Granulocyte microvesicles with a high plasmin generation capacity promote clot lysis and improve outcome in septic shock.

Microvesicles (MVs) have previously been shown to exert profibrinolytic capacity, which is increased in patients with septic shock (SS) with a favorable outcome. We, therefore, hypothesized that the plasmin generation capacity (PGC) could confer to MVs a protective effect supported by their capacity to lyse a thrombus, and we investigated the mechanisms involved. Using an MV-PGC kinetic assay, ELISA, and flow cytometry, we found that granulocyte MVs (Gran-MVs) from SS patients display a heterogeneous PGC profile driven by the uPA (urokinase)/uPAR system. In vitro, these MVs lyse a thrombus according to their MV-PGC levels in a uPA/uPAR-dependent manner, as shown in a fluorescent clot lysis test and a lysis front retraction assay. Fibrinolytic activators conveyed by MVs contribute to approximately 30% of the plasma plasminogenolytic capacity of SS patients. In a murine model of SS, the injection of high PGC Gran-MVs significantly improved mouse survival and reduced the number of thrombi in vital organs. This was associated with a modification of the mouse coagulation and fibrinolysis properties toward a more fibrinolytic profile. Interestingly, mouse survival was not improved when soluble uPA was injected. Finally, using a multiplex array on plasma from SS patients, we found that neutrophil elastase correlates with the effect of high-PGC-capacity plasma and modulates the Gran-MV plasmin generation capacity by cleaving uPA-PAI-1 complexes. In conclusion, we show that the high PGC level displayed by Gran-MVs reduces thrombus formation and improves survival, conferring to Gran-MVs a protective role in a murine model of sepsis.

Hydrocephalus despite extra ventricular drainage in adults: a new description of multiloculated hydrocephalus.

Multiloculated hydrocephalus constitutes a challenging pathology due to intracerebral haemorrhage or ventriculitis leading to iterative shunt revision frequently described in paediatric neurosurgery, but poorly reported in adults. Nevertheless, this potential complication of intraventricular haemorrhage, already drained in emergency, should be considered with special interest, as ideal management of cerebrospinal drainage remains debated in such situation. We thus report herein the case of intraventricular haemorrhage in an adult complicated of multiloculated hydrocephalus, as an illustrative plea for endoscopic surgery.

Lung-Dependent Areas Collapse, Monitored by Electrical Impedance Tomography, May Predict the Oxygenation Response to Prone Ventilation in COVID-19 Acute Respiratory Distress Syndrome.

OBJECTIVES: ICUs have had to deal with a large number of patients with acute respiratory distress syndrome COVID-19, a significant number of whom received prone ventilation, which is a substantial consumer of care time. The selection of patients that we have to ventilate in prone position seems interesting. We evaluate the correlation between the percentage of collapsed dependent lung areas in the supine position, monitoring by electrical impedance tomography and the oxygenation response (change in Pao2/Fio2 ratio) to prone position. DESIGN: An observational prospective study. SETTING: From October 21, 2020, to 30 March 30, 2021. At the Sainte Anne military teaching Hospital and the Timone University Hospital. PATIENTS: Fifty consecutive patients admitted in our ICUs, with COVID-19 acute respiratory distress syndrome and required mechanical, were included. Twenty-four (48%) received prone ventilation. Fifty-eight prone sessions were investigated. INTERVENTIONS: An electrical impedance tomography recording was made in supine position, daily and repeated just before and just after the prone session. The daily dependent area collapse was calculated in relation to the previous electrical impedance tomography recording. Prone ventilation response was defined as a Pao2/Fio2 ratio improvement greater than 20%. MEASUREMENT AND MAIN RESULTS: The main outcome was the correlation between dependent area collapse and the oxygenation response to prone ventilation. Dependent area collapse was correlated with oxygenation response to prone ventilation (R2 = 0.49) and had a satisfactory prediction accuracy of prone response with an area under the curve of 0.94 (95% CI, 0.87-1.00; p < 0.001). Best Youden index was obtained for a dependent area collapse greater than 13.5 %. Sensitivity of 92% (95% CI, 78-97), a specificity of 91% (95% CI, 72-97), a positive predictive value of 94% (95% CI, 88-100), a negative predictive value of 87% (95% CI, 78-96), and a diagnostic accuracy of 91% (95% CI, 84-98). CONCLUSIONS: Dependent lung areas collapse (> 13.5%), monitored by electrical impedance tomography, has an excellent positive predictive value (94%) of improved oxygenation during prone ventilation.

Severe Aortic Thrombosis and Profound Hypothermia: A Case Report.

BACKGROUND: Blood clot formation is a multifactorial process and has been related many times in intensive care units. Here is presented a multiple thrombosis formation in a rewarming patient. CASE DESCRIPTION: A 68-year-old patient was admitted to our intensive care unit after lying on the floor for an unknown time. She presented a severe hypothermia at 26° and a severe cardiogenic shock. Because she was confused and was hypoxemic, she had been intubated at her admission. After intravascular warming, we could stop sedative medications. She presented a right hemiparesis and acute left leg ischemia. Computed tomography (CT) scan revealed a constituted left Sylvian stroke and a massive clot along the aorta. She required a surgical embolectomy and fasciotomy. She died after she presented a severe bowel ischemia on the third day after her admission. CONCLUSION: Relevant hypothesis for blood clot formation in this patient may include prolonged lying position or blood temperature variation. Hypothermia and rewarming responsibilities may explain multiple thrombosis development. HOW TO CITE THIS ARTICLE: Schmitt J, Esnault P, Sartre M, Cungi PJ, Meaudre E. Severe Aortic Thrombosis and Profound Hypothermia: A Case Report. Indian J Crit Care Med 2021;25(5):588-589.

Ability of Fibrin Monomers to Predict Progressive Hemorrhagic Injury in Patients with Severe Traumatic Brain Injury.

BACKGROUND: Progressive hemorrhagic injury (PHI) is common in patients with severe traumatic brain injury (TBI) and is associated with poor outcomes. TBI-associated coagulopathy is frequent and has been described as risk factor for PHI. This coagulopathy is a dynamic process involving hypercoagulable and hypocoagulable states either one after the other either concomitant. Fibrin monomers (FMs) are a direct marker of thrombin action and thus reflect coagulation activation. This study sought to determine the ability of FM to predict PHI after severe TBI. METHODS: We conducted a prospective, observational study including all severe TBI patients admitted in the trauma center. Between September 2011 and September 2016, we enrolled patients with severe TBI into the derivation cohort. Between October 2016 and December 2018, we recruited the validation cohort on the same basis. Study protocol included FM measurements and standard coagulation test at admission and two computed tomography (CT) scans (upon arrival and at least 6 h thereafter). A PHI was defined by an increment in size of initial lesion (25% or more) or the development of a new hemorrhage in the follow-up CT scan. Multivariate logistic regression analysis was applied to identify predictors of PHI. RESULTS: Overall, 106 patients were included in the derivation cohort. Fifty-four (50.9%) experienced PHI. FM values were higher in these patients (151 [136.8-151] vs. 120.5 [53.3-151], p < 0.0001). The ROC curve demonstrated that FM had a fair accuracy to predict the occurrence of PHI with an area under curve of 0.7 (95% CI [0.6-0.79]). The best threshold was determined at 131.7 µg/ml. In the validation cohort of 54 patients, this threshold had a negative predictive value of 94% (95% CI [71-100]) and a positive predictive value of 49% (95% CI [32-66]). The multivariate logistic regression analysis identified 2 parameters associated with PHI: FM ≥ 131.7 (OR 6.8; 95% CI [2.8-18.1]) and Marshall category (OR 1.7; 95% CI [1.3-2.2]). Coagulopathy was not associated with PHI (OR 1.3; 95% CI [0.5-3.0]). The proportion of patients with an unfavorable functional neurologic outcome at 6-months follow-up was higher in patients with positive FM: 59 (62.1%) versus 16 (29.1%), p < 0.0001. CONCLUSIONS: FM levels at admission had a fair accuracy to predict PHI in patients with severe TBI. FM values ≥ 131.7 µg/ml are independently associated with the occurrence of PHI.

Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults.

This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.

Spontaneous Hyperventilation in Severe Traumatic Brain Injury: Incidence and Association with Poor Neurological Outcome.

BACKGROUND: Hypocapnia induces cerebral vasoconstriction leading to a decrease in cerebral blood flow, which might precipitate cerebral ischemia. Hypocapnia can be intentional to treat intracranial hypertension or unintentional due to a spontaneous hyperventilation (SHV). SHV is frequent after subarachnoid hemorrhage. However, it is understudied in patients with severe traumatic brain injury (TBI). The objective of this study was to describe the incidence and consequences on outcome of SHV after severe TBI. METHODS: We conducted a retrospective, observational study including all intubated TBI patients admitted in the trauma center and still comatose 24 h after the withdrawal of sedation. SHV was defined by the presence of at least one arterial blood gas (ABG) with both PaCO2 < 35 mmHg and pH > 7.45. Patient characteristics and outcome were extracted from a prospective registry of all intubated TBI admitted in the intensive care unit. ABG results were retrieved from patient files. A multivariable logistic regression model was developed to determine factors independently associated with unfavorable outcome (defined as a Glasgow Outcome Scale between 1 and 3) at 6-month follow-up. RESULTS: During 7 years, 110 patients fully respecting inclusion criteria were included. The overall incidence of SHV was 69.1% (95% CI [59.9-77]). Patients with SHV were more severely injured (median head AIS score (5 [4-5] vs. 4 [4-5]; p = 0.016)) and exhibited an elevated morbidity during their stay. The proportion of patients with an unfavorable functional neurologic outcome was significantly higher in patients with SHV: 40 (52.6%) versus 6 (17.6%), p = 0.0006. After adjusting for confounders, SHV remains an independent factor associated with unfavorable outcome at the 6-month follow-up (OR 4.1; 95% CI [1.2-14.4]). CONCLUSIONS: SHV is common in patients with a persistent coma after a severe TBI (overall rate: 69%) and was independently associated with unfavorable outcome at 6-month follow-up.

Duret hemorrhage complicating a sinking skin flap syndrome.

Duret hemorrhage has always been reported during an episode of increased intracranial pressure with transtentorial herniation. We reported a Duret hemorrhage occurring during an episode of intracranial hypotension resulted in sinking skin flap syndrome which was responsible for acute paradoxal descending transtentorial herniation and Duret hemorrhage, 10 days after large hemicraniectomy which could indicate early cranioplasty.

Post-traumatic Anterior Cerebral Artery Rupture after a Severe Traumatic Brain Injury.

Blunt cerebrovascular injuries (BCVI) have been increasingly recognized in the past decade due to the initiation of different screening protocols. We present the case of an anterior cerebral artery rupture with free contrast extravasation following a severe traumatic brain injury. Epidemiology, modalities of screening and treatment of BCVI are discussed. This report reminds that the screening of BCVI may be essential after a severe traumatic brain injuries (TBI). HOW TO CITE THIS ARTICLE: Mathais Q, Esnault P, Joubert C, Dragone C, Meaudre E. Post-traumatic Anterior Cerebral Artery Rupture after a Severe Traumatic Brain Injury. Indian Journal of Critical Care Medicine, January 2019;23(1):54-55.

Early-Onset Ventilator-Associated Pneumonia in Patients with Severe Traumatic Brain Injury: Incidence, Risk Factors, and Consequences in Cerebral Oxygenation and Outcome.

BACKGROUND: Early-onset ventilator-associated pneumonia (EOVAP) occurs frequently in severe traumatic brain-injured patients, but potential consequences on cerebral oxygenation and outcome have been poorly studied. The objective of this study was to describe the incidence, risk factors for, and consequences on cerebral oxygenation and outcome of EOVAP after severe traumatic brain injury (TBI). METHODS: We conducted a retrospective, observational study including all intubated TBI admitted in the trauma center. An EOVAP was defined as a clinical pulmonary infection score >6, and then confirmed by an invasive method. Patient characteristics, computed tomography (CT) scan results, and outcome were extracted from a prospective register of all intubated TBI admitted in the intensive care unit (ICU). Data concerning the cerebral oxygenation monitoring by PbtO2 and characteristics of EOVAP were retrieved from patient files. Multivariate logistic regression models were developed to determine the risk factors of EOVAP and to describe the factors independently associated with poor outcome at 1-year follow-up. RESULTS: During 7 years, 175 patients with severe TBI were included. The overall incidence of EOVAP was 60.6% (47.4/1000 days of ventilation). Significant risk factors of EOVAP were: therapeutic hypothermia (OR 3.4; 95% CI [1.2-10.0]), thoracic AIS score ≥3 (OR 2.4; 95% CI [1.1-5.7]), and gastric aspiration (OR 5.2, 95% CI [1.7-15.9]). Prophylactic antibiotics administration was a protective factor against EOVAP (OR 0.3, 95% CI [0.1-0.8]). EOVAP had negative consequences on cerebral oxygenation. The PbtO2 was lower during EOVAP: 23.5 versus 26.4 mmHg (p <0.0001), and there were more brain hypoxia episodes: 32 versus 27% (p = 0.03). Finally, after adjusting for confounders, an EOVAP was an independent factor associated with unfavorable neurologic functional outcome at the 1-year follow-up (OR 2.71; 95% CI [1.01-7.25]). CONCLUSIONS: EOVAP is frequent after a severe TBI (overall rate: 61%), with therapeutic hypothermia, severe thoracic lesion, and gastric aspiration as main risk factors. EOVAP had a negative impact on cerebral oxygenation measured by PbtO2 and was independently associated with unfavorable outcome at 1-year follow-up. This suggests that all precautions available should be taken to prevent EOVAP in this population.

Early neurological wake-up test in intubated brain-injured patients: A long-term, single-centre experience.

BACKGROUND: In prehospital setting, a severe traumatic brain injury (TBI) requires tracheal intubation, sedation and mechanical ventilation pending the initial imagery. An early neurological wake-up test (ENWT), soon after the initial imaging assessment, allows a rapid neurological reassessment. This strategy authorises an initial clinical examination of reference with which will be compared the later examinations. The main objective of this study was to describe the characteristics of the patients who underwent an ENWT, and to determine its causes of failure. METHODS: We conducted a retrospective, observational, single-centre study including all intubated TBI admitted in the trauma centre. An ENWT was defined as cessation of sedation within 24h after TBI. Data concerning patient characteristics, CT-scan results, and outcomes were extracted from a prospective register of all intubated TBI admitted in the ICU. Characteristic of ENWT and causes of failure were retrieved from patient files. A multivariate logistic regression model was developed to determine the risk factors of ENWT failure. RESULTS: During 7 years, 242 patients with intubated TBI were included. An ENWT was started in 96 patients, for an overall rate at 40%. The ENWT was stopped in 38 patients (39.5%), mostly due to neurological deterioration in 27 cases (71%) or respiratory distress in 10 cases (26%). Significant predictors of ENWT failure were: the presence of subdural hematoma with a thickness >5mm on first imagery (OR=3.2; 95%CI [1.01-10.28]), and an initial GCS score <5 (OR=7.4; 95%CI [1.92-28.43]). Prevalence of poor outcome at 1year was lesser in patients with successful ENWT compared to those with failure or absence of ENWT: 4% vs. 48% and 49% (p<0.0001). CONCLUSIONS: The ENWT is achieved in 40% of patients, with a success rate of 60.5%. In presence of a subdural hematoma with a thickness >5mm or an initial GCS score <5, an ENWT failure may be expected.

Outcome Comparison in Children Undergoing Extracorporeal Life Support Initiated at a Local Hospital by a Mobile Cardiorespiratory Assistance Unit or at a Referral Center.

PURPOSE: To compare characteristics and outcome in children undergoing extracorporeal life support initiated in an extracorporeal life support center or at the patient's bedside in a local hospital, by means of a mobile cardiorespiratory assistance unit. METHODS: A retrospective study in a single PICU during 6 years. Extracorporeal life support was started either in our center (control group) or in the local hospital (mobile cardiorespiratory assistance unit group). The data collected were demographics, markers of patient's preextracorporeal life support condition, and outcome. RESULTS: One hundred twenty-six children underwent extracorporeal life support, 105 in the control group and 21 in the mobile cardiorespiratory assistance unit group. There was no difference between groups in terms of age, weight, or Pediatric Risk of Mortality II score. There was a significant difference in organ failure etiology between groups, with more respiratory cases in the mobile cardiorespiratory assistance unit group (76.2%) and more cardiac surgery cases in the control group (60%; p < 0.001). The duration of extracorporeal life support was longer in the mobile cardiorespiratory assistance unit group than in the control group (10 [1-36] vs 5 [0-33] d; p = 0.003). PICU length of stay and mortality (60% vs 47.6%; p = 0.294) were not significantly different between the two groups. To allow comparison of a more homogenous population, a subgroup analysis was performed including only respiratory failure patients from the two groups (R-control group [n = 22] and R-mobile cardiorespiratory assistance unit group [n = 16]). PICU length of stay was 17 (3-64) days in the R-control group and 23 (1-45) days in the R-mobile cardiorespiratory assistance unit group (p = 0.564), and PICU mortality rate was 54.5% in the R-control group and 43.8% in the R-mobile cardiorespiratory assistance unit group (p = 0.511). There was no difference between the R-groups for age, weight, Pediatric Risk of Mortality II score, and markers of kidney or liver dysfunction, and lactate blood levels. CONCLUSION: Extracorporeal life support can be safely initiated at children's bedside in the local hospital and then transported to the specialized referral center. Our results support the validity of an interregional organization of mobile cardiorespiratory assistance unit teams.

Impairment of cardiac metabolism and sympathetic innervation after aneurysmal subarachnoid hemorrhage: a nuclear medicine imaging study.

INTRODUCTION: Although aneurysmal subarachnoid hemorrhage (SAH) is often complicated by myocardial injury, whether this neurogenic cardiomyopathy is associated with the modification of cardiac metabolism is unknown. This study sought to explore, by positron emission tomography/computed tomography, the presence of altered cardiac glucose metabolism after SAH. METHODS: During a 16-month period, 30 SAH acute phase patients underwent myocardial (18)F- fluorodesoxyglucose positron emission tomography ((18)F-FDGPET), (99m)Tc-tetrofosmin and (123)I-meta-iodobenzylguanidine ((123)I-mIBG) scintigraphy, respectively, assessing glucose metabolism, cardiac perfusion, and sympathetic innervation. Patients with initial abnormalities were followed monthly for two months for (18)F-FDG, and six months later for (123)I-mIBG. RESULTS: In this SAH population, acute cardiac metabolic disturbance was observed in 83% of patients (n = 25), and sympathetic innervation disturbance affected 90% (n = 27). Myocardial perfusion was normal for all patients. The topography and extent of metabolic defects and innervation abnormalities largely overlapped. Follow-up showed rapid improvement of glucose metabolism in one or two months. Normalization of sympathetic innervation was slower; only 27% of patients (n = 8) exhibited normal (123)I-mIBG scintigraphy after six months. Presence of initial altered cardiac metabolism was not associated with more unfavorable cardiac or neurological outcomes. CONCLUSIONS: These findings support the hypothesis of neurogenic myocardial stunning after SAH. In hemodynamically stable acute phase SAH patients, cardiomyopathy is characterized by diffuse and heterogeneous (18)F-FDG and (123)I-mIBG uptake defect. TRIAL REGISTRATION: Clinicaltrials.gov NCT01218191. Registered 6 October 2010.

Tracheal intubation difficulties in the setting of face and neck burns: myth or reality?

INTRODUCTION: Face and/or neck burn (FNB) exposes patients to the double respiratory risk of obstruction and hypoxia, and these risks may require a tracheal intubation. This study aims to describe the incidence and the characteristics of difficult intubation in FNB patients. METHODS: We conducted a 5-year retrospective, single-center study including all patients meeting the following criteria: 18 years of age or older, an FNB at least 1% of burned surface area with a severity equal to or greater than the superficial second degree, and intubation and a burn center admission within the first 24 hours after the burn. Patients were compared according to the difficulty of their intubation. RESULTS: Between January 2007 and December 2011, we included 134 patients. The incidence of difficult intubation was 11.2% but was greater in the burn center than in the pre-burn center: 16.9% vs 3.5% (P = .02). The most important difference between patients with or without difficult intubation was the time between the burn injury and the intubation: 210 (105-290) vs 120 (60-180) minutes (P = .047). After multivariate analysis, an intubation performed at a burn center was independently associated with difficult intubation: odds ratio = 3.2; 95% confidence interval, 1.1-528. CONCLUSIONS: This study underlines the high incidence of difficult intubation in FNB patients, greater than 11.2%, and demonstrates that intubation is more difficult when realized at a burn center, probably because it is performed later, allowing for development of cervical and laryngeal edema.

[Reverse Takotsubo cardiomyopathy after iatrogenic epinephrine injection requiring percutaneous extracorporeal membrane oxygenation]. / « Reverse Tako-Tsubo ¼ après injection iatrogène d'adrénaline nécessitant l'intervention d'une équipe mobile d'assistance circulatoire: à propos d'un cas.

PURPOSE: Takotsubo cardiomyopathy is characterized by the sudden onset of reversible left ventricular dysfunction. Associated refractory cardiogenic shock is a rare occurrence and may require extracorporeal membrane oxygenation (ECMO). We report a case of a patient who, following the inadvertent injection of 1 mg of epinephrine, presented with reverse Takotsubo cardiomyopathy and refractory cardiogenic shock that required the implementation of a percutaneous ECMO. CLINICAL FEATURES: A 49-yr-old female patient presented with reverse Takotsubo cardiomyopathy in the operating room after an inadvertent injection of epinephrine. The development of refractory cardiogenic shock required emergent use of a mobile percutaneous ECMO system. It was possible to wean this support after four days, and the patient was later discharged without cardiac or neurological sequelae. The investigations performed confirmed the iatrogenic nature of this reverse Takotsubo cardiomyopathy. CONCLUSION: Takotsubo cardiomyopathy following an injection of epinephrine remains a rare but increasingly described occurrence. The severity of the symptoms appears to be patient dependent, but refractory cardiogenic shock may occur and require significant circulatory support. If this situation occurs in a hospital where this necessary equipment is lacking, a mobile ECMO unit appears to be a viable solution to optimize the patient's chances of survival.

ABO blood type and functional neurological outcome in patients with severe traumatic brain injury.

BACKGROUND: The ABO blood system has been involved in the pathogenesis of several diseases, including coagulopathy and bleeding complications. In trauma patients, blood type A has been associated with acute respiratory distress syndrome, and recently, blood type O has been associated with all-cause mortality. The purpose of this study was to assess the association between ABO blood types and long-term functional outcomes in critically ill patients with severe traumatic brain injury (TBI). METHODS: We conducted a single-center, retrospective, observational study including all patients admitted to the intensive care unit with severe TBI (defined as a Glasgow Coma Scale score of ≤8) between January 2007 and December 2018. Patient characteristics and outcomes were extracted from a prospective registry of all intubated patients admitted to the intensive care unit for TBI. ABO blood types were retrospectively retrieved from patient medical records. The association between ABO blood type (A, B, AB, and O) and unfavorable functional outcome (defined by a Glasgow Outcome Scale score between 1 and 3) 6 months after injury was assessed in univariate and multivariate analysis. RESULTS: A total of 333 patients meeting the inclusion criteria were included. There were 151 type O (46%), 131 type A (39%), 37 type B (11%), and 12 type AB patients (4%). No significant differences in baseline demographic, clinical, or biological characteristics were observed between blood types. The prevalence of unfavorable outcome was significantly different between the four groups. After adjustment for confounders, blood type O was significantly associated with unfavorable outcome at 6 months (odds ratio, 1.97; confidence interval [1.03-3.80]; p = 0.042). The prevalence of coagulopathy or progressive hemorrhagic injury was not statistically different between blood types ( p = 0.575 and p = 0.813, respectively). CONCLUSION: Blood type O appears to be associated with unfavorable long-term functional outcome in critically ill patients with severe TBI. Further studies are needed to detail the mechanism underlying this relationship. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.