Mohammed Alshahrani

Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-analysis*

Introduction: A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the feasibility of undertaking a larger trial investigating the efficacy and safety of withholding proton pump inhibitors in critically ill patients. Methods: In 10 ICUs, we randomized adult ICU patients anticipated to be mechanically ventilated for greater than or equal to 48 hours to receive 40 mg of IV pantoprazole daily or placebo. We excluded patients who had acute or recent gastrointestinal bleed, used dual antiplatelet agents, had a medical condition requiring proton pump inhibitor treatment, or had already received more than one dose of acid suppression daily. Patients, families, clinicians, and research staff were blinded. We conducted a systematic review and meta-analysis of similar trials. Main Results: Ninety-one patients (49 pantoprazole and 42 placebo) from 10 centers in Canada, Saudi Arabia, and Australia were enrolled. All feasibility goals were met: 1) recruitment rate was 2.6 patients per month; 2) consent rate was 77.8%; and 3) protocol adherence was 97.7%. Upper gastrointestinal bleeding developed in 6.1% of patients in the pantoprazole group and 4.8% in the placebo group (p = 1.0). Ventilator-associated pneumonia developed in 20.4% of patients in the pantoprazole group and 14.3% in the placebo group (p = 0.58). C. difficile was identified in 4.1% pantoprazole patients and in 2.4% placebo patients (p = 1.0). We meta-analyzed five trials (604 patients) of proton pump inhibitors versus placebo; there was no statistically significant difference in the risk of upper gastrointestinal bleeding, infections, or mortality. Conclusions: Our results support the feasibility of a larger trial to evaluate the safety of withholding stress ulcer prophylaxis. Although the results are imprecise, there was no alarming increase in the risk of upper gastrointestinal bleeding; the effect of proton pump inhibitors on ventilator-associated pneumonia and C. difficile remain unclear.

Efficacy and safety of stress ulcer prophylaxis in critically ill patients: a network meta-analysis of randomized trials

PurposeStress ulcer prophylaxis (SUP) is commonly prescribed in the intensive care unit. However, data from systematic reviews and conventional meta-analyses are limited by imprecision and restricted to direct comparisons. We conducted a network meta-analysis of randomized clinical trials (RCTs) to examine the safety and efficacy of drugs available for SUP in critically ill patients.MethodsWe searched MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials through April 2017 for randomized controlled trials that examined the efficacy and safety of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), and sucralfate for SUP in critically ill patients. No date or language restrictions were applied. Data on study characteristics, methods, outcomes, and risk of bias were abstracted by two reviewers.ResultsOf 96 potentially eligible studies, we included 57 trials enrolling 7293 patients. The results showed that PPIs are probably more effective for preventing clinically important gastrointestinal bleeding (CIB) than H2RAs [odds ratio (OR) 0.38; 95% confidence interval (95% CI) 0.20, 0.73], sucralfate (OR 0.30; 95% CI 0.13, 0.69), and placebo (OR 0.24; 95% CI 0.10, 0.60) (all moderate quality evidence). There were no convincing differences among H2RA, sucralfate, and placebo. PPIs probably increase the risk of developing pneumonia compared with H2RAs (OR 1.27; 95% CI 0.96, 1.68), sucralfate (OR 1.65; 95% CI 1.20, 2.27), and placebo (OR 1.52; 95% CI 0.95, 2.42) (all moderate quality). Mortality is probably similar across interventions (moderate quality). Estimates of baseline risks of bleeding varied significantly across studies, and only one study reported on Clostridium difficile infection. Definitions of pneumonia varied considerably. Most studies on sucralfate predate pneumonia prevention strategies.ConclusionsOur results provide moderate quality evidence that PPIs are the most effective agents in preventing CIB, but they may increase the risk of pneumonia. The balance of benefits and harms leaves the routine use of SUP open to question.

Re-evaluating the Inhibition of Stress Erosions (REVISE): a protocol for pilot randomized controlled trial.

INTRODUCTION Clinicians routinely administer stress ulcer prophylaxis to mechanically ventilated patients in the intensive care unit (ICU), most commonly prescribing proton pump inhibitors (PPIs). However, the incidence of gastrointestinal (GI) bleeding from stress ulceration is low and recent observational studies suggest these agents may increase infections. Therefore, a large randomized clinical trial (RCT) is needed to inform modern practice. The aim of this multicenter pilot trial is to determine the feasibility of performing a large RCT to investigate the efficacy and safety of withholding intravenous pantoprazole. METHODS AND ANALYSIS We will include adult critically ill patients who have an anticipated duration of ventilation of ≥48 hours. We will exclude patients with acute or recent GI bleeding, pregnancy, dual antiplatelet therapy, poor prognosis or intent to withdraw life support, or previous enrolment in this or a confounding trial. Following informed consent, patients will be randomized to receive the intervention of placebo (0.9% NaCl) or intravenous pantoprazole 40 mg daily. Patients, families, clinicians, data collectors, adjudicators of outcome and statisticians will be blind to allocation. The three primary feasibility outcomes are the informed consent rate, recruitment rate, and protocol adherence. Clinical outcomes include clinically important upper GI bleeding, ventilator-associated pneumonia (VAP), Clostridium difficile infection, length of stay and mortality in ICU and hospital. ETHICS AND APPROVAL This study has been approved by Health Canada, and research ethics board (REB) at each of the participating centers. TRIAL REGISTRATION NUMBER This trial was registered on 31 October 2014. The trial registration number is NCT02290327. FUNDING REVISE Pilot Trial is funded by Research Grant awarded by Physicians Services Incorporated, Dammam University Research Funds, Capital Health Authority Research Award Halifax, and Royal Adelaide Hospital Project Committee Grant.

Statistical analysis plan for the Pneumatic CompREssion for PreVENting Venous Thromboembolism (PREVENT) trial: a study protocol for a randomized controlled trial

BackgroundThe Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults.Methods/designIn this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is “incident” proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%.DiscussionConsistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data.Trial registrationClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013;Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

Stress ulcer prophylaxis: Back to square one

Pharmacologic prophylaxis against stress ulcer-related gastrointestinal (GI) bleeding with acid suppression has been the standard of care for decades. Worldwide, proton pump inhibitors (PPIs) are more commonly used than histamine-2-receptor antagonists. However, recent observational studies suggest that PPIs increase the risk of ventilator-associated pneumonia (VAP) and Clostridium difficile infection (CDI). Further, the incidence of GI bleeding appears to be lower than in the past, perhaps related to immediate resuscitation and enteral nutrition. a large randomized trial is needed to test the efficacy and safety of withholding PPIs in the ICU.

Effect of private versus emergency medical systems transportation in motor vehicle accident victims: Trauma Center Experience in Saudi Arabia

Objective: To assess the effect of the mode of transportation of trauma patients (emergency medical service [EMS] vs. non-EMS) on their final clinical outcome in terms of mortality and length of hospital stay. Materials And Methods: A retrospective study included all patients who were involved in motor vehicle crashes, and who were transferred immediately to an emergency department of a trauma care center from December 2008 to December 2012. Patients were classified into two groups: those brought through EMS and those brought by non-EMS (private transport). Information on demographic characteristics including age and gender was recorded and medical data such as blood pressure, pulse, oxygen saturation, temperature, initial Glasgow Coma Score (GCS), saturation, temperature, initial Glasgow Coma Score (GCS), injury severity score (ISS), and final outcome (discharged or expired) were obtained. Descriptive statistics, mean and standard deviation (SD) were computed for continuous variables and statistical significance was tested by t-test or Mann-Whitney U-test. Categorical variables were described by frequency distribution and percentages; Chi-square or Fisher′s exact test as appropriate were employed to test for statistical significance. Logistics regression was performed with mortality as dependent variable and mode of transport and all demographic and prehospital variables as independent variables. A general linear model analysis was performed to test whether the mode of transport was significant to length of hospital stay in EMS and non-EMS clients. Results: Out of 308 patients identified during the study period, 232 were transported through EMS and 76 through non-EMS. The two groups were similar with regard to mortality and length of stay. The crude mortality rate was 30.6% (95% confidence interval [CI]: 24.64-36.53) in the EMS group and 28.9% (95% CI: 18.44-38.76) in the non-EMS group (p = 0.785). The average length of hospital stay was 9 days (interquartile range [IQR] = 8, 95% CI: 7.3-10.1) for the EMS group and 8 days (IQR = 9.5, 95% CI: 6.7-10.9) for the non-EMS group (p = 0.803). Multivariate analysis showed that of the study variables, only the injury severity score (ISS) and Glasgow coma score (GCS) were significant to mortality (p < 0.01), and GCS was more significant to the length of hospital stay (p < 0.01). Conclusions: There was no significant difference between the EMS and non-EMS groups as they relate to mortality and length of stay in hospital. However, the mortality and length of hospital stay was statistically significant to ISS and GCS.

958: EXTRACORPOREAL MEMBRANE OXYGENATION FOR SEVERE MERS-COV: A RETROSPECTIVE OBSERVATIONAL STUDY.

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) 1.044, p 0.02). Non-ECPR ECMO patients had lower mortality at last follow-up (21.4%) than those treated with mechanical ventilation alone (42.2%; HR 0.168, p 0.03) despite having a higher median Murray Score (3.75 vs. 3.0, p=0.05). There was no difference in age or nadir PaO2/FiO2 ratio between ECMO and nonECMO patients (p=0.07 and 0.09). Conclusions: In a small cohort of critically ill influenza patients admitted with ARDS during the 2015–2016 H1N1 season, older age and severity of respiratory acidosis increased mortality risk. Our data also suggest that at a high-volume ECMO referral center, non-ECPR VV-ECMO may be associated with improved survival. Larger studies are needed to confirm if severely ill influenza patients can benefit from VV-ECMO.

Severe generalized tetanus: A case report and literature review

Tetanus is a toxin-mediated disease produced by the bacterium Clostridium tetani characterized by generalized rigidity and muscle spasms that may cause respiratory arrest and death. Tetanus typically gains access to the body through apparent or unapparent wounds. Implementation of mandatory vaccination programs has successfully decreased the prevalence of this disease worldwide. We report a case of severe, generalized tetanus in a male patient who presented to the emergency department with dysphagia and back stiffness with no clear history of any trauma, except small subungual hematoma found on physical examination. The patient was admitted to the Intensive Care Unit, received the full supportive therapy for tetanus, and discharged home in good condition.