Written by Clay Smith
Administration of neostigmine and atropine vs placebo, in addition to usual care for post-dural puncture headache (PDPH), was highly effective in this RCT involving healthy postpartum women.
Why does this matter?
There is little high quality evidence for medical treatment of PDPH. Neostigmine is an acetylcholinesterase inhibitor (increases acetylcholine), and atropine is an anticholinergic, primarily acting on muscarinic receptors. Why would someone be given a cholinergic and anticholinergic at the same time? Neostigmine is used for post-operative ileus to increase gut motility. Atropine is co-administered to reduce some of the side effects, like bradycardia, nausea, or increased secretions. The authors gave this combo to a patient with post-op ileus and PDPH, who was scheduled for a blood patch, and noted marked improvement in headache and no need for the blood patch. Had they stumbled upon something that might actually work for PDPH?
This will get you UP and going, literally
This was a RCT of 85 postpartum patients with PDPH who all received usual therapy, analgesics and IV hydration, and were randomized to receive slow IV injection of 20 μg/kg neostigmine and 10 μg/kg atropine in 20 mL of 0.9% saline given over 5 minutes every 8 hours or saline placebo. Patients were excluded who had only mild headache, chronic headaches, stroke, seizure, heart block, asthma, weight <50kg, or inability to take PO.
Pain measured on visual analog scale (VAS) ≤3 out of 10 was markedly better at all time points from 6 to 72 hours in the neo/atropine group. Pain relief was dramatic in the treatment arm. The placebo patients never had pain on VAS <5/10, whereas the neo/atropine group was down to 2/10 at 24h and 1/10 at 36-72h. No patients in the treatment arm needed a blood patch, vs. 16% in the placebo group. No patients in the placebo group had increased adverse effects; the treatment group had an increase in abdominal cramping, muscle twitching, and overactive bladder. None of the treatment arm patients needed more than 2 doses. So, how does this work? See the figure. The cholinergic agent, neostigmine increases CSF production and cerebral vasoconstriction and the anticholinergic agent, atropine, does the same via a different mechanism.
The biggest issue is generalizability. This was a highly select group of previously healthy postpartum women. It might be a good idea to wait until more is published in a larger, more diverse population before we jump into this. Neostigmine is not a benign drug and may cause profound bradycardia and bronchospasm in some patients.
Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache: A Randomized Controlled Trial. Anesth Analg. 2018 Aug 29. doi: 10.1213/ANE.0000000000003734. [Epub ahead of print]
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Reviewed by Thomas Davis