A comparison of the area of histochemical dysfunction after focal cerebral ischaemia during anaesthesia with isoflurane and halothane in the rat

The investigations that have thus far evaluated the cerebral protective properties of isoflurane have provided conflicting results. Protection would be most likely to occur in the circumstances of incomplete cerebral ischaemia in which there is a penumbral zone of marginal perfusion. The present investigation sought to evaluate further the protective properties of isoflurane in that circumstance. Middle cerebral artery occlusion (MCAO) was performed in Sprague-Dawley rats anaesthetized with 1.2 MAC concentrations of either halothane or isoflurane. At the end of four hours of MCAO, the brains were removed, sectioned and incubated in the histochemical stain 2-3-triphenyltetrazolium (TTC). An image analysis system was used to measure the area of reduced or absent TTC staining in four coronal planes spanning the distribution of the middle cerebral artery. There was no difference between halothane and isoflurane anaesthetized animals with respect to the area of brain with evidence of histochemical dysfunction. It is concluded that isoflurane is not protective (relative to the status of halothane anaesthetized control animals) when administered at 1.2 MAC concentration during four hours of focal (incomplete) cerebral ischaemia in the rat.     

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.     

A clinical assessment of desflurane anaesthesia and comparison with isoflurane

In 48 randomly assigned ASA I adult patients undergoing elective orthopaedic procedures, we compared the pharmacodynamics of desflurane (DF) and isoflurane (IF), and their pharmacokinetics during rapid induction of deep anaesthesia (via face mask, to 1.5–2 MAC, after thiopentone), maintenance of anaesthesia at 1.25 MAC, and emergence therefrom. During induction, laryngeal reactions ranging from mild crowing to laryngospasm occurred more frequently with DF than with IF (15/24 DF, 5/24 IF; P < 0.05) and was more severe (9/ 24 DF, 1/24 IF, excluding the mildest form, P < 0.05). As a result, induction of anaesthesia was not accomplished faster with DF, in spite of a faster equilibration between exhaled and inhaled concentrations. Emergence from DF was more rapid and less complicated by delirium. Pharmacokinetically, the exhaled concentration of DF reached 90% of the inhaled concentration within five minutes of induction, whereas that of IF lagged behind and remained 25% below the inhaled concentration (1 vs 1.34 ± 0.05) even one hour after induction. Premature ventricular contractions did not occur in any patient even during periods of difficulty with the airway and oxygen desaturation. It is concluded that DF is a safe anaesthetic, pharmacokinetically superior to IF but clinically inferior for induction of anaesthesia via a face mask. Because of the fast equilibration, the exhaled concentration of DF can be controlled more precisely by the dial setting of the vaporiser.     

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg⁻¹ po and an inhalational induction with up to 3 MAC of either agent in 70% N₂O and O₂. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg⁻¹) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T₁ > 95%, T₄/T₁ > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. L’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg⁻¹ et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N₂O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg⁻¹). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T₁ > 95%, T₄/T₁ > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

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Supported in part by a grant from Abbott Laboratories, Chicago, Illinois.     

Airway irritation produced by volatile anaesthetics during brief inhalation: comparison of halothane,enflurane, isoflurane and sevoflurane

Eleven male volunteers were studied to compare the airway irritation produced by the four anaesthetic agents: halothane, enflurane, isoflurane and sevoflurane at two concentrations, equivalent to one and two MAC. Tidal volume, respiratory frequency and functional residual capacity changes induced by 15 sec inhalation of the anaesthetics were measured using respiratory inductive plethysmograph. Appearance of the cough reflex was also observed. The order of subjective airway irritation was evaluated by the volunteers. Inhalation of the anaesthetic agents induced a decrease in tidal volume, increase in respiratory frequency and decrease in functional residual capacity. Significant changes were considered to have occurred if tidal volume and respiratory frequency changed by more than 30% from the resting values for at least ten seconds, or if functional residual capacity changed by more than 30% of the value at resting tidal volume, for at least ten seconds. Each change was induced most frequently by isoflurane followed by enflurane, halothane and, least frequently, by sevoflurane. The orders of appearance of the cough reflex and of subjective airway irritation were similar. Sevoflurane did not elicit a cough reflex. It is concluded that sevoflurane was the least irritant anaesthetic and is considered to be the most suitable for inhalational induction of anaesthesia. Sept volontaires du sexe masculin font partie dune étude visant à comparer les ejfets irritants de quatre agents anesthésiques sur les voies respiratoires: l’halothane, l’enflurane, l’ isoflurane et le sévoflurane, à deux concentration qui équivalent soit à MAC 1, soit à MAC 2. On mesure les changements de volume courant, de fréquence respiratoire et de capacité résiduelle fonctionnelle à l’aide d’un pléthysmographie à induction. On note l’apparition du réflexe de toux. De plus, on évalue le degré subjectif d’irritation éprouvé par les sujets. L’inhalation d’agents anesthésiques cause une baisse du volume courant, une augmentation de la fréquence respiratoire et une diminution de la capacité résiduelle fonctionnelle. On considère significatifs les changements de volume courant et de fréquence respiratoire de plus de 30% des valeurs de repos pour au moins dix secondes, les changements de capacité résiduelle fonctionnelle de plus de 30% de sa valeur au volume courant de repos pour au moins dix secondes. Les changements sont initiés principalement par l’isoflurane, suivi par l’enflurane, l’halothane et moins fréquemment par le sévoflurane. L’ordre d’apparition du réflexe de toux et de l’impression subjective d’irritation des voies aériennes est identique. Le sévoflurane ne provoque pas de réflexe de toux. On conclut que le sévoflurane est le moins irritant des anesthesiques et qu’on peut le considerer comme celui qui convient le mieux à l’induction de l’anesthésie par inhalation.     

The microcirculation during enflurane and isoflurane anaesthesia in dogs

The effects of enflurane and isoflurane of 0.75 and 1.5 MAC on capillary blood flow were studied by the microsphere (9 ± 1 μm in diameter) method in two groups of seven dogs. Simultaneously, changes in the arteriolo-venular shunt were studied by collection of venous blood at a rate of 4.8 ml · min^?1 for two minutes. Enflurane anaesthesia at 0.75 MAC decreased capillary blood flow in the thyroid glands (35% of control), left and right ventricular wall (59% and 50%), adrenal gland (59%), liver (63%), spleen (56%), pancreas (35%), omentum (20%), and small intestine (60%) and at 1.5 MAC it decreased further in the thyroid glands (15%), left and right ventricular wall (31% and 32%), adrenal gland (42%), liver (47%), spleen (31%), pancreas (23%), omentum (20%), stomach (45%), and small intestine (54%). No marked changes were noted in the brain, kidney, large intestine or skeletal muscle. The arteriolo-venular shunt was decreased in the kidney from an initial rate of 12.1 to 3.8% at 0.75 MAC and to 2.5% at 1.5 MAC enflurane. In contrast, during isoflurane anaesthesia, capillary blood flow remained unchanged, except for a decrease to the thyroid glands (43%) and right ventricular wall (74%) during 1.5 MAC anaesthesia. However, the arteriolo-venular shunt was increased in the brain from 12.0 to 29.7% and 33.0% during 0.75 and 1.5 MAC isoflurane anaesthesia, respectively. It also increased from 25.0 to 41.0% and 46.3% in the skeletal muscle, and from 8.9 to 19.9% and 17.4% in the whole systemic circulation. These data indicate that capillary blood flow is better preserved during isoflurane than during enflurane anaesthesia, but is associated with increased arteriolo-venular shunting.     

A comparison of the cerebral pressure-flow relationship for halothane and isoflurane at haemodynamically equivalent end-tidal concentrations in the rabbit

The cerebral pressure-flow relationship for halothane and isoflurance was studied at end-tidal concentrations which resulted in similar baseline mean arterial pressure (MAP). Two groups of New Zealand white rabbits (n = 8; each group) were studied with five regional blood flow determinations in each animal. Blood flow was determined by injecting radioactive microspheres during the following conditions: injection 1: after stable 2.05 per cent end-tidal isoflurane (1.0 MAC) Group I; or after stable 0.74 +/- 0.04 per cent end-tidal halothane (0.53 MAC) Group H. Injections 2-5: after MAP was increased 20, 40, 60, and 80 per cent respectively above baseline MAP by phenylephrine infusion. Baseline MAP was the same for both groups (64.3 +/- 3.1 vs 67.2 +/- 2.0 mmHg; mean +/- SEM; Group I and H respectively). Baseline total CBF (tCBF; 0.68 +/- 0.03 vs 0.86 +/- 0.05) and hemispheric CBF (hCBF; 0.64 +/- 0.03 vs 0.96 +/- 0.06) were significantly greater in Group H; no significant difference between groups was seen for baseline posterior fossa CBF (pCBF; 0.79 +/- 0.06 vs 0.75 +/- 0.04). For each experiment a pressure-flow curve was generated by curvilinear regression analysis. Significantly greater phenylephrine concentrations were required for injections 2-5 in Group H. Mean slopes and intercepts were derived for each group. Within each group comparison of the pressure-flow curves for hCBF vs MAP and pCBF vs MAP showed autoregulation was less impaired in posterior fossa structures (cerebellum and brain stem) for both anaesthetic agents (P less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of sevoflurane with halothane,enflurane, and isoflurane on bronchoconstriction caused by histamine

This study was conducted to assess the effect of sevoflurane on lung resistance and compliance, and its responsiveness to histamine. We studied eight dogs to compare the effect of sevoflurane, isoflurane, enflurane, and halothane on bronchoconstriction caused by histamine. Baseline values of pulmonary resistance (R_L) and dynamic pulmonary compliance (C_dyn) were measured prior to administration of histamine. Histamine (2, 4, and 8 μg · kg⁻¹) were administered iv, and the values of R_L and C_dyn at the time of peak effect were recorded. Under 1 or 2 MAC anaesthesia, sevoflurane as well as the other three anaesthetics had no bronchoactive effects. The four anaesthetics, including sevoflurane, demonstrated inhibitory effect on increases in R_L and decreases in C_dyn caused by histamine. At 1 MAC anaesthesia, % changes in R_L caused by 2, 4, or 8 μg · kg⁻¹ of histamine were 38 ± 11, 85 ± 21, or 132 ± 24% (mean ± SE) for halothane, and 65 ± 11, 132 ± 15, or 172 ± 19% for sevoflurane, respectively. Sevoflurane was less effective than halothane in preventing increases in R_L. In preventing decreases in C_dyn, sevoflurane was less effective than halothane only at 8 μg · kg⁻¹ of histamine under 1 and 2 MAC anaesthesia. There was no difference in attenuating effect on changes in R_L and C_dyn between sevoflurane and isoflurane or enflurane. We concluded that sevoflurane was less potent than halothane in attenuating changes in R_L and C_dyn in response to iv histamine. Cette étude a été réalisée dans le but d’évaluer les effets du sévoflurane sur la résistance et la compliance pulmonaires en réponse à l’histamine. Les effets du sévoflurane, de l’isoflurane, de l’enflurane et de l’halothane sur la bronchoconstriction induite par l’histamine sont comparés sur huit chiens. Avant l’administration d’histamine, on mesure les valeurs initiales de la résistance (R_L) et de la compliance dynamique (C_dyn) pulmonaires. L’histamine (2, 4, 8 μg · kg⁻¹) est administrée par la voie veineuse et les valeurs maximales de la R_L et de la C_dyn sont enregistrées. Les quatre anesthésiques, dont le sévoflurane inhibent l’augmentation de la R_L et la diminution de la C_dyn provoquées par l’histamine. A MAC 1 d’anesthésie, les pourcentages de changement de R_L produits par 2, 4, ou 8 μg · kg⁻¹ d’histamine sont respectivement de 38 ± 11, 85 ± 21, ou 132 ± 24% (moyenne + SD) pour l’halothane, et de 65 ± 11, 132 ± 15, ou 172 ± 19% pour le sévoflurane. Le sévoflurane est moins efficace que l’halothane pour prévenir les augmentations de R_L. Le sévoflurane est moins efficace pour prevenir la diminution de C_dyn mais seulement à 8 μg · kg⁻¹ d’histamine sous anesthésie à MAC 1 et 2. Le sévoflurane, l’halothane et l’isoflurane ne sont pas de différents pour amortir les changements de R_L et C_dyn. Nous concluons que le sévoflurane est moins puissant que l’halothane pour diminuer la réponse à l’histamine de la R_L et de la C_dyn.     

Chest wall motion during halothane anaesthesia in infants and young children

Chest wall motion during anaesthesia may differ from the awake state because of the effect of anaesthetic agents on the muscles of respiration. The purpose of this study was twofold (1) to describe the pattern of chest wall motion in infants and children during halothane anaesthesia (HA) using respiratory inductive plethysmography (RIP) and (2) to calibrate the voltage output of RIP in units of volume. Seven infants (2.3 +/- 1.7 mo, 5.9 +/- 0.7 kg) and five children (2.9 +/- 1.1 yr, 15.5 +/- 1.5 kg) were studied. Since results in both age groups were qualitatively similar they are presented as a single group. Respiratory excursions of the rib cage (RC) and abdomen (ABD) were measured using RIP. Airflow was measured with a pneumotachograph. During spontaneous breathing the analogue signals of airflow, pressure, RC and ABD were recorded. Measurements were taken during (1) halothane anaesthesia and (2) during emergence from anaesthesia. The XY plots of the RC and ABD signals were plotted for each period. In addition the voltage output of the respiratory excursions of the RC and ABD signals was converted to units of volume using the simultaneous solution of equation method. The accuracy of conversion factors was validated by regression analysis of the predicted and measured tidal volume using breaths sampled at random throughout the entire period of study. Regression analysis of this relationship gave a slope between 0.85 and 1.15 (r2 value greater than 0.7) in five of the twelve patients. The pattern of chest wall motion in the XY plots showed synchronous motion between RC and ABD signals during HA in nine of the twelve patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Uterine and umbilical blood flow velocity during epidural anaesthesia for Caesarean section

The purpose of this study was to use colour Doppler to determine the effect of epidural anaesthesia on the uterine and umbilical blood flow velocities. After determining the precision of the technique, Doppler insonation of the uterine and umbilical arteries was performed in consenting non-labouring patients requesting epidural anaesthesia for Caesarean section. Patients in Group I were normal and those in Group II were at high risk for uteroplacental blood flow abnormalities. The pulsatility indexes (PI) of both uterine and umbilical arteries were compared at the following times: control, after fluid and after anaesthesia using repeated measure analysis of variance. In Group I (n = 30) the PI increased from 0.72 to 0.82 in the left uterine artery and from 0.71 to 0.85 in the right uterine artery (P < 0.05). In Group II (n = 10) the PI increased from 0.67 to 0.85 in the left uterine artery (NS) and from 0.98 to 1.38 in the right uterine artery (P < 0.05). There was no change in the PI in the umbilical artery. We conclude that the PI of the uterine arteries increases after epidural anaesthesia with lidocaine, epinephrine and fentanyl but there is no change in the umbilical PI. While these changes do not appear to be clinically important in the low-risk population, further studies are required to determine the impact on fetuses at high risk for in utero hypoxaemia.     

Mechanisms of inhibition of endothelium-dependent relaxation by halothane,isoflurane, and sevoflurane

Volatile anaesthetics inhibit endothelium-dependent relaxation, but the underlying mechanism(s) have not been clarified. In an attempt to elucidate the mechanism(s), we determined the effects of halothane, isoflurane and sevoflurane on relaxation induced by acetylcholine and sodium nitro-prusside (SNP) and the cGMP formation elicited by exogenous nitric oxide (NO) and SNP in rat aortas. Acetylcholine (10^?7?10^?5M) - induced relaxation was attenuated by halothane (2%), isoflurane (2%) and sevoflurane (4%). SNP (10^?8 M) - induced relaxation was reduced by halothane (2%), but not by isoflurane (2%) or sevoflurane (4%). The cGMP level of NO-stimulated aorta was reduced by halothane (2%) and sevoflurane (4%), but not by isoflurane (2%). The cGMP level of SNP (10^?7 M) - stimulated aorta was reduced by halothane (2%), but not by isoflurane (2%) and sevoflurane (4%). We conclude that the mechanisms responsible for the inhibition of endothelium-dependent relaxation differ among anaesthetics. Isoflurane inhibits the relaxation mainly by inhibiting the formation of NO in the endothelium. In contrast, the effect of halothane on endotheliumdependent relaxation may be largely due to the inhibition of action of NO in the vascular smooth muscle and the effect of sevoflurane may be to inactivate NO or to inhibit the action of NO.     

Comparison of the direct effects of sevoflurane,isoflurane and halothane on isolated canine coronary arteries

We have demonstrated previously, using dog epicardial arteries of different sizes, that isoflurane, like adenosine, is preferentially a small coronary artery dilator, whereas halothane, like nitroglycerin, is a large artery dilator. The present study was designed to compare the direct effects of sevoflurane with those of isoflurane and halothane. Proximal large coronary arteries with an outer diameter (o.d.) of 2.5–3.2 mm and distal small arteries of 0.6–0.9 mm o.d. were isolated from dogs and then cut into vascular rings. They were precontracted with KCl (20 mM), and their relaxant responses to anaesthetics were compared relative to the maximal responses induced by papaverine. Sevoflurane, halothane and isoflurane (1–3 human MAC) induced dose-dependent relaxation of these arteries. The relaxant response to sevoflurane did not differ between large and small arteries. However, the relaxant response of the large arteries to halothane (1.5–2.3%) was greater than that of small arteries (P < 0.01) and the response of small arteries to isoflurane (3.5%) was greater than that of large arteries (P < 0.05). In large arteries, the potency of the relaxant effect at equivalent human MAC could be ranked as halothane ≥ sevoflurane > isoflurane, and, in small epicardial arteries as isoflurane > sevoflurane ≫ halothane. We conclude that, unlike isoflurane, sevoflurane is not a preferential dilator of small coronary arteries. Nous avons déjà démontré sur des artères canines épicardiques de différents calibres, que l’isoflurane, comme l’adénosine est un dilatateur préférentiel des petites artères coronaires, alors que l’halothane, comme la nitroglycérine, est un dilatateur des grosses artères. L’étude présente vise à comparer les effets directs du sévoflurane avec ceux de l’isoflurane et de l’halothane. Chez le chien, on isole et sectionne en anneaux de grosses artères coronaires d’un diamètre externe de 2,5 à 3,2 mm et des petites artères coronaires distales de 0,6 à 0,9 mm. Elles sont préalablement contractées avec du KCl (20 mM) et leurs propriétés relaxantes en présence d’anesthésiques sont comparées à la réponse maximale provoquée par la papavérine. Il n’y a pas de différence entre le sévoflurane, l’halothane et l’isoflurane (MAC 1–3 humain); ils provoquent tous une relaxation artérielle qui dépend de la dose. L’effet relaxant du sévoflurane est identique que ce soit sur les grosses ou les petites artères. Cependant, la relaxation des grosses artères en réponse à l’halothane (1,5–2,3%) est plus importante que celle des petites artères (P < 0,01) et la réponse des petites artères à l’isoflurane (3,5%) est plus marquée que celle des grosses artères (P < 0,05). Pour les grosses artères, la puissance de l’effet relaxant à un MAC humain équivalent pourrait être classifiée dans l’ordre: halothane ≥ sévoflurane > isoflurane; et sur les petites artères épicardiques ainsi: isoflurane > sévoflurane ≫ halothane. Nous concluons que contrairement à l’isoflurane, le sévoflurane n’est pas un dilatateur préférentiel des petites artères coronaires.     

Epidural anaesthesia and blood flow velocity in mother and fetus

Doppler ultrasound has recently been used to assess changes in blood velocity in the uterine and umbilical arteries. Alterations in the ratio of systolic to diastolic velocity (S/D ratio) are believed to reflect changes in placental vascular resistance. We have used this technique to assess potential beneficial or detrimental effects of epidural anaesthesia on blood flow to the placenta. Continuous wave Doppler ultrasound was used to measure the S/D ratio in the uterine and umbilical arteries of 12 patients undergoing epidural anaesthesia prior to elective caesarean section. Anaesthesia was achieved using lidocaine and epinephrine. The S/D ratio in both the uterine and umbilical arteries remained unaltered either by the fluid preload or by the epidural anaesthesia. It is concluded that epidural anaesthesia using this technique has neither a beneficial nor detrimental effect on uterine or umbilical blood velocity in the uncomplicated pregnancy.     

Preservation of renal blood flow during hypotension induced with fenoldopam in dogs

The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine-1, (DA1) and dopamine-2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 +/- 8 per cent from control with infusion of fenoldopam (3.4 +/- 2.0 micrograms.kg-1.min-1) and 34 +/- 4 per cent with infusion of sodium nitroprusside (5.9 micrograms.kg-1.min-1) (NS). Renal blood flow (RBF) increased during fenoldopam-induced hypotension 11 +/- 7 per cent and decreased 21 +/- 8 per cent during sodium nitroprusside-induced hypotension (P less than 0.01). Sodium nitroprusside is a non-selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine-1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension.     

Induction reflex actions with intravenous nalbuphine as an adjunct to isoflurane

Ninety unpremedicated patients undergoing mask anaesthesia were assigned to one of three groups according to the volatile anaesthetic and the acute intravenous premedication administered. Group I received saline placebo as premedication and halothane by inhalation. Group II received saline placebo and isoflurane by inhalation. Group III received nalbuphine 0.1 mg.kg-1 IV as premedication and isoflurance by inhalation. Mean time to loss of consciousness (71 sec) did not differ among groups. The dosage of thiopentone required to induce loss of consciousness was decreased by 15 per cent (from 3.9 to 3.3 mg.kg-1) by nalbuphine premedication (P less than 0.05), and time to induction of surgical anaesthesia using isoflurane was decreased by 15 per cent (P less than 0.05). The incidence of reflex actions (coughing, laryngospasm, breath holding, hiccoughs and movement) during induction was no different in the saline-premedicated halothane or isoflurane groups. Acute intravenous nalbuphine premedication decreased significantly the incidence of reflex actions during induction of isoflurane anaesthesia from 77 per cent to 37 per cent (P less than 0.02). Desaturation episodes (SaO2 less than 90 per cent) were more frequent with isoflurane inductions compared with halothane (55 per cent vs 17 per cent, P less than 0.01). Apnoeic episodes accounted for the majority of desaturations associated with nalbuphine premedication, while excitatory reflexes (coughing and laryngospasm) accounted for more desaturations with isoflurane alone.     

Anaesthesia by intravenous emulsified isoflurane in mice

An emulsion of isoflurane in Intralipid™ for intravenous (iv) injection was formulated and its anaesthetic properties determined in mice. The major advantage of iv delivery of volatile agents is to accelerate the induction of anaesthesia by circumventing the anaesthetic circuitry and the lung’s functional residual capacity. Isoflurane was added to Intralipid™ in varying concentrations. The ED₅₀ (n = 34) and LD₅₀ (n = 20) were determined by a single iv bolus injection. Anaesthesia was also induced and maintained for 30 min (n = 5) by continuous infusion and the time to emergence was measured. The ED₅₀ and LD₅₀ were 0.7 ± 0.2 μl and 2.4 ± 0.2 μl of isoflurane equivalent respectively. An average infusion rate of 1.6 ± 0.4 μl · min⁻¹ of isoflurane equivalent was required for maintenance following which the average emergence time was 193 ± 35 secs. The only negative effect was local skin ulceration with an inadvertent interstitial injection. We conclude that iv induction and maintenance with emulsified isoflurane in Intralipid™ can be carried out with safety and reproducibility in the mouse. Further larger animal studies are warranted assessing the haemodynamic, toxicological, physiochemical and pharmacokinetic characteristics of these and other similar preparations. Une émulsion d’isoflurane dans l’Intralipid™ pour injection intraveineuse est préparée et ses propriétés anesthésiques sont déterminées chez la souris. L’avantage principal de l’administration iv d’agents volatils est d’accélérer la vitesse d’induction de l’anesthésie en court-circuitant le circuit anesthésique et la capacité résiduelle fonctionnelle pulmonaire. De l’isoflurane est ajouté à l’Intralipid™ en variant les concentrations. L’ED₅₀ (n = 34) et la LD₅₀ (n = 20) sont déterminées pour une injection unique en bolus. De plus, l’anesthésie est induite et entretenue pendant 30 min (n = 5) par perfusion continue et le temps de récupération mesuré. L’ED₅₀ et la LD₅₀ sont respectivement de 0,7 ± 0,2 μl et de 2,4 ± 0,2 μl d’équivalent isoflurane. En moyenne, une vitesse de perfusion de 1,6 ± 0,4 μl · min⁻¹ est nécessaire pour l’entretien; par la suite, le temps moyen de récupération est de 193 ± 35 sec. Le seul effet négatif consiste en une ulcération locale au site d’une injection interstitielle accidentelle. Nous concluons que l’induction et l’entretien iv avec une émulsion d’isoflurane dans l’Intralipid™ peuventêtre réalisés avec sécurité et reproducibilité chez la souris. Des études ultérieures chez des animaux plus gros sont justifiées pour évaluer les caractéristiques hémodynamiques, toxicologiques, physicochimiques et pharmacocinétiques de ce type de préparation.

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This study was performed at the Department of Pharmacology at The University of British Columbia and presented at the Resident’s competition at the Canadian Anaesthestists’ Society annual meeting in Halifax, Nova Scotia, June 1993.     

Metabolism of desflurane and isoflurane to fluoride ion in surgical patients

The metabolism of isoflurane and the investigational volatile anaesthetic desflurane to fluoride ion was examined in 25 surgical patients. The patients were randomly assigned to four groups, to receive isoflurane or desflurane at either 0.65 MAC or 1.25 MAC. Anaesthesia was induced in all patients with thiopentone and midazolam and included nitrous oxide 60% in addition to the volatile agent. Blood was drawn before induction and at the end of the operation for determination of serum fluoride ion concentration. Plasma fluoride ion concentrations increased (+ 1.36 +/- 0.93 microM, P less than 0.01) in patients receiving isoflurane but were unchanged (-0.13 +/- 0.50 microM) in patients receiving desflurane. Metabolic release of fluoride ion is less with desflurane than with isoflurane during administration of the anaesthetics to surgical patients, and is unlikely to be of clinical significance.     

Propofol anaesthesia in paediatric ambulatory patients: a comparison with thiopentone and halothane

The purpose of this study was to evaluate the haemodynamic changes during induction, as well as the speed and quality of recovery when propofol (vs thiopentone and/or halothane) was used for induction and maintenance of anaesthesia in paediatric outpatients. One hundred unmedicated children, 3–12-yr-old, scheduled for ambulatory surgery were studied. The most common surgical procedures performed were eye muscle surgery (42%), plastic surgery (21%), dental restoration (15%), and urological procedures (15%). The children were randomized to an anaesthetic regimen for induction/maintenance as follows: propofol/propofol infusion; propofol/halothane; thiopentone/halothane; halothane for both induction and maintenance. Succinylcholine 1.5 mg · kg^?1 was used to facilitate tracheal intubation and N₂O/O₂ were used as the carrier gases in each case. All maintenance drugs were titrated according to the clinical response of the patient to prevent movement and/or maintain BP ± 20% of baseline. Two patients (4%) who received propofol expressed discomfort during injection. The mean propofol dose required to prevent movement was 267 ± 83 μg · kg^?1 · min^?1. The overall pattern of haemodynamic changes, as well as awakening (extubation) times were not different among the four groups. Children who received propofol recovered faster (22 vs 29–36 min) (P < 0.05), were discharged home sooner (101 vs 127–144 min) (P < 0.05), and had less postoperative vomiting (4 vs 24–48%) (P < 0.05) than all others. There were no serious complications or adverse postoperative sequelae in any of the patients in the study. It is concluded that induction and maintenance of anaesthesia with propofol is a well-tolerated anaesthetic technique in children, and is associated with faster recovery and discharged as well as less vomiting than when halothane is used.     

Regional differences in skin blood flow and temperature during total spinal anaesthesia

Three patients were studied to determine the changes in regional skin temperature and blood flow during extensive sympathetic blockade following total spinal anaesthesia (TSA). Skin temperature was measured at the right upper arm, the right anterior chest at the nipple level, the right hand and the foot, using infrared thermography. Skin blood flow of the right upper arm (C6 area) was measured with a laser Doppler flowmeter. The temperature of the truncal area, arm and leg decreased by 1 degree C following TSA, whereas the temperature of the hand and foot increased by 3 degrees C. The mean blood flow in three patients decreased to 26.1, 61.4, 51.7% of the control values 15 min after TSA. Our results indicate that extensive sympathetic nervous blockade during total spinal anaesthesia induces regional different changes in skin temperature and decrease in truncal skin blood flow.