■抗蛇毒血清是全球治疗蛇毒的一线药物,尽管很少有安慰剂对照临床试验证明有效性。我们旨在研究红腹黑蛇(Pseudechis卟啉)咬伤中的早期抗蛇毒血清是否会预防全身性肌毒性。
我们对澳大利亚蛇咬伤项目(2014年7月至2020年6月)招募的患者进行了抗蛇毒血清治疗红腹黑蛇咬伤的多中心随机安慰剂对照试验。此外,我们报告了同期所有红腹黑蛇咬伤的患者,比较相同的结果。2岁以上有明确红腹黑蛇咬伤和早期全身效应的患者在咬伤后6小时内随机接受50%的葡萄糖(安慰剂)或虎蛇抗蛇毒血清。或在队列组中接受由治疗临床医生确定的抗蛇毒血清.主要结果是具有肌毒性(峰值肌酸激酶活性>1,000U/L)的患者比例。次要结果是:48小时内总肌酸激酶升高的曲线下面积,抗蛇毒血清后的毒液的存在,和不良反应。我们分析了随机对照试验患者以及随机对照试验和队列患者的组合。
■招募了15名患者参加随机对照试验,一组68例未随机分组的患者被纳入分析.治疗后,给予安慰剂的7例患者中有2例的肌酸激酶活性峰值>1,000U/L,而给予抗蛇毒血清的8例患者中没有一例(差异有利于抗蛇毒血清;29%;95%置信区间:-18%至+70%;P=0.2).安慰剂组患者48小时内肌酸激酶总升高曲线下面积中位数为0U/L。h(四分位数间距:0-124U/Lh),与给予抗蛇毒血清者无显著差异:197U/L*h(四分位距:0-66,353U/L*h;P=0.26)。在6例接受抗蛇毒血清浓度测定的患者中未检测到抗蛇毒血清后的毒液。两名服用抗蛇毒血清的患者出现了立即的超敏反应,一次严重的过敏反应,另一个有血清病。结合随机和非随机患者,36例(8%)抗蛇毒血清在咬伤后6小时内的肌酸激酶活性峰值>1,000U/L,17例(36%)患者在咬伤后6小时内未接受抗蛇毒血清(差异为29%;95%置信区间:8%-44%;P<0.004)。总的来说,13/36(36%)在6小时内服用抗蛇毒血清的患者出现超敏反应,6例严重过敏反应(17%)。
■我们发现早期抗蛇毒作用于红腹黑蛇咬伤,只有3名患者需要在6小时内给予抗蛇毒血清以防止1名患者的肌毒性(需要治疗的人数=3)。然而,三分之一服用抗蛇毒血清的患者出现超敏反应,六分之一有严重的过敏反应。这项研究的主要局限性是招募到随机对照试验的患者人数很少。
■在咬伤后6小时内服用红腹黑蛇毒血清似乎降低了肌毒性患者的比例,但三分之一的患者有不良反应。
UNASSIGNED: Antivenom is first line treatment for snake envenomation worldwide, despite few placebo controlled clinical trials demonstrating effectiveness. We aimed to investigate whether early antivenom in red-bellied black snake (Pseudechis porphyriacus) bites would prevent systemic myotoxicity.
UNASSIGNED: We undertook a multicentre randomized placebo-controlled
trial of
antivenom for red-bellied black snake bites with patients recruited from the Australian Snakebite Project (July 2014 to June 2020). In addition, we report all patients with red-bellied black snake bites during the same period, comparing the same outcomes. Patients over 2 years of age with definite red-bellied black snake bites and early systemic effects were randomized to receive 50 per cent glucose (placebo) or tiger snake antivenom within 6 hours post-bite, or in the cohort group received antivenom determined by the treating clinician. The primary outcome was the proportion of patients with myotoxicity (peak creatine kinase activity >1,000 U/L). Secondary outcomes were: area under the curve of total creatine kinase elevation over 48 hours, presence of venom post-antivenom, and adverse reactions. We analyzed both the randomized control
trial patients and the combination of randomized control
trial and cohort patients.
UNASSIGNED: Fifteen patients were recruited to the randomized controlled
trial, and a cohort of 68 patients who were not randomized were included in the analysis. After treatment, two of seven patients given placebo had a peak creatine kinase activity >1,000 U/L versus none of the eight given antivenom (difference in favour of antivenom; 29 per cent; 95 per cent confidence interval:-18 per cent to +70 per cent; P = 0.2). The median area under the curve of total creatine kinase elevation over 48 hours in patients given placebo was 0 U/L*h (interquartile range: 0-124 U/L*h), which was not significantly different to those given antivenom: 197 U/L*h (interquartile range: 0-66,353 U/L*h; P = 0.26). Venom was not detected post-antivenom in six patients with measured venom concentrations given antivenom. Two patients given antivenom had immediate hypersensitivity reactions, one severe anaphylaxis, and another had serum sickness. Combining randomized and not randomized patients, three of 36 (8 per cent) administered antivenom less than 6 hours post-bite had a peak creatine kinase activity >1,000 U/L versus 17/47 (36 per cent) patients not receiving antivenom less than 6 hours post-bite (difference in favour of antivenom 29 per cent; 95 per cent confidence interval: 8 per cent to 44 per cent; P < 0.004). Overall, 13/36 (36 per cent) patients administered antivenom within 6 hours had hypersensitivity reactions, six severe anaphylaxis (17 per cent).
UNASSIGNED: We found that early antivenom was effective in red-bellied black snake bites, and only three patients need to be given antivenom within 6 hours to prevent myotoxicity in one (number needed to treat = 3). However, one in three patients administered antivenom developed a hypersensitivity reaction, and one in six had severe anaphylaxis. The major limitation of this
study was the small number of patients recruited to the randomized controlled
trial.
UNASSIGNED: Administration of antivenom in red-bellied black snake envenomation within 6 hours post-bite appeared to decrease the proportion of patients with myotoxicity, but a third of patients had adverse reactions.