ExpToxicPathoI1999;51: 151-162 URBAN & FISCHER IDepartment of Anaesthesiology, Johannes Gutenberg University, Mainz, Germany Departments of 2Neurology, 3Pathology, and 4Anaesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD, USA Poor outcome after hypoxia-ischemia in newborns is associated with physiological abnormalities during early recovery Possible relevance to secondary brain injury after head trauma in infants ANSGAR M. BRAMBRINK 1 , REBECCA N. ICHORD 2 , LEE J. MARTIN 3 , RAYMOND C. KOEHLER 4 , and RICHARD J. TRA YSTMAN 4 Address for correspondence: ANSGAR M. BRAMBRINK, M.D., Department of Anaesthesiology, Johannes Gutenberg Uni- versity Mainz, LangenbeckstraBe 1, D - 55131 Mainz, Germany; e-mail: brambrin@mail.uni-mainz.de Key words: Brain injury, infants; Head trauma; Hypoxia, brain injury; Ischemia, brain injury; Newborns, brain injury. Summary "Secondary hypoxia/ischemia" (i.e. regional impairment of oxygen and substrate delivery) results in secondary dete- rioration after traumatic brain injury in adults as well as in children and infants. However, detailed analysis regarding critical physiological abnormalities resulting from hypo- xia/ischemia in the immature brain, e.g. acid-base-status, serum glucose levels and brain temperature, and their in- fluence on outcome, are only available from non-traumatic experimental models. In recent studies on hypoxic/asphyxic cardiac arrest in neonatal piglets, we were able to predict short-term outcome using specific physiologic abnormalities immediately after the insult. Severe acidosis, low serum glucose levels and fever after resuscitation were associated with an adverse neurologic recovery one day after the insult. The occurrence of clinically apparent seizure activity during later recovery increased mortality (epileptic state), and survivors had greater neocortical and striatal brain damage. Brain damage after transient hypoxia/ischemia and "se- condary brain injury" after head trauma may have some me- chanistic overlap, and these findings on physiological pre- dictors of outcome may also apply to pathologic conditions in the post-traumatic immature brain. Evaluation of data from other models of brain injury will be important to develop candidate treatment strategies for head-injured infants and children and may help to initiate specific studies about the possible role of these physiological predictors of brain damage in the traumatically injured immature brain. Introduction Traumatic brain injury in infants, as in adults, results from (1) direct impact injury, (2) indirect ("secondary") injury related to hypermetabolism and impaired local sub- strate delivery [i.e. ischemia and/or hypoxia], (3) reactive ("delayed") inflammation mediated by immune com- petent cells and (4) delayed retrograde neurodegeneration in locations remote from the impact site. Children and infants who suffer severe traumatic brain injury need immediate treatment by several different spe- cialists, e.g. emergency physicians, anaesthesiologists, and intensive care physicians. Although the primary im- pact injury cannot be rescued, all subsequent medical interventions have to prevent further exacerbation or pro- gression of cerebral injury and aim to improve long term neurological outcome. Thus, protection against sub- sequent "secondary injury", i.e. hypoxic-ischemic and/or "delayed injury" due to inflammation and/or apoptotic neurodegenration (CONTI et a11998, MARTIN et al. 1998) is of key interest for the post traumatic treatment regime. Recently, a four year effort to develop empirical, evi- dence-based guidelines for the management of patients with severe head injury resulted in a list of recommen- dations (BULLOCK et al. 1996). These were generated by review of almost 3000 articles, thus based solely on pub- lished literature. The final report was peer-reviewed, then formally accepted by the American Association of Neu- rological Surgeons and is now endorsed by the World Health Organisation's Neurotrauma Subcommittee. Three issues are considered of paramount interest to improve outcome in head injured patients. (l) The existence of an organised trauma care system generally results in a favourable outcome of patients after traumatic brain injury (SMITH et al. 1990, Thompson et al. 1992). An optimal trauma care system includes promptly available specialists, i.e. emergency physicians, ana- esthesiologists, trauma surgeons, neurosurgeons, critical care physicians; and appropriate and continuously staffed facilities, i.e. computed tomography (CT) scanner, opera- ting rooms, an intensive care unit and laboratory, 0940-2993/99/51/02-151 $ 12.00/0 151