Gut toxicity in Russell’s and hump-nosed Viper envenomation

Varan Perananthan, Thilini Wijerathne, Fahim Mohamed, Indika Gawarammana, Andrew Dawson, Nicholas Buckley

Objective: Abdominal pain is known to be an early clinical predictor of severe systemic Russell’s Viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain still remains unknown, but might be due to intestinal microvascular endothelial damage. This study hypothesised gut toxicity could be detected using a novel biomarker Intestinal Fatty Acid Binding Protein (I-FABP). We also wanted to explore the mechanisms and consequences of this toxicity. C-reactive protein (CRP) is a non-specific inflammatory biomarker and procalcitonin is a more specific marker of sepsis triggered by bacterial endotoxin. We hypothesised that severe gut injury might lead to gut barrier failure, translocation of gut microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake bite severity, including worsening effects on coagulopathy and renal function, previously attributed to direct venom effects.

Methods: Serial plasma samples of 20 RV envenomations with abdominal pain, 20 Hump-Nosed Viper (HNV) envenomations with abdominal pain and 25 healthy controls were retrospectively assayed for IFABP (Hycult Biotech, Netherlands). The RV patient samples were also assayed for Procalcitonin, CRP and venom levels.

Results: The median I-FABP for healthy controls was 270.1 pg/mL (IQR 153.5 – 558.0 pg/mL) compared to RV 1941.0 pg/mL (715.5 – 7043.0 pg/mL) and HNV 1538.0 pg/mL (IQR 1014.0 – 1866.0 pg/mL). I-FABP was significantly elevated in both RV and HNV samples compared to healthy controls (p<0.001). Median procalcitonin levels on RV samples were elevated 30.12 ng/ml (IQR 13.1 – 59.7 ng/ml), with a level >2 ng/mL indicative of severe sepsis and correlated with I-FABP (p=0.03). CRP levels on Russell’s Viper samples were 17.2 mg/L (IQR 2.9 – 44.7 mg/mL) and had an insignificant correlation with I-FABP (p=0.07).
RV venom levels were only obtained on 6 samples with a median of 331.5 (IQR 1.75 – 2868 ng/mL) with a correlation with I-FABP (p=0.40).

Conclusion: I-FABP was significantly elevated in patients with Russell’s and Hump Nose viper bite, suggesting that direct gut toxicity could be the cause of abdominal pain. I-FABP levels were significantly correlated with procalcitonin. This is consistent with the hypothesis that gut toxicity results in gut barrier failure allowing for the translocation of gut microorganisms into systemic circulation and worsening severity. Abdominal pain is already an established marker of clinical severity in RV envenomation. Further research is required to determine whether I-FABP can be used as a quantitative marker indicating severity in viper envenomation and whether it indicates risk of complications and correlates with other biomarkers such as coagulation studies, creatinine and neurophysiological changes.

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