Effects of sedatives and opioids on trigger and cycling asynchronies throughout mechanical ventilation: an observational study in a large dataset from critically ill patients

Candelaria De Haro,For The Asynchronies In The Intensive Care Unit (Asynicu) Group ,Yoanna Skrobik,Josefina López-Aguilar,Gastón Murias,Sol Fernandez-Gonzalo,Jaume Montanyà,Robert M Kacmarek,Rudys Magrans,Rafael Fernández,Ana Ochagavia,Montserrat Rue,Guillermo M Albaiceta,Carles Subirà,Lluís Blanch,Umberto Lucangelo,Gemma Gomà,Enrico Lena

doi:10.1186/s13054-019-2531-5

Abstract

BackgroundIn critically ill patients, poor patient-ventilator interaction may worsen outcomes. Although sedatives are often administered to improve comfort and facilitate ventilation, they can be deleterious. Whether opioids improve asynchronies with fewer negative effects is unknown. We hypothesized that opioids alone would improve asynchronies and result in more wakeful patients than sedatives alone or sedatives-plus-opioids.MethodsThis prospective multicenter observational trial enrolled critically ill adults mechanically ventilated (MV) > 24 h. We compared asynchronies and sedation depth in patients receiving sedatives, opioids, or both. We recorded sedation level and doses of sedatives and opioids. BetterCare™ software continuously registered ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI) as well as MV modes. All variables were averaged per day. We used linear mixed-effects models to analyze the relationships between asynchronies, sedation level, and sedative and opioid doses.ResultsIn 79 patients, 14,166,469 breaths were recorded during 579 days of MV. Overall asynchronies were not significantly different in days classified as sedatives-only, opioids-only, and sedatives-plus-opioids and were more prevalent in days classified as no-drugs than in those classified as sedatives-plus-opioids, irrespective of the ventilatory mode. Sedative doses were associated with sedation level and with reduced DC (p < 0.0001) in sedatives-only days. However, on days classified as sedatives-plus-opioids, higher sedative doses and deeper sedation had more IEE (p < 0.0001) and higher AI (p = 0.0004). Opioid dosing was inversely associated with overall asynchronies (p < 0.001) without worsening sedation levels into morbid ranges.ConclusionsSedatives, whether alone or combined with opioids, do not result in better patient-ventilator interaction than opioids alone, in any ventilatory mode. Higher opioid dose (alone or with sedatives) was associated with lower AI without depressing consciousness. Higher sedative doses administered alone were associated only with less DC.Trial registrationClinicalTrial.gov, NCT03451461

Highlights

In critically ill patients, poor patient-ventilator interaction may worsen outcomes
Patients receiving sedatives had a lower level of consciousness than those receiving opioids-only; sedativesplus-opioids decreased the level of consciousness, but did not result in fewer asynchronies than the other treatments
In sedatives-plus-opioids days, the sedative dose was directly associated with the rate of asynchronies and with a lower level of consciousness, whereas higher opioid doses were associated with a lower asynchrony index (AI) without worsening level of consciousness

Summary

Introduction

Sedatives are often administered to improve comfort and facilitate ventilation, they can be deleterious. Whether opioids improve asynchronies with fewer negative effects is unknown. We hypothesized that opioids alone would improve asynchronies and result in more wakeful patients than sedatives alone or sedatives-plus-opioids. Optimizing patient-ventilator interaction may improve outcomes [4]. Adjusting ventilator settings can decrease asynchronies and associated anxiety and dyspnea [5, 6]. Sedatives can cause ventilatory depression affecting respiratory drive and timing, worsening patient-ventilator interaction in proportion to decreasing level of consciousness [7, 8]; these effects appear to differ with different drugs [9, 10]. Sedation is associated with deleterious side effects. Forgoing or minimizing sedatives during MV is increasingly recommended [15,16,17]

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