Esketamine counters opioid-induced respiratory depression

Jonkman, Kelly; Rijnsoever, E. van; Olofsen, Erik; Aarts, Leon; Sarton, Elise; Velzen, Monique van; Niesters, Marieke; Dahan, Albert

doi:10.1016/j.bja.2018.02.021

Cited by 95 publications

(102 citation statements)

References 47 publications

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“…As we previously showed, breathing activity is initiated when remifentanil plasma concentrations drop to about 2 ng/ml. 15,16 We observed no differences in pain scores and morphine consumption in the PACU (table 3). This could be related to the inability of the nociception level to impact postoperative events when using short-acting opioids or to the use of preemptive morphine treatment.…”

Section: Secondary Endpointsmentioning

confidence: 75%

Nociception-guided versus Standard Care during Remifentanil–Propofol Anesthesia

et al. 2019

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Editor’s Perspective What We Already Know about This Topic The nociception level index (Medasense Biometrics Ltd., Ramat Gan, Israel), is a reliable measure of moderate to intense noxious stimulation during anesthesia and surgery What This Article Tells Us That Is New In a randomized trial in patients having major abdominal surgery, compared to standard practice, nociception level-guided analgesia resulted in 30% less intraoperative remifentanil consumption Background The multidimensional index of nociception, the nociception level, outperforms blood pressure and heart rate in detection of nociceptive events during anesthesia. We hypothesized that nociception level–guided analgesia reduces opioid consumption and suboptimal anesthesia events such as low blood pressure and use of vasoactive medication. Methods In this single-blinded randomized study, 80 American Society of Anesthesiologists class I–III adult patients of either sex, scheduled for major abdominal procedures under remifentanil/propofol anesthesia by target-controlled infusion, were included. During the procedure nociception level, noninvasive blood pressure, and heart rate were monitored. Patients were randomized to receive standard clinical care or nociception level–guided analgesia. In the nociception level–guided group, remifentanil concentration was reduced when index values were less than 10 or increased when values were above 25 for at least 1 min, in steps of 0.5 to 1.0 ng/ml. Propofol was titrated to bispectral index values between 45 and 55. The primary outcomes of the study were remifentanil and propofol consumption and inadequate anesthesia events. Results Compared with standard care, remifentanil administration was reduced in nociception level–guided patients from (mean ± SD) 0.119 ± 0.033 to 0.086 ± 0.032 μg · kg-1 · min-1 (mean difference, 0.039 μg · kg-1 · min-1; 95% CI, 0.025–0.052 μg · kg-1 · min-1; P < 0.001). Among nociception level–guided patients, 2 of 40 (5%) experienced a hypotensive event (mean arterial pressure values less than 55 mm Hg) versus 11 of 40 (28%) patients in the control group (relative risk, 0.271; 95% CI, 0.08–0.77; P = 0.006). In the nociception level–guided group, 16 of 40 (40%) patients received vasoactive medication versus 25 of 40 (63%) patients in the standard care group (relative risk, 0.64; 95% CI, 0.40–0.99; P = 0.044). Conclusions Nociception level-guided analgesia during major abdominal surgery resulted in 30% less remifentanil consumption.

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Section: Secondary Endpointsmentioning

confidence: 75%

Nociception-guided versus Standard Care during Remifentanil–Propofol Anesthesia

et al. 2019

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“…infusion of the NMDA receptor antagonist esketamine at a subanesthetic dose dose-dependently reversed respiratory depression induced by i.v. remifentanil 35 . This was underpinned by a stimulatory effect on ventilatory CO 2 chemosensitivity that was otherwise reduced by remifentanil alone 35 .…”

Section: Recent Advances In Countering Opioid-induced Respiratory Depmentioning

confidence: 99%

“…This was underpinned by a stimulatory effect on ventilatory CO 2 chemosensitivity that was otherwise reduced by remifentanil alone 35 . The esketamine effect had a rapid onset of action and it was driven by plasma pharmacokinetics 35 . By contrast, esketamine had little or no effect on resting ventilation.…”

Section: Recent Advances In Countering Opioid-induced Respiratory Depmentioning

confidence: 99%

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Countering opioid-induced respiratory depression by non-opioids that are respiratory stimulants

2020

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Strong opioid analgesics are the mainstay of therapy for the relief of moderate to severe acute nociceptive pain that may occur post-operatively or following major trauma, as well as for the management of chronic cancer-related pain. Opioid-related adverse effects include nausea and vomiting, sedation, respiratory depression, constipation, tolerance, and addiction/abuse liability. Of these, respiratory depression is of the most concern to clinicians owing to the potential for fatal consequences. In the broader community, opioid overdose due to either prescription or illicit opioids or co-administration with central nervous system depressants may evoke respiratory depression. To address this problem, there is ongoing interest in the identification of non-opioid respiratory stimulants to reverse opioid-induced respiratory depression but without reversing opioid analgesia. Promising compound classes evaluated to date include those that act on a diverse array of receptors including 5-hydroxytryptamine, D1-dopamine, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) receptor antagonists, and nicotinic acetylcholine as well as phosphodiesterase inhibitors and molecules that act on potassium channels on oxygen-sensing cells in the carotid body. The aim of this article is to review recent advances in the development potential of these compounds for countering opioid-induced respiratory depression.

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“…These factors should be considered when considering ketamine treatment. The second question has recently been addressed by Jonkman et al [64]. They showed that ketamine effectively counteracts opioid-induced respiratory depression, possibly through its (indirect) actions at the AMPA receptor [65].…”

Section: Expert Opinionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

Kamp

Olofsen

et al. 2019

Expert Opinion on Drug Metabolism & Toxicology

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Introduction: Chronic neuropathic pain (NP) is an incapacitating illness caused by a lesion of the somatosensory nervous system and is associated with several diseases or syndromes. Since current treatment options lack adequate efficacy in the majority of patients, ketamine is often administered to treat refractory NP. Areas covered: This review gives an overview of new ketamine pharmacokinetic data including data on intranasal and inhaled ketamine. The outcome of seven systematic reviews and meta-analyses, published since 2012, on ketamine efficacy in NP is discussed. The reader will additionally get an understanding of ketamine's complex metabolism with emphasis on the metabolite hydroxynorketamine. Expert opinion: Proof of sustained, large effects of ketamine in the treatment of NP from randomized controlled clinical trials is lacking, although we cannot exclude selective ketamine efficacy in patients with central sensitization, opioid-induced hyperalgesia or opioid tolerance. Interestingly, data from observational trials and case series do suggest the efficacy of ketamine in producing effective pain relief in NP with positive patient-related outcome measures. Additional randomized trials in often illdefined groups of chronic pain patients are not useful and we suggest to conduct future studies in NP patients with central sensitization and/or with opioid refractory severe NP.

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Esketamine counters opioid-induced respiratory depression

Abstract: Esketamine effectively countered remifentanil-induced respiratory depression, an effect that was attributed to an increase in remifentanil-reduced ventilatory CO chemosensitivity.

Cited by 95 publications

References 47 publications

Nociception-guided versus Standard Care during Remifentanil–Propofol Anesthesia

Nociception-guided versus Standard Care during Remifentanil–Propofol Anesthesia

Countering opioid-induced respiratory depression by non-opioids that are respiratory stimulants

Pharmacokinetic and pharmacodynamic considerations for NMDA-receptor antagonist ketamine in the treatment of chronic neuropathic pain: an update of the most recent literature

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