Pujo Jean Marc, Houcke Stephanie, Lontsi Ngoulla Guy Roger, Laurent Vivian, Signaté Boubacar, Mutricy Rémi, Frémery Alexis, Nkontcho Flaubert, Ben Amara Ibtissem, Gutiérrez José María, Resiere Dabor, Kallel Hatem
Emergency Department, Cayenne General Hospital, Cayenne, French Guiana.
Tropical Biome and Immunopathology CNRS UMR-9017, Inserm U 1019, Université de Guyane, Cayenne, French Guiana.
Lancet Reg Health Am. 2025 Jan 18;42:100994. doi: 10.1016/j.lana.2025.100994. eCollection 2025 Feb.
Snakebite (SB) envenoming is an acute emergency requiring early care delivery. However, sometimes, patients can take several hours before receiving antivenom (AV). We conducted this study to assess the effectiveness of antivenom in the recovery of clotting parameters in patients consulting tardily after SB envenoming in French Guiana. The primary endpoint of our study was to investigate the time needed from SB to recovery from SB-induced coagulopathy. The secondary endpoint was to investigate the time needed from AV administration to recovery from SB-induced coagulopathy in patients receiving AV (late or very late administration).
This prospective observational study was conducted in the Intensive Care Unit (ICU) of Cayenne General Hospital between January 2016 and September 2023. We included all patients hospitalized for SB envenoming who either did not receive AV or received it more than 6 h after SB. We excluded patients who received antivenom in less than 6 h from the SB and those who received incomplete AV doses.
We included 58 patients in the No AV group, 51 in the late AV group (6 h ≤ AV < 12 h), and 50 in the very late AV group (AV≥12 h). The median age of patients was 42 years (IQR: 29-53), 65.4% were male and 34.6% were female (104 and 55 out of 159 patients) without difference regarding the demographic parameters between groups. Data regarding ethnicity was not available. The median time from SB to AV was 8.5 h (IQR: 6.9-10) in the late AV group and 21.1 h (IQR: 16.7-27.4) in the very late AV group (p < 0.001). The time from SB to normal clotting parameters was shorter in patients receiving late AV than in those receiving very late AV and those not receiving AV. No differences were observed in the time from SB and recovery of fibrinogen and activated partial thromboplastin time (aPTT) between very late AV and no AV. However, the International Normalized Ratio (INR) recovery was shorter in the very late AV group than in the no AV group. On the other hand, the time from AV to normal fibrinogen was shorter in patients receiving very late AV than in patients receiving late AV (Log-Rank = 0.020). Meanwhile, the time from AV to normal INR or normal aPTT was similar in patients receiving very late AV compared to patients receiving late AV (Log-Rank = 0.722 and 0.740, respectively).
Late AV administration effectively reverses coagulopathic manifestations after SB envenoming. However, very late AV administration did not improve the correction of some clotting parameters when compared to patients not receiving AV. Our findings could be explained by the combination of venom toxicokinetics and the kinetics of the synthesis of clotting factors.
No funding.
蛇咬伤中毒是一种需要早期治疗的急性紧急情况。然而，有时患者在接受抗蛇毒血清（AV）之前可能需要数小时。我们开展这项研究，以评估抗蛇毒血清对法属圭亚那蛇咬伤中毒后延迟就诊患者凝血参数恢复的有效性。我们研究的主要终点是调查从蛇咬伤到蛇咬伤所致凝血病恢复所需的时间。次要终点是调查接受抗蛇毒血清（延迟或非常延迟给药）的患者从抗蛇毒血清给药到蛇咬伤所致凝血病恢复所需的时间。
这项前瞻性观察性研究于2016年1月至2023年9月在卡宴综合医院重症监护病房（ICU）进行。我们纳入了所有因蛇咬伤中毒住院且未接受抗蛇毒血清或在蛇咬伤后6小时以上接受抗蛇毒血清的患者。我们排除了在蛇咬伤后不到6小时接受抗蛇毒血清的患者以及接受抗蛇毒血清剂量不全的患者。
我们在未接受抗蛇毒血清组纳入了58例患者，在延迟抗蛇毒血清组（6小时≤抗蛇毒血清给药时间＜12小时）纳入了51例患者，在非常延迟抗蛇毒血清组（抗蛇毒血清给药时间≥12小时）纳入了50例患者。患者的中位年龄为42岁（四分位间距：29 - 53岁），65.4%为男性，34.6%为女性（159例患者中的104例和55例），各组之间的人口统计学参数无差异。关于种族的数据不可用。延迟抗蛇毒血清组从蛇咬伤到抗蛇毒血清给药的中位时间为8.5小时（四分位间距：6.9 - 10小时），非常延迟抗蛇毒血清组为21.1小时（四分位间距：16.7 - 27.4小时）（p＜0.001）。接受延迟抗蛇毒血清的患者从蛇咬伤到正常凝血参数的时间比接受非常延迟抗蛇毒血清的患者和未接受抗蛇毒血清的患者短。在非常延迟抗蛇毒血清组和未接受抗蛇毒血清组之间，从蛇咬伤到纤维蛋白原恢复以及活化部分凝血活酶时间（aPTT）恢复的时间未观察到差异。然而，非常延迟抗蛇毒血清组的国际标准化比值（INR）恢复时间比未接受抗蛇毒血清组短。另一方面，接受非常延迟抗蛇毒血清的患者从抗蛇毒血清给药到正常纤维蛋白原的时间比接受延迟抗蛇毒血清的患者短（对数秩检验=0.020）。同时，接受非常延迟抗蛇毒血清的患者与接受延迟抗蛇毒血清的患者相比，从抗蛇毒血清给药到正常INR或正常aPTT的时间相似（对数秩检验分别为0.722和0.740）。
延迟给予抗蛇毒血清可有效逆转蛇咬伤中毒后的凝血病表现。然而，与未接受抗蛇毒血清的患者相比，非常延迟给予抗蛇毒血清并未改善某些凝血参数的纠正情况。我们的研究结果可以通过毒液毒代动力学和凝血因子合成动力学的结合来解释。
无资金支持。
