Catherine A Welch

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

IntroductionTo 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.MethodsAdmissions 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.ResultsIn 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.ConclusionThe 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.

Community-acquired pneumonia on the intensive care unit: secondary analysis of 17,869 cases in the ICNARC Case Mix Programme Database

IntroductionThis paper describes the case mix, outcome and activity for admissions to intensive care units (ICUs) with community-acquired pneumonia (CAP).MethodsWe conducted a secondary analysis of a high quality clinical database, the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database, of 301,871 admissions to 172 adult ICUs across England, Wales and Northern Ireland, 1995 to 2004. Cases of CAP were identified from pneumonia admissions excluding nosocomial pneumonias and the immuno-compromised. It was not possible to review data from the time of hospital admission; therefore, some patients who developed hospital-acquired/nosocomial pneumonia may have been included.ResultsWe identified 17,869 cases of CAP (5.9% of all ICU admissions). There was a 128% increase in admissions for CAP from 12.8 per unit to 29.2 per unit during the study period compared to only a 24% rise in total ICU admissions (p < 0.001). Eighty-five percent of admissions were from within the same hospital. Fifty-nine percent of cases were admitted to the ICU <2 days, 21.5% between 2 and 7 days, and 19.5% >7 days after hospital admission. Between 1995 and 1999 and 2000 and 2004 there was a rise in admissions from accident and emergency (14.8% to 16.8%; p < 0.001) and high dependency units (6.9% to 11.9%; p < 0.001) within the same hospital, those aged >74 (18.5 to 26.1%; p < 0.001), and mean APACHE II score (6.83 to 6.91; p < 0.001). There was a fall in past history of severe respiratory problems (8.7% to 6.4%; p < 0.001), renal replacement therapy (1.6% to 1.2%; p < 0.01), steroid treatment (3.4% to 2.8%; p < 0.05), sedation/paralysis (50.2% to 40.4%; p < 0.001), cardiopulmonary resuscitation prior to admission (7.5% to 5.5%; p < 0.001), and septic shock (7.3% to 6.6%; p < 0.001). ICU mortality was 34.9% and ultimate hospital mortality 49.4%. Mortality was 46.3% in those admitted to the ICU within 2 days of hospital admission rising to 50.4% in those admitted at 2 to 7 days and 57.6% in those admitted after 7 days following hospital admission.ConclusionCAP makes up a small, but important and rising, proportion of adult ICU admissions. Survival of over half of all cases vindicates the use of ICU facilities in CAP management. Nevertheless, overall mortality remains high, especially in those admitted later in their hospital stay.

Admission factors associated with hospital mortality in patients with haematological malignancy admitted to UK adult, general critical care units: a secondary analysis of the ICNARC Case Mix Programme Database

IntroductionPatients with haematological malignancy admitted to intensive care have a high mortality. Adverse prognostic factors include the number of organ failures, invasive mechanical ventilation and previous bone marrow transplantation. Severity-of-illness scores may underestimate the mortality of critically ill patients with haematological malignancy. This study investigates the relationship between admission characteristics and outcome in patients with haematological malignancies admitted to intensive care units (ICUs) in England, Wales and Northern Ireland, and assesses the performance of three severity-of-illness scores in this population.MethodsA secondary analysis of the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database was conducted on admissions to 178 adult, general ICUs in England, Wales and Northern Ireland between 1995 and 2007. Multivariate logistic regression analysis was used to identify factors associated with hospital mortality. The Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II and ICNARC score were evaluated for discrimination (the ability to distinguish survivors from nonsurvivors); and the APACHE II, SAPS II and ICNARC mortality probabilities were evaluated for calibration (the accuracy of the estimated probability of survival).ResultsThere were 7,689 eligible admissions. ICU mortality was 43.1% (3,312 deaths) and acute hospital mortality was 59.2% (4,239 deaths). ICU and hospital mortality increased with the number of organ failures on admission. Admission factors associated with an increased risk of death were bone marrow transplant, Hodgkins lymphoma, severe sepsis, age, length of hospital stay prior to intensive care admission, tachycardia, low systolic blood pressure, tachypnoea, low Glasgow Coma Score, sedation, PaO2:FiO2, acidaemia, alkalaemia, oliguria, hyponatraemia, hypernatraemia, low haematocrit, and uraemia. The ICNARC model had the best discrimination of the three scores analysed, as assessed by the area under the receiver operating characteristic curve of 0.78, but all scores were poorly calibrated. APACHE II had the highest accuracy at predicting hospital mortality, with a standardised mortality ratio of 1.01. SAPS II and the ICNARC score both underestimated hospital mortality.ConclusionsIncreased hospital mortality is associated with the length of hospital stay prior to ICU admission and with severe sepsis, suggesting that, if appropriate, such patients should be treated aggressively with early ICU admission. A low haematocrit was associated with higher mortality and this relationship requires further investigation. The severity-of-illness scores assessed in this study had reasonable discriminative power, but none showed good calibration.

Dermatological conditions in intensive care: a secondary analysis of the Intensive Care National Audit & Research Centre (ICNARC) Case Mix Programme Database

IntroductionDermatology is usually thought of as an outpatient specialty with low mortality, however some skin conditions require intensive care. These conditions are relatively rare and hence are best studied using clinical databases or disease registries. We interrogated a large, high-quality clinical database from a national audit of adult intensive care units (ICUs), with the aim of identifying and characterising patients with dermatological conditions requiring admission to ICU.MethodsData were extracted for 476,224 admissions to 178 ICUs in England, Wales and Northern Ireland participating in the Case Mix Programme over the time period December 1995 to September 2006. We identified admissions with dermatological conditions from the primary and secondary reasons for admission to ICU.ResultsA total of 2,245 dermatological admissions were identified. Conditions included infectious conditions (e.g. cutaneous cellulitis, necrotising fasciitis), dermatological malignancies, and acute skin failure (e.g. toxic epidermal necrolysis, Stevens–Johnson syndrome and autoimmune blistering diseases). These represent 0.47% of all ICU admissions, or approximately 2.1 dermatological admissions per ICU per year. Overall mortality was 28.1% in the ICU and 40.0% in hospital. Length of stay in intensive care was longest for those with acute skin failure (median 4.7 days for ICU survivors and 5.1 days for ICU non-survivors).ConclusionWe have identified patients who not only require intensive care, but also dermatological care. Such patients have high mortality rates and long ICU stays within the spectrum of the UK ICU population, similar to other acute medical conditions. This highlights the importance of skin failure as a distinct entity comparable to other organ system failures.

Case mix, outcomes and comparison of risk prediction models for admissions to adult, general and specialist critical care units for head injury: a secondary analysis of the ICNARC Case Mix Programme Database

IntroductionThis report describes the case mix and outcome (mortality, intensive care unit (ICU) and hospital length of stay) for admissions to ICU for head injury and evaluates the predictive ability of five risk adjustment models.MethodsA secondary analysis was conducted of data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme, a high quality clinical database, of 374,594 admissions to 171 adult critical care units across England, Wales and Northern Ireland from 1995 to 2005. The discrimination and calibration of five risk prediction models, SAPS II, MPM II, APACHE II and III and the ICNARC model plus raw Glasgow Coma Score (GCS) were compared.ResultsThere were 11,021 admissions following traumatic brain injury identified (3% of all database admissions). Mortality in ICU was 23.5% and in-hospital was 33.5%. Median ICU and hospital lengths of stay were 3.2 and 24 days, respectively, for survivors and 1.6 and 3 days, respectively, for non-survivors. The ICNARC model, SAPS II and MPM II discriminated best between survivors and non-survivors and were better calibrated than raw GCS, APACHE II and III in 5,393 patients eligible for all models.ConclusionTraumatic brain injury requiring intensive care has a high mortality rate. Non-survivors have a short length of ICU and hospital stay. APACHE II and III have poorer calibration and discrimination than SAPS II, MPM II and the ICNARC model in traumatic brain injury; however, no model had perfect calibration.

Outcomes following oesophagectomy in patients with oesophageal cancer: a secondary analysis of the ICNARC Case Mix Programme Database

IntroductionThis report describes the case mix and outcomes of patients with oesophageal cancer admitted to adult critical care units following elective oesophageal surgery in England, Wales and Northern Ireland.MethodsAdmissions to critical care following elective oesophageal surgery for malignancy were identified using data from the Intensive Care National Audit and Research Centre (ICNARC) Case Mix Programme Database. Information on admissions between December 1995 and September 2007 were extracted and the association between in-hospital mortality and patient characteristics on admission to critical care was assessed using multiple logistic regression analysis. The performance of three prognostic models (Simplified Acute Physiology Score (SAPS) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and the ICNARC physiology score) was also evaluated.ResultsBetween 1995 and 2007, there were 7227 admissions to 181 critical care units following oesophageal surgery for malignancy. Overall mortality in critical care was 4.4% and in-hospital mortality was 11%, although both declined steadily over time. Eight hundred and seventy-three (12.2%) patients were readmitted to critical care, most commonly for respiratory complications (49%) and surgical complications (25%). Readmitted patients had a critical care unit mortality of 24.7% and in-hospital mortality of 33.9%. Overall in-hospital mortality was associated with patient age, and various physiological measurements on admission to critical care (partial pressure of arterial oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio, lowest arterial pH, mechanical ventilation, serum albumin, urea and creatinine). The three prognostic models evaluated performed poorly in measures of discrimination, calibration and goodness of fit.ConclusionsSurgery for oesophageal malignancy continues to be associated with significant morbidity and mortality. Age and organ dysfunction in the early postoperative period are associated with an increased risk of death. Postoperative serum albumin is confirmed as an additional prognostic factor. More work is required to determine how this knowledge may improve clinical management.

Drotrecogin alfa (activated): real-life use and outcomes for the UK

IntroductionIn March 2001, the results of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study were published, which indicated a 6.1% absolute reduction in 28-day mortality. Drotrecogin alfa (activated; DrotAA) was subsequently approved for use in patients with severe sepsis.MethodsIn December 2002, critical care units in England, Wales and Northern Ireland were invited to participate in an audit of DrotAA. Data for each infusion of DrotAA were linked to case mix and outcome data from a national audit. Use of DrotAA was described and a nonrandomized comparison of effectiveness was conducted.Results1,292 infusions of DrotAA were recorded in 112 units; 61% commenced during the first 24 hours in the unit. The majority (77%) of patients had three or more organs failing; lung (42%) and abdomen (40%) were the most common primary sites of infection. Crude hospital mortality was high (45%); at 28 days, only 18% had left acute hospital and 19% were still in the unit. For 30%, the full 96-hour infusion was not completed; 24% of infusions were interrupted; 8.1% experienced one or more serious adverse events, of which 77% were serious bleeding events. Of eight relative risks estimated from individually-matched (0.75 to 0.85) and propensity-matched (0.82 to 0.90) controls, seven were consistent with the results of PROWESS. Restricting the analysis to patients receiving DrotAA during the first 24 hours resulted in larger treatment effects (relative risks 0.62 to 0.81). For all matches, similar patterns were seen across subgroups. No effect of DrotAA was seen for two organs failing or lower severity scores, compared with a significant mortality reduction for three or more organs failing or higher severity scores.ConclusionUse of DrotAA was approximately one in 16 for admissions meeting the definition for severe sepsis and with two or more organs failing. Patients receiving DrotAA were younger and more severely ill but were less likely to have serious conditions in their past medical history. Nonrandomized estimates for the effectiveness of DrotAA were consistent with the findings of PROWESS. DrotAA appeared not to be effective in patients with less severe disease.

Post hoc insights from PAC-Man--the U.K. pulmonary artery catheter trial.

Objectives:To provide descriptive information on patients considered for management with a pulmonary artery catheter (PAC) in U.K. intensive care units and to generate hypotheses to guide future research by examining subsets of patients included in the PAC-Man Study. Design:Randomized controlled trial. Setting:U.K. general intensive care units. Patients:Adult critically ill patients deemed to require management with a PAC by the treating clinician. Interventions:Management with a PAC. Measurements and Main Results:A Cox proportional hazards model was used to estimate interactions between treatment effect and time to randomization, age, surgical status, Sequential Organ Failure Score (SOFA) at randomization, organs supported at randomization, and use of flow measurement devices. Type of hospital and size of unit were tested for an interaction with the treatment effect using multilevel logistic regression modeling. There was no effect (or trend) on hospital survival related to the timing of randomization in relation to intensive care unit admission, type of organ support or SOFA score at randomization, age, type of hospital, or size of intensive care unit. No overall difference in acute hospital outcome was seen between use of a PAC and no flow measurement (p = .748) or between use of an alternative flow measurement device and no flow measurement (p = .395). Conclusions:Post hoc analyses of the PAC-Man Study data set revealed no benefit associated with being managed with a PAC in critically ill patients. However, such analyses are limited, and adequately powered clinical trials are needed of specific population subsets receiving targeted therapies delivered early in the patient’s critical illness to optimize the likelihood of reversing or preventing further organ dysfunction. Furthermore, the utility of other flow measurement devices must be investigated as these have already become integrated into critical care management without adequate evaluation.

The association between deprivation and hospital mortality for admissions to critical care units in England

INTRODUCTION Few studies have investigated the association between level of social deprivation and acute hospital outcome for admissions to adult general critical care units. It is important to be aware if an association exists because risk prediction models do not adjust for deprivation. MATERIALS AND METHODS Deprivation was measured using the Index of Multiple Deprivation (IMD) 2004, developed using 2001 census data in England. Eighty-four thousand four hundred twenty-three admissions to 138 adult general critical care units in England were selected from the Case Mix Programme Database from 1 year before to 1 year after the census date and linked to the IMD using postcodes. Logistic regression analysis was used to investigate a possible association between quintile of IMD and acute hospital mortality. RESULTS As deprivation increased, acute hospital mortality also increased (P < .001). This association remained after adjusting for age, sex, acute severity, medial history, source of admission, and reason for admission to critical care (adjusted odds ratio for most vs least deprived quintile, 1.19; 95% confidence interval, 1.10-1.28). CONCLUSIONS There is an association between increasing deprivation and increasing risk of mortality for admissions to adult general critical care unit units in England. Further research is required to identify other unmeasured potential confounders (eg, smoking, alcohol consumption) as possible explanations for this association.

The increasing burden of alcoholic liver disease on United Kingdom critical care units: secondary analysis of a high quality clinical database

OBJECTIVES To investigate the effect of increasing alcohol consumption on the number of admissions to adult, general critical/intensive care units (ICUs) in England and Wales with alcoholic liver disease, their case mix, mortality, and impact on critical care and hospital activity by extrapolating from admissions to ICUs over the last 10 years. METHODS Secondary analysis of a high quality clinical database from a national clinical audit using data from 385,429 admissions to174 ICUs in England and Wales between December 1995 and July 2005, of which 4219 (1.1%) had alcoholic liver disease. The extrapolated total number of admissions with alcoholic liver disease and total number of ICU bed-days occupied were calculated. Changes over time in the case mix (age, sex and APACHE II and ICNARC risk prediction models), mortality at ultimate discharge from acute hospital, and length of stay in ICU and in hospital were explored. RESULTS The percentage of ICU admissions with alcoholic liver disease increased from 0.65% in 1996 to 1.35% in 2005, but the case mix remained similar. Mortality decreased and length of stay increased over this period. The extrapolated total number of admissions to all 229 adult, general critical care units in England and Wales increased from 550 in 1996 to 1513 in 2005, and the extrapolated total number of bed-days occupied by these admissions increased from around 3100 to over 10,000. CONCLUSIONS Admissions to ICUs in England and Wales with alcoholic liver disease tripled over the 10-year period from 1996 to 2005. The continuing increase in alcohol consumption means that this trend is likely to continue.