Hans Domanovits

Platelet Function Predicts Myocardial Damage in Patients With Acute Myocardial Infarction

Background—Platelet activation is a hallmark of acute coronary syndromes. Numerous lines of evidence suggest a mechanistic link between von Willebrand factor or platelet hyperfunction and myocardial damage in patients with acute coronary syndromes. Thus, we assessed whether platelet function under high shear rates (collagen adenosine diphosphate closure times [CADP-CTs]) measured with the platelet function analyzer (PFA-100) may be enhanced in patients with myocardial infarction (MI) and whether it may predict the extent of myocardial damage as measured by creatine kinase (CK-MB) or troponin T (TnT) levels. Methods and Results—Patients with acute chest pain or symptoms suggestive of acute coronary syndromes (n=216) were prospectively examined at an emergency department. CADP-CT was significantly shorter in patients with MI, particularly in those with an ST-segment-elevation MI (STEMI) compared with the other patient groups (unstable angina, stable coronary artery disease, or controls). Furthermore, CADP-CT and collagen epinephrine–CT at presentation were independent predictors of myocardial damage as measured by CK-MB or TnT. Patients with MI whose CADP-CT values fell in the first quartile had 3-fold higher CK-MB and TnT levels than those in the fourth quartile. Conclusions—Patients with STEMI have significantly enhanced platelet function when measured under high shear rates. CADP-CT is an independent predictor of the severity of MI, as measured by markers of cardiac necrosis. Measurement of platelet function with the PFA-100 may help in the risk stratification of patients presenting with MI.

Improved outcome prediction in unconscious cardiac arrest survivors with sensory evoked potentials compared with clinical assessment

Objective: To compare the prognostic ability of sensory evoked potentials in cardiac arrest survivors with the outcome predicted by a panel of experienced emergency physicians based on detailed prehospital, clinical, and laboratory data. Design: Inception cohort study. Setting: Medical intensive care unit and department of emergency medicine at a university hospital. Patients: A total of 162 unconscious, mechanically ventilated patients who survived ≥24 hrs after resuscitation from cardiac arrest. Interventions: Recording of sensory evoked potentials and outcome prediction after review of detailed clinical and laboratory data by emergency physicians within 24 hrs after cardiac arrest. Measurements and Main Results: At 6 months, the outcome of 36 patients was classified as favorable and 126 patients were rated as poor. After review of prehospital data, emergency physicians predicted favorable vs. poor outcome with a sensitivity of 70% and a specificity of 65%. After additional assessment of data 1 hr after cardiac arrest, the sensitivity of emergency physician predictions increased to 80%, whereas the specificity decreased to 48%. Outcome prediction by emergency physicians was most accurate after obtaining detailed patient data 24 hrs after cardiac arrest (sensitivity, 81%; specificity, 58%). In 35 of 36 patients with favorable outcomes, the cortical evoked potential N70 peak was detected between 72 and 128 msec. Of 113 patients with an N70 peak latency > 130 msec or an absent N70 peak, all except one had a poor outcome. By using a cutoff of 130 msec, the N70 peak latency alone had a sensitivity of 94% and a specificity of 97%. The predictive accuracy of the N70 peak latency was significantly higher than the clinical assessment 24 hrs after cardiac arrest (91% vs. 76%, p = .0003). Conclusion: In unconscious cardiac arrest survivors, a recording of long‐latency sensory evoked potentials is more accurate in predicting individual outcome than an emergency physician review of clinical data.

Cumulative Epinephrine Dose during Cardiopulmonary Resuscitation and Neurologic Outcome

For more than 90 years, epinephrine has been used in cardiopulmonary resuscitation to improve myocardial and cerebral perfusion [1]. The recommended standard dose of 1 mg of epinephrine administered intravenously [2] was first used more than 30 years ago [3-5]. Numerous attempts have been made to find either an optimal dose for epinephrine [6-8] or new vasopressor agents [9-11] to treat patients with cardiac arrest. The use of epinephrine in cardiopulmonary resuscitation continues to be controversial [12]. Despite its advantages [13-17], epinephrine has deleterious side effects during cardiac arrest and after restoration of spontaneous circulation [18-25]. Both the standard epinephrine dose and the recommendation of unlimited subsequent epinephrine doses administered every 3 to 5 minutes [2] remain matters of debate. In children, administration of more than two epinephrine doses is associated with poor prognosis [26]. Because it is difficult to determine whether outcomes are related to the duration of the resuscitative efforts or to the adverse effects of repeated epinephrine doses, the association between epinephrine dose and outcome in adults has not yet been defined. Although epinephrine can restore spontaneous circulation, favorable neurologic function does not necessarily ensue. In a retrospective cohort study, we investigated the association between cumulative epinephrine dose used in advanced cardiac life support and neurologic outcome in patients with witnessed, normothermic ventricular fibrillation cardiac arrest and unsuccessful initial defibrillation. Methods From 1 August 1991 to 31 December 1995, data were collected on patients admitted to the Department of Emergency Medicine at the University Hospital of Vienna, Austria, after cardiac arrest that occurred before or during hospitalization. Collection was done according to the recommended guidelines for uniform reporting of data on out-of-hospital cardiac arrest [27]. The procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional or regional) and with the Helsinki Declaration of 1975, as revised in 1983. Patients Included patients had witnessed, nontraumatic, normothermic cardiac arrest of presumed cardiac origin. To exclude the influence of the initial rhythm on outcome [28-30], we focused on patients whose initial rhythm was ventricular fibrillation. Cardiac arrest was defined as the absence of both spontaneous respiration and palpable pulses. Patients were excluded if spontaneous circulation returned within 3 minutes after the initial three countershocks and if they had an additional cardiac arrest within 6 months after the first. We also excluded patients with known unfavorable overall performance or cerebral performance (New York Heart Association class 3 or 4 or a cerebral performance category [CPC] of 3 or 4) before cardiac arrest, a factor that is known to affect outcome [31-33]. Return of spontaneous circulation was defined as any, even transient (nonsustained), return of a palpable arterial pulse [27]. Acute care consisted of basic and advanced cardiac life support performed by the Vienna Ambulance Service or in-hospital emergency medical technicians and physicians according to standard protocol [2]. The interval from the time of collapse (the presumed time of cardiac arrest) to basic or advanced life support was defined as the no-flow duration, and the interval from the beginning of life support until the return of spontaneous circulation or termination of resuscitative efforts was called the low-flow duration. The cumulative epinephrine dose was defined as the overall dose of epinephrine subsequently administered during advanced cardiac life support. One physician was responsible for obtaining data through interviews with the ambulance physicians, paramedics, bystanders, and families and from computerized patient records. Outcome Measures Cerebral function, expressed in terms of CPC, was assessed prospectively on arrival at the emergency department and 6 hours, 12 hours, 24 hours, 2 days, 3 days, 1 week, 1 month, and 6 months after return of spontaneous circulation [27, 34]. The CPC category is based on the Glasgow outcome performance categories [35]. The performance categories are defined as follows: CPC 1, conscious and alert with normal function or only slight disability; CPC 2, conscious and alert with moderate disability; CPC 3, conscious with severe disability; CPC 4, comatose or in a persistent vegetative state; and CPC 5, certifiably brain dead or dead by traditional criteria. The best CPC score achieved within 6 months was used for calculation. A CPC score of 1 or 2 represents favorable functional neurologic recovery because patients with these scores have sufficient cerebral function for independent activities of daily living. A CPC score of 3, 4, or 5 reflects unfavorable functional neurologic recovery. The investigator assessing the CPC score by examining the patients according to a neuropsychiatric protocol was blinded to the resuscitation data. Statistical Analysis Data are given as the median and interquartile range (the difference between the 25th and 75th percentiles) unless otherwise specified. We used the Kruskal-Wallis test and the Mann-Whitney U test to compare continuous variables and used the chi-square test or the Fisher exact test to compare proportions. We calculated Spearman rank correlation coefficients to assess the relation between the cumulative epinephrine dose, the no-flow and low-flow durations, and the sum of these durations. Logistic regression analysis was used to assess the association between neurologic recovery and cumulative epinephrine dose. To control for potential cofounders, we included the following variables in the logistic regression model: age, sex, body mass index, bystander-administered basic life support (yes or no), site of cardiac arrest (in the hospital or outside of the hospital), no-flow duration, and low-flow duration. The logistic regression model was tested for collinearity of the independent variables by using standard procedures. No substantial collinearity between the independent variables was found. Logistic regression coefficients were converted to odds ratios with 95% CIs. All data were computed by using SPS for Windows, release 6.0 (SPS, Inc., Chicago, Illinois). A P value less than 0.05 was considered statistically significant. Results Within the 65-month study period, 698 patients who were having or had had cardiac arrest were admitted to the emergency department. Of these, 178 fulfilled the inclusion criteria and were enrolled. The median age of the 178 patients was 61 years (range, 50 to 71 years), and 148 patients (83%) were male. In 160 patients (90%), cardiac arrest occurred outside of the hospital. The estimated median no-flow duration was 2 minutes (interquartile range, <1 to 10 minutes), and the median low-flow duration was 16 minutes (interquartile range, 7 to 34 minutes). The median no-flow duration can be attributed to the 57 patients (32%) who underwent bystander-administered basic life support and to the 32 patients (18%) whose cardiac arrest was witnessed by emergency medical service personnel. The median no-flow duration in the patients who had bystander-administered basic life support was 1 minute (interquartile range, <1 to 2.5 minutes). This duration can be explained by the fact that in 35 patients, basic life support was initiated immediately after arrest. If arrest is witnessed by emergency medical service personnel, the no-flow duration can be expected to be 0 minutes. In all 32 patients whose cardiac arrest was witnessed by emergency medical service personnel, spontaneous circulation could be restored. Twenty-four of these patients (75%) showed favorable functional neurologic recovery. Of 119 patients whose cardiac arrest was not witnessed by emergency medical service personnel, 39 (33%) had favorable functional neurologic recovery. The median cumulative epinephrine dose administered intravenously during cardiopulmonary resuscitation was 4 mg (interquartile range, 1 to 6 mg). The median epinephrine dose administered every fifth minute was 1.2 mg (interquartile range, 0.6 to 2.1 mg). Patients with and without Return of Spontaneous Circulation In 151 patients (84%), spontaneous circulation was restored. Compared with patients in whom spontaneous circulation was not restored, patients with restoration of spontaneous circulation had a similar no-flow duration (2 minutes [interquartile range, <1 to 9 minutes] and 1 minute [interquartile range, <1 to 10 minutes]; P > 0.2) and a shorter low-flow duration (13 minutes [interquartile range, 5 to 24 minutes] and 80 minutes [interquartile range, 58 to 119 minutes]; P < 0.001) and received a lower cumulative dose of epinephrine (3 mg [interquartile range, 1 to 6 mg] and 8 mg [interquartile range, 4 to 18 mg]; P < 0.001). Restoration of spontaneous circulation was possible with increasing cumulative doses of epinephrine, but good functional neurologic recovery was less likely (Figure 1 and Figure 2). Figure 1. Patients who achieved restoration of spontaneous circulation (striped bars) after administration of epinephrine. Figure 2. Patients who achieved good neurologic outcome after administration of epinephrine (striped bars). Patients with Favorable and Unfavorable Functional Neurologic Recovery after Return of Spontaneous Circulation Of 151 patients with return of spontaneous circulation, neurologic recovery was favorable in 63 (42%). Within a 6-month observation period, 80 patients died (median duration of survival, 4 days [interquartile range, 0.5 to 14 days; range, 0.4 hours to 111 days]). Of the 80 patients who died within the 6-month observation period, 77 had unfavorable functional neurologic recovery (median duration of survival, 4 days [interquartile range, 0.5 to 13 days]). Durations of survival in the 3 patients with favora

acute Renal Infarction: Clinical Characteristics of 17 Patients

We analyzed the medical records of patients with an established diagnosis of acute renal infarction to identify predictive parameters of this rare disease. Seventeen patients (8 male) who were admitted to our emergency department between May 1994 and January 1998 were diagnosed by contrast-enhanced computed tomography (CT) as having acute renal infarction (0.007% of all patients). We screened the records of the 17 patients for a history with increased risk for thromboembolism, clinical symptoms, and urine and blood laboratory results known to be associated with acute renal infarction. A history with increased risk for thromboembolism with 1 or more risk factors was found in 14 of 17 patients (82%); risk factors were atrial fibrillation (n = 11), previous embolism (n = 6), mitral stenosis (n = 6), hypertension (n = 9), and ischemic cardiac disease (n = 7). All patients reported persisting pain predominantly from the flank (n = 11), abdomen (n = 4), and lower back (n = 2). On admission, elevated serum lactate dehydrogenase was found in 16 (94%) patients, and hematuria was found in 12 (71%) of 17 patients. After 24 hours all patients showed an elevated serum lactate dehydrogenase, and 14 (82%) had a positive test for hematuria. Our findings suggest that in all patients presenting with the triad--high risk of a thromboembolic event, persisting flank/abdominal/lower back pain, elevated serum levels of lactate dehydrogenase and/or hematuria within 24 hours after pain onset--contrast-enhanced CT should be performed as soon as possible to rule out or to prove acute renal infarction.

Perioperative -Blockers for Preventing Surgery-Related Mortality and Morbidity: A Systematic Review and Meta-Analysis

BACKGROUND:Perioperative &bgr;-blockers are suggested to reduce cardiovascular mortality, myocardial–ischemia/infarction, and supraventricular arrhythmias after surgery. We reviewed the evidence regarding the effectiveness of perioperative &bgr;-blockers for improving patient outcomes after cardiac and noncardiac surgery. METHODS:Eleven large databases were searched from the time of their inception until October 2005. Various online-resources were consulted for the identification of unpublished trials and conference abstracts. We included randomized, controlled trials comparing perioperative &bgr;-blockers with either placebo or the standard-of-care. Of the 3680 retrieved titles, 69 met inclusion criteria for analysis. Odds ratios (OR) assuming random effects were computed in the absence of significant clinical heterogeneity. RESULTS:&bgr;-Blockers reduced the frequency of ventricular tachyarrhythmias [OR (cardiac surgery): 0.28, 95% CI 0.13–0.57; OR (noncardiac surgery): 0.56, 95% CI 0.21–1.45], atrial fibrillation/flutter [OR (cardiac surgery): 0.37, 95% CI 0.28–0.48], other supraventricular arrhythmias [OR (cardiac surgery): 0.25, 95% CI 0.18–0.35; OR (noncardiac surgery): 0.43, 95% CI 0.14–1.37], and myocardial ischemia [OR (cardiac surgery): 0.49, 95% CI 0.17–1.4; OR (noncardiac surgery): 0.38, 95% CI 0.21–0.69]. Length of hospitalization was not reduced [weighted mean difference (cardiac surgery): −0.35 days, 95% CI −0.77–0.07; weighted mean difference (noncardiac surgery): −5.59 days, 95% CI −12.22–1.04] and, in contrast to previous reports, &bgr;-blockers did not reduce mortality [OR (cardiac surgery): 0.55, 95% CI 0.17–1.83; OR (noncardiac surgery): 0.78, 95% CI 0.33–1.87], and they had no influence on the occurrence of perioperative myocardial infarction [OR (cardiac surgery): 0.89, 95% CI 0.53–1.5; OR (noncardiac surgery): 0.59; 0.25–1.39]. CONCLUSIONS:&bgr;-Blockers reduced perioperative arrhythmias and myocardial ischemia, but they had no effect on myocardial infarction, mortality, or length of hospitalization.

Severity assessment of acute pulmonary embolism with spiral CT: evaluation of two modified angiographic scores and comparison with clinical data.

Spiral computed tomography (CT) has shown promising results in the detection of acute pulmonary embolism. The aim of this study was to investigate whether the severity of acute pulmonary embolism could be quantitatively assessed with spiral CT examinations and to test the potential clinical impact of this information. In a consecutive series of 123 patients screened with spiral CT for suspected acute pulmonary embolism, 31 patients (25%) had evidence of emboli. The severity of pulmonary arterial obstruction in those 31 spiral CT examinations was evaluated by two independent observers using angiographic scores previously described by Walsh (29) and Miller (30), adapted to the needs of spiral CT. Clinical patient subgroups were defined according to oxygen saturation, heart rate, and echocardiographic signs of right ventricular strain. CT severity scores were then correlated to each other and to clinical parameters using the Spearman rank test. Interobserver agreement was calculated using the analysis of variance. Both modified Walsh and Miller scores were readily reproducible and showed interobserver agreements of 0.85 and 0.96, respectively (p = 0.001). Patients with mild and marked clinical abnormalities showed statistically significant differences between CT severity scores. Differences between severity scores of patients with moderate and marked clinical abnormalities were somewhat significant. No significant mean severity score differences were seen between patients with mild and moderate clinical abnormalities. Although correlations of severity scores and detailed clinical parameters within the defined subgroups were moderate to poor, threshold scores greater than 10 (Miller) and greater than 11 (Walsh) always indicated marked clinical abnormalities. The modified scores presented in this study constitute a readily reproducible method for the quantitative assessment of acute pulmonary embolism severity on spiral CT examinations.

Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm.

OBJECTIVE Vascular inflammation is a hallmark in the development of abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a novel vascular anti-inflammatory factor. A (GT)(n) dinucleotide repeat in the HO-1 gene promoter shows a length polymorphism that modulates the level of gene transcription. Short (< 25 GT) repeats are associated with an increased HO-1 upregulation in response to inflammatory stimuli than are longer repeats. We hypothesised that patients with AAA had less frequently short repeats in the HO-1 gene promoter compared to patients with coronary (CAD) or peripheral artery disease (PAD), or healthy controls. METHODS 70 consecutive patients with atherosclerotic AAA, each 70 age- and sex-matched patients with CAD and PAD as well as 61 unmatched healthy atherosclerosis-free controls for a total of 271 individuals were studied. The frequency of carriers of short repeats in the HO-1 gene promoter was determined and compared between the groups. RESULTS In the AAA group, 29 patients (41%) were carriers of short (GT)(n) repeats compared to 47 patients (67%) in the CAD group, 44 patients (63%) in the PAD group and 35 healthy controls (59%). Patients with AAA were less frequently carriers of short repeats compared to age- and sex-matched patients with CAD (OR = 0.38, p = 0.006) and PAD (OR = 0.35, p = 0.01). Healthy controls exhibited short alleles more frequently than patients with AAA (p = 0.04), but comparable to CAD (p = 0.3) and PAD patients (p = 0.7). CONCLUSION Patients with AAA were less frequently carriers of short (< 25 GT) repeats in the HO-1 gene promoter than patients with atherosclerosis or healthy subjects. This suggests that short alleles, and thus, facilitated upregulation of HO-1, may be a protective anti-inflammatory factor against the development of AAA.

Successful resuscitation of a verapamil-intoxicated patient with percutaneous cardiopulmonary bypass

OBJECTIVE To describe our experience with the use of percutaneous cardiopulmonary bypass as a therapy for cardiac arrest in an adult patient intoxicated with verapamil. DESIGN Case report. SETTING Emergency department of a university hospital. PATIENT A patient with cardiac arrest after severe verapamil intoxication. INTERVENTIONS Percutaneous cardiopulmonary bypass and theophylline therapy. CASE REPORT A 41-yr-old white male had taken 4800-6400 mg of verapamil in a suicide attempt. On arrival of the ambulance physician, the patient was conscious with weak palpable pulses and was transported to a nearby hospital. The patient developed a pulseless electrical activity, and cardiopulmonary resuscitation was started. Despite all advanced life support efforts, the patient remained in cardiac arrest. Therefore, he was transferred under ongoing cardiopulmonary resuscitation to our department, where percutaneous cardiopulmonary bypass was initiated immediately (2.5 hrs after cardiac arrest). The first verapamil serum concentration obtained at admittance to our institution was 630 ng/mL. After several ineffective intravenous epinephrine applications, the administration of 0.48 g of theophylline as an intravenous bolus 6 hrs and 18 mins after cardiac arrest led to the return of spontaneous circulation. The patient remained stable and was transferred to an intensive care unit the same day. He woke up on the 12th day and was extubated on the 18th day. After transfer to a neuropsychiatric rehabilitation hospital, he recovered totally. CONCLUSION In patients with cardiac arrest attributable to massive verapamil overdose, percutaneous extracorporeal cardiopulmonary bypass can provide adequate tissue perfusion and sufficient cerebral oxygen supply until the drug level is reduced and restoration of spontaneous circulation can be achieved.

The association between blood lactate concentration on admission, duration of cardiac arrest, and functional neurological recovery in patients resuscitated from ventricular fibrillation

ObjectiveTo assess the association between arterial lactate concentration on admission and the duration of human ventricular fibrillation cardiac arrest, and to what degree the arterial lactate concentration on admission is an early predictor of functional neurological recovery in human cardiac arrest survivors.DesignCohort study. Arterial lactate concentrations and out-of-hospital data concerning cardiac arrest and cardiopulmonary resuscitation were collected retrospectively according to a standardized protocol. Functional neurological recovery was assessed prospectively at regular intervals for 6 months.SettingEmergency department of an urban tertiary care hospital.PatientsA total of 167 primary survivors of witnessed out-of-hospital ventricular fibrillation cardiac arrest.MeasurementsThe association between arterial lactate concentration on admission, the duration of cardiac arrest, and functional neurological recovery was assessed. Further, we assessed whether admission concentrations of arterial lactate and duration of cardiac arrest can predict unfavorable functional neurological recovery. Functional neurological recovery was measured in cerebral performance categories (CPC). No or minimal functional impairment (CPC 1 and 2) was defined as favorable outcome; the remaining categories (CPC 3, 4 and 5) were defined as unfavorable functional neurological recovery.ResultsIn 167 patients, a weak association between total duration of cardiac arrest and admission levels of lactate (r=0.49, P<0.001) could be shown. With increasing admission concentrations of arterial lactate functional neurological recovery was more likely to be unfavorable (OR 1.15 per mmol/1 increase, 95 % CI 1.04–1.27). Nevertheless, only at very high levels of lactate (16.3 mmol/1) could unfavorable neurological recovery be detected with 100 % specificity, yielding a very low sensitivity of 16 %.ConclusionsThe arterial admission lactate concentration after out-of-hospital ventricular fibrillation cardiac arrest is a weak measure of the duration of ischemia. High admission lactate levels are associated with severe neurological impairment. However, this parameter has poor prognostic value for individual estimation of the severity of subsequent functional neurological impairment.

Treatment of Ocular Toxocariasis with Albendazole

The purpose of this study was to evaluate the efficacy of combined albendazole and steroid treatment for uveitis caused by Toxocara canis in immunocompetent patients. Five patients (7 eyes) with ocular larva migrans syndrome (OLM) were used in this study. Toxocariasis was suspected based on clinical manifestations and confirmed by anti-toxocara IgG and Western blot analysis. Systemic albendazole (adults: 800 mg b.i.d.; children: 400 mg b.i.d.) was given in conjunction with steroids. Visual acuity before and after therapy, inflammatory response, side effects and toxicity were evaluated. Treatment resulted in an improved visual acuity in all patients. Mean initial Snellen visual acuity was 20/40, and mean final acuity was 20/20. There were no recurrences of uveitis throughout the observation period (average: 13.8 months; range: 3 days to 24 months). These findings suggest that albendazole, in combination with systemic steroids, is a useful regimen to treat ocular larva migrans syndrome.