Addition of Neostigmine and Atropine to Conventional Management of Postdural Puncture Headache

A Randomized Controlled Trial

Ahmed Abdelaal Ahmed Mahmoud, MD, FCAI; Amr Zaki Mansour, MD; Hany Mahmoud Yassin, MD; Hazem Abdelwahab Hussein, MD; Ahmed Moustafa Kamal, MD; Mohamed Elayashy, MD, FCAI; Mohamed Farid Elemady, MD; Hany W. Elkady, MD; Hatem Elmoutaz Mahmoud, MD; Barbara Cusack, LRCP&SI, MB MCh, NUI, MCAI; Hisham Hosny, MD; Mohamed Abdelhaq, MD


Anesth Analg. 2018;127(6):1434-1439. 

In This Article


During the study period, 3462 parturients had cesarean deliveries, 619 (17.9%) had general anesthesia, and 2843 (82.1%) had spinal anesthesia. Of those with spinal anesthesia, 312 (11%) developed PDPH. Only 98 patients, 31.4% of 312 patients who developed PDPH and 3.5% of the spinal anesthesia patients, reported a VAS score ≥5 and were assessed for study eligibility. Two patients were excluded because of a history of migraine headache, and 6 patients refused participation. Of the remaining 90 participants, 45 were assigned to the neostigmine/atropine group and 45 were assigned to the placebo group. Four participants in the neostigmine/atropine group and 1 in the placebo group were excluded because they were treated at other hospitals and discontinued the study intervention. Forty-one participants in neostigmine/atropine group and 44 in the placebo were evaluated (Consort Flowchart and Supplemental Digital Content 1, Figure 1, The participant characteristics and the onset of headache are shown in Table 1. None of the between-group differences were significant.

The estimated mean difference of the main outcome, VAS, between groups was −2.56 (95% confidence interval [CI], −3.09 to −2.02, P< .001), which indicates a significant difference between groups with a significant overall treatment effect. As shown in Table 2, the median difference (with 95% CI) for VAS between the neostigmine/atropine and the placebo group at all the measurements from 0 to 72 hours was derived by Hodges–Lehmann estimate. The reduction in VAS after intervention from baseline at all predetermined evaluations from 6 to 72 hours was significant in both groups (linear mixed-effects repeated measures model with baseline covariate adjustment, P< .001). The VAS was significantly lower in the neostigmine/atropine group than in the placebo group at each measurement between 6 and 72 hours, P< .001 (Supplemental Digital Content 2, Figure 2, There was no interaction between group and time (P = .259).

All patients in the neostigmine/atropine group achieved a VAS ≤ 3 after 2 doses; none experienced a recurrent headache, and none received an EBP because they failed to report a VAS ≥ 5. Seven patients in the placebo group (15.9%) were treated for persistent PDPH and a VAS ≥ 5 after 72 hours (P = .008; Table 3). Six of the 7 cases treated with EBP had an adequate response (VAS < 5); 1 case required a second EBP. No EBP-related complications were reported. There were no differences in the incidence of neck stiffness and nausea and vomiting in the 2 groups at 72 hours following intervention (Table 3).

Binary logistic regression found no differences in the incidence of neck stiffness (odds ratio, 2.33; 95% CI, 0.33–16.18; P = .39) or nausea and vomiting (odds ratio, 1; 95% CI, 0.199–5.01; P> .99; Table 4).

The incidence of abdominal cramps (8 participants, 19.5% versus none, P = .002), muscle twitches (6 participants, 14.6% versus none, P = .008), and urinary bladder hyperactivity (5 participants, 12.2% versus none, P = .016) was higher in the experimental group than in the placebo group. The occurrence of diarrhea, bronchospasm, and muscle cramps was comparable in the 2 groups (Table 5).