Intra-operative remifentanil is associated with increased postoperative analgesic requirements and opioid consumption. Dexmedetomidine has characteristics suggesting it may substitute for intra-operative remifentanil during general anaesthesia, but existing literature has reported conflicting results. We undertook this meta-analysis to investigate whether general anaesthesia including dexmedetomidine would result in less postoperative pain than general anaesthesia including remifentanil. The MEDLINE and PubMed electronic databases were searched up to October 2018. Only randomised trials including patients receiving general anaesthesia and comparing dexmedetomidine with remifentanil administration were included. Meta-analyses were performed mostly employing a random effects model. The primary outcome was pain score at rest (visual analogue scale, 0-10) at two postoperative hours. The secondary outcomes included: pain score at rest at 24 postoperative hours; opioid consumption at 2 and 24 postoperative hours; and rates of hypotension, bradycardia, shivering and postoperative nausea and vomiting. Twenty-one randomised trials, including 1309 patients, were identified. Pain scores at rest at two postoperative hours were lower in the dexmedetomidine group, with a mean difference (95%CI) of À0.7 (À1.2 to À0.2), I 2 = 85%, p = 0.004, and a moderate quality of evidence. Secondary pain outcomes were also significantly better in the dexmedetomidine group. Rates of hypotension, shivering and postoperative nausea and vomiting were at least twice as frequent in patients who received remifentanil. Time to analgesia request was longer, and use of postoperative morphine and rescue analgesia were less, with dexmedetomidine, whereas episodes of bradycardia were similar between groups. There is moderate evidence that intra-operative dexmedetomidine during general anaesthesia improves pain outcomes during the first 24 postoperative hours, when compared with remifentanil, with fewer side effects.
Fentanyl is an opioid initially developed for parenteral administration. While oral administration is not an option due to a high first-pass metabolism, its high potency and lipophilicity have made a number of new routes of administration feasible. The transdermal therapeutic system offers an excellent option for long-term treatment of cancer and chronic pain, achieving stable plasma concentrations over the treatment period. The recent change from reservoir to matrix systems has made these systems more convenient to wear and safer to use, while being bioequivalent. In contrast, the patient-controlled iontophoretic transdermal system has been developed to enable on-demand delivery of transdermal bolus doses of fentanyl to treat postoperative pain. It offers a needle-free system to provide patient-controlled analgesia otherwise offered by intravenous pumps. However, due to technical difficulties the system is currently not clinically available. Oral transmucosal fentanyl utilizes the rapid uptake through the buccal mucosa to achieve high plasma concentrations rapidly and is indicated to treat breakthrough pain in patients who are not opioid-naive. The recently introduced fentanyl buccal tablets offer slightly better pharmacokinetics for the same indication. The intranasal route is another option to achieve rapid uptake of fentanyl, and is currently being investigated to provide acute and breakthrough pain relief. Transpulmonary administration of fentanyl remains experimental and this route of administration is not yet in clinical use. Overall, the specific pharmacological and physicochemical properties of fentanyl have made this compound highly suitable for novel routes of administration in a range of clinical indications.
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