Prolonged Halothane Anesthesia Research Articles

Biochemical and haematological changes following prolonged halothane anaesthesia in horses

Six healthy horses were anaesthetised with halothane (1·2 times the horse minimal alveolar concentration) in oxygen for more than 12 hours. Serum bilirubin, aspartate aminotransferase, alkaline phosphatase and L-iditol dehydrogenase values were significantly (P<0·05) increased for up to nine days after anaesthesia. These changes suggest au anaesthesia related liver dysfunction. Creatine kinase increased to an average of more than 1400 iu litre −1 24 hours after anaesthesia and this change is indicative of muscle cell disruption. Renal-associated biochemical results, (that is serum creatinine and inorganic phosphate concentrations) were significantly increased transiently and are indicative of reduced renal function during and immediately after anaesthesia. Plasma concentrations of eicosanoids (6-keto-PGF 1 a , PGF 2 a , pge and thromboxane) following anaesthesia were not different from preanaesthetic values. The magnitude of liver and muscle cell related increases in serum enzyme activities resulting from prolonged halothane anaesthesia was in excess of that previously reported for anaesthesia of shorter duration.

Hemodynamic and respiratory responses to variable arterial partial pressure of oxygen in halothane-anesthetized horses during spontaneous and controlled ventilation

SUMMARY Cardiovascular and respiratory responses to variable Pao2 were measured in 6 horses anesthetized only with halothane during spontaneous (sv) and controlled (cv) ventilation. The minimal alveolar concentration (mac) for halothane in oxygen was determined in each spontaneously breathing horse prior to establishing Pao2 study conditions—mean ± sem,0.95 ± 0.03 vol%. The Pao2 conditions conditions of &gt; 250, 120, 80, and 50 mm of Hg were studied in each horse anesthetized at 1.2 mac of halothane and positioned in left lateral recumbency. In response to a decrease in Pao2, total peripheral resistance and systolic and distolic arterial blood pressure decreased (P &lt; 0.05) during sv. Cardiac output tended to increase because heart rate increased (P &lt; 0.05) during these same conditions. During cv, cardiovascular function was usually less than it was at comparable Pao2 during sv (P &lt; 0.05). Heart rate, cardiac output, and left ventricular work increased (P &lt; 0.05) in response to a decrease in Pao2, whereas total peripheral resistance decreased (P &lt; 0.05). During sv, cardiac output and stroke volume increased and arterial blood pressure and total peripheral resistance decreased with duration of anesthesia at Pao2 &gt; 250 mm of Hg. During sv, minute expired volume increased (P &lt; 0.05) because respiratory frequency tended to increase as Pao2 decreased. Decrease in Paco2 (P &lt; 0.05) also accompanied these respiratory changes. Although oxygen utilization was nearly constant over all treatment periods, oxygen delivery decreased (P &lt; 0.05) with decrease in Pao2, and was less (P &lt; 0.05) during cv, compared with sv, for comparable Pao2 values. Muscle and hepatic-derived serum biochemical values were substantially increased and evidence of depressed renal function was observed in these horses immediately after anesthesia recovery. These serum biochemical changes exceeded values in horses previously studied during prolonged halothane anesthesia in the absence of low Pao2.

Advantages and Guidelines for Using Nitrous Oxide

Nitrous oxide is useful as an adjunct to methoxyflurane anesthesia and prolonged halothane anesthesia. Nitrous oxide is also useful in the debilitated patient in which the potent volatile anesthetics induce excessive cardiovascular depression. Finally nitrous oxide is useful for smoothing an inadequate anesthetic plane induced by the potent volatile anesthetics.

Studies on the nasal clearance of 238PU and 241AM nitrates

Accidental intakes of Plutonium-238( 238Pu) and Americium-241 ( 241Am) nitrates which occur by inhalation will result in partial deposition in the nose. In these experiments nasal clearance was examined in rats after instillation of a 3μl aliquot of the nitrate solution at three different sites in the nose (6, 12, 18mm beyond the nares), and after light or prolonged halothane anaesthesia. Total transfer and transfer rates to blood were also estimated, and compared with those for the lung. The overall clearance rate was significantly ( P<0.05) different at each instillation site, and least at 18mm beyond the nares. The rate of nasal clearance did not appear to be affected by the duration of anaesthesia. Total transfer to blood did not vary between sites, with approximately 3% transfer of both actinides at 24h. Transfer rates to blood were significantly ( P<0.01) less from the nose than from the lung.

Growth of Allogeneic Sarcoma in Mice Subjected to Halothane Anesthesia and/or Surgical Stress

The present study was designed to clarify mechanisms involved in suppression of cell-mediated immunity reported in patients undergoing major surgery with general anesthesia by determining the effects of halothane anesthesia with and without surgery on the growth of Sarcoma I (Sa I), a tumor allogeneic to BALB/c mice. Mice were given subcutaneous injections of 5 X 10(6) tumor cells from A/Jax mice and then immediately exposed to 0.5%-1.0% halothane for 1 hr without surgery (n = 7) or with surgery (midline laparotomy; n = 12). In control groups mice were also injected with tumor cells but were not exposed to prolonged halothane anesthesia. Some of them received only Sa I (n = 6), while the rest (n = 7) were also laparotomized. The rejection time of Sa I in mice exposed to halothane anesthesia was significantly longer (15.4 +/- 1.25 days) than in untreated controls (12.0 +/- 0.68 days) (P less than 0.05). In the mice exposed to halothane tumor growth was also greater. Surgical stress per se did not significantly affect growth or rejection time of Sa I (11.0 +/- 0.66 vs 12.0 +/- 0.68 days). Similarly, the combination of surgical stress with halothane anesthesia did not affect the immunosuppression associated with halothane alone (12.9 +/- 1.3 vs 15.4 +/- 1.25; P less than 0.05). The results indicate that halothane anesthesia per se may be associated with impairment of cell-mediated immunity under experimental conditions.

Absence of ??-Adrenergic Receptor Involvement in Cerebrovascular Dilation by Halothane in Monkeys

We determined, in monkeys, whether halothane-induced cerebrovascular dilation is mediated by beta-adrenergic receptors and whether cerebrovascular tone progressively returns to baseline values during prolonged halothane anesthesia. Total cerebral blood flow (CBF), cerebral perfusion pressure, plasma halothane concentration, and arterial blood gas tensions and pH were measured in 14 rhesus monkeys mechanically ventilated with 0.5% (inspired) halothane, 33% O2 and balance N2O. Halothane was increased to 2.0% and the measurements repeated 30 and 60 min later. Then either 0.9% NaCl (controls n = 6) or propranolol (n = 8), 1.0 mg/kg was infused intravenously over 10 min, and the measurements repeated at 70, 90, 120, and 150 min. After 30 min at 2.0% halothane, CBF increased in the controls by 50% (P less than 0.05) from 92 +/- 8 (mean +/- SD) to 137 +/- 39 ml X 100 g-1 X min-1 and in the propranolol group by 30% (P less than 0.05) from 106 +/- 33 to 137 +/- 28 ml X 100 g-1 X min-1. After 2.5 hr of 2.0% halothane anesthesia, CBF remained elevated above baseline levels, but by only 28 and 23% in the control and propranolol groups, respectively. Cerebrovascular resistance was identical in both groups (0.55 +/- 0.33 vs 0.53 +/- 0.13 mm Hg X ml-1 X 100 g 1 X min 1). The results show that there is only a 10-20% return of CBF toward baseline levels after up to 2.5 hr of 2% halothane anesthesia. The results also indicate that halothane-induced cerebrovascular dilation is not mediated by beta-adrenergic receptors.

Absence of ??-Adrenergic Receptor Involvement in Cerebrovascular Dilation by Halothane in Monkeys

We determined, in monkeys, whether halothane-induced cerebrovascular dilation is mediated by β-adrenergic receptors and whether cerebrovascular tone progressively returns to baseline values during prolonged halothane anesthesia. Total cerebral blood flow (CBF), cerebral perfusion pressure, plasma halothane concentration, and arterial blood gas tensions and pH were measured in 14 rhesus monkeys mechanically ventilated with 0.5% (inspired) halothane, 33% O2 and balance N2O. Halothane was increased to 2.0% and the measurements repeated 30 and 60 min later. Then either 0.9% NaCl (controls n = 6) or propranolol (n = 8), 1.0 mg/kg was infused intravenously over 10 min, and the measurements repeated at 70, 90, 120, and 150 min. After 30 min at 2.0% halothane, CBF increased in the controls by 50% (P < 0.05) from 92 ± 8 ( ± sd) to 137 ± 39 ml·100 g−1·min−1 and in the propranolol group by 30% (P < 0.05) from 106 ± 33 to 137 ± 28 ml·100 g−1·min−1. After 2.5 hr of 2.0% halothane anesthesia, CBF remained elevated above baseline levels, but by only 28 and 23% in the control and propranolol groups, respectively. Cerebrovascular resistance was identical in both groups (0.55 ± 0.33 vs 0.53 ± 0.13 mm Hg·ml−1·100 g−1·min−1). The results show that there is only a 10–20% return of CBF toward baseline levels after up to 2.5 hr of 2% halothane anesthesia. The results also indicate that halothane-induced cerebrovascular dilation is not mediated by β-adrenergic receptors.

Cerebrovascular adaptation to prolonged halothane anesthesia is not related to cerebrospinal fluid pH.

The purpose of this study was to evaluate the time-dependent effects of steady-state halothane anesthesia on cerebrovascular variables and their relationship to cerebrospinal fluid (CSF) pH. Eight mongrel dogs underwent a 7-h anesthetic, receiving halothane (1.0% end-tidal), O2 (50%), and balance N2. Cerebral blood flow (CBF) was measured by injection of radioactively labeled microspheres. CSF was sampled from the cisterna magna and cerebral venous blood from the superior sagittal sinus. Measurements were made at 2 h postinduction and hourly for 5 h thereafter. Total CBF at 2 h postinduction was 148 +/- 36 ml X 100 g-1 X min-1 and showed a significant decay over the subsequent 5 h to 70 +/- 3 ml X 100 g-1 X min-1. Regional variations were noted, those areas with highest initial flows showing both a greater relative and absolute reduction in flow. Cerebral vascular resistance increased significantly (39%), as did mean arterial pressure (15%). CSF pH values remained constant throughout the experiment. Arterial blood acid-base physiology was also unchanged. Sagittal sinus PCO2 increased significantly from 43 +/- 4 to 49 +/- 3 mmHg while sagittal sinus pH decreased from 7.31 +/- 0.01 to 7.37 +/- 0.02, consistent with the normalization of CBF. Cerebral metabolic oxygen consumption did not change significantly. The authors conclude that time-dependent changes in cerebrovascular parameters under prolonged steady-state halothane anesthesia are not due to changes in CSF pH and thus brain extracellular acid-base chemistry.

Increasing Myocardial Oxygen Demand during Prolonged Halothane Anesthesia in Dogs

The effect of prolonged halothane anesthesia on myocardial oxygen uptake and coronary blood flow is unknown. This 5.5-hr study was undertaken to determine whether myocardial changes occur in dogs during prolonged steady-state halothane anesthesia. Hourly data were collected beginning 1.5 hr after induction of steady-state anesthesia. When compared to values obtained at 1.5 hr of halothane anesthesia, no significant myocardial changes were observed during the initial 3.5 hr. However, after 4.5 hr, mean arterial blood pressure increased 14% (P less than 0.01), coronary sinus flow increased 22% (P less than 0.05), and myocardial oxygen uptake increased 19% (P less than 0.05). At 5.5 hr mean arterial pressure was 18% (P less than 0.01), coronary sinus flow 31% (P less than 0.01), and myocardial oxygen uptake 21% (P less than 0.05) above levels measured at 1.5 hr. At 5.5 hr whole body oxygen uptake was 6% (P less than 0.01) above the 1.5 hr value. Cardiac output, heart rate, and systemic and coronary vascular resistances did not change significantly. This study demonstrates that duration of anesthesia is an important factor in determining the metabolic oxygen requirements of the heart. During prolonged anesthesia, the increase in myocardial oxygen demands may have an unfavorable effect on the myocardial oxygen supply-demand relationship.

Normalization of Cerebral Blood Flow During Prolonged Halothane Anesthesia

Normalization of Cerebral Blood Flow During Prolonged Halothane Anesthesia

Effects of Halothane and Fentanyl on the Rate of CSF Production in Dogs

Using the open ventriculocisternal perfusion method, the rate of cerebrospinal fluid (CSF) production was examined in dogs anesthetized with either halothane (0.8%) or fentanyl (3.0 micrograms/kg/min for 20 min, then 0.2 micrograms/kg/min, intravenously), and nitrous oxide (60-70%) in oxygen. Halothane decreased the mean rate of CSF production from 0.047 +/- 0.006 ml/min (mean +/- SEM) in controls to 0.033 +/- 0.005 ml/min. This effect persisted throughout 3.0-3.5 h of anesthesia. When the expired concentration of halothane was decreased from 0.8% to less than 0.1%, the mean rate of CSF production returned to control values within 45-50 min. Fentanyl produced no change in the mean rate of CSF production compared to controls. These data suggest that increased CSF volume does not contribute to increased intracranial pressure during prolonged halothane anesthesia. In patients at risk for increased intracranial pressure due to increased CSF volume, either halothane or fentanyl may be preferable to anesthetics that may increase CSF production, e.g., enflurane.

Normalization of cerebral blood flow during prolonged halothane anesthesia.

Normalization of cerebral blood flow during prolonged halothane anesthesia.

Changes in granulopoiesis in the rat associated with prolonged halothane anesthesia.

Rats were continuously exposed to 0.45 per cent halothane in air for periods from 24 to 115 hours. Control and experimental animals were sacrificed at regular intervals and the following tests were made: peripheral white cell and differential counts, bone marrow sections and differential counts, marrow leukocyte alkaline phosphatase staining and hepatic histology. Tritiated thymidine (3HT) uptake was studied in control and experimental rats, and the progression of this label into more mtture cell types determined. Halothane exerted on effect on dividing granulocytic cells of the marrow which was evident after 24 hours' exposure but was not reflected in significant changes in circulating granulocytes until 54 hours' exposure. DNA synthesis was not primarily affected. The results suggest the primary site of action to be on the cytoplasm of the granulocytcs.