Prolongation of the QT interval by volatile anesthetics in chronically instrumented dogs

The influence of volatile anesthetics on ventricular repolarization in vivo (QT interval) has not been studied in a systematic fashion. The purpose of this investigation was to characterize the electrocardiographic and hemodynamic actions of the volatile anesthetics halothane, isoflurane, and enflurane in chronically instrumented dogs. Because autonomic nervous system tone may influence ECG findings, experiments were completed with and without concomitant pharmacologic autonomic nervous system blockade. In six groups comprising 50 experiments with 21 instrumented dogs, anesthesia was mask-induced with nitrous oxide, oxygen, and one of the volatile anesthetics and maintained with the volatile anesthetic in 100% oxygen for 2 hours. Changes in the ECG and in hemodynamics were compared to the conscious state. In the absence of autonomic nervous system blockade, halothane and isoflurane significantly prolonged the QT interval (0.24 +/- 0.01 to 0.30 +/- 0.01 second and 0.22 +/- 0.01 to 0.28 +/- 0.01 second, respectively), whereas enflurane produced no change in ventricular repolarization (0.24 +/- 0.01 to 0.26 +/- 0.01 second). All of the volatile anesthetics increased the QT interval corrected for changes in basal heart rate (QTc), and all agents decreased intravascular pressure and dP/dt. Following autonomic nervous system blockade, halothane, isoflurane, and enflurane significantly increased the QT interval and QTc. The results demonstrate that ventricular repolarization is directly altered by the volatile anesthetics independent of changes in autonomic nervous tone. Whether or not such effects are additive with other congenital or acquired forms of QTc prolongation has yet to be examined. The present results indicate that caution should be used during the administration of volatile anesthetics to patients with abnormalities of the QT interval.     

The effects of volatile anesthetics on the Q-Tc interval

OBJECTIVE: To examine the effects of halothane, isoflurane, and sevoflurane on Q-Tc interval (corrected for heart rate) during inhalation induction of anesthesia. DESIGN: Prospective, double-blind, randomized study. SETTING: Departments of Cardiology and Anesthesiology in a university hospital. PARTICIPANTS: Patients undergoing noncardiac surgery. INTERVENTIONS: A total of 65 American Society of Anesthesiologists physical status I-II patients, aged 16 to 50 years, undergoing general anesthesia, were randomly allocated to receive halothane, isoflurane, or sevoflurane. MEASUREMENTS AND MAIN RESULTS: The time to reach the predetermined end-tidal concentrations of 3 minimum alveolar concentration was 6 to 10 minutes. When compared with preinduction values, heart rate decreased after halothane (p < 0.01) and sevoflurane (p < 0.05) administration; in contrast, heart rate increased after induction of anesthesia with isoflurane (p < 0.05). The mean QRS intervals were not significantly changed after halothane, isoflurane, or sevoflurane. The Q-Tc interval was increased with isoflurane compared with baseline (465 +/- 23 v 441 +/- 18 msec, p < 0.01), not changed with sevoflurane (441 +/- 17 v 434 +/- 19 ms, p > 0.05), and shortened with halothane (426 +/- 23 v 445 +/- 21 msec, p < 0.01). CONCLUSION: Sevoflurane or halothane may be preferred to isoflurane in patients with conditions that are known to induce a prolonged Q-Tc interval. The effects of Q-Tc interval changes resulting from different anesthetic agents on morbidity and the incidence of arrhythmias during anesthesia warrant further investigation.     

Flumazenil improves cognitive and neuromotor emergence and attenuates shivering after halothane-, enflurane- and isoflurane-based anesthesia

PURPOSE: To conduct a randomized, placebo-controlled, double-blinded, clinical experiment testing the hypothesis that flumazenil, a benzodiazepine antagonist, may affect recovery from halothane-, enflurane- and isoflurane-based anesthesia. METHOD: Patients who underwent surgery under N(2)O/O(2) plus halothane (n=100), enflurane (n=100) or isoflurane (n=70) anesthesia were administered flumazenil 1 mg or placebo upon emergence from anesthesia, and their postanesthesia vital signs, vigilance, neurological recovery, shivering, amnesia reversal, and general subjective feeling were assessed. RESULTS: A ten-point vigilance score showed better recovery of flumazenil-treated patients compared to those who received placebo (60-min after halothane anesthesia: 9.9 +/- 0.1 vs 9.5 +/- 0.2, P <0.01; after enflurane: 10 +/- 0 vs 9.4 +/- 0.2, P <0.01; after isoflurane: 10.0 +/- 0 vs 9.3 +/- 0.1, P <0.01). Halothane- and enflurane-flumazenil-treated patients (but not isoflurane) reached a better neurological score (2.97 +/- 0.05 or 3 +/- 0) compared to placebo (2.8 +/- 0.4 or 2.6 +/- 0.4, P <0.01), respectively. Reversal of amnesia was superior in the flumazenil group at 60 min and at 24 hr postsurgery, and more flumazenil patients rated recovery as "pleasant". Flumazenil patients shivered less than placebo patients despite their lower core temperature (at 30 min: halothane: 11% vs 28%, P <0.05; enflurane: 11% vs 30%, P <0.05; isoflurane: 17% for both groups). CONCLUSION: Flumazenil improves recovery of high cortical and neuromotor functions following halothane, enflurane and isoflurane anesthesia, reduces shivering and improves the overall quality of emergence, including patients' subjective feeling.     

Effects of sevoflurane versus propofol on QT interval.

BACKGROUND: Prolongation of the QT interval is an alteration of the electrocardiogram (ECG) that may result in a potentially dangerous polymorphic ventricular tachycardia known as torsade de pointes. Michaloudis et al. investigated the effect of isoflurane and halothane on the QT interval in premedicated and non premedicated children, and in premedicated adults. Isoflurane significantly prolonged the QTc interval, in contrast to halothane, which shortened the QTc interval. The aim of the study was to evaluate the effect of sevoflurane on the QT interval in patients undergoing non-cardiac surgery. METHODS: One hundred and eighty patients classified as ASA physical status I-III were enrolled and 102 were excluded. Patients had been scheduled for elective non cardiac surgery. Exclusions criteria were: cardiovascular impairment or chronic obstructive lung disease, medication affecting QT interval, and an abnormal prolongation of the QTc interval (440 ms). The patients were then randomly allocated to one of two groups, one receiving sevoflurane anesthesia and the other receiving propofol anesthesia. In all patients, a 12 lead ECG was recorded before surgery, after intubation, after extubation. The investigators reading the ECG were blinded to the type of induction and anesthesia used. The following variables were recorded or calculated: heart rate, P-R interval, QRS interval, QT interval, QTc interval according to Bazett's formula, systolic, diastolic and mean blood pressure. RESULTS: The sevoflurane significantly prolongs the QT and the QTc interval, whereas the induction and total intravenous anesthesia with propofol significantly shortens the QT but not the QTc interval. CONCLUSIONS: The amount the sevoflurane-associated QT prolongation may possibly be of clinical significance in some patients presenting long QT syndrome, hypokalemia, or in presence of other agents or factors that lengthen QT.     

Actions of halothane, isoflurane, and enflurane on the regional action potential characteristics of canine Purkinje fibers

The effects of halothane, isoflurane, and enflurane on proximal (false tendon) and distal (apical) canine Purkinje fibers were measured in vitro to assess their comparative effects on fibers exhibiting characteristically long (proximal) and short (distal) action potential duration. High- and low-dose anesthetic effects were evaluated in three groups of six left ventricular preparations and were compared with the changes occurring at identical times in six control preparations using analysis of variance with repeated measures. Under control conditions in all groups, the action potential duration, measured at 90% repolarization (APD90, mean +/- SEM), of proximal fibers was longer than that of distal fibers (320 +/- 16 vs 252 +/- 11 ms, P less than or equal to 0.01). Halothane (0.3 and 0.7 mM), isoflurane (0.4 and 0.8 mM), and enflurane (0.6 and 1.0 mM) produced a dose-dependent decrease (P less than or equal to 0.01) of proximal fiber APD90 with less (P less than or equal to 0.01) change of distal fiber APD90 and reduced (P less than or equal to 0.05) regional differences of APD90 at the higher dose. The decreases of proximal fiber APD90 were greater (P less than or equal to 0.01) for 1.0 mM (1.7 MAC) enflurane (-66 +/- 7 ms) and 0.8 mM (3.0 MAC) isoflurane (-69 +/- 9 ms) than for 0.7 mM (2.9 MAC) halothane (-33 +/- 8 ms). We conclude that the regional actions of anesthetics on Purkinje fiber repolarization may influence conduction during the relative refractory period and the occurrence of arrhythmias associated with disparity of regional refractory characteristics in the ventricular conduction system.     

Comparison of enflurane, halothane, and isoflurane for diagnostic and therapeutic procedures in children with malignancies

The authors performed a randomized, prospective trial comparing enflurane, halothane, and isoflurane (each administered with nitrous oxide) to establish which inhaled anesthetic produced the fewest complications and the most rapid induction of anesthesia for children undergoing general anesthesia for diagnostic procedures as oncology outpatients. Sixty-six children, ranging from 8 months to 18 years, underwent a total of 124 anesthetics. Induction of anesthesia (time from placement of facemask to beginning of skin preparation) was faster with halothane (2.7 +/- 1.0 min, mean +/- SD, n = 46) than with enflurane (3.2 +/- 0.8 min, n = 43) or isoflurane (3.3 +/- 1.2 min, n = 35). Emergence from anesthesia (time from completion of the procedure to spontaneous eye opening) was more rapid with enflurane (4.7 +/- 4.4 min) than with halothane (6.2 +/- 4.5 min) or isoflurane (6.2 +/- 3.9 min). Total time from the start of procedure until discharge was longer with isoflurane (25.1 +/- 6.8 min) than with enflurane (21.5 +/- 8.6 min) or halothane (22.3 +/- 7.6 min). During induction, the incidence of laryngospasm was greatest with isoflurane (23%) and the incidence of excitement least with halothane (13%). During the maintenance of, emergence from, and recovery from anesthesia, coughing occurred most frequently with isoflurane. During the recovery period, headache occurred most frequently with halothane (9%); there were no significant differences in the incidence of nausea, vomiting, hunger, or depressed effect. The authors conclude that the rapid induction and minimal airway-related complications associated with halothane anesthesia make it an excellent anesthetic agent for pediatric patients undergoing short diagnostic procedures.     

Sustained prolongation of the QTc interval after anesthesia with sevoflurane in infants during the first 6 months of life

BACKGROUND: Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population. METHODS: In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia. RESULTS: Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P< 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P< 0.01). Analogous differences were found for the JTc interval. CONCLUSIONS: Despite a shorter elimination time than better known inhalational anesthetics, sevoflurane induction and anesthesia results in sustained prolongations of QTc and JTc interval in infants in the first 6 months of life. Electrocardiogram monitoring until the QTc interval has returned to preanesthetic values may increase safety after sevoflurane anesthesia.     

Cardiovascular effects of and interaction between calcium blocking drugs and anesthetics in chronically instrumented dogs. V. Role of pharmacokinetics and the autonomic nervous system in the interactions between verapamil and inhalational anesthetics

To assess the role of both pharmacokinetics and the autonomic nervous system in the interaction between inhalational anesthetics and verapamil, dogs were chronically instrumented to measure heart rate, PR interval, dP/dt, cardiac output, and aortic blood pressure. In a first group of seven dogs, studied awake and during halothane (1.2%), enflurane (2.5%), and isoflurane anesthesia (1.6%), verapamil was infused for 30 min in doses calculated to obtain similar plasma concentrations (83 +/- 10, 82 +/- 6, 81 +/- 10, and 77 +/- 9 ng.ml-1, respectively). For the latter purpose, the infusion dose was 3 and 2 micrograms.kg-1.min-1 awake and during anesthesia, respectively, preceded by a loading dose of 200, 150, and 100 micrograms.kg-1, awake, during isoflurane, and halothane and enflurane, respectively. In awake dogs, verapamil induced an increase in heart rate (24 +/- 5 bpm) and PR interval (35 +/- 9 msec) and a decrease in mean arterial pressure (-5 +/- 2 mmHg) and dP/dt (-494 +/- 116 mmHg/s). Although plasma concentrations were similar in awake and in anesthetized dogs, the only statistically significant changes induced by verapamil were an increase in heart rate and a decrease in dP/dt during halothane and enflurane, while left atrial pressure increased only with enflurane. In a second group of six dogs, verapamil pharmacokinetics were determined in the presence and absence of a ganglionic blocking drug (chlorisondamine, 2 mg.kg-1 iv). Blockade of ganglionic transmission resulted in a decrease in both initial volume of distribution and total clearance of verapamil--changes similar to those previously reported with inhalational anesthetics.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sustained Prolongation of the QTc Interval after Anesthesia with Sevoflurane in Infants during the First 6 Months of Life

Background: Sevoflurane, an inhalational anesthetic frequently administered to infants, prolongs the QT interval of the electrocardiogram in adults. A long QT interval resulting in fatal arrhythmia may also be responsible for some cases of sudden death in infants. As the QT interval increases during the second month of life and returns to the values recorded at birth by the sixth month, we evaluated the effect of sevoflurane on the QT interval during and after anesthesia in this particular population.

Methods: In this prospective two-group trial we examined pre-, peri-, and postoperative electrocardiograms of 36 infants aged 1 to 6 months scheduled for elective inguinal or umbilical hernia repair. Anesthesia was induced and maintained with either sevoflurane, or the well-established pediatric anesthetic halothane. Heart rate corrected (c) QTc and JTc interval (indicator of intraventricular conduction delays) were recorded from electrocardiograms before and during anesthesia, and at 60 min after emergence from anesthesia.

Results: Prolonged QTc was observed during sevoflurane anesthesia (mean [+/-SD], 473 +/- 19 ms, P < 0.01). Sixty minutes after emergence from anesthesia, QTc was still prolonged (433 +/- 15 ms) in infants treated with sevoflurane compared with those treated with halothane (407 +/- 33 ms, P < 0.01). Analogous differences were found for the JTc interval.     

Effect of Low-dose Droperidol on the QT Interval during and after General Anesthesia: A Placebo-controlled Study

Background: Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia.

Methods: One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted.

Results: Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period.     

Effect of low-dose droperidol on the QT interval during and after general anesthesia: a placebo-controlled study

BACKGROUND: Since the effects of antiemetic doses of droperidol on the QT interval have not been previously studied, the authors designed a randomized, double-blind, placebo-controlled study to evaluate the intraoperative and postoperative effects of small-dose droperidol (0.625 and 1.25 mg intravenous) on the QT interval when used for antiemetic prophylaxis during general anesthesia. METHODS: One hundred twenty outpatients undergoing otolaryngologic procedures with a standardized general anesthetic technique were enrolled in this study. After anesthetic induction and before the surgical incision, 60 patients were given either saline or 0.625 or 1.25 mg intravenous droperidol in a total volume of 2 ml. A standard electrocardiographic lead II was recorded immediately before and every minute after the injection of the study medication during a 10-min observation period. The QTc (QT interval corrected for heart rate) was evaluated from the recorded electrocardiographic strips. In 60 additional patients, a 12-lead electrocardiogram was obtained before and at specific intervals up to 2 h after surgery to assess the effects of droperidol and general anesthesia on the QTc. Any abnormal heartbeats or arrhythmias during the operation or the subsequent 2-h monitoring interval were also noted. RESULTS: Intravenous droperidol, 0.625 and 1.25 mg, prolonged the QT interval by an average of 15 +/- 40 and 22 +/- 41 ms, respectively, at 3-6 min after administration during general anesthesia, but these changes did not differ significantly from that seen with saline (12 +/- 35 ms) (all values mean +/- SD). There were no statistically significant differences among the three study groups in the number of patients with greater than 10% prolongation in QTc (vs. baseline). Although general anesthesia was associated with a 14- to 16-ms prolongation of the QTc interval in the early postoperative period, there was no evidence of droperidol-induced QTc prolongation after surgery. Finally, there were no ectopic heartbeats observed on any of the electrocardiographic rhythm strips or 12-lead recordings during the perioperative period. CONCLUSION: Use of a small dose of droperidol (0.625-1.25 mg intravenous) for antiemetic prophylaxis during general anesthesia was not associated with a statistically significant increase in the QTc interval compared with saline. More importantly, there was no evidence of any droperidol-induced QTc prolongation immediately after surgery.     

Suppression of motor evoked potentials by inhalation anesthetics

The purpose of this study was to record evoked action potentials from forearm muscles in response to single-shock supramaximal electrical stimulation of motor cortex in room air and under different concentrations (0.5-1.5%) of isoflurane, enflurane, and halothane anesthesia in rats. Anesthesia was induced with a mixture of fentanyl and droperiodol, which was then followed by 10-min inhalation of each gas anesthetic under controlled ventilation. Increasing concentrations of isoflurane (n = 12) caused a progressive increase in onset latency and a decrease in peak-to-peak amplitude and duration. Similar increases in latency and decreases in amplitude and duration occurred under enflurane (n = 10) and halothane (n = 10) anesthesia. The three anesthetics caused a significant latency increase over baseline (room air) values for concentrations from 0.5 to 1.5% (p < 0.01). The amplitude and duration of muscle responses under all three volatile anesthetics at 0.5-1.5% concentrations were significantly lower than baseline (p < 0.01). Isoflurane, enflurane, and halothane anesthesia significantly altered the muscle response evoked by motor cortex stimulation in experimental animals.     

QT dispersion in patients with end-stage renal failure and during hemodialysis.

Interlead variability of the QT interval in surface electrocardiogram (ECG), i.e., QT dispersion, reflects regional differences in ventricular recovery time, and it has been linked to the occurrence of malignant arrhythmias in different cardiac diseases. The purpose of the study was to assess the effect of hemodialysis on QT and corrected QT (QTc) interval and dispersion in chronic hemodialyzed patients. Data of 34 nondiabetic patients (male/female = 21/13; mean age, 54 +/- 15 yr) on chronic hemodialysis were studied. Polysulfone capillaries and bicarbonate dialysate containing (in mEq/L) 135 Na+, 2.0 K+, 1.5 Ca2+, and 1.0 Mg2+ were used. Simultaneous 12-lead ECG were recorded before and after hemodialysis in a standard setting. The QT intervals for each lead were measured manually on enlarged (x3) ECG by one observer using calipers. Each QT interval was corrected for patient heart rate: QTc = QT/square root of RR (in milliseconds [ms]). The average cycle intervals were 853 +/- 152 ms predialysis and 830 +/- 173 ms postdialysis; the difference was not significant. The maximal QT interval changed significantly from 449 +/- 43 to 469 +/- 41 ms (P < 0.01). The corrected maximal QT interval increased significantly from 482 +/- 42 to 519 +/- 33 ms (P < 0.01). The QT dispersion changed from 56 +/- 15 to 85 +/- 12 ms (P < 0.001) and the corrected QT interval dispersion from 62 +/- 18 to 95 +/- 17 ms (P < 0.001). During hemodialysis, the serum potassium and phosphate levels decreased from 5.5 +/- 0.8 to 3.9 +/- 0.5 (mM) and from 2.3 +/- 0.5 to 1.6 +/- 0.4 (mM), respectively, whereas calcium increased from 2.2 +/- 0.23 to 2.5 +/- 0.22 (mM). It is concluded that hemodialysis increases the QT and QTc interval and QT and QTc dispersion in patients with end-stage renal failure. Thus, it may be stated that the nonhomogeneity of regional ventricular repolarization increases during hemodialysis. Measurement of QT and QTc dispersion is a simple bedside method that can be used for analyzing ventricular repolarization during hemodialysis.     

Effects of halothane and quinidine on intracardiac conduction and QTc interval in pentobarbital-anesthetized dogs.

To confirm in vitro data that halothane and quinidine depressed cardiac conduction and prolonged action potential (AP) duration, the electrocardiogram and His bundle electrogram were recorded in dogs during basal pentobarbital anesthesia, after 1% halothane or quinidine (2.38 +/- 0.22 micrograms/mL serum concentration [mean +/- SEM]), or both. Purkinje fibers from a second dog were superfused with blood from the intact (support) dog, and APs were recorded. In the intact dogs, 1% halothane caused no changes in the electrocardiogram or His bundle electrogram. Quinidine prolonged QRS duration, QT interval, and rate-corrected QT (P < 0.05). Ventricular conduction (HS interval) slowed, and atrial effective refractory period increased (P < 0.05). Quinidine combined with halothane widened QRS, QT, and rate-corrected QT, prolonged the HS interval, and increased the vulnerability of the atrioventricular node to conduction block. Three of 20 dogs developed torsades de pointes-type ventricular tachycardia during simultaneous quinidine and halothane administration. In cross-superfused Purkinje fibers, the AP duration to 50% repolarization was shortened, and conduction time was prolonged by 1% halothane (both P < 0.05). Quinidine decreased AP amplitude, prolonged AP duration to 90% repolarization, and slowed conduction (P < 0.05). Quinidine combined with halothane decreased AP amplitude, and prolonged both AP duration to 90% repolarization and conduction (P < 0.05). When 1% halothane and therapeutic concentrations of quinidine are administered in dogs, depressed conduction and an acquired long QT syndrome with malignant ventricular arrhythmias may develop.     

The effects of sevoflurane, isoflurane and desflurane on QT interval of the ECG

BACKGROUND AND OBJECTIVE: To determine if there is any significant difference between the effects of desflurane, isoflurane and sevoflurane on the QT interval, QT dispersion, heart rate corrected QT interval and QTc dispersion of the electrocardiogram. METHODS: The study was conducted in a prospective, double blind and randomized manner in a teaching hospital. Ninety ASA I patients, aged 16-50 yr, undergoing general anaesthesia for noncardiac surgery were studied. RESULTS: There was no significant change in QT intervals during the study in any group (P > 0.05). QT dispersion in the sevoflurane group 49+/-14 ms vs. 37+/-10 ms; in the desflurane group 55+/-16 and 62+/-21 ms vs. 35+/-14 ms and in the isoflurane group 54+/-26 and 59+/-24 ms vs. 42+/-19 ms were significantly increased at 3 and 10 min after 1 MAC of steady end-tidal anaesthetic concentration compared with baseline values (P < 0.05). QTc values in the sevoflurane group were 444+/-24 and 435+/-2 1ms vs. 413+/-19 ms (P < 0.05), in the isoflurane group were 450+/-26 and 455+/-34 ms vs. 416+/-34 ms (P < 0.05), in the desflurane group were 450+/-26 and 455+/-34 ms vs. 416+/-34 ms (P < 0.05) at 3 and 10 min after reaching 1 MAC of anaesthetic concentration and significantly increased compared with baseline values. QTc dispersion increased significantly with sevoflurane 62+/-14 ms vs. 45+/-16 ms (P < 0.05); isoflurane 70+/-36 ms at 3 min and 75+/-36 ms at 10 min after reaching 1 MAC of anaesthetic concentration vs. 50+/-24 ms (P < 0.05); desflurane 67+/-25 ms at 3 min and 74+/-27 ms at 10 min after 1 MAC concentration vs. 41+/-22 ms (P < 0.05). CONCLUSION: Sevoflurane, isoflurane and desflurane all prolonged QTd, QTc and QTcd but there were no significant intergroup differences.     

Cardiovascular effects of acute changes in extracellular ionized calcium concentration induced by citrate and CaCl2 infusions in chronically instrumented dogs, conscious and during enflurane, halothane, and isoflurane anesthesia

To study the cardiovascular effects of low blood ionized calcium ion concentrations [Ca2+] induced by citrate infusion followed by high [Ca2+], induced by CaCl2 infusion awake and during enflurane (2.5% ET), halothane (1.2% ET), and isoflurane (1.6% ET) anesthesia, dogs were chronically instrumented to measure heart rate, aortic, left atrial, and left ventricular (LV) blood pressures, and cardiac output. In conscious dogs low [Ca2+] (decreased 0.35 mM); increased heart rate (HR) and mean aortic pressure (MAP) and decreased stroke volume (SV) and LV dP/dtmax. Low [Ca2+] increased HR during all three anesthetics and decreased LV dP/dtmax except during isoflurane anesthesia. Low [Ca2+] produced more hemodynamic depression during enflurane anesthesia than during anesthesia with halothane or isoflurane increasing left atrial pressure and decreasing MAP and SV. The differences seen were partially related to decreased systemic vascular resistance during halothane and isoflurane anesthesia. In conscious dogs following high [Ca2+] (increased 0.37 mM); only MAP and LV dP/dtmax increased. LVdP/dtmax was also increased by high [Ca2+] during all three anesthetics without a change in MAP. Cardiac output increased during halothane and isoflurane anesthesia but was unchanged during enflurane. It would appear that the hemodynamic sensitivity for the effects of changing [Ca2+] was enflurane greater than halothane greater than isoflurane greater than awake. The results suggest that the effects of changes in [Ca2+] induced by citrate and CaCl2 infusion are modified by the three volatile anesthetics.     

Effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in normovolemic and hypovolemic cirrhotic rats

The effects of ketamine, halothane, enflurane, and isoflurane on systemic and splanchnic hemodynamics in cirrhotic rats that were either normovolemic or hypovolemic following hemorrhage were characterized. Rats received at random either ketamine (30 mg/kg iv, 1.5 mg.kg-1.min-1 iv), halothane, enflurane, or isoflurane (1 MAC). Conscious rats were considered the control group. Four weeks before hemodynamic studies bile duct ligation was performed in all rats to induce cirrhosis. Hemodynamic measurements were performed using the radioactive microsphere method 1 h after the onset of anesthesia and 30 min after hemorrhage. Anesthetized rat lungs were mechanically ventilated with room air. Before hemorrhage cardiac index was higher in conscious rats and in rats receiving isoflurane than in the other groups (P less than 0.001). Hepatic arterial blood flow was similar in conscious rats and in those receiving isoflurane or halothane and was higher than in those receiving ketamine or enflurane. The lowest splanchnic and portal venous tributary blood flows were observed in rats receiving enflurane. After hemorrhage cardiac index was significantly less than before hemorrhage in all groups, except in rats receiving enflurane. After hemorrhage portal venous tributary blood flow decreased significantly in all groups except in enflurane group. During halothane and enflurane anesthesia hepatic arterial blood flow and hepatic arterial fraction of cardiac output decreased (P less than 0.01) and they were maintained in the other groups. After hemorrhage hepatic arterial fraction of cardiac output in conscious rats was higher than in those receiving ketamine, halothane, or enflurane (P less than 0.05) and was similar to those receiving isoflurane.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of halothane, isoflurane and enflurane on isolated rat heart muscle

Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.     

Systolic time intervals by intratracheal pneumocardiogram and the effects of inhalation anesthetics on cardiac function using this technic

Intratracheal pressure change due to cardiogenic oscillation was obtained by a high gain pressure transducer attached to the endotracheal tube while the patient was apneic during the operation. Such pressure change has been called as intratracheal pneumocardiogram (ITCG), which consists of wide waves and some spikes. Systolic time interval (STI) was obtained by measuring the intervals between certain spikes. The STIs measured by ITCG were compared with those by echocardiogram and by the conventional method. Also the effects of halothane, enflurane and isoflurane on cardiac performance were evaluated using the STI by ITCG. The STI measured by ITCG correlated well with that by echocardiogram, which indicated that the STI by ITCG was a useful noninvasive method to monitor the cardiac performance during general anesthesia. The STI by ITCG showed that the left ventricular ejection time (LVET) decreased in halothane and enflurane anesthesia. The pre-ejection period (PEP) and the PEP/LVET ratio increased in all three types of anesthesia. Especially the PEPs during halothane and enflurane at 1.8 MAC (minimum alveolar concentration) were greater than that of isoflurane. The results suggest that isoflurane has less cardiac depressive action than halothane and enflurane.     

Effects of inhalational anesthetics on verapamil pharmacokinetics in dogs

Six dogs were chronically instrumented in order to collect aortic blood samples and record mean arterial pressure, cardiac output and heart rate. Each animal received verapamil 200 micrograms X kg-1 by 10-min intravenous infusions on four occasions in random sequence: awake, and during halothane 1.2%, enflurane 2.5%, and isoflurane 1.6% anesthesia. Rate of initial distribution of verapamil was reduced during anesthetic exposure. Verapamil intercompartmental clearance from the central compartment to the peripheral compartment was decreased during exposure to halothane and isoflurane, and tended to decrease during enflurane exposure as well. Verapamil terminal volume of distribution at steady-state was reduced by halothane, enflurane, and isoflurane exposure as compared with awake: 65 +/- 10, 80 +/- 9, and 93 +/- 191, respectively, versus 132 +/- 121 (mean +/- SEM; P less than 0.05). Verapamil total clearance was also reduced by halothane, enflurane, and isoflurane as compared with awake: 37 +/- 4, 39 +/- 2 and 41 +/- 31 X h-1, respectively, versus 64 +/- 71 X h-1 (P less than 0.05). Verapamil administered to awake animals resulted in a decrease from baseline in mean arterial pressure; 95 +/- 8 mmHg versus 108 +/- 4 mmHg (P less than 0.05): and an increase in cardiac output; 2.60 +/- 0.33 1 X min-1 versus 1.93 +/- 0.22 1 X min-1 (P less than 0.05). During halothane, enflurane, and isoflurane anesthesia, verapamil administration resulted in a similar decrease in mean arterial pressure; however cardiac output decreased, in contrast to the increase noted in awake animals.(ABSTRACT TRUNCATED AT 250 WORDS)