Outcomes and Long-Term Survival of Adolescent and Young Adult Patients Admitted to the Intensive Care Unit Following Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Experience of 152 Patients.

BACKGROUND AND OBJECTIVES: Prognostic factors reliably predicting outcomes for critically ill adolescent and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (allo-HSCT) are lacking. We assessed transplant and intensive care unit (ICU)-related factors impacting patient outcomes. PATIENTS AND METHODS: AYA patients who underwent allo-HSCT and required ICU admission at a Tertiary care Centre, during the period of 2003-2013, were included in this retrospective review. This was a non-interventional study. Only outcomes after the first allo-HSCT and index ICU admissions were analyzed. Disease-, transplant-, and ICU-related variables were analyzed to identify risk factors predictive of survival. RESULTS: Overall, 152 patients were included (males, 60.5%); median age at transplantation was 24 years (interquartile range [IQR] 18-32.5); median age at admission to the ICU was 25.8 years (IQR 19-34). Eighty-four percent underwent transplantation for a hematological malignancy; 129 (85%) received myeloablative conditioning. Seventy-one percent of ICU admissions occurred within the first year after allo-HSCT. ICU admission was primarily due to respiratory failure (47.3%) and sepsis (43.4%). One hundred and three patients (68%) died within 28 days of ICU admission. The 1- and 5-year overall survival rates were 19% and 17%, respectively. Main causes for ICU-related death were refractory septic shock with multiorgan failure (n = 49, 32%) and acute respiratory distress syndrome (ARDS) (n = 39, 26%). Univariate analysis showed that ICU mortality was associated with an Acute Physiology and Chronic Health Evaluation (APACHE) II score >20, a sequential organ failure assessment (SOFA score) > 12, a high lactate level, anemia, thrombocytopenia, leukopenia, hyperbilirubinemia, a high international normalized ratio (INR) and acute graft-versus-host disease (GVHD). Multivariate analysis identified thrombocytopenia, high INR, and acute GVHD as independent predictors of mortality. CONCLUSIONS: In AYA allo-HSCT patients admitted to the ICU, mortality remains high. Higher SOFA and APACHE scores, the need for organ support, thrombocytopenia, coagulopathy, and acute GVHD predict poor outcomes.

Assessing the readiness of hospitals in Riyadh Province for efficient and timely stroke management: A pilot study.

OBJECTIVES: To assess the readiness of hospitals in Riyadh to establish acute stroke centers by following the Australian Clinical Guidelines for Stroke Management. METHODS: This study was a quantitative cross-sectional observational study conducted among hospitals in the central region of Saudi Arabia (Jan 2018 - April 2018). A self-administered questionnaire/survey tool was adapted from an Australian survey developed by the Stroke Foundation in Melbourne, Australia.The data were analyzed using SPSS version 21.0. Appropriate statistical tests (chi-square and Fisher's exact test) were used for bivariate analyses. RESULTS: A total of 3932 stroke patient visits were recorded in 37 hospitals in the central region of Saudi Arabia. The most common limitations of acute stroke services were that 25 (67.57%) of the hospitals had no stroke unit and 21 (56.76%) had inadequate clinical staff. Magnetic resonance imaging and computed tomography were available in 32 (86.49%) and 36 (97.30%) hospitals, respectively. Only two-thirds of hospitals 25 (67.57%) followed protocols for rapid Emergency Department (ED) triage. CONCLUSION: We found that most of our hospitals were not fully prepared to address acute stroke management in a manner that was reasonably consistent with international guidelines. We recommend raising the hospital's requirements a higher level to be in line with the stroke guidelines.

Critically ill patients with diabetes and Middle East respiratory syndrome: a multi-center observational study.

BACKGROUND: Diabetes is a risk factor for infection with coronaviruses. This study describes the demographic, clinical data, and outcomes of critically ill patients with diabetes and Middle East Respiratory Syndrome (MERS). METHODS: This retrospective cohort study was conducted at 14 hospitals in Saudi Arabia (September 2012-January 2018). We compared the demographic characteristics, underlying medical conditions, presenting symptoms and signs, management and clinical course, and outcomes of critically ill patients with MERS who had diabetes compared to those with no diabetes. Multivariable logistic regression analysis was performed to determine if diabetes was an independent predictor of 90-day mortality. RESULTS: Of the 350 critically ill patients with MERS, 171 (48.9%) had diabetes. Patients with diabetes were more likely to be older, and have comorbid conditions, compared to patients with no diabetes. They were more likely to present with respiratory failure requiring intubation, vasopressors, and corticosteroids. The median time to clearance of MERS-CoV RNA was similar (23 days (Q1, Q3: 17, 36) in patients with diabetes and 21.0 days (Q1, Q3: 10, 33) in patients with no diabetes). Mortality at 90 days was higher in patients with diabetes (78.9% versus 54.7%, p < 0.0001). Multivariable regression analysis showed that diabetes was an independent risk factor for 90-day mortality (odds ratio, 2.09; 95% confidence interval, 1.18-3.72). CONCLUSIONS: Half of the critically ill patients with MERS have diabetes; which is associated with more severe disease. Diabetes is an independent predictor of mortality among critically patients with MERS.

Ribavirin and Interferon Therapy for Critically Ill Patients With Middle East Respiratory Syndrome: A Multicenter Observational Study.

BACKGROUND: The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. METHODS: This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. RESULTS: Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a; none received rIFN-ß1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73-1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30-1.44]; P = .29). CONCLUSIONS: In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-ß1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome.

BACKGROUND: Noninvasive ventilation (NIV) has been used in patients with the Middle East respiratory syndrome (MERS) with acute hypoxemic respiratory failure, but the effectiveness of this approach has not been studied. METHODS: Patients with MERS from 14 Saudi Arabian centers were included in this analysis. Patients who were initially managed with NIV were compared to patients who were managed only with invasive mechanical ventilation (invasive MV). RESULTS: Of 302 MERS critically ill patients, NIV was used initially in 105 (35%) patients, whereas 197 (65%) patients were only managed with invasive MV. Patients who were managed with NIV initially had lower baseline SOFA score and less extensive infiltrates on chest radiograph compared with patients managed with invasive MV. The vast majority (92.4%) of patients who were managed initially with NIV required intubation and invasive mechanical ventilation, and were more likely to require inhaled nitric oxide compared to those who were managed initially with invasive MV. ICU and hospital length of stay were similar between NIV patients and invasive MV patients. The use of NIV was not independently associated with 90-day mortality (propensity score-adjusted odds ratio 0.61, 95% CI [0.23, 1.60] P = 0.27). CONCLUSIONS: In patients with MERS and acute hypoxemic respiratory failure, NIV failure was very high. The use of NIV was not associated with improved outcomes.

Macrolides in critically ill patients with Middle East Respiratory Syndrome.

OBJECTIVES: Macrolides have been reported to be associated with improved outcomes in patients with viral pneumonia related to influenza and other viruses, possibly because of their immune-modulatory effects. Macrolides have frequently been used in patients with Middle East Respiratory Syndrome (MERS). This study investigated the association of macrolides with 90-day mortality and MERS coronavirus (CoV) RNA clearance in critically ill patients with MERS. METHODS: This retrospective analysis of a multicenter cohort database included 14 tertiary-care hospitals in five cities in Saudi Arabia. Multivariate logistic-regression analysis was used to determine the association of macrolide therapy with 90-day mortality, and the Cox-proportional hazard model to determine the association of macrolide therapy with MERS-CoV RNA clearance. RESULTS: Of 349 critically ill MERS patients, 136 (39%) received macrolide therapy. Azithromycin was most commonly used (97/136; 71.3%). Macrolide therapy was commonly started before the patient arrived in the intensive care unit (ICU) (51/136; 37.5%), or on day1 in ICU (53/136; 39%). On admission to ICU, the baseline characteristics of patients who received and did not receive macrolides were similar, including demographic data and sequential organ failure assessment score. However, patients who received macrolides were more likely to be admitted with community-acquired MERS (P=0.02). Macrolide therapy was not independently associated with a significant difference in 90-day mortality (adjusted odds ratio [OR]: 0.84; 95% confidence interval [CI] :0.47-1.51; P=0.56) or MERS-CoV RNA clearance (adjusted HR: 0.88; 95% CI:0.47-1.64; P=0.68). CONCLUSIONS: These findings indicate that macrolide therapy is not associated with a reduction in 90-day mortality or improvement in MERS-CoV RNA clearance.

Caloric intake and the fat-to-carbohydrate ratio in hypercapnic acute respiratory failure: Post-hoc analysis of the PermiT trial.

BACKGROUND: The effect of moderate caloric enteral intake in critically ill patients with hypercapnic acute respiratory failure (HCARF) is unclear. We studied the impact of permissive underfeeding (PUF) compared with standard feeding (SF) on various HCARF outcomes. MATERIALS AND METHODS: The PermiT trial randomized 894 patients to either PUF (40-60% caloric requirement) or SF (70-100% requirement) with similar protein intake and found no difference in mortality, mechanical ventilation (MV) duration and ventilator-free days. In this post-hoc study, we restricted analysis to mechanically-ventilated patients with HCARF (PaCO2 >45 mmHg on the first two study days) and assessed the impact of trial interventions and fat-to-carbohydrate ratio on outcomes. RESULTS: One-hundred-twenty patients had HCARF (59 PUF and 61 SF, age 53.7 ± 17.8 years, body mass index 31.1 ± 11.2 kg/m2, Acute Physiology and Chronic Health Evaluation II score 21.7 ± 7.1 and day-1 PaCO2 61 ± 16 mmHg). Caloric intake was 815 ± 270 kcal/day in PUF group and 1289 ± 407 kcal/day in SF group. The two groups had similar PaCO2 levels during ICU stay. The 90-day mortality (33.9% versus 35.6%, p = 0.85), MV duration (10.7 ± 6.8 versus 11.1 ± 8.1 days, p = 0.56) and ventilator-free days (52.9 ± 38.6 versus 51.2 ± 38.0 days, p = 0.80) were also similar in PUF and SF groups, respectively. Ventilator-free days and 90-day mortality were similar when the fat-to-carbohydrate ratio was < or ≥ the median value (0.73) in all patients and in PUF and SF groups. CONCLUSIONS: In patients with HCARF, SF and PUF were associated with similar PaCO2, MV duration, ventilator-free days and mortality. Fat-to-carbohydrate ratio was not associated with mortality or ventilator-free days. TRIAL REGISTRATION: ISRCTN Registry: ISRCTN68144998.

Critically ill healthcare workers with the middle east respiratory syndrome (MERS): A multicenter study.

BACKGROUND: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) leads to healthcare-associated transmission to patients and healthcare workers with potentially fatal outcomes. AIM: We aimed to describe the clinical course and functional outcomes of critically ill healthcare workers (HCWs) with MERS. METHODS: Data on HCWs was extracted from a multi-center retrospective cohort study on 330 critically ill patients with MERS admitted between (9/2012-9/2015). Baseline demographics, interventions and outcomes were recorded and compared between survivors and non-survivors. Survivors were approached with questionnaires to elucidate their functional outcomes using Karnofsky Performance Status Scale. FINDINGS: Thirty-Two HCWs met the inclusion criteria. Comorbidities were recorded in 34% (11/32) HCW. Death resulted in 8/32 (25%) HCWs including all 5 HCWs with chronic renal impairment at baseline. Non-surviving HCW had lower PaO2/FiO2 ratios 63.5 (57, 116.2) vs 148 (84, 194.3), p = 0.043, and received more ECMO therapy compared to survivors, 9/32 (28%) vs 4/24 (16.7%) respectively (p = 0.02).Thirteen of the surviving (13/24) HCWs responded to the questionnaire. Two HCWs confirmed functional limitations. Median number of days from hospital discharge until the questionnaires were filled was 580 (95% CI 568, 723.5) days. CONCLUSION: Approximately 10% of critically ill patients with MERS were HCWs. Hospital mortality rate was substantial (25%). Patients with chronic renal impairment represented a particularly high-risk group that should receive extra caution during suspected or confirmed MERS cases clinical care assignment and during outbreaks. Long-term repercussions of critical illness due to MERS on HCWs in particular, and patients in general, remain unknown and should be investigated in larger studies.

Corticosteroid Therapy for Critically Ill Patients with Middle East Respiratory Syndrome.

RATIONALE: Corticosteroid therapy is commonly used among critically ill patients with Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients' clinical condition at the time of corticosteroid therapy initiation. OBJECTIVES: To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. METHODS: ICU patients with MERs were included from 14 Saudi Arabian centers between September 2012 and October 2015. We performed marginal structural modeling to account for baseline and time-varying confounders. MEASUREMENTS AND MAIN RESULTS: Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (quartile 1 [Q1]-Q3, 1.0-7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141 of 151 [93.4%] vs. 121 of 158 [76.6%]; P < 0.0001) and had higher 90-day crude mortality (112 of 151 [74.2%] vs. 91 of 158 [57.6%]; P = 0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio, 0.75; 95% confidence interval, 0.52-1.07; P = 0.12) but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio, 0.35; 95% CI, 0.17-0.72; P = 0.005). CONCLUSIONS: Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

Critically Ill Patients With the Middle East Respiratory Syndrome: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 14 Saudi Arabian hospitals. PATIENTS: Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n = 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non-Middle East respiratory syndrome etiology (non-Middle East respiratory syndrome severe acute respiratory infection) (n = 222). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non-Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78]; p < 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252]; p < 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7]; p = 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%; p < 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%; p = 0.003), vasopressor support (79.4% vs 55.0%; p < 0.001), and renal replacement therapy (48.8% vs 22.1%; p < 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non-Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02-8.56; p < 0.001). CONCLUSIONS: Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

Permissive Underfeeding or Standard Enteral Feeding in High- and Low-Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial.

RATIONALE: The optimal nutritional strategy for critically ill adults at high nutritional risk is unclear. OBJECTIVES: To examine the effect of permissive underfeeding with full protein intake compared with standard feeding on 90-day mortality in patients with different baseline nutritional risk. METHODS: This is a post hoc analysis of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients) trial. MEASUREMENTS AND MAIN RESULTS: Nutritional risk was categorized by the modified Nutrition Risk in Critically Ill score, with high nutritional risk defined as a score of 5-9 and low nutritional risk as a score of 0-4. Additional analyses were performed by categorizing patients by body mass index, prealbumin, transferrin, phosphate, urinary urea nitrogen, and nitrogen balance. Based on the Nutrition Risk in Critically Ill score, 378 of 894 (42.3%) patients were categorized as high nutritional risk and 516 of 894 (57.7%) as low nutritional risk. There was no association between feeding strategy and mortality in the two categories; adjusted odds ratio (aOR) of 0.84 (95% confidence interval [CI], 0.56-1.27) for high nutritional risk and 1.01 (95% CI, 0.64-1.61) for low nutritional risk (interaction P = 0.53). Findings were similar in analyses using other definitions, with the exception of prealbumin. The association of permissive underfeeding versus standard feeding and 90-day mortality differed when patients were categorized by baseline prealbumin level (≤0.10 g/L: aOR, 0.57 [95% CI, 0.31-1.05]; >0.10 and ≤0.15 g/L: aOR, 0.79 [95% CI, 0.42-1.48]; >0.15 g/L: aOR, 1.55 [95% CI, 0.80, 3.01]; interaction P = 0.009). CONCLUSIONS: Among patients with high and low nutritional risk, permissive underfeeding with full protein intake was associated with similar outcomes as standard feeding.

The incidence of increased ICP in ICU patients with non-traumatic coma as diagnosed by ONSD and CT: a prospective cohort study.

BACKGROUND: Unexplained coma after critical illness can be multifactorial. We evaluated the diagnostic ability of bedside Optic Nerve Sheath Diameter [ONSD] as a screening test for non-traumatic radiographic cerebral edema. METHODS: In a prospective study, mixed medical-surgical intensive care units [ICU] patients with non-traumatic coma [GCS < 9] underwent bedside ultrasonographic ONSD measurements. Non-traumatic radiographic cerebral edema [NTRCE] was defined as > 5 mm midline shift, cisternal, sulcal effacement, or hydrocephalus on CT. RESULTS: NTRCE was identified in 31 of 102 patients [30.4 %]. The area under the ROC curve for detecting radiographic edema by ONSD was 0.785 [95 % CI 0.695-0.874, p <0.001]. ONSD diameter of 0.57 cm was found to be the best cutoff threshold with a sensitivity 84 % and specificity 71 %, AUC 0.785 [95 % CI 0.695-0.874, p <0.001]. Using ONSD as a bedside test increased the post-test odds ratio [OR] for NTRCE by 2.89 times [positive likelihood ratio], whereas post-test OR for NTRCE decreased markedly given a negative ONSD test [ONSD measurement less than 0.57 cm]; negative likelihood ratio 0.22. CONCLUSIONS: The use of ONSD as a bedside test in patients with non-traumatic coma has diagnostic value in identifying patients with non-traumatic radiographic cerebral edema.

Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults.

BACKGROUND: The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among critically ill adults, with maintenance of the full recommended amount of protein in both groups. METHODS: At seven centers, we randomly assigned 894 critically ill adults with a medical, surgical, or trauma admission category to permissive underfeeding (40 to 60% of calculated caloric requirements) or standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups. The primary outcome was 90-day mortality. RESULTS: Baseline characteristics were similar in the two groups; 96.8% of the patients were receiving mechanical ventilation. During the intervention period, the permissive-underfeeding group received fewer mean (±SD) calories than did the standard-feeding group (835±297 kcal per day vs. 1299±467 kcal per day, P<0.001; 46±14% vs. 71±22% of caloric requirements, P<0.001). Protein intake was similar in the two groups (57±24 g per day and 59±25 g per day, respectively; P=0.29). The 90-day mortality was similar: 121 of 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440 patients (28.9%) in the standard-feeding group died (relative risk with permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16; P=0.58). No serious adverse events were reported; there were no significant between-group differences with respect to feeding intolerance, diarrhea, infections acquired in the intensive care unit (ICU), or ICU or hospital length of stay. CONCLUSIONS: Enteral feeding to deliver a moderate amount of nonprotein calories to critically ill adults was not associated with lower mortality than that associated with planned delivery of a full amount of nonprotein calories. (Funded by the King Abdullah International Medical Research Center; PermiT Current Controlled Trials number, ISRCTN68144998.).

Hypocapnia in aneurysmal subarachnoid hemorrhage: incidence and association with poor clinical outcomes.

BACKGROUND: The impact of hypocapnia on outcome in aneurysmal subarachnoid hemorrhage (SAH) is unclear, although hypocapnia is associated with poor outcome in other brain injuries. We sought to determine the incidence and impact of hypocapnia in mechanically ventilated patients with aneurysmal SAH. METHODS: We assembled a retrospective cohort of 102 consecutive mechanically ventilated patients with aneurysmal SAH admitted to an academic neurosurgical intensive care unit (ICU). Ventilation records, arterial blood gas data, and clinical outcomes were reviewed. The primary outcome was 3-month Glasgow Outcome Scale, with secondary outcomes of ICU and hospital mortality and symptomatic vasospasm. RESULTS: Hypocapnia was common (92% of patients had 1 or more PaCO2 measurements <35 mm Hg), with 68% of these measurements occurring while breathing spontaneously with minimal ventilator support. Median duration of hypocapnia was 4 days (interquartile range, 2 to 12). Forty-eight percent of all PaCO2 measurements on a given day were below 30 mm Hg. Unfavorable outcome (Glasgow Outcome Scale <4) occurred in 52 of 89 patients (58.4%). ICU and hospital mortality was 26.5% and 32.4%, respectively, and 34% developed symptomatic vasospasm. Duration of hypocapnia was associated with unfavorable outcome (adjusted odds ratio 1.33 for each additional day of hypocapnia) and symptomatic vasospasm (adjusted odds ratio 1.25 for each additional day of hypocapnia), but not ICU or hospital mortality. These associations appeared robust in sensitivity analyses to address potential misclassification and ascertainment bias. CONCLUSIONS: Hypocapnia is common in ventilated patients with aneurysmal SAH, and a significant proportion of this developed spontaneously despite minimal ventilator support. The duration of hypocapnia is independently associated with poor functional outcomes and symptomatic vasospasm. Further study is warranted to confirm a causal link between hypocapnia and poor outcomes, and to confirm whether tight control of PaCO2 might improve outcomes in aneurysmal SAH.

Permissive underfeeding versus target enteral feeding in adult critically ill patients (PermiT Trial): a study protocol of a multicenter randomized controlled trial.

BACKGROUND: Nutritional support is an essential part of the management of critically ill patients. However, optimal caloric intake has not been systematically evaluated. We aim to compare two strategies of enteral feeding: permissive underfeeding versus target feeding. METHOD/DESIGN: This is an international multi-center randomized controlled trial in critically ill medical- surgical adult patients. Using a centralized allocation, 862 patients will be randomized to permissive underfeeding or target feeding. Patients in the permissive group receive 50% (acceptable range is 40% to 60%) of the calculated caloric requirement, while those in the targeted group receive 100% (acceptable range 70% to 100%) of the calculated caloric requirement. The primary outcome is 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, 28-day, and 180-day mortality as well as health care-associated infections, organ failure, and length of stay in the ICU and hospital. The trial has 80% power to detect an 8% absolute reduction in 90-day mortality assuming a baseline risk of death of 25% at an alpha level of 0.05. DISCUSSION: Patient recruitment started in November 2009 and is currently active in five centers. The Data Monitoring Committee advised continuation of the trial after the first interim analysis. The study is expected to finish by November 2013. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68144998.