Caroline Vanlersberghe

The Role of COX-2 Inhibitors in Pain Modulation

NSAIDs are the analgesics that are most commonly used world-wide. In the past few years, there have been significant advances in explaining the mechanism of action and clinical efficacy of the drugs belonging to this pharmacological family. Recent data relating to the role of cyclo-oxygenase (COX)-2 in the development of neuronal hyperexcitability and pain hypersensitivity have opened new perspectives in our understanding of the therapeutic effects of these drugs in several painful conditions. The main objective of this brief review is to deal with some physiopathological and pharmacological aspects concerning the role of NSAIDs, with special reference to COX-2 inhibitors, in the treatment of pain.

Comparison of remifentanil and propofol infusions for sedation during regional anesthesia

Background and Objectives. Patients treated with regional anesthesia often require concomitant medication for comfort and sedation. Propofol is widely used for this purpose. Remifentanil, a new ultra‐short‐acting opioid, exhibits at low doses distinct sedative properties that may be useful for supplementation of regional anesthesia. This study compared the effectiveness of remifentanil and propofol infusions for providing sedation during regional block placement and surgery. Methods. In an open, prospective trial, 28 patients were randomly allocated to receive continuous infusions of remifentanil (6 μg/kg/h) or propofol (3 mg/kg/h) for sedation during spinal or axillary regional anesthesia. Infusion rates were titrated to maintain a sedation level ≥ 2 as assessed with the Observers Assessment of Alertness Scale. Vital signs were measured continuously, during and for 2 hours after ending study drug infusion. Results. Similar scores for comfort and sedation were obtained in both groups during placement of the regional block and during surgery. Degree of sedation correlated with drug infusion rate of remifentanil (P < .002) but not for propofol. Respiratory rate decreased in the remifentanil group in absence of surgery (P < .05). Mean arterial pressure and heart rate were 20% lower in the propofol group (P < .05). Return to alertness occurred after 10 ± 6 minutes in the remifentanil group and after 16 ± 15 minutes in the propofol group. Similar incidences of hypotension, bradycardia, and nausea and vomiting were found in both groups, but intraoperative respiratory depression and nausea were more prominent in the remifentanil group. Conclusions. When titrated to the same sedation level, remifentanil provided a smoother hemodynamic profile than propofol during regional anesthesia. The frequent occurrence of remifentanil‐induced respiratory depression requires cautious administration of this agent. The incidence of adverse reactions seen with both agents during and after their administration makes the management of such sedative infusion techniques difficult.

Preoperative ketorolac administration has no preemptive analgesic effect for minor orthopaedic surgery

The utility of preoperative ketorolac administration to reduce the intensity and duration of postoperative pain was compared with placebo in a randomized double‐blind design of 60 ASA 1–2 patients scheduled for minor orthopaedic surgery. No opioids nor local anaesthetic blocks were used during surgery. The patients received either 30 mg ketorolac IV before surgery followed by a placebo injection after surgery or the reverse. Postoperative pain intensity was assessed repeatedly for 6 h using a visual analogue scale. No differences in pain intensity were observed between the two groups except for the initial 15‐min postoperative assesments in the ketorolac group. The time to first rescue morphine administration and the total morphine consumption during the 6‐h observation period were similar. It is concluded that the preoperative administration of ketorolac did not provide a significant preemptive analgesic benefit with regard to postoperative pain relief and opioid dose‐sparing effect.

Remifentanil, an Esterase-Metabolised Opioid

SummaryEsterase hydrolysis is a metabolic pathway that can be exploited to increase the rate of metabolism and elimination and so reduce the duration of the pharmacodynamic effects of drugs. Previously applied to β-adrenergic blocking agents and muscle relaxants, this concept was recently used to develop an esterase-metabolised opioid, remifentanil.Remifentanil has a predictable rapid onset, short duration and rapid offset of analgesic effect. This is likely to allow easy titration of analgesia to changing anaesthesia requirements during surgery. The metabolism of remifentanil by non-specific esterases in the blood and tissues prevents accumulation, even when given at high dosages over prolonged periods. Clinical recovery from anaesthesia is very rapid, irrespective of the age or physical status of the patient or the type or duration of surgery. In addition, the non-organ dependent elimination of remifentanil obviates the usual requirement for opioid dose adjustments in patients with hepatic impairment.Adverse events of remifentanil are those typical of μ-opioid receptor agonists. including respiratory depression, muscle rigidity, hypotension and bradycardia.Thus, the major benefits of remifentanil, the prototype esterase-metabolised opioid, are the achievement of intense, titratable intraoperative analgesia allowing for rapid clinical recovery without the risk of inducing recurrent postoperative respiratory depression. In addition, residual opioid activity disappears rapidly following discontinuation of the drug.