Oxygen transport, consumption and utilization during barbiturate intoxication.

Factors related to oxygen availability and requirements were measured on 51 occasions in 14 patients intoxicated with short-acting barbiturates. Patients had no clinical signs of circulatory shock. The cardiac index was normal (3.4 +/- 1.1 1/min/m2) but there was a slight decrease of the mean arterial oxygen content (17.2 +/- 3.0 ml/100 ml). Oxygen transport was normal (571 +/- 199 ml/min/m2). However, the arteriovenous oxygen differences were decreased (3.4 +/- 1.0 ml/100 ml). Oxygen consumption was reduced (110 +/- 42 ml/min/m2) and the oxygen extraction ratio (oxygen consumption/oxygen transport) was decreased (0.20 +/- 0.05), thus confirming a decreased oxygen utilization. Arterial concentration of lactate was normal. Accordingly the observed decrease in oxygen consumption was related to a reduction in oxygen requirements during barbiturate intoxication rather than due to an imbalance between availability and metabolic requirements for oxygen.

Abnormal temperature control after intoxication with short-acting barbiturates.

Changes in rectal and toe temperatures were measured in 16 patients who had been intoxicated with short-acting barbiturates. The lowest temperatures observed in the group of 16 patients averaged 35.5 +/- 2.0 degrees C. In 11 patients, the interval between intoxication and admission was documented. There was a significant correlation (r = 0.83) between the time of estimated intoxication and hypothermia. Patients who were admitted soon after the ingestion of the barbiturates had the lowest rectal temperatures. These observations indicate that hypothermia is a usual clinical sign in the initial period after intoxication with a short-acting barbiturate. Except for 2 patients, rectal temperature exceeded 38 degrees C during the interval of recovery with the maximum rectal temperature averaging 39.0 +/- 0.8 degrees C. Hyperthermia was not related to infection of the airways, lungs, urinary tract, or bloodstream. In 11 patients, pathogenic organisms were recovered from the airway and/or urine, but there was no difference in the highest rectal temperature in these patients (39.0 +/- 0.9 degrees C) when compared with 5 patients from whom no pathogenic organisms were recovered (39.2 +/- 0.7 degrees C). Accordingly, there was no evidence that hyperthermia was due to infection. The skin temperatures of the ventrum of the first toe were not typically decreased during hypothermia. To the contrary, increases in skin temperatures were often observed during hypothermia. These observations provide evidence of altered thermoregulation with increased surface heat loss accounting for the hypothermia in the early course and heat conservation with hyperthermia during the later course of intoxication by short-acting barbiturates.

The measurement of the work of breathing for the clinical assessment of ventilator dependence.

The work of breathing was measured in 10 normal subjects and in 28 critically ill patients with acute complications of obstructive pulmonary disease treated with assisted ventilation. The measurement of the work of breathing was found to be a useful objective variable for determining the capability for independent ventilation. Dependence on mechanical ventilation was observed when the respiratory work was greater than or equal to 1.7 kg-m/min. Patients were ordinarily capable of spontaneous ventilation when the respiratory work was less than or equal to 1.0 kg-m/min. Discontinuation of assisted ventilation was likely to be successful in those patients whose respiratory work was less than or equal to 1.5 kg-m/min if the patient was able to increase and maintain his work capability by a factor of two when breathing against an inspiratory resistance of 5 cm H2O for 10 min. Failure to increase the respiratory work when breathing against an inspiratory resistance indicated limitations in respiratory mechanics and was associated with the need for prolonged assisted ventilation. The measurement of the work of breathing against an inspiratory resistance of 5 cm H2O was useful in the identification and quantification of ventilatory reserve in patients with obstructive pulmonary disease.

Afterload reduction with phentolamine in patients with acute pulmonary edema.

Phentolamine in amounts of 10 to 40 microgram/kg/min was infused intravenously for the emergency treatment of acute pulmonary edema due to left ventricular failure. Fourteen patients with arteriosclerotic heart disease, ranging in age from 52 to 87 years, had clinical and roentgenographic signs of pulmonary edema. The pulmonary artery wedge pressure was increased to an average of 24 mm Hg and the cardiac index was decreased to 1.9 liters/min/m2 or less prior to the administration of phentolamine. A reduction in the pulmonary artery wedge pressure to 14 mm Hg and an increase in the cardiac index to 2.5 liters/min/m2 was observed in response to this alpha adrenergic blocking agent. Reduction in peripheral resistance with phentolamine was associated with reversal of pulmonary edema.

Bacterial shock.

Bacterial shock due to Gram-negative bacilli is best managed by prompt control of the infection with appropriate antibiotics and surgical drainage or excision. Corticosteroids for purposes of controlling systemic reactions to bacteria and their toxins constitute adjunctive therapy. Volume repletion and respiratory support may be of the greatest importance for temporary support of these critically ill patients. Vasoactive drugs including dopamine and isoproterenol should be used very sparingly and only as very temporary expedients.

Relationship between pulmonary hemodynamics and arterial pH and carbon dioxide tension in critically ill patients.

To ascertain the clinical significance of derangements in arterial pH and arterial carbon dioxide tension (PaCO2) in modifying pulmonary arterial pressures and pulmonary vascular resistance in critically ill patients, the relationship between these two sets of variables was evaluated in 75 patients. No significant differences in pulmonary hemodynamic values were found among patients with acidemia, a normal pH, or alkalemia, even at extreme pH values; and there was no consistent relationship between PaCO2 and each of the pulmonary hemodynamic measurements. In patients who initially had a normal pH but subsequently developed acidemia or alkalemia, there was also no significant correlation between changes in pH and pulmonary hemodynamic values. We conclude that abnormalities of pulmonary hemodynamic values in seriously ill patients are usually due to factors other than acid-base derangements. Of practical importance is the observation that the predictability of the pulmonary arterial wedge pressure from the pulmonary arterial diastolic pressure is not invalidated by acid-base disturbances.

Pulmonary edema during volume infusion.

The relationship between left ventricular filling pressure and plasma colloid osmotic pressure to pulmonary edema was examined in a group of 37 patients, the majority of whom were hypovolemic. Sixteen patients developed pulmonary edema during fluid infusion. In the 21 patients who did not develop pulmonary edema, the left ventricular filling pressure was slightly elevated but the colloid osmotic pressure was not reduced. The majority of these patients were treated with colloid solutions (group I). In five of the 16 patients who developed pulmonary edema, the left ventricular filling pressure was elevated and there was no reduction in the plasma colloid osmotic pressure. These patients received only colloids (group II). In the other 11 patients who developed pulmonary edema, the left ventricular filling pressure was normal but the plasma colloid osmotic pressure was reduced to 16 +/- 2 torr (group III). The colloid osmotic pressure in this group was significantly less than in the other two groups (P less than 0.01). Most of these patients received large volumes of crystalloid solutions. After administration of furosemide, clearing of pulmonary edema in this group was associated with normalization of the plasma colloid osmotic pressure. Infusion of large volumes of crystalloids in hypovolemic patients can be hazardous, for reduction of the plasma colloid osmotic pressure may predispose to the development of pulmonary edema even when the left ventricular filling pressure remains normal.

Oxygen delivery, anoxic metabolism and hemoglobin-oxygen affinity (P50) in patients with acute myocardial infarction and shock.

Changes in systemic oxygen delivery after acute myocardial infarction were investigated in 21 patients. In seven patients with shock, circulatory failure was characterized by a significant reduction in cardiac index, a decrease in oxygen transport and oxygen consumption and an increase in concentration of blood lactate; a decrease in the affinity of hemoglobin for oxygen (increased P50) was also noted. The P50 averaged 28.8 plus or minus 0.87 (standard error of the mean) torr in patients with shock and 26.0 plus or minus 0.45 torr (P less than 0.05) in patients without circulatory failure. However, there was no significant difference in oxygen extraction from arterial blood between the two groups. The time course of the changes in P50, cardiac index and oxygen consumption was separately examined in 12 patients. In six patients with shock, P50 increased by an average of 4.6 plus or minus 2.05 torr (P less than 0.05) and this augmentation accounted for an estimated 18 percent increase in oxygen release. Maximal P50 values were observed after 24 hours of circulatory failure. In the absence of shock, no consistent changes in P50, cardiac index or oxygen consumption were observed. These data indicate that a reduction in oxygen delivery after acute myocardial infarction is followed by a compensatory increase in P50. This change in P50 accounts for increases in oxygen availability independently of changes in cardiac output.

Reduction in colloid osmotic pressure associated with fatal progression of cardiopulmonary failure.

The relationship between colloid osmotic pressure (COP) and the severity of cardiopulmonary failure was investigated in 99 consecutive patients admitted to our Shock Unit including 41 survivors and 58 fatal cases. The COP was significantly lower (p less than 0.001) in fatal cases in comparison to survivors. None of 21 patients in whom COP was less than 10.5 torr survived. A progressive increase in survival with typical S-shaped distribution was observed as COP increased from 10 to 19 torr, above which all patients survived. These preliminary observations demonstrated that reduction in COP in critically ill patients is associated with increases in mortality. The mechanisms by which lowering of COP may be related to fatal progression of cardiopulmonary failure is the subject of continuing study.