Adaptations of the peripheral circulation to PEEP.

The purpose of this study was to determine the role of changes in the parameters of venous return on the homeostatic adaption to the application of PEEP. We studied 13 dogs anesthetized with alpha-chloralose, intubated, and ventilated. We measured central venous pressure (CVP), arterial pressure (Pao) and cardiac output by thermal dilution. The cardiac output was transiently stopped by inflating a balloon in the right atrium, and the subsequent plateau in the CVP was used to obtain mean circulatory filling pressure (MCFP). Total blood volume was measured with Evans blue. To measure vascular capacitance and compliance, we rapidly infused 4 ml/kg or 8 ml/kg of blood and repeated the MCFP measurement. The same volume was withdrawn after the measurement. The volume and MCFP were used to construct pressure-volume (P-V) lines, and the unstressed volume was calculated by extrapolating the P-V to zero pressure. The P-V appeared linear in the range studied. PEEP produced a left shift of the curves and, thus, a decrease in unstressed volume. The shift with 20 cm H2O of PEEP was greater than with 10 cm H2O of PEEP. The rise in MCFP matched the rise in CVP so that the pressure gradient for venous return did not change. However, there was also an increase in the resistance to venous return, which resulted in a lower cardiac output than expected for the rise in MCFP. In conclusion, homeostatic adjustments to PEEP included a decrease in vascular capacitance, which is partially offset by a rise in the resistance to venous return.     

Thrombolysis and Counterpulsation to Improve Survival in Myocardial Infarction Complicated by Hypotension and Suspected Cardiogenic Shock or Heart Failure: Results of the TACTICS Trial

Background: Sustained hypotension, cardiogenic shock, and heart failure all imply a poor prognosis in acute myocardial infarction (MI). We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation (IABP) to standard treatment for MI, in an international trial among hospitals without primary angioplasty capabilities.Methods: We randomized 57 patients with MI complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure to receive either fibrinolytic therapy and IABP or fibrinolysis alone. The primary end point was all-cause mortality at 6 months.Results: In all, IABP was inserted in 27 of 30 assigned patients a median 30 minutes after fibrinolysis began and continued for a median 34 hours. Of the 27 patients assigned to fibrinolysis alone, 9 deteriorated such that IABP was required. The IABP group was at slightly higher risk at baseline, but the incidence of the primary end point did not differ significantly between groups (34% for combined treatment versus 43% for fibrinolysis alone; adjusted P = 0.23). Patients with Killip class III or IV showed a trend toward greater benefit from IABP (6-month mortality 39% for combined therapy versus 80% for fibrinolysis alone; P = 0.05).Conclusions: While early IABP use was not associated with a definitive survival benefit when added to fibrinolysis for patients with MI and hemodynamic compromise in this small trial, its use suggested a possible benefit for patients with the most severe heart failure or hypotension.Abbreviated Abstract. We assessed the benefit of adding 48 hours of intra-aortic balloon counterpulsation to fibrinolytic therapy among 57 patients with acute myocardial infarction complicated by sustained hypotension, possible cardiogenic shock, or possible heart failure. The primary end point, mortality at 6 months, did not differ between groups (34% for combined treatment versus 43% for fibrinolysis alone [n = 27]; adjusted P = 0.23), although patients with Killip class III or IV did show a trend toward greater benefit from IABP (39% for combined therapy versus 80% for fibrinolysis; P = 0.05).     

Long-term experience with sotalol in the treatment of complex ventricular arrhythmias

Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.     

Effect of Psychosocial Interventions on Quality of Life in Patients With Chronic Heart Failure: A Meta-analysis of Randomized Controlled Trials

BackgroundPatients with chronic heart failure (CHF) usually experience poor quality of life (QoL). Psychosocial interventions tend to affect QoL in CHF. The aim of this study was to explore: 1) the effectiveness of psychosocial interventions on patients' QoL; 2) the magnitude of this effect; and 3) factors that appear to moderate the reported effect on QoL.Methods and ResultsMeta-analysis of the data of 1,074 intervention patients and 1,106 control patients from 16 randomized controlled trials (RCTs) that reported QoL measures in treatment and control groups before and after a psychosocial intervention. Subgroup analyses were conducted between: 1) face-to-face versus telephone interventions; 2) interventions that included only patients versus those that included patients and their caregivers; and 3) interventions conducted by a physician and a nurse only, versus those conducted by a multidisciplinary team. Psychosocial interventions improved QoL of CHF patients (standardized mean difference 0.46, confidence interval [CI] 0.19–0.72; P < .001). Face-to-face interventions showed greater QoL improvement compared with telephone interventions (χ² = 5.73; df = 1; P < .02). Interventions that included caregivers did not appear to be significantly more effective (χ² = 1.12; df = 1; P > .29). A trend was found for multidisciplinary team approaches being more effective compared with nonmultidisciplinary approaches (χ² = 1.96; df = 1; P = .16).ConclusionsA significant overall QoL improvement emerged after conducting psychosocial interventions with CHF patients. Interventions based on a face-to-face approach showed greater benefit for patients' QoL compared with telephone-based approaches. No significant advantage was found for interventions conducted by a multidisciplinary team compared with a physician and nurse approach, or for psychosocial interventions which included patients' caregivers compared with patient-only approaches.     

Immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children

Objective: To determine the immunity to hepatitis B, poliomyelitis and measles in fully vaccinated Aboriginal and Torres Strait Island children in north Queensland.
Methodology: A cross-sectional survey of immunity in a sample of children; 101 fully vaccinated Aboriginal and Torres Strait Island children, with a median age of 24.5 months, from 10 communities in North Queensland participated in this study. The main outcome measures were the prevalence of adequate antibody levels against hepatitis B, poliomyelitis and measles.
Results: Only 54% (95% Cl 44–63%) of the children had adequate immunity (10 m iu/mL) to hepatitis B, and one child had been infected despite vaccination. Although all the children (95% Cl 96–100%) had adequate immunity (i.e. neutralizing antibodies at a dilution of 1:8) to poliovirus 2, only 93% (95% Cl 86–96%) and 60% (95% Cl 50–69%) had adequate immunity to polioviruses 1 and 3, respectively. Nearly all (96%; 95% Cl 90–98%) of the children had adequate immunity (i.e. detectable IgG antibody) to measles.
Conclusions: Although a relatively low proportion of the children had adequate antibody levels against hepatitis B the clinical significance of this observation is uncertain. Further studies are needed to determine whether fully vaccinated Torres Strait Island children have been adequately protected and whether they require a booster dose of hepatitis B vaccine. A substantial proportion of fully vaccinated Aboriginal and Torres Strait Island children are inadequately protected against poliomyelitis, and therefore any such child with acute flaccid paralysis should be investigated fully for poliomyelitis. Vaccinated Aboriginal and Torres Strait Island children are well protected against measles, as are other Australian children.     

New treatment strategies for malignant gliomas

Malignant gliomas are the most prevalent type of primary brain tumor in adults. Despite progress in brain tumor therapy, the prognosis of malignant glioma patients remains dismal. The median survival of patients with glioblastoma muhiforme, the most common grade of malignant glioma, is 10-12 months. Conventional therapy of surgery, radiation and chemotherapy is largely palliative. Essentially, tumor recurrence is inevitable. Salvage treatments upon recurrence are palliative at best and rarely provide significant survival benefit. Therapies targeting the underlying molecular pathogenesis of brain tumors are urgently required. Common genetic abnormalities in malignant glioma specimens are associated with aberrant activation or suppression of cellular signal transduction pathways and resistance to radiation and chemotherapy.