Delirium and Mortality in Critically Ill Children: Epidemiology and Outcomes of Pediatric Delirium
Traube, C et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 891–898
Objectives: Delirium occurs frequently in adults and is an independent predictor of mortality. However, the epidemiology and outcomes of pediatric delirium are not well-characterized. The primary objectives of this study were to describe the frequency of delirium in critically ill children, its duration, associated risk factors, and effect on in-hospital outcomes, including mortality. Secondary objectives included determination of delirium subtype, and effect of delirium on duration of mechanical ventilation, and length of hospital stay.
Design: Prospective, longitudinal cohort study. Setting: Urban academic tertiary care PICU. Patients: All consecutive admissions from September 2014 through August 2015. Interventions: Children were screened for delirium twice daily throughout their ICU stay. Measurements and Main Results: Of 1,547 consecutive patients, delirium was diagnosed in 267 (17%) and lasted a median of 2 days (interquartile range, 1–5). Seventy-eight percent of children with delirium developed it within the first 3 PICU days. Most cases of delirium were of the hypoactive (46%) and mixed (45%) subtypes; only 8% of delirium episodes were characterized as hyperactive delirium. In multivariable analysis, independent predictors of delirium included age less than or equal to 2 years old, developmental delay, severity of illness, prior coma, mechanical ventilation, and receipt of benzodiazepines and anticholinergics. PICU length of stay was increased in children with delirium (adjusted relative length of stay, 2.3; CI = 2.1–2.5; p < 0.001), as was duration of mechanical ventilation (median, 4 vs 1 d; p < 0.001). Delirium was a strong and independent predictor of mortality (adjusted odds ratio, 4.39; CI = 1.96–9.99; p < 0.001).
Conclusions: Delirium occurs frequently in critically ill children and is independently associated with mortality. Some in-hospital risk factors for delirium development are modifiable. Interventional studies are needed to determine best practices to limit delirium exposure in at-risk children.
Tuesday, 16 May 2017
The Untapped Potential of Patient and Family Engagement in the Organization of Critical Care
The Untapped Potential of Patient and Family Engagement in the Organization of Critical Care
Haines, K J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 899–906
Objective: There is growing interest in patient and family participation in critical care—not just as part of the bedside, but as part of educational and management organization and infrastructure. This offers tremendous opportunities for change but carries risk to patients, families, and the institution. The objective is to provide a concise definitive review of patient and family organizational participation in critical care as a high-risk population and other vulnerable groups. A pragmatic, codesigned model for critical care is offered as a suggested approach for clinicians, researchers, and policy-makers. Data Sources: To inform this review, a systematic search of Ovid Medline, PubMed, and Embase was undertaken in April 2016 using the MeSH terms: patient participation and critical care. A second search was undertaken in PubMed using the terms: patient participation and organizational models to search for other examples of engagement in vulnerable populations. We explicitly did not seek to include discussions of bedside patient-family engagement or shared decision-making. Study Selection: Two reviewers screened citations independently. Included studies either actively partnered with patients and families or described a model of engagement in critical care and other vulnerable populations. Data Extraction: Data or description of how patient and family engagement occurred and/or description of model were extracted into a standardized form. Data Synthesis: There was limited evidence of patient and family engagement in critical care although key recommendations can be drawn from included studies. Patient and family engagement is occurring in other vulnerable populations although there are few described models and none which address issues of risk. Conclusions: A model of patient and family engagement in critical care does not exist, and we propose a pragmatic, codesigned model that takes into account issues of psychologic safety in this population. Significant opportunity exists to document processes of engagement that reflect a changing paradigm of healthcare delivery.
Haines, K J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 899–906
Objective: There is growing interest in patient and family participation in critical care—not just as part of the bedside, but as part of educational and management organization and infrastructure. This offers tremendous opportunities for change but carries risk to patients, families, and the institution. The objective is to provide a concise definitive review of patient and family organizational participation in critical care as a high-risk population and other vulnerable groups. A pragmatic, codesigned model for critical care is offered as a suggested approach for clinicians, researchers, and policy-makers. Data Sources: To inform this review, a systematic search of Ovid Medline, PubMed, and Embase was undertaken in April 2016 using the MeSH terms: patient participation and critical care. A second search was undertaken in PubMed using the terms: patient participation and organizational models to search for other examples of engagement in vulnerable populations. We explicitly did not seek to include discussions of bedside patient-family engagement or shared decision-making. Study Selection: Two reviewers screened citations independently. Included studies either actively partnered with patients and families or described a model of engagement in critical care and other vulnerable populations. Data Extraction: Data or description of how patient and family engagement occurred and/or description of model were extracted into a standardized form. Data Synthesis: There was limited evidence of patient and family engagement in critical care although key recommendations can be drawn from included studies. Patient and family engagement is occurring in other vulnerable populations although there are few described models and none which address issues of risk. Conclusions: A model of patient and family engagement in critical care does not exist, and we propose a pragmatic, codesigned model that takes into account issues of psychologic safety in this population. Significant opportunity exists to document processes of engagement that reflect a changing paradigm of healthcare delivery.
Extracorporeal Membrane Oxygenation for Adult Community-Acquired Pneumonia: Outcomes and Predictors of Mortality
Extracorporeal Membrane Oxygenation for Adult Community-Acquired Pneumonia: Outcomes and Predictors of Mortality
Ramanathan, K et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 814–821
Objectives: Extracorporeal membrane oxygenation is a rescue therapy used to support severe cardiorespiratory failure. Data on outcomes from severe community-acquired pneumonia in adults receiving rescue extracorporeal membrane oxygenation are mainly confined to single-center experiences or specific pathogens. We examined data from the Extracorporeal Life Support Organisation registry to identify risk factors for poor outcomes in adult patients with community-acquired pneumonia. Design: Retrospective data analysis.
Setting: Extracorporeal Life Support Organization Registry database. Patients: We collected deidentified data on adult patients (> 18 yr) receiving extracorporeal membrane oxygenation for community-acquired pneumonia between 2002 and 2012. Patients with incomplete data or brain death were excluded. The primary outcome measure was in-hospital mortality. Other measurements included demographic information, pre-extracorporeal membrane oxygenation mechanical ventilation and biochemical variables, inotrope requirements, extracorporeal membrane oxygenation mode, duration, and complications. Initial univariate analysis assessed potential associations between survival and various pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis to identify predictors of mortality.
Interventions: None.
Measurements and Main Findings: One thousand fifty-five patients, who satisfied inclusion criteria, were included in the final analysis. There was an increase in the number of patients cannulated per annum over the 10-year period studied. Univariate analysis identified pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation variables associated with high mortality. Further multiple regression analysis identified certain pre-extracorporeal membrane oxygenation factors as predictors of mortality, including duration of mechanical ventilation prior to extracorporeal membrane oxygenation, lower arterial pressure, fungal pneumonia, and advancing age. Type and duration of extracorporeal membrane oxygenation, neurologic complications, and presence of more than three complications on extracorporeal membrane oxygenation were also associated with higher mortality.
Conclusions: The majority (66%) of adults with community-acquired pneumonia supported on extracorporeal membrane oxygenation survived. Certain potentially modifiable risk factors were associated with increased mortality.
Ramanathan, K et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 814–821
Objectives: Extracorporeal membrane oxygenation is a rescue therapy used to support severe cardiorespiratory failure. Data on outcomes from severe community-acquired pneumonia in adults receiving rescue extracorporeal membrane oxygenation are mainly confined to single-center experiences or specific pathogens. We examined data from the Extracorporeal Life Support Organisation registry to identify risk factors for poor outcomes in adult patients with community-acquired pneumonia. Design: Retrospective data analysis.
Setting: Extracorporeal Life Support Organization Registry database. Patients: We collected deidentified data on adult patients (> 18 yr) receiving extracorporeal membrane oxygenation for community-acquired pneumonia between 2002 and 2012. Patients with incomplete data or brain death were excluded. The primary outcome measure was in-hospital mortality. Other measurements included demographic information, pre-extracorporeal membrane oxygenation mechanical ventilation and biochemical variables, inotrope requirements, extracorporeal membrane oxygenation mode, duration, and complications. Initial univariate analysis assessed potential associations between survival and various pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation factors. Variables with p values of less than 0.1 were considered for logistic regression analysis to identify predictors of mortality.
Interventions: None.
Measurements and Main Findings: One thousand fifty-five patients, who satisfied inclusion criteria, were included in the final analysis. There was an increase in the number of patients cannulated per annum over the 10-year period studied. Univariate analysis identified pre-extracorporeal membrane oxygenation and extracorporeal membrane oxygenation variables associated with high mortality. Further multiple regression analysis identified certain pre-extracorporeal membrane oxygenation factors as predictors of mortality, including duration of mechanical ventilation prior to extracorporeal membrane oxygenation, lower arterial pressure, fungal pneumonia, and advancing age. Type and duration of extracorporeal membrane oxygenation, neurologic complications, and presence of more than three complications on extracorporeal membrane oxygenation were also associated with higher mortality.
Conclusions: The majority (66%) of adults with community-acquired pneumonia supported on extracorporeal membrane oxygenation survived. Certain potentially modifiable risk factors were associated with increased mortality.
Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome
Randomized Clinical Trial of a Combination of an Inhaled Corticosteroid and Beta Agonist in Patients at Risk of Developing the Acute Respiratory Distress Syndrome
Festic, E et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 798–805
Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance.
Design: Double-blind, randomized clinical trial (ClinicalTrials.gov : NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days.
Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%).
Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.
Festic, E et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 798–805
Objectives: Effective pharmacologic treatments directly targeting lung injury in patients with the acute respiratory distress syndrome are lacking. Early treatment with inhaled corticosteroids and beta agonists may reduce progression to acute respiratory distress syndrome by reducing lung inflammation and enhancing alveolar fluid clearance.
Design: Double-blind, randomized clinical trial (ClinicalTrials.gov : NCT01783821). The primary outcome was longitudinal change in oxygen saturation divided by the FIO2 (S/F) through day 5. We also analyzed categorical change in S/F by greater than 20%. Other outcomes included need for mechanical ventilation and development of acute respiratory distress syndrome. Setting: Five academic centers in the United States. Patients: Adult patients admitted through the emergency department at risk for acute respiratory distress syndrome. Interventions: Aerosolized budesonide/formoterol versus placebo bid for up to 5 days.
Measurements and Main Results: Sixty-one patients were enrolled from September 3, 2013, to June 9, 2015. Median time from presentation to first study drug was less than 9 hours. More patients in the control group had shock at enrollment (14 vs 3 patients). The longitudinal increase in S/F was greater in the treatment group (p = 0.02) and independent of shock (p = 0.04). Categorical change in S/F improved (p = 0.01) but not after adjustment for shock (p = 0.15). More patients in the placebo group developed acute respiratory distress syndrome (7 vs 0) and required mechanical ventilation (53% vs 21%).
Conclusions: Early treatment with inhaled budesonide/formoterol in patients at risk for acute respiratory distress syndrome is feasible and improved oxygenation as assessed by S/F. These results support further study to test the efficacy of inhaled corticosteroids and beta agonists for prevention of acute respiratory distress syndrome.
The Obesity Paradox Is Not Observed in Critically Ill Patients on Early Enteral Nutrition
The Obesity Paradox Is Not Observed in Critically Ill Patients on Early Enteral Nutrition
Harris, K et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 828–834
Objectives: To investigate the association between body mass index and mortality in a large, ICU population and determine if the relationship is observed among a subgroup of patients ordered early enteral nutrition.
Design: Retrospective cohort study within a national clinical mixed ICU database of patients admitted between January 1, 2008, and June 30, 2015. Setting: Initial ICU admissions among patients monitored by tele-ICU programs and recorded in the Philips eICU Research Institute database.
Patients: A total of 1,042,710 adult patient stays with ICU length of stay more than 24 hours, of which 74,771 were ordered enteral nutrition within the first 48 hours. Intervention: None.
Measurements and Main Results: Patient stays from 409 ICUs were included. The average age, Acute Physiology and Chronic Health Evaluation IV score, and hospital mortality were 63.6 years, 56.7, and 9.0%, respectively. Hospital mortality among body mass index categories was estimated by multivariable modified Poisson regression models. Compared with the body mass index category 25.0–29.9 kg/m2, hospital mortality was higher among underweight (body mass index, < 18.5; relative risk, 1.35; 95% CI, 1.32–1.39), normal weight (body mass index, 18.5–24.9; relative risk, 1.10; 95% CI, 1.09–1.12), and the extremely obese (body mass index, ≥ 50.0; relative risk, 1.10; 95% CI, 1.05–1.15). However, the risk was not statistically different from patients with body mass index 30.0–49.9 kg/m2. Among patients ordered early enteral nutrition, the risk of mortality in the body mass index category 25.0–29.9 kg/m2 was not statistically different from those in the normal weight or extremely obese groups.
Conclusions: A survival advantage for overweight and obese patients was observed in this large cohort of critically ill patients. However, among those ordered early enteral nutrition, the survival disadvantage for body mass index categories less than 25.0 kg/m2 was minimal or unobservable when compared with higher body mass index categories.
Harris, K et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 828–834
Objectives: To investigate the association between body mass index and mortality in a large, ICU population and determine if the relationship is observed among a subgroup of patients ordered early enteral nutrition.
Design: Retrospective cohort study within a national clinical mixed ICU database of patients admitted between January 1, 2008, and June 30, 2015. Setting: Initial ICU admissions among patients monitored by tele-ICU programs and recorded in the Philips eICU Research Institute database.
Patients: A total of 1,042,710 adult patient stays with ICU length of stay more than 24 hours, of which 74,771 were ordered enteral nutrition within the first 48 hours. Intervention: None.
Measurements and Main Results: Patient stays from 409 ICUs were included. The average age, Acute Physiology and Chronic Health Evaluation IV score, and hospital mortality were 63.6 years, 56.7, and 9.0%, respectively. Hospital mortality among body mass index categories was estimated by multivariable modified Poisson regression models. Compared with the body mass index category 25.0–29.9 kg/m2, hospital mortality was higher among underweight (body mass index, < 18.5; relative risk, 1.35; 95% CI, 1.32–1.39), normal weight (body mass index, 18.5–24.9; relative risk, 1.10; 95% CI, 1.09–1.12), and the extremely obese (body mass index, ≥ 50.0; relative risk, 1.10; 95% CI, 1.05–1.15). However, the risk was not statistically different from patients with body mass index 30.0–49.9 kg/m2. Among patients ordered early enteral nutrition, the risk of mortality in the body mass index category 25.0–29.9 kg/m2 was not statistically different from those in the normal weight or extremely obese groups.
Conclusions: A survival advantage for overweight and obese patients was observed in this large cohort of critically ill patients. However, among those ordered early enteral nutrition, the survival disadvantage for body mass index categories less than 25.0 kg/m2 was minimal or unobservable when compared with higher body mass index categories.
A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation
A Quantile Analysis of Plateau and Driving Pressures: Effects on Mortality in Patients With Acute Respiratory Distress Syndrome Receiving Lung-Protective Ventilation
Villar, J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 843–850
Objectives: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome.
Design: A secondary analysis of existing data from previously reported observational studies. Setting: A network of ICUs. Patients: We studied 778 patients with moderate to severe acute respiratory distress syndrome. Interventions: None.
Measurements and Main Results: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001).
Conclusions: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.
Villar, J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 843–850
Objectives: The driving pressure (plateau pressure minus positive end-expiratory pressure) has been suggested as the major determinant for the beneficial effects of lung-protective ventilation. We tested whether driving pressure was superior to the variables that define it in predicting outcome in patients with acute respiratory distress syndrome.
Design: A secondary analysis of existing data from previously reported observational studies. Setting: A network of ICUs. Patients: We studied 778 patients with moderate to severe acute respiratory distress syndrome. Interventions: None.
Measurements and Main Results: We assessed the risk of hospital death based on quantiles of tidal volume, positive end-expiratory pressure, plateau pressure, and driving pressure evaluated at 24 hours after acute respiratory distress syndrome diagnosis while ventilated with standardized lung-protective ventilation. We derived our model using individual data from 478 acute respiratory distress syndrome patients and assessed its replicability in a separate cohort of 300 acute respiratory distress syndrome patients. Tidal volume and positive end-expiratory pressure had no impact on mortality. We identified a plateau pressure cut-off value of 29 cm H2O, above which an ordinal increment was accompanied by an increment of risk of death. We identified a driving pressure cut-off value of 19 cm H2O where an ordinal increment was accompanied by an increment of risk of death. When we cross tabulated patients with plateau pressure less than 30 and plateau pressure greater than or equal to 30 with those with driving pressure less than 19 and driving pressure greater than or equal to 19, plateau pressure provided a slightly better prediction of outcome than driving pressure in both the derivation and validation cohorts (p < 0.0000001).
Conclusions: Plateau pressure was slightly better than driving pressure in predicting hospital death in patients managed with lung-protective ventilation evaluated on standardized ventilator settings 24 hours after acute respiratory distress syndrome onset.
The value of direct observation to reduce catheter-associated urinary tract infection
The value of direct observation to reduce catheter-associated urinary tract infection
Hickin, S L et al
Intensive and Critical Care Nursing Published online: April 26, 2017, Articles in press
Urinary tract catheterization and monitoring of the urinary output is indispensable in critically ill patients as might indicate intravascular circulating volume, organ perfusion, and pending shock (Paratz et al., 2014; Eastwood et al., 2015). The presence of a urinary catheter however involves the risk of infection. We read with interest the article by Galiczewski and Shurpin (2017) about the efficiency of direct observation to reduce bladder catheter utilization and catheter-associated urinary tract infections in the ICU.
Hickin, S L et al
Intensive and Critical Care Nursing Published online: April 26, 2017, Articles in press
Urinary tract catheterization and monitoring of the urinary output is indispensable in critically ill patients as might indicate intravascular circulating volume, organ perfusion, and pending shock (Paratz et al., 2014; Eastwood et al., 2015). The presence of a urinary catheter however involves the risk of infection. We read with interest the article by Galiczewski and Shurpin (2017) about the efficiency of direct observation to reduce bladder catheter utilization and catheter-associated urinary tract infections in the ICU.
Nurses’ knowledge and perception of delirium screening and assessment in the intensive care unit: Long-term effectiveness of an education-based knowledge translation intervention
Nurses’ knowledge and perception of delirium screening and assessment in the intensive care unit: Long-term effectiveness of an education-based knowledge translation intervention
Hickin, S L et al
Intensive and Critical Care Nursing Published online: April 20, 2017, Articles in press
Hickin, S L et al
Intensive and Critical Care Nursing Published online: April 20, 2017, Articles in press
To determine the impact of education on nurses’ knowledge of delirium, knowledge and perception of a validated screening tool, and delirium screening in the ICU.
A quasi-experimental single group pretest-post-test design set in a 16 bed ICU in a Canadian urban tertiary care centre.
Main outcome measures: Nursing knowledge and perception were measured at baseline, 3-month and 18-month periods. Delirium screening was then assessed over 24-months.
Results: During the study period, 197 surveys were returned; 84 at baseline, 53 at 3-months post education, and 60 at the final assessment period 18-months post intervention. The significant improvements in mean knowledge scores at 3-months post intervention (7.2, SD 1.3) were not maintained at 18-months (5.3, SD 1.1). Screening tool perception scores remained unchanged. Improvements in the perception of utility were significant at both time periods (p = 0.03, 0.02 respectively). Physician value significantly improved at 18-months (p = 0.01). Delirium screening frequency improved after education (p < 0.001) demonstrating a positive correlation over time (p < 0.01).
Conclusion: Multifaceted education is effective in improving delirium knowledge and screening; however, without sustained effort, progress is transient. Education improved perceived tool utility and over time utility perception and physician value improved.
Main outcome measures: Nursing knowledge and perception were measured at baseline, 3-month and 18-month periods. Delirium screening was then assessed over 24-months.
Results: During the study period, 197 surveys were returned; 84 at baseline, 53 at 3-months post education, and 60 at the final assessment period 18-months post intervention. The significant improvements in mean knowledge scores at 3-months post intervention (7.2, SD 1.3) were not maintained at 18-months (5.3, SD 1.1). Screening tool perception scores remained unchanged. Improvements in the perception of utility were significant at both time periods (p = 0.03, 0.02 respectively). Physician value significantly improved at 18-months (p = 0.01). Delirium screening frequency improved after education (p < 0.001) demonstrating a positive correlation over time (p < 0.01).
Conclusion: Multifaceted education is effective in improving delirium knowledge and screening; however, without sustained effort, progress is transient. Education improved perceived tool utility and over time utility perception and physician value improved.
Delays From First Medical Contact to Antibiotic Administration for Sepsis
Delays From First Medical Contact to Antibiotic Administration for Sepsis
Seymour, C W et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 759–765
Objective: To evaluate the association between total medical contact, prehospital, and emergency department delays in antibiotic administration and in-hospital mortality among patient encounters with community-acquired sepsis. Design: Retrospective cohort study. Setting: Nine hospitals served by 21 emergency medical services agencies in southwestern Pennsylvania from 2010 through 2012. Patients: All emergency medical services encounters with community acquired sepsis transported to the hospital.
Measurements and Main Results: Among 58,934 prehospital encounters, 2,683 had community-acquired sepsis, with an in-hospital mortality of 11%. Median time from first medical contact to antibiotic administration (total medical contact delay) was 4.2 hours (interquartile range, 2.7–8.0 hr), divided into a median prehospital delay of 0.52 hours (interquartile range, 0.40–0.66 hr) and a median emergency department delay of 3.6 hours (interquartile range, 2.1–7.5 hr). In a multivariable analysis controlling for other risk factors, total medical contact delay was associated with increased in-hospital mortality (adjusted odds ratio for death, 1.03 [95% CI, 1.00–1.05] per 1-hr delay; p < 0.01), as was emergency department delay (p = 0.04) but not prehospital delay (p = 0.61).
Conclusions: Both total medical contact and emergency department delay in antibiotic administration are associated with in-hospital mortality in community-acquired sepsis.
Seymour, C W et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 759–765
Objective: To evaluate the association between total medical contact, prehospital, and emergency department delays in antibiotic administration and in-hospital mortality among patient encounters with community-acquired sepsis. Design: Retrospective cohort study. Setting: Nine hospitals served by 21 emergency medical services agencies in southwestern Pennsylvania from 2010 through 2012. Patients: All emergency medical services encounters with community acquired sepsis transported to the hospital.
Measurements and Main Results: Among 58,934 prehospital encounters, 2,683 had community-acquired sepsis, with an in-hospital mortality of 11%. Median time from first medical contact to antibiotic administration (total medical contact delay) was 4.2 hours (interquartile range, 2.7–8.0 hr), divided into a median prehospital delay of 0.52 hours (interquartile range, 0.40–0.66 hr) and a median emergency department delay of 3.6 hours (interquartile range, 2.1–7.5 hr). In a multivariable analysis controlling for other risk factors, total medical contact delay was associated with increased in-hospital mortality (adjusted odds ratio for death, 1.03 [95% CI, 1.00–1.05] per 1-hr delay; p < 0.01), as was emergency department delay (p = 0.04) but not prehospital delay (p = 0.61).
Conclusions: Both total medical contact and emergency department delay in antibiotic administration are associated with in-hospital mortality in community-acquired sepsis.
Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial
Liberal Versus Restrictive Transfusion Strategy in Critically Ill Oncologic Patients: The Transfusion Requirements in Critically Ill Oncologic Patients Randomized Controlled Trial
Bergamin, F S et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 766–773
Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Design: Single center, randomized, double-blind controlled trial. Setting: Teaching hospital. Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission. Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03). Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.
Bergamin, F S et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 766–773
Objective: To assess whether a restrictive strategy of RBC transfusion reduces 28-day mortality when compared with a liberal strategy in cancer patients with septic shock. Design: Single center, randomized, double-blind controlled trial. Setting: Teaching hospital. Patients: Adult cancer patients with septic shock in the first 6 hours of ICU admission. Interventions: Patients were randomized to the liberal (hemoglobin threshold, < 9 g/dL) or to the restrictive strategy (hemoglobin threshold, < 7 g/dL) of RBC transfusion during ICU stay. Measurements and Main Results: Patients were randomized to the liberal (n = 149) or to the restrictive transfusion strategy (n = 151) group. Patients in the liberal group received more RBC units than patients in the restrictive group (1 [0–3] vs 0 [0–2] unit; p < 0.001). At 28 days after randomization, mortality rate in the liberal group (primary endpoint of the study) was 45% (67 patients) versus 56% (84 patients) in the restrictive group (hazard ratio, 0.74; 95% CI, 0.53–1.04; p = 0.08) with no differences in ICU and hospital length of stay. At 90 days after randomization, mortality rate in the liberal group was lower (59% vs 70%) than in the restrictive group (hazard ratio, 0.72; 95% CI, 0.53–0.97; p = 0.03). Conclusions: We observed a survival trend favoring a liberal transfusion strategy in patients with septic shock when compared with the restrictive strategy. These results went in the opposite direction of the a priori hypothesis and of other trials in the field and need to be confirmed.
Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis
Antipyretic Therapy in Critically Ill Septic Patients: A Systematic Review and Meta-Analysis
Drewry, A M et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 806–813
Objective: This meta-analysis aimed to examine the impact of antipyretic therapy on mortality in critically ill septic adults. Data Sources: Literature searches were implemented in Ovid Medline, Embase, Scopus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, and ClinicalTrials.gov through February 2016.
Study Selection: Inclusion criteria were observational or randomized studies of septic patients, evaluation of antipyretic treatment, mortality reported, and English-language version available. Studies were excluded if they enrolled pediatric patients, patients with neurologic injury, or healthy volunteers. Criteria were applied by two independent reviewers.
Data Extraction: Two reviewers independently extracted data and evaluated methodologic quality. Outcomes included mortality, frequency of shock reversal, acquisition of nosocomial infections, and changes in body temperature, heart rate, and minute ventilation. Randomized and observational studies were analyzed separately.
Data Synthesis: Eight randomized studies (1,507 patients) and eight observational studies (17,432 patients) were analyzed. Antipyretic therapy did not reduce 28-day/hospital mortality in the randomized studies (relative risk, 0.93; 95% CI, 0.77–1.13; I2 = 0.0%) or observational studies (odds ratio, 0.90; 95% CI, 0.54–1.51; I2 = 76.1%). Shock reversal (relative risk, 1.13; 95% CI, 0.68–1.90; I2 = 51.6%) and acquisition of nosocomial infections (relative risk, 1.13; 95% CI, 0.61–2.09; I2 = 61.0%) were also unchanged. Antipyretic therapy decreased body temperature (mean difference, –0.38°C; 95% CI, –0.63 to –0.13; I2 = 84.0%), but not heart rate or minute ventilation.
Conclusions: Antipyretic treatment does not significantly improve 28-day/hospital mortality in adult patients with sepsis.
Drewry, A M et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 806–813
Objective: This meta-analysis aimed to examine the impact of antipyretic therapy on mortality in critically ill septic adults. Data Sources: Literature searches were implemented in Ovid Medline, Embase, Scopus, Cumulative Index of Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, and ClinicalTrials.gov through February 2016.
Study Selection: Inclusion criteria were observational or randomized studies of septic patients, evaluation of antipyretic treatment, mortality reported, and English-language version available. Studies were excluded if they enrolled pediatric patients, patients with neurologic injury, or healthy volunteers. Criteria were applied by two independent reviewers.
Data Extraction: Two reviewers independently extracted data and evaluated methodologic quality. Outcomes included mortality, frequency of shock reversal, acquisition of nosocomial infections, and changes in body temperature, heart rate, and minute ventilation. Randomized and observational studies were analyzed separately.
Data Synthesis: Eight randomized studies (1,507 patients) and eight observational studies (17,432 patients) were analyzed. Antipyretic therapy did not reduce 28-day/hospital mortality in the randomized studies (relative risk, 0.93; 95% CI, 0.77–1.13; I2 = 0.0%) or observational studies (odds ratio, 0.90; 95% CI, 0.54–1.51; I2 = 76.1%). Shock reversal (relative risk, 1.13; 95% CI, 0.68–1.90; I2 = 51.6%) and acquisition of nosocomial infections (relative risk, 1.13; 95% CI, 0.61–2.09; I2 = 61.0%) were also unchanged. Antipyretic therapy decreased body temperature (mean difference, –0.38°C; 95% CI, –0.63 to –0.13; I2 = 84.0%), but not heart rate or minute ventilation.
Conclusions: Antipyretic treatment does not significantly improve 28-day/hospital mortality in adult patients with sepsis.
New-Onset Atrial Fibrillation in the Critically Ill
New-Onset Atrial Fibrillation in the Critically Ill
Moss, T J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 790–797
Objective: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival. Design: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes. Setting: Tertiary care academic center. Patients: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data. Interventions: None.
Measurements and Main Results: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory failure, and sepsis were the strongest predictors of new-onset atrial fibrillation. In propensity-adjusted regression analyses, clinical new-onset atrial fibrillation was associated with increased hospital mortality (odds ratio, 1.63; 95% CI, 1.01–2.63) and longer length of stay (2.25 d; CI, 0.58–3.92). New-onset atrial fibrillation was not associated with survival after hospital discharge (hazard ratio, 0.99; 95% CI, 0.76–1.28 and hazard ratio, 1.11; 95% CI, 0.67–1.83, respectively, for subclinical and clinical new-onset atrial fibrillation).
Conclusions: Automated analysis of continuous electrocardiogram heart rate dynamics detects new-onset atrial fibrillation in many ICU patients. Though often transient and frequently unrecognized, new-onset atrial fibrillation is associated with poor hospital outcomes.
Moss, T J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 790–797
Objective: To determine the association of new-onset atrial fibrillation with outcomes, including ICU length of stay and survival. Design: Retrospective cohort of ICU admissions. We found atrial fibrillation using automated detection (≥ 90 s in 30 min) and classed as new-onset if there was no prior diagnosis of atrial fibrillation. We identified determinants of new-onset atrial fibrillation and, using propensity matching, characterized its impact on outcomes. Setting: Tertiary care academic center. Patients: A total of 8,356 consecutive adult admissions to either the medical or surgical/trauma/burn ICU with available continuous electrocardiogram data. Interventions: None.
Measurements and Main Results: From 74 patient-years of every 15-minute observations, we detected atrial fibrillation in 1,610 admissions (19%), with median burden less than 2%. Most atrial fibrillation was paroxysmal; less than 2% of admissions were always in atrial fibrillation. New-onset atrial fibrillation was subclinical or went undocumented in 626, or 8% of all ICU admissions. Advanced age, acute respiratory failure, and sepsis were the strongest predictors of new-onset atrial fibrillation. In propensity-adjusted regression analyses, clinical new-onset atrial fibrillation was associated with increased hospital mortality (odds ratio, 1.63; 95% CI, 1.01–2.63) and longer length of stay (2.25 d; CI, 0.58–3.92). New-onset atrial fibrillation was not associated with survival after hospital discharge (hazard ratio, 0.99; 95% CI, 0.76–1.28 and hazard ratio, 1.11; 95% CI, 0.67–1.83, respectively, for subclinical and clinical new-onset atrial fibrillation).
Conclusions: Automated analysis of continuous electrocardiogram heart rate dynamics detects new-onset atrial fibrillation in many ICU patients. Though often transient and frequently unrecognized, new-onset atrial fibrillation is associated with poor hospital outcomes.
Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study
Serial Procalcitonin Predicts Mortality in Severe Sepsis Patients: Results From the Multicenter Procalcitonin MOnitoring SEpsis (MOSES) Study
Schuetz,P et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 781–789
Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States. Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol. Setting: Thirteen U.S.-based emergency departments and ICUs.
Patients: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included. Interventions: Procalcitonin was measured daily over the first 5 days.
Measurements and Main Results: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18–3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.
Conclusions: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.
Schuetz,P et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 781–789
Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States. Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol. Setting: Thirteen U.S.-based emergency departments and ICUs.
Patients: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included. Interventions: Procalcitonin was measured daily over the first 5 days.
Measurements and Main Results: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18–3.30; p < 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.
Conclusions: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.
Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis
Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis
McKown, A C et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 774–780
Objectives: To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis. Design: Retrospective observational study. Setting: Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center. Patients: A total of 1,080 critically ill patients with sepsis. Interventions: None.
Measurements and Main Results: The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33–0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5–30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32–0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87–2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63–1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71–1.57; p = 0.783). Conclusions: Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.
McKown, A C et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 774–780
Objectives: To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis. Design: Retrospective observational study. Setting: Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center. Patients: A total of 1,080 critically ill patients with sepsis. Interventions: None.
Measurements and Main Results: The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33–0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5–30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32–0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87–2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63–1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71–1.57; p = 0.783). Conclusions: Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.
Mortality Risk Stratification After Traumatic Brain Injury and Hazard of Death With Titrated Hypothermia in the Eurotherm3235Trial
Mortality Risk Stratification After Traumatic Brain Injury and Hazard of Death With Titrated Hypothermia in the Eurotherm3235Trial
Andrews, P J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 883–890
Objectives: Hypothermia reduces intracranial hypertension in patients with traumatic brain injury but was associated with harm in the Eurotherm3235Trial. We stratified trial patients by International Mission for Prognosis and Analysis of Clinical Trials in [Traumatic Brain Injury] (IMPACT) extended model sum scores to determine where the balance of risks lay with the intervention.
Design: The Eurotherm3235Trial was a randomized controlled trial, with standardized and blinded outcome assessment. Patients in the trial were split into risk tertiles by IMPACT extended model sum scores. A proportional hazard analysis for death between randomization and 6 months was performed by intervention and IMPACT extended model sum scores tertiles in both the intention-to-treat and the per-protocol populations of the Eurotherm3235Trial.
Setting: Forty-seven neurologic critical care units in 18 countries. Patients: Adult traumatic brain injury patients admitted to intensive care who had suffered a primary, closed traumatic brain injury; increased intracranial pressure; an initial head injury less than 10 days earlier; a core temperature at least 36°C; and an abnormal brain CT.
Intervention: Titrated Hypothermia in the range 32-35°C as the primary intervention to reduce raised intracranial pressure.
Measurements and Main Results: Three hundred eighty-six patients were available for analysis in the intention-to-treat and 257 in the per-protocol population. The proportional hazard analysis (intention-to-treat and per-protocol populations) showed that the treatment effect behaves similarly across all risk stratums. However, there is a trend that indicates that patients in the low-risk group could be at greater risk of suffering harm due to hypothermia.
Conclusions: Hypothermia as a first line measure to reduce intracranial pressure to less than 20 mm Hg is harmful in patients with a lower severity of injury and no clear benefit exists in patients with more severe injuries.
Andrews, P J et al
Critical Care Medicine: May 2017 - Volume 45 - Issue 5 - p 883–890
Objectives: Hypothermia reduces intracranial hypertension in patients with traumatic brain injury but was associated with harm in the Eurotherm3235Trial. We stratified trial patients by International Mission for Prognosis and Analysis of Clinical Trials in [Traumatic Brain Injury] (IMPACT) extended model sum scores to determine where the balance of risks lay with the intervention.
Design: The Eurotherm3235Trial was a randomized controlled trial, with standardized and blinded outcome assessment. Patients in the trial were split into risk tertiles by IMPACT extended model sum scores. A proportional hazard analysis for death between randomization and 6 months was performed by intervention and IMPACT extended model sum scores tertiles in both the intention-to-treat and the per-protocol populations of the Eurotherm3235Trial.
Setting: Forty-seven neurologic critical care units in 18 countries. Patients: Adult traumatic brain injury patients admitted to intensive care who had suffered a primary, closed traumatic brain injury; increased intracranial pressure; an initial head injury less than 10 days earlier; a core temperature at least 36°C; and an abnormal brain CT.
Intervention: Titrated Hypothermia in the range 32-35°C as the primary intervention to reduce raised intracranial pressure.
Measurements and Main Results: Three hundred eighty-six patients were available for analysis in the intention-to-treat and 257 in the per-protocol population. The proportional hazard analysis (intention-to-treat and per-protocol populations) showed that the treatment effect behaves similarly across all risk stratums. However, there is a trend that indicates that patients in the low-risk group could be at greater risk of suffering harm due to hypothermia.
Conclusions: Hypothermia as a first line measure to reduce intracranial pressure to less than 20 mm Hg is harmful in patients with a lower severity of injury and no clear benefit exists in patients with more severe injuries.
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