From the Department of Anesthesia, Indiana University School of Medicine, Indianapolis, Indiana.
Division of Human Genetics.
Anesth Analg. 2021 Oct 1;133(4):991-999. doi: 10.1213/ANE.0000000000005579.
Safe postoperative pain relief with opioids is an unmet critical medical need in children. There is a lack of objective, noninvasive bedside tool to assess central nervous system (CNS) effects of intraoperative opioids. Proactive identification of children at risk for postoperative respiratory depression (RD) will help tailor analgesic therapy and significantly improve the safety of opioids in children. Quantitative pupillometry (QP) is a noninvasive, objective, and real-time tool for monitoring CNS effect-time relationship of opioids. This exploratory study aimed to determine the association of QP measures with postoperative RD, as well as to identify the best intraoperative QP measures predictive of postoperative RD in children.
After approval from the institutional review board and informed parental consent, in this prospective, observational study of 220 children undergoing tonsillectomy, QP measures were collected at 5 time points: awake preoperative baseline before anesthesia induction (at the time of enrollment [T1]), immediately after anesthesia induction before morphine administration (T2), 3 minutes after intraoperative morphine administration (T3), at the end of surgery (T4), and postoperatively when awake in postanesthesia recovery unit (PACU) (T5). Intraoperative use of opioid and incidence of postoperative RD were collected. Analyses were aimed at exploring correlations of QP measures with the incidence of RD and, if found significant, to develop a predictive model for postoperative RD.
Perioperative QP measures of percentage pupil constriction (CONQ, P = .027), minimum pupillary diameter (MIN, P = .027), and maximum pupillary diameter (MAX, P = .034) differed significantly among children with and without postoperative RD. A predictive model including the minimum pupillary diameter 3 minutes after morphine administration (MIN3), minimum pupillary diameter normalized to baseline (MIN31), and percentage pupillary constriction after surgery (T4) standardized to baseline (T1) (CONQ41), along with the weight-based morphine dose performed the best to predict postoperative RD in children (area under the curve [AUC], 0.76).
A model based on pre- and intraoperative pupillometry measures including CONQ, MIN, along with weight-based morphine dose-predicted postoperative RD in our cohort of children undergoing tonsillectomy. More studies with a larger sample size are required to validate this finding.
安全的术后镇痛是小儿麻醉领域尚未满足的关键医学需求。目前缺乏客观、无创的床边工具来评估术中阿片类药物对中枢神经系统（CNS）的影响。前瞻性识别有术后呼吸抑制（RD）风险的儿童，有助于制定镇痛治疗方案，并显著提高儿童使用阿片类药物的安全性。瞳孔定量测量（QP）是一种非侵入性、客观和实时的监测 CNS 对阿片类药物作用时间关系的工具。本探索性研究旨在确定 QP 测量与术后 RD 的相关性，并确定术中 QP 测量中预测儿童术后 RD 的最佳指标。
本前瞻性观察性研究纳入 220 例行扁桃体切除术的儿童，在获得机构审查委员会和家长知情同意后，于麻醉诱导前清醒的术前基础状态（麻醉诱导时[T1]）、麻醉诱导前吗啡给药前即刻（T2）、术中吗啡给药后 3 分钟（T3）、手术结束时（T4）和术后麻醉恢复室（PACU）清醒时（T5）共 5 个时间点收集 QP 测量值。收集术中阿片类药物的使用情况和术后 RD 的发生率。分析旨在探索 QP 测量值与 RD 发生率的相关性，如果存在显著相关性，则建立术后 RD 的预测模型。
术后 RD 儿童与无 RD 儿童的瞳孔收缩百分比（CONQ，P=.027）、最小瞳孔直径（MIN，P=.027）和最大瞳孔直径（MAX，P=.034）等围术期 QP 测量值存在显著差异。包括术后 3 分钟时最小瞳孔直径（MIN3）、MIN3 标准化至基础值（MIN31）和术后标准化至基础值（T1）的瞳孔收缩百分比（T4）（CONQ41）和基于体重的吗啡剂量的预测模型，对预测本研究中接受扁桃体切除术的儿童术后 RD 的效果最佳（曲线下面积[AUC]，0.76）。
包括 CONQ、MIN 在内的术前和术中瞳孔测量以及基于体重的吗啡剂量的预测模型可预测本研究中接受扁桃体切除术的儿童术后 RD。需要更大样本量的研究来验证这一发现。
