Use this URL to cite or link to this record in EThOS:
Title: Evaluating outcome in patients with faecal peritonitis admitted to European Intensive Care Units
Author: Tridente, Ascanio
ISNI:       0000 0004 6497 5624
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2017
Availability of Full Text:
Access from EThOS:
Access from Institution:
Faecal Peritonitis is a common cause of sepsis and admission to the Intensive Care Unit (ICU). The Genetics of Sepsis & Septic Shock in Europe (GenOSept) project and the GAinS (Genomic Advances in Sepsis) are genetic epidemiology studies set up to investigate the influence of genetic variation on the host response and outcomes. The studies included two large cohorts of post-operative critically ill patients with sepsis from faecal peritonitis admitted to European and UK ICUs, respectively. In my thesis, I define the clinical characteristics, outcomes and risk factors for mortality in these patients, relying on the clinical data available from these large databases. The GenOSept study provided data for 977 faecal peritonitis patients, recruited to 102 centres across 16 countries between 29/09/2005 and 5/01/2011. The median age was 69.2 years (IQR, Interquartile range 58.3-77.1). The most common causes of faecal peritonitis were perforated diverticular disease (32.1%) and surgical anastomotic breakdown (31.1%). The mortality rate at 28 days was 19.1% and 31.6% at six months. The cause of faecal peritonitis, pre-existing co-morbidities and time from estimated onset of symptoms to surgery did not impact on survival. The strongest independent risk factors associated with an increased rate of death at 6 months included age, higher APACHE (Acute Physiology and Chronic Health Evaluation) II score, acute renal and cardiovascular dysfunction within one week of admission to ICU, hypothermia, lower haematocrit and bradycardia on day 1 of ICU stay. When analysing trends in all variables available for the first week of ICU stay, the trends over the first 7 days ICU stay (primary analysis) retained in multivariate analysis as independently associated with 6 months outcome were worsening thrombocytopaenia (mortality Hazard Ratio, HR=1.02, 95% CI 1.01-1.03, p < 0.001) and renal function (total daily urine output HR=1.02, 95%CI 1.01-1.03, p < 0.001; worsening renal SOFA - Sequential Organ Failure Assessment - sub-score HR=0.87, 95%CI 0.75-0.99, p=0.047), and worsening trends in the highest recorded level of bilirubin (HR=0.99, 95%CI 0.99-0.99, p=0.02) and GCS SOFA sub-score (HR=0.81, 95%CI 0.68-0.98, p=0.028). Changes in renal function (total daily urine output and renal component of the SOFA score), GCS component of the SOFA score, total SOFA and worsening thrombocytopaenia were also independently associated with secondary outcomes (ICU, hospital and 28 day mortality). Dynamic trends over the first 7 days ICU stay in all other measured laboratory and physiological variables and in radiological findings failed to be retained as independently associated with outcome on multivariate analyses. Furthermore, changes in respiratory support, renal replacement therapy and inotrope and/or vasopressor requirements were not independently associated with any of the primary or secondary outcomes. A further set of analyses aimed to develop two prognostic models for the prediction of 28 day and long term (6 months) mortality, using non-parametric bootstrapping techniques of sampling from the UK portion of the GenOSept cohort, to derive a prognostic model. The non-UK portion of the GenOSept cohort, and the GAinS cohort were used for geographic and temporal external validation purposes of the prognostic model. Five variables (age, SOFA score, lowest temperature, highest heart rate, haematocrit) were entered into the prognostic models. The discriminatory performance of the 6 month prognostic model yielded an AuROC (Area under the Receiver Operating Characteristic curve) 0.81 (95% Confidence Interval, CI, 0.76 - 0.86), 0.73 (95% CI 0.69 - 0.78), and 0.76 (95% CI 0.69-0.83) for the derivation, geographic and temporal external validation cohorts, respectively. The 28 day prognostic tool yielded an AuROC 0.82 (95% CI 0.77 - 0.88), 0.75 (95% CI 0.69 - 0.80) and 0.79 (95% CI 0.71-0.87) for the same cohorts. These AuROCs were consistently superior to those obtained with the SOFA and APACHE II scores. Hence, the two prognostic models developed for 6 month and 28 day mortality prediction in critically ill septic patients with FP, in the post-operative phase, enhanced the SOFA score's predictive utility by adding few key variables. External validation in larger cohorts of their predictive capability is needed, before introduction of the scores into clinical practice to inform decision making and the design of clinical studies.
Supervisor: Dockrell, David ; Mills, Gary ; Hinds, Charles Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available