Ketamine Analgo-sedation for Mechanically Ventilated Critically Ill Adults: A Rapid Practice Guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence­based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n=898) and 9 observational studies (n=1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Ketamine analgo-sedation for mechanically ventilated critically ill adults: A rapid practice guideline from the Saudi Critical Care Society and the Scandinavian Society of Anesthesiology and Intensive Care Medicine.

BACKGROUND: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research. METHODS: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities. RESULTS: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied. CONCLUSION: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence.

Patients with influenza admitted to a tertiary-care hospital in Riyadh between 2018 and 2022: characteristics, outcomes and factors associated with ICU admission and mortality.

BACKGROUND: Influenza is a common cause of hospital admissions globally with regional variations in epidemiology and clinical profile. We evaluated the characteristics and outcomes of patients with influenza admitted to a tertiary-care center in Riyadh, Saudi Arabia. METHODS: This was a retrospective cohort of adult patients admitted with polymerase chain reaction-confirmed influenza to King Abdulaziz Medical City-Riyadh between January 1, 2018, and May 31, 2022. We compared patients who required intensive care unit (ICU) admission to those who did not and performed multivariable logistic regression to assess the predictors of ICU admission and hospital mortality. RESULTS: During the study period, 675 adult patients were hospitalized with influenza (median age 68.0 years, females 53.8%, hypertension 59.9%, diabetes 55.1%, and chronic respiratory disease 31.1%). Most admissions (83.0%) were in the colder months (October to March) in Riyadh with inter-seasonal cases even in the summertime (June to August). Influenza A was responsible for 79.0% of cases, with H3N2 and H1N1 subtypes commonly circulating in the study period. Respiratory viral coinfection occurred in 12 patients (1.8%) and bacterial coinfection in 42 patients (17.4%). 151 patients (22.4%) required ICU admission, of which 62.3% received vasopressors and 48.0% mechanical ventilation. Risk factors for ICU admission were younger age, hypertension, bilateral lung infiltrates on chest X-ray, and Pneumonia Severity Index. The overall hospital mortality was 7.4% (22.5% for ICU patients, p < 0.0001). Mortality was 45.0% in patients with bacterial coinfection, 30.9% in those requiring vasopressors, and 29.2% in those who received mechanical ventilation. Female sex (odds ratio [OR], 2.096; 95% confidence interval [CI] 1.070, 4.104), ischemic heart disease (OR, 3.053; 95% CI 1.457, 6.394), immunosuppressed state (OR, 7.102; 95% CI 1.803, 27.975), Pneumonia Severity Index (OR, 1.029; 95% CI, 1.017, 1.041), leukocyte count and serum lactate level (OR, 1.394; 95% CI, 1.163, 1.671) were independently associated with hospital mortality. CONCLUSIONS: Influenza followed a seasonal pattern in Saudi Arabia, with H3N2 and H1N1 being the predominant circulating strains during the study period. ICU admission was required for > 20%. Female sex, high Pneumonia Severity Index, ischemic heart disease, and immunosuppressed state were associated with increased mortality.

Association of early mobility with the incidence of deep-vein thrombosis and mortality among critically ill patients: a post hoc analysis of PREVENT trial.

BACKGROUND: This study assessed the mobility levels among critically ill patients and the association of early mobility with incident proximal lower-limb deep-vein thrombosis and 90-day mortality. METHODS: This was a post hoc analysis of the multicenter PREVENT trial, which evaluated adjunctive intermittent pneumatic compression in critically ill patients receiving pharmacologic thromboprophylaxis with an expected ICU stay ≥ 72 h and found no effect on the primary outcome of incident proximal lower-limb deep-vein thrombosis. Mobility levels were documented daily up to day 28 in the ICU using a tool with an 8-point ordinal scale. We categorized patients according to mobility levels within the first 3 ICU days into three groups: early mobility level 4-7 (at least active standing), 1-3 (passive transfer from bed to chair or active sitting), and 0 (passive range of motion). We evaluated the association of early mobility and incident lower-limb deep-vein thrombosis and 90-day mortality by Cox proportional models adjusting for randomization and other co-variables. RESULTS: Of 1708 patients, only 85 (5.0%) had early mobility level 4-7 and 356 (20.8%) level 1-3, while 1267 (74.2%) had early mobility level 0. Patients with early mobility levels 4-7 and 1-3 had less illness severity, femoral central venous catheters, and organ support compared to patients with mobility level 0. Incident proximal lower-limb deep-vein thrombosis occurred in 1/85 (1.3%) patients in the early mobility 4-7 group, 7/348 (2.0%) patients in mobility 1-3 group, and 50/1230 (4.1%) patients in mobility 0 group. Compared with early mobility group 0, mobility groups 4-7 and 1-3 were not associated with differences in incident proximal lower-limb deep-vein thrombosis (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI] 0.16, 8.90; p = 0.87 and 0.91, 95% CI 0.39, 2.12; p = 0.83, respectively). However, early mobility groups 4-7 and 1-3 had lower 90-day mortality (aHR 0.47, 95% CI 0.22, 1.01; p = 0.052, and 0.43, 95% CI 0.30, 0.62; p < 0.0001, respectively). CONCLUSIONS: Only a small proportion of critically ill patients with an expected ICU stay ≥ 72 h were mobilized early. Early mobility was associated with reduced mortality, but not with different incidence of deep-vein thrombosis. This association does not establish causality, and randomized controlled trials are required to assess whether and to what extent this association is modifiable. TRIAL REGISTRATION: The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103 (registered on 3 November 2013) and Current controlled trials, ID: ISRCTN44653506 (registered on 30 October 2013).

The use of Tocilizumab in COVID-19 critically ill patients with renal impairment: a multicenter, cohort study.

Tocilizumab (TCZ) is recommended in patients with COVID-19 who require oxygen therapy or ventilatory support. Despite the wide use of TCZ, little is known about its safety and effectiveness in patients with COVID-19 and renal impairment. Therefore, this study evaluated the safety and effectiveness of TCZ in critically ill patients with COVID-19 and renal impairment. A multicenter retrospective cohort study included all adult COVID-19 patients with renal impairment (eGFR˂60 mL/min) admitted to the ICUs between March 2020 and July 2021. Patients were categorized into two groups based on TCZ use (Control vs. TCZ). The primary endpoint was the development of acute kidney injury (AKI) during ICU stay. We screened 1599 patients for eligibility; 394 patients were eligible, and 225 patients were included after PS matching (1:2 ratio); there were 75 TCZ-treated subjects and 150 controls. The rate of AKI was higher in the TCZ group compared with the control group (72.2% versus 57.4%; p = 0.03; OR: 1.83; 95% CI: 1.01, 3.34; p = 0.04). Additionally, the ICU length of stay was significantly longer in patients who received TCZ (17.5 days versus 12.5 days; p = 0.006, Beta coefficient: 0.30 days, 95% CI: 0.09, 0.50; p = 0.005). On the other hand, the 30-day and in-hospital mortality were lower in patients who received TCZ compared to the control group (HR: 0.45, 95% CI: 0.27, 0.73; p = 0.01 and HR: 0.63, 95% CI: 0.41, 0.96; p = 0.03, respectively). The use of TCZ in this population was associated with a statistically significantly higher rate of AKI while improving the overall survival on the other hand. Further research is needed to assess the risks and benefits of TCZ treatment in critically ill COVID-19 patients with renal impairment.

Nutrition priorities in obese critically ill patients.

PURPOSE OF REVIEW: During critical illness, several neuroendocrine, inflammatory, immune, adipokine, and gastrointestinal tract hormone pathways are activated; some of which are more intensified among obese compared with nonobese patients. Nutrition support may mitigate some of these effects. Nutrition priorities in obese critically ill patients include screening for nutritional risk, estimation of energy and protein requirement, and provision of macronutrients and micronutrients. RECENT FINDINGS: Estimation of energy requirement in obese critically ill patients is challenging because of variations in body composition among obese patients and absence of reliable predictive equations for energy expenditure. Whereas hypocaloric nutrition with high protein has been advocated in obese critically ill patients, supporting data are scarce. Recent studies did not show differences in outcomes between hypocaloric and eucaloric nutrition, except for better glycemic control. Sarcopenia is common among obese patients, and the provision of increased protein intake has been suggested to mitigate catabolic changes especially after the acute phase of critical illness. However, high-quality data on high protein intake in these patients are lacking. Micronutrient deficiencies among obese critically ill patients are common but the role of their routine supplementation requires further study. SUMMARY: An individualized approach for nutritional support may be needed for obese critically ill patients but high-quality evidence is lacking. Future studies should focus on nutrition priorities in this population, with efficient and adequately powered studies.

Standard dosing of enoxaparin versus unfractionated heparin in critically ill patient with COVID-19: a multicenter propensity-score matched study.

BACKGROUND: Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin and unfractionated heparin (UFH) in critically ill patients with COVID-19.  METHODS: A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groups based on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40 mg SQ every 24 hours versus UFH 5000 Units SQ every 8 hours) throughout their ICU stay. The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS) matching was used to match patients (1:1 ratio) between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate.  RESULTS: A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significant difference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09). CONCLUSION: Prophylactic enoxaparin use in critically ill patients with COVID-19 may significantly reduce all thrombosis cases with similar bleeding risk compared to UFH.

Effect of Helmet Noninvasive Ventilation vs Usual Respiratory Support on Mortality Among Patients With Acute Hypoxemic Respiratory Failure Due to COVID-19: The HELMET-COVID Randomized Clinical Trial.

Importance: Helmet noninvasive ventilation has been used in patients with COVID-19 with the premise that helmet interface is more effective than mask interface in delivering prolonged treatments with high positive airway pressure, but data about its effectiveness are limited. Objective: To evaluate whether helmet noninvasive ventilation compared with usual respiratory support reduces mortality in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. Design, Setting, and Participants: This was a multicenter, pragmatic, randomized clinical trial that was conducted in 8 sites in Saudi Arabia and Kuwait between February 8, 2021, and November 16, 2021. Adult patients with acute hypoxemic respiratory failure (n = 320) due to suspected or confirmed COVID-19 were included. The final follow-up date for the primary outcome was December 14, 2021. Interventions: Patients were randomized to receive helmet noninvasive ventilation (n = 159) or usual respiratory support (n = 161), which included mask noninvasive ventilation, high-flow nasal oxygen, and standard oxygen. Main Outcomes and Measures: The primary outcome was 28-day all-cause mortality. There were 12 prespecified secondary outcomes, including endotracheal intubation, barotrauma, skin pressure injury, and serious adverse events. Results: Among 322 patients who were randomized, 320 were included in the primary analysis, all of whom completed the trial. Median age was 58 years, and 187 were men (58.4%). Within 28 days, 43 of 159 patients (27.0%) died in the helmet noninvasive ventilation group compared with 42 of 161 (26.1%) in the usual respiratory support group (risk difference, 1.0% [95% CI, -8.7% to 10.6%]; relative risk, 1.04 [95% CI, 0.72-1.49]; P = .85). Within 28 days, 75 of 159 patients (47.2%) required endotracheal intubation in the helmet noninvasive ventilation group compared with 81 of 161 (50.3%) in the usual respiratory support group (risk difference, -3.1% [95% CI, -14.1% to 7.8%]; relative risk, 0.94 [95% CI, 0.75-1.17]). There were no significant differences between the 2 groups in any of the prespecified secondary end points. Barotrauma occurred in 30 of 159 patients (18.9%) in the helmet noninvasive ventilation group and 25 of 161 (15.5%) in the usual respiratory support group. Skin pressure injury occurred in 5 of 159 patients (3.1%) in the helmet noninvasive ventilation group and 10 of 161 (6.2%) in the usual respiratory support group. There were 2 serious adverse events in the helmet noninvasive ventilation group and 1 in the usual respiratory support group. Conclusions and Relevance: Results of this study suggest that helmet noninvasive ventilation did not significantly reduce 28-day mortality compared with usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. However, interpretation of the findings is limited by imprecision in the effect estimate, which does not exclude potentially clinically important benefit or harm. Trial Registration: ClinicalTrials.gov Identifier: NCT04477668.

Prevention of gastrointestinal bleeding in critically ill patients.

PURPOSE OF REVIEW: This review focuses on the current literature on the epidemiology and prevention of stress-induced clinically important gastrointestinal bleeding in ICU patients. RECENT FINDINGS: The incidence of stress-induced clinically important gastrointestinal bleeding in critically ill patients seems to be decreasing. Observational studies and an exploratory randomized controlled trial suggest that early enteral nutrition may be effective in preventing gastrointestinal bleeding in patients who are not at high risk. Recent systemic reviews and meta-analyses indicate that proton pump inhibitors and H2 receptor antagonists are more effective than placebo in preventing clinically important gastrointestinal bleeding, especially in high-risk and very high-risk patients, but do not reduce mortality. Although observational data suggested an association of proton pump inhibitors and H2 receptor antagonists with Clostridium difficile infection and pneumonia, this association was not confirmed in randomized controlled trials. SUMMARY: The incidence of stress-induced clinically important gastrointestinal bleeding in critically ill patients seems to have decreased over time. Even though stress ulcer prophylaxis in critically ill patients has been a research focus for decades, many questions remain unanswered, such as which groups of patients are likely to benefit and what pharmacologic agent is associated with the best benefit-to-harm ratio.

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.

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.

Invasive Candidiasis in Critically Ill Patients: A Prospective Cohort Study in Two Tertiary Care Centers.

BACKGROUND: Invasive candidiasis is not uncommon in critically ill patients but has variable epidemiology and outcomes between intensive care units (ICUs). This study evaluated the epidemiology, characteristics, management, and outcomes of patients with invasive candidiasis at 6 ICUs of 2 tertiary care centers. METHODS: This was a prospective observational study of all adults admitted to 6 ICUs in 2 different hospitals between August 2012 and May 2016 and diagnosed to have invasive candidiasis by 2 intensivists according to predefined criteria. The epidemiology of isolated Candida and the characteristics, management, and outcomes of affected patients were studied. Multivariable logistic regression analyses were performed to identify the predictors of non-albicans versus albicans infection and hospital mortality. RESULTS: Invasive candidiasis was diagnosed in 162 (age 58.4 ± 18.9 years, 52.2% males, 82.1% medical admissions, and admission Acute Physiology and Chronic Health Evaluation II score 24.1 ± 8.4) patients at a rate of 2.6 cases per 100 ICU admissions. On the diagnosis day, the Candida score was 2.4 ± 0.9 in invasive candidiasis compared with 1.6 ± 0.9 in Candida colonization (P < .01). The most frequent species were albicans (38.3%), tropicalis (16.7%), glabrata (16%), and parapsilosis (13.6%). In patients with candidemia, antifungal therapy was started on average 1 hour before knowing the culture result (59.6% of therapy initiated after). Resistance to fluconazole, caspofungin, and amphotericin B occurred in 27.9%, 2.9%, and 3.1%, respectively. The hospital mortality was 58.6% with no difference between albicans and non-albicans infections (61.3% and 54.9%, respectively; P = .44). The independent predictors of mortality were renal replacement therapy after invasive candidiasis diagnosis (odds ratio: 5.42; 95% confidence interval: 2.16-13.56) and invasive candidiasis leading/contributing to ICU admission versus occurring during critical illness (odds ratio: 2.87; 95% confidence interval: 1.22-6.74). CONCLUSIONS: In critically ill patients with invasive candidiasis, non-albicans was responsible for most cases, and mortality was high (58.6%). Antifungal therapy was initiated after culture results in 60% suggesting low preclinical suspicion. Study registration: NCT01490684; registered in ClinicalTrials.gov on February 11, 2012.

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.).

Trophic or full nutritional support?

PURPOSE OF REVIEW: Full nutritional support during the acute phase of critical illness has traditionally been recommended to reduce catabolism and prevent malnutrition. Approaches to achieve full nutrition include early initiation of nutritional support, targeting full nutritional requirement as soon as possible and initiation of supplemental parenteral nutrition when enteral nutrition does not reach the target. RECENT FINDINGS: Existing evidence supports early enteral nutrition over delayed enteral nutrition or early parenteral nutrition. Recent randomized controlled trials have demonstrated that permissive underfeeding or trophic feeding is associated with similar outcomes compared with full feeding in the acute phase of critical illness. In patients with refeeding syndrome, patients with high nutritional risk and patients with shock, early enteral nutrition targeting full nutritional targets may be associated with worse outcomes compared with less aggressive enteral nutrition strategy. SUMMARY: A two-phase approach for nutritional support may more appropriately account for the physiologic changes during critical illness than one-phase approach. Further evidence is awaited for the optimal protein amount during critical illness and for feeding patients at high nutritional risk or with acute gastrointestinal injury.

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.

Outbreaks in the adult ICUs.

PURPOSE OF REVIEW: Infectious disease outbreaks in the critical care setting are common and serious consequence. This article reviews and summarizes recent outbreaks in the adult ICUs. RECENT FINDINGS: Outbreaks of multidrug-resistant bacteria, fungi, and emerging viruses in ICUs from different countries are common. Outbreak investigation relies on epidemiologic methods, microbiologic studies, and molecular typing methods. Overuse of antibiotics, gaps in implementing infection prevention measures, and contaminated environment are common causes of ICU outbreaks. ICU staff awareness of and preparedness for such outbreaks are crucial for outbreak prevention and control. Specific infection control measures vary according to outbreak transmission mode and cause. SUMMARY: Outbreaks remain a significant threat to healthcare systems. Proper implementation of infection prevention practices and judicious use of antibiotics are needed for outbreak prevention in adult ICUs. Surveillance, proper outbreak investigation, adherence to infection prevention and control measures, and thorough disinfection of contaminated areas are required to successfully manage outbreaks.

Incidence, risk factors and outcomes of seizures occurring after craniotomy for primary brain tumor resection.

OBJECTIVE: To determine the incidence, risk factors and outcomes of early post-craniotomy seizures. METHODS: This was a retrospective cohort study of all patients who underwent craniotomy for primary brain tumor resection (2002-2011) and admitted postoperatively to the intensive care unit. The patients were divided into 2 groups depending on the occurrence of seizures within 7 days. RESULTS: One-hundred-ninety-three patients were studied: 35.8% had preoperative seizure history and 16.6% were on prophylactic antiepileptic drugs (AEDs). Twenty-seven (14%) patients had post-craniotomy seizures. The tumors were mostly meningiomas (63% for the post-craniotomy seizures group versus 58.1% for the other group; p=0.63) and supratentorial (92.6% for the post-craniotomy seizures versus 78.4% for the other group, p=0.09) with tumor diameter=3.7+/-1.5 versus 4.2+/-1.6 cm, (p=0.07). One (3.1%) of the 32 patients on prophylactic AEDs had post-craniotomy seizures compared with 12% of the 92 patients not receiving AEDs preoperatively (p=0.18). On multivariate analysis, predictors of post-craniotomy seizures were preoperative seizures (odds ratio, 2.62; 95% confidence interval, 1.12-6.15) and smaller tumor size <4 cm (odds ratio, 2.50; 95% confidence interval, 1.02-6.25). Post-craniotomy seizures were not associated with increased morbidity or mortality. CONCLUSION: Early seizures were common after craniotomy for primary brain tumor resection, but were not associated with worse outcomes. Preoperative seizures and smaller tumor size were independent risk factors.

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.

Critically ill patients with Middle East respiratory syndrome coronavirus infection.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency medicine 2016. Other selected articles can be found online at http://www.biomedcentral.com/collections/annualupdate2016. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.