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Biomedical subjects

J H Tinker

Publications and source records attributed to J H Tinker.

At least 73 records · Page 4Linked to original sources

Efficacy of dopamine, dobutamine, and epinephrine during emergence from cardiopulmonary bypass in man.

Hemodynamic effects of dobutamine and dopamine (both 5, 10, 15 microgram/kg/min) and epinephrine (0.04 microgram/kg/min) were studied immediately following cessation of cardiopulmonary bypass in 34 patients with preoperative evidence of left ventricular dysfunction. Significant increases in mean cardiac index were seen with dobutamine (15, 25, and 26% respectively), and epinephrine (30%). The largest increases occurred with dopamine (44, 53, and 64 percent respectively). Responses varied from patient to patient, however. Seven patients developed marked output increases without concomitant increases in arterial pressure, whereas seven others showed "satisfying" increases in arterial pressure without appreciable output increases. Heart rate increases were small and few arrhythmias were noted. We conclude that dopamine, epinephrine, and dobutamine all are effective inotropic agents during the immediate post-bypass period, with variations discussed in detail. None possess the disturbing chronotropic and arrhythmogenic effects of isoproterenol (previously studied). Efficacy of administration of inotropic drugs seems best assessed by serial output measurements during this period.

Arrhythmias, Cardiac↗

Perioperative myocardial infarction in patients with coronary artery disease with and without aorta--coronary artery bypass grafts.

The incidence of perioperative myocardial infarction (MI) was examined in 148 patients with known coronary artery disease (CAD) who underwent 226 noncardiac surgical procedures. In 168 operations in 99 patients who had prior coronary artery bypass grafting (CABG) there were no perioperative MI's whereas in the 49 patients who had not undergone prior CABG who underwent 58 noncardiac operations, there were three MI's (5 percent). The lower (p less than 0.02) incidence of perioperative MI in patients with CAD who had had prior CABG suggests a protective effect for subsequent noncardiac operation, which could not be explained by other differences in cardiac status between the groups. All three MI's occurred in patients with three-vessel CAD, evidence that this should be added to prior MI as a significant risk factor. The study indicates also that patients with prior CABG have less risk of MI during and following anesthesia and noncardiac operation than do patients without CABG who have had a previous MI.

Adult↗

The nonlinear responses of cerebral metabolism to low concentrations of halothane, enflurane, isoflurane, and thiopental.

The relationship between cerebral oxygen consumption (CMRO2) and anesthetic concentration has been assumed (based upon isolated measurements) to be approximately linear at concentrations less than 1 MAC. The shapes of the anesthetic dose-response curves for both CMRO2 and cerebral blood flow (CBF) were examined by multiple measurements made at small, progressive concentration increments from 0 to 2 MAC halothane (six dogs), enflurane (six dogs), and isoflurane (six dogs), and during a constant 23 mg/kg/hr infusion of thiopental (six dogs). The EEG was continuously recorded and changes in EEG patterns from "awake" to "anesthetic" were correlated with changes in anesthetic concentration, CBF, and CMRO2. The significance of changes in the slopes of regression lines for CMRO2 before, during and after changes in EEG patterns from "awake" to "anesthetic" were then determined. Contrary to previous inferences, CMRO2 dose-response curves were found to be nonlinear at anesthetic concentrations less than 1 MAC for all anesthetics studied. CMRO2 decreased precipitously until a stable "anesthetic" pattern was observed on the EEG; thereafter, CMRO2 decreased at a markedly reduced rate. The onset of this change occurred at concentrations well below MAC for the inhalational anesthetics. With the thiopental infusion, CMRO2 decreased most rapidly during the first 25 minutes. With halothane and enflurane, CBF was maximal during the period of transition in the EEG from an "awake" to an "anesthetic" pattern. CBF was elevated at all concentrations of isoflurane studied. CBF decreased rapidly during thiopental infusion until the EEG pattern changed from "awake" to "anesthetic" and then more slowly. The results demonstrate that the change in the EEG to an "anesthetic" pattern, which occurs at concentrations well below MAC, is accompanied by an abrupt metabolic depression. It is speculated that these events coincide with the onset of functional depression.

Animals↗

Anterior shift of the dominant EEG rhytham during anesthesia in the Java monkey: correlation with anesthetic potency.

EEG amplitude dominance in awake man is posterior. During EEG monitoring in patients, the authors observed the abrupt appearance of anterior amplitude dominance during induction of anesthesia with halothane, enflurane, or thiopental. This EEG change is coincident with loss of eyelid reflex and loss of ability to respond to command. This EEG change was studied with several anesthetics in five Java monkeys to determine alveolar anesthetic concentration at which it occurred and to observe the effects of various stimuli on it. EEG recordings were obtained after equilibration at each level with increasing concentrations of halothane, enflurane or isoflurane in oxygen and each agent again in 30 per cent N2O, in separate experiments in the same animals. EEG amplitude dominance became anterior in each animal with each anesthetic and combination at concentrations less than MAC, which was also determined in the same experiments. At lower concentrations, stimulation at equilibrated anesthetic concentrations resulted in abrupt EEG return to posterior amplitude dominance. The end-tidal anesthetic concentration at which persistence of anterior EEG dominance was seen after stimulation was approximately 0.4 MAC for each anesthetic and combination tested. This is interpreted as support for physical solution-lipid solubility theories of anesthetic action. In addition, an EEG change common to various anesthetics may increase the clinical usefulness of EEG monitoring. It is speculated that this EEG change may signal loss of awareness. If so, observance of sustained anterior EEG amplitude dominance may provide assurance of obliteration of awareness during anesthesia.

Anesthetics↗

Elevation of plasma bromide levels in patients following halothane anesthesia: Time correlation with total halothane dosage.

Plasma bromide concentrations of 25 patients were determined before and after halothane anesthesia. A high correlation (r greater than .70) between exposure to halothane in MAC-hours and plasma bromide levels 24, 48 and 72 hours later was found. Peak bromide levels occurred 48-72 hours after anesthesia in 16 patients (64 per cent), and ranged from 52 mug/ml (0.65 mEq/l) to 180 mug/mo (2.25 mEq/l). Bromide levels remained elevated for prolonged periods (at least 22 days in some patients). Possible sedative or psychoactive effects of increased plasma bromide levels are discussed.

Bromides↗

Dobutamine for inotropic support during emergence from cardiopulmonary bypass.

Dobutamine, a recently introduced derivative of dopamine, is reported to retain inotropic properties with less pronounced chronotropic and arrhythmogenic effects than isoproterenol. The drug was evaluated in two doses, 5 mug/kg/min and 10 mug/kg/min, in two groups of ten patients each, during emergence from cardiopulmonary bypass. A third group of five patients was studied similarly with isoproterenol, 0.02 mug/kg/min. Cardiac index increased 16 and 28 per cent eith the two doses of dobutamine, respectively, and 9 per cent with isoproterenol. Heart rate, in contrast, increased 6 and 15 per cent with dobutamine (not significant) and 44 per cent with isoproterenol (significant). Dobutamine seemed to associated with fewer arrhythmias than isoproterenol. It is concluded that dobutamine, 5-10 mug/kg/min, is suitable for use during emergence from cardiopulmonary bypass and may possess advantages over isoproterenol.

Adult↗

Sodium nitroprusside: pharmacology, toxicology and therapeutics.

Sodium nitroprusside is a potent, effective, and readily reversible direct vasodilating agent. It is broken down by hemoglobin into cyanide, which is in part detoxified by liver and kidney to thiocyanate. Some cyanide, especially in nitroprusside- "resistant" individuals who need large amounts of the drug, appears to remain free to cause cyanide poisoning. Patients requiring inordinate amounts probably should not continue to receive the drug, although maximum dosage limits for long-term therapy are not established. Blood thiocyanate levels do not indicate the extent to which free cyanide is limiting oxygen utilization in essential tissue, nor do blood cyanide levels. Metabolic acidosis, elevated lactate levels, elevated lactate/pyruvate ratios, and elevated mixed venous blood oxygen content are at present the best indications of the presence of cyanide poisoning during nitroprusside administration. Nitroprusside appears useful for induction of hypotension during surgery, and for treatment of hypertensive emergencies from all causes, although continuance for more than a few days is probably unwise. The reductions of cardiac afterload and ventricular filling pressure by nitroprusside appear useful in treatment of severe myocardial failure or infarction, but studies of myocardial cyanide toxicity are needed before complete acceptance of this therapy is warranted. Initial dose rates between 0.5 and 1.5 mug/kg/min are recommended only as starting points for very careful titration. Total projected intra-operative dosage should be calculated as quickly as possible and should not exceed 3-3.5 mg/kg. It is hoped that future studies will reveal the maximum dose of nitroprusside that can safely be metabolized in a 24-hour period, and may indicate that cofactors of rhodanase such as thiosulfate, or cobalamins such as hydroxocobalamin, can be administered with nitroprusside to prevent cyanide poisoning.

Anesthesia, General↗