1. Impact Of Intensity Of Glucose Control On Lactate Levels In Children After Cardiac Surgery
Fule BK1, Kanthimathinathan HK3 Gan CS1, Davies P2, Laker S1, Morris KP1
1Paediatric Intensive Care Unit, 2Statistics Advisory Service , Birmingham Children’s Hospital, Birmingham UK, 3Paediatric Intensive Care Unit, Evelina London Children’s Hospital, UK,
Introduction
Increased lactate is commonly seen following cardiac surgery, is associated with hyperglycaemia and does not necessarily reflect worse outcome1. A previous paediatric RCT suggested lower lactate levels when tight glycaemic control was targeted compared to normal glucose control2.
The mechanism by which insulin lowers lactate levels could relate to a reduction of glucose as a metabolic substrate for lactate production. Non-metabolic effects of insulin (ameliorating inflammatory response, improving tissue perfusion) could also play a role in decreasing lactate levels.
Aim
We investigated the effect of a more intensive blood glucose (BG)/insulin algorithm on post-operative blood lactate levels in children undergoing cardiac surgery.
Method
A sub-group of children recruited into a randomised trial (CHiP3) comparing tight glycaemic control (TGC) (insulin if BG > 7 mmol/l) with normal control (insulin if BG > 12 mmol/l) were studied.
Inclusion criteria were the following:
Admission post cardiac surgery
Recruitment within 6 hours of PICU admission
Initial blood glucose > 7mmol/L
Blood gas data available
Glucose and lactate levels were averaged for +/- 2 hours around 0, 6, and 12 hour time-points after randomisation.
Two sample t-tests were performed to compare changes in lactate and glucose, for the whole patient cohort and subsequently for sub-groups according to their initial BG level (Group 1: 7-12mmol/L, Group 2: >12mmol/L).
Results
Data from 71 patients (38 TGC, 33 normal), age 5 days to 14 years were analysed.
Admission hyperglycaemia was associated with admission hyperlactataemia (p<0.001).
Children in the TGC group experienced a larger fall in blood glucose at 6 hours (p=0.03) , this was more evident in those in Group 2 (p<0.001) (Figure 1 & 2)
TGC compared to normal glucose control was not associated with lower lactate levels in the whole study population (p=0.33 at 6 hours and p=0.23 at 12 hours) (Figure 1)
However within Group 2 (initial BG >12 mmol/L) there was a trend towards lower levels of lactate in the TGC group (p=0.06 at 6 hours and p=0.13 at 12 hours).
Conclusion
This analysis of a sub-group of patients recruited to the CHiP trial within our hospital was unable to demonstrate a significant link between a more rapid reduction in blood glucose and lactate in all children randomised to TGC.
A number of factors may explain why we could not confirm the association demonstrated by Vlasselaers:
smaller study population
specific patient group (cardiac surgery)
different glucose targets in the treatment arms
lower doses of insulin used.
Our data suggest that an association may exist within a sub-set of patients who have more pronounced hyperglycaemia, requiring higher doses of insulin.
Further study is needed to investigate the potential mechanisms involved.
References
1. Jackman L et al Intensive Care Med (2009) 35:537–545
2. Vlasselaers D et al The Lancet, (2009) 663:
3. Macrae D et al N Engl J Med. (2014) 370(2):
Figure 1
Change in glucose and lactate levels (mmol/l) from randomisation to 6 and 12 hours.
Data shown as mean (95% CI)
Figure 2
Group 1
Group 2
Change in glucose and lactate levels (mmol/l) from randomisation to 6 and 12 hours. Data shown as mean (95% CI) and displayed separately for Group 1 (initial BG 7-12 mmol/l) and Group 2 (BG > 12 mmol/l).