Characteristics and outcomes of patients with COVID-19 admitted to ICU in a tertiary hospital in Stockholm, Sweden.

BACKGROUND: Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU. METHODS: We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. RESULTS: Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. CONCLUSION: This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.

Endotoxin induces differentiated contractile responses in porcine pulmonary arteries and veins.

BACKGROUND/AIMS: Sepsis-induced lung injury is characterized by pulmonary hypertension, edema and deteriorated gas exchange. As in vivo studies have indicated that bacterial endotoxin predominantly induces a pulmonary venous constriction, we aimed to investigate effects of endotoxin on isolated porcine pulmonary vessels. METHODS: Pulmonary arteries and veins were examined using in vitro isometric force recordings. Endothelin-receptor protein expression and distribution were analyzed by Western blot and immunohistochemistry. Freshly isolated preparations and vessels incubated (24 h) with/without endotoxin (10 µg·ml(-1)) were compared. The contractile responses to phenylephrine, UK14.304, U46619, PGF(2α), endothelin-1 (ET-1) and sarafotoxin were recorded, as well as the relaxation in response to acetylcholine, isoproterenol and nitroprusside. RESULTS: In freshly isolated vessels, phenylephrine-induced contractions had a 5-times larger amplitude in arteries than in veins. The amplitude of the contractions in response to sarafotoxin was nearly 2 times larger in veins than in arteries, but there was no difference in responses to ET-1. Endotoxin markedly reduced phenylephrine-induced contractions in both arteries and veins, whereas the responses to ET-1 and sarafotoxin were augmented in veins only. No apparent changes in ET receptor expression or distribution were detected with Western blot or immunohistochemistry. CONCLUSION: Endotoxin differentially and selectively alters the contractile responses of porcine pulmonary vessels in vitro, towards a situation where the α-1 adrenergic responses of arteries are attenuated and the ET responses of veins are augmented. In situations with high adrenergic activity and high circulating ET levels, such as sepsis, these results may provide a mechanism contributing to pulmonary hypertension and edema formation.

Inhaled tezosentan reduces pulmonary hypertension in endotoxin-induced lung injury.

The vasoconstrictive and proinflammatory peptide endothelin 1 (ET-1) is highly involved in the pathogenesis of sepsis and associated lung injury. Systemic administration of ET-receptor antagonists has been beneficial in experimental pulmonary hypertension. We wanted to study the effects of inhaled tezosentan, a dual endothelin-receptor antagonist on endotoxin-induced pulmonary hypertension, deterioration of gas exchange, and edema formation. After 2 h of endotoxemia, 28 anesthetized, mechanically ventilated pigs were randomized to either inhaled tezosentan 0.5 mg x kg (TEZO(0.5), n = 7), 0.05 mg x kg (TEZO(0.05), n = 7), intravenous 0.5 mg x kg (TEZO(iv), n = 7), or control (n = 7). Cardiopulmonary hemodynamics and gas-exchange parameters were recorded as well as extravascular lung water and pulmonary capillary pressure. In addition, plasma levels of tezosentan and ET-1 were analyzed. The protocol lasted for 5 h. Endotoxin-induced pulmonary hypertension (mean pulmonary artery pressure) was efficiently reduced by all treatments (TEZO(0.5) 24 +/- 2, TEZO(0.05) 27 +/- 2, TEZO(iv) 26 +/- 1, and control 37 +/- 2 mmHg at 4 h). TEZO(0.5) and TEZO(iv) also reduced pulmonary capillary pressure. All treatments led to a modest reduction in extravascular lung water, whereas no effects were noted on oxygenation or systemic circulation. Despite similar effects on pulmonary hypertension systemic treatment resulted in significantly higher plasma levels of ET-1 (twofold) and tezosentan (10- to 100-fold). Inhalation of the dual ET-receptor antagonist tezosentan was feasible and efficiently counteracted endotoxin-induced pulmonary hypertension. These effects were obtained with only minor systemic uptake of tezosentan and without affecting circulating levels of plasma ET-1 as compared with intravenous administration.