[Complex management of type 2 heparin-induced thrombocytopenia in patients with major bleeding tendency: two case report]. / Prise en charge de la thrombopénie induite par l'héparine immuno-allergique de type 2 au travers de deux cas cliniques chez des patients à risque hémorragique majeur.

Type 2 heparin-induced thrombocytopenia (HIT 2) is a rare pro-thrombotic disorder occurring in patients treated with heparin. It is defined as a clinical-biological syndrome associating the sudden onset of a thrombocytopenia, characterized by a drop of more than 50% of the initial platelet count, and thrombosis. We report two cases of HIT 2 occurring in patients with major bleeding tendency. The first HIT occurred in a patient whose management, in accordance with current guidelines, made it possible to control the thrombocytopenia and the anticoagulation despite the complexity of adapting and monitoring treatments in the context of recent cerebral hemorrhage. The second refers to an autoimmune HIT, which occurred in a patient whose management required the use of alternative therapies to the standard treatments suggested for HIT 2, to correct the severe refractory thrombocytopenia.

Management of severe traumatic brain injury (first 24hours).

The latest French Guidelines for the management in the first 24hours of patients with severe traumatic brain injury (TBI) were published in 1998. Due to recent changes (intracerebral monitoring, cerebral perfusion pressure management, treatment of raised intracranial pressure), an update was required. Our objective has been to specify the significant developments since 1998. These guidelines were conducted by a group of experts for the French Society of Anesthesia and Intensive Care Medicine (Société francaise d'anesthésie et de réanimation [SFAR]) in partnership with the Association de neuro-anesthésie-réanimation de langue française (ANARLF), The French Society of Emergency Medicine (Société française de médecine d'urgence (SFMU), the Société française de neurochirurgie (SFN), the Groupe francophone de réanimation et d'urgences pédiatriques (GFRUP) and the Association des anesthésistes-réanimateurs pédiatriques d'expression française (ADARPEF). The method used to elaborate these guidelines was the Grade® method. After two Delphi rounds, 32 recommendations were formally developed by the experts focusing on the evaluation the initial severity of traumatic brain injury, the modalities of prehospital management, imaging strategies, indications for neurosurgical interventions, sedation and analgesia, indications and modalities of cerebral monitoring, medical management of raised intracranial pressure, management of multiple trauma with severe traumatic brain injury, detection and prevention of post-traumatic epilepsia, biological homeostasis (osmolarity, glycaemia, adrenal axis) and paediatric specificities.

The limits of succinylcholine for critically ill patients.

BACKGROUND: Urgent tracheal intubations are common in intensive care units (ICU), and succinylcholine is one of the first-line neuromuscular blocking drugs used in these situations. Critically ill patients could be at high risk of hyperkalemia after receiving succinylcholine because one or more etiologic factors of nicotinic receptor upregulation can be present, but there are few data on its real risk. Our objectives in this study were to determine the factors associated with arterial potassium increase (ΔK) and to assess the occurrence of acute hyperkalemia ≥6.5 mmol/L after succinylcholine injection for intubation in the ICU. METHODS: In a prospective, observational study, all critically ill patients intubated with succinylcholine in an ICU were screened. Only intubations with arterial blood gases and potassium measurements before and after (K(after)) a succinylcholine injection were studied. RESULTS: During 18 months, 131 critically ill patients were intubated after receiving succinylcholine with arterial potassium before and after intubation (K(after)) for a total of 153 intubations. After multivariate analysis, the only factor associated with ΔK was the length of ICU stay before intubation (ρ = 0.561, P < 0.001). The factors associated with K(after) ≥6.5 mmol/L (n = 11) were the length of ICU stay (P < 0.001) and the presence of acute cerebral pathology (P = 0.047). The threshold of 16 days was found highly predictive of acute hyperkalemia ≥6.5 with 37% (95% confidence interval: 19%-58%) of K(after) ≥6.5 after the 16th day compared with only 1% (95% confidence interval: 0%-4%) of K(after) ≥6.5 when succinylcholine was injected during the first 16 days. CONCLUSIONS: This study shows that the risk of ΔK after succinylcholine injection is strongly associated with the length of ICU stay. The risk of acute hyperkalemia ≥6.5 mmol/L is highly significant after 16 days.

Teaching improves adherence to clinical guidelines in the treatment of oral anticoagulation-related severe bleeding in the emergency department.

OBJECTIVE: To assess compliance and impact of a teaching program on guidelines for the management of severe bleeding under oral anticoagulation therapy in emergency departments (EDs). DESIGN AND SETTING: Multicenter, before-after observational studies in six French EDs. PATIENTS: Forty-five patients in 2003 and 54 patients in 2005 consecutively admitted with severe bleeding under oral anticoagulation therapy. INTERVENTIONS: A specific teaching program on management of severe bleeding under oral anticoagulation therapy, performed by an expert physician. MEASUREMENTS AND RESULTS: Primary end-point was the use of prothrombin complex concentrate-vitamin K association between the two study periods. Nine patients (20%) in 2003 and 29 patients (54%) in 2005 received this association (P < 0.01). Almost one-third of patients had only withholding oral anticoagulation therapy. Adverse events and mortality rate did not differ between the two phases. CONCLUSIONS: Compliance with guidelines on the management of severe bleeding under oral anticoagulation remains poor and might be improved by specific teaching program.

Transcranial Doppler ultrasound goal-directed therapy for the early management of severe traumatic brain injury.

OBJECTIVE: To evaluate the usefulness of early transcranial Doppler ultrasound (TCD) goal-directed therapy after severe traumatic brain injury initiated before invasive cerebral monitoring is available. DESIGN: Prospective, observational clinical study. SETTING: Surgical intensive care unit, university hospital. PATIENTS AND PARTICIPANTS: Twenty-four severely brain-injured patients. INTERVENTIONS: All patients had TCD measurements immediately on admission (T0) and when invasive cerebral monitoring was available (T1). TCD was considered abnormal when two out of three measured values were outside the following limits: Vm<30 cm/s, Vd<20 cm/s, PI > 1.4. When admission TCD was abnormal, attending physicians modified treatment to increase cerebral perfusion pressure. MEASUREMENTS AND RESULTS: Admission TCD was performed 18+/-11 min (T0) after admission, whereas cerebral invasive monitoring was available 242+/-116 min (T1) after admission. At T0, 11 (46%) patients had abnormal TCD values (group 1) and 13 had normal TCD values (group 2); mean arterial pressure was comparable between groups. All group 1 patients received mannitol and/or norepinephrine. At T1, mean arterial pressure was increased compared to admission in group 1 (105+/-17 mmHg vs. 89+/-15 mmHg, p<0.05) and only two patients had still an abnormal TCD. Although group 1 patients had higher intracranial pressure than those of group 2 (32+/-13 mmHg vs. 22+/-10 mmHg, p<0.01), both cerebral perfusion pressure and jugular venous oxygen saturation were comparable between the groups. CONCLUSIONS: The use of TCD at hospital admission allows identification of severely brain-injured patients with brain hypoperfusion. In such high-risk patients, early TCD goal-directed therapy can restore normal cerebral perfusion and might then potentially help in reducing the extent of secondary brain injury.

Ultra-rapid management of oral anticoagulant therapy-related surgical intracranial hemorrhage.

OBJECTIVE: Intracranial hemorrhage in patients receiving oral anticoagulant (OAC) therapy is associated with poor neurological outcome. Prothrombin complex concentrate (PCC) is the gold-standard therapy to normalize hemostasis but remains underused. Ultra-rapid reversal of anticoagulation could reduce the time to biological and surgical hemostasis, and might improve outcome. We report the use of bolus infusions of PCC to immediately reverse anticoagulation and allow for urgent neurosurgical care. DESIGN: Prospective, observational study. SETTING: Neurosurgical intensive care unit, university hospital. PATIENTS AND PARTICIPANTS: Eighteen patients with OAC-associated intracranial hemorrhage requiring urgent neurosurgical intervention. INTERVENTIONS: All patients received 20 UI/kg of PCC as an intravenous bolus infusion (3 min) and 5 mg of enteral vitamin K. Surgery was started immediately, without waiting for blood sample results. MEASUREMENTS AND RESULTS: Serial blood samples were performed to assess prothrombin time. Coagulation was considered normal when the international normalized ratio was

Changes in cerebral energy metabolites induced by impact-acceleration brain trauma and hypoxic-hypotensive injury in rats.

The aim of this study was to describe, in rats, brain energy metabolites changes after different levels of head trauma (T) complicated by hypoxia-hypotension (HH). Male Sprague Dawley rats (n = 7 per groups) were subjected to T by impact-acceleration with 450-g weight drop from 1.50 or 1.80 m (T 1.50 or T 1.80), or to a 15-min period of HH (controlled hemorrhage to mean arterial pressure [MAP] of 40 mm Hg, and mechanical ventilation with N(2) 90%/O(2) 10%), or to their association (T followed by HH). Invasive MAP, intraparenchymental intracranial pressure (ICP), and cerebral blood flow (CBF using Laser Doppler flowmetry) were recorded during the 5 post-traumatic hours. Cerebral microdialysis was used to measure each hour interstitial brain glucose, lactate, pyruvate, and glutamate. For the entire period, the levels of cerebral glucose, pyruvate, and glutamate were not statistically different between groups. In addition, there were no differences associated with the lactate-glucose ratio. Lactate was significantly higher overtime only in T 1.80 + HH group (p < 0.001 vs. every other groups). The lactate-pyruvate ratio increased with trauma level, and was significantly different vs. sham for the entire study period in T 1.50 + HH, in T 1.80, and in T 1.80 + HH. There was no correlation between CBF variations and the lactate-pyruvate ratio (r(2) = 0.00001). The cerebral perfusion pressure was greater than 70 mm Hg in all groups. The prolonged post-traumatic impairment in brain energy metabolism may be related to traumatic brain injury (TBI) severity. It became worse when T was complicated by HH, but was not related to changes in CBF.

Endothelial oxidative stress induced by serum from patients with severe trauma hemorrhage.

OBJECTIVE: Shock induces oxidative stress by ischemia-reperfusion phenomenon. Endothelial cells are involved in the inflammatory response and oxidative stress responsible for microcirculation impairment and organ failure. We examined the potential of serum from patients to induce in vitro reactive oxygen species production by cultured human umbilical vein endothelial cells (HUVECs). PATIENTS: Three groups were compared: hemorrhagic shock trauma patients, isolated brain injured patients, and healthy volunteers. METHODS: In the hemorrhagic shock group we sought a correlation between reactive oxygen species production and severity of shock. Serum was separated and perfused in an in vitro model of perfused HUVECs. Ex vivo reactive oxygen species production was assessed by fluorescence microscopy using dichlorodihydrofluorescein, an intracellular dye oxidized by H2O2. Results are expressed in proportional change from baseline and normalized by protidemia to control for variation related to hemodilution. RESULTS: Reactive oxygen species production by endothelial cells exposed to serum from hemorrhagic shock patients (46.2+/-24.9%) was significantly greater than in those with brain injury (3.9+/-35.1%) and in healthy volunteers (-6.8+/-5.8%). In the hemorrhagic shock group dichlorodihydrofluorescein fluorescence was strongly correlated positively to Simplified Acute Physiology Score II and lactatemia and negatively to [HCO3-]. CONCLUSIONS: Serum from trauma patients with hemorrhagic shock induces reactive oxygen species formation in naive endothelial cells which is correlated to shock severity.

Critically ill old and the oldest-old patients in intensive care: short- and long-term outcomes.

OBJECTIVE: The purpose of this study was to examine characteristics and outcome of the old, very old and oldest-old ICU patients DESIGN. This is a cohort study. SETTING: The study was set in a ten-bed medical ICU in a university hospital. PARTICIPANTS. There were 410 patients classified in three subgroups: old, 75-79 years ( n=184; 44.4%), very old, 80-84 ( n=137, 33.4%) and the oldest-old, >or=85 ( n=91; 22.2%). MEASUREMENTS: Underlying medical conditions, organ dysfunction, severity of illness, length of stay, use of mechanical ventilation, therapeutic activity and nosocomial infections were recorded. Multivariate analysis was conducted to identify risk factors for ICU and long-term mortality. RESULTS: Characteristics at ICU admission did not differ among the three groups. ICU length of stay, therapeutic activity, mechanical ventilation and nosocomial infection(s) decreased with age. ICU survival rates for those below 75, 75-79, 80-84 and over 85 years were 80, 68, 75 and 69%, respectively; survival rates at 3 months were 54, 56 and 51%, respectively. APACHE II score [odds ratio (OR): 1.11] was identified as the only factor associated with ICU mortality, and age (OR: 2.17, for patients >or=85 years old and 1.82, for patients 80-84 years old) and limitation of activity before admission (OR: 1.74) as factors associated with long-term mortality. CONCLUSION: In a population of patients >or=75 years old, very old age is not directly associated with ICU mortality. After ICU discharge, deaths occurred predominantly during the first 3 months: age and prior limitation of activity were associated with the risk of dying.

Diagnosis and follow-up of infections in intensive care patients: value of C-reactive protein compared with other clinical and biological variables.

OBJECTIVE: To evaluate diagnostic and prognostic values of C-reactive protein (CRP) dosage in critically ill patients. DESIGN: Prospective, observational study. SETTING: Medical intensive care unit (ICU) in a university hospital. PATIENTS: A consecutive series of 74 patients admitted to the ICU. INTERVENTION: CRP measurements at admission and every 4 days thereafter. MEASUREMENTS AND MAIN RESULTS: At admission, 28 patients (38%) had microbiologically proven infections. Compared with uninfected patients, their mean +/- SD CRP level was 191 +/- 123 vs. 83 +/- 91 mg/L (p < .0001), respectively, white blood cell count was 15.3 +/- 7.5 vs. 11.4 +/- 5.3 G/L (p = .01), and the systemic inflammatory response syndrome (SIRS) was present for 96% vs. 67% (p = .008). No threshold value could be identified to discriminate between these two populations. Multivariate analysis retained CRP and SIRS as the only variables independently associated with the presence of an infection. The combination of CRP > or = 50 mg/L with SIRS was identified as the best model to diagnose infection at admission. This multivariate model performed better than temperature, CRP alone, and white blood cell count. Among the 28 infected patients, 10 recovered; CRP values decreased significantly in this population as compared with patients with persistent infection (-130 +/- 110 vs. 12 +/- 97 mg/L, respectively; p = .004). A CRP decrease > or = 50 mg/L between admission and day 4 was the best cutoff value to diagnose recovery (sensitivity 89%, specificity 79%). CONCLUSION: CRP in combination with SIRS was useful to diagnose infection in ICU patients; a CRP decrease > or = 50 mg/L between admission and day 4 was the best predictor of recovery.