Pharmacotherapy of ventricular fibrillation. A prospective study in an emergency medical service

This prospective study investigated the effects of standard pharmacotherapy in out-of-hospital ventricular fibrillation (VF) after i.v. or endobronchial (e.b.) administration of epinephrine and lidocaine. METHODS. Only patients presenting with out-of-hospital VF were included in this study, whereby VF of noncardiac origin was excluded. Cardiopulmonary resuscitation (CPR) was performed according to the guidelines of the American Heart Association. Basic life support was initiated by Emergency Medical Service (EMS) technicians. The first step of advanced life support was immediate defibrillation by the EMS physician. Epinephrine was given in doses of 2.5 mg e.b. or 1.0 mg i.v. If indicated, patients received 200-500 mg lidocaine e.b. or 100 mg i.v. The course of CPR was tape-recorded and 2-3 blood samples were taken from each patient for drug monitoring. Plasma levels of epinephrine and lidocaine were measured by high-pressure liquid and gas chromatography, respectively, and then correlated to the course of CPR. RESULTS. Forty-seven patients presented VF on arrival of the EMS physician. Restoration of spontaneous circulation was achieved in 64% (Table 3), and 30% of the patients were discharged from hospital without major neurologic deficits. Immediate defibrillation before initiation of pharmacotherapy produced a success rate of 15.8%, whereas defibrillation after drug therapy was successful in 61.5% of cases. Following e.b. instillation of 2.5 mg epinephrine (Fig. 1), median peak concentrations of epinephrine (40.2, range 4.0-79.8 ng/ml) were reached after 3-4 min and plasma levels greater than or equal to 10 ng/ml were seen for 20 min. After i.v. injection of 1.0 mg epinephrine (Fig. 2) maximum concentrations (71.6, range 4.7-104.2 ng/ml) were measured after 1-2 min and plasma levels decreased below 10 ng/ml after 10 min. Following e.b. instillation of 400-500 mg lidocaine mean lidocaine concentrations within the therapeutic range (2-5 micrograms/ml) were reached after 4-5 min and remained within these limits for 20-30 min. Peak concentrations were obtained after 12 min. Doses of 200-320 mg lidocaine e.b. failed to achieve therapeutic plasma levels (Fig. 3). Regarding the pharmacodynamic aspects of drug therapy, 22.5% of the initial survivors were resuscitated from VF without therapeutic epinephrine, presenting with mean endogenous epinephrine concentrations of 7.1 ng/ml, 51.6% of patients were resuscitated after epinephrine therapy with plasma concentrations greater than 20 ng/ml. In only 1 case could a relationship be demonstrated between the administration of lidocaine and resuscitation success. CONCLUSION. In CPR, the e.b. administration of epinephrine and lidocaine is a reliable alternative to the i.v. injection route of these drugs. Recommended doses are 2.5 mg for epinephrine and 400-500 mg for lidocaine. Resuscitation from VF requires immediate epinephrine therapy if initial defibrillation is not successful. Lidocaine has no effect on resuscitation from VF and therefore should be used specifically for antiarrhythmic therapy after restoration of spontaneous circulation.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Dural sinus thrombosis: study using intermediate field strength MR imaging

The magnetic resonance (MR) images of six patients with thrombosis of a dural sinus were reviewed. The diagnosis had been verified by computed tomographic scans in three patients and arteriograms in two; in the sixth patient, only MR imaging was used to confirm the clinical syndrome. In all patients, high-intensity signal was seen from the thrombus within the affected dural sinus on all echoes. This persistent signal intensity allowed intravascular clot to be distinguished from normal causes of increased signal such as flow-related enhancement (entry phenomenon) and even-echo rephasing. MR imaging demonstrated the cause of the thrombosis in three patients: two were secondary to adjacent tumors, and one was secondary to unsuspected mastoiditis. Complications such as infarction were also demonstrated. Using MR imaging, one can easily and safely diagnose thrombosis of a dural sinus. MR should be the imaging method of choice in patients suspected of having thrombosis of a dural sinus.     

Clinical MR imaging with a Helmholtz-type surface coil

Limited-field-of-view radio-frequency receiver antennas provide improved near-field sensitivity for magnetic resonance imaging by decreasing the antenna volume. The Helmholtz-type surface coil, consisting of two flat rings, is an organ-encompassing antenna that takes advantage of this principle to yield an improved signal-to-noise ratio (S/N). The coil was tested in a group of 50 patients and 16 healthy volunteers. Images obtained with the Helmholtz coil demonstrated quantitatively superior S/N of 2.2-fold or greater than that of comparison body coil images, as well as qualitatively superior anatomic resolution.     

Low-artifact intravascular devices: MR imaging evaluation

Flow-phantom magnetic resonance (MR) imaging, with use of both spin-echo (SE) and gradient-echo (GRE) techniques at 1.5 T, was performed on the percutaneous Greenfield (beta-III titanium alloy [TMA wire]), Amplatz (MP32-N alloy), and Simon nitinol filters and TMA wire facsimiles of the bird's nest, Gunther, new retrievable, and Amplatz vena caval filters. SE imaging allowed detection of thrombi as small as 5 X 5 mm trapped within the percutaneous Greenfield, Simon nitinol, and TMA-wire facsimile filters; with the MP32-N Amplatz filter, a larger volume of thrombus (10 X 20-mm clots) was necessary for clot detection. GRE imaging allowed detection of intraluminal tilting of the percutaneous Greenfield and facsimile Amplatz (TMA-wire) filters. GRE imaging was useful for demonstrating postfilter turbulence due to clots, which was greatest for the Amplatz filter. Imaging of facsimile vascular devices made of tantalum or TMA wire did not cause the severe "black-hole" MR artifacts typical of the stainless-steel devices. SE and GRE imaging were very useful for determining caval patency in two patients with previously placed Mobin-Uddin filters. Noninvasive MR evaluation of blood vessels in the presence of a variety of low-artifact intravascular devices appears feasible.     

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist,SC-53228: Impact upon Leukotriene B4- and 12(R)-HETE- mediated events

Leukotriene B₄ (LTB₄) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB₄ and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid}, a first-generation LTB₄ receptor antagonist, inhibited the chemotactic actions of LTB₄ when given orally with an ED₅₀ value of 1.7 mg/kg. The second-generation LTB₄ receptor antagonist, SC-53228 [(+)-(S)-7-(3-{2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy} propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid], inhibited LTB₄-induced chemotaxis when given intragastrically with an ED₅₀ value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED₅₀ value of 5.8 mg/kg. When dosed orally over a range of 0.03–100 mg/kg, SC-53228 gaveC _max plasma concentrations of 0.015–41.1g/ml. SC-53228 inhibited LTB₄-primed membrane depolarization of human neutrophils with an IC₅₀ value of 34 nM. As a potent LTB₄ receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB₄ and/or 12(R)-HETE are implicated as inflammatory mediators.