Septic Shock Conditions Research Articles

LEUCÉMIE PROLYMPHOCYTAIRE DE PHÉNOTYPE B DE MAUVAIS PRONOSTIC

Introduction : B cell prolymphocytic leukemia is a rare disease with poor prognosis compared with chronic lymphocytic leukemia. Case report : Patient aged 75 years old, diabetic and hypertensive, with a massive splenomegaly associated with leukocytosis exceeding 100000/mm3 predominantly prolymphocytic, invading the bone marrow. Immunophenotyping showed CD19 +, CD20 +, CD22 +, CD5 part, CD23+ CD79b + FMC7 stronger and stronger, Smg + in vafour for a type B-cell prolymphocytic leukemia. The evolution was rapidly unfavorable despite an first line treatment of eight cycles of COP (cyclophosphamide, vincristine and prednisone). Partial remission was short, followed by the reappearance of the splanomegaly, new increase in the of Prolymphocyte tate with thrombocytopenia and profound anemia. The patient had received two courses of Fludarabine. Dath occurred after eighteen months of follow up due to a state of septic shock and tumor lysis syndrome. Discussion : This malignancy accounts for 2% of all chronic lymphocytic leukemia with 80% phenotype B. It frequently affects patients of 70 years old with a clear male predominance. The prognosis is more severe than that of chronic lymphocytic leukemia. Anemia 100000/mm3 are the factors of poor prognosis. The median survival was 65 months reported by Shvidel et al. in a series of 35 observations. Conclusion : Promising results are reported with new treatments. The antibady anti-CD20 has been used successfully for the second type of B-cell prolymphocytic leukemia after relapse. The allograft or autograft are indicated, but it is mostly used in patients, who have contraindications to a heavy treatment.

Analysis of some sepsis markers: C-reactive protein, Procalcitonin, Osteopontin and suPAR

Sepsis appears to be due to an uncontrolled pro and anti-inflammatory response leading to organ dysfunction until shock and death.Accuracy of diagnosis and appropriate treatment affect the outcome. Aim of the study was to investigate if the levels of Osteopontin (OPN) and Soluble Urokinase-type Plasminoge Activator Receptor (suPAR) might be early markers of sepsis and if these markers play a role in predicting the progression to septic shock. Methods:The levels of OPN, suPAR, C-reactive protein (CRP) and procalcitonin (PCT) were measured in patients at higher risk of infection. The samples were collected from the day of admission for the following fifteenth day. During recovery Sistemic Inflammatory Response Syndrome (SIRS) criteria, blood chemistry data, blood gas- analysis, lactate and diuresis were collected. Microbiological culture were performed according to the clinical condition. Results: 29 patients were enrolled in the study, including 14 subjects with positive blood cultures.The values of OPN, PCT, suPAR and CRP were significantly increased in patients with positive blood cultures than those with negative blood cultures.Analysing changes of the levels of OPN, suPAR, PCT and CRP in patients with septic shock, the values of OPN increased in advance to the clinical diagnosis of septic shock, while the values of suPAR and PCT slight delay compared to those OPN.The levels of CRP were independent from the onset of septic shock state. Conclusions: These preliminary data suggest that Osteopontin and suPAR can be used as early markers of sepsis and might be useful in monitoring of septic outcome to predict a possible evolution to septic shock.

San Antonio Vasopressin in Shock Symposium Report

The San Antonio Vasopressin Symposium reviewed substantial accumulated data concerning vasopressin in haemorrhagic, septic, and cardiac arrest shock conditions and found that there is considerable evidence to support the use of vasopressin in overcoming vasopressin deficiency or insufficiency. The value of vasopressin in the setting of trauma requires further investigation. It was concluded that a large, multicenter controlled trial of vasopressin is needed to assess the therapeutic benefit of vasopressin replacement in the setting of trauma with haemorrhagic shock that is prolonged and profound.

Regulation of NF-κB Circuitry by a Component of the Nucleosome Remodeling and Deacetylase Complex Controls Inflammatory Response Homeostasis

The MTA1 coregulator (metastatic tumor antigen 1), a component of the nucleosome remodeling and deacetylase (NuRD) complex, has been intimately linked with human cancer, but its role in inflammatory responses remains unknown. Here, we discovered that MTA1 is a target of inflammation, and stimulation of macrophages with Escherichia coli lipopolysaccharide (LPS) stimulates MTA1 transcription via the NF-kappaB pathway. Unexpectedly, we found that MTA1 depletion in LPS-stimulated macrophages impairs NF-kappaB signaling and expression of inflammatory molecules. MTA1 itself acts as a transcriptional coactivator of inflammatory cytokines in LPS-stimulated macrophages, and in contrast, it acts as a corepressor in resting primary macrophages as its depletion induced cytokine expression. LPS stimulates S-nitrosylation of histone deacetylase 2 (HDAC2) and interferes with its binding to MTA1, which, in turn, resulted in the loss of corepressor behavior of MTA1.HDAC complex in activated macrophages. Consequently, the net levels of inflammatory cytokines in LPS-stimulated macrophages from MTA1(-/-) mice were high compared with wild-type mice. Accordingly, MTA1(-/-) mice were much more susceptible than control mice to septic shock induced by LPS, revealing that MTA1 protects mice from deregulated host inflammatory response. These findings reveal a previously unrecognized, critical homeostatic role of MTA1, both as a target and as a component of the NF-kappaB circuitry, in the regulation of inflammatory responses.

Clinical and microbiological characteristics of bloodstream infections in a tertiary hospital in Maceió, Alagoas, Brazil

We observed the clinical and microbiological characteristics of several stages of bloodstream infections (BSI), as well as the mortality attributed to it in a tertiary hospital in the northeast of Brazil (in the city of Maceió, Alagoas). A prospective cohort of 143 patients who had at least one positive blood culture was enrolled in the study. Their clinical evolution was followed up for 30 days from October 2005 to December 2006. The relation among the qualitative variables was verified through Chi-square test. The significance level was 5%. The statistical package adopted was SPSS 15.0 for Windows. Up to the thirtieth day, 30.1% of the patients presented bacteremia and 69.9% developed sepsis. Among these, 20.3% developed severe sepsis and 10.5% septic shock. The mortality attributed to it was 37.8%. In bacteremia, sepsis, severe sepsis, and septic shock conditions, mortality rates were 9.3%, 50%, 65.5%, and 84.6%, respectively. Respiratory (32.2%) and urinary (14%) sources and the ones related to central venous catheter (14%) were prevalent. In the wards 55.12% of the cases developed sepsis, whereas in the intensive care units, the rate was 87.69% (p < 0.05). Chronic renal failure, diabetes mellitus, and neuropathy were present in 21.7%, 26.6%, and 29.4% of the cases, respectively. Coagulase-negative Staphylococcus (25.9%), Staphylococcus aureus (21%), and Klebsiella pneumoniae (14%) were the most present microorganism in the sample. The high morbidity and mortality rates in this study are attributed to the lack of knowledge on BSI characteristics and on instituted protocols for detection and treatment in early stages.

Renin‐Angiotensin‐Aldosterone System During Extracorporeal Membrane Oxygenation (ECMO) in a Pig Model of Septic Shock

ECMO is used to provide cardiopulmonary support to critically ill patients, but the ability of the renin‐angiotensin‐aldosterone system to function appropriately during ECMO remains unclear. In this study, plasma renin activity (PRA) and aldosterone (ALDO) were compared at baseline and before and after stabilization on veno‐arterial ECMO for 2 hours in anesthetized piglets either during control (n=10) or endotoxin‐induced septic shock (n=9) states. In control piglets, ECMO was able to maintain mean arterial pressure (MAP) at baseline levels and PRA and ALDO remained unchanged. In contrast, endotoxin induced a 46% decrease (p&lt;0.01) in MAP, and while ECMO could maintain flow at this decreased MAP, it did not return MAP to baseline. PRA appropriately increased in response to shock, but ultimately dropped by 54% (p&lt;0.01) in early ECMO. ALDO increased in response to shock, and remained constant during ECMO. There was a strong correlation between PRA and ALDO at baseline (r=0.90, p&lt;0.01) and on ECMO in control piglets (r= 0.70, p&lt;0.01), but septic shock disrupted that relationship. Plasma sodium concentrations increased (p&lt;0.01) from 137 ± 3.3 to 145 ± 0.7 mEq/L in shock, and with sustained ALDO, remained at this elevated level throughout ECMO. Results suggest that ALDO sodium regulating ability remains intact during ECMO but PRA is attenuated during ECMO in the endotoxic shock state.

Clinical and microbiological characteristics of bloodstream infections in a tertiary hospital in Maceió, Alagoas, Brazil

We observed the clinical and microbiological characteristics of several stages of bloodstream infections (BSI), as well as the mortality attributed to it in a tertiary hospital in the northeast of Brazil (in the city of Maceió, Alagoas). A prospective cohort of 143 patients who had at least one positive blood culture was enrolled in the study. Their clinical evolution was followed up for 30 days from October 2005 to December 2006. The relation among the qualitative variables was verified through Chi-square test. The significance level was 5%. The statistical package adopted was SPSS 15.0 for Windows. Up to the thirtieth day, 30.1% of the patients presented bacteremia and 69.9% developed sepsis. Among these, 20.3% developed severe sepsis and 10.5% septic shock. The mortality attributed to it was 37.8%. In bacteremia, sepsis, severe sepsis, and septic shock conditions, mortality rates were 9.3%, 50%, 65.5%, and 84.6%, respectively. Respiratory (32.2%) and urinary (14%) sources and the ones related to central venous catheter (14%) were prevalent. In the wards 55.12% of the cases developed sepsis, whereas in the intensive care units, the rate was 87.69% (p<0.05). Chronic renal failure, diabetes melitus, and neuropathy were present in 21.7%, 26.6%, and 29.4% of the cases, respectively. Coagulase-negative Staphylococcus (25.9%), Staphylococcus aureus (21%), and Klebsiella pneumoniae (14%) were the most present microorganism in the sample. The high morbidity and mortality rates in this study are attributed to the lack of knowledge on BSI characteristics and on instituted protocols for detection and treatment in early stages.

Septischer Kreislaufschock und septische Kardiomyopathie

Septic shock is not only a circulatory shock but is also a cardiac shock, the consequence of a potentially reversible heart impairment known as septic cardiomyopathy. Disturbances of macrocirculation as well as microcirculation, an individually heterogeneous reduction of cardiac function, and an extensive impairment of demand-oriented regulation of heart function characterize the septic shock state. Bacterial toxins, inflammatory mediators, and a disseminated intravasal coagulopathy are responsible for these disturbances; for the impairment of cardiac regulation, the interaction of endotoxin with the cardiac pacemaker current I(f) also plays a role. Circulatory shock as well as septic cardiomyopathy should be quantified: The lowering of systemic vascular resistance characterizes the extent of circulatory shock, and the reduction of relative cardiac output in relation to afterload characterizes the extent of septic cardiomyopathy. The intensity of circulatory as well as of cardiac impairment correlates with an unfavorable prognosis. Treatment of septic circulatory shock and of septic cardiomyopathy is predominantly symptomatic; first causal approaches are under investigation.

Vasopressin Regulation During Extracorporeal Membrane Oxygenation (ECMO) in a Pig Model of Septic Shock

ECMO is used to provide cardiopulmonary support to critically ill neonates. Vasopressin (VP) plays a vital role in regulating mean arterial pressure (MAP) and regional blood flow in hypotensive disorders, but whether endogenous VP levels can be sustained during ECMO is unclear. In this study, 11 anesthetized, cardiac catheterized piglets were put on veno‐arterial ECMO either during control or endotoxin‐induced septic shock states. ECMO blood flow was delivered to maintain MAP at baseline levels. Plasma VP (pVP) was compared before and after stabilization on ECMO for 2 hours. ECMO caused pVP to drop by 30% (p&lt;0.01) in both control and septic shock conditions. This drop may be due to the ECMO circuit adding to total circulating volume without additional release of VP. To test whether right atrial pressure (RAP) influence on VP release may be disrupted during ECMO due to partial cardiac bypass of blood flow, the relationship between pVP and hemodynamics during control was examined with stepwise regression. Pre‐ECMO, pVP negatively correlated with RAP and heart rate (r=0.83, p&lt;0.05), but not MAP. In contrast, during ECMO, this pVP relationship with RAP was lost, but a strong positive correlation (r=0.76, p&lt;0.05) between pVP and MAP became evident. Results indicate that during ECMO, low pressure atrial baroreceptors no longer regulate VP release, but VP control of MAP is maintained. Supported by US Army CRADA 0709‐T‐C454

A 52-Year-Old Man with Malaise and a Petechial Rash

Capnocytophaga canimorsus is a Gram-negative, fusiform, rod-shaped organism that is part of the normal oral flora of dogs, cats, and other animals. A significant number of Emergency Department (ED) patients are surgically or functionally asplenic and may be at marked risk for overwhelming post-splenectomy infection (OPSI). OPSI has a mortality rate estimated to be up to 70%. The risk of sepsis is estimated to be 30-60 times greater after splenectomy, and C. canimorsus is one of the organisms that can cause catastrophic OPSI. To describe a case of C. canimorsus septic shock in a post-splenectomy patient and review the epidemiology of OPSI, the role of the spleen in protecting the body from infection, and the potential role of early goal-directed therapy in the resuscitation of patients with OPSI. A 52 year-old man with a past medical history significant for idiopathic thrombocytopenic purpura (status post-splenectomy), and non-Hodgkin lymphoma (treated for cure), was brought to the ED with the chief complaints of light-headedness, malaise, and a rapidly spreading rash. He was found to be hypotensive, tachycardic, and tachypneic, and had a marked lactic acidosis. He was aggressively resuscitated with large volume fluid resuscitation and treated empirically with broad-spectrum antibiotics for septic shock of unclear etiology. His clinical course was complicated by acute lung injury and renal failure. Blood cultures grew C. canimorsus; he was extubated on hospital day 7 and discharged home several days later in good condition. Patients status-post-splenectomy are at greatly increased risk for infection from encapsulated organisms and other organisms, including C. canimorsus, which is part of the normal oral flora of dogs, cats, and other animals. It can be spread to humans by bites, scratches, or less invasive forms of animal-human contact. C. canimorsus infection can lead to OPSI. Early recognition and aggressive clinical management, including early goal-directed therapy and rapid administration of antibiotics, may minimize the morbidity and mortality of this condition and other etiologies of severe sepsis and septic shock.

Building a continuous multicenter infection surveillance system in the intensive care unit: Findings from the initial data set of 9,493 patients from 71 Italian intensive care units

To describe the epidemiology of infections in intensive care units (ICUs), whether present at admission or acquired during the stay. Prospective data collection lasting 6 months in 71 Italian adult ICUs. Patients were screened for infections and risk factors at ICU admission and daily during their stay. Out of 9,493 consecutive patients admitted to the 71 ICUs, 11.6% had a community-acquired infection, 7.4% a hospital-acquired infection, and 11.4% an ICU-acquired infection. The risk curve of acquiring infection in the ICU was higher in patients who entered without infection than in those already infected (log-rank test, p < .0001; at 15 days, 44.0% vs. 34.6%). Hospital mortality (27.8% overall) was higher in patients admitted with infection than in those who acquired infection in the ICU (45.0% vs. 32.4%, p < .0001). Although the presence of infection per se did not influence mortality, the conditions of severe sepsis and septic shock were strong prognostic factors (odds ratio, 2.3 and 4.8, respectively). Apart from ICU-acquired peritonitis, no other site of infection reached statistical significance as an independent prognostic factor for hospital mortality. Adding specific data on infections and risk factors to a well-established electronic data collection system is a reliable basis for a continuous multicenter infection surveillance program in the ICU. Given the well-established importance of infection prevention programs, our data suggest that the improvement of the treatment of severe sepsis and septic shock is the key to lower infection-related mortality in the ICU. This calls for closer attention to severe infections in surveillance programs.

Effect of deletion of the lpxM gene on virulence and vaccine potential of Yersinia pestis in mice

Yersinia pestis undergoes an obligate flea-rodent-flea enzootic life cycle. The rapidly fatal properties of Y. pestis are responsible for the organism's sustained survival in natural plague foci. Lipopolysaccharide (LPS) plays several roles in Y. pestis pathogenesis, prominent among them being resistance to host immune effectors and induction of a septic-shock state during the terminal phases of infection. LPS is acylated with 4-6 fatty acids, the number varying with growth temperature and affecting the molecule's toxic properties. Y. pestis mutants were constructed with a deletion insertion in the lpxM gene in both virulent and attenuated strains, preventing the organisms from synthesizing the most toxic hexa-acylated lipid A molecule when grown at 25 degrees C. The virulence and/or protective potency of pathogenic and attenuated Y. pestis DeltalpxM mutants were then examined in a mouse model. The DeltalpxM mutation in a virulent strain led to no change in the LD(50) value compared to that of the parental strain, while the DeltalpxM mutation in attenuated strains led to a modest 2.5-16-fold reduction in virulence. LPS preparations containing fully hexa-acylated lipid A were ten times more toxic in actinomycin D-treated mice then preparations lacking this lipid A isoform, although this was not significant (P>0.05). The DeltalpxM mutation in vaccine strain EV caused a significant increase in its protective potency. These studies suggest there is little impact from lipid A modifications on the virulence of Y. pestis strains but there are potential improvements in the protective properties in attenuated vaccine strains.

Small Intestinal Perforation and Necrotizing Fasciitis After Abdominal Liposuction

Liposuction, the most common aesthetic procedure performed in the United States, is not without risk, but the overall complication rate in the literature varies from less than 1% to 9.3%. A 55-year-old woman who had undergone abdominal liposuction with bilateral breast augmentation was hospitalized in a state of profound septic shock. A diagnosis of necrotizing fasciitis was made on the basis of findings that included abdominal skin discoloration, subcutaneous emphysema, and air in the subcutaneous plane seen on abdominal computed tomography (CT) scan. During the operative procedure for abdominal wall debridement, extensive necrosis of abdominal wall fascia with leakage of bilious fluid from defects in the rectus sheath was found. Subsequent peritoneal cavity exploration showed two perforations in the mid ileum with gross peritoneal cavity contamination.

Vasopressin maintains tissue oxygenation in a piglet model of septic shock

Vasopressin (VP) can acutely reverse hypotension in catecholamine-resistant septic shock, yet there is concern that its potent vasoconstriction may increase tissue ischemia. Thus, we compared the effects of VP (100 ng/kg/min; n=10) on O2 utilization and tissue perfusion in endotoxin (ETX; 10–30 μg/kg iv)-induced shock, to that of no treatment (UNTX; n=9) or first line drugs dopamine (DA; 50 μg/kg/min; n=7) or norepinephrine (NE; 1 μg/kg/min; n=8). ETX caused a 45% decrease in mean arterial pressure (MAP), 30% drop in cardiac output, 40% decrease in O2 delivery, and 3-fold increase in the pulmonary to systemic vascular resistance ratio (PVR/SVR). VP restored MAP whereas NE and DA did not. VP reversed the PVR/SVR increase which helped maintain PaO2 and prevented escalating pulmonary hypertension. Whole body O2 consumption was maintained in UNTX, VP- and NE-treated groups via reduced shunt fraction QS/QT and more efficient % O2 extracted whereas O2 consumption decreased with DA. VP preserved flow to the brain, heart, and kidneys, which revealed no pathologic tissue changes suggestive of ischemia. In comparison, NE and DA preserved flow to the heart, but not to the brain, and DA further decreased flow to the kidneys. Although DA increased flow to the small bowel, VP and NE shunted flow away from the gastrointestinal tract in favor of vital organs, with no further small bowel ischemic damage. Results indicate that VP promotes better whole body O2 utilization in hypotensive conditions of septic shock by sparing pulmonary vasoconstriction, and causing preferential vital organ perfusion. (Supported by USAMRAA grant DAMD 170310072)

Retroperitoneal gas gangrene after colonoscopic polypectomy without bowel perforation in an otherwise healthy individual: report of a case

Abdominal gas gangrene caused by clostridia species is rare and usually associated with organ perforation, immune suppression, or advanced malignoma. A 61-year-old man was admitted with severe back pain 1 day after uncomplicated colonoscopic polypectomy. With the exception of preexisting minor depression, the patient had been previously in excellent health. The computed tomography scan showed retroperitoneal emphysema in the left psoas muscle. During exploratory laparotomy, a spreading retroperitoneal phlegmon with pneumoretroperitoneum and a secondary peritonitis were found. A macroscopic perforation of the gut, particularly at the polypectomy sites was excluded. After the operation, the patient evolved in a septic shock condition and had pulmonary failure. Before hyperbaric oxygen therapy could be employed, the patient died. The autopsy showed a massive gas gangrene of the retroperitoneum caused by Clostridium perfringens, but no macroscopic bowel perforation was detected. This is the first report of a case of gas gangrene after uncomplicated polypectomy without macroscopic perforation in an otherwise healthy individual. A microperforation due to mucosal defect after polypectomy was most likely the entry point for the bacteria. We conclude that clostridial myonecrosis should be considered in unclear abdominal infections, even if the patient's history is not typical as in the present case.

Power cut: Mitochondrial dysfunction in sepsis

Sepsis represents a whole-body inflammatory response to infection that will often progress to multiple organ failure. In this state, organ function is altered in an acutely ill patient such that homoeostasis cannot be maintained without interventions such as mechanical ventilation to support gas exchange, renal dialysis to act as a surrogate kidney removing nitrogenous waste products and excess fluid, and/or catecholamines to elevate critically low blood pressures in the condition of septic shock. Multiple organ failure is both common and potentially deadly. A quarter of patients admitted to British intensive care units have sepsis1 and it is the predominant cause of mortality in the critically ill. Indeed, patients with the failure of three or more organs have a 50% chance of dying.

Protective Role of Angiopoietin-1 in Endotoxic Shock

Angiopoietin-1 (Ang1) plays an essential role in embryonic vasculature development, protects the adult peripheral vasculature from leakage, and has antiinflammatory properties. Because endotoxin-induced shock is a condition with microvascular leakage resulting from inflammation, we examined the potential therapeutic benefit of Ang1 in a murine model of lipopolysaccharide (LPS)-induced endotoxic shock. To induce endotoxic shock, LPS was injected intraperitoneally into C57BL/6 mice. Half of the mice received an intravenous application of 1.0x10(9) plaque-forming units of an adenoviral construct expressing human Ang1 (AdhAng1); in the other half an identical vector expressing green fluorescent protein (AdGFP) was injected as a control. In the AdhAng1-treated mice, hepatic transfection and high expression of circulating Ang1 protein were observed. Whereas in LPS-treated control mice, hemodynamic function was severely depressed 12 hours after LPS injection (decrease of blood pressure from 91+/-3 to 49+/-7 mm Hg, dP/dt(max) from 7284+/-550 to 2699+/-233 mm Hg/s, cardiac output from 11.3+/-1.2 to 2.8+/-0.8 mL/min; P<0.0005), in LPS-treated AdhAng1 mice blood pressure fell only to 76+/-3 mm Hg, dP/dt(max) to 5091+/-489 mm Hg/s, and cardiac output to 6.7+/-1.4 mL/min (P<0.05). This resistance to LPS-induced hemodynamic changes was reflected by an improved Kaplan-Meier survival rate of the AdhAng1 mice. Histological analysis revealed that lung injury after LPS injection was markedly attenuated in AdhAng1 mice. In addition, LPS-induced increase in lung water content and pulmonary myeloperoxidase activity was significantly reduced. Furthermore, LPS-induced increases in the expression level of vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and E-selectin protein in the lungs were markedly lower in AdhAng1 mice than in control mice. Finally, in the mice overexpressing Ang1, pulmonary endothelial NO synthase (eNOS) expression and activity remained preserved after LPS challenge, providing evidence that the beneficial effect of Ang1 in endotoxic shock is mediated by eNOS-derived NO. Our study demonstrates an improved mortality rate in mice with endotoxic shock pretreated with an adenoviral construct encoding Ang1. The enhanced survival rate induced by Ang1 was accompanied by an improvement in hemodynamic function, reduced lung injury, a lower expression of inflammatory adhesion molecules, and preserved eNOS activity in the lung tissue. Ang1 may therefore have utility as an adjunctive agent for the treatment of septic shock condition.

Infective endocarditis in the intensive care unit: clinical spectrum and prognostic factors in 228 consecutive patients.

To identify factors associated with in-hospital outcome of adult patients admitted to the ICU with infective endocarditis (IE). Retrospective study performed in the two medical ICUs of a teaching hospital. The charts of all 228 consecutive patients aged 18 years or older admitted with infective IE between January 1993 and December 2000 were reviewed. All patients satisfied the modified Duke's criteria for definite IE. There were 146 episodes of native valve endocarditis and 82 of prosthetic valve endocarditis. Staphylococcus aureus was the predominant causative micro-organism. Most complications occurred early during the course of IE. One-half of the patients underwent cardiac surgery during the same hospitalization and had a better outcome than nonoperated patients. The overall in-hospital mortality rate was 45% (102/228). Multivariate analysis revealed the following clinical factors in patients with native valve IE as independently associated with outcome: septic shock (odds ratio 4.81), cerebral emboli (3.00), immunocompromised state (2.88), and cardiac surgery (0.475); in patients with prosthetic valve IE the factors were: septic shock (4.07), neurological complications (3.1), and immunocompromised state (3.46). IE still carries high morbidity and mortality rates for the subset of patients requiring ICU admission. Most complications occur early making the decision process for optimal medical and surgical management more difficult. Surgical treatment appears to improve in-hospital outcome.

Mitochondrial nitric oxide metabolism in rat muscle during endotoxemia

In this study, heart and diaphragm mitochondria produced 0.69 and 0.77 nmol nitric oxide (NO)/min mg protein, rates that account for 67 and 24% of maximal cellular NO production, respectively. Endotoxemia and septic shock occur with an exacerbated inflammatory response that damages tissue mitochondria. Skeletal muscle seems to be one of the main target organs in septic shock, showing an increased NO production and early oxidative stress. The kinetic properties of mitochondrial nitric oxide synthase (mtNOS) of heart and diaphragm were determined. For diaphragm, the K M values for O 2 and L-Arg were 4.6 and 37 μM and for heart were 3.3 and 36 μM. The optimal pH for mtNOS activity was 6.5 for diaphragm and 7.0 for heart. A marked increase in mtNOS activity was observed in endotoxemic rats, 90% in diaphragm and 30% in heart. Diaphragm and heart mitochondrial O 2 − and H 2O 2 production were 2- to 3-fold increased during endotoxemia and Mn-SOD activity showed a 2-fold increase in treated animals, whereas catalase activity was unchanged. One of the current hypotheses for the molecular mechanisms underlying the complex condition of septic shock is that the enhanced NO production by mtNOS leads to excessive peroxynitrite production and protein nitration in the mitochondrial matrix, causing mitochondrial dysfunction and contractile failure.

Case review: septic shock in the pregnant patient

This case study involves a 36-year-old female at 15 weeks gestation who presented with severe lower abdominal pain post amniocentesis and subsequently deteriorated into a state of septic shock whilst in the ED. The circumstances surrounding this patient's presentation and subsequent clinical course are presented. The assessment and management of septic shock is also described with specific consideration to this patient's pregnant state.