Opioid-induced Hyperalgesia in Patients With Chronic Pain: A Systematic Review of Published Cases.

INTRODUCTION: Opioid-induced hyperalgesia (OIH) remains an issue in patients with chronic pain. Multiple cases of OIH in patients with chronic pain exposed to opioids have been reported worldwide. The objective of this systematic review was to summarize the evidence of OIH from clinical reports. METHODS: We searched the PubMed, Cochrane, EMBASE, and LILACS databases for case reports and case series of OIH published up to December 2020, with the aim to summarize the evidence for OIH in patients with chronic pain from clinical reports and to discuss issues relevant to the clinical diagnosis and management of OIH. RESULTS: We retrieved and reviewed 41 articles describing 72 cases. Clinical features of OIH were observed in patients of both sexes, all ages, and with various types of pain treated with different classes of opioids. OIH was reported at all doses, but most published studies reported a pattern of OIH following treatment with very high daily doses of opioids (median oral morphine equivalent dose of 850 mg). OIH was diagnosed clinically in all cases. Three different strategies for OIH management were described: opioid rotation, opioid cessation, and the use of adjuvant pharmacotherapies. All had statistically similar success rates for OIH treatment: 72%, 57%, and 79%, respectively. The decrease in pain was achieved rapidly (mean: 8 d; range: 1 to 28 d). Adjuvant therapies resulted in the largest decrease in dose. Ketamine and dexmedetomidine were the most widely used adjuvant drugs. CONCLUSION: The key finding is that clinical symptoms of OIH can be resolved when this condition is diagnosed and managed.

Comparison of Train of Four Measurements with Kinemyography NMT DATEX and Accelerography TOFscan.

INTRODUCTION: This study was designed to compare the Datex neuromuscular transmission (NMT) kinemyography (NMTK) device with the TOFscan (TS) accelerometer during the onset and recovery of neuromuscular blockade. PATIENTS AND METHODS: This prospective study included adult patients who were scheduled to undergo elective surgery with general anesthesia and orotracheal intubation. The TS accelerometer was randomly placed at the adductor pollicis on one hand, and the NMTK was placed on the opposite arm. Anesthesia was initiated with remifentanil target-controlled infusion (TCI) and 2.0-3.0 mg/kg of propofol. Thereafter, 0.5 mg/kg of atracurium or 0.6 mg/kg of rocuronium was injected. If needed, additional neuromuscular blocking agents were administered to facilitate surgery. First, we recorded the train of four (TOF) response at the onset of neuromuscular blockade to reach a TOF count of 0. Second, we recorded the TOF response at the recovery of neuromuscular blockade to obtain a T4/T1 90% by both TS and NMTK. RESULTS: There were 32 patients, aged 38-83 years, with the American Society of Anesthesiologists (ASA) Physical Status Classification I-III included and analyzed. Surgery was abdominal, gynecologic, or head and neck. The Bland and Altman analysis for obtaining zero responses during the onset showed a bias (mean) of 2.7 s (delay) of TS in comparison to NMTK, with an upper/lower limit of agreement of [104; -109 s] and a bias of 36 s of TS in comparison to NMTK, with an upper/lower limit of agreement of [-21.8, -23.1 min] during recovery (T4/T1 > 90%). CONCLUSIONS: Under the conditions of the present study, the two devices are not interchangeable. Clinical decisions for deep neuromuscular blockade should be made cautiously, as both devices appear less accurate with significant variability.

Perioperative adverse events attributed to α2-adrenoceptor agonists in patients not at risk of cardiovascular events: systematic review and meta-analysis.

BACKGROUND: Several systematic reviews have reported the benefits of perioperative α2-adrenoceptor agonist use for various conditions, but safety evidence is poorly documented. METHODS: We performed a systematic review focusing on adverse events. We searched the MEDLINE, Embase, LILACS, Cochrane, and Clinical Trials Register databases for RCTs comparing the effects of α2-adrenoceptor agonists and placebo during non-cardiovascular surgery under general anaesthesia, for any indication, in patients not at risk of cardiovascular events. The primary outcome was the incidence of severe adverse events during or after α2-adrenoceptor agonist administration. The secondary endpoints were other adverse events. A meta-analysis was carried out on the combined data. Evidence quality was rated by the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We included 56 studies (4868 patients). Our review, based on moderate-quality evidence, revealed that hypotension occurred frequently during the preoperative and postoperative periods, for both clonidine and dexmedetomidine. Bradycardia was reported only with dexmedetomidine. In contrast, dexmedetomidine seemed to protect against intraoperative hypertension and tachycardia. Subgroup analysis suggested that the risk of hypotension and bradycardia persisted after cessation of treatment. Interestingly, intraoperative hypotension and postoperative bradycardia were not observed with a bolus dosage of dexmedetomidine less than 0.5 µg kg-1 or with continuous administration alone. CONCLUSIONS: Pooled data for the incidence of adverse events associated with use of α2-adrenoceptor agonists in various perioperative contexts provide high-confidence evidence for a risk of hypotension and bradycardia, and protective effects against hypertension and tachycardia. PROTOCOL REGISTRATION: CRD42017071583.