Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients

Chen, Ken; Lu, Zhenghao; Yi, Xin; Cai, Yong; Chen, Yi; Pan, Shu Ming

doi:10.1002/14651858.cd010269.pub2

Cited by 116 publications

(104 citation statements)

References 91 publications

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“…A recent Cochrane meta-analysis pooled seven randomized controlled trials comparing sedation with dexmedetomidine to benzodiazepines, propofol, or “standard care” which included propofol or midazolam. 67 The risk of delirium was numerically lower with dexmedetomidine but not statistically significant (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.63 to 1.14). Subgroup analyses showed the risk of delirium was lower in patients receiving dexmedetomidine than in those receiving benzodiazepines (RR 0.81; 95% CI 0.59 to 1.09; 1007 participants) or propofol (RR 0.37; 95% CI 0.16 to 0.87; 495 participants).…”

Section: Delirium Preventionmentioning

confidence: 99%

“…Subgroup analyses showed the risk of delirium was lower in patients receiving dexmedetomidine than in those receiving benzodiazepines (RR 0.81; 95% CI 0.59 to 1.09; 1007 participants) or propofol (RR 0.37; 95% CI 0.16 to 0.87; 495 participants). 67 Overall, the authors found high rates of heterogeneity between the studies, including the baseline risk for delirium, time in ICU prior to enrollment and assessment, frequency and duration of delirium assessments, and levels of sedation targeted, all of which would bias delirium outcomes. They recommended that further studies stratify randomized patients based on delirium risk.…”

Section: Delirium Preventionmentioning

confidence: 99%

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Intensive Care Unit Delirium

2016

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Section: Delirium Preventionmentioning

confidence: 99%

Section: Delirium Preventionmentioning

confidence: 99%

Intensive Care Unit Delirium

2016

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“…Gabapentin, klonidin, deksmedetotimidin gibi bazı ilaçların uyku üzerine pozitif etkileri olduğu söylenmesine rağ-men yoğun bakım hastalarında yeterli veri yoktur. Dexmedetomidinin kritik hastalarda mekanik ventilasyon süresi ve yoğun bakım süresini azaltmakla birlikte deliryum üzerine etkisi farklı bulunmamıştır (42).…”

Section: İlaçlar Ve Uykuunclassified

Sleep in Intensive Care: Is there or not?

Ersoy¹,

Demir²,

Topeli³

2016

Yoğun Bakim Derg

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“…The α 2 agonists have been of intense interest in the pediatric critical care literature as sedative agents . An alternative mechanism of action to opioids and benzodiazepines makes them attractive to clinicians.…”

Section: Introductionmentioning

confidence: 99%

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study

Hayden

Bardol

Doherty

et al. 2019

Pediatric Anesthesia

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Background Clonidine is in widespread off‐label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilized in clinical practice and in research studies. Within these studies, clonidine has inconsistently shown useful sedation properties. One of the reasons attributed to the inconsistent signs of efficacy is suboptimal clonidine dosing. Aims This study aims to propose a target plasma concentration and simulate clonidine pharmacokinetics (PK) in a cohort of mechanically ventilated children to evaluate the adequacy of clonidine dosage regimens used in clinical practice and research studies. Methods A literature search was undertaken to identify a clonidine pharmaockinetic‐pharmacodynamics (PKPD) model, from which a target concentration for sedation was defined. Using a previously published PK model, the projected plasma concentrations of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed. Results A target plasma concentration of above 2 µg/L was proposed. Nine dosage regimens (four intravenous boluses, four intravenous infusions, and one nasogastric route boluses) were evaluated ranging from 1 µg/kg eight hourly intravenous boluses to a regimen up to 3 µg/kg/hr continuous intravenous infusion. Regimens with a loading dose of 2 µg/kg followed by variable continuous infusion of up to 2 µg/kg/hr titrated according to sedation score appear most suitable. Doses should be halved in neonates. Conclusion The variety of dosage regimens in the previous studies of clonidine along with difficulties in the conduct of interventional studies may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by higher than current practice maintenance dose infusion is required to achieve adequate steady‐state concentrations early in treatment. Further PKPD studies will aid in the determination of the optimal clonidine dosage regimen.

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Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients

Abstract: Alpha-2 agonists for long-term sedation during mechanical ventilation in critically ill patients.

Cited by 116 publications

References 91 publications

Intensive Care Unit Delirium

Intensive Care Unit Delirium

Sleep in Intensive Care: Is there or not?

Optimizing clonidine dosage for sedation in mechanically ventilated children: A pharmacokinetic simulation study

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