Besselink Marc Gh, van Santvoort Hjalmar C, Buskens Erik, Boermeester Marja A, van Goor Harry, Timmerman Harro M, Nieuwenhuijs Vincent B, Bollen Thomas L, van Ramshorst Bert, Witteman Ben Jm, Rosman Camiel, Ploeg Rutger J, Brink Menno A, Schaapherder Alexander Fm, Dejong Cornelis Hc, Wahab Peter J, van Laarhoven Cees Jhm, van der Harst Erwin, van Eijck Casper Hj, Cuesta Miguel A, Akkermans Louis Ma, Gooszen Hein G
Department of Surgery, University Medical Center Utrecht, Utrecht, Netherlands.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands; Department of Epidemiology, University Medical Center Groningen, Groningen, Netherlands.
Lancet. 2008 Feb 23;371(9613):651-659. doi: 10.1016/S0140-6736(08)60207-X. Epub 2008 Feb 14.
Infectious complications and associated mortality are a major concern in acute pancreatitis. Enteral administration of probiotics could prevent infectious complications, but convincing evidence is scarce. Our aim was to assess the effects of probiotic prophylaxis in patients with predicted severe acute pancreatitis.
In this multicentre randomised, double-blind, placebo-controlled trial, 298 patients with predicted severe acute pancreatitis (Acute Physiology and Chronic Health Evaluation [APACHE II] score > or =8, Imrie score > or =3, or C-reactive protein >150 mg/L) were randomly assigned within 72 h of onset of symptoms to receive a multispecies probiotic preparation (n=153) or placebo (n=145), administered enterally twice daily for 28 days. The primary endpoint was the composite of infectious complications--ie, infected pancreatic necrosis, bacteraemia, pneumonia, urosepsis, or infected ascites--during admission and 90-day follow-up. Analyses were by intention to treat. This study is registered, number ISRCTN38327949.
One person in each group was excluded from analyses because of incorrect diagnoses of pancreatitis; thus, 152 individuals in the probiotics group and 144 in the placebo group were analysed. Groups were much the same at baseline in terms of patients' characteristics and disease severity. Infectious complications occurred in 46 (30%) patients in the probiotics group and 41 (28%) of those in the placebo group (relative risk 1.06, 95% CI 0.75-1.51). 24 (16%) patients in the probiotics group died, compared with nine (6%) in the placebo group (relative risk 2.53, 95% CI 1.22-5.25). Nine patients in the probiotics group developed bowel ischaemia (eight with fatal outcome), compared with none in the placebo group (p=0.004).
In patients with predicted severe acute pancreatitis, probiotic prophylaxis with this combination of probiotic strains did not reduce the risk of infectious complications and was associated with an increased risk of mortality. Probiotic prophylaxis should therefore not be administered in this category of patients.
感染性并发症及相关死亡率是急性胰腺炎的主要关注点。肠道给予益生菌可预防感染性并发症，但确凿证据匮乏。我们的目的是评估益生菌预防对预测为重症急性胰腺炎患者的影响。
在这项多中心随机、双盲、安慰剂对照试验中，298例预测为重症急性胰腺炎（急性生理与慢性健康状况评分[APACHE II]≥8分、Imrie评分≥3分或C反应蛋白>150mg/L）的患者在症状出现72小时内被随机分配，接受多种益生菌制剂（n = 153）或安慰剂（n = 145），每天经肠道给药两次，共28天。主要终点是住院期间及90天随访期内感染性并发症的综合情况，即感染性胰腺坏死、菌血症、肺炎、泌尿道感染或感染性腹水。分析采用意向性治疗。本研究已注册，注册号为ISRCTN38327949。
每组各有1人因胰腺炎诊断错误被排除在分析之外；因此，对益生菌组的152例个体和安慰剂组的144例个体进行了分析。两组在患者特征和疾病严重程度方面基线情况大致相同。益生菌组46例（30%）患者发生感染性并发症，安慰剂组41例（28%）患者发生感染性并发症（相对危险度1.06，95%可信区间0.75 - 1.51）。益生菌组24例（16%）患者死亡，安慰剂组9例（6%）患者死亡（相对危险度2.53，95%可信区间1.22 - 5.25）。益生菌组9例患者发生肠道缺血（8例死亡），安慰剂组无1例发生（p = 0.004）。
在预测为重症急性胰腺炎的患者中，使用这种益生菌菌株组合进行预防并不能降低感染性并发症的风险，且与死亡率增加相关。因此，这类患者不应给予益生菌预防。
