Effects of Nalbuphine on Gastrointestinal Function in Post-Operative Critical Ill Patients Admitted to the ICU: A Multicenter Randomized Controlled Trial.

Yun Yan,Enxia Dong,Xijing Zhang,Aiguang Li,Xinyu Li,Bin Li,Chong Lei,Guifen Gan,Binxiao Su,Guangming Wang,Yu Chen

doi:10.3389/fmed.2022.836872

Abstract

BackgroundGastrointestinal (GI) function can be a significant problem in critically ill patients and is associated with detrimental outcomes. The administration of opioids for pain reduction is thought to contribute to GI dysfunction. We tested whether nalbuphine, a mixed agonist/antagonist opioid modulator, can promote GI recovery in postoperative critical patients admitted to the intensive care unit (ICU) and compared it with fentanyl, a selective mu opioid receptor (MOR) agonist.MethodsThis is a multicenter, single-blind, randomized controlled trial to investigate whether nalbuphine improves the GI recovery in ICU patients after surgery, and compared it with fentanyl. The primary outcome was the time to first defecation. Secondary outcomes included the use of sedatives, enemas or laxatives, the acute gastrointestinal injury (AGI) grade, the incidence of vomiting, and the lengths of ICU and hospital stays.ResultsWe randomized 436 patients, and a total of 369 patients were included in the modified intention-to-treat population (mITT) (185 to the nalbuphine group and 184 to the fentanyl group). The baseline demographic characteristics of the two groups were comparable after randomization. There was no significant difference in the time to defecation between the two groups [hazard ratio (HR) 0.94, 95% CI 0.74–1.19, p = 0.62]. There was no significant difference in the secondary outcomes between the two groups.ConclusionWe found no evidence that nalbuphine administration can improve the GI function in postoperative critical patients admitted to the ICU compared with fentanyl. However, the CI was wide and we could not exclude the clinically important difference.

Highlights

Gastrointestinal (GI) dysfunction frequently occurs in critically ill patients; it has an incidence of 50% on the 1st day of admission to the intensive care unit (ICU); and GI dysfunction is associated with increased mortality, the length of ICU stay, and medical costs [1, 2]
Patients were excluded if they had a high Acute Physiologic Chronic Health Evaluation II (APACHE II) score ≥ 23 [13], had an acute gastrointestinal injury (AGI) grade ≥ 3, had severe liver dysfunction (Child-Pugh Grade C), were pregnant, had long time usage of opioids and sedatives, were currently in another trial, and had contraindications for taking the study drugs
We excluded patients without any recorded information and randomized number produced by randomized mistakes in the modified intention-to-treat population (mITT) analysis

Summary

Introduction

Gastrointestinal (GI) dysfunction frequently occurs in critically ill patients; it has an incidence of 50% on the 1st day of admission to the intensive care unit (ICU); and GI dysfunction is associated with increased mortality, the length of ICU stay, and medical costs [1, 2]. The mu opioid receptor (MOR) mainly mediates the inhibition of GI tract. It is crucial to balance GI function and opioid administration. Gastrointestinal (GI) function can be a significant problem in critically ill patients and is associated with detrimental outcomes. A mixed agonist/antagonist opioid modulator, can promote GI recovery in postoperative critical patients admitted to the intensive care unit (ICU) and compared it with fentanyl, a selective mu opioid receptor (MOR) agonist

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Discussion

Conclusion