Search

The administration of exogenous oxygen to support adequate gas exchange is the cornerstone of respiratory care. In the past few years, other gaseous molecules have been introduced in clinical practice to treat the wide variety of physiological derangement seen in critical care patients.Inhaled nitric oxide (NO) is used for its unique selective pulmonary vasodilator effect. Recent studies showed that NO plays a pivotal role in regulating ischemia-reperfusion injury and it has antibacterial and antiviral activity.Helium, due to its low density, is used in patients with upper airway obstruction and lower airway obstruction to facilitate gas flow and to reduce work of breathing.Carbon monoxide (CO) is a poisonous gas that acts as a signaling molecule involved in many biologic pathways. CO's anti-inflammatory and antiproliferative effects are under investigation in the setting of acute respiratory distress and idiopathic pulmonary fibrosis.Inhaled anesthetics are widely used in the operative room setting and, with the development of anesthetic reflectors, are now a valid option for sedation management in the intensive care unit.Many other gases such as xenon, argon, and hydrogen sulfide are under investigation for their neuroprotective and cardioprotective effects in post-cardiac arrest syndrome.With all these therapeutic options available, the clinician must have a clear understanding of the physiologic basis, therapeutic potential, and possible adverse events of these therapeutic gases. In this review, we will present the therapeutic gases other than oxygen used in clinical practice and we will describe other promising therapeutic gases that are in the early phases of investigation.

(1) The use of high-flow nasal cannula (HFNC) combined with frequent respiratory monitoring in patients with acute hypoxic respiratory failure due to COVID-19 has been shown to reduce intubation and mechanical ventilation. (2) This prospective, single-center, observational study included consecutive adult patients with COVID-19 pneumonia treated with a high-flow nasal cannula. Hemodynamic parameters, respiratory rate, inspiratory fraction of oxygen (FiO2), saturation of oxygen (SpO2), and the ratio of oxygen saturation to respiratory rate (ROX) were recorded prior to treatment initiation and every 2 h for 24 h. A 6-month follow-up questionnaire was also conducted. (3) Over the study period, 153 of 187 patients were eligible for HFNC. Of these patients, 80% required intubation and 37% of the intubated patients died in hospital. Male sex (OR = 4.65; 95% CI [1.28; 20.6], p = 0.03) and higher BMI (OR = 2.63; 95% CI [1.14; 6.76], p = 0.03) were associated with an increased risk for new limitations at 6-months after hospital discharge. (4) 20% of patients who received HFNC did not require intubation and were discharged alive from the hospital. Male sex and higher BMI were associated with poor long-term functional outcomes.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension. Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6). Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7–10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and V./Q. matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13–4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2–0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15–6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the V./Q. ratio. Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure. Clinical trial registered with www.clinicaltrials.gov (NCT 02503241).

Background: Patients with COVID-19 can develop acute respiratory distress syndrome (ARDS), which is associated with high mortality. The aim of this study was to examine the functional and morphological features of COVID-19-associated ARDS and to compare these with the characteristics of ARDS unrelated to COVID-19. Methods: This prospective observational study was done at seven hospitals in Italy. We enrolled consecutive, mechanically ventilated patients with laboratory-confirmed COVID-19 and who met Berlin criteria for ARDS, who were admitted to the intensive care unit (ICU) between March 9 and March 22, 2020. All patients were sedated, paralysed, and ventilated in volume-control mode with standard ICU ventilators. Static respiratory system compliance, the ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air, ventilatory ratio (a surrogate of dead space), and D-dimer concentrations were measured within 24 h of ICU admission. Lung CT scans and CT angiograms were done when clinically indicated. A dataset for ARDS unrelated to COVID-19 was created from previous ARDS studies. Survival to day 28 was assessed. Findings: Between March 9 and March 22, 2020, 301 patients with COVID-19 met the Berlin criteria for ARDS at participating hospitals. Median static compliance was 41 mL/cm H2O (33–52), which was 28% higher than in the cohort of patients with ARDS unrelated to COVID-19 (32 mL/cm H2O [25–43]; p

To evaluate whether the use of inhaled nitric oxide (iNO)200 improves respiratory function.This retrospective cohort study used data from pregnant patients hospitalized with severe bilateral coronavirus disease 2019 (COVID-19) pneumonia at four teaching hospitals between March 2020 and December 2021. Two cohorts were identified: 1) those receiving standard of care alone (SoC cohort) and 2) those receiving iNO200 for 30 minutes twice daily in addition to standard of care alone (iNO200 cohort). Inhaled nitric oxide, as a novel therapy, was offered only at one hospital. The prespecified primary outcome was days free from any oxygen supplementation at 28 days postadmission. Secondary outcomes were hospital length of stay, rate of intubation, and intensive care unit (ICU) length of stay. The multivariable-adjusted regression analyses accounted for age, body mass index, gestational age, use of steroids, remdesivir, and the study center.Seventy-one pregnant patients were hospitalized for severe bilateral COVID-19 pneumonia: 51 in the SoC cohort and 20 in the iNO200 cohort. Patients receiving iNO200 had more oxygen supplementation-free days (iNO200: median [interquartile range], 24 [23-26] days vs standard of care alone: 22 [14-24] days, P=.01) compared with patients in the SoC cohort. In the multivariable-adjusted analyses, iNO200 was associated with 63.2% (95% CI 36.2-95.4%; P.001) more days free from oxygen supplementation, 59.7% (95% CI 56.0-63.2%; P.001) shorter ICU length of stay, and 63.6% (95% CI 55.1-70.8%; P.001) shorter hospital length of stay. No iNO200-related adverse events were reported.In pregnant patients with severe bilateral COVID-19 pneumonia, iNO200 was associated with a reduced need for oxygen supplementation and shorter hospital stay.

During the COVID-19 pandemic, a shortage of mechanical ventilators was reported and ventilator sharing between patients was proposed as an ultimate solution. Two lung simulators were ventilated by one anesthesia machine connected through two respiratory circuits and T-pieces. Five different combinations of compliances (30–50 mL × cmH2O−1) and resistances (5–20 cmH2O × L−1 × s−1) were tested. The ventilation setting was: pressure-controlled ventilation, positive end-expiratory pressure 15 cmH2O, inspiratory pressure 10 cmH2O, respiratory rate 20 bpm. Pressures and flows from all the circuit sections have been recorded and analyzed. Simulated patients with equal compliance and resistance received similar ventilation. Compliance reduction from 50 to 30 mL × cmH2O−1 decreased the tidal volume (VT) by 32% (418 ± 49 vs. 285 ± 17 mL). The resistance increase from 5 to 20 cmH2O × L−1 × s−1 decreased VT by 22% (425 ± 69 vs. 331 ± 51 mL). The maximal alveolar pressure was lower at higher compliance and resistance values and decreased linearly with the time constant (r² = 0.80, p &lt, 0.001). The minimum alveolar pressure ranged from 15.5 ± 0.04 to 16.57 ± 0.04 cmH2O. Cross-flows between the simulated patients have been recorded in all the tested combinations, during both the inspiratory and expiratory phases. The simultaneous ventilation of two patients with one ventilator may be unable to match individual patient’s needs and has a high risk of cross-interference.

Extracorporeal carbon dioxide removal (ECCO2R) is a promising strategy to manage acute respiratory failure. We hypothesized that ECCO2R could be enhanced by ventilating the membrane lung with a sodium hydroxide (NaOH) solution with high CO2 absorbing capacity. A computed mathematical model was implemented to assess NaOH–CO2 interactions. Subsequently, we compared NaOH infusion, named “alkaline liquid ventilation”, to conventional oxygen sweeping flows. We built an extracorporeal circuit with two polypropylene membrane lungs, one to remove CO2 and the other to maintain a constant PCO2 (60 ± 2 mmHg). The circuit was primed with swine blood. Blood flow was 500 mL × min−1. After testing the safety and feasibility of increasing concentrations of aqueous NaOH (up to 100 mmol × L−1), the CO2 removal capacity of sweeping oxygen was compared to that of 100 mmol × L−1 NaOH. We performed six experiments to randomly test four sweep flows (100, 250, 500, 1000 mL × min−1) for each fluid plus 10 L × min−1 oxygen. Alkaline liquid ventilation proved to be feasible and safe. No damages or hemolysis were detected. NaOH showed higher CO2 removal capacity compared to oxygen for flows up to 1 L × min−1. However, the highest CO2 extraction power exerted by NaOH was comparable to that of 10 L × min−1 oxygen. Further studies with dedicated devices are required to exploit potential clinical applications of alkaline liquid ventilation.