Twenty-four hour infusion of human recombinant activated protein C (Xigris) early in severe acute pancreatitis: The XIG-AP 1 trial.

OBJECTIVE: Patients with severe acute pancreatitis were excluded from major trials of human recombinant activated protein C (Xigris) because of concern about pancreatic haemorrhage although these individuals have an intense systemic inflammatory response that may benefit from treatment. The object of this study was to provide initial safety data evaluating Xigris in severe acute pancreatitis. DESIGN: Prospective clinical trial recruiting between November 2009 and October 2011. Patients received human recombinant activated protein C (Xigris) for 24 h by intravenous infusion (24 µg/kg/h) in addition to standard clinical care. A matched historical control group treated within the same hospital unit were used to compare outcomes. Of 166 consecutive admitted patients, 43 met the screening criteria for severe acute pancreatitis and 19 were recruited, all contributing to the analyses. RESULTS: Compared to historical controls, there were fewer bleeding events in the Xigris group although the finding did not reach significance (Xigris 0% vs. Control 21%, p = 0.13), similarly further intervention appeared less frequent (11% vs. 47%, p = 0.07) in the treatment group. Length of stay was shorter for patients receiving Xigris (19 vs. 41 days, p = 0.03) as was inotrope use (5% vs. 32%, p = 0.02); mortality and incidence of infections in both groups were similar. Biomarker protein C increased while IL-6 decreased following infusion. CONCLUSIONS: A 24-hr infusion of Xigris appears safe when used in patients with severe acute pancreatitis. TRIAL REGISTRATION: Eudract Number 2007-003635-23.

Bedside electronic capture of clinical observations and automated clinical alerts to improve compliance with an Early Warning Score protocol.

BACKGROUND: Failure to comply with clinical protocols and failure of communication to ensure delivery of the most appropriate timely clinical responses to patients whose conditions are acutely deteriorating have been shown to be significant causative factors associated with inhospital adverse events. OBJECTIVE: To determine whether automated clinical alerts increase compliance with an Early Warning Score (EWS) protocol and improve patient outcomes. METHODS: We performed a historically controlled study of bedside electronic capture of observations and automated clinical alerts. The primary outcome measure was hospital length of stay (LOS); secondary outcome measures were compliance with the EWS protocol, cardiac arrest incidence, critical care utilisation and hospital mortality. RESULTS: Between baseline and intervention, 1481 consecutive patients were recruited generating 13 668 observation sets. There was a reduction in hospital LOS between the baseline and alert phase (9.7 days v 6.9 days, P < 0.001). EWS accuracy improved from 81% to 100% with electronic calculation. Clinical attendance to patients with EWS 3, 4 or 5 increased from 29% at baseline to 78% with automated alerts (P < 0.001). For patients with an EWS > 5, clinical attendance increased from 67% at baseline to 96% with automatic alerts (P < 0.001). CONCLUSIONS: Electronic recording of patient observations linked to a computer system that calculates patient risk and then issues automatic graded alerts can improve clinical attendance to unstable general medical ward patients.

Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.

OBJECTIVES: This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients. METHODS: A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially. RESULTS: Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002). CONCLUSIONS: Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

Open pancreatic necrosectomy in the multidisciplinary management of postinflammatory necrosis.

OBJECTIVE: To examine clinical outcome in a consecutive cohort of patients undergoing open necrosectomy for postinflammatory necrosis. BACKGROUND INFORMATION: The last decade has witnessed major developments in the surgical management of pancreatic necrosis. Minimally invasive approaches have become established. However, there are limited data from contemporary open necrosectomy, in particular where multidisciplinary care and aggressive interventional radiology are used. This report provides data on outcome from open necrosectomy in a tertiary referral Hepatobiliary unit over the last decade. METHODS: During the period January 1, 2000 to July 31, 2008, 1535 patients were admitted with a final discharge code of acute pancreatitis. Twenty-eight (1.8%) of all admissions underwent open surgical necrosectomy. Twenty-four (86%) were tertiary referral patients. RESULTS: The median APACHE II score on admission was 10.5 (5-26). Median logistic organ dysfunction score on admission was 3 (0-10). Median LODS score after surgery was 2 (0-8). Twenty patients (71%) underwent radiologically guided drainage of collections before surgery. Thirty-day mortality occurred in 2 (7%), 4 further deaths occurred in patients after discharge from intensive care resulting in a total of 6 (22%) episode-related deaths. CONCLUSIONS: Modern open necrosectomy can be performed without the procedure-related deterioration in organ dysfunction associated with major debridement. Multidisciplinary care with an emphasis on aggressive radiologic intervention before and after surgery results in acceptable outcomes in this cohort of critically ill patients. Newer laparoscopic techniques must demonstrate similar outcomes in the setting of stage-matched severity before wider acceptance.

The epidemiology of severe sepsis in England, Wales and Northern Ireland, 1996 to 2004: secondary analysis of a high quality clinical database, the ICNARC Case Mix Programme Database.

INTRODUCTION: To evaluate the impact of recent evidence-based treatments for severe sepsis in routine clinical care requires an understanding of the underlying epidemiology, particularly with regard to trends over time. We interrogated a high quality clinical database to examine trends in the incidence and mortality of severe sepsis over a nine-year period. METHODS: Admissions with severe sepsis occurring at any time within 24 hours of admission to critical care were identified to an established methodology using raw physiological data from the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, containing data from 343,860 admissions to 172 adult, general critical care units in England, Wales and Northern Ireland between December 1995 and January 2005. Generalised linear models were used to assess changes in the incidence, case mix, outcomes and activity of these admissions. RESULTS: In total, 92,672 admissions (27.0%) were identified as having severe sepsis in the first 24 hours following admission. The percentage of admissions with severe sepsis during the first 24 hours rose from 23.5% in 1996 to 28.7% in 2004. This represents an increase from an estimated 18,500 to 31,000 admissions to all 240 adult, general critical care units in England, Wales and Northern Ireland. Hospital mortality for admissions with severe sepsis decreased from 48.3% in 1996 to 44.7% in 2004, but the total number of deaths increased from an estimated 9,000 to 14,000. The treated incidence of severe sepsis per 100,000 population rose from 46 in 1996 to 66 in 2003, with the associated number of hospital deaths per 100,000 population rising from 23 to 30. CONCLUSION: The population incidence of critical care admission with severe sepsis during the first 24 hours and associated hospital deaths are increasing. These baseline data provide essential information to those wishing to evaluate the introduction of the Surviving Sepsis Campaign care bundles in UK hospitals.