Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients

Pandharipande, Pratik P.; Pun, Brenda T.; Herr, Daniel; Maze, Mervyn; Girard, Timothy D.; Miller, Russell R.; Shintani, Ayumi; Thompson, Jennifer L.; Jackson, James C.; Deppen, Stephen A.; Stiles, Renée A.; Dittus, Robert S.; Bernard, Gordon R.; Ely, E. Wesley

doi:10.1001/jama.298.22.2644

Cited by 1,272 publications

(1,021 citation statements)

References 41 publications

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“…The current PRE-DELIRIC model may require on-going validation as new therapies and interventions emerge. For example, the use of new sedatives or analgesics may affect the development of delirium [33][34][35] and consequently could affect the performance of the model. Different risk factors may emerge in the future that may need to be investigated and included in the current PRE-DELIRIC model.…”

Section: Discussionmentioning

confidence: 99%

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

et al. 2014

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This is the accepted version of the paper.This version of the publication may differ from the final published version. Methods: A prospective multicenter cohort study was performed in eight intensive care units (ICUs) in six countries. The 10 predictors (age, APACHE-II, urgent and admission category, infection, coma, sedation, morphine use, urea level, metabolic acidosis) were collected within 24 hours after ICU admission. The confusion assessment method for the Intensive Care Unit (CAM-ICU) was used to identify ICU delirium. CAM-ICU screening compliance and inter-rater reliability measurements were used to secure the quality of the data. Permanent repository linkResults: 2,852 adult ICU patients were screened of which 1,824 (64%) were eligible for the study. Main reasons for exclusion were length of stay <1day (19.1%) and sustained coma (4.1%). CAM-ICU compliance was mean (SD) 82±16% and inter-rater reliability 0.87±0.17. The median delirium incidence was 22.5% (IQR 12.8%-36.6%). Although the incidence of all ten predictors differed significantly between centers, the area under the receiver operating characteristic (AUROC) curve of the 8 participating centers remained good: 0.77 (95%CI:0.74-0.79). The linear predictor and intercept of the prediction rule were adjusted and resulted in improved recalibration of the PRE-DELIRIC model. Conclusions:In this multinational study we recalibrated the PRE-DELIRIC-model. Despite differences in the incidence of predictors between the centers in the different countries the performance of the PRE-DELIRICmodel remained good. Following validation of the PRE-DELIRIC model it may facilitate implementation of strategies to prevent delirium and aid improvements in delirium management of ICU patients.4

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Section: Discussionmentioning

confidence: 99%

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

et al. 2014

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“…The benefit attributed to remifentanil in some of the above studies could have been either a surrogate of the harmful effect of midazolam or dependent upon an interaction between the choice of opioid and midazolam. A recent study reported the harmful effects of lorazepam when compared with dexmedetomidine in a mixed surgical and medical ICU population [23].…”

Section: Discussionmentioning

confidence: 99%

A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients

et al. 2010

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A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients Abstract Purpose: To compare the quality of analgesia provided by a remifentanil-based analgesia regime with that provided by a fentanylbased regime in critically ill patients. Methods: This was a registered, prospective, two-center, randomized, triple-blind study involving adult medical and surgical patients requiring mechanical ventilation (MV) for more than 24 h. Patients were randomized to either remifentanil infusion or a fentanyl infusion for a maximum of 30 days. Sedation was provided using propofol (and/or midazolam if required). Results: Primary outcome was the proportion of patients in each group maintaining a target analgesia score at all time points. Secondary outcomes included duration of MV, discharge times, and morbidity. At planned interim analysis (n = 60), 50% of remifentanil patients (n = 28) and 63% of fentanyl patients (n = 32) had maintained target analgesia scores at all time points (p = 0.44). There were no significant differences between the groups with respect to mean duration of ventilation (135 vs. 165 h, p = 0.80), duration of hospital stay, morbidity, or weaning. Interim analysis strongly suggested futility and the trial was stopped. Conclusions: The use of remifentanil-based analgesia in critically ill patients was not superior regarding the achievement and maintenance of sufficient analgesia compared with fentanyl-based analgesia.

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“…One major limitation of the trial was the depth of sedation, which was chosen by the primary team. Baseline RASS scores for the dexmedetomidine and lorazepam groups were -3 and -4 respectively [35]. Had lighter or 'cooperative' sedation goals been achieved (closer to 0 to -1), the incidence of drug-induced coma would likely have been less (particularly with lorazepam), and results may have diff ered.…”

Section: Comparative Trialsmentioning

confidence: 98%

“…Th ere are, however, several important trials comparing agents. Th e Maximizing Effi cacy of Targeted Sedation and Reducing Neurological Dysfunction (MENDS) trial was the fi rst randomized, double-blind trial evaluating the eff ect of sedative agents on delirium-free and coma-free days [35]. Th e two agents compared in this trail were lorazepam and dexmedetomidine.…”

Section: Comparative Trialsmentioning

confidence: 99%

‘Cooperative Sedation’: Optimizing Comfort while Maximizing Systemic and Neurological Function

Goodwin¹,

Lewin²,

Mirski³

2012

Annual Update in Intensive Care and Emergency Medicine

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Effect of Sedation With Dexmedetomidine vs Lorazepam on Acute Brain Dysfunction in Mechanically Ventilated Patients

Cited by 1,272 publications

References 41 publications

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

A prospective, randomized, double-blind, multicenter study comparing remifentanil with fentanyl in mechanically ventilated patients

‘Cooperative Sedation’: Optimizing Comfort while Maximizing Systemic and Neurological Function

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