Sepsis is a complex syndrome with its wide spectrum of severity, and is one of the most common causes of death in Critical Care Units. The Surviving Sepsis campaign launched in 2004, is aimed at improving diagnosis, management and survival of patients with sepsis. Care bundles are a group of best evidence based interventions which when instituted together, gives maximum outcome benefit. Care Bundles are simple, uniform and have universal practical applicability. Surviving Sepsis campaign guidelines in 2008 incorporated two sepsis care bundles. The Resuscitation bundle includes seven key interventions to be achieved in 6-h while four interventions have to be completed within 24-h in the Management bundle. Compliance with a bundle implies achieving all the specified goals in that bundle. Limitations to care bundles include the quality of the evidence on which they are based, and that the relative contributions of each element of the bundle are not known. Several observational studies support the hypothesis that sepsis care bundles have an important role in improving outcomes from sepsis. Critical Care Units should develop management strategies to ensure compliance with the sepsis bundles in order to decrease hospital mortality due to severe sepsis.

Acute kidney injury (AKI) is a common sequel of sepsis in the intensive care unit. It is being suggested that sepsis-induced AKI may have a distinct pathophysiology and identity. Availability of biomarkers now enable us to detect AKI as early as four hours after it′s inception and may even help us to delineate sepsis-induced AKI. Protective strategies such as preferential use of vasopressin or prevention of intra-abdominal hypertension may help, in addition to the other global management strategies of sepsis. Pharmacologic interventions have had limited success, may be due to their delayed usage. Newer developments in extracorporeal blood purification techniques may proffer effects beyond simple replacement of renal function, such as metabolic functions of the kidney or modulation of the sepsis cascade.

Context: Diffused endothelial dysfunction in sepsis leads to an increase in systemic capillary permeability, the renal component manifesting as microalbuminuria. The degree of microalbuminuria correlates with the severity of the acute insult, the quantification of which may serve to predict sepsis and mortality in critically ill patients. Aims: To evaluate whether the degree of microalbuminuria could differentiate patients with sepsis from those without and predict mortality in critically ill patients. Settings and Design: Prospective, non-interventional study in a 20-bed Intensive Care Unit (ICU) of a tertiary care hospital. Methods and Materials: After exclusions, between Jan-May2007, 94 consecutive adult patients were found eligible. Albumin-creatinine ratio (ACR, mg/g) was measured in urine samples collected on ICU admission (ACR1) and at 24 hours (ACR2). Results: Patients were classified into two groups: those with sepsis, severe sepsis and septic shock (n = 30) and those without sepsis [patients without systemic inflammatory response syndrome (SIRS) and with SIRS due to noninfectious causes] (n = 64). In the sepsis group, median ACR1 [206.5 (IQR129.7-506.1)] was significantly higher compared to the non sepsis group [76.4 (IQR29-167.1)] (P = 0.0016, Mann Whitney). The receiver operating characteristics (ROC) curve analysis showed that at a cut off value 124 mg/g, ACR1 may be able to discriminate between patients with and without sepsis with a sensitivity of 80%, specificity of 64.1%, positive predictive value (PPV) of 51.1% and negative predictive value (NPV) of 87.3%. The median ACR2 [154 (IQR114.4-395.3)] was significantly higher (P = 0.004) in nonsurvivors (n = 13) as compared to survivors [50.8 (IQR 21.6-144.7)]. The ROC curve analysis revealed that ACR2 at a cut-off of 99.6 mg/g could predict ICU mortality with sensitivity of 85%, specificity of 68% with a NPV of 97% and PPV of 30%. Conclusion: Absence of significant microalbuminuria on ICU admission is unlikely to be associated with sepsis. At 24 hours, absence of elevated levels of microalbuminuria is strongly predictive of ICU survival, equivalent to the time-tested APACHE II scores.

Introduction: This study aims to compare two vasoconstrictors: - norepinephrine and phenylephrine - in the management of dopamine- resistant septic shock. Materials and Methods: We performed a randomized, prospective, controlled trial in 54 septic shock patients, with persistent hypotension despite adequate volume resuscitation and continued dopamine infusion ~25μg/kg/h. Patients were randomly allocated into two groups to receive either norepinephrine or phenylephrine infusion (n = 27 each) titrated to achieve a target of SBP > 90mm Hg, MAP > 75 mm Hg, SVRI > 1100 dynes.s/cm5m2, CI > 2.8 L/min/m2, DO2I > 550 ml/min/m2, and VO2I > 150 ml/min/m2 for continuous 6 h. All the parameters were recorded every 30 min and increment in dose of studied drug was done in the specified dose range if targets were not achieved. Data from pulmonary arterial and hepatic vein catheterization, thermodilution catheter, blood gas analysis, blood lactate levels, invasive blood pressure, and oxygen transport variables were compared with baseline values after achieving the targets of therapy. Differences within and between groups were analyzed using a one-way analysis of variance test and Fischer′s exact test. Results: No difference was observed in any of the investigated parameters except for statistically significant reduction of heart rate (HR) (P< 0.001) and increase in stroke volume index (SVI) (P< 0.001) in phenylephrine group as compared to nonsignificant change in norepinephrine group. Conclusions: Phenylephrine infusion is comparable to norepinephrine in reversing hemodynamic and metabolic abnormalities of sepsis patients, with an additional benefit of decrease in HR and improvement in SVI.

Background: Septic shock remains a major cause of multiple organ failure and is associated with a high mortality rate. In 1994, direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX; Toray Industries Inc., Tokyo Japan) was developed in Japan and has since been used for the treatment of septic shock arising from endotoxemia. Materials and Method: We treated 36 patients with septic shock using direct hemoperfusion with PMX. The patients were analyzed in two groups based on whether they had undergone surgery prior to DHP-PMX treatment (surgical group: surgical treatment before DHP-PMX, medical group: no surgical treatment). In surgical group, DHP-PMX was started within three hours after the surgical treatment. Various factors were measured before and after DHP-PMX. Results: The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 27.4 ± 8.8, and the mean sepsis-related organ failure assessment (SOFA) score was 11.8 ± 4.9 before DHP-PMX. The SOFA score was significantly higher (P = 0.0091) and the PaO2/FiO2 ratio (P/F ratio) was significantly lower (P = 0.0037) in medical group than in surgical group prior to DHP-PMX. A chi-square test showed that the survival rate in surgical group was significantly better than in medical group (P = 0.0027). The survival rate of surgical group (84.2%) was judged to be very good because the predicated survival rate based on the APACHE II score (25.0) was only 46.5%. On the other hand, the survival rate of medical group (35.3%) was almost equal to that predicted by the APACHE II score (30.6; predicted survival rate, 27.4%). Conclusion: The results of this study suggest the utility of early DHP-PMX in surgical group.

Justification: Pediatric sepsis is a commonly encountered global issue. Existing guidelines for sepsis seem to be applicable to the developed countries, and only few articles are published regarding application of these guidelines in the developing countries, especially in resource-limited countries such as India and Africa. Process: An expert representative panel drawn from all over India, under aegis of Intensive Care Chapter of Indian Academy of Pediatrics (IAP) met to discuss and draw guidelines for clinical practice and feasibility of delivery of care in the early hours in pediatric patient with sepsis, keeping in view unique patient population and limited availability of equipment and resources. Discussion included issues such as sepsis definitions, rapid cardiopulmonary assessment, feasibility of early aggressive fluid therapy, inotropic support, corticosteriod therapy, early endotracheal intubation and use of positive end expiratory pressure/mechanical ventilation, initial empirical antibiotic therapy, glycemic control, and role of immunoglobulin, blood, and blood products. Objective: To achieve a reasonable evidence-based consensus on the basis of published literature and expert opinion to formulating clinical practice guidelines applicable to resource-limited countries such as India. Recommendations: Pediatric sepsis guidelines are presented in text and flow chart format keeping resource limitations in mind for countries such as India and Africa. Levels of evidence are indicated wherever applicable. It is anticipated that once the guidelines are used and outcomes data evaluated, further modifications will be necessary. It is planned to periodically review and revise these guidelines every 3-5 years as new body of evidence accumulates.