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Systematic review and meta-analysis
Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), Wijaya et al. from the Universitas Pelita Harapan, Tangerang, Banten, Indonesia, Cedars-Sinai Medical Center, Los Angeles, CES University, El Poblado, Medellín, Antioquia, Colombia. collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords [“tranexamic acid” and “meningioma”] and its synonyms from Cochrane Central Register of Controlled Trials Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusion, anesthesia duration, surgical duration, and complication rate. Each included study’s quality was assessed using the JADAD scale.
For qualitative and quantitative data synthesis, they included five RCTs (n = 321) with a mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. The meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]).
The current study showed that TXA was associated with reduced intraoperative blood loss and intraoperative and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable 1).
Randomized controlled trials
Patients with supratentorial meningiomas and deemed suitable for surgical resection will be recruited in the trial. Patients will be randomized to receive either a single administration of 20 mg/kg TXA or a placebo of the same volume with a 1:1 allocation ratio after anesthesia induction. The primary endpoint is the cumulative incidence of early postoperative seizures within 7 days after craniotomy. Secondary outcomes include the incidence of non-seizure complications, changes in hemoglobin level from baseline, intraoperative blood loss, erythrocyte transfusion volume, Karnofsky Performance Status, all-cause mortality, length of stay, and total hospitalization cost.
Ethics and dissemination: This trial is registered at ClinicalTrial.gov and approved by the Chinese Ethics Committee of Registering Clinical Trials (ChiECRCT20200224). The findings will be disseminated in peer-reviewed journals and presented at national or international conferences relevant to the subject fields.
Trial registration number: NCT04595786 2).
conducted a prospective, randomized double-blind clinical study. The patient scheduled to undergo excision of intracranial meningioma were randomly assigned to receive intraoperatively either intravenous TXA or placebo. Patients in the TXA group received an intravenous bolus of 20 mg/kg over 20 min followed by an infusion of 1 mg/kg/h up to surgical wound closure. Efficacy was evaluated based on total blood loss and transfusion requirements. Postoperatively, thrombotic complications, convulsive seizure, and hematoma formation were noted.
Ninety-one patients were enrolled and randomized: 45 received TXA (TXA group) and 46 received placebo (group placebo). Total blood loss was significantly decreased in the TXA group compared to the placebo (283 ml vs. 576 ml; P < 0.001). Transfusion requirements were comparable in the two groups (P = 0.95). The incidence of thrombotic complications, convulsive seizure, and hematoma formation were similar in the two groups.
TXA significantly reduces intraoperative blood loss but did not significantly reduce transfusion requirements in adults undergoing resection of intracranial meningioma 3).
Thirty patients aged 18-65 years undergoing elective meningioma resection surgery were given either tranexamic acid or placebo (0.9% saline), tranexamic acid at a loading dose of 20 mg/kg, and infusion of 1 mg/kg/h during surgery. The intraoperative blood loss, coagulation profile, and the surgical field using the Likert scale were assessed.
The patients in the tranexamic group had significantly decreased intraoperative blood loss compared to the placebo group (616.42 ± 393.42 ml vs. 1150.02 ± 416.1 ml) (P = 0.02). The quality of the surgical field was better in the tranexamic group (median score 4 vs. 2 on Likert Scale) (P < 0.001). Patients in the tranexamic group had an improved coagulation profile and decreased blood transfusion requirement (p=0.016). The blood collected in the closed suction drain in 24 h postsurgery was less in the tranexamic acid group compared to the placebo group (84.7 ± 50.4 ml vs. 127.6 ± 62.2 ml) (P = 0.047).
Tranexamic acid bolus followed by infusion reduces perioperative blood loss by 46.43% and blood transfusion requirement with improved surgical field and coagulation profile in patients undergoing intracranial meningioma resection surgery 4).
In the Department of Neurosurgery, All India Institute of Medical Sciences (AIIMS), New Delhi, India, Sixty adults undergoing elective craniotomy for meningioma excision were randomized to receive either tranexamic acid or placebo, initiated prior to skin incision. Patients in the tranexamic acid group received an intravenous bolus of 20mg/kg over 20min followed by an infusion of 1mg/kg/h till the conclusion of surgery. Intraoperative blood loss, transfusion requirements, and estimating surgical hemostasis using a 5-grade scale were noted. Postoperatively, the extent of tumor excision on CT scan and complications were observed. Demographics, tumor characteristics, amount of fluid infusion, and duration of surgery and anesthesia were comparable between the two groups. The amount of blood loss was significantly less in the tranexamic acid group compared to the placebo (830mlvs 1124ml; p=0.03). The transfusion requirement was less in the tranexamic acid group (p>0.05). The patients in the tranexamic acid group fared better on a 5-grade surgical hemostasis scale with more patients showing good hemostasis (p=0.007). There were no significant differences between the groups regarding the extent of tumor removal, perioperative complications, hospital stay, or neurologic outcome. To conclude, the administration of tranexamic acid significantly reduced blood loss in patients undergoing excision of meningioma. Fewer patients in the tranexamic acid group received blood transfusions. Surgical field hemostasis was better achieved in patients who received tranexamic acid 5).
A man in his 40s with a history of coronary artery disease previously treated with a drug-eluting stent presented for elective craniotomy and resection of an asymptomatic but enlarging meningioma. During his craniotomy, he received desmopressin and tranexamic acid for surgical bleeding. Postoperatively, the patient developed chest pain and was found to have an ST-elevation myocardial infarction (MI). Because of the patient’s recent neurosurgery, standard post-MI care was contraindicated and he was managed symptomatically in the intensive care unit. The echocardiogram on a postoperative day 1 demonstrated no regional wall motion abnormalities and an ejection fraction of 60%. His presentation was consistent with the thrombosis of his diagonal stent. He was transferred out of the intensive care unit on postoperative day 1 and discharged home on postoperative day 3 6).
Raghavendra et al. report the intraoperative use of tranexamic acid to secure complete hemostasis as a rescue measure in intracranial meningioma resection in uncontrollable bleeding 7).
Three of 13 patients with intracranial meningiomas showed the pre-and postoperative elevation of tissue-type plasminogen activator (t-PA) related fibrinolytic activity in euglobulin fractions (EFA). During the operation, two of these three patients showed a significant elevation of the level of fibrinogen degradation products and oozing in the operating field. However, oozing was not observed in the third patient who had been given tranexamic acid preoperatively. Fibrin autography revealed that a broad lytic band of mol wt 50-60 kDa, probably free t-PA, appeared in the plasma obtained from two of the three patients after the operation when EFA elevated significantly. In all patients studied, the t-PA antigen levels were normal preoperatively but increased both during and after the operation, and correlated mainly with the intensities of a lytic band of mol wt 110 kDa, probably t-PA complexed with its major inhibitor (PAI-1). These results suggest that excessive fibrinolysis can induce local hemorrhagic diathesis during operation and may be related to t-PA function in plasma 8).