Anesthesia and analgesia
-
Anesthesia and analgesia · Nov 1997
Quantitative differences in the production and toxicity of CF2=BrCl versus CH2F-O-C(=CF2)(CF3) (compound A): the safety of halothane does not indicate the safety of sevoflurane.
Carbon dioxide absorbents degrade both halothane and sevoflurane to toxic unsaturated compounds (CF2=CBrCl and CH2F-O-C[=CF2][CF3] [i.e., Compound A], respectively). Given the long history of safe administration of halothane, comparable toxicities of these degradation products would imply a similar safety of sevoflurane. We therefore examined CF2=CBrCl in the context of four issues relevant to previous studies of the toxicity of Compound A: 1) reactivity of the degradation product in vitro; 2) rate of its production in vitro; 3) its in vivo toxicity; 4) importance of the beta-lyase pathway to the toxicity in vivo. We found the following. 1) CF2=CBrCl is less reactive than Compound A, degrading in human serum albumin at one-fifth the rate of Compound A. 2) Over a 3-h period of "anesthesia," a standard circle system containing Baralyme (Allied Healthcare Products, Inc., St. Louis, MO) produces 30 times as much Compound A from a minimum alveolar anesthetic concentration (MAC) concentration of sevoflurane as CF2=CBrCl from a MAC concentration of halothane; with soda lime, the difference is 60-fold. Correcting for differences in uptake of halothane versus sevoflurane decreases the differences to 20-40 times. 3) For a 3-h administration to rats, the partial pressure of Compound A causing minimal renal injury or necrosis of half the affected tubule cells exceeds the partial pressure of CF2=CBrCl causing minimal injury or necrosis of half the affected tubule cells by a factor of approximately 4-6. Thus, the ratio of production (Item 2 above) to the partial pressure causing injury with CF2=CBrCl is approximately a quarter of that ratio for Compound A. 4) Compounds that block the beta-lyase pathway either do not change (acivicin) or decrease (aminooxyacetic acid; AOAA) renal injury from CF2=CBrCl in rats, whereas these compounds increase (acivicin) or do not change (AOAA) injury from Compound A. We conclude that the safety of halothane cannot be used to support the safety of sevoflurane. ⋯ Carbon dioxide absorbents degrade halothane and sevoflurane to unsaturated compounds nephrotoxic to rats. Relative to sevoflurane's degradation product, halothane's degradation product has less toxicity relative to production, less reactivity, and a different mechanism of injury. The clinical absence of halothane nephrotoxicity does not necessarily indicate a similar absence for sevoflurane.
-
Anesthesia and analgesia · Nov 1997
The effects of isoflurane and halothane on left ventricular afterload in dogs with dilated cardiomyopathy.
The effects of volatile anesthetics, including isoflurane (ISO) and halothane (HAL), on determinants of left ventricular (LV) afterload have not been comprehensively described in experimental models of, or patients with, heart failure. We tested the hypothesis that ISO and HAL produce beneficial alterations in LV afterload when evaluated with aortic input impedance and interpreted using a three-element Windkessel model in dogs before and after development of pacing-induced cardiomyopathy. Hemodynamics and aortic pressure and blood flow waveforms were recorded in the conscious state and during 1.1- and 1.5-minimum alveolar anesthetic concentration (MAC) ISO and HAL anesthesia on separate days in chronically instrumented dogs (n = 6). Dogs were then paced at 220-240 bpm for 20 +/- 3 days (mean = SEM) to develop cardiomyopathy, and the experiments were repeated after pacing had been temporarily discontinued. ISO decreased mean arterial pressure (MAP), mean aortic blood flow (MAQ), and total arterial resistance (R) and increased total arterial compliance (C) and characteristic aortic impedance (Zc) in dogs before pacing. HAL decreased MAP and MAQ and increased C but did not alter R and Zc. Chronic rapid LV pacing increased HR and LV end-diastolic pressure and decreased MAP, LV systolic pressure, and the peak rate of increase of LV pressure. MAQ, C, R, and Zc were unchanged. ISO and HAL decreased arterial pressure but did not affect C and Zc in the presence of LV dysfunction. HAL, but not ISO, increased R at 1.1 MAC, which indicates that this drug increases resistance to LV ejection. In contrast to findings in normal dogs, these results indicate that neither ISO nor HAL reduce arterial hydraulic resistance to LV ejection or favorably improve the rectifying properties of the aorta in dogs with pacing-induced cardiomyopathy. ⋯ Isoflurane and halothane produce favorable alterations in the determinants of left ventricular afterload before, but not after, the production of experimental left ventricular dysfunction by sustained, rapid cardiac pacing in chronically instrumented dogs.
-
Anesthesia and analgesia · Nov 1997
Randomized Controlled Trial Multicenter Study Comparative Study Clinical TrialA randomized, blind comparison of remifentanil and alfentanil during anesthesia for outpatient surgery.
We compared remifentanil, an esterase-metabolized opioid, with alfentanil as part of balanced anesthesia with at least 0.8% isoflurane during outpatient surgery in a randomized, double-blind trial. One hundred two patients received remifentanil, and 99 patients received alfentanil. Patients who received remifentanil experienced significantly fewer stress responses to surgical stimuli (52.9% and 65.7%, P < 0.05); significantly fewer remifentanil patients responded to skin closure (11% and 22%, P < 0.05) than patients who received alfentanil. Significantly more patients in the alfentanil group required extra analgesia compared with the remifentanil group (P < 0.05). Time to respond to verbal command was shorter for alfentanil than remifentanil (median 7 min vs 9 min), and times to spontaneous respiration (median 5 min vs 8 min), adequate respiratory rate (median 6 min vs 9 min), and tracheal extubation (median 6 min vs 9 min) were significantly shorter for alfentanil in comparison with remifentanil (P < 0.05). Remifentanil patients, however, showed significantly better recovery of psychomotor and psychometric function between 30 and 90 min after surgery (P < 0.05). The incidences of hypotension intraoperatively and shivering postoperatively were significantly higher with remifentanil. No unexpected or serious adverse events were recorded with remifentanil; however, one patient who received alfentanil experienced severe recurrent respiratory depression after surgery. The metabolic profile of remifentanil allowed better intraoperative analgesia without compromising recovery. ⋯ The pharmacological profile of remifentanil, a new opioid for use in anesthesia, suggests that rapid recovery will occur after its use. This study of 200 outpatients shows that the differences suggested from kinetic studies are not always borne out in clinical practice, although later recovery variables did, in fact, favor remifentanil.
-
Anesthesia and analgesia · Nov 1997
Randomized Controlled Trial Clinical TrialTranexamic acid is effective in decreasing postoperative bleeding and transfusions in primary coronary artery bypass operations: a double-blind, randomized, placebo-controlled trial.
We evaluated the effects of tranexamic acid (TA) administered before and after cardiopulmonary bypass (CPB) in a prospective, randomized, placebo-controlled, double-blind study of adult patients undergoing primary coronary artery bypass grafting surgery. Patients received placebo (n = 30) or TA 15 mg/kg before CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30) or TA 15 mg/kg after CPB, followed by a TA infusion of 1 mg x kg(-1) x h(-1) for 5 h (n = 30). Demographic, medical, surgical, laboratory, mediastinal chest tube drainage (MCTD), hemoglobin loss, transfusion, and outcome data were collected. Allogenic blood product administration was tightly controlled. The demographic, medical, and surgical characteristics were similar in all three groups. The median postoperative MCTD and hemoglobin loss in the pre-CPB TA group (710 mL, 8.6 g) was significantly less (P < 0.001) compared with the control (1202 mL, 44.2 g) and post-CPB TA groups (1020 mL, 23.4 g). The percentage of patients who received no allogenic blood products was 27% for the pre-CPB TA group and 33% for the post-CPB TA group (not significant). These percentages were significantly lower than those in the placebo group (66%, P < 0.001). The median number of allogenic blood products administered to the pre-CPB TA group (0 units) was significantly less compared with the control group (4.5 units). The thromboelastogram and fibrinogen split product levels in the pre-CPB TA group indicated better platelet function and less activation of the fibrinolytic system compared with the other two groups (P < 0.05). There were no intergroup differences in reoperation, myocardial infarction, stroke, infections, or death. These data support the use of pre-CPB TA to decrease patient exposure to postcardiopulmonary bypass allogenic blood products. ⋯ In this randomized, placebo-controlled trial, we investigated the efficacy of tranexamic acid to decrease bleeding and blood transfusions after open-heart operations. Tranexamic acid administered before and during the operation was effective in decreasing both bleeding and transfusions. When tranexamic acid was administered immediately after the operation, it had a minor beneficial effect.