Duprey Matthew S, Allison Harmony, Garpestad Erik, Riselli Andrew M, Faugno Anthony, Anketell Eric, Devlin John W
School of Public Health, Brown University, Providence, RI, USA.
Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA.
Crit Care Res Pract. 2022 Mar 20;2022:7541378. doi: 10.1155/2022/7541378. eCollection 2022.
Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. . In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days.
Only 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N ( = 6) and ( = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. 66.6%; = 1.0). No patient experienced opioid withdrawal.
Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.
在接受阿片类药物治疗的重症成年患者中，便秘很常见。纳洛西醇（N）是一种外周作用的μ受体拮抗剂（PAMORA），可能会减少便秘。本试验的目的是评估N在预防接受阿片类药物治疗的ICU成年患者便秘方面的疗效和安全性。在这项单中心、双盲、随机试验中，入住接受静脉注射阿片类药物（≥100μg芬太尼/天）且没有17项排除标准中的任何一项的医学ICU的成年患者，被随机分为每日接受N（25mg）或安慰剂（P），并随机接受N（25mg）或安慰剂（P）以及每日两次100mg多库酯，直至ICU出院、10天、出现腹泻（≥3次自发排便（SBM）/24小时）或出现与研究药物相关的严重不良事件。当连续3天没有SBM时，启动4步泻药方案。
在1/17 - 10/19入组期间筛选的1542名成年患者中，只有318名（20.6%）符合所有纳入标准。其中，只有19/381（4.9%）符合所有合格标准。在7例拒绝同意后，12例患者被随机分组。由于入组无效，研究提前终止。N组（n = 6）和P组（n = 6）相似。首次SBM的时间（N组41.4±31.7小时 vs. P组32.5±25.4小时，P = 0.56）相似。N组的最大每日腹压显著更低（N组10±4 vs. P组13±5，P = 0.002）。N组的每日SOFA评分中位数（IQR）更高（N组7（4，8） vs. P组4（3，5），P < 0.001）。泻药方案的使用相似（N组83.3% vs. P组66.6%；P = 0.51）。腹泻发生率很高但相似（N组66.6% vs. P组66.6%；P = 1.0）。没有患者经历阿片类药物戒断。
对于评估使用PAMORA预防便秘的ICU试验，存在重要的招募挑战。尽管样本量不足，但我们的结果表明，如果与安慰剂不同，纳洛西醇导致首次SBM的时间差异可能很小。纳洛西醇对腹压、SOFA的影响以及两者之间的相互作用需要进一步研究。
