Russell R. Miller

Multicenter Implementation of a Severe Sepsis and Septic Shock Treatment Bundle

RATIONALEnSevere sepsis and septic shock are leading causes of intensive care unit (ICU) admission, morbidity, and mortality. The effect of compliance with sepsis management guidelines on outcomes is unclear.nnnOBJECTIVESnTo assess the effect on mortality of compliance with a severe sepsis and septic shock management bundle.nnnMETHODSnObservational study of a severe sepsis and septic shock bundle as part of a quality improvement project in 18 ICUs in 11 hospitals in Utah and Idaho.nnnMEASUREMENTS AND MAIN RESULTSnAmong 4,329 adult subjects with severe sepsis or septic shock admitted to study ICUs from the emergency department between January 2004 and December 2010, hospital mortality was 12.1%, declining from 21.2% in 2004 to 8.7% in 2010. All-or-none total bundle compliance increased from 4.9-73.4% simultaneously. Mortality declined from 21.7% in 2004 to 9.7% in 2010 among subjects noncompliant with one or more bundle element. Regression models adjusting for age, severity of illness, and comorbidities identified an association between mortality and compliance with each of inotropes and red cell transfusions, glucocorticoids, and lung-protective ventilation. Compliance with early resuscitation elements during the first 3 hours after emergency department admission caused ineligibility, through lower subsequent severity of illness, for these later bundle elements.nnnCONCLUSIONSnTotal severe sepsis and septic shock bundle compliances increased substantially and were associated with a marked reduction in hospital mortality after adjustment for age, severity of illness, and comorbidities in a multicenter ICU cohort. Early resuscitation bundle element compliance predicted ineligibility for subsequent bundle elements.

Clinical Findings and Demographic Factors Associated With ICU Admission in Utah Due to Novel 2009 Influenza A(H1N1) Infection

BACKGROUNDnNovel 2009 influenza A(H1N1) infection has significantly affected ICUs. We sought to characterize our regions clinical findings and demographic associations with ICU admission due to novel A(H1N1).nnnMETHODSnWe conducted an observational study from May 19, 2009, to June 30, 2009, of descriptive clinical course, inpatient mortality, financial data, and demographic characteristics of an ICU cohort. A case-control study was used to compare the ICU cohort to Salt Lake County residents.nnnRESULTSnThe ICU cohort of 47 influenza patients had a median age of 34 years, Acute Physiology and Chronic Health Evaluation II score of 21, and BMI of 35 kg/m2. Mortality was 17% (8/47). All eight deaths occurred among the 64% of patients (n = 30) with ARDS, 26 (87%) of whom also developed multiorgan failure. Compared with the Salt Lake County population, patients with novel A(H1N1) were more likely to be obese (22% vs 74%; P < .001), medically uninsured (14% vs 45%; P < .001), and Hispanic (13% vs 23%; P < .01) or Pacific Islander (1% vs 26%; P < .001). Observed ICU admissions were 15-fold greater than expected for those with BMI > or = 40 kg/m2 (standardized morbidity ratio 15.8, 95% CI, 8.3-23.4) and 1.5-fold greater than expected among those with BMI of 30 to 39 kg/m(2) for age-adjusted and sex-adjusted rates for Salt Lake County.nnnCONCLUSIONSnSevere ARDS with multiorgan dysfunction in the absence of bacterial infection was a common clinical presentation. In this cohort, young nonwhites without medical insurance were disproportionately likely to require ICU care. Obese patients were particularly susceptible to critical illness due to novel A(H1N1) infection.

Survival After Shock Requiring High-Dose Vasopressor Therapy

BACKGROUNDnSome patients with hypotensive shock do not respond to usual doses of vasopressor therapy. Very little is known about outcomes after high-dose vasopressor therapy (HDV). We sought to characterize survival among patients with shock requiring HDV. We also evaluated the possible utility of stress-dose corticosteroid therapy in these patients.nnnMETHODSnWe conducted a retrospective study of patients with shock requiring HDV in the ICUs of five hospitals from 2005 through 2010. We defined HDV as receipt at any point of ≥ 1 μg/kg/min of norepinephrine equivalent (calculated by summing norepinephrine-equivalent infusion rates of all vasopressors). We report survival 90 days after hospital admission. We evaluated receipt of stress-dose corticosteroids, cause of shock, receipt of CPR, and withdrawal or withholding of life support therapy.nnnRESULTSnWe identified 443 patients meeting inclusion criteria. Seventy-six (17%) survived. Survival was similar (20%) among the 241 patients with septic shock. Among the 367 nonsurvivors, 254 (69%) experienced withholding/withdrawal of care, and 115 (31%) underwent CPR. Stress-dose corticosteroid therapy was associated with increased survival (P = .01).nnnCONCLUSIONSnOne in six patients with shock survived to 90 days after HDV. The majority of nonsurvivors died after withdrawal or withholding of life support therapy. A minority of patients underwent CPR. Additionally, stress-dose corticosteroid therapy appears reasonable in patients with shock requiring HDV.

Platelet–Monocyte Aggregate Formation and Mortality Risk in Older Patients With Severe Sepsis and Septic Shock

BACKGROUNDnAging-related changes in platelet and monocyte interactions may contribute to adverse outcomes in sepsis but remain relatively unexamined. We hypothesized that differential platelet-monocyte aggregate (PMA) formation in older septic patients alters inflammatory responses and mortality.nnnMETHODSnWe prospectively studied 113 septic adults admitted to the intensive care unit with severe sepsis or septic shock. Patients were dichotomized a priori into one of two groups: older (age ≥ 65 years, n = 28) and younger (age < 65 years, n = 85). PMA levels were measured in whole blood via flow cytometry within 24 hours of admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by monocytes upon PMA formation, were determined by commercial assays. Patients were followed for the primary outcome of 28-day, all-cause mortality.nnnRESULTSnElevated PMA levels were associated with an increased risk of mortality in older septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64-49.61). This association remained after adjusting for potential confounding variables in multivariate regression. Receiver operating curve analyses demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day mortality in older septic patients (area under the receiver operating curve 0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were significantly associated with mortality.nnnCONCLUSIONSnIncreased PMA formation, and associated proinflammatory monokine synthesis, predicts mortality in older septic patients. Although larger studies are needed, our findings suggest that heightened PMA formation in older septic patients may contribute to injurious inflammatory responses and an increased risk of mortality.

Physical Therapy on the Wards After Early Physical Activity and Mobility in the Intensive Care Unit

Background Weakness and debilitation are common following critical illness. Studies that assess whether early physical activity initiated in the intensive care unit (ICU) continues after a patient is transferred to a ward are lacking. Objective The purpose of this study was to assess whether physical activity and mobility initiated during ICU treatment were maintained after patients were discharged from a single ICU to a ward. Design This was a cohort study. Methods Consecutive patients who were diagnosed with respiratory failure and admitted to the respiratory ICU (RICU) at LDS Hospital underwent early physical activity and mobility as part of usual care. Medical data, the number of requests for a physical therapy consultation or nursing assistance with ambulation at ICU discharge, and mobility data were collected during the first 2 full days on the ward. Results Of the 72 patients who participated in the study, 65 had either a physical therapy consultation or a request for nursing assistance with ambulation at ward transfer. Activity level decreased in 40 participants (55%) on the first full ward day. Of the 61 participants who ambulated 100 ft (30.48 m) or more on the last full RICU day, 14 did not ambulate, 22 ambulated less than 100 ft, and 25 ambulated 100 ft or more on the first ward day. Limitations Limitations include lack of data regarding why activity was not performed on the ward, lack of longitudinal follow-up to assess effects of activity, and lack of generalizability to patients not transferred to a ward or not treated in an ICU with an early mobility program. Conclusions Despite the majority of participants having a physical therapy consultation or a request for nursing assistance with ambulation at the time of transfer to the medical ward, physical activity levels decreased in over half of participants on the first full ward day. The data suggest a need for education of ward staff regarding ICU debilitation, enhanced communication among care providers, and focus on the importance of patient-centered outcomes during and following ICU treatment.

Right and Left Heart Failure in Severe H1N1 Influenza A Infection

Influenza infection can affect cardiac function. The recent pandemic of H1N1 influenza A provided an opportunity to study echocardiographic findings in critically ill infected patients. We hypothesised that critically ill patients with H1N1 infection would have a higher incidence of right and left heart failure than is seen in unselected populations of patients with septic shock and/or acute respiratory distress syndrome (ARDS). We retrospectively studied all patients admitted to four intensive care units at three hospitals in Salt Lake County, UT, USA, with laboratory-confirmed H1N1 infection in whom a clinical echocardiogram was available. 23 out of 48 patients had qualifying echocardiograms. Right ventricular (RV) dilatation (50–80%) and at least moderate systolic impairment (23%) were common, higher than the range described in general populations with ARDS. Left ventricular systolic dysfunction was present in 17% of patients. No single echocardiographic parameter was associated with 28-day mortality or ventilator-free days to 28 days. Critically ill patients with H1N1 infection frequently exhibit right heart dilatation and failure. RV basal dilatation was extremely common. These patients have less left heart failure than expected on the basis of prior descriptions of influenza myopericarditis or of general populations of septic patients.

Point: Should Positive End-Expiratory Pressure in Patients With ARDS Be Set on Oxygenation? Yes

Funding/Support: This work was supported in part by the National Institutes of Health [HHSN268200536171C/N01-HR-56171; HHSN268200536169C/N01-HR-56169; HHSN268200536175C/N01-HR-56175; HHSN268200536170C/N01-HR-56170]. n n n nFinancial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr MacIntyre has been a consultant for CareFusion Corporation since 1985. Dr Hite currently is a National Institutes of Health-funded investigator for studies related to ARDS. He also serves as a consultant (data safety and monitoring board chair) for a clinical trial sponsored by Cumberland Pharmaceuticals Inc and is a shareholder in Discovery Laboratories, Inc (both unrelated to the content of this article). Dr Hite has been an unfunded speaker on the subject of mechanical ventilation and ARDS, which is relevant to the content of this article. Dr Truwit has received National Institutes of Health grant funding in ARDS and an ARDS-surfactant grant from PneumoPartners. Drs Miller, Brower, and Morris have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. n n n nReproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

A perspective on early mobilization for adult patients with respiratory failure: Lessons for the pediatric population

OBJECTIVEnTo summarize the evidence for early mobilization programs in critically ill pediatric and adult patients with respiratory failure. This paper describes our review of the literature and outlines the morbidities associated with immobility, mechanical ventilation and sedation.The clinical management of acutely ill pediatric patients with respiratory failure traditionally consists of mechanical ventilation, sedation and prolonged immobilization. Although the most severely ill patients require these therapies for survival, each therapy comes with adverse consequences. Early mobilization may reduce complications and confer benefit for children with respiratory failure or those who require prolonged mechanical ventilator support.nnnDESIGNnSystematic review of the literature pertaining to early mobilization in pediatric and adult patients with respiratory failure. We searched Medline, PubMed, CINAHL and Cochrane database of controlled trials. Randomized controlled trials (RCTs), observational cohort studies, case control studies and population-based analysis were considered for inclusion. Two reviewers (MM and EH) independently selected pertinent studies.nnnRESULTSnNo studies of early mobilization in pediatric populations were found. Five adult studies were identified for review; two randomized controlled trials and three observational studies. All studies suggested an improvement in morbidity and economic benefit with implementation of early mobilization.nnnCONCLUSIONSnEarly mobilization in critically ill adult patients with respiratory failure is associated with a decrease in duration of sedatives, ventilator dependant days, ICU and hospital length of stay. The paucity of studies of early mobilization suggest that implementation of early mobilization is not widely practiced. Studies of early mobilization therapy in the adult patient requiring prolonged mechanical ventilator support are reviewed, and the physiologic rational and observed obstacles to integration of an early mobilization program are discussed. The adult data and scientific evidence are combined to support an opinion about the possible benefits of early mobilization programs. The generalizability of the findings and the feasibility of implementing early mobilization in critically ill children who require prolonged mechanical ventilator support are also considered.

Valproate for agitation in critically ill patients: A retrospective study

Purpose: The purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium. Materials and methods: This retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models. Results: Fifty‐three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (−185 &mgr;g/d, P = .0003) and lorazepam equivalents (−2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects. Conclusions: Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation.

Variation in the Contents of Sepsis Bundles and Quality Measures. A Systematic Review.

RATIONALEnSepsis contributes to one in every two to three inpatient hospital deaths. Early recognition and treatment are instrumental in reducing mortality, yet there are substantial quality gaps. Sepsis bundles containing quality metrics are often used in efforts to improve outcomes. Several prominent organizations have published their own bundles, but there are few head-to-head comparisons of content.nnnOBJECTIVESnWe sought to determine the degree of agreement on component elements of sepsis bundles and the associated timing goals for completion of each element. We additionally sought to evaluate the amount of variation between metrics associated with bundles.nnnMETHODSnWe reviewed the components of and level of agreement among several sepsis resuscitation and management bundles. We compared the individual bundle elements, together with their associated goals and metrics. We performed a systematic review (PubMed 2008-2015) and searched publically available online content, supplemented by interviews with key informants, to identify eight distinct bundles. Bundles are presented as current as of April 2015.nnnMEASUREMENTS AND MAIN RESULTSnBroadly, elements of care covered early resuscitation and short-term management. Bundles varied from 6 to 10 elements, and there were 12 distinct elements listed across all bundles. Only lactate collection and broad-spectrum antibiotics were common to all eight bundles, although there were seven elements included in at least 75% of the bundles. Timing goals for the collection of lactate and antibiotic administration varied among bundles from within 1 to 6 hours of diagnosis or admission. Notably, no bundle included metrics evaluating timeliness or completeness of sepsis recognition.nnnCONCLUSIONSnThere is a lack of consensus on component elements and timing goals across highly recognized sepsis bundles. These differences highlight an urgent need for comparative effectiveness research to guide future implementation and for metrics to evaluate progress. None of the widely instituted bundles include metrics to evaluate sepsis recognition or diagnostic accuracy.