Ann Thorac Surg 2006;81:190
© 2006 The Society of Thoracic Surgeons
Original article: Cardiovascular
Mark Stecker, MD, PhD
Department of Neurology, Geisinger Medical Center, 100 N Academy Rd, Danville, PA 17822
This study  is important for a number of reasons. Most significant is the demonstration in this and a series of other experimental studies of a reliable, reproducible animal model in which the effects of various interventions on neurologic outcome after hypothermic circulatory arrest (HCA) can be tested. Assessing the magnitude of the effects of different interventions in this stable model will be very important in developing optimal intraoperative cerebral protection strategies.
The fundamental problem for clinicians raised by this experiment is knowing when the effects of an intervention in an animal study should trigger additional studies or change the clinical practice. Deciding what action to take depends on more than finding a statistically significant effect. It is also necessary to understand: (1) if the mechanism, whereby the intervention exerts its effects, makes sense based on human pathophysiology; (2) if the intervention is likely to be practical in humans; (3) if the type of effect demonstrated is likely to be clinically significant; and (4) if the intervention shows large enough effects to be clinically significant.
The administration of hypertonic saline solutions is practical and effective in humans when cerebral edema is the primary mechanism of injury, but evidence for efficacy in other conditions is weak when cerebral edema is a secondary mechanism of injury. In humans, ischemia can occur with HCA and may result in cerebral edema although the edema is typically maximal many hours to days after surgery and is not commonly severe in adults. In addition, the effect of saline dextran infusion in this study on behavioral scores is only present on the second day after surgery and does not persist to the end of the 7-day study period as would be desirable in clinical practice. Finally, although the histopathologic scores showed a statistically significant improvement with the saline dextran infusion, the use of multiple outcome measures tends to increase the probability of type I errors unless a multivariable statistical approach is used.
Thus the data in this study is too preliminary to consider clinical applications at this point. However, this and other carefully performed studies by the authors hold great promise. It will be especially important for the authors to not only look for statistically significant effects of interventions, but to compare the magnitude of effect produced by a test intervention with the magnitude of the effect produced by an intervention, such as temperature, that is well studied in humans. This will allow clinicians to more readily understand the impact of the animal studies.
- Kaakinen T, Alaoja H, Heikkinen J, et al. Hypertonic saline dextran improves outcome after hypothermic circulatory arresta study in a surviving porcine model. Ann Thorac Surg 2006;81:183-190.[Abstract/Free Full Text]