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, Rudys Magrans, Josefina López-Aguilar, Jaume Montanyà, Enrico Lena, Carles Subirà, Sol Fernandez-Gonzalo, Gemma Gomà, Rafael Fernández, Guillermo M Albaiceta, Yoanna Skrobik, Umberto Lucangelo, Gastón Murias, Ana Ochagavia, Robert M Kacmarek, Montserrat Rue, Lluís Blanch, Asynchronies in the Intensive Care Unit (ASYNICU) Group, Candelaria de Haro, Josefina López-Aguilar, Rudys Magrans, Sol Fernández-Gonzalo, Gemma Gomà, Encarna Chacón, Anna Estruga, Ana Ochagavia, Lluís Blanch, Jaume Montanya, Bernat Sales, Enrico Lena, Umberto Lucangelo, Rafael Fernández, Carles Subirà, Guillermo M Albaiceta, Enrique Fernández-Mondejar, Gastón Murias, Robert M Kacmarek, Candelaria de Haro, Rudys Magrans, Josefina López-Aguilar, Jaume Montanyà, Enrico Lena, Carles Subirà, Sol Fernandez-Gonzalo, Gemma Gomà, Rafael Fernández, Guillermo M Albaiceta, Yoanna Skrobik, Umberto Lucangelo, Gastón Murias, Ana Ochagavia, Robert M Kacmarek, Montserrat Rue, Lluís Blanch, Asynchronies in the Intensive Care Unit (ASYNICU) Group, Candelaria de Haro, Josefina López-Aguilar, Rudys Magrans, Sol Fernández-Gonzalo, Gemma Gomà, Encarna Chacón, Anna Estruga, Ana Ochagavia, Lluís Blanch, Jaume Montanya, Bernat Sales, Enrico Lena, Umberto Lucangelo, Rafael Fernández, Carles Subirà, Guillermo M Albaiceta, Enrique Fernández-Mondejar, Gastón Murias, Robert M Kacmarek

Abstract

Background: In 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.

Methods: This 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.

Results: In 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.

Conclusions: Sedatives, 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 registration: ClinicalTrial.gov, NCT03451461.

Keywords: Asynchronies; Double cycling; Ineffective inspiratory efforts during expiration; Mechanical ventilation; Opioids; Sedatives.

Conflict of interest statement

Drs. Blanch and Murias are inventors of the Corporació Sanitaria Parc Taulí owned US patent: “Method and system for managing related patient parameters provided by a monitoring device,” US Patent No. 12/538,940. Blanch, Montanya, Murias, and Lucangelo own stock options of BetterCare S.L., which is a research and development spinoff of Corporació Sanitària Parc Taulí (Spain). Kacmarek is a consultant for Medtronic and Orange Medical and has received research grants from Medtronic and VennerMedical. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Mean percentages of asynchronous breaths estimated with the generalized linear mixed-effects model by treatment groups. Data are represented as mean (95% CI). Statistical significance (two-sided) among groups is indicated; p values are adjusted by the Bonferroni method
Fig. 2
Fig. 2
Mean levels of SAS and SOFA estimated with the linear mixed-effects model by treatment groups. Data are represented as mean (95% CI). Statistical significance (two-sided) among groups is indicated; p values are adjusted by the Bonferroni method. The within-subject residuals of the SOFA model departure from the theoretical normal distribution (see Additional file 5: Figure S4 left)
Fig. 3
Fig. 3
Effect of the dose of sedatives and opioids administered on asynchronies. Average change in asynchronies per one unit change in dose equivalent
Fig. 4
Fig. 4
Mean percentages of asynchronous breaths estimated with the generalized linear mixed-effects model according to mechanical ventilator mode, by treatment groups. Data are represented as mean (95% CI)

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