Halothane-nitrous Oxide Anesthesia Research Articles

Myocardial Blood Flow and Oxygen Consumption During Halothane-Nitrous Oxide Anaesthesia for Coronary Revascularization

The effects of halothane on myocardial blood flow and myocardial oxygen balance were studied in seven male patients with stable angina and normal left ventricular function. Patients were receiving maintenance doses of β-receptor antagonists and underwent coronary artery bypass surgery. Anaesthesia consisted of halothane and 50% nitrous oxide in oxygen. Halothane decreased myocardial blood flow and myocardial oxygen consumption by 29% and 32%, respectively, after induction of anaesthesia, and during sternotomy. Myocardial lnctatc production was not observed at any time. Cardiac index, stroke volume index, mean arterial pressure and mean diastolic arterial pressure were decreased significantly after induction of anaesthesia and during sternotomy. Heart rate remained unchanged. The global myocardial oxygen supply and demand relationship was maintained. The results suggest that halothane is a safe anaesthetic for coronary revascularization in patients with unimpaired left ventricular function.

Central haemodynamics and regional blood flow during halothane-nitrous oxide anaesthesia and controlled ventilation. An experimental study in the rat.

The haemodynamic effects of halothane-N2O/O2 anaesthesia with controlled ventilation were studied in rats, using the microsphere method. Mean arterial blood pressure was significantly reduced but only minor effects on cardiac output (CO), heart rate, and systemic vascular resistance were seen. During anaesthesia, there were significantly increased fractions of CO delivered to brain, lungs, small intestine and liver (hepatic artery), while the fractions to spleen, stomach and carcass were decreased. Fractional distribution and regional blood flow to heart, kidneys, adrenals and preportal area remained unchanged. When anaesthesia was prolonged from 60 to 90 min, no further changes in central or regional haemodynamics were seen. Considering the minor effects on central haemodynamics and the absence of changes in central and regional haemodynamics at 60 and 90 min, this anaesthesia model should be useful in experimental research.

PROLONGED SUXAMETHONIUM INFUSION DURING NITROUS OXIDE ANAESTHESIA SUPPLEMENTED WITH HALOTHANE OR FENTANYL

The neuromuscular blockade produced by a prolonged infusion of suxamethonium was studied using train-of-four stimulation in 40 patients receiving either halothane-nitrous oxide or fentanyl-nitrous oxide anaesthesia. Initially, a depolarizing (phase I) block was observed in all patients followed by phase II block which was associated with tachyphylaxis to suxamethonium; the latter changes occurring more rapidly in the halothane group. Infusions were continued for more than 150 min in 17 patients and there was a late decrease in suxamethonium requirement in those who received halothane, but not fentanyl. Ten minutes after the suxamethonium infusion was stopped, most patients received neostigmine which was followed by rapid recovery of neuromuscular transmission.

Rebreathing and end-tidal CO2 during spontaneous breathing with the Bain circuit

In order to examine the relationship between end-tidal CO2 (Fetco2) and inspired CO2 (Fico2) in anaesthetized patients breathing spontaneously with a Bain breathing circuit and afresh gasvolume (\(\dot VF\)) of 100 ml · kg-1 · min-1, the respiratory rate (f) and minute ventilation (\(\dot VE\)) was changed in two groups of six patients each by the induction or reversal of narcotic respiratory depression. During light nitrous oxide-halothane anaesthesia (Group I), the intravenous injection of 0.1 mg · kg-1 of alphaprodine caused arapid fall in Fco2 from 2.3 ± 0.5 per cent to 0.7 ± 0.1 per cent concomitant with the reduction inf(37 ± 5 to 16 ± 4) breath -min-1 and\(\dot VE\) (137 ± 29 to 55 ± 13 ml · kg-1 · min-1), while the Fetco2 rose gradually from 5.2 ± 0.9 percent to 6.4 ± 0.9 per cent over a ten-minute period. During light nitrous oxide-halothane anaesthesia supplemented by alphaprodine (Group II), 0.2 mg of naloxone intravenously caused a rise in Fico2 from 0.5 ± 0.3 per cent to 2.9 ± 0.6 per cent simultaneous with arise in f (11 ± 2 to 25 ± 7 breath · min-1) and\(\dot VE\) (70 ± 25 to 133 ± 34 ml · kg-1 · min-1), while the FETco2 declined gradually over a ten-minute period from 7.6 ± 0.7 per cent to 6.4 ± 0.4 per cent.

Rat somatosensory (SmI) cortex: II. Laminar and columnar organization of noxious and non-noxious inputs.

The laminar and columnar organization of the rat SmI cortex was investigated under halothanenitrous oxide anaesthesia during microelectrode penetrations perpendicular to the cortical surface, using histological reconstruction of the electrode tracks. Neurons were studied in terms of receptive field properties (see companion paper) and laminar distribution. Neurons driven by non-noxious cutaneous stimulation and others by non-noxious deep stimulation, applied on contralateral receptive fields, could be recorded in the same penetration. Modality specific penetrations were observed in 48% of cases only. This finding suggests that there is little submodality segregation in the rat SmI cortex. Receptive fields successively observed in a given penetration were usually overlapping. “Modality-specific” columns were less often observed than “place-specific” columns during radial penetrations. Neurons driven by non-noxious stimulation as well as neurons driven by noxious stimulation could be recorded successively in the same penetration. Neurons driven by non-noxious cutaneous stimulation were found in layers II to V and were rare in layer VI. In contrast, nociceptive specific neurons were found almost exclusively in layers Vb and VI and convergent neurons in layer V. The size of the receptive fields was a function of the laminar position of the neurons: receptive fields were, on the average, small in layer IV, larger in layer II–III and V and even larger in layer VI. The somatotopic organization of the receptive fields of neurons driven by noxious stimulation was different from that of neurons driven by non-noxious stimulation. Such a difference was due in part to the larger size of the receptive fields of the neurons driven by noxious stimulation and also to their different topographical organization. These results provide new data concerning the functions of the rat SmI cortex. Namely they show that the cortical processing of somatic non-noxious and noxious inputs is based on laminar as well as columnar patterns of organization.

Rat somatosensory (SmI) cortex: I. Characteristics of neuronal responses to noxious stimulation and comparison with responses to non-noxious stimulation.

Single unit responses to noxious and non-noxious somatic stimulation were investigated in the somatosensory (SmI) cortex of rats under halothane-nitrous oxide anaesthesia. Four categories of neurons were observed: (1) neurons driven by non-noxious cutaneous stimulation, (2) neurons driven by non-noxious deep stimulation, (3) neurons driven by noxious stimulation only (nociceptive specific neurons), (4) neurons driven by noxious as well as non-noxious stimulation (convergent or nociceptive non-specific neurons). The receptive fields of the neurons driven by contralateral cutaneous non-noxious stimulation were small. These neurons responded phasically to cutaneous stimulation in the majority of cases. Neurons driven by stimulation of deep receptors (e.g. joint movement) could also be recorded in the same part of SmI cortex. Neurons driven by noxious stimulation had large receptive fields and were often tonically driven by noxious stimulation. Convergent (or nociceptive non-specific) neurons could often be inhibited from body parts not included in their excitatory receptive field. Some neurons driven by noxious stimulation were able to encode stimulus parameters such as temperature of a hot water bath or surface of the skin area stimulated. The different categories of neurons defined above could be successively recorded during a given electrode penetration. Evidence for the somatotopic organization of the different categories of inputs was obtained. These results strongly suggest that the first somatosensory (SmI) neocortex is involved in nociception.

Hypothermia Plus Thiopental: Prolonged Electroencephalographic Suppression

Duration of EEG suppression was compared to three groups of patients undergoing hypothermic cardiopulmonary bypass (CPB) at 25-30 degrees C under halothane-nitrous oxide anesthesia. Group I (n = 8) received three doses of thiopental (8 mg/kg i.v.): 1) for induction of anesthesia, 2) immediately after the institution of CPB, and 3) just after emergence from CPB. Group II (n = 5) received no thiopental. Group III (n = 4) received thiopental, 8 mg/kg administered intravenously, during CPB only. An unexpectedly prolonged duration of EEG suppression (26.1 min) was noticed in Group I patients with thiopental and hypothermia in combination, as compared with 4.8 min of suppression in Group II patients during hypothermic CPB without thiopental. To rule out a possible cumulative effect of thiopental administration, Group III patients were studied. With only a single dose of thiopental, administered during CPB, 29.3 min of EEG suppression was noticed. Mild cardiovascular depression occurred with thiopental administration during induction of anesthesia, whereas mild-to-moderate depression was associated with thiopental administration following emergence from CPB. It appears that thiopental and hypothermia, when administered in combination in modest doses during CPB, result in profound depression of cerebral electrical activity and presumably cerebral metabolism.

Pharmacokinetics and pharmacodynamics of d-tubocurarine in infants, children, and adults.

The pharmacokinetics and pharmacodynamics of d-tubocurarine (dTc) were determined in neonates (0-2 months, n = 7), infants (2-12 months, n = 7), children (1-12 years, n = 9), and adults (12-30 years, n = 8) during 70% nitrous oxide, 0.58 MAC halothane anesthesia. dTc was administered by infusion, while blood for determination of plasma dTc concentrations was obtained, and the EMG of the adductor pollicis recorded. The plasma dTc concentration at which 50% depression of EMG twitch height occurs (Cpss(50)) was 0.18 +/- 0.09 micrograms/ml in neonates, and 0.27 +/- 0.06 micrograms/ml in infants, both significantly lower than the values of 0.42 +/- 0.14 and 0.53 +/- 0.14 micrograms/ml for children and adults, respectively. The steady-state distribution volume (Vdss) was 0.74 +/- 0.33 l/kg in neonates, significantly greater than the values of 0.52 +/- 0.22, 0.41 +/- 0.12, and 0.30 +/- 0.10 l/kg in infants, children, and adults, respectively. The elimination half-life (t beta 1/2) was 174 +/- 60 min in neonates, significantly longer than the values of 90 +/- 23 and 89 +/- 18 min in children and adults, respectively. Plasma clearance did not differ with age. We also determined D50, the product of Vdss and Cpss(50). D50, the quantity of drug present at steady-state to produce 50% paralysis, did not differ between groups. The authors conclude that during comparable nitrous oxide-halothane anesthesia, neonates and infants have an increased sensitivity to dTc, as determined by CPss(50). However, because of the larger Vdss in younger patients, dose size should not differ with age. In addition, because of the longer t beta 1/2 in neonates, second and subsequent doses should be required at less frequent intervals.

Anesthetic Induction with Alfentanil

Alfentanil, a new ultra short-acting, potent, synthetic narcotic was evaluated as an anesthetic induction agent in 20 unsedated, patients premedicated with atropine about to undergo general surgical operations with halothane-nitrous oxide anesthesia (group I) and in 22 patients premedicated with lorazepam and atropine [nine with mitral valvular disease (group II), and 13 with coronary artery disease (group III)], about to undergo open-heart surgery with alfentanil-oxygen anesthesia. Patients in groups II and III had radial and thermodilution pulmonary arterial catheters in place before anesthetic induction. Following pretreatment with pancuronium (1.5 mg/70 kg) and while breathing pure oxygen, alfentanil was administered intravenously at a rate of 50 μg/kg/min until the patient was unconscious. Cardiovascular dynamics were measured before and after pancuronium, at the point of unconsciousness, following succinylcholine paralysis, and 1 and 4 minutes after endotracheal intubation. The time of induction and the incidence of arrhythmias, chest wall rigidity, and pain on injection were also recorded. Loss of consciousness was rapid, 134 ± 28, 47 ± 19, and 75 ± 22 seconds in groups I, II, and III, respectively. Alfentanil resulted in a transient small decrease in systolic arterial blood pressure with loss of consciousness in groups II and III but no change in right atrial and mean pulmonary arterial pressures or cardiac output throughout the study period. Patients in group I had no change in any cardiovascular variable measured. The only significant undesirable side effect was chest wall rigidity, which occurred in 50% of group I and 22% and 31 % of groups II and III, respectively. No patient remembered any aspect of laryngoscopy, endotracheal intubation, or surgery and only one thought the anesthetic induction was unpleasant. These data indicate that rapid infusion with alfentanil results in a rapid, pleasant anesthetic induction with little change in cardiovascular dynamics and a minimum of side effects.

Hypothermia Plus Thiopental:

Duration of EEG suppression was compared to three groups of patients undergoing hypothermic cardiopulmonary bypass (CPB) at 25-30 degrees C under halothane-nitrous oxide anesthesia. Group I (n = 8) received three doses of thiopental (8 mg/kg i.v.): 1) for induction of anesthesia, 2) immediately after the institution of CPB, and 3) just after emergence from CPB. Group II (n = 5) received no thiopental. Group III (n = 4) received thiopental, 8 mg/kg administered intravenously, during CPB only. An unexpectedly prolonged duration of EEG suppression (26.1 min) was noticed in Group I patients with thiopental and hypothermia in combination, as compared with 4.8 min of suppression in Group II patients during hypothermic CPB without thiopental. To rule out a possible cumulative effect of thiopental administration, Group III patients were studied. With only a single dose of thiopental, administered during CPB, 29.3 min of EEG suppression was noticed. Mild cardiovascular depression occurred with thiopental administration during induction of anesthesia, whereas mild-to-moderate depression was associated with thiopental administration following emergence from CPB. It appears that thiopental and hypothermia, when administered in combination in modest doses during CPB, result in profound depression of cerebral electrical activity and presumably cerebral metabolism.

Baroreceptor Reflexes and Pulmonary Hemodynamics during Halothane and Halothane-Nitrous Oxide Anesthesia in the Dog

The effects of reflexly induced changes in sympathetic nerve activity on pulmonary hemodynamics during halothane and halothane-nitrous oxide anesthesia were investigated. Perfusion pressure was changed in the isolated carotid sinuses (60 to 180 mm Hg) of vagotomized, open-chested dogs, anesthesized at three end-tidal halothane concentrations of 0.66% +/- 0.02% (H1), 0.88% +/- 0.02% (H2), and 1.16% +/- 0.03% (H3) with and without 67% nitrous oxide. At no levels of carotid sinus pressure were pulmonary vascular resistance or pulmonary input resistance affected by halothane or nitrous oxide. With increasing carotid sinus stimulation, pulmonary vascular resistance increased at high levels of carotid sinus pressure at the H3 halothane level and with nitrous oxide at the H1 level. Changes in pulmonary input resistance were opposite in direction to baroreceptor stimulation and were greatest at the H3 level with nitrous oxide. Thus for a wide range of baroreceptor stimulation, pulmonary vascular resistance and pulmonary input resistance remained constant at end-tidal halothane concentrations of approximately 0.9%, with or without nitrous oxide. Only when halothane concentrations were significantly above or below 0.9% did reflex changes become significant, particularly with respect to the pulmonary component of the resistive load upon the right ventricle.

Gastric Fluid Volume and pH after Fentanyl, Enflurane, or Halothane-Nitrous Oxide Anesthesia with or without Atropine or Glycopyrrolate

Gastric Fluid Volume and pH after Fentanyl, Enflurane, or Halothane-Nitrous Oxide Anesthesia with or without Atropine or Glycopyrrolate

Effect of anaesthesia and surgery on endocrine function in elderly patients.

The effect of halothane-nitrous oxide anaesthesia and abdominal surgery on endocrine function was investigated in 18 elderly patients whose ages ranged from 65 to 77 (mean 69 years). Cortisol levels in plasma increased significantly during anaesthesia and surgery, and the increases were slightly higher than those in young adults. Plasma aldosterone increased and insulin levels did not change during the procedures, and these levels were lower than in younger adults. The endocrine responses in elderly patients were similar in magnitude to those in young adults. Therefore it appears that no special hormonal treatment is necessary for elderly patients undergoing routine surgical procedures.

A Kullback Leibler-nearest neighbor rule classification of EEGs: The EEG population screening problem, an anesthesia level EEG classification application

A new methodology, a Kullback Leibler-nearest neighbor (KL-NN) rule method is introduced for the EEG population screening problem. It is applied to the classification of anesthesia levels of humans in surgery by the analysis of EEGs alone. Stationary epoch multichannel EEGs are considered. In the EEG population screening problem, the category or state of an individual is classified by comparison of his/her EEG with labeled sample EEGs taken from other individuals. In the KL-NN method, a measure of dissimilarity is computed between a new to-be-classified EEG and each of the labeled sample EEGs. The measure of dissimilarity is a Kullback Leibler measure of the dissimilarity between the sample covariance functions of the EEG time series, computed as if the EEGs were Gaussian distributed. The new EEG is classified to have the same categorical label of its nearest neighbor EEG, (or of a majority of its nearest neighbor EEGs) in the minimum KL number sense. The KL-NN rule has the important statistical property that, with only a relatively small number of categorically labeled sample EEGs, the KL-NN rules yield a statistically reliable estimate of the best achievable discriminability between categorical EEG populations. In an application of the KL-NN rule method, the level of anesthesia insufficient for deep surgery was distinguished from the anesthesia level sufficient for deep surgery on humans in surgery under halothane-nitrous oxide anesthesia. Analysis was carried out on 20- sec EEG epochs from 18 different individuals. The results were that the probabilities of correct classification of anesthesia levels, based on the analysis of two and four EEG data channels, were 85 and 89% respectively. Ninty-seven percent of 62 independent two-channel EEGs, from the same 18- individual population, were classified correctly against the labeled sample EEG däta.

Halothane-Nitrous Oxide Anesthesia in a Patient Receiving High-Dose Propranolol

Halothane-Nitrous Oxide Anesthesia in a Patient Receiving High-Dose Propranolol

Limb blood flow. The influence of temperature during halothane-nitrous oxide anesthesia.

Twenty adult patients were examined before anesthesia, during anesthesia, and at the end of surgery to determine the influence of body cooling on limb blood flow during prolonged halothane-nitrous oxide anesthesia. Measurements included temperature, mean arterial pressure, and leg blood flow. Cooling was prevented in ten patients by warmed anesthetic gases. The mean tympanic temperature at end of surgery was 37 degrees C for the warmed (W) and 35 degrees C for the unwarmed (UW) patients, a significant difference. The mean value for leg blood flow was significantly decreased in the UW patients (W = 5.0 vs UW = 3.1 mL/100 cc of tissue/min). These results indicate that body cooling during prolonged inhalation anesthesia was associated with a reduced limb blood flow. Therefore, pulmonary warming may be of potential benefit under similar conditions to help prevent intraoperative vascular complications.

Gastric Fluid Volume and pH after Fentanyl, Enflurane, or Halothane-Nitrous Oxide Anesthesia with or without Atropine or Glycopyrrolate

Gastric fluid volume and pH were determined immediately following the induction of anesthesia and again after 2 hours of anesthesia consisting of 60% nitrous oxide plus either fentanyl, enflurane, or halothane. Adult patients undergoing elective, but not upper abdominal, operations were subjects for this study. Preanesthetic medication included intramuscular morphine with or without either atropine (0.4 mg) or glycopyrrolate (0.2 mg). Gastric fluid volume after 2 hours of anesthesia was significantly less (p < 0.05) than immediately after induction of anesthesia. Gastric volume was similar for all anesthetics and was not influenced by the inclusion of anticholinergic drugs in the preanesthetic medication. Compared with control gastric pH (only patients with an initial pH less than 3.5 were studied) there was no change in pH after 2 hours of fentanyl anesthesia with or without either atropine or glycopyrrolate. Likewise, pH did not change during halothane anesthesia without anticholinergic drugs. Enflurane anesthesia with or without anticholinergic drugs and halothane combined with atropine or glycopyrrolate were associated with significant increases (p < 0.05) in gastric pH. Glycopyrrolate was associated with greater increases in pH than was atropine (p < 0.05). These data suggest that gastric fluid production is minimal during anesthesia irrespective of anesthetic drugs or preanesthetic medication. Halothane or enflurane, but not fentanyl, when combined with glycopyrrolate preanesthetic medication was associated with the greatest increase in gastric pH. However, the increased pH was not seen in all patients and often the increase was not sufficiently great to protect against pneumonitis should aspiration have occurred.

Continuous in-vivo blood-gas determination in man: reliability and safety of a new device.

The Sentorr is a gas chromatograph that monitors Pa2 and PaCO2 every 4 min from a probe placed through an intraarterial cannula. The accuracy of this device and complications resulting from its use were studied in 46 patients undergoing cardiac surgical procedures with oxygen to nitrous oxide-halothane anesthesia. Sentorr blood-gas values were compared with simultaneous samples analyzed with standard electrodes. During relatively steady states of respiration and circulation, and in the lower (50-125 torr) range of oxygen tensions, the measurements correlated closely (r = 0.92). The device also functioned well during low-flow states, but during hypothermic cardiopulmonary bypass, the correlation was only fair (r = 0.62). When nitrous oxide was present in the inspired gas, Sentorr PaO2 readings were a third lower than actual PO2 measurements, an effect corroborated by an in-vitro experiment. Directional changes of oxygen and carbon dioxide tensions were always correct in all situations. Placement of the probe in a radial artery was unsatisfactory because it significantly interfered with blood pressure measurement and resulted in inaccurate results for this patient population. The brachial artery was a satisfactory site for insertion, although attenuation of the arterial pressure tracing by the presence of a Sentorr probe resulted in systolic pressure readings that averaged 12 torr lower with mean arterial pressure readings 5 torr lower. No increase in morbidity due to use of a Sentorr probe for brachial arterial pressure monitoring could be identified. The most potentially serious complication encountered was transient loss of a palpable pulse without interruption of blood flow in one or more distal arteries after decannulation. This was observed in seven patients (four of whom had diminished distal pulses whith normal flow before cannulation).

Cardiovascular Effects of Dibutyryl cyclic AMP During Nitrous Oxide Halothane Anesthesia

The effects of dibutyryl cyclic AMP (db-cAMP) on cardiovascular hemodyna-mics and changes in blood sugar and serum insulin levels were evaluated in GOF-anesthetized man. Observations were made on 15 patients of both sexes and ranging in age from 24 to 63 yrs who were to undergo surgery. Sixty minutes before induction, each patient was given a moderate dose of atropine as preme-dications. Stroke volume and cardiac output were measured by a Minnesota impedance cardiograph, arterial blood pressure was measured by auscultation, total peripheral resistance was calculated from the mean arterial pressure and cardiac output, the heart rate was obtained from an ECG monitor, blood sugar and serum insulin levels were determined from venous blood, and the insulin-glucose ratio was calculated from the insulin and blood sugar levels. Twenty minutes after GOF anesthesia, 5mg/kg of db-cAMP were injected and its effects were studied for 30 minutes prior to surgery with the following results:1) Db-cAMP increased the heart rate slightly and lowered systolic and diastolic pressure while increasing pulse pressure slightly.2) Both the stroke volume and cardiac output increased after db-cAMP injec-tion.3) Total peripheral resistance decreased remarkably after db-cAMP injection.4) Blood sugar and serum insulin levels both increased remarkably, with a slight increase in the insulin-glucose ratio after db-cAMP administration.

Hypertension during Anesthesia on Discontinuation of Sodium Nitroprusside-induced Hypotension

The authors had observed that on intraoperative discontinuation of sodium nitroprusside being administered to induce hypotension, mean arterial pressure increased to above the pre-hypotension level. Twelve patients who recieved hypotensive anesthesia for surgical correction of cerebral aneurysms were studied to evaluate the role of the renin-angiotensin system in this phenomenon. In the awake state, mean arterial pressure was 100 +/- 2 torr and plasma renin activity 3.0 +/- 0.1 ng/ml/hr. Thirty minutes after the establishment of stable halothane-nitrous oxide anesthesia, mean arterial pressure decreased to 85 +/- 1 torr and plasma renin activity increased to 4.4 +/- 0.1 ng/ml/hr. No appreciable change in either occurred over the next two hours of operation. During sodium nitroprusside-induced hypotension, mean arterial pressure decreased to 49 +/- 2 torr and plasma renin activity increased to 15.2 +/- 0.2 ng/ml/hr. Thirty minutes after discontinuation of sodium nitroprusside administration, mean arterial pressure increased to 112 +/- 2 torr, which was not only higher than the prehypotension level, but also significantly higher than that recorded in the awake state. Plasma renin activity at that time was 10.9 +/- 0.1 ng/ml/hr. As the half-life of plasma renin is 15 min, the data suggest that the persistently increased plasma renin activity is probably responsible for the increase of arterial pressure following sodium nitroprusside-induced hypotension.