Maria Koreny

Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis.

OBJECTIVE Melatonin is involved in the regulation of the sleep-wake cycle and exhibits multiple interactions with the neuroendocrine and the immune system. Melatonin secretion in healthy individuals follows a stable circadian rhythm. Critical illness, continuous administration of drugs, and loss of external zeitgeber might impair the circadian rhythm of melatonin secretion in the intensive care unit (ICU), thereby compromising the physiologic stress-induced immune response. DESIGN Prospective, controlled clinical study. SETTING Medical intensive care unit in a university hospital. PATIENTS Seventeen septic, sedated ICU patients (group A); 7 nonseptic ICU patients (group B); and 21 control patients (group C) were studied. MEASUREMENTS AND MAIN RESULTS 6-Sulfatoxymelatonin (aMT6s) was determined from urine samples taken at 4-hr intervals over a total period of 24 hrs. aMT6s was measured by enzyme-linked immunosorbent assay. Circadian mesors, phase amplitudes, and timing of the acrophase were assessed by cosinor analysis. Differences between groups were calculated by contingency data analysis and by analysis of variance. Circadian mesors of urinary aMT6s were 3904 +/- 1597, 2622 +/- 927, and 3183 +/- 1514 ng/4 hrs in groups A, B, and C, respectively (p = NS). aMT6s exhibited significant circadian periodicity in only 1/17 (6%) patients of group A but in 6/7 (86%) patients of group B and in 18/23 (78%) patients of group C (group A vs. groups B and C: p = .0001) Phase amplitudes were markedly lower in group A (1071 +/- 1005 ng/4 hrs) compared with group B (2284 +/- 581 ng/4 hrs, p = .009) and C (2838 +/- 2255 ng/4 hrs, p = .006). The acrophase was significantly delayed in patients of group A (10:35 am +/- 255 mins) compared with group B (05:43 am +/- 114 mins, p = .01) and group C (4:20 am +/- 107 mins, p < .0001). In sepsis survivors, aMT6s excretion profiles tended to normalize, but still lacked a significant circadian rhythm at ICU discharge. CONCLUSION The present study revealed striking abnormalities in urinary aMT6s excretion in septic ICU patients. In contrast, circadian rhythm was preserved in nonseptic ICU patients, indicating that impaired circadian melatonin secretion in septic patients is mainly related to the presence of severe sepsis and/or concomitant medication. Further investigations are required to examine the underlying pathophysiologic mechanism and the clinical implications of this finding.

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 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.

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.

Effects of milrinone on pulmonary gas exchange in catecholamine-dependent heart failure

Hemodynamic benefits of milrinone administration are accompanied by adverse effects on arterial oxygenation in mechanically ventilated patients with end-stage heart failure. Particular attention should be focused on pulmonary gas exchange variables after initiation of milrinone treatment in the critically ill patient.