February 2013 Published Online First 30 May 2013
To cite: Johnson C, Rimmer J, Mount G, et al. J R Army Med Corps 2013;159:307–311.
ABSTRACT Snake bite envenomation causes a significant health burden globally, especially in austere or resource poor settings. This case series describes envenomation in two adults and two children presenting to the Role 3 Medical Treatment Facility in Camp Bastion, Afghanistan. Each case has similarities with respect to the coagulopathy of envenomation but differs in terms of time delay to presentation and response to treatment, including reactions to antivenom. We discuss the challenges and ethical dilemmas in delayed-presentation snakebite, the diagnosis and treatment of coagulopathy and the role of antivenom and surgical debridement.
INTRODUCTION Treatment of snakebite envenomation in an austere deployed setting is recognised in the military medical literature as a potentially complex and serious medical challenge.1 While there is recent guidance on the management of acute snakebite envenomation outlined in the Clinical Guidelines for Operations (CGOs)2 which are currently under revision, delayed presentation following envenomation is unusual in regions where access to healthcare facilities is readily available3 and this kind of guidance may not cover the clinical scenarios faced in a deployed setting. There are estimated to be about 5 million episodes of snakebite envenomation annually leading to approximately 125 000 deaths.4 The most affected are healthy individuals such as children and farming populations in resource poor settings and away from healthcare centres in low-income countries. We present a case series of probable viper envenomation presenting to the emergency department (ED) at the Role 3 Medical Treatment Facility (R3MTF) at Camp Bastion, Afghanistan, during 2012. They occurred in the Southern Helmand area in Afghanistan National Army (ANA) troops and civilian children, so CGOs and Defence Instructions and Notices may not directly apply to this population. These cases highlight the clinical and ethical challenges involved in both the delayed presentation of viper envenomation, as well as the treatment of refractory coagulopathy and tissue damage following envenomation in adults and children. In resource-poor settings with limited access to medical facilities late presentation following envenomation may be more common due to the distance to healthcare facilities and this series adds to the literature for the management of these cases in remote and isolated environments.
DELAYED PRESENTATION OF SNAKEBITE ENVENOMATION Case 1 An Afghan child, estimated to be 5-years-old, presented to the R3MTF about 9 h after a snakebite to
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
his right hand. On arrival, the child was drowsy (Glasgow Coma Scale (GCS) 13) with facial swelling and bleeding from mucus membranes. The patient was electively intubated in the ED and transferred to the intensive treatment unit (ITU). Full blood count and clotting were measured before and after treatment with Pakistani polyvalent snake antivenom diluted in 250 ml of normal saline over 2 h. Liver function tests were mildly deranged (2000 NA NA +ve NA
11.4 155 29.5 * 0.3 >2000 NA NA
13.9 40 20.8 20.9 * NA 3118 6.4 +ve +ve
11.4 129 18.1 18.9 2.38
9.1 136 22.6 40.7 * >4000 92 NA +ve
NA NA 17.0 18.7 0.67 >4000
16.9 60 * * * Positive 1361 NA
12.4 857 19 24.4 1.24 Positive 527 NA
5800 1.1 −ve −ve
NA −ve
Normal range 13.5–17.5 g/dl 150–430 109/l 11.5–15.5 s 25–38 s 1.5–4 g/dl >8.0 ug/ml=+ 55–170 U/l
+ve
*Not measurable. Hb, haemoglobin; Plt, platelets; PT, prothombin time; aPTT, activated partial thromboplastin time; CK, creatanine kinase; WBCT, whole blood clotting time; ROTEM, rotational thromboelastometry; NA, not applicable.
experience with this type of presentation among the deployed staff, and there was a debate regarding the most appropriate management of the right arm, for which the working diagnosis was of compartment syndrome; intracompartmental pressure monitoring was not available. While some felt fasciotomy was most appropriate, others felt the risk of subsequent acute renal failure, which could be fatal without available haemo-filtration, outweighed the benefit of a minimal surgical approach and advocated amputation. The physicians ultimately decided that a fasciotomy would be the most appropriate first line approach as maintaining a functional dominant hand was felt to be worth the potential risk of complications. The patient was transferred to the operating theatre and given prophylactic hydrocortisone, chlorpheniramine and ranitidine prior to the administration of 10 vials of Pakistani polyvalent antivenom diluted in 250 ml of normal saline over 2 h. While the coagulopathy was not fully reversed, a WBCT prior to skin incision was negative. A further pool of platelets, one unit of FFP and one unit of packed red cells were administered during surgery in an attempt to normalise the residual coagulopathy. Following fasciotomy to the hand, forearm and arm, the underlying tissue improved in colour and circulation returned (Figure 4), with Doppler ultrasound demonstrating arterial flow to the wrist. The patient remained haemodynamically stable throughout the operation and was transferred to ITU postoperatively. Renal function, electrolytes and creatine kinase (CK) were monitored overnight due to the risk of rhabdomyolysis after reperfusion of the arm; the CK peaked at 5800, coagulation normalised and a WBCT repeated 20 h after admission was negative. The patient was extubated on Day 2 and transferred to the ward before returning to theatre the following day for partial closure of the fasciotomy wounds and skin grafting. He was subsequently discharged to a local Afghan healthcare facility for continuation of his care.
Case 3 A 21-year-old ANA soldier presented to the R3MTF approximately 4 days after suffering envenomation to the right big toe. He had been evaluated by a Special Forces medic at the time of the bite and reportedly given a dose of antivenom, the type and amount of which was unknown. The patient subsequently developed oedema and ecchymosis of the right foot extending 308
proximally to involve the right calf. By the time of presentation to the R3MTF, he also had diffuse oedema and bruising of the right upper extremity, apparently related to the infusion of antivenom at this site. Clinical history and examination failed to reveal subjective weakness or other neurological features. He was not distressed or dyspnoeic and denied chest pain, fever, rigors or other infectious symptoms. He was slightly hypertensive and afebrile. He had an oedematous right upper arm with intact sensation and radial pulses, his left arm had diffuse bruising, but no oedema. The right leg had mild to moderate diffuse oedema from the foot to the mid-thigh, with concomitant bruising. Distal pulses and sensation were intact in both lower limbs. His initial blood results are shown in column E of Table 1 and his remaining blood results, including renal and liver function, were normal. Although he presented 96 h after envenomation, he remained coagulopathic and because of his risk of continued bleeding and bruising with an already established anaemia and thrombocytopenia, a course of antivenom was given (five vials of Pakistani equine polyvalent snake antivenom diluted in 250 ml of normal saline administered over 2 h). Unfortunately, despite pretreatment with a corticosteroid and an antihistamine, the patient developed a delayed allergic reaction to the infusion with notable tachycardia, tachypnoea, a mild wheeze and rigors. The infusion was discontinued after 200 ml and his symptoms resolved with a single dose of adrenaline. The following day, the patient’s coagulation studies had nearly returned to normal (PT=17.8 s, aPTT=18.7 s), his fibrinogen was detectable at 0.669 g/dl and his WBCT was negative. He was discharged to the Afghan military healthcare system without additional issues or concerns.
REFRACTORY COAGULOPATHY FOLLOWING ENVENOMATION Case 4 A 25-year-old ANA soldier presented approximately 3 h after envenomation to his left leg. On presentation, he was haemodynamically stable and complaining only of mild pain and numbness in the area of the bite. Initially laboratory studies (Table 1 column G) were notable for a significant coagulopathy, with PT and aPTT beyond the limits of measurement, a significantly depressed fibrinogen and a positive WBCT. Antivenom therapy with Pakistani polyvalent antivenom diluted in 250 ml of normal
Johnson C, et al. J R Army Med Corps 2013;159:307–311. doi:10.1136/jramc-2013-000047
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Case report
Figure 1 (A) ROTEM analysis from a 5-year-old child with presumed viper envenomation. (B) Normal ROTEM analysis (http://www.rotem.de/site/ index.php?option=com_content&view=article&id=2&Itemid=8&lang=en accessed 20 Sept 2012).
saline over 2 h was administered. The PT remained elevated at 26.2 s and he was treated with an additional five vials of antivenom 2 h after the initial dose. This treatment resulted in an improved, although not normalised, PTof 19 s. He was discharged to the local ANA clinic from the ward 36 h after admission. He returned 3 days later with continued bleeding at the snakebite site and significant left leg bruising. The haemoglobin had fallen to 7.7 g/dl and his coagulopathy had also worsened with PT and aPTT again beyond the measurable limit. Despite a second course of 10 vials of antivenom in the ED, his coagulopathy continued and he received a further 10 vials on arrival to the ward. This provided only minor improvement, so further antivenom therapy was continued—a further three standard courses of five vials and three further courses of two vials were required to overcome his coagulopathy. In total, 51 vials of antivenom were required. He tolerated this treatment without
obvious adverse effects and was discharged to the ANA medical system for continued care.
SNAKE SPECIES It is unknown which species of snake was responsible for each of the envenomations described above. The snakes found in Afghanistan are known to be the saw scaled viper (Echis carinatus multisquamatus), snub-nosed viper (Macrovipera lebetina), McMahon’s viper (Eristicophis macmahonii) and false horned viper (Pseudocerasates persicus).1 The clinical presentation and response to treatment suggest that the bites were caused by the bite of E carinatus multisquamatus. (Figure 5) with the exception of the last case, which was likely caused by a species not covered by the Pakistani antivenom, which in this part of the world is likely to be E macmahonii.1
DISCUSSION The treatment of snakebite envenomation in the deployed military setting provides several significant management challenges. Envenomation often affects children and may present outside the usual timeframe usually seen in Western countries. The signs
Figure 2 Necrotic right hand with multiple bulla and poor capillary refill.
Figure 3
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Necrosis extending from the forearm to the distal elbow. 309
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Case report
Figure 5 Saw scaled viper Echis carinatus multisquamatus (http:// www.latoxan.com/VENOM/SNAKE/Echis-carinatus-multisquamatus.php accessed 18 Feb 2013).
Figure 4 Fasciotomy to the hand and forearm and up to the shoulder. and symptoms following snakebite envenomation also vary according to the type of snake encountered. Typically, viperidae (vipers) envenomates with a haemotoxin causing coagulopathy and muscle breakdown, while elapids envenomate with a neurotoxin. However, these are not exclusive, the venom from elapids can have a haemotoxic effect and that of the viperidae can be neurotoxic. Initial management focuses on obtaining a complete history and physical examination, assessing a patient’s airway, breathing, and circulation and measuring set of vital signs. Thereafter, management focuses on the three major manifestations of snakebite envenomation: local tissue effects, coagulopathy related to venom haemotoxin and systemic effects of envenomation such as neurotoxicity, cardiovascular toxicity and angioedema3 and is aided by basic laboratory blood tests including the measurement of coagulation. The US Department for Defense Armed Forces Pest Management Board describes the symptoms of viper envenomation simply as ‘usually causing sharp pain at site, followed by edema & necrosis. Patients may develop blood-filled blisters at bite site. Heart rate & blood pressure usually increase’.5 The coagulopathy typically caused by viper envenomation is not fully understood6 but is thought to be due to the release of procoagulant enzymes that stimulate the clotting cascade, overwhelming the stored clotting factors resulting in non-coagulable blood; fibrin is formed but broken down by fibrinolysis and a consumptive coagulopathy ensues. In addition to the disseminated intravascular coagulopathy, digestive hydrolases and proteolytic enzymes increase permeability and cause tissue swelling.
Box 1 The whole blood clotting time ▸ An unsophisticated measure of coagulopathy often used where more sophisticated haematological testing is not available. ▸ Approximately 2 ml of whole blood is placed in a plain test tube or universal container and left at room temperature. ▸ A negative result is blood which has clotted at or before 20 min has elapsed. A positive result is unclotted blood at 20 min: this shows the presence of a coagulopathy but does not provide any further information as to the cause. 310
Patients present with pain and swelling around the envenomation site, bleeding, especially from mucus membranes and venepuncture sites, and often a petechial rash. In addition to routine measurement of PT and aPTT, a fibrinogen level and measurement of whole blood clotting time can aid in the assessment of haematological clotting function.7 An alternative assessment tool, thromboelastography (TEG), has been explored in association with snakebite envenomation in an effort to triage paediatric snakebite patients and may be a more accurate predictor of disease severity than the internationalised normalised ratio.8 In our deployed military environment, the use of thromboelastometry (ROTEM), a comparable test with TEG, is well established 9 and understood due to its extensive use in trauma, and thus it was used as a more familiar marker of coagulopathy than the WBCT. We appreciate that the relative complexity and equipment needed make TEG/ROTEM inappropriate for use in all settings where snake envenomation occurs. Several scoring systems and algorithms have been proposed to aid in the decision making process regarding the use of antivenom10 and recently, an evidence-informed, consensus-driven unified treatment algorithm for the management of pit viper snakebites in the USA has been developed.3 While the algorithm is a useful starting point, we appreciate that it deals with a different population of snakes and available antivenom; however, some recommendations are probably transferable. For example, according to this algorithm, snakebite patients with evidence of coagulopathy, neurotoxicity or significant systemic effects from envenomation should receive treatment with antivenom. The dose of the antivenom is region-specific and in the case of Afghanistan the initial dose of the Pakistani polyvalent antivenom recommended (by CGOs and local standard operating procedures) is 10 vials2 with further therapy titrated to clinical response, which include improvements in haematological disturbances, halting local tissue effects, and resolution of systemic and neurological effects.8 The dose for adults and children is the same. However, its use is still controversial11 and major adverse side effects of antivenom are related to its immunogenic potential and may include severe systemic reactions, anaphylaxis and serum sickness.12 There is emerging literature showing that antivenom appears to be safe in a paediatric population;13 a recent randomised controlled trial from Sri Lanka14 investigated the use of adrenaline, promethiazine and hydrocortisone prior to the administration of antivenom and suggested that low dose of subcutaneous adrenaline was the only treatment to exhibit an effect in reducing reaction rate to antivenom and that using hydrocortisone
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Case report alongside the adrenaline negated this effect. While this is only a single trial, it is something which should be considered in situations where the quality of the antivenom is poor and the likelihood of an adverse reaction is high. The use of steroids and antihistamines is an established practice prior to the administration of antivenom and we used these ourselves with varying success in cases 2 and 3. This case series provides a few additional discussion points. The use of antivenom remains a potent treatment option, even when there is a significant delay from the time of the snakebite to initial care. In a similar fashion to an acute presentation, clinicians faced with a delayed presentation of snakebite envenomation should rely on a complete history, examination and basic laboratory testing to direct treatment. The treatment of refractory coagulopathy in snakebite envenomation is not well described in the current literature. The US algorithm for the management of snakebite envenomation notes that failure to achieve treatment goals following the administration of two course of antivenom is uncommon.3 It is noted, however, that the clinical effects of envenomation are dynamic and recurrence or delayed-onset of significant clinical effects may be seen in up to 50% of cases.3 Serial examinations and laboratory testing are required, and it should be noted that certain clinical effects, such as coagulopathy, may be less responsive to continued antivenom administration as shown in our case series. The role of surgery in snakebite envenomation is controversial and published studies are usually from single centres. There appears to be a role for serial wound debridement, followed by skin grafting;15 however, amputation does not appear to be supported in the literature. There are a few published cases of compartment syndrome16 17 such as case 2, and although in those sporadic cases a minimal approach with fasciotomies appears to result in a good functional outcome,16 the approach remains controversial with little evidence to support its routine practice.17 In our case, the basis of the discussion in the ED was whether we could get away with a less drastic approach than amputation to try and ensure the child was left with a functioning right hand. While the appearances are graphic we would argue that the outcome was less devastating than an amputation. Although the coagulopathy was not fully resolved prior to taking the child to theatre, the WBCT was negative and the antivenom had been given along with platelets and FFP prior to surgery. It was felt that the surgery resulted in an excellent outcome with almost immediate restoration of circulation to large parts of the arm.
antivenom appears to continue to be effective several days after initial envenomation. When assessing the severity of coagulopathy, ROTEM may be quicker than, and as effective as, WBCT and other standard measures of the coagulation cascade when it is readily available. Surgical intervention should be as minimal as possible, with serial debridement and skin grafting the mainstay of surgical management, but consideration should be given to escharotomy if a suspicion of compartment syndrome exists. Contributors CJ: data collection, writing, editing, submitting. JR and GM: data collection. IG: specialist advice. EN: writing, editing, overall responsibility, senior author, corresponding author. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
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SUMMARY In a military environment snakebite envenomation is likely to continue to be a challenging presentation both in children and adults. Our cases suggest that, despite the risk of side effects,
16 17
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Lamb L, Ross DA, Lalloo DG, et al. Management of venomous bites and stings in British military personnel deployed in Iraq, Afghanistan and Cyprus. J R Army Med Corps 2008;154(4 Suppl):2–40. Clinical Guidelines for Operations. Joint Doctrine Publication 4–03.1 ( JDP 4–03.1). 2008. Lavonas EJ, Ruha AM, Banner W, et al. Rocky mountain poison and drug center, Denver Health and Hospital Authority. Unified treatment algorithm for the management of crotaline snakebite in the United States: results of an evidence-informed consensus workshop. BMC Emerg Med 2011;11:2–15. Girish KS, Kemparaju K. Overlooked issues of snakebite management: time for strategic approach. Current Topics Med Chem 2011;11:2494–508. http://www.afpmb.org/content/venomous-animals-g (accessed 22 Oct 2012). Lavonas EJ. Coagulopathy: the most important thing we still don’t know about snakebite. West J Emerg Med 2012;13:75–6. Punguyire D, Iserson KV, Stolz U, et al. Bedside whole-blood clotting times: validity after snakebites. J Emerg Med 2013;44:663–7. Hadley GP, McGarr P, Mars M. The role of thromboelastography in the management of children with snake bite in Southern Africa. Trans R So Trop Med Hyg 1999;93:177–9. Doughty HA, Woolley T, Thomas GOR. Massive transfusion. J R Army Med Corps 2011;157(3 Suppl 1):277–83. Spiller HA, Bosse GM, Ryan ML. Use of antivenom for snakebites reported to United States poison centers. Am J Emerg Med 2010;28:780–5. Lavonas EJ. Antivenoms for snakebite: design, function, and controversies. Current Pharmacol Biotechnol 2012;13:1980–6. Schaeffer TH, Khatri V, Reifler LM, et al. Incidence of immediate hypersensitivity reaction and serum sickness following administration of Crotalidae polyvalent immune Fab antivenom: a meta-analysis. Acad Emerg Med 2012; 19:121–31. Farrar HC, Grayham T, Bolden B, et al. The use and tolerability of crotalidae polyvalent immune FAB (ovine) in pediatric envenomations. Current Topics Med Chem 2011;11:2494–508. De Silva HA, Pathmeswaran A, Ranasinha CD, et al. Low-Dose adrenaline, promethazine, and hydrocortisone in the prevention of acute adverse reactions to antivenom following snakebite: a randomised, double-blind, placebo-controlled trial. PLoS Med 2010;8:e1000435. doi:10.1371/journal.pmed.1000435 Laohawiriyakamol S, Sangkhat S, Chiengkriwate P, et al. Surgery in management of snake envenomation in children. World J Pediatr 2011;7:361–4. Roberts RS, Csencsitz TA, Heard CW Jr. Upper extremity compartment syndromes following pit viper envenomation. Clin Pediatr 2012;51:945–9. Cumpston KL. Is there a role for fasciotomy in Crotalinae envenomations in North America? Clinical Toxicology 2011;49:351–65.
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Challenges of managing snakebite envenomation in a deployed setting Christopher Johnson, J Rimmer, G Mount, I Gurney and E D Nicol J R Army Med Corps 2013 159: 307-311 originally published online May 29, 2013
doi: 10.1136/jramc-2013-000047 Updated information and services can be found at: http://jramc.bmj.com/content/159/4/307
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