Anesthesia and analgesia
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Anesthesia and analgesia · Nov 2002
Randomized Controlled Trial Clinical TrialIsoflurane dosage for equivalent intraoperative electroencephalographic suppression in patients with and without epidural blockade.
We conducted a prospective, randomized, controlled trial to establish the effect of epidural blockade on isoflurane requirements for equivalent intraoperative electroencephalographic (EEG) suppression. Fifty patients undergoing abdominal hysterectomy received combined epidural and general anesthesia or general anesthesia alone with isoflurane and alfentanil. Isoflurane was administered by computer-controlled closed-loop feedback to maintain an EEG 95% spectral edge frequency of 17.5 Hz, a target chosen on the basis of a pilot study. In epidural patients, end-tidal isoflurane concentration (FE'(ISO)) was 0.19% smaller (95% confidence interval [CI], -0.32% to -0.06%; P < 0.01), mean arterial blood pressure was 17 mm Hg lower (95% CI, -24 to -9 mm Hg; P < 0.0001), and body temperature was 0.4 degrees C lower (95% CI, -0.7 to 0 degrees C; P < 0.05) than in controls. EEG bispectral index (BIS) was 4 points higher (95% CI, 1 to 7; P < 0.05). EEG median frequency and heart rate were similar in both groups. Epidural patients were 76% more likely (95% CI, 58% to 94%; P < 0.001) to require metaraminol for hypotension and were 28% more likely (95% CI, 3% to 53%; P < 0.05) to require glycopyrrolate for bradycardia. After surgery, the time to eye opening in epidural patients was 2.3 min shorter (95% CI, -4.2 to -0.5 min; P < 0.05). Time to eye opening correlated better with FE'(ISO) in the last 30 s of anesthesia (FE'(ISO) = 0.07 x time to eye opening + 0.31; r(2) = 0.59; P < 0.0001) than with BIS from the same period (BIS = 64 - 1.25 x time to eye opening; r(2) = 0.22; P < 0.001) (P < 0.0001). To maintain similar intraoperative spectral edge frequency, patients receiving combined epidural and general anesthesia require 21% less isoflurane than those receiving general anesthesia alone. This smaller isoflurane dose is associated with faster emergence from anesthesia. ⋯ The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia. The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia.
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Anesthesia and analgesia · Nov 2002
Randomized Controlled Trial Clinical TrialThe effect of the addition of epinephrine on early systemic absorption of epidural ropivacaine in humans.
The addition of epinephrine to ropivacaine has not been recommended because ropivacaine has intrinsic vasoconstrictor properties. However, few pharmacokinetic data are available on the addition of epinephrine to epidural ropivacaine in humans. In this prospective, double-blinded study, we randomized patients having elective abdominal hysterectomy to receive epidural ropivacaine 1.5 mg/kg, diluted in 15 mL, either with (epinephrine group, n = 12) or without (plain group, n = 12) epinephrine 5 microg/mL and then measured arterial and venous plasma concentrations of ropivacaine at intervals up to 180 min. We found that arterial and venous plasma ropivacaine concentrations were smaller in the epinephrine group compared with the plain group in the first 60 min after the drug administration (P < 0.01). Mean (+/- SD) maximum total plasma ropivacaine concentration was smaller in the epinephrine group (arterial, 0.92 +/- 0.32 microg/mL; venous, 0.82 +/- 0.33 microg/mL) compared with the plain group (1.31 +/- 0.39 microg/mL and 1.31 +/- 0.50 microg/mL, respectively; P = 0.01). Time to maximum total plasma ropivacaine concentration was not significantly different between groups (mean +/- SD; arterial, 16 +/- 2 min; venous, 23 +/- 2 min in the epinephrine group versus 9 +/- 2 min and 12 +/- 3 min, respectively, in the plain group; P = 0.08). Arterial plasma ropivacaine concentrations were larger than venous concentrations during the first hour (P < 0.01); the arterio-venous difference decreased exponentially, and the rate and magnitude of this decrease was unaffected by epinephrine. We conclude that the addition of epinephrine 5 microg/mL to ropivacaine reduced the early systemic plasma concentrations of ropivacaine after epidural injection and may be useful for decreasing the risk of toxicity from systemic absorption of epidural ropivacaine. ⋯ The addition of epinephrine 5 microg/mL to epidural ropivacaine reduced the systemic arterial and venous plasma concentrations of ropivacaine in the first hour and the maximum plasma concentration of ropivacaine. Epinephrine may be a useful additive for reducing the risk of systemic toxicity when large doses of ropivacaine are given epidurally.
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Anesthesia and analgesia · Nov 2002
Isoflurane does not produce a second window of preconditioning against myocardial infarction in vivo.
The administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction similar to those of ischemic preconditioning. A second window of preconditioning (SWOP) against myocardial infarction can also be elicited by brief episodes of ischemia when this occurs 24 h before prolonged coronary artery occlusion. Whether remote exposure to a volatile anesthetic also causes delayed myocardial protection is unknown. We tested the hypothesis that the administration of isoflurane 24 h before ischemia produces a SWOP against infarction. Barbiturate-anesthetized dogs (n = 25) were instrumented for measurement of hemodynamics, including aortic and left ventricular (LV) pressures and LV +dP/dt(max), and subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Two groups of dogs received 1.0 minimum alveolar anesthetic concentration isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Infarct size was 27% +/- 3% of the LV area at risk in the absence of pretreatment with isoflurane. Acute, but not remote, administration of isoflurane reduced infarct size (12% +/- 1% and 31% +/- 3%, respectively). No differences in hemodynamics or transmural myocardial perfusion during or after occlusion were observed between groups. The results indicate that isoflurane does not produce a SWOP when administered 24 h before prolonged myocardial ischemia in vivo. ⋯ Isoflurane mimics the beneficial effects of ischemic preconditioning by protecting myocardium against infarction when it is administered shortly before a prolonged ischemic episode. However, unlike ischemic preconditioning, isoflurane does not produce a second window of protection 24 h after administration in dogs.
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Anesthesia and analgesia · Nov 2002
Physiological and psychological influences on postoperative fatigue.
Fatigue is common after major surgery and delays recovery. We studied the role of physiological and psychological factors in determining fatigue and physical well being after surgery in 102 patients undergoing primary hip arthroplasty. Self-administered questionnaires were used to measure the intensity of feelings of fatigue, vigor, depression, and subjective physical well being on the day before surgery, on the third and seventh postoperative days, and 1 and 6 mo after surgery. The physiological response to surgery was determined by sequential measurements of circulating norepinephrine, epinephrine, cortisol, interleukin-6, and C-reactive protein during the 7 days after surgery. The peak value of each variable was used for statistical analysis. Physical well being decreased significantly at 3 and 7 days but increased significantly at 1 and 6 mo. Fatigue decreased significantly at 1 and 6 mo. Multiple regression analysis showed that the main predictor of worse physical well being at 3 days was the size of the C-reactive protein response. Subsequently, the main predictor was the level of preoperative well being. The severity of fatigue and vigor after surgery were predicted mostly by the preoperative levels of the respective variable. We conclude that fatigue after hip arthroplasty was not predicted by physiological variables but was largely predicted by preoperative levels of fatigue. ⋯ Fatigue is common after major surgery and delays recovery. It is usually attributed to the physiological response to surgery. We studied patients undergoing hip arthroplasty and found that the severity of postoperative fatigue was not predicted by physiological changes. Instead, it was predicted by the preoperative level of fatigue.
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Anesthesia and analgesia · Nov 2002
Comparative StudyPropofol phosphate, a water-soluble propofol prodrug: in vivo evaluation.
After a single IV injection of the water-soluble propofol prodrug propofol phosphate (PP) in mice, rats, rabbits, and pigs, propofol was produced rapidly (1-15 min), inducing dose-dependent sedative effects. In mice, the hypnotic dose (HD(50)), lethal dose (LD(50)), and safety index (defined as a ratio: LD(50)/HD(50)) were 165.4 mg/kg, 600.6 mg/kg, and 3.6, respectively. Propofol was produced with half-lives of 5.3 +/- 0.6 min in rats, 2.1 +/- 0.6 min in rabbits, and 4.4 +/- 2.4 min in pigs. The maximal concentration was dose and species dependent. The elimination half-life was 24 +/- 12 min in rats, 21 +/- 16 min in rabbits, and 225 +/- 56 min in pigs. Propofol generated from PP produced pharmacological effects similar to those described in the literature. We found a correlation between PP dose and duration of sedation with propofol concentrations larger than 1.0 microg/mL, which produced somnolence and sedation in rats and pigs. Adequate sedation and, at large enough doses, anesthetic-level sedation were produced after the administration of PP. Overall, PP, the water-soluble prodrug of propofol, seems to be a viable development candidate for sedative and anesthetic applications. ⋯ Propofol phosphate, a water-soluble prodrug of the widely used IV anesthetic propofol, was developed and evaluated in mice, rats, rabbits, and pigs after IV injection. The results of the study clearly demonstrate the feasibility of the prodrug approach to achieve sedative and anesthetic levels of propofol in laboratory animals; this warrants further evaluation in humans.