Effect of Sedatives and Opioids on Patient-Ventilator Asynchronies in Critically Ill Patients

Background: Sedation improves comfort during invasive mechanical ventilation (MV) in critically ill patients, but its deleterious effects are increasingly being recognized. We aimed to describe the relationship between patient-ventilator, sedation levels and administered molecules (sedatives and/or opioids). Methods: Prospective multicentre observational trial of critically ill adults mechanically ventilated >24 hours. Level of sedation and sedative and opioid doses were recorded. Asynchronies were continuously classified in all patients with Better Care™ software as: ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI). The relationship between asynchronies, sedation level, sedative and opioid doses were analysed with linear mixed-effects models. Findings: Between October 2011 and January 2013, 79 enrolled patients accounted for 579 days of ventilatory support (14,166,469 breaths). Overall AI, IEE and DC were similar in sedatives-only, opioids-only, or sedatives-plus-opioids recipients. All asynchronies were higher in subjects receiving no drugs. Sedative doses were associated with sedation level and with reduced DC (p<0.001) in sedative-alone recipients. However, sedative-opioid combination recipients with higher sedative doses and deeper sedation had more AI and IEE events. Opioid dosing was inversely associated with AI, IEE, and DC (p<0.01) in opioids-only recipients; opiate recipient had similar sedation levels. Interpretation: A sedatives plus opioids combination provided no benefit in patient-ventilator interaction than sedatives-only or opioids-only regimens. Higher sedative doses were only associated with lower DC asynchronies. Incremental opioids were associated with less overall asynchronies without affecting sedation level. Funding: This work was funded by projects PI09/91074 and PI13/02204 in the National R D I Plan and the ISCIII-European Regional Development Fund, CIBER Enfermedades Respiratorias, Fundacion Mapfre, Fundacio Parc Tauli, Plan Avanza TSI-020302-2008-38, MCYIN and MITYC (Spain). Declaration of interests: Blanch and Murias are inventors of one Corporacio Sanitaria Parc Tauli owned US patent: "Method and system for managed 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 Corporacio Sanitaria Parc Tauli (Spain). Kacmarek is a consultant for Medtronic and Orange Medical and has received research grants from Medtronic and Venner Medical. Other authors have no conflicts of interest. Ethical Approval Statement: The institutional review boards approved the protocol and waived informed consent because the study was non-interventional, posed no added risk to the patient, and did not interfere with usual care.