Gérard Audibert

Reversal of late septic shock with supraphysiologic doses of hydrocortisone

OBJECTIVES Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting. DESIGN Prospective, randomized, double-blind, placebo-controlled study. SETTING Two intensive care units of a University hospital. PATIENTS Forty-one patients with septic shock requiring catecholamine for >48 hrs. INTERVENTIONS Patients were randomly assigned either hydrocortisone (100 mg i.v. three times daily for 5 days) or matching placebo. MEASUREMENTS AND MAIN RESULTS Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for > or =24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p = .007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p = .005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p = .091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups. CONCLUSIONS Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency.

Comparison of norepinephrine and dobutamine to epinephrine for hemodynamics, lactate metabolism, and gastric tonometric variables in septic shock: a prospective, randomized study

Objectives: To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock. Design: A prospective, intervention, randomized clinical trial. Setting: Adult medical/surgical intensive care unit in a university hospital. Patients: 30 patients with a cardiac index (CI) > 3.5 l · min–1· m–2 and a mean arterial pressure (MAP) ≤ 60 mmHg after volume loading and dopamine 20 μg/kg per min and either oliguria or hyperlactatemia. Interventions: Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI. Measurements and main results: Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 ± 1.5 to 5.9 ± 1.0 mmol/l; p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 ± 1.5 to 2.7 ± 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 ± 5.4 to 21 ± 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 ± 5 to 14 ± 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 ± 0.11 to 7.16 ± 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2– arterial PCO2) increased (from 10 ± 2.7 to 14 ± 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 ± 0.11 to 7.35 ± 0.07) and the PCO2 gap (from 10 ± 3.0 to 4 ± 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h. Conclusions: Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.

Multivariate Analysis of Predictors of Cerebral Vasospasm Occurrence After Aneurysmal Subarachnoid Hemorrhage

BACKGROUND AND PURPOSE The role of type of treatment on cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage (SAH) has not been studied. Through multivariate analysis we determined the independent prognostic factors of the occurrence of symptomatic vasospasm following aneurysmal SAH in a study cohort of 244 patients undergoing either surgical or endovascular treatment. The prognostic factors of sequelae after aneurysmal SAH were studied as well. METHODS Symptomatic vasospasm was defined as the association of deterioration in a patients neurological condition between 3 and 14 days after SAH with no other explanation and an increase in mean transcranial Doppler velocities of >120 cm/s. The prognostic factors were registered on admission and during the intensive care stay. RESULTS Symptomatic vasospasm occurred in 22.2% surgical patients compared with 17.2% endovascular treatment patients (P=0.37). Multivariate analysis revealed that the probability of occurrence of symptomatic vasospasm decreased with age >50 years (relative risk [RR], 0.47 [0.25 to 0.88]) and severe World Federation of Neurological Surgeons (WFNS) grade measured on admission (RR, 0.43 [0.20 to 0.90]) and increased with hyperglycemia occurring during the intensive care stay (RR, 1.94 [1.04 to 3.63]). No difference in risk of symptomatic vasospasm could be identified between surgical and endovascular treatment. Symptomatic vasospasm (OR, 4.73 [CI, 1. 77 to 12.6]) as well as WFNS grade of >2 (OR, 8.95 [3.46 to 23.2]), treatment complications (OR, 8.39 [3.16 to 22.3]), and secondary brain insults were associated with an increased risk of 6-month sequelae. CONCLUSIONS Age <50 years, good neurological grade, and hyperglycemia were all associated with an increased risk of cerebral vasospasm whereas treatment was not. This provides a basis for future clinical prospective randomized trials comparing both treatments.

Assessment of White Matter Injury and Outcome in Severe Brain Trauma: A Prospective Multicenter Cohort

Background:Existing methods to predict recovery after severe traumatic brain injury lack accuracy. The aim of this study is to determine the prognostic value of quantitative diffusion tensor imaging (DTI). Methods:In a multicenter study, the authors prospectively enrolled 105 patients who remained comatose at least 7 days after traumatic brain injury. Patients underwent brain magnetic resonance imaging, including DTI in 20 preselected white matter tracts. Patients were evaluated at 1 yr with a modified Glasgow Outcome Scale. A composite DTI score was constructed for outcome prognostication on this training database and then validated on an independent database (n = 38). DTI score was compared with the International Mission for Prognosis and Analysis of Clinical Trials Score. Results:Using the DTI score for prediction of unfavorable outcome on the training database, the area under the receiver operating characteristic curve was 0.84 (95% CI: 0.75–0.91). The DTI score had a sensitivity of 64% and a specificity of 95% for the prediction of unfavorable outcome. On the validation-independent database, the area under the receiver operating characteristic curve was 0.80 (95% CI: 0.54–0.94). On the training database, reclassification methods showed significant improvement of classification accuracy (P < 0.05) compared with the International Mission for Prognosis and Analysis of Clinical Trials score. Similar results were observed on the validation database. Conclusions:White matter assessment with quantitative DTI increases the accuracy of long-term outcome prediction compared with the available clinical/radiographic prognostic score.

Differential Quantitative Blood Cultures in the Diagnosis of Catheter-Related Sepsis in Intensive Care Units

The aim of this prospective study was to compare differential blood cultures and quantitative catheter tip cultures for the diagnosis of catheter-related sepsis. Over a period of 2 years, 283 central venous catheters were inserted in 190 adult patients. Catheters were removed when they were no longer needed or when infection was suspected. Immediately before removal of the central venous catheters, blood cultures were performed, with blood drawn simultaneously from the catheter and the peripheral vein. After removal, quantitative catheter culture was performed according to the Brun-Buisson modified Cleri technique. Fifty-five quantitative catheter cultures were positive. They were classified as contaminated (n = 18), colonized (n = 23), or infected (n = 14). Differential blood cultures correctly identified 13 infections. With a catheter/peripheral cfu ratio of 8, differential blood cultures had a sensitivity of 92.8% and a specificity of 98.8%. When the catheters were removed because of suspected infection, differential blood cultures had a sensitivity of 92.8% and a specificity of 100%. Differential blood culture, a technique that does not necessitate catheter removal, seems effective in the diagnosis of catheter-related sepsis in patients in the intensive care unit.

Improvement of donor myocardial function after treatment of autonomic storm during brain death.

Background. In experimental brain death models, autonomic storm (AS) triggers severe myocardial dysfunction, which can be attenuated by pharmacologic treatment. The aim of this study was to determine the incidence of AS in a cohort of human organ donors and to evaluate the potential interest of AS treatment on myocardial function, cardiac harvesting and transplantation. Methods. The cohort consisted of 152 patients. Among them, 46 patients were initially considered as potential cardiac donors (main criteria: age <60 years, no history of cardiac disease). AS diagnosis included increased systolic arterial pressure >200 mm Hg associated with tachycardia >140 beats/min. Heart acceptance criteria were associated creatine kinase (CK), troponin Ic, and left ventricle ejection fraction (LVEF) estimated by echocardiography and visual inspection. Results. AS was observed in 29 patients (63%). Hypertension was treated in 12 patients (esmolol n=6, urapidil n=5, nicardipine). Cardiac harvesting was performed in 28 donors (61%). LVEFs were significantly higher after AS treatment (no AS: 55.4±13.4%, untreated AS: 49.0±18.8%, treated AS: 63.9+±10.3%, P=0.049). AS treatment was found to be independently associated with LVEF in >50% of the cases (P=0.034). Treatment of AS or the lack of AS were associated with an increased probability of successful cardiac transplantation (OR=8.8; 95% CI 2.1–38.3, P=0.002). Conclusions. Treatment of hypertension during AS may attenuate brain death-induced myocardial dysfunction and increase the number of available cardiac grafts.

Diffusion tensor imaging to predict long-term outcome after cardiac arrest: a bicentric pilot study.

Background:Prognostication in comatose survivors of cardiac arrest is a major clinical challenge. The authors’ objective was to determine whether an assessment with diffusion tensor imaging, a brain magnetic resonance imaging sequence, increases the accuracy of 1 yr functional outcome prediction in cardiac arrest survivors. Methods:Prospective, observational study in two intensive care units. Fifty-seven comatose survivors of cardiac arrest underwent brain magnetic resonance imaging. Fractional anisotropy (FA), a diffusion tensor imaging value, was measured in predefined white matter regions, and apparent diffusion coefficient was assessed in predefined grey matter regions. Prediction of unfavorable outcome at 1 yr was compared using four prognostic models: FA global, FA selected, apparent diffusion coefficient, and clinical classifiers. Results:Of the 57 patients included in the study, 49 had an unfavorable outcome at 12 months. Areas under the receiver operating characteristic curve (95% CI) to predict unfavorable outcome for the FA global, FA selected, clinical, and apparent diffusion coefficient models were 0.92 (0.82–0.98), 0.96 (0.87–0.99), 0.78 (0.65–0.88), and 0.86 (0.74–0.94), respectively. The FA selected model had the best overall accuracy for predicting outcome, with a score above 0.44 having 94% (95% CI, 83–99%) sensitivity and 100% (95% CI, 63–100%) specificity for the prediction of unfavorable outcome. Conclusion:Quantitative diffusion tensor imaging indicates that white matter damage is widespread after cardiac arrest. A prognostic model based on FA values in selected white matter tracts seems to predict accurately 1 yr functional outcome. These preliminary results need to be confirmed in a larger population.

Endocrine response after severe subarachnoid hemorrhage related to sodium and blood volume regulation.

BACKGROUND: Hyponatremia is often associated with, and worsens, the prognosis of severe aneurysmal subarachnoid hemorrhage (SAH). Several possible endocrine perturbations of variable severity and variable sodium and water intake have been described in SAH. However, a comprehensive study of the different hormonal systems involved in sodium and water homeostasis and circulating blood volume modifications is still needed. Our aim was to assess water and sodium regulation after severe SAH by investigating blood volume and several hormonal regulatory systems in the context of hyponatremia prevention by controlled sodium intake. METHODS: Nineteen mechanically ventilated patients with severe SAH, were prospectively studied. Replacement of sodium was at least 4.5 mmol · kg−1 · d−1 and adjusted on natriuresis. Hormones involved in electrolyte and water homeostasis: vasopressin, renin, angiotensin, aldosterone, and natriuretic peptides were assessed every 3 days for 12 days. Red blood cell volume was measured by the isotopic method (technetium–labeled red blood cells), in the first 48 h after admission and at day 7. Cardiac function was assessed using electrocardiogram, transthoracic echocardiography, and troponin Ic (cTnI). Outcome was assessed at 3 mo. RESULTS: After SAH onset, hyponatremia, but not decreased circulating blood volume, was prevented by high sodium and water infusion adapted to renal excretion. The hormonal profiles were characterized by an increase in renin, angiotensin II, natriuretic peptide concentrations associated with increased troponin Ic, stable low levels of vasopressin, and the absence of increased aldosterone concentrations. There were no correlations between hormone concentrations and natriuresis. CONCLUSION: After severe SAH, in the context of multiple clinical interventions, increased natriuresis and low blood volume are consistent with cerebral salt wasting syndrome, probably related to the sequence of severe SAH, highly increased sympathetic tone, hyperreninemic hypoaldosteronism syndrome, and increased natriuretic peptides release.

Rheologic effects of plasma substitutes used for preoperative hemodilution.

This study was designed to compare the influence of various plasma substitutes, administered for preoperative hemodilution, on blood rheology. We studied 40 patients, ASA grade I, who underwent elective facial reconstructive surgery and received 4% albumin (n = 10), 3.5% dextran 40 (n = 10), gelatin (n = 10), or hydroxyethyl starch (HES) (n = 10). Ten patients, undergoing the same surgical procedure without hemodilution, were chosen as controls. After hemodilution, hematocrit was decreased approximately 30%. Fibrinogen decreased in all tested groups except in the gelatin group. Plasma viscosity decreased with albumin (1.13 ± 0.05 to 1.06 ± 0.03 mPa·s; P < 0.01) and increased with HES (1.15 ± 0.04 to 1.22 ± 0.05 mPa·s; P < 0.01). At a high shear rate, the blood viscosity decreased in all groups. In contrast, at a low shear rate and at 40% corrected hematocrit, the blood viscosity decreased in the albumin (15.9 ± 1.9 to 13.1 ± 2.1 mPa·s; P < 0.01) and the dextran 40 (16.9 ± 2.9 to 12.8 ± 2.5 mPa·s; P < 0.01) groups and was unchanged in the gelatin and the HES groups. Erythrocyte aggregation (measured with primary aggregation time) was markedly decreased in the albumin (3.27 ± 1.74 to 7.03 ± 2.95 s; P < 0.01) and in the dextran 40 (2.72 ± 0.58 to 6.24 ± 2.55 s; P < 0.001) groups, unchanged with HES, and increased with gelatin (2.41 ± 0.90 to 1.55 ± 0.33 s). These findings suggest that albumin and dextran 40 may be the plasma substitutes of choice for preoperative hemodilution when this technique aims to improve rheologic conditions.

Therapeutic optimization including inhaled nitric oxide in adult respiratory distress syndrome in a polyvalent intensive care unit.

OBJECTIVE To investigate the effects of inhaled nitric oxide (NO) in adult respiratory distress syndrome (ARDS) associated with a therapeutic optimization strategy on oxygen parameters, barotrauma, and evolution in a medical and surgical intensive care unit. DESIGN Prospective study. MATERIALS AND METHODS Twenty consecutive patients with ARDS were studied (Murray score 3.6 +/- 0.2). Eleven were surgical patients and nine were medical patients. All fulfilled the extracorporeal membrane oxygenation entry criteria. The APACHE II score predicted mortality was 39%. All were ventilated with FiO2 1 with positive end-expiratory pressure (PEEP) of 11 +/- 1 cm H2O. Therapeutic optimization included permissive hypercapnia, tracheal gas insufflation, prone position, continuous hemofiltration, treatment of infection, and pleural drainage. We used NO continuously inhaled at a concentration ranging from 5 to 10 ppm. MEASUREMENTS AND MAIN RESULTS After 1 hour, inhaled NO improved PaO2 in all patients except one (78 +/- 11 to 130 +/- 25 mm Hg) (p < 0.05), allowing a reduction of FiO2 and PEEP. After 24 hours, mean pulmonary arterial pressure decreased from 31 +/- 3 to 25 +/- 2 mm Hg (p < 0.05). Systemic hemodynamics were unaffected. Oxygen delivery increased from 531 +/- 135 to 603 +/- 125 mL/minute/m-2 (p < 0.05). Barotraumatic lesions were present in only one patient. Reversal of ARDS was obtained in 16 patients, of whom 14 (70%) were discharged. CONCLUSIONS This study was shorter to demonstrate an improvement in the survival rate. Nevertheless, these preliminary results are encouraging. Because of its safety, effectiveness, and easy use, inhaled NO should be used as a part of a therapeutic optimization protocol before considering more invasive and expensive procedures, such as extracorporeal respiratory support or intravascular oxygenation.