Multimodal therapies for postoperative nausea and vomiting, and pain.

Postoperative nausea and vomiting (PONV) and pain are two of the major concerns for patients presenting for surgery. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, anaesthetic technique, and surgical procedure. Antiemetics work on several different receptor sites to prevent or treat PONV. This is probably why numerous studies have now demonstrated that using more than one antiemetic is usually more effective and results in fewer side-effects than simply increasing the dose of a single antiemetic. A multimodal approach to PONV should not be limited to drug therapy alone but should involve a holistic approach starting before operation and continuing intraoperatively with risk reduction strategies to which are added prophylactic antiemetics according to the assessed patient risk for PONV. With the increasing understanding of the pathophysiology of acute pain, especially the occurrence of peripheral and central hypersensitization, it is unlikely that a single drug or intervention is sufficiently broad in its action to be adequately effective, especially with moderate or greater pain. Although morphine and its congeners are usually the foundation of pain management regimens, as their dose increases so does the incidence of side-effects. Thus, the approach for the management of acute postoperative pain is to use multiple drugs or modalities (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects.

Age-associated differences in the inhibition of mitochondrial permeability transition pore opening by cyclosporine A.

BACKGROUND: Inhibiting mitochondrial permeability transition pore (mPTP) opening is a key protection of the myocardium from ischemia/reperfusion (I/R) injury. Here, we investigated age-associated differences in the ability of cyclosporine A (CsA) to protect the heart and to modulate mPTP opening during I/R injury in vivo and its opening induced by reactive oxygen species (ROS) in vitro. METHODS: Fischer 344 male rats were assigned from their respective age groups, young or old groups, to (1) I/R or (2) I/R+CsA. All animals were subjected to 30 min of ischemia following 120 min of reperfusion to determine myocardial infarct size in vivo. To measure mPTP opening in vivo, left ventricular tissues were collected 10 min after reperfusion and nicotinamide adenine dinucleotide (NAD(+)) levels were measured. In parallel experiments, rat ventricular myocytes were prepared from young and old hearts, loaded with tetramethylrhodamine ethylester and then subjected to oxidative stress in the presence or absence of CsA, and the mPTP opening time was measured using laser scanning confocal microscopy. RESULTS: CsA reduced myocardial infarct size in young I/R rats. Whereas CsA failed to significantly affect myocardial infarct size in old I/R rats, NAD(+) levels were better preserved in young CsA-treated rats, but this relative improvement was not observed in old rats. CsA also significantly prolonged the time necessary to induce mPTP opening in young cardiomyocytes, but not in cardiomyocytes isolated from the old rats. CONCLUSIONS: mPTP regulation is dysfunctional in the aged myocardium and this could account for loss of cardioprotection with aging.

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements.

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.