Questions. Background to the ICNARC Case Mix Programme

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Length of stay, survival and organ support of admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland Questions What were the length of stay, survival and organ support of admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland participating in the Case Mix Programme (CMP) from 1 January 2012 to 31 December 2012? Background to the ICNARC Case Mix Programme The Intensive Care National Audit & Research Centre (ICNARC) was established in 1994 on a two-year (1994-1995), pump-priming grant from the Department of Health (England) and Welsh Health Common Services Authority (Wales), ICNARC became an independent Registered Charity in July, 1994 (Registered Charity Number: 1039417). ICNARC s aim is to foster improvements in the organisation and practice of adult critical care (intensive and high dependency care) to improve patient care and outcomes. Towards achieving part of this aim, ICNARC coordinates a national, comparative audit of patient outcomes from adult, critical care units in England, Wales and Northern Ireland known as the Case Mix Programme (CMP). Currently, 95% of adult, general critical care units in England, Wales and Northern Ireland are participating in the CMP. The CMP is a voluntary, performance assessment programme using high quality clinical data to facilitate local quality improvement through routine feedback of comparative outcomes and key quality indicators to clinicians/managers in adult critical care units. The CMP recruits predominantly adult, general critical care units. Adult, general critical care units are defined as either standalone intensive care units (ICUs) or combined intensive care/high dependency units (ICU/HDUs). Participation in the CMP is entirely voluntary. CMP specified data are recorded prospectively and abstracted retrospectively by trained data collectors according to precise rules and definitions - set out in the ICNARC Case Mix Programme Dataset Specification. Data collectors from each unit are trained prior to

commencing data collection with retraining of existing staff, or training of new staff, also available. CMP training courses are held at least four times per year. CMP specified data are collected on consecutive admissions to each participating critical care unit and are submitted to ICNARC quarterly. Data are validated locally, on data entry, and then undergo extensive central validation, for completeness, illogicalities and inconsistencies, with data validation reports returned to units for correction and/or confirmation. The validation process is repeated until all queries have been resolved and then the data are incorporated into the CMP Database (CMPD). Participating units receive comparative data analysis reports on outcomes and key quality indicators, in which they can identify their own unit data and compare with all units participating in the CMP. In addition, staff at units can interrogate the CMPD by submitting analysis requests which are provided free-of-charge. Data collected for the CMP include alphanumeric unit/admission identifiers, demographics (e.g. age, sex, ethnicity), case mix (e.g. acute severity, comorbidity, surgical status, reason for admission), outcome (e.g. unit/acute hospital survival) and activity (e.g. unit/acute hospital length of stay) for each admission to each critical care unit. Available data for report 136,880 admissions to 205 critical care units 1 January 2012 31 December 2012 Selection of Cases All admissions with septic shock to adult, general critical care units (i.e. excluding admissions to specialist critical care units or standalone high dependency units) in England, Wales and Northern Ireland that were participating in the CMP from 1 January 2012 to 31 December 2012.

Definitions for variables included Sepsis was defined as meeting at least three of the four systemic inflammatory response syndrome (SIRS) criteria during the first 24 hours following admission to the critical care unit, plus evidence of infection from the primary or secondary reason for admission to the critical care unit. Severe sepsis was defined as sepsis (as above) plus the presence of at least one organ dysfunction during the first 24 hours following admission to the critical care unit. Septic shock was defined as severe sepsis (as above) including the presence of cardiovascular organ dysfunction. Physiological definitions of the SIRS criteria and organ dysfunctions were matched as closely as possible to those used in the PROWESS trial. 1 These definitions are summarised in Table 1. The definitions have been modified slightly from those used in previous publications from the CMPD, 2,3 to ensure compatibility across versions of the Case Mix Programme Dataset. Age was defined as the age in whole years on the date of admission to the critical care unit. The critical care unit length of stay was the duration in days from the date and time of admission to the critical care unit to the date and time of discharge from the critical care unit or the date and time of death. The post-unit acute hospital length of stay was the duration in days from the date and time of discharge from the critical care unit to the date and time of death or discharge from acute hospital. The total acute hospital length of stay was the duration in days from the date of original admission to an acute hospital to the date of ultimate discharge from an acute hospital or death. The number of organs supported was defined as the number of organ systems (out of basic or advanced respiratory, basic or advanced cardiovascular, neurological and renal) for which the number of calendar days of support was at least one, as per the Critical Care Minimum Data Set (CCMDS) definitions. Admissions with renal dysfunction were defined as those with a renal SOFA 4 score of 2, 3 or 4. Admissions with renal failure were defined as those with a renal SOFA 4 score of 3 or 4. 1 Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344:699 709. 2 Padkin A, Goldfrad C, Brady AR, Young D, Black N, Rowan K. Epidemiology of severe sepsis occurring in the first 24 hrs in intensive care units in England, Wales, and Northern Ireland. Crit Care Med 2003; 31:2332 8. 3 Harrison DA, Welch CA, Eddleston J. 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. Crit Care 2006; 10:R42. 4 Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H et al. The SOFA (Sepsisrelated Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996;22:707 10

An admission was identified as receiving renal support if the number of calendar days of renal support (recorded for the CCMDS) was at least 1. One calendar day of renal support was considered to be renal support at any point in a calendar day (00:00 to 23:59) with any part-days considered as total calendar days. Admissions with respiratory dysfunction were defined as those with a respiratory SOFA 4 score of 2, 3 or 4. Admissions with respiratory failure were defined as those with a respiratory SOFA 4 score of 3 or 4. An admission was identified as receiving advanced respiratory support if the number of calendar days of advanced respiratory support (recorded for the CCMDS) was at least 1. One calendar day of advanced respiratory support was considered to be advanced respiratory support at any point in a calendar day (00:00 to 23:59) with any part-days considered as total calendar days. Critical care unit mortality was defined as the status at discharge from the critical care unit. Post-unit mortality was defined as the status at ultimate discharge from acute hospital, wherever, for those patients who survived their first admission to critical care. Acute hospital mortality was defined as the status at ultimate discharge from acute hospital, wherever. Table 1: Definitions of the criteria for systemic inflammatory response syndrome (SIRS), infection, and organ dysfunction used in the PROWESS trial and in the Case Mix Programme Database (CMPD); Severe sepsis was considered to be present if all three were satisfied and septic shock was considered to be present if all three were satisfied and cardiovascular organ dysfunction was present SIRS PROWESS trial 1 Satisfaction of SIRS criteria required three of the following to be present within a 24-hour period: CMPD Satisfaction of SIRS criteria required three of the following to be present within the first 24 hours in the critical care unit: Temperature Heart rate Respiratory Core temperature >38.0 C or <36.0 C. If only oral or axillary temperature available, 0.5 C added to measured value. Hypothermia must be confirmed by a rectal or central temperature. >90 beats min -1. If patients have a medical condition or are receiving treatment that would prevent tachycardia, patient only needed to meet two of the remaining SIRS criteria. >20 breaths min -1 or PaCO 2 <32 mmhg Central temperature >38.0 C or <36.0 C. If only non-central temperature available, 0.5 C added to measured value. Hypothermia must be confirmed by a central temperature. >90 beats min -1. If heart block or myxoedema is recorded reason for admission, only two of the remaining SIRS criteria need be met. >20 breaths min -1 or PaCO 2 <32 mmhg

rate White cell count Infection Organ dysfunction Cardiovascular PROWESS trial 1 or mechanical ventilation for an acute process. >12,000 mm -3 or <4,000 mm -3 or >10% immature neutrophils on a differential count. Known or suspected infection. Satisfaction of organ dysfunction criteria required at least one of these to have been induced by sepsis and present for >24 hours: SBP <90 mmhg or MAP <70 mmhg for 1 hour despite adequate fluid resuscitation or use of vasopressors in an attempt to maintain SBP >90 mmhg or MAP >70 mmhg. Adequate resuscitation defined as an intravenous fluid bolus (e.g., >500 ml crystalloid) over 30 mins or pulmonary artery occlusion pressure >12 mmhg or central venous pressure >8 mmhg. CMPD (<4.3 kpa) in a non-ventilated admission or mechanical ventilation in the first 24 hours in an admission not previously receiving home ventilation. >12,000 mm -3 or <4,000 mm -3. Diagnosis of infection as primary or secondary reason for ICU admission. Satisfaction of organ dysfunction criteria required at least one of these to be present during the first 24 hours in critical care: SBP <90 mmhg or MAP <70 mmhg. Renal Respiratory Hematological Metabolic Urine output <0.5 ml kg -1 body weight for 1 hour, despite adequate fluid resuscitation. If pre-existing renal impairment (creatinine >twice upper limit normal) prior to onset of sepsis, admission needed to meet another organ dysfunction criteria. PaO 2 /FiO 2 ratio <250 mmhg. If the lung is the sole organ meeting an organ dysfunction criterion, in addition to being the suspected site of infection, the PaO 2 /FiO 2 ratio must be <200 mmhg. Platelet count <80,000 mm -3 or a 50% decrease from the highest value in the previous 3 days. ph <7.30 or base deficit <5.0 mmol l -1 in association with a plasma lactate >1.5 times the upper limit of normal. Mean hourly urine output <0.5 ml kg -1 body weight in the first 24 hours in critical care or for the duration of stay if <24 hours in critical care. If on chronic renal replacement therapy, admission needed to meet another organ dysfunction criteria. Body weight is assumed to be 70kg. PaO 2 /FiO 2 ratio <250 mmhg (<33.3 kpa). If the lung is the sole organ meeting an organ dysfunction criterion and primary/secondary reason for admission to the unit indicated lung infection, PaO 2 /FiO 2 must be <200 mmhg (<26.6 kpa). Platelet count <80,000 mm -3. Base deficit <5.0 mmol l -1. CMPD, Case Mix Programme Database; SIRS, systemic inflammatory response syndrome; SBP, systolic blood pressure; MAP, mean arterial pressure

Results Table 2: Number and case mix of admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland participating in the CMP 1 January 2012 31 December 2012 Number of admissions with septic 22,081 (16.1) [136,880] shock (%) [N] Age, [N] [22,081] 64.0 (16.7) 67 (54,77) Gender, males (%) [N] 11,605 (52.6) [22,081] N: number of admissions; SD: standard deviation; IQR: interquartile range. Table 3: Unit mortality and acute hospital mortality of admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland participating in the CMP 1 January 2012 31 December 2012 Critical care unit mortality, deaths 6,100 (27.6) [22,081] (%) [N] Post-unit mortality*, deaths (%) 1,952 (13.2) [14,777] [N] Acute hospital mortality*, deaths 7,724 (37.6) [20,549] (%) [N] N: number of admissions; SD: standard deviation; IQR: interquartile range. *Excluding readmissions to the critical care unit

Table 4: Organ dysfunction and support for admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland participating in the CMP Number of organs supported, [N] Number with renal dysfunction (SOFA score 2, 3 or 4), n (%) [N] All Unit survivors Unit non-survivors Number with renal failure (SOFA score 3 or 4), n (%) [N] All Unit survivors Unit non-survivors Number receiving renal support, n (%) [N] Days of renal support (all) Unit survivors, [N] Unit non-survivors, [N] Days of renal support (receivers) Unit survivors, [N] Unit non-survivors, [N] Number with respiratory dysfunction (SOFA score 2, 3 or 4), n (%) [N] All Unit survivors Unit non-survivors Number with respiratory failure (SOFA score 3 or 4), n (%) [N] All Unit survivors Unit non-survivors Number receiving advanced respiratory support, n (%) [N] 1 January 2012 31 December 2012 [22,080] 2.1 (0.6) 2 (2,2) 8,158 (36.9) [22,081] 4,672 (29.2) [15,981] 3,486 (57.1) [6,100] 5,214 (23.6) [22,081] 2,564 (16.0) [15,981] 2,650 (43.4) [6,100] 4,440 (20.1) [22,081] [22,080] 1.1 (3.4) 0 (0,0) [15,980] 0.9 (3.1) 0 (0,0) [6,100] 1.7 (4.0) 0 (0,2) [4,440] 5.4 (5.9) 3 (2,7) [2,309] 5.9 (6.1) 4 (3,7) [2,131] 4.8 (5.6) 3 (2,6) 17,340 (78.5) [22,081] 11,857 (74.2) [15,981] 5,483 (89.9) [6,100] 8,017 (36.3) [22,081] 4,714 (29.5) [15,981] 3,303 (54.1) [6,100] 13,797 (62.5) [22,081]

Days of advanced respiratory support (all) [22,080] 4.8 (9.0) 2 (0,5) Unit survivors, [N] [15,980] 4.6 (9.0) 1 (0,5) Unit non-survivors, [N] [6,100] 5.2 (9.1) 2 (1,6) Days of advanced respiratory support (receivers) [13,797] 7.7 (10.4) 4 (2,9) Unit survivors, [N] [9,004] 8.2 (10.7) 4 (2,10) Unit non-survivors, [N] [4,793] 6.7 (9.8) 3 (2,8) N: number of admissions; SD: standard deviation; IQR: interquartile range.

Table 5: Length of stay of admissions with septic shock to adult, general critical care units in England, Wales and Northern Ireland participating in the CMP 1 January 2012 31 December 2012 Critical care unit length of stay (days) All, [N] Unit survivors, [N] Unit non-survivors, [N] Post-unit length of stay* (days) Acute hospital survivors, [N] Acute hospital nonsurvivors, [N] Acute hospital length of stay* (days) Acute hospital survivors, [N] Acute hospital nonsurvivors, [N] [22,079] 7.6 (10.7) 4.1 (1.9,9.0) [15,979] 8.2 (10.8) 4.7 (2.4,9.6) [6,100] 5.9 (10.1) 2.4 (0.9,7.1) [14,471] 23.3 (31.4) 13 (6,28) [12,521] 23.6 (31.6) 14 (7,28) [1,950] 21.2 (29.8) 10 (3,27) [20,446] 28.3 (36.1) 17 (8,35) [12,730] 34.8 (39.1) 23 (13,43) [7,716] 17.5 (27.2) 9 (3,21) N: number of admissions; SD: standard deviation; IQR: interquartile range. *Excluding readmissions to the critical care unit

Acknowledgement Please acknowledge the source of these data in all future presentations (oral and/or written), as follows: These data derive from the Case Mix Programme Database. The Case Mix Programme is the national, comparative audit of patient outcomes from adult critical care coordinated by the Intensive Care National Audit & Research Centre (ICNARC). These analyses are based on data for 136,880 admissions to 205 adult, general critical care units based in NHS hospitals geographically spread across England, Wales and Northern Ireland. For more information on the representativeness and quality of these data, please contact ICNARC.