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
Randomized Controlled Trial Comparative Study Clinical TrialSpinal 2-chloroprocaine: a comparison with lidocaine in volunteers.
Subarachnoid lidocaine has been the anesthetic of choice for outpatient spinal anesthesia. However, its use is associated with transient neurologic symptoms (TNS). Preservative-free formulations of 2-chloroprocaine are now available and may compare favorably with lidocaine for spinal anesthesia. In this double-blinded, randomized, crossover study, we compared spinal chloroprocaine and lidocaine in 8 volunteers, each receiving 2 spinal anesthetics: 1 with 40 mg 2% lidocaine and the other with 40 mg 2% preservative-free 2-chloroprocaine. Pinprick anesthesia, tolerance to transcutaneous electrical stimulation and thigh tourniquet, motor strength, and a simulated discharge pathway were assessed. Chloroprocaine produced anesthetic efficacy similar to lidocaine, including peak block height (T8 [T5-11] versus T8 [T6-12], P = 0.8183) and tourniquet tolerance (46 +/- 6 min versus 38 +/- 24 min, P = 0.4897). Chloroprocaine anesthesia resulted in faster resolution of sensory (103 +/- 13 min versus 126 +/- 16 min, P = 0.0045) and more rapid attainment of simulated discharge criteria (104 +/- 12 min versus 134 +/- 14 min, P = 0.0007). Lidocaine was associated with mild to moderate TNS in 7 of 8 subjects; no subject complained of TNS with chloroprocaine (P = 0.0004). We conclude that the anesthetic profile of chloroprocaine compares favorably with lidocaine. Reliable sensory and motor blockade with predictable duration and minimal side effects make chloroprocaine an attractive choice for outpatient spinal anesthesia. ⋯ The spinal anesthetic profile of chloroprocaine (40 mg) compares favorably with the same dose of spinal lidocaine. Reliable sensory and motor blockade with predictable duration and minimal side effects and without signs of transient neurological symptoms make chloroprocaine an attractive choice for outpatient spinal anesthesia.
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Anesthesia and analgesia · Jan 2004
Randomized Controlled Trial Clinical TrialThe sunburn pain model: the stability of primary and secondary hyperalgesia over 10 hours in a crossover setting.
It was our aim to study the within-day stability and between-day repeatability of ultraviolet B (UVB) light-induced primary and secondary hyperalgesia over 10 h. Twenty hours after UVB irradiation of a skin spot (r = 2.5 cm) on the upper leg of 8 healthy volunteers the areas of secondary hyperalgesia to pinprick and pain tolerance thresholds to heat (HPTT) and electrical stimuli (5 and 250 Hz, electrical pain tolerance thresholds [EPTT]) were assessed. Measurements were repeated for 10 h at 2-h intervals and in 2 different sessions. Large areas of secondary hyperalgesia to pin prick were observed (5995 mm(2); SD, 1645). Primary hyperalgesia was evidenced by significant decreases of HPTT (mean difference, 6.5 degrees C; 95% confidence interval, 6.1-6.8; P < 0.001) and EPTT at 250 Hz (mean difference, 0.45 mA; 95% confidence interval, 0.13-0.78; P < 0.05) compared to normal skin. There was no trend within one session of either primary (P = 0.14 for HPTT) or secondary hyperalgesia (P = 0.95) and no difference between the two sessions (primary hyperalgesia, P = 0.28; secondary hyperalgesia, P = 0.07). The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia. ⋯ The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia.
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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.
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Anesthesia and analgesia · Jan 2004
Randomized Controlled Trial Clinical TrialThe effect of preoperative antiplatelet/anticoagulant prophylaxis on postoperative blood loss in cardiac surgery.
In this study we sought to determine whether preoperative treatment with antiplatelet and/or anticoagulant drugs influences postoperative blood loss after coronary artery bypass graft surgery. Although prophylactic treatment to prevent ischemic events preoperatively is often necessary, the treatment frequently continues until there may be a risk of increased bleeding (i.e., within 5-7 days before surgery). With patient consent, a preincision blood sample was collected prospectively from 93 adult subjects who presented randomly. They consisted of 3 groups regarding their primary preoperative regimen: 1) no preoperative treatment within the week before surgery; 2) platelet adenosine diphosphate (ADP) receptor antagonist; 3) ADP receptor antagonist plus IV heparin. Postoperative chest tube drainage (24 h) in the group that received ADP antagonist alone was more (P < 0.05) than either of the other groups: 503 +/- 56; 633 +/- 55; 439 +/- 29 mL (mean +/- SEM) for Groups 1, 2, and 3, respectively. Combined treatment with ADP antagonist plus heparin infusion appeared to prevent the increased blood loss with the ADP antagonist alone. Preincision and postoperative plasma fibrinogen concentrations were largest (P < 0.05) in the group that received the combination treatment; mean +/- SEM for groups 1, 2, and 3 preincision, 311 +/- 17, 366 +/- 16, and 423 +/- 18 mg/dL, and postoperatively, 229 +/- 16, 267 +/- 13, and 312 +/- 16 mg/dL. Postoperative fibrinogen showed strong dependence on preoperative fibrinogen in all groups (r = 0.576 to 0.825; P = 0.01 to 10(-6)). Prevention of the increased blood loss in the ADP receptor antagonist group by the addition of a heparin infusion may have been attributable to a conservation of coagulation factors, as evidenced by the increased plasma fibrinogen concentrations with combined prophylactic treatment. ⋯ The objective of this study was to determine whether preoperative treatment with antiplatelet and/or anticoagulant drugs influences the extent of blood loss in the 24-h period after cardiac surgery.