Anesthesia and analgesia
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Anesthesia and analgesia · Jan 2004
Randomized Controlled Trial Clinical TrialMyocardial protection using fructose-1,6-diphosphate during coronary artery bypass graft surgery: a randomized, placebo-controlled clinical trial.
In vitro and in vivo studies suggest that fructose-1,6-diphosphate (FDP), an intermediary glycolytic pathway metabolite, ameliorates ischemic tissue injury through increased high-energy phosphate levels and may therefore have cardioprotective properties in patients undergoing coronary artery bypass graft (CABG) surgery. We designed a randomized, placebo-controlled, double-blinded, sequential-cohort, dose-ranging safety study to test 5 FDP dosage regimens in patients (n = 120; 60 FDP, 60 control) undergoing CABG surgery. Of these dosage regimens, 3 produced no benefit, 1 produced improved cardiac function, and 1 required adjustment as a result of metabolic acidosis. This suggests that we achieved the intended effect of a dose-ranging study. The expected response was observed in patients treated with 250 mg/kg FDP IV before surgery and 2.5 mM FDP as a cardioplegic additive (n = 15). These patients had lower serum creatine kinase-MB levels 2, 4, and 6 h after reperfusion (P < 0.05), fewer perioperative myocardial infarctions (P < 0.05), and improved postoperative cardiac function, as evidenced by higher left ventricular stroke work index (LVSWI) 6, 12, and 16 h (P < 0.01) and cardiac index (CI) at 12 and 16 h (P < 0.05) after reperfusion. Overall efficacy of FDP was tested across all regimens that included IV FDP (n = 88; 44 FDP, 44 control) using 2 (FDP versus placebo) x 3 (dose size) factorial analyses. Area-under-curve (AUC) analysis demonstrated a significant increase in CI (AUC-16h, P = 0.013) and LVSWI (AUC-16h, P = 0.003) and reduction in CK-MB levels (AUC-16h, P < 0.05) in FDP-treated patients. The internal consistency of this dataset suggests that FDP may provide myocardial protection in CABG surgery and supports previous laboratory and clinical studies of FDP in ischemic heart disease. ⋯ Fructose-1,6-diphosphate (FDP) may increase high-energy phosphate levels under anaerobic conditions and therefore ameliorate ischemic injury. A dose-ranging safety study for FDP was conducted in patients undergoing coronary artery surgery. Preischemic provision of FDP significantly improved cardiac function and reduced perioperative ischemic injury. These myocardial protective effects may improve patient outcome after cardiac surgery.
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Anesthesia and analgesia · Jan 2004
Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain.
Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states. ⋯ Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.
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Anesthesia and analgesia · Jan 2004
Randomized Controlled Trial Clinical TrialPharmacodynamic interactions between cisatracurium and rocuronium.
The onset and duration of maintenance doses of neuromuscular blocking drugs may be influenced by the original neuromuscular blocking drug used. We assessed the effect of the interaction between steroidal and benzo-isoquinolinium compounds on the clinical duration of maintenance doses of cisatracurium. Sixty adult patients undergoing anesthesia with isoflurane, nitrous oxide, and oxygen were randomized to receive the following: Group I = rocuronium 0.6 mg/kg followed by cisatracurium 0.03 mg/kg when the first twitch in the train-of-four (TOF) recovered to 25%, Group II = cisatracurium 0.15 mg/kg followed by cisatracurium 0.03 mg/kg, and Group III = rocuronium 0.6 mg/kg followed by rocuronium 0.15 mg/kg. Neuromuscular blockade was monitored using acceleromyography (TOF-Guard, Boxtel, The Netherlands). The clinical duration (mean +/- SD) of the first 2 maintenance doses was 41 +/- 10, 31 +/- 7++, and 25 +/- 8++ min, and 39 +/- 11, 30 +/- 6+, 29 +/- 9* min in Groups I-III, respectively (*P < 0.05, +P < 0.01, ++P < 0.001; Group I versus II and III). Thus, the clinical duration of the first two maintenance doses of cisatracurium was prolonged when administered after rocuronium. ⋯ We assessed the clinical effect of administering cisatracurium after an intubating dose of rocuronium in 60 patients undergoing isoflurane/nitrous oxide and oxygen anesthesia. The clinical duration of the first two maintenance doses of cisatracurium administered after rocuronium was significantly prolonged. This supports the contention that combinations of structurally dissimilar neuromuscular blocking drugs result in a synergistic effect.