Fatal Septic Shock Research Articles

Plasma markers of hypercoagulability in patients with serious infections and risk of septic shock.

Hyperthrombinogenesis due to bacterial septicemia may aggravate the risk of irreversible septic shock. In 22 patients with septicemia complicating urinary or alimentary infections, daily assessment of hemostasis was performed throughout 1 week. Standard screening of hemostasis revealed significantly increased mean values of prothrombin time, fibrinogen, and fibrinogen degradation product (FDP) concentration. However, platelet counts, activated partial thromboplastin times (APTT), thrombin times, ethanol gelation tests, and antithrombin activity remained within the normal range. By contrast, except for insignificant changes in protein C activity and activated factor VII content, specific markers of plasma hypercoagulability, that is, thrombin-antithrombin (TAT) complexes, prothrombin activating factor F 1+2, activated factor XII (XIIa), and dimer D were all markedly increased. Pathologic levels of TAT and Xlla were found in 82% and 73% of all plasma samples, respectively. The augmentation of TAT correlated with prolongation of thrombin time and increases in F 1+2 levels. The increase in XIIa correlated with thrombocytopenia, prolongation of APTT, exhaustion of antithrombin, and accumulation of F 1+2 and FDP in the plasma. Moreover, a significant increase in XIIa, stronger positivity of the ethanol gelation test, a greater increase in FDP, and a more pronounced decrease in protein C activity were observed in 8 patients with fatal septic shock. This study suggests the usefulness of TAT and XIIa measurements in the early recognition of plasma hypercoagulation in serious infections.

Increased lactate/pyruvate ratio with normal b-hydroxybutyrate/acetoacetate ratio and lack of oxygen supply dependency in a patient with fatal septic shock

We report a case of fatal septic shock, with hyperlactatemia and blood cultures positive for Streptococcus pneumoniae, in a 70-year-old patient. On two occasions (5 days, and 2 days before the patient's death), the relationship between oxygen delivery (DO2) and consumption (VO2) was examined in conjunction with two presumed markers of tissue oxygenation: the lactate/pyruvate ratio (L/P), and the beta-hydroxybutyrate acetoacetate ratio (beta OHB/AcAc). Increasing DO2 by about 30% ("oxygen flux test") failed to increase VO2. The beta OHB/AcAc ratio remained within normal limits, thus suggesting uncompromised tissue oxygenation at the hepatic level. The L/P ratio remained persistently above normal limits, thus suggesting actual organ or regional hypoxia. This case shows that during an overwhelming septic shock, the "oxygen flux test" can be negative, despite the presence of hyperlactatemia and of an increased L/P ratio suggestive of impaired tissue oxygenation.

Fatal <i>Yersinia enterocolitica</i> Septicemia after Transfusion of Red Cells – Case Report and Review of the Literature

Whereas up to 10% (median: 0.046-0.1%) of platelet concentrates are regarded to be bacterially contaminated, approximately only one out of 9 million transfused red blood cell (RBC) units bears the chance of death from sepsis due to contamination with psychrophilic bacteria, mainly <i>Yersiniα enterocoliticα. </i>We report the clinical course and the bacteriological examination of unavoidable fatal septic shock resulting from transfusion of a RBC unit contaminated with <i>Y. enterocoliticα </i>in a 47-year-old man who underwent cystectomy due to bladder cancer. The case is discussed in the light of different recommended measures during collecting and processing of blood donations that could be suitable to prevent bacterial contamination.

Fatal Pneumococcal Septic Shock in a Patient with Ulcerative Colitis

Fatal Pneumococcal Septic Shock in a Patient with Ulcerative Colitis

Fatal Septic Shock with Multiple Organ Failure Due to Campylobacter jejuni

Fatal Septic Shock with Multiple Organ Failure Due to Campylobacter jejuni

Fatal Septic Shock Due to Lancefield Group G Streptococci.

We describe two cases of fatal septic shock caused by Lancefield group G streptococci. Both were community-acquired and occurred in previously healthy adults. Both patients died in severe multiple organ failure despite prompt antibiotic therapy. Serological typing of bacterial cultures identified the T-protein antigen as serotype 300, but this was thought to be of little relevance to the pathogenesis; T-protein antigens are useful as epidemiological markers. M-typing and PCR (polymerase chain reaction) detection of the streptococcal pyrogenic exotoxin genes were found to be negative suggesting that this highly pathogenic organism may represent a new M-type.

Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality.

Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflorescein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C-reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leukocytes from patients who died was significantly higher (P < 0.001) than paired controls, and greater (P < 0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte-derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.

High dose recombinant tumour necrosis factor (rTNFα) administered by isolation perfusion for advanced tumours of the limbs: a model for biochemotherapy of cancer

INTRODUCTION TUMOUR NECROSIS FACTOR (TNFa) was discovered as a serum factor in mice treated with BCG and endotoxin, producing haemorrhagic and coagulative necrosis of tumours in recipient mice [I]. In fact, TNFa is the first cytokine which is able to produce very fast and effective necrosis of tumours more efficiently than chemotherapy itself. Therefore, efforts were made to clone the gene. In 1985, the human TNFu gene [2] was cloned and expressed in E. coli, followed in the same year, by the murine TNFa gene [3, 41. It is commonly accepted that the human TNFo structure is a non-glycosylated trimer of 157 amino acids with several cysteine bounds [S, 61. The trimer has three receptor binding sites apparently situated between each part of the trimer. There are two membrane receptors for TNFo of different molecular weights currently named ~55 and ~75 [7]. The recombinant TNFn (rTNFn) was made available for clinical trials, but unfortunately it was found, at that time, to cause fatal septic shock in humans (reviewed in ref [S]). It is not surprising, therefore, that phase I and II studies in humans were hampered by high levels of toxicity and seldom showed antitumour effects [9-151. In 1988, we considered using isolated limb perfusion for administering efficient high dose TNFo combined to interferony and melphalan. The results in melanoma-in-transit-metastases and soft tissue sarcoma of the limbs have been astonishingly high in terms of complete response rate [ 161. During the past 5 years, we have treated, with our Dutch colleagues, approximately 200 cases. Side-effects were always acceptable and have been drastically reduced recently by improving the technique. A comprehensive study of the cases, including immunohistology, pathophysiology, immunology and biochemistry, allows us to propose that isolation perfusion of the limbs with high dose TNFcl is a model for biochemotherapy of cancer.

Extracorporeal endotoxin removal in a canine model of septic shock: Asaio J. 1994; 40/3: M654–M657

The authors induced endotoxic shock in an animal model and attempted to treat this state by direct hemoperfusion over a modified anion sorbent column. It has been shown that the reversal of septic shock correlates with the efficiency of extracorporeal endotoxin removal. In this experiment, there were five control animals (sham) and five test animals (hemoperfusion over sorbent column). The efficacy of treatment was evaluated by survival at 24 hr, changes in mean arterial pressure, blood-acid base balance, and plasma endotoxin levels. There was 0% survival in the control group and 100% survival in the test group. The control dogs never recovered from shock or metabolic acidosis, but the test animals were at their initial values for these parameters by 6 hr. The endotoxin levels measured at 6 hr were higher in the control group (265 +/- 88 ng/ml) as compared with the test group (7.0 +/- 6.2 ng/ml). Direct hemoperfusion over a modified sorbent column effectively removed endotoxin and reversed the course of fatal septic shock.

CD14 Is a pattern recognition receptor

Septic shock caused by a diverse group of bacterial pathogens is a serious human disease. Recognition of bacterial envelope constituents is one mechanism used by mammalian cells to initiate responses leading to bacterial killing or, unfortunately, responses that also cause fatal septic shock. Here we show that CD14 plays a key role in initiating cell activation by a group of bacterial envelope components from Gram-negative and Gram-positive microorganisms, as well as mycobacteria. We propose that CD14 is a receptor used by mammalian cells to recognize and signal responses to a diverse array of bacterial constituents. This finding defines the molecular basis for innate microbial immunity; implicit in these findings are new possibilities for therapeutics.

Extracorporeal endotoxin removal in a canine model of septic shock.

The authors induced endotoxic shock in an animal model and attempted to treat this state by direct hemoperfusion over a modified anion sorbent column. It has been shown that the reversal of septic shock correlates with the efficiency of extracorporeal endotoxin removal. In this experiment, there were five control animals (sham) and five test animals (hemoperfusion over sorbent column). The efficacy of treatment was evaluated by survival at 24 hr, changes in mean arterial pressure, blood-acid base balance, and plasma endotoxin levels. There was 0% survival in the control group and 100% survival in the test group. The control dogs never recovered from shock or metabolic acidosis, but the test animals were at their initial values for these parameters by 6 hr. The endotoxin levels measured at 6 hr were higher in the control group (265 +/- 88 ng/ml) as compared with the test group (7.0 +/- 6.2 ng/ml). Direct hemoperfusion over a modified sorbent column effectively removed endotoxin and reversed the course of fatal septic shock.

Extracorporeal Membrane Oxygenation for Refractory Septic Shock in Children

To review demographic data and outcome of children who received extracorporeal membrane oxygenation (ECMO) for refractory septic shock. Review of medical charts of nine children receiving ECMO for culture-proven refractory septic shock treated in a multidisciplinary pediatric intensive care unit. Median age was 12 years and median weight was 45 kg. Median inotrope requirements (micrograms/kg per minute) before ECMO were dopamine, 15; dobutamine, 12.5; epinephrine, 4; and norepinephrine, 3.5. Four children received two inotropes concurrently, and five received three or more. All nine patients had severe respiratory failure; eight had evidence of other organ system dysfunction, with six having five or more organ system dysfunctions. Median PRISM score was 27. Median duration of ECMO was 137 hours. Within 24 hours of starting ECMO, 7 of 9 children had all inotropes stopped. Four patients died and five survived, all of whom are leading normal lives. In this small group of children with probably fatal septic shock, ECMO was successfully supported the circulation and 5 of the 9 children survived. We suggest that septic shock should not be considered a contraindication to ECMO.

Mediastinitis from odontogenic infection: Report of three cases and review of the literature

Descending necrotizing mediastinitis secondary to dental infection occurs infrequently. The diagnosis of this condition is difficult and often a surgical approach is delayed due to initial clinical improvement after antimicrobial therapy. An incorrect evaluation of this apparent improvement may result in fatal mediastinitis and septic shock. We report 3 cases of mediastinitis of odontogenic origin. In one patient, a nonproductive cough was the first sign of thoracic involvement. A total of 25 similar cases of mediastinitis from odontogenic infection have been collected from the literature in the last 15 years. Some features have to be emphasized, such as the polymicrobial flora, the higher prevalence in males, and the high mortality rate of approximately 44%.

Ascites revealing peritoneal and hepatic extramedullary hematopoiesis with peliosis in agnogenic myeloid metaplasia: Case report and review of the literature

A 61-year-old man presented with ascites in the course of agnogenic myeloid metaplasia (AMM). Ascitic fluid was exudative and contained mature and immature leukocytes, erythroid cells, and megakaryocytes as observed on a bone marrow smear. Peritoneal biopsy showed myeloid metaplasia, and liver biopsy revealed intrasinusoidal myeloid metaplasia and peliosis. Ascites cleared after abdominal radiotherapy but treatment resulted in transient aplasia. Subsequently, portal hypertension was demonstrated by hepatic transjugular catheterization. Complications of splenomegaly led to splenectomy and splenorenal shunt followed by fatal acute hepatitis and septic shock. A review of the literature and an analysis of mechanisms of ascites occurring in AMM, especially peritoneal implants of myeloid tissue and occurrence of peliosis in myeloproliferative disorders, are presented.

Pyomyoma Associated with Polymicrobial Bacteremia and Fatal Septic Shock: Case Report and Review of the Literature

case of fatal septic shock due to pyomyoma (suppurative leiomyoma of the uterus) is reported. This unusual cause of sepsis and polymicrobial bacteremia should be rapidly identified because surgical therapy is essential for cure. Nine additional cases reported since 1945 are reviewed. Pyomyoma develops in association with either recent pregnancy or in postmenopausal patients who frequently have underlying vascular disease. The triad of: 1) bacteremia or sepsis; 2) leiomyoma uteri; and 3) no other apparent source of infection should suggest the diagnosis of pyomyoma.

Local and general defence mechanisms in bacterial and chemical peritonitis.

The inflammatory reaction in peritonitis often leads to profound systemic changes, indeed peritonitis accounts for half of all cases of fatal septic shock (1). Although there are numerous causes of peritonitis, the clinical picture is almost the same in most peritonitis patients. Thus, from a clinical point of view, a widespread inflammatory reaction in the peritoneum, whatever the cause, seems to form the basis for the systemic reactions which follow (2).

Comparative effects of dopamine, naloxone, and prostacyclin in the resuscitation of fecal- Escherichia coli peritonitis-induced septic shock in neonatal swine

To explain the high neonatal mortality from peritonitis-induced septic shock despite current resuscitation practices, the efficacy of dopamine, naloxone, and prostacyclin was evaluated in an experimental neonatal model. Hemodynamics were monitored and survival was measured in anesthetized neonatal swine, which were subjected to fatal fecal-Escherichia coli peritonitis-induced septic shock. All the animals received fluid resuscitation, antibiotics, and bicarbonate to correct acidosis. Pharmacologic resuscitation began when cardiac output dropped below baseline in the experimental groups. Although significant differences were observed between groups in cardiac output, mean arterial and mean pulmonary arterial pressures, left ventricular stroke work, stroke volume, and pulmonary vascular resistance indices (P less than 0.02), and each animal exhibited favorable hemodynamic responses during the first several hours of dopamine and naloxone infusion, these drugs failed to prolong survival. Also, 5 of the 9 naloxone-treated pigs (56%), died with histologically proven intestinal ischemia (P less than 0.02). Thus, dopamine, naloxone, and prostacyclin (at doses commonly recommended for the treatment of septic shock) fail to positively influence the fatal course of this condition, and the use of naloxone in this model is associated with profound intestinal ischemia.

Plasma kallikrein-kinin system in septicemia.

Plasma prekallikrein and functional kallikrein inhibition were studied in 18 surgical patients with complicating septicemia using chromogenic peptide substrate assays. Nine patients died and nine survived. In all 18 patients plasma prekallikrein values were reduced markedly when septicemia was diagnosed. During treatment gradually increasing values were found in the survivors, whereas values remained low in the fatal cases. Significantly reduced functional plasma kallikrein inhibition was associated with the development of fatal septic shock. The findings show that determination of these components of the plasma kallikrein-kinin system gives valuable information of prognostic value in patients with septicemia. Furthermore, the chromogenic peptide substrate assays used are fast and easy to perform and therefore suitable for intensive care medicine.

Percutaneous cholecystostomy.

Percutaneous cholecystostomy was performed in 13 patients; five patients had suspected acute cholecystitis and eight patients had suspected obstruction of the common bile duct. An anterior abdominal wall approach was used in nine patients, right anterior axillary line puncture in four. One patient developed peritonitis and fatal septic shock after inadvertent cholecystostomy catheter removal. None of the other patients became septic, developed peritonitis, or had any other complication related to cholecystostomy. Two of the patients had external drainage as outpatients for more than 6 months without complication. Technical and clinical points are reviewed.