Elevated Intraoperative Serum Lactate During Craniotomy Is Associated With New Neurological Deficit and Longer Length of Stay.

BACKGROUND: Hundreds of thousands of craniotomies are performed annually in the United States. During craniotomy, elevated serum lactate is a concerning and not infrequent occurrence. Elevated intraoperative serum lactate may occur as a result of global hypoperfusion or localized intracerebral ischemia from surgical retraction or inadequate blood supply. The distinction between systemic and hypoperfusion confined to the brain is important because the treatment differs. For example, fluid resuscitation may be indicated in the former but not the latter. METHODS: To address whether elevated intraoperative serum lactate is associated with hypoperfusion confined to the brain or systemic hypoperfusion, we performed a retrospective cohort study of elective adult (age above 18) craniotomy cases. These included 436 surgeries which were performed at our institution under general anesthesia between May 2011 and August 2013. RESULTS: Elevated intraoperative serum lactate in craniotomy patients is associated with new neurological deficits (odds ratio, 2.11) and longer length of stay (20% less likely to be discharged on a given day). Elevated lactate was not associated with systemic complications such as myocardial infarction or mortality. CONCLUSIONS: Our findings highlight the importance of conducting a definitive prospective study analyzing the clinical impact and mechanism behind hyperlactatemia in the craniotomy population. Knowledge of the serum lactate level may be of value in guiding intraoperative anesthetic and surgical decision-making.

Comprehensive analyses of ventricular myocyte models identify targets exhibiting favorable rate dependence.

Reverse rate dependence is a problematic property of antiarrhythmic drugs that prolong the cardiac action potential (AP). The prolongation caused by reverse rate dependent agents is greater at slow heart rates, resulting in both reduced arrhythmia suppression at fast rates and increased arrhythmia risk at slow rates. The opposite property, forward rate dependence, would theoretically overcome these parallel problems, yet forward rate dependent (FRD) antiarrhythmics remain elusive. Moreover, there is evidence that reverse rate dependence is an intrinsic property of perturbations to the AP. We have addressed the possibility of forward rate dependence by performing a comprehensive analysis of 13 ventricular myocyte models. By simulating populations of myocytes with varying properties and analyzing population results statistically, we simultaneously predicted the rate-dependent effects of changes in multiple model parameters. An average of 40 parameters were tested in each model, and effects on AP duration were assessed at slow (0.2 Hz) and fast (2 Hz) rates. The analysis identified a variety of FRD ionic current perturbations and generated specific predictions regarding their mechanisms. For instance, an increase in L-type calcium current is FRD when this is accompanied by indirect, rate-dependent changes in slow delayed rectifier potassium current. A comparison of predictions across models identified inward rectifier potassium current and the sodium-potassium pump as the two targets most likely to produce FRD AP prolongation. Finally, a statistical analysis of results from the 13 models demonstrated that models displaying minimal rate-dependent changes in AP shape have little capacity for FRD perturbations, whereas models with large shape changes have considerable FRD potential. This can explain differences between species and between ventricular cell types. Overall, this study provides new insights, both specific and general, into the determinants of AP duration rate dependence, and illustrates a strategy for the design of potentially beneficial antiarrhythmic drugs.