Barry D. Fuchs

Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult

Judith Jacobi, PharmD, FCCM, BCPS; Gilles L. Fraser, PharmD, FCCM; Douglas B. Coursin, MD; Richard R. Riker, MD; Dorrie Fontaine, RN, DNSc, FAAN; Eric T. Wittbrodt, PharmD; Donald B. Chalfin, MD, MS, FCCM; Michael F. Masica, MD, MPH; H. Scott Bjerke, MD; William M. Coplin, MD; David W. Crippen, MD, FCCM; Barry D. Fuchs, MD; Ruth M. Kelleher, RN; Paul E. Marik, MDBCh, FCCM; Stanley A. Nasraway, Jr, MD, FCCM; Michael J. Murray, MD, PhD, FCCM; William T. Peruzzi, MD, FCCM; Philip D. Lumb, MB, BS, FCCM. Developed through the Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), in collaboration with the American Society of Health-System Pharmacists (ASHP), and in alliance with the American College of Chest Physicians; and approved by the Board of Regents of ACCM and the Council of SCCM and the ASHP Board of Directors

Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial.

BACKGROUND Approaches to removal of sedation and mechanical ventilation for critically ill patients vary widely. Our aim was to assess a protocol that paired spontaneous awakening trials (SATs)-ie, daily interruption of sedatives-with spontaneous breathing trials (SBTs). METHODS In four tertiary-care hospitals, we randomly assigned 336 mechanically ventilated patients in intensive care to management with a daily SAT followed by an SBT (intervention group; n=168) or with sedation per usual care plus a daily SBT (control group; n=168). The primary endpoint was time breathing without assistance. Data were analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00097630. FINDINGS One patient in the intervention group did not begin their assigned treatment protocol because of withdrawal of consent and thus was excluded from analyses and lost to follow-up. Seven patients in the control group discontinued their assigned protocol, and two of these patients were lost to follow-up. Patients in the intervention group spent more days breathing without assistance during the 28-day study period than did those in the control group (14.7 days vs 11.6 days; mean difference 3.1 days, 95% CI 0.7 to 5.6; p=0.02) and were discharged from intensive care (median time in intensive care 9.1 days vs 12.9 days; p=0.01) and the hospital earlier (median time in the hospital 14.9 days vs 19.2 days; p=0.04). More patients in the intervention group self-extubated than in the control group (16 patients vs six patients; 6.0% difference, 95% CI 0.6% to 11.8%; p=0.03), but the number of patients who required reintubation after self-extubation was similar (five patients vs three patients; 1.2% difference, 95% CI -5.2% to 2.5%; p=0.47), as were total reintubation rates (13.8%vs 12.5%; 1.3% difference, 95% CI -8.6% to 6.1%; p=0.73). At any instant during the year after enrolment, patients in the intervention group were less likely to die than were patients in the control group (HR 0.68, 95% CI 0.50 to 0.92; p=0.01). For every seven patients treated with the intervention, one life was saved (number needed to treat was 7.4, 95% CI 4.2 to 35.5). INTERPRETATION Our results suggest that a wake up and breathe protocol that pairs daily spontaneous awakening trials (ie, interruption of sedatives) with daily spontaneous breathing trials results in better outcomes for mechanically ventilated patients in intensive care than current standard approaches and should become routine practice.

Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock

Principle:Serum lactate is a potentially useful biomarker to risk-stratify patients with severe sepsis; however, it is plausible that elevated serum lactate is simply a manifestation of clinically apparent organ dysfunction and/or shock (i.e., refractory hypotension). Objective:To test whether the association between initial serum lactate level and mortality in patients presenting to the emergency department (ED) with severe sepsis is independent of organ dysfunction and shock. Design:Single-center cohort study. The primary outcome was 28-day mortality and the risk factor variable was initial venous lactate (mmol/L), categorized as low (<2), intermediate (2–3.9), or high (≥4). Potential covariates included age, sex, race, acute and chronic organ dysfunction, severity of illness, and initiation of early goal-directed therapy. Multivariable logistic regression analyses were stratified on the presence or absence of shock. Setting:The ED of an academic tertiary care center from 2005 to 2007. Patients:Eight hundred thirty adults admitted with severe sepsis in the ED. Interventions:None. Measurements and Main Results:Mortality at 28 days was 22.9% and median serum lactate was 2.9 mmol/L. Intermediate (odds ratio {lsqb;OR{rsqb; = 2.05, p = 0.024) and high serum lactate levels (OR = 4.87, p < 0.001) were associated with mortality in the nonshock subgroup. In the shock subgroup, intermediate (OR = 3.27, p = 0.022) and high serum lactate levels (OR = 4.87, p = 0.001) were also associated with mortality. After adjusting for potential confounders, intermediate and high serum lactate levels remained significantly associated with mortality within shock and nonshock strata. Conclusions:Initial serum lactate was associated with mortality independent of clinically apparent organ dysfunction and shock in patients admitted to the ED with severe sepsis. Both intermediate and high serum lactate levels were independently associated with mortality.

Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest

BACKGROUND Comatose survivors of out-of-hospital cardiac arrest (OHCA) have high in-hospital mortality due to a complex pathophysiology that includes cardiovascular dysfunction, inflammation, coagulopathy, brain injury and persistence of the precipitating pathology. Therapeutic hypothermia (TH) is the only intervention that has been shown to improve outcomes in this patient population. Due to the similarities between the post-cardiac arrest state and severe sepsis, it has been postulated that early goal-directed hemodyamic optimization (EGDHO) combined with TH would improve outcome of comatose cardiac arrest survivors. OBJECTIVE We examined the feasibility of establishing an integrated post-cardiac arrest resuscitation (PCAR) algorithm combining TH and EGDHO within 6h of emergency department (ED) presentation. METHODS In May, 2005 we began prospectively identifying comatose (Glasgow Motor Score<6) survivors of OHCA treated with our PCAR protocol. The PCAR patients were compared to matched historic controls from a cardiac arrest database maintained at our institution. RESULTS Between May, 2005 and January, 2008, 18/20 (90%) eligible patients were enrolled in the PCAR protocol. They were compared to historic controls from 2001 to 2005, during which time 18 patients met inclusion criteria for the PCAR protocol. Mean time from initiation of TH to target temperature (33 degrees C) was 2.8h (range 0.8-23.2; SD=h); 78% (14/18) had interventions based upon EGDHO parameters; 72% (13/18) of patients achieved their EGDHO goals within 6h of return of spontaneous circulation (ROSC). Mortality for historic controls who qualified for the PCAR protocol was 78% (14/18); mortality for those treated with the PCAR protocol was 50% (9/18) (p=0.15). CONCLUSIONS In patients with ROSC after OHCA, EGDHO and TH can be implemented simultaneously.

Underuse of lung protective ventilation: analysis of potential factors to explain physician behavior.

Objective:To determine the frequency of use of low-tidal-volume ventilation in appropriate patients with acute lung injury (ALI) and the factors associated with the choice of tidal volume. Design:Prospective observational cohort study of patients identified with ALI or acute respiratory distress syndrome from September 2000 to November 2002. Setting:Medical and surgical intensive care unit (ICU) at an academic tertiary-care hospital. Measurements and Main Results:Measurements included the proportion for whom the ventilation tidal volume (TV) was ≤7.5 mL/kg predicted body weight (PBW) on days 2, 4, and 7 of ALI and the proportion for whom the ventilation TV was ≤6.5 and ≤8.5 mL/kg/PBW (sensitivity analysis). Demographic and clinical characteristics of patients undergoing ventilation with low and high TV were compared. Of 88 total patients studied, 39% had ventilation with TV ≤7.5 mL/kg/PBW on day 2 of ALI, 49% on day 4, and 56% on day 7. In contrast, 49% of patients had ventilation with TV >8.5 mL/kg/PBW on day 2 of ALI, 30% on day 4, and 24% on day 7. The use of low TV was significantly associated with clinical parameters indicative of worse disease severity, including low values for Pao2 (p = .01), Pao2/Fio2 (p = .08), and static compliance of the respiratory system (p = .006). Conclusions:Ventilation with a low TV was used in a minority of patients with ALI, despite results published in 1998 and 2000 supporting this approach. This may be related to clinicians’ underrecognition of less severe cases of ALI, their reserving of low-TV ventilation for more severe cases, or both.

Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial

BACKGROUND Acute kidney injury often goes unrecognised in its early stages when effective treatment options might be available. We aimed to determine whether an automated electronic alert for acute kidney injury would reduce the severity of such injury and improve clinical outcomes in patients in hospital. METHODS In this investigator-masked, parallel-group, randomised controlled trial, patients were recruited from the hospital of the University of Pennsylvania in Philadelphia, PA, USA. Eligible participants were adults aged 18 years or older who were in hospital with stage 1 or greater acute kidney injury as defined by Kidney Disease Improving Global Outcomes creatinine-based criteria. Exclusion criteria were initial hospital creatinine 4·0 mg/dL (to convert to μmol/L, multiply by 88·4) or greater, fewer than two creatinine values measured, inability to determine the covering provider, admission to hospice or the observation unit, previous randomisation, or end-stage renal disease. Patients were randomly assigned (1:1) via a computer-generated sequence to receive an acute kidney injury alert (a text-based alert sent to the covering provider and unit pharmacist indicating new acute kidney injury) or usual care, stratified by medical versus surgical admission and intensive care unit versus non-intensive care unit location in blocks of 4-8 participants. The primary outcome was a composite of relative maximum change in creatinine, dialysis, and death at 7 days after randomisation. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01862419. FINDINGS Between Sept 17, 2013, and April 14, 2014, 23,664 patients were screened. 1201 eligible participants were assigned to the acute kidney injury alert group and 1192 were assigned to the usual care group. Composite relative maximum change in creatinine, dialysis, and death at 7 days did not differ between the alert group and the usual care group (p=0·88), or within any of the four randomisation strata (all p>0·05). At 7 days after randomisation, median maximum relative change in creatinine concentrations was 0·0% (IQR 0·0-18·4) in the alert group and 0·6% (0·0-17·5) in the usual care group (p=0·81); 87 (7·2%) patients in the alert group and 70 (5·9%) patients in usual care group had received dialysis (odds ratio 1·25 [95% CI 0·90-1·74]; p=0·18); and 71 (5·9%) patients in the alert group and 61 (5·1%) patients in the usual care group had died (1·16 [0·81-1·68]; p=0·40). INTERPRETATION An electronic alert system for acute kidney injury did not improve clinical outcomes among patients in hospital. FUNDING Penn Center for Healthcare Improvement and Patient Safety.

Cost savings attributable to reductions in intensive care unit length of stay for mechanically ventilated patients.

Objectives:To estimate the actual cost savings that could be achieved through reductions in intensive care unit (ICU) length of stay and duration of mechanical ventilation by determining the short-run marginal variable cost of an ICU and ventilator day. Research Design:Retrospective cohort study in a university-affiliated teaching hospital. Subjects:All patients receiving mechanical ventilation in the ICU for more than 48 hours (n = 1778) from July 1, 2005 to June 30, 2006. Measures:The hospitals administrative and cost databases were used to determine total costs, variable costs, and direct-variable costs for each patient on each individual ICU and hospital day. Results:Direct-variable costs comprised 19.3% of total ICU costs and 18.4% of total hospital costs. Marginal direct-variable costs (the cost of each additional ICU day) were small compared with the average daily total cost (

Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia

649 to

Severe Sepsis Cohorts Derived From Claims-based Strategies Appear to be Biased Toward a More Severely Ill Patient Population*

839 vs.

ANGPT2 Genetic Variant Is Associated with Trauma-associated Acute Lung Injury and Altered Plasma Angiopoietin-2 Isoform Ratio

1751, in US dollars). In survivors with ICU lengths of stay more than 3 days, the mean direct-variable cost of the last ICU day was