Systemic and Cerebral Effects of Physiotherapy in Mechanically Ventilated Subjects.

BACKGROUND: Physiotherapy may result in better functional outcomes, shorter duration of delirium, and more ventilator-free days. The effects of physiotherapy on different subpopulations of mechanically ventilated patients on respiratory and cerebral function are still unclear. We evaluated the effect of physiotherapy on systemic gas exchange and hemodynamics as well as on cerebral oxygenation and hemodynamics in mechanically ventilated subjects with and without COVID-19 pneumonia. METHODS: This was an observational study in critically ill subjects with and without COVID-19 who underwent protocolized physiotherapy (including respiratory and rehabilitation physiotherapy) and neuromonitoring of cerebral oxygenation and hemodynamics. PaO2 /FIO2 , PaCO2 , hemodynamics (mean arterial pressure [MAP], mm Hg; heart rate, beats/min), and cerebral physiologic parameters (noninvasive intracranial pressure, cerebral perfusion pressure using transcranial Doppler, and cerebral oxygenation using near-infrared spectroscopy) were assessed before (T0) and immediately after physiotherapy (T1). RESULTS: Thirty-one subjects were included (16 with COVID-19 and 15 without COVID-19). Physiotherapy improved PaO2 /FIO2 in the overall population (T1 = 185 [108-259] mm Hg vs T0 = 160 [97-231] mm Hg, P = .02) and in the subjects with COVID-19 (T1 = 119 [89-161] mm Hg vs T0 = 110 [81-154] mm Hg, P = .02) and decreased the PaCO2 in the COVID-19 group only (T1 = 40 [38-44] mm Hg vs T0 = 43 [38-47] mm Hg, P = .03). Physiotherapy did not affect cerebral hemodynamics, whereas increased the arterial oxygen part of hemoglobin both in the overall population (T1 = 3.1% [-1.3 to 4.9] vs T0 = 1.1% [-1.8 to 2.6], P = .007) and in the non-COVID-19 group (T1 = 3.7% [0.5-6.3] vs T0 = 0% [-2.2 to 2.8], P = .02). Heart rate was higher after physiotherapy in the overall population (T1 = 87 [75-96] beats/min vs T0 = 78 [72-92] beats/min, P = .044) and in the COVID-19 group (T1 = 87 [81-98] beats/min vs T0 = 77 [72-91] beats/min, P = .01), whereas MAP increased in the COVID-19 group only (T1 = 87 [82-83] vs T0 = 83 [76-89], P = .030). CONCLUSIONS: Protocolized physiotherapy improved gas exchange in subjects with COVID-19, whereas it improved cerebral oxygenation in non-COVID-19 subjects.

Clinical presentation of secondary infectious complications in COVID-19 patients in intensive care unit treated with tocilizumab or standard of care.

OBJECTIVES: The hypothesis of this study is that tocilizumab should affect common signs of infection due to its immunosuppressive properties. Primary aim of the study was to investigate whether the administration of tocilizumab to critically ill patients with COVID-19, led to a different clinical presentation of infectious complications compared to patients who did not receive tocilizumab. Secondary aim was investigating differences in laboratory parameters between groups. METHODS: Single-centre retrospective study, enrolling COVID-19 patients who developed a microbiologically confirmed infectious complication [ventilator associated pneumonia or bloodstream infection] after intensive care unit [ICU] admission and either treated with tocilizumab or not [controls]. RESULTS: A total of 58 patients were included, 25 treated with tocilizumab and 33 controls. Median time from tocilizumab administration to infection onset was 10 days [range 2-26]. Patients were 78% male, with median age 65 years [range 45-79]. At first clinical presentation of the infectious event, the frequency of hypotension [11/25, 44% vs. 11/33, 33%], fever [8/25, 32% vs. 10/33, 30%] or hypothermia [0/25,0%, vs. 2/33, 6%], and oxygen desaturation [6/25, 28% vs 4/33, 12%], as well as the frequency of SOFA score increase of ≥ 2 points [4/25, 16%,vs. 4/33, 12%] was similar in tocilizumab treated patients and controls [p>0.1 for all comparisons]. Among laboratory parameters, C-Reactive Protein elevation was reduced in tocilizumab treated patients compared to controls [8/25, 32% vs. 22/33, 67%, p=0.009]. CONCLUSION: The clinical features of infectious complications in critically ill patients with COVID-19 admitted to ICU were not affected by tocilizumab.

Early Effects of Passive Leg-Raising Test, Fluid Challenge, and Norepinephrine on Cerebral Autoregulation and Oxygenation in COVID-19 Critically Ill Patients.

Background: Coronavirus disease 2019 (COVID-19) patients are at high risk of neurological complications consequent to several factors including persistent hypotension. There is a paucity of data on the effects of therapeutic interventions designed to optimize systemic hemodynamics on cerebral autoregulation (CA) in this group of patients. Methods: Single-center, observational prospective study conducted at San Martino Policlinico Hospital, Genoa, Italy, from October 1 to December 15, 2020. Mechanically ventilated COVID-19 patients, who had at least one episode of hypotension and received a passive leg raising (PLR) test, were included. They were then treated with fluid challenge (FC) and/or norepinephrine (NE), according to patients' clinical conditions, at different moments. The primary outcome was to assess the early effects of PLR test and of FC and NE [when clinically indicated to maintain adequate mean arterial pressure (MAP)] on CA (CA index) measured by transcranial Doppler (TCD). Secondary outcomes were to evaluate the effects of PLR test, FC, and NE on systemic hemodynamic variables, cerebral oxygenation (rSo2), and non-invasive intracranial pressure (nICP). Results: Twenty-three patients were included and underwent PLR test. Of these, 22 patients received FC and 14 were treated with NE. The median age was 62 years (interquartile range = 57-68.5 years), and 78% were male. PLR test led to a low CA index [58% (44-76.3%)]. FC and NE administration resulted in a CA index of 90.8% (74.2-100%) and 100% (100-100%), respectively. After PLR test, nICP based on pulsatility index and nICP based on flow velocity diastolic formula was increased [18.6 (17.7-19.6) vs. 19.3 (18.2-19.8) mm Hg, p = 0.009, and 12.9 (8.5-18) vs. 15 (10.5-19.7) mm Hg, p = 0.001, respectively]. PLR test, FC, and NE resulted in a significant increase in MAP and rSo2. Conclusions: In mechanically ventilated severe COVID-19 patients, PLR test adversely affects CA. An individualized strategy aimed at assessing both the hemodynamic and cerebral needs is warranted in patients at high risk of neurological complications.

Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study.

BACKGROUND: In COVID-19 patients with acute respiratory distress syndrome (ARDS), the effectiveness of ventilatory rescue strategies remains uncertain, with controversial efficacy on systemic oxygenation and no data available regarding cerebral oxygenation and hemodynamics. METHODS: This is a prospective observational study conducted at San Martino Policlinico Hospital, Genoa, Italy. We included adult COVID-19 patients who underwent at least one of the following rescue therapies: recruitment maneuvers (RMs), prone positioning (PP), inhaled nitric oxide (iNO), and extracorporeal carbon dioxide (CO2) removal (ECCO2R). Arterial blood gas values (oxygen saturation [SpO2], partial pressure of oxygen [PaO2] and of carbon dioxide [PaCO2]) and cerebral oxygenation (rSO2) were analyzed before (T0) and after (T1) the use of any of the aforementioned rescue therapies. The primary aim was to assess the early effects of different ventilatory rescue therapies on systemic and cerebral oxygenation. The secondary aim was to evaluate the correlation between systemic and cerebral oxygenation in COVID-19 patients. RESULTS: Forty-five rescue therapies were performed in 22 patients. The median [interquartile range] age of the population was 62 [57-69] years, and 18/22 [82%] were male. After RMs, no significant changes were observed in systemic PaO2 and PaCO2 values, but cerebral oxygenation decreased significantly (52 [51-54]% vs. 49 [47-50]%, p < 0.001). After PP, a significant increase was observed in PaO2 (from 62 [56-71] to 82 [76-87] mmHg, p = 0.005) and rSO2 (from 53 [52-54]% to 60 [59-64]%, p = 0.005). The use of iNO increased PaO2 (from 65 [67-73] to 72 [67-73] mmHg, p = 0.015) and rSO2 (from 53 [51-56]% to 57 [55-59]%, p = 0.007). The use of ECCO2R decreased PaO2 (from 75 [75-79] to 64 [60-70] mmHg, p = 0.009), with reduction of rSO2 values (59 [56-65]% vs. 56 [53-62]%, p = 0.002). In the whole population, a significant relationship was found between SpO2 and rSO2 (R = 0.62, p < 0.001) and between PaO2 and rSO2 (R0 0.54, p < 0.001). CONCLUSIONS: Rescue therapies exert specific pathophysiological mechanisms, resulting in different effects on systemic and cerebral oxygenation in critically ill COVID-19 patients with ARDS. Cerebral and systemic oxygenation are correlated. The choice of rescue strategy to be adopted should take into account both lung and brain needs. Registration The study protocol was approved by the ethics review board (Comitato Etico Regione Liguria, protocol n. CER Liguria: 23/2020).

Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review.

In critically ill patients with acute respiratory distress syndrome (ARDS) coronavirus disease 2019 (COVID-19), a high incidence of thromboembolic and hemorrhagic events is reported. COVID-19 may lead to impairment of the coagulation cascade, with an imbalance in platelet function and the regulatory mechanisms of coagulation and fibrinolysis. Clinical manifestations vary from a rise in laboratory markers and subclinical microthrombi to thromboembolic events, bleeding, and disseminated intravascular coagulation. After an inflammatory trigger, the mechanism for activation of the coagulation cascade in COVID-19 is the tissue factor pathway, which causes endotoxin and tumor necrosis factor-mediated production of interleukins and platelet activation. The consequent massive infiltration of activated platelets may be responsible for inflammatory infiltrates in the endothelial space, as well as thrombocytopenia. The variety of clinical presentations of the coagulopathy confronts the clinician with the difficult questions of whether and how to provide optimal supportive care. In addition to coagulation tests, advanced laboratory tests such as protein C, protein S, antithrombin, tissue factor pathway inhibitors, D-dimers, activated factor Xa, and quantification of specific coagulation factors can be useful, as can thromboelastography or thromboelastometry. Treatment should be tailored, focusing on the estimated risk of bleeding and thrombosis. The aim of this review is to explore the pathophysiology and clinical evidence of coagulation disorders in severe ARDS-related COVID-19 patients.