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Background: Intense pain in the first 12 hours after major abdominal surgery requires the use of large amounts of analgesics, mainly opioids, which may produce undesirable effects. Buprenorphine (BUP) is not typically used intravenously in this setting, particularly in combination with morphine (MO), due to concerns that BUP might inhibit the analgesic effect of MO. Objective: This study compared the analgesic effect of BUP and MO separately and in combination for postoperative pain control in patients undergoing abdominal surgery. Methods: In this double-blind study, adult patients were randomized to receive 1 of 4 regimens for 12 hours: a basal BUP infusion (BUP-i) of 0.4 µg/kg/h + BUP boluses (BUP-b) of 0.15 µg/kg each; a basal MO infusion (MO-i) of 10 µg/kg/h + MO boluses (MO-b) of 5 µg/kg each; a basal BUP-i of 0.4 µg/kg/h + MO-b of 5 µg/kg each; or a basal MO-i of 10 µg/kg/h + BUP-b of 0.15 µg/kg each. Bolus doses were delivered by intravenous patient-controlled anesthesia, with a bolus lockout time of 7 minutes. Diclofenac 75 mg IM q6h was available as rescue pain medication. Every 15 minutes during the first 2 postoperative hours and hourly thereafter, patients used visual analog scales to rate their pain (from 0 = totally free of pain to 10 = unbearable pain), level of sedation (from 1 = totally awake to 10 = heavily sedated), and satisfaction with treatment (from 1 = totally unsatisfied to 10 = fully satisfied). Blood pressure, heart rate, respiration rate, and arterial blood oxygen saturation (SpO 2) were monitored, and adverse effects reported by patients or noted by clinicians were recorded at the same times. Study end points included total opioid consumption (infusion + boluses), demand:delivery ratio, and use of rescue medication. Results: One hundred twenty patients (63 men, 57 women; age range, 21-80 years; weight range, 40-120 kg) were included in the study. Seventy-four percent had other mild, treated diseases (American Society of Anesthesiologists physical class 2). Pain visual analog scale ratings were comparably high in all groups during the first 2 postoperative hours. Pain intensity ratings at 3 to 12 hours were significantly lower in those who received BUP-i + BUP-b compared with the other treatment groups ( P = 0.018). The drug requirement during the postoperative period decreased significantly in all groups ( P = 0.01); however, there was a significant difference between groups in the demand:delivery ratio at 3 to 12 hours (group * psydrug interaction, P = 0.026). The numerically lowest demand:delivery ratio was seen with BUP-i + BUP-b. BUP-i was associated with a significantly lower heart rate compared with the other groups ( P = 0.027); there were no drug-related differences in respiration rate, SpO 2, or sedation. Patients' level of satisfaction with treatment was significantly higher in the group that received BUP-i + BUP-b compared with the other 3 groups ( P < 0.001). Postoperative nausea and vomiting were mild and occurred at a similar incidence in all groups, as did rescue diclofenac use. Conclusions: In these patients undergoing abdominal surgery, the BUP-i + BUP-b regimen controlled postoperative pain as well as did MO-i + MO-b or the combinations of BUP and MO. BUP neither inhibited the analgesia provided by MO nor induced undesired sedation or hemodynamic or respiratory effects.

Heatstroke (HS) is a life-threatening condition, manifested by systemic inflammation and multiorgan failure. Rapid recognition and treatment are life saving. We report a laboratory-oriented characterization of HS by low plasma C-reactive protein (CRP) level and propose its usefulness in distinguishing this type of hyperpyrexia from central nervous system–associated high core temperature. After institutional review board approval, records of patients admitted to general intensive care unit between August 2008 and September 2011 with core temperature 39.0°C or higher due to HS or meningoencephalitis (ME) were reviewed. Patients' demographics, CRP on admission and 24 to 48 hours later, serum creatinine, creatine phosphokinase, platelets count, international normalized ratio, alanine transaminase, serum pH, and lactate levels were retrieved. Thirty-six patients were admitted to the intensive care unit with high core temperature: 19 patients, aged 21 to 85 years, had HS; 17 individuals, aged 22 to 81 years, had ME. None of the HS individuals had infection. Twelve HS patients were previously healthy; in 13 patients, the event occurred postexercise. Mean admission CRP levels was 2.1 ± 3.3 mg/L in the HS group compared with 129 ± 84 mg/L in the ME patients (P < .0001); mean 24- to 48-hour CRP levels were 14.6 ± 16.8 vs 139 ± 98 mg/L, respectively (P < .0001). There were no clinically significant differences between the groups regarding laboratory parameters indicative of end-organ damage. Six HS patients underwent computed tomography and/or lumbar puncture before starting intensive cooling, due to misdiagnosis; 5 of them died subsequently. Low serum CRP levels characterize non–central nervous system–associated HS. This available laboratory test could identify noninfectious hyperthermic patients upon admission, saving precious time until treatment and avoiding unnecessary diagnostic tests.

Ketamine induces a short-term effect on postoperative pain when administered intravenously immediately before or during acute pain. Repeated administration of low-dose ketamine may induce long-term pain relief in chronic pain syndromes. The aim of our study was to determine whether ketamine's effect on acute postoperative pain could be enhanced and prolonged and analgesia consumption reduced if it was administered intramuscularly in repeated and escalating subanesthetic doses many hours before surgery. Patients who were scheduled for tumor resection under general anesthesia were randomly and blindly given preoperative IM ketamine (K) or normal saline (placebo [P]) following 1 of 3 consecutive protocols (2 groups/protocol, 20 patients/group): 1 dose (25-mg ketamine or 1-mL saline) at 4 hours preoperatively (K1 or P1); 2 doses (10- and 25-mg ketamine or 1-mL saline twice) at 11 and 4 hours (K2 or P2); or 3 doses (5-, 10-, and 25-mg ketamine or 1-mL saline thrice) at 17, 11, and 4 hours preoperatively (K3 or P3). No other preoperative medications were given. Postoperatively, all patients received morphine (1.5 mg/bolus) via an intravenous patient-controlled analgesia (PCA) device. A total of 120 patients took part in the study. Patients' ages ranged from 15 to 75 years; mean weight (76 [14] kg; range, 50–120), gender (69 men, 51 women), and race were equally distributed among the groups. There were no significant differences in intraoperative parameters among the groups. The patients' mean self-rated 48-hour pain scores on a numerical rating scale were lower in the K2 and K3 groups than in their corresponding placebo groups (K2: 1.67 [1.04] vs P2: 3.62 [1.93] [ P = 0.0004]; K3: 2.22 [1.37] vs P3: 3.25 [1.76] [ P = 0.046]). These groups also used ∼35% less morphine compared with the placebo groups (K2: 28.4 [20.4] mg, K3: 26.6 [16.0] mg vs P2: 42.4 [30.4] mg, P3: 40.9 [21.2] mg [ P ≤ 0.02]). Intravenous PCA usage among K2 and K3 patients was ∼50% less than the usage among their placebo counterparts ( P < 0.05). The 1-ketamine-injection patients' pain scores and analgesic consumption were similar to those of their placebo groups. The 25-mg-ketamine injections caused dizziness that lasted up to 2 minutes. Our 48-hour data suggest that 2 or 3 escalating subanesthetic doses of IM ketamine injected consecutively hours before surgery attenuated postoperative pain and reduced morphine consumption in these subjects. ClinicalTrials.gov identifier: NCT01070108.

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.

Introduction Pneumoperitoneum-associated ischemia–reperfusion (IR) may initiate renal dysfunction. Whether oxidants are responsible for renal structural damage, such as cell apoptosis, has not yet been evaluated. We investigated such eventuality in an isolated rat kidney model. Methods Thirty-five rat kidneys with their vessels and ureter were harvested and perfused within a closed environment at flow of 15 ml min −1 . After stabilization, kidneys were assigned to one of five groups ( n  = 7 per group): CO 2 -induced intrachamber pressure of 8, 12, or 0 mmHg (control), and 8 or 12 mmHg pressure applied to kidneys from rats treated pre-experimentally with tungsten for 14 days. Pressurization lasted 60 min. Results Organ perfusion pressure raised as intrachamber pressure increased. Urinary output decreased in the two pressurized nonpretreated groups. Intrachamber pressure was directly associated with an increase in postexperimental xanthine oxidase tissue levels. Twofold apoptosis was documented ( p  < 0.05) in cortex of nonpretreated kidney in the 12 mmHg group compared with the 8 or 0 mmHg groups. Tungsten pretreatment significantly ( p  < 0.05) attenuated the abnormalities documented in the 12 mmHg group, but less so in the 8 mmHg pressurized nontreated counterparts. Conclusions Pneumoperitoneal pressure applied to isolated perfused kidney is associated with renal apoptosis. This rapidly induced structural renal damage is oxidant dependent and can be attenuated by antioxidants. Further studies may shed more light on the role of antioxidants in preventing pneumoperitoneum-induced kidney dysfunction.

Acute pulmonary embolism increases pulmonary vascular resistance and may lead to acute right ventricular failure and cardiocirculatory collapse and respiratory failure, possibly resulting in substantial morbidity and mortality. Inhaled nitric oxide (NO) dilates pulmonary blood vessels and has been used to reduce pulmonary vascular resistance in patients with chronic thromboembolic pulmonary hypertension and acute respiratory distress syndrome. This case series describes our experience with inhaled NO administered to four patients suffering from acute massive pulmonary embolism following abdominal surgery. The four described patients recovering from small bowel resection, pancreatoduodenectomy, hemipelvectomy, or recent gastrointestinal bleeding had severe respiratory and hemodynamic deterioration due to pulmonary embolism. Each received inhaled NO (20-25 ppm) via the inspiratory side of the breathing circuit of the ventilator. Pulmonary and systemic blood pressures, heart rate, and lung gas exchange improved in all the patients within minutes after the initiation of NO administration. Inhaled NO may be useful in treating acute massive pulmonary embolism. This potential application warrants further investigation.

Background Oxidants (and their generator, xanthine oxidase [XO]) play a role in inducing acute lung injury (ALI) expressed both structurally and functionally. Such damage has recently been demonstrated in the presence of pancreas ischemia–reperfusion (IR). We now investigated whether methylene blue (MB), a clinically used coloring agent and antioxidant in itself, protected the lung exposed to pancreas IR. Materials and Methods Isolated pancreata (eight replicates/group) were (1) continuously perfused (controls), (2) made ischemic (IR-0) for 40 min and reperfused without treatment, (3) organs procured from allopurinol-treated rats made ischemic and reperfused with allopurinol, and (4) made ischemic and treated upon reperfusion with three different doses of MB contained in the perfusate. All perfusate solutions were directed into the isolated lungs’ circulation whereby they were perfused for 60 min. Results Pancreas injury was documented in all IR organs by abnormally high reperfusion pressure, wet-to-dry ratio, amylase and lipase concentrations, and abnormal XO activity and reduced glutathione in the circulation. Lungs paired with IR-0 pancreata developed ∼60% increase in ventilatory plateau pressure and final P o 2 /Fi o 2 decrease by 35%. Their weight during reperfusion and bronchoalveolar lavage (BAL) volume and contents increased 1.5–2.5 times the normal values; XO and reduced glutathione values were abnormal both in the BAL and in the lung tissues. Lungs exposed to IR effluents containing allopurinol or 68 μM MB were minimally damaged, whereas perfusion solutions containing 42 or 128 μM MB were ineffective in preventing lung injury. Conclusions Ex vivo pancreas IR-induced ALI is preventable by MB, although at a narrow dose range.

Background Hepatic blood flow is known to decrease during pneumoperitoneum. Studies have shown that such changes affect kidney urinary output through the sympathetic pathway known as the hepatorenal reflex. This study investigated the potential role of the hepatorenal reflex in pneumoperitoneum-induced oliguria. The authors hypothesized that oliguria detectable during pneumoperitoneum is caused by activation of the hepatorenal reflex. Methods Denervation of the sympathetic nervous structure was performed in 15 rats by applying 1 ml of 90 % aqueous phenol solution circumferentially to the portal vein and vena cava area at their entrance to the liver. The same was applied to only the peritoneum in 15 nondenervated rats. After 2 weeks, the rats were divided into three subgroups (5 rats per subgroup) that were exposed respectively to carbon dioxide-induced pneumoperitoneum at 0, 10, and 15 mmHg for 2 h. Statistical analysis was performed using Student’s t test and analyses of variance. Results Denervation did not affect the preinsufflation parameters. The denervated and the nondenervated 0-mmHg subgroups presented with similar parameters. The postinsufflation mean urine output was significantly lower in the nondenervated than in the denervated 10- and 15-mmHg subgroups ( p  = 0.0097). The denervated rats had a final creatinine clearance 29 % lower than the preinsufflation value ( p  = 0.83), whereas the nondenervated animals presented a 79 % drop in creatinine clearance ( p  = 0.02). Conclusion The study findings indicate that the hepatorenal reflex plays an important role in the pathophysiology of oliguria that occurs during pneumoperitoneum in the rat.

The need to control high costs of running operating rooms while providing for timely patient care led us to assess the time wasted in the operating room (OR). OR use by two general surgery and two orthopedic departments in a metropolitan public hospital were analyzed, and the time elapsed when a scheduled OR remained unused or the patient was still awaiting surgery was measured. OR “time-waste” defined as the time in which the scheduled OR was not busy with the scheduled patient amounted to 79 hours over the 30-day study period (15% of total time). It was wasted owing to inappropriately prepared patients (12%), unavailability of surgeons (7%), insufficient nursing staff, anesthesiologists, or OR assignment to emergency surgery (59%), congestion of the postanesthesia care unit (10%), and delay in transport to the OR (2%) Another issue delineated was the frequent occurrence of surgical cases running longer than their scheduled time (termed “spill-over”), outrunning the staffing expectations after 3:00 pm and delaying admission of add-on and emergency procedures, adding 33% to the time wasted. A quality-assurance committee review resulted in implementation of new guidelines, and within 3 months several underlying causes were rectified, and time-waste and spill over time was reduced by 35%. Surgical time predictions were also improved. Shortage of nurses and anesthesiologists, and OR emergency reassignment remained the major causes of OR waste time. Continuous surveillance on OR suite—patients’ prompt care, repeated evaluation, and wise staff deployment—could maximize OR efficiency.

Background Disturbed liver function tests are associated with the pneumoperitoneum applied for biliary and non-biliary laparoscopic surgical procedures. The extent, duration and reversibility of such an injury are unknown. An isolated organ model was used to assess reversibility of liver injury in a CO 2 –pneumoperitoneum-like environment. Methods Rat livers ( n = 63) were isolated and perfused within a chamber pressurized at 0, 3, 5, 8, 12, 15 or 18 mmHg for 60 minutes. Pressure was annulled during the ensuing 61–90 minutes in one-half of the groups and markers of liver function were measured and recorded. Results Inflow pressure level, flow rate, effluent partial O 2 and CO 2 pressures, O 2 extraction rate, lactate dehydrogenase level, lactic to pyruvic acid ratio, and total xanthine oxidase and dehydrogenase levels became abnormal, starting at 15 minutes after a pressure >5 mmHg was applied in the chamber. Signs of injury slowly reversed towards baseline values in all groups except for the 15 mmHg and 18 mmHg-pressurized ones, even after pressure had been annulled for 30 minutes. Conclusions CO 2 -pneumoperitoneum-like conditions directly injured rat liver tissue to a degree which correlated with the amount of applied pressure. Damage caused by pressure ≥15 mmHg was no longer reversible if it had been applied over a 60-minute period.