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Created July 23, 2019, last updated almost 4 years ago.
Collection: 105, Score: 1455, Trend score: 0, Read count: 1994, Articles count: 12, Created: 2019-07-23 06:05:41 UTC. Updated: 2021-02-07 07:06:53 UTC.Notes
- Remifentanil infusions above 0.20-0.25 μg/kg/min are associated with hyperalgesia (OIH = Opioid Induced Hyperalgesia) and tolerance (AOT = Acute Opioid Tolerance) respectively.
- Some of these effects can be mitigated by multimodal analgesia (notably ketamine), and possibly by gradual weaning of a remifentanil infusion.
- The findings have been predominately identified in rats and volunteer human studies. The clinical and longterm significance is still uncertain.
- Although OIH and AOT arise from different physiological mechanisms, they are clinically difficult (if not impossible) to differentiate.
- The clinical priority for management is prevention.
Daniel Jolley
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Collected Articles
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The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. ⋯ Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.
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Randomized Controlled Trial
Gradual withdrawal of remifentanil infusion may prevent opioid-induced hyperalgesia.
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Curr Opin Anaesthesiol · Aug 2017
ReviewOpioid-induced hyperalgesia in clinical anesthesia practice: what has remained from theoretical concepts and experimental studies?
This article reviews the phenomenon of opioid-induced hyperalgesia (OIH) and its implications for clinical anesthesia. The goal of this review is to give an update on perioperative prevention and treatment strategies, based on findings in preclinical and clinical research. ⋯ Since the immediate postoperative period is not ideal to initiate long-term treatment for OIH, the best strategy is to prevent its occurrence. A multimodal approach, including choice of opioid, dose limitations and addition of nonopioid analgesics, is recommended.
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J Pain Symptom Manage · Mar 2015
Opioid-induced hyperalgesia (OIH): a real clinical problem or just an experimental phenomenon?
Although opioid-induced hyperalgesia (OIH) is mentioned as a potential cause of opioid dose escalation without adequate analgesia, true evidence in support of this notion is relatively limited. Most studies conducted in the context of acute and experimental pain, which seemingly demonstrated evidence for OIH, actually might have measured other phenomena such as acute opioid withdrawal or tolerance. ⋯ Thus far, with the exception of a few clinical case reports on OIH in patients with cancer pain and one prospective study in patients with chronic neuropathic pain, evidence for OIH in patients with chronic or cancer-related pain is lacking. Whether experimental pain models are necessary for establishing the clinical diagnosis of OIH, and which specific model is preferred, are yet to be determined.
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Expert Opin Drug Saf · May 2014
Review Meta AnalysisAn evidence based systematic review of remifentanil associated opioid-induced hyperalgesia.
Therapeutic opioid use continues to grow, with greater than a fivefold increase in usage of fentanyl-based products over a 10-year period. Opioids are known for their side-effect profile, including bradycardia and respiratory depression; questions remain, however, regarding lesser known side effects such as opioid-induced hyperalgesia (OIH). ⋯ There is conflicting evidence regarding the existence of remifentanil OIH. Outcomes evaluating measures of hyperalgesia frequently conclude that remifentanil OIH exists, while those evaluating opioid consumption do not. Therefore, remifentanil does induce a degree of hyperalgesia, but we do not believe that it reaches a level of clinical significance that requires prevention. If a significant concern for the development of remifentanil OIH is suspected, we suggest using the least possible effective dose of remifentanil as the primary prevention strategy.
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Frontiers in pharmacology · Jan 2014
ReviewIntraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review.
The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. ⋯ AOT - defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH - defined as decreased pain threshold after chronic opioid treatment, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug's effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.
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The unique pharmacology of remifentanil makes it a popular intra-operative analgesic. Short-acting opioids like remifentanil have been associated with acute opioid tolerance and/or opioid-induced hyperalgesia, two phenomena which have different mechanisms and are pharmacologically distinct. Clinical studies show heterogeneity of remifentanil infusion regimens, durations of infusion, maintenance of anaesthesia, cumulative dose of remifentanil and pain measures, which makes it difficult to draw conclusions about the incidence of acute tolerance or hyperalgesia. ⋯ Infusion rates greater than 0.2 μg.kg-1 .min-1 are characterised by lower mechanical/pressure/cold/pain thresholds, which suggests hyperalgesia. The use of concurrent multimodal analgesia, especially N-methyl-D-aspartate receptor antagonists, may be an effective preventive strategy. The clinical significance and long-term consequences of these entities is still uncertain.
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Review Meta Analysis Comparative Study
Intra-operative analgesia with remifentanil vs. dexmedetomidine: a systematic review and meta-analysis with trial sequential analysis.
Intraoperative dexmedetomidine infusions result in less postoperative pain, hypotension, shivering and PONV than remifentanil.
pearl -
What’s the relevance?
Remifentanil’s ultrashort-acting kinetics have driven its growth as a reliable technique for maintaining intraoperative analgesia. It is now one of the most widely used synthetic opioids in anesthesia.
However these unique pharmacological characteristics are associated with both Opioid Induced Hyperalgesia and Acute Opioid Tolerance, and possibly increase the risk of chronic pain after surgery.
Details:
Niedermayer and team performed a large, multicenter, propensity-matched observational study of remifentanil use during intra-abdominal surgery, and its association with postoperative pain in the PACU. Importantly the patients receiving epidural analgesia in addition to TIVA GA were also included. Volatile GA was excluded.
Among 16,420 patients meeting inclusion criteria, 3,652 GA/TIVA patients received remifentanil and were matched to 3,318 controls, and 829 GA/epi received remifentanil, being matched to 631 controls. Mean remifentanil infusions rates were 0.11 and 0.13 mcg/kg/min for non-EA and EA groups respectively.
They showed:
Among GA-only patients, remifentanil was associated with higher PACU pain scores (both on arrival and discharge), greater analgesic requirements and more PONV – however there was no decrease of either time-to-extubation or PACU discharge.
Interestingly, the epidural analgesia cohort also showed higher PACU pain scores when receiving remifentanil.
The rapid nociceptive changes due to remifentil are well known, however real clincial consequences remain unclear. This large observational study highlights the detrimental analgesic effects of remifentanil in the most immediate post-op period, reminding anesthetists and anesthesiologists that gold-standard intraoperative analgesia may come at a cost.
Dig deeper
Explore collected articles answering: Is remifentanil associated with Opioid Induced Hyperalgesia and Acute Opioid Tolerance?
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Randomized Controlled Trial
Remifentanil during cardiac surgery is associated with chronic thoracic pain 1 yr after sternotomy.
Chronic thoracic pain after cardiac surgery is a serious condition affecting many patients. The aim of this study was to identify predictors for chronic thoracic pain after sternotomy in cardiac surgery patients by analysing patient and perioperative characteristics. ⋯ In this follow-up study in cardiac surgery patients, intraoperative remifentanil was predictive for chronic thoracic pain in a dose-dependent manner. Randomized studies designed to evaluate the influence of intraoperative remifentanil on chronic thoracic pain are needed to confirm these results.
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J. Cardiothorac. Vasc. Anesth. · Aug 2010
Randomized Controlled Trial Comparative StudyDifferent anesthetic techniques associated with different incidences of chronic post-thoracotomy pain: low-dose remifentanil plus presurgical epidural analgesia is preferable to high-dose remifentanil with postsurgical epidural analgesia.
To investigate the relationships between 2 anesthetic techniques, or the extent of allodynia around the surgical wound, and the occurrence of chronic post-thoracotomy pain. ⋯ High-dose remifentanil (0.14-0.26 microg/kg/min) without epidural analgesia during surgery is associated with a large area of allodynia around the wound. These patients develop a much higher incidence of chronic pain than those receiving low-dose remifentanil with epidural analgesia during surgery.
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Anesthesia and analgesia · Nov 2020
Randomized Controlled TrialComparison of Pupillometry With Surgical Pleth Index Monitoring on Perioperative Opioid Consumption and Nociception During Propofol-Remifentanil Anesthesia: A Prospective Randomized Controlled Trial.
Intraoperative pupillometry monitoring is a feasible surrogate for nociception assessment, resulting in both lower intraoperative remifentanil consumption and lower peak post-operative pain.
pearl