Lower levels of magnesium on hospital admission for intracerebral hemorrhage (ICH) are associated with larger hematoma volumes and growth, as well as worse functional outcomes at 3 months, suggesting an important role of magnesium in coagulation and hemostasis, according to new research.
“In our study, the lower the magnesium level at the time of presentation to the emergency room, the larger the hematomas, the greater the hematoma growth over the next several hours, and the worse the patient’s outcome tended to be,” first author, Eric M. Liotta, MD, assistant professor of neurology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois, told Medscape Medical News.
The study was published online August 22 in Neurology.
Important Role in Coagulation
For the study the investigators analyzed data on 290 patients presenting at Northwestern Memorial Hospital between November 2006 and March 2016 with spontaneous ICH.
The mean patient age was 65 years, and 52% of patients were female. The mean serum magnesium level was 2.0 ± 0.3 mg/dL.
After a multivariate adjustment for such factors as age, sex, hematoma location, and time from onset to initial computed tomography (CT), the researchers found that patients with lower admission magnesium levels were significantly more likely to have larger hematoma volumes upon initial presentation (P = .006), as well greater hematoma growth (P = .008) and larger final hematoma volumes (P = .002).
In addition, among those presenting within 6 hours of symptom onset (175 patients [60%]), lower magnesium levels at admission were linked to worse functional outcomes at 3 months (P = .01) after a multifactorial adjustment for age, Glasgow Coma Scale score on admission, initial hematoma volume, and time from symptom onset to CT.
Calcium deficiency has been thought to play a mechanistic role in the coagulation and platelet dysfunction that are known to worsen functional outcomes in ICH, and the new findings suggest magnesium may play even greater role, the authors note.
“[In addition to calcium], magnesium also plays an important role in coagulation through the tissue factor–activated factor VII pathway, factor IX, and platelet aggregation,” they write. “In fact, magnesium may have a more potent effect on platelet aggregation than calcium,” they add.
However, Dr Liotta noted that the findings don’t necessarily confirm a direct role of magnesium in hematoma growth and outcomes.
“It is possible that magnesium doesn’t play a direct role in the growth of the hematoma but is instead associated with some other harmful factor,” he said.
“[For instance], there is the possibility that large hemorrhages in the brain may absorb or consume magnesium from the blood stream as part of the process of stopping the hemorrhage, but I don’t have any evidence of that.”
Clinical Implications Unclear
Also unclear are the clinical implications, particularly regarding the key question of whether provision of magnesium to patients with low levels could affect outcomes.
Previous research examining magnesium administration in stroke patients has not shown benefits in functional outcomes. However, these studies have had various important caveats, including some focusing on patients with acute ischemic stroke, who would not have been expected to benefit from enhanced hemostasis. In other studies, magnesium was administered without regard to baseline serum levels.
The authors note that the recent Field Administration of Stroke Therapy – Magnesium (FAST-MAG) study, published in the New England Journal of Medicine in 2015, did “accomplish the impressive feat” of administering magnesium to suspected stroke patients in the hyperacute phase in the field before hospital admission, the authors said.
However, that study also failed to show a neuroprotective effect in reducing disability at 90 days.
Dr Liotta noted that more research is needed to provide the basis for any change in clinical approach for spontaneous ICH.
“Our study doesn’t provide evidence that increasing magnesium levels with an infusion would necessarily make a difference in patient outcome. Before we could start using magnesium as a therapy for intracerebral hemorrhage, we would still need to confirm our finding in another group of patients, identify the right patients to try magnesium in, identify the right dose of magnesium, and then study the effect of magnesium in a clinical trial; that’s a long process and a lot of work still needs to be done,” said Dr Liotta.
Nevertheless, the study should help get those wheels in motion, he added.
“We think this is an exciting study because it identifies a potential target for future investigation that could possibly develop in to a new therapy, and successful therapies for intracerebral hemorrhage have been hard to come by.”
New Possibilities
Commenting on the findings, neurologist Pierre Fayad, MD, director of the Nebraska Stroke Center at the University of Nebraska Medical Center in Omaha, and a fellow of the American Academy of Neurology, agreed that the findings could have important implications, once replicated.
“The study is quite provocative in that it opens up new possibilities for causation of worse outcomes after intracerebral hemorrhage,” he said.
“If confirmed, it will open up the possibility of a treatment for intracerebral hemorrhage, where none currently exists or is approved,” he added.
“Magnesium is cheap, easy to administer, and with few side effects. So, if proven, this could be a first treatment for stroke, and most EDs [emergency departments] and hospitals can use it overnight.”
The authors and Dr Fayad have disclosed no relevant financial relationships.
Neurology. Published online August 22, 2017. Abstract
For more Medscape Neurology news, join us on Facebook and Twitter
Tidak ada komentar:
Posting Komentar