Musings on hypertension in pregnancy
Dr Mike Khoury
Sure, that pun makes no sense. If you can think of something better (help with HELLP?), I’d like to hear from you. There are plenty of resources out there about managing these conditions, both in the community and in hospitals. They vary somewhat but there’s a general consensus about keeping systolic blood pressure below 140mmHg, preventing seizures, and delivering babies safely and emergently if you can’t do both of those things.
If you want to know, and you should, check out RANZCOG’s official recommendation.
But I wanted to speak on some of the more quizzical parts of the syndrome. Things I would sit there pondering for hours on end in a fellowship study session, fully knowing everyone else is thinking the same thing but is too embarrassed to ask.
What does “eclampsia” mean?
You’d be right to think you’ve never seen another word that looks remotely like this in medicine. It’s modern Latin by way of medieval French who in turn borrowed it from the Ancient Greeks. It’s initial form, “eklampein” meant to “shine.” It eventually came to be “eklampsis,” which was their word for “sudden light” (aka lightning) – and gradually became applied to the sudden onset convulsions seen in pregnant women. Take home message, it’s the Greek word for lightning. I presume that pre-eclampsia is therefore the Greek word for “thunder” – but only if the storm is moving away from you, I guess.
Why is magnesium sulfate measured in grams instead of millimoles like in every other treatment regime?
A ten millimole vial of magnesium sulfate is roughly equivalent to 2.5 grams. The MAGPIE trial, conducted in England in 2002, used 5g ampoules of the stuff. That’s simply how the drug company decided to package it. They used ⅘ of it (4g) in the trial but that’s how it came out of the box. I’ve asked six obstetricians about this – five said it never crossed their minds, and the sixth said that the 10mmol is used for replacement therapy whereas the higher-dose “gram” ampoules (henceforth known as “grampoules”) are resuscitative. It’s worth noting that the vials do state both units on them.
Maybe this isn’t super important, but this is how my mind works.
1g of MgSO4 = 98.6mg elemental Mg = 8.12 mEq elemental Mg = 4.06 mmol Mg
What did the MAGPIE study show, anyway?
Magpies are horrible. According to www.magpiealert.com, which is a completely real website, 68% of swooping victims are cyclists. According to an unsourced ABC article from October 2020, 60 eye-related magpie injuries presented to Victorian hospitals in 2020.
But I digress.
The MAGPIE study(1) recruited 10,141 women across 33 countries, at greater than twenty weeks gestation, with systolic blood pressure greater than 140mmHg and another clinical feature of pre-eclampsia (usually proteinuria). Women allocated magnesium sulphate had a 58% lower risk of eclampsia than those allocated placebo. A follow up study determined that the intervention posed no risk to the foetus.
Want a bit more geeky detail on MAGPIE?
- Multi-centre, international, randomised, placebo controlled trial
- P: Women with pre-eclampsia in whom there was uncertainty about whether to use magnesium sulphate
- Included regardless of whether they had received another anti-convulsive therapy
- I: IV Magnesium Sulphate 4g loading dose followed by 24 hour maintenance at 1g/hr (or 5g IM into each buttock followed by 5g IM q4h x24h)
- C: Placebo (normal saline)
- O: Eclampsia (and, if randomised before delivery, death of baby before hospital discharge)
- Powered to find 50% decrease in risk of convulsions and 15% reduction in baby mortality (Target n = 10800-12750)
- 10141 patients randomised → 10110 kept to analysis
- Less eclamptic seizures in treatment group – 0.8% vs 1.6% or 11 fewer eclampsia per 1000 patients (95% CI 7-16, p <0.0001).
- 58% (CI 40-71%) lower RR giving a NNT of 91 (CI 63-143)
- In patients with severe pre-eclampsia NNT 63 | Non-severe NNT 109
- No difference in baby mortality (12.7% for intervention vs 12.4% for placebo)
Pre-eclampsia can be treated in the community in low-risk, closer-to-twenty-weeks patients provided close monitoring is possible. More specifically, these patients have “pregnancy-induced hypertension” – effectively the same thing but without the additional symptoms (proteinuria, clonus, headaches, and so on). These patients can be treated with everyone’s favourite slow-release dihydropiridine calcium channel blocker, nifedipine. But some hospitals advocate for methyldopa, which sounds like a nu-metal band from a small town in Indiana and seems, honestly, just as obscure.
So, I went hunting for some evidence. A paper published in the AHA’s Hypertension journal in 2008 by Podymow and August entitled “Update on the Use of Antihypertensive Drugs in Pregnancy” summed it up fantastically. Methyldopa, 0.5 to 3 grams per day (in two doses) has an excellent safety profile to the foetus. Nifedipine, as you may recall, can inhibit labour.
That’s all I’ve got for today.
If you came here looking for a management flow chart, Queensland Health has already perfected it, so have a look here.
- Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. The Lancet. 2002 Jun;359(9321):1877–90.
Mike is a senior registrar at the Alfred currently sitting his fellowship exams. He is apologetically Canadian – sorry. His medical interests are junior teaching, environmental medicine and retrieval. Outside of medicine, he likes to repeat his own jokes – sorry.