Abstract
OBJECTIVE:
To evaluate the efficacy of occipital nerve block compared with standard care, defined as acetaminophen with caffeine, for treatment of acute headache in pregnancy.
METHODS:
We conducted a single-center, unblinded, parallel, randomized controlled trial of pregnant patients with headache and pain score higher than 3 on the visual rating scale. Patients with secondary headache, preeclampsia, or allergy or contraindication to study medications were excluded. Participants were randomized to occipital nerve block or standard care (oral 650 mg acetaminophen and 200 mg caffeine). Crossover treatment was given at 2 hours and second-line treatment at 4 hours to those with worsening visual rating scale score or visual rating scale score higher than 3. The primary outcome was headache improvement to a visual rating scale score of 3 or lower within 2 hours of initial therapy. Secondary outcomes included serial visual rating scale scores, receipt of crossover or second-line therapy, patient satisfaction, and perinatal outcomes. Outcomes were assessed in an intention-to-treat analysis. We estimated that a sample of 62 would provide 80% power to detect a difference from 85% to 50% between groups.
RESULTS:
From February 2020 to May 2022, 62 participants were randomized to occipital nerve block (n=31) or standard care (n=31). Groups were similar except payer status. The primary outcome, headache improvement to visual rating scale score of 3 or lower, was not significantly different between groups (64.5% vs 51.6%, P=.30). The occipital nerve block group experienced lower median [interquartile range] visual rating scale scores at 1 hour (2 [0–5] vs 6 [2–7], P=.014), and more patients in the occipital nerve block group had visual rating scale scores of 3 or lower at 1 hour. Among patients receiving crossover treatment at 2 hours, the standard care group had a significantly lower visual rating scale score 1 hour after crossover to occipital nerve block than the occipital nerve block group receiving crossover to standard care (P=.028). There were no significant differences in second-line treatment, refractory headache, satisfaction, or complications. Patients receiving occipital nerve block delivered earlier (36.6 weeks vs 37.8 weeks), but preterm birth did not differ between groups.
CONCLUSION:
Occipital nerve block is an effective and quick-acting treatment option for acute headache in pregnancy.
CLINICAL TRIAL REGISTRATION:
Primary headaches (tension, migraine, and cluster) are common in the reproductive population. Eighty-eight percent of headaches in patients of reproductive age meet criteria for tension headache and 17% for migraine headache.1,2 Despite an anticipated improvement during pregnancy, primary headache disorders can initially present or worsen during pregnancy.3
Headache treatment during pregnancy is made more difficult by clinician discomfort with treatment options, concern for masking secondary headaches, and fear of potential fetal effects from headache treatments.4,5 As a result, treatment of headache disorders is often delayed during pregnancy, placing patients at increased risk for worsening of primary headache disorders and development of refractory headaches.6 Although there has been a recent push by both the American Headache Society and the American College of Obstetricians and Gynecologists to improve headache management in pregnancy, there continues to be a paucity of data on treatment options.7–9 Improvement in the diagnosis and treatment of headache has the potential to improve patient care and satisfaction and to reduce the progression of headache disorders.
Occipital nerve block is a well-established treatment for tension and migraine headache in the nonpregnant population with both abortive and prophylactic treatment benefits.10–16 Occipital nerve block is a safe, commonly performed procedure that involves a subcutaneous injection of local anesthetic with or without a steroid component bilaterally into the area around the occipital nerves.17 The local anesthetics typically used are lidocaine and bupivacaine, both of which are routinely used in the pregnant population with epidural placement. However, there is a gap in the literature on the efficacy and safety of occipital nerve block in pregnant individuals.18 Our previous systematic review identified no randomized trials evaluating occipital nerve block in pregnancy.9 Furthermore, a search of Clinicaltrials.gov revealed no other pertinent trials. Therefore, our objective was to evaluate the efficacy of occipital nerve block compared with standard care for the treatment of acute headache in pregnancy. We hypothesized that bupivacaine occipital nerve block compared with an oral cocktail of acetaminophen and caffeine would result in a greater proportion of pregnant patients with a satisfactory response to treatment.
METHODS
This is an open-label, parallel-design (based on CONSORT [Consolidated Standards of Reporting Trials] abstract guidelines), randomized controlled trial conducted at a single academic center evaluating headache response in pregnant people who received bupivacaine occipital nerve block compared with oral acetaminophen and caffeine.19 The trial was approved by the IRB (IRB-300003628) and registered with ClinicalTrials.gov (NCT03951649) before enrollment. A Data and Safety Monitoring Board including an obstetrician–gynecologist (ob-gyn), epidemiologist, and neonatologist with no ties to the study design or evaluation of results monitored patient safety. We enrolled pregnant people lrom February 2020 through May 2022. CONSORT guidelines were followed.19
All pregnant people, with documented fetal cardiac activity regardless of gestational age, who presented to the obstetric triage or antepartum units were screened for inclusion if headache symptoms were reported. Inclusion criteria were age 16 years or older, live intrauterine singleton pregnancy, and report of headache with a minimum pain score of 4 on a visual rating scale. Participants were excluded if they had any of the following: preexisting diagnosis of gestational hypertension or preeclampsia, blood pressure of 140/90 mm Hg or higher, new-onset focal neurologic symptoms, altered level of consciousness (defined as not being oriented to person, place, situation, or year), recent seizure, underlying brain abnormality associated with headache, fever, use of more than 3 g of acetaminophen within 24 hours, occipital nerve block in the past 3 months, reported allergy to study medications (bupivacaine, acetaminophen, or caffeine), or non–English-speaking (Appendix 1, available online at http://links.lww.com/AOG/D400).
The occipital nerve blocks were performed by ob-gyn residents and maternal–fetal medicine fellows. Before study initiation, participating ob-gyn residents and maternal–fetal medicine fellows underwent comprehensive occipital nerve block training by a board-certified neurologist, and competency was assessed before their participation in the trial by accurately simulating the procedure. To further ensure competency, the first occipital nerve block placed by each resident or maternal–fetal medicine fellow was observed by the principal investigator or a resident physician who had previously demonstrated clinical competency. Ongoing education was provided throughout the study period with biannual simulation. During the entirety of the trial, a physician was always available to administer occipital nerve block.
After providing informed consent, patients were randomized 1:1 to occipital nerve block (subcutaneous 5 mL of 5% bupivacaine in bilateral greater or lesser occipital notches) or standard care (oral 650 mg acetaminophen and 200 mg caffeine). Randomization was accomplished by a web-based randomization sequence using blocks of variable sizes and maintained centrally by the study statistician. Randomization group was revealed at the time treatment was started. Blinding was not performed.
For all participants, treatment was performed in the triage room or antepartum room in which the participant was admitted. Before headache treatment, a 10-point visual rating scale was obtained and recorded by research personnel. Treatment time was defined as the time at which the initial treatment was administered. For standard care, this was the time the medication was given; for occipital nerve block, this was the time the needle was inserted into the occipital notch. At 1 hour after treatment, a visual rating scale was obtained by nursing staff, medical students, resident physicians, or advanced practice clinicians. If headache pain resolved, defined as a visual rating scale score of 0, the participant was discharged to home (at the discretion of the managing team provided that there was no other indication for further observation or admission). If the headache persisted, the visual rating scale was assessed again 2 hours after primary treatment. If pain was not resolved or improved to mild range, defined as a visual rating scale score of 3 or lower, crossover treatment was administered. The visual rating scale was again obtained at 1 hour after crossover treatment; if pain was resolved (visual rating scale score 0), the participant was discharged to home. If pain continued to be present, a visual rating scale was obtained at 2 hours after crossover treatment. If pain was not resolved (visual rating scale score 0) or improved to mild pain (visual rating scale score 3 or lower), second-line treatment with oral promethazine 25 mg and diphenhydramine 25 mg was given. A visual rating scale again was obtained 1 hour after second-line treatment. If pain was not resolved or improved to mild pain (visual rating scale score 3 or lower) at 1 hour after second-line treatment, the attending physician was notified, and a neurology consult was placed per physician preference. If the patient developed new neurologic symptoms at any point during treatment, the study protocol was stopped, and emergency neurology consultation was requested.
The primary outcome, based on guidelines from the International Headache Society, was improvement of headache to mild range (visual rating scale score 3 or lower) at 2 hours after initial treatment.20 If the participant was discharged at the 1 hour time point as a result of headache resolution, the primary outcome was achieved. Additional prespecified outcomes included the following: response to treatment, defined by visual rating scale score at 1 hour after primary treatment; need for crossover treatment; response to crossover treatment at 1 and 2 hours; need for second-line treatment; response to second-line treatment at 1 hour; need for neurology consult; need for admission for treatment of headache; complications from treatment within 7 days; duration of headache resolution at 7 days; satisfaction with treatment at 7 and 28 days; re-presentation for treatment of headache within 28 days; development of hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia as defined per the American College of Obstetricians and Gynecologists within 28 days of treatment; mode of delivery (vaginal vs cesarean); gestational age at birth (weeks); and birth weight (grams).21
Trained research staff performed and recorded the initial screening, enrollment, informed consent, and randomization processes. Demographic data and medical history were abstracted from the chart. The primary outcome and secondary visual rating scale outcomes were collected at the time of assessment by clinical staff. Other secondary outcomes were collected by trained residents in obstetrics and gynecology and maternal–fetal medicine fellows (E.T.B., G.D.C., and A.M.D.) at 7 and 28 days by telephone assessment and chart review. All charts were reviewed by maternal–fetal medicine fellows after assigned estimated date of delivery to assess birth and neonatal outcomes. All data were entered into the electronic database by trained research staff or the three authors noted previously. REDCap (Research Electronic Data Capture), an established, secure, web-based data capture and management tool, was used for all data collection.
A sample size calculation based on the primary outcome was developed before study initiation. Sample size and power estimates were modeled with the assumption that pain improvement was a dichotomous outcome, with the end point being resolution of pain or improvement in pain to mild severity (visual rating scale score of 3 or lower). The improvement of headache with standard care (oral acetaminophen 500 mg, aspirin 500 mg, and caffeine 130 mg) has been reported as achieving a 50% pain reduction at 65 minutes.22 Given that aspirin is not felt to be a potent antiheadache medication, we assumed the same or similar response to the oral cocktail of acetaminophen 650 mg and caffeine 200 mg. A randomized controlled trial evaluating treatment of acute headache with occipital nerve block showed a response of 90% at 45 minutes, and a retrospective study evaluating the use of occipital nerve block in the setting of headache prophylaxis showed 82% with mild or significant response.23,24 To detect an 85% resolution rate in occipital nerve block in this trial, we estimated that a total of 62 patients (31 receiving occipital nerve block and 31 receiving standard care) would be sufficient to achieve 80% power at a 5% significance level.
Baseline demographic and clinical characteristics were compared between groups with two-sample t tests or Wilcoxon rank-sum tests for continuous variables and χ2 test of association for categorical variables. Fisher exact tests were used as appropriate. Outcomes were assessed in an intention-to-treat analysis. All analyses were performed with SAS 9.4 and were evaluated at a 0.05 level of significance.
RESULTS
From February 2020 to May 2022, 301 patients were screened. A total of 239 were excluded: 180 were ineligible (two not under primary obstetric care, one with no intrauterine pregnancy, 18 with visual rating scale scores lower than 4, 64 meeting criteria for preeclampsia evaluation, five with history of seizure, two with underlying brain abnormality, two febrile, 11 unable to receive treatment medications, 28 who declined treatment medications, three with focal neurologic exam findings, 44 meeting multiple exclusion criteria), 54 declined to participate, and five met other exclusion criteria. Sixty-two participants provided consent and were randomized to one of two arms (Fig. 1). All participants received allocated initial intervention of occipital nerve block or standard care. No participants were lost to follow-up for the primary outcome of visual rating scale score at 2 hours.
Fig. 1.
CONSORT (Consolidated Standards of Reporting Trials) diagram. Standard care is defined as oral 650 mg acetaminophen with 200 mg caffeine. Occipital nerve block is defined as subcutaneous 5 mL of 5% bupivacaine in the bilateral occipital notches.
Bushman. Occipital Nerve Block and Pregnancy. Obstet Gynecol 2023.
There were no statistically significant differences in baseline demographics, pregnancy characteristics, or maternal comorbidities of chronic hypertension or diabetes between groups except for payer status, with more participants randomized to occipital nerve block being privately insured (Table 1). When headache-specific characteristics were compared, there was no difference in reported headache history, prior diagnosis of primary headache disorder (Table 1), headache subtype, or headache symptoms, including headache duration, symptom laterality, pain quality, pain intensity, or associated symptoms between groups (Table 2). Specifically, there was no difference in baseline visual rating scale scores between occipital nerve block and standard care (7/10 vs 8/10 visual rating scale, P=.14), systolic blood pressure (130.8±12.3 mm Hg vs 129.2±9.1 mm Hg, P=.57), diastolic blood pressure (78.6±9.6 mm Hg vs 75.1±9.7 mm Hg, P=.16), duration of headache (37.8 hours vs 24.1 hours, P=.11) or headache treatment with acetaminophen before arrival (61.3% vs 51.6%, P=.44) (Table 2).
Table 1.
Demographics of Pregnant Participants Seeking Acute Treatment of Headache Randomized to Occipital Nerve Block or Standard Care (Oral Acetaminophen and Caffeine)
| Characteristic | Occipital Nerve Block (n=31) | Standard Care (n=31) | P * |
|---|---|---|---|
| Maternal age (y) | 28.4±4.8 | 27.3±5.3 | .38 |
| Race and ethnicity | .11 | ||
| Black, non-Hispanic | 15 (48.4) | 22 (71.0) | |
| Hispanic | 2 (6.5) | 3 (9.7) | |
| White, non-Hispanic | 14 (45.2) | 6 (19.4) | |
| BMI (kg/m2) | |||
| At first prenatal visit | 33.8±10.4 | 36.3±10.5 | .34 |
| At randomization | 36.4±10.5 | 37.2±10.7 | .76 |
| Insurance type | .03 | ||
| None or self-pay | 2 (6.5) | 1 (3.2) | |
| Public | 17 (54.8) | 26 (83.9) | |
| Private | 12 (38.7) | 4 (12.9) | |
| Nulliparous | 6 (19.4) | 8 (25.8) | .54 |
| Tobacco use | 4 (12.9) | 4 (12.9) | >.99 |
| Marijuana use | 2 (6.5) | 2 (6.5) | >.99 |
| Other illicit substance use | 1 (3.2) | 0 (0.0) | >.99 |
| Gestational age (wk) | |||
| At 1st prenatal visit | 13.6±11.3 | 13.3±6.2 | .91 |
| At randomization | 28.2±8.3 | 27.2±7.5 | .62 |
| Chronic hypertension | 9 (29.0) | 4 (12.9) | .12 |
| Diabetes | 6 (19.4) | 3 (9.7) | .47 |
| Headache before pregnancy | 12 (38.7) | 18 (58.1) | .13 |
| Known primary headache disorder | 9 (29.0) | 14 (45.2) | .19 |
| Migraine | 8 (25.8) | 12 (38.7) | .28 |
| Tension | 1 (3.2) | 2 (6.5) | >.99 |
BMI, body mass index.
Data are mean±SD or n (%) unless otherwise specified.
Student’s t test for continuous data; χ2 or Fisher exact test for categorical data.
Table 2.
Headache Characteristics of Pregnant Participants Seeking Acute Treatment of Headache Randomized to Occipital Nerve Block or Standard Care (Oral Acetaminophen and Caffeine)
| Characteristic | Occipital Nerve Block (n=31) | Standard Care (n=31) | P * |
|---|---|---|---|
| Headache subtype | >.99 | ||
| Migraine | 18 (58.1) | 19 (61.3) | .80 |
| Tension | 8 (25.8) | 8 (25.8) | >.99 |
| Other | 5 (16.1) | 4 (12.9) | >.99 |
| VRS score on arrival | 7 (6–8) | 8 (7–10) | .14 |
| Blood pressure on arrival (mm Hg) | |||
| Systolic | 130.8±12.3 | 129.2±9.1 | .57 |
| Diastolic | 78.6±9.6 | 75.1±9.7 | .16 |
| Duration of headache before arrival (h) | 37.8±34.7 | 25.1±24.2 | .11 |
| Headache symptoms | |||
| Duration 4–72 h | 18 (58.1) | 23 (74.2) | .18 |
| Duration 30 min–7 d | 14 (45.2) | 8 (25.8) | .11 |
| Unilateral | 4 (12.9) | 10 (32.3) | .07 |
| Bilateral | 16 (51.6) | 15 (48.4) | .80 |
| Pulsating | 7 (22.6) | 8 (25.8) | .77 |
| Pressing or tightening | 13 (41.9) | 16 (51.6) | .45 |
| Mild or moderate pain intensity | 6 (19.4) | 4 (12.9) | .49 |
| Moderate or severe pain intensity | 22 (71.0) | 23 (74.2) | .78 |
| Aggravated by routine physical activity | 5 (16.1) | 9 (29.0) | .22 |
| Nausea, emesis, or both | 10 (32.3) | 15 (48.4) | .20 |
| Photophobia | 14 (45.2) | 17 (54.8) | .45 |
| Phonophobia | 4 (12.9) | 6 (19.4) | .49 |
| Aura (speech or vision) | 4 (12.9) | 4 (12.9) | >.99 |
| Headache medications used before arrival | |||
| Acetaminophen | 19 (61.3) | 16 (51.6) | .44 |
| Butalbital, acetaminophen, and caffeine | 3 (9.7) | 2 (6.5) | >.99 |
| Prochlorperazine | 5 (16.1) | 4 (12.9) | >.99 |
| Metoclopramide | 1 (3.2) | 0 (0.0) | >.99 |
| Diphenhydramine | 0 (0.0) | 1 (3.2) | >.99 |
| Other | 0 (0.0) | 2 (6.5) | .49 |
VRS, visual rating scale.
Data are n (%), median (interquartile range), or mean±SD unless otherwise specified.
Student’s t test for continuous data; χ2 or Fisher exact for categorical data.
There was no statistically significant difference in the primary outcome of the proportion of patients who experienced headache resolution or improvement to mild range at 2 hours after initial therapy between groups (64.5% vs 51.6%, P=.30) (Table 3). However, the occipital nerve block group had lower median [interquartile range] visual rating scale scores at 1 hour (2 [0–5] vs 6 [2–7], P=.014), with more participants receiving occipital nerve block having visual rating scale scores of 3 or lower at 1 hour (58.1% vs 32.3%, P=.04) (Table 2). Improved scores at 1 hour resulted in 18 patients (58.1%) leaving triage within 1 hour of occipital nerve block as a result of headache resolution, compared with only 10 (32.3%) who received standard care. There was no difference in visual rating scale score 2 hours after treatment (P>.99) (Table 3).
Table 3.
Outcomes Among Pregnant Participants Seeking Headache Treatment Randomized to Occipital Nerve Block or Standard Care (Oral Acetaminophen and Caffeine)
| Outcome | Occipital Nerve Block (n=31) | Standard Care (n=31) | P * |
|---|---|---|---|
| Primary outcome | |||
| VRS score | |||
| 3 or lower 2 h after treatment† | 20 (64.5), (0.48–0.81) | 16 (51.6), (0.34–0.69) | .30 |
| 2 h after treatment† | 6.0 (4.0–8.0) | 6.5 (2.5–8.0) | >.99 |
| Secondary outcomes for all participants | |||
| VRS score 1 h after initial treatment | 2 (0–5) | 6 (2–7) | .014 |
| 0 | 8 (25.8) | 4 (12.9) | .20 |
| 3 or lower, discharged to home | 18 (58.1), (0.41–0.75) | 10 (32.3), (0.16–0.49) | .04 |
| Secondary outcomes among remaining participants† | |||
| Received crossover treatment at 2 h‡ | 9 (29.0) | 14 (45.2) | .19 |
| Indication for crossover treatment | .54 | ||
| Worsening VRS score | 7 (77.8) | 13 (92.9) | |
| VRS score higher than 3 2 h after initial treatment | 2 (18.2) | 1 (7.1) | |
| VRS score 1 h after crossover treatment | 6 (4–8) | 3 (0–4) | .028 |
| 0, discharged to home | 0 (0.0) | 4 (28.6) | .13 |
| VRS score 2 h after crossover treatment | 6 (4–7) | 6 (4–7) | .94 |
| 3 or lower, discharged to home | 2 (18.2) (0.00–0.49) | 10 (71.4) (0.48–0.95) | .008 |
| Received 2nd-line treatment at 4 h | 5 (16.7) | 5 (16.1) | >.99 |
| Indication for 2nd-line treatment | >.99 | ||
| Worsening VRS score | 5 (100) | 4 (80.0) | |
| VRS score higher than 3 2 h after initial treatment | 0 (0.0) | 1 (20.0) | |
| VRS score 1 h after 2nd-line treatment | 6 (4–7) | 4 (3–5) | .61 |
| 3 or lower | 1 (20.0) | 2 (40.0) | >.99 |
| Refractory headache§ | 4 (80.0) | 3 (60.0) | >.99 |
| Neurology consultation | 4 (100) | ||
| Neuroimaging obtained | 4 (100) | ||
| Secondary cause of headache identified | 1 (25.0) | ||
| Deviation from study protocol | .15 | ||
| None | 23 (74.2) | 28 (90.3) | |
| Declined crossover treatment | 1 (3.2) | 1 (3.2) | |
| Other or missing | 7 (22.6) | 2 (6.5) |
VRS, visual rating scale.
Data are n (%), 95% CI; or median (interquartile range) unless otherwise specified.
Student t test or Wilcoxon rank-sum tests for continuous data; χ2 or Fisher exact tests for categorical data.
If headache was significantly improved at 1 hour, patient could leave before VRS assessment at 2 hours (n=28 total patients). One patient delivered after occipital nerve block instead of being discharged because of a decision for delivery before VRS assessment at 2 hours.
Two patients in the occipital nerve block group did not receive crossover treatment because they were withdrawn from the study as a result of decision for delivery. One patient in the standard care group declined crossover treatment.
Visual rating scale score higher than 3 2 hours after second-line treatment. This prompted neurology consultation.
Among remaining participants (ie, those with visual rating scale scores higher than 3 at 2 hours after initial treatment), nine (29.0%) in the occipital nerve block group and 14 (45.2%) in the standard care group received crossover treatment at 2 hours after initial treatment; there was no difference in need for crossover treatment (P=.19). Two patients in the occipital nerve block group did not receive crossover treatment because of onset of symptoms concerning for preeclampsia after randomization. One patient in the standard care group declined crossover treatment but did receive second-line treatment. The standard care group had significantly lower median [interquartile range] visual rating scale scores at 1 hour after crossover to occipital nerve block than the occipital nerve block group receiving crossover to standard care (6 [4–8] vs 3 [0–4], P=.028). At 2 hours after crossover treatment with occipital nerve block, participants were more likely to have resolution or improvement in headache to mild range and discharge to home (2 [18.2%] vs 10 [71.4%], P=.008) (Table 3).
Among remaining participants, after initial treatment and crossover treatment, five (16.7%) in the occipital nerve block group and five (16.1%) in the standard group received second-line treatment (at 4 hours after initial treatment); there was no difference in need for second-line treatment (P=.99) (Table 3). There was no difference in response to second-line treatment, refractory headache, need for neurology consult, or need for neuroimaging (Table 3).
There was no difference in day 7 or 28 follow-up assessments (Table 4). At 7 days after treatment, regardless of randomization group, participants were equally likely to report complete resolution of headache (60.9% vs 78.3%, P=.20), duration of headache resolution (6 days vs 1 day, P=.13), satisfaction with treatment (P=.92), and likelihood to recommend treatment (P=.21). In addition, there was no difference in the development of hypertensive disorders of pregnancy (29.2% vs 8.7%, P=.14). At the 28-day follow-up assessment, findings remained consistent for all variables with no difference between treatment groups. Pregnancy outcomes were similar, with no difference in birth weight or mode of delivery. However, participants initially randomized to occipital nerve block were more likely to be delivered at an earlier gestational age (36.6±2.4 weeks vs 37.8±1.8 weeks, P=.025), but preterm birth did not differ between groups (Table 4). No adverse events were reported in either group.
Table 4.
Maternal Outcomes 7 and 28 Days After ONACT (Occipital Nerve Block Compared With Acetaminophen and Caffeine for Headache Treatment in Pregnancy) Randomization and Pregnancy Outcomes
| Outcome | Occipital Nerve Block (n=31) | Standard Care (n=31) | P * |
|---|---|---|---|
| Posttreatment day 7 | |||
| Complete resolution of headache | 14 (60.9) | 18 (78.3) | .20 |
| Duration of complete resolution (d) | 6 (0.5–7) | 1 (0–5) | .13 |
| Satisfaction with treatment | .92 | ||
| Strongly satisfied | 12 (52.2) | 10 (43.5) | |
| Satisfied | 5 (21.7) | 4 (17.4) | |
| Neutral | 3 (13.0) | 5 (21.7) | |
| Dissatisfied | 1 (4.4) | 1 (4.4) | |
| Very dissatisfied | 2 (8.7) | 3 (13.0) | |
| Likelihood of recommending treatment to others | .21 | ||
| Very likely | 17 (73.9) | 12 (57.1) | |
| Likely | 3 (13.0) | 4 (19.1) | |
| Neutral | 1 (4.4) | 4 (19.1) | |
| Unlikely | 2 (8.7) | 0 (0.0) | |
| Very unlikely | 0 (0.0) | 1 (4.8) | |
| Patient-reported complication† | 0 (0.0) | 2 (8.7) | .23 |
| ED evaluation for headache | 5 (20.8) | 1 (4.4) | .19 |
| New diagnosis of pregnancy-induced hypertension | 7 (22.6) | 2 (6.7) | .15 |
| New maternal or fetal complication | 4 (12.9) | 1 (3.2) | .35 |
| Posttreatment day 28 | |||
| Satisfaction with treatment | .18 | ||
| Strongly satisfied | 4 (21.1) | 11 (50.0) | |
| Satisfied | 6 (31.6) | 3 (13.6) | |
| Neutral | 7 (36.8) | 4 (18.2) | |
| Dissatisfied | 0 (0.0) | 1 (4.6) | |
| Very dissatisfied | 2 (10.5) | 3 (13.6) | |
| Likelihood of recommending treatment to others | .65 | ||
| Very likely | 13 (68.4) | 13 (59.1) | |
| Likely | 2 (10.5) | 2 (9.1) | |
| Neutral | 3 (15.8) | 3 (13.6) | |
| Unlikely | 1 (5.3) | 1 (4.6) | |
| Very unlikely | 0 (0.0) | 3 (13.6) | |
| New diagnosis of pregnancy-induced hypertension | 9 (29.0) | 4 (12.9) | .12 |
| New maternal or fetal complication | 4 (12.9) | 4 (12.9) | >.99 |
| Pregnancy outcomes | |||
| Gestational age at delivery (wk) | 36.6±2.4 | 37.8±1.8 | .025 |
| Preterm birth | |||
| Before 37 wk | 14 (46.7) | 11 (35.5) | .37 |
| Before 35 wk | 4 (13.3) | 1 (3.2) | .20 |
| Before 28 wk | 1 (3.3) | 0 (0.0) | .49 |
| Birth weight (g) | 2,852.2±579.4 | 2,932.9±552.6 | .58 |
| Less than 2,500 | 5 (16.7) | 6 (19.4) | .78 |
| Mode of delivery | .33 | ||
| Vaginal | 21 (70.0) | 18 (58.1) | |
| Cesarean | 9 (30.0) | 13 (41.9) | |
| Adverse events‡ | 0 | 0 | NA |
ED, emergency department; NA, not applicable.
Data presented as n (%), median (interquartile range), or mean±SD unless otherwise specified.
Student’s t test or Wilcoxon rank-sum tests for continuous data; χ2 or Fisher exact tests for categorical data.
Two patients in the standard care group who crossed over to occipital nerve block reported pain at the injection site.
Maternal death, fetal death, neonatal death, maternal intensive care unit admission, maternal cardiac arrest, new neurologic event (eg, seizure, stroke), prolonged maternal postpartum hospitalization (more than 5 days).
DISCUSSION
In this randomized controlled trial of pregnant people undergoing treatment for acute moderate to severe headache, treatment with occipital nerve block resulted in lower visual rating scale scores at 1 hour, shorter triage evaluation, and improved visual rating scale response at 1 hour after crossover treatment in those receiving occipital nerve block. Occipital nerve block is safe in pregnancy and was well tolerated by study participants, with no difference in reported satisfaction or complications compared with oral therapy. As a result, occipital nerve block should be considered an acceptable alternative, second-line, or primary treatment for acute headache in pregnancy.
To the best of our knowledge, there are no prior published randomized controlled trials of treatment with occipital nerve block for moderate to severe headache in pregnancy. We performed a systematic review of randomized trials evaluating headache treatment in pregnancy that yielded only three results.9 One evaluated nonpharmacologic treatment (lifestyle modification) of headache in pregnancy; another assessed acupuncture for women with tension-type headache; and the third evaluated metoclopramide 10 mg intravenously with diphenhydramine 25 mg intravenously compared with codeine 30 mg orally in normotensive patients in the second or third trimester with primary headache.3,25,26 Prior studies evaluating occipital nerve block in pregnancy focused primarily on treatment of postdural headache.27,28 One retrospective study evaluated occipital nerve block for refractory migraine and demonstrated that occipital nerve block was effective and did not mask a diagnosis of preeclampsia.18 With the exception of the aforementioned observational study, the use of occipital nerve block in pregnancy is based on expert opinion and is endorsed by the American Headache Society as a potential treatment option.16
This trial provides rigorous prospective randomized data on the effect of occipital nerve block compared with standard oral therapy in the setting of acute headache in pregnancy. On the basis of retrospective data on occipital nerve block outside of pregnancy, we hypothesized that occipital nerve block would result in improved visual rating scale scores at 2 hours. Our study found no difference at 2 hours, but the reduction in visual rating scale scores at 1 hour is encouraging. Our data suggest that occipital nerve block is a quick-acting, effective treatment for acute headache in pregnancy. Furthermore, in an emergency care setting or for refractory headache, occipital nerve block has some improved outcome metrics compared with standard care.
This study provides evidence to guide future, larger randomized controlled trials on acute headache treatment in pregnancy. Future studies may be powered to test the potential prophylactic benefits of occipital nerve block to reduce the overall need for acute treatment of headache in pregnancy, which our study was not powered to detect. In addition, resource utilization studies are needed to quantify the effects of faster headache resolution in the obstetric triage setting.
This study has several strengths. First, this randomized controlled trial fills an important knowledge gap surrounding a common symptom in women of reproductive age, in that we identified no prior study that published prospective data involving occipital nerve block in pregnancy, based on a previous systematic review.9 Second, our randomized trial mitigates risk of bias and confounding by indication associated with retrospective studies; our intervention groups were balanced with regard to key baseline characteristics. Furthermore, this study yields high-quality evidence on the effectiveness and tolerability of occipital nerve block in pregnancy. Most important, our study provides rigorous data on management options for acute headache in pregnancy, with our study being only the fourth to date to address headache treatment in pregnancy in a randomized fashion.9
We acknowledge limitations. The trial was conducted at a single academic center in the Southeast United States, potentially limiting generalizability to other populations. The response to occipital nerve block was lower in our study than what has been observed in prior studies in a nonpregnant population. We were ultimately underpowered to detect a difference in visual rating scale response at 2 hours despite improved response at 1 hour being observed. Although blinding was not implemented because of the nature of the intervention, performance bias was minimized by providing equal access to crossover treatment and second-line therapy. The visual rating scale score could also be considered another limitation. However, visual rating scale scores are the recommended and endorsed mode of headache evaluation despite being a subjective measure.20
Even though this is a negative trial based on our chosen primary outcome, occipital nerve block significantly reduced visual rating scale scores at 1 hour and resulted in more rapid turnaround in our maternal emergency room related to resolution or satisfactory improvement in headaches. In pregnant people seeking acute treatment for moderate to severe headache in pregnancy, occipital nerve block did not result in a difference in 2-hour visual rating scale scores compared with standard oral therapy (acetaminophen and caffeine) but appears to be as effective and is safe. Given the multiple limitations that pregnant people face in acute headache treatment, occipital nerve block should be considered as a primary, secondary, or alternative acute headache treatment in pregnancy. These results support the option of occipital nerve block use for pregnant patients with moderate to severe headache in pregnancy.
Supplementary Material
Authors’ Data Sharing Statement.
Will individual participant data be available (including data dictionaries)? No.
What data in particular will be shared? Not available.
What other documents will be available? Not available.
When will data be available (start and end dates)? Not applicable.
By what access criteria will data be shared (including with whom, for what types of analyses, and by what mechanism)? Not applicable.
Financial Disclosure
Alan T. Tita disclosed that his institution received funding from Pfizer. Rachel G. Sinkey disclosed that her institution received funding from the NIH and AHA. The other authors did not report any potential conflicts of interest.
All aspects of this project were supported and funded by the Center for Women’s Reproductive Health at the University of Alabama, Birmingham.
Each author has confirmed compliance with the journal’s requirements for authorship.
Footnotes
Presented at the Society for Maternal-Fetal Medicine’s 43rd Annual Pregnancy Meeting, February 6–11, 2023, San Francisco, California.
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