Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study. (Betters)

Compher C, Chittams J, Sammarco T, et al. Greater Protein and Energy Intake May Be Associated With Improved Mortality in Higher Risk Critically Ill Patients: A Multicenter, Multinational Observational Study. Crit Care Med. 2017 Feb; 45(2):156-163.

OBJECTIVES: Controversy exists about the value of greater nutritional intake in critically ill patients, possibly due to varied patient nutritional risk. The objective of this study was to investigate whether clinical outcomes vary by protein or energy intake in patients with risk evaluated by the NUTrition Risk in the Critically Ill score.

DESIGN: Prospective observational cohort.

SETTING: A total of 202 ICUs.

PATIENTS: A total of 2,853 mechanically ventilated patients in ICU greater than or equal to 4 days and a subset of 1,605 patients in ICU greater than or equal to 12 days.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: In low-risk (NUTrition Risk in the Critically Ill, < 5) and high-risk (NUTrition Risk in the Critically Ill, ≥ 5) patients, mortality and time to discharge alive up to day 60 were assessed relative to nutritional intake over the first 12 days using logistic regression and Cox proportional hazard regression, respectively. In high-risk but not low-risk patients, mortality was lower with greater protein (4-d sample: odds ratio, 0.93; 95% CI, 0.89-0.98; p = 0.003 and 12-d sample: odds ratio, 0.90; 95% CI, 0.84-0.96; p = 0.003) and energy (4-d sample: odds ratio, 0.93; 95% CI, 0.89-0.97; p < 0.001 and 12-d sample: odds ratio, 0.88; 95% CI, 0.83-0.94; p < 0.001) intake. In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, mortality, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant. In high-risk but not low-risk patients, time to discharge alive was shorter with greater protein (4-d sample: hazard ratio, 1.05; 95% CI, 1.01-1.09; p = 0.01 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03-1.16; p = 0.002) and energy intake (4-d sample: hazard ratio, 1.05; 95% CI, 1.01-1.09; p = 0.02 and 12-d sample: hazard ratio, 1.09; 95% CI, 1.03-1.16; p = 0.002). In the 12-day sample, there was significant interaction among NUTrition Risk in the Critically Ill category, time to discharge alive, and protein and energy intake, whereas in the 4-day sample, the test for interaction was not significant.

CONCLUSIONS: Greater nutritional intake is associated with lower mortality and faster time to discharge alive in high-risk, longer stay patients but not significantly so in nutritionally low-risk patients.

Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. (Betters)

Beesley SJ, Wilson EL, Lanspa MJ, et al. Relative Bradycardia in Patients With Septic Shock Requiring Vasopressor Therapy. Crit Care Med. 2017 Feb; 45(2) :225-233.

OBJECTIVES: Tachycardia is common in septic shock, but many patients with septic shock are relatively bradycardic. The prevalence, determinants, and implications of relative bradycardia (heart rate, < 80 beats/min) in septic shock are unknown. To determine mortality associated with patients who are relatively bradycardic while in septic shock.

DESIGN: Retrospective study of patients admitted for septic shock to study ICUs during 2005-2013.

SETTING: One large academic referral hospital and two community hospitals.

PATIENTS: Adult patients with septic shock requiring vasopressors.

INTERVENTION: None.

MEASUREMENTS: Primary outcome was 28-day mortality. We used multivariate logistic regression to evaluate the association between relative bradycardia and mortality, controlling for confounding with inverse probability treatment weighting using a propensity score.

RESULTS: We identified 1,554 patients with septic shock, of whom 686 (44%) met criteria for relative bradycardia at some time. Twenty-eight-day mortality in this group was 21% compared to 34% in the never-bradycardic group (p < 0.001). Relatively bradycardic patients were older (65 vs 60 yr; p < 0.001) and had slightly lower illness severity (Sequential Organ Failure Assessment, 10 vs 11; p = 0.004; and Acute Physiology and Chronic Health Evaluation II, 27 vs 28; p = 0.008). After inverse probability treatment weighting, covariates were balanced, and the association between relative bradycardia and survival persisted (p < 0.001).

CONCLUSIONS: Relative bradycardia in patients with septic shock is associated with lower mortality, even after adjustment for confounding. Our data support expanded investigation into whether inducing relative bradycardia will benefit patients with septic shock.

Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. (Betters)

Helmerhorst HJ, Arts DL, Schultz MJ,et al. Metrics of Arterial Hyperoxia and Associated Outcomes in Critical Care. Crit Care Med. 2017 Feb;45(2):187-195.

OBJECTIVE: Emerging evidence has shown the potential risks of arterial hyperoxia, but the lack of a clinical definition and methodologic limitations hamper the interpretation and clinical relevance of previous studies. Our purpose was to evaluate previously used and newly constructed metrics of arterial hyperoxia and systematically assess their association with clinical outcomes in different subgroups in the ICU.

DESIGN: Observational cohort study.

SETTING: Three large tertiary care ICUs in the Netherlands.

PATIENTS: A total of 14,441 eligible ICU patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: In total, 295,079 arterial blood gas analyses, including the PaO2, between July 2011 and July 2014 were extracted from the patient data management system database. Data from all admissions with more than one PaO2 measurement were supplemented with anonymous demographic and admission and discharge data from the Dutch National Intensive Care Evaluation registry. Mild hyperoxia was defined as PaO2 between 120 and 200 mm Hg; severe hyperoxia as PaO2 greater than 200 mm Hg. Characteristics of existing and newly constructed metrics for arterial hyperoxia were examined, and the associations with hospital mortality (primary outcome), ICU mortality, and ventilator-free days and alive at day 28 were retrospectively analyzed using regression models in different subgroups of patients. Severe hyperoxia was associated with higher mortality rates and fewer ventilator-free days in comparison to both mild hyperoxia and normoxia for all metrics except for the worst PaO2. Adjusted effect estimates for conditional mortality were larger for severe hyperoxia than for mild hyperoxia. This association was found both within and beyond the first 24 hours of admission and was consistent for large subgroups. The largest point estimates were found for the exposure identified by the average PaO2, closely followed by the median PaO2, and these estimates differed substantially between subsets. Time spent in hyperoxia showed a linear and positive relationship with hospital mortality.

CONCLUSIONS: Our results suggest that we should limit the PaO2 levels of critically ill patients within a safe range, as we do with other physiologic variables. Analytical metrics of arterial hyperoxia should be judiciously considered when interpreting and comparing study results and future studies are needed to validate our findings in a randomized fashion design.

Improving Hospital Survival and Reducing Brain Dysfunction at Seven California Community Hospital… (Betters)

Barnes-Daly MA, Phillips G, Ely EW. Improving Hospital Survival and Reducing Brain Dysfunction at Seven California Community Hospitals: Implementing PAD Guidelines Via the ABCDEF Bundle in 6,064 Patients. Crit Care Med. 2017 Feb; 45(2):171-178.

OBJECTIVES: To track compliance by an interprofessional team with the Awakening and Breathing Coordination, Choice of drugs, Delirium monitoring and management, Early mobility, and Family engagement (ABCDEF) bundle in implementing the Pain, Agitation, and Delirium guidelines. The aim was to study the association between ABCDEF bundle compliance and outcomes including hospital survival and delirium-free and coma-free days in community hospitals.

DESIGN: A prospective cohort quality improvement initiative involving ICU patients.

SETTING: Seven community hospitals within California’s Sutter Health System.

PATIENTS: Ventilated and nonventilated general medical and surgical ICU patients enrolled between January 1, 2014, and December 31, 2014.

MEASUREMENTS AND MAIN RESULTS: Total and partial bundle compliance were measured daily. Random effects regression was used to determine the association between ABCDEF bundle compliance accounting for total compliance (all or none) or for partial compliance (“dose” or number of bundle elements used) and outcomes of hospital survival and delirium-free and coma-free days, after adjusting for age, severity of illness, and presence of mechanical ventilation. Of 6,064 patients, a total of 586 (9.7%) died before hospital discharge. For every 10% increase in total bundle compliance, patients had a 7% higher odds of hospital survival (odds ratio, 1.07; 95% CI, 1.04-1.11; p < 0.001). Likewise, for every 10% increase in partial bundle compliance, patients had a 15% higher hospital survival (odds ratio, 1.15; 95% CI, 1.09-1.22; p < 0.001). These results were even more striking (12% and 23% higher odds of survival per 10% increase in bundle compliance, respectively, p < 0.001) in a sensitivity analysis removing ICU patients identified as receiving palliative care. Patients experienced more days alive and free of delirium and coma with both total bundle compliance (incident rate ratio, 1.02; 95% CI, 1.01-1.04; p = 0.004) and partial bundle compliance (incident rate ratio, 1.15; 95% CI, 1.09-1.22; p < 0.001).

CONCLUSIONS: The evidence-based ABCDEF bundle was successfully implemented in seven community hospital ICUs using an interprofessional team model to operationalize the Pain, Agitation, and Delirium guidelines. Higher bundle compliance was independently associated with improved survival and more days free of delirium and coma after adjusting for age, severity of illness, and presence of mechanical ventilation.

Suspected Cerebral Edema in Diabetic Ketoacidosis: Is There Still a Role for Head CT in Treatment Decisions? (Colman)

Soto-Rivera CL, Asaro LA, Agus MS, DeCourcey DD. Suspected Cerebral Edema in Diabetic Ketoacidosis: Is There Still a Role for Head CT in Treatment Decisions?  Pediatr Crit Care Med. 2017 Jan 19. [Epub ahead of print]

OBJECTIVES: Neurologic deterioration associated with cerebral edema in diabetic ketoacidosis is typically sudden in onset, progresses rapidly, and requires emergent treatment. The utility of brain imaging by head CT in decisions to treat for cerebral edema has not been previously studied. The objective of this study was to describe the characteristics of pediatric patients with diabetic ketoacidosis who develop altered mental status and evaluate the role of head CT in this cohort.

DESIGN: Retrospective analysis of clinical, biochemical, and radiologic data.

SETTING: Tertiary care children’s hospital (2004-2010).

PATIENTS: Six hundred eighty-six admissions of patients (< 26 yr) with diabetic ketoacidosis.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Altered mental status was documented during 96 of 686 diabetic ketoacidosis admissions (14%). Compared with alert patients, those with altered mental status were younger (median, 12.0 vs 13.1 yr; p = 0.007) and more acidotic (pH, 7.04 vs 7.19; p < 0.001), with higher serum osmolality (328 vs 315 mOsm/kg; p < 0.001) and longer hospital length of stay (4.5 vs 3 d; p = 0.002). Head CT was performed during 60 of 96 diabetic ketoacidosis admissions with altered mental status (63%), 16 (27%) of which had abnormal results. Hyperosmolar therapy for cerebral edema was given during 23 of the 60 admissions (38%), during which 12 (52%) had normal head CT results, eight of these 12 (67%) after cerebral edema treatment and four (33%) before. Of the 11 admissions with abnormal head CT results that received hyperosmolar therapy, four head CT scan (36%) occurred after hyperosmolar treatment and seven (64%) before. For the 11 admissions with head CT before cerebral edema treatment, there was a median 2-hour delay between head CT and hyperosmolar therapy.

CONCLUSIONS: In this single-center retrospective study, there was no evidence that decisions about treatment of patients with diabetic ketoacidosis and suspected cerebral edema were enhanced by head CT, and head CT may have led to a significant delay in hyperosmolar therapy.

Long-Term Survival and Causes of Late Death in Children Treated With Extracorporeal Membrane Oxygenation. (Colman)

von Bahr V, Hultman J, Eksborg S, et al. Long-Term Survival and Causes of Late Death in Children Treated With Extracorporeal Membrane Oxygenation. Pediatr Crit Care Med. 2017 Jan 10.

OBJECTIVE: Extracorporeal membrane oxygenation has been used in patients with severe circulatory or respiratory failure since the 1970s, but the knowledge on long-term survival in this group is scarce. The aim of the present study was to investigate the 10-year survival rates and causes of late death in children treated with extracorporeal membrane oxygenation.

DESIGN: Single-center, retrospective cohort study.

SETTING: Tertiary referral center for extracorporeal life support.

PATIENTS: Neonatal and pediatric patients treated with extracorporeal membrane oxygenation from 1987 to December 2013.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Survival status was obtained from the national Causes of Death registry. Patient background data along with data on survival and causes of death were collected. Survival rates were calculated using the Kaplan-Meier method. Of 400 subjects, 76% survived to discharge. The median follow-up time in survivors was 7.2 years. There was a high mortality rate within the first months after discharge. In the group of patients who survived the first 90 days after treatment, the 10-year survival rates were 93% in neonates and 89% in pediatric patients and were particularly beneficial in patients whose indication for extracorporeal membrane oxygenation was meconium aspiration syndrome, trauma, or infectious diseases. Late deaths were seen in some diagnostic groups, but the Kaplan-Meier curves plateaued over time.

CONCLUSIONS: Children who survive the first months after treatment with extracorporeal membrane oxygenation have a high long-term survival rate. The prognosis is especially favorable in patients with reversible conditions.

Amiodarone Versus Lidocaine for Pediatric Cardiac Arrest Due to Ventricular Arrhythmias: A Systematic Review. (Colman)

McBride ME, Marino BS, Webster G, et al. Amiodarone Versus Lidocaine for Pediatric Cardiac Arrest Due to Ventricular Arrhythmias: A Systematic Review. Pediatr Crit Care Med. 2016 Dec 23.

OBJECTIVE: We performed a systematic review as part of the International Liaison Committee on Resuscitation process to create a consensus on science statement regarding amiodarone or lidocaine during pediatric cardiac arrest for the 2015 International Liaison Committee on Resuscitation’s Consensus on Science and Treatment Recommendations.

DATA SOURCES: Studies were identified from comprehensive searches in PubMed, Embase, and the Cochrane Library.

STUDY SELECTION: Studies eligible for inclusion were randomized controlled and observational studies on the relative clinical effect of amiodarone or lidocaine in cardiac arrest.

DATA EXTRACTION: Studies addressing the clinical effect of amiodarone versus lidocaine were extracted and reviewed for inclusion and exclusion criteria by the reviewers. Studies were rigorously analyzed thereafter.

DATA SYNTHESIS: We identified three articles addressing lidocaine versus amiodarone in cardiac arrest: 1) a prospective study assessing lidocaine versus amiodarone for refractory ventricular fibrillation in out-of-hospital adults; 2) an observational retrospective cohort study of inpatient pediatric patients with ventricular fibrillation or pulseless ventricular tachycardia who received lidocaine, amiodarone, neither or both; and 3) a prospective study of ventricular tachycardia with a pulse in adults. The first study showed a statistically significant improvement in survival to hospital admission with amiodarone (22.8% vs 12.0%; p = 0.009) and a lack of statistical difference for survival at discharge (p = 0.34). The second article demonstrated 44% return of spontaneous circulation for amiodarone and 64% for lidocaine (odds ratio, 2.02; 1.36-3.03) with no statistical difference for survival at hospital discharge. The third article demonstrated 48.3% arrhythmia termination for amiodarone versus 10.3% for lidocaine (p < 0.05). All were classified as lower quality studies without preference for one agent.

CONCLUSIONS: The confidence in effect estimates is so low that International Liaison Committee on Resuscitation felt that a recommendation to use of amiodarone over lidocaine is too speculative; we suggest that amiodarone or lidocaine can be used in the setting of pulseless ventricular tachycardia/ventricular fibrillation in infants and children.

A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. (Colman)

Carcillo JA, Sward K, Halstead ES, et al. A Systemic Inflammation Mortality Risk Assessment Contingency Table for Severe Sepsis. Pediatr Crit Care Med. 2016 Dec 9. [Epub ahead of print]

OBJECTIVES: We tested the hypothesis that a C-reactive protein and ferritin-based systemic inflammation contingency table can track mortality risk in pediatric severe sepsis.

DESIGN: Prospective cohort study.

SETTING: Tertiary PICU.

PATIENTS: Children with 100 separate admission episodes of severe sepsis were enrolled.

INTERVENTIONS: Blood samples were attained on day 2 of sepsis and bi-weekly for biomarker batch analysis. A 2 × 2 contingency table using C-reactive protein and ferritin thresholds was developed.

MEASUREMENTS AND MAIN RESULTS: A C-reactive protein of 4.08 mg/dL and a ferritin of 1,980 ng/mL were found to be optimal cutoffs for outcome prediction at first sampling (n = 100) using the Youden index. PICU mortality was increased in the “high-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL category (6/13 [46.15%]) compared with the “intermediate-risk” C-reactive protein greater than or equal to 4.08 mg/dL and ferritin less than 1,980 ng/mL or C-reactive protein less than 4.08 mg/dL and ferritin greater than or equal to 1,980 ng/mL categories (2/43 [4.65%]), and the “low-risk” C-reactive protein less than 4.08 mg/dL and ferritin less than 1,980 ng/mL category (0/44 [0%]) (odds ratio, 36.43 [95% CI, 6.16-215.21]). The high-risk category was also associated with the development of immunoparalysis (odds ratio, 4.47 [95% CI, 1.34-14.96]) and macrophage activation syndrome (odds ratio, 24.20 [95% CI, 5.50-106.54]). Sixty-three children underwent sequential blood sampling; those who were initially in the low-risk category (n = 24) and those who subsequently migrated (n = 19) to the low-risk category all survived, whereas those who remained in the “at-risk” categories had increased mortality (7/20 [35%]; p < 0.05).

CONCLUSIONS: A C-reactive protein- and ferritin-based contingency table effectively assessed mortality risk. Reduction in systemic inflammation below a combined threshold C-reactive protein of 4.08 mg/dL and ferritin of 1,980 ng/mL appeared to be a desired response in children with severe sepsis.