Cerebral oxygenation and energy metabolism in bacterial meningitis

Introduction: In a recent retrospective study of patients with severe bacterial meningitis we demonstrated that cerebral
oxidative metabolism was affected in approximately 50% of the cases. An increase of lactate/pyruvate (LP) ratio above
the upper normal limit, defined according to according to Reinstrup et al., indicates impaired cerebral oxidative
metabolism which in turn may be caused either by insufficient oxygenation or mitochondrial dysfunction. This study had
two primary objectives: Firstly to verify in a prospective study that cerebral energy metabolism is frequently impaired in
severe bacterial meningitis; secondly to examine whether it is correct to separate the diagnosis of cerebral ischemia
from mitochondrial dysfunction based exclusively on the biochemical pattern obtained during intracerebral microdialysis.
Method: A prospective clinical study including patients with severe community acquired bacterial meningitis admitted to
the Department of Infectious Diseases, Odense University Hospital, during the period January 2014 to June 2016. We
relate data from measurements of brain tissue oxygen tension (PbtO2) to simultaneously recorded data reflecting
cerebral cytoplasmic redox state evaluated from cerebral interstitial lactate/pyruvate (LP) ratio obtained by
microdialysis. Each patient was equipped with an IM3 Bolt Kit through a drill hole in the skull. An Intracranial pressure
(ICP) catheter, a PbtO2 probe and a Brain Microdialysis Catheter was inserted. The dialysates were collected in
microvials and analyzed for glucose, lactate, pyruvate, glutamate and glycerol every 60 minutes and LP ratio calculated.
Simultaneous measurements of PbtO2 and ICP were recorded.
Results: The study population included 9 patients. Median age was 69 years (range 56-76 years). In 5 patients the
bacterial meningitis was caused by S. pneumoniae, in another 2 patients it was caused by other strains of
streptococcus and in 2 patients the bacterial agent remained unknown. During the initial 3 hours of multi-modal
monitoring median ICP was 12 mmHg and median PbtO2 was 17 mmHg. During the period 24-48 hours after start of
monitoring median PbtO2 was 23 mmHg. Two patients exhibited normal LP ratios during the whole study period. Six
patients had LP ratios above 30 recardless of PbtO2 levels that were obtained simultaneously with normal or increased
levels of pyruvate and defined as mitochondrial dysfunction. In one patient a pattern indicating cerebral ischemia with
LP ratios above 30 and a decrease in PbtO2 was seen. Clinical outcome was evaluated utilizing Glasgow Outcome
Score (GOS) at three months after admittance and the median score was 3.
Conclusion: The present prospective study verifies that compromised cerebral energy metabolism is frequent in patients
with severe community acquired bacterial meningitis. The combined data obtained from simultaneous measurements of
PbtO2 and cerebral LP ratio supports the hypothesis that is possible to separate cerebral ischemia from mitochondrial
dysfunction from the biochemical pattern obtained by microdialysis, i.e. in ischemia the increase in LP ratio is
associated with a simultaneous decrease in pyruvate below normal limit while in mitochondrial dysfunction the increase
in LP ratio occurs at an unchanged or increase level of pyruvate.