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When Snakes Bite: Pre-Hospital CareSnake envenomation diagnosis methods -
The 20 Minutes Whole Blood Clotting test was performed on all victims presenting to one of the study centres during the study period.
Out of those with incoagulable blood on admission, the snake species could be determined in 7 cases: 5 were N. naja and 2 were white-lipped pit vipers Trimeresurus cf. No snakebite victim presented with gum bleeding, gut bleeding, or blood in urine on admission.
S2 Table compares clinical features on admission of snakebite victims with identified and unidentified snake species. As the number of cases in which the snake species could be identified by PCR sequencing was low, we investigated baseline characteristics and circumstances of the bite that may influence the sensitivity of this method.
Results are summarized in Table 4. The median time to reach the center was significantly longer in patients with a negative PCR. The probability of a positive PCR result was significantly lower among patients who had used first aid measures.
In particular, applying local remedies e. was associated with a 2-fold decrease in the probability of a positive PCR. Local bleeding also increased the probability of a positive PCR by 1. A total of 67 Eight were put under mechanical ventilation and nine were transferred to a tertiary care centre.
Of these 5 deaths, 4 had been bitten by a B. caeruleus and 1 by a N. Between the 1st of April and the 31st of October , individuals with a history of snakebite presented to one of three study centres in southern Nepal.
In Most species identified were non-venomous ones. The non-venomous checkered keelback X. piscator was the most frequently identified species, followed by the spectacled cobra N. naja and the common krait B. Other venomous species contributing to the snakebite burden in this study comprised several pitvipers O.
monticola , Trimeresurus sp. albolabris , and T. popeiorum as well as various additional elapid snakes, including the first cases of envenoming by the greater black krait Bungarus niger and the king cobra O.
hannah ever reported in Nepal. As few victims Morphological identification of preserved specimens by a qualified herpetologist is the gold standard for species identification.
However, this method is seldom used, as snakes are rarely captured and preserved, and as care-providers working in snakebite treatment centres generally lack the appropriate expertise [ 19 — 21 ]. Alternative approaches must therefore be developed to complement morphological identification.
Molecular techniques have shown promising results in animal models [ 30 — 33 ], and the present study shows that PCR amplification of a mitochondrial gene region from snake trace DNA is feasible in field setting. Sampling is straight forward and requires minimal training see SOP in supplementary material , and the storage and transport conditions for the Prionix evidence collection tubes room temperature and protected from light can easily be met.
The PCR yielded a positive result in This could probably be improved if several factors shown in this study to be associated with a lower sensitivity, such as inappropriate first-aid measures use of tourniquet or application of local remedies on the bite site or prolonged time to reach the treatment centre, were corrected or improved by public health interventions.
Although the sensitivity of the PCR did not seem to be affected by whether the species was venomous or not, envenoming status did have an effect. This may be due to confounding effects of venom injection. An on-going study conducted by the authors is expected to complement this preliminary data and validate PCR-aided sequencing of snake trace DNA on a larger cohort of patients.
Although molecular tools are not yet appropriate for point-of-care POC testing and hence cannot be used to guide clinical management, the encouraging results presented here, if confirmed in larger studies, suggest that they could be used as reference tests in future epidemiological and clinical studies.
Progress in the development and validation of POC tests for snake species has indeed been hindered by the difficult implementation of the diagnostic gold standard morphological identification in rural regions where most bites occur.
Besides, molecular tools could be very useful in clarifying the contribution of different snake species to the snakebite burden, and help identify new medically important species. The species found to have caused neurotoxicity in this study were the two species of cobra N. naja and N.
kaouthia and three different species of krait B. caeruleus , B. lividus , and B. Of these, only two N. naja and B. caeruleus are included in the production of the Indian polyvalent antivenoms that are available in Nepal.
No pre-clinical data exist on the efficacy of Indian polyvalent antivenoms to neutralize the venoms of these two species in Nepal, and no clinical data have been published so far.
In this study, patients bitten by a krait had significantly higher chances of being put under mechanical ventilation and being transferred to an intensive care unit compared to those being bitten by a cobra see supplementary information. This is consistent with published literature which suggests that krait bites often result in poorer outcomes for patients, and high mortality rates [ 34 , 35 ].
The efficacy of the available Indian antivenom in reversing envenoming by kraits is increasingly being questioned, and several case series have reported little or no benefit of immunotherapy [ 17 , 36 — 38 ]. The frequency of neurotoxicity observed in our study is consistent with elapid snake species being most commonly involved in envenoming bites in Nepal.
The fact that we did not observe late-appearing signs such as broken neck sign, muscle weakness and loss of gag reflex may be due to the early presentation of victims to the health centre and the prompt initiation of antivenom therapy.
Interestingly, among those patients who presented with incoagulable blood on admission were five victims of N. naja bites. This is not the first report of apparent coagulopathy following bites by this species [ 39 ], and a few in vitro studies have reported anticoagulant activities in N.
naja venoms [ 40 — 42 ], however, these results need to be interpreted with caution. In fact, the 20 Minutes Whole Blood Clotting Test can give erroneous results if performed incorrectly, in particular if the tubes used bear traces of detergent [ 14 ].
The present study has several limitations, the principal one being that the study population differed between study sites.
Snakebite victims admitted to Bharatpur District Hospital were only included if they presented with signs of neurotoxic envenoming. It is therefore not surprising that all snakes identified in this centre were venomous, resulting in an overestimation of the contribution of venomous species and in particular elapids to the snakebite burden.
When Bharatpur was excluded from the analysis, venomous species accounted for only The checkered keelback and the spectacled cobra remained the most common species identified see supplementary information. Another limitation relates to the geographical coverage of the study.
The list of species identified here is not representative of all snakes causing bites in Nepal. In particular, species found in mountain regions although present, e.
monticola were probably under-represented in our study. The fact that the biting species could be identified only in a relatively small proportion of patients Although we cannot exclude that some selection bias occurred in the present study, its impact is likely to be minimal.
We compared bite circumstances and baseline characteristics of snakebite victims with or without identification of snake species S1 and S2 Tables. Differences were seen with regard to season of bite, location and activity at the time of bite and consultation of a traditional healer.
However, the magnitude of these differences was minimal. Moreover, the epidemiological characteristics of our study population are consistent with other published reports [ 2 — 5 , 8 , 43 , 44 ], further ruling out the possibility of selection bias and reaffirming the external validity of our findings.
Finally, morphological identification and molecular analysis results were both available in only 21 cases, limiting our ability to evaluate the diagnostic performance of the molecular diagnosis method.
Findings presented here thus need to be interpreted with caution. A follow-up prospective validation study is ongoing in Nepal and Myanmar to address this issue. Snakebite envenoming is an important health problem in Nepal, accounting for up to Neurotoxicity following the bites of elapid snakes is of particular concern.
This study for the first time addresses the distribution and medical importance of snake species contributing to the burden of snakebite in Nepal. It provides crucial information for clinicians and health workers involved in the management of snakebite victims in Nepal.
It notably highlights that the majority of bites are caused by non-venomous snakes, and that the diversity of venomous snake species involved in bites is greater than previously believed. Finally, this study provides initial evidence on the utility of forensic DNA-based methods in the identification of biting snake species.
We are grateful to Mamit Rai for his kind help with project coordination and data entry. We also thank all paramedical staff involved in managing the snakebite patients in the three study centres. Conceived and designed the experiments: EA FC UK SKS.
Performed the experiments: SKS PH LB DPP AG. Analyzed the data: EA PH LB UK. Wrote the paper: EA FC SKS. Critical review of the manuscript: UK PH LB DPP AG. Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Snakebite is an important medical emergency in rural Nepal.
Author Summary Snakebite is an important medical problem in sub-tropical and tropical regions, including Nepal where tens of thousands of people are bitten every year.
Introduction In rural Nepal snakebite is an important public health problem. Methods Study setting and population The study was conducted in three centres, namely the Snake Bite Treatment Centre of Damak Red Cross Society and the Snake Bite Management Centre of Charali, both in Jhapa district, and Bharatpur District Hospital, Bharatpur, Chitwan district.
Molecular analysis Whenever the bite site could be located, trace DNA of the biting snake was collected by rubbing the cotton swab of a Prionix evidence collection tube on the bite site see Standard Operating Procedure in supplementary material.
Features of envenoming Local envenoming was defined as the presence of one or more of the following: 1 necrosis, 2 bullae or blisters, 3 enlarged regional lymph nodes plus either local bleeding or ecchymosis or swelling and 4 swelling extending at least halfway between two articulations.
Clinical management of patients The clinical management of snakebite victims followed the Nepal national protocol and WHO SEARO guidelines [ 14 ]. Ethical aspects The study was conducted in accordance with the Declaration of Helsinki , as revised in Seoul, , and in compliance with the protocol, Good Clinical Practices GCP and Nepal regulatory requirements.
Results Between the 1 st of April and the 31 st of October , a total of patients were found eligible to be included in the study Fig 1.
Download: PPT. Fig 1. Flow diagram showing numbers of individuals screened and included in each study centre. Table 1. Epidemiological characteristics The baseline characteristics and circumstances of the bites of the snakebite victims for whom a species could be ascertained, are summarized in Table 2.
Table 2. Table 3. Factors affecting PCR positive rate As the number of cases in which the snake species could be identified by PCR sequencing was low, we investigated baseline characteristics and circumstances of the bite that may influence the sensitivity of this method. Table 4. Factors associated with a positive PCR among snake bite victims.
Management and outcome A total of 67 Discussion Between the 1st of April and the 31st of October , individuals with a history of snakebite presented to one of three study centres in southern Nepal.
Supporting Information. S1 Checklist. STARD checklist. s DOC. S1 Text. no caption. s DOCX. S2 Text. Standard Operating Procedure SOP for the collection, storage and shipment of swab samples.
s PDF. S1 Table. In patients with envenoming, determine which snake or group of snakes is most likely involved. Administer an appropriate antivenom monovalent, combination of monovalent antivenoms, or polyvalent that covers the likely snake s. Admit the patient for observation or adjunctive treatment eg, mechanical ventilation if required.
This process is summarised in Box 3. All patients presenting with a suspected snakebite require an initial full set of investigations INR, aPTT, full blood count, biochemistry, CK level.
Most patients will have no clinical or laboratory features of envenoming when first assessed. Once this initial assessment is complete, these patients can have their PBI if present removed in a critical care area.
If no clinical features of envenoming occur within an hour of PBI removal, patients should be moved to a general clinical area and observed. Evidence of envenoming exists if neurotoxicity develops or the INR, aPTT or CK level becomes abnormal, and antivenom treatment should be considered based on the timing, severity and specific abnormality.
Investigations conducted 1 hour after removal of the PBI may coincide approximately with those required 6 hours after the bite; in this instance, only one set of blood tests are required.
If results of 6-hour laboratory investigations are normal, hour investigations can be delayed a few hours if necessary to avoid recall of overnight laboratory staff.
For the rare circumstances in which a PBI is left on for more than 6 hours, a final set of blood tests and a neurological examination should be done 6 hours after removal of the PBI.
Accumulating data suggest that antivenom might prevent certain envenoming syndromes if used early, 5 , 13 , 27 but may have little, if any, effect once major envenoming syndromes are established.
However, there is no high-level evidence to guide us in this regard. In the absence of evidence from properly conducted trials, clinicians have to balance the risks of giving antivenom anaphylaxis and serum sickness against the potential benefit of giving it early without waiting for confirmation of envenoming.
Any early evidence of envenoming, such as non-specific systemic symptoms or mild coagulopathy, may be an indication for antivenom. Discussion with a clinical toxicologist may be beneficial in these circumstances. Absolute and relative indications for antivenom are listed in Box 4.
Determination of the snake or snake group involved and therefore the appropriate antivenom to be administered requires:.
Observation of the specific clinical syndrome characterised by the clinical and laboratory features at presentation or subsequently Box 2. In some cases, an expert may be available for snake identification, or the person bitten may be a snake handler who can identify the snake.
Snake identification should only be performed by experts such as professional herpetologists and museum curators. Some professional snake handlers may be able to provide accurate identification of the snakes in their possession, which should be used rather than the SVDK.
If there is any doubt about the snake involved, it may be safer to administer polyvalent antivenom or two monovalent antivenoms according to species endemic to the region. In most parts of southern and central—eastern Australia, one vial each of brown snake and tiger snake antivenom will cover the clinically important snakes in the local area, based on the clinical envenoming syndrome.
One vial of relevant snake monovalent antivenom is required to treat both children and adults for all snake types. Recovery of most clinical syndromes of snake envenoming takes time because of their irreversibility or slow reversibility eg, synthesis of new clotting factors required for VICC to resolve.
Some guidelines or previous studies have suggested more than one vial of antivenom should be used for some snakes or in some situations. Antivenom must be given in a critical care area, and staff must be prepared to treat anaphylaxis.
It is advisable to use a small-bore cannula 18—20 G in adults for antivenom infusion and to have a second, large-bore cannula 16—14 G in adults inserted ready for emergency resuscitation Box 5. Antivenom is given diluted in — mL of isotonic saline smaller dilutions should be used for children over 15—30 minutes.
The rate of antivenom administration does not appear to be associated with increased reactions. Reactions appear to be more common with larger-volume antivenoms. Serum sickness can be treated with prednisolone 25 mg daily for 5—7 days. Patients who are given antivenom must be admitted for repeat laboratory testing and observation to determine when envenoming has resolved and to identify complications.
Measurement of INR, aPTT, creatinine level and CK level for myotoxic snakes and a full blood count should be done 6 and 12 hours after administration of antivenom, and then once to twice daily until there is sustained improvement. Thrombotic microangiopathy should be excluded in all patients with VICC by observing no change in creatinine level and platelet count over the first 24 hours.
The role of clotting factor replacement in treating VICC remains contentious. A recent randomised controlled trial of fresh frozen plasma FFP versus no additional treatment within 4 hours of administration of antivenom for VICC found that FFP results in more rapid restoration of clotting function in most patients, but with no decrease in time to discharge.
In the meantime, it is reasonable to administer FFP after giving antivenom to patients who have active bleeding and an imminent threat to their life. FFP is the best factor replacement rather than cryoprecipitate or Prothrombinex-VF [CSL Bioplasma] because patients are deficient in fibrinogen, factor V and factor VIII.
Complications of snake envenoming are rare and generally occur in patients presenting late with severe neuromuscular paralysis, rhabdomyolysis or thrombotic microangiopathy with acute renal failure. Major bleeding may require clotting factor replacement, such as FFP, and supportive care.
Thrombotic microangiopathy may require haemodialysis, but there is no evidence to support the use of plasmapheresis. Significant rhabdomyolysis with acute renal failure is rare but should be treated with generous fluid therapy and close monitoring for electrolyte imbalances eg, hyperkalaemia.
Severe neuromuscular paralysis may require intubation and mechanical ventilation for days or weeks. However, they may develop hypersensitivity reactions to venom, which must be considered in the differential diagnosis. Uncomplicated snakebite can be managed in a hospital with basic laboratory facilities, appropriate antivenom stocks, a critical care area in which to monitor for and treat anaphylaxis, and a clinician capable of treating complications, including anaphylaxis.
Primary retrieval or early interhospital transfer to large centres is not routinely required. However, patients with a suspected snakebite or definite envenoming should be transferred immediately to a hospital with a laboratory that can do a formal INR test, unless it can be done locally with the result available within 2 hours.
Patients with definite systemic envenoming can be admitted to any hospital with close nursing observation, critical care resources and after-hours medical support after antivenom administration — an emergency department observation or short-stay unit is ideal in larger hospitals.
Admission to an intensive care unit is only necessary for patients with major complications, including those with neurotoxic paralysis, thrombotic microangiopathy or severe myotoxicity requiring mechanical ventilation. Expert advice to support these guidelines is available at any time through the National Poisons Information Centre on 13 11 Activation of the clotting pathway by prothrombin activator toxins and consumption of clotting factors fibrinogen, factor V and factor VIII lead to a consumptive coagulopathy.
A descending flaccid paralysis that classically first involves the eye muscles ptosis, diplopia and blurred vision , followed by bulbar muscles, respiratory muscle paralysis and limb paralysis. Provides a good marker of envenoming by all black snakes, including mulga snakes, but is not clinically important.
aPTT is moderately abnormal 1. Non-specific systemic symptoms include nausea, vomiting, abdominal pain, diarrhoea, diaphoresis and headache.
Summary management of snake bite Figure In: eTG complete [internet]. Melbourne: Therapeutic Guidelines Limited, Jul Many reactions will resolve with this step, and the infusion can then be restarted at a slower rate. Lie patient flat, commence high-flow oxygen, support airway and ventilation if required.
Severe antivenom reactions with hypotension will have reduced venous return; supine posture and fluid resuscitation are essential. For hypotension, hypoxaemia, wheeze or upper airway obstruction, give intramuscular adrenaline 0. Alternatively, those experienced with intravenous infusions of adrenaline may go straight to Step 5.
Consider a cautious intravenous infusion of adrenaline — avoid blood pressure surges. Patients with envenoming may be severely coagulopathic, and high blood pressure may cause or worsen intracerebral haemorrhage. Some patients can have exaggerated, hypertensive responses to intramuscular bolus adrenaline, especially to second doses.
If there is no response to Steps 1—4, consider starting a cautious and closely monitored intravenous infusion of adrenaline, which can be reduced as soon as blood pressure starts to recover, preventing blood pressure surges. Use 1 mg in mL by infusion pump: start at 0.
Be aware that as the reaction resolves, adrenaline requirements will fall, the blood pressure will rise and the infusion rate will need to be rapidly reduced. Provenance: Not commissioned; externally peer reviewed.
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Centers for Disease Control and Prevention. Venomous snakes. Venomous snake bites: symptoms and first aid. Snake bites in children. Clemson University. Identifying copperhead snakes. National Wildlife Federation. Government of Alberta. Tennessee Wildlife Resources Agency.
Cottonmouth, Agkistrodon piscivorus. Cottonmouth water moccasin. Coral snake. World Health Organization. Control of neglected tropical diseases. Healthdirect Australia. Snake bites. UC Davis Health System. Six tips for preventing snake bites. South Carolina Department of Natural Resources.
Eastern diamondback rattlesnake. Snakebite envenoming. By Kathi Valeii As a freelance writer, Kathi has experience writing both reported features and essays for national publications on the topics of healthcare, advocacy, and education.
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Myths to Avoid.
The clinical manifestations and diagnosis of snakebites worldwide and the principles Snake envenomation diagnosis methods envenomagion of snakebites Outdoor bootcamp sessions the United Diangosis are Snake envenomation diagnosis methods separately. See "Snakebites diganosis Clinical manifestations and diagnosis" and "Bites by Crotalinae snakes rattlesnakes, water moccasins [cottonmouths], or copperheads in the United States: Clinical manifestations, evaluation, and diagnosis" and "Evaluation and management of coral snakebites". FIRST AID. General principles — Although evidence is limited, generally agreed-upon principles for first aid of snakebite victims are as follows [ ]:. Why UpToDate? Product Editorial Subscription Options Subscribe Sign in. Learn how UpToDate can help you.
Of those, around five dixgnosis will die from venomous snake bites. It's Snwke to Snake envenomation diagnosis methods diagnosix medical attention after a venomous snake bite. Envenomatjon or Snake envenomation diagnosis methods to the nearest emergency room where hospital staff will administer antivenom. This article explains snake bite symptoms, diagnosis, treatment, and prevention. Snake bite symptoms may vary depending on what type of snake bit you. However, some general symptoms accompany many snake bites. Snake bites can result in some common, general symptoms, including:.
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