Use of halothane in a semi-closed circuit

Halothane was administered to 10 ASA or 11 patients undergoing elective peripheral surgery. The vaporizer was included in the delivery gas line of the semiclosed system. L?we's square root of time model of uptake was used to calculate the required doses of halothane. In order to reach an alveolar concentration corresponding to 1.3 MAC, 0.5 vol % of halothane (1.3 MAC) combined with 60 vol % of nitrous oxide (0.6 MAC) were administered at a fresh of 20 ml.kg-1. The ventilation controlled in order to maintain end-tidal CO2 partial pressure at a 5 vol %. Inspiratory halothane concentration was measured during the inspiratory plateau. The alveolar fraction was defined as being the mean end expiratory concentration. The latter was well above the theoretical values during the first 9 min of anaesthesia (0.85% at the 4 th min). This concentration then decreased progressively, becoming less than the expected value after 15 min (0.4% at the 30 th min). L?we's model would therefore seem to lead to a gross overestimation of the amount of anaesthetic vapour to be delivered to a patient at the beginning of anaesthesia, and an underestimation thereafter.     

Uptake and elimination of isoflurane and halothane by children and adults

The rate of increase of alveolar concentrations (FA/FI) of isoflurane and halothane was studied in children and adults during general anaesthesia and controlled ventilation. After 30 min of body equilibrium, elimination curves of the volatile anaesthetics were determined by measurement of alveolar (FA/FA0; infrared technique) and venous concentrations (gas chromatography). The distribution and elimination half-times (t1/2 alpha, t1/2 beta), clearance (Cl), volume of central and peripheral compartment (V1, Vz) and the volume of distribution at steady state (Vss) were calculated from the intercepts and slopes of a two-compartment model. During the uptake of anaesthetic concentrations of isoflurane and halothane, the FA/FI ratio of each gas was found to rise significantly faster in children than in adults. The reason for the more rapid approach to equilibrium in children seems to be related to physiological differences. Irrespective of age, uptake of isoflurane was more rapid than that of halothane, as it is less soluble. Similarly, isoflurane was eliminated from the lung or blood faster than halothane. Moreover, anaesthetic wash-out in children differed from that in adults. In the paediatric age group t1/2 beta under isoflurane was shorter than in adults, whereas halothane excretion took longer in children. This could be accounted for by the larger volumes of distribution Vz and Vss in the young, due to higher organ affinity of halothane. From our data we conclude that age significantly affects uptake and elimination of volatile anaesthetics and the control of anaesthesia is easiest with isoflurane in paediatric patients.     

Redistribution of halothane and sevoflurane under simulated conditions of acute airway obstruction

Forty patients having surgery requiring muscle paralysis and tracheal intubation were randomly allocated to receive either halothane (n = 20) or sevoflurane (n = 20). Following intravenous anaesthesia and tracheal intubation, inhalation induction of anaesthesia was simulated. After attaining an end-tidal anaesthetic concentration of 2 MAC for the respective agent, the airway was obstructed for 3 min. The end-tidal anaesthetic concentration was measured for the first three breaths following the period of airway obstruction. The decrease in alveolar concentration of sevoflurane following 3 min of airway obstruction was found to be significantly greater than that of halothane. We conclude that even if the airway obstructs completely during inhalational induction of general anaesthesia, awakening would be faster with sevoflurane than with halothane.     

CONTROL OF END-TIDAL HALOTHANE CONCENTRATION: Part A: Anaesthesia Breathing System and Feedback Control of Gas Delivery

Conventional anaesthetic breathing systems are not designedto control end-tidal gas concentrations, nor can they be usedto measure accurately the uptake of oxygen or of anaestheticagent. We built and tested a leak-tight closed-loop anaestheticbreathing system with low solubility to volatile anaestheticagents and with efficient gas mixing. The system included awater-sealed spirometer, a small carbon dioxide absorber, acoaxial tube to the patient a circulating pump and feedbackcontrollers for system volume and anaesthetic concentration.Feedback control was implemented to adjust and control automaticallythe end-tidal anaesthetic concentration and the volume of thesystem with oxygen supplied through a mass flow controller andwith halothane supplied by a titrating syringe. Controller gains,as a function of body weight, were found using a nine-compartmenttissue uptake model. Stability was maintained with ±50%changes in alveolar ventilation and cardiac output. During subsequentinvestigations in an animal model, arterial, mixed venous andcerebral venous blood halothane concentrations were measuredto show that the feedback-controlled halothane induction wasoptimized. We conclude that feedback control appears to be clinicallyapplicable for adjusting the end-tidal Concentration and systemvolume to provide a rapid and optimized induction of anaesthesia. ^*Present address: Department of Anesthesiology, University ofUtah, 50 North Medical Drive, Salt Lake City, Utah 84132, U.S.A.     

EFFECTS OF HALOTHANE, ETHER AND CYCLOPROPANE ON RESPIRATION

Dogs have been anaesthetized with halothane, ether and cyclopropane,and the depth was kept constant at any desired level by maintainingan unvarying gas concentration in alveolar air. Under thesesteady-state conditions carbon dioxide response curves havebeen elicited at different depths of anaesthesia. All threeanaesthetic drugs caused a progressive reduction of ventilationvolumes as the concentration was increased. In one subject therewas an augmentation of ventilation at moderate levels of etheranaesthesia. Halothane, ether and cyclopropane all producedapnoea at an alveolar concentration approximately 2.2 timesthe minimum concentration required to maintain surgical anaesthesia. ^*Author's present address: Department of Anesthesiology, AmericanUniversity of Beirut, Lebanon.     

Halothane-Relaxant Anaesthesia in Elderly Patients

Twenty-three elderly patients, scheduled for elective cholecystectomy, were studied during halothane-relaxant anaesthesia. Anaesthesia was induced with thiopentone and maintained with halothane in 12 patients, six of whom had also received premedication. Eleven patients were anaesthetized with halothane, without thiopentone induction and with no premedication. Measurements of central haemodynamics were performed awake and during anaesthesia at end-tidal halothane concentrations of 0.5 and 1.0%; at the lower concentration, measurements were also made after addition of nitrous oxide. Premedication and thiopentone had no influence on the subsequent halothane anaesthesia. Halothane caused reductions of cardiac index, mean arterial blood pressure and oxygen uptake. However, neither right atrial nor pulmonary capillary venous pressure increased and the arterio-venous oxygen content difference decreased. These findings differ from those made by others in younger subjects and are probably attributable to a dose-dependent reduction in systemic vascular resistance. The addition of nitrous oxide had only minor effects on central circulation. The results suggest that the age of the patients influences their reaction to halothane anaesthesia.     

CONTROLLED ANAESTHESIA: AN APPROACH USING PATIENT CHARACTERISTICS IDENTIFIED DURING UPTAKE

A system to control the alveolar anaesthetic concentration ofpatients undergoing halothane anaesthesia with controlled ventilationis described. Parameters characterizing the alveolar concentrationresponse are determined on-line from breath-by-breath measurementof the inspired and end-tidal concentrations and the mixed venousanaesthetic partial pressure is estimated throughout the procedure.The method does not depend on the use of reference models orpre-programming and the inspired concentration required to controlthe alveoLar concentration is determined as induction proceeds.Results using both computer simulations and data from patientsundergoing routine clinical anaesthesia are analysed. Off-lineverification results illustrate the operation of the techniqueand in 20 cases the inspired concentration, as controlled bythe anaesthetist, was compared with that predicted by the automatedsystem. These results indicate the feasibility of the systemas a method for the control of anaesthesia. ^*Present address: N.A.M. Ltd, Assen, The Netherlands     

Oxygen Uptake and Central Circulation During Ketamine Anaesthesia

Cardiac output, oxygen uptake and plasma catecholamines were studied in patients when awake and during ketamine anaesthesia prior to and during upper abdominal surgery. Oxygen uptake was determined by using a masspectrometer and cardiac output was measured according to the Fick principle. Plasma catecholamines were analysed by high performance liquid chromatography. Stroke volume had fallen by 27% while heart rate had increased after 15 min of anaesthesia, maintaining cardiac output at the awake level. Concomitantly, the oxygen uptake had fallen by 18%. During the succeeding hour of anaesthesia and surgery, cardiac output displayed a transient decrease and oxygen uptake returned to the awake value. The plasma adrenaline concentration fell during the initial phase of anaesthesia and then returned to the awake level. The noradrenaline concentration was increased during the whole anaesthetic period. The data suggest a relationship between oxygen uptake and cardiac output during ketamine anaesthesia, similar to that seen during neuroleptnitrous oxide and halothane anaesthesia, except for the initial hyperkinetic period following the induction. No relationship could be shown between catecholamine concentrations in plasma and the central haemodynamics.     

Immunomodulating effects of halothane in mice

Twenty mice were acutely exposed to 1.5% halothane anaesthesia for 4 h. The mice were sequentially killed during the first 3 days after halothane exposure. Another 14 mice were chronically exposed to 0.25% halothane for 1 h daily, four times weekly for 3 months. The mice were sequentially killed every week. Acute exposure to halothane anaesthesia resulted in an increase in lymphocyte count per spleen, a decrease in serum IgG concentrations (Day 2), a reduction in spontaneous 3H-thymidine lymphocytic uptake (Day 1), and an increase in concanavalin-A-stimulated uptake. All immunometric assays returned to control levels on Day 3 after halothane exposure. Chronic non-anaesthetic concentrations of halothane exposure produced a decrease in serum IgG concentrations and an increase in spontaneous and stimulated lymphocyte 3H-thymidine uptake. It is concluded that acute exposure of mice to anaesthetic halothane results in a transient depression of the immune response, while chronic non-anaesthetic concentrations produce a differential effect on the two moieties of the immune system, a depressed humoral response and overactive cellular response.     

Low-dose halothane produces airway dilatation but does not alter parenchymal mechanics in the normal canine lung

The purpose of this study was to examine whether halothane reduces the contractile tone of the normal lung and to distinguish the effects of halothane on airways from those on lung tissue. We also tested whether a mathematical model was capable of quantitatively describing the mechanical changes in the lung produced by halothane. We measured lung impedence (Zlω) a complex function of real (lung resistance) and imaginary (reactance) parts) at low frequencies in dogs using a forced volume oscillation technique before and during 1 MAC halothane anaesthesia. Halothane produced small changes in 2l((ω). The lung resistance tended to decrease during halothane anaesthesia whereas the lung reactance did not show change. Using an alveolar capsule technique to separate the airways from the lung tissue components, these lung mechanical changes were induced mainly by alterations in lung tissue and not in the airways. Our mathematical model featured a single airway leading to an alveolar region surrounded by a viscoelastic lung tissue. In the model analysis, estimates of airway resistance and inertance decreased by the administration of halothane. In contrast, estimates of lung tissue elastance and resistance did not change during halothane anaesthesia. These modeling results were consistent with those obtained by direct alveolar pressure measurements. Our results suggest that a low concentration of halothane dilates the airways but does not alter the parenchymal mechanics in the normal lung, and that the model provides a quantitative tool to assess lung mechanics precisely, if respiratory signals are measured only at the true airway opening.     

Renin-angiotensin-aldosterone system and plasma vasopressin in surgical patients anaesthetized with halothane or isoflurane

The effects of halothane and isoflurane anaesthesia on plasma renin activity and plasma concentrations of aldosterone and vasopressin were investigated in 20 cholecystectomy patients. Plasma renin activity rose significantly during both halothane and isoflurane anaesthesia without surgery, and increased further after the commencement of operation. Plasma aldosterone increased slightly during halothane and isoflurane anaesthesia, but the highest concentrations, three times the control values, were measured during surgery in both groups. Plasma vasopressin decreased during halothane and isoflurane anaesthesia to half of the control values, but rose significantly during cholecystectomy. During anaesthesia and surgery there were no significant differences in the mean arterial pressures of the groups. The results demonstrate that isoflurane stimulates the renin-angiotensin system to a similar extent as halothane, although it causes hypotension by a different mechanism. The activation of the renin-angiotensin-aldosterone system may be an essential compensatory mechanism, which antagonizes the decrease of blood pressure. Plasma vasopressin probably has no role in regulating blood pressure during anaesthesia.     

Effect of age on epinephrine-induced arrhythmias during halothane anaesthesia in pigs

The effect of age on the arrhythmogenicity of epinephrine during halothane anaesthesia was studied in pigs of two different age groups. At a stable alveolar concentration of 0.84 volumes per cent halothane, ventricular arrhythmias could not be elicited in one- to three-day-old pigs by a 100 micrograms X kg-1 infusion of epinephrine. PVCs were produced in 50- to 55-day-old pigs at a mean epinephrine dose of 9.55 micrograms X kg-1. Heart rate, systolic blood pressure, and rate-pressure product were significantly higher before and during the epinephrine infusion in the 50- to 55-day-old pigs. It is concluded that there is an age dependent effect upon epinephrine induced arrhythmias during halothane anaesthesia in pigs.     

EFFECT OF ANAESTHESIA WITH CYCLOPROPANE, HALOTHANE OR THIOPENTONE ON THE VASCULAR COMPARTMENT IN SHEEP

Measurements of the volume and protein content of the plasma,and the red cell and haemoglobin content, haematocrit and gastension of the blood were made on normal, adult sheep duringthree consecutive 2-hour periods: control, anaesthesia and recovery.During the period of anaesthesia, cyclopropane, halothane orthiopentone was administered. Red cells were removed from thecirculation during the control periods and during anaesthesiawith thiopentone or halothane, but returned during the recoveryperiods. The red cell concentration increased both during andafter the administration of cyclopropane, and reached a value30 per cent higher than the mean concentration present duringthe control period. Cyclopropane anaesthesia was not accompaniedby a significant loss of fluid or protein from the circulation,but the rate of protein loss increased after the cyclopropanewas withdrawn. No significant changes in either the volume ofplasma or the total plasma protein occurred during the earlystages of either halothane or thiopentone anaesthesia, but ineach case the mean plasma protein concentration was significantlylower during anaesthesia than during the control period.     

The influence of halothane on spermatogenesis in surgical patients

Seventeen male patients delivered a sperm sample before and 80-90 days after halothane anaesthesia, acting as their own control. The sample was tested according to WHO criteria. There was no difference before and after anaesthesia. We conclude that halothane used in normal anaesthetic concentration in combination with nitrous oxide during arthroscopic knee surgery had no certain effect on the quality of sperm.     

BREATH-BY-BREATH HALOTHANE MONITORING DURING ANAESTHESIA: A study in children

The use of a halothane meter in routine paediatric anaesthesiawith controlled ventilation is described. The results demonstratethe accuracy achieved in the control of the alveolar halothaneconcentration. Measurement of the alveolar halothane concentrationrevealed responses to surgical stimulation otherwise obscuredby neuromuscular blockade, and this may indicate insufficientdepth of anaesthesia.     

Electro-acupuncture modification of halothane anaesthesia in the dog

The effects of electro-acupuncture on minimum alveolar anaesthetic concentration (MAC) was studied during halothane anaesthesia in the dog. Following induction of anaesthesia, MAC was determined in duplicate. Ten dogs then received electro-acupuncture bilaterally at San Yin Chiao for 30 minutes. MAC was determined in duplicate while electro-acupuncture was continued. Electro-acupuncture significantly lowered MAC from 1.2 percent to 1.0 per cent (p< 0.01). A crossover experimental design was used in an additional eleven dogs. Here MAC was lowered from 1.17 per cent to 1.04 per cent (p < 0.05). Electro-acupuncture produces a small but statistically significant reduction in halothane MAC.     

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 Different Responses of the Hepatic Arterial Bed to Hypovolaemia and to Halothane Anaesthesia

Ten dogs were subjected to a period of hypovolaemia (bleeding volume: 2% of body weight) and to a period of halothane anaesthesia (end-tidal halothane concentration: 1%). Mean arterial blood pressure decreased to 79% of control value during hypovolaemia and to 58% of control value during halothane anaesthesia. Mean total peripheral and preportal vascular resistances increased during hypovolaemia and were unchanged during halothane. Mean hepatic arterial and portal venous blood flows decreased to 82% and 55% of control values, respectively, during hypovolaemia, and to 41% and 56% of control value, respectively, during exposure to halothane. Mean hepatic arterial resistance was unchanged during hypovolaemia, but increased during halothane. Mean hepatic oxygen consumption did not change significantly during hypovolaemia, but decreased during halothane anaesthesia, in spite of an increased extraction of oxygen from both the hepatic arterial and the portal venous blood. Possible mechanisms which may maintain oxygen supply to the liver by increasing the hepatic arterial fraction of total liver blood flow when portal venous blood flow is reduced are discussed. It is concluded that this mechanism is upset or inhibited during halothane anaesthesia.     

EFFECTS OF ANAESTHESIA AND SURGERY ON PLASMA ALDOSTERONE CONCENTRATION AND RENIN ACTIVITY IN MAN

The effects of various anaesthetic agents and surgery on theplasma concentrations of aldosterone and on renin activity wereinvestigated in 76 patients. The plasma concentration of aldosteronewas increased markedly by 2.5 times the control value during45 min of ether anaesthesia. It was increased also during halothane,methoxyflurane and enflurane anaesthesia. Spinal anaesthesiadid not alter significantly the plasma concentration of aldosterone.Plasma renin activity and ACTH concentration were increasedslightly during general anaesthesia.     

Comparison of the effects of halothane, isoflurane and methoxyflurane on the electroencephalogram of the horse

We have investigated in eight ponies the effects of three different end- tidal concentrations of halothane, isoflurane and methoxyflurane on median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential (DD) of the middle latency auditory evoked potential (MLAEP). The three concentrations of each agent were chosen to represent approximately the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane anaesthesia, F95 decreased progressively as halothane concentration increased, from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%. DD was lower during anaesthesia with the highest concentration (21 (6.5)) compared with the lowest (27.6 (11.4)). There were no significant changes in F50. During isoflurane anaesthesia, there was a small, but significant increase in F95 between the intermediate and highest concentrations (10.2 (1.5) to 10.8 (1.6)). There were no changes in F50 and DD. Values of F95, F50 and DD at all isoflurane concentrations were similar to those of halothane at the highest concentration. During methoxyflurane anaesthesia, F95 and F50 decreased progressively as methoxyflurane concentration was increased, from 21.3 (0.7) and 6.5 (1), respectively, at 0.26%, to 20.1 (0.6) and 5.6 (0.8), respectively, at 0.39%. DD was lower during anaesthesia with the highest concentration of methoxyflurane (25.7 (7.8)) compared with the lowest (39.7 (20.6)). Values of F95, F50 and DD at all methoxyflurane concentrations were higher than those seen with halothane at the lowest concentration. The different relative positions of the dose-response curves for EEG and MLAEP changes compared with antinociception (MAC) changes suggest differences in the mechanisms of action of these three agents. These differences may explain the incomplete adherence to the Meyer-Overton rule.