Abstract
IntroductionIntensive care unit mortality is strongly associated with organ failure rate and severity. The sequential organ failure assessment (SOFA) score is used to evaluate the impact of a successful tight glycemic control (TGC) intervention (SPRINT) on organ failure, morbidity, and thus mortality.MethodsA retrospective analysis of 371 patients (3,356 days) on SPRINT (August 2005 - April 2007) and 413 retrospective patients (3,211 days) from two years prior, matched by Acute Physiology and Chronic Health Evaluation (APACHE) III. SOFA is calculated daily for each patient. The effect of the SPRINT TGC intervention is assessed by comparing the percentage of patients with SOFA ≤5 each day and its trends over time and cohort/group. Organ-failure free days (all SOFA components ≤2) and number of organ failures (SOFA components >2) are also compared. Cumulative time in 4.0 to 7.0 mmol/L band (cTIB) was evaluated daily to link tightness and consistency of TGC (cTIB ≥0.5) to SOFA ≤5 using conditional and joint probabilities.ResultsAdmission and maximum SOFA scores were similar (P = 0.20; P = 0.76), with similar time to maximum (median: one day; IQR: [1,3] days; P = 0.99). Median length of stay was similar (4.1 days SPRINT and 3.8 days Pre-SPRINT; P = 0.94). The percentage of patients with SOFA ≤5 is different over the first 14 days (P = 0.016), rising to approximately 75% for Pre-SPRINT and approximately 85% for SPRINT, with clear separation after two days. Organ-failure-free days were different (SPRINT = 41.6%; Pre-SPRINT = 36.5%; P < 0.0001) as were the percent of total possible organ failures (SPRINT = 16.0%; Pre-SPRINT = 19.0%; P < 0.0001). By Day 3 over 90% of SPRINT patients had cTIB ≥0.5 (37% Pre-SPRINT) reaching 100% by Day 7 (50% Pre-SPRINT). Conditional and joint probabilities indicate tighter, more consistent TGC under SPRINT (cTIB ≥0.5) increased the likelihood SOFA ≤5.ConclusionsSPRINT TGC resolved organ failure faster, and for more patients, from similar admission and maximum SOFA scores, than conventional control. These reductions mirror the reduced mortality with SPRINT. The cTIB ≥0.5 metric provides a first benchmark linking TGC quality to organ failure. These results support other physiological and clinical results indicating the role tight, consistent TGC can play in reducing organ failure, morbidity and mortality, and should be validated on data from randomised trials.
Highlights
Intensive care unit mortality is strongly associated with organ failure rate and severity
To test the link between tight glycemic control (TGC) and sequential organ failure assessment (SOFA) score we developed the conditional probability of SOFA ≤5 given good control or P(SOFA ≤5 | cTIB ≥0.5)
For individual organ failures (IOF), Specialised Relative Insulin and Nutrition Titration (SPRINT) = 2,681 of (Max 5 × 3,356 total possible) or 16.0%, which was lower than Pre-SPRINT = 3,049 out of (5 × 3,211 total possible) or 19.0%, with (P < 0.0001). These results indicate that organ failures were reduced in both numbers and time over which failures were experienced with SPRINT
Summary
Intensive care unit mortality is strongly associated with organ failure rate and severity. Tight glycemic control (TGC) by intensive insulin therapy (IIT) has been successful at reducing mortality and/or organ failure in some prior studies [18,19,20,21]. It is interesting to note that while mortality was reduced for patients with length of stay three days or longer, differences in Kaplan-Meier plots do not appear before 10 to 15 days for these studies. These results suggest that earlier resolution of organ failure and dysfunction, and the resulting reduced morbidity, is a leading cause of at least part of the improvement. While some studies showed benefit from TGC, several others have not achieved similar results [25,26,27], and did not necessarily achieve (where reported) the same affect in mitigating organ failure
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