Effects of intravenous fat emulsions on lung function in patients with acute respiratory distress syndrome or sepsis

Objective. To investigate whether rapid or slowly infused intravenous fat emulsions affect the ratio of prostaglandin I-2/thromboxane A(2) in arterial blood, pulmonary hemodynamics, and gas exchange. Design. Prospective, controlled, randomized, crossover study. Setting., Operative intensive care unit of a university hospital. Patients. Eighteen critically ill patients. Ten patients were stratified with severe sepsis, and eight patients had acute respiratory distress syndrome (ARDS). Interventions: Patients were assigned randomly to receive intravenous fat emulsions (0.4 x resting energy expenditure) over 6 hrs (rapid fat infusion) or 24 hrs (slow fat infusion) along with a routine parenteral nutrition regimen, by using a crossover study design. Measurements and Main Results. Systemic and pulmonary hemodynamics as well as gas exchange measurements were recorded via respective indwelling catheters. Arterial thromboxane B-2 and 6-keto-prostaglandin-F-1 alpha. plasma concentrations were obtained by radioimmunoassay, and 6-keto-prostagiandin-F-1 alpha/thromboxane B-2 ratios (P/T ratios) were calculated. Data were collected immediately before and 6, 12, 18, and 24 hrs after onset of fat infusion. In the ARDS group, PIT ratio increased by rapid fat infusion. Concomitantly, pulmonary shunt fraction, alveolar-arterial oxygen tension difference [P(A-a)O-2]/PaO2, and cardiac index increased as well, whereas pulmonary vascular resistance and PaO2/FIO2 declined. After slow fat infusion, a decreased P/T ratio was revealed. This was accompanied by decreased pulmonary shunt fraction, lowered P(A-a)o(2)/PaO2, and increased Pao(2)/FIO2. Correlations between plasma concentrations of 6-keto-prostagiandin-F-1 alpha or thromboxane B-2 and measures of respiratory performance could be shown during rapid and slow fat infusion, respectively. In the sepsis group, the P/T ratio remained unchanged at either infusion rate, but pulmonary shunt fraction and P(A-a)O-2/PaO2 decreased after rapid fat infusion, whereas Pao(2)/FIO2 increased. Conclusion: Pulmonary hemodynamics and gas exchange are related to changes of arterial prostanoid levels in ARDS patients, depending on the rate of fat infusion. In ARDS but not in sepsis patients clear of pulmonary organ failure, a changing balance of prostaglandin 12 and thromboxane A2 may modulate gas exchange, presumably via interference with hypoxic pulmonary vasoconstriction.