Anesthesia and analgesia
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Anesthesia and analgesia · Jan 1998
Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats.
In concentrations of 10-20 ppm, inhaled nitric oxide (NO) decreases pulmonary artery pressure and attenuates vascular remodeling in pulmonary hypertensive rats. Because NO is potentially toxic, it is important to know whether lower concentrations attenuate vascular remodeling produced by different etiologies. Therefore, we determined the effects of prolonged, small-dose inhaled NO administration on hypoxic and monocrotaline (MCT)-induced pulmonary vascular remodeling. Rats were subjected to normoxia, hypoxia (normobaric 10% oxygen), or hypoxia plus NO in concentrations of 50 ppb, 200 ppb, 2 ppm, 20 ppm, and 100 ppm for 3 wk. A second group of normoxic rats was given MCT (60 mg/kg intraperitoneally) alone or in the presence of 2, 20, and 100 ppm of NO. Subsequently, pulmonary artery smooth muscle thickness and the number of muscular arteries (percentage of total arteries) were determined. Right ventricular hypertrophy was determined by right to left ventricle plus septum weight ratio (RV/LV + S). Pulmonary artery smooth muscle thickness and the percent muscular arteries were increased by hypoxia and MCT. The hypoxic increase in thickness was attenuated by all concentrations of NO, with 100 ppm being greatest, whereas NO had no effect on MCT rats. NO attenuated the increase in percent muscular arteries in hypoxic but not MCT rats. The RV/LV + S was increased by hypoxia and MCT compared with normoxia. Hypoxia-induced RV hypertrophy was decreased by all concentrations of inhaled NO, although attenuation with 50 ppb was less than with 200 ppb, 20 ppm, and 100 ppm. In MCT rats 2 and 100 ppm NO increased RV hypertrophy, whereas 20 ppm had no effect. In conclusion, inhaled NO in concentrations as low as 50 ppb attenuates the pulmonary vascular remodeling and RV hypertrophy secondary to hypoxia. In contrast, concentrations as high as 100 ppm do not attenuate MCT-induced pulmonary remodeling. These results demonstrate that extremely low concentrations of NO may attenuate remodeling but that the effectiveness is dependent on the mechanism inducing pulmonary remodeling. ⋯ The authors determined whether inhaled NO, a selective pulmonary vasodilator, attenuates pulmonary vascular remodeling caused by two models of pulmonary hypertension: chronic hypoxia and monocrotaline injection. Analysis of pulmonary vascular morphology suggests that very low concentrations of NO effectively attenuate hypoxic remodeling but that NO is not effective in monocrotaline-induced pulmonary remodeling.
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Anesthesia and analgesia · Jan 1998
Randomized Controlled Trial Clinical TrialThe pharmacodynamics of mivacurium preceded by atracurium or cisatracurium in children.
We evaluated whether mivacurium maintains its short duration of effect when preceded by atracurium or cisatracurium in 45 children during propofol/alfentanil/N2O/O2 anesthesia. Neuromuscular response was recorded by using an adductor pollicis electromyogram (EMG). Children were randomized to receive two doses of atracurium (350 micrograms/kg and 70 micrograms/kg in Group AM), cisatracurium (64 micrograms/kg and 10 micrograms/kg in Group CM), or mivacurium (200 micrograms/kg and 100 micrograms/kg in Group MM), followed by a final dose of mivacurium 100 micrograms/kg. The second and third doses of the muscle relaxants were administered at 25% EMG recovery. After the final dose of mivacurium, the times to 95% of EMG recovery in groups AM, CM, and MM were (median with 10-90 percentile range) 33.0 (28.0-40.0) min, 30.7 (26.0-40.3) min, and 10.3 (8.0-14.0) min, respectively (P < 0.0001). The recovery times to a train-of-four ratio of 0.70 were 30.3 (24.7-37.0) min, 28.0 (24.7-37.7) min, and 10.3 (8.0-13.7) min for groups AM, CM, and MM, respectively (P < 0.0001). Thus, the duration of effect of mivacurium was prolonged by 200% if preceded by either atracurium or cisatracurium. ⋯ We compared the pharmacodynamics of mivacurium given alone or preceded by atracurium or cisatracurium in children. The duration of effects of mivacurium was prolonged by 200% if preceded by either atracurium or cisatracurium. This implies that mivacurium has a short duration of effect only when given as a single relaxant.
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Anesthesia and analgesia · Jan 1998
The inhibitory effects of thiopental, midazolam, and ketamine on human neutrophil functions.
We investigated the effect of thiopental, midazolam, and ketamine (at clinically relevant concentrations and at 0.1 and 10 times these concentrations) on several aspects of human neutrophil functions. The three intravenous (i.v.) anesthetics significantly decreased chemotaxis, phagocytosis, and reactive oxygen species (ROS) (O2-, H2O2, OH) production of neutrophils in a dose-dependent manner. At clinically relevant concentrations, thiopental and midazolam significantly depressed these neutrophil functions. However, ketamine at the clinical plasma concentration did not impair chemotaxis or ROS production, except phagocytosis. In contrast, the three anesthetics had no effect on the levels of ROS production by a cell-free ROS generating system. In addition, intracellular calcium concentrations in neutrophils stimulated by N-formyl-L-methionyl-L-leucil-L-phenylalanine were dose-dependently decreased in the presence of each of the three anesthetics. The suppression of an increase in intracellular calcium concentrations may be responsible for the inhibition of neutrophil functions by the i.v. anesthetics. ⋯ Neutrophils play an important role in the antibacterial host defense system and autotissue injury. We found that thiopental and midazolam (but not ketamine), at clinically relevant concentrations, impaired the neutrophil functions.
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Anesthesia and analgesia · Jan 1998
Randomized Controlled Trial Clinical TrialPremedication of pediatric tonsillectomy patients with oral transmucosal fentanyl citrate.
We assessed the safety and efficacy of oral transmucosal fentanyl citrate (Fentanyl Oralet; Abbott Laboratories, Abbott Park, IL), administered preoperatively to provide both preoperative sedation and postoperative analgesia, in a randomized, double-blind, placebo-controlled study in 40 children, 2-10 yr of age, scheduled for tonsillectomy. In the preoperative holding area, one group (Group O) received Fentanyl Oralet (fentanyl 10-15 micrograms/kg), and the other (Group IV) received only the candy matrix. Patients in Group O received an i.v. injection of saline, and those in Group IV received an i.v. injection of fentanyl (2 micrograms/kg) after removal of the first tonsil. Except for the opioid, patients received a standard anesthetic. Preoperative sedation and cooperation were assessed. Postoperative pain was evaluated using an objective pain scale. Patients in Group O were more sedated but no more cooperative at the induction of anesthesia compared with those in Group IV. No patient vomited preoperatively or experienced preoperative or postoperative desaturation. Time to postanesthesia care unit (PACU) discharge was not different between groups. There was no significant difference in the number of patients requiring morphine in the PACU (6 of 21 in Group O versus 10 of 19 in Group IV). Plasma fentanyl concentrations were not a reliable indicator of the need for postoperative morphine. Among the patients who required morphine postoperatively, there was an 11-fold variation in plasma fentanyl concentrations at the time of morphine administration. Derived pharmacokinetic parameters were similar to those previously reported in children; bioavailability of the fentanyl in Fentanyl Oralet was 0.33. We conclude that premedication with Fentanyl Oralet did not differ with i.v. fentanyl in regard to the induction of anesthesia and postoperative analgesia. ⋯ In this double-blind, randomized study, we studied the efficacy of Fentanyl Oralet (10-15 micrograms/kg) preoperatively for providing postoperative analgesia in children undergoing tonsillectomy. We found no incidence of preoperative desaturation or vomiting in any patient. This is in contrast to other studies, in which there was a longer time interval between Fentanyl Oralet completion and induction of anesthesia. The bio-availability of the fentanyl in Fentanyl Oralet was estimated to be 33%, which is less than that reported in adults (approximately 50%). There was no difference in postoperative opioid requirements between patients who received 2 micrograms/kg of fentanyl i.v. and those who received Fentanyl Oralet.
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Anesthesia and analgesia · Jan 1998
Meta AnalysisDoes acute normovolemic hemodilution reduce perioperative allogeneic transfusion? A meta-analysis. The International Study of Perioperative Transfusion.
The objective of this study was to systematically review the literature and to statistically summarize the evidence evaluating acute normovolemic hemodilution (ANH). Prospective, randomized, controlled trials of ANH that reported either the proportion of patients exposed to allogeneic blood or the units of allogeneic blood transfused were included. All types and languages of publication were eligible. Of 1573 identified publications, 24 trials (containing a total of 1218 patients) were included in the meta-analysis. When all trials were pooled, ANH reduced the likelihood of exposure to allogeneic blood (odds ratio [OR] 0.31, 95% confidence interval [CI] 0.15, 0.62) and the total units of allogeneic blood transfused (weighted mean difference [WMD] -2.22 U, 95% CI -3.57, -0.86). However, there was marked heterogeneity of the results. In trials using a protocol to guide perioperative transfusion, ANH failed to reduce either the likelihood of transfusion (OR 0.64, 95% CI 0.31, 1.31) or the units administered (WMD -0.25 U, 95% CI -0.60, 0.10). Adverse events were incompletely reported. It is possible that biased experimental design is, in part, responsible for the reported efficacy of this technique. ⋯ after a systematic literature review, 24 randomized trials examining the role of acute normovolemic hemodilution were identified, pooled, and summarized using statistical techniques. Many studies reported an impressive reduction in blood transfused. Closer examination suggests that these reductions in blood exposure may be due to flawed study design.