Clinical outcome and predictors of mortality in children with sepsis,severe sepsis,and septic shock from Rohtak,Haryana: A prospective observational study

Background:

Information regarding early predictive factors for mortality and morbidity in sepsis is limited from developing countries.

Methods:

A prospective observational study was conducted to determine the clinical outcome and predictors of mortality in children with sepsis, severe sepsis, and septic shock. Children aged 1 month to 14 years admitted to a tertiary care pediatric intensive care unit (PICU) with a diagnosis of sepsis, severe sepsis, or septic shock were enrolled in the study. Hemodynamic and laboratory parameters which discriminate survivors from nonsurvivors were evaluated.

Results:

A total of 50 patients (30 [60%] males) were enrolled in the study, of whom 21 (42%) were discharged (survivors) and rest 29 (58%) expired (nonsurvivor). Median (interquartile range) age of enrolled patients were 18 (6, 60) months. Mortality was not significantly predicted individually by any factor including age (odds ratio [OR] [95% confidence interval [CI]]: 0.96 [0.91-1.01], P = 0.17), duration of PICU stay (OR [95% CI]: 1.18 [0.99-1.25], P = 0.054), time lag to PICU transfer (OR [95% CI]: 1.02 [0.93-1.12], P = 0.63), Pediatric Risk of Mortality (PRISM) score at admission (OR [95% CI]: 0.71 [0.47-1.04], P = 0.07) and number of organ dysfunction (OR [95% CI]: 0.03 [0.01-1.53], P = 0.08).

Conclusion:

Mortality among children with sepsis, severe sepsis, and septic shock were not predicted by any individual factors including the time lag to PICU transfer, duration of PICU stay, presence of multiorgan dysfunction, and PRISM score at admission.     

Time-course of sFlt-1 and VEGF-A release in neutropenic patients with sepsis and septic shock: a prospective study

Background  

Septic shock is the most feared complication of chemotherapy-induced febrile neutropenia. So far, there are no robust biomarkers that can stratify patients to the risk of sepsis complications. The VEGF-A axis is involved in the control of microvascular permeability and has been involved in the pathogenesis of conditions associated with endothelial barrier disruption such as sepsis. sFlt-1 is a soluble variant of the VEGF-A receptor VEGFR-1 that acts as a decoy receptor down-regulating the effects of VEGF-A. In animal models of sepsis, sFlt-1 was capable to block the barrier-breaking negative effects of VEGF-A and to significantly decrease mortality. In non-neutropenic patients, sFlt-1 has been shown to be a promising biomarker for sepsis severity.     

Left atrial function for outcome prediction in severe sepsis and septic shock: An echocardiographic study

Left ventricular function and B-type natriuretic peptide (BNP) assessments are used to predict mortality in septic patients. Left atrial function has never been used to prognosticate outcome in septic patients.

Objectives:

To assess if deterioration of left atrial function in patients with severe sepsis and septic shock could predict mortality.

Methods:

We studied 30 patients with severe sepsis or septic shock with a mean age of 49.8±16.17. Echocardiographic parameters were measured on admission, Day 4, and Day 7, which comprised left ventricular ejection fraction (EF), and atrial function that is expressed as atrial ejection force (AEF). All patients were subjected to BNP assay as well. Multivariate analyses adjusted for APACHE II score was used for mortality prediction.

Results:

The underlying source for sepsis was lung in 10 patients (33%), blood in 7 patients (23.3%), abdomen in 7 patients (23.7%), and 3 patients (10%) had UTI as a cause of sepsis. Only one patient had CNS infection. In-hospital mortality was 23.3% (7 patients). Admission EF showed a significant difference between survivors and non survivors, 49.01±6.51 vs.. 56.44±6.93% (P<0.01). On the other hand, admission AEF showed insignificant changes between the same groups, 10.9±2.81 vs. 9.41±2.4 k/dynes P=0.21, while BNP was significantly higher in the non survivors, 1123±236.08 vs. 592.7±347.1 pg/ml (P<0.001). The predicatable variables for mortality was Acute Physiology and Chronic Health Evaluation II score, BNP, then EF.

Conclusion:

In septic patients, left atrial function unlike the ventricular function and BNP levels can not be used as an independent predictor of mortality.     

Effectiveness of a hospital-wide infection control programme on the incidence of healthcare-associated infections and associated severe sepsis and septic shock: a prospective interventional study

Objectives

To evaluate whether a hospital-wide infection control programme (ICP) is effective at reducing the burden of healthcare-associated infections (HAIs) and associated severe sepsis/septic shock or death (severe HAIs).

Procalcitonin kinetics as a prognostic marker in severe sepsis/septic shock

Background and Aims:

To evaluate the prognostic value of change (fall) in serum procalcitonin level (PCT) in critically ill adults with severe sepsis/septic shock.

Methods:

This was a prospective observational study in a general purpose Intensive Care Unit of a teaching Institute. PCT was measured at admission (D0) and after 72–96 h (D4) by electrochemi-luminescence immunoassay (BRAHMS PCT kit) in adults (>18 years) admitted with severe sepsis or septic shock. Change in procalcitonin values from D0 to D4 was correlated with the primary outcome, that is, 28 days mortality. All results are reported as median (interquartile range).

Results:

A total of 171 (100 males) of 181 patients were included. The median age was 46 years (range 19–79). 137 patients were in septic shock and 34 in severe sepsis. The sequential organ failure assessment (SOFA) score in all patients was 11 (9–14).91 (53.2%) patients survived at 28 days (survivors). The baseline procalcitonin was similar in two groups (3.48 [1.04–15.85] vs. 5.27 [1.81–23.57] ng/ml in survivors and nonsurvivors [NS] respectively). The procalcitonin change was 1.58 (0.20–8.52) in survivors and 0.28 (–1.38–6.17) in NS (P = 0.01). The C-statistic of percentage change in procalcitonin from D0 to D4 to predict survival was 0.73 (95% confidence interval [CI]: 0.65–0.82) when compared to 0.78 (95% CI: 0.71–0.86) for change of SOFA score. For an absolute fall in procalcitonin of >1 ng/ml, a 70% fall predicted survival with 75% sensitivity and 64% specificity.

Conclusions:

In critically ill-patients with severe sepsis/septic shock, change (fall) in procalcitonin is associated with good outcome.     

Early goal-directed therapy in the treatment of severe sepsis and septic shock.

BACKGROUND: Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. METHODS: We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. RESULTS: Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001). CONCLUSIONS: Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.     

Safety and efficacy of polymyxin B in multidrug resistant Gram-negative severe sepsis and septic shock

Background and Aims:

The emergence of multidrug resistant strains of Gram-negative bacteria, especially the lactose nonfermenters like Pseudomonas and Acinetobacter, in the intensive care units have prompted renewed worldwide interest in the polymyxins. However, perceived nephrotoxicity has been a major vexation limiting their early and regular use in severe sepsis. This study was conducted to assess the safety and efficacy of polymyxin B in patients with severe sepsis and septic shock.

Materials and Methods:

Forty-five patients with sepsis admitted in our medical-surgical intensive care units were identified from pharmacy records to have received polymyxin B. We retrospectively reviewed the clinical and microbiologic outcomes as well as occurrence of renal failure temporally related to the use of intravenous polymyxin B.

Results:

polymyxin B was used in severe sepsis and septic shock with the isolated organism being resistant to other available antimicrobials or clinical deterioration despite carbapenem use. Overall mortality was 52% and among patients who received at least eight days of intravenous polymyxin B, 67% patients with initial septic shock and 62% with severe sepsis survived. The target multidrug resistant organism was cleared in 88% of subjects evaluated by repeat microbiologic testing. Acute renal failure developed in only two patients (4%).

Conclusions:

Polymyxin B has acceptable effectiveness against nosocomial multidrug resistant Gram-negative sepsis. The associated nephrotoxicity has been found to be significantly lower than previously reported even in patients with background renal impairment and established risk factors of renal failure.     

Prognostic value of venoarterial carbon dioxide gradient in patients with severe sepsis and septic shock

Aim

To investigate the changes in the venoarterial carbon-dioxide gradient (V-a Pco₂) and its prognostic value for survival of patients with severe sepsis and septic shock.

Methods

The study was conducted in General Hospital Holy Spirit from January 2004 to December 2007 and included 71 conveniently sampled adult patients (25 women and 46 men), who fulfilled the severe sepsis and septic shock criteria and were followed for a median of 8 days (interquartile range, 12 days). The patients were divided in two groups depending on whether or not they had been mechanically ventilated. Both groups of patients underwent interventions with an aim to achieve hemodynamic stability. Mechanical ventilation was applied in respiratory failure. Venoarterial carbon dioxide gradient was calculated from the difference between the partial pressure of arterial CO₂ and the partial pressure of mixed venous CO₂, which was measured with a pulmonary arterial Swan-Ganz catheter. The data were analyzed using Kaplan-Meier survival analysis, along with a calculation of the hazard ratios.

Results

There was a significant difference between non-ventilated and ventilated patients, with almost 4-fold greater hazard ratio for lethal outcome in ventilated patients (3.85; 95% confidence interval, 1.64-9.03). Furthermore, the pattern of changes of many other variables was also different in these two groups (carbon dioxide-related variables, variables related to acid-base status, mean arterial pressure, systemic vascular resistance, lactate, body mass index, Acute Physiology and Chronic Health Evaluation II, Simplified Acute Physiology II Score, and Sepsis-related Organ Failure Assessment score). Pco₂ values (with a cut-off of 0.8 kPa) were a significant predictor of lethal outcome in non-ventilated patients (P = 0.015) but not in ventilated ones (P = 0.270).

Conclusion

V-a Pco₂ was a significant predictor of fatal outcome only in the non-ventilated group of patients. Ventilated patients are more likely to be admitted with a less favorable clinical status, and other variables seem to have a more important role in their outcome.Although oxygen delivery (Do₂) in septic shock can be elevated, oxygen consumption (Vo₂) is impaired (1). This could be a consequence of mitochondrial dysfunction in sepsis (2,3). Blood circulation is slow and consequently the elimination of CO₂ from the tissue is slower, making the tissue CO₂ concentration high. Venoarterial carbon dioxide gradient (V-a Pco₂) was calculated from the difference between the partial pressure of arterial CO₂ (Paco₂) and the partial pressure of mixed venous CO₂ (Pvco₂), which was measured with a pulmonary arterial Swan-Ganz catheter. The venoarterial CO₂ gradient (V-a Pco₂) is influenced by two other factors: the dissociative curve of CO₂ and tissue blood flow. The curve of CO₂ dissociation from hemoglobin follows the so-called Haldane''s effect, in which oxygen and its bonding with hemoglobin allows easier release of carbon dioxide in lungs (4). Experimental models have shown that in toximia, venous hypercapnia is a more significant contributor to the increase in the venoarterial CO₂ gradient than arterial CO₂ values (4-7). Elevated V-a Pco₂ has also been described in patients with sepsis, cardiogenic shock, acute myocardial infarction, and congestive heart failure, as well as cardiac arrest following cardiopulmonary resuscitation and heart surgery (8-13).In septic patients, the significance of the connection between an elevation of V-a Pco₂ and the course and outcome of the illness is not sufficiently known. It has been established that V-a Pco₂ shows a negative exponential relationship with the cardiac index (CI) (14,15). The negative association with CI has been observed not only in septic shock patients but also in postoperative patients without sepsis. In patients with a lethal outcome, CI was reduced, but V-a Pco₂ was not an independent predictor of outcome (14,16).The aim of this study was to investigate the changes in V-a Pco₂ to better understand the possibilities of using it as a predictor of clinical outcomes in patients with severe sepsis and septic shock.     

Extracorporeal cytokine elimination as rescue therapy in refractory septic shock: a prospective single-center study

Sepsis is the most common cause of death in medical intensive care units (ICU). If sepsis progresses to refractory septic shock, mortality may reach 90–100% despite optimum current therapy. Extracorporeal cytokine adsorption in addition to regular therapy was studied prospectively in refractory septic shock patients on a medical ICU. Refractory shock was defined as increasing vasopressor dose required to maintain mean arterial blood pressure above 65 mmHg or increasing lactate levels despite protocol-guided shock therapy for 6 h. We analysed noradrenaline requirements after 6 and 12 h (primary endpoint), lactate clearance after 6 and 12 h, SOFA-scores in the first days and achievement of shock reversal (i.e., normalization of lactate concentrations and sustained discontinuation of vasopressors; secondary endpoints). Twenty consecutive patients with refractory septic shock were included; CytoSorb^® treatment was started after 7.8 ± 3.7 h of shock therapy. Following the initiation of adsorption therapy, noradrenaline dose could be significantly reduced after 6 (?0.4 µg/kg/min; p = 0.03) and 12 h (?0.6 µg/kg/min; p = 0.001). Lactate clearance improved significantly. SOFA-scores on day 0, 1 and 2 remained unchanged. Shock reversal was achieved in 13 (65%) patients; 28-day survival was 45%. In severe septic shock unresponsive to standard treatment, haemodynamic stabilization was achieved using cytokine adsorption therapy, resulting in shock reversal in two-thirds of these patients. The study was registered in the German Register for Clinical Trials (DRKS) No. 00005149.     

The impact of selenium administration on severe sepsis or septic shock: a meta-analysis of randomized controlled trials

IntroductionThe efficacy of selenium administration to treat severe sepsis or septic shock remains controversial. We conduct a systematic review and meta-analysis to explore the impact of selenium administration on severe sepsis or septic shock.MethodsWe search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through May 2020 for randomized controlled trials (RCTs) assessing the effect of selenium administration on severe sepsis or septic shock. Meta-analysis is performed using the random-effect model.ResultsFive RCTs involving 1482 patients are included in the meta-analysis. Overall, compared with control group in septic patients, selenium administration is not associated with reduced 28-day mortality (RR=0.93; 95% CI=0.73 to 1.19; P=0.58), but results in substantially decreased all-cause mortality (RR=0.78; 95% CI=0.63 to 0.98; P=0.03) and length of hospital stay (MD=-3.09; 95% CI=-5.68 to -0.50; P=0.02).ConclusionSelenium administration results in notable decrease in all-cause mortality and length of hospital stay, but shows no substantial influence on the 28-day mortality, length of ICU stay, duration of vasopressor therapy, the incidence of acute renal failure, adverse events, and serious adverse events for septic patients.     

A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock

The use of high-dose corticosteroids in the treatment of severe sepsis and septic shock remains controversial. Our study was designed as a prospective, randomized, double-blind, placebo-controlled trial of high-dose methylprednisolone sodium succinate for severe sepsis and septic shock. Diagnosis was based on the clinical suspicion of infection plus the presence of fever or hypothermia (rectal temperature greater than 38.3 degrees C [101 degrees F] or less than 35.6 degrees C [96 degrees F]), tachypnea (greater than 20 breaths per minute), tachycardia (greater than 90 beats per minute), and the presence of one of the following indications of organ dysfunction: a change in mental status, hypoxemia, elevated lactate levels, or oliguria. Three hundred eighty-two patients were enrolled. Treatment--either methylprednisolone sodium succinate (30 mg per kilogram of body weight) or placebo--was given in four infusions, starting within two hours of diagnosis. No significant differences were found in the prevention of shock, the reversal of shock, or overall mortality. In the subgroup of patients with elevated serum creatinine levels (greater than 2 mg per deciliter) at enrollment, mortality at 14 days was significantly increased among those receiving methylprednisolone (46 of 78 [59 percent] vs. 17 of 58 [29 percent] among those receiving placebo; P less than 0.01). Among patients treated with methylprednisolone, significantly more deaths were related to secondary infection. We conclude that the use of high-dose corticosteroids provides no benefit in the treatment of severe sepsis and septic shock.     

Early goal-directed therapy reduces mortality in adult patients with severe sepsis and septic shock: Systematic review and meta-analysis

Introduction:

Survival sepsis campaign guidelines have promoted early goal-directed therapy (EGDT) as a means for reduction of mortality. On the other hand, there were conflicting results coming out of recently published meta-analyses on mortality benefits of EGDT in patients with severe sepsis and septic shock. On top of that, the findings of three recently done randomized clinical trials (RCTs) showed no survival benefit by employing EGDT compared to usual care. Therefore, we aimed to do a meta-analysis to evaluate the effect of EGDT on mortality in severe sepsis and septic shock patients.

Methodology:

We included RCTs that compared EGDT with usual care in our meta-analysis. We searched in Hinari, PubMed, EMBASE, and Cochrane central register of controlled trials electronic databases and other articles manually from lists of references of extracted articles. Our primary end point was overall mortality.

Results:

A total of nine trails comprising 4783 patients included in our analysis. We found that EGDT significantly reduced mortality in a random-effect model (RR, 0.86; 95% confidence interval [CI], 0.72–0.94; P = 0.008;   I² =50%). We also did subgroup analysis stratifying the studies by the socioeconomic status of the country where studies were conducted, risk of bias, the number of sites where the trials were conducted, setting of trials, publication year, and sample size. Accordingly, trials carried out in low to middle economic income countries (RR, 0.078; 95% CI, 0.67–0.91; P = 0.002; I² = 34%) significantly reduced mortality compared to those in higher income countries (RR, 0.93; 95% CI, 0.33–1.06; P = 0.28; I² = 29%). On the other hand, patients receiving EGDT had longer length of hospital stay compared to the usual care (mean difference, 0.49; 95% CI, –0.04–1.02; P = 0.07; I² = 0%).

Conclusion:

The result of our study showed that EGDT significantly reduced mortality in patients with severe sepsis and septic shock. Paradoxically, EGDT increased the length of hospital stay compared to usual routine care.     

Activated cytotoxic T cells and NK cells in severe sepsis and septic shock and their role in multiple organ dysfunction

To evaluate the role of activated cytotoxic cells in patients with severe sepsis (n = 32) or septic shock (n = 8), direct (granzymes A and B) as well as indirect markers (cytokines) for cytotoxic cell activation were measured. Elevated IL-12p40 levels had been detected in 58% of the sepsis patients, whereas only a few had detectable TNF-alpha, IFN-gamma, or IL-12p70 levels. Granzymes A and B levels were elevated in 42.5% and 22.5%, respectively. IL-12p40 inversely correlated with disease severity. Inflammatory parameters (IL-6) and coagulation markers were significantly lower and higher, respectively, in patients with elevated IL-12p40 and granzyme B levels, as compared to those with normal levels. Elevation of granzyme A directly correlated with the increase of apoptotic markers. Activated cytotoxic cells reflected by elevated granzymes A and/or B were found in 50% of our sepsis patients. This group showed a higher mortality and a worse organ function.     

TNFR2 expression on non-bone marrow-derived cells is crucial for lipopolysaccharide-induced septic shock and downregulation of soluble TNFR2 level in serum

Persistently high serum levels of soluble tumor-necrosis factor (TNF) receptor 2 (sTNFR2) have been observed in septic shock and many inflammatory diseases. However, its origin and regulation during these pathological processes are still largely unknown. In this study, murine bone marrow (BM) chimeras selectively expressing TNFR2 on either BM-derived or non-BM-derived cells were generated and challenged with lipopolysaccharide (LPS). The results show that TNFR2 expression on non-BM-derived cells is crucial for both the sensitivity of mice to LPS and the downregulation of sTNFR2 in serum. Most importantly, sTNFR2 was released from both BM- and non-BM-derived cells. Non-BM TNFR1 expression influenced the sensitivity of mice to LPS challenge but not the level of serum sTNFR2. These results provide the first in vivo evidence for the origin and regulation of sTNFR2 in serum and could aid in the development of novel anti-TNF strategies against septic shock.     

Timing of antibiotics in septic patients: a prospective cohort study

ObjectivesTo evaluate the effect of timing and appropriateness of antibiotics administration on mortality in patients diagnosed with sepsis according to the Sepsis-3 definition.MethodsThis prospective cohort study was conducted in patients diagnosed with sepsis according to the Sepsis-3 definition at the emergency department of Korea University Ansan Hospital from January 2016 to January 2019. The time to antibiotics was defined as the time in hours from emergency department arrival to the first antibiotic administration. Cox proportional hazards regression analysis was used to estimate the association between time to antibiotics and 7-, 14- and 28-day mortality.ResultsOf 482 patients enrolled onto this study, 203 (42.1%) of 482 and 312 (64.7%) of 482 were diagnosed with septic shock and high-grade infection respectively. The median time to receipt of antibiotic therapy was 115 minutes. Antibiotics were administered within 3 and 6 hours in 340 (70.4%) of 482 and 450 (93.2%) of 482 patients respectively. Initial appropriate empirical antibiotics were administered in 375 (77.8%) of 482 patients. The time to and appropriateness of the initial antibiotics were not associated with 7-, 14- and 28-day mortality in multivariate analysis. The Sequential Organ Failure Assessment (SOFA) score (adjusted hazard ratio (aHR) 1.229, 95% confidence interval (CI) 1.093–1.381, p 0.001) and initial lactate levels (aHR 1.128, 95% CI 1.034–1.230, p 0.007), Charlson comorbidity index (aHR 1.115, 95% CI 1.027–1.210, p 0.014), 2-hour lactate level (aHR 1.115, 95% CI 1.027–1.210, p 0.009) and SOFA score (aHR 1.077, 95% CI 1.013–1.144, p 0.018) affected 7-, 14- and 28-day mortality respectively. Subgroup analysis with septic shock, bacteraemia and high-grade infection did not affect mortality rates.ConclusionsTime to receipt of antibiotics may not affect the prognosis of patients with sepsis if a rapid and well-trained resuscitation is combined with appropriate antibiotic administration within a reasonable time.     

Clinical effects of direct hemoperfusion using a polymyxin-B immobilized column in solid organ transplanted patients with signs of severe sepsis and septic shock. A pilot study

BACKGROUND: Polymyxin B (PMX-B) is a polycationic antibiotic, known to bind the lipid A portion of endotoxin, a cell wall component found exclusively in gram negative bacteria (GNB). An extracorporeal hemoperfusion device (TORAYMYXIN) has been developed: PMX is covalently bound on the surface of an insoluble carrier material so that the endotoxin can be inactivated in the blood without exerting its toxicity on the brain and kidney. The aim of this study was to clarify the efficacy, safety and clinical effects of direct hemoperfusion with an immobilized polymyxin-B fiber column (DHP-PMX) in solid organ transplanted patients with severe sepsis or septic shock. METHODS: From June 2004 to May 2005, 15 patients (10 men and 5 women), mean age 55 years old (46-65 range), underwent kidney or liver transplantation and developed severe sepsis or septic shock, as defined by the Consensus Conference of American College Physicians/Society of Critical Care Medicine (ACCP/SCCM) criteria. GNB were detected in all the patients receiving conventional treatments including antibiotic therapy, vasopressive or inotropic agents, and ventilation support. The DHP-PMX treatment was performed three times in each patient. Hemodynamic and respiratory parameters, dosage of vasopressor/inotropic drugs were assessed at baseline and after each treatment. RESULTS: No adverse events occurred. From baseline to 3rd treatment, mean arterial pressure (MAP) was increased (from 63+/-5 to 83+/-4 mmHg), while the dosage of dobutamine (from 7.5+/-3 to 3+/-2 mcg/kg/min) and noradrenaline (from 1.3+/-0.45 to 0.05+/-0.02 mcg/kg/min) were reduced. The PaO2/FiO2 ratio increased (from 234+/-38.47 to 290+/-107.48 mmHg). CONCLUSION: The use of DHP-PMX in association with conventional therapy may be an important aid in patients with sepsis.