Fekri Abroug

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.

Prevalence and factors of intensive care unit conflicts: the conflicus study.

RATIONALE Many sources of conflict exist in intensive care units (ICUs). Few studies recorded the prevalence, characteristics, and risk factors for conflicts in ICUs. OBJECTIVES To record the prevalence, characteristics, and risk factors for conflicts in ICUs. METHODS One-day cross-sectional survey of ICU clinicians. Data on perceived conflicts in the week before the survey day were obtained from 7,498 ICU staff members (323 ICUs in 24 countries). MEASUREMENTS AND MAIN RESULTS Conflicts were perceived by 5,268 (71.6%) respondents. Nurse-physician conflicts were the most common (32.6%), followed by conflicts among nurses (27.3%) and staff-relative conflicts (26.6%). The most common conflict-causing behaviors were personal animosity, mistrust, and communication gaps. During end-of-life care, the main sources of perceived conflict were lack of psychological support, absence of staff meetings, and problems with the decision-making process. Conflicts perceived as severe were reported by 3,974 (53%) respondents. Job strain was significantly associated with perceiving conflicts and with greater severity of perceived conflicts. Multivariate analysis identified 15 factors associated with perceived conflicts, of which 6 were potential targets for future intervention: staff working more than 40 h/wk, more than 15 ICU beds, caring for dying patients or providing pre- and postmortem care within the last week, symptom control not ensured jointly by physicians and nurses, and no routine unit-level meetings. CONCLUSIONS Over 70% of ICU workers reported perceived conflicts, which were often considered severe and were significantly associated with job strain. Workload, inadequate communication, and end-of-life care emerged as important potential targets for improvement.

Evolution of Mortality over Time in Patients Receiving Mechanical Ventilation

RATIONALE Baseline characteristics and management have changed over time in patients requiring mechanical ventilation; however, the impact of these changes on patient outcomes is unclear. OBJECTIVES To estimate whether mortality in mechanically ventilated patients has changed over time. METHODS Prospective cohort studies conducted in 1998, 2004, and 2010, including patients receiving mechanical ventilation for more than 12 hours in a 1-month period, from 927 units in 40 countries. To examine effects over time on mortality in intensive care units, we performed generalized estimating equation models. MEASUREMENTS AND MAIN RESULTS We included 18,302 patients. The reasons for initiating mechanical ventilation varied significantly among cohorts. Ventilatory management changed over time (P < 0.001), with increased use of noninvasive positive-pressure ventilation (5% in 1998 to 14% in 2010), a decrease in tidal volume (mean 8.8 ml/kg actual body weight [SD = 2.1] in 1998 to 6.9 ml/kg [SD = 1.9] in 2010), and an increase in applied positive end-expiratory pressure (mean 4.2 cm H2O [SD = 3.8] in 1998 to 7.0 cm of H2O [SD = 3.0] in 2010). Crude mortality in the intensive care unit decreased in 2010 compared with 1998 (28 versus 31%; odds ratio, 0.87; 95% confidence interval, 0.80-0.94), despite a similar complication rate. Hospital mortality decreased similarly. After adjusting for baseline and management variables, this difference remained significant (odds ratio, 0.78; 95% confidence interval, 0.67-0.92). CONCLUSIONS Patient characteristics and ventilation practices have changed over time, and outcomes of mechanically ventilated patients have improved. Clinical trials registered with www.clinicaltrials.gov (NCT01093482).

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.

An Official ATS/ERS/ESICM/SCCM/SRLF Statement: Prevention and Management of Acute Renal Failure in the ICU Patient: an international consensus conference in intensive care medicine.

OBJECTIVES To address the issues of Prevention and Management of Acute Renal Failure in the ICU Patient, using the format of an International Consensus Conference. METHODS AND QUESTIONS Five main questions formulated by scientific advisors were addressed by experts during a 2-day symposium and a Jury summarized the available evidence: (1) Identification and definition of acute kidney insufficiency (AKI), this terminology being selected by the Jury; (2) Prevention of AKI during routine ICU Care; (3) Prevention in specific diseases, including liver failure, lung Injury, cardiac surgery, tumor lysis syndrome, rhabdomyolysis and elevated intraabdominal pressure; (4) Management of AKI, including nutrition, anticoagulation, and dialysate composition; (5) Impact of renal replacement therapy on mortality and recovery. RESULTS AND CONCLUSIONS The Jury recommended the use of newly described definitions. AKI significantly contributes to the morbidity and mortality of critically ill patients, and adequate volume repletion is of major importance for its prevention, though correction of fluid deficit will not always prevent renal failure. Fluid resuscitation with crystalloids is effective and safe, and hyperoncotic solutions are not recommended because of their renal risk. Renal replacement therapy is a life-sustaining intervention that can provide a bridge to renal recovery; no method has proven to be superior, but careful management is essential for improving outcome.

Airway pressures, tidal volumes, and mortality in patients with acute respiratory distress syndrome

Objective:To determine the usual practice for setting tidal volume and other ventilatory parameters in patients with acute respiratory distress syndrome (ARDS) in the late 1990s and to determine the independent effects of these practices on intensive care unit mortality. Design:Subanalysis of a prospective observational study. Multivariable logistic regression was used to analyze the effects of ventilatory management on mortality. Setting:A total of 361 intensive care units in 20 countries in March 1998. Patients:A total of 467 mechanically ventilated patients with ARDS. Interventions:None. Measurements and Main Results:The mean tidal volume used in the first week of ARDS was 8.8 mL/kg measured body weight, and there was great variability in these tidal volumes (sd = 2.0). Tidal volumes were significantly lower in patients with (n = 265) than without (n = 202) a recorded plateau pressure (8.6 vs. 9.1 mL/kg, p = .01). The overall intensive care unit mortality rate was 60.2%. In addition to the strong influence of organ failures and higher levels of inspired oxygen, late-onset ARDS (onset after >48 hrs of mechanical ventilation; odds ratio, 2.09) was independently associated with mortality. In addition, lower levels of positive end-expiratory pressure were independently associated with higher mortality (odds ratio, 0.91; 1 cm of H2O increments). Neither inspiratory pressures nor tidal volumes were independently associated with mortality, and there was no evidence of increased mortality with the use of lower inspiratory pressures. Conclusions:This descriptive study demonstrated considerable interpatient variability in tidal volumes during the study period. In addition to traditional prognostic indicators, timing of ARDS onset and the use of low levels of positive end-expiratory pressure or no positive end-expiratory pressure during the first week may adversely influence outcome in ARDS patients.

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.

Determinants of Procedural Pain Intensity in the Intensive Care Unit. The Europain® Study

RATIONALE Intensive care unit (ICU) patients undergo several diagnostic and therapeutic procedures every day. The prevalence, intensity, and risk factors of pain related to these procedures are not well known. OBJECTIVES To assess self-reported procedural pain intensity versus baseline pain, examine pain intensity differences across procedures, and identify risk factors for procedural pain intensity. METHODS Prospective, cross-sectional, multicenter, multinational study of pain intensity associated with 12 procedures. Data were obtained from 3,851 patients who underwent 4,812 procedures in 192 ICUs in 28 countries. MEASUREMENTS AND MAIN RESULTS Pain intensity on a 0-10 numeric rating scale increased significantly from baseline pain during all procedures (P < 0.001). Chest tube removal, wound drain removal, and arterial line insertion were the three most painful procedures, with median pain scores of 5 (3-7), 4.5 (2-7), and 4 (2-6), respectively. By multivariate analysis, risk factors independently associated with greater procedural pain intensity were the specific procedure; opioid administration specifically for the procedure; preprocedural pain intensity; preprocedural pain distress; intensity of the worst pain on the same day, before the procedure; and procedure not performed by a nurse. A significant ICU effect was observed, with no visible effect of country because of its absorption by the ICU effect. Some of the risk factors became nonsignificant when each procedure was examined separately. CONCLUSIONS Knowledge of risk factors for greater procedural pain intensity identified in this study may help clinicians select interventions that are needed to minimize procedural pain. Clinical trial registered with www.clinicaltrials.gov (NCT 01070082).

Influence of body mass index on outcome of the mechanically ventilated patients

Background There are limited data on the impact of body mass index on outcomes in mechanically ventilated patients. Methods Secondary analysis of a cohort including 4698 patients mechanically ventilated. Patients were screened daily for management of mechanical ventilation, complications (acute respiratory distress syndrome, sepsis, ventilator associated pneumonia, barotrauma), organ failure (cardiovascular, respiratory, renal, hepatic, haematological) and mortality in the intensive care unit. To estimate the impact of body mass index on acute respiratory distress syndrome and mortality, the authors constructed models using generalised estimating equations (GEE). Results Patients were evaluated based on their body mass index: 184 patients (3.7%) were underweight, 1995 patients (40%) normal weight, 1781 patients (35.8%) overweight, 792 patients (15.9%) obese and 216 patients (4.3%) severely obese. Severely obese patients were more likely to receive low tidal volume based on actual body weight but high volumes based on predicted body weight. In obese patients, the authors observed a higher incidence of acute respiratory distress syndrome and acute renal failure. After adjustment, the body mass index was significantly associated with the development of acute respiratory distress syndrome: compared with normal weight; OR 1.69 (95% CI 1.07 to 2.69) for obese and OR 2.38 (95% CI 1.15 to 4.89) for severely obese. There were no differences in outcomes (duration of mechanical ventilation, length of stay and mortality in intensive care unit and hospital) based on body mass index categories. Conclusions In this cohort, obese patients were more likely to have significant complications but there were no associations with increased mortality.