ISSN East Cent. Afr. J. surg. Snake Bite: A review of Current Literature

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1 Snake Bite: A review of Current Literature S.B. Dreyer, J.S. Dreyer Department of Surgery, Dumfrie & Galloway Royal Infirmary, Dumfrie, United Kingdom Correpondence to: Stephan B Dreyer, Core urgical trainee, Wet of Scotland Deanery tephan_1908@hotmail.com Snake bite i a ignificant public health problem in rural area of many part of the world 1. Venomou nake are found worldwide, except for a few iland and the frozen environment. Snake bite mot commonly affect thoe living in the tropical and ub-tropical area of Africa, Aia, the America and Oceania. The morbidity and mortality reulting from bite are ignificant. Huge variation in management, coupled with many patient traditional cultural belief and lack of reource contribute to a huge dieae burden from nake bite 2. The World Health Organiation (WHO) recently recognied nake bite a a neglected tropical dieae and thi ha led to a global nake bite initiative to improve clinical outcome following nake bite 3. The aim of thi paper i to review current literature on the incidence, pathophyiology and management of nake bite. The aim i to help clinician to a better undertanding of the management of bite, epecially when in ituation with minimal reource and lack of anti-venom, which i where mot nake bite occur. Thi review dicue a afe approach to clinical management in a field with limited evidence. A treatment guide to ue of anti-venom i included to facilitate rapid deciion making in treful clinical ituation. Surgeon in rural hopital in low and middle income countrie are often involved in the management of nake bite patient due to the nature of tiue damage caued by venom or wrong primary management, or becaue urgeon might be amongt the more enior taff available to help manage critically ill patient in uch ditrict hopital. Mot urgeon are outide their comfort zone, however, when they have to manage a nake bite patient, and thi paper attempt to provide a tructured approach to management. Burden of Dieae Snake bite ha recently been recognied by the World Health Organiation a a neglected tropical dieae 1. An exact etimation of the incidence of nake bite ha not yet been achieved and remain an epidemiological challenge 2,4. Etimate vary greatly and no accurate morbidity and mortality data exit. Swaroop and Grabb 5 firt attempted to quantify the global burden of nakebite but admitted that their data wa flawed. Their tudy uggeted that the global annual mortality from nakebite i between and Thi wa calculated motly from hopital data and the author recognied the gro inaccuracy from thee reult ince mot bite go unreported or take place in region where data i not accurately collected 5. More recent attempt to determine the annual global death from nake bite vary between and ,6,7. Etimate are that the number of bite may be around 5 million per year with more than 2.5 million envenoming 6,7. The highet incidence appear to be in Latin America, ub-saharan Africa, South and South-Eat Aia 6,7. Interetingly, mortality rate were le in Latin American countrie than Africa and Aia with imilar incidence of bite 7. The reaon for thi i unclear, but ha been uggeted to be due to increaed availability and better developed local anti-venom, or better local guideline on management of bite 7. There remain very little evidence detailing the extent of morbidity, long term diability and major pychological impact from nakebite. Thi i of particular importance ince many victim are agricultural worker and a return to work will likely provide ignificant pychological tre. Diability may alo hamper the victim functional ability to work. 45 COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

2 Some tudie ugget permanent difigurement or diability in 18-19% of victim 8,9. Thi i motly due to local tiue necroi reulting in debridement, amputation or permanent carring. Hypoxic brain injury econdary to neurotoxic bite or haemorrhagic complication from envenoming are alo caue of long term diability 2. Significant renal injury can lead to dependence on dialyi following envenoming and i common after bite from Ruell viper in South Aia 10. Permanent diability and difigurement i of particular concern to the majority of nakebite victim, ince mot bite occur in region with poor acce to healthcare or income upport uch a Sub-Saharan Africa and South Eat Aia 7. Pathophyiology Bite occur mot commonly on the lower extremity a a reult of accidentally tepping cloe to the nake 11. Thi i particularly o in low and middle income countrie where victim ue rural footpath, often at night. In region where it i cutomary to leep on the ground or on low bed, bite occur at night a cold blooded nake earch for a warm environment. There ha been growing report of exotic venomou nake bite in the Wetern world due to increaing number being kept a pet. Here victim are often bitten on the upper extremity when attempting to handle the nake, often while intoxicated 11. Mot venomou bite occur from pecie with anteriorly located fang, uch a the Viperidae and Elapidae pecie. Envenoming from poterior fanged nake i rare, yet can be highly dangerou, a with bite from pecie uch a the boomlang (Dipholidu typu). Snake venom are complex collection of peptide, enzyme and other toxin that vary greatly even amongt ub-pecie 2,11. Thi allow the venom to induce everal ytemic repone in potential prey. The mot clinically ignificant toxin are thoe that caue tiue necroi and adverely affect the neurological, cardiovacular and coagulation ytem 2. Snake venom contain multiple compound that caue ytemic effect. Thee vary from neurotoxic pre- and pot ynaptic blocker, to cytotoxic compound uch a Phopholipae A2 that caue evere local necroi 2,12,13. The toxicology of nake venom i complex and there remain great heterogeneity amongt pecie, making development of anti-venom difficult and challenging 14. Probably the mot common clinical effect of nake bite i tiue necroi that can caue extenive oft tiue detruction. Envenoming by a wide range of pecie, particularly the Viperidae uch a the puffadder and rattlenake pecie are reponible for tiue necroi through cytotoxic compound. Cell lyi, increaed vacular permeability and thromboi within the micro-circulation lead to cell death, evere local inflammation and ichaemia 2,12. The ytemic inflammatory repone yndrome i triggered to varying degree and can reult in evere local and ytemic epi. Debridement i often required 2,11,12. Compartment yndrome and the requirement for faciotomy are not a common a previouly thought, and can be prevented by good medical management 15. Snake bite induced nephropathy i a common equel to cytotoxic envenoming leading to acute renal failure 12. Rhabdomyolyi, cardio-vacular compromie, change within the micro-circulation and coagulopathy all contribute to nephropathy 12. Pathological change that can be een in the kidney include acute tubular necroi, glomerulonephriti and vaculiti, producing a range of clinical manifetation 12. Snake venom i thought to caue neurotoxicity excluively by affecting the peripheral nervou ytem with almot no penetrance into the central nervou ytem 2,16. Toxicology i complex, affecting both pre- and pot-ynaptic receptor. The clinical effect vary greatly, with the mot feared that of repiratory depreion and neurogenic hock 2. In certain pecie uch a the black mamba (Dendroapi polylepi), ymptom of neurotoxicity tart with metallic tate, ptoi and gradual bulbar paralyi 2,15. Thee patient carry a high rik of death and hould be treated with great urgency (ee management ection). Patient with ignificant envenoming can have profound cardio-vacular compromie leading to a variety of clinical manifetation with multi-factorial caue. Increaed vacular permeability and 46 COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

3 dilatation i thought to be implicated, and may be due to the releae of cytokine uch a bradykinin 2,17. Cardiogenic hock i een in evere bite econdary to cardiac pecific myotoxic compound and venom induced conduction defect. Thi can be further complicated by ichaemia econdary to coronary artery thromboi econdary to coagulopathy 18. Snake bite induced coagulopathy i a complex and divere clinical problem. It i reponible for a large proportion of nake bite mortality and can be lethal due to complex pathophyiology which i often only revered with anti-venom 13,15. Venom heterogeneity reult in diruption of the coagulation pathway at variou tage. A range of haemotatic diturbance can be een due to veel damage due to cytokine and trauma, reduced coagulability, dieminated intravacular coagulation and the development of pro-thrombotic tate 13. Diintegrin, lectin and phopholipae are example of ubtance that are thought to inhibit haemotai 2,13. In ome pecie nake venom contain procoagulant factor, uch a factor V, X, XIII and pro-thrombin activator reulting in a pro-thrombotic tate 2,13. Platelet aggregation can be either inhibited or induced depending on the venom ub-type. Laboratory reult of patient are often dramatically deranged without correlating clinical manifetation 13. It i important that nake bite coagulopathy i managed differently to the more common caue of deranged clotting, a uual treatment can be ineffective and dangerou (ee management ection). Management The management of venomou nake bite remain a challenge for even the experienced clinician. Lack of emergency tranport and rural location of mot bite reult in patient often preenting late after the clinical effect of envenoming i well etablihed 2, 19. The cultural belief of many rural population further exacerbate the problem with traditional healer often attempting to manage the bite uing traditional method 2, 8. Poor education amongt rural population and healthcare profeional alike reult in poor firt aid meaure that often woren the effect of envenoming 8, 19. Some tudie in Africa have uggeted that late preentation i not aociated with wore outcome 4, 8. Thee concluion can be challenged: with neurotoxic bite late preentation can reult in repiratory failure and hypoxic death while haemotoxic envenoming can lead to fatal coagulopathy if untreated. A major obtacle in nake bite treatment i the correct identification of the reponible nake. Snake bite pecie vary greatly from one geographic region to another, even within countrie. Thi make developing a national or regional treatment trategy problematic. In 40% of cae the patient doe not identify the nake and mitaking for a different pecie i common 15, 20. Even expert herpetologit can miidentify the nake, reulting in inappropriate treatment with anti-venom 2, 20. Attempting to kill or capture the nake that caued the bite further endanger the individual attempting thi, a well a being detrimental to the local eco-ytem. Capturing the nake reponible for identification hould therefore be dicouraged. The difficultie facing clinician treating nake bite i further exacerbated by the lack of availability of anti-venom and modern medical equipment. Mot bite occur in the rural tropic and ub-tropic in low and middle income countrie where acce to health care i difficult and reource are limited 7. Clinician often face treating patient with advanced tage of envenoming without anti-venom. A ytematic approach to managing the clinical yndrome reulting from nake bite i an effective and afe trategy for clinician even with limited reource 15, 20. Firt Aid Suggetion for initial treatment of nake bite vary greatly 2, 15. Mot important are to avoid the ue of a tourniquet and tranport the patient to medical care a oon a poible 2, 15. Attempt to clean or incie the wound and to uck out any venom are ineffective and hould be dicouraged 15. The Sutherland technique of preure immobiliation involve compreion bandaging of the affected limb along a plinted upport 21. Thi ha been widely taught to reduce venom tranport but there i no evidence that 47 COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

4 thi i indeed ucceful 10, 15, 22, 23. It may be effective in treatment of bite in which the venom i mainly tranported via the lymphatic 15. Direct preure pad application, on the other hand, ha been hown to reduce venom uptake in experimental etting, although the evidence for the clinical benefit of thi technique i limited 10, 23. Educating health care profeional and firt aider in thee technique i fraud with difficulty and inaccuracy; patient are more likely to be harmed by over-tight bandaging reulting in a tourniquet effect 15, 23. Tourniquet hould be dicouraged for ue in immediate care except for bite with neurotoxic venom (e.g. mamba pecie) that are confidently identified; tourniquet hould be removed within 90 minute of application 15, 24, 25. Tourniquet ue a a firt aid meaure i aociated with increaed hopital tay and wore outcome 8. The ichaemic effect of tourniquet ue can greatly increae the tiue damage reulting from cytotoxic envenoming which account for 90% of bite in Africa 15. All patient that uffer venomou nake bite hould be reucitated a per Advanced Trauma Life Support (ATLS ) guideline 26. The mot rapid threat to life i with neurotoxic bite in which repiratory depreion econdary to mucle paralyi i a frequent caue of mortality 2, 15. The airway mut be ecured while enuring adequate oxygenation. Patient may become hypotenive due to direct neurotoxicity, cardiogenic hock, bleeding or epi. Shock mut be urgently treated with IV fluid therapy with appropriate monitoring. Avoiding hypoglycaemia and hypothermia are important reucitative adjunct meaure prior to definitive treatment. All patient hould receive tetanu vaccination. Syndromic Management The hortage of anti-venom globally, particularly in the rural tropic, provide a major challenge to nakebite management. Management of the pecific clinical yndrome caued by envenoming can be effective, whether anti-venom i available or not 15,20. A decribed previouly, nake venom produce different clinical yndrome depending on the venom contituent and varie greatly 14, 15. Local Necroi / Painful Progreive welling Bite from Viperidae (e.g. puff-adder, diamondback rattlenake) and ome Elapidae (e.g. krait, cape cobra) pecie are aociated with evere cytotoxic effect 14, 15. Thi i the mot common preentation aociated with nake bite in many part of the world, particularly Africa. The cytotoxic effect of the venom progre rapidly and may be evere in patient preenting late. Due to local tiue necroi and the chemical nature of cytotoxic venom, the adminitration of anti-venom can be fairly ineffective once tiue damage ha occurred 14. Clinical management of thee bite can be very effective dealt with in a ytematic fahion 15. Patient preenting with progreive tiue necroi hould be reucitated a tated above. It i worth keeping in mind that ome nake uch a the African pitting cobra can have neuro- and cytotoxic venom and progreive paralyi i a greater initial threat to life 15. The affected limb hould be elevated and patient hould receive adequate analgeia. Fluid reucitation i an important apect of management. The cytotoxic effect of the venom can caue fluid lo and patient are at rik of acute kidney injury from procee cauing myoglobinuria 14. The affected limb hould be monitored cloely for tiue necroi. If debridement i required, it i recommended that thi i performed 5-7 day after the bite 15. Thi allow adequate demarcation margin to develop and can avoid unneceary return to the operating theatre in an untable patient. Anti-biotic therapy i only indicated if ign of epi are preent. Complication of cytotoxic envenoming include compartment yndrome, rhabdomyolyi, myoglobinuria and acute renal failure. Compartment yndrome i uncommon and hould be managed with faciotomy, if required on clinical ground 15. Femoral veel entrapment by the inguinal ligament can occur rarely, reulting in an ichaemic lower limb 27. Carpal tunnel yndrome from bite to the upper limb uually recover with elevation and analgeia COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

5 Not all patient uffering from cytotoxic bite require anti-venom. The indication include compartment yndrome or eriou aociated complication uch a coagulopathy or adult repiratory ditre yndrome (Table 1). Thi i required in le than 10% of cytotoxic bite 15. Table 1 Indication for Anti-Venom Alway ue anti-venom with appropriate medical taff and monitoring available. Treat reaction appropriately and enure adrenaline, cortico-teroid and anti-hitamine are available prior to adminitration Airway/Breathing Swelling affecting airway Bulbar paralyi affecting breathing / wallowing Repiratory ditre (ARDS) after cytotoxic bite Circulation All confirmed envenoming from pecie with haematoxic venom e.g. boomlang Sytemic bleeding Sign of intra-cerebral bleeding Significant deranged clotting meaurement eg APTT/PT, TEG Shock not reponive to fluid therapy Cardiac arrhythmia Diability Triad of Pin and needle, profue weating and exceive alivation with metallic tate [ugget evere neurotoxic envenomation] Evidence of evere/progreive neurotoxicity (low threhold in pecie known for neurotoxicity uch a black mamba) Seizure / reduced conciou level / evere headache [uggeting intra-cerebral haemorrhage] Severe local welling More than ½ of limb within 24 hour Significant welling involving digit Rapid extenion within few hour Compartment yndrome / veel entrapment Repeating Anti-Venom Continued bleeding 1-2 hour after initiating anti-venom Deteriorating neurological function after 1-2hour Continued coagulopathy a per laboratory meaurement after 6 hour Progreive Paralyi Neurotoxic envenoming can caue rapid deterioration and death. Thi i commonly caued by Elapidae uch a the black mamba in outhern Africa and cobra pecie 14, 15, 20. Some patient may have minor local tiue damage or they may have evere necroi and aociated coagulopathy. In neurotoxic envenoming the application of an arterial tourniquet i indicated whilt awaiting hopital tranfer, a the initial rik to life i much greater from neurotoxicity than tiue necroi 15. Initial 49 COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

6 management of neurotoxic envenoming i appropriate reucitation with primary attention to Airway and Breathing. Thi i crucial in order to prevent repiratory failure econdary to bulbar and repiratory paralyi. Patient with evere envenoming will require intubation and full repiratory upport and thi hould not be delayed if indicated during primary urvey. Mucle-relaxant hould be avoided, unle abolutely required for initial intubation 15. Thee patient require anti-venom in almot all cae. Lack of information regarding the nake reponible hould not delay anti-venom adminitration if clinical ign and ymptom are highly uggetive of neurotoxicity. Thi include difficulty in wallowing, peri-oral paraetheiae, metallic tate, exceive alivation and repiratory failure. If patient are upporting their own repiratory function but a rapid onet generalied weakne occur, then anti-venom adminitration i required to prevent repiratory complication 15. Early intubation hould be conidered a thi allow repiratory upport prior to inevitable repiratory failure. Unlike in cytotoxic envenoming, anti-venom i very ucceful in revering ynaptic neurotoxicity 14, 24. If patient are ventilated and anti-venom adminitrated then recovery can be excellent, unle the venom alo had ignificant cytotoxic or coagulopathic effect. Coagulopathy Coagulopathy can be the primary venomou effect of ome bite, or in conjunction with neurotoxic or cytotoxic venom. The coagulopathic effect vary greatly depending on the venom and the haematological interference it produce. It i worth remembering that even if the coagulopathic effect of venom can produce extremely abnormal laboratory reult, thee do not alway tranpire into clinical morbidity or mortality. Mot nake bite coagulopathy reult in haemorrhagic tendency, but can rarely reult in pro-thrombotic event and overall i a major ource of nakebite mortality globally, cauing a many a 50% of death 13. A dicued previouly, underlying mechanim of coagulopathy vary greatly. Unlike other more common clinical caue of coagulopathy, thoe reulting from nake bite are not uccefully treated uing tandard treatment trategie. The only ucceful treatment i adminitration of anti-venom. The indication for anti-venom include peritent bleeding from minor kin wound, clinical evidence of intra-cranial haemorrhage, ytemic bleeding or ignificantly deranged laboratory meaurement of coagulation 13, 15. Patient may require repeated adminitration of anti-venom depending on clinical repone. Blood coagulation profile hould be rechecked ix hour after adminitration of anti-venom and, if till abnormal, a repeat doe i indicated 2. The clinician hould keep in mind that coagulopathy i often aociated with concurrent cyto- or neurotoxic envenoming. Thee patient hould be reucitated and managed a required for all the clinical equelae of the bite. Anti-venom Anti-venom wa firt developed by Calmette in the late 19 th century 2, 14. Immunoglobulin are extracted and purified, uually from animal erum after previou immunization to that pecific venom. Antivenom can be mono- or polypecific, depending on whether it i effective againt a ingle or multiple pecie venom. Polyvalent anti-venom i uually created geographically to cater pecifically for the mot common bite in that particular region. The large variability in inter- and intra-pecie venom contitution make development of anti-venom challenging. Thi i compounded by the requirement of having venom from all the particular pecie available to manufacturing companie. Economical and ditribution difficultie reult in anti-venom being unavailable to large population that are at particular rik of nake bite. Anti-venom reaction are common, with more than 10% of patient developing a reaction. Thee vary from early Type I hyperenitivity reaction to late erum ickne type reaction. Hyperenitivity i due to the ue of animal erum and patient with previou expoure to animal erum are at particular rik. The ue of pre-adminitration enitivity teting i inaccurate, wate time in patient that are critically ill and hould therefore be avoided 2. Anti-venom hould alway be adminitered, reource 50 COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

7 permitting, with uitable monitoring and reucitation equipment available. Intra-mucular adrenaline i the treatment of choice in patient with immediate reaction. Corticoteroid and anti-hitamine are indicated a in other caue of anaphylaxi. Patient who receive anti-venom mut be monitored for at leat 2 hour pot-adminitration. The lack of anti-venom availability and the rik of it adminitration mut alway be conidered by the clinician treating a patient with nakebite. The majority of bite victim can be managed afely and uccefully without anti-venom. Adminitration mut, however, not be delayed in cae in which antivenom i indicated (Table 1). Clinician mut familiarie themelve with regional anti-venom availability and whom to contact to obtain thee in cae of a venomou bite. Concluion Snake bite i a huge public health concern, motly affecting thoe in rural area in low and middle income countrie with poor acce to healthcare. Thi i further complicated by a lack of availability of anti-venom, and no good quality evidence bae on how to manage bite mot effectively. Thi paper help to provide clinician who might have to treat nake bite patient with information on the identification and management of the yndromic equelae of nake bite, with or without the availability of anti-venom. It i eential that the evidence bae for effective nake bite treatment i expanded in order to reduce the devatating public health impact of thi neglected tropical dieae. Reference 1. World Health Organiation. Neglected Tropical Dieae: Snakebite. [ Acceed 08/09/ Warrell DA (2010). Snake Bite. Lancet 375: William D, Gutierrez JM, Harrion R et al (2010). The Global Snake Bite Initiative: an antidote for nake bite. Lancet 375: Chippaux JP (2011). Etimate of the burden of nakebite in ub-saharan Africa: a metaanalytic approach. Toxicon 57: Swaroop S, Grab B (1954) Snakebite mortality in the world. Bull World Health Organ 10: Chippaux JP (1998). Snake-bite: appraial of the global ituation. Bull World Health Organ 76: Katuriratne A, Wickremainghe AR, de Silva N et al (2008). The Global Burden of Snakebite: a literature analyi and modelling baed on regional etimate of envenoming and death. PLoS Med 5 (11): Godpower MC, Thatcher TD, Shehu M (2011). The effect of pre-hopital care for venomou nake bite on outcome in Nigeria. Tran Roy Soc Trop Med Hyg 105: Pugh RN, Theakton RD, Reid HA (1980). Malumfahi Endemic Dieae Reearch Project, XIII. Epidemiology of human encounter with the pitting cobra, Naja nigricolli, in the Malumfahi area of northern Nigeria. Ann Trop Med Paraitol 74: Tun-Pe, Phillip RE, Warrell DA, et al (1987). Acute and chronic pituitary failure reembling Sheehan yndrome following bite by Ruell viper in Burma. Lancet 2: Norri RL, Auerbach PS, Nelon EE, Bite and Sting (2008) In: Saviton Textbook of Surgery, Saunder-Elevier, Philadelphia, p Sitprija V (2006). Snakebite nephropathy. Nephrology 11: White J (2005). Snake venom and coagulopathy. Toxicon 35: Gutierrez JM, Leon G, Burnouf T (2011). Antivenom for the treatment of nakebite envenoming: The road ahead. Biological 39: Blaylock RS (2005). The identification and yndromic management of nakebite in South Africa. SA Fam Pract (9): COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

8 16. Gubenek F, Ritonja A, Cotic V, et al (1982). Ditribution of vipera ammodyte toxic phopholipae A in the cat and it ability to cro the blood brain barrier. Toxicon 20: Rocha e Silva M, Beraldo WT, Roenfeld G (1949). Bradykinin, a hypotenive and mooth mucle timulating factor releaed from plama globulin by nake venom and by trypin. Am J Phyiol 156: Ducancel F (2005). Endothelin-like peptide. Cell Mol Life Sci 62: Gutierrez JM, Theakton RDG, Warrell DA (2006). Confronting the neglected problem of nake bite envenoming: the need for a global partnerhip. PLoS Med 3(6): Ariaratnam CA, Sheriff MHR, Arambepola C et al (2009). Syndromic approach to treatment of nake bite in Sri Lanka baed on reult of a propective national hopital-baed urvey of patient envenomed by identified nake. Am J Trop Med Hyg 81(4): Sutherland SK, Coulter AR, Harri RD (1979). Rationaliation of firt-aid meaure for elapid nakebite. Lancet 1: Anker RL, Straff on WG, Loielle DS et al (1982). Retarding the uptake of mock venom in human: comparion of three firt-aid treatment. Med J Aut 1: Canale E, Ibiter GK, Currie BJ (2009). Invetigating preure bandaging for nakebite in a imulated etting: bandage type, training and the effect of tranport. Emerg Med Autrala 2009; 21: Warrell DA (1999). WHO/SEARO Guideline for the clinical management of nake bite in the Southeat Aian region. SE J Trop Med Publ Hlth 30 (uppl 1): Gold BS, Dart RC, Barih RA (2002). Bite of venomou nake. N Eng J Med 347(5): American College of Surgeon Committee on Trauma (2008). Advanced trauma life upport for doctor [8 th Edition], American college of Surgeon, Chicago. 27. Blaylock RSM (2003). Femoral veel entrapment and compartment yndrome following nakebite. S Afr J Surg 41 (3) : COSECSA/ASEA Publication -Eat and Central African Journal of Surgery. November/December 2013 Vol. 18 (3)

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