Major bleeding complications in critically ill patients with COVID-19 pneumonia.

As patients with COVID-19 pneumonia admitted to intensive care unit (ICU) have high rates of thrombosis, high doses of thromboprophylaxis have been proposed. The associated bleeding risk remains unknown. We investigated major bleeding complications in ICU COVID-19 patients and we examined their relationship with inflammation and thromboprophylaxis. Retrospective monocentric study of consecutive adult patients admitted in ICU for COVID-19 pneumonia requiring mechanical ventilation. Data collected included demographics, anticoagulation status, coagulation tests and outcomes including major bleeding and thrombotic events. Among 56 ICU COVID-19 patients, 10 (18%) patients had major bleeding and 16 (29%) thrombotic events. Major bleeding occurred later than thrombosis after ICU admission [17(14-23) days versus 9(3-11) days respectively (p = 0.005)]. Fibrinogen concentration always decreased several days [4(3-5) days] before bleeding; D-dimers followed the same trend. All bleeding patients were treated with anticoagulants and anticoagulation was overdosed for 6 (60%) patients on the day of bleeding or the day before. In the whole cohort, overdose was measured in 22 and 78% of patients receiving therapeutic anticoagulation during fibrinogen increase and decrease respectively (p < 0.05). Coagulation disorders had biphasic evolution during COVID-19: first thrombotic events during initial hyperinflammation, then bleeding events once inflammation reduced, as confirmed by fibrinogen and D-dimers decrease. Most bleeding events complicated heparin overdose, promoted by inflammation decrease, suggesting to carefully monitor heparin during COVID-19. Thromboprophylaxis may be adapted to this biphasic evolution, with initial high doses reduced to standard doses once the high thrombotic risk period ends and fibrinogen decreases, to prevent bleeding events.

Development and validation of a pre-hospital "Red Flag" alert for activation of intra-hospital haemorrhage control response in blunt trauma.

BACKGROUND: Haemorrhagic shock is the leading cause of early preventable death in severe trauma. Delayed treatment is a recognized prognostic factor that can be prevented by efficient organization of care. This study aimed to develop and validate Red Flag, a binary alert identifying blunt trauma patients with high risk of severe haemorrhage (SH), to be used by the pre-hospital trauma team in order to trigger an adequate intra-hospital standardized haemorrhage control response: massive transfusion protocol and/or immediate haemostatic procedures. METHODS: A multicentre retrospective study of prospectively collected data from a trauma registry (Traumabase®) was performed. SH was defined as: packed red blood cell (RBC) transfusion in the trauma room, or transfusion ≥ 4 RBC in the first 6 h, or lactate ≥ 5 mmol/L, or immediate haemostatic surgery, or interventional radiology and/or death of haemorrhagic shock. Pre-hospital characteristics were selected using a multiple logistic regression model in a derivation cohort to develop a Red Flag binary alert whose performances were confirmed in a validation cohort. RESULTS: Among the 3675 patients of the derivation cohort, 672 (18%) had SH. The final prediction model included five pre-hospital variables: Shock Index ≥ 1, mean arterial blood pressure ≤ 70 mmHg, point of care haemoglobin ≤ 13 g/dl, unstable pelvis and pre-hospital intubation. The Red Flag alert was triggered by the presence of any combination of at least two criteria. Its predictive performances were sensitivity 75% (72-79%), specificity 79% (77-80%) and area under the receiver operating characteristic curve 0.83 (0.81-0.84) in the derivation cohort, and were not significantly different in the independent validation cohort of 2999 patients. CONCLUSION: The Red Flag alert developed and validated in this study has high performance to accurately predict or exclude SH.

European trauma guideline compliance assessment: the ETRAUSS study.

INTRODUCTION: Haemorrhagic shock is the leading cause of preventable death in trauma patients. The 2013 European trauma guidelines emphasise a comprehensive, multidisciplinary, protocol-based approach to trauma care. The aim of the present Europe-wide survey was to compare 2015 practice with the 2013 guidelines. METHODS: A group of members of the Trauma and Emergency Medicine section of the European Society of Intensive Care Medicine developed a 50-item questionnaire based upon the core recommendations of the 2013 guidelines, employing a multistep approach. The questionnaire covered five fields: care structure and organisation, haemodynamic resuscitation targets, fluid management, transfusion and coagulopathy, and haemorrhage control. The sampling used a two-step approach comprising initial purposive sampling of eminent trauma care providers in each European country, followed by snowball sampling of a maximum number of trauma care providers. RESULTS: A total of 296 responses were collected, 243 (81 %) from European countries. Those from outside the European Union were excluded from the analysis. Approximately three-fourths (74 %) of responders were working in a designated trauma centre. Blunt trauma predominated, accounting for more than 90 % of trauma cases. Considerable heterogeneity was observed in all five core aspects of trauma care, along with frequent deviations from the 2013 guidelines. Only 92 (38 %) of responders claimed to comply with the recommended systolic blood pressure target, and only 81 (33 %) responded that they complied with the target pressure in patients with traumatic brain injury. Crystalloid use was predominant (n = 209; 86 %), and vasopressor use was frequent (n = 171, 76 %) but remained controversial. Only 160 respondents (66 %) declared that they used tranexamic acid always or often. CONCLUSIONS: This is the first European trauma survey, to our knowledge. Heterogeneity is significant across centres with regard to the clinical protocols for trauma patients and as to locally available resources. Deviations from guidelines are frequent, differ from region to region and are dependent upon specialty training. Further efforts are required to provide consensus guidelines and to improve their implementation across European countries.

Fluid resuscitation and vasopressors in severe trauma patients.

PURPOSE OF REVIEW: To discuss the fluid resuscitation and the vasopressor support in severe trauma patients. RECENT FINDINGS: A critical point is to prevent a potential increase in bleeding by an overly aggressive resuscitative strategy. Indeed, large-volume fluid replacement may promote coagulopathy by diluting coagulation factors. Moreover, an excessive level of mean arterial pressure may induce bleeding by preventing clot formation. SUMMARY: Fluid resuscitation is the first-line therapy to restore intravascular volume and to prevent cardiac arrest. Thus, fluid resuscitation before bleeding control must be limited to the bare minimum to maintain arterial pressure to minimize dilution of coagulation factors and complications of over fluid resuscitation. However, a strategy of low fluid resuscitation needs to be handled in a flexible way and to be balanced considering the severity of the hemorrhage and the transport time. A target systolic arterial pressure of 80-90 mmHg is recommended until the control of hemorrhage in trauma patients without brain injury. In addition to fluid resuscitation, early vasopressor support may be required to restore arterial pressure and prevent excessive fluid resuscitation. It is crucial to find the best alchemy between fluid resuscitation and vasopressors, to consider hemodynamic monitoring and to establish trauma resuscitative protocols.

Cangrelor for cardiopulmonary bypass in patients with heparin-induced thrombocytopenia: it is not so easy.

Anticoagulation management for cardiopulmonary bypass (CPB) is challenging in patients with acute heparin-induced thrombocytopenia (HIT). The strategy of combining cangrelor intraoperatively with heparin for CPB anticoagulation is of increasing interest but exposes to specific unresolved problems. We report the case of a patient requiring surgical pulmonary embolectomy for pulmonary embolism at the very acute phase of HIT, with a high titre of anti-PF4/heparin antibodies and severe thrombocytopenia. For CPB management, cangrelor was administered in combination with heparin prescribed and monitored as usual. Surgery was successfully performed, but postoperatively, the patient developed a new thrombotic event. We discussed the specific problems associated with such strategy, including the dose of cangrelor and its monitoring, the management of the cell-saver, the risk of heparin rebound and the risk of platelet transfusion. These issues must be addressed before considering the combination of cangrelor and unfractionated heparin as a standard of care for CBP.

Comprehensive analysis of coagulation factor delivery strategies in a cohort of trauma patients.

PURPOSE: The 5th edition of The European recommendations for the management of major bleeding and coagulopathy following trauma leaves room for various coagulation factor administration strategies. The present study examines these strategies reporting prevalence and timing of administration, quantity dispensed, and transfusion ratios in French trauma centers and their compliance with recommendations alongside associated mortality data. METHODS: All adult patients, admitted directly to participating centers between 2011 and 2019, were extracted from a trauma registry. Two subpopulations were studied: severe hemorrhage (SH) and massive transfusion (MT) groups. RESULTS: A total of 19,396 patients were included, among whom 8.4% (1630) experienced SH and 3% (579) received MT. Within the first 24 hours, 10% received fresh frozen plasma (FFP), rising to 93% and 99% in the subgroups of patients experiencing SH and MT respectively. Only, 8% received fibrinogen concentrate (FC), increasing to 75% and 92% in subgroups SH and MT respectively. Co-administration of FFP and FC became the dominant strategy with 68% of patients at 6 h and 72% at 24 h in SH subgroup. In unadjusted data, mortality was systematically lower in groups that complied with recommendations, a lower mortality than expected was mostly observed in contrast to non-compliant subgroups. The per-patient compliance to studied recommendations was 21% and 22% in SH and MT subgroups. CONCLUSION: The main hemostatic strategy for major bleeding combined the administration of both FFP and FC, favoring an early additional supply of fibrinogen. Compliance with the recommendations was low in SH and MT subgroups.

The conundrum of the definition of haemorrhagic shock: a pragmatic exploration based on a scoping review, experts' survey and a cohort analysis.

PURPOSE: Traumatic hemorrhagic shock (THS) is a complex, dynamic process and, no consensual definition of THS is available. This study aims (1) to explore existing definitions of traumatic hemorrhagic shock (THS), (2) to identify essential components of these definitions and (3) to illustrate in a pragmatic way the consequences of applying five of these definitions to a trauma registry. METHODS: We conducted (1) a scoping review to identify the definitions used for traumatic hemorrhagic shock (THS); (2) an international experts survey to rank by relevance a selection of components extracted from these definitions and (3) a registry-based analysis where several candidate definitions were tested in a large trauma registry to evaluate how the use of different definitions affected baseline characteristics, resources use and patient outcome. RESULTS: Sixty-eight studies were included revealing 52 distinct definitions. The most frequently used was "a systolic blood pressure (SBP) less than or equal to 70 mmHg or between 71 and 90 mmHg if the heart rate is greater than or equal to 108 beats per min". The expert panel identified base excess, blood lactate concentration, SBP and shock index as the most relevant physiological components to define THS. Five definitions of THS were tested and highlighted significant differences across groups on important outcomes such as the proportion of massive transfusion, the need for surgery, in-hospital length of stay or in-hospital mortality. CONCLUSIONS: This study demonstrates a large heterogeneity in the definitions of THS suggesting a need for standardization. Five candidate definitions were identified in a three-step process to illustrate how each shapes study cohort composition and impacts outcome. The results inform research stakeholders in the choice of a consensual definition.

Long-term outcome following blunt cerebrovascular injuries: occurrence of ischemic complications, treatment, and outcome.

PURPOSE: Blunt cerebrovascular injuries (BCVI) are a rare but serious complication after trauma. Among patients with BCVI, neurological status is altered in 30% of cases and the prognosis seems to be associated with ischemic complications. The aim of this study was to assess the long-term outcome of BCVI-associated ischemic events. METHODS: This retrospective cohort study (2011-2017) included all patients admitted for severe trauma with identified BCVI in two level-1 trauma centers. Patients were considered to have a poor neurological outcome with a GOS-E between 2 and 5 and a good neurological outcome with GOS-E between 6 and 8. A multivariate logistic regression identified risk factors for poor neurological outcome at 1 year. RESULTS: Of the 6,294 patients admitted in both trauma centers between 2011 and 2017, 81 patients presenting BCVI were identified (incidence of 1.3%). The median age was 35 years (24-44) with a median Injury Severity Score of 28 (17-41). 29 patients (50%) had a good neurological prognosis, while 25 patients (43%) had a poor neurological prognosis at 1 year. Ischemic stroke occurred in 11 patients (13.6%) within a median time of 2 days (2-2.5). No ischemic stroke occurred in the first year after ICU discharge in both groups. In our study, good prognosis at 1 year was not associated with ischemic complications [3 (10) vs 3 (12) p = 1]. CONCLUSION: Ischemic complications after BCVI are rare, occur within the first week and do not seem to impact independently the 1-year neurological prognosis.

Management of moderate to severe traumatic brain injury: an update for the intensivist.

Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements. Even while evidence from randomized clinical trials is still lacking for many of the recommended interventions, these protocols and algorithms can be useful to define a clear standard of therapy where novel interventions can be added or be compared to. Over the past decade, more attention has been paid to holistic management, in which hemodynamic, respiratory, inflammatory or coagulation disturbances are detected and treated accordingly. Considerable variability with regards to the trajectories of recovery exists. Even while most of the recovery occurs in the first months after TBI, substantial changes may still occur in a later phase. Neuroprognostication is challenging in these patients, where a risk of self-fulfilling prophecies is a matter of concern. The present article provides a comprehensive and practical review of the current best practice in clinical management and long-term outcomes of moderate to severe TBI in adult patients admitted to the intensive care unit.

Trauma centre admissions for traumatic brain injury in France: One-year epidemiological analysis of prospectively collected data.

INTRODUCTION: In France, there is a lack of recent data on Traumatic brain injury (TBI), remaining a major global health challenge in terms of morbidity and mortality. The present study reports the epidemiology and the factors associated with mortality of patients with TBI admitted to 9 French trauma centres. METHOD: Patients ≥ 15 years old admitted, between the 1st of January and the 31st of December 2017, following TBI (Abbreviated Injury Scale head ≥ 2) were included. Descriptive analyses were carried out and a logistic regression was used in order to identify in-hospital mortality predictors. RESULTS: 1,177 patients (889 males (76%), median age 42 [26-59]) were admitted following TBI. Road traffic accidents were the primary mechanism of TBI. Mechanisms leading to TBI were highly correlated with age. The in-hospital mortality was 23%. In-hospital mortality increased with age, from 15% in 15-24-year-olds to 71% among patients aged 85 years and older. Age, relevant past medical history, Glasgow coma scale motor score, subdural haematoma, systolic arterial blood pressure < 110 mmHg, pupillary abnormality and haemoglobin level were significantly associated with in-hospital mortality. CONCLUSIONS: TBI is still a major public health concern affecting mostly young patients, victims of road traffic accidents and elderly patients, victims of falls. These findings could help clinicians adjusting medical approaches, targeting prevention measures and planning new research projects according to these French TBI population characteristics.

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia.

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24-4.09; p = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12-4.03; p = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24-0.64; p = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11-0.56; p = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32-0.91; p = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% p < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.

Effect of fibrinogen concentrate administration on early mortality in traumatic hemorrhagic shock: A propensity score analysis.

BACKGROUND: Fibrinogen concentrate is widely used in traumatic hemorrhagic shock despite weak evidence in the literature. The aim of the study was to evaluate the effect of fibrinogen concentrate administration within the first 6 hours on 24-hour all-cause mortality in traumatic hemorrhagic shock using a causal inference approach. METHODS: Observational study from a French multicenter prospective trauma registry was performed. Hemorrhagic shock was defined as transfusion of four or more red blood cell units within the first 6 hours after admission. The confounding variables for the outcome (24-hour all-cause mortality) and treatment allocation (fibrinogen concentrate administration within the first 6 hours) were chosen by a Delphi method. The propensity score was specified with a data-adaptive algorithm and a doubly-robust approach with inverse proportionality of treatment weighting allowed to compute the average treatment effect. Sensitivity analyses were performed. RESULTS: Of 14,336 patients in the registry during the study period, 1,027 in hemorrhagic shock were analyzed (758 receiving fibrinogen concentrate within 6 hours and 269 not receiving fibrinogen concentrate). The average treatment effect, expressed as a risk difference, was -0.031 (95% confidence interval, -0.084 to 0.021). All sensitivity analysis confirmed the results. CONCLUSIONS: Fibrinogen concentrate administration within the first 6 hours of a traumatic hemorrhagic shock did not decrease 24-hour all-cause mortality. LEVEL OF EVIDENCE: Prognostic, level III.

Blood product needs and transfusion timelines for the multisite massive Paris 2015 terrorist attack: A retrospective analysis.

OBJECTIVE: Hemorrhage is the leading cause of death after terrorist attack, and the immediacy of labile blood product (LBP) administration has a decisive impact on patients' outcome. The main objective of this study was to evaluate the transfusion patterns of the Paris terrorist attack victims, November 13, 2015. METHODS: We performed a retrospective analysis including all casualties admitted to hospital, aiming to describe the transfusion patterns from admission to the first week after the attack. RESULTS: Sixty-eight of 337 admitted patients were transfused. More than three quarters of blood products were consumed in the initial phase (until November 14, 11:59 PM), where 282 packed red blood cell (pRBC) units were transfused along with 201 plasma and 25 platelet units, to 55 patients (16% of casualties). Almost 40% of these LBPs (134 pRBC, 73 plasma, 8 platelet units) were transfused within the first 6 hours after the attack. These early transfusions were massive transfusion (MT) for 20 (6%) of 337 patients, and the average plasma/red blood cell ratio was 0.8 for MT patients who received 366 (72%) of 508 LBPs.The median time from admission to pRBC transfusion was 57 (25-108) minutes and 208 (52-430) minutes for MT and non-MT patients, respectively. These same time intervals were 119 (66-202) minutes and 222 (87-381) minutes for plasma and 225 (131-289) minutes and 198 (167-230) minutes for platelets. CONCLUSION: Our data suggest that improving transfusion procedures in mass casualty setting should rely more on shortening the time to bring LBP to the bedside than in increasing the stockpile. LEVEL OF EVIDENCE: Epidemiological study, Therapeutic IV.

Direct transport vs secondary transfer to level I trauma centers in a French exclusive trauma system: Impact on mortality and determinants of triage on road-traffic victims.

BACKGROUND: Transporting a severely injured patient directly to a trauma center (TC) is consensually considered optimal. Nevertheless, disagreement persists regarding the association between secondary transfer status and outcome. The aim of the study was to compare adjusted mortality between road traffic trauma patients directly or secondarily transported to a level 1 trauma center (TC) in an exclusive French trauma system with a physician staffed prehospital emergency medical system (EMS). METHODS: A retrospective cohort study was performed using 2015-2017 data from a regional trauma registry (Traumabase®), an administrative database on road-traffic accidents and prehospital-EMS records. Multivariate logistic regression models were computed to determine the role of the modality of admission on mortality and to identify factors associated with secondary transfer. The primary outcome was day-30 mortality. Results: During the study period, 121.955 victims of road-traffic accident were recorded among which 4412 trauma patients were admitted in the level 1 regional TCs, 4031 directly and 381 secondarily transferred from lower levels facilities. No significant association between all-cause 30-day mortality and the type of transport was observed (Odds ratio 0.80, 95% confidence interval (CI) [0.3-1.9]) when adjusted for potential confounders. Patients secondarily transferred were older, with low-energy mechanism and presented higher head and abdominal injury scores. Among all 947 death, 43 (4.5%) occurred in lower-level facilities. The population-based undertriage leading to death was 0.15%, 95%CI [0.12-0.19]. CONCLUSION: In an exclusive trauma system with physician staffed prehospital care, road-traffic victims secondarily transferred to a TC do not have an increased mortality when compared to directly transported patients.

Integrating eFAST in the initial management of stable trauma patients: the end of plain film radiography.

BACKGROUND: The initial management of a trauma patient is a critical and demanding period. The use of extended focused assessment sonography for trauma (eFAST) has become more prevalent in trauma rooms, raising questions about the real "added value" of chest X-rays (CXRs) and pelvic X-rays (PXR), particularly in haemodynamically stable trauma patients. The aim of this study was to evaluate the effectiveness of a management protocol integrating eFAST and excluding X-rays in stable trauma patients. METHODS: This was a prospective, interventional, single-centre study including all primary blunt trauma patients admitted to the trauma bay with a suspicion of severe trauma. All patients underwent physical examination and eFAST (assessing abdomen, pelvis, pericardium and pleura) before a whole-body CT scan (WBCT). Patients fulfilling all stability criteria at any time in transit from the scene of the accident to the hospital were managed in the trauma bay without chest and PXR. RESULTS: Amongst 430 patients, 148 fulfilled the stability criteria (stability criteria group) of which 122 (82 %) had no X-rays in the trauma bay. No diagnostic failure with an immediate clinical impact was identified in the stability criteria group (SC group). All cases of pneumothorax requiring chest drainage were identified by eFAST associated with a clinical examination before the WBCT scan in the SC group. The time spent in the trauma bay was significantly shorter for the SC group without X-rays compared to those who received any X-ray (25 [20; 35] vs. 38 [30; 60] min, respectively; p < 0.0001). An analysis of the cost and radiation exposure showed savings of 7000 Є and 100 mSv, respectively. CONCLUSIONS: No unrecognized diagnostic with a clinical impact due to the lack of CXR and PXR during the initial management of stable trauma patients was observed. The eFAST associated with physical examination provided the information necessary to safely complete the WBCT scan. It allowed a sensible cost and radiation saving.