Midazolam Disposition in Patients Undergoing Continuous Venovenous Hemodialysis

Bolon, Magali; Bastien, O.; Flamens, C.; Paulus, S.; Boulieu, Roselyne

doi:10.1177/00912700122010933

Cited by 21 publications

(20 citation statements)

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“…Prolonged sedation additionally caused by an accumulation of conjugated 1-hydroxymidazolam was also observed in septic shock patients with severe renal failure [ 26 , 27 ]. Bolon et al [ 28 ] showed that in such cases, dialysis is rather effective in eliminating the conjugated metabolite than midazolam itself. Therefore, for patients needing dialysis, liver function plays a key role in midazolam clearance.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2018

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“…Step 6 Patients worldwide have been sedated in intensive care units (ICUs) for decades; however, many controversies still surround the issue of how to monitor for sedation in the ICU setting. 1,2 The main aim of sedation in the critically ill patient is to make the patient calm, cooperative, and able to communicate by providing relief from agitation, anxiety, and pain. 3,4 Benzodiazepines have a high affinity for ␥aminobutyric acid (GABA) receptors.…”

Section: Discussionmentioning

confidence: 99%

“…5 Midazolam is a shortacting benzodiazepine with a rapid onset of action; it has been widely used as a sedative in mechanically ventilated patients since its introduction to United States and Canadian markets in 1986 and 1988, respectively. [2][3][4][5][6][7] The half-life of midazolam is approximately 3 hours; however, there is wide interindividual variability in both healthy individuals and critically ill patients. 7,8 Midazolam undergoes hydroxylation by hepatic cytochrome P450 (CYP) isoenzyme 3A4 to form three metabolites, which are cleared renally.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequently, another research group investigated the disposition and removal of midazolam and both conjugated and unconjugated ␣ 1 -hydroxymidazolam metabolites in three anuric patients receiving continuous venovenous hemodialysis. 2 They found that midazolam and the unconjugated ␣ 1 -hydroxymidazolam metabolite were not removed by hemodialysis, whereas the conjugated ␣ 1 -hydroxymidazolam was removed. A similar trial assessed midazolam pharmacokinetics in critically ill patients with acute renal failure who were undergoing continuous venovenous hemofiltration.…”

Section: Renal Failurementioning

confidence: 99%

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Clinical Pharmacokinetic Monitoring of Midazolam in Critically Ill Patients

Spina

Ensom

2007

Pharmacotherapy

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Midazolam is a commonly used sedative in critically ill, mechanically ventilated patients in intensive care unit (ICU) settings worldwide. We used a nine-step decision-making algorithm to determine whether therapeutic monitoring of midazolam in the ICU is warranted. Midazolam has a higher clearance and shorter half-life than other benzodiazepines, and prolonged sedation is achieved with continuous infusion. There appears to be very good correlation between plasma concentrations of both midazolam and its active metabolite, alpha1-hydroxymidazolam, and the degree of sedation. However, due to high interpatient variability, it is not possible to predict the level of sedation in any given individual based on plasma concentration of midazolam or its metabolites. Moreover, no simple and practical assay is available to quantitate midazolam plasma concentrations in the acute ICU setting. Many scales are available to assess the sedative effects of midazolam. Because the plasma concentration of midazolam required to achieve a constant level of sedation is highly variable, it is usually more prudent for the clinician to monitor for sedation with a validated clinical scale than by plasma concentrations alone. Various physiologic parameters, including age-related effects, compromised renal function, and liver dysfunction affect the pharmacokinetics of midazolam and alpha1-hydroxymidazolam. Although routine drug monitoring for all critically ill patients receiving midazolam is not recommended, this practice is likely beneficial in patients with neurologic damage in whom sedation cannot be assessed and in patients who have renal failure with a prolonged time to awakening.

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“…PHARMACOTHERAPY Volume 40, Number 12, 2020 observed because of a widely variable half-life due to redistribution into adipose tissue and an active metabolite that is renally eliminated and only partially cleared by renal replacement therapies. [55][56][57] Midazolam should be avoided or limited to intermittent dosing in these at-risk populations unless no other options exist. 58…”

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confidence: 99%

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID‐19

Adams¹,

Altshuler

Barlow

et al. 2020

Pharmacotherapy

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Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short-and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

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Midazolam Disposition in Patients Undergoing Continuous Venovenous Hemodialysis

Cited by 21 publications

References 6 publications

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

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

Clinical Pharmacokinetic Monitoring of Midazolam in Critically Ill Patients

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID‐19

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