Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial

Ydemann, Mogens; Nielsen, Bendt; Henneberg, Steen Winther; Jakobsen, Janus Christian; Wetterslev, Jørn; Lauritsen, Torsten; Steen, Nick; Edström, Birgitte; Afshari, Arash; Bruun, Solveig; Burgdorf, Bende; Christensen, Susanne Born; Ellekvist, Marguerite; Falcon, Lars; Goth, Louise Salling; Gullaksen, Kim Vinther; Jans, Øivind; Jensen, Mona Kildahl; Johansen, Mathias; Knage, Kirsten; Lunn, Troels Haxholdt; Mondrup, Frederik; Niegsch, Mark; Nielsen, Isabell; Reinhardt, Sidsel

doi:10.1016/s2352-4642(17)30127-x

Cited by 16 publications

(25 citation statements)

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“…an RCT to evaluate postoperative agitation after administering IV clonidine at 3 µg/kg 20 minutes before surgery for children aged 1-5 years who were scheduled for anesthesia with sevoflurane and fentanyl. 27 In accordance with our findings, their results showed that clonidine premedication had a 44% lower relative risk of postoperative agitation than a placebo. 27 As to adverse events, we found that clonidine premedication has a comparable effect on the oculocardiac reflex compared with placebo.…”

Section: Ta B L E 3 Results Of Subgroup Analysessupporting

confidence: 91%

“…27 In accordance with our findings, their results showed that clonidine premedication had a 44% lower relative risk of postoperative agitation than a placebo. 27 As to adverse events, we found that clonidine premedication has a comparable effect on the oculocardiac reflex compared with placebo. None of the children in the clonidine groups experienced significant hemodynamic instability, such as postoperative hypotension, bradycardia, rebound hypertension, or respiratory depression.…”

Section: Ta B L E 3 Results Of Subgroup Analysessupporting

confidence: 91%

“…Our meta‐analysis showed that IV clonidine premedication produced an 11% lower incidence of emergence agitation than a placebo. Ydemann et al conducted an RCT to evaluate postoperative agitation after administering IV clonidine at 3 µg/kg 20 minutes before surgery for children aged 1‐5 years who were scheduled for anesthesia with sevoflurane and fentanyl . In accordance with our findings, their results showed that clonidine premedication had a 44% lower relative risk of postoperative agitation than a placebo …”

Section: Discussionsupporting

confidence: 84%

“…26 Our meta-analysis showed that IV clonidine premedication produced an 11% lower incidence of emergence agitation than a placebo. Ydemann et al 27 conducted…”

Section: Ta B L E 3 Results Of Subgroup Analysesmentioning

confidence: 99%

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Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Hsu

Chu

Bai

et al. 2019

Pediatric Anesthesia

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Background Postoperative vomiting and pain are common, unpleasant phenomena in pediatric patients undergoing ophthalmic surgery. Clonidine has antiemetic and analgesic properties and thus may be used as premedication to reduce postoperative vomiting and pain. Aim To assess whether clonidine premedication may safely decrease postoperative vomiting and postoperative pain in pediatric patients who received an ophthalmic surgery. Methods We systematically searched PubMed, EMBASE, Cochrane Library, and Scopus databases from their inception to September 2018. Randomized clinical trials comparing clonidine premedication with a placebo or an active comparator that investigated postoperative vomiting or postoperative pain in pediatric patients undergoing ophthalmic surgery were included. The primary outcome was postoperative vomiting. The secondary outcome was postoperative pain. We also evaluated the safety of clonidine premedication by tracking hemodynamic instability associated with its use. Results Ten studies with 979 patients were eligible for inclusion. Clonidine achieved a significantly lower incidence of postoperative vomiting within 6 hours postoperatively, 6‐24 hours postoperatively, and at the end of the study (risk difference: −0.15; 95% confidence interval: −0.32 to −0.05; risk difference: −0.15; 95% confidence interval: −0.29 to 0.01; and risk difference: −0.23; 95% confidence interval: −0.34 to −0.12, respectively) than placebo. For the subgroup of patients who received strabismus surgery, clonidine produced a lower incidence of postoperative vomiting than placebo (risk difference: −0.19; 95% confidence interval: −0.29 to −0.05). Compared to benzodiazepine, clonidine achieved a lower incidence of postoperative vomiting at the end of the study (risk difference: −0.19; 95% confidence interval: −0.31 to −0.07); the effect was only observed in patients receiving clonidine 4 μg/kg. Furthermore, children receiving clonidine had lower postoperative pain scores, lower analgesic requirements, and more of them were pain‐free compared to those who received a placebo. No patient using clonidine had any major hemodynamic instability. Conclusion Compared to placebo or benzodiazepine, clonidine premedication was effective in reducing postoperative vomiting in pediatric patients undergoing ophthalmic surgery. Clonidine premedication also provided more reduction in postoperative pain when compared to placebo. The use of clonidine premedication was not associated with adverse hemodynamic events.

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Section: Ta B L E 3 Results Of Subgroup Analysessupporting

confidence: 91%

Section: Ta B L E 3 Results Of Subgroup Analysessupporting

confidence: 91%

Section: Discussionsupporting

confidence: 84%

“…26 Our meta-analysis showed that IV clonidine premedication produced an 11% lower incidence of emergence agitation than a placebo. Ydemann et al 27 conducted…”

Section: Ta B L E 3 Results Of Subgroup Analysesmentioning

confidence: 99%

See 2 more Smart Citations

Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Hsu

Chu

Bai

et al. 2019

Pediatric Anesthesia

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“…Clonidine, the first congener of the α 2 ‐adrenoceptor agonist, is mainly used as an analgesic agent in the rodent and clinical studies. There is increasing behavioural evidence suggesting that clonidine may be effective in the management of neuropathic pain (Bharti, Dontukurthy, Bala, & Singh, ; Engelman & Marsala, ; Ydemann et al, ). Clonidine is approved by the United States Food and Drug Administration for epidural administration as a treatment for neuropathic cancer pain.…”

Section: α2‐adrenoceptors As a Target For Neuropathic Pain Treatment;mentioning

confidence: 99%

Spinal α₂‐adrenoceptors and neuropathic pain modulation; therapeutic target

Bahari

Meftahi

2019

British J Pharmacology

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Neuropathic pain can arise from disease or damage to the nervous system. The most common symptoms of neuropathic pain include spontaneous pain, allodynia, and hyperalgesia. There is still limited knowledge about the factors that initiate and maintain neuropathic pain. However, ample evidence has proved the antinociceptive role of spinal α‐adrenoceptors following nerve injury. It is well‐documented that https://www.sciencedirect.com/topics/neuroscience/norepinephrine descending pathways from supraspinal loci exert an inhibitory influence on the spinal cord nociceptive neurons, mostly through the activation of spinal α2‐adrenoceptors. This, in turn, suppresses transmission of pain input and the hyperexcitability of spinal dorsal horn neurons. There is considerable evidence demonstrating that spinal application of α2‐adrenoceptor https://www.sciencedirect.com/topics/neuroscience/agonists leads to analgesic effects in animal models of neuropathic pain. Today, despite the recent rapid development of neuroscience and drug discovery, effective drugs with clear basic mechanisms have remained a mystery. Here, we give an overview of the cellular mechanisms through which brainstem adrenergic descending inhibitory processing can alter spinal pain transmission to the higher centres, and how these pathways change in neuropathic pain conditions focusing on the role of spinal α2‐adrenoceptors in the spinal dorsal horn. We then suggest that α2‐adrenoceptor agonist may be useful to treat neuropathic pain. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Le delirium postopératoire

Verdonk

2019

Anesthésie & Réanimation

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Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial

Cited by 16 publications

References 34 publications

Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Spinal α₂‐adrenoceptors and neuropathic pain modulation; therapeutic target

Le delirium postopératoire

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Intraoperative clonidine for prevention of postoperative agitation in children anaesthetised with sevoflurane (PREVENT AGITATION): a randomised, placebo-controlled, double-blind trial

Cited by 16 publications

References 34 publications

Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Safety and efficacy of clonidine on postoperative vomiting and pain in pediatric ophthalmic surgery: A systematic review and meta‐analysis

Spinal α2‐adrenoceptors and neuropathic pain modulation; therapeutic target

Le delirium postopératoire

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Spinal α₂‐adrenoceptors and neuropathic pain modulation; therapeutic target