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Aims: To assess the impact of valdecoxib on the incidence of macular edema, after scleral buckling surgery., Methods: Prospective randomized double masked placebo controlled study. Patients undergoing scleral buckle surgery over 18 months were recruited and randomized to receive either oral valdecoxib or placebo. Patients also received two doses of either parecoxib (pro-drug of valdecoxib) intravenously 40 mg 6 hourly day one postoperative or identical placebo injection Patients underwent retinal examination, optical coherence tomography and retinal thickness analyzer scan of the macula preoperatively, and at 2 and 6 weeks postoperatively. Outcome measures were the incidence of macular edema, retinal thickness, visual acuity, contrast sensitivity and presence of persistent subretinal fluid., Results: Interim analysis was performed with 116 patients were recruited, 58 to each treatment arm. The incidence of macular edema in all patients was 5% at visit 1 and 2.2% at visit 2 postoperatively. This incidence was much lower than the expected incidence used in the power calculation to determine study size. It was therefore apparent that a much larger study population would be required to test for an effect and that this was not achievable within the study time period. The study was therefore terminated early. There was no evidence of a difference between COX 2 inhibitor and placebo groups in the incidence of edema, retinal thickness or visual outcome. The presence of residual subretinal fluid at the macula was significantly reduced by COX 2 inhibitor treatment., Conclusions: The rate of cystoid macular edema after scleral buckling surgery is low and is not influenced by prophylactic use of valdecoxib. The rate of residual subretinal fluid was reduced by COX 2 inhibitor treatment. Enhanced antiinflammatory therapy has the potential to improve outcomes in scleral buckling surgery.

Pain is a leading cause of morbidity worldwide, with published data showing its prevalence as high as 50% for chronic pain in the European population. This prevalence is likely to continue to rise, particularly in elderly people with comorbid conditions and complex aetiologies of pain. There is thus a rapidly growing demand for safe and effective pain management. Management of mild-to-moderate pain has traditionally been based upon the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the synthetic non-opioid analgesic paracetamol (acetaminophen), the latter of which acts centrally, inhibiting brain cyclo-oxygenase (COX) and nitric oxide synthase. Both the NSAIDs and paracetamol are effective for mild-to-moderate pain and are widely recommended and used. However, NSAIDs may not be tolerated due to gastrointestinal (GI) symptoms and can result in potentially fatal peptic ulceration and bleeding. Selective COX-2 inhibitors were developed to reduce the GI side effects and complications, but large-scale studies have highlighted another serious potential effect of anti-inflammatory drugs: cardiovascular events. Both the European Medicines Agency (EMEA) and the Food and Drugs Administration (FDA) in the US have issued advice to apply cautions and restrictions when prescribing COX-2 inhibitors, particularly for patients at increased cardiovascular risk and for long-term use. The FDA also applied cardiovascular warnings with regard to nonselective NSAIDs. Both the EMEA and the FDA have recommended using the lowest effective dose for the shortest duration. These concerns and warnings have left physicians seeking safe alternatives to anti-inflammatory drugs for both short- and long-term uses in many patients. These developments have generated a climate of uncertainty in the absence of official guidance on the selection of alternative analgesic regimens. Amongst the possible strategies, combinations of drugs that provide analgesic efficacy at reduced individual doses may confer the optimal risk-benefit ratio for pain management in the long term or in patients at increased cardiovascular risk. Weak opioids devoid of serious organ-damaging effects combined with paracetamol may well be safer for long-term therapy. Fixed-dose combinations of paracetamol with weak opioids, such as codeine, dextropropoxyphene or tramadol are currently available. Paracetamol plus tramadol is an effective and safe multimodal analgesic regimen for the management of both acute and chronic moderate-to-severe pain. Re-evaluating the role of weak opioids, such as tramadol, and combinations in pain management may prove a valuable option for prescribers seeking alternatives to anti-inflammatory drugs.

The need for a clinically applicable method of detecting splanchnic hypoxia has led to experimental animal studies which indicated the usefulness of intestinal pulse oximetry. Pulse oximetry relies on detection of photoplethysmographic signals. Before developing a pulse oximeter for the measurement of organ oxygen saturation peri-operatively, we designed a system based on a reflectance photoplethysmographic probe to investigate photoplethysmographic signals from human viscera (bowel, liver, and kidney). Recordings were obtained simultaneously from the abdominal viscera and the finger using identical probes. The probe was held sequentially for up to 2 min on the surface of viscera of 12 patients during routine laparotomy. Measurable splanchnic photoplethysmographic signals were recorded for the first time in humans. There were no statistically significant differences between photoplethysmographic amplitudes from viscera and those from the finger. Our results indicate the feasibility of pulse oximetry for the measurement of visceral oxygenation in humans.

Direct cerebral monitoring is not yet in routine use in the intensive care unit or the operating theatre, despite the brain's sensitivity to ischaemia, and the potentially devastating consequences. Instead, reliance is placed upon indirect indicators such as general physiological parameters and observation of reflexes such as pupillary size and reaction to light. Complexity in the collection of artefact-free data and in the interpretation of the encephalogram, in the presence of anaesthetic/sedative drugs has deterred its widespread use. However, modern methods of processing and integrating data, (electroencephalographic/evoked potentials, haemodynamic and oxygen measures) together with the availability of powerful, robust microprocessors may well facilitate the development of on-line systems which can warn of cerebral deterioration. These would be of particular value in critically ill patients, and those at risk during or after operative procedures such as neurosurgery, cardiopulmonary bypass and carotid endarterectomy.

The threshold response to a mechanical nociceptive stimulus was significantly lower on the lame hind limb of lame cows than on the same limb of sound cows. There were no significant differences between the concentrations of cortisol, noradrenaline, adrenaline or dopamine in the blood plasma of the sound and lame cows.

Clinical experience suggests that nitroprusside (SNP) concentrations decay more rapidly in vivo than in vitro. Plasma concentrations of SNP were measured therefore in 20 patients at the end of an infusion, with mean arterial pressure (MAP) and cyanide (HCN) concentrations. Plasma SNP concentrations (20-243 micrograms litre-1; mean = 123.5 micrograms litre-1), were related to infusion rate (r = 0.66, P less than 0.001), and declined rapidly to a mean (SD) of 7.7 (4.5) micrograms litre-1 in 15 min. The decay of SNP correlated closely with the increase in arterial pressure (mean MAP vs log mean plasma SNP concentrations: r = -0.993, P less than 0.001), and was probably biphasic: mean (SD) T1/2 alpha = 0.89 (0.62) min, T1/2 beta = 14.3 (12) min. Mean plasma HCN and mean plasma SNP concentrations decreased together (r = 0.955, P less than 0.001), thus confirming that in vivo decomposition of the drug is the source of HCN.

Forty patients who required day case fibreoptic bronchoscopy were sedated with either nalbuphine 0.2 mg/kg and midazolam 0.05 mg/kg (n = 20), or midazolam 0.05 mg/kg alone (n = 20). Extra midazolam was administered when required. The degree of respiratory depression measured by arterialised venous carbon dioxide levels was recorded together with heart rate, arterial blood pressure, respiratory rate and sedation score, before administration of the drugs and at regular intervals thereafter. Patients who received nalbuphine had slightly higher carbon dioxide levels but respiratory rate and cardiovascular changes were similar in both groups. The addition of nalbuphine to midazolam improves the quality of sedation but prolongs the recovery time and increases the incidence of side effects.

The alterations in plasma levels of immunoreactive metenkephalin (ir-metenkephalin) and catecholamines in adrenal vein and arterial blood in response to endotoxin, as well as the effects of subsequent naloxone administration, have been investigated in a canine model. Animals were anaesthetised with alpha chloralose and allowed to breathe spontaneously. The left lumbar adrenal vein was cannulated and an intermittent choke allowed retrograde sampling of the adrenal effluent. Severe shock was produced by the administration of a large bolus of E. coli endotoxin (5 mg/kg) followed by a continuous infusion (2 mg/kg per hour). One hour after induction of shock the circulating volume was expanded using a colloidal gelatin solution. Thirty minutes later one group of five animals received a bolus of naloxone (2 mg/kg) followed by a continuous infusion of (1.5 mg/kg per hour), while a control group of five animals was given an equivalent volume of isotonic saline. The production of endotoxin shock was associated with marked increases in adrenal vein and systemic levels of adrenaline and noradrenaline. Naloxone administration transiently limited the fall in adrenal vein levels of adrenaline and noradrenaline (P less than 0.05) following volume replacement and was associated with a sustained increase in systemic adrenaline levels (P less than 0.05). Changes in mean arterial pressure confirmed a significant haemodynamic response to naloxone (P less than 0.05). Alterations in ir-metenkephalin levels in the adrenal vein closely followed the changes in catecholamines, whereas arterial levels rose progressively and were unaffected by naloxone. We conclude that in canine endotoxin shock the opiate antagonist naloxone can transiently increase catecholamine levels in the adrenal effluent and produce a more sustained rise in systemic adrenaline levels. Moreover, the adrenal medulla is not the only source of circulating ir-metenkephalin.

Trimetaphan nitroprusside (TNP) is a new potent hypotensive agent developed to induce and maintain decreases in arterial pressure unaccompanied by resistance. This study investigated its properties and compared them with those of sodium nitroprusside (SNP) in anaesthetized greyhounds. The mean dose response to TNP was obtained by measuring haemodynamic changes in five dogs. With increasing doses, stepwise decreases in mean arterial pressure and progressive increases in heart rate occurred: cardiac index did not change significantly. In a further six greyhounds, SNP and TNP were alternately infused to induce and maintain a 30% reduction in arterial pressure for 30 min. Both drugs were short-acting, decreased systemic vascular resistance and caused tachycardia. Infusion of TNP produced lower plasma and red cell cyanide concentrations; SNP maintained hypotension with significantly less tachycardia. We conclude that there was no outstanding advantage of TNP over SNP when given as a short-term infusion in greyhounds.

Eighteen healthy volunteers were studied in a double-blind trial to determine which dose of nalbuphine (0.05, 0.1 or 0.2 mg/kg) may be combined with midazolam 0.05 mg/kg to provide a safe outpatient intravenous sedative technique. The ventilatory response to carbon dioxide and end tidal PCO2 were measured before and after the drugs were administered. A mild degree of respiratory depression occurred, which was maximal at 3-30 minutes after injection. This was not related to dose except that nalbuphine 0.05 mg/kg resulted in the slowest respiratory rates. The implications of these findings for clinical practice are discussed.