High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients

Amigoni, Angela; Vettore, Elia; Brugnolaro, Valentina; Brugnaro, Luca; Gaffo, D; Masola, Maristella; Antonio, Miguel; Pettenazzo, Andrea

doi:10.1111/apa.12777

Cited by 32 publications

(42 citation statements)

References 20 publications

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“…The incidence of withdrawal reported in the literature varies from 10% [31], 37% [4], and even 48% [32]. Withdrawal symptoms are linked to discontinuation of either opioids or benzodiazepines and result from central nervous system irritability, gastrointestinal dysfunction, and autonomic nervous system dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…On both sides of this optimal state are the states of “oversedation” and “undersedation”, both with major drawbacks. Excessive sedation is associated with poor outcomes like prolonged mechanical ventilation, longer hospitalisation, more nosocomial infections, and more frequent withdrawal symptoms [2–4]. Insufficient sedation involves risks of agitation and complications like unplanned extubation or catheter removal.…”

Section: Introductionmentioning

confidence: 99%

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Implementation and evaluation of a paediatric nurse-driven sedation protocol in a paediatric intensive care unit

Dreyfus

Javouhey

Denis

et al. 2017

Ann. Intensive Care

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BackgroundOptimal sedation and analgesia is a challenge in paediatric intensive care units (PICU) because of difficulties in scoring systems and specific metabolism inducing tolerance and withdrawal. Excessive sedation is associated with prolonged mechanical ventilation and hospitalisation. Adult and paediatric data suggest that goal-directed sedation algorithms reduce the duration of mechanical ventilation. We implemented a nurse-driven sedation protocol in a PICU and evaluated its impact.MethodsWe conducted a before and after protocol implementation study in a population of children aged 0–18 years who required mechanical ventilation for at least 24 h between January 2013 and March 2015. After the protocol implementation in January 2014, nurses managed analgesia and sedation following an algorithm that included the COMFORT behaviour scale (COMFORT-B). Duration of mechanical ventilation was the primary outcome; secondary outcomes were total doses and duration of medications, PICU length of stay, incidence of ventilator-associated pneumonia, and occurrence of withdrawal symptoms. Pre–post analysis followed with segmented regression analysis of interrupted time series was used to assess the effect of protocol.ResultsA total of 200 children were analysed, including 107 before implementation and 93 children after implementation of the protocol. After implementation of the protocol, the total number of COMFORT-B scores per day of mechanical ventilation significantly increased from 3.9 ± 2.5 times during the pre-implementation period to 6.6 ± 3.5 times during the post-implementation period (p < 10−3). Mean duration of mechanical ventilation tended to be lower in the post-implementation period (8.3 ± 7.3 vs 6.6 ± 5.6 days, p = 0.094), but changes in either the trend per trimester from pre-implementation to post-implementation (p = 0.933) or the immediate change after implementation (p = 0.923) were not significant with segmented regression analysis. No significant change between pre- and post-implementation was shown for total dose of sedatives, withdrawal symptoms, agitation episodes, or unplanned endotracheal extubations.ConclusionsThese results were promising and suggested that implementation of a nurse-driven sedation protocol in a PICU was feasible. Evaluation of sedation and analgesia was better after the protocol implementation; duration of mechanical ventilation and occurrence of withdrawal symptoms tended to be reduced.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0256-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Implementation and evaluation of a paediatric nurse-driven sedation protocol in a paediatric intensive care unit

Dreyfus

Javouhey

Denis

et al. 2017

Ann. Intensive Care

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“…For trials evaluated with the Newcastle‐Ottawa tool (N = 29), the number of stars awarded ranged from two to eight. Most studies (N = 20) were awarded a score of three stars or less, indicating a high risk of bias . Nine studies could not be attributed any score for the comparability item because of the lack of control group.…”

Section: Resultsmentioning

confidence: 99%

“…Many patients are still exposed to opioids and benzodiazepines at high doses for prolonged periods despite guidelines promoting daily sedation interruption or sedation with lighter targets . Upon discontinuation of these drugs, patients may be at risk for iatrogenic withdrawal . In critically ill patients, this syndrome was associated with prolonged mechanical ventilation, paediatric intensive care unit (PICU) and hospital length of stay .…”

Section: What Is Known and Objectivementioning

confidence: 99%

“…[3][4][5][6][7][8][9] Upon discontinuation of these drugs, patients may be at risk for iatrogenic withdrawal. [10][11][12][13][14] In critically ill patients, this syndrome was associated with prolonged mechanical ventilation, paediatric intensive care unit (PICU) and hospital length of stay. 10,[15][16][17][18] Recent data suggest that exposure to regular opioids or benzodiazepines as short as 3 days can induce withdrawal symptoms upon discontinuation.…”

Section: What Is K Nown and Objec Tivementioning

confidence: 99%

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Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies

et al. 2018

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Summary What is known and objective Many critically ill patients are exposed to opioids and benzodiazepines at high doses for prolonged periods, and upon discontinuation of these drugs, they may be at risk for iatrogenic withdrawal. Although this syndrome was associated with worse outcomes in the critically ill, limited guidance exists regarding its evaluation, prevention and treatment. This systematic review examined the frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and/or benzodiazepines in critically ill neonates, children and adults. Methods The literature search was conducted in PubMed, Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane register of systematic reviews, DARE, CINAHL, Trip database, CMA infobase and NICE evidence from inception to February 2018. Grey literature was examined. We included studies reporting frequency, risk factors or symptomatology of iatrogenic withdrawal of opioids, benzodiazepines (or both) in critically ill patients. We considered all study designs except case reports and case series. We excluded studies on neonatal abstinence syndrome, alcohol withdrawal, studies on chronic opioid and/or benzodiazepine users and studies on prevention or treatment of withdrawal in critical care patients. Two independent reviewers applied the inclusion and exclusion criteria. Pairs of reviewers independently abstracted data and evaluated methodological quality using the Cochrane Collaboration Tool, Newcastle‐Ottawa or QUADAS‐2. Details regarding study design, outcomes, definition, evaluation and type of withdrawal (opioid, benzodiazepine or mixed) were collected. Cumulative doses and duration of opioids and benzodiazepines were collected. Results and discussion We identified 21 866 unique citations and 153 full texts were assessed for eligibility. Thirty‐four studies were included; the majority were observational and few included adults. In prospective studies, mixed withdrawal was observed in 7.5%‐100% of patients in paediatric studies and ranged from 16.7% to 55% in adults. Symptomatology of withdrawal was not well described. Risk factors included higher cumulative dose and prolonged administration of opioids and benzodiazepines. What is new and conclusion Iatrogenic withdrawal appears to be a frequent syndrome in critical care patients who received regular doses of opioids and/or benzodiazepines for ≥72 hours. Larger studies are required, especially in critically ill adults, to better define the syndrome and its symptomatology.

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Sedation of the Critically Ill Child

Brouwers

Vaassen

Vos

et al. 2017

Total Intravenous Anesthesia and Target Controlled Infusions

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High doses of benzodiazepine predict analgesic and sedative drug withdrawal syndrome in paediatric intensive care patients

Abstract: Withdrawal syndrome should be considered after three or more days of analgesic or sedative treatment. A high dose of benzodiazepine increases the risk of developing withdrawal symptoms.

Cited by 32 publications

References 20 publications

Implementation and evaluation of a paediatric nurse-driven sedation protocol in a paediatric intensive care unit

Implementation and evaluation of a paediatric nurse-driven sedation protocol in a paediatric intensive care unit

Frequency, risk factors and symptomatology of iatrogenic withdrawal from opioids and benzodiazepines in critically Ill neonates, children and adults: A systematic review of clinical studies

Sedation of the Critically Ill Child

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