Microbiology, time course and clinical characteristics of infection in critically ill patients receiving packed red blood cell transfusion.

BACKGROUND AND OBJECTIVES: Packed red blood cell transfusion has been associated with increased infection in a variety of critically ill patient populations. We evaluated the microbiology and time course of infection in transfused patients in the intensive care unit (ICU) as no data exist on these parameters. MATERIALS AND METHODS: We performed a retrospective review of data for all patients admitted to a 24-bed medical-surgical ICU at Cooper University Hospital from July 2003 to September 2006 and entered in the Project Impact database. RESULTS: A total of 2432 patients were admitted during the study period, of which 609 underwent transfusion. Transfused patients were more likely to develop a nosocomial infection (10.5% vs. 4.9%, P < 0.001). ICU and hospital length of stay were longer in the transfused group (P < 0.001 for both). Mortality was also greater (13.1% vs. 8.7%, P = 0.001). Transfused patients had a shorter time from hospital admission to first infection (P < 0.001) and ICU admission to first infection (P < 0.001). Multivariate analysis confirmed transfusion as an independent risk factor for infection, mortality, hospital and ICU length of stay. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus and Acinetobacter occurred more often in transfused patients. Acinetobacter accounted for a disproportionate share of infections among transfused patients (P < 0.001). CONCLUSIONS: Transfused ICU patients have a higher incidence of nosocomial infection and worse outcomes. Transfused patients had a shorter onset of infection. Acinetobacter infection appears to be particularly common among these patients. Further investigation is merited to better elucidate the mechanism for these findings and their therapeutic and clinical implications.

Image-based monitoring of one-lung ventilation.

BACKGROUND AND OBJECTIVES: With the increasing demand for one-lung ventilation in both thoracic surgery and other procedures, identifying the correct placement becomes increasingly important. Currently, endobronchial intubation is suspected based on a combination of auscultation and physiological findings. We investigated the ability of the visual display of airflow-induced vibrations to detect single-lung ventilation with a double-lumen endotracheal tube. METHODS: Double-lumen tubes were placed prior to surgery. Tracheal and endobronchial lumens were alternately clamped to produce unilateral lung ventilation of right and left lung. Vibration response imaging, which detects vibrations transmitted to the surface of the thorax, was performed during both right- and left-lung ventilation. Geographical area of vibration response image as well as amount and distribution of lung sounds were assessed. RESULTS: During single-lung ventilation, the image and video obtained from the vibration response imaging identifies the ventilated lung with a larger and darker image on the ventilated side. During single-lung ventilation, 87.2 +/- 5.7% of the measured vibrations was detected over the ventilated lung and 12.8 +/- 5.7% over the non-ventilated lung (P < 0.0001). It was also noted that during single-lung ventilation, the vibration distribution in the non-ventilated lung had a majority of vibration detected by the medial sensors closest to the midline (P < 0.05) as opposed to the midclavicular sensors when the lung is ventilated. CONCLUSIONS: During single-lung ventilation, vibration response imaging clearly showed increased vibration in the lung that is being ventilated. Distribution of residual vibration differed in the non-ventilated lung in a manner that suggests transmission of vibrations across the mediastinum from the ventilated lung. The lung image and video obtained from vibration response imaging may provide useful and immediate information to help one-lung ventilation assessment.

Coronary endothelial dysfunction after heart transplantation predicts allograft vasculopathy and cardiac death.

BACKGROUND: Coronary endothelial dysfunction may be an early marker for cardiac allograft vasculopathy (CAV) in orthotopic heart transplant recipients. Using serial studies with intravascular ultrasound and Doppler flow-wire measurements, we have previously demonstrated that annual decrements in coronary endothelial function are associated with progressive intimal thickening. The present study tested whether endothelial dysfunction predicts subsequent clinical events, including cardiac death and CAV development. METHODS AND RESULTS: Seventy-three patients were studied yearly beginning at transplantation until a prespecified end point was reached. End points were angiographic evidence of CAV (>50% stenosis) or cardiac death (graft failure or sudden death). At each study, coronary endothelial function was measured with intracoronary infusions of adenosine (32-microgram bolus), acetylcholine (54 microgram over 2 minutes), and nitroglycerin (200 microgram) into the left anterior descending coronary artery; intravascular ultrasound images and Doppler velocities were recorded simultaneously. Of the 73 patients studied, 14 reached an end point during the study (6 CAV and 8 deaths, including 4 with known CAV, 1 graft failure, and 3 sudden). On the last study performed, the group with an end point had decreased epicardial (constriction of 11.1+/-2.9% versus dilation of 1.7+/-2.2%, P=0.01) and microvascular (flow increase of 75+/-20% versus 149+/-16%, P=0.03) endothelium-dependent responses to acetylcholine compared with the patients who did not reach an end point. Responses to adenosine and nitroglycerin did not differ significantly. CONCLUSIONS: Endothelial dysfunction, as detected by abnormal responses to acetylcholine, preceded the development of clinical end points. These data implicate endothelial dysfunction in the development of clinically significant vasculopathy and suggest that serial studies of endothelial function have clinical utility.

Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography.

A small animal model of sepsis that reproduces the vasodilation, hypotension, increased cardiac output, and response to treatment seen in patients with septic shock would be useful for studies of pathophysiology and treatment, but no current models replicate all of these features. Mice were made septic by cecal ligation and puncture and resuscitated with fluids and antibiotics every 6 h. Blood pressure was measured in anesthetized mice with manometric catheters, and echocardiography was performed in these animals every 6 h. Survival in treated septic mice was improved compared with untreated mice (44% versus 0%, p < 0.01). In control mice, heart rate (HR, 420 +/- 31 beats/min), mean arterial pressure (Pa, 100 +/- 8 mm Hg), stroke volume (SV, 26 +/- 4 microl), and cardiac output (12.5 +/- 6.6 ml/min) were unchanged over 48 h. In septic mice Pa was significantly decreased (102 +/- 14 to 65 +/- 19 mm Hg, p < 0.02), starting at 12 h. HR and cardiac output increased significantly (HR, 407 +/- 70 to 524 +/- 76 beats/min, cardiac output, 11.6 +/- 2.0 to 17.1 +/- 1.5 ml/min, p < 0.01). SV (24 +/- 5 microl) remained constant. This fluid-resuscitated, antibiotic-treated model replicates the mortality, hypotension, and hyperdynamic state seen in clinical sepsis. Precise determination of serial hemodynamics in this model may be useful to elucidate pathophysiologic mechanisms and to evaluate new therapies for septic shock.

Assessing coronary blood flow dynamics with the TIMI frame count method: comparison with simultaneous intracoronary Doppler and ultrasound.

This study compared the TIMI frame count (TFC), which has been proposed as a method for quantifying coronary blood flow, with coronary flow and microvascular function measured with intracoronary Doppler and intracoronary ultrasound. Coronary blood flow volume was calculated from coronary blood velocity (by intracoronary Doppler) and lumen area (by intracoronary ultrasound) in the LAD in 46 post-heart transplant patients at baseline and after intracoronary adenosine. TFC correlated significantly with average peak coronary blood velocity (r = -0.42; P = 0.004) and coronary lumen area (r = 0.39; P = 0.008), but not with coronary blood flow volume (r = -0.01; P = 0.96) or the coronary flow reserve response to adenosine (r = 0.09; P = 0.58). In conclusion, TFC is a simple method of assessing coronary blood velocity but not volumetric flow. While TFC does not predict coronary flow reserve, as a measure of velocity it does provide an assessment of basal microvascular tone, information that is complementary to that afforded by flow reserve measurements.

The contemporary management of acute myocardial infarction.

The contemporary management of acute myocardial infarction continues to evolve rapidly. The ultimate goal of therapy is timely, complete, and sustained myocardial reperfusion. There is a powerful time-dependent effect on mortality, and thus the balance between the time and likelihood of maximal reperfusion is crucial in deciding whether to use primary percutaneous balloon angioplasty or thrombolysis as the initial reperfusion strategy. Newer thrombolytic agents allow for equivalent coronary reperfusion compared with the standard accelerated alteplase (tPA) regimen with the advantage of easier dosing regimens. Low molecular weight heparin has been shown to be superior to unfractionated heparin and likely will be the standard of care in the near future. The use of glycoprotein IIb/IIIa inhibitors has been shown to decrease the short- and long-term complication rates in patients with acute coronary syndromes treated medically and with percutaneous coronary interventions; however, the choice of the optimal agent and dosing regimen in various clinical settings remains controversial. Combination therapy with low-dose fibrinolytics, glycoprotein IIb/IIIa inhibitors, and low molecular weight heparin, with or without subsequent early planned percutaneous coronary interventions, may provide the optimal strategy for maximal coronary reperfusion, but the results of large, randomized mortality trials currently underway need to be analyzed. Risk stratification will continue to play a major role in determining which patients should receive a specific therapy. The care of the patient with an acute myocardial infarction will continue to be a challenge requiring the proper selection from the vast pharmaceutic and interventional options available.

Electrocardiographic diagnosis of acute myocardial infarction: Current concepts for the clinician.

BACKGROUND: Over the past 2 decades, the 12-lead electrocardiogram has attained special significance for the diagnosis and triage of patients with chest pain because timely detection of myocardial injury and a rapid assessment of myocardium at risk proved pivotal to implementing effective reperfusion therapies during acute myocardial infarction. However, this wealth of information could still be underutilized by clinicians who may restrict their diagnostic quest in patients with chest pain to the more classic electrocardiographic signs. METHODS: The medical literature on electrocardiographic manifestations of acute myocardial infarction was extensively reviewed. RESULTS: The widespread utilization of both coronary angiography and methods to determine myocardial function and metabolism in patients with acute myocardial infarction over the last 10 years has provided the means for rigorous comparisons with electrocardiographic information. We summarize these electrocardiographic signs and patterns in terms of their relevance to the clinician to help reduce the incidence of "nondiagnostic electrocardiograms" and improve timely decision-making. CONCLUSIONS: The electrocardiogram continues to be an invaluable tool in the initial evaluation of patients with chest pain. The plethora of data currently available on electrocardiographic changes correlating with myocardial injury allows clinicians to make faster and better decisions than ever before.

Evidence of transcellular permeability pathway in microvessels.

We used video fluorescence microscopy of the vascular bed in the cremaster muscle of rat and mouse to study the transfer of plasmalemma vesicles (caveolae) across the microvessel barrier in situ. The water-soluble styryl pyridinium dye RH414, which adsorbs to and fluoresces at the membrane-water interface, was used as a marker for vesicular traffic through endothelial cells. Fluorescein isothiocyanate (FITC), similar in molecular size to the styryl pyridinium probe, was used to mark for dye transfer by the paracellular pathway. Transcellular dye flux was determined by comparing the fluorescence intensities of RH414 and FITC on either side of the vessel wall (i.e., in microvessel lumen and in muscle tissue at various distances from the microvessel wall). We observed that RH414 accumulated in the interstitium more rapidly than FITC. We next studied the role of the 60-kDa albumin-binding glycoprotein gp60, hypothesized to activate transcellular permeability, in stimulating the transcellular vesicle traffic. Introduction of anti-gp60 antibody into the microvessel to cross-link and activate gp60 markedly increased the transvascular flux of RH414. Control isotype-matched antibody had no effect on the RH414 flux. The sterol-binding agent filipin, which disassembles caveolae, inhibited the RH414 flux induced by gp60 cross-linking. The transfer of styryl pyridinium dyes in intact microvessels suggests that plasmalemmal membrane traffic across the skeletal muscle microvessel barrier is a constitutively active process. The results indicate that the gp60-dependent pathway is important in regulating endothelial permeability in situ via a transcellular mechanism.

The intermediate CCU admission: a preliminary study.

In the current health care era, increasing emphasis is being placed on cost reduction. Admitting only high-risk patients to coronary care units (CCU) may reduce hospital costs and charges without adverse clinical outcomes. Recently, guidelines published by the Agency for Healthcare Policy and Research (AHCPR) on suggest that intermediate-risk patients be admitted to an intermediate CCU (ICCU), but the safety and appropriateness of this approach has not been prospectively evaluated. The authors hypothesized that admitting intermediate-risk patients with to an ICCU would be cheaper than admitting to a CCU with comparable safety supporting AHCPR guidelines. To evaluate this, a retrospective cohort study was conducted. Two hundred forty-three intermediate-risk patients consecutively admitted to the CCU (n = 134) and admitted to the ICCU (n = 109) between June 1, 1992 and April 1, 1994 were compared using AHCPR definitions of intermediate risk and a previously published risk prediction model to exclude both very low- and high-risk patients. Extensive demographic, clinical, and diagnostic testing, and treatment, procedural, and outcome data were collected by a trained nurse data collector at the time of admission. Fifty-nine percent of all study patients had at least two coronary risk factors. Twenty-one percent had diabetes. Ninety-eight percent had at least one AHCPR intermediate risk factor for cardiac complications. The two groups (CCU versus ICCU) were quite similar in baseline characteristics: men (56 versus 55%), age (57 +/- 17 versus 60 +/- 17 years), diabetes (22 versus 20%), previous myocardial infarction (30 versus 36%), previous coronary artery surgery (21 versus 21%), and rest pain (78 versus 66%). The use of coronary angiography (44 versus 52%), angioplasty (24 versus 21%), and coronary artery surgery (13 versus 11%) were also similar. The incidence of myocardial infarction or death was similar (3 versus 5%), and length of stay was also similar between groups (6.7 +/- 4.2 versus 6.5 +/- 4.1 days), but cost was less for patients admitted to the ICCU ($13,481 +/- 9,450 versus $10,619 +/- 8,732, P < 0.015). These preliminary data suggest intermediate-risk patients, as identified by AHCPR guidelines, can be treated in an ICCU at lower cost than in a CCU, with reasonable safety. A small incidence of myocardial infarction in ICCU-admitted patients occurs, requiring availability of cardiac resuscitation and continued monitoring of electrocardiographic and enzymatic abnormalities. Admission to ICCU poses no barrier to recommended patient evaluation and management.

Probable Kawasaki disease in a 52-year-old man presenting with acute myocardial infarction treated with percutaneous revascularization.

This is a case report of a 52-year-old man who presented with an acute myocardial infarction. In the process of performing an angiogram to delineate the anatomy for possible percutaneous transluminal coronary angioplasty, large, diffuse coronary aneurysms were observed. When the vessel was opened, several aneurysms were seen to contain thrombus. The size, location, and diffuseness of the aneurysms are suggestive of Kawasaki disease.

Endothelial- and nitric oxide-dependent effects on oxidative metabolism of intact artery.

Oxidative metabolism and its possible modulation by nitric oxide (NO) was examined in endothelial-intact and endothelial-denuded segments of porcine carotid arteries. Endothelial-intact arteries displayed appropriate NO-mediated vasorelaxation to acetylcholine (ACh). Endothelial-denuded arteries demonstrated absent vasorelaxation to ACh stimulation and depressed contractile responsiveness to K(+) depolarization, which was normalized by inhibition of NO synthesis by N(omega)-nitro-L-arginine methylester (L-NAME). Confirmation that carotid arteries continued to produce NO despite removal of the endothelium was indicated by detection of NO metabolites in the incubation medium bathing the arteries. O(2) consumption and the oxidation of glucose and fatty acid were depressed in endothelial-denuded arteries. Depression of O(2) consumption and glucose oxidation was completely reversed by treatment with L-NAME. We conclude that endogenous NO produced by non-endothelial vascular cells depresses contractility, O(2) consumption, and oxidation of energy substrates in vascular smooth muscle. The endothelium may play a role in oxidative metabolism of vascular smooth muscle possibly by modulating the effects of NO produced by other cells of the vessel wall, or by other factors.

Validated risk stratification model accurately predicts low risk in patients with unstable angina.

BACKGROUND: In the mid 1990s, two unstable angina risk prediction models were proposed but neither has been validated on separate population or compared. OBJECTIVES: The purpose of this study was to compare patient outcome among high, medium and low risk unstable angina patients defined by the Agency for Health Care Policy and Research (AHCPR) guideline to similar risk groups defined by a validated model from our institution (RUSH). METHODS: Four hundred sixteen patients consecutively admitted to the hospital with unstable angina between January 1, 1995, and December 31, 1997, were prospectively evaluated for risk factors. The presence of major adverse events such as myocardial infarction (MI), death and heart failure was assessed for each patient by chart review. RESULTS: The composite end point of heart failure, MI or death occurred in 3% and 5% of the RUSH and AHCPR low risk categories, respectively, and in 8% and 10% of AHCPR and RUSH high risk categories, respectively. Recurrent ischemic events were best predicted by the RUSH model (high: 24% vs. medium: 12% and low: 10%, p = 0.029), but not by the AHCPR model (high: 14% vs. medium: 13% and low: 9%, p = 0.876). The RUSH model identified five times more low risk patients than the AHCPR model. CONCLUSIONS: Both models identify patients with low and high event rates of MI, death or heart failure. However, the RUSH model allowed for five times more patients to be candidates for outpatient evaluation (low risk) with a similar observed event rate to the AHCPR model; also, the RUSH model more successfully predicted ischemic complications. We conclude that the RUSH model can be used clinically to identify patients for early noninvasive evaluation, thereby improving cost effectiveness of care.

NADH/NAD redox state of cytoplasmic glycolytic compartments in vascular smooth muscle.

The cytoplasmic NADH/NAD redox potential affects energy metabolism and contractile reactivity of vascular smooth muscle. NADH/NAD redox state in the cytosol is predominately determined by glycolysis, which in smooth muscle is separated into two functionally independent cytoplasmic compartments, one of which fuels the activity of Na(+)-K(+)-ATPase. We examined the effect of varying the glycolytic compartments on cystosolic NADH/NAD redox state. Inhibition of Na(+)-K(+)-ATPase by 10 microM ouabain resulted in decreased glycolysis and lactate production. Despite this, intracellular concentrations of the glycolytic metabolite redox couples of lactate/pyruvate and glycerol-3-phosphate/dihydroxyacetone phosphate (thus NADH/NAD) and the cytoplasmic redox state were unchanged. The constant concentration of the metabolite redox couples and redox potential was attributed to 1) decreased efflux of lactate and pyruvate due to decreased activity of monocarboxylate B-H(+) transporter secondary to decreased availability of H(+) for cotransport and 2) increased uptake of lactate (and perhaps pyruvate) from the extracellular space, probably mediated by the monocarboxylate-H(+) transporter, which was specifically linked to reduced activity of Na(+)-K(+)-ATPase. We concluded that redox potentials of the two glycolytic compartments of the cytosol maintain equilibrium and that the cytoplasmic NADH/NAD redox potential remains constant in the steady state despite varying glycolytic flux in the cytosolic compartment for Na(+)-K(+)-ATPase.