A guest post by Rory Spiegel (@CaptainBasilEM) who blogs on nihilism and the art of doing nothing at emnerd.com.
Kids are just small adults, or so says the Control of Hyperglycemia in Pediatric Intesive Care (ChiPS) trial. This impressively large RCT of 1369 pediatric ICU patients (under 16 years old) requiring at least 12 hours of vasoactive support and mechanical ventilation, examined how controlling blood glucose levels affects outcomes. Subjects were randomized to either tight glucose control (72-126mg/dL) or conventional control (less than 216 mg/dL). Patients were followed for 30 days to see if mortality and rates of ventilator dependence differed between the two groups.
Simply put the trial was negative. Though the tight glucose control group received more insulin and had lower mean daily blood glucose levels during the first 10 days after randomization, there was no statistical difference between days alive and off the ventilator between the two groups. Patients in the tight glycemic control group were less likely to receive renal replacement therapy (an odds ratio of 0.64 CI 0.45-0.89), but conversely were far more likely to suffer an episode of severe hypoglycemia (below 36mg/dL) with an absolute difference of 4.8%.
Unfortunately thanks to the authors’ spectacular display of subgroup analysis there is nothing simple about this publication. 60% of the population was admitted to the ICU after cardiac surgery. The remaining 40% were there for other reasons, though further details were not specified. A multitude of endpoints in both the cardiac and non-cardiac subgroups were examined. As with the entire cohort, there was no difference in mortality or ventilator-free days in either subgroup. The authors did observe a decrease in length of stay and mean healthcare costs in the subgroup of patients who did not undergo cardiac surgery and were treated using the tight glycemic parameters.
Though the authors conclude that these findings are at best hypothesis building and should not be used to guide therapy, this subgroup analysis will inevitably be misinterpreted, suggesting that pediatric ICU patients who have not undergone cardiac surgery will benefit from a strict glycemic regimen. This is clearly not the case. What this trial amounts to is a negative study with both negative primary and secondary endpoints that upon subgroup analysis uncovered statistical differences equally likely to be caused by chance as by the aggressive glucose management.
This trial is a reminder of our continued insistence of applying disease-oriented outcomes with questionable efficacy over the long term to an acutely ill population. The NICE-SUGAR trial established that tight glucose control was detrimental in an acutely ill adult population, the ChiP trial has demonstrated these lessons can now be applied to our smaller counterparts.
“A Randomized Trial of Hyperglycemic Control in Pediatric Intensive Care” www.ncbi.nlm.nih.gov/pubmed/24401049