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

Disclosures

Anesth Analg. 2018;127(6):1434-1439. 

In This Article

Results

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, http://links.lww.com/AA/C542). 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, http://links.lww.com/AA/C543). 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).

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