Effects on management and outcome of severe sepsis and septic shock patients admitted to the intensive care unit after implementation of a sepsis program: a pilot study

This prospective observational study enrolled consecutive patients with a diagnosis of severe sepsis/septic shock admitted to an ICU of the 780-bed University Hospital of Modena from January 2005 to June 2007. The study was approved by the local ethical committee and the need for informed consent was waived in view of the observational and anonymous nature of the study. The ICU consists of nine beds and approximately 800 adult patients are admitted annually (70% surgical patients). Staffing at any time consists of one attending physician, one resident physician and three to four nurses.

The inclusion criteria were: a) documented or suspected infection; b) two or more systemic inflammatory response syndrome criteria [13] and c) the onset of an organ dysfunction related to infection: gas exchange impairment (partial pressure of arterial oxygen (PaO₂)/fraction of inspired oxygen (FiO₂) < 250 mmHg), mean arterial pressure (MAP) below 65 mmHg, acute renal dysfunction (1.5-fold baseline creatinine increase or urine output < 0.5 ml/Kg/h for two hours), total bilirubin above 4 mg/dL, platelet count below 80,000 cells/mm³ (or a 100,000 cells/mm³ decrease) or lactate blood concentration above 4.0 mM. Patients with persistence of MAP below 65 mmHg after an adequate fluid infusion (see below) were classified as having septic shock. Patients with severe decompensated chronic liver disease included in the waiting list for liver transplantation were excluded from the study.

Data collection began one month after the start of an in-hospital educational program on sepsis (see below) and only the first episode of severe sepsis/septic shock was considered in each patient. The management of patients was evaluated by analysis of interventions and sepsis bundles [3]. We identified five resuscitation (6-hours bundle) and four management (24-hours bundle) interventions: blood cultures collection before antibiotic administration; empiric antibiotic therapy within three hours from diagnosis; control of infection source within six hours; adequate fluid resuscitation before vasopressor administration; central venous oxygen saturation (ScvO₂) above 70% within six hours; blood glucose median below 150 mg/dL in the first 24 hours; low-dose hydrocortisone administration in association with vasopressor support; recombinant human activated protein C (rhAPC) if administration indicated; plateau inspiratory pressure below 30 cmH₂O in patients with acute lung injury (ALI)/adult respiratory distress syndrome (ARDS). The term adequate fluid resuscitation indicates a central venous pressure above 6 mmHg (above 8 mmHg if mechanically ventilated) or a global end-diastolic volume by trans-pulmonary thermodilution (PiCCO system, Pulsion, Germany) above 700 ml/m².

Two of the authors (LR and LD) not involved in the clinical management of the patients, collected the above interventions by analysis of clinical charts and any uncertain data was audit with the attending physician. The interventions were classified as completed and not completed. An intervention not applied because not applicable (e.g. low plateau inspiratory pressure in patient without ALI/ARDS) was defined as completed. The time zero for bundles timing was the time in which the three study inclusion criteria were documented by clinical notes. Type of admission, grade of sepsis, primary site of infection, simplified acute physiology score (SAPS) II and simplified organ failure assessment (SOFA) score the day of sepsis diagnosis [14, 15], ICU and hospital length of stay, and hospital mortality were also recorded for each patient. Predicted hospital mortality was calculated by SAPS II score.

The education phase of our hospital program named "Sopravvivere alla Sepsi nel Policlinico di Modena" (Surviving to Sepsis in Policlinico Hospital of Modena) started on November 2004 and continued throughout the study period. It included basic, advanced and refresh courses with conference lectures and practice training for nurses and physicians of all hospital departments. From November 2004 to June 2007 almost 250 physicians (out of 400) and 300 nurses (out of 950) of our hospital participated in educational courses. A specific protocol for early recognition and management of patients with severe sepsis/septic shock was prepared, approved and promoted (e.g. specific meetings, hospital intra-net, poster displayed in the staff working area) in all hospital wards (June 2006). The protocol includes: i) clinical data needed for severe sepsis/septic shock identification; ii) instruction for 'sepsis team' activation; iii) detailed instructions for early goal directed resuscitation, collection of microbiological samples and antibiotic therapy; and iv) special recommendations on bicarbonate use, low-dose dopamine and glycaemia control. The sepsis team is available 24 hours per day and is formed by two attending physicians: an intensivist and an infectious disease specialist. The team is activated by and collaborates with the attending physician and the nursing department staff in providing the interventions required for each patient with severe sepsis and septic shock (e.g. placing central venous line, measuring central venous pressure, providing non-invasive ventilation, assessing for antibiotic strategy and other specific therapy). After the activation by a dedicated telephone number, the time period for team sepsis consultation should be shorter than 60 minutes in patients with severe sepsis and 30 minutes in patients with septic shock. The sepsis team activity (e.g. frequency and percentage of appropriate activation, mean time before consultation, percentage of ICU admission, patient outcome) is regularly recorded and discussed with members of the "Sopravvivere alla Sepsi" group and with the hospital administrators.

The outcome measurements included intervention compliance, ICU and in-hospital length of stay and in-hospital mortality. For data analysis, the study period was divided: in semesters, in order to assess the progression of learning process and in two periods, before and after June 2006, in order to assess the impact of 'sepsis team' on patient outcome. Students' t-test, chi-squared, Fisher's exact test, and analysis of variance single-factor analysis were used when appropriate. Univariate and multivariate logistic regression were performed, with hospital mortality as dependent variable and individual interventions, bundles and sepsis team admission as independent variables. Variables with P < 0.20 from univariate analysis were included in the backward logistic regression model that was also corrected for possible confounders such as age, SOFA and SAPS II scores, the presence of shock, lactate blood concentration (first data after study inclusion) and sepsis team period. The goodness of fit was assessed by the Hosmer-Lemeshow test. A value of P < 0.05 was considered significant. The statistical software package SPSS 15.0 (SPSS Inc., Chicago, IL, USA) was used for statistical analysis.