Evaluating the Transition From Dexmedetomidine to Clonidine for the Prevention of Withdrawal in Critically Ill Pediatric Patients

Abstract

OBJECTIVES To evaluate clonidine for preventing withdrawal from dexmedetomidine infusions and describe the incidence of withdrawal symptoms and adverse cardiovascular effects in critically ill pediatric patients. METHODS Retrospective, descriptive study of patients in Advocate Children's Hospital-Park Ridge PICU who received dexmedetomidine infusion for ≥72 hours, followed by clonidine for ≥48 hours, between January 1, 2015, and August 31, 2017. RESULTS Thirty-eight patients (median age 4.3 years; IQR, 2–11.5) received 39 dexmedetomidine courses. The median duration of dexmedetomidine exposure was 7.6 days (IQR, 5–11.5) at an average dose of 1 mcg/kg/hr. The median dose of clonidine at initiation was 8.3 mcg/kg/day (for <50 kg) and 4.1 mcg/kg/day (for ≥50 kg). The most common oral administration frequency was every 8 hours. Dexmedetomidine infusions for 7 days or longer and a higher dexmedetomidine dose 24 hours prior to clonidine transition both correlated with increased initial clonidine doses. Fourteen patients (37%) had at least 1 WAT-1 score of ≥3 during the transition between dexmedetomidine and clonidine, with 7 (18%) requiring an increase in sedation. Adverse cardiovascular events were possibly attributable to dexmedetomidine and/or clonidine in 4 patients. CONCLUSIONS Patients receiving prolonged infusions of dexmedetomidine may transition to clonidine to help prevent withdrawal symptoms. Duration of dexmedetomidine infusion of 7 days or longer and higher average dexmedetomidine dose 24 hours prior to the transition are important considerations when determining the initial clonidine dose. Transition from dexmedetomidine to clonidine was found to be safe and efficacious in our patients, with minimal adverse effects.

Evaluation of an Enteral Clonidine Taper following Prolonged Dexmedetomidine Exposure in Critically Ill Children

“…18 However, the study by Liu et al along with other previous studies have not excluded patients with exposure to other continuous infusion sedative agents, and thus can influence findings as it relates specifically to dexmedetomidine exposure and withdrawal symptoms. 10,[12][13][14]17,18 Similarly, this study found that this institution's enteral clonidine dosing strategy (►Table 1) initiated at 5 µg/kg/dose (maximum dose of 200 µg/dose) every 8 hours (15 µg/kg/day) could be an effective discontinuation strategy. Although 98.1% of all patients experienced at least one withdrawal symptom, based on the clinical judgment of the practitioners, only 13 patients (12.4%) required a taper modification, suggesting that this enteral clonidine strategy could be effective.…”

“…Previous studies have relied on the Withdrawal Assessment Tool (WAT-1), a scoring system developed and validated to monitor for the development of iatrogenic opioid and benzodiazepine withdrawal, to identify the development of central α 2 -adrenergic agonist withdrawal. 10,[12][13][14]17,18,21 The WAT-1 is a 12-point scale scoring system, which includes tremor and agitation in its criteria, but the tool is not Clonidine for Prolonged Dexmedetomdine in Critically Ill Children Crabtree et al…”

“…Previous studies have relied on the Withdrawal Assessment Tool (WAT-1), a scoring system developed and validated to monitor for the development of iatrogenic opioid and benzodiazepine withdrawal, to identify the development of central α 2 -adrenergic agonist withdrawal. 10,[12][13][14]17,18,21 The WAT-1 is a 12-point scale scoring system, which includes tremor and agitation in its criteria, but the tool is not inclusive of other proposed dexmedetomidine withdrawal symptoms including alterations in HR, BP, and sleep patterns. 21 Using this study's predefined classification to assess dexmedetomidine withdrawal symptoms, the study identified that 103 of 105 total patients (98.1%) had at least one symptom of withdrawal after dexmedetomidine discontinuation, the most common being hypertension, lending toward the need for a more specific dexmedetomidine withdrawal tool than the WAT-1 to identify central α 2adrenergic agonist withdrawal.…”

“…Additionally, there is significant variation in current conversion practices with clonidine dosing ranging from 1.4 to 18 µg/kg/day, divided at differing frequencies. 11,13,[16][17][18] This study aims to describe the use of an enteral clonidine transition for the prevention and management of dexmedetomidine withdrawal in critically ill children not exposed to other continuous infusion sedative agents. Secondary outcomes seek to describe the characteristics of dexmedetomidine exposure associated with a need for a clonidine taper modification and to describe the prevalence of dexmedetomidine withdrawal symptoms.…”

Biased, Bitopic, Opioid–Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction

“…Notably, however, some studies have found that combining adrenergic drugs with opioids actually decreases the risks of cardiovascular effects [53] (Yu et al, 2011). Finally, an additional risk of combining opioids with adrenergic drugs is the cross-tolerance that develops between the drugs, so that over-use of adrenergic agonists can itself lead to withdrawal symptoms [66][67][68]. Despite these potential drawbacks, the literature on opioid-adrenergic combinations is broadly positive about their benefits.…”