Inflammatory Response and Phenotyping in Severe Acute Respiratory Infection From the Middle East Respiratory Syndrome Coronavirus and Other Etiologies.

OBJECTIVES: In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. DESIGN: Prospective cohort study. SETTING: A tertiary care ICU in Riyadh, Saudi Arabia. PATIENTS: Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1ß, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1ß, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). CONCLUSIONS: One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

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.

Preferences for the measurement and supplementation of magnesium, phosphate and zinc in ICUs: The international WhyTrace survey.

BACKGROUND: Patients admitted to the Intensive Care Unit (ICU) often have low magnesium, phosphate and zinc levels. Monitoring of serum concentrations and supplementation may be important, but there is no consensus on optimal practice. The objective of the WhyTrace survey was to describe current practice regarding the measurement and supplementation of magnesium, phosphate and zinc in ICUs. METHODS: A 54-item electronic questionnaire was developed in accordance with SURGE, SUrvey Reporting GuidelinE, to address international clinical practice in the ICU. National investigators recruited ICUs in ten countries with one physician responding per ICU using a unique e-mail distributed survey-link. RESULTS: The questionnaire was sent to clinicians in 336 ICUs of whom 283 (84%) responded. In 62% of the ICUs, a standard procedure was in place regarding the measurement of serum magnesium levels, in 58% for phosphate and in 9% for zinc. Zinc was never or rarely measured in 64% of ICUs. The frequency of requesting serum levels varied from twice daily to once weekly. Regarding supplementation, 66% of ICUs had a standard procedure for magnesium, 63% for phosphate and 15% for zinc. Most procedures recommended supplementation when serum levels were below the lower reference level, but some used the upper reference levels as the threshold for supplementation and others decided on a case-by-case basis. CONCLUSION: The practice of measuring and supplementing magnesium, phosphate and zinc differed substantially between ICUs. Our findings indicate that there is a need for high-quality prospective data on frequencies of measurements, treatment goals and effects of supplementation on patient-important outcomes.

Protein intake and outcome in critically ill patients.

PURPOSE OF REVIEW: The objective of this review is to describe the impact of protein intake on the outcomes of critically ill patients in the literature published in the preceding 2 years. RECENT FINDINGS: Observational studies showed inconsistent results regarding the association of higher protein intake and outcomes of critically ill patients. Randomized controlled trials that directly compared higher versus lower protein intake in ICU patients are scarce, varied considerably in their designs and primary outcomes, and generally had relatively small differences in the amount of delivered protein between the study arms. Systematic reviews of existing studies showed no difference in mortality with higher protein intake. In addition, there is uncertainty regarding high protein provision in the early phase of critical illness. SUMMARY: The optimal amount of protein intake in critically ill patients remains largely unclear and is considered a high priority for research. Ongoing clinical trials are likely to provide additional evidence on several important questions including the dose, timing, type of protein and the interaction with caloric intake and exercise.

Serum Lactate as an Independent Predictor of In-Hospital Mortality in Intensive Care Patients.

PURPOSE: The aim of this study was to check if serum lactate was independently associated with mortality among critically ill patients. MATERIALS AND METHODS: This was a single-center, retrospective cohort study. All adult patients (>18 years of age) who had at least 1 measurement of lactate within 24 hours of admission to intensive care unit (ICU) between January 2002 and December 2017 were included in the analysis. Patients were stratified into 3 groups: those with a serum lactate of <2 mmol/L (normal level), 2 to 4 mmol/L (intermediate level), and >4 mmol/L (high level). The primary outcome was in-hospital mortality. Secondary outcomes included ICU and hospital lengths of stay and mechanical ventilation duration. To determine the association between lactate level and hospital mortality, bivariate and multivariate logistic regression analyses were performed. RESULTS: Of the 16,447 patients admitted to the ICU, 8167 (49.65%) had normal levels, 4648 (28.26%) had an intermediate, and 3632 (22.09%) had high lactate levels. Hospital mortality was the highest in high lactate level, followed by the intermediate and the normal level group (47.4% vs 26.5% vs 19.6%; P < .0001). Intermediate and high lactate levels were independent predictors of hospital mortality (odds ratio [OR], 1.32; 95% confidence interval [CI]: 1.20-1.46, and 1.94; 95% CI, 1.75-2.16, respectively) as well as ICU mortality (OR, 1.47; 95% CI, 1.30-1.66 and 2.56; 95% CI, 2.27-2.88, respectively). CONCLUSIONS: Intensive care unit serum lactate is associated with increased ICU and hospital mortality, independent of comorbidities, organ dysfunction, or hemodynamic status.

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.).

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.

Association between troponin-I levels and outcome in critically ill patients admitted to non-cardiac intensive care unit with high prevalence of cardiovascular risk factors.

BACKGROUND: The association of troponin-I levels and outcome in medical-surgical ICU patients has been studied before in populations with low to moderate prevalence of cardiovascular risk factors. The objective in this article is to examine the association of troponin-I levels with hospital mortality in patients with high prevalence of cardiovascular risk factors who were admitted with medical-surgical indications to a non-cardiac intensive care unit. METHODS: This was a retrospective study of adult patients admitted to a tertiary medical-surgical ICU between July 2001 and November 2011. Data were extracted from prospectively collected ICU and clinical laboratory databases. Patients were stratified based on the highest troponin-I level in the first 72 h of admission into four groups (Group I < 0.03, Group II = 0.03-0.3, Group III = 0.3-3 and Group IV > 3 ng/mL). Hospital mortality was the primary outcome. To study the association between elevated troponin-I and hospital mortality, we carried out multivariate logistic regression analyses with Group I as a reference group. RESULTS: During the study period, 3368 patients had troponin-I levels measured in the first 72 h, of whom 1293 (38.3%) were diabetic and 1356 (40.2%) were chronically hypertensive. Among the study population, 2719 (81%) had elevated troponin-I levels (0.03 ng/mL and higher). Hospital mortality increased steadily as the troponin-I levels increased. Hospital mortality was 23.4% for Group I, 33.2% for Group II (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 0.84, 1.38), 49.6% for Group III (aOR = 1.64, 95% CI 1.24, 2.17), and 57.4% for Group IV (aOR 1.80, 95% CI 1.30, 2.49). The association of increased mortality with increased troponin level was observed whether patients had underlying advanced heart failure or not. Subgroup analysis showed an increased mortality in patients aged < 50 years, non-diabetics and not on vasopressors. CONCLUSION: In a population with high prevalence of diabetes and hypertension, elevated troponin-I was frequently observed in medical-surgical critically ill patients, and showed a level-dependent association with hospital mortality.

Management and outcomes of patients presenting with sepsis and septic shock to the emergency department during nursing handover: a retrospective cohort study.

BACKGROUND: Clinical handover is an important process for the transition of patient-care responsibility to the next healthcare provider, but it may divert the attention of the team away from active patients. This is challenging in the Emergency Department (ED) because of highly dynamic patient conditions and is likely relevant in conditions that requires time-sensitive therapies, such as sepsis. We aimed to examine the management and outcomes of patients presenting with sepsis and septic shock to the ED during nursing handover. METHODS: This retrospective cohort study was conducted at a 115-bed ED and more than 200,000 annual ED visits, within a 900-bed academic tertiary care center. Data on Surviving Sepsis Campaign (SSC) bundle elements and hospital mortality were collected for all ≥14-year-old patients who presented to the ED with a diagnosis of sepsis and septic shock between January 1, 2011 and October 30, 2013. Our primary outcome was time to antibiotics, were other SSC bundle elements and mortality counted as secondary outcomes. Patients were divided into two groups: 1) handover time group, comprising patients who presented an hour before or after the start of handover time (6-8 AM/PM), and 2) non-handover time group, comprising patients who presented over the remaining 20 h. RESULTS: During the study period, 1330 patients presented with sepsis or septic shock (228, handover time group; 1102, non-handover time group). No significant differences were found between the handover time and non-handover time groups, respectively, in median time to antibiotic administration (100 [interquartile range (IQR) 57-172] vs. 95 [IQR 50-190] minutes; P = 0.07), median time to serum lactate result (162 [IQR 108-246] vs. 156 [IQR 180-246] minutes; P = 0.33) and median time to obtain blood culture (54 [IQR 36-119] vs. 52 [IQR 28-103] minutes; P = 0.52), and hospital mortality rate (29.4% vs. 28.9%; P = 0.89). CONCLUSION: No significant differences were found in median time of SSC bundle elements or hospital mortality between patients who presented during the handover and non-handover times.

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.

Feasibility of Using Convalescent Plasma Immunotherapy for MERS-CoV Infection, Saudi Arabia.

We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

Structure, Organization, and Delivery of Critical Care in Asian ICUs.

OBJECTIVES: Despite being the epicenter of recent pandemics, little is known about critical care in Asia. Our objective was to describe the structure, organization, and delivery in Asian ICUs. DESIGN: A web-based survey with the following domains: hospital organizational characteristics, ICU organizational characteristics, staffing, procedures and therapies available in the ICU and written protocols and policies. SETTING: ICUs from 20 Asian countries from April 2013 to January 2014. Countries were divided into low-, middle-, and high-income based on the 2011 World Bank Classification. SUBJECTS: ICU directors or representatives. MEASUREMENTS AND MAIN RESULTS: Of 672 representatives, 335 (50%) responded. The average number of hospital beds was 973 (SE of the mean [SEM], 271) with 9% (SEM, 3%) being ICU beds. In the index ICUs, the average number of beds was 21 (SEM, 3), of single rooms 8 (SEM, 2), of negative-pressure rooms 3 (SEM, 1), and of board-certified intensivists 7 (SEM, 3). Most ICUs (65%) functioned as closed units. The nurse-to-patient ratio was 1:1 or 1:2 in most ICUs (84%). On multivariable analysis, single rooms were less likely in low-income countries (p = 0.01) and nonreferral hospitals (p = 0.01); negative-pressure rooms were less likely in private hospitals (p = 0.03) and low-income countries (p = 0.005); 1:1 nurse-to-patient ratio was lower in private hospitals (p = 0.005); board-certified intensivists were less common in low-income countries (p < 0.0001) and closed ICUs were less likely in private (p = 0.02) and smaller hospitals (p < 0.001). CONCLUSIONS: This survey highlights considerable variation in critical care structure, organization, and delivery in Asia, which was related to hospital funding source and size, and country income. The lack of single and negative-pressure rooms in many Asian ICUs should be addressed before any future pandemic of severe respiratory illness.

Prevalence and predictors of out-of-range cuff pressure of endotracheal and tracheostomy tubes: a prospective cohort study in mechanically ventilated patients.

BACKGROUND: Maintaining the cuff pressure of endotracheal tubes (ETTs) within 20-30 cmH2O is a standard practice. The aim of the study was to evaluate the effectiveness of standard practice in maintaining cuff pressure within the target range. METHODS: This was a prospective observational study conducted in a tertiary-care intensive care unit, in which respiratory therapists (RTs) measured the cuff pressure 6 hourly by a handheld manometer. In this study, a research RT checked cuff pressure 2-4 h after the clinical RT measurement. Percentages of patients with cuff pressure levels above and below the target range were calculated. We identified predictors of low-cuff pressure. RESULTS: We analyzed 2120 cuff-pressure measurements. The mean cuff pressure was 27 ± 2 cmH2O by the clinical RT and 21 ± 5 cmH2O by the research RT (p < 0.0001). The clinical RT documented that 98.0 % of cuff pressures were within the normal range. The research RT found the cuff pressures to be within the normal range in only 41.5 %, below the range in 53 % and above the range in 5.5 %. Low cuff pressure was found more common with lower ETT size (OR, 0.34 per 0.5 unit increase in ETT size; 95 % CI, 0.15-0.79) and with lower peak airway pressure (OR per one cm H2O increment, 0.93; 95 % CI, 0.87-0.99) on multivariate analysis. CONCLUSIONS: Cuff pressure is frequently not maintained within the target range with low-cuff pressure being very common approximately 3 h after routine measurements. Low cuff pressure was associated with lower ETT size and lower peak airway pressure. There is a need to redesign the process for maintaining cuff pressure within the target range.

The prevalence of acute kidney injury in patients with community-acquired pneumonia who required mechanical ventilation.

BACKGROUND: Community-acquired pneumonia (CAP) is a common reason for intensive care unit (ICU) admission and sepsis. Acute kidney injury (AKI) is a frequent complication of community-acquired pneumonia and is associated with increased short- and long-term morbidity and mortality and healthcare costs. OBJECTIVE: Describe the prevalence of AKI in patients with CAP requiring mechanical ventilation and evaluate its association with inhospital mortality. DESIGN: Retrospective cohort. SETTING: Intensive care unit. PATIENTS AND METHODS: We included patients with CAP on mechanical ventilation. Patients were categorized according to the development of AKI in the first 24 hours of ICU admission using the Kidney Disease Improving Global Outcomes (KDIGO) classification from no AKI, stage 1 AKI, stage 2 AKI, and stage 3 AKI. MAIN OUTCOME MEASURES: The primary outcome was hospital mortality. Secondary outcomes were ICU mortality, hospital and ICU length of stay, ventilation duration, tracheostomy, and renal replacement therapy requirement. RESULTS: Of 1536 patients included in the study, 829 patients (54%) had no AKI while 707 (46%) developed AKI. In-hospital mortality was 288/829 (34.8%) for patients with no AKI, 43/111 (38.7%) for stage 1 AKI, 86/216 (40%) for stage 2 AKI, and 196/380 (51.7%) for stage 3 AKI (P<.0001). Multivariate analysis revealed that stages 1, 2, or 3 AKI compared to no AKI were not independently associated with in-hospital mortality. Older age, vasopressor use; decreased Glasgow coma scale, PaO2/Fio2 ratio and platelet count, increased bilirubin, lactic acid and INR were associated with increased mortality while female sex was associated with reduced mortality. CONCLUSION: Among mechanically ventilated patients with CAP, AKI was common and was associated with higher crude mortality. The higher mortality could not be attributed alone to AKI, but rather appeared to be related to multi-organ dysfunction. LIMITATIONS: Single-center retrospective study with no data on baseline serum creatinine and the use of estimated baseline creatinine distributions based on the MDRD (Modification of Diet in Renal Disease)equation which may lead to an overestimation of AKI. Second, we did not have data on the microbiology of pneumonia, appropriateness of antibiotic therapy or the administration of other medications that have been demonstrated to be associated with AKI.

Practice and Predictors of Do-Not-Resuscitate Orders in a Tertiary-Care Intensive Care Unit in Saudi Arabia.

Introduction: The objective of this study was to describe Do-Not-Resuscitate (DNR) practices in a tertiary-care intensive care unit (ICU) in Saudi Arabia, and determine the predictors and outcomes of patients who had DNR orders. Methods: This retrospective cohort study was based on a prospectively collected database for a medical-surgicalIntensive CareDepartment in a tertiary-care center in Riyadh, Saudi Arabia (1999-2017). We compared patients who had DNR orders during the ICU stay with those with "full code." The primary outcome was hospital mortality. The secondary outcomes included ICU mortality, tracheostomy, duration of mechanical ventilation, and length of stay in the ICU and hospital. Results: Among 24790 patients admitted to the ICU over the 19-year study period, 3217 (13%) had DNR orders during the ICU stay. Compared to patients with "full code," patients with DNR orders were older (median 67 years [Q1, Q3: 55, 76] versus 57 years [Q1, Q3: 33, 71], p < 0.0001), were more likely to be females (43% versus 38%, p < 0.0001), had worse premorbid functional status (WHO performance status scores 4-5: 606[18.9%] versus 1894[8.8%], p < 0.0001), higher prevalence of comorbid conditions, and higher APACHE II score (median 28 [Q1, Q3: 23, 34] versus 19 [Q1, Q3: 13, 25], p < 0.0001) and were more likely to be mechanically ventilated (83% versus 55%, p < 0.0001). Patients had DNR orders were more likely to die in the ICU (67.8% versus 8.5%, p < 0.0001) and hospital (82.4% versus 18.1%, p < 0.0001). On multivariable logistic regression analysis, the following were associated with an increased likelihood of DNR status: increasing age (odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01-1.02), higher APACHE II score (OR 1.09, 95% CI 1.08-1.10), and worse WHO performance status score. Patients admitted in recent years (2012-2017 versus 2002-2005) were less likely to have DNR orders (OR 0.35, 95% CI 0.32-0.39, p < 0.0001). Patients with DNR orders had higher ICU mortality, more tracheostomies, longer duration of mechanical ventilation and length of ICU stay compared to patients with with "full code" but they had shorter length of hospital stay. Conclusion: In a tertiary-care hospital in Saudi Arabia, 13% of critically ill patients had DNR orders during ICU stay. This study identified several predictors of DNR orders, including the severity of illness and poor premorbid functional status.

Noninvasive Ventilation in Critically Ill Patients With Severe Acute Respiratory Infections.

BACKGROUND: The objective of this study was to evaluate the association between noninvasive ventilation (NIV) compared with invasive ventilation and mortality in subjects with severe acute respiratory infection. METHODS: This was a retrospective multi-center study of subjects with severe acute respiratory infection treated with ventilatory support between September 2012 and June 2018. We compared the 90-d mortality of subjects managed initially with NIV (NIV group) with those managed with invasive ventilation only (invasive ventilation group), adjusting by propensity score. RESULTS: Of 383 subjects, 189 (49%) were in the NIV group and 194 (51%) were in the invasive ventilation group. Of the subjects initially treated with NIV, 117 (62%) were eventually intubated. Crude 90-d mortality was lower in the NIV group versus the invasive ventilation group (42 [22.2%] vs 77 [39.7%]; P < .001). After propensity score adjustment, NIV was associated with lower 90-d mortality than invasive ventilation (odds ratio 0.54, 95% CI 0.38-0.76; P < .001). The association of NIV with mortality compared with invasive ventilation was not different across the studied subgroups. CONCLUSIONS: In subjects with severe acute respiratory infection and acute respiratory failure, NIV was commonly used. NIV was associated with a lower 90-d mortality. The observed high failure rate suggests the need for further research to optimize patient selection and facilitate early recognition of NIV failure.

Statistical analysis plan for the replacing protein via enteral nutrition in a stepwise approach in critically ill patients (REPLENISH) randomized clinical trial.

BACKGROUND: The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU day five until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve a moderate amount of enteral protein would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: In this multicenter randomized trial, critically ill patients will be randomized to receive supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition to achieve a high amount of enteral protein (range of 2-2.4 g/kg/day) or no supplemental enteral protein to achieve a moderate amount of enteral protein (0.8-1.2 g/kg/day). The primary outcome is 90-day all-cause mortality; other outcomes include functional and health-related quality-of-life assessments at 90 days. The study sample size of 2502 patients will have 80% power to detect a 5% absolute risk reduction in 90-day mortality from 30 to 25%. Consistent with international guidelines, this statistical analysis plan specifies the methods for evaluating primary and secondary outcomes and subgroups. Applying this statistical analysis plan to the REPLENISH trial will facilitate unbiased analyses of clinical data. CONCLUSION: Ethics approval was obtained from the institutional review board, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (RC19/414/R). Approvals were also obtained from the institutional review boards of each participating institution. Our findings will be disseminated in an international peer-reviewed journal and presented at relevant conferences and meetings. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04475666 . Registered on July 17, 2020.

Outcomes of patients admitted to the intensive care unit with community-acquired pneumonia in a tertiary care center in Riyadh, Saudi Arabia.

BACKGROUND: Community-acquired pneumonia (CAP) is a leading cause of intensive care unit (ICU) morbidity and mortality. Despite extensive international epidemiological and clinical studies to improve those patients' outcomes, local statistics in Saudi Arabia are limited. The objective of this study is to describe the clinical characteristics and outcomes of patients admitted to the ICU with the diagnosis of CAP reflecting the experience of a tertiary center over an 18-year period. METHODS: A retrospective cohort study included all consecutive adult ICU patients diagnosed with CAP between 1999 and 2017. Baseline demographics, patients' risk factors, and initial admission laboratory investigations were compared between survivors and nonsurvivors. A multivariate regression model was used to predict mortality. RESULTS: During the study period, there were 3438 patients admitted to the ICU with CAP (median age 67 [Quartile 1, 3 (Q1, Q3) 51, 76] years) and 54.4% were males, of whom 1007 (29.2%) died. The survivors compared with nonsurvivors were younger (65 vs. 70 years), less likely to have chronic liver disease (2.4% vs. 10.5%), chronic renal failure (8.1% vs. 14.4%), and be immunocompromised (10.2% vs. 18.2%), and less frequently required mechanical ventilation or vasopressors (46.2% vs. 80.5% and 29.6% vs. 55.9%, respectively). Acute Physiology and Chronic Health Evaluation (APACHE) II score was significantly higher among nonsurvivors (median score 26 vs. 20) with a longer duration of mechanical ventilation and ICU stay. Using a multivariate regression model, age, APACHE II score, bilirubin level, vasopressors, and mechanical ventilation were significantly associated with increased mortality, while diabetes was associated with lower mortality. CONCLUSION: Around one-third of patients admitted to the ICU with CAP died. Mortality was significantly associated with age, APACHE II score, vasopressor use, and mechanical ventilation. A comprehensive national registry is needed to enhance epidemiological data and to guide initiatives for improving CAP patients' outcomes.

Replacing protein via enteral nutrition in a stepwise approach in critically ill patients: the REPLENISH randomized clinical trial protocol.

BACKGROUND: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amount of enteral protein (range 2-2.4 g/kg/day) given from ICU day 5 until ICU discharge or ICU day 90 as compared to no supplemental enteral protein to achieve moderate amount enteral protein (0.8-1.2 g/kg/day) would reduce all-cause 90-day mortality in adult critically ill mechanically ventilated patients. METHODS: The REPLENISH (Replacing Protein Via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial is an open-label, multicenter randomized clinical trial. Patients will be randomized to the supplemental protein group or the control group. Patients in both groups will receive the primary enteral formula as per the treating team, which includes a maximum protein 1.2 g/kg/day. The supplemental protein group will receive, in addition, supplemental protein at 1.2 g/kg/day starting the fifth ICU day. The control group will receive the primary formula without supplemental protein. The primary outcome is 90-day all-cause mortality. Other outcomes include functional and quality of life assessments at 90 days. The trial will enroll 2502 patients. DISCUSSION: The study has been initiated in September 2021. Interim analysis is planned at one third and two thirds of the target sample size. The study is expected to be completed by the end of 2025. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04475666 . Registered on July 17, 2020.