Riadh Boukef

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.

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.

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.

Elevated Plasma B-Type Natriuretic Peptide Concentrations Directly Inhibit Circulating Neprilysin Activity in Heart Failure

OBJECTIVES This study sought to hypothesize that elevated B-type natriuretic peptide (BNP) could act as an endogenous neprilysin inhibitor. BACKGROUND A hallmark of acute decompensated heart failure (ADHF) is the overproduction of natriuretic peptides (NPs) by stretched cardiomyocytes. Various strategies have been developed to potentiate the beneficial effect of the NPs, including the recent use of neprilysin angiotensin receptor inhibitors. Contrary to rodents, human BNP is poorly sensitive to neprilysin degradation while retaining affinity to neprilysin. METHODS We enrolled 638 patients presenting to the emergency department with acute dyspnea of which 468 had ADHF and 169 had dyspnea of noncardiac origin. We also included 46 patients with stable chronic heart failure (HF) and 10 age-matched healthy subjects. Plasma samples were collected within 4 h after emergency department admission. BNP, neprilysin concentration and activity, and the neprilysin substrate substance P concentration were measured. RESULTS We found that when plasma BNP rose above 916 pg/ml, neprilysin activity was markedly reduced (p < 0.0001) and stratified 95% of the population into 2 groups: BNP <916 pg/ml/neprilysin activity ≥ 0.21 nmol/ml/min and BNP ≥916 pg/ml/neprilysin activity <0.21 nmol/ml/min with very different prognoses. In vitro, BNP was responsible for neprilysin inhibition. Neprilysin activity was inversely correlated with the concentration of substance P (ρ = -0.80; p < 0.0001). CONCLUSIONS Besides being an effector of the cardiac response to cardiomyocyte stretching in ADHF, elevated plasma BNP is also an endogenous neprilysin inhibitor. A biologically relevant BNP threshold discriminates 2 populations of HF patients with different vasoactive peptide profiles and outcome. If confirmed, this may identify an important threshold for managing HF patients.

A canine study of immunotherapy in scorpion envenomation

ObjectiveTo evaluate the effects of scorpion venom and antivenom in experimental envenomation.DesignProspective, controlled animal study.SettingUniversity research laboratorySubjectsTwenty-nine anesthetized and ventilated dogs.InterventionsThe first group of animals had venom alone (0.05 mg/kg). Animals from the second group had simultaneous administration of 10 ml of scorpion antivenom (SAV). In the third and fourth groups, 10 ml and 40 ml SAV, respectively, were injected 10 min following venom.Measurements and resultsHemodynamic parameters using right heart catheter were recorded and dosage of catecholamines, neuropeptide Y (NPY), endothelin-1, and atrial natriuretic peptide (ANP) were performed at baseline and during 60 min following envenomation. In the control group, at 5 min, there was a sharp increase in pulmonary artery occluded pressure (PAOP, from 2 mmHg to 23 mmHg), mean arterial pressure (MAP, from 125 mmHg to 212 mmHg) and systemic vascular resistance (SVR, from 2,450 dyn sec-1 m5 to 5,775 dyn sec-1 m5, P<0.05 for all). Heart rate, cardiac output, and stroke volume decreased. There was a 40-fold increase in epinephrine and norepinephrine plasma concentrations. Circulating NPY and ANP dosages increased too. PAOP and MAP decreased thereafter to reach baseline levels. Simultaneous administration of SAV with venom totally offset the hallmarks of scorpion envenomation. Delayed administration of SAV at any dosage failed to alter the features of scorpion envenomation.ConclusionWhile simultaneous administration of SAV and scorpion venom is effective in preventing scorpion envenomation-related manifestations, delayed administration of SAV, either at standard or elevated dosages, failed to alter any of the scorpion envenomation features.

Paracetamol vs piroxicam to relieve pain in renal colic. Results of a randomized controlled trial.

PURPOSE We tested whether paracetamol could improve pain relief in patients visiting the emergency department with acute renal colic as compared to piroxicam, a nonsteroidal anti-inflammatory drug (NSAID). MATERIALS AND METHODS Patients with a diagnosis of acute renal colic were prospectively randomized to receive either intravenous paracetamol (1 g) or intramuscular piroxicam (20 mg). We monitored patients for visual analog scale (VAS), heart rate, arterial blood pressure, need for rescue therapy, and adverse events at different time points for 90 minutes. We recorded admission requirement and new visit for renal colic at 72 hours. The primary end point was pain relief at 90 minutes, defined as a decrease of 50% or more as compared to the initial VAS. The secondary objectives were comparison of the 2 groups for VAS at any time points and the occurrence of adverse events. RESULTS Of the 226 eligible patients, 100 entered the study. Fifty patients received paracetamol and 50 received NSAID. Pain relief at 90 minutes was obtained in 40 patients receiving paracetamol (80%) and 24 (48%) receiving NSAID (P = .002). Visual analog scale was lower in the paracetamol group since 45 minutes. Only 2 adverse events were observed. CONCLUSION A single therapy with intravenous paracetamol more efficiently relieved pain in acute renal colic than did intramuscular piroxicam.

Accuracy of Two Scores in the Diagnosis of Stroke Subtype in a Multicenter Cohort Study

STUDY OBJECTIVE The distinction between hemorrhagic and ischemic stroke has critical implications for management. For that purpose, clinical scores have been proposed to be used in areas with limited health care resources where brain computed tomographic (CT) scan is not readily available. We conducted this study to evaluate the predictive value of the Allen and Siriraj scores in the differential diagnosis of stroke subtypes. METHODS We prospectively collected data for 4 years on the clinical characteristics of patients with stroke in a multicenter study. For all patients, we calculated the Allen and the Siriraj scores and we assessed their accuracy in predicting stroke subtypes with receiver operating characteristics (ROC) curves. RESULTS We assessed 1,023 patients. Of these, 82.7% (n=846) had ischemic stroke. The area under the ROC curve was higher for Siriraj score compared with the Allen score (0.780 versus 0.702; P=.04). Using the original cutoff points, Siriraj score has a sensitivity for the diagnosis of hemorrhage of 60% and a specificity of 95%; the corresponding values for the Allen score are 55% and 70%, respectively. The negative predictive value was higher for Siriraj score compared to the Allen score (90% versus 80%). The diagnosis of stroke subtype was best predicted at Siriraj score less than -4. CONCLUSION Siriraj score is a valid and useful tool for predicting stroke subtype in a clinical setting in which financial constraints make systematic brain CT scan unfeasible.

Standard versus Newer Antibacterial Agents in the Treatment of Severe Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized Trial of Trimethoprim-Sulfamethoxazole versus Ciprofloxacin

BACKGROUND. Although the use of antibiotics in the treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD) is largely accepted, controversy remains regarding whether the choice of antibiotic has any impact on outcome. Our aim was to compare the effects of the combination of trimethoprim and sulfamethoxazole and ciprofloxacin in patients treated for severe COPD exacerbation requiring mechanical ventilation. METHODS. In a randomized, double-blind trial, we included 170 patients with an acute exacerbation of COPD requiring mechanical ventilation. Enrolled patients received trimethoprim-sulfamethoxazole (n = 85) or ciprofloxacin (n = 85) for 10 days. Main outcomes were hospital death and need for an additional course of antibiotics. Secondary outcomes were duration of mechanical ventilation, length of hospital stay, and exacerbation-free interval. RESULTS. Combined hospital death and additional antibiotic prescription rates were similar in the 2 groups (16.4% vs 15.3% for trimethoprim-sulfamethoxazole group vs ciprofloxacin group; difference, 1.1%; 95% confidence interval [CI] -9.8% to 12.0%; P = .832). Hospital death occurred in 7 patients (8.2%) receiving trimethoprim-sulfamethoxazole and 8 patients (9.4%) receiving ciprofloxacin (difference, -1.2%; 95% CI, -9.7 to 7.3; P = .90). The need for an additional antibiotic course was observed in 8 patients in the trimethoprim-sulfamethoxazole group and 5 patients in the ciprofloxacin group (difference, 2.3%; 95% CI, -5.4 to 10.0; P = .549). The mean exacerbation-free interval (+/- standard deviation) was similar in both treatment groups (83 +/- 25 vs 79 +/- 22 for the trimethoprim-sulfamethoxazole group vs ciprofloxacin group; difference, 4 days; 95% CI, -15 to 19 days; P = .41). Duration of mechanical ventilation and hospital stay was not significantly different between the 2 groups. CONCLUSIONS. In patients with acute exacerbation of COPD requiring mechanical ventilation, efficacy of trimethoprim-sulfamethoxazole was not inferior to ciprofloxacin. Trial registration. ClinicalTrials.gov identifier: NCT00791505.

Phloroglucinol as an adjuvant analgesic to treat renal colic

PURPOSE We tested whether the addition of phloroglucinol to piroxicam could improve pain relief in patients with acute renal colic visiting the emergency department. MATERIALS AND METHODS Patients with a diagnosis of acute renal colic were prospectively randomized to receive intravenous phloroglucinol (200 mg) or placebo combined with intramuscular piroxicam (20 mg). We monitored the visual analogic scale (VAS), heart rate, arterial blood pressure, need for rescue therapy, and adverse events at different time points for 1 hour. We recorded admission requirement and new visit at 72 hours for renal colic. The primary end point was to assess pain relief at 1 hour, defined as a decrease of 50% or more as compared with the initial VAS. The secondary objectives were to compare the 2 groups for VAS at any time points, the need for rescue therapy, and the occurrence of adverse events. RESULTS Of the 309 eligible patients, 253 entered the study. A total of 126 patients received phloroglucinol and 127 patients received placebo. Pain relief at 1 hour was obtained in 89 patients (71%) receiving phloroglucinol and 89 patients (70%) receiving placebo (P = .89). There were no differences in VAS between the 2 groups at any time points. Rescue therapy was required in 37 patients (29%) receiving phloroglucinol and 38 patients (30%) receiving placebo (P = .51). Number of adverse events was similar with phloroglucinol and placebo: 20 (16%) and 16 (13%), respectively (P = .44). CONCLUSIONS There was no evidence that the addition of phloroglucinol improved the efficiency of piroxicam to relieve pain in acute renal colic.

Acupuncture vs intravenous morphine in the management of acute pain in the ED

BACKGROUND Acupuncture is one of the oldest techniques to treat pain and is commonly used for a large number of indications. However, there is no sufficient evidence to support its application in acute medical settings. METHODS This was a prospective, randomized trial of acupuncture vs morphine to treat ED patients with acute onset moderate to severe pain. Primary outcome consists of the degree of pain relief with significant pain reduction defined as a pain score reduction ≥50% of its initial value. We also analyzed the pain reduction time and the occurrence of short-term adverse effects. We included in the protocol 300 patients with acute pain: 150 in each group. RESULTS Success rate was significantly different between the 2 groups (92% in the acupuncture group vs 78% in the morphine group P<.001). Resolution time was 16±8 minutes in the acupuncture group vs 28±14 minutes in the morphine group (P<.005). Overall, 89 patients (29.6%) experienced minor adverse effects: 85 (56.6%) in morphine group and 4 (2.6%) in acupuncture group (P<.001). No major adverse effects were recorded during the study protocol. In patients with acute pain presenting to the ED, acupuncture was associated with more effective and faster analgesia with better tolerance. CONCLUSION This article provides an update on one of the oldest pain relief techniques (acupuncture) that could find a central place in the management of acute care settings. This should be considered especially in todays increasingly complicated and polymedicated patients to avoid adverse drug reactions.