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

Abstract

BackgroundAnalgosedation 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.MethodsForty-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).ResultsAverage 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.ConclusionCorrelations 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.Electronic supplementary materialThe online version of this article (10.1186/s40560-018-0331-7) contains supplementary material, which is available to authorized users.

Hyperinflammation Reduces Midazolam Metabolism in Critically Ill Adults with COVID-19

“…This appears to be high compared to previous investigations [ 17 – 19 ]. Our median plasma concentration is comparable to the finding by Nies et al They observed a median midazolam concentration of roughly 1500 µg/L for RASS -5 [ 20 ]. The difference in median concentrations are probably due to the fact that on the one hand, the study by Bremer et al included post-operative ICU patients and the study by Oldenhof et al included only 17 patients, and on the other hand that the study by Nies et al included more long term severe ICU patients.…”

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age

“…Intravenous continuous infusions may be indicated when seizures persist under a maximal treatment: therapeutic options include midazolam or lidocaine [124]. Despite pediatricians' concern on midazolam (MID) use in spontaneously breathing infants, due to the risk of respiratory failure, midazolam may be started with a loading dose and then clinically titrated to effect: its advantages are the rapid metabolic inactivation, clearance and comparatively short elimination half-time [125]. A therapeutic range is not used in the clinical practice.…”

Negative drift of sedation depth in critically ill patients receiving constant minimum alveolar concentration of isoflurane, sevoflurane, or desflurane: a randomized controlled trial

“…The literature reports a weak drug–response relationship in both inhalational and intravenous sedative agents, partly attributed to polypharmacy and the high pathophysiological heterogeneity of mechanically ventilated patients [ 16 , 17 ].…”

“…The number of observations per patient was 1019 ± 430, 852 ± 797, and 1158 ± 436 for the isoflurane, sevoflurane, and desflurane groups. The duration of sedation per group in rounded hours was comparable across groups: 18 [16][17][18][19][20][21]; 17 ; 18 [15][16][17][18][19][20][21][22] for isoflurane, sevoflurane, and desflurane, respectively (p = 0.71).…”