Faculty Bibliography

Sepsis, acute lung injury, and ARDS contribute substantially to the expanding burden of critical illness within our ICUs. Each of these processes is characterized by a myriad of injurious events, including apoptosis, microvascular dysfunction, abnormal coagulation, and dysregulated host immunity. Only recently have platelets--long considered merely effectors of thrombosis--been implicated in inflammatory conditions and the pathobiology of these disease processes. A growing body of evidence suggests a prominent role for maladaptive platelet activation and aggregation during sepsis and ARDS and has begun to underscore the pluripotential influence of platelets on outcomes in critical illness. Not only do platelets enhance vascular injury through thrombotic mechanisms but also appear to help orchestrate pathologic immune responses and are pivotal players in facilitating leukocyte recruitment to vulnerable tissue. These events contribute to the organ damage and poor patient outcomes that still plague the care of these high-risk individuals. An understanding of the role of platelets in critical illness also highlights the potential for both the development of risk stratification schema and the use of novel, targeted therapies that might alter the natural history of sepsis, acute lung injury, and ARDS. Future studies of adenosine, platelet polyphosphates, and the platelet transcriptome/proteome also should add considerably to our ability to unravel the mysteries of the versatile platelet.

OBJECTIVE:To determine the demographic and clinical features, hospital complications, and predictors of 90-day mortality in neurologic patients with acute severe hypertension. DESIGN/METHODS:Studying the Treatment of Acute hyperTension (STAT) was a multicenter (n=25) observational registry of adult critical care patients with severe hypertension treated with intravenous therapy. SETTING/METHODS:Emergency department or intensive care unit. PATIENTS/METHODS:A qualifying blood pressure measurement>180 mm Hg systolic or >110 mm Hg diastolic (>140/90 mm Hg for subarachnoid hemorrhage) was required for inclusion in the STAT registry. Patients with a primary neurologic admission diagnosis were included in the present analysis. INTERVENTIONS/METHODS:All patients were treated with at least one parenteral (bolus or continuous infusion) antihypertensive agent. MEASUREMENTS AND MAIN RESULTS/RESULTS:Of 1,566 patients included in the STAT registry, 432 (28%) had a primary neurologic diagnosis. The most common diagnoses were subarachnoid hemorrhage (38%), intracerebral hemorrhage (31%), and acute ischemic stroke (18%). The most common initial drug was labetalol (48%), followed by nicardipine (15%), hydralazine (15%), and sodium nitroprusside (13%). Mortality at 90 days was substantially higher in neurologic than in non-neurologic patients (24% vs. 6%, p<.0001). Median initial blood pressure was 183/95 mm Hg and did not differ between survivors and nonsurvivors. In a multivariable analysis, neurologic patients who died experienced lower minimal blood pressure values (median 103/45 vs. 118/55 mm Hg, p<.0001) and were less likely to experience recurrent hypertension requiring intravenous treatment (29% vs. 51%, p=.0001) than those who survived. Mortality was also associated with an increased frequency of neurologic deterioration (32% vs. 10%, p<.0001). CONCLUSION/CONCLUSIONS:Neurologic emergencies account for approximately 30% of hospitalized patients with severe acute hypertension, and the majority of those who die. Mortality in hypertensive neurologic patients is associated with lower minimum blood pressure values, less rebound hypertension, and a higher frequency of neurologic deterioration. Excessive blood pressure reduction may contribute to poor outcome after severe brain injury.

OBJECTIVE:To describe long-term temporal trends in patient characteristics, processes of care, and in-hospital outcomes among unselected admissions within the contemporary coronary care unit. DESIGN/METHODS:Hospital administrative database that records both payment and operation data. SETTING/METHODS:Coronary care unit of a large, academic, tertiary-care medical institution. PATIENTS/METHODS:A total of 29,275 patients admitted from January 1, 1989 through December 31, 2006. INTERVENTIONS/METHODS:Unadjusted time-trend plots were created for all variables of interest, and multivariable modeling of coronary care unit death was performed. MEASUREMENTS AND MAIN RESULTS/RESULTS:Temporal trends in Coronary Care Unit and in-hospital mortality, length-of-stay, demographic characteristics, discharge diagnoses, Coronary Care Unit procedures, and Charlson comorbidity scores were evaluated. Admission severity increased significantly over time (p < .001), but hospital length-of-stay decreased (p < .001). The proportion of coronary care unit admissions with non-ST-segment elevation myocardial infarction increased (p < .001), whereas ST-segment elevation myocardial infarction decreased (p < .001). The prevalence of non-cardiovascular diagnoses increased, with the rate greatest for comorbid critical illnesses, including sepsis, acute kidney injury, and respiratory failure (all p < .001). The use of non-cardiac procedures, such as mechanical ventilation and central venous catheterization, also increased over time (p < .001). Unadjusted coronary care unit and in-hospital mortality did not change during the study period, although death did decrease in the adjusted setting. CONCLUSIONS:Substantial changes have occurred over time in patient characteristics, diagnoses, and procedures within the coronary care unit of a large, academic medical center. In particular, there have been significant increases in noncardiovascular critical illness, the results of which may be influencing patient outcomes. These findings underscore an existing need to clarify the role of the coronary care unit in contemporary cardiovascular care and to develop strategies for optimal training, staffing, and clinical investigation.

BACKGROUND:Little is known about the association of kidney dysfunction and outcome in acute severe hypertension. This study aimed to measure the association between baseline chronic kidney disease (estimated glomerular filtration rate), acute kidney injury (AKI, decrease in estimated glomerular filtration rate > or =25% from baseline) and outcome in patients hospitalized with acute severe hypertension. METHODS AND RESULTS/RESULTS:The Studying the Treatment of Acute Hypertension (STAT) registry enrolled patients with acute severe hypertension, defined as > or =1 blood pressure measurement >180 mm Hg systolic and/or >110 mm Hg diastolic and treated with intravenous antihypertensive therapy. Data were compared across groups categorized by admission estimated glomerular filtration rate and AKI during admission. On admission, 79% of the cohort (n=1566) had at least mild chronic kidney disease (estimated glomerular filtration rate <60 mL/min in 46%, <30 mL/min in 22%). Chronic kidney disease patients were more likely to develop heart failure (P<0.0001), non-ST-elevation myocardial infarction (P=0.003), and AKI (P<0.007). AKI patients were at greater risk of heart failure and cardiac arrest (P< or =0.0001 for both). Subjects with AKI experienced higher mortality at 90 days (P=0.003). Any acute loss of estimated glomerular filtration rate during hospitalization was independently associated with an increased risk of death (odds ratio, 1.05; P=0.03 per 10-mL/min decline). Other independent predictors of mortality included increasing age (P<0.0001), male gender (P=0.016), white versus black race (P=0.003), and worse baseline kidney function (P=0.003). CONCLUSIONS:Chronic kidney disease is a common comorbidity among patients admitted with acute severe hypertension, and AKI is a frequent form of acute target organ dysfunction, particularly in those with baseline chronic kidney disease. Any degree of AKI is associated with a greater risk of morbidity and mortality.

BACKGROUND:Limited data are available on the care of patients with acute severe hypertension requiring hospitalization. We characterized contemporary practice patterns and outcomes for this population. METHODS:STAT is a 25-institution, US registry of consecutive patients with acute severe hypertension (>180 mm Hg systolic and/or >110 mm Hg diastolic; >140 and/or >90 for subarachnoid hemorrhage) treated with intravenous therapy in a critical care setting. RESULTS:One thousand five hundred eighty-eight patients were enrolled (January 2007 to April 2008). Median age was 58 years (interquartile range 49-70 years), 779 (49%) were women, and 892 (56%) were African American; 27% (n = 425) had a prior admission for acute hypertension and 486 (31%) had chronic kidney disease. Median qualifying blood pressure (BP) was 200 (186, 220) systolic and 110 (93, 123) mm Hg diastolic. Initial intravenous antihypertensive therapies used to control BP varied, with 1,009 (64%) patients requiring multiple drugs. Median time to achieve a systolic BP <160 mm Hg (<140 mm Hg for subarachnoid hemorrhage) was 4.0 (0.8, 12) hours; 893 (60%) had reelevation to >180 (>140 for subarachnoid hemorrhage) after initial control; and 63 (4.0%) developed iatrogenic hypotension. Hospital mortality was 6.9% (n = 109) with an aggregate 90-day mortality rate of 11% (174/1,588); 59% (n = 943) had acute/worsening end-organ dysfunction during hospitalization. The 90-day readmission rate was 37% (523/1,415), of which one quarter (132/523) was due to recurrent acute severe hypertension. CONCLUSION/CONCLUSIONS:This study highlights heterogeneity in care, BP control, and outcomes of patients hospitalized with acute severe hypertension.

BACKGROUND: Little is known about predictors of survival in patients with persistent shock following acute myocardial infarction (MI) despite a patent infarct artery. METHODS: We examined data from TRIUMPH, a multicenter randomized clinical trial of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine, in patients with persistent vasopressor-dependent cardiogenic shock complicating acute MI at least 1 hour after established infarct-related artery patency. Patients who died within 30 days were compared with those who survived. Continuous variables were assessed using the Wilcoxon rank sum and categorical variables using the chi(2) test. Prespecified baseline variables were included in a multivariable logistic regression model to predict mortality. A second model incorporating baseline vasopressors and dosages and a third model including change in systolic blood pressure at 2 hours were also developed. Bootstrapping was used to assess the stability of model variables. RESULTS: Of 396 patients, 180 (45.5%) died within 30 days. Systolic blood pressure (SBP), measured on vasopressor support, and creatinine clearance were significant predictors of mortality in all models. The number of vasopressors and norepinephrine dose were also predictors of mortality in the second model, but the latter was no longer significant when change in SBP at 2 hours was added as a covariate in the third model. CONCLUSIONS: The SBP, creatinine clearance, and number of vasopressors are significant predictors of mortality in patients with persistent vasopressor-dependent cardiogenic shock following acute MI despite a patent infarct artery. These prognostic variables may be useful for risk-stratification and in selecting patients for investigation of additional therapies

With an aging U.S. population and a declining physician supply, the care of critically ill patients will soon be reaching a level of crisis. At the same time, the evidence continues to mount in support of intensivist staffing to improve both patient outcomes and resource utilization in intensive care units (ICUs). Whereas the vast majority of medical and surgical ICUs are staffed by physicians trained in critical care medicine, that is not commonly the case in coronary care units (CCUs) in this country. Despite that, the breadth and diversity of comorbidities in patients that occupy our CCU beds is continuously growing. No longer is the CCU merely an observation unit for peri-infarction complications, but rather it has truly become an ICU for patients with cardiovascular disease. With this in mind, there becomes a growing need for intensivist-trained cardiologists and a push for the development of critical care training pathways in our cardiovascular fellowship programs.