Admissions with neutropenic sepsis in adult, general critical care units in England, Wales and Northern Ireland Question What were the: age; gender; APACHE II score; ICNARC physiology score; critical care unit and acute hospital mortality; critical care unit and acute hospital length of stay for adult, general critical care units in England, Wales and Northern Ireland participating in the Case Mix Programme (CMP) from April 2007 to September 2010 for each of the following groups? Admissions with neutropenic sepsis following chemotherapy compared to those with no recent chemotherapy Admissions with non-neutropenic sepsis following chemotherapy compared to those with no recent chemotherapy Admissions with neutropenic sepsis following chemotherapy who were ventilated in the first 24 hours, compared to those that were not ventilated in the first 24 hours Available data for report 303,314 admissions to 204 adult, general critical care units 1 April 2007 30 September 2010 Selection of Cases All admissions to adult, general critical care units (i.e. excluding admissions to specialist critical care units or standalone high dependency units) that were participating in the Case Mix Programme (CMP) from 1 April 2007 to 30 September 2010.
Definitions for variables included Age was calculated as the age in whole years at the point of admission to the critical care unit. The APACHE II and ICNARC physiology scores were calculated from raw physiology data using standardised computer algorithms. Admissions aged less than 16 years or staying less than 8 hours in the critical care unit were excluded from calculation of an APACHE II score. Critical care unit mortality was defined as the status at discharge from the critical care unit. Acute hospital mortality was defined as the status at ultimate discharge from acute hospital, wherever. The critical care unit length of stay was the duration in days and fractions of 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. An admission was identified as having neutropenic sepsis if they had severe sepsis (see definition below) and their lowest white blood cell count was less than 2. An admission was identified as having non-neutropenic sepsis if they had severe sepsis and their lowest white blood cell count was greater than or equal to 2. The Case Mix Programme Database (CMPD) contains data that were collected, primarily, for case mix adjustment. Virtually all of the admission data relates to the first 24 hours following admission to the critical care unit, with some data on medical history and reasons for admission. Thus, the CMPD can be used to identify admissions that had sepsis or severe sepsis at admission to the unit or that developed sepsis or severe sepsis during the first 24 hours in the unit, but cannot be used to identify admissions that developed sepsis or severe sepsis after the first 24 hours following admission to the unit. 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. 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. 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.
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 SIRS Temperature Heart rate Respiratory rate White cell count Infection Organ dysfunction Cardiovascular PROWESS trial 1 Satisfaction of SIRS criteria required three of the following to be present within a 24-hour period: 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 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 CMPD Satisfaction of SIRS criteria required three of the following to be present within the first 24 hours in the critical care unit: 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 (<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. 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.
PROWESS trial 1 CMPD >12 mmhg or central venous pressure >8 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: Descriptive statistics for admissions with neutropenic sepsis to adult, general critical care units in England, Wales and Northern Ireland, April 2007 to September 2010 Chemotherapy Number of neutropenic sepsis admissions 1,140 (35.3) (%*) [3,226] Age, mean (SD) 57.5 (14.9) 61 (50, 68) Gender, number of males (%) 645 (56.6) APACHE II score, mean (SD) 27.9 (6.3) 27 (24, 31) [1,104] ICNARC physiology score, mean (SD) 28.1 (10.2) 27 (20, 35) No Chemotherapy 1,743 (4.6) [37,706] 61.3 (17.1) 64 (51, 75) 901 (51.7) 23.4 (7.3) 23 (18, 28) [1,623] 31.1 (10.3) 31 (23, 38)
Critical care unit mortality, deaths (%) 508 (44.6) Acute hospital mortality**, deaths (%) 588 (55.1) [1,068] Unit length of stay (days), Total acute hospital length of stay (days)**, Number of admissions receiving ventilatory support within the first 24 hours of their stay in the unit (%) [632] 2 (1, 5) [508] 3 (1, 8) 29 (15, 51) [480] 13 (3, 28) [588] 20 (7, 37.5) [1,068] 495 (43.4) 856 (49.1) 973 (58.2) [1,672] 7 (3, 16) [887] 1 (1, 4) [856] 3 (1, 10) 31 (18, 52) [699] 5 (1, 14) [973] 14 (3, 33) [1,672] 1,291 (74.1) IQR: interquartile range; N: number of admissions; SD: standard deviation * Percentage of sepsis admissions by chemotherapy status ** Excluding readmissions to the critical care unit during the hospital stay Excluding admissions aged less than 16 years or staying less than 8 hours in the critical care unit Table 3: Descriptive statistics for admissions with non-neutropenic sepsis to adult, general critical care units in England, Wales and Northern Ireland, April 2007 to September 2010 Chemotherapy Number of non-neutropenic sepsis admissions 2,086 (64.7) (%*) [3,226] Age, mean (SD) 60.9 (13.7) 63 (54, 71) Gender, number of males (%) 1,242 (59.5) APACHE II score, mean (SD) 23.8 (6.3) 23 (19, 27) [2,040] ICNARC physiology score, mean (SD) 22.5 (9.0) 21 (16, 28) Critical care unit mortality, deaths (%) 772 (37.0) Acute hospital mortality**, deaths (%) 930 (53.0) [1,756] No Chemotherapy 35,963 (95.4) [37,706] 63.1 (16.9) 66 (53, 76) [35,963] 19,119 (53.2) [35,963] 19.3 (6.8) 19 (15, 23) [35,105] 22.7 (9.1) 22 (16, 28) [35,963] 9,750 (27.1) [35,962] 12,753 (38.9) [32,785]
Unit length of stay (days), Total acute hospital length of stay (days)**, Number of admissions receiving ventilatory support within the first 24 hours of their stay in the unit (%) [1,314] 3 (1, 8) [772] 27 (15, 49) [826] 12 (5, 24) [930] 18 (9, 36) [1,756] 1,097 (52.6) [2,084] 4 (2, 10) [26,211] 3 (1, 8) [9,749] [35,960] 23 (13, 44) [20,032] 10 (4, 23) [12,753] 18 (9, 36) [32,785] 21,265 (59.1) [35,960] IQR: interquartile range; N: number of admissions; SD: standard deviation * Percentage of sepsis admissions by chemotherapy status ** Excluding readmissions to the critical care unit during the hospital stay Excluding admissions aged less than 16 years or staying less than 8 hours in the critical care unit Table 4: Descriptive statistics for admissions with neutropenic sepsis following chemotherapy to adult, general critical care units in England, Wales and Northern Ireland, April 2007 to September 2010 Ventilated in the first 24 hours Number of neutropenic sepsis admissions post 495 (17.2) chemotherapy (%*) [2,883] Age, mean (SD) 57.8 (14.9) 61 (50, 69) Gender, number of males (%) 280 (56.6) APACHE II score, mean (SD) 30.0 (6.7) 30 (25, 33) [476] ICNARC physiology score, mean (SD) 33.9 (9.6) 33 (27, 41) Critical care unit mortality, deaths (%) 299 (60.4) Acute hospital mortality**, deaths (%) 314 (69.0) [455] Unit length of stay (days), 10 (5, 17.5) [196] Not Ventilated in the first 24 hours 645 (22.4) [2,883] 57.2 (14.8) 61 (50, 68) 365 (56.6) 26.4 (5.5) 26 (23, 29) [628] 23.7 (8.2) 22 (18, 28) 209 (32.4) 274 (44.7) [613] 3 (2, 6) [436]
Total acute hospital length of stay (days)**, 2 (1, 5) [299] 4 (1, 11) 39 (25, 70) [141] 11.5 (2, 25) [314] 19 (5, 37) [455] 3 (1, 6) [209] 3 (1, 6) 24 (12, 43) [339] 15 (4, 31) [274] 21 (9, 38) [613] IQR: interquartile range; N: number of admissions; SD: standard deviation * Percentage of neutropenic sepsis admissions ** Excluding readmissions to the critical care unit during the hospital stay Excluding admissions aged less than 16 years or staying less than 8 hours in 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 303,314 admissions to 204 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.