Souheil Elatrous

Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic Shock The CRISTAL Randomized Trial

IMPORTANCE Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear. OBJECTIVE To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock. DESIGN, SETTING, AND PARTICIPANTS A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012. INTERVENTIONS Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay. MAIN OUTCOMES AND MEASURES The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy. RESULTS Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, -0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, -0.04 to 2.10] days; P = .03). CONCLUSIONS AND RELEVANCE Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00318942.

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.

Serotherapy in scorpion envenomation: a randomised controlled trial

BACKGROUND Evidence for the benefit of scorpion antivenom, the only specific treatment for scorpion envenomation, is scarce, despite its common use. We did a prospective, randomised, controlled trial to assess the efficacy of routine administration of scorpion antivenom to scorpion-stung patients, irrespective of clinical severity. METHODS We included 825 consecutive patients older than 10 years, who presented to the accident and emergency department of the hospital in Tozeur, Tunisia. We graded severity by absence (grade I) or presence (grade II) of systemic manifestations of scorpion envenomation. Patients were randomly assigned placebo (n=413) or 20 mL bivalent intraveneous scorpion antivenom (n=412). All patients were observed for 4 h. Patients who developed life-threatening symptoms were admitted to the intensive-care unit. At the end of 4 h observation we reassessed grade and discharged grade II patients and admitted grade II patients. We assessed the preventive and curative effects of scorpion antivenom by prevention of worsening grade or by improvement from grade II to grade I. FINDINGS Distribution of severity grades was similar in the two groups at baseline, as were the cure rates (55% scorpion antivenom, 66% placebo, absolute difference, 11% [95% CI -4.8 to 26.8]; p=0.234). Preventive effects were seen in 94% and 96% of patients in the scorpion antivenom and placebo groups, respectively, who were initially grade I and who remained symptom-free (absolute difference, 2% [-1.27 to 5.27]; p=0.377). Time from scorpion sting to administration of scorpion antivenom did not affect curative and preventive effects. INTERPRETATION We found no benefit in routine administration of scorpion antivenom after scorpion sting, irrespective of clinical severity. Future studies should focus on patients with the most severe symptoms and signs.

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.

Noninvasive ventilation and weaning in patients with chronic hypercapnic respiratory failure: a randomized multicenter trial.

RATIONALE The use of noninvasive ventilation (NIV) as an early weaning/extubation technique from mechanical ventilation remains controversial. OBJECTIVES To investigate NIV effectiveness as an early weaning/extubation technique in difficult-to-wean patients with chronic hypercapnic respiratory failure (CHRF). METHODS In 13 intensive care units, 208 patients with CHRF intubated for acute respiratory failure (ARF) who failed a first spontaneous breathing trial were randomly assigned to three groups: conventional invasive weaning group (n = 69), extubation followed by standard oxygen therapy (n = 70), or NIV (n = 69). NIV was permitted as rescue therapy for both non-NIV groups if postextubation ARF occurred. Primary endpoint was reintubation within 7 days after extubation. Secondary endpoints were: occurrence of postextubation ARF or death within 7 days after extubation, use of rescue postextubation NIV, weaning time, and patient outcomes. MEASUREMENTS AND MAIN RESULTS Reintubation rates were 30, 37, and 32% for invasive weaning, oxygen-therapy, and NIV groups, respectively (P = 0.654). Weaning failure rates, including postextubation ARF, were 54, 71, and 33%, respectively (P < 0.001). Rescue NIV success rates for invasive and oxygen-therapy groups were 45 and 58%, respectively (P = 0.386). By design, intubation duration was 1.5 days longer for the invasive group than in the two others. Apart from a longer weaning time in NIV than in invasive group (2.5 vs. 1.5 d; P = 0.033), no significant outcome difference was observed between groups. CONCLUSIONS No difference was found in the reintubation rate between the three weaning strategies. NIV decreases the intubation duration and may improve the weaning results in difficult-to-wean patients with CHRF by reducing the risk of postextubation ARF. The benefit of rescue NIV in these patients deserves confirmation.

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.

Efficacy of serotherapy in scorpion sting: a matched-pair study.

BACKGROUND/OBJECTIVE Although evidence of scorpion antivenin effectiveness in the clinical setting is lacking, scorpion antivenin is generally considered the only specific treatment for scorpion sting irrespective of its clinical severity. We conducted a matched-pair study to assess the efficacy of systematic administration of scorpion antivenin. METHODS Among 600 stung patients who participated in a study on the efficacy of high-dose hydrocortisone after scorpion sting, 135 (cases) had been treated with 10 to 20 mL intravenous scorpion antivenin (neutralizing 10 LD50 venom/mL). Controls were matched on disease severity on arrival to the emergency department. The severity of envenomation was graded I or II according to the absence (grade I) or the presence (grade II) of systemic manifestations of scorpion envenomation. Assessment of scorpion antivenin efficacy was based on the rate of changing severity grade in both groups (clinical improvement or worsening during an observation period of at least 4 hours). RESULTS Both groups were similar with respect to clinical severity (36 patients were graded II in each group), age, sex, time-lapse between scorpion sting and ED arrival, and the administration of adjunctive therapy such as hydrocortisone. By the 4-hour evaluation, 50% and 64% of patients initially graded II exhibited a substantial clinical improvement in cases and controls, respectively, suggesting similar effects in cases and controls. There was no difference in preventive effects: 13% and 10% of cases and controls developed systemic manifestations of scorpion envenomation during the 4-hour observation period; 23% of cases and 17% controls were hospitalized by this time. There was no difference in the duration of hospitalization. Three cases developed anaphylactic shock as a consequence of scorpion antivenin administration, while 1 scorpion antivenin-untreated patient died from refractory shock. CONCLUSION Systematic administration of scorpion antivenin irrespective of clinical severity did not alter the clinical course of scorpion sting. A prospective study is needed concerning the response of the more severe scorpion envenomations.

A controlled trial of nebulized salbutamol and adrenaline in acute severe asthma

ObjectiveTo compare efficacy and safety of nebulisation of adrenaline (2 mg over 10 min) and salbutamol (5 mg over 10 min) in acute severe asthma.DesignProspective randomized and double blind study.SettingIntensive care unit of a University teaching hospital.Patients and participants22 asthmatic patients presenting to the emergency room with acute severe asthma.InterventionsPatients were randomly assigned to receive either adrenaline (n=11) or salbutamol (n=11) via a nebulizer. Additional treatment comprised hydrocortisone hemisuccinate (100 mg) and supplemental oxygen (7l/min). The efficacy and safety of both drugs were evaluated at 20 and 40 min.ResultsA statistically significant increase in the Peak Expiratory Flow (PEF) was achieved at the 20th min in both groups (from 85±38 l/min to 120±45 l/min;p<0.001; and from 107±28 l/min to 145±19 l/min;p<0.001; in adrenaline group and salbutamol group respectively). With both drugs, PEF further increased at 40 min to a level that was statistically significant when compared to the 20 min evaluation. The magnitude of the absolute variation in PEF was similar with both drugs. Both drugs induced a significant decrease in heart rate, respiratory frequency and PaCO2 while the increase of PaO2/FIO2 ratio was not significant. The decrease of respiratory frequency at 40 min was more important with salbutamol (p=0.03). No side effects were recorded in both groups.ConclusionAfter a single dose, nebulized adrenaline (2 mg) proved as effective and safe as salbutamol (5 mg) in acute severe asthma.

Prednisone in COPD exacerbation requiring ventilatory support: an open-label randomised evaluation

Recommendation of the use of systemic steroids in chronic obstructive disease (COPD) exacerbation rely on trials that excluded patients requiring ventilatory support. In an open-label, randomised evaluation of oral prednisone administration, 217 patients with acute COPD exacerbation requiring ventilatory support were randomised (with stratification on the type of ventilation) to usual care (n=106) or to receive a daily dose of prednisone (1 mg·kg−1) for up to 10 days (n=111). There was no difference regarding the primary end-point, intensive care unit mortality, which was 17 (15.3%) deaths versus 15 (14%) deaths in the steroid-treated and control groups, respectively (relative risk 1.08, 95% CI 0.6–2.05). Analysis according to ventilation modalities showed similar mortality rates. Noninvasive ventilation failed in 15.7% and 12.7% (relative risk 1.25, 95% CI 0.56–2.8; p=0.59), respectively. Both study groups had similar median mechanical ventilation duration and intensive care unit length of stay, which were 6 (interquartile range 6–12) days versus 6 (3.8–12) days and 9 (6–14) days versus 8 (6–14) days, respectively. Hyperglycaemic episodes requiring initiation or alteration of current insulin doses occurred in 55 (49.5%) patients versus 35 (33%) patients in the prednisone and control groups, respectively (relative risk 1.5, 95% CI 1.08–2.08; p=0.015). Prednisone did not improve intensive care unit mortality or patient-centred outcomes in the selected subgroup of COPD patients with severe exacerbation but significantly increased the risk of hyperglycaemia. In COPD exacerbation needing ventilatory support, prednisone has no impact on ICU mortality or related patient outcome http://ow.ly/qxGq0