Theodore C. Smith

Cerebral Circulation During General Anesthesia and Hyperventilation in Man

Studies of cerebral circulation and gaseous metabolism were performed in six healthy young volunteers during anesthesia induced with thiopental and maintained with nitrous oxide and d-tubocurarine. The blood thiopental level was very low when measurements were made, and intravenous d-tubocurarine has been shown not to affect cerebral flow or metabolism. Therefore 70 per cent nitrous oxide was probably the agent chiefly responsible for the changes observed. When Paco2 was normal, cerebral blood flow remained normal, but cerebral oxygen uptake decreased 23 per cent. About one third of this decrease was caused by a small decline in body temperature, with the remainder most likely owing to nitrous oxide. When mean arterial Pco2 was decreased to 18.3 mm. of mercury, cerebral blood flow was halved, and mean jugular venous Pco2 declined to 19.8 mm. of mercury, a level generally assumed to be associated with suboptimal cerebral oxygenation. However, cerebral metabolic rate for oxygen did not decrease further at this low Paco2.

Respiratory Interactions of Ketamine and Morphine

Six healthy, consenting volunteer males received ketamine iv in five logarithmically scaled doses totaling 3 mg/kg on three occasions each. The sessions differed only in the initial injection of an unknown drug: placebo, morphine sulfate 0.2 mg/kg, or morphine sulfate 0.4 mg/kg. Initial and terminal steady-state ventilatory responses to CO2 (VERCO2) and isohypercapnic ventilation (end-tidal CO2 49.8 ± 2.4 mmHg) during drug administration assessed CO2-mediated ventilatory drive. Oxygen concentration of 40% ablated hypoxic drive contribution. Morphine caused a decrease of isohypercapnic ventilation (VE) of 8.2 ± 1.2 l/min after 0.2 mg/kg. Doubling the dose to 0.4 mg/kg gave a further depression of 6.6 ± 1.8 l/min. No subject lost consciousness after morphine. Over a dose range of 0.39 to 3.0 mg/kg ketamine caused log-linear dose-related depression of 1.6 ± 0.3 l/min for each doubling of dose, although the first significant depression of 4.9 ± 1.1 l/min did not occur until the third dose (1.1 mg/kg) in the absence of morphine. All subjects were unconscious after 1.8 mg/kg ketamine. Slopes of the VERCO2 did not differ from control, regardless of the pretreatment, placebo, or morphine in the two doses. Ketamine alone, 3.0 mg/kg, caused a displacement of VERCO2 of +2.0 ± 1.2 mmHg in CO2, while combination of ketamine and morphine in either dose caused a +10 mmHg displacement of VERCO2. Thus, ketamine appears qualitatively similar but less potent than premedicant doses of morphine in depressing respiration despite near equipotency in producing loss of consciousness.

CEREBRAL CARBOHYDRATE METABOLISM DURING HYPOCARBIA IN MAN: STUDIES DURING NITROUS OXIDE ANESTHESIA.

Brain carbohydrate metabolism was studied in 11 healthy male volunteers during anesthesia induced with intravenous thiopental (5 mg./kg.) and maintained with 70 per cent N2O-30 per cent O2 and d-tubocurarine. When arterial PCO2 (PaCO2) was normal, oxygen and glucose consumption were reduced approximately 25 per cent from the normal value in conscious man; but no change in the pattern of glucose utilization was noted. A reduction in PaCO2 below 20 mm. of mercury was accompanied by a decreased aerobic and an increased anaerobic utilization of glucose. Mild, readily reversible changes in the EEG pattern also occurred when PaCO2 was less than 20 mm. of mercury. Clinical implications of these changes are discussed. The validity of several indices of cerebral carbohydrate metabolism is considered.

Time Course of Ventilatory Depression after Thiopental and Midazolam in Normal Subjects and in Patients with Chronic Obstructive Pulmonary Disease

Using a dual isohypercapnic technique, the authors compared the effect on ventilatory control of midazolam (0.2 mg/kg) and thiopental (3.5 mg/kg) in normal volunteers and in subjects with chronic obstructive pulmonary disease (COPD). In normal volunteers the slope of the CO2 response curve decreased from 1.77 ± 0.16 1*min-1* mmHg-1 (mean ± SEM) to a minimum of 1.14 ± 0.17 1* min-1* mmHg-1 3.5 min after midazolam, returning to 1.32 ± 0.21 1*min-1* mmHg-1 15 min after injection. In the same subjects, the slope of the CO2 response curve fell from 1.89 ± 0.18 1*min-1*ramHg“1 to a minimum of 1.37 ± 0.29 I*min-1* mrnHg-1 one minute after injection of thiopental, returning to 1.69 ± 0.22 1 * min-1* mmHg-1 15 min after injection. These changes were not statistically significant. In subjects with clinical COPD, the slope of the CO2 response curve decreased from 1.89 ± 0.63 1 * min-1* mmHg-1 to a minimum of 0.39 ± 0.19 1*min-1* mmHg-1 two minutes after injection of midazolam (P < 0.05 compared with control), while 15 min after injection, the slope recovered to only 0.62 ± 0.40 1 * min-1* mmHg-1 (P < 0.05 compared with control). In the same subjects, the slope of the CO2 response curve decreased from 1.53 ± 0.17 to a minimum of 0.69 ± 0.25 1*min-1-mmHg-1 0.5 min after injection of thiopental, recovering to 1.47 ± 0.28 1 * min-1* mmHg-1 15 min after injection. This was significantly greater than the corresponding slope after midazolam (P < 0.05). The authors conclude that while the time course of ventilatory depression after thiopental is similar in normal volunteers and in patients with COPD, the ventilatory depression 15 minutes after midazolam is more profound in patients with COPD than in normal subjects.

Electrocautery-induced reprogramming of a pacemaker using a precordial magnet

Demand pacemakers may be susceptible to inhibition from electromagnetic interference (EMI) emitted by an electrocautery (1-7). While demand pacemakers may automatically revert to an asynchronous mode in the presence of continuous EM1 from any source (8), this sometimes does not occur in the presence of intermittent or modulating electromagnetic fields (9). If inhibition occurs, contemporary advice dictates that a magnet be placed over the pacemaker generator, converting it to the asynchronous mode (9). The following case report presents an unusual complication resulting from the use of a magnet to prevent electrocautery-induced inhibition of a demand pacemaker.

Median Effective Doses (ed50) of Halothane in Adults and Children

Median effective doses of halothane (ED50), determined in 73 pediatric subjects and 31 adults grouped according to age, were: 1.20 per cent at 0 to 6 months; 1.16 per cent at 6 to 24 months; 1.07 per cent at 24 to 48 months; and 0.9 per cent in adults. The dose-response curves for all groups did not deviate significantly from parallelism. Halothane was 1.28 and 1.12 times more potent in producing anesthesia in adults than in the 0-to-6-months and 6-to-24-months group. Potency in the 24-to-48-months group did not differ significantly from potency in adults or in younger children. In contrast, taking hypotension as a measure of circulatory effect, halothane is a less potent cardiovascular depressant in adults than in young children.

Motion of the Diaphragm in Patients with Chronic Obstructive Pulmonary Disease while Spontaneously Breathing versus during Positive Pressure Breathing after Anesthesia and Neuromuscular Blockade

Background Diaphragmatic excursion during spontaneous ventilation (SV) in normal supine volunteers is greatest in the dependent regions (bottom). During positive pressure ventilation (PPV) after anesthesia and neuromuscular blockade and depending on tidal volume, the nondependent region (top) undergoes the greatest excursion, or the diaphragm moves uniformly. The purpose of this study was to compare diaphragmatic excursion (during SV and PPV) in patients with chronic obstructive pulmonary disease (COPD) with patients having normal pulmonary function. Methods Twelve COPD patients and 12 normal control subjects were compared. Cross-table diaphragmatic fluoroscopy was performed while patients breathed spontaneously. After anesthetic induction and pharmacologic paralysis and during PPV, diaphragmatic fluoroscopy was repeated. For analytic purposes, the diaphragm was divided into three segments: top, middle, and bottom. Percentage of excursion of each segment during SV and PPV in normal subjects was compared with the percentage of excursion of each segment in patients with COPD. Results There was no significant difference in the pattern of regional diaphragmatic excursion (as a percentage of total excursion)—top, middle, bottom—when comparing COPD patients with control subjects during SV and PPV. In the control subjects, regional diaphragmatic excursion was 16 ± (5), 33 ± (5), 51 ± (4) during SV and 49 ± (13), 32 ± (6), 19 ± (9) during PPV. In COPD patients, regional diaphragmatic excursion was 18 ± (7), 34 ± (5), 49 ± (7) during SV and 47 ± (10), 32 ± (6), 21 ± (9) during PPV. Conclusion Regional diaphragmatic excursion in patients with COPD during SV and PPV is similar to that in persons with normal pulmonary function.

Effects of continuous positive-pressure breathing on functional residual capacity and arterial oxygenation during intra-abdominal operations: studies in man during nitrous oxide and d-tubocurarine anesthesia.

The effects of 0, 5, 10, and 15 cm H2O end-expiratory pressure (EEP) were studied in 24 patients receiving nitrous oxide– d-tubocurarine anesthesia for intra-abdominal operations. Functional residual capacity (FRC) of every patient was increased during continuous positive-pressure breathing (CPPB). Pao2 increased an average of 1.6 torr/cm H2O EEP in the 12 patients with the lowest Pao2s (<100 torr at zero EEP). Nonobese patients more than 50 years old showed the greatest improvement in Pao2. The other 12 patients (Pao2 > 100 torr at zero EEP) had variable changes in Pao2, averaging 0.2 torr/cm H2O EEP. No patient suffered an important decrease in Pao2 with CPPB. Clinical signs suggesting interference with cardiac output did not occur in the absence of blood loss.

Intravenous Δ9-tetrahydrocannabinol: Effects on Ventilatory Control and Cardiovascular Dynamics

Δ9-Tetrahydrocannabinol (THC), the active component of marijuana, was studied to determine whether it might be useful for preanesthetic medication. Ten healthy subjects received THC intravenously in logarithmically spaced incremental doses. Four subjects received a total cumulative dose of 135 μg/kg and four others, 201 μg/kg. Two of the ten subjects discontinued the study because of anxiety reactions. Ventilatory minute volume at a controlled elevated CO2 tension, 48 = 2 (SD) torr, changed minimally with THC, –0.49 1/min/50 per cent increase in dose. THC shifted the ventilatory response to CO2 2.7 torr dextrad at 20 1/min without a change in slope. Dose-related tachycardia was the most marked cardiovascular effect. Heart rates increased to more than 100/min in five of six subjects. Cardiac index increased from 4.04 = 0.62 1/min/m2before THC to 6.92 = 2.34 1/min/m2after 134 μg/kg. Mean arterial pressure increased slightly, and total peripheral resistance fell. The cardiovascular changes suggest betaadrenergic stimulation. Intense mental effects and anxiety prohibited higher THC doses.

Effects of Acute and Chronic Ethanol Administration on Isoflurane Requirement in Mice

Inspired isoflurane concentration for anesthetizing 50 percent of adult albino mice (ED50) was 1.33 percent (1.20 to 1.47, 95 percent confidence interval). Ethanol anesthetizing dose was 5.09 (4.74 to 5.47) gm./kg. intraperitoneally (I.P.). Twenty, 39, and 79 percent of this ethanol anesthetic dose reduced isoflurane ED50 by 0, 8, and 70 percent, respectively. Thus, acute combinations of ethanol and isoflurane are more effective than either alone but less than the expected sum.Mice receiving no other fluid than 10 percent alcohol developed cross-tolerance to isoflurane. After 10 days of continuous alcohol ingestion, isoflurane ED50 increased to 1.54 (1.36 to 1.75) and after 20 days to 1.69 (1.55 to 1.84) percent. Combined with 2 and 4 gm./kg. of alcohol I.P., isoflurane ED50 in these mice decreased to 1.34 (1.26 to 1.42) and 0.73 (0.62 to 0.85) percent. Cross-tolerance acquired by these alcohol-consuming mice persisted through 55 days after stopping alcohol (ED50 1.65 percent), but returned to control values after 80 days (1.32 percent).