Background
In this study, we explored whether awake prone position (PP) can impact prognosis of severe hypoxemia coronavirus disease 2019 (COVID-19) patients.
Methods This was a prospective observational study of severe, critically ill adult COVID-19 patients admitted to the intensive care unit. Patients were divided into two groups: group G1, patients who benefited from a vigilant and effective PP (>4 hours minimum/24) and group G2, control group. We compared demographic, clinical, paraclinical and evolutionary data.
Results Three hundred forty-nine patients were hospitalized during the study period, 273 met the inclusion criteria. PP was performed in 192 patients (70.3%). The two groups were comparable in terms of demographic characteristics, clinical severity and modalities of oxygenation at intensive care unit (ICU) admission. The mean PaO2/ FIO2 ratios were 141 and 128 mm Hg, respectively (P=0.07). The computed tomography scan was comparable with a critical >75% in 48.5% (G1) versus 54.2% (G2). The median duration of the daily PP session was 13±7 hours per day. The average duration of spontaneous PP days was 7 days (4–19). Use of invasive ventilation was lower in the G1 group (27% vs. 56%, P=0.002). Healthcare-associated infections were significantly lower in G1 (42.1% vs. 82%, P=0.01). Duration of total mechanical ventilation and length of ICU stay were comparable between the two groups. Mortality was significantly higher in G2 (64% vs. 28%, P=0.02).
Conclusions Our study confirmed that awake PP can improve prognosis in COVID-19 patients. Randomized controlled trials are needed to confirm this result.
Background There is a lack of data on extravascular lung water index (EVLWi), pulmonary vascular permeability index (PVPi), and global end-diastolic volume index (GEDVi) during prone position ventilation (PPV) in coronavirus disease 2019 (COVID-19) patients. The objectives of this study were to analyze trends in EVLWi, PVPi, and GEDVi during PPV and the relationships between these parameters and PaO2/FiO2. Methods: In this preliminary retrospective observational study, we performed transpulmonary thermodilution (TPTD) in seven mechanically ventilated COVID-19 patients without cardiac and pulmonary comorbidities requiring PPV for 18 hours, at specific times (30 minutes pre-PPV, 18 hours after PPV, and 3 hours after supination). EVLWi, PVPi and GEDVi were measured. The relationships between PaO2/FiO2 and EVLWi, and PVPi and GEDVi values, in the supine position were analyzed by linear regression. Correlation and determination coefficients were calculated. Results: EVLWi was significantly different between three time points (analysis of variance, P=0.004). After 18 hours in PPV, EVLWi was lower compared with values before PPV (12.7±0.9 ml/kg vs. 15.3±1.5 ml/kg, P=0.002). Linear regression showed that only EVLWi was correlated with PaO2/FiO2 (β =–5.757; 95% confidence interval, –10.835 to –0.679; r=–0.58; R2 =0.34; F-test P=0.029). Conclusions: EVLWi was significantly reduced after 18 hours in PPV and values measured in supine positions were correlated with PaO2/FiO2. This relationship can help clinicians discriminate whether deterioration in gas exchange is related to fluid overload or disease progression. Further clinical research should evaluate the role of TPTD parameters as markers to stratify disease severity and guide clinical management.
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Background There are limited data on the clinical effects of prone positioning according to lung morphology. We aimed to determine whether the gas exchange response to prone positioning differs according to lung morphology.
Methods This retrospective study included adult patients with moderate-to-severe acute respiratory distress syndrome (ARDS). The lung morphology of ARDS was assessed by chest computed tomography scan and classified as “diffuse” or “focal.” The primary outcome was change in partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio after the first prone positioning session: first, using the entire cohort, and second, using subgroups of patients with diffuse ARDS matched 2 to 1 with patients with focal ARDS at baseline.
Results Ninety-five patients were included (focal ARDS group, 23; diffuse ARDS group, 72). Before prone positioning, the focal ARDS group showed worse oxygenation than the diffuse ARDS group (median PaO2/FiO2 ratio, 79.9 mm Hg [interquartile range (IQR)], 67.7–112.6 vs. 104.0 mm Hg [IQR, 77.6–135.7]; P=0.042). During prone positioning, the focal ARDS group showed a greater improvement in the PaO2/FiO2 ratio than the diffuse ARDS group (median, 55.8 mm Hg [IQR, 11.1–109.2] vs. 42.8 mm Hg [IQR, 11.6–83.2]); however, the difference was not significant (P=0.705). Among the PaO2/FiO2-matched cohort, there was no significant difference in change in PaO2/FiO2 ratio after prone positioning between the groups (P=0.904).
Conclusions In patients with moderate-to-severe ARDS, changes in PaO2/FiO2 ratio after prone positioning did not differ according to lung morphology. Therefore, prone positioning can be considered as soon as indicated, regardless of ARDS lung morphology.
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Background Severe acute pancreatitis (SAP) is a systemic inflammatory disease, and it can often complicate into acute kidney injury (AKI) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study aimed to evaluate the clinical effectiveness of blood purification using a polymethylmethacrylate (PMMA) hemofilter.
Methods We retrospectively examined 54 patients, who were diagnosed with SAP according to the Japanese criteria from January 2011 to December 2019.
Results Of a total of 54 SAP patients, 26 patients progressively developed AKI and required continuous hemodialysis with a PMMA membrane hemofilter (PMMA-CHD). Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were significantly higher in patients requiring PMMA-CHD than in patients not requiring hemodialysis. The lung injury scores were also significantly higher in patients requiring PMMA-CHD. Of the 26 patients, 16 patients developed ALI/ARDS and required mechanical ventilation. A total of seven patients developed severe ALI/ARDS and received additional intermittent hemodiafiltration using a PMMA hemofilter (PMMA-HDF). Although the length of intensive care unit stay was significantly longer in patients with severe ALI/ARDS, blood purification therapy was discontinued in all the patients. The survival rates at the time of discharge were 92.3% and 92.9% in patients with and without PMMA-CHD, respectively. These real mortality ratios were obviously lower than the estimated mortality ratios predicted by APACHE II scores.
Conclusions These finding suggest that the blood purification using a PMMA hemofilter would be effective for the treatment of AKI and ALI/ARDS in SAP patients.
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Background Data on pulmonary hemodynamic parameters in patients with acute respiratory distress syndrome (ARDS) receiving extracorporeal membrane oxygenation (ECMO) are scarce.
Methods The associations between pulmonary artery catheter parameters for the first 7 days of ECMO, fluid balance, and hospital mortality were investigated in adult patients (aged ≥19 years) who received venovenous ECMO for refractory ARDS between 2015 and 2017.
Results Twenty patients were finally included in the analysis (median age, 56.0 years; interquartile range, 45.5–68.0 years; female, n=10). A total of 140 values were collected for each parameter (i.e., 7 days×20 patients). Net fluid balance was weakly but significantly correlated with systolic and diastolic pulmonary arterial pressures (PAPs; r=0.233 and P=0.011; r=0.376 and P<0.001, respectively). Among the mechanical ventilation parameters, above positive end-expiratory pressure was correlated with systolic PAP (r=0.191 and P=0.025), and static compliance was negatively correlated with diastolic PAP (r=−0.169 and P=0.048). Non-survivors had significantly higher systolic PAPs than in survivors. However, in multivariate analysis, there was no significant association between mean systolic PAP and hospital mortality (odds ratio, 1.500; 95% confidence interval, 0.937–2.404; P=0.091).
Conclusions Systolic PAP was weakly but significantly correlated with net fluid balance during the early ECMO period in patients with refractory ARDS receiving ECMO.
Background Coronavirus disease 2019 (COVID-19) is one of the biggest pandemic causing acute respiratory failure (ARF) in the last century. Seasonal influenza carries high mortality, as well. The aim of this study was to compare features and outcomes of critically-ill COVID-19 and influenza patients with ARF.
Methods Patients with COVID-19 and influenza admitted to intensive care unit with ARF were retrospectively analyzed.
Results Fifty-four COVID-19 and 55 influenza patients with ARF were studied. Patients with COVID-19 had 32% of hospital mortality, while those with influenza had 47% (P=0.09). Patients with influenza had higher Eastern Cooperative Oncology Group, Clinical Frailty Scale, Acute Physiology and Chronic Health Evaluation II and admission Sequential Organ Failure Assessment (SOFA) scores than COVID-19 patients (P<0.01). Secondary bacterial infection, admission acute kidney injury, procalcitonin level above 0.2 ng/ml were the independent factors distinguishing influenza from COVID-19 while prone positioning differentiated COVID-19 from influenza. Invasive mechanical ventilation (odds ratio [OR], 42.16; 95% confidence interval [CI], 9.45–187.97), admission SOFA score more than 4 (OR, 5.92; 95% CI, 1.85–18.92), malignancy (OR, 4.95; 95% CI, 1.13–21.60), and age more than 65 years (OR, 3.31; 95% CI, 0.99–11.03) were found to be independent risk factors for hospital mortality.
Conclusions There were few differences in clinical features of critically-ill COVID-19 and influenza patients. Influenza cases had worse performance status and disease severity. There was no significant difference in hospital mortality rates between COVID-19 and influenza patients.
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We report a patient with severe coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) treated with veno-venous extracorporeal membrane oxygenation (VV ECMO) and programmed multi-level ventilation (PMLV). VV ECMO as a treatment modality for severe ARDS has been described multiple times as a rescue therapy for refractory hypoxemia. It is well known that conventional ventilation can cause ventilator-induced lung injury. Protective ventilation during VV ECMO seems to be beneficial, translating to using low tidal volumes, prone positioning with general concept of open lung approach. However, mechanical ventilation is still required as ECMO per se is usually not sufficient to maintain adequate gas exchange due to hyperdynamic state of the patient and limitation of blood flow via VV ECMO. This report describes ventilation strategy using PMLV during “resting” period of the lung. In short, PMLV is a strategy for ventilating non-homogenous lungs that incorporates expiratory time constants and multiple levels of positive end-expiratory pressure. Using this approach, most affected acute lung injury/ARDS areas can be recruited, while preventing overdistension in healthy areas. To our knowledge, case report using such ventilation strategy for lung resting period has not been previously published.
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Background Africa, like the rest of the world, has been impacted by the coronavirus disease 2019 (COVID-19) pandemic. However, only a few studies covering this subject in Africa have been published. Methods: We conducted a retrospective study of critically ill adult COVID-19 patients—all of whom had a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection— admitted to the intensive care unit (ICU) of Habib Bourguiba University Hospital (Sfax, Tunisia). Results: A total of 96 patients were admitted into our ICU for respiratory distress due to COVID-19 infection. Mean age was 62.4±12.8 years and median age was 64 years. Mean arterial oxygen tension (PaO2)/fractional inspired oxygen (FiO2) ratio was 105±60 and ≤300 in all cases but one. Oxygen support was required for all patients (100%) and invasive mechanical ventilation for 38 (40%). Prone positioning was applied in 67 patients (70%). Within the study period, 47 of the 96 patients died (49%). Multivariate analysis showed that the factors associated with poor outcome were the development of acute renal failure (odds ratio [OR], 6.7; 95% confidence interval [CI], 1.75–25.9), the use of mechanical ventilation (OR, 5.8; 95% CI, 1.54–22.0), and serum cholinesterase (SChE) activity lower than 5,000 UI/L (OR, 5.0; 95% CI, 1.34–19). Conclusions: In this retrospective cohort study of critically ill patients admitted to the ICU in Sfax, Tunisia, for acute respiratory failure following COVID-19 infection, the mortality rate was high. The development of acute renal failure, the use of mechanical ventilation, and SChE activity lower than 5,000 UI/L were associated with a poor outcome.
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Background In this study, we explored whether early application of the prone position (PP) can improve severe hypoxemia and respiratory failure in coronavirus disease 2019 (COVID-19) patients with spontaneous breathing.
Methods This is a prospective observational study of severe, critically ill adult COVID-19 patients admitted to the intensive care unit. All vital parameters were recorded in real time for all patients. Moreover, the results of chest computed tomography (CT), when available, were analyzed.
Results PP was applied in 21 patients who were breathing spontaneously. The application of PP was associated with a significant increase in oxygen saturation measured by pulse oximetry (SpO2) from 82%±12% to 96%±3% (P<0.001) 1 hour later. Moreover, PP was associated with a significant reduction in respiratory rate from 31±10 to 21±4 breaths/min (P<0.001). Furthermore, the number of patients who exhibited signs of respiratory distress after PP was reduced from 10 (47%) to 3 (14%) (P=0.04). Early PP application also led to a clear improvement on CT imaging. It was not, however, associated with a reduction in mortality rate or in the use of invasive mechanical ventilation (P>0.05 for both).
Conclusions Our study confirmed that the early application of PP can improve hypoxemia and tachypnea in COVID-19 patients with spontaneous breathing. Randomized controlled trials are needed to confirm the beneficial effects of PP in COVID-19 patients with spontaneous breathing.
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Background Both coronavirus disease 2019 (COVID-19) and Middle East respiratory syndrome (MERS) can cause acute respiratory distress syndrome (ARDS); however, their ARDS course and characteristics have not been compared, which we evaluate in our study.
Methods MERS patients with ARDS seen during the 2014 outbreak and COVID-19 patients with ARDS admitted between March and December 2020 in our hospital were included, and their clinical characteristics, ventilatory course, and outcomes were compared.
Results Forty-nine and 14 patients met the inclusion criteria for ARDS in the COVID-19 and MERS groups, respectively. Both groups had a median of four comorbidities with high Charlson comorbidity index value of 5 points (P>0.22). COVID-19 patients were older, obese, had significantly higher initial C-reactive protein (CRP), more likely to get trial of high-flow oxygen, and had delayed intubation (P≤0.04). The postintubation course was similar between the groups. Patients in both groups experienced a prolonged duration of mechanical ventilation, and majority received paralytics, dialysis, and vasopressor agents (P>0.28). The respiratory and ventilatory parameters after intubation (including tidal volume, fraction of inspired oxygen, peak and plateau pressures) and their progression over 3 weeks were similar (P>0.05). Rates of mortality in the ICU (53% vs. 64%) and hospital (59% vs. 64%) among COVID-19 and MERS patients (P≥0.54) were very high.
Conclusions Despite some distinctive differences between COVID-19 and MERS patients prior to intubation, the respiratory and ventilatory parameters postintubation were not different. The higher initial CRP level in COVID-19 patients may explain the steroid responsiveness in this population.
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Background Few studies have evaluated the effects of hypothermia on cardiac arrest (CA)-induced liver damage. This study aimed to investigate the effects of hypothermic therapy on the liver in a rat model of asphyxial cardiac arrest (ACA).
Methods Rats were subjected to 5-minute ACA followed by return of spontaneous circulation (RoSC). Body temperature was controlled at 33°C±0.5°C or 37°C±0.5°C for 4 hours after RoSC in the hypothermia group and normothermia group, respectively. Liver tissues in each group were collected at 6 hours, 12 hours, 1 day, and 2 days after RoSC. To examine hepatic inflammation, mast cells were stained with toluidine blue. Superoxide anion radical production was evaluated using dihydroethidium fluorescence straining and expression of endogenous antioxidants (superoxide dismutase 1 [SOD1] and SOD2) was examined using immunohistochemistry.
Results There were significantly more mast cells in the livers of the normothermia group with ACA than in the hypothermia group with ACA. Gradual increase in superoxide anion radical production was found with time in the normothermia group with ACA, but production was significantly suppressed in the hypothermia group with ACA relative to the normothermia group with ACA. SOD1 and SOD2 levels were higher in the hypothermia group with ACA than in the normothermia group with ACA.
Conclusions Experimental hypothermic treatment after ACA significantly inhibited inflammation and superoxide anion radical production in the rat liver, indicating that this treatment enhanced or maintained expression of antioxidants. Our findings suggest that hypothermic therapy after CA can reduce mast cell-mediated inflammation through regulation of oxidative stress and the expression of antioxidants in the liver.
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Background Although the measuring free cortisol is ideal for assessment of hypothalamicpituitary-adrenal function, it is not routinely measured. Salivary cortisol correlates well with the biologically active free cortisol. Therefore, this study measured the morning basal as well as adrenocorticotropic hormone-stimulated salivary cortisol levels in mechanically ventilated patients and compared the results with non-critically ill patients.
Methods We prospectively enrolled 49 mechanically ventilated patients and 120 patients from the outpatient clinic. Serum and saliva samples were collected between 8 AM and 10 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit. The salivary samples were insufficient in 15 mechanically ventilated patients (30.6%), and these patients were excluded from the final analysis.
Results Mechanically ventilated patients (n=34) were significantly older and had lower body mass index and serum albumin levels and higher serum creatinine levels than non-critically ill patients (n=120). After adjustment for these parameters, both basal and stimulated salivary and serum cortisol levels were higher in mechanically ventilated patients. The increase in cortisol was not significantly different between the two groups. Serum cortisol levels showed a positive correlation with salivary cortisol levels. Among mechanically ventilated patients, both basal serum and salivary cortisol levels were lower in survivors than in non-survivors.
Conclusions Both basal total serum and salivary cortisol levels were elevated in mechanically ventilated patients and in non-survivors.
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Background The diagnosis of pediatric acute respiratory distress syndrome (PARDS) is a pragmatic decision based on the degree of hypoxia at the time of onset. We aimed to determine whether reclassification using oxygenation metrics 24 hours after diagnosis could provide prognostic ability for outcomes in PARDS.
Methods Two hundred and eighty-eight pediatric patients admitted between January 1, 2010 and January 30, 2017, who met the inclusion criteria for PARDS were retrospectively analyzed. Reclassification based on data measured 24 hours after diagnosis was compared with the initial classification, and changes in pressure parameters and oxygenation were investigated for their prognostic value with respect to mortality.
Results PARDS severity varied widely in the first 24 hours; 52.4% of patients showed an improvement, 35.4% showed no change, and 12.2% either showed progression of PARDS or died. Multivariate analysis revealed that mortality risk significantly increased for the severe group, based on classification using metrics collected 24 hours after diagnosis (adjusted odds ratio, 26.84; 95% confidence interval [CI], 3.43 to 209.89; P=0.002). Compared to changes in pressure variables (peak inspiratory pressure and driving pressure), changes in oxygenation (arterial partial pressure of oxygen to fraction of inspired oxygen) over the first 24 hours showed statistically better discriminative power for mortality (area under the receiver operating characteristic curve, 0.701; 95% CI, 0.636 to 0.766; P<0.001).
Conclusions Implementation of reclassification based on oxygenation metrics 24 hours after diagnosis effectively stratified outcomes in PARDS. Progress within the first 24 hours was significantly associated with outcomes in PARDS, and oxygenation response was the most discernable surrogate metric for mortality.
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Mitochondria are considered the power house of the cell and are an essential part of the cellular infrastructure, serving as the primary site for adenosine triphosphate production via oxidative phosphorylation. These organelles also release reactive oxygen species (ROS), which are normal byproducts of metabolism at physiological levels; however, overproduction of ROS under pathophysiological conditions is considered part of a disease process, as in sepsis. The inflammatory response inherent in sepsis initiates changes in normal mitochondrial functions that may result in organ damage. There is a complex system of interacting antioxidant defenses that normally function to combat oxidative stress and prevent damage to the mitochondria. It is widely accepted that oxidative stress-mediated injury plays an important role in the development of organ failure; however, conclusive evidence of any beneficial effect of systemic antioxidant supplementation in patients with sepsis and organ dysfunction is lacking. Nevertheless, it has been suggested that antioxidant therapy delivered specifically to the mitochondria may be useful.
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