Dennis L. Fung

Optimal frequency ranges for extracting information on autonomic activity from the heart rate spectrogram.

Heart rate variability spectrum analysis provides useful quantitative indices of neural control of the SA node. This method is attractive both for its simplicity and the lack of invasive instrumentation, particularly for human investigation. The differing spectral characteristics of parasympathetic and sympathetic control of heart rate allows separate measurement. However, there are widely varying opinions as to the appropriate frequency bands to represent these two inputs. We compared the heart rate variability spectra of 16 humans in supine and upright positions. Adequate measures of parasympathetic or sympathetic activity change should correlate respectively inversely or directly with heart rate change. Frequently used spectral measures of sympathetic activation did not correlate with heart rate changes. With optimization of frequency bands, we found that restricting the sympathetic band to frequencies below 0.1 Hz and above 0.05 Hz (0.055 to either 0.086-0.098 Hz), and dividing by total spectral amplitude 0.004-0.5 Hz (to account for parasympathetic fluctuations within the sympathetic band) produced the best results. The parasympathetic band was best from 0.1 Hz to a frequency greater than that of the respiratory sinus arrhythmia. The optimization method detailed here is easily applied to circumstances other than active orthostasis, and should provide a means of empirically determining useful frequency limits.

Fentanyl Pharmacokinetics in Awake Volunteers

A single intravenous dose of fentanyl (either 2 or 4 micrograms/kg body weight) was given to 13 healthy, young volunteer subjects. Serum fentanyl concentration decreased in a triexponential pattern. The terminal half-times were 750 and 853 minutes, respectively. A three-compartment, open, mammillary model is proposed for fentanyl kinetics.

Shock due to protamine hypersensitivity.

A 56-year-old man developed shock and skin flush minutes after the slow administration of 25 mg of protamine sulfate. Prior protamine exposure from treatment of his diabetes with isophane insulin (NPH insulin) was believed to have sensitized this patient to protamine. A review of three other cases of reaction to low doses of protamine revealed that in each, the patient had previously been exposed to protamine. If heparin is used in a patient with a history of treatment of diabetes with isophane insulin, the heparin should be allowed to spontaneously reverse, without pharmacological assistance if possible. If protamine must be used, the patient should be pretreated with glucocorticoid and vasopressors should be immediately available.

The onset of disuse-related potassium efflux to succinylcholine.

Disuse atrophy of skeletal muscle produces resistance to nondepolarizing relaxants and increased potassium efflux after the administration of succinylcholine. These changes appear to be due to development of perijunctional and/or extrajunctional receptors (up-regulation). In this study, the authors searched for the earliest detectable appearance of increased potassium efflux in beagles in whom disuse atrophy was simulated. Seven beagles underwent unilateral cast immobilization of a hind limb. Between 4 and 42 days, they periodically received succinylcholine 0.25 mg/kg while anesthetized with thiamylal and nitrous oxide. Sequential bilateral femoral venous samples showed that the casted limb did not manifest potassium release greater than the upper limit of normal (1 mEq/l) until cast immobilization periods of 14 days or longer. When this occurred, the increase in the potassium concentration in the femoral venous blood of the casted limb exceeded that from the noncasted limb by at least 0.7 mEq/l (P less than 0.01). The range for the onset of this response after casting was 14-42 days, the mean 27.2 days, and the standard deviation 9.8 days. These findings imply that up-regulation of skeletal muscle receptors, associated with exaggerated potassium efflux after administration of succinylcholine, is dependent on progressive development of extrajunctional receptors over surface membrane areas beyond the endplate.

Epidural anesthesia in Eisenmenger's syndrome: a case report.

&NA; A 22‐year‐old woman with Eisenmengers syndrome and significant right‐to‐left shunt was anesthetized for tubal ligation by a continuous lumbar epidural technic. Changes in vital signs, respiratory parameters, and cardiac function were minimal, suggesting to the authors that this procedure should be considered for patients with intracardiac shunts and pulmonary hypertension who require lower abdominal operations.

Emergency anesthesia for asthma patients.

Over 20 years ago, Converse and Smotrilla reported that intraoperative cardiac arrest and mortality were more likely to occur in asthmatic patients than in nonasthmatics. 1 In 1963, Gold reported on the operative course in 196 asthmatic patients. 2 There were no cardiac arrests in his series, but he found a 24% incidence of operative and postoperative respiratory complications compared to 14% in nonasthmatic patients. In a retrospective study of 54 aspirinsensitive asthmatics, 3 the incidence of tachycardia greater than 140/rain was 11%, and 50% of the patients developed postoperative wheezing. Tachycardia and arrhythmias (supraventricutar tachycardia, bigeminy, and multifocal premature ventricular contractions) were related to the use of aminophylline, ephedrine, or epinephrine. Of particular concern to anesthetists is the possibility of inducing severe bronchospasm by endotracheal intubation or as a response to anesthetic drugs. The control of airway reactivity and the influence of anesthetic drugs on the airway have been reviewed recently by Aviado 4 and Hirshman. s Bronchospasm has been reported following almost every drug used in anesthesia. Mechanisms include allergic (anaphylactic) reactions, histamine (anaphylactoid) release, parasympathetic (irritant) reflex, and beta-adrenergic block.

The changing pharmacodynamics of metocurine identify the onset and offset of canine gastrocnemius disuse atrophy

Background Immobilization of skeletal muscle results in disuse atrophy and resistance to nondepolarizing muscle relaxants. We studied the pharmacodynamics of metocurine (MTC) to identify the development and recovery of disuse-related resistance to MTC.

Bilateral Phrenic-nerve Block in Man: Technical Problems and Respiratory Effects

Attempts were made to produce bilateral phrenic nerve blocks in 11 normal volunteers in order to evaluate the respiratory effects. The study demonstrated that selective bilateral block of the phrenic nerves is difficult to achieve, even with the use of a nerve stimulator, because the sympathetic, vagus, and recurrent laryngeal nerves may be blocked inadvertently. The results in three subjects with evidence of pure bilateral phrenic nerve blocks indicated that in the sitting position ventilation is not impared, inspirtory capacity is reduced 25 per cent, and there is an altered sensation in breathing as well as breath holding. The subjects became acutely aware of their breathing, which was deeper and slower. The feeling of discomfort during breath-holding was less intense, and thus more tolerable, during phrenic-nerve block.

Predicting cardiac autonomic neuropathy in type I (insulin-dependent) diabetes mellitus

A total of 24 subjects with type I insulin-dependent diabetes mellitus were studied. Cardiac parasympathetic function was measured by supine heart rate variability (HRV) in the respiratory frequency 0.10–0.50 Hz and the sympathetic index was measured as the ratio of HRV between 0.055 and 0.098 Hz to that between 0.004 and 0.5 Hz. Factors assessing diabetic control and complications, and factors unrelated to diabetes but possibly influencing HRV, were recorded. Association with depressed HRV was assessed with correlation, and prediction of depressed HRV was determined with multiple regression. Factors associated with depressed HRV but not independently predictive were renal dysfunction and elevated thyroid stimulating hormone. Elevated glycosylated haemoglobin was not significantly correlated with depressed HRV. Four factors (presence of diabetic retinopathy, male gender, duration of diabetes and increasing age) were significant in the regression and sufficed to predict 81% of the sample variance. The relative weights (β) were −0.65, 0.40, −0.40 and 0.26, respectively. Supine sympathetic index was not sufficient to demonstrate sympathetic dysfunction. It is proposed that the regression model may be used to identify patients likely to have cardiac parasympathetic autonomic dysfunction.

Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles: exaggerated resistance to metocurine in gastrocnemius muscle.

BACKGROUND Patients in the intensive care unit may have muscle weakness in the recovery phase, and disuse atrophy may play a role in this weakness. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation. METHODS Six dogs were anesthetized with pentobarbital to a sufficient depth that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks. Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 microg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NONMEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment. RESULTS The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716+/-1,208 ng/ml (mean +/- SD), which was significantly different from 257+/-34 ng/ml, the value on day 0. There were no pharmacokinetic differences. CONCLUSION The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.