Maas MB, Jahromi BS, Batra A, et al. Magnesium and Risk of Bleeding Complications From Ventriculostomy Insertion. Stroke. 2020 Sep;51(9):2795-800
Reviewed by Wazim Mohamed, MD
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Hemorrhagic complications are principal mediators of poor neurological outcomes after any neurosurgical procedure and risk can be challenging to predict aside from overt coagulopathy. Magnesium’s role in hemostasis is well established. This observational, single-center study investigated the association between low magnesium and risk of catheter tract hemorrhage (CTH). Consecutive patients, over 12 years, presenting with intracerebral hemorrhage (ICH) or subarachnoid hemorrhage (SAH) requiring EVD placement who had magnesium level within 12 hours prior to EVD placement were included. EVD placement was per standard practices. Head CT obtained within 48 hours of EVD was compared to the pre procedure imaging for evaluation of CTH. The volume of CTH was calculated using semi-automated software. Magnesium levels in patients with and without CTH were compared using Wilcoxon rank-sum test and a logistic regression analysis was performed to evaluate the association between magnesium and CTH after correcting for covariates. Interactions between magnesium and other covariates including exposure to antiplatelet medications were assessed. The effect of change in magnesium levels from baseline was also assessed in a multivariable model.
327 patients were included in the study, 116 with ICH and 211 with SAH. All patients with prior anticoagulant use (13.9% ICH and 0.9% SAH) had their effects reversed prior to EVD insertion. EVDs were predominantly inserted at bedside (78%). The number of catheter passes was not recorded. CTH occurred in 50 (15.3%) patients (21 with ICH and 29 with SAH). The median CTH volume was 1.14 ml (0.41 – 4.32). A lower median magnesium level was seen in patients with CTH (1.8 [1.7-1.9] vs. 2.0 [1.8-2.2]; p<0.0001) which corresponded to an unadjusted OR 0.68 (95% CI 0.59-0.79; p<0.0001) per 0.1 mg/dL of magnesium. The adjusted model found an independent association between CTH and magnesium (OR 0.67 [95% CI 0.56-0.78]; p<0.001) which was also confirmed in separate models for ICH and SAH. Approximately one-third of the patients were on antiplatelet medications and 60% of those were transfused platelets while 19% were given desmopressin. An interaction was found between baselines magnesium level and antiplatelet exposure with a greater benefit in patients on antiplatelets (OR 0.75 [95% CI 0.62-0.89] vs. OR 0.62 [95% CI 0.39-0.92]). Among patients on antiplatelets, the effect of magnesium on CTH was deemed higher (OR 0.38 [95% CI 0.21-0.62]) per 0.1 mg/dL. Change in magnesium levels showed a similar effect on bleeding risk (OR 0.68 [95% CI 0.52–0.85] per 0.1 mg/dL; p=0.002) as baseline magnesium (OR 0.67 [95% CI 0.54–0.81]; p<0.001).
The authors conclude that lower baseline magnesium level was an independent predictor of catheter tract hemorrhage, an effect that was more prominent in patients on antiplatelets. Magnesium is essential for factor IX activity and accelerates factor X activation via the tissue factor-factor VIIa complex. It increases ADP expression and platelet aggregation in vitro, while decreasing the antithrombotic mechanisms mediated by protein C and S. These properties render magnesium as a modifiable risk factor to prevent bleeding complications during surgery. Importantly, magnesium sulfate is inexpensive and safe with a simple administration process. There have been multiple studies that demonstrate larger hematoma volumes, greater hematoma expansion and worse outcomes, including death, related to low magnesium levels.
This study is limited by its observational nature. It was also performed at a single center, academic institution with an advanced care delivery system, which is evident from the low complication rate and CTH reported. Most CTH reported were of smaller volumes, and the extent to which they may affect long-term outcomes is uncertain. Finally, the number of passes for EVD insertion was not available in this study, which may be a major confounder for developing CTH.
Overall, this article emphasizes the return to basics and focuses on easily modifiable risk factors to prevent adverse outcomes. Further studies, including meta-analyses, evaluating the role of magnesium for hemostatic efficacy in patients undergoing neurosurgical procedures, will be of interest to the community.