Faculty Bibliography

Objective: We present a patient who developed prolonged coma following treatment of ethanol withdrawal with large doses of diazepam and demonstrated prolonged elimination toxicokinetics. Case report: A 68-year-old man who drank 5-6 alcoholic beverages/day was admitted for an elective transcatheter aortic valve replacement. Two days post-procedure, he developed agitation and was presumptively treated for ethanol withdrawal with diazepam (470 mg IV over 24 hours). He remained comatose for four days prompting a toxicology consult. On day 7 of persistent coma from presumed benzodiazepine excess, flumazenil (0.5 mg) was administered; he opened his eyes for the first time, began speaking, and answering simple questions, but 30 minutes later was comatose again. Flumazenil infusion 0.25mg/h was trialed with unclear effect. His hospitalization was complicated by gastrointestinal bleeding and mild ischemic stroke deemed noncontributory to his clinical status. The flumazenil infusion was discontinued 1 week later. His evaluation was extensive (brain magnetic resonance imaging and computerised tomography, lumbar puncture, and blood cultures) and unremarkable. On hospital week 4, he became only gradually more awake, and was eventually discharged to a rehabilitation facility on hospital week 6, awake, conversive but still confused. Six weeks later, he was discharged home fully recovered. He remains amnestic to his hospitalization. Serum diazepam and nordiazepam concentrations were determined via liquid-chromatography mass-spectrometry. Concentrations obtained four days after the last dose were: diazepam 963 mug/L (therapeutic: 200-1000 mug/L) and nordiazepam 240 mug/L (therapeutic: 100-1500 mug/L). Elimination kinetics were calculated with apparent half-lives of 294 hours and 797 hours for diazepam and nordiazepam, respectively. Genotyping of CYP3A4 and CYP2C19, the two primary metabolizers of diazepam, demonstrated no abnormalities.
Conclusion(s): Diazepam demonstrated extremely atypical elimination kinetics despite normal renal and hepatic function. Acute tolerance which is expected after prolonged benzodiazepine exposure was not clearly demonstrated. The relationship between his serum concentration and clinical status is unclear at this time

The left ventricular outflow tract (LVOT) velocity time integral (VTI) is an easily measured echocardiographic stroke volume index analog. Low values predict adverse outcomes in left ventricular failure. We postulate the left ventricular VTI may be a signal of right ventricular dysfunction in acute pulmonary embolism, and therefore a predictor of poor outcomes. We retrospectively reviewed echocardiograms on all Pulmonary Embolism Response Team activations at our institution at the time of pulmonary embolism diagnosis. Low LVOT VTI was defined as ⩽ 15 cm. We examined two composite outcomes: (1) in-hospital death or cardiac arrest; and (2) shock or need for primary reperfusion therapies. Sixty-one of 188 patients (32%) had a LVOT VTI of ⩽ 15 cm. Low VTI was associated with in-hospital death or cardiac arrest (odds ratio (OR) 6, 95% CI 2, 17.9; p = 0.0014) and shock or need for reperfusion (OR 23.3, 95% CI 6.6, 82.1; p < 0.0001). In a multivariable model, LVOT VTI ⩽ 15 remained significant for death or cardiac arrest (OR 3.48, 95% CI 1.02, 11.9; p = 0.047) and for shock or need for reperfusion (OR 8.12, 95% CI 1.62, 40.66; p = 0.011). Among intermediate-high-risk patients, low VTI was the only variable associated with the composite outcome of death, cardiac arrest, shock, or need for reperfusion (OR 14, 95% CI 1.7, 118.4; p = 0.015). LVOT VTI is associated with adverse short-term outcomes in acute pulmonary embolism. The VTI may help risk stratify patients with intermediate-high-risk pulmonary embolism.

BACKGROUND:Temporary mechanical circulatory support (MCS) devices provide hemodynamic assistance for shock refractory to pharmacological treatment. Most registries have focused on single devices or specific etiologies of shock, limiting data regarding overall practice patterns with temporary MCS in cardiac intensive care units. METHODS:The CCCTN (Critical Care Cardiology Trials Network) is a multicenter network of tertiary CICUs in North America. Between September 2017 and September 2018, each center (n=16) contributed a 2-month snapshot of consecutive medical CICU admissions. RESULTS:Of the 270 admissions using temporary MCS, 33% had acute myocardial infarction-related cardiogenic shock (CS), 31% had CS not related to acute myocardial infarction, 11% had mixed shock, and 22% had an indication other than shock. Among all 585 admissions with CS or mixed shock, 34% used temporary MCS during the CICU stay with substantial variation between centers (range: 17%-50%). The most common temporary MCS devices were intraaortic balloon pumps (72%), Impella (17%), and veno-arterial extracorporeal membrane oxygenation (11%), although intraaortic balloon pump use also varied between centers (range: 40%-100%). Patients managed with intraaortic balloon pump versus other forms of MCS (advanced MCS) had lower Sequential Organ Failure Assessment scores and less severe metabolic derangements. Illness severity was similar at high- versus low-MCS utilizing centers and at centers with more advanced MCS use. CONCLUSIONS:There is wide variation in the use of temporary MCS among patients with shock in tertiary CICUs. While hospital-level variation in temporary MCS device selection is not explained by differences in illness severity, patient-level variation appears to be related, at least in part, to illness severity.

Importance/UNASSIGNED:Single-center and claims-based studies have described substantial changes in the landscape of care in the cardiac intensive care unit (CICU). Professional societies have recommended research to guide evidence-based CICU redesigns. Objective/UNASSIGNED:To characterize patients admitted to contemporary, advanced CICUs. Design, Setting, and Participants/UNASSIGNED:This study established the Critical Care Cardiology Trials Network (CCCTN), an investigator-initiated multicenter network of 16 advanced, tertiary CICUs in the United States and Canada. For 2 months in each CICU, data for consecutive admissions were submitted to the central data coordinating center (TIMI Study Group). The data were collected and analyzed between September 2017 and 2018. Main Outcomes and Measures/UNASSIGNED:Demographics, diagnoses, management, and outcomes. Results/UNASSIGNED:Of 3049 participants, 1132 (37.1%) were women, 797 (31.4%) were individuals of color, and the median age was 65 years (25th and 75th percentiles, 55-75 years). Between September 2017 and September 2018, 3310 admissions were included, among which 2557 (77.3%) were for primary cardiac problems, 337 (10.2%) for postprocedural care, 253 (7.7%) for mixed general and cardiac problems, and 163 (4.9%) for overflow from general medical ICUs. When restricted to the initial 2 months of medical CICU admissions for each site, the primary analysis population included 3049 admissions with a high burden of noncardiovascular comorbidities. The top 2 CICU admission diagnoses were acute coronary syndrome (969 [31.8%]) and heart failure (567 [18.6%]); however, the proportion of acute coronary syndrome was highly variable across centers (15%-57%). The primary indications for CICU care included respiratory insufficiency (814 [26.7%]), shock (643 [21.1%]), unstable arrhythmia (521 [17.1%]), and cardiac arrest (265 [8.7%]). Advanced CICU therapies or monitoring were required for 1776 patients (58.2%), including intravenous vasoactive medications (1105 [36.2%]), invasive hemodynamic monitoring (938 [30.8%]), and mechanical ventilation (652 [21.4%]). The overall CICU mortality rate was 8.3% (95% CI, 7.3%-9.3%). The CICU indications that were associated with the highest mortality rates were cardiac arrest (101 [38.1%]), cardiogenic shock (140 [30.6%]), and the need for renal replacement therapy (51 [34.5%]). Notably, patients admitted solely for postprocedural observation or frequent monitoring had a mortality rate of 0.2% to 0.4%. Conclusions and Relevance/UNASSIGNED:In a contemporary network of tertiary care CICUs, respiratory failure and shock predominated indications for admission and carried a poor prognosis. While patterns of practice varied considerably between centers, a substantial, low-risk population was identified. Multicenter collaborative networks, such as the CCCTN, could be used to help redesign cardiac critical care and to test new therapeutic strategies.

Despite improvements in the management of in-hospital cardiac arrest over the past decade, in-hospital cardiac arrest continues to be associated with poor prognosis. This has led to the development of rapid response systems, hospital-wide efforts to improve patient outcomes by centering on prompt identification of decompensating patients, expert clinical management, and continuous quality improvement of processes of care. The rapid response system may include cardiac arrest teams, which are centered on identification and treatment of patients with in-hospital cardiac arrest. However, few evidence-based guidelines exist to guide the formation of such teams, and the degree of their variation across the United States has not been well described.

Objective: Pulmonary embolism response teams (PERTs)have become increasingly popular at institutions around the country, although only anecdotal evidence is available to support their efficacy. PERTs are mechanisms for rapid involvement of a multidisciplinary team in the management of a time-sensitive condition with many treatment options spanning multiple specialties. We aimed to evaluate time to management of pulmonary embolisms and outcomes since 2016 under our institution's PERT. Method(s): We retrospectively reviewed 151 patients with PERT activations since inception, collecting data on demographics, time to treatment, treatment modality, and in-hospital outcomes. Result(s): The average age was 62.4 years (range, 30-95 years), and 54% of patients were male; 39.4% of patients had normal echocardiographic recordings, with 27% showing right ventricular (RV)hypokinesis, 9.1% showing elevated pulmonary artery pressures, and 6.1% showing RV enlargement. Anticoagulation alone was received by 91.4% of patients; 4.5% had catheter-directed therapy (CDL), and 3.0% had systemic administration of tissue plasminogen activator (tPA). The average time to invasive intervention was 665 minutes (95% confidence interval [CI], 249-1080 minutes)for CDL and 22 minutes (95% CI, 0-456 minutes)for systemic tPA. Average time to anticoagulation was 3 minutes (95% CI, 154-160 minutes). For patients with echocardiographic findings suggestive of RV strain, 21.4% (95% CI, 0.04-0.51)had tPA or an invasive intervention. Of patients with echocardiographic findings consistent with RV strain who underwent conservative management, 80% were discharged home after an average length of stay of 6.0 days (95% CI, 4.5-7.5). Twenty (14.1%; 95% CI, 5.5-22.5)patients receiving anticoagulation alone had bleeding events, whereas none of the patients undergoing CDL or tPA had bleeding. Sixteen (11.2%; 95% CI, 5.7-16.3)patients who had anticoagulation died in the hospital or were discharged to hospice, and none of the patients receiving CDL or tPA died or were discharged to hospice. The odds of in-hospital death were lower for patients receiving anticoagulation than for those without (odds ratio, 0.29), suggesting appropriate identification of high-risk patients. Average hospital stay was 6.5 days (95% CI, 4.9-8.5)for patients who received anticoagulation, 5.3 days for CDL (95% CI, 0-11.2), and 8 days for tPA (95% CI, 2.6-13.4). Conclusion(s): We found that a dedicated PERT team leads to efficient delivery of care and excellent outcomes. The majority of pulmonary embolisms can be managed with anticoagulation alone. CDT and systemic tPA are safe adjunctive treatments for select patients.

OBJECTIVES/OBJECTIVE:To characterise the variation in composition, leadership, and activation criteria of rapid response and cardiac arrest teams in five north-eastern states of the USA. DESIGN/METHODS:Cross-sectional study consisting of a voluntary 46-question survey of acute care hospitals in north-eastern USA. SETTING/METHODS:Acute care hospitals in New York, New Jersey, Rhode Island, Vermont, and Pennsylvania. PARTICIPANTS/METHODS:Surveys were completed by any member of the rapid response team (RRT) with a working knowledge of team composition and function. Participants were all Medicare-participating acute care hospitals, including teaching and community hospitals as well as hospitals from rural, urban and suburban areas. RESULTS:Out of 378 hospitals, contacts were identified for 303, and 107 surveys were completed. All but two hospitals had an RRT, 70% of which changed members daily. The most common activation criteria were clinical concern (95%), single vital sign abnormalities (77%) and early warning score (59%). Eighty one per cent of hospitals had a dedicated cardiac arrest team.RRT composition varied widely, with respiratory therapists, critical care nurses, physicians and nurse managers being the most likely to attend (89%, 78%, 64% and 51%, respectively). Consistent presence of critical care physicians was uncommon and both cardiac arrest teams and teams were frequently led by trainee physicians, often without senior supervision. CONCLUSIONS:As the largest study to date in the USA, we have demonstrated wide heterogeneity, rapid team turnover and a lack of senior supervision of RRT and cardiac arrest teams. These factors likely contribute to the mixed results seen in studies of RRTs.

Background Clinical investigations of shock in cardiac intensive care units (CICUs) have primarily focused on acute myocardial infarction (AMI) complicated by cardiogenic shock (AMICS). Few studies have evaluated the full spectrum of shock in contemporary CICUs. Methods and Results The Critical Care Cardiology Trials Network is a multicenter network of advanced CICUs in North America. Anytime between September 2017 and September 2018, each center (n=16) contributed a 2-month snap-shot of all consecutive medical admissions to the CICU. Data were submitted to the central coordinating center (TIMI Study Group, Boston, MA). Shock was defined as sustained systolic blood pressure <90 mm Hg with end-organ dysfunction ascribed to the hypotension. Shock type was classified by site investigators as cardiogenic, distributive, hypovolemic, or mixed. Among 3049 CICU admissions, 677 (22%) met clinical criteria for shock. Shock type was varied, with 66% assessed as cardiogenic shock (CS), 7% as distributive, 3% as hypovolemic, 20% as mixed, and 4% as unknown. Among patients with CS (n=450), 30% had AMICS, 18% had ischemic cardiomyopathy without AMI, 28% had nonischemic cardiomyopathy, and 17% had a cardiac cause other than primary myocardial dysfunction. Patients with mixed shock had cardiovascular comorbidities similar to patients with CS. The median CICU stay was 4.0 days (interquartile range [IQR], 2.5-8.1 days) for AMICS, 4.3 days (IQR, 2.1-8.5 days) for CS not related to AMI, and 5.8 days (IQR, 2.9-10.0 days) for mixed shock versus 1.9 days (IQR, 1.0-3.6) for patients without shock ( P<0.01 for each). Median Sequential Organ Failure Assessment scores were higher in patients with mixed shock (10; IQR, 6-13) versus AMICS (8; IQR, 5-11) or CS without AMI (7; IQR, 5-11; each P<0.01). In-hospital mortality rates were 36% (95% CI, 28%-45%), 31% (95% CI, 26%-36%), and 39% (95% CI, 31%-48%) in AMICS, CS without AMI, and mixed shock, respectively. Conclusions The epidemiology of shock in contemporary advanced CICUs is varied, and AMICS now represents less than one-third of all CS. Despite advanced therapies, mortality in CS and mixed shock remains high. Investigation of management strategies and new therapies to treat shock in the CICU should take this epidemiology into account.

Keywords: pulmonary embolism; submassive; survey.