Characteristics of Rapid Response Calls in the United States: An Analysis of the First 402,023 Adult Cases From the Get With the Guidelines Resuscitation-Medical Emergency Team Registry Objectives: To characterize the rapid response team activations, and the patients receiving them, in the American Heart Association-sponsored Get With The Guidelines Resuscitation-Medical Emergency Team cohort between 2005 and 2015. Design: Retrospective multicenter cohort study. Setting: Three hundred sixty U.S. hospitals. Patients: Consecutive adult patients experiencing rapid response team activation. Interventions: Rapid response team activation. Measurements and Main Results: The cohort included 402,023 rapid response team activations from 347,401 unique healthcare encounters. Respiratory triggers (38.0%) and cardiac triggers (37.4%) were most common. The most frequent interventions—pulse oximetry (66.5%), other monitoring (59.6%), and supplemental oxygen (62.0%)—were noninvasive. Fluids were the most common medication ordered (19.3%), but new antibiotic orders were rare (1.2%). More than 10% of rapid response teams resulted in code status changes. Hospital mortality was over 14% and increased with subsequent rapid response activations. Conclusions: Although patients requiring rapid response team activation have high inpatient mortality, most rapid response team activations involve relatively few interventions, which may limit these teams’ ability to improve patient outcomes.

Antibiotic- and Fluid-Focused Bundles Potentially Improve Sepsis Management, but High-Quality Evidence Is Lacking for the Specificity Required in the Centers for Medicare and Medicaid Service’s Sepsis Bundle (SEP-1)* Objective: To address three controversial components in the Centers for Medicare and Medicaid Service’s sepsis bundle for performance measure (SEP-1): antibiotics within 3 hours, a 30 mL/kg fluid infusion for all hypotensive patients, and repeat lactate measurements within 6 hours if initially elevated. We hypothesized that antibiotic- and fluid-focused bundles like SEP-1 would probably show benefit, but evidence supporting specific antibiotic timing, fluid dosing, or serial lactate requirements would not be concordant. Therefore, we performed a meta-analysis of studies of sepsis bundles like SEP-1. Data Sources: PubMed, Embase, ClinicalTrials.gov through March 15, 2018. Study Selection: Studies comparing survival in septic adults receiving versus not receiving antibiotic- and fluid-focused bundles. Data Extraction: Two investigators (D.J.P., P.Q.E.). Data Synthesis: Seventeen observational studies (11,303 controls and 4,977 bundle subjects) met inclusion criteria. Bundles were associated with increased odds ratios of survival (odds ratio [95% CI]) in 15 studies with substantial heterogeneity (I2 = 61%; p < 0.01). Survival benefits were consistent in the five largest (1,697–12,486 patients per study) (1.20 [1.11–1.30]; I2 = 0%) and six medium-sized studies (167–1,029) (2.03 [1.52–2.71]; I2 = 8%) but not the six smallest (64–137) (1.25 [0.42–3.66]; I2 = 57%). Bundles were associated with similarly increased survival benefits whether requiring antibiotics within 1 hour (n = 7 studies) versus 3 hours (n = 8) versus no specified time (n = 2); or 30 mL/kg fluid (n = 7) versus another volume (≥ 2 L, n = 1; ≥ 20 mL/kg, n = 2; 1.5–2 L or 500 mL, n = 1 each; none specified, n = 4) (p = 0.19 for each comparison). In the only study employing serial lactate measurements, survival was not increased versus others. No study had a low risk of bias or assessed potential adverse bundle effects. Conclusions: Available studies support the notion that antibiotic- and fluid-focused sepsis bundles like SEP-1 improve survival but do not demonstrate the superiority of any specific antibiotic time or fluid volume or of serial lactate measurements. Until strong reproducible evidence demonstrates the safety and benefit of any fixed requirement for these interventions, the present findings support the revision of SEP-1 to allow flexibility in treatment according to physician judgment.

Clinical Examination for the Prediction of Mortality in the Critically Ill: The Simple Intensive Care Studies-I Objectives: Caregivers use clinical examination to timely recognize deterioration of a patient, yet data on the prognostic value of clinical examination are inconsistent. In the Simple Intensive Care Studies-I, we evaluated the association of clinical examination findings with 90-day mortality in critically ill patients. Design: Prospective single-center cohort study. Setting: ICU of a single tertiary care level hospital between March 27, 2015, and July 22, 2017. Patients: All consecutive adults acutely admitted to the ICU and expected to stay for at least 24 hours. Interventions: A protocolized clinical examination of 19 clinical signs conducted within 24 hours of admission. Measurements Main Results: Independent predictors of 90-day mortality were identified using multivariable logistic regression analyses. Model performance was compared with established prognostic risk scores using area under the receiver operating characteristic curves. Robustness of our findings was tested by internal bootstrap validation and adjustment of the threshold for statistical significance. A total of 1,075 patients were included, of whom 298 patients (28%) had died at 90-day follow-up. Multivariable analyses adjusted for age and norepinephrine infusion rate demonstrated that the combination of higher respiratory rate, higher systolic blood pressure, lower central temperature, altered consciousness, and decreased urine output was independently associated with 90-day mortality (area under the receiver operating characteristic curves = 0.74; 95% CI, 0.71–0.78). Clinical examination had a similar discriminative value as compared with the Simplified Acute Physiology Score-II (area under the receiver operating characteristic curves = 0.76; 95% CI, 0.73–0.79; p = 0.29) and Acute Physiology and Chronic Health Evaluation-IV (using area under the receiver operating characteristic curves = 0.77; 95% CI, 0.74–0.80; p = 0.16) and was significantly better than the Sequential Organ Failure Assessment (using area under the receiver operating characteristic curves = 0.67; 95% CI, 0.64–0.71; p < 0.001). Conclusions: Clinical examination has reasonable discriminative value for assessing 90-day mortality in acutely admitted ICU patients. In our study population, a single, protocolized clinical examination had similar prognostic abilities compared with the Simplified Acute Physiology Score-II and Acute Physiology and Chronic Health Evaluation-IV and outperformed the Sequential Organ Failure Assessment score.

Epidemiology and Outcomes of Cancer-Related Versus Non–Cancer-Related Sepsis Hospitalizations* Objective: Cancer and its treatment are known to be important risk factors for sepsis, contributing to an estimated 12% of U.S. sepsis admissions in the 1990s. However, cancer treatment has evolved markedly over the past 2 decades. We sought to examine how cancer-related sepsis differs from non–cancer-related sepsis. Design: Observational cohort. Setting: National Readmissions Database (2013–2014), containing all-payer claims for 49% of U.S. population. Patients: A total of 1,104,363 sepsis hospitalizations. Interventions: We identified sepsis hospitalizations in the U.S. National Readmissions Database using explicit codes for severe sepsis, septic shock, or Dombrovskiy criteria (concomitant codes for infection and organ dysfunction). We classified hospitalizations as cancer-related versus non–cancer-related sepsis based on the presence of secondary diagnosis codes for malignancy. We compared characteristics (site of infection and organ dysfunction) and outcomes (in-hospital mortality and 30-d readmissions) of cancer-related versus non–cancer-related sepsis hospitalizations. We also completed subgroup analyses by age, cancer types, and specific cancer diagnoses. Measurements and Main Results: There were 27,481,517 hospitalizations in National Readmissions Database 2013–2014, of which 1,104,363 (4.0%) were for sepsis and 4,150,998 (15.1%) were cancer related. In-hospital mortality in cancer-related sepsis was 27.9% versus 19.5% in non–cancer-related sepsis. The median count of organ dysfunctions was indistinguishable, but the rate of specific organ dysfunctions differed by small amounts (e.g., hematologic dysfunction 20.1% in cancer-related sepsis vs 16.6% in non–cancer-related sepsis; p < 0.001). Cancer-related sepsis was associated with an adjusted absolute increase in in-hospital mortality ranging from 2.2% to 15.2% compared with non–cancer-related sepsis. The mortality difference was greatest in younger adults and waned with age. Patients (23.2%) discharged from cancer-related sepsis were rehospitalized within 30 days, compared with 20.1% in non–cancer-related sepsis (p < 0.001). Conclusions: In this cohort of over 1 million U.S. sepsis hospitalizations, more than one in five were cancer related. The difference in mortality varies substantially across age spectrum and is greatest in younger adults. Readmissions were more common after cancer-related sepsis.

Declining Mortality of Cirrhotic Variceal Bleeding Requiring Admission to Intensive Care: A Binational Cohort Study* Objectives: We aimed to describe changes over time in admissions and outcomes, including length of stay, discharge destinations, and mortality of cirrhotic patients admitted to the ICU for variceal bleeding, and to compare it to the outcomes of those with other causes of ICU admissions. Design: Retrospective analysis of data captured prospectively in the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. Settings: One hundred eighty-three ICUs in Australia and New Zealand. Patients: Consecutive admissions to these ICUs for upper gastrointestinal bleeding related to varices in patients with cirrhosis between January 1, 2005, and December 31, 2016. Interventions: None. Measurements and Main Results: ICU admissions for variceal bleeding in cirrhotic patients accounted for 4,003 (0.6%) of all 720,425 nonelective ICU admissions. The proportion of ICU admissions for variceal bleeding fell significantly from 0.8% (83/42,567) in 2005 to 0.4% (53/80,388) in 2016 (p < 0.001). Hospital mortality rate was significantly higher within admissions for variceal bleeding compared with nonelective ICU admissions (20.0% vs 15.7%; p < 0.0001), but decreased significantly over time, from 24.6% in 2005 to 15.8% in 2016 (annual decline odds ratio, 0.93; 95% CI, 0.90–0.96). There was no difference in the reduction in mortality from variceal bleeding over time between liver transplant and nontransplant centers (p = 0.26). Conclusions: Admission rate to ICU and mortality of cirrhotic patients with variceal bleeding has declined significantly over time compared with other causes of ICU admissions with the outcomes comparable between liver transplant and nontransplant centers.

A Core Outcome Set for Critical Care Ventilation Trials Objectives: Our objective was to obtain international consensus on a set of core outcome measures that should be recorded in all clinical trials of interventions intended to modify the duration of ventilation for invasively mechanically ventilated patients in the ICU. Design: A two-stage consensus process was undertaken between December 2015 and January 2018. Stage 1 included an online three-round Delphi study and three consensus meetings. Stage 2 included three consensus meetings. Setting: The setting was international, including Europe, North and South America, Australia, Asia, and Africa. Participants: Organization members representing intensive care survivors and carers; nursing, allied health professionals, and critical care physicians; clinical trials groups and trial investigators; and industry. Interventions: None. Measurements and Main Results: Delphi study outcomes were scored by participants from one (least important) to nine (most important). Consensus criteria for including the outcome in the core set were more than 70% of responses rating the outcome above seven and not more than 15% rating the outcome less than 3. From 222 participants, 183 from 38 organizations in 27 countries contributed to the consensus process. Stage 1: Delphi response rates from 200 participants ranged from 89% to 90% across three rounds. Forty-seven outcomes were ranked as follows: 19 met consensus criteria for inclusion and were considered at three consensus meetings (33 participants). Six outcomes were agreed for the core set as follows: extubation, reintubation, duration of mechanical ventilation, length of stay, health-related quality of life, and mortality. Stage 2: Three consensus meetings (37 participants) agreed on the measures for each outcome. Conclusions: We used rigorous and well-established methods to develop a core outcome set for use in all clinical trials evaluating interventions intended to modify duration of mechanical ventilation. This core outcome set will inform the design of future trials in this field by strengthening methodological quality and improving comparability across trials.

Implementation of a Bundled Consent Process in the ICU: A Single-Center Experience* Objectives: A bundled consent process, where patients or surrogates provide consent for all commonly performed procedures on a single form at the time of ICU admission, has been advocated as a method for improving both rates of documented consent and patient/family satisfaction, but there has been little published literature about the use of bundled consent. We sought to determine how residents in an academic medical center with a required bundled consent process actually obtain consent and how they perceive the overall value, efficacy, and effects on families of this approach. Design: Single-center survey study. Setting: Medical ICUs in an urban academic medical center. Subjects: Internal medicine residents. Interventions: We administered an online survey about bundled consent use to all residents. Quantitative and qualitative data were analyzed. Measurements and Main Results: One-hundred two of 164 internal medicine residents (62%) completed the survey. A majority of residents (55%) reported grouping procedures and discussing general risks and benefits; 11% reported conducting a complete informed consent discussion for each procedure. Respondents were divided in their perception of the value of bundled consent, but most (78%) felt it scared or stressed families. A minority (26%) felt confident that they obtained valid informed consent for critical care procedures with the use of bundled consent. An additional theme that emerged from qualitative data was concern regarding the validity of anticipatory consent. Conclusions: Resident physicians experienced with the use of bundled consent in the ICU held variable perceptions of its value but raised concerns about the effect on families and the validity of consent obtained with this strategy. Further studies are necessary to further explore what constitutes best practice for informed consent in critical care.

Randomized Clinical Trial of an ICU Recovery Pilot Program for Survivors of Critical Illness* Objectives: To examine the effect of an interdisciplinary ICU recovery program on process measures and clinical outcomes. Design: A prospective, single-center, randomized pilot trial. Setting: Academic, tertiary-care medical center. Patients: Adult patients admitted to the medical ICU for at least 48 hours with a predicted risk of 30-day same-hospital readmission of at least 15%. Interventions: Patients randomized to the ICU recovery program group were offered a structured 10-intervention program, including an inpatient visit by a nurse practitioner, an informational pamphlet, a 24 hours a day, 7 days a week phone number for the recovery team, and an outpatient ICU recovery clinic visit with a critical care physician, nurse practitioner, pharmacist, psychologist, and case manager. For patients randomized to the usual care group, all aspects of care were determined by treating clinicians. Measurements and Main Results: Among the primary analysis of enrolled patients who survived to hospital discharge, patients randomized to the ICU recovery program (n = 111) and usual care (n = 121) were similar at baseline. Patients in the ICU recovery program group received a median of two interventions compared with one intervention in the usual care group (p < 0.001). A total of 16 patients (14.4%) in the ICU recovery program group and 26 patients (21.5%) in the usual care group were readmitted to the study hospital within 30 days of discharge (p = 0.16). For these patients, the median time to readmission was 21.5 days (interquartile range, 11.5–26.2 d) in the ICU recovery program group and 7 days (interquartile range, 4–21.2 d) in the usual care group (p = 0.03). Four patients (3.6%) in the ICU recovery program and 14 patients (11.6%) in the usual care group were readmitted within 7 days of hospital discharge (p = 0.02). The composite outcome of death or readmission within 30 days of hospital discharge occurred in 20 patients (18%) in the ICU recovery program group and 36 patients (29.8%) in usual care group (p = 0.04). Conclusions: This randomized pilot trial found that a multidisciplinary ICU recovery program could deliver more interventions for post ICU recovery than usual care. The finding of longer time-to-readmission with an ICU recovery program should be examined in future trials.

Practice Patterns and Ethical Considerations in the Management of Venovenous Extracorporeal Membrane Oxygenation Patients: An International Survey* Objectives: To characterize physicians’ practices and attitudes toward the initiation, limitation, and withdrawal of venovenous extracorporeal membrane oxygenation for severe respiratory failure and evaluate factors associated with these attitudes. Design: Electronic, cross-sectional, scenario-based survey. Setting: Extracorporeal membrane oxygenation centers affiliated with the Extracorporeal Life Support Organization and the International Extracorporeal Membrane Oxygenation Network. Subjects: Attending-level physicians with experience managing adult patients receiving venovenous extracorporeal membrane oxygenation. Interventions: None. Measurements and Main Results: Five-hundred thirty-nine physicians in 39 countries across six continents completed the survey. Factors that influenced the decision to limit extracorporeal membrane oxygenation initiation included older patient age (46.9%), additional organ failures (37.7%), and prolonged mechanical ventilation (35.1%). Patient comorbidities (70.5%), patient’s wishes (56.0%), and etiology of respiratory failure (37.7%) were factors that influenced the decision to withdraw extracorporeal membrane oxygenation. In multivariable analysis, factors associated with increased odds of withdrawing life-sustaining therapies included pulmonary fibrosis, stroke, surrogate’s desire to withdraw, lack of knowledge regarding patient’s or surrogate’s wishes in the setting of fibrosis, not initiating extracorporeal membrane oxygenation in the baseline scenario, and respondent religiosity. Factors associated with decreased odds of withdrawal included practicing in an environment where it is not legally possible to make decisions against patient or surrogate wishes. Most respondents (90.5%) involved other physicians in treatment decisions for extracorporeal membrane oxygenation patients, whereas only 53.2%, 45.3%, and 29.5% of respondents involved surrogates, awake patients, or bedside nurses, respectively. Conclusions: Patient and physician-level factors were associated with decision-making regarding extracorporeal membrane oxygenation initiation and withdrawal, including patient prognosis and knowledge of patient or surrogate wishes. Respondents reported low rates of engaging in shared decision-making when managing patients receiving extracorporeal membrane oxygenation.

Are Peripherally Inserted Central Catheters Suitable for Cardiac Output Assessment With Transpulmonary Thermodilution?* Objectives: Peripherally inserted central catheters are increasingly used in ICU as an alternative to centrally inserted central catheters for IV infusion. However, their reliability for hemodynamic measurements with transpulmonary thermodilution is currently unknown. We investigated the agreement between transpulmonary thermodilution measurements obtained with bolus injection through peripherally inserted central catheter and centrally inserted central catheter (reference standard) using a transpulmonary thermodilution–calibrated Pulse Contour hemodynamic monitoring system (VolumeView/EV1000). Design: Prospective method-comparison study. Setting: Twenty-bed medical-surgical ICU of a teaching hospital. Patients: Twenty adult ICU patients who required hemodynamic monitoring because of hemodynamic instability and had both peripherally inserted central catheter and centrally inserted central catheter in place. Intervention: The hemodynamic measurements obtained by transpulmonary thermodilution after injection of a cold saline bolus via both centrally inserted central catheter and either a single-lumen 4F or a double-lumen 5F peripherally inserted central catheter using were compared. In order to rule out bias related to manual injection, measurements were repeated using an automated rapid injection system. Measurements and Main Results: A total of 320 measurements were made. Cardiac index was significantly higher when measured with double-lumen 5F peripherally inserted central catheter than with centrally inserted central catheter (mean, 4.5 vs 3.3 L/min/m2; p < 0.0001; bias, 1.24 L/min/m2 [0.27, 2.22 L/min/m2]; bias percentage, 31%). Global end-diastolic index, extravascular lung water index, and stroke volume index were also overestimated (853 ± 240 vs 688 ± 175 mL/m2, 12.2 ± 4.2 vs 9.4 ± 2.9 mL/kg, and 49.6 ± 14.9 vs 39.5 ± 9.6 mL/m2, respectively; p < 0.0001). Lower, albeit significant differences were found using single-lumen 4F peripherally inserted central catheter (mean cardiac index, 4.2 vs 3.7 L/min/m2; p = 0.043; bias, 0.51 L/min/m2 [–0.53, 1.55 L/min/m2]; bias percentage, 12.7%). All differences were confirmed, even after standardization of bolus speed with automated injection. Conclusions: Bolus injection through peripherally inserted central catheter for transpulmonary thermodilution using EV1000 led to a significant overestimation of cardiac index, global end-diastolic index, extravascular lung water index, and stroke volume index, especially when double-lumen 5F peripherally inserted central catheter was used (ClinicalTrial.gov NCT03834675).