Joaquim Mateo

Sequential-Design, Multicenter, Randomized, Controlled Trial of Early Decompressive Craniectomy in Malignant Middle Cerebral Artery Infarction (DECIMAL Trial)

Background and Purpose— There is no effective medical treatment of malignant middle cerebral artery (MCA) infarction. The purpose of this clinical trial was to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction. Methods— We conducted in France a multicenter, randomized trial involving patients between 18 and 55 years of age with malignant MCA infarction to compare functional outcomes with or without decompressive craniectomy. A sequential, single-blind, triangular design was used to compare the rate of development of moderate disability (modified Rankin scale score ≤3) at 6 months’ follow-up (primary outcome) between the 2 treatment groups. Results— After randomization of 38 patients, the data safety monitoring committee recommended stopping the trial because of slow recruitment and organizing a pooled analysis of individual data from this trial and the 2 other ongoing European trials of decompressive craniectomy in malignant MCA infarction. Among the 38 patients randomized, the proportion of patients with a modified Rankin scale score ≤3 at the 6-month and 1-year follow-up was 25% and 50%, respectively, in the surgery group compared with 5.6% and 22.2%, respectively, in the no-surgery group (P=0.18 and P=0.10, respectively). There was a 52.8% absolute reduction of death after craniectomy compared with medical therapy only (P<0.0001). Conclusions— In this trial, early decompressive craniectomy increased by more than half the number of patients with moderate disability and very significantly reduced (by more than half) the mortality rate compared with that after medical therapy.

The use of dabigatran in elderly patients.

Recent approval by the US Food and Drug Administration (FDA) of dabigatran etexilate, an oral direct thrombin inhibitor, for the prevention of stroke in patients with atrial fibrillation will likely extend its administration in elderly patients. The risk of major overdosage of dabigatran etexilate in this population is, however, much increased owing to frequent renal function impairment, low body weight, drug interactions that cannot be detected with a routine coagulation test, and no antagonist available. We report herein 2 clinical cases, including 1 fatal case, illustrating our concern regarding the risk of bleeding events in elderly patients.

Impact of continuous venovenous hemofiltration on organ failure during the early phase of severe sepsis: A randomized controlled trial*

Objective:The impact of continuous venovenous hemofiltration on sepsis-induced multiple organ failure severity is controversial. We sought to assess the effect of early application of hemofiltration on the degree of organ dysfunction and plasma cytokine levels in patients with severe sepsis or septic shock. Design:Prospective, randomized, open, multicenter study setting, 12 French intensive care units. Patients:A total of 80 patients were enrolled within 24 hours of development of the first organ failure related to a new septic insult. Interventions:Patients were randomized to group 1 (HF), who received hemofiltration (25 mL/kg/hr) for a 96-hour period, or group 2 (C) who were managed conventionally. Measurements and Main Results:The primary end point was the number, severity, and duration of organ failures during 14 days, as evaluated by the Sepsis-Related Organ Failure Assessment score, on an intention-to-treat analysis. Strict guidelines were provided to perform continuous hemofiltration under the same conditions and bearing the same objectives in all centers. Because of inclusion stagnation, the trial was discontinued after an interim analysis by which time 76 patients had been randomized. The number and severity of organ failures were significantly higher in the HF group (p < 0.05). No modifications in plasma cytokine levels could be detected. Conclusion:These data suggest that early application of standard continuous venovenous hemofiltration is deleterious in severe sepsis and septic shock. This study does not rule out an effect of high-volume hemofiltration (>35 mL/kg/hr) on the course of sepsis.

Factors associated with septic shock and mortality in generalized peritonitis: comparison between community-acquired and postoperative peritonitis.

IntroductionThe risk factors associated with poor outcome in generalized peritonitis are still debated. Our aim was to analyze clinical and bacteriological factors associated with the occurrence of shock and mortality in patients with secondary generalized peritonitis.MethodsThis was a prospective observational study involving 180 consecutive patients with secondary generalized peritonitis (community-acquired and postoperative) at a single center. We recorded peri-operative occurrence of septic shock and 30-day survival rate and analyzed their associations with patients characteristics (age, gender, SAPS II, liver cirrhosis, cancer, origin of peritonitis), and microbiological/mycological data (peritoneal fluid, blood cultures).ResultsFrequency of septic shock was 41% and overall mortality rate was 19% in our cohort. Patients with septic shock had a mortality rate of 35%, versus 8% for patients without shock. Septic shock occurrence and mortality rate were not different between community-acquired and postoperative peritonitis. Age over 65, two or more microorganisms, or anaerobes in peritoneal fluid culture were independent risk factors of shock. In the subgroup of peritonitis with septic shock, biliary origin was independently associated with increased mortality. In addition, intraperitoneal yeasts and Enterococci were associated with septic shock in community-acquired peritonitis. Yeasts in the peritoneal fluid of postoperative peritonitis were also an independent risk factor of death in patients with septic shock.ConclusionsUnlike previous studies, we observed no difference in incidence of shock and prognosis between community-acquired and postoperative peritonitis. Our findings support the deleterious role of Enterococcus species and yeasts in peritoneal fluid, reinforcing the need for prospective trials evaluating systematic treatment against these microorganisms in patients with secondary peritonitis.

Impaired plasma B-type natriuretic peptide clearance in human septic shock.

Introduction:High B-type natriuretic peptide (BNP) levels are reported in the context of septic shock. We hypothesized that high BNP levels might be related to an alteration in BNP clearance pathway, namely neutral endopeptidase (NEP) 24.11. NEP 24.11 activity was measured in septic shock and in cardiogenic shock patients. We further evaluated whether baseline plasma BNP can predict fluid responsiveness and whether BNP can still be released in plasma despite high initial BNP levels, in response to overloading. Material and Methods:Prospective observational study. Patients in severe sepsis (S) or in septic shock (SS) needing a fluid challenge were included. Stroke volume (SV) and BNP were measured before (SV1, BNP1) and 45 mins after (SV2, BNP2) a standardized fluid challenge. DeltaBNP was defined as the difference between BNP2 and BNP1. NEP 24.11 activity was determined by fluorometry in 12 SS and 4 S patients before fluid challenge and in 5 cardiogenic shock patients. Results:Twenty-three patients (61 ± 18 years old, Simplified Acute Physiology Score II: 54 ± 21; 19 SS, 4 S; BNP1: 1371 ± 1434 pg/mL) were studied. BNP1 concentrations were significantly higher in SS than in S (1643 ± 1437 vs. 80 ± 35 pg/mL; p = 0.002). There was no correlation between baseline BNP and fluid responsiveness. Nine of the 11 patients with BNP1 >1000 pg/mL were fluid responders. DeltaBNP was greater in fluid nonresponders than in fluid responders (22 ± 27% vs. 6 ± 11%, p = 0.028). Plasma BNP was higher in SS than in cardiogenic shock patients (1367 ± 1438 vs. 750 ± 346 respectively; p = 0.027). NEP 24.11 activity was lower in SS than in S patients (0.10 ± 0.06 nmole/mL/min vs. 0.50 ± 0.22 nmole/mL/min, p <0.0001) cardiogenic shock patients (0.10 ± 0.06 nmole/mL/min vs. 0.58 ± 0.19 nmole/mL/min; p = 0.002). Conclusion:High levels of BNP might be related to an alteration in BNP clearance. During sepsis, high BNP levels are not predictive of fluid nonresponsiveness. Nevertheless, in fluid nonresponders, acute ventricular stretching can result in further BNP release.

Decompressive Craniectomy and Early Cranioplasty for the Management of Severe Head Injury: A Prospective Multicenter Study on 147 Patients

OBJECTIVE In emergency care of patients with severe blunt head injury, uncontrollable high intracranial pressure is one of major causes of morbidity and mortality. The purpose of this study was to evaluate the efficacy of aggressive surgical treatment in managing uncontrollable elevated intracranial pressure coupled with early skull reconstruction. METHODS This was a prospective study on a series of 147 consecutive patients, managed according to the same protocol by five different neurosurgical units, for severe head injuries (Glasgow coma scale score ≤8/15 and high intracranial pressure >25 mm Hg) during a five-year period. All patients received a wide decompressive craniectomy and duroplasty in the acute phase, and a cranioplasty was also performed within 12 weeks (median 6 weeks, range 4-12 weeks). RESULTS The emergency decompressive surgery was performed within 28 hours (median 16 hours, range 6-28 hours) after sustaining the head injury. The median preoperative Glasgow coma scale score was 6/15 (range 3-8/15). At a mean follow-up of 26 months (range 14-74 months) 14 patients were lost to long-term follow-up, leaving only 133 patients available for the study. The outcome was favorable in 89 (67%, Glasgow outcome score 4 or 5), it was not favorable in 25 (19%, Glasgow outcome score 2 and 3), and 19 patients (14%) died. A younger age (<50 years) and earlier operation (within 9 hours from trauma) had a significant effect on positive outcomes (P < 0.0001 and P < 0.03, respectively). CONCLUSIONS A prompt aggressive surgery, including a wide decompressive craniectomy coupled with early cranioplasty, could be an effective treatment method to improve the outcome after a severe closed head injury reducing, perhaps, many of the complications related to decompressive craniectomy.

Predictive factors for 1-year outcome of a cohort of patients with severe traumatic brain injury (TBI): Results from the PariS-TBI study

Abstract Objectives: To assess outcome and predicting factors 1 year after a severe traumatic brain injury (TBI). Methods: Multi-centre prospective inception cohort study of patients aged 15 or older with a severe TBI in the Parisian area, France. Data were collected prospectively starting the day of injury. One-year evaluation included the relatives-rating of the Dysexecutive Questionnaire (DEX-R), the Glasgow Outcome Scale–Extended (GOSE) and employment. Univariate and multivariate tests were computed. Results: Among 257 survivors, 134 were included (mean age 36 years, 84% men). Good recovery concerned 19%, moderate disability 43% and severe disability 38%. Among patients employed pre-injury, 42% were working, 28% with no job change. DEX-R score was significantly associated with length of education only. Among initial severity measures, only the IMPACT prognostic score was significantly related to GOSE in univariate analyses, while measures relating to early evolution were more significant predictors. In multivariate analyses, independent predictors of GOSE were length of stay in intensive care (LOS), age and education. Independent predictors of employment were LOS and age. Conclusions: Age, education and injury severity are independent predictors of global disability and return to work 1 year after a severe TBI.

Cutaneous Ear Lobe Pco2 at 37°C To Evaluate Microperfusion in Patients With Septic Shock

BACKGROUND Tissue hypercarbia is related to hypoperfusion and microcirculatory disturbances in patients with septic shock. Transcutaneous Pco₂ devices using a heated sensor to arterialize the tissue have been used as an alternative method for estimation of Paco₂. This study investigates whether a cutaneous sensor attached to an ear lobe and regulated to 37°C could be used to measure cutaneous Pco₂ (Pcco₂) and evaluate microperfusion in patients with septic shock. METHODS Fifteen stable patients in an ICU were studied as a control group. Forty-six patients with septic shock who were ventilated were enrolled as the study group. The difference of the gradients between Pcco₂ and Paco₂ (Pc-aco₂) and between Pcco₂ and end-tidal Pco₂(Pc-etco₂) were evaluated for 36 h. Variations of the Pc-aco₂ and Pc-etco₂ during fluid challenge were compared with microcirculatory skin blood flow (mBFskin) assessed by laser Doppler flowmetry. RESULTS The baseline levels for Pc-aco₂ and Pc-etco₂ were significantly higher in the patients with septic shock than in the control group (14.8 [12.6] vs 6 [2.7] mm Hg and 25 [16.3] vs 9 [3.8] mm Hg, P < .0001, respectively). During the following 36 h, the Pc-aco₂ and Pc-etco₂ for the surviving patients with septic shock decreased significantly compared with the nonsurvivors (P < .01). The evolution of macrohemodynamic parameters showed no differences between survivors and nonsurvivors. At hour 24, a Pc-aco₂ > 16 mm Hg and a Pc-etco₂ > 26 mm Hg were related to poor outcome. Pc-aco₂ and Pc-etco₂ variations during fluid challenge were inversely correlated with changes in mBFskin (r² = 0.7). CONCLUSIONS Ear lobe cutaneous Pco₂ at 37°C represents a noninvasive technique to assess tissue Pco₂ measurement. Pc-aco₂ and Pc-etco₂ were related to outcome and provide continuous information on microperfusion in patients with septic shock.

Factors Associated With the Mediastinal Spread of Cervical Necrotizing Fasciitis

BACKGROUND We conducted a study to determine factors associated with the occurrence of mediastinitis in patients hospitalized for cervical necrotizing fasciitis (CNF). METHODS We reviewed the medical records of 130 consecutive patients in an intensive care unit (ICU) who were hospitalized with a diagnosis of CNF. Two radiologists reviewed cervical and thoracic computed tomography (CT) scans to determine the source and extension of the infection in each patient. RESULTS Among the cohort of 130 patients with CNF, 37 (28%) had mediastinitis at the time of their admission (which in 13 cases was superior, or above the aortic arch, and in 24 cases inferior). Cervical necrotizing fasciitis complicated by mediastinitis resulted in a longer stay in the ICU than did CNF without mediastinitis, of a mean of 29 days (range, 18 to 39 days) versus 14 days (range, 9 to 19) days, respectively (p<0.0001). Multivariate analysis revealed that the presence of mediastinitis was associated with oral intake of glucocorticoids before admission (odds ratio [OR], 2.17; range, 0.99 to 4.76), a pharyngeal focus of CNF (OR, 2.17; range, 1.04 to 4.53), or gas seen on an initial CT scan (OR, 4.49; range, 2.15 to 9.38). Both a pharyngeal focus of fasciitis and the presence of gas were strong independent predictors of inferior mediastinitis (OR, 15.1; range, 4.9 to 46.4; p<0.0001). CONCLUSIONS The present study is the first to describe three independent factors associated with extension of cervical fasciitis to the thoracic cavity, including glucocorticoid intake before admission, and confirms previous reports of a high incidence of mediastinitis in patients with CNF.

Diastolic arterial blood pressure: a reliable early predictor of survival in human septic shock.

BACKGROUND Emphasis in therapy of human septic shock is shifting towards reliable end points and predictors of survival. Rationale is to study whether the evolution of cardiovascular reactivity in view of the administered doses of norepinephrine is an early predictor of in-hospital survival and to determine the optimal threshold of norepinephrine therapy and its consequences on renal function. METHODS Observational study of a prospective cohort of patients in septic shock, hospitalized in intensive care unit at least 24 hours before requiring norepinephrine. Excluded were patients requiring <72 hours of continuous norepinephrine (16 patients) or who received corticosteroids. Hemodynamic parameters (heart rate, blood pressure, urinary output, and temperature) were continuously monitored. RESULTS Of 68 patients, 45 survived [intensive care unit stay of 24 (12-36) days, hospital stay of 36 (27-66) days], and 23 died 5 (3-10) days after septic shock onset and norepinephrine treatment. Multivariate analysis revealed four independent positive predictive factors of short-term (10 days) outcome: Simplified Acute Physiology Score (SAPS) II <50 [odds ratio (OR) 6.4, 95% confidence interval (95% CI) 1.3-30.7, p < 0.011], and on day 3 Logistic Organ Dysfunction System (LODS) score <6 (OR 29.1, 95% CI 2.7-314.3, p = 0.0056), norepinephrine concentration <0.5 mug/kg/min (OR 17.6, 95% CI 2.2-142.0, p < 0.0007), diastolic arterial pressure >50 mm Hg (OR 24.8, 95% CI 2.9-215.9, p < 0.004), but not systolic arterial pressure. CONCLUSIONS Septic shock survival increases when dose of 0.5 mug/kg/min of norepinephrine continuously improves vascular tone within the first 48 hours, or when diastolic arterial pressure (>50 mm Hg) is restored. Norepinephrine has beneficial effects on renal function. Predictive value of LODS score on day 3 is demonstrated, while SAPS II is confirmed as the only reliable predictive factor in first 24 hours.