Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial

Abstract

Background: Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences.

Methods: Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume.

Results: Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm³ (interquartile range (IR): 0.0-2.35) in the rIPC group compared with 1.30 cm³ (IR: 0.29-3.66) in the control group (p = 0.09).

Conclusions: Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery.

Trial registration: German Clinical Trials Register, DRKS00010409 . Retrospectively registered on 13 October 2016.

Keywords: Brain metastasis; Brain tumor; Glioma; Ischemic preconditioning; Neurooncology; Neurosurgery; Stroke.

Fig. 1

a shows a postoperative subtraction, b a postoperative diffusion-weighted image (DWI, b 1000), and c the corresponding apparent diffusion coefficient (ADC) map. Images a–c show an example of a postoperative ischemia with restricted diffusion in the genu of the corpus callosum in a patient diagnosed with an anaplastic oligodendroglioma

Fig. 2

Flowchart of the trial profile. One hundred seven patients were assessed for eligibility, of whom 60 were included and randomly assigned to one of two treatment groups (29 patients in the rIPC group and 31 patients in the control group). Two patients were excluded after randomization: early postoperative MRI was not evaluated in 2 patients in the rIPC group. Therefore, 58 patients were assessed for occurrence of postoperative ischemia

Fig. 3

Ischemic preconditioning and postoperative ischemic lesions: the bar graph shows the incidence of new ischemic lesions in both treatment groups. The incidence of postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27). Pearson chi-square test, p = 0.03

Fig. 4

Ischemic preconditioning and infarct volume: the boxplot shows the median infarct volume in both treatment groups. The median infarct volume was 0.36 cm³ (IR: 0.0–2.35) in the rIPC group compared with 1.30 cm³ (IR: 0.29–3.66) in the control group. Mann-Whitney U test, p = 0.09