New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility.

BACKGROUND: It is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α(1),ß(1),ß(2)-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions. METHODS AND RESULTS: In 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II-IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF(c)). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF(c)-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF(c) relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months. CONCLUSIONS: Despite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.

Presurgical fentanyl vs caudal block and the incidence of adverse respiratory events in children after orchidopexy.

BACKGROUND: There is controversy about the etiology of early postoperative hypoxemia. Age, weight, intubation, surgical procedure, use of muscle relaxants, and/or administration of opioids may affect the incidence of early postoperative hypoxemia. In this prospective, randomized, and single-blinded study, we evaluated whether the administration of caudal analgesia vs i.v. fentanyl affected the number of children who develop postextubation adverse upper airway respiratory events, (upper airway obstruction, laryngospasm) and/or early postoperative hypoxemia. METHODS/MATERIALS: Institutional approval and written parental informed consents were obtained. Thirty-eight healthy outpatient boys, aged 1-6 years, scheduled for elective orchidopexy were randomized to receive pain relief either with a presurgical caudal block or by i.v. fentanyl. The primary outcome of the study was the number of children who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia. RESULTS: The number of boys who developed postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia in the caudal group was less compared with those in the fentanyl group (P = 0.04). CONCLUSIONS: Compared to fentanyl, placement of a presurgical caudal block in boys scheduled for orchidopexy was associated with a lower incidence of postextubation adverse upper airway respiratory events and/or early postoperative hypoxemia.

Caudal regional anesthesia, ropivacaine concentration, postoperative analgesia, and infants.

In this randomized, double-blind trial we evaluated the quality and duration of analgesia and motor effects after caudal block using 1 mL/kg of ropivacaine 0.1% (Group 1), 0.15% (Group 2), 0.175% (Group 3) compared to 0.2% (Group 4) in infants 1-12 mo old. Postoperatively, the number of infants who received pain medication differed among the groups (P < 0.0005). There were more infants in Groups 1 and 2 compared with Group 4 and there was no difference between Groups 3 and 4. In the postanesthesia care unit, infants in Groups 1 and 2 received more pain medication than did those in Group 4 (P = 0.0098). In the day surgery unit, there was a significant difference among the groups (P = 0.0326); infants in Groups 3 and 4 required no pain medication. The analgesia duration differed among the groups (P = 0.034). Infants in Groups 1 and 2 had a shorter duration, and there was no difference between Groups 3 and 4. Infants in Group 4 took longer to regain their motor power compared with those in Group 3 (P = 0.0347). We conclude that in infants, ropivacaine 0.175% provided postoperative analgesia and duration similar to that of ropivacaine 0.2%, whereas ropivacaine 0.1% and 0.15% did not, and it was associated with fewer motor effects.

Recurrent low-level troponin I elevation is a worse prognostic indicator than occasional injury pattern in patients hospitalized with heart failure.

BACKGROUND: Elevated troponin at baseline is associated with higher mortality in heart failure (HF) patients, but the prognostic role of recurrently elevated troponin is not well described. METHODS AND RESULTS: We performed chart reviews of 196 HF patients without acute coronary syndrome, with at least three Troponin I (TnI) measurements on different admissions. For the analyses, three sets of TnI values closest to baseline, one year and two years were selected for each patient. Based on the three sets of TnI, the lowest value of TnI (minimum), the highest value of TnI (maximum), median value of TnI and delta TnI (3rd TnI-baseline TnI) were derived for each patient. The study population of 196 patients had 632 person-year follow-up, consisted predominantly of elderly (68 ± 10 years) male patients (99%) with mean ejection fraction of 26 ± 13%. Using multivariate Cox proportional hazards model only minimum TnI, but not the maximum, median or delta of TnI values, was significantly associated with mortality (HR: 13.7, 95% CI: 3.7 to 50.8, p<0.001). As a categorical variable, minimum TnI value of >0.04ng/ml was also independently associated with mortality (p=0.01, HR=1.6, 95% CI: 1.1 to 2.3). CONCLUSIONS: In HF patients without acute coronary syndrome, the persistence of TnI elevation, even at low levels, is associated with a worse survival than sporadic TnI elevations of higher magnitude or any single elevation in TnI; and a recurrent elevation of TnI >0.04ng/ml portends a poor prognosis.

Impact of alpha 1-adrenergic antagonist use for benign prostatic hypertrophy on outcomes in patients with heart failure.

Previous clinical trials have shown that alpha(1)-adrenergic antagonists are not effective in subjects with heart failure (HF) and might increase HF rates when used for hypertension. However, alpha(1)-adrenergic antagonists may be prescribed to subjects with HF who have symptomatic benign prostatic hyperplasia. We sought to determine any association between alpha(1)-adrenergic antagonist use, commonly prescribed for benign prostatic hyperplasia, and the clinical outcomes of subjects with HF receiving contemporary therapy. An existing database of 388 subjects with decompensated HF admissions from 2002 to 2004 at the Veterans Affairs Hospital was analyzed according to the use of alpha(1)-adrenergic antagonists at discharge. Covariate-adjusted Cox proportional hazard models were used to examine any association with future admissions for decompensated HF and total mortality. Alpha-1-adrenergic antagonist therapy was prescribed in 25% of our HF population, predominantly for benign prostatic hyperplasia, and was not associated with significant increases in the combined risk of all-cause mortality and rehospitalization for HF (hazard ratio 1.24, 95% confidence interval 0.93 to 1.65, p = 0.14), HF hospitalization (hazard ratio 1.20, 95% confidence interval 0.85 to 1.70, p = 0.31), or all-cause mortality (hazard ratio 1.10, 95% confidence interval 0.78 to 1.56, p = 0.57). In patients not receiving beta-blocker therapy, alpha(1)-adrenergic antagonist therapy was significantly associated with increased HF hospitalizations (hazard ratio 1.94, 95% confidence interval 1.14 to 3.32, p = 0.015). In conclusion, in patients with chronic HF, the use of alpha(1)-adrenergic antagonists was significantly associated with more HF hospitalizations when prescribed without concomitant beta blockade. Thus, background beta-blocker therapy appears to be protective against the potential harmful effects of alpha(1)-adrenergic antagonist therapy in patients with HF.

A double-blind comparison of intravenous ondansetron and placebo for preventing postoperative emesis in 1- to 24-month-old pediatric patients after surgery under general anesthesia.

UNLABELLED: We assessed the efficacy and safety of ondansetron (0.1 mg/kg IV) prophylactically administered before surgery for prevention of postoperative vomiting (POV) in a double-blind, placebo-controlled study of 670 pediatric patients, 1- to 24-mo-old, undergoing elective surgery under general anesthesia. The study enrolled 335 children in each treatment group (ondansetron versus placebo). Significantly fewer children treated with ondansetron exhibited emesis or discontinued the study prematurely after surgery (ondansetron, 11%; placebo, 28%; odds ratio = 0.33; P < 0.0001). The number required to treat prophylactically with ondansetron to prevent POV was approximately six. Ondansetron treatment also resulted in fewer patients requiring rescue medication or assumed to have had rescue upon early discontinuation from the study during the postoperative period (ondansetron, 5%; placebo, 10%) and less emesis (0 of 6) after rescue medication when compared with placebo (7 of 21). The incidence of POV and other antiemetic effects of ondansetron were similar in children aged 1-12 mo and 13-24 mo and in children prospectively expected or not expected to require opioids as part of their anesthetic or analgesic management. Ondansetron was well tolerated; the incidence of adverse events considered possibly related to study drug was similar between treatment groups (ondansetron, 1.8%; placebo, 1.5%). IMPLICATIONS: This prospective, randomized, double-blind, placebo-controlled study establishes the efficacy and tolerability of IV ondansetron (0.1 mg/kg) in the prevention of postoperative emesis in 1- to 24-mo-old pediatric patients undergoing elective surgery under general anesthesia.