Standards for Studies of Neurological Prognostication in Comatose Survivors of Cardiac Arrest: A Scientific Statement From the American Heart Association.

Significant improvements have been achieved in cardiac arrest resuscitation and postarrest resuscitation care, but mortality remains high. Most of the poor outcomes and deaths of cardiac arrest survivors have been attributed to widespread brain injury. This brain injury, commonly manifested as a comatose state, is a marker of poor outcome and a major basis for unfavorable neurological prognostication. Accurate prognostication is important to avoid pursuing futile treatments when poor outcome is inevitable but also to avoid an inappropriate withdrawal of life-sustaining treatment in patients who may otherwise have a chance of achieving meaningful neurological recovery. Inaccurate neurological prognostication leading to withdrawal of life-sustaining treatment and deaths may significantly bias clinical studies, leading to failure in detecting the true study outcomes. The American Heart Association Emergency Cardiovascular Care Science Subcommittee organized a writing group composed of adult and pediatric experts from neurology, cardiology, emergency medicine, intensive care medicine, and nursing to review existing neurological prognostication studies, the practice of neurological prognostication, and withdrawal of life-sustaining treatment. The writing group determined that the overall quality of existing neurological prognostication studies is low. As a consequence, the degree of confidence in the predictors and the subsequent outcomes is also low. Therefore, the writing group suggests that neurological prognostication parameters need to be approached as index tests based on relevant neurological functions that are directly related to the functional outcome and contribute to the quality of life of cardiac arrest survivors. Suggestions to improve the quality of adult and pediatric neurological prognostication studies are provided.

Critical care providers' support of families in bereavement: a mixed-methods study.

PURPOSE: When people die in intensive care units (ICUs), as many as half of their family members may experience a severe grief reaction. While families report a need for bereavement support, most ICUs do not routinely follow-up with family members. Clinicians are typically involved in supporting families during death and dying, yet little is known about how they work with families in bereavement. Our goal was to explore how clinicians support bereaved families, identify factors that facilitate and hinder support, and understand their interest and needs for follow-up. METHODS: Mixed-methods study of nurses and physicians working in one of nine adult medical-surgical ICUs in academic hospitals across Canada. Qualitative interviews followed quantitative surveys to reflect, expand, and explain the quantitative results. RESULTS: Both physicians and nurses perceived that they provided empathetic support to bereaved families. Emotional engagement was a crucial element of support, but clinicians were not always able to engage with families because of their roles, responsibilities, experiences, or unit resources. Another important factor that could facilitate or challenge engagement was the degree to which families accepted death. Clinicians were interested in participating in a follow-up bereavement program, but their participation was contingent on time, training, and the ability to manage their own emotions related to death and bereavement in the ICU. CONCLUSIONS: Multiple opportunities were identified to enhance current bereavement support for families, including the desire of ICU clinicians for formal follow-up programs. Many psychological, sociocultural, and structural factors would need to be considered in program design.

RéSUMé: OBJECTIF: Lorsque des personnes décèdent dans une unité de soins intensifs (USI), jusqu'à la moitié des membres de leur famille pourraient souffrir d'une réaction émotionnelle grave. Bien que les familles rapportent le besoin d'un soutien en cas de deuil, la plupart des USI ne font pas un suivi de routine avec les membres de la famille. Les cliniciens sont traditionnellement impliqués dans le soutien aux familles pendant la mort et le décès, mais nous ne connaissons que peu de choses concernant leur travail avec les familles en deuil. Notre objectif était d'explorer la façon dont les cliniciens viennent en soutien aux familles en deuil, d'identifier les facteurs qui facilitent ou entravent le soutien, et de comprendre leur intérêt et leurs besoins en matière de suivi. MéTHODE: Nous avons réalisé une étude par méthodes mixtes auprès du personnel infirmier et des médecins travaillant dans l'une de neuf USI médico-chirurgicales pour adultes dans des hôpitaux universitaires du Canada. Des entretiens qualitatifs suivaient des sondages quantitatifs afin de refléter, approfondir et expliquer les résultats quantitatifs. RéSULTATS: Selon leur perception, les médecins et le personnel infirmier fournissent un soutien empathique aux familles en deuil. L'implication émotionnelle a été identifiée comme étant un élément crucial du soutien, mais les cliniciens ne sont pas toujours capables de s'impliquer auprès des familles en raison de leurs rôles, de leurs responsabilités, de leurs expériences ou des ressources de l'unité. Un autre facteur important qui pourrait faciliter ou au contraire entraver leur implication est la mesure dans laquelle les familles acceptent la mort. Les cliniciens seraient intéressés à participer à un programme de suivi de deuil, mais leur participation dépend de leur temps, de leur formation et de leur capacité à gérer leurs propres émotions liées à la mort et au deuil à l'USI. CONCLUSION: De nombreuses cibles ont été identifiées pour améliorer le soutien actuel aux familles en deuil, y compris le désir des cliniciens de l'USI de disposer de programmes formels de suivi. Il faudra toutefois tenir compte de nombreux facteurs psychologiques, socioculturels et structurels dans la conception de tels programmes.

Beta-blockers and Traumatic Brain Injury: A Systematic Review, Meta-analysis, and Eastern Association for the Surgery of Trauma Guideline.

OBJECTIVE: To determine if beta-(ß)-blockers improve outcomes after acute traumatic brain injury (TBI). BACKGROUND: There have been no new inpatient pharmacologic therapies to improve TBI outcomes in a half-century. Treatment of TBI patients with ß-blockers offers a potentially beneficial approach. METHODS: Using MEDLINE, EMBASE, and CENTRAL databases, eligible articles for our systematic review and meta-analysis (PROSPERO CRD42016048547) included adult (age ≥ 16 years) blunt trauma patients admitted with TBI. The exposure of interest was ß-blocker administration initiated during the hospitalization. Outcomes were mortality, functional measures, quality of life, cardiopulmonary morbidity (e.g., hypotension, bradycardia, bronchospasm, and/or congestive heart failure). Data were analyzed using a random-effects model, and represented by pooled odds ratio (OR) with 95% confidence intervals (CI) and statistical heterogeneity (I). RESULTS: Data were extracted from 9 included studies encompassing 2005 unique TBI patients with ß-blocker treatment and 6240 unique controls. Exposure to ß-blockers after TBI was associated with a reduction of in-hospital mortality (pooled OR 0.39, 95% CI: 0.27-0.56; I = 65%, P < 0.00001). None of the included studies examined functional outcome or quality of life measures, and cardiopulmonary adverse events were rarely reported. No clear evidence of reporting bias was identified. CONCLUSIONS: In adults with acute TBI, observational studies reveal a significant mortality advantage with ß-blockers; however, quality of evidence is very low. We conditionally recommend the use of in-hospital ß-blockers. However, we recommend further high-quality trials to answer questions about the mechanisms of action, effectiveness on subgroups, dose-response, length of therapy, functional outcome, and quality of life after ß-blocker use for TBI.

Improving Appropriate Neurologic Prognostication after Cardiac Arrest. A Stepped Wedge Cluster Randomized Controlled Trial.

RATIONALE: Predictions about neurologic prognosis that are based on early clinical findings after out-of-hospital cardiac arrest (OHCA) are often inaccurate and may lead to premature decisions to withdraw life-sustaining treatments (LST) in patients who might otherwise survive with good neurologic outcomes. OBJECTIVES: To improve adherence to recommendations for appropriate neurologic prognostication after OHCA and reduce deaths from premature decisions to withdraw LST. METHODS: This was a pragmatic stepped wedge cluster randomized controlled trial evaluating a multifaceted quality intervention (education, pathways, local champions, audit-feedback). The primary outcome was appropriate neurologic prognostication, defined as (1a) no early withdrawal of LST (WLST) (within 72 h) based on estimates of poor neurologic prognosis and (1b) no WLST between 72 hours and 7 days in absence of clinical predictors of poor neurologic prognosis or (2) surviving beyond 7 days. Secondary outcomes were deaths from early WLST and survival with good neurologic outcome. MEASUREMENTS AND MAIN RESULTS: Between June 1, 2011, and June 30, 2014, a total of 905 patients with OHCA were enrolled from ICUs of 18 Ontario hospitals. Rates of appropriate neurologic prognostication increased after the intervention (68% vs. 74% patients; odds ratio [OR], 1.79; 95% confidence interval [CI], 1.01-3.19; P = 0.05). However, rates of survival to hospital discharge (46% vs. 50%; OR, 1.71; 95% CI, 0.97-3.01; P = 0.06) and survival with good neurologic outcome remained similar (38% vs. 43%; OR, 1.43; 95% CI, 0.84-2.86; P = 0.19). CONCLUSIONS: A multicenter quality intervention improved rates of appropriate neurologic prognostication after OHCA but did not increase survival with good neurologic outcome. Clinical trial registered with www.clinicaltrials.gov (NCT 01472458).

Nonbeneficial treatment Canada: definitions, causes, and potential solutions from the perspective of healthcare practitioners*.

OBJECTIVE: Many healthcare workers are concerned about the provision of nonbeneficial treatment in the acute care setting. We sought to explore the perceptions of acute care practitioners to determine whether they perceived nonbeneficial treatment to be a problem, to generate an acceptable definition of nonbeneficial treatment, to learn about their perceptions of the impact and causes of nonbeneficial treatment, and the ways that they feel could reduce or resolve nonbeneficial treatment. DESIGN: National, bilingual, cross-sectional survey of a convenience sample of nursing and medical staff who provide direct patient care in acute medical wards or ICUs in Canada. MAIN RESULTS: We received 688 responses (response rate 61%) from 11 sites. Seventy-four percent of respondents were nurses. Eighty-two percent of respondents believe that our current means of resolving nonbeneficial treatment are inadequate. The most acceptable definitions of nonbeneficial treatment were "advanced curative/life-prolonging treatments that would almost certainly result in a quality of life that the patient has previously stated that he/she would not want" (88% agreement) and "advanced curative/life-prolonging treatments that are not consistent with the goals of care (as indicated by the patient)" (83% agreement). Respondents most commonly believed that nonbeneficial treatment was caused by substitute decision makers who do not understand the limitations of treatment, or who cannot accept a poor prognosis (90% agreement for each cause), and 52% believed that nonbeneficial treatment was "often" or "always" continued until the patient died or was discharged from hospital. Respondents believed that nonbeneficial treatment was a common problem with a negative impact on all stakeholders (> 80%) and perceived that improved advance care planning and communication training would be the most effective (92% and 88%, respectively) and morally acceptable (95% and 92%, respectively) means to resolve the problem of nonbeneficial treatment. CONCLUSIONS: Canadian nurses and physicians perceive that our current means of resolving nonbeneficial treatment are inadequate, and that we need to adopt new techniques of resolving nonbeneficial treatment. The most promising strategies to reduce nonbeneficial treatment are felt to be improved advance care planning and communication training for healthcare professionals.

Predicting neurologic outcome after targeted temperature management for cardiac arrest: systematic review and meta-analysis.

OBJECTIVES: Targeted temperature management improves survival and neurologic outcomes for adult out-of-hospital cardiac arrest survivors but may alter the accuracy of tests for predicting neurologic outcome after cardiac arrest. DATA SOURCES: We systematically searched Medline, Embase, CINAHL, and CENTRAL from database inception to September 2012. STUDY SELECTION: Citations were screened for studies that examined diagnostic tests to predict poor neurologic outcome or death following targeted temperature management in adult cardiac arrest survivors. DATA EXTRACTION: Data on study outcomes and quality were abstracted in duplicate. We constructed contingency tables for each diagnostic test and calculated sensitivity, specificity, and positive and negative likelihood ratios. DATA SYNTHESIS: Of 2,737 citations, 20 studies (n = 1,845) met inclusion criteria. Meta-analysis showed that three tests accurately predicted poor neurologic outcome with low false-positive rates: bilateral absence of pupillary reflexes more than 24 hours after a return of spontaneous circulation (false-positive rate, 0.02; 95% CI, 0.01-0.06; summary positive likelihood ratio, 10.45; 95% CI, 3.37-32.43), bilateral absence of corneal reflexes more than 24 hours (false-positive rate, 0.04; 95% CI, 0.01-0.09; positive likelihood ratio, 6.8; 95% CI, 2.52-18.38), and bilateral absence of somatosensory-evoked potentials between days 1 and 7 (false-positive rate, 0.03; 95% CI, 0.01-0.07; positive likelihood ratio, 12.79; 95% CI, 5.35-30.62). False-positive rates were higher for a Glasgow Coma Scale motor score showing extensor posturing or worse (false-positive rate, 0.09; 95% CI, 0.06-0.13; positive likelihood ratio, 7.11; 95% CI, 5.01-10.08), unfavorable electroencephalogram patterns (false-positive rate, 0.07; 95% CI, 0.04-0.12; positive likelihood ratio, 8.85; 95% CI, 4.87-16.08), myoclonic status epilepticus (false-positive rate, 0.05; 95% CI, 0.02-0.11; positive likelihood ratio, 5.58; 95% CI, 2.56-12.16), and elevated neuron-specific enolase (false-positive rate, 0.12; 95% CI, 0.06-0.23; positive likelihood ratio, 4.14; 95% CI, 1.82-9.42). The specificity of available tests improved when these were performed beyond 72 hours. Data on neuroimaging, biomarkers, or combination testing were limited and inconclusive. CONCLUSION: Simple bedside tests and somatosensory-evoked potentials predict poor neurologic outcome for survivors of cardiac arrest treated with targeted temperature management, and specificity improves when performed beyond 72 hours. Clinicians should use caution with these predictors as they carry the inherent risk of becoming self-fulfilling.

Economic evaluation of decompressive craniectomy versus barbiturate coma for refractory intracranial hypertension following traumatic brain injury.

OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as second-tier strategies when intracranial hypertension following severe traumatic brain injury is refractory to first-line treatments. Uncertainty surrounds the decision to choose either treatment option. We investigated which strategy is more economically attractive in this context. DESIGN: We performed a cost-utility analysis. A Markov Monte Carlo microsimulation model with a life-long time horizon was created to compare quality-adjusted survival and cost of the two treatment strategies, from the perspective of healthcare payer. Model parameters were estimated from the literature. Two-dimensional simulation was used to incorporate parameter uncertainty into the model. Value of information analysis was conducted to identify major drivers of decision uncertainty and focus future research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a population of patients (mean age = 25 yr) who developed refractory intracranial hypertension following traumatic brain injury. INTERVENTIONS: We compared two treatment strategies: decompressive craniectomy and barbiturate coma. MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an average gain of 1.5 quality-adjusted life years relative to barbiturate coma, with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year gained. Decompressive craniectomy resulted in a greater quality-adjusted life expectancy 86% of the time and was more cost-effective than barbiturate coma in 78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At older age, decompressive craniectomy continued to increase survival but at higher cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive craniectomy for the treatment of refractory intracranial hypertension following traumatic brain injury provides better value in terms of costs and health gains than barbiturate coma. However, decompressive craniectomy might be less economically attractive for older patients. Further research, particularly on natural history of severe traumatic brain injury patients, is needed to make more informed treatment decisions.

Beta blockers for acute traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) is associated with a systemic hyperadrenergic state. Through activation of beta adrenoreceptors, catecholamines may induce hypermetabolism and increase both cardiac and cerebral oxygen demands. We conducted a systematic review to appraise the available evidence examining the safety and efficacy of beta blockers in patients with acute TBI. METHODS: We systematically searched CENTRAL, MEDLINE, EMBASE and the reference lists of relevant articles from database inception until March 19, 2013. The outcomes assessed were in-hospital mortality, functional outcome and quality of life. Common adverse effects of beta blockers were examined including clinically significant hypotension, bradycardia, bronchospasm and congestive heart failure. Data on study outcomes and quality were abstracted in duplicate. The results were summarized descriptively and quantitatively. RESULTS: One randomized controlled trial was found with a high risk of bias. Eight retrospective cohort studies were found with a moderate risk of bias; however, only four of these studies were identified as unique after excluding overlapping cases. The cohort studies reported mortality outcomes; however, none of these included studies assessed functional outcomes or quality of life. Meta-analysis on the cohort studies (n = 4,782 patients) demonstrated that exposure to beta blockers after TBI was associated with a reduction in the adjusted odds of in-hospital mortality by 65 % (pooled adjusted odds ratio 0.35; 95 % CI 0.27-0.45). CONCLUSIONS: The current body of evidence is suggestive of a benefit of beta blockers following TBI. However, methodologically sound randomized controlled trials are indicated to confirm the efficacy of beta blockers in patients with TBI.

Safety and efficacy of noninvasive ventilation in patients with blunt chest trauma: a systematic review.

INTRODUCTION: This systematic review looks at the use of noninvasive ventilation (NIV), inclusive of noninvasive positive pressure ventilation (NPPV) and continuous positive pressure ventilation (CPAP), in patients with chest trauma to determine its safety and clinical efficacy in patients with blunt chest trauma who are at high risk of acute lung injury (ALI) and respiratory failure. METHODS: We searched the MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Pairs of reviewers abstracted relevant clinical data and assessed the methodological quality of randomized controlled trials (RCTs) using the Cochrane domain and observational studies using the Newcastle-Ottawa Scale. RESULTS: Nine studies were included (three RCTs, two retrospective cohort studies and four observational studies without a comparison group). There was significant heterogeneity among the included studies regarding the severity of injuries, degree of hypoxemia and timing of enrollment. One RCT of moderate quality assessed the use of NPPV early in the disease process before the development of respiratory distress. All others evaluated the use of NPPV and CPAP in patients with blunt chest trauma after the development of respiratory distress. Overall, up to 18% of patients enrolled in the NIV group needed intubation. The duration of NIV use was highly variable, but NIV use itself was not associated with significant morbidity or mortality. Four low-quality observational studies compared NIV to invasive mechanical ventilation in patients with respiratory distress and showed decreased ICU stay (5.3 to 16 days vs 9.5 to 15 days), complications (0% to 18% vs 38% to 49%) and mortality (0% to 9% vs 6% to 50%) in the NIV group. CONCLUSIONS: Early use of NIV in appropriately identified patients with chest trauma and without respiratory distress may prevent intubation and decrease complications and ICU length of stay. Use of NIV to prevent intubation in patients with chest trauma who have ALI associated with respiratory distress remains controversial because of the lack of good-quality data.

Traumatic brain injury in intoxicated patients.

BACKGROUND: We sought to evaluate the effect alcohol intoxication may have had in nonsurgically treated patients with severe traumatic brain injury. METHODS: The Montreal General Hospital Traumatic Brain Injury Registry was used to identify all adult patients with a Glasgow Coma Scale score < or =8 at admission, within a 15-month period. All charts were retrospectively reviewed. RESULTS: Twenty-three patients had toxic blood alcohol levels (BAL > or =21.7 mmol/L), 24 were alcohol negative (BAL <3 mmol/L), and 10 were alcohol-influenced or had unknown BAL. Patients were more likely to have intracranial pressure monitoring if they had multiple intracranial hemorrhages, sustained multiple injuries, or had a post-resuscitative Glasgow Coma Scale score < or =8. Intoxicated patients had a mean delay of 151 minutes more in the insertion time of an intracranial pressure monitoring device, compared with alcohol-negative patients. CONCLUSIONS: Alcohol was a confounding factor in the treatment of some of our patients.

Understanding Early Decisions to Withdraw Life-Sustaining Therapy in Cardiac Arrest Survivors. A Qualitative Investigation.

RATIONALE: Early withdrawal of life-sustaining therapy contributes to the majority of deaths following out-of-hospital cardiac arrest (OHCA), despite current recommendations for delayed neurological prognostication (≥72 h) after treatment with targeted temperature management. Little is known about clinicians' experiences of early withdrawal of life support decisions in patients with OHCA. OBJECTIVES: To explore clinicians' experiences and perceptions of early withdrawal of life support decisions and barriers to guideline-concordant neurological prognostication in comatose survivors of OHCA treated with targeted temperature management. METHODS: We conducted qualitative interviews with intensive care unit (ICU) physicians and nurses following withdrawal of life support in comatose patients with OHCA treated with targeted temperature management. The study was carried out across 18 academic and community hospitals participating in a multicenter, stepped-wedge, cluster-randomized controlled trial designed to improve quality-of-care processes for patients after OHCA in Ontario, Canada. We used a focused thematic analysis to capture barriers to guideline-concordant neurological prognostication and used these barriers to identify potentially modifiable issues. MEASUREMENTS AND MAIN RESULTS: The core thematic finding was a high emotional burden of ICU family-team communication in which strong feelings inhibited information transfer and delayed decision making following OHCA. Four subthemes describing sources of communication strain were identified: (1) requests from family members to provide early outcome predictions, (2) incomplete family comprehension of critical care, (3) family requests for early withdrawal of life support based on their understanding of patients' preferences and values, and (4) family-team communication gaps related to prognostic uncertainty. Participants worried that gaps in timely and clear prognostic information contributed to surrogates' perceptions of a poor outcome and to inappropriately early decisions to withdraw life support. CONCLUSIONS: Family-team communication difficulties may be an underestimated factor leading to early withdrawal of life support in ICUs for individuals who initially survive OHCA.

Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest.

BACKGROUND: Withdrawing life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of hospital death after out-of-hospital cardiac arrest (OHCA). Although current guidelines recommend against WLST-N before 72h (WLST-N<72), this practice is common and may increase mortality. We sought to quantify these effects. METHODS: In a secondary analysis of a multicenter OHCA trial, we evaluated survival to hospital discharge and survival with favorable functional status (modified Rankin Score ≤3) in adults alive >1h after hospital admission. Propensity score modeling the probability of exposure to WLST-N<72 based on pre-exposure covariates was used to match unexposed subjects with those exposed to WLST-N<72. We determined the probability of survival and functionally favorable survival in the unexposed matched cohort, fit adjusted logistic regression models to predict outcomes in this group, and then used these models to predict outcomes in the exposed cohort. Combining these findings with current epidemiologic statistics we estimated mortality nationally that is associated with WLST-N<72. RESULTS: Of 16,875 OHCA subjects, 4265 (25%) met inclusion criteria. WLST-N<72 occurred in one-third of subjects who died in-hospital. Adjusted analyses predicted that exposed subjects would have 26% survival and 16% functionally favorable survival if WLST-N<72 did not occur. Extrapolated nationally, WLST-N<72 may be associated with mortality in approximately 2300 Americans each year of whom nearly 1500 (64%) might have had functional recovery. CONCLUSIONS: After OHCA, death following WLST-N<72 may be common and is potentially avoidable. Reducing WLST-N<72 has national public health implications and may afford an opportunity to decrease mortality after OHCA.

Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: a pilot trial.

BACKGROUND: Probiotics are live microorganisms that may confer health benefits when ingested. Randomized trials suggest that probiotics significantly decrease the incidence of ventilator-associated pneumonia (VAP) and the overall incidence of infection in critically ill patients. However, these studies are small, largely single-center, and at risk of bias. The aim of the PROSPECT pilot trial was to determine the feasibility of conducting a larger trial of probiotics to prevent VAP in mechanically ventilated patients in the intensive care unit (ICU). METHODS: In a randomized blinded trial, patients expected to be mechanically ventilated for ≥72 hours were allocated to receive either 1 × 10(10) colony-forming units of Lactobacillus rhamnosus GG or placebo, twice daily. Patients were excluded if they were at increased risk of L. rhamnosus GG infection or had contraindications to enteral medication. Feasibility objectives were: (1) timely recruitment; (2) maximal protocol adherence; (3) minimal contamination; and (4) estimated VAP rate ≥10 %. We also measured other infections, diarrhea, ICU and hospital length of stay, and mortality. RESULTS: Overall, in 14 centers in Canada and the USA, all feasibility goals were met: (1) 150 patients were randomized in 1 year; (2) protocol adherence was 97 %; (3) no patients received open-label probiotics; and (4) the VAP rate was 19 %. Other infections included: bloodstream infection (19.3 %), urinary tract infections (12.7 %), and skin and soft tissue infections (4.0 %). Diarrhea, defined as Bristol type 6 or 7 stools, occurred in 133 (88.7 %) of patients, the median length of stay in ICU was 12 days (quartile 1 to quartile 3, 7-18 days), and in hospital was 26 days (quartile 1 to quartile 3, 14-44 days); 23 patients (15.3 %) died in the ICU. CONCLUSIONS: The PROSPECT pilot trial supports the feasibility of a larger trial to investigate the effect of L. rhamnosus GG on VAP and other nosocomial infections in critically ill patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT01782755 . Registered on 29 January 2013.

Prophylactic magnesium for improving neurologic outcome after aneurysmal subarachnoid hemorrhage: systematic review and meta-analysis.

PURPOSE: Neurologic disability is common after aneurysmal subarachnoid hemorrhage (aSAH). Our objective was to systematically review the prophylactic use of magnesium to improve neurologic outcomes in these patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials to June 2012 for randomized and quasi-randomized controlled trials of intravenous magnesium in adults after aSAH, given before radiologic vasospasm or delayed cerebral ischemia (DCI) and compared with any control group. Two reviewers independently extracted data on study population, interventions, and outcomes (good neurologic outcome [primary outcome], cerebral infarction, DCI, radiographic vasospasm, mortality, adverse events). Analyses used random-effects models. RESULTS: Of 702 citations, 13 trials (n = 2401) met the selection criteria. Meta-analyses showed that magnesium did not increase the probability of good neurologic outcome (risk ratio [RR], 1.02; 95% confidence interval [CI], 0.97-1.07; P = .49; 12 trials, n = 2345) or decrease the risks of cerebral infarction (RR, 0.69; 95% CI, 0.46-1.05; P = .08; 5 trials, n = 572), radiographic vasospasm (RR, 0.86; 95% CI, 0.71-1.04; P = .13; 7 trials, n = 438), or mortality (RR, 0.98; 95% CI, 0.80-1.20; P = .86; 11 trials, n = 2092). Magnesium did reduce the risk of DCI (RR, 0.73; 95% CI, 0.56-0.96; P = .02; 10 trials, n = 1095). Data on adverse events were generally sparse. CONCLUSIONS: Despite decreasing the incidence of DCI in patients with aSAH, prophylactic intravenous magnesium does not improve neurologic outcome or decrease cerebral infarction, radiographic vasospasm, or mortality.