Arnold Aberman, MD.

When the United States embarked on its effort to provide universal health insurance, the Canadian Medicare System was cited as a possible model for American health care. Often touted as an example of low-cost, high quality medicine, the Canadian system has mirrored the problems of health care across its southern border. With rocketing health care expenditures and financing having largely been decentralized to the individual provinces, local officials have struggled to cut costs and services. A central focus of these efforts has been a move to decrease the numbers of physicians, most notably a 10% decrease in medical school class size in 1993. While some Western provinces have experimented with the privatization of health care, the Canadian system still remains the epitome of government operated fee-for-service medicine. Given the likelihood of dramatic change in the American Medicare system, Canadian academic centers offer a unique perspective on the impact of capitation, evolving relationships with government payors, and the flip side of market oriented reforms. At the helm of one of Canada's largest schools is Arnold Aberman, MD, dean of the University of Toronto Faculty of Medicine. Born in Montreal, Quebec, Aberman received his MD from McGill University, but then did his residency both in Canada and the US, followed by a pulmonary fellowship at Albert Einstein College of Medicine and the Cardiovascular Research Institute of the University of California, San Francisco. Interviewed at his office in Toronto, Aberman reflected on the trials and tribulations confronting medicine on both sides of the 48th parallel.

Oxygen transport and oxygen consumption in critically ill patients.

We performed a prospective study in 28 critically ill patients to document variations in oxygen consumption and oxygen transport that occur spontaneously, without any experimental interventions designed to change DO2. Each study consisted of from three to five sets of measurements, including thermal dilution cardiac output and blood gases. The interval between any two measurements ranged from 20 to 60 minutes. It was concluded that changes in VO2 and DO2 can occur spontaneously in patients with normal lactates, even when there are no experimental interventions. These spontaneous changes in VO2 and DO2 make it extremely difficult to interpret studies that demonstrate that VO2 is transport-limited. The changes in DO2 can likely be explained by changes in oxygen demand.

Clarification of the effects of changes in P50 on oxygen transport.

In summary, a shift to the right in the O2-Hb curve in patients with anemia and decreased cardiac output and normal PaO2 will increase PvO2. This shift is mediated through increases in red cell 2,3-DPG. The stimulus for the increase in 2,3-DPG is most likely due to the decrease in SvO2. In hypoxemia caused by a decreased PAO2 (altitude), an increase in P50 may have no effect on PvO2 and in fact if the PaO2 is low enough, a left shift may increase the PvO2. Animals and man most successful at adapting to high altitudes reflect this fundamental physiological effect and have a left-shifted curve. This decrease in P50 is probably related to an intrinsic property of the hemoglobin and not to changes in 2,3-DPG. In hypoxemia caused by shunt, an increase in P50 increase the PvO2 regardless of the PaO2. Patients with congenital cyanotic heart disease have an increased P50 mediated through an increase in 2,3-DPG.

Silicon compounds as substrates and inhibitors of acetylcholinesterase.

Several trimethylsilyl derivatives were found to be ligands of acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7): trimethylsilylethyl acetate (III) and trimethylsilylmethyl acetate (V) are substrates of the enzyme, whereas trimethylsilylethanol (VIII) is a competitive inhibitor. The silicon compounds have kinetic parameters similar to those of their carbon analogues, except for trimethylsilylmethyl acetate, which is a substrate of acetylcholinesterase, whereas its carbon analogue is not susceptible to enzymic hydrolysis.

Continuous monitoring of mixed venous oxygen saturation in hemodynamically unstable patients.

A balloon-tipped catheter has recently become available which, when placed in the pulmonary artery, in addition to enabling the usual measurements of pulmonary arterial pressure, pulmonary capillary wedge pressure, and cardiac output by thermodilution, measures mixed venous oxygen saturation (SvO2) by spectrophotometry. Unlike the measurement of cardiac output by thermodilution, which is done intermittently, the continuous measurement of SvO2 is an effective method of monitoring hemodynamically unstable patients, since changes in cardiac output will immediately become apparent via a corresponding change in SvO2. This is of particular benefit in patients in whom knowledge of the immediate effects of therapy is important. It is also of value in assessing the time of onset of action and duration of action when a cardioactive drug is given to increase cardiac output. We suggest that monitoring SvO2 will provide an earlier indication of the effect of both diagnostic and therapeutic interventions and, therefore, will improve our management in such patients.

The management of medical emergencies in otolaryngology.

We have tried to present the clinically relevant medical problems that otolaryngologists may face and to suggest management plans. Emergencies are divided by specific problems into general chemical, metabolic, and surgical categories. Space limitation allows only discussion of the most important problems but will hopefully stimulate interest in the remainder.

Mixed venous oxygen saturation. Its role in the assessment of the critically ill patient.

Except in the presence of left to right shunts, slow aspiration from the distal lumen of a catheter placed in the pulmonary artery can provide a sample of mixed venous blood. The oxygen saturation of such a sample (SvO2) is dependent on arterial oxygen saturation, hemoglobin concentration, cardiac output, and tissue oxygen demands. A fall in SvO2 usually implies anemia, arterial oxygen desaturation, and/or decreased cardiac output; however, a normal or high value does not exclude such disturbances. When employed in conjunction with the other indicators of tissue oxygenation available in an intensive care unit, SvO2 can be useful as a guide for both prognosis and urgency of therapy.

Selected developments in the understanding of diabetic ketoacidosis.

Advances in the understanding of diabetic ketoacidosis have contributed to the recent decrease in the morbidity and mortality associated with this condition. The role of counterregulatory hormones in its pathogenesis is considerable, but insulin deficiency is necessary for diabetic ketoacidosis to develop. Therapy begins with identification and treatment of the factors precipitating ketosis. Isotonic saline is the fluid of choice for initial intravenous therapy; subsequently 0.45% saline is appropriate. Sodium bicarbonate is necessary only if the arterial pH is less than 7.1, and phosphate should be given only when the serum phosphate level is below 0.5 mg/dl (0.16 mmol/l). Factors other than pH are important in causing the hyperkalemia so commonly seen at the time of presentation, but whether or not hyperkalemia is present potassium supplementation is almost always necessary and should be given as long as the urinary output is adequate. Intravenous doses of insulin as low as 5 to 15 U/h are sufficient in most cases, but the occasional patient will require larger amounts. Close clinical and biochemical monitoring is necessary for successful management.

Changes in blood P50. Effects on oxygen delivery when arterial hypoxemia is due to shunting.

The theoretic effect of increased values for the oxygen pressure at an oxygen saturation of 50 percent on oxygen delivery in arterial hypoxemia due to right-to-left shunting was analyzed using a mathematical model of the oxygen-hemoglobin equilibrium curve. We found that, regardless of the size of the shunt, a rightward shift of the curve resulted in increased mixed venous oxygen tension, increased arterial oxygen pressure, and, hence, a decreased alveolar-arterial oxygen pressure difference compared to the standard curve (hemoglobin level, cardiac output, and oxygen consumption remaining constant).

The hypoxic ventilatory response in patients with high-affinity hemoglobin.

In an attempt to determine whether PO2 or O2 saturation is stimulus for the hypoxic ventilatory drive, we studied 2 brothers with the high O2 affinity hemoglobin Ranier (P50 approximately equal to 12 mm Hg). The ventilatory response to PO2 was normal. The O2 saturation did decrease slightly, and the ventilatory response to the decrease in O2 saturation was greatly exaggerated. We conclude that these findings are consistent with either of 2 possibilities: (1) that PO2 provides the stimulus to the hypoxic ventilatory response, or (2) that patients with high-affinity hemoglobin have increased sensitivity to arterial O2 desaturation.

Lactic acidosis presenting as acute respiratory failure.

Two patients with chronic obstructive pulmonary disease and chronic respiratory failure who developed acute lactic acidosis are described. The initial arterial blood gas values in both patients had the pattern of acute respiratory failure with no metabolic disturbance. It was the calculation of the "anion gap" that provided the clue to the presence of metabolic acidosis, which was then confirmed with the measurement of serum lactate. We emphasize that complete laboratory data and clinical information may be essential for accurate diagnosis and understanding of mixed acid-base disturbances and, hence, for initiation of appropriate treatment.

Changes in pulmonary mechanics and gas exchange following thoracocentesis.

In nine patients with large pleural effusions, we studied the changes in pulmonary mechanics and gas exchange that occurred in the first three hours following removal of 600 to 1,800 ml of fluid by thoracocentesis. There was a small but significant increase in the functional residual capacity and total lung capacity but no change in residual volume and vital capacity. Calculated pulmonary shunt fraction did not change. We could not relate the subjective improvements noted by patients after thoracocentesis to the changes in pulmonary volumes or blood gas levels.

Abnormalities in pulmonary function after brief exposure to toxic metal fumes.

A 26-year-old welder became ill after exposure to zinc and cadmium fumes at work. His initial clinical course was consistent with that of metal fume fever, but persistence of symptoms and signs beyond the usual duration in this condition led to suspicion of a toxic pulmonary reaction to cadmium. The finding of high percentages of both metals in the urine confirmed this diagnosis. Pulmonary function tests showed restriction of lung volumes, with increased elastic recoil and reduced diffusion, but no evidence of airways obstruction. Chest roentgenograms indicated central pulmonary edema, which cleared in 6 days. Follow-up assessment 2 years later showed incomplete improvement of the restrictive ventilatory defect.

Crossover PO2, a measure of the variable effect of increased P50 on mixed venous PO2.

The effect on mixed venous Po2 of a shift to the right in the oxygen hemoglobin equilibrium curve, without a change in either arterial Po2 or oxygen uptake, depends on the difference between the arterial oxygen saturation differences and the venous oxygen saturation differences of the shifted and standard curves. For every rightward-shifted oxygen hemoglobin equilibrium curve there is a Po2, which I call the crossover Po2, at which mixed venous Po2 is the same for the standard and shifted curve. Crossover Po2 depends upon the hemoglobin concentration and the arteriovenous oxygen content difference. I demonstrate that in hypoxemic patients, especially if anemia and shock are present, the arterial Po2 may be less than the crossover Po2; thus, an increased blood P50, the Po2 at oxygen saturation of 50 per cent (pH 7.40, temperature 37 degrees C), cannot increase the mixed venous Po2.

In vitro changes in blood P50 and erythrocyte 2,3-diphosphoglycerate concentration.

We studied in vitro changes in P50 and erythrocyte 2,3-diphosphoglycerate concentration occurring in blood 2 to 8 h after venipuncture. When blood was incubated at 37 degrees C, significant decreases in P50 were observed at 2, 4, and 8 hr. Such a change was significantly less when blood was kept at 4 degrees C. The rate of decrease in P50 was not changed when pH was altered by adding either lactic acid or sodium bicarbonate to the blood before incubation at 37 degrees C for 2 h. The erythrocyte 2,3-diphosphoglycerate concentration of blood incubated at 37 degrees C did not change by 2 h, but had significantly decreased by 4 h. To avoid in vitro changes, we recommend that P50 be determined as soon as possible for blood sampling.