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Biomedical subjects

Steven M Hollenberg

Publications and source records attributed to Steven M Hollenberg.

14 recordsLinked to original sources
PubMed2006

Early microcirculatory perfusion derangements in patients with severe sepsis and septic shock: relationship to hemodynamics, oxygen transport, and survival.

STUDY OBJECTIVE: To study early microcirculatory perfusion indices in patients with severe sepsis/septic shock, compare early microcirculatory indices in sepsis survivors versus nonsurvivors, and identify systemic hemodynamic/oxygen transport variables that correlate with early microcirculatory perfusion indices. METHODS: This prospective observational study used orthogonal polarization spectral imaging to directly visualize the sublingual microcirculation in patients with severe sepsis/septic shock treated with early goal-directed therapy. We performed initial imaging within 6 hours of early goal-directed therapy initiation and late follow-up studies at 24-hour intervals until death or resolution of organ dysfunction. We imaged 5 sublingual sites and analyzed the data offline in a blinded fashion. We calculated 3 microcirculatory perfusion indices: flow velocity score, flow heterogeneity index, and capillary density. We analyzed early data to compare survivors versus nonsurvivors and examine correlations with systemic hemodynamic measurements. We used a linear mixed-effects model for longitudinal analyses. RESULTS: We performed 66 orthogonal polarization spectral studies in 26 sepsis patients. Early microcirculatory indices were more markedly impaired (lower flow velocity and more heterogeneous perfusion) in nonsurvivors compared with survivors. These same early indices, flow velocity and heterogeneity, were also more markedly impaired with increasing severity of systemic cardiovascular dysfunction (lower arterial pressure or increasing vasopressor requirement). CONCLUSION: Early microcirculatory perfusion indices in severe sepsis and septic shock are more markedly impaired in nonsurvivors compared with survivors and with increasing severity of global cardiovascular dysfunction.

Aged↗
PubMed2006

Cardiac arrhythmias in the intensive care unit.

Cardiac arrhythmias are a common problem encountered in the intensive care unit (ICU) and represent a major source of morbidity. Arrhythmias are most likely to occur in patients with structural heart disease. The inciting factor for an arrhythmia in a given patient may be an insult such as hypoxia, infection, cardiac ischemia, catecholamine excess (endogenous or exogenous), or an electrolyte abnormality. Management includes correction of these imbalances as well as medical therapy directed at the arrhythmia itself. The physiological impact of arrhythmias depends on ventricular response rate and duration, and the impact of a given arrhythmia in a given situation depends on the patient's cardiac physiology and function. Similarly, urgency and type of treatment are determined by the physiological impact of the arrhythmia as well as by underlying cardiac status. The purpose of this review is to provide an update regarding current concepts of diagnosis and acute management of arrhythmias in the ICU. A systematic approach to diagnosis and evaluation will be presented, followed by consideration of specific arrhythmias.

Anti-Arrhythmia Agents↗
PubMed2005

Perioperative cardiac issues: postoperative arrhythmias.

This article reviews current concepts about the diagnosis and acute management of postoperative arrhythmias. A systematic approach to diagnosis of arrhythmias and evaluation of predisposing factors is presented, followed by consideration of common bradyarrhythmias and tachyarrhythmias in the postoperative setting. Postoperative arrhythmias are common and represent a major source of morbidity after surgical procedures, both cardiac and noncardiac. Postoperative dysrhythmias are most likely to occur in patients with structural heart disease. The initiating factor for an arrhythmia following surgery is usually a transient insult such as hypoxemia, cardiac ischemia, catecholamine excess, or electrolyte abnormality. Management includes correction of these imbalances and, if clinically indicated, medical therapy directed at the arrhythmia itself.

Anti-Arrhythmia Agents↗
PubMed2005

Update on acute coronary syndromes and ST-elevation myocardial infarction.

PURPOSE: The goal of modern therapy of acute myocardial infarction is twofold: to achieve rapid reperfusion of ischemic myocardium and to decrease subsequent remodeling, which can have deleterious effects on ventricular function and prognosis. The current paradigm for treatment of most patients with acute coronary syndromes is the consideration of an 'early invasive' strategy. RECENT FINDINGS: Studies published this year have reinforced the importance of early reperfusion, solidified the evidence for early institution of aggressive adjunctive treatment, and added newer therapies to the existing armamentarium. This review evaluates published data from the past year encompassing advancements in percutaneous coronary intervention, drug-eluting stents, glycoprotein IIb/IIIa antagonists, thienopyridines, HMG-CoA reductase inhibitors, aldosterone blockade, low-molecular-weight heparins, direct thrombin inhibitors, implantable cardioverter-defibrillators, and beta-blockade in the treatment of acute coronary syndrome and ST-segment elevation myocardial infarction. In addition to patency of the epicardial coronary arteries, the role of the microvascular has become an area of recent interest. SUMMARY: As novel modalities and approaches are put to the test of clinical trials, evidence-based therapies may help to lessen the adverse effects of myocardial ischemia and reduce future cardiovascular events.

Humans↗
PubMed2005

Mouse models of resuscitated shock.

Studies of sepsis in humans are difficult because the seriousness of the disease mandates immediate intervention and because the heterogeneity of patient presentations imposes substantial limitations on clinical trials. Thus, animal models have been used extensively to explore the pathogenesis of sepsis and to generate preclinical data for therapeutic interventions. Translation of findings in these models into therapeutic strategies has been difficult, in part because of limitations in preclinical models and in part to imperfect understanding of the pathophysiology of sepsis. It is important to use an animal model that reproduces the relevant physiologic parameters present in patients with septic shock. Mouse models are particularly useful for the dissection of molecular mechanisms of disease because of the proliferation of transgenic strains. We have developed a murine model of sepsis with fluid resuscitation and antibiotic treatment that reproduces the timing and degree of mortality seen in patients with septic shock. Using continuous micromanometric pressure monitoring and assessment of hemodynamics by echocardiography, we have shown that this model reproduces the hyperdynamic state with hypotension seen in clinical sepsis. The use of transgenic technology in appropriate murine models is exciting because of its potential to permit significant strides in our understanding of the molecular mechanisms of sepsis, multiple organ system failure, and other diseases. The use of reproducible and clinically relevant mouse models of shock is essential for delineation of pathogenetic mechanisms and for initial testing of potential therapeutic strategies.

Animals↗
PubMed2004

Changes in coronary endothelial function predict progression of allograft vasculopathy after heart transplantation.

OBJECTIVE: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. We used serial studies to evaluate changes in coronary endothelial function in patients with and without clinically evident CAV. BACKGROUND: In serial studies with intravascular ultrasound (IVUS) and Doppler flow wire measurements, we previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. METHODS: We studied 45 patients annually, beginning at transplantation until pre-specified end-points (angiographic CAV or cardiac death) were reached. At each study, we measured coronary endothelial function using intracoronary infusions of adenosine, acetylcholine, and nitroglycerin. We simultaneously recorded IVUS images and Doppler velocities. RESULTS: Of the 45 patients studied, 9 reached end-points during the study (6 had CAV and 3 died). The mean annual change in area response to acetylcholine was -4.5% +/- 3.0% in patients who reached end-points and -0.9% +/- 1.5% in those who did not (p = 0.04). The mean annual decrement in flow response to acetylcholine was greater in patients who reached end-points (-31% +/- 11% vs -5% +/- 5%, p = 0.08). Responses to adenosine and nitroglycerin did not differ. CONCLUSIONS: When serial responses were evaluated, patients with end-points had more rapid decreases in endothelial function. The rate of disease progression may be more important than the absolute degree of intimal thickening in early CAV. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function may provide important prognostic information about the development of CAV after heart transplantation.

Blood Flow Velocity↗
PubMed2004

Recognition and treatment of cardiogenic shock.

Cardiogenic shock has long been a difficult problem for clinicians. The most common cause is left ventricular pump failure after myocardial infarction, but other important causes include mechanical complications of infarction, right ventricular dysfunction, prolonged cardiopulmonary bypass, valvular disease, and cardiomyopathy. Cardiogenic shock is the leading cause of in-hospital death after myocardial infarction. Despite advances in management of heart failure and acute myocardial infarction, clinical outcomes had remained frustratingly poor, with reported mortality rates ranging from 50 to 80%. Recently, however, survival rates have been improving. Improved understanding of the pathophysiology of cardiogenic shock has led to renewed emphasis on the notion that stunned or hibernating myocardium may recover function with hemodynamic support and restoration of flow. This concept has underscored the importance of expeditious initiation of supportive measures to maintain blood pressure and cardiac output, including both medications and intraaortic balloon counterpulsation. Finally, the theory that coronary revascularization would be beneficial by reversing the vicious cycle in which ischemia causes myocardial dysfunction, which in turn worsens ischemia, which had been supported by an extensive body of observational and registry studies, has now been strongly buttressed by the results of two randomized, controlled trials, both of which show improved mortality with early revascularization for cardiogenic shock in the setting of acute infarction.

Journal Article↗
PubMed2004

Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update.

OBJECTIVE: To provide the American College of Critical Care Medicine with updated guidelines for hemodynamic support of adult patients with sepsis. DATA SOURCE: Publications relevant to hemodynamic support of septic patients were obtained from the medical literature, supplemented by the expertise and experience of members of an international task force convened from the membership of the Society of Critical Care Medicine. STUDY SELECTION: Both human studies and relevant animal studies were considered. DATA SYNTHESIS: The experts articles reviewed the literature and classified the strength of evidence of human studies according to study design and scientific value. Recommendations were drafted and graded levels based on an evidence-based rating system described in the text. The recommendations were debated, and the task force chairman modified the document until <10% of the experts disagreed with the recommendations. CONCLUSIONS: An organized approach to the hemodynamic support of sepsis was formulated. The fundamental principle is that clinicians using hemodynamic therapies should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis by monitoring a combination of variables of global and regional perfusion. Using this approach, specific recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult patients were promulgated.

Adult↗
PubMed2004

Vasopressor and inotropic support in septic shock: an evidence-based review.

OBJECTIVE: In 2003, critical care and infectious disease experts representing 11 international organizations developed management guidelines for vasopressor and inotropic support in septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and to improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. METHODS: The modified Delphi methodology used for grading recommendations built on a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along five levels to create recommendation grades from A to E, with A being the highest grade. Pediatric considerations to contrast adult and pediatric management are in the article by Parker et al. on p. S591. CONCLUSION: An arterial catheter should be placed as soon as possible in patients with septic shock. Vasopressors are indicated to maintain mean arterial pressure of <65 mm Hg, both during and following adequate fluid resuscitation. Norepinephrine or dopamine are the vasopressors of choice in the treatment of septic shock. Norepinephrine may be combined with dobutamine when cardiac output is being measured. Epinephrine, phenylephrine, and vasopressin are not recommended as first-line agents in the treatment of septic shock. Vasopressin may be considered for salvage therapy. Low-dose dopamine is not recommended for the purpose of renal protection. Dobutamine is recommended as the agent of choice to increase cardiac output but should not be used for the purpose of increasing cardiac output above physiologic levels.

Cardiotonic Agents↗
PubMed2003

Update on therapy for acute and chronic heart failure. Applying advances in outpatient management.

Care of patients with heart failure is often challenging and involves proper therapeutic selection from the pharmacologic, interventional, and mechanical options available. In this article, Drs Almeda and Hollenberg discuss the latest approaches and guidelines to treatment of acute and chronic heart failure in patients with left ventricular systolic dysfunction. They review the benefits, risks, and myriad considerations that physicians need to assess before making choices about best medical management.

Acute Disease↗
PubMed2002

Adenosine deaminase inhibition attenuates microvascular dysfunction and improves survival in sepsis.

The ability of increased endogenous adenosine to mitigate microvascular derangements in sepsis was studied. Pentostatin (2'-deoxycoformycin), an inhibitor of adenosine deaminase, was administered to mice immediately after induction of sepsis by cecal ligation and puncture. Intravital video microscopy of cremasteric postcapillary venules was performed. Leukocyte rolling and adhesion were significantly increased in septic mice compared with control mice. Treatment of septic mice with pentostatin significantly decreased leukocyte rolling and adhesion (6.02 +/- 0.09 versus 1.72 +/- 0.12 rolling cells/min, 2.07 +/- 0.04 versus 0.62 +/- 0.05 adherent cells/100 microm per minute; p < 0.001). Albumin leakage (ratio) was significantly attenuated in septic animals treated with pentostatin (0.42 +/- 0.05 versus 0.21 +/- 0.04; p < 0.01). Circulating levels of interleukin-6, tumor necrosis factor-alpha, and soluble tumor necrosis factor type II receptor were decreased in septic mice treated with pentostatin. Survival was significantly improved at 48 hours in mice treated with pentostatin. These results suggest an important role for adenosine in modulating both leukocyte-dependent and -independent mechanisms of endothelial injury in sepsis. Exploiting the advantageous action of endogenous adenosine represents a potentially useful and novel therapeutic approach for the treatment of sepsis.

Adenosine Deaminase↗
PubMed2002

Arterial elasticity among normotensive subjects and treated and untreated hypertensive subjects: influence of race.

OBJECTIVES: To determine arterial elasticity in normotensives and in treated and untreated hypertensive Black and White subjects. METHODS: A prospective multicenter, controlled clinical trial evaluated large (C-) and small (C2) artery elasticity indices among 3 groups: 1) normotensive subjects with or without a family history of hypertension; 2) controlled and treated hypertensive subjects; and 3) untreated and uncontrolled hypertensive subjects. Blood pressure was measured using a mercury manometer and arterial compliance or elasticity was determined using a CVProfilor DO-2020 CardioVascular Profiling System (Hypertension Diagnostics, Inc, Eagan, Minn). These parameters were measured in triplicate 3 minutes apart in a random sequence, with the patient in a supine position. Two-way ANOVA was used for statistical evaluation. RESULTS: One hundred seventy eight subjects met stratification and enrollment criteria. The mean age was 46 years. 109 were White and 69 were Black. [table: see text] CONCLUSION: Small and large arterial elasticity indices are reduced as hypertension status worsens. Age and height were important covariates of C1 and C2. Race was not found to be a significant predictor of either C1 or C2. Large and small artery elasticity indices do not differ between White and Black subjects with varying degrees of hypertension after adjusting for covariates. More studies with a larger number of subjects are required.

Adolescent↗