William K. Hamilton

Multicenter Study of General Anesthesia. II. Results

A prospective, stratified, randomized clinical trial of the safety and efficacy of four general anesthetic agents (enflurane, fentanyl, halothane, and isoflurane) was conducted in 17,201 patients (study population). Patients were studied before, during, and after anesthesia for up to 7 days. Nineteen patients died (0.11%), and in seven of these (0.04%) the anesthetic may have been a contributing factor. The rates of death, myocardial infarction, and stroke in the study population were so low (less than 0.15%) that no conclusions regarding the relative rates of these outcomes among the four anesthetic agents could be reached. The rates of 16 of 66 types of adverse outcomes in the study population were significantly different among the four study agents. Most of these outcomes were minor. However, severe ventricular arrhythmia (P less than 10(-6)) was more common with halothane, severe hypertension (P less than 10(-6)) and severe bronchospasm (P = 0.028) were more common with fentanyl, and severe tachycardia (P = 0.001) was more common with isoflurane. Recovery from anesthesia during the first 30 min was slowest in those patients who received halothane (P less than or equal to 0.001). In addition, patients who received fentanyl experienced less pain during the first hour in the recovery room (P less than 10(-6)). In conclusion, clinically important differences do exist for some outcomes among the four study agents.

A Comparison of Arterial Gas Tensions, Radiographs and Physical Examination

A study was made on 27 patients undergoing elective surgery. Preoperative and postoperative chest roentgenograms and arterial blood-gas studies were compared. Temperature, pulse rate, respiratory frequency, and clinical observations were noted. A high incidence (19 of 27) of low oxygen tensions occurring with normal or increased ventilation was observed. No correlation could be established between roentgen-ray or clinical finding on the one hand and laboratory findings on the other. The concept is presented that the findings represent “miliary” atelectasis occurring so diffusely as to escape detection by physical or radiographic examination. More severe reductions in ventilation-perfusion ratios and complete atelectasis are best considered as a continuum since they produce the same effects and may not be distinguishable. Postoperative patients present a pattern of near constant tidal volume without sighing, known to produce these changes. That these changes occur without airway obstruction is suggested by improvement with deep breathing. Although appearing benign, decreases in oxygen tension may be of serious magnitude.

Succinylcholine-induced hyperkalemia in patients with renal failure?

The effect of succinylcholine, 1 mg/kg, iv, on serum potassium was studied in ten patients without and ten patients with renal failure. Increases in serum potassium after succinylcholine in patients with renal failure were not significantly different from those in patients without renal failure. The largest increase was 0.7 mEq/l. Absence of myoglobinemia, myoglobinuria, and large increases in serum creatine phosphokinase activity suggest that there was no significant skeletal muscle damage. We conclude that succinylcholine in this dose is not contraindicated in patients with renal failure in the absence of uremic neuropathy.

Multicenter study of general anesthesia. I. Design and patient demography.

A prospective randomized clinical trial of enflurane, fentanyl, halothane, and isoflurane is described. The 17,201 patients were stratified into two groups (preanesthetic medication and no preanesthetic medication) and were randomized to one of four study agents: enflurane, fentanyl, halothane, and isoflurane. Fifteen university-affiliated hospitals in the United States and Canada participated. All patients were first assessed preoperatively. Data were collected during anesthesia, in the immediate recovery period, and for up to 7 days after anesthesia/surgery. The mean age of the patients was 43 yr, the mean height 167 cm, and the mean weight 68 kg. Sixty-five percent of patients were female. In this study 90.7% of patients were classified as ASA Physical Status 1 or 2, and 34.7% of patients smoked. It is concluded that pooling of data across institutions was valid and does allow determination of the efficacy and relative safety of the four study agents.

Effect of Nitrous Oxide on Middle Ear Mechanics and Hearing Acuity

Hearing loss was observed in a few patients following nitrous oxide anesthesia. We hypothesized that the defect could result from changes In middle car pressure incident to increased airway pressure and/or differential solubility of nitrous oxide and nitrogen. Consequently, we tested middle car mechanics (Zwislocki Acoustic Bridge) and hearing acuity before, during and after breathing nitrous oxide and nonnitrous oxide mixtures, both with and without positive pharyngeal airway pressure. Decreased compliance and increased resistance occurred in all instances but was greater when nitrous oxide was present. Positive airway pressure appeared to be without effect The observed changes persisted only in patients receiving N2O anesthesia for adenotonsillectomy. A conductivetype hearing loss of short duration was also noted in this group.

An in vivo study of halothane uptake and elimination in the rat brain with fluorine nuclear magnetic resonance spectroscopy

A recent NMR study reported the elimination of halothane from the brain of rabbits to be ten times slower than expected, based on known anesthetic solubility and cerebral blood flow. The authors conducted a study in five rats using fluorine nuclear magnetic resonance (NMR) spectroscopy to see if major pharmacokinetic discrepancies are associated with the uptake, maintenance, and elimination of halothane from the brain. The rats underwent a 60-min period of halothane anesthesia. They employed a spatially selective NMR spectroscopy technique known as surface coil “depth-pulsing” to assure that the fluorine NMR signals originated in brain tissue, and not in the scalp, muscle, adipose tissue, and bone marrow that surround the brain. After the inspired anesthetic concentration was decreased to zero, the amplitude of the fluorine NMR signal decreased to 40% of its maximum value within 34 ± 8.0 minutes (n = 5), rather than after 7 h as in the recent study, where the fluorine signal may have contained substantial contributions from metabolites tissues outside the brain. Fluorine was barely detectable in all of the animals 90 min after stopping the administration of halothane. The authors results are in agreement with model calculations the several other investigations.

The Relation of Postoperative Atelectasis to the Solubility of Gas Filling the Lungs at Termination of Anesthesia

This study was undertaken to test the hypothesis that thorough ventilation of lungs with gas of low solubility at the termination of anesthesia protects against postoperative atelectasis. Two similar groups of patients were studied. Each group received a 10-minute period of test gas administration at termination of anesthesia, one receiving room air, the other 100 per cent oxygen, following which all patients breathed room air for the remainder of their convalescence. Atelectasis was defined as a fall in PaO2 from preoperative to postoperative values without generalized hypoventilation or decreased inspired oxygen concentration. Arterial blood studies were performed 1-hour and 24-hours postoperatively. In addition, the clinical records of all patients were scrutinized for evidence of postoperative pulmonary complications. No difference in incidence of atelectasis or pulmonary complications was detected in either group. The hypothesis was, therefore, rejected.

Twelfth Annual Becton, Dickinson and Company Oscar Schwidetzky Memorial Lecture

T A faculty meeting recently a colleague A expressed to me the simplicity of my job as chairman of the Department of Anesthesia. In what I hope was a joking manner, he said, “You need only know a bit of pharmacology, how to measure blood pressure, and then find enough people to run your operating rooms.” After commenting about his lack of insight, I dismissed his remarks. Subsequently, I rethought them and realized that in the broadest sense he was absolutely correct. Generously interpreted, his remarks cover an extremely broad area. Certainly we are deeply involved in pharmacology, and we are constantly committed to the measurement and evaluation of blood pressure and its components. Our consuming interest in manpower today says much as to the most important of these 3the personnel to carry out the tasks we have. These 3 problems are sufficiently complex to challenge the best of us. At least my colleague’s remarks provide me with infinite leeway when pressed to select a title for a presentation such as this.