Considerations for Inotrope and Vasopressor Use in Critically Ill Patients With Pulmonary Arterial Hypertension.

ABSTRACT: Pulmonary arterial hypertension (PAH) is a rare and progressive cardiopulmonary disease, characterized by pulmonary vasculopathy. The disease can lead to increase pulmonary arterial pressures and eventual right ventricle failure due to elevated afterload. The prevalence of PAH in patients admitted to the intensive care unit (ICU) is unknown, and pulmonary hypertension (PH) in the ICU is more commonly the result of left heart disease or hypoxic lung injury (PH due to left heart disease and PH due to lung diseases and/or hypoxia, respectively), as opposed to PAH. Management of patients with PAH in the ICU is complex as it requires a careful balance to maintain perfusion while optimizing right-sided heart function. A comprehensive understanding of the underlying physiology and underlying hemodynamics is crucial for the management of this population. In this review, we summarized the evidence for use of vasopressors and inotropes in the management of PH and extrapolated the data to patients with PAH. We strongly believe that the understanding of the hemodynamic consequences of inotropes and vasopressors, especially from data in the PH population, can lead to better management of this complex patient population.

Characteristics of Heart Failure Patients With or Without Hypotension When Transitioning From Nitroprusside to Sacubitril-Valsartan.

BACKGROUND: Sacubitril-valsartan is an angiotensin receptor-neprilysin inhibitor indicated for the treatment of patients with symptomatic heart failure with reduced ejection fraction (HFrEF). Little is known about outcomes of HFrEF patients transitioned from sodium nitroprusside (SNP) to sacubitril-valsartan during an admission for acute decompensated heart failure. We sought to describe characteristics of patients initiated on sacubitril-valsartan while receiving SNP and, in particular, those patients who did and did not experience hypotension requiring interruption or discontinuation of sacubitril-valsartan. METHODS: We performed a retrospective case series of adult patients (>18 years) with HFrEF (left ventricular ejection fraction ≤40%) admitted to the University of Michigan cardiac intensive care unit between July 2018 to September 2020 who received sacubitril-valsartan while on SNP. RESULTS: A total of 15 patients with acute decompensated heart failure were initiated on sacubitril-valsartan while on SNP. The mean age was 57 ± 15.9 years. Seven (46.7%) patients experienced hypotension. The patients in the cohort who experienced hypotension were numerically older (60 ± 17 vs. 55 ± 15.5), and the majority were white (86%). Patients with hypotension had a numerically lower left ventricular ejection fraction (13 ± 4.2 vs. 18 ± 8.2) and higher serum creatinine (1.4 ± 0.54 vs. 0.88 ± 0.25). Seven (100%) patients received a diuretic on the day of sacubitril-valsartan initiation in those who experienced hypotension compared with 2 (25%) in those who did not experience hypotension. CONCLUSIONS: In almost half of patients admitted to the cardiac intensive care unit with acutely decompensated HFrEF, significant hypotension was seen when initiating sacubitril-valsartan while on SNP. Future studies should evaluate appropriate patients for this transition and delineate appropriate titration parameters.

Coronavirus Disease-2019 in Heart Transplant Recipients in Southeastern Michigan: A Case Series.

BACKGROUND: Since coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019, the number of cases has risen exponentially. Clinical characteristics and outcomes among patients with orthotopic heart transplant (OHT) with COVID-19 remain poorly described. METHODS: We performed a retrospective case series of patients with OHT with COVID-19 admitted to 1 of 2 hospitals in Southeastern Michigan between March 21 and April 22, 2020. Clinical data were obtained through review of the electronic medical record. Final date of follow-up was May 7, 2020. Demographic, clinical, laboratory, radiologic, treatment, and mortality data were collected and analyzed. RESULTS: We identified 13 patients with OHT admitted with COVID-19. The mean age of patients was 61 ± 12 years, 100% were black males, and symptoms began 6 ± 4 days before admission. The most common symptoms included subjective fever (92%), shortness of breath (85%), and cough (77%). Six patients (46%) required admission to the intensive care unit. Two patients (15%) died during hospitalization. CONCLUSIONS: Black men may be at increased risk for COVID-19 among patients with OHT. Presenting signs and symptoms in this cohort are similar to those in the general population. Elevated inflammatory markers on presentation appear to be associated with more severe illness.

Causes and characteristics of death in patients with acute hypoxemic respiratory failure and acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) are associated with high in-hospital mortality. However, in cohorts of ARDS patients from the 1990s, patients more commonly died from sepsis or multi-organ failure rather than refractory hypoxemia. Given increased attention to lung-protective ventilation and sepsis treatment in the past 25 years, we hypothesized that causes of death may be different among contemporary cohorts. These differences may provide clinicians with insight into targets for future therapeutic interventions. METHODS: We identified adult patients hospitalized at a single tertiary care center (2016-2017) with AHRF, defined as PaO2/FiO2 ≤ 300 while receiving invasive mechanical ventilation for > 12 h, who died during hospitalization. ARDS was adjudicated by multiple physicians using the Berlin definition. Separate abstractors blinded to ARDS status collected data on organ dysfunction and withdrawal of life support using a standardized tool. The primary cause of death was defined as the organ system that most directly contributed to death or withdrawal of life support. RESULTS: We identified 385 decedents with AHRF, of whom 127 (33%) had ARDS. The most common primary causes of death were sepsis (26%), pulmonary dysfunction (22%), and neurologic dysfunction (19%). Multi-organ failure was present in 70% at time of death, most commonly due to sepsis (50% of all patients), and 70% were on significant respiratory support at the time of death. Only 2% of patients had insupportable oxygenation or ventilation. Eighty-five percent died following withdrawal of life support. Patients with ARDS more often had pulmonary dysfunction as the primary cause of death (28% vs 19%; p = 0.04) and were also more likely to die while requiring significant respiratory support (82% vs 64%; p <  0.01). CONCLUSIONS: In this contemporary cohort of patients with AHRF, the most common primary causes of death were sepsis and pulmonary dysfunction, but few patients had insupportable oxygenation or ventilation. The vast majority of deaths occurred after withdrawal of life support. ARDS patients were more likely to have pulmonary dysfunction as the primary cause of death and die while requiring significant respiratory support compared to patients without ARDS.

The association of glucose control on in-hospital mortality in the cardiac intensive care unit.

BACKGROUND: Current guidelines recommend maintaining serum blood glucose (BG) levels between 150 and 180 mg/dL for patients admitted to the intensive care unit (ICU); however, these recommendations are based on randomized controlled trials among general ICU patients and observational studies among specific subgroups. Little is known about the impact of glucose control among patients cared for in the cardiac intensive care unit (CICU). METHODS: This was a retrospective cohort analysis of patients >18 years of age admitted to the University of Michigan CICU from December 2016 through December 2020 with at least one BG measurement during CICU admission. The primary outcome was in-hospital mortality. The secondary outcome was CICU length of stay. RESULTS: A total of 3217 patients were included. When analyzed based on quartiles of mean CICU BG, there were significant differences in in-hospital mortality across BG quartiles for those with diabetes mellitus (DM) and those without DM. In multivariable logistic regression, age, Elixhauser comorbidity score, use of mechanical ventilation, any hypoglycemic event, and any BG value >180 mg/dL were significant predictors for in-hospital mortality in both patients with and without DM, yet average BG was only predictive of in-hospital mortality in patients without DM. CONCLUSIONS: This study highlights the importance of glucose control in critically ill adult patients admitted to the CICU. The trends in mortality based on quartiles and deciles of average BG suggest a difference in optimal blood glucose levels in those with and without DM. However, regardless of diabetes status, mortality increases with higher average BG.

Implementation of a Nurse-Driven Spontaneous Awakening Trial Protocol in a Cardiac Intensive Care Unit.

BACKGROUND: In patients receiving mechanical ventilation, spontaneous awakening trials reduce morbidity and mortality when paired with spontaneous breathing trials. However, spontaneous awakening trials are not performed every day they are indicated and little is known about spontaneous awakening trial protocol use in cardiac intensive care units. LOCAL PROBLEM: Spontaneous awakening trial completion rate at the study institution was low and no trial protocol was regularly used. METHODS: A preintervention-postintervention retrospective cohort study was performed in adult patients with at least 24 hours of invasive mechanical ventilation in Michigan Medicine's cardiac intensive care unit. Patients with SARS-CoV-2 infection were excluded. Data included demographics, sedation, mechanical ventilation duration, and in-hospital mortality. A nurse-driven spontaneous awakening trial protocol modified for the cardiac intensive care unit was implemented in October 2020. RESULTS: Compared with the preintervention cohort (n = 29, May through July 2020), the postintervention cohort (n = 27, October 2020 through February 2021) had a higher ratio of number of trials performed to number of days eligible for trial (0.91 vs 0.52; P < .01). Median continuous sedative infusion duration was shorter after intervention (2.3 vs 3.6 days; P = .02). Median mechanical ventilation duration (3.8 vs 4.7 days; P = .18) and mortality (41% vs 41%; P = .95) were similar between groups. CONCLUSIONS: Spontaneous awakening trial protocol implementation led to a higher trial completion rate and a shorter duration of continuous sedative infusion. Larger studies are needed to assess the impact of protocolized spontaneous awakening trials on cardiac intensive care unit patient outcomes.

Atypical Antipsychotic Safety in the CICU.

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Validating Measures of Disease Severity in Acute Respiratory Distress Syndrome.

Rationale: Quantifying acute respiratory disease syndrome (ARDS) severity is essential for prognostic enrichment to stratify patients for invasive or higher-risk treatments; however, the comparative performance of many ARDS severity measures is unknown.Objectives: To validate ARDS severity measures for their ability to predict hospital mortality and an ARDS-specific outcome (defined as death from pulmonary dysfunction or the need for extracorporeal membrane oxygenation [ECMO] therapy).Methods: We compared five individual ARDS severity measures including the ratio of arterial oxygen tension/pressure to fraction of inspired oxygen (PaO2/FiO2 ratio), oxygenation index, ventilatory ratio, lung compliance, and radiologic assessment of lung edema (RALE); two ARDS composite severity scores including the Murray Lung Injury Score, and a novel score combining RALE, PaO2/FiO2 ratio, and ventilatory ratio; and the Acute Physiology and Chronic Health Evaluation IV score, using data collected at ARDS onset in patients hospitalized at a single center in 2016 and 2017. Discrimination of hospital mortality and the ARDS-specific outcome was evaluated using the area under the receiver operator characteristic curve (AUROC). Measure calibration was also evaluated.Results: Among 340 patients with ARDS, 125 (37%) died during hospitalization and 36 (10.6%) had the ARDS-specific outcome, including one who received ECMO. Among the five individual ARDS severity measures, the RALE score had the highest discrimination of the ARDS-specific outcome (AUROC = 0.67; 95% confidence interval [CI], 0.58-0.77), although other ARDS severity measures had similar performance. However, their ability to discriminate overall mortality was low. In contrast, the Acute Physiology and Chronic Health Evaluation IV score best discriminated overall mortality (AUROC = 0.73; 95% CI, 0.67-0.79) but was unable to discriminate the ARDS-specific outcome (AUROC = 0.54; 95% CI, 0.44-0.65). Among ARDS composite severity scores, the lung injury score had an AUROC = 0.67 (95% CI, 0.58-0.75) for the ARDS-specific outcome whereas the novel score had an AUROC = 0.70 (95% CI, 0.61-0.79). Patients grouped by quartile of the novel score had a 6%, 2%, 10%, and 24% rate of the ARDS-specific outcome.Conclusions: Although most ARDS severity measures had poor discrimination of hospital mortality, they performed better at predicting death from severe pulmonary dysfunction or ECMO needs. A novel composite score had the highest discrimination of this outcome.