Analgosedation in extracorporeal membrane oxygenation: a retrospective UK cohort study

Abstract

Editor—Patients often require high doses of analgesic and sedative drugs (opioids, benzodiazepines, and propofol) when receiving extracorporeal membrane oxygenation (ECMO). 1 Shekar K. Roberts J.A. Mullany D.V. et al. Increased sedation requirements in patients receiving extracorporeal membrane oxygenation for respiratory and cardiorespiratory failure. Anaesth Intensive Care. 2012; 40: 648-655 Crossref PubMed Google Scholar Reasons for higher drug doses are not clearly understood but could include patient factors, pharmacokinetic factors, and effects of ECMO circuit on pharmacokinetics. 2 Shekar K. Fraser J.F. Smith M.T. Roberts J.A. Pharmacokinetic changes in patients receiving extracorporeal membrane oxygenation. J Crit Care. 2012; 27 (741.e9–741.e18) Crossref PubMed Scopus (219) Google Scholar Patient factors including age, sex, critical illness-induced organ dysfunction, augmented renal clearance, and extremes of body weight can affect plasma concentrations of drugs such as fentanyl, midazolam, and propofol. 3 Dzierba A.L. Abrams D. Brodie D. Medicating patients during extracorporeal membrane oxygenation: the evidence is building. Crit Care. 2017; 21: 66 Crossref PubMed Scopus (71) Google Scholar ,4 Erstad B.L. Barletta J.F. Drug dosing in the critically ill obese patient—a focus on sedation, analgesia, and delirium. Crit Care. 2020; 24: 315 Crossref PubMed Scopus (10) Google Scholar Drugs used for analgosedation are lipophilic and sequester in the ECMO circuit increasing their apparent volumes of distribution, 5 Shekar K. Roberts J.A. Mcdonald C.I. et al. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012; 16: R194 Crossref PubMed Scopus (190) Google Scholar with the effect of reduced plasma drug concentrations. This could explain why patients on ECMO require higher drug doses to achieve equivalent analgosedation. 6 Grap M.J. Munro C.L. Wetzel P.A. et al. Sedation in adults receiving mechanical ventilation: physiological and comfort outcomes. Am J Crit Care. 2012; 21: e53-e64 Crossref PubMed Scopus (0) Google Scholar Our primary objective was to report peak continuous infusion dose rates and median daily doses per kg of body mass for analgosedation used for ECMO patients over the duration of their ECMO treatment. Our secondary objective was to explore associations between doses of these drugs and patient and ECMO factors (Table 1). Table 1Multivariable linear regression models describing associations of analgosedation dose with demographic and clinical factors. Intercept of each model is predicted drug dose per kg per day for a VV ECMO patient. 95% CI = 95% Confidence Interval. Veno-venous (V-V), veno-arterial (V-A), veno-venous-arterial (V-V-A) extracorporeal membrane oxygenation (ECMO). Acute Physiology and Chronic Health Evaluation (APACHE II) score. Substance use disorder = history of recurrent use of illicit drugs. Fentanyl Independent variable Effect size 95% CI P-value Intercept 99.04 80.24–117.84 <0.001 Age, yr −0.13 −0.50 to 0.24 0.502 APACHE II score −1.26 −2.12 to−0.39 0.005 Charlson Comorbidity Index −3.98 −8.37 to 0.42 0.076 Substance use disorder 11.04 −3.19 to 25.3 0.128 V-A ECMO −23.70 −37.88 to−9.52 0.001 V-VA ECMO −21.63 −51.01 to 7.75 0.899 COVID-19 −4.66 −15.30 to 5.98 0.390 Model summary: adjusted R-squared: 0.06. F statistic: 6.342; P < 0.001. Midazolam Independent variable Effect size 95% CI P-value Intercept 2.27 1.50–3.03 <0.001 Age, yr −0.01 −0.03 to 0.00 0.085 APACHE II score −0.001 −0.04 to 0.03 0.936 Charlson Comorbidity Index −0.09 −0.27 to 0.10 0.370 Substance use disorder −0.03 −0.55 to 0.49 0.904 V-A ECMO −0.30 −0.99 to 0.38 0.385 V-VA ECMO 1.59 −0.01 to 3.18 0.051 COVID-19 0.86 0.49 to 1.24 <0.001 Model summary: adjusted R-squared: 0.09. F statistic: 5.628; P < 0.001. Propofol Independent variable Effect size 95% CI P-value Intercept 62.50 54.76–70.24 <0.001 Age, yr −0.32 −0.47 to −0.16 <0.001 APACHE II score −0.59 −0.95 to −0.23 0.002 Charlson Comorbidity Index 0.87 −0.96 to 2.69 0.351 Substance use disorder 4.84 −0.83 to 10.51 0.094 V-A ECMO −11.01 −17.29 to −4.72 <0.001 V-VA ECMO −8.37 −20.56 to 3.83 0.179 COVID-19 −2.40 −6.70 to 1.90 0.273 Model summary: adjusted R-squared: 0.10. F statistic: 9.488; P < 0.001 Open table in a new tab