Human protein C concentrates in adult septic patients

Some case reports and case series suggest that protein C concentrates may improve the outcome in patients with congenital or acquired protein C deficiency (not only in those with sepsis induced purpura fulminans). We reviewed the published literature on the use of protein C concentrates in adult septic patients and found that it is limited to less than 70 patients reported in observational studies with a 70% survival, and added our personal experience (two adult patients with sepsis and contraindications to recombinant activated protein C)

Human protein C concentrate in pediatric septic patients

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis

Human protein C concentrate in pediatric septic patients

Severe sepsis and septic shock are leading causes of morbidity and mortality in the pediatric population. Unlike what is suggested for the adult population, recombinant human activated protein C (rhAPC) is contraindicated in children. Long before rhAPC was considered for use in pediatric patients, case reports appeared on the safe administration of protein C zymogen. Therefore, we conducted a systemic review of currently available data on protein C zymogen (PC) use among children affected by severe sepsis or septic shock. A total number of 13 case series or case reports and a dose-finding study were found on the use of PC in the pediatric intensive care unit, reporting on 118 treated children, with an overall survival of 84%. There was no bleeding complication, the only reported complication being a single mild allergic reaction. These studies show that PC is safe, not associated with bleeding and possibly useful for improving coagulation abnormalities of sepsis

When ˝clinician˝ does not rhyme with ˝communication˝

It is sad to say that communication skills, whether needed by a clinician to give a prognosis to a terrified patient or required by a petrified speaker during a congress presentation, are very often lacking from the modern-day biomedical professional’s armamentarium

Administration of protein C concentrates in patients without congenital deficit: a systematic review of the literature

Endogenous protein C levels are frequently decreased in septic patients, probably due to increased conversion to activated protein C. Protein C levels inversely correlate with morbidity and mortality of septic patients regardless of age, infecting microorganisms, presence of shock, disseminated intravascular coagulation, degree of hypercoagulation, or severity of illness. Taken together, these considerations suggest a strong correlation between protein C pathways and survival from severe sepsis/septic shock, and reinforce the rationale for the attempts to normalize plasma activity of protein C to improve survival, hamper coagulopathy, and modulate inflammation. We therefore conducted a systematic review of all manuscripts describing protein C concentrates administration in adult and pediatric populations. We identified 28 studies, for a total of 340 patients, 70 of whom died (20.6%). Septic patients were the most represented in this review of case reports and case series. In the majority of these patients sepsis was associated with meningitis, purpura fulminans or disseminated intravascular coagulation. No bleeding complications related to the study drug were reported and most studies underlined normalization of inflammatory markers and of coagulation abnormalities. We conclude that protein C concentrate is an attractive option in septic patients (especially those with meningitis, purpura fulminans, or disseminated intravascular coagulation) and that its cost-benefit ratio must be studied with a large multicenter randomized control trial, possibly including also high risk patients with septic shock and multiple organ failure

Intraoperative use of tranexamic acid to reduce transfusion rate in patients undergoing radical retropubic prostatectomy: double blind, randomised, placebo controlled trial

Objectives To determine the efficacy of intraoperative treatment with low dose tranexamic acid in reducing the rate of perioperative transfusions in patients undergoing radical retropubic prostatectomy

validation of a decision making strategy for systolic anterior motion following mitral valve repair

Low cardiac output syndrome and hypotension are dreadful consequences of systolic anterior motion (SAM) after a mitral valve (MV) repair. The management of SAM in the operating room remains controversial. We validate a recently suggested two-step management method and classification of this complication. This was a teaching hospital-based observational study. We validated a novel two-step conservative management method, consisting in intravascular volume expansion and discontinuation of inotropic drugs (step 1), and increasing the afterload by ascending aorta manual compression while administering esmolol e.v. (step 2). We also validate a novel classification of SAM: easy-to-revert (responding to step 1), difficult-to-revert (responding to step 2), or persistent. Fifty patients had an easy-to-revert while 26 had a difficult-to-revert SAM; 4 patients had a persistent condition (promptly diagnosed through our decisional algorithm) and underwent an immediate second pump run to repeat the mitral repair surgery. We confirmed that SAM after a repair of a degenerative MV is common and validated a simple two-step conservative management method that allows to clearly identify those few patients who require immediate surgical revision

Decreasing mortality with drotrecogin alfa in high risk septic patients A meta-analysis of randomized trials in adult patients with multiple organ failure and mortality >40%

Objective. Sepsis is a complex inflammatory disease, rising in response to infection. Drotrecogin alfa, approved in 2001 for severe sepsis, has been withdrawn from the market. The aim of this study was to assess if drotrecogin alfa-activated can reduce mortality in the more severe septic patients. Methods. We searched PubMed, Embase, Scopus, BioMedCentral, and in Clinicaltrials. gov databases to identify every randomized study performed on drotrecogin alfa-activated in any clinical setting in humans, without restrictions on dose or time of administration. Our primary end-point was mortality rate in high risk patients. Secondary endpoints were mortality in all patients, in patients with an Acute Physiology and Chronic Health Evaluation (APACHE) 2 score ≥ 25 and in those with an APACHE 2 score ≤25. Results. Five trials were identified and included in the analysis. They randomized 3196 patients to drotrecogin alfa and 3111 to the control group. Drotrecogin alfa was associated with a reduction in mortality (99/263 [37.6%] vs 115/244 [47.1%], risk ratios (RR) = 0.80[0.65; 0.98], p = 0.03) in patients with multiple organ failure and a mortality risk in the control group of >40%, but not in the overall population or in lower risk populations. Conclusions. In high risk populations of patients with multiple organ failure and a mortality of >40% in the control group, Drotrecogin alfa may still have a role as a lifesaving treatment. No beneficial effect in low risk patients was found. An individual patient meta-analysis including all randomized controlled trial on sepsis is warranted, along with new studies on similar drugs such as protein C zymogen

Urinary neutrophil gelatinase-associated lipocalin as an early predictor of prolonged intensive care unit stay after cardiac surgery.

Neutrophil gelatinase-associated lipocalin (NGAL) is a protein of lipocalin family highly expressed in various pathologic states and is an early biomarker of acute kidney injury in cardiac surgery. We performed an observational study to evaluate the role of NGAL in predicting postoperative intensive care stay in high-risk patients undergoing cardiac surgery. We enrolled 27 consecutive patients who underwent high-risk cardiac surgery with cardiopulmonary bypass. Urinary NGAL (uNGAL) was measured before surgery, at intensive care unit (ICU) arrival and 24 h later. Univariate and multivariate predictors of ICU stay were performed. uNGAL was 18.0 (8.7–28.1) ng/mL at baseline, 10.7 (4.35–36.0) ng/mL at ICU arrival and 29.6 (9.65–29.5) 24 h later. The predictors of prolonged ICU stay at the multivariate analysis were body mass index (BMI), uNGAL 24 h after surgery, and aortic cross-clamp time. The predictors of high uNGAL levels 24 h after at a multivariate analysis were preoperative uNGAL and logistic European System for Cardiac Operative Risk Evaluation. At a multivariate analysis the only independent predictors of prolonged ICU stay were BMI, uNGAL 24 h after surgery and aortic cross-clamp time

A survey on the use of intra-aortic balloon pump in cardiac surgery

Intra-aortic balloon pump (IABP) is an established tool in the management of cardiac dysfunction in cardiac surgery. The best timing for IABP weaning is unknown and varies greatly among cardiac centers. The authors investigated the differences in IABP management among 66 cardiac surgery centers performing 40,675 cardiac surgery procedures in the 12-month study period. The centers were contacted through email, telephone, or in person interview. IABP management was very heterogeneous in this survey: In 43% centers it was routinely removed on the first postoperative day, and in 34% on the second postoperative day. In 50% centers, it was routinely removed after extubation of the patients whereas in 15% centers it was removed while the patients were sedated and mechanically ventilated. In 66% centers, patients were routinely receiving pharmacological inotropic support at the time of removal of IABP. The practice of decreasing IABP support was also heterogeneous: 57% centers weaned by reducing the ratio of beat assistance whereas 34% centers weaned by reducing balloon volume. We conclude that the management of IABP is heterogeneous and there is a need for large prospective studies on the management of IABP in cardiac surgery