Monitoring of sedation depth in intensive care unit by therapeutic drug monitoring? A prospective observation study of medical intensive care patients

Richard J Nies; Carsten Müller; Roman Pfister; Philipp S Binder; Nicole Nosseir; Felix S Nettersheim; Kathrin Kuhr; Martin H J Wiesen; Matthias Kochanek; Guido Michels

doi:10.1186/s40560-018-0331-7

Monitoring of sedation depth in intensive care unit by therapeutic drug monitoring? A prospective observation study of medical intensive care patients

J Intensive Care. 2018 Sep 14:6:62. doi: 10.1186/s40560-018-0331-7. eCollection 2018.

Authors

Affiliations

¹ 1Department III of Internal Medicine, Heart Center, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
² 6Department of Cardiology, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
³ 2Center of Pharmacology, Department of Therapeutic Drug Monitoring, University Hospital of Cologne, Gleueler Str. 24, 50931 Cologne, Germany.
⁴ St. Katharinen-Hospital GmbH, Kapellenstrasse 1-5, 50226 Frechen, Germany.
⁵ 4Institute of Medical Statistics and Computational Biology, University of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
⁶ 5Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany.

Abstract

Background: Analgosedation is a cornerstone therapy for mechanically ventilated patients in intensive care units (ICU). To avoid inadequate sedation and its complications, monitoring of analgosedation is of great importance. The aim of this study was to investigate whether monitoring of analgosedative drug concentrations (midazolam and sufentanil) might be beneficial to optimize analgosedation and whether drug serum concentrations correlate with the results of subjective (Richmond Agitation-Sedation Scale [RASS]/Ramsay Sedation Scale) and objective (bispectral (BIS) index) monitoring procedures.

Methods: Forty-nine intubated, ventilated, and analgosedated critically ill patients treated in ICU were clinically evaluated concerning the depth of sedation using RASS Score, Ramsay Score, and BIS index twice a day. Serum concentrations of midazolam and sufentanil were determined in blood samples drawn at the same time. Clinical and laboratory data were statistically analyzed for correlations using the Spearman's rank correlation coefficient rho (ρ).

Results: Average age of the population was 57.8 ± 16.0 years, 61% of the patients were males. Most frequent causes for ICU treatments were sepsis (22%), pneumonia (22%), or a combination of both (25%). Serum concentrations of midazolam correlated weakly with RASS (ρ = - 0.467) and Ramsay Scores (ρ = 0.476). Serum concentrations of sufentanil correlated weakly with RASS (ρ = - 0.312) and Ramsay Scores (ρ = 0.295). Correlations between BIS index and serum concentrations of midazolam (ρ = - 0.252) and sufentanil (ρ = - 0.166) were low.

Conclusion: Correlations between drug serum concentrations and clinical or neurophysiological monitoring procedures were weak. This might be due to intersubject variability, polypharmacy with drug-drug interactions, and complex metabolism, which can be altered in critically ill patients. Therapeutic drug monitoring is not beneficial to determine depth of sedation in ICU patients.

Keywords: Analgosedation; Drug monitoring; Intensive care; Midazolam; Richmond Agitation-Sedation Scale; Sufentanil.