Uptake of halothane and isoflurane by mother and baby during Caesarean section

Twenty-three patients undergoing Caesarean section receivedeither 0.5% halothane or 0.8% isoflurane to supplement nitrousoxide-oxygen anaesthesia. We studied the rate of uptake of theagents by the mother and fetus by measuring partial pressuresin maternal arterial (Pa) and fetal umbilical venous (Puv) blood.Mean induction-delivery interval did not differ between thehalothane (10.8 mm) and isoflurane (11.7 mm) groups. There wereno differences in maternal heart rate, arterial pressure, pHand blood-gas tensions and fetal pH, blood-gas tensions or Apgarscores between the two groups. Isoflurane uptake by the motherwas more rapid than halothane; at delivery, mean Pa of isofluraneas a fraction of the inspired partial pressure (P1) was 0.44compared with 0.35 for halothane (P < 0.05). Mean Puv asa fraction of maternal Pa at delivery was 0.71 for both agents;thus placental transfer was the same for both agents. Consequentlymean Puv/P1 was greater for isoflurane (0.32) than halothane(0.26) (P < 0.05). We conclude that both halothane and isofluraneare suitable agents for general anaesthesia for Caesarean section.The rate of uptake of isoflurane by the mother during Caesareansection was more rapid than halothane. The rate of uptake bythe fetus from the mother was the same for halothane and isoflurane,so that fetal partial pressure as a fraction of the inspiredpartial pressure was greater for isoflurane than halothane.      

Time course of potentiation of mivacurium by halothane and isoflurane in children

We studied 40 children, aged 1-15 yr, to analyse the time course of potentiation of mivacurium produced by halothane and isoflurane. A steady infusion requirement of mivacurium to maintain 90% neuromuscular block was established during thiopentone-alfentanil-nitrous oxide- oxygen anaesthesia. Patients were then allocated randomly to receive 1 MAC end-tidal concentration of either halothane (group Hal) or isoflurane (group Iso) while neuromuscular block was maintained at 90%. Both volatile agents decreased the infusion requirements of mivacurium in an exponential manner in that maximal potentiation occurred only after 30-80 min. Maximal reduction in infusion rate (32% in group Hal and 70% in group Iso; P < 0.0001) did not depend on the age of the child but became established sooner the younger the child in the case of isoflurane (P = 0.002).      

Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children

To determine in adults and children the dose-response relationship and the duration of action of pipecuronium bromide during fentanyl-nitrous oxide (N2O), isoflurane, and halothane anesthesia, the authors studied 30 ASA Physical Status 1-2 adults (age: 16-55 yr) and 30 ASA Physical Status 1-2 children (age: 1.7-11.5 yr) during minor elective surgery. Patients were anesthetized with N2O/O2 (60:40) supplemented with either fentanyl (4 micrograms/kg), or isoflurane (adults, 0.9%; children, 1.2%), or halothane (adults, 0.6%; children, 0.7%). Neuromuscular (NM) blockade was measured by electromyography. Incremental iv doses of pipecuronium were administered to determine the cumulative dose-response relationship of pipecuronium until a 95% twitch depression (ED95) had been obtained. In adults, ED50 was 31.7 +/- 2.9 micrograms/kg (mean +/- SE) during fentanyl-N2O/O2, reduced by isoflurane (18.0 +/- 4.8 micrograms/kg, P less than 0.05) but not by halothane (25.0 +/- 2.6 micrograms/kg, NS). ED95 was 59.4 +/- 5.4 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (42.3 +/- 2.5 micrograms/kg, P less than 0.05), but not by halothane (49.7 +/- 3.1 micrograms/kg, NS). In children, ED50 was 43.9 +/- 4.7 micrograms/kg during fentanyl-N2O/O2, reduced by isoflurane (23.1 +/- 1.6 micrograms/kg, P less than 0.05), and halothane (33.2 +/- 3.2 micrograms/kg, P less than 0.05). ED95 was 79.3 +/- 9.8 micrograms/kg during fentanyl-N2O/O2, and reduced by isoflurane (49.1 +/- 3.1 micrograms/kg, P less than 0.05), but not by halothane (62.5 +/- 7.3 micrograms/kg, NS). Comparison between adults and children reveals no statistically significant differences, except for ED50 during fentanyl-N2O/O2 anesthesia which was increased in children.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Bispectral Index in children: comparing isoflurane and halothane

Background. The Bispectral Index (BIS) has been calibrated forseveral general anaesthetic agents including isoflurane. Halothaneis still used in paediatric anaesthesia. Compared with othervolatile anaesthetics, halothane has a different receptor affinityand differing effects on the EEG. There are limited data evaluatingthe BIS with halothane. We set out to compare the BIS usinghalothane and isoflurane at a clinically relevant equipotentconcentration (1 MAC) and at a reproducible measure of anaestheticeffect (awakening). Methods. Forty children aged between 2 and 15 yr were enrolledin a masked randomized trial—20 in each group. Anaesthesiawas induced with sevoflurane or propofol. Either halothane orisoflurane were given to obtain an end-tidal concentration of1 MAC for 15 min. The BIS was then recorded. The BIS was alsorecorded at awakening. Values (mean (SD)) were compared witha t test. Results. At 1 MAC the BIS for halothane was significantly greaterthan isoflurane (56.5 (8.1) vs 35.9 (8.5), P<0.0001). Atawakening there was no significant difference (BIS halothane;81.1 (11.9), BIS isoflurane; 82.5 (16.4)). The difference inmeans at awakening was 1.4 (95% CI –8.2 to 11.1). Conclusions. At equipotent concentrations of halothane and isofluraneBIS valves were significantly greater with halothane. At awakeningthe BIS values were equivalent for each agent. This findingis consistent with the BIS being more affected by the agentused at higher concentrations of anaesthetic. The BIS must beinterpreted with caution when using halothane. Br J Anaesth 2004; 92: 14–17     

Comparison of inhalation induction with isoflurane or halothane in children

Thirty-six children (mean age 2.4 years) premedicated with oral chloral hydrate 70 mg kg-1 and atropine 0.03 mg kg-1 were anaesthetized with either 3.75% isoflurane or 2.5% halothane in 70% nitrous oxide in oxygen. The eyelash reflex disappeared in 39 +/- 7 s (mean +/- SD) with isoflurane and in 56 +/- 16 s with halothane (P less than 0.001). Tachypnoea was seen with both anaesthetics. Coughing, breath holding, stridorous breathing and respiratory depression were seen during isoflurane but not during halothane induction (P less than 0.01). In nine of 20 children anaesthetized with isoflurane, the ventilation had to be assisted before intubation. Endotracheal intubation was possible in 224 +/- 35 s with isoflurane and in 281 +/- 64 s with halothane (P less than 0.01). Intubating conditions were satisfactory in 80% of the children anaesthetized with either volatile agent. Cardiovascular responses to endotracheal intubation were minimal with both anaesthetics. No cardiac dysrhythmias were noted. Heart rate was higher during isoflurane than during halothane induction. Diastolic arterial pressure was lower during isoflurane than during halothane induction immediately and 5 min after intubation.     

Anaesthesia and the QT intervalEffects of isoflurane and halothane in unpremedicated children

The effects of isoflurane and halothane on the QT interval were investigated during induction of anaesthesia. Fifty-one unpremedicated, ASA grade 1 children were studied. Anaesthesia was induced with either isoflurane ( n  = 25) or halothane ( n  = 26) and was maintained to the end of the study with end-tidal concentrations of between 2.5% and 3%. Recordings of the electrocardiograph, heart rate and systolic arterial pressure were obtained at the following times: before induction of anaesthesia; 1 min and 3 min after stable end-tidal concentrations of anaesthetic agent had been reached; 1 min and 3 min following vecuronium administration; at the time of tracheal intubation and 1 min and 3 min later. Isoflurane significantly prolonged the QT interval (p < 0.001), in contrast to halothane which shortened it (p < 0.01). Heart rate remained largely unchanged during isoflurane anaesthesia but it decreased in the presence of halothane (p < 0.001). In both groups, systolic arterial pressure decreased significantly after induction of anaesthesia (p < 0.001) and remained so to the end of the study. In the isoflurane group, 12 children developed ECG repolarisation abnormalities and in one child an arrhythmia was noticed. In the halothane group, one child developed repolarisation changes while arrhythmias were observed in 10 children. There were no adverse sequelae. It is concluded that halothane may be a better anaesthetic agent than isoflurane for use in children with a prolonged QT interval.     

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia in children

The hemodynamic and cardiovascular effects of isoflurane and halothane anesthesia were studied in 15 unpremedicated ASA I children using measurements of heart rate, blood pressure and M-mode echocardiography (echo). The children (ages 2 to 7.3 yr) were randomly assigned to receive either isoflurane (N = 8) or halothane (N = 7) with oxygen. End-tidal carbon dioxide concentrations (range 30-44 mmHg) were monitored throughout the study in each child. The experimental protocol was completed prior to intubation and the initiation of surgery. Within each anesthetic group, preinduction (control) hemodynamic and echo measurements were compared with measurements obtained at two sequential equipotent end-tidal anesthetic concentrations (0.74% and 2.22% isoflurane; or 0.5% and 1.5% halothane). We also compared the data of the isoflurane group with that of the halothane group at each equipotent end-tidal anesthetic concentration. Preinduction hemodynamic (heart rate, blood pressure) and echo measurements (left ventricular dimensions and function) were similar between the two anesthetic groups. With isoflurane or halothane administration, blood pressure decreased significantly, while heart rate remained essentially unchanged. The observed alterations in heart rate and blood pressure were similar in both study groups at each equipotent end-tidal anesthetic concentration. In contrast, there were marked differences in the echo measurements of the two anesthetic groups. Halothane was associated with a significant dose-dependent decrease in echo-measured left-ventricular shortening fraction and mean velocity of circumferential fiber shortening. These echo measurements were not significantly altered by isoflurane at either end-tidal anesthetic concentration. These alterations suggest halothane is associated with significant myocardial depression in normal children, while myocardial function is well preserved during isoflurane anesthesia.     

Prolonged anaesthesia with isoflurane and halothane

Hepatic function was assessed pre-operatively and on the first and sixth postoperative days in 40 healthy patients who underwent prolonged maxillofacial surgery with isoflurane or halothane anaesthesia. No major changes were observed in hepatic enzymes or bilirubin. One-stage prothrombin time and Factor VII concentrations decreased on the first postoperative day and this change was more pronounced in the halothane group. The results support the use of isoflurane rather than halothane for prolonged anaesthesia in respect of the synthesising function of the liver.     

Cerebrovascular responses to carbon dioxide in children anaesthetized with halothane and isoflurane

To determine the effects of isoflurane and halothane on cerebrovascular reactivity to CO2, 30 children aged one to six years were anaesthetized with isoflurane or halothane in an air and oxygen mixture with an FIO2 of 0.3. The end-tidal concentrations (0.5 minimum alveolar concentration (MAC) or 1.0 MAC) of isoflurane or halothane were age-adjusted. After achieving a steady-state at both 0.5 MAC and 1.0 MAC isoflurane and halothane, the end-tidal carbon dioxide tension (PETCO2) was randomly adjusted to 20, 40, or 60 mmHg. Cerebral blood flow velocity (CBFV) and the cerebrovascular resistance index (RI+) in the middle cerebral artery (MCA) were measured by a transcranial Doppler monitor. Three measurements of CBFV and RI+ were obtained at each PETCO2 and isoflurane or halothane concentration. Any rise in the PETCO2 caused an increase in CBFV during both 0.5 MAC (r2 = 0.99 and 0.99) and 1.0 MAC (r2 = 0.96 and 0.95) isoflurane and halothane anaesthesia, respectively (P less than 0.05). The CBFV for isoflurane increased as PETCO2 increased from 20 to 60 mmHg for both 0.5 MAC and 1.0 MAC (P less than 0.05). The CBFV for halothane increased as PETCO2 increased from 20 to 40 mmHg for both 0.5 MAC and 1.0 MAC halothane (P less than 0.05), but did not change as PETCO2 increased from 40 to 60 mmHg for both 0.5 MAC and 1.0 MAC halothane. The RI+ showed an inverse relationship with CBFV at each PETCO2 for 0.5 MAC (r2 = 0.98 and 0.99) and 1.0 MAC (r2 = 0.76 and 0.53) isoflurane and halothane, respectively (P less than 0.05). The CBFV did not differ significantly between 0.5 and 1.0 MAC isoflurane and halothane at corresponding PETCO2 values. The cerebrovascular response to CO2 at 20 mmHg between 0.5 MAC and 1.0 MAC halothane was not significantly different. These data strongly suggest that isoflurane and halothane in doses up to 1.0 MAC do not affect the cerebrovascular reactivity of the MCA to CO2 in anaesthetized, healthy children.     

The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children

The respiratory effects of halothane, isoflurane and enflurane were assessed during nitrous oxide anaesthesia (N2O 50%) in three groups of unstimulated, spontaneously breathing children who weighed 10-20 kg and were aged 1-6 years. Respiratory variables were measured or calculated from capnographic and pneumotachographic recordings at three multiples of minimal alveolar concentration (MAC). The slope of the carbon dioxide response was measured. Similar increases in end tidal carbon dioxide were found for the three agents at each MAC multiple, and similar decreases in tidal volume and in the slope of the ventilatory response to carbon dioxide. A dose-related tachypnoea occurred with halothane and a significant decrease in the duration of inspiration and the duration of each breath at the deepest level of anaesthesia. A significant increase in both these times occurred with enflurane, and a decrease in respiratory rate. No change in respiratory rate occurred with isoflurane at increasing alveolar concentrations whereas at each level of anaesthesia inspiratory time was significantly reduced.     

The influence of halothane, isoflurane and sevoflurane on rocuronium infusion in children

BACKGROUND: Rocuronium is a non-depolarizing neuromuscular blocking agent with intermediate duration of action and without significant cumulative properties, suitable for continuous infusion. This study was designed to determine the infusion requirements in children under nitrous oxide and fentanyl, halothane, isoflurane or sevoflurane anaesthesia. METHODS: Forty children, 3-11 years old, ASA physical status group I or II were studied. They were randomly allocated to receive fentanyl-nitrous oxide, 1 MAC halothane-nitrous oxide, 1 MAC isoflurane-nitrous oxide or 1 MAC sevoflurane-nitrous oxide anaesthesia. Rocuronium, 0.6 mg(-1) was used to facilitate endotracheal intubation. Electromyographic response of adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using Relaxograph (Datex, Helsinki, Finland). Once the first twitch response (T1) returned to 5%, muscle relaxation was maintained by continuous infusion of rocuronium, adjusted automatically in a closed-loop system to maintain a stable 90-99% T1 depression. The block was considered stable if it changed by no more than 2% over a 10-min observation period. RESULTS: Halothane, isoflurane and sevoflurane groups had ower infusion requirements than the fentanyl-nitrous oxide group (P<0.00075). Rocuronium requirement (mean +/- SD) at one hour from the commencement of anaesthesia was 16.7+/-2.3, 13.6+/-3.7, 13.1+/-5.1 and 8.4+/-1.6 microg x kg(-1) x min(-1) for children receiving fentanyl-nitrous oxide, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: The rocuronium infusion rate required to maintain stable 90-99% T1 depression was reduced by approximately 20% with halothane and isoflurane anaesthesia, and by 50% with evoflurane anaesthesia when compared to fentanyl-nitrous oxide anaesthesia. Significant patient-to-patient variability of infusion rate makes monitoring of neuromuscular transmission necessary.     

Atracurium infusion requirements in children during halothane, isoflurane, and narcotic anesthesia

We were interested in determining the dose-response relationship of atracurium in children (2-10 yr) during nitrous oxide-isoflurane anesthesia (1%) and the atracurium infusion rate required to maintain about 95% neuromuscular blockade during nitrous oxide-halothane (0.8%), nitrous oxide-isoflurane (1%), or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation at the ulnar nerve at 2 Hz for 2 sec at 10-sec intervals. To estimate dose-response relationships, three groups of five children received 80, 100, 150 micrograms/kg atracurium, respectively. During isoflurane anesthesia, the neuromuscular block produced by 80 micrograms/kg was 23.6% +/- 6.5 (mean +/- SEM), by 100 micrograms/kg was 45% +/- 7.2, and by 150 micrograms/kg was 64% +/- 8.7. The ED50 and ED95 (estimated from linear regression plots of log dose vs probit of effect) were 120 micrograms/kg and 280 micrograms/kg, respectively. At equipotent concentrations, halothane and isoflurane augment atracurium neuromuscular block to the same extent, compared to narcotic anesthesia. Atracurium steady-state infusion requirements averaged 6.3 +/- 0.6 micrograms . kg-1 . min-1 during halothane or isoflurane anesthesia; the requirements during balanced anesthesia were 9.3 +/- 0.8 micrograms . kg-1 . min-1 (P less than 0.05). There was no evidence of cumulation during prolonged atracurium infusion.     

Tracheal extubation in children: halothane versus isoflurane, anesthetized versus awake

The authors compared the incidence of respiratory complications and arterial hemoglobin desaturation during emergence from anesthesia in children whose tracheas were extubated while they were anesthetized or after they were awake and to whom halothane or isoflurane had been administered. One hundred children 1-4 yr of age undergoing minor urologic surgery were studied. After a standard induction technique, patients were randomized to receive either isoflurane or halothane. In 50 patients tracheal extubation was performed while they were breathing 2 MAC of either halothane or isoflurane in 100% oxygen. The remaining 50 patients received 2 MAC (volatile agent plus nitrous oxide) during the operation, but tracheal extubation was delayed until they were awake. A blinded observer recorded the incidence of respiratory complications and continuously measured hemoglobin saturation for 15 min after extubation. When tracheal extubation occurred in deeply anesthetized patients, no differences were found between the two volatile agents. When tracheal extubation of awake patients was performed, the use of isoflurane was associated with more episodes of coughing and airway obstruction than was halothane (P less than 0.05). Awake tracheal extubation following either agent was associated with significantly more episodes of hemoglobin desaturation than was tracheal extubation while anesthetized.     

Differential depression of myocardial contractility by halothane and isoflurane in vitro

Depressant effects of halothane and isoflurane on isolated right ventricular guinea pig papillary muscle bathed in Tyrode's solution at 37 degrees C were examined. Contractions were elicited by stimulation through external field electrodes while tension was recorded continuously and the intracellular cardiac action potential (AP) was monitored simultaneously by microelectrodes. The time differential of tension (dT/dt) and of membrane potential (V) was determined electronically and recorded also. Contractions after rest and at stimulation rates of 0.1, 0.25, 0.5, 1, 2, and 3 Hz were studied. With normal APs, isoflurane (1.3 and 2.5%) depressed peak tension significantly less at high frequencies than did equivalent doses of halothane (0.75 or 1.5%). Isoflurane depressed dT/dt max less than halothane at all frequencies. At 0.3 Hz stimulation, isoflurane (1-4%) significantly increased the normal AP duration by 7-11%. Slow calcium-dependent APs and accompanying contractions were studied in partially depolarized muscles (-40 to -45 mV resting potential in 26 mM K+ Tyrode's solution) stimulated with 0.1 microM isoproterenol. Following rest and at 0.1, 0.25, 0.5, 1, 2, and 3 Hz, both isoflurane (1.3% or 2.5%) and enflurane (1.7% or 3.5%) markedly depressed the late-peaking slow AP contraction observed with low-frequency stimulation. Halothane (0.75% or 1.5%) caused a similar contractile depression (40-60%) at all frequencies. In contrast, isoflurane depressed early peaking tension and the dT/dt max at frequencies greater than 1 Hz significantly less than did halothane or enflurane. At 0.3 Hz, 2% and 4% isoflurane caused 9% and 17% depression of slow AP maximum rate of depolarization (Vmax), but significantly prolonged the AP duration. Isoflurane altered the pattern of tension development in a different manner than halothane, suggesting differing mechanisms of myocardial depression by these anesthetics.     

Haemodynamic effects of atropine during halothane or isoflurane anaesthesia in infants and small children

In this study, two-dimensional and pulsed Doppler echocardiography were used to measure cardiovascular changes before and after IV atropine in 31 infants and small children during halothane (n = 15) or isoflurane (n = 16) anaesthesia. Prior to induction of anaesthesia heart rate (HR), mean blood pressure (MBP), and two0dimensional echocardiographic dimensions of the left ventricle and pulmonary artery bloodflow velocity were measured by pulsed Doppler echocardiography. Cardiovascular measurements were repeated while anaesthesia was maintained at 1.5 MAC halothane (n = 15) or isoflurane (n = 16). Atropine 0.02 mg·kg⁻¹ IV was then administered and two minutes later, a third set of cardiovascular data was obtained. Heart rate decreased during halothane anaesthesia but did not change significantly during isoflurane anaesthesia. Mean blood pressure, cardiac output (CO) and stroke volume (SV) decreased similarly during 1.5 MAC halothane or isoflurane anaesthesia. Ejection fraction (EF) decreased and left ventricular end-diastolic volume (LVEDV) increased significantly in bothgroups, but decreases in EF (32 ± 5 percentvs18 ± 5 per cent) and increases in LVEDV (18 ± 7 per cent vs7 ± 5 per cent) were significantly greater during halothane than during isoflurane anaesthesia. Following atropine, HR increased more in the patients maintained with halothane (31 ± 6 per cent), than during isoflurane anaesthesia (18 ± 5 per cent). Atropine increased CO in both groups of patients, but SV and EF remained unchanged. When compared with awake values, HR increased similarly and significantly (18 ± 4 per cent) following atropine in both groups, and CO returned to control levels. Halothane decreased EF and increased LVEDV more than isoflurane at 1.5 MAC end— expired anaesthetic levels. Atropine did not diminish the myocardial depression produced by halothane or isoflurane. The increase in CO following atropine during halothane and isoflurane anaesthesia in infants and small children is the result of increases in HR alone. Nous avons utilisé un appareil à échocardiographie bi-dimensionnelle couplé à un Doppler pulsé chez des bébés et de jeunes enfants pour évaluer l’impact hémodynamique de l’halothane (n = 15) et de l’isoflurane (n = 16) et la modification possible de ces effets par l’atropine. Nous avons mesure la frequence cardiaque (FC), la pression artérielle moyenne (PAM), la dimension de la cavité ventriculaire gauche (par écho bi-dimensionnelle) et la vélocité du flot sanguin pulmonaire (par Doppler) et ce, en trois occasions soit avant l’induction, après l’instauration de 1.5 MAC d’halothane ou d’isoflurane et finalement, deux minutes après l’injection IV de 0.02 mg·kg⁻¹ d’atropine. On ne nota une baisse de la frequence cardiaque qu’avec l’halothane tandis que la PAM, le débit cardiaque (DC) et le volume d’éjection (VE) diminuaient autant avec l’un ou l’autre anesthésique. La diminution de la fraction d’éjection (FE) et l’augmentation du volume télédiastolique du ventricule gauche (VTDVG) significatives pour les deux groupes, étaienl plus marqué avec l’halothane qu’avec l’isoflurane: FE 32 ± 5 pour cent vs18 ±5 pour cent; VTDVG 18 ± 7 pour cent vs 7 ± 5 pour cent. Avec l’atropine, la FC monta plus dans le groupe halothane (31 ± 6 pour cent) que dans le groupe isoflurane (18 ± 5 pour cent), le DC augmentant dans les deux groupes, alors que le VE et la FE demeuraient inchangés. Comparée aux mesures pré-induction, l’atropine amenait une hausse significative de la FC, semblable dans les deux groupes (18 ± 4 pour cent) et restaurait le DC. Donc, chez les bebes et les jeunes enfants, a 1.5 MAC, l’halothane diminue la FE et augmente le VTDVG plus que ne le fait l’isoflurane. L’atropine ne modifie pas la depression myocardique et elle ne restaure le DC que par une hausse de la FC.

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Supported by PHS Grant No. 8507300 from the College of Medicine, University of Iowa Hospital, Iowa City, IA.