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
Clinical Trial Controlled Clinical TrialClonidine prolongs spinal anesthesia in newborns: a prospective dose-ranging study.
Spinal anesthesia may reduce the incidence of morbidity that follows general anesthesia in neonates and in former preterm infants. However, bupivacaine alone provides a block too short for complete surgery in up to 40% of the patients. Clonidine lengthens spinal anesthesia in adults and caudal block in children without significant side effects. We conducted a controlled, prospective, dose-ranging study of clonidine in spinal anesthesia in 75 neonates, including 50% of former preterm infants, undergoing elective inguinal herniorrhaphy. Patients were given a spinal anesthetic with either 0.5% plain isobaric bupivacaine (1 mg/kg), or bupivacaine plus 0.25, 0.5, 1, or 2 micro g/kg clonidine. Mean arterial blood pressure, heart rate, SpO(2), sensory block extension and duration were the main data recorded. Mean arterial blood pressure, heart rate, SpO(2), and block extension were similar in the five groups. Duration of spinal block increased from 67 (58-82) min in the control group up to 111 (93-125) min in the group receiving 1 micro g/kg clonidine (P < 0.003). Transient hypotension occurred more often (P < 0.05), and caffeine was given more often, when 2 micro g/kg clonidine was given. We conclude that 1 micro g/kg clonidine provides a significant improvement in spinal anesthesia duration in newborns without significant side effects. ⋯ Spinal anesthesia is suitable but often too short for complete surgery in newborns. This controlled, randomized, prospective, dose-ranging study was conducted in 75 neonates to test the hypothesis that clonidine could significantly lengthen bupivacaine spinal block. Clonidine 1 micro g/kg, added to spinal isobaric bupivacaine, doubles the duration of the block without significant deleterious hemodynamic or respiratory side effects.
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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.