Role of Serotonin in Patients with Acute Respiratory Failure

Abstract

An early event in the evolution of acute respiratory failure (ARF) is thought to be the activation of platelets, their pulmonary entrapment and subsequent release of the smooth muscle constrictor serotonin (5HT). This study tests the thesis that inhibition of 5HT will improve lung function. The etiology of ARF in the 18 study patients was sepsis (N = 10), aspiration (N = 3), pancreatitis (N = 1), embolism (N = 2), and abdominal aortic aneurysm surgery (N = 2). Patients were divided into two groups determined by whether their period of endotracheal intubation was less than or equal to 4 days (early ARF, N = 12) or greater than 4 days (late ARF, N = 6). Transpulmonary platelet counts in the early group showed entrapment of 26,300 ± 5900 platelets/mm3 in contrast to the late group where there was no entrapment (p < 0.05). The platelet 5HT levels in the early group were 55 ± 5 ng/109 platelets, values lower than 95 ± 15 ng/109 platelets in the late ARF group (p < 0.05), and 290 ± 70 ng/109 platelets in normals. The selective 5HT receptor antagonist, ketanserin was given as an intravenous bolus over 3 minutes in a dose of 0.1 mg/kg, followed by a 30-minute infusion of 0.08 mg/kg. During this period mean arterial pressure (MAP) fell from 87 ± 5 to 74 ± 6 mmHg (mean ± SEM) (p < 0.05). One and one-half hours following the start of therapy, MAP returned to baseline. At this time, patients with early ARF showed decreases in: physiologic shunt (JOURNAL/ansu/04.02/00000658-198408000-00008/ENTITY_OV0422/v/2017-07-25T071302Z/r/image-pngRS/JOURNAL/ansu/04.02/00000658-198408000-00008/ENTITY_OV0422/v/2017-07-25T071302Z/r/image-pngRT)*** from 26 ± 3 to 19 ± 3 (p < 0.05); peak inspiratory pressure from 35 ± 2 to 32 ± 2 cmH2O (p < 0.05) and in mean pulmonary arterial pressure from 32 ± 2 to 29 ± 1 mmHg (p < 0.05). At 4 hours all changes returned to baseline levels. In early ARF ketanserin did not alter pretreatment values of: pulmonary arterial wedge pressure, 17 ± 3 mmHg; cardiac index, 2.8 ± 0.3 L/min.m2; platelet count, 219,000 ± 45,000/mm3; platelet 5HT, 55 ± 5 ng/109 platelets; plasma 5HT, 142 ± 21 ng/ml; plasma thromboxane B2, 190 ± 30 pg/ml; or plasma 6-keto-PGF1α, 40 ± 10 pg/ml. Ketanserin infusion in patients with late ARF yielded no benefit. In both ARF groups the decreases in JOURNAL/ansu/04.02/00000658-198408000-00008/ENTITY_OV0422/v/2017-07-25T071302Z/r/image-pngRS/JOURNAL/ansu/04.02/00000658-198408000-00008/ENTITY_OV0422/v/2017-07-25T071302Z/r/image-pngRT were inversely related to the duration of intubation (r = 0.70; p < 0.05). The data indicate that platelet entrapment and 5HT released in the first 4 days of ARF results in significant impairment of lung function by constriction of, the pulmonary vasculature and bronchi.