Efficacy and Outcomes After Vasopressin Guideline Implementation in Septic Shock.

BACKGROUND: In septic shock, the dose of norepinephrine (NE) at which vasopressin (AVP) should be added is unknown. Following an increase in AVP price, our medical intensive care unit (MICU) revised its vasopressor guidelines to reserve AVP for patients requiring greater than 50 µg/min of NE. OBJECTIVE: The purpose of this study is to compare efficacy and safety outcomes for patients admitted before the guideline revision with those for patients admitted after the revision. METHODS: This was a single-center, retrospective cohort study of patients admitted to Vanderbilt University Medical Center from November 1, 2014, to November 30, 2015. Before June 1, 2015, the vasopressor guidelines recommended initiation of AVP for patients requiring 10 µg/min of NE or greater. After June 1, 2015, the guidelines recommended initiation of AVP at a NE dose of 50 µg/min or greater. RESULTS: Time to achieve goal mean arterial pressure (MAP) was shorter in the postintervention group (2.0 vs 1.3 hours; P = 0.03) in univariate analysis but not after adjusting for prespecified confounders. Incidence of new arrhythmias was similar between the 2 groups (14.9% vs 10.9%; P = 0.567). In multivariable analysis accounting for baseline severity of illness, admission after the revision was associated with decreased 28-day mortality (odds ratio = 0.34; 95% CI = 0.16-0.71; P = 0.004). CONCLUSIONS: Use of a vasopressor guideline restricting AVP initiation in septic patients to those on at least 50 µg/min of NE appeared to be safe and did not affect the time to reach goal MAP.

Incidence and characterization of acute kidney injury after acetaminophen overdose.

PURPOSE: Acute kidney injury (AKI) occurs in 2-10% of patients with acetaminophen (APAP) overdose. Elevation in creatinine (SCr) typically occurs 2 to 5 days after ingestion, with a mean peak on day 7, and normalization over a month. However, it remains unclear whether renal impairment occurs without hepatotoxicity. We hypothesized that APAP-associated acute renal failure occurs in patients with and without severe liver dysfunction after APAP overdose. MATERIALS AND METHODS: We retrospectively evaluated all patients admitted to the Medical Intensive Care Unit at a tertiary hospital and received acetylcysteine between June 2009 and December 2014. Of the 303 patients meeting these criteria, 139 of these patients received acetylcysteine for APAP overdose. Of these patients, 138 had Model for End-Stage Liver Disease (MELD) Scores on Day 1 of admission. Using a modified MELD (m-MELD) score, only containing total bilirubin and international normalized ratio not the SCr, the median m-MELD score was calculated. Patients with m-MELD scores below the median were compared to those with scores above the median (low m-MELD score <2.9 or high m-MELD score >2.9). RESULTS: Baseline demographics were similar in the two groups with the exception of more hypertension in the low m-MELD group (24 vs 7%; P= .02). Time to admission was shorter in the low m-MELD group (7.9 ± 9.3 vs. 25.7 ± 29.2 hours; P= .001). The mean admission APAP level was 96.9 (±119) µg/mL in the low compared to 52.3 (±85.3) µg/mL in the high m-MELD group (P= .012). Day one SCr (1.2 ± 0.9 vs 2.7 ± 2.2 mg/dL; P< .0001) and change from baseline to highest SCr (0.2 ± 0.3 vs. 2.7 ± 3.3 mg/dL; P< .0001) were both lower in the low m-MELD group compared to the high m-MELD group. In addition, renal failure resolved upon discharge in all 2 patients (3%) with AKI in the low m-MELD group as compared to only 19 patients (44%) in the high m-MELD group. CONCLUSIONS: Mean day one SCr, maximum change in SCr, and lack of renal failure resolution were higher in patients with higher m-MELD scores. However, patients with low m-MELD scores presented much earlier than patients with high m-MELD scores and 26% developed AKI.

B-Type Natriuretic Peptide, Aldosterone, and Fluid Management in ARDS.

BACKGROUND: Conservative fluid management increases ventilator-free days without influencing overall mortality in acute respiratory distress syndrome. Plasma concentrations of B-type natriuretic peptide (a marker of ventricular filling) or aldosterone (a marker of effective circulating volume) may identify patients for whom fluid management impacts survival. METHODS: This was a retrospective analysis of the Fluid and Catheter Treatment Trial (FACTT), a randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. Using plasma collected at study enrollment, we measured B-type natriuretic peptide and aldosterone by immunoassay. Multivariable analyses examined the interaction between B-type natriuretic peptide or aldosterone concentration and fluid strategy with regard to 60-day in-hospital mortality. RESULTS: Among 625 patients with adequate plasma, median B-type natriuretic peptide concentration was 825 pg/mL (interquartile range, 144-1,574 pg/mL), and median aldosterone was 2.49 ng/dL (interquartile range, 1.1-4.3 ng/dL). B-type natriuretic peptide did not predict overall mortality, correlate with fluid balance, or modify the effect of conservative vs liberal fluid management on outcomes. In contrast, among patients with lower aldosterone concentrations, conservative fluid management increased ventilator-free days (17.1 ± 9.8 vs 12.5 ± 10.3, P < .001) and decreased mortality (19% vs 30%, P = .03) (P value for interaction = .01). CONCLUSIONS: In acute respiratory distress syndrome, B-type natriuretic peptide does not modify the effect of fluid management on outcomes. Lower initial aldosterone appears to identify patients for whom conservative fluid management may improve mortality.

Outcomes of Nurse Practitioner-Delivered Critical Care: A Prospective Cohort Study.

BACKGROUND: Acute care nurse practitioners (ACNPs) are increasingly being employed in ICUs to offset physician shortages, but no data exist about outcomes of critically ill patients continuously cared for by ACNPs. METHODS: Prospective cohort study of all admissions to an adult medical ICU in an academic, tertiary-care center between January 1, 2011, and December 31, 2013. The primary end point of 90-day survival was compared between patients cared for by ACNP and resident teams using Cox proportional hazards regression. Secondary end points included ICU and hospital mortality and ICU and hospital length of stay. RESULTS: Among 9,066 admissions, there was no difference in 90-day survival for patients cared for by ACNP or resident teams (adjusted hazard ratio [HR], 0.94; 95% CI, 0.85-1.04; P = .21). Although patients cared for by ACNPs had lower ICU mortality (6.3%) than resident team patients (11.6%; adjusted OR, 0.77; 95% CI, 0.63-0.94; P = .01), hospital mortality was not different (10.0% vs 15.9%; adjusted OR, 0.87; 95% CI, 0.73-1.03; P = .11). ICU length of stay was similar between the ACNP and resident teams (3.4 ± 3.5 days vs 3.7 ± 3.9 days [adjusted OR, 1.01; 95% CI, 0.93-1.1; P = .81]), but hospital length of stay was shorter for patients cared for by ACNPs (7.9 ± 11.2 days) than for resident patients (9.1 ± 11.2 days) (adjusted OR, 0.87; 95% CI, 0.80-0.95; P = .001). CONCLUSION: Outcomes are comparable for critically ill patients cared for by ACNP and resident teams.

Medication Desensitization: Characterization of Outcomes and Risk Factors for Reactions.

BACKGROUND: Although its mechanisms are poorly understood, desensitization has been used to induce a temporary state of immune unresponsiveness in patients who have IgE-, non-IgE-, or pharmacologically mediated reactions when a drug has no alternatives. OBJECTIVES: The purpose of this study was to characterize the outcomes and identify risk factors for reactions during drug desensitization. METHODS: A retrospective review of electronic medical records of adult patients undergoing drug desensitization from January 1, 2011, to December 31, 2013, was conducted in 2 intensive care units at a tertiary medical center. We used multivariate analysis to determine if specified risk factors were associated with reacting during the desensitization. Reactions were classified according to the pretest probability prior to desensitization, and then, reactions during desensitization were classified based on the occurrence of cutaneous reactions as follows: successful with no reaction, mild reaction, moderate reaction, or failed. Failure could result from any systemic allergic or cutaneous reaction resulting in procedure termination. The desensitizations were also assessed to determine if the patient required de-escalation secondary to a reaction. RESULTS: A total of 88 desensitizations were performed in 69 patients. Desensitization was completed with no cutaneous reaction in 85% of patients. No baseline characteristic, medication class (P = 0.46), or indication for desensitization (P = 0.59) was associated with having a reaction. Reported histories of urticaria (P < 0.0001) and labored breathing (P = 0.003) during prior exposure were significant in identifying patients who might have a reaction during desensitization. However, neither history of urticaria nor labored breathing was independently associated with having a reaction in multivariate analysis (OR = 0.979, 95% CI = 0.325-2.952, P = 0.970, and OR = 1.626, 95% CI = 0.536-4.931, P = 0.739, respectively). CONCLUSIONS: Drug desensitization is safe for patients who have no alternative for therapy. Reported allergy histories of urticaria and labored breathing are both associated with having a reaction during the desensitization process.

Impact of Initial Central Venous Pressure on Outcomes of Conservative Versus Liberal Fluid Management in Acute Respiratory Distress Syndrome.

OBJECTIVES: In acute respiratory distress syndrome, conservative fluid management increases ventilator-free days without affecting mortality. Response to fluid management may differ based on patients' initial central venous pressure. We hypothesized that initial central venous pressure would modify the effect of fluid management on outcomes. DESIGN: Retrospective analysis of the Fluid and Catheter Treatment Trial, a multicenter randomized trial comparing conservative with liberal fluid management in acute respiratory distress syndrome. We examined the relationship between initial central venous pressure, fluid strategy, and 60-day mortality in univariate and multivariable analysis. SETTING: Twenty acute care hospitals. PATIENTS: Nine hundred thirty-four ventilated acute respiratory distress syndrome patients with a central venous pressure available at enrollment, 609 without baseline shock (for whom fluid balance was managed by the study protocol). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among patients without baseline shock, those with initial central venous pressure greater than 8 mm Hg experienced similar mortality with conservative and liberal fluid management (18% vs 18%; p = 0.928), whereas those with central venous pressure of 8 mm Hg or less experienced lower mortality with a conservative strategy (17% vs 36%; p = 0.005). Multivariable analysis demonstrated an interaction between initial central venous pressure and the effect of fluid strategy on mortality (p = 0.031). At higher initial central venous pressures, the difference in treatment between arms was predominantly furosemide administration, which was not associated with mortality (p = 0.122). At lower initial central venous pressures, the difference between arms was predominantly fluid administration, with additional fluid associated with increased mortality (p = 0.013). CONCLUSIONS: Conservative fluid management decreases mortality for acute respiratory distress syndrome patients with a low initial central venous pressure. In this population, the administration of IV fluids seems to increase mortality.

Response to fluid boluses in the fluid and catheter treatment trial.

BACKGROUND: Recent emphasis has been placed on methods to predict fluid responsiveness, but the usefulness of using fluid boluses to increase cardiac index in critically ill patients with ineffective circulation or oliguria remains unclear. METHODS: This retrospective analysis investigated hemodynamic responses of critically ill patients in the ARDS Network Fluid and Catheter Treatment Trial (FACTT) who were given protocol-based fluid boluses. Fluid responsiveness was defined as ≥ 15% increase in cardiac index after a 15 mL/kg fluid bolus. RESULTS: A convenience sample of 127 critically ill patients enrolled in FACTT was analyzed for physiologic responses to 569 protocolized crystalloid or albumin boluses given for shock, low urine output (UOP), or low pulmonary artery occlusion pressure (PAOP). There were significant increases in mean central venous pressure (9.9 ± 4.5 to 11.1 ± 4.8 mm Hg, P < .0001) and mean PAOP (11.6 ± 3.6 to 13.3 ± 4.3 mm Hg, P < .0001) following fluid boluses. However, there were no significant changes in UOP, and there were clinically small changes in heart rate, mean arterial pressure, and cardiac index. Only 23% of fluid boluses led to a ≥ 15% change in cardiac index. There was no significant difference in the frequency of fluid responsiveness between boluses given for shock or oliguria vs boluses given only for low PAOP (24.0% vs 21.8%, P = .59). There were no significant differences in 90-day survival, need for hemodialysis, or return to unassisted breathing between patients defined as fluid responders and fluid nonresponders. CONCLUSIONS: In this cohort of critically ill patients with ARDS who were previously resuscitated, the rate of fluid responsiveness was low, and fluid boluses only led to small hemodynamic changes.

An Electronic Tool for the Evaluation and Treatment of Sepsis in the ICU: A Randomized Controlled Trial.

OBJECTIVES: To determine whether addition of an electronic sepsis evaluation and management tool to electronic sepsis alerting improves compliance with treatment guidelines and clinical outcomes in septic ICU patients. DESIGN: A pragmatic randomized trial. SETTING: Medical and surgical ICUs of an academic, tertiary care medical center. PATIENTS: Four hundred and seven patients admitted during a 4-month period to the medical or surgical ICU with a diagnosis of sepsis established at the time of admission or in response to an electronic sepsis alert. INTERVENTIONS: Patients were randomized to usual care or the availability of an electronic tool capable of importing, synthesizing, and displaying sepsis-related data from the medical record, using logic rules to offer individualized evaluations of sepsis severity and response to therapy, informing users about evidence-based guidelines, and facilitating rapid order entry. MEASUREMENTS AND MAIN RESULTS: There was no difference between the electronic tool (218 patients) and usual care (189 patients) with regard to the primary outcome of time to completion of all indicated Surviving Sepsis Campaign 6-hour Sepsis Resuscitation Bundle elements (hazard ratio, 1.98; 95% CI, 0.75-5.20; p = 0.159) or time to completion of each element individually. ICU mortality, ICU-free days, and ventilator-free days did not differ between intervention and control. Providers used the tool to enter orders in only 28% of available cases. CONCLUSIONS: A comprehensive electronic sepsis evaluation and management tool is feasible and safe but did not influence guideline compliance or clinical outcomes, perhaps due to low utilization.

Pharmacist leadership in ICU quality improvement: coordinating spontaneous awakening and breathing trials.

BACKGROUND: Coordinating efforts across disciplines in the intensive care unit is a key component of quality improvement (QI) efforts. Spontaneous awakening trials (SATs) and spontaneous breathing trials (SBTs) are considered key components of guidelines, yet unfortunately are often not done or coordinated properly. OBJECTIVE: To determine if a pharmacist-driven awakening and breathing coordination (ABC) QI program would improve compliance (ie, process measures) as compared with the previous protocol, which did not involve pharmacists. METHODS: The QI program included pharmacist-led education, daily discussion on rounds, and weekly performance reports to staff. Using a pre-QI versus during-QI versus post-QI intervention design, we compared data from 500 control ventilator-days (pre-QI period) versus 580 prospective ventilator-days (during-QI period). We then evaluated the sustainability of the QI program in 216 ventilator-days in the post-QI period. RESULTS: SAT safety screens were performed on only 20% pre-QI patient-days versus 97% of during-QI patient-days (P < 0.001) and 100% of post-QI patient-days (P = 0.25). The rates of passing the SAT safety screen in pre-QI and during-QI periods were 63% versus 78% (P = 0.03) and 81% in the post-QI period (P = 0.86). The rates of SATs among eligible patients on continuous infusions were only 53% in the pre-QI versus 85% in the during-QI (P = 0.0001) and 87% in the post-QI (P = 1) periods. CONCLUSIONS: In this QI initiative, a pharmacist-driven, interdisciplinary ABC protocol significantly improved process measures compliance, comparing the pre-QI versus during-QI rates of screening, performing, and coordinating SAT and SBTs, and these results were sustained in the 8-month follow-up period post-QI program.

A randomized trial comparing didactics, demonstration, and simulation for teaching teamwork to medical residents.

RATIONALE: Effective teamwork is fundamental to the management of medical emergencies, and yet the best method to teach teamwork skills to trainees remains unknown. OBJECTIVES: In a cohort of incoming internal medicine interns, we tested the hypothesis that expert demonstration of teamwork principles and participation in high-fidelity simulation would each result in objectively assessed teamwork behavior superior to traditional didactics. METHODS: This was a randomized, controlled, parallel-group trial comparing three teamwork teaching modalities for incoming internal medicine interns. Participants in a single-day orientation at the Vanderbilt University Center for Experiential Learning and Assessment were randomized 1:1:1 to didactic, demonstration-based, or simulation-based instruction and then evaluated in their management of a simulated crisis by five independent, blinded observers using the Teamwork Behavioral Rater score. Clinical performance was assessed using the American Heart Association Advanced Cardiac Life Support algorithm and a novel "Recognize, Respond, Reassess" score. MEASUREMENTS AND MAIN RESULTS: Participants randomized to didactics (n = 18), demonstration (n = 17), and simulation (n = 17) were similar at baseline. The primary outcome of average overall Teamwork Behavioral Rater score for those who received demonstration-based training was similar to simulation participation (4.40 ± 1.15 vs. 4.10 ± 0.95, P = 0.917) and significantly higher than didactic instruction (4.40 ± 1.15 vs. 3.10 ± 0.51, P = 0.045). Clinical performance scores were similar between the three groups and correlated only weakly with teamwork behavior (coefficient of determination [Rs(2)] = 0.267, P < 0.001). CONCLUSIONS: Among incoming internal medicine interns, teamwork training by expert demonstration resulted in similar teamwork behavior to participation in high-fidelity simulation and was more effective than traditional didactics. Clinical performance was largely independent of teamwork behavior and did not differ between training modalities.

Chlorhexidine bathing and health care-associated infections: a randomized clinical trial.

IMPORTANCE: Daily bathing of critically ill patients with the broad-spectrum, topical antimicrobial agent chlorhexidine is widely performed and may reduce health care-associated infections. OBJECTIVE: To determine if daily bathing of critically ill patients with chlorhexidine decreases the incidence of health care-associated infections. DESIGN, SETTING, AND PARTICIPANTS: A pragmatic cluster randomized, crossover study of 9340 patients admitted to 5 adult intensive care units of a tertiary medical center in Nashville, Tennessee, from July 2012 through July 2013. INTERVENTIONS: Units performed once-daily bathing of all patients with disposable cloths impregnated with 2% chlorhexidine or nonantimicrobial cloths as a control. Bathing treatments were performed for a 10-week period followed by a 2-week washout period during which patients were bathed with nonantimicrobial disposable cloths, before crossover to the alternate bathing treatment for 10 weeks. Each unit crossed over between bathing assignments 3 times during the study. MAIN OUTCOMES AND MEASURES: The primary prespecified outcome was a composite of central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), ventilator-associated pneumonia (VAP), and Clostridium difficile infections. Secondary outcomes included rates of clinical cultures that tested positive for multidrug-resistant organisms, blood culture contamination, health care-associated bloodstream infections, and rates of the primary outcome by ICU. RESULTS: During the chlorhexidine bathing period, 55 infections occurred: 4 CLABSI, 21 CAUTI, 17 VAP, and 13 C difficile. During the control bathing period, 60 infections occurred: 4 CLABSI, 32 CAUTI, 8 VAP, and 16 C difficile. The primary outcome rate was 2.86 per 1000 patient-days during the chlorhexidine and 2.90 per 1000 patient-days during the control bathing periods (rate difference, -0.04; 95% CI, -1.10 to 1.01; P = .95). After adjusting for baseline variables, no difference between groups in the rate of the primary outcome was detected. Chlorhexidine bathing did not change rates of infection-related secondary outcomes including hospital-acquired bloodstream infections, blood culture contamination, or clinical cultures yielding multidrug-resistant organisms. In a prespecified subgroup analysis, no difference in the primary outcome was detected in any individual intensive care unit. CONCLUSION AND RELEVANCE: In this pragmatic trial, daily bathing with chlorhexidine did not reduce the incidence of health care-associated infections including CLABSIs, CAUTIs, VAP, or C difficile. These findings do not support daily bathing of critically ill patients with chlorhexidine. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02033187.

Addition of acute care nurse practitioners to medical and surgical rapid response teams: a pilot project.

Background Vanderbilt University Hospital's original rapid response team included a critical care charge nurse and a respiratory therapist. A frequently identified barrier to care was the time delay between arrival of the rapid response team and arrival of the primary health care team. Objective To assess the impact of adding an acute care nurse practitioner to the rapid response team. Methods Acute care nurse practitioners were added to surgical and medical rapid response teams in January 2011 to diagnose and order treatments on rapid response calls. Results In 2011, the new teams responded to 898 calls, averaging 31.8 minutes per call. The most frequent diagnoses were respiratory distress (18%), postoperative pain (13%), hypotension (12%), and tachyarrhythmia (10%). The teams facilitated 360 transfers to intensive care and provided 3056 diagnostic and therapeutic interventions. Communication with the primary team was documented on 97% of the calls. Opportunities for process improvement were identified on 18% of the calls. After implementation, charge nurses were surveyed, with 96% expressing high satisfaction associated with enhanced service and quality. Conclusions Teams led by nurse practitioners provide diagnostic expertise and treatment, facilitation of transfers, team communication, and education.

Remote source document verification in two national clinical trials networks: a pilot study.

OBJECTIVE: Barriers to executing large-scale randomized controlled trials include costs, complexity, and regulatory requirements. We hypothesized that source document verification (SDV) via remote electronic monitoring is feasible. METHODS: Five hospitals from two NIH sponsored networks provided remote electronic access to study monitors. We evaluated pre-visit remote SDV compared to traditional on-site SDV using a randomized convenience sample of all study subjects due for a monitoring visit. The number of data values verified and the time to perform remote and on-site SDV was collected. RESULTS: Thirty-two study subjects were randomized to either remote SDV (N=16) or traditional on-site SDV (N=16). Technical capabilities, remote access policies and regulatory requirements varied widely across sites. In the adult network, only 14 of 2965 data values (0.47%) could not be located remotely. In the traditional on-site SDV arm, 3 of 2608 data values (0.12%) required coordinator help. In the pediatric network, all 198 data values in the remote SDV arm and all 183 data values in the on-site SDV arm were located. Although not statistically significant there was a consistent trend for more time consumed per data value (minutes +/- SD): Adult 0.50 +/- 0.17 min vs. 0.39 +/- 0.10 min (two-tailed t-test p=0.11); Pediatric 0.99 +/- 1.07 min vs. 0.56 +/- 0.61 min (p=0.37) and time per case report form: Adult: 4.60 +/- 1.42 min vs. 3.60 +/- 0.96 min (p=0.10); Pediatric: 11.64 +/- 7.54 min vs. 6.07 +/- 3.18 min (p=0.10) using remote SDV. CONCLUSIONS: Because each site had different policies, requirements, and technologies, a common approach to assimilating monitors into the access management system could not be implemented. Despite substantial technology differences, more than 99% of data values were successfully monitored remotely. This pilot study demonstrates the feasibility of remote monitoring and the need to develop consistent access policies for remote study monitoring.