Frank D. Sutton

Theophylline-induced seizures in adults. Correlation with serum concentrations.

Eight patients developed grand mal seizures during intravenous theophylline therapy. None had a history of neurologic disorder, and all were acutely ill with severe pulmonary or cardiovascular disease, or both. Serum theophylline concentrations obtained within 1 hour of the seizure ranged from 25 mug/ml to 70mug/ml, with a mean value (53 plus or minus 4.8 mug/ml) more than twice the upper limit of the recommended therapeutic concentration. This serum theophylline concentration was greater than the concentration found in a group of patients with less severe drug-related symptoms (35 plus or minus 1.8 mug/ml, P less than 0.01). A third group of patients without drug-related symptoms had a mean theophylline serum concentration of 19 plus or minus 2.0 mug/ml, which was less than that found in either group with toxicity symptoms (P less than 0.05). Factors predisposing to the high serum concentrations in the patients with seizures were both higher drug dosage, compared with the other groups (P less than 0.01), and hepatic dysfunction, which was more common in both groups with drug-related symptoms.

Complications of assisted ventilation: A prospective study of 354 consecutive episodes

Abstract Three hundred fourteen consecutive patients were studied prospectively during 354 episodes of assisted ventilation in a 5 month period. These patients ranged in age from 15 to 95 years, and ventilatory support was required for from 1 hour to 54 days. Over-all survival was 64 per cent. Eighteen complications were studied prospectively, of which three (intubation of the right mainstem bronchus, endotracheal tube malfunction and alveolar hypoventilation) were associated with decreased survival. Four hundred individual complications or potential complications were observed. Intubation of the right mainstem bronchus was associated with alveolar hyperventilation, atelectasis and/or tension pneumothorax in a significant number of cases (all, P

Decreased hypoxic ventilatory drive in the obesity-hypoventilation syndrome☆

Most patients with extreme obesity do not exhibit alveolar hypoventilation, but an intriguing minority do. The mechanism(s) of this phenomenon remain unknown. A disorder in ventilatory control has been suggested as a major factor in the pathogenesis of the obesity-hypoventilation syndrome. Accordingly, hypoxic and hypercapnic ventilatory drives were measured in 10 patients with the typical symptoms of the syndrome: obesity, hypersomnolence, hypercapnia, hypoxemia, polycythemia and cor pulmonale. Hypoxic ventilatory drive, measured as the shape parameter A, averaged 21.9 +/- 5.35, approximately one-sixth that in normal controls, A = 126 +/- 8.6 (P less than 0.01). The ventilatory response to hypercapnia also was markedly reduced, the slope of the response averaging 0.51 +/- 0.005, or about one-third the normal value of 1.83 +/- 0.13 (P less than 0.01). This decreased responsiveness in hypoxic and hypercapnic ventilatory drive was consistent throughout the group. The depression in ventilatory drive found in the obesity-hypoventilation syndrome may be causally related to the alveolar hypoventilation manifested by these patients.

Progesterone for Outpatient Treatment of Pickwickian Syndrome

Ten patients with the Pickwickian syndrome, characterized by obesity, hypoxemia, hypercapnia, polycythemia, and cor pulmonale, underwent long-term treatment as outpatients with medroxyprogesterone acetate. Although there was no significant weight change in the group, PaO2 rose 12.6 +/- 2.7 mm Hg (SEM) from 49 +/- 2.6 mm Hg to 62 +/- 2.3 mm Hg (P less than 0.001), while PaCO2 fell 13 +/- 2.6 mm Hg from 51 +/- 1.9 mm Hg to 38 +/- 1.2 mm Hg (P less than 0.001). Hematocrit fell from 56 +/- 2.5% to 50 +/- 1.2%, a mean fall of 6% (P less than 0.01), during medroxyprogesterone acetate therapy. In the 2 patients who had cardiac catheterization before and during medroxyprogesterone acetate therapy, mean pulmonary arterial pressure fell 13 and 19 mm Hg. There were no recurrences of cor pulmonale during treatment. These effects on arterial blood gas values and clinical state were sustained during therapy. On withdrawal of medroxyprogesterone acetate during 1-month period, arterial oxygen and carbon dioxide tensions deteriorated to their previous pretreatment values. Reinstitution of medroxyprogesterone acetate caused improvement in both the oxygen and carbon dioxide tensions. We conclude that sublingual medroxyprogesterone acetate therapy is useful in the management of the Pickwickian syndrome.

Left ventricular ejection fraction in severe chronic obstructive airways disease

The subject of left ventricular involvement in chronic obstructive airways disease is controversial. We measured left ventricular ejection fraction (LVEF) in 120 patients with severe chronic obstructive airways disease, 92 of them acutely decompensated and 28 stable. A bedside radionuclide technic using a scintillation probe was used to measure LVEF. Of the 28 patients with acute respiratory failure, LVEF was normal (larger than or equal to 55 per cent) in 60 and subnormal in 32. Of the 28 patients with stable chronic obstructive airways disease, LVEF was normal in 12 and low in 16. Coronary artery disease could be demonstrated clinically or at autopsy in 13 of the patients with acute and in 7 of the patients with stable chronic obstructive airways disease. LVEF was 28 plus or minus 10.4 per cent (average plus or minus SEM) in the patients with acute chronic obstructive airways disease and coronary artery disease which was significantly different (P smaller than 0.001) from LVEF in patients without coronary artery disease (61 plus or minus 1.9 per cent). In the patients stable with chronic obstructive airways disease and coronary artery disease, LVEF was (42 plus or minus 3.5 per cent), significantly different (P smaller than 0.001) from LVEF in those without coronary artery disease (55 plus or minus 2.1 per cent). There was no relationship between LVEF and arterial oxygen, or carbon dioxide tension, or pH. Results suggest that LVEF is normal in patients with severe lung disease alone and that reduced LVEF in patients with chronic obstructive airways disease can reasonably be ascribed to coronary artery disease.