The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomised controlled trials

The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomised controlled trials
 Zhang XW et al.
Critical Care 2015, 19:417

Introduction: Mild induced hypothermia (MIH) is believed to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. However, a recently published trial demonstrated that hypothermia at 33 °C did not confer a benefit compared with that of 36 °C. Thus, a systematic review and meta-analysis of randomised controlled trials (RCTs) was made to investigate the impact of MIH compared to controls on the outcomes of adult patients after cardiac arrest. Methods: We searched the following electronic databases: PubMed/MEDLINE, the Cochrane Library, Embase, the Web of Science, and Elsevier Science (inception to December 2014). RCTs that compared MIH with controls with temperature >34 °C in adult patients after cardiac arrest were retrieved. Two investigators independently selected RCTs and completed an assessment of the quality of the studies. Data were analysed by the methods recommended by the Cochrane Collaboration. Random errors were evaluated with trial sequential analysis.
Results: Six RCTs, including one abstract, were included. The meta-analysis of included trials revealed that MIH did not significantly decrease the mortality at hospital discharge (risk ratio (RR) = 0.92; 95 % confidence interval (CI), 0.82–1.04; p = 0.17) or at 6 months or 180 days (RR = 0.94; 95 % CI, 0.73–1.21; p = 0.64), but it did reduce the mortality of patients with shockable rhythms at hospital discharge (RR = 0.74; 95 % CI, 0.59–0.92; p = 0.008) and at 6 months or 180 days. However, MIH can improve the outcome of neurological function at hospital discharge (RR = 0.80; 95 % CI, 0.64–0.98; p = 0.04) especially in those patients with shockable rhythm but not at 6 months or 180 days. Moreover, the incidence of complications in the MIH group was significantly higher than that in the control group. Finally, trial sequential analysis indicated lack of firm evidence for a beneficial effect.
Conclusion: The available RCTs suggest that MIH does not appear to improve the mortality of patients with cardiac arrest while it may have a beneficial effect for patients with shockable rhythms. Although MIH may result in some adverse events, it helped lead to better outcomes regarding neurological function at hospital discharge. Large-scale ongoing trials may provide data better applicable to clinical practice.

The experiences of nurses implementing the Modified Early Warning Score and a 24-hour on-call Mobile Intensive Care Nurse: An exploratory study

The experiences of nurses implementing the Modified Early Warning Score and a 24-hour on-call Mobile Intensive Care Nurse: An exploratory study
Stafseth K S et al.
Article in Press


Aims and objectives: To explore experiences of nurses implementing and using the Modified Early Warning Score (MEWS) and a Mobile Intensive Care Nurse (MICN) providing 24-hour on-call nursing support.
Background: To secure patient safety in hospital wards, nurses may increase the quality of care using a tool to detect the failure of vital functions. Possibilities for support can be provided through on-call supervision from a qualified team or nurse.
Design: This exploratory qualitative investigation used focus group interviews with nurses from two wards of a university hospital in Norway.
Methods: A purposive sample of seven registered nurses was interviewed in focus groups. A semi-structured guide and an inductive thematic analysis were used to identify interview themes.
Results: Three themes emerged: (1) experiences with the early recognition of deterioration using the MEWS, (2) supportive collaboration and knowledge transfer between nurses and (3) a “new” precise language using the score for communicating with physicians. The use of scores and support were perceived as improving care for deteriorating patients and for supporting the collaboration of nurses with other professionals.
Conclusion: In our study, nurses described increased confidence in the recognition of deteriorating patients and in the management of such situations. The non-critical attitude, supportive communication and interactive learning according to the MICN were essential elements for success.

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States

A Multicenter Evaluation of Prolonged Empiric Antibiotic Therapy in Adult ICUs in the United States
Thomas, Z et al.
Critical Care Medicine: December 2015 - Volume 43 - Issue 12 - p 2527–2534


Objective: The purpose of this study is to determine the rate of prolonged empiric antibiotic therapy in adult ICUs in the United States. Our secondary objective is to examine the relationship between the prolonged empiric antibiotic therapy rate and certain ICU characteristics. Design: Multicenter, prospective, observational, 72-hour snapshot study. Setting: Sixty-seven ICUs from 32 hospitals in the United States. Patients: Nine hundred ninety-eight patients admitted to the ICU between midnight on June 20, 2011, and June 21, 2011, were included in the study. Intervention: None.
Measurements and Main Results: Antibiotic orders were categorized as prophylactic, definitive, empiric, or prolonged empiric antibiotic therapy. Prolonged empiric antibiotic therapy was defined as empiric antibiotics that continued for at least 72 hours in the absence of adjudicated infection. Standard definitions from the Centers for Disease Control and Prevention were used to determine infection. Prolonged empiric antibiotic therapy rate was determined as the ratio of the total number of empiric antibiotics continued for at least 72 hours divided by the total number of empiric antibiotics. Univariate analysis of factors associated with the ICU prolonged empiric antibiotic therapy rate was conducted using Student t test. A total of 660 unique antibiotics were prescribed as empiric therapy to 364 patients. Of the empiric antibiotics, 333 of 660 (50%) were continued for at least 72 hours in instances where Centers for Disease Control and Prevention infection criteria were not met. Suspected pneumonia accounted for approximately 60% of empiric antibiotic use. The most frequently prescribed empiric antibiotics were vancomycin and piperacillin/tazobactam. ICUs that utilized invasive techniques for the diagnosis of ventilator-associated pneumonia had lower rates of prolonged empiric antibiotic therapy than those that did not, 45.1% versus 59.5% (p = 0.03). No other institutional factor was significantly associated with prolonged empiric antibiotic therapy rate.
Conclusions: Half of all empiric antibiotics ordered in critically ill patients are continued for at least 72 hours in absence of adjudicated infection. Additional studies are needed to confirm these findings and determine the risks and benefits of prolonged empiric therapy in the critically ill.

Nutritional Status and Mortality in the Critically Ill

Nutritional Status and Mortality in the Critically Ill
Mogensen, K et al
December 2015 - Volume 43 - Issue 12


Objectives: The association between nutritional status and mortality in critically ill patients is unclear based on the current literature. To clarify this relation, we analyzed the association between nutrition and mortality in a large population of critically ill patients and hypothesized that mortality would be impacted by nutritional status. Design: Retrospective observational study.
Setting: Single academic medical center. Patients: Six thousand five hundred eighteen adults treated in medical and surgical ICUs between 2004 and 2011. Interventions: None. Measurements and Main Results: All cohort patients received a formal, in-person, standardized evaluation by a registered dietitian. The exposure of interest, malnutrition, was categorized as nonspecific malnutrition, protein-energy malnutrition, or well nourished and determined by data related to anthropometric measurements, biochemical indicators, clinical signs of malnutrition, malnutrition risk factors, and metabolic stress. The primary outcome was all-cause 30-day mortality determined by the Social Security Death Master File. Associations between nutrition groups and mortality were estimated by bivariable and multivariable logistic regression models. Adjusted odds ratios were estimated with inclusion of covariate terms thought to plausibly interact with both nutrition status and mortality. We used propensity score matching on baseline characteristics to reduce residual confounding of the nutrition status category assignment. In the cohort, nonspecific malnutrition was present in 56%, protein-energy malnutrition was present in 12%, and 32% were well nourished. The 30-day and 90-day mortality rates for the cohort were 19.1% and 26.6%, respectively. Nutritional status is a significant predictor of 30-day mortality following adjustment for age, gender, race, medical versus surgical patient type, Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis: nonspecific malnutrition 30-day mortality odds ratio, 1.17 (95% CI, 1.01–1.37); protein-energy malnutrition 30-day mortality odds ratio, 2.10 (95% CI, 1.70–2.59), all relative to patients without malnutrition. In the matched cohort, the adjusted odds of 30-day mortality in the group of propensity score-matched patients with protein-energy malnutrition was two-fold greater than that of patients without malnutrition. Conclusion: In a large population of critically ill adults, an association exists between nutrition status and mortality.

What is the right temperature to cool post-cardiac arrest patients?

What is the right temperature to cool post-cardiac arrest patients?
Chandrasekaran PN et al.
Critical Care 2015, 19:406


Background: Brain ischemia and reperfusion injury leading to tissue degeneration and loss of neurological function following return of spontaneous circulation after cardiac arrest (CA) is a well-known entity. Two landmark trials in 2002 showed improved survival and neurological outcome of comatose survivors of out-of-hospital cardiac arrest (OHCA) of presumed cardiac origin when the patients were subjected to therapeutic hypothermia of 32 to 34 °C for 12 to 24 hours. However, the optimal target temperature for these cohorts is yet to be established and also it is not clear whether strict fever management and maintaining near normal body temperature are alone sufficient to improve the outcome.
Methods: Objective: The objective is to determine whether a hypothermic goal of a near-normal body temperature of 36 °C reduces all-cause mortality compared with a moderate hypothermia of 33 °C for the unconscious survivors of OHCA of presumed cardiac origin when subjected randomly to these different targeted temperatures.
Design: A multicenter, international, open label, randomized controlled trial. Setting: Thirty-six ICUs in Europe and Australia participated in this study.Participants: Unconscious adults (older than 18 years of age) who survived (Glasgow coma scale less than 8) OHCA due to presumed cardiac origin with subsequent persistent return of spontaneous circulation (more than 20 minutes without chest compressions).
Intervention: The above participant cohorts were randomized to targeted body temperature of either 33 °C or 36 °C for 36 hours after the CA with gradual rewarming of both groups to 37 °C (hourly increments of 0.5 °C) after the initial 28 hours. Body temperatures in both the groups were then maintained below 37.5 °C for 72 hours after the initial 36 hours.
Outcomes: Primary outcome measure of all-cause mortality in both the groups at the end of the trial with the secondary outcome measure of all-cause mortality, composite neurological function as evaluated by cerebral performance category scale and modified ranking scale at the end of 180 days were studied.
Results: Out of the 939 participants, all-cause mortality at the end of the trial was 50 % in the 33 °C group (225 of 466 patients) compared with 48 % in the 36 °C group (235 of 473 patients); the hazard ratio with a temperature of 33 °C was 1.06 (95 % confidence interval (CI) 0.89 to 1.28, P = 0.51). At the end of 180 days, 54 % of patients in the 33 °C group versus 52 % in the 36 °C group had died or had poor neurological outcome according to cerebral performance category (risk ratio 1.02, 95 % CI 0.88 to 1.16, P = 0.78) but the modified ranking scale at the end of 180 days was unchanged (52 %) in both groups (risk ratio 1.01, 95 % CI 0.89 to 1.14, P = 0.87).
Conclusions: Maintaining targeted lower normothermia of 36 °C had similar outcomes compared with induced moderate hypothermia of 33 °C for unconscious survivors of OHCA of presumed cardiac cause.

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship

Impact of antibacterials on subsequent resistance and clinical outcomes in adult patients with viral pneumonia: an opportunity for stewardship
Crotty MP et al.
Critical Care 2015, 19:404


Introduction: Respiratory viruses are increasingly recognized as significant etiologies of pneumonia among hospitalized patients. Advanced technologies using multiplex molecular assays and polymerase-chain reaction increase the ability to identify viral pathogens and may ultimately impact antibacterial use.
Method: This was a single-center retrospective cohort study to evaluate the impact of antibacterials in viral pneumonia on clinical outcomes and subsequent multidrug-resistant organism (MDRO) infections/colonization. Patients admitted from March 2013 to November 2014 with positive respiratory viral panels (RVP) and radiographic findings of pneumonia were included. Patients transferred from an outside hospital or not still hospitalized 72 hours after the RVP report date were excluded. Patients were categorized based on exposure to systemic antibacterials: less than 3 days representing short-course therapy and 3 to 10 days being long-course therapy.
Results: A total of 174 patients (long-course, n = 67; short-course, n = 28; mixed bacterial-viral infection, n = 79) were included with most being immunocompromised (56.3 %) with active malignancy the primary etiology (69.4 %). Rhinovirus/Enterovirus (23 %), Influenza (19 %), and Parainfluenza (15.5 %) were the viruses most commonly identified. A total of 13 different systemic antibacterials were used as empiric therapy in the 95 patients with pure viral infection for a total of 466 days-of-therapy. Vancomycin (50.7 %), cefepime (40.3 %), azithromycin (40.3 %), meropenem (23.9 %), and linezolid (20.9 %) were most frequently used. In-hospital mortality did not differ between patients with viral pneumonia in the short-course and long-course groups. Subsequent infection/colonization with a MDRO was more frequent in the long-course group compared to the short-course group (53.2 vs 21.1 %; P = 0.027).
Conclusion: This study found that long-course antibacterial use in the setting of viral pneumonia had no impact on clinical outcomes but increased the incidence of subsequent MDRO infection/colonization.

Safety and Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study

Safetyand Efficacy of Combined Extracorporeal CO2 Removal and Renal Replacement Therapy in Patients With Acute Respiratory Distress Syndrome and Acute Kidney Injury: The Pulmonary and Renal Support in Acute Respiratory Distress Syndrome Study
Allardet-Servent, J et al.
Critical Care Medicine: December 2015 - Volume 43 - Issue 12 - p 2570–2581


Objective: To assess the safety and efficacy of combining extracorporeal CO2 removal with continuous renal replacement therapy in patients presenting with acute respiratory distress syndrome and acute kidney injury. Design: Prospective human observational study.
Settings: Patients received volume-controlled mechanical ventilation according to the acute respiratory distress syndrome net protocol. Continuous venovenous hemofiltration therapy was titrated to maintain maximum blood flow and an effluent flow of 45 mL/kg/h with 33% predilution.
Patients: Eleven patients presenting with both acute respiratory distress syndrome and acute kidney injury required renal replacement therapy. Interventions: A membrane oxygenator (0.65 m2) was inserted within the hemofiltration circuit, either upstream (n = 7) or downstream (n = 5) of the hemofilter. Baseline corresponded to tidal volume 6 mL/kg of predicted body weight without extracorporeal CO2 removal. The primary endpoint was 20% reduction in PaCO2 at 20 minutes after extracorporeal CO2 removal initiation. Tidal volume was subsequently reduced to 4 mL/kg for the remaining 72 hours. Measurements and Main Results: Twelve combined therapies were conducted in the 11 patients. Age was 70 ± 9 years, Simplified Acute Physiology Score II was 69 ± 13, Sequential Organ Failure Assessment score was 14 ± 4, lung injury score was 3 ± 0.5, and PaO2/FIO2 was 135 ± 41. Adding extracorporeal CO2 removal at tidal volume 6 mL/kg decreased PaCO2 by 21% (95% CI, 17–25%), from 47 ± 11 to 37 ± 8 Torr (p < 0.001). Lowering tidal volume to 4 mL/kg reduced minute ventilation from 7.8 ± 1.5 to 5.2 ± 1.1 L/min and plateau pressure from 25 ± 4 to 21 ± 3 cm H2O and raised PaCO2 from 37 ± 8 to 48 ± 10 Torr (all p < 0.001). On an average of both positions, the oxygenator’s blood flow was 410 ± 30 mL/min and the CO2 removal rate was 83 ± 20 mL/min. The oxygenator blood flow (p <0 .001="" and="" br="" co2="" concern.="" hemofilter.="" higher="" membrane="" no="" of="" oxygenator="" p="0.083)" placed="" rate="" removal="" safety="" the="" there="" upstream="" was="" were="" when="">Conclusions: Combining extracorporeal CO2 removal and continuous venovenous hemofiltration in patients with acute respiratory distress syndrome and acute kidney injury is safe and allows efficient blood purification together with enhanced lung protective ventilation.

Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients: a systematic review and meta-analysis of randomized controlled trials

Risks and benefits of stress ulcer prophylaxis in adult neurocritical care patients:a systematic review and meta-analysis of randomized controlled trials
Bolin Liu
Critical Care 2015, 19:409


Introduction: Neurocritical care patients are at high risk for stress-related upper gastrointestinal (UGI) bleeding. The aim of this meta-analysis was to evaluate the risks and benefits of stress ulcer prophylaxis (SUP) in this patient group.
Methods: A systematic search of major electronic literature databases was conducted. Eligible studies were randomized controlled trials (RCTs) in which researchers compared the effects of SUP (with proton pump inhibitors or histamine 2 receptor antagonists) with placebo or no prophylaxis in neurocritical care patients. The primary outcome was UGI bleeding, and secondary outcomes were all-cause mortality and nosocomial pneumonia. Study heterogeneity was sought and quantified. The results were reported as risk ratios/relative risks (RRs) with 95 % confidence intervals (CIs).
Results: We included 8 RCTs comprising an aggregate of 829 neurocritical care patients. Among these trials, one study conducted in a non–intensive care unit setting that did not meet our inclusion criteria was ultimately included based on further evaluation. All studies were judged as having a high or unclear risk of bias. SUP was more effective than placebo or no prophylaxis at reducing UGI bleeding (random effects: RR 0.31; 95 % CI 0.20–0.47; P < 0.00001; I 2 = 45 %) and all-cause mortality (fixed effects: RR 0.70; 95 % CI 0.50–0.98; P = 0.04; I 2 = 0 %). There was no difference between SUP and placebo or no prophylaxis regarding nosocomial pneumonia (random effects: RR 1.14; 95 % CI 0.67–1.94; P = 0.62; I 2 = 42 %). The slight asymmetry of the funnel plots raised the concern of small trial bias, and apparent heterogeneity existed in participants, interventions, control treatments, and outcome measures.
Conclusions: In neurocritical care patients, SUP seems to be more effective than placebo or no prophylaxis in preventing UGI bleeding and reducing all-cause mortality while not increasing the risk of nosocomial pneumonia. The robustness of this conclusion is limited by a lack of trials with a low risk of bias, sparse data, heterogeneity among trials, and a concern regarding small trial bias. Trial registration International Prospective Register of Systematic Reviews (PROSPERO) identifier: CRD42015015802. Date of registration: 6 Jan 2015.

Pain-related Somato Sensory Evoked Potentials: a potential new tool to improve the prognostic prediction of coma after cardiac arrest

Pain-related Somato Sensory Evoked Potentials: a potential new tool to improve the prognostic prediction of coma after cardiac arrest
Zanatta P et al.
Critical Care 2015, 19:403


Introduction: Early prediction of a good outcome in comatose patients after cardiac arrest still remains an unsolved problem. The main aim of the present study was to examine the accuracy of middle-latency SSEP triggered by a painful electrical stimulation on median nerves to predict a favorable outcome.
Methods: No- and low-flow times, pupillary reflex, Glasgow motor score and biochemical data were evaluated at ICU admission. The following were considered within 72 h of cardiac arrest: highest creatinine value, hyperthermia occurrence, EEG, SSEP at low- (10 mA) and high-intensity (50 mA) stimulation, and blood pressure reactivity to 50 mA. Intensive care treatments were also considered. Data were compared to survival, consciousness recovery and 6-month CPC (Cerebral Performance Category).
Results: Pupillary reflex and EEG were statistically significant in predicting survival; the absence of blood pressure reactivity seems to predict brain death within 7 days of cardiac arrest. Middle- and short-latency SSEP were statistically significant in predicting consciousness recovery, and middle-latency SSEP was statistically significant in predicting 6-month CPC outcome. The prognostic capability of 50 mA middle-latency-SSEP was demonstrated to occur earlier than that of EEG reactivity.
Conclusions: Neurophysiological evaluation constitutes the key to early information about the neurological prognostication of postanoxic coma. In particular, the presence of 50 mA middle-latency SSEP seems to be an early and reliable predictor of good neurological outcome, and its absence constitutes a marker of poor prognosis. Moreover, the absence 50 mA blood pressure reactivity seems to identify patients evolving towards the brain death.

Comparison of community-acquired, hospital-acquired, and intensive care unit-acquired acute respiratory distress syndrome: a prospective observational cohort study

Comparison of community-acquired, hospital-acquired, and intensive care unit-acquired acute respiratory distress syndrome: a prospective observational cohort study

Critical Care 2015, 19:384

Kao, Kuo-Chin et al



Introduction: Acute respiratory distress syndrome (ARDS) is a syndrome characterized by diffuse pulmonary edema and severe hypoxemia that usually occurs after an injury such as sepsis, aspiration and pneumonia. Little is known about the relation between the setting where the syndrome developed and outcomes in ARDS patients.
Methods: This is a 1-year prospective observational study conducted at a tertiary referred hospital. ARDS was defined by the Berlin criteria. Community-acquired ARDS, hospital-acquired ARDS and intensive care unit (ICU)-acquired ARDS were defined as ARDS occurring within 48 hours of hospital or ICU admission, more than 48 hours after hospital admission and ICU admission. The primary and secondary outcomes were short- and long- term mortality rates and ventilator-free and ICU-free days.
Results: Of the 3002 patients screened, 296 patients had a diagnosis of ARDS, including 70 (23.7 %) with community-acquired ARDS, 83 (28 %) with hospital-acquired ARDS, and 143 (48.3 %) with ICU-acquired ARDS. The overall ICU mortality rate was not significantly different in mild, moderate and severe ARDS (50 %, 50 % and 56 %, p = 0.25). The baseline characteristics were similar other than lower rate of liver disease and metastatic malignancy in community-acquired ARDS than in hospital-acquired and ICU-acquired ARDS. A multiple logistic regression analysis indicated that age, sequential organ function assessment score and community-acquired ARDS were independently associated with hospital mortality. For community-acquired, hospital-acquired and ICU-acquired ARDS, ICU mortality rates were 37 % 61 % and 52 %; hospital mortality rates were 49 %, 74 % and 68 %. The ICU and hospital mortality rates of community-acquired ARDS were significantly lower than hospital-acquired and ICU-acquired ARDS (p = 0.001 and p = 0.001). The number of ventilator-free days was significantly lower in ICU-acquired ARDS than in community-acquired and hospital-acquired ARDS (11 ± 9, 16 ± 9, and 14 ± 10 days, p = 0.001). The number of ICU-free days was significantly higher in community-acquired ARDS than in hospital-acquired and ICU-acquired ARDS (8 ± 10, 4 ± 8, and 3 ± 6 days, p = 0.001). Conclusions: Community-acquired ARDS have lower short- and long-term mortality rates than hospital-acquired or ICU-acquired ARDS.

Extracorporeal decarboxylation in patients with severe traumatic brain injury and ARDS enables effective control of intracranial pressure

Extracorporeal decarboxylation in patients with severe traumatic brain injury and ARDS enables effective control of intracranial pressure

Critical Care 2015, 19:381

Munoz-Bendix, c. et al


Introduction: Acute respiratory distress syndrome (ARDS) with concomitant impairment of oxygenation and decarboxylation represents a complex problem in patients with increased intracranial pressure (ICP). Permissive hypercapnia is not an option to obtain and maintain lung-protective ventilation in the presence of elevated ICP. Pumpless extracorporeal lung assist (pECLA) devices (iLA Membrane Ventilator; Novalung, Heilbronn, Germany) can improve decarboxylation without aggravation associated with invasive ventilation. In this pilot series, we analyzed the safety and efficacy of pECLA in patients with ARDS and elevated ICP after severe traumatic brain injury (TBI).
Methods: The medical records of ten patients (eight male, two female) with severe ARDS and severe TBI concurrently managed with external ventricular drainage in the neurointensive care unit (NICU) were retrospectively analyzed. The effect of pECLA on enabling lung-protective ventilation was evaluated using the difference between plateau pressure and positive end-expiratory pressure, defined as driving pressure (ΔP), during the 3 days preceding the implant of pECLA devices until 3 days afterward. The ICP threshold was set at 20 mmHg. To evaluate effects on ICP, the volume of daily cerebrospinal fluid (CSF) drainage needed to maintain the set ICP threshold was compared pre- and postimplant.
Results: The ΔP values after pECLA implantation decreased from a mean 17.1 ± 0.7 cm/H 2 O to 11.9±0.5 cm/H 2 O (p = 0.011). In spite of this improved lung-protective ventilation, carbon dioxide pressure decreased from 46.6 ± 3.9 mmHg to 39.7 ± 3.5 mmHg (p = 0.005). The volume of daily CSF drainage needed to maintain ICP at 20 mmHg decreased significantly from 141.5 ± 103.5 ml to 62.2 ± 68.1 ml (p = 0.037). Conclusions: For selected patients with concomitant severe TBI and ARDS, the application of pECLA is safe and effective. pECLA devices improve decarboxylation, thus enabling lung-protective ventilation. At the same time, potentially detrimental hypercapnia that may increase ICP is avoided. Larger prospective trials are warranted to further elucidate application of pECLA devices in NICU patients.

An Environmental Scan for Early Mobilization Practices in U.S. ICUs

An Environmental Scan for Early Mobilization Practices in U.S. ICUs

Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2360–2369

Bakhru, RN. Et al


Objective: Early mobilization improves patient outcomes. However, diffusion of this intervention into standard ICU practice is unknown. Dissemination and implementation efforts may be guided by an environmental scan to detail readiness for early mobilization, current practice, and barriers to early mobilization. Design: A telephone survey. Setting: U.S. ICUs. Subjects: Five hundred randomly selected U.S. ICUs stratified by regional hospital density and hospital size. Interventions: None.
Measurements and Main Results: We surveyed 687 ICUs for a 73% response rate (500 ICUs); 99% of respondents were nursing leadership. Fifty-one percent of hospitals reported an academic affiliation. Surveyed ICUs were most often mixed medical/surgical (58%) or medical (22%) with a median of 16 beds (12–24). Thirty-four percent reported presence of a dedicated physical and/or occupational therapy team for the ICU. Overall, 45% of ICUs reported early mobilization practice; two thirds of ICUs with early mobilization practice reported using a written early mobilization protocol. In ICUs with early mobilization practice, 52% began the intervention at admission and 74% enacted early mobilization for both ventilated and nonventilated patients. Early mobilization was provided a median of 6 days per week, twice daily. Factors independently associated with early mobilization protocols include dedicated physical/occupational therapy (odds ratio, 3.34; 95% CI, 2.13–5.22; p < 0.01), American Hospital Association region 2 (odds ratio, 3.33; 95% CI, 1.04–10.64; p = 0.04), written sedation protocol (odds ratio, 2.36; 95% CI, 1.25–4.45; p < 0.01), daily multidisciplinary rounds (odds ratio, 2.31; 95% CI, 1.29–4.15; p < 0.01), and written daily goals for patients (odds ratio, 2.17; 95% CI, 1.02–4.64; p = 0.04). Commonly cited barriers included equipment, staffing, patient and caregiver safety, and competing priorities. In ICUs without early mobilization adoption, 78% have considered implementation but cite barriers including competing priorities and need for further planning. Conclusions: Diffusion regarding benefits of early mobilization has occurred, but adoption into practice is lagging. Mandates for multidisciplinary rounds and formal sedation protocols may be necessary strategies to increase the likelihood of successful early mobilization implementation. Methods to accurately assess and compare institutional performance via practice audit are needed.

Diagnosis and management of inhalation injury: an updated review

Diagnosis and management of inhalation injury: an updated review

Critical Care 2015, 19:351 

Walker, PF. et al.


In this article we review recent advances made in the pathophysiology, diagnosis, and treatment of inhalation injury. Historically, the diagnosis of inhalation injury has relied on nonspecific clinical exam findings and bronchoscopic evidence. The development of a grading system and the use of modalities such as chest computed tomography may allow for a more nuanced evaluation of inhalation injury and enhanced ability to prognosticate. Supportive respiratory care remains essential in managing inhalation injury. Adjuncts still lacking definitive evidence of efficacy include bronchodilators, mucolytic agents, inhaled anticoagulants, nonconventional ventilator modes, prone positioning, and extracorporeal membrane oxygenation. Recent research focusing on molecular mechanisms involved in inhalation injury has increased the number of potential therapies.

Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome

Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome

Critical Care 2015, 19:374 

Toner, P. et al.


Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS. 

Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study

Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study

Critical Care 2015, 19:371
Wang N et al


Introduction: Early and aggressive volume resuscitation is fundamental in the treatment of hemodynamic instability in critically ill patients and improves patient survival. However, one important consequence of fluid administration is the risk of developing fluid overload (FO), which is associated with increased mortality in patients with acute kidney injury (AKI). We evaluated the impact of fluid balance on mortality in intensive care unit (ICU) patients with AKI.
Methods: The data were extracted from the Beijing Acute Kidney Injury Trial. This trial was a prospective, observational, multicenter study conducted in 30 ICUs among 28 tertiary hospitals in Beijing, China, from 1 March to 31 August 2012. In total, 3107 patients were admitted consecutively, and 2526 patients were included in this study. The data from the first 3 sequential days were analyzed. The AKI severity was classified according to the Kidney Disease: Improving Global Outcomes guidelines. The daily fluid balance was recorded, and the cumulative fluid balance was registered at 24, 48, and 72 h. A multivariate analysis was performed with Cox regression to determine the impact of fluid balance on mortality in patients with AKI.
Results: Among the 2526 patients included, 1172 developed AKI during the first 3 days. The mortality was 25.7 % in the AKI group and 10.1 % in the non-AKI group (P < 0.001). The daily fluid balance was higher, and the cumulative fluid balance was significantly greater, in the AKI group than in the non-AKI group. FO was an independent risk factor for the incidence of AKI (odds ratio 4.508, 95 % confidence interval 2.900 to 7.008, P < 0.001) and increased the severity of AKI. Non-surviving patients with AKI had higher cumulative fluid balance during the first 3 days (2.77 [0.86–5.01] L versus 0.93 [−0.80 to 2.93] L, P < 0.001) than survivors did. Multivariate analysis revealed that the cumulative fluid balance during the first 3 days was an independent risk factor for 28-day mortality. Conclusions: In this multicenter ICU study, the fluid balance was greater in patients with AKI than in patients without AKI. FO was an independent risk factor for the incidence of AKI and increased the severity of AKI. A higher cumulative fluid balance was an important factor associated with 28-day mortality following AKI.

Ventilator-derived carbon dioxide production to assess energy expenditure in critically ill patients: proof of concept

Ventilator-derived carbon dioxide production to assess energy expenditure in critically ill patients: proof of concept

Critical Care 2015, 19:370

Stapel, SN. et al


Introduction: Measurement of energy expenditure (EE) is recommended to guide nutrition in critically ill patients. Availability of a gold standard indirect calorimetry is limited, and continuous measurement is unfeasible. Equations used to predict EE are inaccurate. The purpose of this study was to provide proof of concept that EE can be accurately assessed on the basis of ventilator-derived carbon dioxide production (VCO 2 ) and to determine whether this method is more accurate than frequently used predictive equations.
Methods: In 84 mechanically ventilated critically ill patients, we performed 24-h indirect calorimetry to obtain a gold standard EE. Simultaneously, we collected 24-h ventilator-derived VCO 2 , extracted the respiratory quotient of the administered nutrition, and calculated EE with a rewritten Weir formula. Bias, precision, and accuracy and inaccuracy rates were determined and compared with four predictive equations: the Harris–Benedict, Faisy, and Penn State University equations and the European Society for Clinical Nutrition and Metabolism (ESPEN) guideline equation of 25 kcal/kg/day.
Results: Mean 24-h indirect calorimetry EE was 1823 ± 408 kcal. EE from ventilator-derived VCO 2 was accurate (bias +141 ± 153 kcal/24 h; 7.7 % of gold standard) and more precise than the predictive equations (limits of agreement −166 to +447 kcal/24 h). The 10 % and 15 % accuracy rates were 61 % and 76 %, respectively, which were significantly higher than those of the Harris–Benedict, Faisy, and ESPEN guideline equations. Large errors of more than 30 % inaccuracy did not occur with EE derived from ventilator-derived VCO 2 . This 30 % inaccuracy rate was significantly lower than that of the predictive equations.
Conclusions: In critically ill mechanically ventilated patients, assessment of EE based on ventilator-derived VCO 2 is accurate and more precise than frequently used predictive equations. It allows for continuous monitoring and is the best alternative to indirect calorimetry.

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk

Arterial Catheter Use in the ICU: A National Survey of Antiseptic Technique and Perceived Infectious Risk


Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2346–2353


Cohen, David M. et al


Objectives: Recent studies have shown that the occurrence rate of bloodstream infections associated with arterial catheters is 0.9–3.4/1,000 catheter-days, which is comparable to that of central venous catheters. In 2011, the Centers for Disease Control and Prevention published new guidelines recommending the use of limited barrier precautions during arterial catheter insertion, consisting of sterile gloves, a surgical cap, a surgical mask, and a small sterile drape. The goal of this study was to assess the attitudes and current infection prevention practices used by clinicians during insertion of arterial catheters in ICUs in the United States. Design: An anonymous, 22-question web-based survey of infection prevention practices during arterial catheter insertion. Setting: Clinician members of the Society of Critical Care Medicine. Subjects: Eleven thousand three hundred sixty-one physicians, nurse practitioners, physician assistants, respiratory therapists, and registered nurses who elect to receive e-mails from the Society of Critical Care Medicine. Interventions: None. Measurements and Main Results: There were 1,265 responses (11% response rate), with 1,029 eligible participants after exclusions were applied. Only 44% of participants reported using the Centers for Disease Control and Prevention–recommended barrier precautions during arterial catheter insertion, and only 15% reported using full barrier precautions. The mean and median estimates of the incidence density of bloodstream infections associated with arterial catheters were 0.3/1,000 catheter-days and 0.1/1,000 catheter-days, respectively. Thirty-nine percent of participants reported that they would support mandatory use of full barrier precautions during arterial catheter insertion. Conclusions: Barrier precautions are used inconsistently by critical care clinicians during arterial catheter insertion in the ICU setting. Less than half of clinicians surveyed were in compliance with current Centers for Disease Control and Prevention guidelines. Clinicians significantly underestimated the infectious risk posed by arterial catheters, and support for mandatory use of full barrier precautions was low. Further studies are warranted to determine the optimal preventive strategies for reducing bloodstream infections associated with arterial catheters.

Ten Myths and Misconceptions Regarding Pain Management in the ICU

Ten Myths and Misconceptions Regarding Pain Management in the ICU

Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2468–2478


Sigakis, Matthew J. G.et al


Objectives: The aim of this article is to expose common myths and misconceptions regarding pain assessment and management in critically ill patients that interfere with effective care. We comprehensively review the literature refuting these myths and misconceptions and describe evidence-based strategies for improving pain management in the ICU. Data Sources: Current peer-reviewed academic journals, as well as standards and guidelines from professional societies. Study Selection: The most current evidence was selected for review based on the highest degree of supportive evidence. Data Extraction: Data were obtained via medical search databases, including OvidSP, and the National Library of Medicine’s MEDLINE database via PubMed. Data Synthesis: After a comprehensive literature review, conclusions were drawn based on the strength of evidence and the most current understanding of pain management practices in ICU. Conclusions: Myths and misconceptions regarding management of pain in the ICU are prevalent. Review of current evidence refutes these myths and misconceptions and provides insights and recommendations to ensure best practices. 

Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections

Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections

Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2283–2291

Vincent, Jean-Louis et al.



Objective: Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique. 
Design: Observational study. Setting: Nine ICUs in six European countries. Patients: Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion. Interventions: None. 
Measurements and Main Results: We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up to 57% of patients. 
Conclusions: Polymerase chain reaction/electrospray ionization-mass spectrometry provides rapid pathogen identification in critically ill patients. The ability to rule out infection within 6 hours has potential clinical and economic benefits.

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine as First-Line Vasoactive Drugs in Pediatric Septic Shock

Double-Blind Prospective Randomized Controlled Trial of Dopamine Versus Epinephrine asFirst-Line Vasoactive Drugs in Pediatric Septic Shock


Critical Care Medicine: November 2015 - Volume 43 - Issue 11 - p 2292–2302



Ventura, Andréa M. C. et al


Objectives: The primary outcome was to compare the effects of dopamine or epinephrine in severe sepsis on 28-day mortality; secondary outcomes were the rate of healthcare–associated infection, the need for other vasoactive drugs, and the multiple organ dysfunction score. Design: Double-blind, prospective, randomized controlled trial from February 1, 2009, to July 31, 2013. Setting: PICU, Hospital Universitário da Universidade de São Paulo, Brazil. Patients: Consecutive children who are 1 month to 15 years old and met the clinical criteria for fluid-refractory septic shock. Exclusions were receiving vasoactive drug(s) prior to hospital admission, having known cardiac disease, having already participated in the trial during the same hospital stay, refusing to participate, or having do-not-resuscitate orders.
Interventions: Patients were randomly assigned to receive either dopamine (5–10 μg/kg/min) or epinephrine (0.1–0.3 μg/kg/min) through a peripheral or intraosseous line. Patients not reaching predefined stabilization criteria after the maximum dose were classified as treatment failure, at which point the attending physician gradually stopped the study drug and started another catecholamine.
Measurements and Main Results: Physiologic and laboratory data were recorded. Baseline characteristics were described as proportions and mean (± SD) and compared using appropriate statistical tests. Multiple regression analysis was performed, and statistical significance was defined as a p value of less than 0.05. Baseline characteristics and therapeutic interventions for the 120 children enrolled (63, dopamine; 57, epinephrine) were similar. There were 17 deaths (14.2%): 13 (20.6%) in the dopamine group and four (7%) in the epinephrine group (p = 0.033). Dopamine was associated with death (odds ratio, 6.5; 95% CI, 1.1–37.8; p = 0.037) and healthcare–associated infection (odds ratio, 67.7; 95% CI, 5.0–910.8; p = 0.001). The use of epinephrine was associated with a survival odds ratio of 6.49.
Conclusions: Dopamine was associated with an increased risk of death and healthcare–associated infection. Early administration of peripheral or intraosseous epinephrine was associated with increased survival in this population. Limitations should be observed while interpreting these results

Rehospitalizations Following Sepsis: Common and Costly

Rehospitalizations Following Sepsis: Common and Costly

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2085–2093


Chang, Dong W. et al.

Objective: Although recent studies have shown that 30-day readmissions following sepsis are common, the overall fiscal impact of these rehospitalizations and their variability between hospitals relative to other high-risk conditions, such as congestive heart failure and acute myocardial infarction, are unknown. The objectives of this study were to characterize the frequency, cost, patient-level risk factors, and hospital-level variation in 30-day readmissions following sepsis compared with congestive heart failure and acute myocardial infarction. 
Design: A retrospective cohort analysis of hospitalizations from 2009 to 2011. Setting: All acute care, nonfederal hospitals in California. Patients: Hospitalizations for sepsis (n = 240,198), congestive heart failure (n = 193,153), and acute myocardial infarction (n = 105,684) identified by administrative discharge codes. Interventions: None. Measurements and Main Results: The primary outcomes were the frequency and cost of all-cause 30-day readmissions following hospitalization for sepsis compared with congestive heart failure and acute myocardial infarction. Variability in predicted readmission rates between hospitals was calculated using mixed-effects logistic regression analysis. The all-cause 30-day readmission rates were 20.4%, 23.6%, and 17.7% for sepsis, congestive heart failure, and acute myocardial infarction, respectively. The estimated annual costs of 30-day readmissions in the state of California during the study period were $500 million/yr for sepsis, $229 million/yr for congestive heart failure, and $142 million/yr for acute myocardial infarction. The risk- and reliability-adjusted readmission rates across hospitals ranged from 11.0% to 39.8% (median, 19.9%; interquartile range, 16.1–26.0%) for sepsis, 11.3% to 38.4% (median, 22.9%; interquartile range, 19.2–26.6%) for congestive heart failure, and 3.6% to 40.8% (median, 17.0%; interquartile range, 12.2–20.0%) for acute myocardial infarction. Patient-level factors associated with higher odds of 30-day readmission following sepsis included younger age, male gender, Black or Native American race, a higher burden of medical comorbidities, urban residence, and lower income. 
Conclusion: Sepsis is a leading contributor to excess healthcare costs due to hospital readmissions. Interventions at clinical and policy levels should prioritize identifying effective strategies to reduce sepsis readmissions

Variations in the Operational Process of Withdrawal of Life-Sustaining Therapy

Variations in the Operational Process of Withdrawal of Life-Sustaining Therapy

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p e450–e457  


van Beinum, A. et al.

Objective: The process of withdrawal of life-sustaining therapy remains poorly described in the current literature despite its importance for patient comfort and optimal end-of-life care. We conducted a structured review of the published literature to summarize patterns of withdrawal of life-sustaining therapy processes in adult ICUs. Data Sources: Electronic journal databases were searched from date of first issue until April 2014. Study Selection: Original research articles describing processes of life-support therapy withdrawal in North American, European, and Australian ICUs were included. Data Extraction: From each article, we extracted definitions of withdrawal of life-sustaining therapy, descriptions and order of interventions withdrawn, drugs administered, and timing from withdrawal of life-sustaining therapy until death. Data Synthesis: Fifteen articles met inclusion criteria. Definitions of withdrawal of life-sustaining therapy varied and focused on withdrawal of mechanical ventilation; two studies did not present operational definitions. All studies described different aspects of process of life-support therapy withdrawal and measured different time periods prior to death. Staggered patterns of withdrawal of life-support therapy were reported in all studies describing order of interventions withdrawn, with vasoactive drugs withdrawn first followed by gradual withdrawal of mechanical ventilation. Processes of withdrawal of life-sustaining therapy did not seem to influence time to death.
Conclusions: Further description of the operational processes of life-sustaining therapy withdrawal in a more structured manner with standardized definitions and regular inclusion of measures of patient comfort and family satisfaction with care is needed to identify which patterns and processes are associated with greatest perceived patient comfort and family satisfaction with care

Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU

Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU


Critical Care 2015, 19:364


Campbell J et al.


Introduction: The number of patients admitted to ICU who have liver cirrhosis is rising. Current prognostic scoring tools to predict ICU mortality have performed poorly in this group. In previous research from a single centre, a novel scoring tool which modifies the Child-Turcotte Pugh score by adding Lactate concentration, the CTP + L score, is strongly associated with mortality. This study aims to validate the use of the CTP + L scoring tool for predicting ICU mortality in patients admitted to a general ICU with cirrhosis, and to determine significant predictive factors for mortality with this group of patients. This study will also explore the use of the Royal Free Hospital (RFH) score in this cohort.
Methods: A total of 84 patients admitted to the Glasgow Royal Infirmary ICU between June 2012 and Dec 2013 with cirrhosis were included. An additional cohort of 115 patients was obtained from two ICUs in London (St George’s and St Thomas’) collected between October 2007 and July 2009. Liver specific and general ICU scoring tools were calculated for both cohorts, and compared using area under the receiver operating characteristic (ROC) curves. Independent predictors of ICU mortality were identified by univariate analysis. Multivariate analysis was utilised to determine the most predictive factors affecting mortality within these patient groups.
Results: Within the Glasgow cohort, independent predictors of ICU mortality were identified as Lactate (p < 0.001), Bilirubin (p = 0.0048), PaO 2 /FiO 2 Ratio (p = 0.032) and PT ratio (p = 0.012). Within the London cohort, independent predictors of ICU mortality were Lactate (p < 0.001), PT ratio (p < 0.001), Bilirubin (p = 0.027), PaO 2 /FiO 2 Ratio (p = 0.0011) and Ascites (p = 0.023). The CTP + L and RFH scoring tools had the highest ROC value in both cohorts examined.
Conclusion: The CTP + L and RFH scoring tool are validated prognostic scoring tools for predicting ICU mortality in patients admitted to a general ICU with cirrhosis. 

Time to Appropriate Antibiotic Therapy Is an Independent Determinant of Postinfection ICU and Hospital Lengths of Stay in Patients with Sepsis

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2133–2140

Zhang, D

Objective: To assess the timing of appropriate antibiotic therapy as a determinant of postinfection hospital and ICU lengths of stay in patients with sepsis. Design: Single-center retrospective cohort study (January 2008–December 2012). Setting: One thousand two hundred fifty–bed academic hospital. Patients: One thousand fifty-eight consecutive blood culture positive patients. Interventions: We retrospectively identified adult patients with severe sepsis or septic shock. Timing of appropriate antibiotic therapy was determined from blood culture collection time to the administration of the first dose of antibiotic therapy with documented in vitro susceptibility against the identified pathogen. We constructed generalized linear models to examine the determinants of attributable lengths of stay. Measurements and Main Results: The median (interquartile range) time from blood culture collection to the administration of appropriate antibiotic therapy was 6.7 hours (0.0–23.3 hr). Linear regression analysis adjusting for severity of illness and comorbid conditions identified time to appropriate antibiotic therapy to be an independent determinant of postinfection ICU length of stay (0.095-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.057–0.132 d; p < 0.001) and postinfection hospital length of stay (0.134-d increase per hr of time to deliver appropriate antibiotic therapy; 95% CI, 0.074–0.194 d; p < 0.001). Other independent determinants associated with increasing ICU length of stay and hospital length of stay were mechanical ventilation (both ICU and hospital lengths of stay) and incremental peak WBC counts (hospital length of stay only). Incremental changes in severity of illness assessed by Acute Physiology and Chronic Health Evaluation II scores and comorbidity burden assessed by the Charlson comorbidity score were independently associated with decreases in ICU length of stay and hospital length of stay. Conclusions: We identified time to appropriate antibiotic therapy in patients with sepsis to be an independent determinant of postinfection ICU and hospital lengths of stay. Clinicians should implement local strategies aimed at timely delivery of appropriate antibiotic therapy to improve outcomes and reduce length of stay.

Practice Patterns and Outcomes Associated With Choice of Initial Vasopressor Therapy for Septic Shock

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2141–2146

Fawzy, A et al

Objectives: Clinical guidelines recommend norepinephrine as initial vasopressor of choice for septic shock, with dopamine suggested as an alternative vasopressor in selected patients with low risk of tachyarrhythmias and absolute or relative bradycardia. We sought to determine practice patterns and outcomes associated with vasopressor selection in a large, population-based cohort of patients with septic shock that allows for assessment of outcomes in clinically important subgroups. Design: We performed a retrospective cohort study to determine factors associated with choice of dopamine as compared with norepinephrine as initial vasopressor for patients with septic shock. We used propensity score matching to compare risk of hospital mortality based on initial vasopressor. We performed multiple sensitivity analyses using alternative methods to address confounding and hospital-level clustering. We investigated interaction between vasopressor selection and mortality in clinical subgroups based on arrhythmia and cardiovascular risk. Setting: Enhanced administrative data (Premier, Charlotte, NC) from 502 U.S. hospitals during the years 2010–2013. Subjects: A total of 61,122 patients admitted with septic shock who received dopamine or norepinephrine as initial vasopressor during the first 2 days of hospitalization. Interventions: None. Measurements and Main Results: Norepinephrine (77.6%) was the most frequently used initial vasopressor during septic shock. Dopamine was preferentially selected by cardiologists, in the Southern United States, at nonteaching hospitals, for older patients with more cardiovascular comorbidities and was used less frequently over time. Patients receiving dopamine experienced greater hospital mortality (propensity-matched cohort: n = 38,788; 25% vs 23.7%; odds ratio, 1.08; 95% CI, 1.02–1.14). Sensitivity analyses showed similar results. Subgroup analyses showed no evidence for effect modification based on arrhythmia risk or underlying cardiovascular disease. Conclusions: In a large population-based sample of patients with septic shock in the United States, use of dopamine as initial vasopressor was associated with increased mortality among multiple clinical subgroups. Areas where use of dopamine as initial vasopressor is more common represent potential targets for quality improvement intervention.

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2155–2163

Neto, AS et al

Objective: Protective mechanical ventilation with low tidal volumes is standard of care for patients with acute respiratory distress syndrome. The aim of this individual patient data analysis was to determine the association between tidal volume and the occurrence of pulmonary complications in ICU patients without acute respiratory distress syndrome and the association between occurrence of pulmonary complications and outcome in these patients. Design: Individual patient data analysis. Patients: ICU patients not fulfilling the consensus criteria for acute respiratory distress syndrome at the onset of ventilation. Interventions: Mechanical ventilation with low tidal volume. Measurements and Main Results: The primary endpoint was development of a composite of acute respiratory distress syndrome and pneumonia during hospital stay. Based on the tertiles of tidal volume size in the first 2 days of ventilation, patients were assigned to a “low tidal volume group” (tidal volumes≤ 7 mL/kg predicted body weight), an “intermediate tidal volume group” (> 7 and < 10 mL/kg predicted body weight), and a “high tidal volume group” (≥ 10 mL/kg predicted body weight). Seven investigations (2,184 patients) were included. Acute respiratory distress syndrome or pneumonia occurred in 23% of patients in the low tidal volume group, in 28% of patients in the intermediate tidal volume group, and in 31% of the patients in the high tidal volume group (adjusted odds ratio [low vs high tidal volume group], 0.72; 95% CI, 0.52–0.98; p = 0.042). Occurrence of pulmonary complications was associated with a lower number of ICU-free and hospital-free days and alive at day 28 (10.0 ± 10.9 vs 13.8 ± 11.6 d; p < 0.01 and 6.1 ± 8.1 vs 8.9 ± 9.4 d; p < 0.01) and an increased hospital mortality (49.5% vs 35.6%; p < 0.01). Conclusions: Ventilation with low tidal volumes is associated with a lower risk of development of pulmonary complications in patients without acute respiratory distress syndrome.

Protocols and Hospital Mortality in Critically Ill Patients: The United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study

Critical Care Medicine: October 2015 - Volume 43 - Issue 10 - p 2076–2084

Objective: Clinical protocols may decrease unnecessary variation in care and improve compliance with desirable therapies. We evaluated whether highly protocolized ICUs have superior patient outcomes compared with less highly protocolized ICUs. Design: Observational study in which participating ICUs completed a general assessment and enrolled new patients 1 day each week. Patients: A total of 6,179 critically ill patients. Setting: Fifty-nine ICUs in the United States Critical Illness and Injury Trials Group Critical Illness Outcomes Study. Interventions: None. Measurements and Main Results: The primary exposure was the number of ICU protocols; the primary outcome was hospital mortality. A total of 5,809 participants were followed prospectively, and 5,454 patients in 57 ICUs had complete outcome data. The median number of protocols per ICU was 19 (interquartile range, 15–21.5). In single-variable analyses, there were no differences in ICU and hospital mortality, length of stay, use of mechanical ventilation, vasopressors, or continuous sedation among individuals in ICUs with a high versus low number of protocols. The lack of association was confirmed in adjusted multivariable analysis (p = 0.70). Protocol compliance with two ventilator management protocols was moderate and did not differ between ICUs with high versus low numbers of protocols for lung protective ventilation in acute respiratory distress syndrome (47% vs 52%; p = 0.28) and for spontaneous breathing trials (55% vs 51%; p = 0.27). Conclusions: Clinical protocols are highly prevalent in U.S. ICUs. The presence of a greater number of protocols was not associated with protocol compliance or patient mortality.

Dynamics of end expiratory lung volume after changing positive end-expiratory pressure in acute respiratory distress syndrome patients

Critical Care 2015, 19:340

Garnero A et al

Introduction: Lung recruitment maneuvers followed by an individually titrated positive end-expiratory pressure (PEEP) are the key components of the open lung ventilation strategy in acute respiratory distress syndrome (ARDS). The staircase recruitment maneuver is a step-by-step increase in PEEP followed by a decremental PEEP trial. The duration of each step is usually 2 minutes without physiologic rationale.
Methods: In this prospective study, we measured the dynamic end-expiratory lung volume changes (ΔEELV) during an increase and decrease in PEEP to determine the optimal duration for each step. PEEP was progressively increased from 5 to 40 cmH 2 O and then decreased from 40 to 5 cmH 2 O in steps of 5 cmH 2 O every 2.5 minutes. The dynamic of ΔEELV was measured by direct spirometry as the difference between inspiratory and expiratory tidal volumes over 2.5 minutes following each increase and decrease in PEEP. ΔEELV was separated between the expected increased volume, calculated as the product of the respiratory system compliance by the change in PEEP, and the additional volume.
Results: Twenty-six early onset moderate or severe ARDS patients were included. Data are expressed as median [25th-75th quartiles]. During the increase in PEEP, the expected increased volume was achieved within 2[2-2] breaths. During the decrease in PEEP, the expected decreased volume was achieved within 1 [1–1] breath, and 95 % of the additional decreased volume was achieved within 8 [2–15] breaths. Completion of volume changes in 99 % of both increase and decrease in PEEP events required 29 breaths.
Conclusions: In early ARDS, most of the ΔEELV occurs within the first minute, and change is completed within 2 minutes, following an increase or decrease in PEEP.

Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients:a phase II randomized controlled trial

Critical Care 2015, 19:329

Palacio de Azevedo R et al

Introduction Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients. 

Methods: We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1–2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14.
Results: We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7 % versus 62.3 ±24.5 %, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (–4.0 (–6.0 to 0) versus –1.0 (–4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0–8.0) versus 3.0 (1.0–5.7), p = 0.016), including more days with diarrhea (2.0 (1.0–4.0) versus 1.0 (0–2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups.
Conclusions: Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score.

Improvement of antibiotic therapy and ICU survival in severe non-pneumococcal community-acquired pneumonia: a matched case–control study

Critical Care 2015, 19:335

Gattarello S et al

Introduction: We aimed to compare intensive care unit mortality due to non-pneumococcal severe community-acquired pneumonia between the periods 2000–2002 and 2008–2014, and the impact of the improvement in antibiotic strategies on outcomes. Methods: This was a matched case–control study enrolling 144 patients with non-pneumococcal severe pneumonia: 72 patients from the 2000–2002 database (CAPUCI I group) were paired with 72 from the 2008–2014 period (CAPUCI II group), matched by the following variables: microorganism, shock at admission, invasive mechanical ventilation, immunocompromise, chronic obstructive pulmonary disease, and age over 65 years. Results: The most frequent microorganism was methicillin-susceptible Staphylococcus aureus (22.1 %) followed by Legionella pneumophila and Haemophilus influenzae (each 20.7 %); prevalence of shock was 59.7 %, while 73.6 % of patients needed invasive mechanical ventilation. Intensive care unit mortality was significantly lower in the CAPUCI II group (34.7 % versus 16.7 %; odds ratio (OR) 0.78, 95 % confidence interval (CI) 0.64–0.95; p = 0.02). Appropriate therapy according to microorganism was 91.5 % in CAPUCI I and 92.7 % in CAPUCI II, while combined therapy and early antibiotic treatment were significantly higher in CAPUCI II (76.4 versus 90.3 % and 37.5 versus 63.9 %; p < 0.05). In the multivariate analysis, combined antibiotic therapy (OR 0.23, 95 % CI 0.07–0.74) and early antibiotic treatment (OR 0.07, 95 % CI 0.02–0.22) were independently associated with decreased intensive care unit mortality. Conclusions: In non-pneumococcal severe community-acquired pneumonia , early antibiotic administration and use of combined antibiotic therapy were both associated with increased intensive care unit survival during the study period.

Acute respiratory distress syndrome: does histology matter?

Critical Care 2015, 19:337

Lorente JA

Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4 % of cases. The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases. On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance.

Daily estimation of the severity of organ dysfunctions in critically ill children by using the PELOD-2 scor

Daily estimation of the severity of organ dysfunctions in critically ill children by using the PELOD-2 score

Critical Care 2015, 19:324

Leteurtre S et al

Introduction: Daily or serial evaluation of multiple organ dysfunction syndrome (MODS) scores may provide useful information. We aimed to validate the daily (d) PELOD-2 score using the set of seven days proposed with the previous version of the score.
Methods: In all consecutive patients admitted to nine pediatric intensive care units (PICUs) we prospectively measured the dPELOD-2 score at day 1, 2, 5, 8, 12, 16, and 18. PICU mortality was used as the outcome dependent variable. The discriminant power of the dPELOD-2 scores was estimated using the area under the ROC curve and the calibration using the Hosmer-Lemeshow chi-square test. We used a logistic regression to investigate the relationship between the dPELOD-2 scores and outcome, and between the change in PELOD-2 score from day1 and outcome. Results: We included 3669 patients (median age 15.5 months, mortality rate 6.1 %, median length of PICU stay 3 days). Median dPELOD-2 scores were significantly higher in nonsurvivors than in survivors (p < 0.0001). The dPELOD-2 score was available at least at day 2 in 2057 patients: among the 796 patients without MODS on day1, 186 (23.3 %) acquired the syndrome during their PICU stay (mortality 4.9 % vs. 0.3 % among the 610 who did not; p < 0.0001). Among the1261 patients with MODS on day1, the syndrome worsened in 157 (12.4 %) and remained unchanged or improved in 1104 (87.6 %) (mortality 22.9 % vs. 6.6 %; p < 0.0001). The AUC of the dPELOD-2 scores ranged from 0.75 (95 % CI: 0.67-0.83) to 0.89 (95 % CI: 0.86-0.91). The calibration was good with a chi-square test between 13.5 (p = 0.06) and 0.9 (p = 0.99). The PELOD-2 score on day1 was a significant prognostic factor; the serial evaluation of the change in the dPELOD-2 score from day1, adjusted for baseline value, demonstrated a significant odds ratio of death for each of the 7 days. Conclusion: This study suggests that the progression of the severity of organ dysfunctions can be evaluated by measuring the dPELOD-2 score during a set of 7 days in PICU, providing useful information on outcome in critically ill children. Its external validation would be useful

Early mobilisation in intensive care units in Australia and Scotland: a prospective,observational cohort study examining mobilisation practises and barriers

Critical Care 2015, 19:336

Harrold ME et al

Introduction: Mobilisation of patients in the intensive care unit (ICU) is an area of growing research. Currently, there is little data on baseline mobilisation practises and the barriers to them for patients of all admission diagnoses.
Methods: The objectives of the study were to (1) quantify and benchmark baseline levels of mobilisation in Australian and Scottish ICUs, (2) compare mobilisation practises between Australian and Scottish ICUs and (3) identify barriers to mobilisation in Australian and Scottish ICUs. We conducted a prospective, observational, cohort study with a 4-week inception period. Patients were censored for follow-up upon ICU discharge or after 28 days, whichever occurred first. Patients were included if they were >18 years of age, admitted to an ICU and received mechanical ventilation in the ICU.
Results: Ten tertiary ICUs in Australia and nine in Scotland participated in the study. The Australian cohort had a large proportion of patients admitted for cardiothoracic surgery (43.3 %), whereas the Scottish cohort had none. Therefore, comparison analysis was done after exclusion of patients admitted for cardiothoracic surgery. In total, 60.2 % of the 347 patients across 10 Australian ICUs and 40.1 % of the 167 patients across 9 Scottish ICUs mobilised during their ICU stay (p < 0.001). Patients in the Australian cohort were more likely to mobilise than patients in the Scottish cohort (hazard ratio 1.83, 95 % confidence interval 1.38–2.42). However, the percentage of episodes of mobilisation where patients were receiving mechanical ventilation was higher in the Scottish cohort (41.1 % vs 16.3 %, p < 0.001). Sedation was the most commonly reported barrier to mobilisation in both the Australian and Scottish cohorts. Physiological instability and the presence of an endotracheal tube were also frequently reported barriers.
Conclusions: This is the first study to benchmark baseline practise of early mobilisation internationally, and it demonstrates variation in early mobilisation practises between Australia and Scotland.

Impact of Acute Kidney Injury on Outcome in Patients With Severe Acute RespiratoryFailure Receiving Extracorporeal Membrane Oxygenation

Critical Care Medicine, September 2015 - Volume 43 - Issue 9 - p 1898–1906

Haneya, A et al

Objectives: Extracorporeal lung support is currently used in the treatment of patients with severe respiratory failure until organ recovery and as a bridge to further therapeutic modalities. The aim of our study was to evaluate the impact of acute kidney injury on outcome in patients with acute respiratory distress syndrome under venovenous extracorporeal membrane oxygenation support and to analyze the association between prognosis and the time of occurrence of acute kidney injury and renal replacement therapy initiation. Design: Retrospective observational study. Setting: A large European extracorporeal membrane oxygenation center, University Medical Center Regensburg, Germany. Patients: A total of 262 consecutive adult patients with acute respiratory distress syndrome have been treated with extracorporeal membrane oxygenation between January 2007 and May 2012.