Effects of L-NAME, Aminoguanidine and Hydroxocobalamin on Aortic Contractile Responses in Endotoxemic Rats during Halothane Administration / 대한마취과학회지

BACKGROUND: Recent studies demonstrated that volatile anesthetics suppress the NO-cGMP system in the vascular system. It has been known that the hemodynamic changes produced by volatile anesthetics in septic patients are mediated by upregulation of iNOS leading to excessive release of NO. The mechanisms underlying suppression of the NO-cGMP system by anesthetics are still controversial. It has been elucidated that nitric oxide synthase (NOS) plays a major role in the regulatory function in the L-arginine-NO system. So we examined the effects of NOS inhibitor (L-NAME, aminoguanidine) and NO scavenger (hydroxocobalamin) on vascular smooth muscle contractile function in lipopolysaccharide (LPS)-treated rat aorta during halothane administration. METHODS: Aortic ring preparations were obtained from LPS-treated (1.5 mg/kg, ip, for 18 h) rats. We evaluated the effects of hydroxocobalamin, L-NAME and aminoguanidine on contractile responses to phenylephrine during halothane (1 & 2 MAC) administration respectively. Statistical significances (P<0.05) were analyzed according to data characterictics by repeated measures ANOVA test and student's t-test. RESULTS: The contractile responses to phenylephrine in LPS-treated rats aorta were significantly (P<0.05) increased in the presence of hydroxocobalamin and L-NAME. During the halothane (1 and 2 MAC) administration, the contractile responses to phenylephrine in LPS-treated rats aorta were increased significantly (P<0.05) in the presence of hydroxocobalamin and L-NAME. CONCLUSIONS: From these results, it is suggested that hydroxocobalamin and L-NAME may be useful in the therapy of septic shock.

Effects of Acute Myocardial Ischemia on Regional Function of the Remote Nonischemic Myocardium in Dogs / 대한마취과학회지

INTRODUCTION: During an acute myocardial ischemia, maintenance of overall ventricular function may depend on remote nonischemic myocardium. Whereas fentanyl has minimal hemodynamic effects, volatile anesthetics, including halothane and isoflurane cause negative inotropic and lusitropic effects in normal myocardium. This investigation examined the effects of volatile anesthetics in comparision with fentanyl on compensatory responses to brief left anterior descending coronary artery (LAD) occlusion in remote normal myocardium (left circumflex coronary artery (LCX) supply) in an open-chest canine model. METHODS: Thirty-six mongrel dogs, acutely instrumented for measurement of pressure (left ventricle (LV) and aorta), flows (pulmonary trunk and LCX) and dimensions in ischemic and non-ischemic myocardium, were subjected to a 10-min LAD occlusion during fentanyl (n=10), halothane (n=13), or isoflurane (n=13) anesthesia. Regional contractile function was assessed using percent systolic shortening (%SS) and the preload recruitable stroke work slope (Mw). Diastolic function was evaluated using a regional time constant for intramyocardial pressure decline of LV (IMPtau), peak lengthening rate (dL/dtmax) and a regional chamber stiffness constant (Kp). RESULTS: Acute LAD occlusion caused immediate deterioration of anterior wall function similarly without changes in cardiac index, mean arterial pressure and dP/dtmax in all three groups. LV end-diastolic pressure (LVEDP), LVPtau, and heart rate increased and dP/dtmin decreased to the same extent with regional myocardial ischemia in all groups. During fentanyl anesthesia, acute myocardial ischemia was associated with an increase in %SS (26%) and Mw (48%) in LCX area without changes in IMPtau and dL/dtmax. With halothane or isoflurane anesthesia, %SS, Mw and IMPtau showed similar changes as those in fentanyl in response to LAD occlusion. However, dL/dtmax was increased (47 and 45% in the halothane and isoflurane groups, respectively) and Kp was increased (34 and 33% in the halothane and isoflurane groups, respectively) less compared to fentanyl (78%). Enhanced function in LCX zone was associated with a comparable increase (21~28% from baseline) in LCX flow in all groups. CONCLUSION: Enhanced regional contractility following acute coronary occlusion in nonischemic myocardium during fentanyl anesthesia is well-preserved with volatile anesthetics in an open-chest canine model. In addition, diastolic functions are also enhanced rather than depressed during anesthesia with volatile anesthetics. Halothane and isoflurane, however, do not differ in the compensatory responses to acute regional ischemia.

A Case of Cardiac Arrest due to Drug Interaction between Halothane and Aminophylline: A case report / 대한마취과학회지

Although halothane is generally anesthetic of choice for asthmatics due to its bronchodilatory action, its combined use with aminophylline should be discouraged. This report is a 43-year-old male who had primary closure and open reduction internal fixation (ORIF) for facial avulsion injury and zygomatic tripod fracture under N2O-O2-halothane anesthesia. About 90 minutes after the procedure, the patient who had aminophylline infusion for an acute bronchospasm developed a sudden cardiac arrest. The immediate cardiopulmonary resuscitation was applied and the patient was recovered without any neurological deficit. At the time, the serum theophylline concentration of the patient was 16 microgram/ml which was in the range of normal therapeutic dose. The cause for this cardiac arrest by halothane is unknown, but possibly a drug interaction between halothane and aminophylline might have contributed, since halothane sensitizes the heart to exogenous catecholamines.

Effects of Inhalational Anesthetics on Contractile Responses and Nitric Oxide Synthase Activity in Endotoxemic Rats / 대한마취과학회지

BACKGROUND: Recent studies revealed that inhalational anesthetics (IA) attenuate NO production. But the hemodynamic changes produced by IA in septic syndrome patient are still sufficient to threaten patient, surgeon and anesthesiologist. So we examined which IA is proper to maintain vascular contractile force and evaluated the effects of NOS inhibitors on contractile force of septic rat aorta under IA. METHODS: Aortic ring preparation was obtained from LPS-treated (1.5 mg/kg, i.p. for 18h) rats. The development of sepsis was confirmed by iNOS activity and iNOS expression using RT-PCR. Contractile responses of aorta to phenylephrine admministation in the presence or absence of halothane, enflurane and isoflurane were evaluated. We also evaluated the effects of NOS inhibitors, one is NG-nitro-L-arginine methyl ester (L-NAME) and the other is aminoguanidine. Statistical significances (p<0.05) were analyzed according to data characteristics by unpaired t-test and paired t-test. RESULTS: The contractile responses to phenylephrine admministration were attenuated in LPS-treated rings. Isoflurane, even at the dose of 2 MAC, didn't affect the contractile response while both halothane and enflurane decreased the contractile response even at the dose of 1 MAC. The potentiation of contractile responses by NOS inhibitors were not affected during administeration of IA. CONCLUSIONS: From these results, it is suggested that isoflurane is the safest inhalational anesthetic and NOS inhibitors, especially L-NAME, may be very useful in the therapy of septic shock patients during general anesthesia.

The Potency of Mivacurium during Halothane or Enflurane Anesthesia in Infants and Preschool Children / 대한마취과학회지

BACKGROUND: The dose-responses of neuromuscular blocking agents may be influenced by many factors including age and inhalation anesthetics. This study was designed to determine the dose-response relationships of a new, short-acting muscle relaxant, mivacurium during nitrous oxide-halothane or nitrous oxide-enflurane anesthesia in two age groups, infants and 1 to 6 years old preschool children. METHODS: Neuromuscular blockade was monitored by recording the accelerographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relationships, 24 infants or children of two anesthetic subgroups for each age group received single bolus doses of 45~100 g/kg of mivacurium. The ED50 and ED95 were estimated from linear regression plots of log-dose vs probit of twitch depression. The lag time, onset time and maximal depression of twitch height for the selective medium dose were mesured. RESULTS: The ED50 and ED95 for the infants group were 38.2 and 53.3 g/kg during halothane anesthesia, and 29.8 and 48.6 g/kg during enflurane anesthesia, respectively. And, those for preschool children group were 49.4 and 90.7 g/kg during halothane anesthesia, and 32.3 and 81.4 g/kg during enflurane anesthesia, respectively. There was a parallelism of the dose-response curve between halothane and enflurane anesthesia in either age group. Also, there was statistically significant difference in the maximal twitch depression for the selective medium dose of mivacurium between halothane and enflurane anesthesia in either group. CONCLUSIONS: The potency of mivacurium during enflurane anesthesia is higher than that during halothane anesthesia in infants and preschool children, and during either inhalation anesthesia the dose of mivacurium is less required in infants than preschool children.

Effects of Halothane, Fentanyl, and Propofol-Fentanyl Anesthesia on Functional Recovery of Stunned Myocardium in Dogs / 대한마취과학회지

BACKGROUND: Stunned myocardium may be mediated by intracellular Ca2+ overloading or oxygen derived-free radicals. Halothane and propofol have been shown to block Ca2+ channels. Propofol is also known to have antioxidant properties. The present study was aimed to investigate the effects of anesthetics on recovery of postischemic, reperfused myocardium in open-chest dogs. Incidence of ventricular arrhythmia upon ischemia and reperfusion was also determined. METHODS: Forty dogs were subjected to 15 min occlusion of left anterior descending coronary artery (LAD) followed by 3 hr reperfusion during halothane (n=10), fentanyl (n=12), or propofol plus fentanyl (n=11) anesthesia. Regional contractile function was assessed using percent systolic shortening (%SS), the preload recruitable stroke work slope (Mw), and peak systolic intramyocardial pressure (IMPs). Diastolic function was evaluated using time constant for isovolumic intramyocardial pressure decline of left ventricle (IMP-tau) and percent post-systolic shortening (%PSS). RESULTS: %SS in the halothane, fentanyl, and propofol-fentanyl groups was similar at 3 hours of reperfusion (58%, 60%, and 55% of baseline value, respectively). Moreover, Mw recovered to the baseline values in the early reperfusion period in all three groups. However, IMP-tau was significantly prolonged in the halothane group throughout the 3 hour reperfusion period, whereas it remained unchanged in the fentanyl and propofol-fentanyl groups. Coronary occlusion was associated with 9, 33, and 0% mortality rate due to ventricular fibrillation upon ischemia and reperfusion in the halothane, fentanyl, and propofol-fentanyl groups, respectively. CONCLUSION: These findings indicate that halothane, but not fentanyl and propofol- fentanyl, impairs myocardial relaxation, while recovery pattern of contractile function do not differ among three groups, and that halothane and propofol reduce reperfusion arrhythmia in the canine model of myocardial stunning.

EEG Spectral Analysis during Administation of Combined Inhalation Anesthetics in Rats / 대한마취과학회지

BACKGROUND: The electroencephalogram(EEG) has long been used to study the effects of anesthetic drugs on central nervous system function. This study was designed to evaluate the accuracy of two EEG parameters for assessing anesthetic depth during inhalation of 1.5 MAC three inhalation anesthetics (halothane, enflurane, and isoflurane) with 50%-N2O in rats. METHODS: Total 15 rats weighing between 300~350 g, with 5 rats for each anesthetic group were tested for investigation the anesthetic depth. EEG spectrum analysis was evaluated for three inhalation anesthetics which all were added with 50%-N2O. The spectral edge frequency(SEF), median power frequency(MPF) were obtained from the EEG spectrum analysis of raw EEG via fast Fourier transform(FFT). RESULTS: Raw EEG of halothane demonstrated sigmoidal shaped EEG, enflurane abundant spike waves, and isoflurane burst suppression. When 50%-N2O was added to each anesthetic group, the characteristics of the raw EEG were disappeared. EEG spectrum analysis enabled to distinguish the effects of each anesthetic on the anesthetic depth. EEG spectrum analysis demonstrated after 50%-N2O was added that the values of MPF and SEF were significantly decresed as 2.5 Hz and 6.5 Hz from 5.2 Hz and 14.2 Hz respectively. CONCLUSIONS: It is speculated that SEF and MPF was decreased due to the suppression of cerebral electrical activity. The decreases of SEF and MPF from analysis of EEG spectra confirm that the addition of 50%-N2O to each inhalation anesthetics enabled the deeper anesthetic depth.

Effects of Intravenous Anesthetics on EEG Spectral Analysis during Cesarean Section / 대한마취과학회지

BACKGROUND: Anesthesia induces the spectral changes in EEG. Attempts to relate these spectral changes to adequacy of anesthesia have been hindered due to the complex waveforms of EEG. The objective of this investigation is to monitor the awareness of patients during cesarean section by means of EEG spectral analysis. METHODS: 20 patients for cesarean section aged from 24 to 39 and ASA class I or II, were maintained with O2(50%)-N2O(50%)-enflurane(0.8%). And they were administered with midazolam(0.07 mg/kg) in group I(n=6), fentanyl(1 microgram/kg) in group II(n=7), and fentanyl(2 microgram/kg) in group III(n=7) after birth. The density of each spectral band in EEG (delta 1-3.25 Hz, theta 3.5-7.75 Hz, alpha 8-12.15 Hz and beta 13-31.75Hz) was analyzed to derive total density, delta ratio and median power frequency. RESULTS: The spectral data demonstrated that the alpha rhythm was dominant in pre-induction period and beta rhythm was abundant both in the immediate post-induction period and after birth for all three groups. Delta ratio and median power frequency decreased after injection of midazolam and fentanyl in all three groups. None of patients could recall the memory about experience during cesarean section. CONCLUSIONS: These findings indicate that EEG spectral analysis is potentially useful to determine the changes of cerebroelectrical activity but difficult to monitor the awareness of patients during cesarean section.

Effects of General Anesthesia in Patients with Abnormal Liver Function / 대한마취과학회지

Recently, halothane has been commonly used as an inhalation anesthetic agent, but it is generally accepted that it can cause postoperative hepatic dysfunction. Therefore, other anesthetic agents which have relatively less hepatotoxic effects have been recommended. This study was undertaken to evaluate the postoperative hepatic changes in patients with abnormal liver function or hepatobiliary diseases. Patients were divided into three subgroups hepatobiliary, other hepatobiliary and jaundice, or HBsAG(+) for the two anesthetic agents, enflurane and Thalamonal. Liver function tests were performed before surgery, and on the 3rd, 5th and 9th postoperative days. The results were as follows: 1) SGOT and SGPT showed a more statistically significant decrease in Thalamonal anesthesia than in enflurane anesthesia in hepatobiliary and jaundice or HBsAg(+) groups. However, in the other hepatobiliary groups, there were no significant differences between the anesthetics. 2) Total protein, albumin, total bilirubin, direct bilirubin and alkaline phosphatase levels were not shown to be significantly different between the use of the two anesthetics in all groups. It is suggested that postoperative hepatic changes may have improved more significantly in Thalamonal anesthesia than in enflurane anesthesia in hepatobiliary patients with abnormal liver function and jaundice or HBsAg(+) patients.