Systemic and organ dysfunction response during infusion of recombinant human activated protein C (rhAPC) in severe sepsis and septic shock.

AIM: The aim of this study was the assessment of the efficacy of recombinant human activated protein C (rhAPC) in septic patients. METHODS: A continuous observational prospective study on ICU patients with severe sepsis and septic shock was carried out. Applying the inclusion criteria of a national trial on the use of rhAPC, 15 patients (12 males and 3 females) were enrolled, mean age was 65.9 (SD 9.6), APACHE II score was > or =25. The following variables were assessed on 7 time-points (T1-T7): overall SOFA score; organ-specific SOFA score; APACHE II score; PCR, APTT, INR, fibrinogen, platelet count. Wilcoxon's statistical test and Spearman's correlation test (rho coefficient) between the SOFA and APACHE II scores were used. Test results with a P value below 0.05 were deemed significant. RESULTS: A significant correlation was identified between the APACHE II and SOFA scores. No significant change was found in Friedman's test and the respiratory, haematological and hepatic SOFA score, whereas cardiovascular, renal and neurological SOFA scores showed a significant trend between the ranks at the 7 time-points (chi2=14; df=6; P=0.029). During rhAPC treatment Friedman's test showed significant changes of PCR values over the 7 time-points (chi2=19.2; df=6; P=0.02). Wilcoxon's test indicated a significant decrease in the values recorded during the T2-T6 period. On day 28, 12 of the 15 patients originally enrolled were still alive. Mortality rate was therefore 20% (CI 95%). CONCLUSIONS: RhAPC is the first biological agent approved for the treatment of severe sepsis and septic shock. Our experience is confined to patients with severe sepsis and septic shock, and some severity indexes showed a modulation of the inflammatory processes and haemostatic balance, 2 factors which play a key role in the evolution of sepsis and organ dysfunction.

Sepsis and organ dysfunction: an ongoing challenge.

In recent years the problem of infection has become increasingly significant, especially in intensive care hospital wards such as Intensive Care Units (ICU), emergency medicine, surgery and critically ill patient care departments. Sepsis is a complex, multifactorial syndrome that can develop into conditions of different severity, described as severe sepsis or septic shock. In these conditions the triggering event may coincide with the functional impairment of one or more vital organs or systems, thus leading to poorer prognosis in patients with overt signs of sepsis or systemic inflammation syndromes. The available data are quite alarming, as most prevention and treatment is performed empirically and requires considerable human and technological resources. Clinical signs are often misleading and, in some circumstances, it may be difficult or even impossible to identify the source of the infection which might otherwise be removed relatively simply, using proper antimicrobial treatment or a less invasive surgical removal of the area from which the infection originates based on needle-guided radiology. In addition, the complex pathophysiological mechanisms involved can be an obstacle to gaining a full understanding of the various biohumoral interactions or mediators action mechanisms. It may not be easy to enroll patients belonging to homogeneous groups in terms of age, underlining disease, immune profile or genetic predisposition, although the use of specific severity indexes has proved helpful also to establish the prognosis. Although the interpretation of generalised inflammation as a warning sign also in the absence of clear signs of infection or a state of overt inflammation has to rely largely on simple intuition, it has helped to drive experimental and clinical research work towards the investigation of interaction between different factors such as infection and sepsis, or inflammation and coagulation. An additional useful tool is the possibility of modulating the endothelial response which may support the process of disseminated thrombosis typical of sepsis evolution. In this context the improvement of standards of care can shed light on the efficacy of different treatments.

Hemodynamic effects of plasma exchange in septic patients: preliminary report.

To assess the effects of plasma exchange on the hemodynamic performance of septic patients, we studied 12 septic patients (11 males and 1 female, age range 19-64, mean 39 +/- 17 years). After cardiovascular stabilization, plasma exchange was performed in the spontaneous mode via a femorofemoral arteriovenous shunt; during the treatment the infusion rate of cardiovascular drugs and the mechanical ventilation setting were not modified. Heart rate, pulmonary artery occlusion pressure, and peripheral vascular resistance did not change significantly. The stroke volume index increased significantly (from 49 +/- 9 to 60 +/- 9 ml/min/m2; p < 0.05) as well as the cardiac index (from 5.5 +/- 1.2 to 6.3 +/- 0.8 liters/min/m2, the oxygen delivery (from 785 +/- 166 to 872 +/- 118 ml/min/m2; p < 0.05), and the left ventricular stroke work index/pulmonary artery occlusion pressure ratio (from 4.03 +/- 1.92 to 5.07 +/- 2.54; p < 0.05). The oxygen consumption did not change. Four patients survived. In conclusion, in our patients plasma exchange was associated with an improvement in cardiac function, possibly due to the elimination of some sepsis mediator(s) with negative inotropic properties.

[Clinical course and histopathology of acute oliguric and non-oliguric renal insufficiency]. / Clinica ed istopatologia dell'insufficienza renale acuta oligurica e non oligurica.

A retrospective analysis of clinical course and hystopathologic lesions of 23 patients with multiple system organ failure (MSOF) showed that: non-oliguric acute renal failure is more frequent than the oliguric one; the prognosis is severe in both forms; hystopathologic findings are similar. Since acute tubular necrosis during sepsis is characterized by an high incidence of microthrombosis, the prophylactic use of heparin could be justified.

[Medical therapy of acute cardiogenic pulmonary edema. Critical review]. / La terapia medica dell'edema polmonare acuto cardiogeno. Revisione critica.

After a survey of conventional and modern therapeutic strategies in pulmonary edema, a simple clinical approach to the management of this cardiac emergency is suggested. The central role of chlorpromazine, as a vasodilator drug, is also stressed.