Differential Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by S -Ketamine and Clonidine in Humans

Koppert, Wolfgang; Sittl, Reinhard; Scheuber, Karin; Alsheimer, Monika; Schmelz, Martin; Schüttler, J.

doi:10.1097/00000542-200307000-00025

Cited by 315 publications

(216 citation statements)

References 49 publications

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“…However, long-term therapy with methadone appears to result in OIH as well, and this strategy may suffer limitations. Nevertheless, human studies producing OIH in response to brief infusions of remifentanil provide evidence that ketamine effectively limits hyperalgesia when coadministered, re-invigorating the concept of NMDA receptor antagonism as an effective maneuver [16]. One largescale human trial utilizing dextromethorphan, chosen for its NMDA receptor antagonism, in combination with morphine (MorphiDex®) aimed to reduce pain scores and morphine requirements in chronic pain patients [21].…”

Section: Discussionmentioning

confidence: 99%

“…However, there is insufficient evidence to either support or refute the occurrence of OIH in the clinical setting [15]. Koppert et al studied normal volunteers randomized to opioid infusion in a double-blind placebo-controlled design to assess hyperalgesia induced by electrical stimulation to the forearm [16]. Following induction with the conditioning stimulus hyperalgesia was quantified with von Frey filament mechanical stimulation.…”

Section: Human Data Supporting Oihmentioning

confidence: 99%

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Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Brush¹

2012

J. Med. Toxicol.

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While opioids remain a valid and effective analgesic strategy for patients suffering from a wide variety of painful conditions, they are not a panacea. Increasingly, physicians must balance patient expectations of adequate pain control with known limitations of opioid pharmaceuticals including adverse effects, tolerance, addiction, withdrawal, and drug diversion. Further complicating the issue over the last decade is a growing body of evidence suggesting chronic opioid use may unexpectedly worsen the perception of pain in some individuals. This syndrome, termed opioid-induced hyperalgesia (OIH), fundamentally changes our understanding of opioid pharmacodynamics and may influence our approach to management of chronic pain. This manuscript describes the concept OIH and provides an overview of basic science and clinical research to date attempting to characterize this syndrome, as well as ascertain its clinical relevance. The potential existence of OIH in humans is framed within the context of our current understanding of opioids and our prescribing patterns so that physicians may begin to incorporate these ideas into their philosophy of pain management as further information develops. Animal studies reliably validate OIH in controlled models. Rigorous research protocols in humans are lacking, and we cannot yet confidently conclude that OIH manifests in clinically significant ways. However, clinicians should consider the possibility of OIH when evaluating outcomes of patients on chronic opioid therapy.Keywords Opioids . Hyperalgesia . Opioid-induced hyperalgesia . Chronic pain Current Opioid ParadigmPhysicians regularly prescribe opioids for control of moderate to severe pain in the acute care setting. This includes administration in emergency, outpatient, and inpatient environments for patients suffering from a variety of acute and chronic painful conditions. Our current paradigm for opioid utilization suggests they provide effective analgesia for short-term use in most patients. Unfortunately, the risk of adverse effects or addiction is not rare and may be difficult to accurately quantify [1]. Regular prescription of opioids also occurs in the long-term care setting for patients with cancer-related pain offering effective pain relief and limited concern for addiction. However, long-term use of opioids for treatment of certain chronic conditions such as back pain, fibromyalgia, or neuropathic pain syndromes sparks more debate regarding therapeutic efficacy, adverse effects, and potential for misuse, abuse, and diversion of prescription opioids. Concerns regarding opioid use for patients with chronic non-cancer pain may relate to a subset of these patients who require significant dose escalation over time, visit multiple providers seeking opioid prescriptions, and report insufficient pain relief despite high dose therapy. These scenarios generate several concerns including the possibility that chronic opioid administration may be an ineffective strategy for long-term analgesia. Emerging evidence suggests t...

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Section: Discussionmentioning

confidence: 99%

Section: Human Data Supporting Oihmentioning

confidence: 99%

Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Brush¹

2012

J. Med. Toxicol.

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“…This definition, however, is subject to an inherent bias due to a possible hyperalgesia caused by remifentanil which Koppert et al (2003) noted even after a short remifentanil infusion in volunteers with experimental pain. As a result, there may be an overestimation in PID in these two studies and study I which also employed the same method of calculating the PID.…”

Section: Fhr Tracings Delivery Mode Uaph and Apgar Scoresmentioning

confidence: 99%

“…Secondly, there is an acute opioidinduced hyperalgesia through enhancement of the N-methyl-D-aspartic acid (NMDA) receptor response which has been noted in rat dorsal horn cell cultures after as little as 36 minutes exposure to clinically relevant concentrations of remifentanil (Zhao and Joo 2008). Volunteer studies suggest that a similarly rapid post-infusion hyperalgesia exists in humans as well, while development of an acute tolerance was not observed during a 3 hour infusion with clinically relevant doses (Koppert et al 2003, Angst et al 2009). The current investigation is unable to clarify the degree to which these two possible mechanisms -pain increase as labour progresses and development of acute hyperalgesia -would affect the results.…”

Section: Fhr Tracings Delivery Mode Uaph and Apgar Scoresmentioning

confidence: 99%

“…Possibly, better systemic analgesia with remifentanil could be achievd by using adjunct medication with synergistic analgesic properties but different side effects, especially if the adjunct medication could prevent the development of acute hyperalgesia as suggested in chapter 6.1. Nitrous oxide, ketamine or clonidine could be employed (Koppert et al 2003, Richebé et al 2005). This again is, however, highly speculative and would need further experimental and clinical research not only due to of the uncertainty of whether the observations in rodents and human volunteers could be translated to labour analgesia, but also because of the potential risks associated with combination treatments.…”

Section: Sedation and Dizzinessmentioning

confidence: 99%

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Intravenous patient-controlled analgesia with remifentanil in early labour

Volmanen¹

2011

Acta Anaesthesiologica Scandinavica

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Cover design Raimo Ahonen JUVENES PRINT TAMPERE 2010Volmanen, Petri, Intravenous patient controlled analgesia with remifentanil in early labour. AbstractIn four prospective clinical trials, 114 parturients used intravenous patient-controlled remifentanil analgesia during the 1 st stage of labour. The median effective dose per bolus was ascertained to be 0.4 μg/kg and the pain scores were reduced with this by a median of 2 on a numerical scale (0-10). Compared with nitrous oxide, 15 parturients included in a cross-over study reported a larger reduction in pain scores during remifentanil analgesia (1.5 vs. 0.5, p = 0.001) and better pain relief scores (2.5 vs. 0.5 on a ranked five point scale 0-4, p < 0.001). In a parallel study including 45 parturients, epidural analgesia (EDA, 20 ml bupivacaine 0.625 mg/ml and fentanyl 2 μg/ml) was associated with lower pain scores (5.2 vs. 7.3 with remifentanil, p = 0.004) but variables related to satisfaction with analgesia (pain relief score, proportion of mothers with desire to continue with the given medication and termination of the study due to inadequate pain relief) were similar. A comparison of two methods for timing the remifentanil bolus during the uterine contraction cycle suggested that delaying the bolus does not improve analgesia. A period effect was noted in the cross-over trial with higher pain scores and increased drug consumption during the second study period suggesting acute hyperalgesia.Side effects of remifentanil analgesia included respiratory depression warranting oxygen supplementation in 33% of parturients. Sedation was experienced by the parturients using remifentanil and this was scored as stronger than sedation during nitrous oxide and EDA. The number of parturients with nausea did not increase during remifentanil analgesia. Other maternal side effects included dizziness, a difficulty in visual focusing and itching. Foetal heart rate tracing abnormalities were noted. The incidence of abnormal tracings and decreased UapH were not different, however, from that observed during nitrous oxide or EDA. Apgar scores at 1 and 5 minute indicated no neonatal depression. Keywords

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A randomized phase I trial evaluating the effects of inhaled 50–50% N₂O–O₂ on remifentanil‐induced hyperalgesia and allodynia in human volunteers

Wehrfritz

Schaefer

Troester

et al. 2016

European Journal of Pain

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Nitrous oxide significantly reduced hyperalgesia, allodynia and pain intensity aggravated after remifentanil administration in a human volunteer model. WHAT DOES THIS STUDY ADD?: This study brings the evidence that N2 O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well-known model of electrical pain. N2 O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model.

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Differential Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by S -Ketamine and Clonidine in Humans

Cited by 315 publications

References 49 publications

Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Intravenous patient-controlled analgesia with remifentanil in early labour

A randomized phase I trial evaluating the effects of inhaled 50–50% N₂O–O₂ on remifentanil‐induced hyperalgesia and allodynia in human volunteers

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Differential Modulation of Remifentanil-induced Analgesia and Postinfusion Hyperalgesia by S -Ketamine and Clonidine in Humans

Cited by 315 publications

References 49 publications

Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Complications of Long-Term Opioid Therapy for Management of Chronic Pain: the Paradox of Opioid-Induced Hyperalgesia

Intravenous patient-controlled analgesia with remifentanil in early labour

A randomized phase I trial evaluating the effects of inhaled 50–50% N2O–O2 on remifentanil‐induced hyperalgesia and allodynia in human volunteers

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Product

Resources

About

A randomized phase I trial evaluating the effects of inhaled 50–50% N₂O–O₂ on remifentanil‐induced hyperalgesia and allodynia in human volunteers