3 General methods 62
3.2 Severity scoring 66
After enrolment to either of the clinical studies, the severity of critical illness and any lung injury was calculated by a number of schemes, as outlined below. The purpose of these schemes is to classify disease severity to enable clearer analysis of effects of treatment, and to take into account multiple factors, impacting on survival.
3.2.1
APACHE-‐II
The acute physiology and chronic health evaluation (APACHE) system of scoring critically ill patients is a well established and validated system of severity assessment now in its 4th incarnation as APACHE IV. The system was originally developed in 1981 as APACHE, and updated in 1985 to APACHE II, which remains the most commonly used system. In APACHE-‐II 12 variables are each assigned a score from 0 to 4 depending on the most abnormal measurement in the 1st 24 hours of their ITU stay. Scores are also added to account for the variables of age, past medical history and presence of a surgical condition. This leads to a score between 0 and 71, higher scores indicating an increasing severity and risk of death. The APACHE scoring system is widely used in clinical studies as a marker of disease severity in critically ill patients. 189
3.2.2
The SAPS-‐2 score
The Simplified acute physiology score version 2 (SAPS-‐2) is a physiological disease severity index that uses acute physiological measurements and chronic health status together with the context of the ICU admission to give a score that correlates well to mortality outcomes. It has been developed from logistic regression analysis of a large cohort of critically ill patients.190
3.2.3
SOFA score
The sequential organ system failure assessment (SOFA) is a severity score designed to classify the degree of organ failure a patient suffers whilst critically ill. Organ function in the respiratory, cardiovascular, hepatic, coagulation, neurological and renal systems is assigned a score between 0 and 4. Higher total scores are associated with worse outcomes.191 See table 3.2.
An independent research group found excellent correlations with outcome: a minimum SOFA score greater than 9 in patients over the age of 60 had 100% specificity for death.192 Other groups have found that this score is useful in the quantification of both organ failure on admission to the intensive care unit, and that which develops during the ICU stay, again giving good predictive values for patient outcomes.193 Another study showed that the sequential calculation of this score gave a meaningful prediction of outcome, as not only were high initial scores prognostic of poor outcome, but a deterioration in the initial SOFA score over the first few days of ICU admission was also associated strongly with death.194 When serial SOFA scores were combined with
APACHE-‐2 scores the prognostic prediction is better than with either scoring system alone.195
Table 3.2 Components of the sequential organ failure assessment (SOFA) score Score 0 1 2 3 4 P:F Ratio (kPa) > 53.3 < 53.3 < 40 < 26.6 < 13.3 Platelets (109 mm-3) > 150 < 150 <100 <50 <20 Bilirubin (mmol L-‐1) < 20 20-‐32 33-‐101 102-‐204 >204 GCS 15 13-‐14 10-‐12 6-‐9 <6 Creatinine (mmol L-‐1) OR urine output (ml/day) < 110 110-‐170 171-299 300-‐440 >440 < 500 < 200 Hypotension (infusion rate in ml/kg/min) None MAP<70 mmHg DA <5 DB -‐any dose DA > 5 Adr < 0.1 NA < 0.1 DA > 15 Adr > 0.1 NA > 0.1 MAP= mean arterial pressure, DA= dopamine, DB=dobutamine, Adr= adrenaline, NA=noradrenaline
3.2.4
Murray Lung Injury Score (LIS)
The Murray lung injury score was derived as a tool to predict clinical outcomes in patients with ARDS, as part of an attempt to tighten the definition of ARDS by leading researchers into the condition.147 The score is a calculated by the sum of individual scores for each feature (CXR appearance, hypoxia, positive end-‐expiratory pressure and compliance) divided by the number of features that made up the score. More than one study has failed to show that the LIS is a
predictor of mortality,196, 197 however for patients with a score greater than 2.5 it does predict those likely to follow a complicated course.198
Table 3.3 Components of the Murray lung injury score (LIS) CXR Score
0 No alveolar consolidation
1 Alveolar consolidation confined to 1 quadrant 2 Alveolar consolidation confined to 2 quadrants 3 Alveolar consolidation confined to 3 quadrants 4 Alveolar consolidation in all 4 quadrants Hypoxia score
0 PaO2 / FiO2 > 40 kPa 1 PaO2 / FiO2 30 – 40 kPa 2 PaO2 / FiO2 23.3 – 29.9 kPa 3 PaO2 / FiO2 13.3 – 23.2 kPa 4 PaO2 / FiO2 < 13.3 kPa
Positive end expiratory pressure score (when ventilated) 0 < 5 cm H2O
1 6-‐8 cm H2O 2 9-‐11 cm H2O 3 12-‐14 cm H2O 4 > 15 cm H2O
Respiratory system compliance
0 >80 ml / cm H2O 1 60-79 ml / cm H2O 2 40-59 ml / cm H2O 3 20-39 ml / cm H2O 4 < 19 ml / cm H2O
3.2.5
GOCA
The GOCA scoring system is specifically designed for the characterisation of disease in patients suffering from ARDS, and was advocated by the AECC. This scoring system incorporates the most important factors that influence prognosis in ARDS, and is named by the abbreviation of these components: Gas exchange, organ failure, cause and associated disease. See table 3.4. This system has been designed, not to predict mortality, but to standardise reporting of the spectrum of ARDS.199 Consistent with its design it has been shown to perform less well in mortality prediction than the APACHE-‐2
and SAPS-‐2 scoring systems.200 In this investigation it has been used to characterise the demographics of the patients.
Table 3.4 the components of the GOCA classification of ARDS