Esmolol, the first ultra-short-acting intravenous beta blocker for use in critically ill patients

Esmolol is the first intravenous, short-acting, titratable beta-blocker available for use in critical care and surgical settings. The predominant pharmacodynamic actions of the drug include a reduction in HR, BP, rate-pressure product, LVEF, and cardiac index. A desirable pharmacokinetic feature of esmolol is its esterase-induced rapid metabolic inactivation, which results in a return of all hemodynamic parameters to pretreatment levels within 30 minutes after discontinuation of the infusion. Control over the magnitude and duration of beta-blockade and the relative cardioselectivity of esmolol make it an ideal agent for use in critically ill patients, including those who, because of other conditions, are at risk if treated with beta-blockers. The clinical indications for esmolol therapy include SVT and perioperative tachycardia and hypertension. In patients with myocardial ischemic conditions (acute myocardial infarction and unstable angina), esmolol was safe and produced clinically significant reductions in HR and rate-pressure product. In general, untoward reactions to esmolol have been minimal, mild, and transient. Although attention must be given to the possibility of systolic hypotension during esmolol administration, this complication often occurs at doses beyond those which provide optimal therapeutic response and may be avoided by titrating to the minimal effective dose. If systolic hypotension occurs, it is reversible by either reducing the dose or discontinuing the esmolol infusion. A nursing plan of care should be developed for patients receiving esmolol therapy. Dosage and administration must be individualized. Careful titration of the esmolol infusion and monitoring of therapeutic and safety parameters by nursing professionals will promote the achievement of maximum beta-blocker effect while avoiding persistent and unnecessary adverse reactions.     

Moderate soft tissue trauma delays new bone formation only in the early phase of fracture healing.

The aim of this study was to investigate the effect of a moderate soft tissue trauma to the course of fracture healing in a standardized animal model. Thirty-eight Wistar rats were randomly divided into a fracture group (F, n = 19) and a group with a fracture and a soft tissue trauma (F + STT, n = 19). The fracture and the soft tissue trauma were created using an impact device with a standardized energy. All fractures were stabilized by two Kirschner wires. Three rats were measured for blood flow and sacrificed at days 1, 3, 7, and 14, and seven rats at day 28, from both groups. A three-point bending test was performed on the healed tibia after 28 days. During the first 24 h there was a reduction in blood flow, which was more pronounced in the F + STT group than in the F group. From histological sections, the shape of the callus formation, as well as the tissue distribution of newly formed bone, fibrous cartilage and fibrous connective tissue were determined. Distinctly more periosteal new bone formed and a larger callus formed at days 3 and 7 in group F compared to group F + STT. However, by days 14 and 28, the ossification and overall callus size no longer showed differences between the two groups. A fast recovery of blood flow and callus formation took place in the F + STT group, which led to similar histological and biomechanical results in fracture healing observed after 28 days between the two groups.     

Intraperitoneal P-32 after negative second-look laparotomy in ovarian carcinoma

Thirty-one patients underwent a negative second-look laparotomy between 1976 and 1986. Fourteen patients received intraperitoneal chromic phosphate (P-32) after a negative second-look laparotomy. There has been no local recurrence (zero of 14) and no deaths attributable to recurrent disease. Local control and disease-free survival are 100%, with a minimum follow-up of 2 years and a mean follow-up of 4 years. Seventeen patients received no further therapy because of patient refusal, poor diffusion, or other contraindications to P-32 installation. Four of 17 patients undergoing negative second-look procedures without the addition of P-32 have subsequently recurred. This difference is highly suggestive (P = .076). There have been no major complications with the addition of P-32. The use of intraperitoneal P-32 after negative second-look laparotomies on ovarian carcinoma is well tolerated and effective in preventing recurrence.     

Deprivation and survival from breast cancer.

We studied the association between deprivation and survival from breast cancer in 29,676 women aged 30 and over who were diagnosed during the period 1980-89 in the area covered by the South Thames Regional Health Authority. The measure of deprivation was the Carstairs Index of the census enumeration district of each woman''s residence at diagnosis. We studied the impact of stage at diagnosis, morphology and type of treatment on this association, with the relative survival rate and the hazard ratio as measures of outcome. There was a clear gradient in survival, with better survival for women from more affluent areas. At all ages, women in the most deprived category had a 35% greater hazard of death than women from the most affluent areas after adjustment for stage at diagnosis, morphological type and type of treatment. In younger women (30-64 years), the survival gradient by deprivation category cannot be explained by these prognostic factors. In older women (65-99 years), part of the unadjusted gradient in survival can be explained by differences in the stage of disease: older women in the most deprived category were more often diagnosed with advanced disease. Other factors, so far unidentified, are responsible for the gradient in breast cancer survival by deprivation category. The potential effect on breast cancer mortality of eliminating the gradient in survival by deprivation category is substantial (7.4%). In women aged 30-64 years, 10% of all deaths within 5 years might be avoidable, while in older women this figure is 5.8%.     

Reduced incidence and severity of accelerated graft atherosclerosis in cardiac transplant recipients treated with prophylactic antilymphocyte globulin.

Allograft coronary artery disease (ACAD) is the major factor limiting long-term survival of cardiac transplant recipients (CTRs). Although cyclosporine based triple drug immunosuppression has not decreased the occurrence of ACAD, some preliminary data suggests that prophylactic antilymphocyte preparations may reduce the incidence of this problem. All CTRs at Henry Ford Hospital have uniformly received prophylactic Minnesota Antilymphocyte Globulin (ALG), thereby providing a unique opportunity to investigate this hypothesis. One hundred three CTRs were followed for a median duration of 34 months with annual angiograms begun one year after transplant. Patients who died without an angiogram were considered to have ACAD based on autopsy results or if their death was clinically suspicious. Ninety-two patients underwent at least one angiogram. Fourteen patients had abnormal angiograms. Nine patients were identified as having ACAD by non-angiographic criteria. Five had autopsy proven disease, 3 died suspiciously, and 1 underwent successful re-transplantation for ACAD. By Kaplan-Meier analysis, the risk of developing ACAD was 12% in 1 year, 16% in 2 years, 22% in 3 years, 26% in 4 years, and 29% in 5 years. Risk of ACAD increased with older recipient's age, higher triglyceride levels, and diabetes, but was not affected by active CMV infection, number of acute rejection episodes, and HLA mismatching. These results suggest that prophylactic ALG reduces the occurrence of ACAD.     

Clinical reactivation after liver transplantation with an unusual minor strain of hepatitis B virus in an occult carrier.

Hepatitis B virus (HBV) DNA is detectable in a number of liver transplant candidates who are negative for hepatitis B surface antigen (HBsAg). After liver transplantation (LT), such patients may have molecular and/or serologic evidence of HBV replication. However, clinical disease from reactivation of occult HBV infection after LT has not been described. We report a patient who underwent LT for cryptogenic cirrhosis and had to be retransplanted twice for hepatic artery thrombosis. The patient was negative for HBsAg and positive for anti-hepatitis B core (HBc) and anti-HBs before all LT procedures and developed acute hepatitis B shortly after receiving the third graft. The HBV strain isolated at that time exhibited an unusual in frame insertion of a CAG motif within the HBV polymerase (HBV(INS+)). HBV(INS+) was detected retrospectively as a minor species in pretransplantation sera and the explanted native liver by insertion-specific polymerase chain reaction. This case in an occult HBV carrier shows that clinically apparent, endogenous reinfection of the graft may occur with minor HBV variants that are not detectable in pretransplantation samples by standard diagnostic procedures. This has implications for the analysis of sources of acute hepatitis B in patients after LT and possibly for consideration of antiviral prophylaxis in anti-HBc/anti-HBs/HBV DNA-positive patients.