COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients

OBJECTIVES: To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19–related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)–related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18–58 d) versus 16 days (IQR, 19–39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6–28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9–27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7–25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival

In vitro validation and characterization of pulsed inhaled nitric oxide administration during early inspiration

Purpose: Admixture of nitric oxide (NO) to the gas inspired with mechanical ventilation can be achieved through continuous, timed, or pulsed injection of NO into the inspiratory limb. The dose and timing of NO injection govern the inspired and intrapulmonary effect site concentrations achieved with different administration modes. Here we test the effectiveness and target reliability of a new mode injecting pulsed NO boluses exclusively during early inspiration. Methods: An in vitro lung model was operated under various ventilator settings. Admixture of NO through injection into the inspiratory limb was timed either (i) selectively during early inspiration ("pulsed delivery"), or as customary, (ii) during inspiratory time or (iii) the entire respiratory cycle. Set NO target concentrations of 5-40 parts per million (ppm) were tested for agreement with the yield NO concentrations measured at various sites in the inspiratory limb, to assess the effectiveness of these NO administration modes. Results: Pulsed delivery produced inspiratory NO concentrations comparable with those of customary modes of NO administration. At low (450 ml) and ultra-low (230 ml) tidal volumes, pulsed delivery yielded better agreement of the set target (up to 40 ppm) and inspiratory NO concentrations as compared to customary modes. Pulsed delivery with NO injection close to the artificial lung yielded higher intrapulmonary NO concentrations than with NO injection close to the ventilator. The maximum inspiratory NO concentration observed in the trachea (68 +/- 30 ppm) occurred with pulsed delivery at a set target of 40 ppm. Conclusion: Pulsed early inspiratory phase NO injection is as effective as continuous or non-selective admixture of NO to inspired gas and may confer improved target reliability, especially at low, lung protective tidal volumes

Induction of severe hypoxemia and low lung recruitability for the evaluation of therapeutic ventilation strategies: a translational model of combined surfactant-depletion and ventilator-induced lung injury

Background: Models of hypoxemic lung injury caused by lavage-induced pulmonary surfactant depletion are prone to prompt recovery of blood oxygenation following recruitment maneuvers and have limited translational validity. We hypothesized that addition of injurious ventilation following surfactant-depletion creates a model of the acute respiratory distress syndrome (ARDS) with persistently low recruitability and higher levels of titrated "best" positive end-expiratory pressure (PEEP) during protective ventilation. Methods: Two types of porcine lung injury were induced by lung lavage and 3 h of either protective or injurious ventilation, followed by 3 h of protective ventilation (N = 6 per group). Recruitment maneuvers (RM) and decremental PEEP trials comparing oxygenation versus dynamic compliance were performed after lavage and at 3 h intervals of ventilation. Pulmonary gas exchange function, respiratory mechanics, and ventilator-derived parameters were assessed after each RM to map the course of injury severity and recruitability. Results: Lung lavage impaired respiratory system compliance (C-rs) and produced arterial oxygen tensions (PaO2) of 84 +/- 13 and 80 +/- 15 (FIO2 = 1.0) with prompt increase after RM to 270-395 mmHg in both groups. After subsequent 3 h of either protective or injurious ventilation, PaO2/FIO2 was 104 +/- 26 vs. 154 +/- 123 and increased to 369 +/- 132 vs. 167 +/- 87 mmHg in response to RM, respectively. After additional 3 h of protective ventilation, PaO2/FIO2 was 120 +/- 15 vs. 128 +/- 37 and increased to 470 +/- 68 vs. 185 +/- 129 mmHg in response to RM, respectively. Subsequently, decremental PEEP titration revealed that C-rs peaked at 36 +/- 10 vs. 25 +/- 5 ml/cm H2O with PEEP of 12 vs. 16 cmH(2)O, and PaO2/FIO2 peaked at 563 +/- 83 vs. 334 +/- 148 mm Hg with PEEP of 16 vs. 22 cmH(2)O in the protective vs. injurious ventilation groups, respectively. The large disparity of recruitability between groups was not reflected in the C-rs nor the magnitude of mechanical power present after injurious ventilation, once protective ventilation was resumed. Conclusion: Addition of transitory injurious ventilation after lung lavage causes prolonged acute lung injury with diffuse alveolar damage and low recruitability yielding high titrated PEEP levels. Mimicking lung mechanical and functional characteristics of ARDS, this porcine model rectifies the constraints of single-hit lavage models and may enhance the translation of experimental research on mechanical ventilation strategies

Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m

Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide: n = 7, 250 mg 3 times/day; placebo: n = 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo, P = 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (P < 0.001) without a group difference (P = 0.68). Arterial Po2 fell to 36 ± 9 mmHg (P < 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (P = 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both P < 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.NEW & NOTEWORTHY This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention. Keywords: AMS; Diamox; HAPE; acetazolamide; acute mountain sicknes