Use of oral clonidine for sedation in ventilated paediatric intensive care patients

Arenas-López, Sara; Riphagen, Shelley; Tibby, Shane M.; Durward, Andrew; Tomlin, Steve; Davies, Graham; Murdoch, Ian A.

doi:10.1007/s00134-004-2319-0

Cited by 72 publications

(83 citation statements)

References 20 publications

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“…Clonidine, when used in combination with intravenous opioids, reduces total opioid use in infants 42. Thus, clonidine is likely to be effective when combined with oral morphine.…”

Section: Discussionmentioning

confidence: 99%

Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Kim²,

et al. 2009

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Objective To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome. Methods Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of ≥9) were enrolled at 2 hospitals during 2002–2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 μg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation. Results The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8–15 days]) than in the placebo group (15 days [95% confidence interval: 12–17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age. Conclusions In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.

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“…Clonidine, when used in combination with intravenous opioids, reduces total opioid use in infants 42. Thus, clonidine is likely to be effective when combined with oral morphine.…”

Section: Discussionmentioning

confidence: 99%

Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Kim²,

et al. 2009

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“…For ICU patients in general, appropriate sedation can avert delirium, which has a highly adverse impact on later prognosis [85][86][87][88][89]. Clonidine has been applied in this setting [90][91][92], but dexmedetomidine is currently the only ␣ 2 -agonist approved for use in the ICU in several countries. Dexmedetomidine is distinguished by the quality of sedation it confers [93]: patients sedated with dexmedetomidine are characteristically easy to rouse but lapse into a tranquil, sleep-like state with no respiratory depression [94] when left undisturbed.…”

Section: Sedationmentioning

confidence: 99%

Perioperative use of α2-adrenoceptor agonists and the cardiac patient

Aantaa

Jalonen

2006

European Journal of Anaesthesiology

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The centrally acting alpha2-adrenoceptor agonists clonidine and dexmedetomidine have been used with success to provide haemodynamic stability for patients undergoing surgery. Particularly in the case of patients with overt or underlying cardiac disease the actions of alpha2-adrenoceptor agonists, which include maintenance of stable systemic blood pressure and low heart rate and a reduction in overall oxygen consumption, can be expected to reduce the risk of procedure-related cardiac events. This expectation has been corroborated in clinical trials with clonidine, dexmedetomidine and mivazerol and meta-analyses; additional large controlled trials would be instructive in establishing a robust estimate of the scale of the benefit. In addition, alpha2-adrenoceptor agonists used as premedication have been shown to substantially reduce anaesthetic requirements among surgical patients, and the use of these agents has been associated with a reduced risk of postoperative delirium, which may be expected to improve considerably the postoperative course for at-risk patients. Dexmedetomidine is the only alpha2-adrenoceptor agonist currently approved for use in the intensive care unit. A distinctive feature of dexmedetomidine in that setting is that in addition to haemodynamic stability it confers a distinctive and advantageous quality of sedation: patients are tranquil but responsive to requests from attending staff. This review examines the pharmacological principles underlying the use of alpha2-adrenoceptor agonists as adjuncts to surgery and clinical experience in that indication.

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“…Arenas-López et al [18] demonstrated a consistent and adequate level of sedation in the majority of cases at clonidine plasma concentrations of 0.9-2.5 ng/ml. Sumiya et al [19] reported that the plasma clonidine concentration of 0.3-0.8 ng/ml would be sufficient to produce a satisfactory sedation in pediatric surgery.…”

Section: Discussionmentioning

confidence: 99%

Effects of clonidine on the activity of the rat glutamate transporter EAAT3 expressed inXenopusoocytes

Woo

Han

Baik

et al. 2012

Korean J Anesthesiol

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BackgroundClonidine has been shown to be a potent neuroprotectant by acting at α2 receptors on glutamatergic neurons to inhibit the release of glutamate. The aim of this study is to investigate the effects of clonidine on the activity of EAAT3 that can regulate extracellular glutamate.MethodsEAAT3 was expressed in the Xenopus oocytes. Using a two-electrode voltage clamp, membrane currents were recorded after application of 30 µM L-glutamate both in the presence and absence of various concentrations of clonidine. To determine the effects of clonidine on the Km and Vmax of EAAT3 and the reversibility of clonidine effects, membrane currents were recorded after the application of various concentrations of L-glutamate both in the presence and absence of 1.50 × 10-7 M clonidine.ResultsClonidine reduced the EAAT3 responses to L-glutamate in a concentration-dependent manner. This inhibition was statistically significant at higher concentrations than at the clinically relevant range. Clonidine at 1.50 × 10-7 M reduced the Vmax, but did not affect the Km of EAAT3 for L-glutamate.ConclusionsThese results suggest that the direct inhibition of EAAT3 activity is not related to the sedation effect of clonidine and that the clonidine-induced reduction of EAAT3 activity provides additional data for the possible involvement of glutamatergic hyperactivity in the proconvulsant effect of clonidine.

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Use of oral clonidine for sedation in ventilated paediatric intensive care patients

Abstract: Oral clonidine may be a safe and effective sedative in combination with morphine and lorazepam for young children with single-organ, respiratory failure. This agent may also exhibit opioid and benzodiazepine sparing effects in this patient group. A full pharmacokinetic study is warranted.

Cited by 72 publications

References 20 publications

Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Clonidine as an Adjunct Therapy to Opioids for Neonatal Abstinence Syndrome: A Randomized, Controlled Trial

Perioperative use of α2-adrenoceptor agonists and the cardiac patient

Effects of clonidine on the activity of the rat glutamate transporter EAAT3 expressed inXenopusoocytes

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