Beneficial of adding Tocilizumab to standard care in critical forms of Covid-19 pneumonia: Study on paired series.

INTRODUCTION: Tocilizumab (TCZ), a humanized monoclonal antibody directed against interleukin-6 (IL-6) receptors, has been tried in various studies as a Covid-19 therapy with controversial results. AIM: To evaluate the effectiveness of adding TCZ to standard care (SC) in critical Covid-19 patients. METHODS: it was designed retrospectively as a comparative study on two paired series of critical patients affected with Covid-19: the 1st group received TCZ plus SC versus a 2nd group which received only SC. The matching criteria were age, sex and severity score and the matching was based on the propensity score matching (PSM) by the nearest neighbor. Outcomes were: survival, mechanical ventilation (MV) and nosocomial infections. RESULTS: Ninety patients were included by pairing estimated successful (PSM > 0.5 in more than 50% in each group for all matching criteria). 55.5% of SC group progressed to stage 3-acute respiratory distress syndrome (ARDS) versus 31% of TCZ+SC patients (p=0.03). No effect of TCZ was found on mortality (49% in each group, p=1) nor on MV use (p=0.67). ICU stay was more prolonged in TCZ+SC group (16 versus 8 days, p<10-3). The administration of TCZ induced a significant decrease in CRP but not changed the IL-6 dosage. Nosocomial infections occurred in 18 (40%) of TCZ+SC group comparatively to 15 (33,5%) of SC group, p=0.66. CONCLUSION: Tocilizumab reduced the risk of progression to severe ARDS probably due to its immune-modulating properties. But no beneficial effect was found on survival or on the use of ventilation.

Shunt in critically ill Covid-19 ARDS patients: Prevalence and impact on outcome (cross-sectional study).

PURPOSE: To examine critical Covid-19-acute respiratory distress syndrome (C-ARDS) patients requiring mechanical ventilation (MV), using transthoracic echocardiography (TTE) coupled with bubble test (BT), in order to search a right/left shunt. METHODS: A Cross-sectional and comparative study comparing several parameters according to the presence or not of shunt. RESULTS: 75 patients were included. Twenty-three shunts (31%) were detected: patent foramen oval (PFO) type [n=11 (15%)] and trans-pulmonary transit of bubbles (TPBT) [n = 12 (16%)]. The shunt did not affect P/F ratio (P/F=77 vs 81, p=0.97), nor mortality. CONCLUSION: A right/left shunt was detected in a third of studied patients similarly between PFO and TPBT without significant impact on P/F ratio or outcome.

COVID-19-induced acute kidney injury in critically ill patients: epidemiology, risk factors, and outcome.

BACKGROUND: The kidney represents a potential target for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Clinical data about acute kidney injury (AKI) during SARS-CoV-2 infection are lacking. We aimed to investigate the proportion, risk factors, and prognosis of AKI in critical patients affected with SARS-CoV-2. METHODS: A case/control study was conducted in two intensive care units of a tertiary teaching hospital. RESULTS: Among 109 patients, 75 were male (69%) with median age at 64 years and 48 (44%) developed AKI within 4 days (interquartile range [IQR], 1-9). Of them, 11 (23%), 9 (19%), and 28 (58%) were classified as stage 1, 2, and 3, respectively. AKI patients were older and presented more sepsis, acute respiratory distress syndrome, and rhabdomyolysis; higher initial urea and creatinine; more marked inflammatory syndrome and hematological disorders; and required more mechanical ventilation and vasopressors. An elevated D-dimers level (odds ratio [OR], 12.83; 95% confidence interval [CI], 1.9-85) was an independent factor of AKI. Sepsis was near to significance (OR, 5.22; 95% CI, 0.94-28; P=0.058). AKI was independently related to mortality (OR, 6.8; 95% CI, 1.49-105) and significantly reduced the survival (14.7 days; IQR, 12-17 vs. 19.9 days; IQR, 17-22.7; P=0.011) in AKI and no AKI group respectively. Hypoxemia with the ratio of the arterial partial pressure of oxygen and the inspiratory concentration of oxygen <70, and vasopressors were identified as mortality factors. CONCLUSIONS: AKI occurred in almost half the studied patients and significantly worsened their prognosis. A high D-dimers level and sepsis contributed significantly to its development.

Ultrasound assessment of the diaphragm during the first days of mechanical ventilation compared to spontaneous respiration: a comparative study.

INTRODUCTION: In critically ill patients, the diaphragm is subject to several aggressions mainly those induced by mechanical ventilation (MV). Currently, diaphragmatic ultrasound has become the most useful bedside for the clinician to evaluate diaphragm contractility. AIM:   To examine the effects of MV on the diaphragm contractility during the first days of ventilation. METHODS: Two groups of subjects were studied: a study group (n=30) of adults receiving MV versus a control group (n=30) of volunteers on spontaneous ventilation (SV). Using an ultrasound device, we compared the diaphragmatic thickening fraction (DTF). Secondly, we analysed the relationship between DTF and weaning. RESULTS: comparatively to SV group, patients of MV group have a higher end expiratory diameter (EED) (2.09 ± 0.6 vs. 1.76 ± 0.32 mm, p=0.01) and a lower DTF (39.9 ± 12.5%  vs.  49.0 ± 20.5%, p=0.043). Fourteen among the 30 ventilated patients successfully weaned. No significant correlation was shown between DTF and weaning duration (Rho= - 0.464, p=0.09). A DTF value > 33% was near to be significantly associated with weaning success (OR=2; 95% CI= [1.07-3.7], p=0.05) with a sensitivity at 85.7%. CONCLUSIONS: diaphragmatic contractility was altered from the first days of MV. A DTF value >32,7% was associated to the weaning success and that may be useful to predict successful weaning with sensitivity at 85.7%.

Ultrasound variations of diaphragm activity between prone position versus supine position in ventilated patients: a cross-sectional comparative study.

PURPOSE: To evaluate the effect of the positioning from the supine position (SP) to the prone position (PP) on the diaphragm activity in ventilated patients; using the ultrasound (US) imaging. METHODS: A cross-sectional comparative study before/after PP was conducted on 40 ICU patients over 18 years who received invasive ventilation (IV) for at least 48 h. The considered ventilator modes were: assisted control volume with a low trigger flow (between - 2 and 2 L/mn) and pressure support mode. US diaphragmatic assessments were performed at SP and at 60 min of PP. Both End-inspiratory and End-expiratory diameters (EID/EED) were taken at 3 levels of axillary lines and determined by the average values of multiple measures. Diaphragmatic thickening fraction (DTF) was calculated as: DTF = (EID - EED/EED) × 100. Pairing and ANOVA tests were used for comparisons. RESULTS: Forty ventilated patients (42 years of median age) at 4 days [2-7] of median duration of ventilation were examined during the two positions: SP versus PP. EID decreased from the SP to the PP (2.8 mm in SP vs. 2.4 mm in PP, p = 0.001). No difference was showed regarding the expiratory thickness. Overall, DTF didn't change in PP (37.4 vs. 42.05%, p = 0.36). When the patient was placed in PP, the best DTF value was showed at the posterior part of diaphragm (posterior: 45%, median: 31% and anterior: 38%, p = 0.049). CONCLUSION: The ventral placement in ventilated patients reduced end-inspiratory diameter and tended to decrease DTF. In PP, the best contractile activity was detected at the posterior region of diaphragm.

Appropriateness of empiric antimicrobial therapy with imipenem/colistin in severe septic patients: observational cohort study.

BACKGROUND: Empiric antimicrobial therapy (EAMT) using imipenem/colistin is commonly prescribed as a first line therapy in critically ill patients with severe sepsis. We aimed to assess the appropriateness of prescribing imipenem/colistin as EAMT in ICU patients. METHODS: A 3-year observational prospective study included ICU patients that required imipenem/colistin as EAMT. The EAMT was assessed according to microbiological and clinical outcomes. The outcomes were: delay in apyrexia, delay in the decrease of the biological inflammatory parameters (BIP), the requirement for vasoactive agents, bacteriological eradication, length of stay, ventilator days and 30-day mortality. RESULTS: 79 administrations of EAMT in 70 patients were studied. EAMT was appropriate in 52% of the studied cases. An ICU stay > 6 days was related to inappropriateness, and chronic respiratory failure was associated with appropriateness. In the appropriate EAMT group, we showed: earlier apyrexia, shorter delay in the decrease of the BIP and a reduced significant vasopressors requirement. Furthermore, EAMT improved survival with a median gain of 4 days. Inappropriate EAMT increased the mortality risk by six. The acquisition of NI in ICU was also an independent factor of mortality. CONCLUSIONS: EAMT using imipenem-colistin was appropriate in half of the cases and inappropriateness was associated with an increased ICU mortality risk.