Shortened Taper Duration after Implementation of a Standardized Protocol for Iatrogenic Benzodiazepine and Opioid Withdrawal in Pediatric Patients: Results of a Cohort Study

Vipond, Jane M; Heiberger, Amy L; Thompson, Paul A.; Huber, Jody N

doi:10.1097/pq9.0000000000000079

Cited by 8 publications

(21 citation statements)

References 29 publications

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“…Our study is the largest published study on the efficacy of a methadone and lorazepam weaning protocol and confirms the findings of other studies in that a standardized approach to weaning reduces the time to wean patients off opioids 11,12,14 and, more recently, benzodiazepines. 3,28 The design of this protocol incorporated both dose and length of therapy into the individualized wean plan as both factors have been strongly associated with the risk of withdrawal. This approach is similar to the protocol recently published by researchers at Children's Hospital Los Angeles.…”

Section: Discussionmentioning

confidence: 99%

Exposure-Based Methadone and Lorazepam Weaning Protocol Reduces Wean Length in Children

Wilson¹,

Ragsdale²,

Sehgal³

et al. 2021

The Journal of Pediatric Pharmacology and Therapeutics

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OBJECTIVE Determine if a standardized methadone and lorazepam weaning protocol that is based on dose and duration of exposure can reduce the length of opioid and benzodiazepine weaning and shorten hospital stay. METHODS Retrospective cohort study performed in a 24-bed medical/surgical PICU. A total of 177 patients on opioid and/or benzodiazepine infusions for >3 days were included; 75 patients pre protocol (June 2012– June 2013) were compared with 102 patients post implementation of a standardized weaning protocol of methadone and lorazepam (March 2014–March 2015). The recommended wean was based on duration of infusions of >3 days up to 5 days (no wean), 5 to 13 days (short wean), and ≥14 days (long wean). RESULTS Median number of days on methadone for patients on opioid infusions for 5 to 13 days was reduced from 8.5 to 5.7 days (p = 0.001; n = 45 [pre], n = 68 [post]) and for patients on opioid infusions for ≥14 days, from 29.7 to 11.5 days (p = 0.003; n = 9 [pre], n = 9 [post]) after protocol implementation. The median number of days on lorazepam for patients on benzodiazepine infusions for 5 to 13 days was reduced from 8.1 to 5.2 days (p = 0.020; n = 43 [pre], n = 55 [post]) and for patients on benzodiazepine infusions for ≥14 days, from 27.4 to 9.3 days (p = 0.011; n = 9 [pre], n = 8 [post]). There was no difference in methadone or lorazepam wean length for patients on 3 to 5 days of infusions. There was no difference in adverse events or hospital length of stay. CONCLUSIONS A methadone and lorazepam weaning protocol based on patient's exposure to opioids and benzodiazepines (dose and duration) reduces weaning length.

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Section: Discussionmentioning

confidence: 99%

Exposure-Based Methadone and Lorazepam Weaning Protocol Reduces Wean Length in Children

Wilson¹,

Ragsdale²,

Sehgal³

et al. 2021

The Journal of Pediatric Pharmacology and Therapeutics

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“…While these results may seem intuitive, they contradict with most weaning protocols reported in literature. Most weaning protocols tend to stepwise reduce the infusion rate by a set percentage of the original infusion rate, resulting in the same planned weaning period for all patients (e.g., 10% reduction every 24 h) ( 5 , 6 , 36 ).…”

Section: Discussionmentioning

confidence: 99%

“…Although we could quantify the impact of three drugs on IWS in children, we cannot exclude a confounding effect from drugs not included in the model because of a lack of statistical significance. These include drugs that might contribute to IWS (e.g., sedatives like midazolam) or drugs used to manage IWS during weaning (e.g., clonidine, methadone) ( 5 ). The effects of these drugs on IWS in this study cohort may have been more modest or more variable in nature than the effects of the drugs included in the model.…”

Section: Discussionmentioning

confidence: 99%

“…While risk factors can identify patients who need weaning, they do not inform us how weaning should be performed. Thus, different institutions apply a large variety of weaning strategies ( 5 , 6 ). To reduce the risk of IWS in clinical practice, we need weaning strategies based on a patient’s characteristics and type of drug and dosing history over time.…”

Section: Introductionmentioning

confidence: 99%

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Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children

Goulooze

Ista

Dijk

et al. 2021

AAPS J

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For the management of iatrogenic withdrawal syndrome (IWS) in children, a quantitative understanding of the dynamics of IWS of commonly used opioids and sedatives is lacking. Here, we introduce a new mechanism-based pharmacokinetic-pharmacodynamic (PKPD) modeling approach for studying IWS in pediatric clinical datasets. One thousand seven hundred eighty-two NRSwithdrawal scores of IWS severity were analyzed, which were collected from 81 children (age range: 1 month–18 years) that received opioids or sedatives by continuous infusion for 5 days or more. These data were successfully fitted with a PKPD model consisting of a plasma and a dependence compartment that well characterized the dynamics of IWS from morphine, fentanyl, and ketamine. The results suggest that (1) instead of decreasing the infusion rate by a set percentage at set intervals, it would be better to lengthen the weaning period when higher infusion rates are administered prior to weaning; (2) for fentanyl specifically, the risk of IWS might be lower when weaning with smaller dose reductions every 12 h instead of weaning with greater dose reductions every 48 h. The developed PKPD model can be used to evaluate the risk of IWS over time and the extent to which it is affected by different weaning strategies. The results yield hypotheses that could guide future clinical research on optimal weaning strategies. The mechanism-based PKPD modeling approach can be applied in other datasets to characterize the IWS dynamics of other drugs used in pediatric intensive care. Graphical abstract

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“…3,5,[12][13][14][15] Iatrogenic withdrawal syndrome can be prevented and treated by more gradual weaning of sedatives and analgesics with oral equivalents. [16][17][18] Although this process can be safely carried out even outside a PICU setting, the patient must remain in the hospital; therefore, more gradual weaning regimens or treatment of IWS can result in longer intensive care unit and hospital stays. [19][20][21] Finding the optimal level of sedation can be challenging, and signs of patient discomfort may be present despite appropriate use of the conventionally used sedatives and analgesics such as midazolam and morphine.…”

mentioning

confidence: 99%

Dexmedetomidine and Iatrogenic Withdrawal Syndrome in Critically Ill Children

Geven

Maaskant

Ward

et al. 2021

Critical Care Nurse

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Background Iatrogenic withdrawal syndrome is a well-known adverse effect of sedatives and analgesics commonly used in patients receiving mechanical ventilation in the pediatric intensive care unit, with an incidence of up to 64.6%. When standard sedative and analgesic treatment is inadequate, dexmedetomidine may be added. The effect of supplemental dexmedetomidine on iatrogenic withdrawal syndrome is unclear. Objective To explore the potentially preventive effect of dexmedetomidine, used as a supplement to standard morphine and midazolam regimens, on the development of iatrogenic withdrawal syndrome in patients receiving mechanical ventilation in the pediatric intensive care unit. Methods This retrospective observational study used data from patients on a 10-bed general pediatric intensive care unit. Iatrogenic withdrawal syndrome was measured using the Sophia Observation withdrawal Symptoms-scale. Results In a sample of 102 patients, the cumulative dose of dexmedetomidine had no preventive effect on the development of iatrogenic withdrawal syndrome (P = .19). After correction for the imbalance in the baseline characteristics between patients who did and did not receive dexmedetomidine, the cumulative dose of midazolam was found to be a significant risk factor for iatrogenic withdrawal syndrome (P < .03). Conclusion In this study, supplemental dexmedetomidine had no preventive effect on iatrogenic withdrawal syndrome in patients receiving sedative treatment in the pediatric intensive care unit. The cumulative dose of midazolam was a significant risk factor for iatrogenic withdrawal syndrome.

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Shortened Taper Duration after Implementation of a Standardized Protocol for Iatrogenic Benzodiazepine and Opioid Withdrawal in Pediatric Patients: Results of a Cohort Study

Abstract: Supplemental Digital Content is available in the text.

Cited by 8 publications

References 29 publications

Exposure-Based Methadone and Lorazepam Weaning Protocol Reduces Wean Length in Children

Exposure-Based Methadone and Lorazepam Weaning Protocol Reduces Wean Length in Children

Towards Evidence-Based Weaning: a Mechanism-Based Pharmacometric Model to Characterize Iatrogenic Withdrawal Syndrome in Critically Ill Children

Dexmedetomidine and Iatrogenic Withdrawal Syndrome in Critically Ill Children

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