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We carried out a study in patients with severe neutropenia from hematologic malignancy and suspected gram-negative sepsis to evaluate the clinical significance of endotoxin concentrations in plasma before and during a therapeutic intervention with a human polyclonal immunoglobulin M (IgM)-enriched immunoglobulin preparation (Pentaglobin; Biotest, Dreieich, Germany). Twenty-one patients with acute leukemia or nonHodgkin's lymphoma entered the study upon the development of clinical signs of gram-negative sepsis and received the IgM-enriched immunoglobulin preparation every 6 h for 3 days (total dose, 1.3 liter with 7.8 g of IgM, 7.8 g of IgA, and 49.4 g of IgG), in addition to standardized antibiotic treatment. Concentrations of endotoxin and IgM and IgG antibodies against lipid A and Re lipopolysaccharide (LPS) in plasma were determined by a modified chromogenic Limulus amebocyte lysate test and semiquantitative enzyme linked immunosorbent assay, respectively, before each immunoglobulin infusion and during the following 25 days. Seventeen patients were endotoxin positive; in five of these patients, gram-negative infection was confirmed by microbiologic findings. Prior to therapy, endotoxemia correlated significantly with the occurrence of fever, and a quantitative correlation between the endotoxin concentration and body temperature was found during the individual course of infection in 8 of the 17 patients. Overall mortality from endotoxin-positive sepsis was 41% (7 of 17) and 64% (7 of 11) in patients with symptoms of septic shock. Nonsurvivors had significantly higher maximum concentrations of endotoxin in plasma compared with those of survivors at the first study day (median of 126 versus 34 pg/ml; P < 0.05) and during the whole septic episode (median of 126 versus 61 pglml; P < 0.05). In survivors, immunoglobulin therapy resulted in a significant decrease in endotoxin levels in plasma within the initial 18-h treatment period, from a pretreatment median value of 28 pg/ml to a value of 8 pg/ml (P < 0.05). In the seven patients who died from uncontrollable infection, no effect of therapy on endotoxin levels in plasma was observed. IgM and IgG antibodies against Upid A and Re LPS increased significantly under immunoglobulin treatment, with significant correlations between antibodies against lipid A and Re LPS. These data strongly suggest a prognostic significance of the endotoxin levels in plasma and a potential effect of treatment with a polyclonal IgM-enriched immunoglobulin preparation. Further studies are needed to substantiate these findings and to assess the impact on the clinical course by way of a prospective placebo-controlled clinical trial.Despite the development of new and effective antimicrobial agents and their early application in combination regimens, gram-negative sepsis is still associated with an overall mortality of 20 to 40% (22,39,40) or even 40 to 75% in patients who develop clinical signs of septic shock (3,16,39,40). This high death rate is at least partly attributed to endotoxin, the lip...

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Vasopressin (antidiuretic hormone) is a potent vasoconstrictor and improves coronary blood flow when administered during hypovolemia.The purpose of this study was to investigate the effects of vasopressin on myocardial hemodynamics during and after CPR. After 4 min of ventricular fibrillation and 3 min of open-chest CPR, 14 pigs were randomized into 2 groups receiving either 0.8 U/kg vasopressin, or 0.045 mg/kg epinephrine. Myocardial blood flow was measured using radiolabeled microspheres. During CPR, mean coronary perfusion pressure before, 90 sec and 5 min after drug administration was 30±2.2 (SEM), 61±1.7, 46±1.4 mm Hg in the vasopressin group and 29±2.5, 41±2.2, 28±3.6 mm Hg in the epinephrine group (p < 0.001 at 90 sec and 5 min between groups). At the same points in time, mean myocardial blood flow was 61±5, 148±29, 122±22 ml/min/100 gin the vasopressin group and 57±11,. 84±11, 59±9 ml/min/100 g in the epiniphrine group (p < 0.05 at 90 s and 5 min). After a total of 12 min of arrest, including 8 min of CPR,. restoration of spontaneous circulation was possible in all animals. At 5, 15 and 30 min following resuscitation, mean arterial blood pressure was 90±6.5, 84±4.6 and 75± 4.0 mm Hg in the vasopressin group and 64±4.3, 53±4.9 and 56± 3.8 mm Hg in the epinephrine group (p < 0.01 for all 3 comparisons), whereas heart rate, cardiac index, right atrial pressure and pulmonary artery occlusion pressure showed no intergroup differences. Vasopressin was more effective than epinephrine at the doses used, in increasing coronary perfusion pressure and myocardial blood flow. In the first 30 min after restoration of spontaneous circulation, mean arterial blood pressure was significantly higher in the vasopressin-treated animals. As no detrimental effects which could be ascribed to vasopressin were observed, it may be an alternative to adrenergic vasopressors during CPR.