Clonidine in the sedation of mechanically ventilated children: A pilot randomized trial

Duffett, Mark; Choong, Karen; Foster, Jennifer; Cheng, Ji; Meade, Maureen O.; Menon, Kusum; Cook, Deborah J.

doi:10.1016/j.jcrc.2014.05.029

Cited by 27 publications

(76 citation statements)

References 22 publications

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“…Four trials enrolled children [24–26, 29] and four enrolled adults [27, 28, 30, 31]. Clonidine was administered intravenously in six trials [24, 26–30] and via the enteral route in two trials [25, 31]. The trials that used intravenous clonidine took place in Brazil, the United Kingdom, Germany, India and Italy [24, 26–30], respectively.…”

Section: Resultsmentioning

confidence: 99%

“…The trials that used intravenous clonidine took place in Brazil, the United Kingdom, Germany, India and Italy [24, 26–30], respectively. The doses of clonidine varied considerably, with enteral clonidine doses ranging from 0.1 to 0.2 mg every 8 hours [31] to 5 μg/kg every 6 hours [25]. The doses for IV continuous clonidine infusions ranged from 0.88 to 3 μg/kg/hour [26–30] and some studies used an initial bolus dose [26, 28, 30].…”

Section: Resultsmentioning

confidence: 99%

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Clonidine for sedation in the critically ill: a systematic review and meta-analysis

et al. 2017

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BackgroundThis systematic review and meta-analysis investigates the efficacy and safety of clonidine as a sedative in critically ill patients requiring invasive mechanical ventilation.MethodsWe performed a comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane trial registry. We identified RCTs that compared clonidine to any non-clonidine regimen in critically ill patients, excluding neonates, requiring mechanical ventilation. The GRADE method was used to assess certainty of evidence.ResultsWe included eight RCTs (n = 642 patients). In seven of the trials clonidine was used for adjunctive rather than stand-alone sedation. There was no difference in the duration of mechanical ventilation (mean difference (MD) 0.05 days, 95% confidence interval (CI) = -0.65 to 0.75, I 2 = 86%, moderate certainty), ICU mortality (relative risk (RR) 0.98, 95% CI = 0.51 to 1.90, I 2 = 0%, low certainty), or ICU length of stay (MD 0.04 days, 95% CI = -0.46 to 0.53, I 2 = 16%, moderate certainty), with clonidine. There was a significant reduction in the total dose of narcotics (standard mean difference (SMD) -0.26, 95% CI = -0.50 to -0.02, I 2 = 0%, moderate certainty) with clonidine use. Clonidine was associated with increased incidence of clinically significant hypotension (RR 3.11, 95% CI = 1.64 to 5.87, I 2 = 0%, moderate certainty).ConclusionsUntil further RCTs are performed, data remains insufficient to support the routine use of clonidine as a sedative in the mechanically ventilated population. Clonidine may act as a narcotic-sparing agent, albeit with an increased risk of clinically significant hypotension.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Clonidine for sedation in the critically ill: a systematic review and meta-analysis

et al. 2017

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“…They enrolled children aged 1 month to 18 years in a randomized, double-blind, placebo-controlled, pilot trial. They conclude that clonidine may be a good adjuvant to sedation in these patients [3]. Although there are different routes of administration, our study focused on intravenous infusion.…”

Section: Discussionmentioning

confidence: 99%

“…Clonidine, Sedation, Critically-ill child Opioids and benzodiazepines are the most frequently administered, but long-term use of these drugs is associated with tolerance and withdrawal, suppression of respiratory drive with prolonged ventilation, constipation, and delayed enteric feeding [2,3].…”

Section: Introductionmentioning

confidence: 99%

Intravenous Clonidine: A Useful and Safety Sedation for Critically Ill Children

Carme¹,

David²,

Sergio³

et al. 2017

Int J Pediatr Res

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Aim: To determine usefulness and safety of intravenous infusion of clonidine in critically-ill children.Methods: Prospective, single-centre observational study from January 2013 to December 2014. PICU of Hospital Sant Joan Déu.Results: 73 patients were enrolled. Median age 7.9 months. Reasons for admission: Respiratory failure (42.5%) and post-cardiac surgery (30.1%). Median PICU length of stay: 14 days. 72 patients were intubated. The median days of clonidine use was 4. Reason for choosing clonidine: To improve prior sedation. We found no major adverse effects but some asymptomatic bradycardia. Conclusions:Clonidine seems to be a good alternative for sedation in critically-ill children. KeywordsClonidine, Sedation, Critically-ill child Opioids and benzodiazepines are the most frequently administered, but long-term use of these drugs is associated with tolerance and withdrawal, suppression of respiratory drive with prolonged ventilation, constipation, and delayed enteric feeding [2,3].Clonidine is a mixed alpha-1 and alpha-2 adrenoceptor agonist with a predominant alpha-2 action [4]. It has a sedative effect mediated by binding to post-synaptic alpha-2 receptors in the pontine locus ceruleus, reducing noradrenergic output and thereby facilitating the firing of inhibitory neurones, mainly, the gamma-aminobutyric acid system. Clonidine has an analgesic action through binding to alpha-2 receptors in the dorsal horn and supra-spinal sites and thereby reduce the release of P substance [1,5,6]. It also causes peripheral vasodilatation and a decrease in systolic blood pressure, heart rate and cardiac output by decreasing sympathetic nervous system activity. Clonidine has varying degrees of affinity for other cellular components called Nonadrenergic Imidazoline Binding Sites (NAIBS). It seems that the hypotensive effect of clonidine would owe more to their affinity for one type of NAIBS, called I1 receptors [7].As clonidine is lipid soluble, it penetrates the bloodbrain barrier to reach the hypothalamus and medulla [5]. It does not require transformation in to another substance prior to its action and about 20-40% is bound to protein. 50% of the drug is metabolized in the liver to inactive metabolites which are excreted in the urine

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“…While the majority of trials report laboratory or physiological primary outcomes, mortality was the primary outcome measure in 2 % of trials [31]. Data from a recent feasibility trial of clonidine for sedation suggest that at least 190 patients are needed to show a 1.5-day difference in days of ventilation and many more to show relevant differences for other outcomes such as length of PICU and hospital stay [35]. Laboratory or physiological outcomes [36].…”

Section: Outcome Measuresmentioning

confidence: 99%

Ethics of Drug Research in the Pediatric Intensive Care Unit

et al. 2014

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Critical illness and treatment modalities change pharmacokinetics and pharmacodynamics of medications used in critically ill children, in addition to age-related changes in drug disposition and effect. Hence, to ensure effective and safe drug therapy, research in this population is urgently needed. However, conducting research in the vulnerable population of the pediatric intensive care unit (PICU) presents with ethical challenges. This article addresses the main ethical issues specific to drug research in these critically ill children and proposes several solutions. The extraordinary environment of the PICU raises specific challenges to the design and conduct of research. The need for proxy consent of parents (or legal guardians) and the stress-inducing physical environment may threaten informed consent. The informed consent process is challenging because emergency research reduces or even eliminates the time to seek consent. Moreover, parental anxiety may impede adequate understanding and generate misconceptions. Alternative forms of consent have been developed taking into account the unpredictable reality of the acute critical care environment. As with any research in children, the burden and risk should be minimized. Recent developments in sample collection and analysis as well as pharmacokinetic analysis should be considered in the design of studies. Despite the difficulties inherent to drug research in critically ill children, methods are available to conduct ethically sound research resulting in relevant and generalizable data. This should motivate the PICU community to commit to drug research to ultimately provide the right drug at the right dose for every individual child.

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Clonidine in the sedation of mechanically ventilated children: A pilot randomized trial

Cited by 27 publications

References 22 publications

Clonidine for sedation in the critically ill: a systematic review and meta-analysis

Clonidine for sedation in the critically ill: a systematic review and meta-analysis

Intravenous Clonidine: A Useful and Safety Sedation for Critically Ill Children

Ethics of Drug Research in the Pediatric Intensive Care Unit

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