Dexmedetomidine Infusion Associated with Transient Adrenal Insufficiency in a Pediatric Patient: A Case Report

Tucker, Elizabeth W.; Cooke, David W.; Kudchadkar, Sapna R.; Klaus, Sybil Ann

doi:10.1155/2013/207907

Cited by 10 publications

(8 citation statements)

References 19 publications

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“…(45–47) Despite these favorable qualities, anecdotal evidence suggests that long-term use of dexmedetomidine infusions can result in physiologic tolerance, withdrawal, and adrenal insufficiency. (48–51) Therefore, additional study is warranted.…”

Section: Discussionmentioning

confidence: 99%

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

Kudchadkar

Yaster

Punjabi

2014

Critical Care Medicine

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197

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Objective To examine pediatric intensivist sedation management, sleep promotion, and delirium screening practices for intubated and mechanically ventilated children. Design An international, online survey of questions regarding sedative and analgesic medication choices and availability, sedation protocols, sleep optimization, and delirium recognition and treatment. Setting Member societies of the World Federation of Pediatric Intensive and Critical Care Societies were asked to send the survey to their mailing lists; responses were collected from July 2012 to January 2013. Interventions Survey Measurements and Main Results The survey was completed by 341 respondents, the majority of whom were from North America (70%). Twenty-seven percent of respondents reported having written sedation protocols. Most respondents worked in pediatric intensive care units (PICUs) with sedation scoring systems (70%), although only 42% of those with access to scoring systems reported routine daily use for goal-directed sedation management. The State Behavioral Scale was the most commonly used scoring system in North America (22%), with the COMFORT score more prevalent in all other countries (39%). The most commonly used sedation regimen for intubated children was a combination of opioid and benzodiazepine (72%). Most intensivists chose fentanyl as their first-line opioid (66%) and midazolam as their first-line benzodiazepine (86%), and prefer to administer these medications as continuous infusions. Propofol and dexmedetomidine were the most commonly restricted medications in PICUs internationally. Use of earplugs, eye masks, noise reduction, and lighting optimization for sleep promotion was uncommon. Delirium screening was not practiced in 71% of respondent’s PICUs, and only 2% reported routine screening at least twice a day. Conclusions The results highlight the heterogeneity in sedation practices among intensivists who care for critically ill children, as well as a paucity of sleep promotion and delirium screening in PICUs worldwide.

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Section: Discussionmentioning

confidence: 99%

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

Kudchadkar

Yaster

Punjabi

2014

Critical Care Medicine

Self Cite

197

183

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“…36–38 Nevertheless, an anecdotal report describing clinically significant adrenocortical insufficiency (and a negative adrenocorticotropin hormone-stimulation test) associated with long-term high-dose dexmedetomidine infusion suggests that direct affects on adrenocortical function – while rare – may occur in certain clinical circumstances. 27 Animal studies indicate that ketamine and propofol can reduce adrenocortical responsiveness to exogenously administered adrenocorticotropin hormone, consistent with a direct effect on adrenocortical steroid synthesis. 28,29 However, we are unaware of any clinical studies demonstrating a similar action in humans.…”

Section: Discussionmentioning

confidence: 87%

Sedative-hypnotic Binding to 11β-hydroxylase

et al. 2016

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Background Etomidate potently suppresses adrenocortical steroid synthesis with potentially deleterious consequences by binding to 11β-hydroxylase and inhibiting its function. The authors hypothesized that other sedative-hypnotics currently in clinical use or under development (or their metabolites) might bind to the same site at clinically relevant concentrations. The authors tested this hypothesis by defining etomidate’s affinity for this site and the potencies with which other sedative-hypnotics (and their metabolites) inhibit etomidate binding. Methods 3H-etomidate’s binding to adrenal membranes from Sprague-Dawley rats was characterized with a filtration assay, and its dissociation constant was defined using saturation and homologous ligand competition approaches. Half-inhibitory concentrations of sedative-hypnotics and metabolites were determined from the reduction in specific 3H-etomidate binding measured in the presence of ranging sedative-hypnotic and metabolite concentrations. Results Saturation and homologous competition studies yielded 3H-etomidate dissociation constants of 40 and 21 nM, respectively. Half-inhibitory concentrations of etomidate and cyclopropyl methoxycarbonyl metomidate (CPMM) differed significantly (26 vs. 143 nM, respectively; P < 0.001), and those of the carboxylic acid (CA) metabolites etomidate-CA and CPMM-CA were greater than or equal to 1,000× higher than their respective parent hypnotics. The half-inhibitory concentration of dexmedetomidine was 2.2 µM, whereas those of carboetomidate, ketamine, and propofol were greater than or equal to 50 µM. Conclusion Etomidate’s in vitro dissociation constant for 11β-hydroxylase closely approximates its in vivo adrenocortical half-inhibitory concentration. CPMM produces less adrenocortical suppression than etomidate not only because it is metabolized faster but also because it binds to 11β-hydroxylase with lower affinity. Other sedative-hypnotics and metabolites bind to 11β-hydroxylase and inhibit etomidate binding only at suprahypnotic concentrations.

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“…Although no current clinical studies have described the effects of dexmedetomidine on adrenal steroidogenesis, prolonged high‐dose dexmedetomidine treatment had been suspected to cause transient adrenal insufficiency in pediatric trauma patients . Moreover, in animals, blunted responses of adrenocortical cells to ACTH and decreased cortisol levels have been noticed upon dexmedetomidine administration .…”

Section: Discussionmentioning

confidence: 99%

Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta‐analysis

Wang

Cao

et al. 2015

Clin Exp Pharma Physio

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This study examined the effects of perioperative dexmedetomidine treatment on physiological modulators of surgical stress response. The quality of the included studies was assessed prior to performing meta-analyses of the weighted mean differences in the changes from baseline of stress hormones and interpreted in the light of statistical heterogeneity between the studies. Nineteen studies (844 surgical subjects) data were used for this meta-analysis. Dexmedetomidine administration significantly decreased blood cortisol levels (μg/dL) postoperatively (mean difference with 95% confidence interval (CI) from controls: -18.78 (-28.45, -9.10); P < 0.05). In the subgroup analysis, the mean difference between dexmedetomidine-treated and saline-treated subjects in the changes from baseline of the cortisol levels was -20.10 (-30.96, -9.25; P < 0.05) but, between dexmedetomidine- and comparator-treated subjects, it was not statistically significantly different (-15.13 (-49.78, 19.52); P < 0.05). Compared with controls, dexmedetomidine treatment also decreased adrenaline and noradrenaline levels significantly (mean difference in the percent changes from baseline: -90.41 (-145.79, -35.03)%; P < 0.05 and -62.82 (-85.47, -0.40.17)%; P < 0.05, respectively). Dexmedetomidine also decreased prolactin levels with a mean difference of -19.42 (-39.37, 0.52) μg/L (P = 0.06). In conclusion, perioperative use of dexmedetomidine reduces serum catecholamine and cortisol levels but the decrease in cortisol levels was not statistically different from the comparator anaesthetics. More data will be required to assess the effects of dexmedetomidine on corticotropin, prolactin, and growth hormone.

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Dexmedetomidine Infusion Associated with Transient Adrenal Insufficiency in a Pediatric Patient: A Case Report

Cited by 10 publications

References 19 publications

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

Sedation, Sleep Promotion, and Delirium Screening Practices in the Care of Mechanically Ventilated Children

Sedative-hypnotic Binding to 11β-hydroxylase

Effect of perioperative dexmedetomidine on the endocrine modulators of stress response: a meta‐analysis

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