Lead author Abdelaal Ahmed Mahmoud, MD, FCAI, Faculty of Medicine, Department of Anesthesiology, Beni-Suef University, Beni Suef, Egypt, and affiliated with the Department of Anesthesia, Tallaght University Hospital, Dublin, Ireland, along with colleagues from the Departments of Anesthesiology in both Cairo University, Giza, Egypt, and Fayoum University, Faiyum, Egypt, explored the potential role that the combination of neostigmine/atropine may play as an intervention administered to patients experiencing postdural puncture headache (PDPH). PDHP is a predictable adverse effect of lumbar puncture that is thought to be caused by intracranial hypotension due to reduced cerebrospinal fluid pressure. Brain and spinal trauma, in addition to craniotomy and placement of ventricular shunts, have also been associated with PDHP.

The team conducted a randomized, controlled, double-blind study in which they compared 41 patients assigned to receive atropine (atropine 10 ug/kg) and neostigmine (20 ug/kg) and compared them with 44 patients who received an equal volume of placebo (saline). Using visual analog scales, the team measured a pain score goal of ≤3 at various times, including 6, 12, 24, 36, 48, and 72 hours. The reports of nausea, vomiting, need for an epidural blood patch, and neck stiffness were also considered as secondary outcomes.  

Pain scores were statistically better in patients receiving neostigmine/atropine at all time points measured (P <0.001) and no epidural blood patches where needed when compared to the saline only group, where 7 of the 44 patients required this additional intervention. There were no clinically significant nor statistically significant differences in nausea, vomiting, or neck stiffness between the groups; however; there was a statistically significant increase in adverse effects associated with neostigmine/atropine administration that included urinary bladder spasm, gastrointestinal cramping, and muscle twitching (P <0.01).

Researchers concluded that the administration of neostigmine/atropine in PDPH was effectively treated after only two doses (no patients required more than two doses). This beneficial effect was hypothesized to likely be due to the influence of both drugs on the secretion of CSF and, ultimately, cerebral vascular tone. Previous studies have focused on the use of neostigmine alone, which was unable to pass through the blood-brain barrier.

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