Research Reports - Effect of analgesics and sedatives on the occurrence of spreading depolarizations accompanying acute brain injury

Brain. 2012 Jun 19

Hertle DN, Dreier JP, Woitzik J, Hartings JA, Bullock R, Okonkwo DO, Shutter LA,

Spreading depolarizations are waves of mass neuronal and glial depolarization
that propagate across the injured human cortex. They can occur with depression of
neuronal activity as spreading depressions or isoelectric spreading
depolarizations on a background of absent or minimal electroencephalogram
activity. Spreading depolarizations are characterized by the loss of neuronal ion
homeostasis and are believed to damage functional neurons, leading to neuronal
necrosis or neurological degeneration and poor outcome. Analgesics and sedatives
influence activity-dependent neuronal ion homeostasis and therefore represent
potential modulators of spreading depolarizations. In this exploratory
retrospective international multicentre analysis, we investigated the influence
of midazolam, propofol, fentanyl, sufentanil, ketamine and morphine on the
occurrence of spreading depolarizations in 115 brain-injured patients. A surface
electrode strip was placed on the cortex, and continuous electrocorticographical
recordings were obtained. We used multivariable binary logistic regression to
quantify associations between the investigated drugs and the hours of
electrocorticographical recordings with and without spreading depolarizations or
clusters of spreading depolarizations. We found that administration of ketamine
was associated with a reduction of spreading depolarizations and spreading
depolarization clusters (P < 0.05). Midazolam anaesthesia, in contrast, was
associated with an increased number of spreading depolarization clusters
(P < 0.05). By using a univariate odds ratio analysis, we also found a
significant association between ketamine administration and reduced occurrence of
isoelectric spreading depolarizations in patients suffering from traumatic brain
injury, subarachnoid haemorrhage and malignant hemispheric stroke (P < 0.05). Our
findings suggest that ketamine-or another N-methyl-d-aspartate receptor
antagonist-may represent a viable treatment for patients at risk for spreading
depolarizations. This hypothesis will be tested in a prospective study.

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