Semir Nouira

Once daily oral ofloxacin in chronic obstructive pulmonary disease exacerbation requiring mechanical ventilation: a randomised placebo-controlled trial

BACKGROUND The role of antibiotics in treatment of patients with moderate exacerbations of chronic obstructive pulmonary disease (COPD) is uncertain, but such treatment might be useful in very severe episodes. Our objective was to assess the effects of ofloxacin in patients with exacerbations of COPD who required mechanical ventilation. METHODS We did a prospective, randomised, double-blind, placebo-controlled trial in 93 patients with acute exacerbation of COPD who required mechanical ventilation. Patients were randomly assigned to receive oral ofloxacin 400 mg once daily (n=47) or placebo (46) for 10 days. Primary endpoints were death in hospital and need for an additional course of antibiotics, both separately and in combination. Analysis was by intention to treat. FINDINGS Three patients dropped out of the study. Two (4%) patients receiving ofloxacin died in hospital and ten (22%) did so in the placebo group (absolute risk reduction 17.5%, 95% CI 4.3-30.7, p=0.01). Treatment with ofloxacin significantly reduced the need for additional courses of antibiotics (28.4%, 12.9-43.9, p=0.0006). The combined frequency of death in hospital and need for additional antibiotics was significantly lower in patients assigned to ofloxacin than in those receiving placebo (45.9%, 29.1-62.7, p<0.0001). The duration of mechanical ventilation and hospital stay was significantly shorter in the ofloxacin group than in the placebo group (absolute difference 4.2 days, 95% CI 2.5-5.9; and 9.6 days, 3.4-12.8, respectively). INTERPRETATION New fluoroquinolones, such as ofloxacin, are beneficial in the treatment of COPD exacerbation requiring mechanical ventilation.

Incremental value of biomarkers to clinical variables for mortality prediction in acutely decompensated heart failure: the Multinational Observational Cohort on Acute Heart Failure (MOCA) study.

AIM This study aims to evaluate the incremental value of plasma biomarkers to traditional clinical variables for risk stratification of 30-day and one-year mortality in acutely decompensated heart failure (ADHF). METHODS AND RESULTS Through an international collaborative network, individual patient data on 5306 patients hospitalized for ADHF were collected. The all-cause mortality rate was 11.7% at 30 days and 32.9% at one year. The clinical prediction model (age, gender, blood pressure on admission, estimated glomerular filtration rate <60 mL/min/1.73 m(2), sodium and hemoglobin levels, and heart rate) had a c-statistic of 0.74 for 30-day mortality and 0.73 for one-year mortality. Several biomarkers measured at presentation improved risk stratification when added to the clinical model. At 30 days, the net reclassification improvement (NRI) was 28.7% for mid-regional adrenomedullin (MR-proADM; p<0.001) and 25.5% for soluble (s)ST2 (p<0.001). At one year, sST2 (NRI 10.3%), MR-proADM (NRI 9.1%), amino-terminal pro-B-type natriuretic peptide (NT-proBNP; NRI 9.1%), mid-regional proatrial natriuretic peptide (MR-proANP; NRI 7.4%), B-type natriuretic peptide (NRI 5.5%) and C-reactive protein (CRP; NRI 5.3%) reclassified patients with ADHF (p<0.05 for all). CRP also markedly improved risk stratification of patients with ADHF as a dual biomarker combination with MR-proADM (NRI 36.8% [p<0.001] for death at 30 days) or with sST2 (NRI 20.3%; [p<0.001] for one-year mortality). CONCLUSION In this study, biomarkers provided incremental value for risk stratification of ADHF patients. Biomarkers such as sST2, MR-proADM, natriuretic peptides and CRP, reflecting different pathophysiologic pathways, add prognostic value to clinical risk factors for predicting both short-term and one-year mortality in ADHF.

Is intensive care justified for patients with haematological malignancies

The course of 260 adults with haematological malignancies admitted to a medical intensive care unit was studied to evaluate the value of life support techniques and to research predictive factors. The overall in the medical intensive care unit (MICU) and hospital mortality rates were respectively 43% (113 patients) and 57% (148 patients). Among survivors, 64% (49 patients) were still alive after 6 months and 44% (35 patients) after 1 year. Among 34 haemodialysed patients, the MICU mortality was 67% (23 patients) and among 111 mechanically ventilated patients 85% (94 patients). Prolonged mechanical ventilation, more than seven days, was performed in 11 of the 17 survivors and did not influence long term survival. No individual predictor of mortality was found comparing survivors and non-survivors. However, SAPS, intractable sepsis and failure of more than one organ system were significantly different in non-survivors (p<0.001). Among the 20 patients requiring both mechanical ventilation and haemodialysis, only two left the MICU and both died soon thereafter. We conclude that life support therapy should be initiated in patients with haematological disorders and that prolonged mechanical ventilation is compatible with long term survival. However, the combination of mechanical ventilation and haemodialysis is always associated with a poor prognosis and therefore the use of both techniques simultaneously for one patient is questionable.

Effects of norepinephrine on static and dynamic preload indicators in experimental hemorrhagic shock.

Objective:To investigate the effect of norepinephrine on static (right atrial pressure, pulmonary artery occlusion pressure ) and dynamic (pulse pressure variation and arterial systolic pressure variation) preload indicators in experimental hemorrhagic shock. Design:Prospective controlled experimental study. Setting:Animal research laboratory. Subjects:Six anesthetized and mechanically ventilated dogs. Interventions:Dogs were instrumented for measurement of arterial blood pressure, pulmonary artery catheter derived variables including right atrial pressure, pulmonary artery occlusion pressure, and cardiac output. Simultaneously, pulse pressure variation and systolic pressure variation were calculated. Pulse pressure variation is the difference between the maximal and the minimal value of pulse pressure divided by the mean of the two values and is expressed as a percentage. Systolic pressure variation is the difference between the maximal and the minimal systolic pressure and is expressed as an absolute value. After baseline measurements, hemorrhagic shock was induced by a stepwise cumulative blood withdrawal of 35 mL·kg−1 of body weight. A second set of hemodynamic measurement was made 30 mins after bleeding. The third set was made 30 mins later under norepinephrine. Measurements and Main Results:Mean arterial pressure and cardiac output decreased after hemorrhage (p < .05), whereas right atrial pressure and pulmonary artery occlusion pressure remained unchanged. Baseline pulse pressure variation and systolic pressure variation increased significantly with hemorrhage, from 12% (9%) to 28% (11.5%) (p < .001) and from 12.5 (6.5) to 21 (8.2) mm Hg (p < .05), respectively. Norepinephrine induced a significant increase of cardiac output and a significant decrease of pulse pressure variation and systolic pressure variation but did not significantly change right atrial pressure or pulmonary artery occlusion pressure values. Stroke volume was correlated to pulse pressure variation and systolic pressure variation but was not correlated to right atrial pressure or pulmonary artery occlusion pressure. Conclusion:Our study confirms the superiority of dynamic variables (pulse pressure variation and systolic pressure variation) over static ones (right atrial pressure and pulmonary artery occlusion pressure) in assessing cardiac preload changes in hemorrhagic shock. However, norepinephrine could significantly reduce the value of these dynamic variables and mask a true intravascular volume deficit possibly by shifting blood from unstressed to stressed volume.

Association Between Elevated Blood Glucose and Outcome in Acute Heart Failure Results From an International Observational Cohort

OBJECTIVE The aim of this analysis was to assess the association between elevated blood glucose level and mortality in acute heart failure (AHF). BACKGROUND Elevated blood glucose has been reported to be prognostically meaningful in patients with cardiac diagnoses, such as coronary artery disease. The short-term prognostic impact of hyperglycemia in AHF is unknown, however. METHODS In a multinational cohort of AHF, we examined the ability of blood glucose concentrations at presentation to predict all-cause mortality by 30 days. Fully adjusted models for prognosis included a previous diagnosis of diabetes mellitus as a covariate. RESULTS A total of 6,212 subjects with AHF (mean age, 72 years; 52.5% male) were studied; the median blood glucose concentration on arrival at the hospital was 7.5 mmol/l (135 mg/dl), and 41% had a previous diagnosis of diabetes mellitus (DM). After 30 days, 618 patients (10%) had died. Compared with survivors, decedents had significantly higher median blood glucose concentrations (8.9 mmol/l vs. 7.4 mmol/l; p < 0.0001). In the fully adjusted model, an elevated blood glucose level was an independent predictor of 30-day mortality in AHF (odds ratio: 2.19; 95% confidence interval: 1.69 to 2.83; p < 0.001). The risk associated with an elevated blood glucose level appeared consistent across all subgroups of patients, including patients with preserved (hazard ratio: 5.41; 95% confidence interval: 2.44 to 12.0; p < 0.0001) and impaired systolic function (hazard ratio: 2.37; 95% confidence interval: 1.57 to 3.59; p < 0.0001). Furthermore, in reclassification analyses, elevated blood glucose added significant prognostic information to clinical parameters alone (4.4% net reclassification improvement; p = 0.01). CONCLUSIONS Among patients with AHF, blood glucose concentrations at presentation are powerfully prognostic for 30-day mortality, independent of a diagnosis of diabetes mellitus or other clinical variables. Because blood glucose is easily modifiable, it may represent a valid target for therapeutic intervention.

Predictive value of severity scoring systems : Comparison of four models in Tunisian adult intensive care units

OBJECTIVES To compare the performance of four severity scoring systems: the Acute Physiology and Chronic Health Evaluation (APACHE) II, the new versions of the Mortality Prediction Model (MPM0 and MPM24), and the Simplified Acute Physiology Score (SAPS) II. DESIGN A prospective cohort study. SETTING Three Tunisian intensive care units (ICUs). PATIENTS Consecutive, unselected adult patients (n = 1325). INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Overall, observed death rates were higher than predicted by all models except MPM0. All the evaluated scoring systems had good discrimination power as expressed by area under the receiver operating characteristics curve, but their calibration was less perfect when compared with original validation reports. There were no major differences between the models with regard either to discrimination or calibration performance. CONCLUSION Despite an overall good discrimination, APACHE II, MPM0, MPM24, and SAPS II showed a less satisfactory calibration in our Tunisian sample of ICU patients. Part of the models inaccuracy could be related to quality of care problems in our ICUs, but this issue needs further analysis.

Assessment of left ventricular function in severe scorpion envenomation: Combined hemodynamic and echo-Doppler study

ObjectiveTo assess left ventricular function in patients presenting with pulmonary edema following scorpion envenomation.DesignCohort study.Setting: Medical intensive care unit of a teaching hospital.Patients: Nine consecutive adult patients stung byAndroctonus australis and presenting with pulmonary edema entered the study. Fourteen normal volunteers comprised the control group.InterventionsUpon admission, all patients had right heart catheterization and, within the first 8 h, a Doppler echocardiographic study. Results of Doppler echocardiographic studies were compared to those of controls.Measurements and resultsUsual hemodynamic information (heart and vascular pressures, derived data and tissue oxygenation parameters), left ventricular dimensions and indicators of systolic function, and Doppler-derived parameters of left ventricular filling and diastolic function were obtained upon admission. Serial echocardiographic measurements were repeated daily until full clinical recovery (eight patients) or death (one patient). All patients had a hemodynamic profile of acute congestive heart failure (mean PAOP=24±2 mmHg; mean SVI=22±7 ml/m2; mean CI=2.5±0.5 l/min/m2). However, SVR were not increased (mean=22±3 U/m2). Left ventricle was hypokinetic in all patients with transient mitral regurgitation present in five patients. Left ventricular systolic function was markedly depressed (FS=12±6%; EF=26±12%). An associated diastolic dysfunction is suggested by Doppler records of mitral inflow. Left ventricular systolic function evolved toward normalization within 6±2 days preceded by full clinical recovery.ConclusionsThese data suggest that pulmonary edema in scorpion envenomation is of hemodynamic origin and is related to a severe and prominent impairment of left ventricular systolic function.

Post-translational modifications enhance NT-proBNP and BNP production in acute decompensated heart failure

BACKGROUND Increases in plasma B-type natriuretic peptide (BNP) concentrations in those with acutely decompensated heart failure (ADHF) has been mainly attributed to an increase in NPPB gene transcription. Recently, proBNP glycosylation has emerged as a potential regulatory mechanism in the production of amino-terminal (NT)-proBNP and BNP. The aim of the present study was to investigate proBNP glycosylation, and corin and furin activities in ADHF patients. METHODS AND RESULTS Plasma levels of proBNP, NT-proBNP, BNP, as well as corin and furin concentration and activity were measured in a large cohort of 683 patients presenting with ADHF (n = 468), non-cardiac dyspnoea (non-ADHF: n = 169) and 46 patients with stable chronic heart failure (CHF); the degree of plasma proBNP glycosylation was assessed in a subset of these patients (ADHF: n = 49, non-ADHF: n = 50, CHF: n = 46). Our results showed a decrease in proBNP glycosylation in ADHF patients that paralleled NT-proBNP overproduction (ρ = -0.62, P < 0.001) but less so to BNP. In addition, we observed an increase in furin activity that is positively related to the plasma levels of proBNP, NT-proBNP and BNP overproduction (all P < 0.001, all ρ > 0.88), and negatively related to the degree of proBNP glycosylation (ρ = -0.62, P < 0.001). CONCLUSION These comprehensive results provide a paradigm for the post-translational modification of natriuretic peptides in ADHF: as proBNP glycosylation decreases, furin activity increases. This synergistically amplifies the processing of proBNP into BNP and NT-proBNP. CLINICAL TRIAL REGISTRATION http://clinicaltrials.gov/. Identifier: NCT01374880.

Acute heart failure and cardiogenic shock: a multidisciplinary practical guidance

PurposeAcute heart failure (AHF) causes high burden of mortality, morbidity, and repeated hospitalizations worldwide. This guidance paper describes the tailored treatment approaches of different clinical scenarios of AHF and CS, focusing on the needs of professionals working in intensive care settings.ResultsTissue congestion and hypoperfusion are the two leading mechanisms of end-organ injury and dysfunction, which are associated with worse outcome in AHF. Diagnosis of AHF is based on clinical assessment, measurement of natriuretic peptides, and imaging modalities. Simultaneously, emphasis should be given in rapidly identifying the underlying trigger of AHF and assessing severity of AHF, as well as in recognizing end-organ injuries. Early initiation of effective treatment is associated with superior outcomes. Oxygen, diuretics, and vasodilators are the key therapies for the initial treatment of AHF. In case of respiratory distress, non-invasive ventilation with pressure support should be promptly started. In patients with severe forms of AHF with cardiogenic shock (CS), inotropes are recommended to achieve hemodynamic stability and restore tissue perfusion. In refractory CS, when hemodynamic stabilization is not achieved, the use of mechanical support with assist devices should be considered early, before the development of irreversible end-organ injuries.ConclusionA multidisciplinary approach along the entire patient journey from pre-hospital care to hospital discharge is needed to ensure early recognition, risk stratification, and the benefit of available therapies. Medical management should be planned according to the underlying mechanisms of various clinical scenarios of AHF.

Prediction value of the Canadian CT head rule and the New Orleans criteria for positive head CT scan and acute neurosurgical procedures in minor head trauma: a multicenter external validation study.

STUDY OBJECTIVE The New Orleans Criteria and the Canadian CT Head Rule have been developed to decrease the number of normal computed tomography (CT) results in mild head injury. We compare the performance of both decision rules for identifying patients with intracranial traumatic lesions and those who require an urgent neurosurgical intervention after mild head injury. METHODS This was an observational cohort study performed between 2008 and 2011 on patients with mild head injury who were aged 10 years or older. We collected prospectively clinical head CT scan findings and outcome. Primary outcome was need for neurosurgical intervention, defined as either death or craniotomy, or the need of intubation within 15 days of the traumatic event. Secondary outcome was the presence of traumatic lesions on head CT scan. New Orleans Criteria and Canadian CT Head Rule decision rules were compared by using sensitivity specifications and positive and negative predictive value. RESULTS We enrolled 1,582 patients. Neurosurgical intervention was performed in 34 patients (2.1%) and positive CT findings were demonstrated in 218 patients (13.8%). Sensitivity and specificity for need for neurosurgical intervention were 100% (95% confidence interval [CI] 90% to 100%) and 60% (95% CI 44% to 76%) for the Canadian CT Head Rule and 82% (95% CI 69% to 95%) and 26% (95% CI 24% to 28%) for the New Orleans Criteria. Negative predictive values for the above-mentioned clinical decision rules were 100% and 99% and positive values were 5% and 2%, respectively, for the Canadian CT Head Rule and New Orleans Criteria. Sensitivity and specificity for clinical significant head CT findings were 95% (95% CI 92% to 98%) and 65% (95% CI 62% to 68%) for the Canadian CT Head Rule and 86% (95% CI 81% to 91%) and 28% (95% CI 26% to 30%) for the New Orleans Criteria. A similar trend of results was found in the subgroup of patients with a Glasgow Coma Scale score of 15. CONCLUSION For patients with mild head injury, the Canadian CT Head Rule had higher sensitivity than the New Orleans Criteria, with higher negative predictive value. The question of whether the use of the Canadian CT Head Rule would have a greater influence on head CT scan reduction requires confirmation in real clinical practice.