In vitro evaluation of a new viscoelastometry-based point-of-care analyzer.

INTRODUCTION: The VCM is a point-of-care analyzer using a new viscoelastometry technique for rapid assessment of hemostasis on fresh whole blood. Its characteristics would make it suitable for use in austere environments. The purpose of this study was to evaluate the VCM in terms of repeatability, reproducibility and interanalyzer correlation, reference values in our population, correlation with standard coagulation assays and platelet count, correlation with the TEG5000 analyzer and resistance to stress conditions mimicking an austere environment. METHODS: Repeatability, reproducibility, and interanalyzer correlation were performed on quality control samples (n = 10). Reference values were determined from blood donor samples (n = 60). Correlations with standard biological assays were assessed from ICU patients (n = 30) and blood donors (n = 60) samples. Correlation with the TEG5000 was assessed from blood donor samples. Evaluation of vibration resistance was performed on blood donor (n = 5) and quality control (n = 5) samples. RESULTS: The CVs for repeatability and reproducibility ranged from 0% to 11%. Interanalyzer correlation found correlation coefficients (r2) ranging from 0.927 to 0.997. Our reference values were consistent with those provided by the manufacturer. No robust correlation was found with conventional coagulation tests. The correlation with the TEG5000 was excellent with r2 ranging from 0.75 to 0.92. Resistance to stress conditions was excellent. CONCLUSION: The VCM analyzer is a reliable, easy-to-use instrument that correlates well with the TEG5000. Despite some logistical constraints, the results suggest that it can be used in austere environments. Further studies are required before its implementation.

Reactivation of Epstein-Barr virus among intensive care patients: a prospective observational study.

PURPOSE: Herpesvirus reactivation has been documented among patients in the intensive care unit (ICU) and is associated with increased morbidity and mortality, particularly for cytomegalovirus (CMV). Epstein-Barr virus (EBV) has been poorly studied despite >95% of the population being seropositive. Our preliminary study suggested an association between EBV reactivation and increased morbidity and mortality. This study aimed to investigate this association among patients admitted to the ICU. METHODS: In this multicenter prospective study, polymerase chain reaction was performed to quantify EBV in patients upon ICU admission and then twice a week during their stay. Follow-up was 90 days. RESULTS: The study included 129 patients; 70 (54.3%) had EBV reactivation. On day 90, there was no difference in mortality rates between patients with and without reactivation (25.7% vs 15.3%, p = 0.22). Patients with EBV reactivation at admission had increased mortality compared with those without reactivation and those with later reactivation. EBV reactivation was associated with increased morbidity. Patients with EBV reactivation had fewer ventilator-free days at day 28 than those without reactivation (18 [1-22] vs. 21 days [5-26], p = 0.037) and a higher incidence of acute respiratory distress syndrome (34.3% vs. 17%, p = 0.04), infections (92.9% vs. 78%, p = 0.03), and septic shock (58.6% vs. 32.2%, p = 0.004). More patients with EBV reactivation required renal replacement therapy (30% vs. 11.9%, p = 0.02). EBV reactivation was also associated with a more inflammatory immune profile. CONCLUSION: While EBV reactivation was not associated with increased 90-day mortality, it was associated with significantly increased morbidity.

Severe hypocalcemia at admission is associated with increased transfusion requirements: A retrospective study in a level 1 trauma center.

INTRODUCTION: In recent years, hypocalcemia has been added to the "lethal triad" of the trauma patient, thus constituting the "lethal diamond". Nevertheless, its proper role remains debated. The aim of this study is to evaluate the association between severe hypocalcemia at admission and 24 h- transfusion requirements in severe trauma patients in a level 1 trauma center. STUDY DESIGN AND METHODS: In a monocentric retrospective observational study from January 2015 to May 2021, 137 traumatized adult patients transfused within 24 h after hospital admission was included in the study. The threshold for severe hypo ionized calcemia was ≤ 0.9 mmol/L. RESULTS: 137 patients were included in the study, 23 presented with severe hypo-iCa at admission, 111 moderate hypo-iCa (0.9-1.2 mmol/L) and 3 normal iCa (≥ 1.2 mmol/L). Patients with severe hypo-iCa at admission had higher severity scores (SAPSII 58 IQR [51-70] vs. 45 IQR [32-56]; p = 0.001 and ISS 34 IQR [26-39] vs. 26 IQR [17-34]; p = 0.003). 24 h-transfusion requirements were greater for patients with severe hypo-iCa, regardless of the type of blood products transfused. There was a significant negative correlation between admission iCa and 24 h-transfusion (r = -0.45, p < 0.001). The difference in mortality was not significant between the two groups (24 h mortality: 17 % (4/23) for severe hypo-iCa vs. 8 % (9/114) for non-severe hypo-iCa; p = 0.3). DISCUSSION: This study highlights the high prevalence of severe hypocalcemia in trauma patients and its association with increased 24 h- transfusion requirements.

Study of the Relationship Between Liver Function Markers and Traumatic Rhabdomyolysis: A Retrospective Study of Hemorrhagic Patients Admitted to Intensive Care Unit in a Level I Trauma Center.

BACKGROUND: Traumatic rhabdomyolysis (RM) is common and contributes to the development of medical complications, of which acute renal failure is the best described. Some authors have described an association between elevated aminotransferases and RM, suggesting the possibility of associated liver damage. Our study aims to evaluate the relationship between liver function and RM in hemorrhagic trauma patients. METHODS: This is a retrospective observational study conducted in a level 1 trauma center analyzing 272 severely injured patients transfused within 24 hours and admitted to intensive care unit (ICU) from January 2015 to June 2021. Patients with significant direct liver injury (abdominal Abbreviated Injury Score [AIS] >3) were excluded. Clinical and laboratory data were reviewed, and groups were stratified according to the presence of intense RM (creatine kinase [CK] >5000 U/L). Liver failure was defined by a prothrombin time (PT)-ratio <50% and an alanine transferase (ALT) >500 U/L simultaneously. Correlation analysis was performed using Pearson's or Spearman's coefficient depending on the distribution after log transformation to evaluate the association between serum CK and biological markers of hepatic function. Risk factors for the development of liver failure were defined with a stepwise logistic regression analysis of all relevant explanatory factors significantly associated with the bivariate analysis. RESULTS: RM (CK >1000 U/L) was highly prevalent in the global cohort (58.1%), and 55 (23.2%) patients presented with intense RM. We found a significant positive correlation between RM biomarkers (CK and myoglobin) and liver biomarkers (aspartate transferase [AST], ALT, and bilirubin). Log-CK was positively correlated with log-AST (r = 0.625, P < .001) and log-ALT (r = 0.507, P < .001) and minimally with log-bilirubin (r = 0.262, P < .001). Intensive care unit stays were longer for intense RM patients (7 [4-18] days vs 4 [2-11] days, P < .001). These patients required increased renal replacement therapy use (4.1% vs 20.0%, P < .001) and transfusion requirements. Liver failure was more common (4.6% vs 18.2%, P < .001) for intense RM patients. It was associated with bivariate and multivariable analysis with intense RM (odds ratio [OR], 4.51 [1.11-19.2]; P = .034), need for renal replacement therapy, and Sepsis-Related Organ Failure Assessment Score (SOFA) score on day 1. CONCLUSIONS: Our study established the presence of an association between trauma-related RM and classical hepatic biomarkers. Liver failure was associated with the presence of intense RM in bivariate and multivariable analysis. Traumatic RM could have a role in the development of other system failures, specifically at the hepatic level, in addition to the already known and well-described renal failure.

Step by step transfusion timeline and its challenges in trauma: A retrospective study in a level one trauma center.

BACKGROUND: Hemorrhagic shock is the leading cause of preventable early death in trauma patients. Transfusion management is guided by international guidelines promoting early and aggressive transfusion strategies. This study aimed to describe transfusion timelines in a trauma center and to identify key points to performing early and efficient transfusions. METHODS: This is a monocentric retrospective study of 108 severe trauma patients, transfused within the first 48 h and hospitalized in an intensive care unit between January 2017 and May 2019. RESULTS: One hundred and eight patients were transfused with 1250 labile blood products. Half of these labile blood products were transfused within 3 h of admission and consumed by 26 patients requiring massive transfusion (≥4 red blood cells [RBC] within 1 h). Among these, the median delay from patient's admission to labile blood products prescription was -11 min (-34 to -1); from admission to delivery of labile blood products was 1 min (-20 to 16); and from admission to first transfusion was 20 min (7-37) for RBC, 26 min (13-38) for plasma, and 72 min (51-103) for platelet concentrates. The anticipated prescription of labile blood products and the use of massive transfusion packs and lyophilized plasma units were associated with earlier achievement of high transfusion ratios. CONCLUSION: This study provides detailed data on the transfusion timelines and composition, from prescription to initial transfusion. Transfusion anticipation, use of preconditioned transfusion packs including platelets, and lyophilized plasma allow rapid and high-ratio transfusion practices in severe trauma patients.

Relationship between creatine kinase and liver enzymes in war wounded with rhabdomyolysis.

BACKGROUND: Rhabdomyolysis is a frequent complication in war wounded. Its complex pathophysiology suggests that it not only affects kidneys but also other organs such as the liver. The aim of this study was to evaluate the relationship between creatine kinase (CK) and liver enzymes in war wounded with rhabdomyolysis. METHODS: War wounded admitted to the intensive care unit of Percy Military Hospital between 2009 and 2017 with a rhabdomyolysis (CK peak >1,000 U/L) were included. They were divided in two groups: mild (CK peak <10,000 U/L) and severe rhabdomyolysis (CK peak ≥10,000 U/L). Demographic characteristics, peaks in transaminases, alkaline phosphatase (ALP), bilirubin, and CK were recorded. Mann Whitney-U test and, Fisher's exact test were used as appropriate. A Pearson's correlation test was used to determine the correlation between CK and liver enzymes after a log-normal transformation of the data. RESULTS: Fifty-one patients were included (31 in the mild and 20 in the severe rhabdomyolysis group). Patients in the severe rhabdomyolysis group were more likely victims of explosions (85% vs 39%, p = 0.003). The transaminases peak was significantly higher in the severe rhabdomyolysis group (median AST peak 398 (270-944) vs 91 (63-157) U/L, p <0.0001, and median ALT peak 106 (77-235) vs 45 (34-71) U/L, p<0.0001). Bilirubin and ALP were higher in the severe rhabdomyolysis group (39 (25-49) vs 14(11-23) U/L, p = 0.0031 and 84 (55-170) vs 52 (39-85) U/L, p = 0.0063, respectively). We found a significant positive linear correlation between CK and ALT (r = 0.73, p<0.0001), AST (r = 0.89, p<0.0001), ALP (r = 0.41, p = 0.0035), and bilirubin (r = 0.37, p = 0.0083). CONCLUSION: We found a statistically significant positive correlation between CK and liver enzymes in rhabdomyolysis war wounded, indicating that hepatic damage occurs when rhabdomyolysis is severe and associated with elevated bilirubin and ALP. Further studies are needed to confirm this phenomenon and elucidate the pathophysiological mechanism. LEVEL OF EVIDENCE: IV STUDY TYPE: Diagnostic.

Intravenous immunoglobulins in patients with COVID-19-associated moderate-to-severe acute respiratory distress syndrome (ICAR): multicentre, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a major complication of COVID-19 and is associated with high mortality and morbidity. We aimed to assess whether intravenous immunoglobulins (IVIG) could improve outcomes by reducing inflammation-mediated lung injury. METHODS: In this multicentre, double-blind, placebo-controlled trial, done at 43 centres in France, we randomly assigned patients (1:1) receiving invasive mechanical ventilation for up to 72 h with PCR confirmed COVID-19 and associated moderate-to-severe ARDS to receive either IVIG (2 g/kg over 4 days) or placebo. Random assignment was done with a web-based system and was stratified according to the participating centre and the duration of invasive mechanical ventilation before inclusion in the trial (<12 h, 12-24 h, and >24-72 h), and treatment was administered within the first 96 h of invasive mechanical ventilation. To minimise the risk of adverse events, the IVIG administration was divided into four perfusions of 0·5 g/kg each administered over at least 8 hours. Patients in the placebo group received an equivalent volume of sodium chloride 0·9% (10 mL/kg) over the same period. The primary outcome was the number of ventilation-free days by day 28, assessed according to the intention-to-treat principle. This trial was registered on ClinicalTrials.gov, NCT04350580. FINDINGS: Between April 3, and October 20, 2020, 146 patients (43 [29%] women) were eligible for inclusion and randomly assigned: 69 (47%) patients to the IVIG group and 77 (53%) to the placebo group. The intention-to-treat analysis showed no statistical difference in the median number of ventilation-free days at day 28 between the IVIG group (0·0 [IQR 0·0-8·0]) and the placebo group (0·0 [0·0-6·0]; difference estimate 0·0 [0·0-0·0]; p=0·21). Serious adverse events were more frequent in the IVIG group (78 events in 22 [32%] patients) than in the placebo group (47 events in 15 [20%] patients; p=0·089). INTERPRETATION: In patients with COVID-19 who received invasive mechanical ventilation for moderate-to-severe ARDS, IVIG did not improve clinical outcomes at day 28 and tended to be associated with an increased frequency of serious adverse events, although not significant. The effect of IVIGs on earlier disease stages of COVID-19 should be assessed in future trials. FUNDING: Programme Hospitalier de Recherche Clinique.

Prolonged tactical tourniquet application for extremity combat injuries during war against terrorism in the Sahelian strip.

PURPOSE: This study reports on complications following extended tourniquet application in patients with combat extremity injuries treated by the French Military Health Service in the Sahelian strip. METHODS: A retrospective review was performed in a French forward medical treatment facility deployed in Gao, Mali, between 2015 and 2020. All patients treated for an extremity injury with the application of at least one tourniquet for a minimum of 3 h were included. Prehospital data were injury pattern, associated shock, tourniquet location, and duration. Subsequent complications and surgical procedures performed were analyzed. RESULTS: Eleven patients with a mean age of 27.4 years (range 21-35 years) were included. They represented 39% of all patients in whom a tourniquet was applied. They had gunshot wounds (n = 7) or multiple blast injuries (n = 4) and totaled 14 extremity injuries requiring tourniquet application. The median ISS was 13 (interquartile range: 13). Tourniquets were mostly applied proximally on the limb for a mean duration of 268 min (range 180-360 min). Rhabdomyolysis was present in all cases. The damage control surgeries included debridement, external fixation, vascular repair, and primary amputation. Ten injuries were complicated by compartment syndrome requiring leg or thigh fasciotomy in the field or after repatriation. Two severely injured patients died of their wounds, but the others had a favorable outcome even though secondary amputation was sometimes required. CONCLUSIONS: Extended and proximal tourniquet applications led to significant morbidity related to compartment syndrome and rhabdomyolysis. Hemorrhagic shock, mass casualty incident, and tactical constraints often precluded revising the temporary tourniquet applied under fire.

The implementation of a multinational "walking blood bank" in a combat zone: The experience of a health service team deployed to a medical treatment facility in Afghanistan.

BACKGROUND: We present here a description of the experience in whole-blood transfusion of a health service team deployed to a medical treatment facility in Afghanistan from June 2011 to October 2011. The aim of our work was to show how a "walking blood bank" could provide a sufficient supply. METHODS: We gathered the blood-group types of military personnel deployed to the theater of operations to evaluate our "potential walking blood bank," and we compared these data with our needs. RESULTS: Blood type frequencies among our "potential walking blood bank" were similar to those observed in European or American countries. Our resources could have been limited because of a low frequency of B blood type and negative rhesus in our "potential walking blood bank." Because of the large number of potential donors in the theater of operations, the risk of blood shortage was quite low and we did not face blood shortage despite significant transfusion requirements. Actually, 93 blood bags were collected, including rare blood types like AB and B blood types. CONCLUSION: In our experience, this international "walking blood bank" provided a quick, safe, and sufficient blood supply. More research in this area is needed, and our results should be confirmed by further prospective trials. LEVEL OF EVIDENCE: Therapeutic study, level V.

Epstein-Barr virus reactivation in critically ill immunocompetent patients.

BACKGROUND: Herpes viruses can be reactivated among immunocompetent patients in intensive care unit (ICU). Cytomegalovirus (CMV) and herpes simplex virus (HSV) have been the most studied. We hypothesized that Epstein-Barr virus (EBV) could also be reactivated in immunocompetent patients during their stay in ICU and that this would be associated with morbidity and mortality. METHODS: This prospective observational study included 90 patients with an ICU stay of ≥ 5 days. CMV and HSV were considered when clinically suspected and DNA was researched in blood or bronchoalveolar lavage (BAL). EBV DNA viral quantification was performed in the blood samples. RESULTS: EBV DNA was detected in blood of 61 patients (median length for positivity of 7.5 days). CMV DNA was detected in blood of 16 patients (median length for positivity of 13.5 days) and BAL of 6 patients. HSV1 DNA was detected in the BAL of 28 patients (median length for positivity of 7.5 days). Nineteen patients had no viral reactivation, 1 experienced only CMV, 32 had only EBV, 5 had only HSV, 6 had EBV and CMV, 14 had EBV and HSV, and 9 patients reactivated three viruses. Mortality was higher among patients with EBV reactivation (33/61 vs. 7/25, p = 0.02). Length of stay (21 vs. 10 days, p < 0.001) and length of mechanical ventilation (15 vs. 7 days, p < 0.001) were higher among patients with EBV reactivation. CONCLUSIONS: This study shows that EBV DNA is detected in blood of diverse ICU patients with ≥ 5 days of stay and that it is associated with morbidity and mortality. Larger dynamic prospective studies are needed to correlate viral reactivation with immune system evolution during ICU stay and to determine the role of polyviral reactivations.