Hyperlactatemia associated with elective tumor craniotomy: Protocol for an observational study of pathophysiology and clinical implications

Abstract

Hyperlactatemia occurs frequently after brain tumor surgery. Existing studies are scarce and predominantly retrospective, reporting inconsistent associations to new neurological deficits and prolonged hospital stay. Here we describe a protocol for a prospective observational study of hyperlactatemia during and after elective tumor craniotomy and the association with postoperative outcome, as well as selected pathophysiological aspects, and possible risk factors. We will include 450 brain tumor patients scheduled for elective craniotomy. Arterial blood samples for lactate and glucose measurement will be withdrawn hourly during surgery and until six hours postoperatively. To further explore the association of hyperlactatemia with perioperative insulin resistance, additional blood sampling measuring markers of insulin resistance will be done in 100 patients. Furthermore, in a subgroup of 20 patients, blood from a jugular bulb catheter will be drawn simultaneously with blood from the radial artery to measure the arterial to jugular venous concentration difference of lactate, in order to study the direction of cerebrovascular lactate flux. Functional clinical outcome will be determined by the modified Rankin Scale, length of stay and mortality at 30 days, 6 months, 1 year and 5 years. Clinical outcome will be compared between patients with and without hyperlactatemia. Multivariate logistic regression will be used to identify risk factors for hyperlactatemia. A statistical analysis plan will be publicized to support transparency and reproducibility. Results will be published in a peer-reviewed journal and presented at international conferences.

Fig 1. Timeline for patient inclusion and data collection.

Patients are assessed for study eligibility during their preoperative visit. Preoperative mRS is assessed upon study inclusion. Hourly blood gas test from arterial cannula (N = 450) and jugular vein (N = 20) throughout surgery, starting at skin incision, and continuing for 6 postoperative hours in the Post Anesthesia Recovery Unit. Additional analyses of insulin resistance measured perioperatively and before food intake, the day after surgery, in a subgroup of patients (N = 100). Continuous data collection from perioperative monitoring and patient journal until discharge from hospital. Follow-up mRS assessment 30 days after surgery. Mortality data are obtained from the Danish Cause of Death Register after 30 days, 6 months, 1 year and 5 years.