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To review the clinical benefits of dextromethorphan (DM) in pain management, describe its neuropharmacological properties. A Medline search was made for experimental and clinical data on DM use from 1967 to date using keywords nociception, acute and chronic pain control, N-methyl-D-aspartate, antagonists, dextromethorphan. The 930 DM citations mostly described its antitussive, metabolic and toxicological aspects, animal studies and its possible role in minimizing post-brain ischemia complications in humans. The use of DM in acute pain revealed eight original studies involving 443 patients, as well as two preliminary reports and our own unpublished data on 513 patients. Most of the 956 patients had general anesthesia. Eight studies (154 patients) and one case report dealt with chronic pain management. This N-methyl-D-aspartate (NMDA) receptor antagonist binds to receptor sites in the spinal cord and central nervous system, thereby blocking the generation of central acute and chronic pain sensations arising from peripheral nociceptive stimuli and enabling reduction in the amount of analgesics required for pain control. DM attenuated the sensation of acute pain at doses of 30-90 mg, without major side effects, and reduced the amount of analgesics in 73% of the postoperative DM-treated patients. Studies in secondary pain models in healthy volunteers and in various types of chronic pain showed DM to be associated with unsatisfactory pain relief. DM attenuates acute pain sensation with tolerable side effects. Its availability in oral form bestow advantages over other NMDA antagonists.

To evaluate the effects of gut decontamination on endotoxin, tumor necrosis factor (TNF) levels, and the associated lung injury in a rat model of bowel ischemia. Summary background data:Gut ischemia induces disruption of the intestinal mucosal barrier, allowing translocation of bacteria and endotoxin into the blood, which may trigger a systemic inflammatory response and lung injury. Thirty anesthetized rats were randomized into three groups: (1) ischemia-reperfusion (I/R) alone (a 60-min superior mesenteric artery occlusion and 4 h of reperfusion, n=10); (2) rats that underwent gut decontamination prior to ischemia (I/R+GD, n=10); and (3) control rats (sham operated, n=10). Serum levels of lipopolysaccharide (LPS) and TNF were measured at the end of the experiment. Lung permeability was measured using bovine serum albumin labeled with 125I, and organ injury was assessed histologically. One hour of bowel ischemia and 4 h of reperfusion (I/R) led to elevations of blood LPS and TNF levels of 0.33±0.005 EU/mL and 173±56 pg/mL, which were higher than the sham group (p<0.01). Gut decontamination (I/R+GD) significantly attenuated the LPS and TNF generation, 0.09±0.005 and 56.2±6 pg/mL (p<0.01). Lung injury as assessed by pulmonary permeability index was also reduced by gut decontamination, 2.1 ±0.42 vs 5.3±0.82 in the control group (p<0.03). Surprisingly no difference was detected in the number of pulmonary neutrophils in sequestration between the groups. Our data suggest that gut decontamination can reduce the generation of LPS, TNF, and the severity of lung damage that often follows ischemia and reperfusion of the intestine in rats.

To determine the effect of 90 mg dextromethorphan (DM) p.o. vs placebo 90 min preoperatively, on the immediate and delayed postoperative course. Thirty patients undergoing laparoscopic cholecystectomy or inguinal hernioplasty under general anesthesia were studied. Half (DM) received 90 mg dextromethorphan and half received placebo 90 min before anesthesia. Intravenous Patient Controlled Aanalgesia with morphine was available for two hours within a six-hour observation period; 75 mg diclofenac i.m. prn was given later in PACU and on-ward (24 hr). Pain was assessed using the visual analogue scales. Thermal thresholds for cold and hot sensation and for pain (by limit method) were evaluated at the site of skin incision (primary-) and distantly (secondary hyperalgesia). Von Frey filaments were applied testing touch sensation. Sedation level and morphine consumption were also assessed in PACU. Demographic, surgical and perioperative parameters were similar; no untoward effects were encountered. Pain intensity and sedation were lower, and the feeling of well-being was greater, in the DM patients: one vs five (median), two vs five, five vs two, respectively, P <0.01 (90 min time-point). Thermal application revealed absence of primary and secondary hyperalgesia only in the DM patients; von Frey filaments induced similar pain sensation in both groups. Mean morphine/group, morphine/weight and diclofenac injection rates were approximately 55% lower in the DM group: 2.1 +/- 1.2 (SD) vs 4.7 +/- 2.3, 0.03 +/- 0.02 vs 0.07 +/- 0.03, 1.0 +/- 0.3 vs 2.4 +/- 0.2, respectively, P <0.01. Compared with placebo, DM enabled reduction of postoperative analgesics consumption, improved well-being, and reduced sedation, pain intensity and primary and secondary thermal hyperalgesia.