Venom Concentrations and Clotting Factor Levels in a Prospective Cohort of Russell’s Viper Bites with Coagulopathy

Background Russell’s viper envenoming is a major problem in South Asia and causes venom induced consumption coagulopathy. This study aimed to investigate the kinetics and dynamics of venom and clotting function in Russell’s viper envenoming. Methodology/Principal Findings In a prospective cohort of 146 patients with Russell’s viper envenoming, we measured venom concentrations, international normalised ratio [INR], prothrombin time (PT), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, and von Willebrand factor antigen. The median age was 39y (16–82y) and 111 were male. The median peak INR was 6.8 (interquartile range[IQR]:3.7 to >13), associated with low fibrinogen [median,13), associated with low fibrinogen [median,3 at 6h post-antivenom but had reduced to Conclusions Russell’s viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations

Snake Bite in South Asia: A Review

Snake bite is one of the most neglected public health issues in poor rural communities living in the tropics. Because of serious misreporting, the true worldwide burden of snake bite is not known. South Asia is the world's most heavily affected region, due to its high population density, widespread agricultural activities, numerous venomous snake species and lack of functional snake bite control programs. Despite increasing knowledge of snake venoms' composition and mode of action, good understanding of clinical features of envenoming and sufficient production of antivenom by Indian manufacturers, snake bite management remains unsatisfactory in this region. Field diagnostic tests for snake species identification do not exist and treatment mainly relies on the administration of antivenoms that do not cover all of the important venomous snakes of the region. Care-givers need better training and supervision, and national guidelines should be fed by evidence-based data generated by well-designed research studies. Poorly informed rural populations often apply inappropriate first-aid measures and vital time is lost before the victim is transported to a treatment centre, where cost of treatment can constitute an additional hurdle. The deficiency of snake bite management in South Asia is multi-causal and requires joint collaborative efforts from researchers, antivenom manufacturers, policy makers, public health authorities and international funders

Adjunct treatment in snakebite envenoming: A systematic review of randomised controlled trials

Adjunct therapy in snakebite may be lifesaving if administered appropriately or can be harmful if non-judicious use leads to avoidable delays in administering antivenom. This systematic review analyses the evidence from randomised controlled trials (RCTs) on the efficacy of adjunct treatment administered with antivenom. PubMed, EMBASE, Scopus, Cochrane library and CINAHL were searched for RCTs enrolling patients with snakebite envenoming where a treatment other than antivenom has been assessed for its efficacy within the last 25 y. Fifteen studies met the inclusion criteria. The interventions assessed were categorised as adjunct therapies (heparin or fresh frozen plasma) to reverse haemotoxicity (three studies), antibiotics to prevent local infections (three studies), steroids to reduce local swelling (one study), premedication (adrenaline, steroids and antihistamines, either alone or in combination) to reduce hypersensitivity reactions to antivenom (five studies) and other interventions (three studies). Apart from a beneficial effect of low-dose adrenaline (1:1000, 0.25 ml administered subcutaneously) in preventing antivenom-induced hypersensitivities (OR: 0.54, 95% CI 0.32 to 0.93, two RCTs, 354 participants, moderate certainty evidence) in Sri Lanka, evidence for any other adjunct therapy is either non-existent or needs confirmation by larger better designed trials

Lack of controlled studies on snakebite prevention: a rapid review

Globally, snakebites cause an estimated 80 000–140 000 deaths annually. While there are evidence-based recommendations for managing snakebite victims, recommendations on the prevention of snakebites are limited to expert opinions. We conducted a rapid review to summarise evidence from human studies with a control group on preventing snakebites. Searching PubMed, Web of Science, Scopus, CINAHL and EMBASE with inclusive search terms without language or time limits only yielded three eligible studies (one case control study and two prospective controlled clinical studies), highlighting a knowledge gap. Two studies in Nepal by the same group showed that health education of stakeholders and sleeping under a bednet can significantly reduce snakebite incidence (p<0.05), but these observations are not confirmed elsewhere, and because of the high risk of bias the certainty of evidence was low. The third study from Sri Lanka, which assessed if sleeping above ground would prevent snakebites, had inconclusive results. This demonstrates an urgent need for studies with a control group to guide evidence-based recommendations for snakebite prevention. Potential interventions tested can range from low-cost measures such as wearing appropriate footwear in resource-limited settings to testing the efficacy of chemical, biological (e.g. rodent control) or device-based methods and community-supported platforms tracking snakebite sightings with real-time geolocation data in highly resourced settings

Management of scorpion envenoming: A systematic review and meta-analysis of controlled clinical trials

Background: Scorpion stings cause an estimated 3000 deaths per annum worldwide. We conducted a systematic review of all controlled clinical trials related to scorpion sting management. Methods: We searched PubMed, EMBASE, Scopus, Web of Science and CINAHL and included controlled prospective clinical trials (randomized or non-randomized). The following interventions were assessed: adults and children with scorpion stings treated with (a) steroids vs. placebo, (b) different methods of pain relief, (c) antivenom vs. supportive treatment, (d) prazosin vs. supportive treatment, (e) antivenom vs. prazosin and (f) antivenom plus prazosin vs. prazosin alone. When trials had comparative outcomes, they were combined in a meta-analysis. Data was analysed with Review Manager 5. Dichotomous data were compared with relative risk (RR), and continuous data were compared with mean differences using a fixed effect model. There is no PROSPERO registration number for this study. Results: Antivenom against Centruroides sp. are effective in reversing the clinical syndrome faster than no antivenom treatment in children (RR, 0.02; 95% CI, 0.01 to 0.06; 322 participants; three trials). Antivenom (against Mesobuthus tamulus) and prazosin combination is better than prazosin alone for faster resolution of symptoms (mean difference, -12.59 h; 95% CI, -14.01 to -11.17; 173 participants; three trials). Conclusions: The polyvalent antivenom against Centruroides sp. in USA/Mexico and the monovalent antivenom against M. tamulus in India are effective for rapid resolution of symptoms. Prazosin is useful as an add-on therapy for M. tamulus stings

Oral pyridoxine can substitute for intravenous pyridoxine in managing patients with severe poisoning with isoniazid and rifampicin fixed dose combination tablets: a case report

Abstract Background Fixed drug combination of isoniazid and rifampicin is a rare cause of poisoning even in endemic countries for tuberculosis infection. Severe poisoning can cause severe morbidity and mortality if not treated promptly. Though intravenous pyridoxine is the preferred antidote for severe standard isoniazid poisoning it is not freely available even in best of care centers. We describe a case of severe poisoning with fixed drug combination of isoniazid and rifampicin successfully managed with oral pyridoxine at national hospital of Sri Lanka. Case presentation A 22 year old, Sri Lankan female presented to a local hospital 1 h after self-ingestion of 28 tablets of fixed drug combination of isoniazid and rifampicin which contained 4.2 g of standard isoniazid and 7.2 g of rifampicin. One and half hours after ingestion she developed generalized tonic–clonic seizure with loss of consciousness. She was given intravenous diazepam 5 mg immediately and transferred to national hospital of Sri Lanka, for further care. Upon arrival to tertiary care hospital in 3.5 h of poisoning she had persistent vomiting, dizziness and headache. On examination, she was drowsy but arousable, orange–red discoloration of the body was noted even with the dark skin complexion. She also had orange–red colour urine and vomitus. Pulse rate was 104 beats/min, blood pressure 130/80 mmHg, respiratory rate was 20 breaths/min. The arterial blood gas analysis revealed compensated metabolic acidosis and mildly elevated lactic acid level. Considering the clinical presentation with neurological toxicity and the large amount of isoniazid dose ingested, crushed oral tablets of pyridoxine 4.2 g (equal to standard isoniazid dose ingested) administered immediately via a nasogastric tube since intravenous preparation was not available in the hospital. Simultaneously forced diuresis using intravenous 0.9% saline was commenced in order to enhance excretion of toxic metabolites via kidneys. She had no recurrence of seizures but had acute liver injury subsequently which gradually improved with supportive care. Her liver functions found to be completely normal 1 week after the discharge. Conclusions Poisoning with fixed drug combination of isoniazid and rifampicin tablets is rare but can cause severe morbidity and mortality if not treated promptly. Oral pyridoxine can substitute for intravenous pyridoxine with almost similar efficacy at a low cost in managing patients with acute severe standard isoniazid poisoning in resource poor setting

Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with incomplete clotting factor consumption

Context: Limited information exists on the coagulopathy caused by hump-nosed pit viper ( Hypnale hypnale ) envenoming. Objectives: This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies. Materials and methods . Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26 – 51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5 – 2.2; Range: 1.3 to > 12) and median highest aPTT was 54 s (46 – 72 s; Range: 35 – 170 s). There was low fibrinogen [median: 1.3 g/L;1, – 1.8 g/L; Range: < 0.2 – 2.9], low factor VIII levels [median: 23%; 16 – 37%] and low factor V levels [median: 43%; 23 – 74%]. D-Dimer concentrations [median: 3.4 mg/L; 2 – 7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal. Discussion and Conclusions: Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme

Detection of venom after antivenom is not associated with persistent coagulopathy in a prospective cohort of Russell's viper (Daboia russelii) envenomings.

Background: Venom recurrence or persistence in the circulation after antivenom treatment has been documented many times in viper envenoming. However, it has not been associated with clinical recurrence for many snakes, including Russell's viper (Daboia spp.). We compare the recovery of coagulopathy to the recurrence or persistence of venom in patients with Russell's viper envenoming. Methodology/Principal Findings: The study included patients with Russell's viper (D. russelii) envenoming presenting over a 30 month period who had Russell's viper venom detected by enzyme immunoassay. Demographics, information on the snake bite, and clinical effects were collected for all patients. All patients had serum collected for venom specific enzyme immunoassay and citrate plasma to measure fibrinogen levels and prothrombin time (international normalised ratio; INR). Patients with venom recurrence/persistence were compared to those with no detectable recurrence of venom. There were 55 patients with confirmed Russell's viper envenoming and coagulopathy with low fibrinogen concentrations: 31 with venom recurrence/persistence, and 24 with no venom detected post-antivenom. Fibrinogen concentrations increased and INR decreased after antivenom in both the recurrence and non-recurrence patients. Clinical features, laboratory parameters, antivenom dose and length of hospital were similar for both groups. Pre-antivenom venom concentrations were higher in patients with venom recurrence/persistence with a median venom concentration of 385 ng/mL (16–1521 ng/mL) compared to 128 ng/mL (14–1492 ng/mL; p = 0.008). Conclusion: Recurrence of Russell's viper venom was not associated with a recurrence of coagulopathy and length of hospital stay. Further work is required to determine if the detection of venom recurrence is due to the venom specific enzyme immunoassay detecting both venom-antivenom complexes as well as free venom

Dataset for "Detection of venom after antivenom is not associated with persistent coagulopathy in a prospective cohort of Russell's viper (Daboia russelii) envenomings"

Supplementary data for the journal article: 'Detection of Venom after Antivenom Is Not Associated with Persistent Coagulopathy in a Prospective Cohort of Russell's Viper (Daboia russelii) Envenomings