Protecting the infant brain during cardiac surgery: a systematic review

Abstract

Prevention of brain injury during congenital heart surgery has focused on intraoperative and perioperative neuroprotection and neuromonitoring. Many strategies have been adopted as "standard of care." However, the strength of evidence for these practices and the relationship to long-term outcomes are unknown. We performed a systematic review (January 1, 1990 to July 30, 2010) of neuromonitoring and neuroprotection strategies during cardiopulmonary bypass (CPB) in infants of age 1 year or less. Papers were graded individually and as thematic groups, assigning evidence-based medicine and American College of Cardiology/American Heart Association (ACC/AHA) level of evidence grades. Consensus scores were determined by adjudication. Literature search identified 527 manuscripts; 162 met inclusion criteria. Study designs were prospective observational cohort (53.7%), case-control (21.6%), randomized clinical trial (13%), and retrospective observational cohort (9.9%). Median sample size was 43 (range 3 to 2,481). Primary outcome was evidence of structural brain injury or functional disability (neuroimaging, electroencephalogram, formal neurologic examination, or neurodevelopmental testing) in 43%. Follow-up information was reported in only 29%. The most frequent level of evidence was evidence-based medicine level 4 (33.3%) or ACC/AHA class IIB: level B (42%). The only intervention with sufficient evidence to recommend "the procedure or treatment should be performed" was avoidance of extreme hemodilution during CPB. Data supporting use of current neuromonitoring and neuroprotective techniques are limited. The level of evidence is insufficient to support effectiveness of most of these strategies. Well-designed studies with correlation to clinical outcomes and long-term follow-up are needed to develop guidelines for neuromonitoring and neuroprotection during CPB in infants.

Fig. 1

Search strategy and manuscript selection for inclusion. Cardiac surgery/perfusion strategy: Heart surgery, heart disease, cardiac surgery, heart defect, cardiopulmonary bypass, cardiopulmonary bypass, deep hypothermic circulatory arrest, deep hypothermic circulatory arrest, regional cerebral perfusion, antegrade cerebral perfusion, antegrade cerebral perfusion, regional low flow perfusion, regional low-flow perfusion, intermittent cerebral perfusion, intermittent perfusion, selective cerebral perfusion, retrograde cerebral perfusion, cerebral blood flow velocity, cerebral autoregulation, cerebral passive perfusion. Neuromonitoring: Near-infrared spectroscopy, monitoring, transcranial Doppler, electroencephalography, electroencephalogram, bispectral indices, neuromonitoring, oximetry, jugular venous oximetry, jugular bulb oximetry, optical spectroscopy. Neuroprotection/neuroinjury: brain, neurologic, neuroprotection, neurobehavioral, neurocognitive, cerebral protection, stroke, seizure, disability, developmental disability, neurocognitive testing, choreoathetosis, neurologic injury, brain injury, brain ischemia, cerebral embolus, cerebral thrombosis, air embolus, periventricular leukomalacia, sinovenous thrombosis, sagittal sinus thrombosis, white matter injury, grey matter injury, cortical injury, cerebral infarction, arterial ischemic stroke, watershed infarction, intracerebral hemorrhage, intraparenchymal hemorrhage, Bayley scales of infant development. Medications: phenobarbital, erythropoietin, allopurinol, aprotinin, tranexamic acid, steroids, methylprednisolone, hematocrit, dexamethasone, hemodilution, hypothermia, nasopharyngeal temperature. Search limit: humans, clinical trial, meta-analysis, practice guideline, comparative study, controlled clinical trial, guideline, journal article, multicenter study, English, core clinical journals, all infant (birth to 12 months), publication date from January 1, 1990 to July 30, 2010.

Fig. 2

Distribution of (A) American College of Cardiology/American Heart Association classification, and (B) evidence-based medicine grade for individual manuscripts. (RCT = randomized controlled trial.)