Alexander Geppert

Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias

Objective To compare the rate-lowering effect of diltiazem and two amiodarone regimens in critically ill patients with recent-onset atrial tachyarrhythmias. Design Prospective, randomized, controlled study. Setting Medical cardiologic intensive care unit in a university hospital. Patients Sixty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] III score 70 ± 30, age 67 ± 10 yrs). Interventions Patients with atrial fibrillation (n = 57), atrial flutter (n = 2), or atrial tachycardia (n = 1, and a heart rate consistently >120 beats/min over 30 mins were randomly assigned to one of three intravenous treatment regimens. Group 1 received diltiazem in a 25-mg bolus followed by a continuous infusion of 20 mg/hr for 24 hrs, group 2 received amiodarone in a 300-mg bolus, and group 3 received amiodarone in a 300-mg bolus followed by 45 mg/hr for 24 hrs. Measurements and Main Results The primary study end point was a >30% rate reduction within 4 hrs. The secondary study end point was a heart rate <120 beats/min (a patient was considered to have uncontrolled tachycardia if heart rate was >120 beats/min 4 hrs after study drug). The primary study end point was achieved in 14/20 (70%), 11/20 (55%), and 15/20 (75%) of patients in groups 1, 2, and 3, respectively (&khgr;2 = 1.95, p = .38). Uncontrolled tachycardia was more frequently observed in group 2 (0/20, 9/29 [55%], and 1/20 [5%] of patients in groups 1, 2, and 3, respectively; &khgr;2 = 17, p = .00016). In patients achieving tachycardia control, diltiazem showed a significantly better rate reduction (p = .0001 group 1 vs. group 3, p = .0001 over time;p = .0001 group 1 vs. group 2, p = .001 over time) when compared with the amiodarone groups. Premature drug discontinuation due to hypotension was required significantly more often in group 1 (6/20 [30%], 0/20, and 1/20 [5%] for groups 1, 2, and 3, respectively; &khgr;2 = 10, p = .01). Conclusion Sufficient rate control can be achieved in critically ill patients with atrial tachyarrhythmias using either diltiazem or amiodarone. Although diltiazem allowed for significantly better 24-hr heart rate control, this effect was offset by a significantly higher incidence of hypotension requiring discontinuation of the drug. Amiodarone may be an alternative in patients with severe hemodynamic compromise.

Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines

Background:  Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24‐h hemodynamic effects of levosimendan as add‐on therapy in desperately ill patients with cardiogenic shock requiring catecholamines.

Prophylactic anticoagulation with enoxaparin: Is the subcutaneous route appropriate in the critically ill?

BackgroundSubcutaneously administered low-molecular-weight heparins are widely used for prevention of venous thromboembolism. The appropriateness of the subcutaneous route in critically ill patients has never been established. ObjectiveTo determine anti-Xa activities in critically ill patients and in noncritically ill patients receiving prophylactic doses of subcutaneous enoxaparin. DesignProspective, controlled, open-labeled study. SettingTertiary medical-cardiologic-postoperative intensive care unit and a general medical ward at a university hospital. PatientsA total of 16 intensive care unit patients (group 1; age, 61.1 ± 16 yrs; male/female ratio, 7/9; Acute Physiology and Chronic Health Evaluation II score, 20.9 ± 7; mechanical ventilation, n = 15; vasopressors, n = 13) and 13 noncritically ill medical patients (group 2; age, 61.7 ± 9 yrs; male/female ratio, 7/6) were studied. Body mass index (25.7 ± 5 vs. 24 ± 6 kg/m2, p = not significant) was comparable and serum creatinine levels (0.83 ± 0.25 vs. 1.07 ± 0.3 mg/dL, group 1 vs. 2) were within the normal range in both groups. Patients with impaired renal function, receiving hemofiltration, or requiring therapeutic anticoagulation were not eligible. InterventionsNone. Measurements and Main ResultsAnti-Xa activities were determined at 0, 1, 3, 6, and 12 hrs after a single daily subcutaneous dose of 40 mg enoxaparin on day 1 and at 3 hrs after 40 mg of enoxaparin on days 2–5. Mean anti-Xa levels at 0 to 12 hrs were consistently lower in group 1 compared with group 2 by analysis of variance (p = .001 between groups and over time), as was the area under the curve at 0 to 12 hrs (2.6 ± 1 vs. 4.2 ± 1.7 units·mL−1·hr−1, group 1 vs. 2, p = .008). Significant differences in anti-Xa activity were also found on days 2–5 (p = .001). Peak anti-Xa activities at 3 hrs after administration were negatively correlated with the body mass index (r = −.41, p < .03). No correlation was found between the anti-Xa activity at 3 hrs and the dose of norepinephrine (r = .12, p = .7). ConclusionCritically ill patients with normal renal function demonstrated significantly lower anti-Xa levels in response to a single daily dose of subcutaneous enoxaparin when compared with medical patients in the normal ward.

Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.

PURPOSE Acute renal failure has important prognostic implications in critically ill patients, but the effects of acute renal failure on in-hospital mortality in the subset of patients with cardiogenic shock are not known. SUBJECTS AND METHODS All consecutive patients who presented with acute coronary syndrome at our cardiovascular intensive care unit from 1993 to 2000 and who were in cardiogenic shock were enrolled. Acute renal failure was defined as a urine volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5 mg/dL or > 50% above the baseline value. RESULTS There were 118 patients (83 men [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute renal failure within 24 hours after the onset of shock. In-hospital mortality was 87% (34/39) in patients with acute renal failure and 53% (42/79) in patients without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]: 2.1 to 17; P < 0.001). Other significant univariate predictors of mortality included the peak serum lactate level, epinephrine dose, and the maximum serum creatinine level. Multivariate logistic regression analysis identified acute renal failure as the only independent predictor of mortality. CONCLUSION Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.

Plasma concentrations of interleukin-6, organ failure, vasopressor support, and successful coronary revascularization in predicting 30-day mortality of patients with cardiogenic shock complicating acute myocardial infarction.

Objective:Inflammation may play an important role in the pathogenesis, persistence, and prognosis of cardiogenic shock. We analyzed whether elevated plasma concentrations of inflammatory markers are independently associated with an adverse prognosis (increased 30-day mortality rate) in patients with cardiogenic shock. Design:Retrospective study. Setting:Single-center study, eight-bed intensive care unit at a university hospital. Patients:Retrospective study on stored plasma samples from 38 patients with cardiogenic shock complicating acute myocardial infarction. Interventions:None. Measurements and Main Results:Thirty-day nonsurvivors (n = 23, 61%) had been less frequently successfully revascularized, exhibited more frequently renal failure, needed higher vasopressor doses, and presented with significantly higher interleukin-6 plasma concentrations on intensive care unit admission than 30-day survivors. Univariate hazard ratios (95% confidence interval) for 30-day mortality were 1.49 (1.24–1.80) for every 50 pg/mL increase in the interleukin-6 plasma concentration (p = .00003), 1.06 (1.02–1.10) for every 0.1 &mgr;g·kg−1·min−1 increase in the total vasopressor dose (p = .007), 1.14 (1.04–1.25) for every mmol/L increase in serum lactate (p = .006), 2.47 (1.06–5.73) for acute renal failure (p = .036), and 0.34 (0.14–0.82) for successful revascularization (p = .016). However, interleukin-6 plasma concentrations were correlated with vasopressor need and were significantly higher in patients with acute renal failure and in patients without or unsuccessful revascularization. In a multivariate Cox-proportional hazard model, interleukin-6 was the only significant predictor of 30-day mortality with a hazard ratio of 1.42 (1.12–1.80, p = .004). Accordingly, interleukin-6 concentrations ≥200 pg/mL (the point of maximum interest by receiver operating characteristic analysis with a specificity of 87% and a sensitivity of 74%) were associated with a significantly increased 30-day mortality rate in both patients with and patients without successful revascularization. Conclusions:Interleukin-6 concentrations are an independent predictor of 30-day mortality in patients with acute myocardial infarction complicated by cardiogenic shock.

Soluble selectins and the systemic inflammatory response syndrome after successful cardiopulmonary resuscitation.

Objective Elevated cytokine levels have been reported after ischemia/reperfusion injury and might cause a systemic inflammatory response syndrome (SIRS) after successful cardiopulmonary resuscitation (CPR). It is unknown whether patients with SIRS after CPR exhibit higher levels of soluble adhesion molecules than patients without SIRS and whether SIRS or elevation of adhesion molecules is associated with outcome after CPR. We analyzed the relationships among various CPR-related variables, plasma levels of E- and P-selectin, the occurrence of SIRS after CPR, and the development of sepsis and outcome. Design Prospective, controlled study. Setting Intensive care unit at a university hospital. Patients A total of 25 patients on the second day after successful CPR and 7 non-critically ill control patients. Interventions Blood sampling for determination of plasma levels of soluble (s) E- and P-selectin. Measurements and Main Results SIRS was a frequent finding after CPR (66% of all patients) unrelated to time until return of spontaneous circulation (SIRS, 17 ± 13 mins; no SIRS, 19 ± 16 mins;p = .761), epinephrine dose (SIRS, 4 ± 5 mg; no SIRS, 5 ± 6 mg;p = .906), or serum lactate level after CPR (SIRS, 8.6 ± 2.6 mmol/L; no SIRS, 8.7 ± 4.0 mmol/L;p = .174). sP-selectin levels were higher in patients with SIRS (291.7 ± 227.4 ng/mL) compared with patients without SIRS (113.4 ± 88.4 ng/mL;p = .018) or with non-critically ill patients (116.9 ± 33.4 ng/mL;p = .031). Compared with non-critically ill control patients (42.8 ± 19.4 ng/mL), sE-selectin levels were higher in patients with (96.2 ± 47.3 ng/mL;p = .023) and without SIRS (99.5 ± 65.7 ng/mL;p = .030). sP-selectin was higher in patients developing sepsis within 1 wk after CPR (n = 9) than in patients without sepsis (350.2 ± 233.4 ng/mL vs. 158.5 ± 157.8 ng/mL;p = .022) and sE-selectin levels were higher in nonsurvivors (n = 5) than in survivors (144.2 ± 62.4 ng/mL vs. 85.7 ± 45.3 ng/mL;p = .025) whereas SIRS was unrelated to the development of sepsis (p = .4) and unrelated to survival (p = .4). Conclusions SIRS is an unspecific finding after CPR with only minor impact on outcome. Determination of sP- and sE-selectin early after CPR might help to identify patients at a high risk for sepsis or for an adverse outcome, respectively.

Impact of concomitant treatment with proton pump inhibitors and clopidogrel on clinical outcome in patients after coronary stent implantation

The aim of the study was to evaluate the effect of the concomitant treatment with proton-pump inhibitors (PPIs) and clopidogrel on the incidence of stent thrombosis, acute coronary syndrome (ACS) and death in patients who underwent percutaneous coronary intervention (PCI) and stent implantation. In total, 1,210 patients under dual antiplatelet therapy, who underwent PCI and stent implantation, were included in a prospective registry from January 2003 until December 2006. The patients were divided retrospectively into those with or without long-term PPI treatment (for the duration of dual antiplatelet therapy). All-cause mortality, cardiovascular death, re-hospitalisation for re-ACS, stent thrombosis, as well as the combined endpoint all-cause death, re-ACS or stent thrombosis were evaluated over a mean follow-up period of 7.8 (± 3.63) months (range 1-12 months). Propensity score analysis was performed to reduce potential selection bias and exhibited no significant difference between the two study groups with respect to all-cause mortality, cardiovascular death, re-ACS, stent thrombosis and the combined endpoint. In pre-specified subgroup analyses performed in patients presenting with ACS and referred for acute PCI or for stable patients referred for elective PCI, receiving drug-eluting stents or bare metal stents, in diabetics or non-diabetics, in males or females, and in patients older than 75 years or ≤75 years of age use of PPIs had no significant impact on clinical outcome. Our data suggest that a combined use of clopidogrel as part of dual antiplatelet therapy (DAPT) after coronary stenting and PPIs does not significantly influence the clinical outcome.

Plasma concentrations of von Willebrand factor and intracellular adhesion molecule-1 for prediction of outcome after successful cardiopulmonary resuscitation.

ObjectiveIschemia/reoxygenation following cardiopulmonary resuscitation might cause endothelial injury/activation that could contribute to an adverse outcome after cardiopulmonary resuscitation. We studied plasma concentrations of von Willebrand factor (vWF) antigen and soluble intracellular adhesion molecule (sICAM)-1 as markers of a generalized endothelial injury/activation in relation to outcome after cardiopulmonary resuscitation. DesignRetrospective study on stored plasma samples. SettingIntensive care unit at a university hospital. PatientsThirty-five patients who survived >24 hrs after in- or out-of-hospital cardiopulmonary resuscitation and 15 noncritically ill control patients. InterventionsBlood sampling. Measurements and Main ResultsPlasma concentrations of vWF antigen and sICAM-1 on day 2 after cardiopulmonary resuscitation were higher in patients than in controls (p < .001 and p = .001, respectively). In-hospital cardiopulmonary resuscitation, cardiopulmonary resuscitation duration ≥15 mins, severe cardiovascular failure, and renal dysfunction/failure at the time of blood sampling were associated with significant elevations in vWF antigen and sICAM-1 concentrations. Patients with an unfavorable outcome after cardiopulmonary resuscitation (cerebral performance category ≥3) exhibited higher vWF antigen and sICAM-1 concentrations than patients with good outcome (cerebral performance category 1–2;p < .001 and p = .097, respectively). Renal dysfunction/failure, severe cardiovascular failure, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration ≥15 mins were also associated with higher adverse outcome rates. Combination of these four variables into a cardiac arrest risk score (levels 0–4) showed adverse outcome rates of 100, 56, and 0% in patients with arrest scores of 4, 2–3, and 0–1, respectively. A vWF antigen concentration >166% was an independent predictor of outcome after cardiopulmonary resuscitation (p = .002) and was associated with increased adverse outcome rates in patients with cardiac arrest risk scores of 2–3. Furthermore, both vWF antigen concentrations >166% and sICAM-1 concentrations >500 ng/mL had 100% specificity for an adverse outcome in patients after out-of-hospital cardiopulmonary resuscitation but were less predictive in patients after in-hospital cardiopulmonary resuscitation. ConclusionsvWF antigen and sICAM-1 might be useful adjunctive variables for early determination of outcome in patients after successful out-of-hospital cardiopulmonary resuscitation.

Concentration of Endogenous tPA Antigen in Coronary Artery Disease Relation to Thrombotic Events, Aspirin Treatment, Hyperlipidemia, and Multivessel Disease

Tissue plasminogen activator (tPA) is the major plasminogen activator responsible for dissolving blood clots found in blood vessels. However, elevated concentrations of tPA antigen were found to be related to adverse events in patients with coronary artery disease (CAD). Considerable controversy about the significance of these results exists. The goal of this cross-sectional study was to identify independent determinants for tPA antigen concentrations in patients with CAD, to possibly clarify the above paradoxical relationship. The baseline tPA antigen concentrations of 366 patients with angiographic evidence of coronary sclerosis were determined. Univariate analysis showed that age (P=0.013), angiographic extent of disease (P<0.001), presence of angina at rest (P<0.001), diabetes mellitus (P=0.004), hypercholesterolemia (P=0. 045), hypertriglyceridemia (P=0.015), and chronic intake of nitrates (P<0.001) were significantly and positively related to tPA antigen concentration, while the chronic intake of aspirin was inversely related to tPA antigen (P<0.001). In addition, plasminogen activator inhibitor type 1 (PAI-1) activity was found to be significantly and positively associated with tPA antigen concentration (P<0.001). A multivariate analysis identified chronic low-dose aspirin therapy (P<0.001), PAI-1 activity (P<0.001), hypertriglyceridemia (P=0.005), the type of angina (P=0.026), multivessel disease (P=0.041), and hypercholesterolemia (P=0.043) as significant and independent determinants of tPA antigen. While hypertriglyceridemia and hypercholesterolemia both are related to the underlying disease, the type of angina and the number of involved vessels are linked to the severity and extent of disease, and all of them are indicators of a prothrombotic state found during the progression of CAD. In contrary, low-dose aspirin rather would decrease the likelihood of thrombotic events. The relation of tPA antigen to PAI-1 activity furthermore underlines the relation between tPA antigen concentration and a prothrombotic state. Therefore, the positive or-in case of aspirin therapy-negative correlation of these parameters with tPA antigen concentration would indicate that thrombus formation and simultaneous endothelial cell activation might be major determinants for tPA antigen concentration in CAD.

Elevation of Prostate-Specific Markers After Cardiopulmonary Resuscitation

BACKGROUND-Prostate-specific antigen (PSA), acid phosphatase (AP), and prostatic acid phosphatase (PAP) are serum markers for adenocarcinoma of the prostate gland. Previous studies indicated that prostatic ischemia may also produce elevations of PSA. Cardiopulmonary resuscitation (CPR) is frequently associated with profound tissue hypoperfusion. The present study investigated whether PSA, AP, and PAP are influenced by prolonged CPR. METHODS AND RESULTS-PSA, AP, and PAP were assessed immediately, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after prolonged CPR (>5 minutes) in 14 male and 5 female patients. No changes were noted in women. In men, serum levels increased significantly after CPR and gradually decreased to near baseline values after 7 days. PSA, AP, and PAP values above the normal range were observed in 63%, 71%, and 64% of all patients, respectively. Compared with survivors, nonsurvivors exhibited higher peak serum levels of PSA (98.6+/-14.3 versus 1.1+/-2.2 mcg/L; P<0.03), AP (57.0+/-71 versus 8.6+/-8.8 U/L; P<0.05), and PAP (47.0+/-62 versus 5.7+/-8.0 U/L; P=NS). Patients with poor neurological outcome exhibited higher peak serum levels of PSA (86.4+/-135.5 versus 12.0+/-23.8 mcg/L; P<0.05), AP (50.9+/-68.1 versus 8.7+/-9.6 U/L; P=NS), and PAP (41.6+/-59.5 versus 5.8+/-8.8 U/L; P=NS) than patients with good neurological outcome. CONCLUSIONS-Prolonged CPR is frequently associated with increases of PSA, AP, and PAP serum levels. Therefore, PSA cannot be used for diagnosis of adenocarcinoma of the prostate during the first weeks after CPR. Further evaluation of these parameters as additional prognostic markers after CPR is warranted.