Neuromuscular Blockade in the Pre- and COVID-19 ARDS Patients.

Acute respiratory distress syndrome (ARDS) accounts for a quarter of mechanically ventilated patients, while during the pandemic, it overwhelmed the capacity of intensive care units (ICUs). Lung protective ventilation (low tidal volume, positive-end expiratory pressure titrated to lung mechanics and oxygenation, permissive hypercapnia) is a non-pharmacological approach that is the gold standard of management. Among the pharmacological treatments, the use of neuromuscular blocking agents (NMBAs), although extensively studied, has not yet been well clarified. The rationale is to minimize the risk for lung damage progression, in the already-injured pulmonary parenchyma. By abolishing rigorous spontaneous efforts, NMBAs may decrease the generation of high transpulmonary pressures that could aggravate patients' self-inflicted lung injury. Moreover, NMBAs can harmonize the patient-ventilator interaction. Recent randomized controlled trials reported contradictory results and changed the clinical practice in a bidirectional way. NMBAs have not been documented to improve long-term survival; thus, the current guidance suggests their use only in patients in whom a lung protective ventilation protocol cannot be applied, due to asynchrony or increased respiratory efforts. In the present review, we discuss the published data and additionally the clinical practice in the "war" conditions of the COVID-19 pandemic, concerning NMBA use in the management of patients with ARDS.

Secondary bacterial infections are a leading factor triggering New Onset Atrial Fibrillation in intubated ICU Covid-19 ARDS patients.

BACKGROUND: Cardiac arrhythmias, mainly atrial fibrillation (AF), is frequently reported in COVID-19 patients, more often in Intensive Care Unit (ICU) patients, yet causality has not been virtually explored. Moreover, non-Covid ICU patients frequently present AF, sepsis being the major trigger. We aimed to examine whether sepsis or other factors-apart from Covid-19 myocardial involvement-contribute to elicit New Onset AF (NOAF) in intubated ICU patients. METHODS: Consecutive intubated, Covid-19ARDS patients, were prospectively studied for factors triggering NOAF. Demographics, data on Covid-19 infection duration, laboratory findings (troponin as well), severity of illness and ARDS were compared between NOAF and control group (no AF) on admission. In NOAF patients, echocardiographic findings, laboratory and secondary infection data on the AF day were compared to the preceding days and/or ICU admission data. RESULTS: Among 105 patients screened, 79 were eligible; nineteen presented NOAF (24%). Baseline characteristics did not differ between the NOAF and control groups. Troponin levels were mildly elevated upon ICU admission in both groups. Left ventricular global longitudinal strain was impaired (<16.5%) in 63% vs 78% in the two groups, respectively. The right ventricle was mildly dilated, and pericardial effusion was present in 52 vs 43%, respectively. NOAF occurred on the 18 ± 4.8 days from Covid-19 symptoms' onset, and the 8.5 ± 2.1 ICUday. A septic secondary infection episode occurred in 89.5% of the patients in the NOAF group ( vs 41.6% in the control group (p < 0.001). In fact, NOAF occurred concurrently with a secondary septic episode in 84.2% of the patients. Sepsis presence was the only factor associated to NOAF occurrence (OR 16.63, p = 0.002). Noradrenaline, lactate and inflammation biomarkers gradually increased in the days before AF (all p < 0.05). Echocardiographic findings did not change on NOAF occurrence. CONCLUSION: Secondary infections seem to be major contributors for NOAF occurrence in Covid-19 patients, probably playing the role of the "second hit" in an affected myocardium from Covid-19.

Simulation to minimise patient self-inflicted lung injury: are we almost there?

Computational modelling has been used to enlighten pathophysiological issues in patients with acute respiratory distress syndrome (ARDS) using a sophisticated, integrated cardiopulmonary model. COVID-19 ARDS is a pathophysiologically distinct entity characterised by dissociation between impairment in gas exchange and respiratory system mechanics, especially in the early stages of ARDS. Weaver and colleagues used computational modelling to elucidate factors contributing to generation of patient self-inflicted lung injury, and evaluated the effects of various spontaneous respiratory efforts with different oxygenation and ventilatory support modes. Their findings indicate that mechanical forces generated in the lung parenchyma are only counterbalanced when the respiratory support mode reduces the intensity of respiratory efforts.

Rapidly improving acute respiratory distress syndrome in COVID-19: a multi-centre observational study.

BACKGROUND: Before the pandemic of coronavirus disease (COVID-19), rapidly improving acute respiratory distress syndrome (ARDS), mostly defined by early extubation, had been recognized as an increasingly prevalent subphenotype (making up 15-24% of all ARDS cases), associated with good prognosis (10% mortality in ARDSNet trials). We attempted to determine the prevalence and prognosis of rapidly improving ARDS and of persistent severe ARDS related to COVID-19. METHODS: We included consecutive patients with COVID-19 receiving invasive mechanical ventilation in three intensive care units (ICU) during the second pandemic wave in Greece. We defined rapidly improving ARDS as extubation or a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2:FiO2) greater than 300 on the first day following intubation. We defined persistent severe ARDS as PaO2:FiO2 of equal to or less than 100 on the second day following intubation. RESULTS: A total of 280 intubated patients met criteria of ARDS with a median PaO2:FiO2 of 125.0 (interquartile range 93.0-161.0) on day of intubation, and overall ICU-mortality of 52.5% (ranging from 24.3 to 66.9% across the three participating sites). Prevalence of rapidly improving ARDS was 3.9% (11 of 280 patients); no extubation occurred on the first day following intubation. ICU-mortality of patients with rapidly improving ARDS was 54.5%. This low prevalence and high mortality rate of rapidly improving ARDS were consistent across participating sites. Prevalence of persistent severe ARDS was 12.1% and corresponding mortality was 82.4%. CONCLUSIONS: Rapidly improving ARDS was not prevalent and was not associated with good prognosis among patients with COVID-19. This is starkly different from what has been previously reported for patients with ARDS not related to COVID-19. Our results on both rapidly improving ARDS and persistent severe ARDS may contribute to our understanding of trajectory of ARDS and its association with prognosis in patients with COVID-19.

Ultrasonographic Confirmation of Nasogastric Tube Placement in the COVID-19 Era.

BACKGROUND: Nasogastric tube (NGT) placement is a daily routine in the Intensive Care Unit (ICU), and misplacement of the NGT can cause serious complications. In COVID-19 ARDS patients, proning has emerged the need for frequent NGT re-evaluations. The gold standard technique, chest X-ray, is not always feasible. In the present study we report our experience with the use of ultrasonographic confirmation of NGT position. METHODS: A prospective study in 276 COVID-19 ARDS patients admitted after intubation in the ICU. Ultrasonographic evaluation was performed using longitudinal or sagittal epigastric views. Examinations were performed during the initial NGT placement and every time the patients returned to the supine position after they had been proned or whenever critical care physicians or nurses considered that reconfirmation was necessary. RESULTS: Ultrasonographic confirmation of correct NGT placement was feasible in 246/276 (89.13%) patients upon ICU admission. In 189/246 (76.8%) the tube could be visualized in the stomach (two parallel lines), in 172/246 (69.9%) the ultrasonographic whoosh test ("flash" due to air instillation through the tube, seen with ultrasonography) was evident, while in 164/246 (66.7%) both tests confirmed correct NGT placement. During ICU stay 590 ultrasonographic NGT evaluations were performed, and in 462 (78.14%) cases correct NGT placement were confirmed. In 392 cases, a chest X-ray was also ordered. The sensitivity of ultrasonographic NGT confirmation in these cases was 98.9%, specificity 57.9%, PPV 96.2%, and NPV 3.8%. The time for the full evaluation was 3.8 ± 3.4 min. CONCLUSION: Ultrasonographic confirmation of correct NGT placement is feasible in the initial placement, but also whenever needed thereafter, especially in the COVID-19 era, when changes in posture have become a daily practice in ARDS patients.

Fixed dilated pupils in Covid-19 ARDS patients under rocuronium, reversed after discontinuation.

Neuromuscular Blockade Agents (NMBA) are used in the management of moderate and severe Acute Respiratory Distress Syndrome (ARDS) patients. They have never been reported to present Central Nervous System adverse reactions. Shortage of cis-atracurium during the pandemic, led to the use of rocuronium. We report three patients with Covid-19 ARDS, who presented bilateral dilated, non-reactive pupils, after continuous rocuronium infusion. Brain CT findings were unremarkable and transcranial doppler tracings did not suggest brain edema or hemorrhage. NMBA's discontinuation led to reversal of the pupillary dilation. We believe that impairment of Blood-Brain-Barrier, due to Covid-19, led rocuronium access into the Central Nervous System, leading to this adverse effect. Clinicians should be aware of this adverse reaction when managing patients with Covid-19 ARDS warranting NMBA use.