RESUMEN
OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (-284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (-8 ± 27 dynes; p = 0.4827) or day 2 (-18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.
RESUMEN
BACKGROUND: To describe 24-hour fluid administration in emergency department (ED) patients with suspected infection. METHODS: A prospective, multicenter, observational study conducted in three Danish hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. PRIMARY OUTCOME: 24-hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24-hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors. RESULTS: 734 patients had 24-hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24-hour fluid volumes were 3656 mL (standard deviation [SD]:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference [MD]: 60-79 years: -470 mL [95% CI: -789, -150], +80 years; -974 mL [95% CI: -1307, -640]), do-not-resuscitate orders (MD: -466 mL [95% CI: -797, -135]), and preexisting atrial fibrillation (MD: -367 mL [95% CI: -661, -72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL [95% CI: 820, 1543]), mean arterial pressure < 65 mmHg (MD: 1317 mL [95% CI: 770, 1864]), lactate ≥ 2 mmol/L (MD: 655 mL [95% CI: 306, 1005]), heart rate > 120 min (MD: 566 [95% CI: 169, 962]), low (MD: 1963 mL [95% CI: 813, 3112]) and high temperature (MD: 489 mL [95% CI: 234, 742]), SOFA score > 5 (MD: 1005 mL [95% CI: 501, 510]), and new-onset atrial fibrillation (MD: 498 mL [95% CI: 30, 965]) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients. CONCLUSIONS: Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.
