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.     

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.     

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.     

Sepsis reduces isoflurane MAC in a normotensive animal model of sepsis

Patients with sepsis often require anaesthesia for surgical procedures. Anaesthesia can be unpredictable and the most haemodynamically stable agents are used. No data are available for the minimum alveolar concentration (MAC) requirements in such patients or in animal models of sepsis. We have characterized the effect of sepsis on the MAC of isoflurane in a normotensive rodent model of sepsis. The minimum inhibitory concentration (MIC) of isoflurane to an identical stimulus was determined for rodents subjected to caecal ligation and perforation (CLP n = 8), or sham laparotomy (n = 7). The calculated MAC of isoflurane was reduced in the septic animals compared with the sham animals (MAC of isoflurane, CLP = 0.8% sham = 1.4% P < 0.003). No statistical differences were found in the haemodynamic variables measured in either group. Isoflurane leads to haemodynamic stability during anaesthesia in this animal model of sepsis. However, the MAC requirement for isoflurane is reduced by sepsis. En cas de sepsis, il faut souvent recourir à la chirurgie. Les répercussions anesthésiques sont imprévisibles et il faut utiliser des agents qui assurent la meilleure stabilité hémodynamique possible. Nous ne possédons pas de données sur la concentration alvéolaire minimale (MAC) requise chez le patients septique ou sur un modèle animal. Nous avons déterminé l’influence du sepsis sur le MAC de l’isoflurane sur un modèle de rongeur normotensif. La concentration inhibitrice minimale (MIC) de l’isoflurane à un stimulus identique a été déterminée chez des rongeurs soumis à une ligature et une perforation du caecum (CLP n = 8), ou une laparotomie factice (n = 7). Le MAC calculé de l’isoflurane diminuait chez les animaux septiques comparativement au groupe factice (MAC de l’isoflurane, CLP = 0,8%, factice = 1,4% P< 0,003). Nous n’avons pas trouvé de différence statistique pour les variables hémodynamiques entrer le deux groupes. L’isoflurane procure la stabilité hémodynamique sur ce modèle animal de sepsis. Cependant le MAC de l’isoflurane est abaissé.     

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.     

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.     

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.     

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.     

Safety and efficacy of alfentanil and halothane in paediatric surgical patients

Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the phannacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2–12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group I (n = 19), after halothane was discontinued, alfentanil 50 μg · kg^?1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothane was maintained at 0.5% and alfentanil 25 μg · kg^?1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 μg · kg^?1 was infused. In Group4(n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 μg · kg^?1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4. The four groups were similar in postoperative narcotic analgesic administration and incidence of vomiting. In summary, alfentanil (12.5–50.0 μg · kg^?1) was a safe anaesthetic, whether combined with nitrous oxide alone or with nitrous oxide and halothane.     

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)     

Noninvasive ICG clearance test for estimating hepatic blood flow during halothane and isoflurane anaesthesia

The purpose of this study was to estimate hepatic blood flow during halothane (HAL) or isoflurane (ISO) anaesthesia with the noninvasive indocyanine green (ICG) clearance test. Twenty-four ASA status I adult patients, scheduled for elective surgery without liver disease, were allocated into four groups. Before surgery, ICG clearance was measured twice in patients before and after 1, 2 MAC HAL-N₂O, 1 and 2 MAC ISO-N₂O anaesthesia by ICG clearance meter (Sumitomo Electron-ics™, Japan). This method eliminates the blood sampling and delay of the conventional ICG test. The ICG clearance is displayed in two indices: K (ICG disappearance rate) and R₁₅ (ICG retention rate 15 min after 0.5 mg · kg⁻¹ ICG injection). Indirect blood pressure and heart rate were measured simultaneously. Mean arterial pressure (MAP) decreased by 27, 22 and 29% with 2 MAC HAL-N₂O, and with 1 and 2 MAC ISO-N₂O groups, respectively (P < 0.05). The ICG clearance was less (P < 0.05) in the 2 MAC HAL-N₂O group (K, 0.087 min⁻¹) than with either awake (K, 0.131 min⁻¹) or other groups (K, 0.114 and 0.144 min⁻¹, in the 1 MAC HAL and ISO-N₂O groups, respectively) in spite of a similar degree of the depletion of MAP in 2 MAC ISO-N₂O group (K, 0.124 min⁻¹). We conclude that isoflurane has a more favourable effect on liver circulation than does halothane. Ce travail vise à évaluer le débit sanguin hépatique pendant l’anesthésie à l’halothane (HAL) ou à l’isoflurane (ISO) par l’épreuve de clairance non invasif du vert d’indocyanine (ICG). Vingt-quatre adultes ASA I exempts de toute affection hépatique, programmés pour une chirurgie non urgente sont répartis en quatre groupes. Avant l’intervention, la clairance de l’ICG est mesurée à deux reprises avant et après une anesthésie HAL-N₂O MAC 1 et 2, et ISO-N₂O MAC 1 et 2, avec un appareil de mesure d’ICG (Sumitomo Electronics™, Japon). Cette méthode élimine l’échantillonnage sanguin et le délai propre à l’épreuve d’ICG conventionnelle. La clairance de l’ICG est affichée sous deux index: K (la vitesse de disparition de l’ICG) et R₁₅ (le taux de rétention de l’ICG 15 min après l’injection de 0,5 mg · kg⁻¹ d’ICG). La pression artérielle indirecte et la fréquence cardiaque sont mesurées simultanément. La pression artérielle moyenne (PAM) diminue de 27, 22 et 29% respectivement dans le groupe HAL-N₂O MAC 2, et dans les groupes ISO-N₂O MAC 1 et 2 (P < 0,05). La clairance de l’ICG est moins élevée (P < 0,05) dans le groupe HAL-N₂O MAC 2 (K, 0,087 min⁻¹) que soit dans les groupes éveillés (K, 0,131 min⁻¹) ou les autres groupes (K, 0,114 et 0,144 min⁻¹, respectivement, dans les groupes HAL-N₂O MAC 1 et ISO-N₂O) malgré un niveau de diminution de la PAM identique dans le groupe ISO-N₂O MAC 2 (K, 0,124 min⁻¹). Nous concluons que l’isoflurane a un effet plus favorable sur la circulation hépatique que l’halothane.     

Intrathecal midazolam reduces isoflurane MAC and increases the apnoeic threshold in rats

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - The purpose of this study was to examine the anaesthetic requirement of intrathecal midazolam in a dose-response fashion in...     

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.     

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.     

A comparison of the myocardial metabolic and haemodynamic changes produced by propofol-sufentanil and enflurane-sufentanil anaesthesia for patients having coronary artery bypass graft surgery

The purpose of this study was to compare propofol-sufentanil with enflurane-sufentanil anaesthesia for patients undergoing elective coronary artery bypass graft (CABG) surgery with respect to changes in (1) haemodynamic variables; (2) myocardial blood flow and metabolism; (3) serum cortisol, triglyceride, lipoprotein concentrations and liver function; and (4) recovery characteristics. Forty-seven patients with preserved ventricular function (ejection fraction greater than 40%, left ventricular end diastolic pressure less than or equal to 16 mmHg) were studied. Patients in Group A (n = 24) received sufentanil 0.2 microgram.kg-1 and propofol 1-2 mg.kg-1 for induction of anaesthesia which was maintained with a variable rate propofol (50-200 micrograms.kg-1.min-1) infusion and supplemental sufentanil (maximum total 5 micrograms.kg-1). Patients in Group B (n = 23) received sufentanil 5 micrograms.kg-1 for induction of anaesthesia which was maintained with enflurane and supplemental sufentanil (maximum total 7 micrograms.kg-1). Haemodynamic and myocardial metabolic profiles were determined at the awake-sedated, post-induction, post-intubation, first skin incision, post-sternotomy, and pre-cardiopulmonary bypass intervals. Induction of anaesthesia produced a larger reduction in systolic blood pressure in Group A (156 +/- 22 to 104 +/- 20 mmHg vs 152 +/- 26 to 124 +/- 24 mmHg; P less than 0.05). No statistical differences were detected at any other time or in any other variable including myocardial lactate production (n = 13 events in each group), time to tracheal extubation and time to discharge from the ICU. We concluded that, apart from hypotension on induction of anaesthesia, propofol-sufentanil anaesthesia produced anaesthetic conditions equivalent to enflurane-sufentanil anaesthesia for CABG surgery.     

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.     

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.     

Changes in the cerebral arteriovenous oxygen content difference by surgical incision are similar during sevoflurane and isoflurane anaesthesia

Purpose  

To investigate changes of cerebral arteriovenous oxygen content difference (AVDO₂) induced by surgical incision and to determine carbon dioxide (CO₂) reactivity of the cerebral circulation during sevoflurane and isoflurane anaesthesia.     

Haemodynamic instability and myocardial ischaemia during carotid endarterectomy: A comparison of propofol and isoflurane

The purpose of this study was to compare two anaesthetic protocols for haemodynamic instability (heart rate (HR) or mean arterial pressure (MAP) <80 or > 120% of ward baseline values) measured at one-minute intervals during carotid endarterectomy (CEA). One group received propofol/alfentanil (Group Prop; n = 14) and the other isoflurane I alfentanil (Group Iso; n = 13). Periods of haemodynamic instability were correlated to episodes of myocardial ischaemia as assessed by Holler monitoring (begun the evening before surgery and ceasing the morning of the first postoperative day). In Group Prop, anaesthesia was induced with alfentanil 30 μg · kg^?1 rv, propofol up to 1.5 mg · kg^?1 and vecuronium 0.15 mg · kg^?1, and maintained with infusions of propofol at 3–12 mg · kg^?1· hr^?1 and alfentanil at 30 μg · kg^?1 · hr^?1. In Group Iso, anaesthesia was induced with alfentanil and vecuronium as above, thiopentone up to 4 mg · kg^?1 and maintained with isoflurane and alfentanil infusion. Phenylephrine was infused to support MAP at 110 ± 10% of ward values during cross-clamp of the internal carotid artery (ICA) in both groups. Emergence hypertension and/or tachycardia was treated with labetalol, diazoxide or propranolol. Myocardial ischaemia was defined as ST-segment depression of >-1 mm (60 msec past the J-point) persisting for >-one minute. For the entire anaesthetic course (induction to post-emergence), there was no difference between groups for either duration or magnitude outside the <80 or >120% range for HR or MAP. However, when the period of emergence from anaesthesia (reversal of neuromuscular blockade to post-extubation) was assessed, more patients were hypertensive (P = 0.004) and required vasodilator therapy in Group Iso (10/ 13 vs 5/14; P = 0.038 Fisher’s Exact Test). The mean dose of labetalol was greater in Group Iso (P = 0.035). No patient demonstrated myocardial ischaemia during ICA cross-clamp. On emergence, 6/13 patients in Group Iso demonstrated myocardial ischaemia compared with 1/14 in Group Prop (P = 0.029). Therefore, supporting the blood pressure with phenylephrine, during the period of ICA cross-clamping, appears to be safe as we did not observe any myocardial ischaemia at this time. During emergence from anaesthesia, haemodynamic instability was associated with myocardial ischaemia. Under these specific experimental conditions, with emergence, hypertension and myocardial ischaemia were more prevalent with more frequent pharmacological interventions in patients receiving isoflurane.     

Contractile force and resting tension in the presence of halothane and increased extracellular potassium or decreased extracellular pH in isolated guinea pig atria

To gain a better understanding of the direct actions of halothane on myocardial function in ischaemia, we studied the effects of increasing extracellular potassium concentration and decreasing extracellular pH (acidosis), alone or in combination with halothane, on the contractile force and resting tension in isolated atria. Guinea pig left atria were superfused with Tyrode’s solution and stimulated at 1 Hz. Isometric contractile force and resting tension were measured using a force displacement transducer. Perfusate potassium concentrations were increased from 5.4 mmol · L⁻¹ to either 8.1 mmol · L⁻¹ or 10.8 mmol · L⁻¹ by adding KCl to the standard Tyrode’s solution, and its pH was decreased from 7.4 to either 7.0 or 6.5 by decreasing bicarbonate. In standard Tyrode’s solution (potassium 5.4 mmol · L⁻¹, pH 7.4), halothane 0.5–2% reduced contractile force in a dose-dependent manner (P < 0.05); the effective concentration of halothane for 50% inhibition of contractile force (IC₅₀) was 1.3%. Both increasing extracellular potassium and decreasing extracellular pH decreased the contractile force in a potassium-or pH-dependent fashion. The negative inotropism of halothane (1%) was not altered by increasing potassium concentrations, whereas 1% halothane caused a greater decrease in contractile force at pH 6.5 than at pH 7.4. Halothane (1%) enhanced the acidosis (pH 6.5)-induced increases in resting tension. Arrhythmias were produced in one of eight preparations during acidosis, while four of eight preparations demonstrated arrhythmias during acidosis in the presence of halothane. These data suggest that acidosis and halothane may have a synergistic interaction on the contractile force and resting tension of the atria. The increase in resting tension observed during acidosis/ halothane conditions suggests than an increase in cytosolic calcium is associated with these synergistic interactions between acidosis and halothane. Pour mieux comprendre l’action direct de l’halothane sur la fonction myocardique pendant l’ischémie, nous avons étudié les effets de l’augmentation du potassium extracellulaire et de la diminution du pH extracellulaire (acidose), seuls ou en association avec l’halothane, sur la force contractile et la tension de repos d’oreillettes isolées. Des oreillettes gauches de cobaye furent perfusées avec une solution de Tyrode et stimulées à 1 Hz. La force contractile isométrique et la tension de repos ont été mesurées avec un transducteur de force de déplacement. Les concentrations de potassium perfusées ont été augmentées de 5,4 mmol · L⁻¹ à 8,1 mmol · L⁻¹ ou à 10,8 mmol · L⁻¹ par l’ajout de KCl à la solution standard de Tyrode, et son pH abaissé de 7,4 à 7,0 ou 6,5 par baisse des bicarbonates. Avec la solution standard de Tyrode (potassium 5,4 mmol · L⁻¹, pH 7,4), l’halothane (0.5–2%) diminue la force contractile proportionnellement à la dose (P < 0,05); la concentration efficace d’halothane requise pour produire une inhibition de 50% de la force contractile (IC_5O) a été de 1,3%. L’augmentation du potassium extracellulaire et la diminution du pH extracellulaire réduisent toutes les deux la force contractile proportionnellement au potassium ou au pH. L’inotropisme négatif de l’halothane (1%) n’est pas modifié par l’augmentation de la concentration de potassium alors que l’halothane produit une diminution plus importante de la force contractile à un pH de 6,5 que de 7,4. L’halothane (1%) exagère l’augmentation de la tension de repos induite par l’acidose (pH 6,5). Des arrythmies sont apparues sur une des huit préparations pendant l’acidose en présence d’halothane. Ces données suggèrent que l’acidose et l’halothane pourraient avoir une activité synergique sur le force contractile et la tension de repos des oreillettes. L’augmentation de la tension de repos observée pendant l’acidose combinée à l’halothane suggère l’association d’une augmentation du calcium cytosolique avec des interactions synergiques entre l’acidose et l’halothane.