Supplementary analyses based on actual treatment volume, that is the treatment received (up to 15 mL, 16 to 20 mL, or >20 mL: n = 48, n = 40, and n = 33, respectively), were performed. The results were consistent with those obtained with the intention-to-treat analyses (data not shown).
In this study we evaluated 3 volumes of blood for epidural blood patch in obstetric patients after unintentional dural puncture with an epidural needle. We found that 15, 20, and 30 mL of blood were of similar efficacy with respect to permanent or partial relief of postdural puncture headache. Although the proportion of patients with full and permanent resolution of headache was smaller after 15 mL than after 20 mL and 30 mL, the 95% CIs overlapped and the study was not sufficiently powered to definitively conclude that there was a difference between 15 mL and higher volumes for this outcome. Post blood patch headache pain scores were higher in the 15-mL group. There were no differences in headache pain scores between the 20-mL and 30-mL groups. A postulated risk of large volumes is an increased incidence of back pain. We did not find this to be the case. However, we were unable to administer the planned epidural blood patch volume more often in the 30-mL group than in the lower-volume groups because of patient complaints of back pain during the procedure.
There were no serious complications from the procedure in any group. Taken together, we believe that these findings support an attempt to administer 20 mL of autologous blood when treating postdural puncture headache in obstetric patients after unintentional dural puncture.
Approximately 1% of obstetric patients experience an unintentional dural puncture during attempted insertion of an epidural catheter,1 of whom 55%–80% develop a postdural puncture headache and approximately two thirds receive an epidural blood patch.2,4–7 The nature of the headache is such that it is often severe enough to prevent ambulation or effective interaction between mother and baby. This also increases nursing and anesthetic workload, prolongs hospitalization, and adds substantially to health care costs. These headaches usually persist for a week or more, are moderate to severe in 50% of cases,8 and occasionally persist as chronic headache. Randomized controlled trials have confirmed the greater efficacy of an epidural blood patch in comparison with conservative treatment (bed rest and IV fluid).8,14,15 Unfortunately, in obstetric patients the efficacy varies and is often modest; complete resolution of symptoms, and no recurrence, after a single therapeutic epidural blood patch occurs in only 35%–70% of cases, mainly because of the high rate of recurrence.6,16,25 A number of questions about the method, outcomes, and side effects of epidural blood patch remain unanswered and practice varies substantially.17,21
The volume of blood that would optimize outcomes, including an acceptable incidence of procedural and postprocedural back pain, is controversial. In 1960, Gormley11 claimed a 100% response using 2 to 3 mL of blood, and in 1970 DiGiovanni and Dunbar18 reported a 90% response to 5 to 10 mL. Szeinfeld et al.26 found that an average of 15 mL (range 12 to 18 mL) was effective and spread extensively over 7 to 14 spinal intervertebral segments, but others reported no advantage from 10 to 15 mL rather than 10 mL.27 In 1980, Crawford19 described almost complete success using 20 mL and subsequently claimed even better results with >20 mL.28 Other observational studies have failed to clarify the situation, some reporting better efficacy from volumes larger than 20 mL and others not finding volume to be predictive of outcome.6,29 Most studies were retrospective, and follow-up was not standardized. In the only randomized controlled trial, 7.5 mL and 15 mL produced similar relief, but pain during injection was less with the smaller volume.22
A clinical problem associated with the injection of an increasing volume of blood is back pain. This occurs during and after injection and is attributed to direct nerve root irritation or the acute and sustained neuraxial canal pressure increase that is transmitted to nerve roots,30 meninges, or medullary tissue. This back pain may limit the volume that can be injected. Discomfort often commences after 5 to 7.5 mL,30 and the incidence of pain increases as the volume of blood injected increases. Approximately 50% of women experience pain from injection of 15 mL.22 Our study confirms that this problem is clinically important, because the percentage of women in whom the assigned volume could be injected decreased substantially in the group allocated the highest volume of 30 mL. Detailed studies of the period after an epidural blood patch are scarce, and none evaluated postprocedural pain as a primary outcome, but some report back pain for up to 3 days.5,6,8,22,31 We found a higher overall incidence, probably due to better surveillance, but a similar incidence of clinically relevant lower back pain to previous studies. One quarter of our participants described moderate or severe pain for up to 5 days but most had very low scores, suggesting that this side effect of epidural blood patch should not be a deterrent to performing the procedure. An unexplained finding was that this postprocedural back pain was more intense among women treated with 15 mL of blood, although pain scores were usually very low. The study was not powered to detect differences in serious complications or morbidities, which appear rare but have not been quantified. None was reported in this study, but severe back pain, subdural hematoma, pneumocephalus, cranial nerve palsies, meningism, and epidural abscess continue to be reported sporadically.17
We attempted to control several possible confounding technique variables such as rate of blood injection, vertebral level of the epidural blood patch, and its timing. The relevance of these factors to response to epidural blood patch is uncertain and the intensity of headache at the time of epidural blood patch was similar across groups. Evidence from observational studies suggests that earlier intervention in relation to dural puncture is associated with a higher epidural blood patch failure rate. Banks et al.16 found epidural blood patch was unsuccessful when performed within 24 hours of dural puncture, and Taivenen et al.27 noted that the risk of failure was doubled if epidural blood patch was performed within 4 days of the puncture. It is unclear whether the timing of the procedure actually influences the success rate, or whether patients who require an epidural blood patch later are inherently different from those who require an early blood patch. In our study, univariate logistic regression suggested that a better response was likely if the procedure was delayed until 48 hours or more from the time of dural puncture, but this finding requires confirmation in a randomized trial.
This study has a number of limitations. Recruitment to such a trial is difficult, and it is possible that there were undetected differences in outcomes in different centers and changes across the 5-year study duration. The findings may not apply to treatment of postdural puncture headache resulting from spinal needles, for which epidural blood patch appears to have greater efficacy.14,27,29,31 The results may not be valid in the nonobstetric population, and there may be differences depending on the epidural needle size or design. The attending anesthesiologist was not blinded, and different anesthesiologists are likely to have had different attitudes to continuing injection of blood when the patient complained of back pain. It is likely that the study was underpowered with respect to a number of outcomes. The sample size was derived using selection theory, which allows a treatment to be ranked and selected as superior even if it is actually equivalent to the other treatment considered. This approach allows for smaller sample sizes in comparison with conventional statistical designs used in clinical research and is appropriate when the study would not be feasible on the basis of conventional sample size calculation.32,33 The concepts of significance level and power do not have direct analogs in the methodology based on selection theory, but the probability of selecting a superior treatment can be interpreted as the study power. Using conventional statistical methods for the selection of the number of patients required, the study did not appear feasible. For example, a 3-arm trial in which the primary end point was a permanent response to the epidural blood patch, evaluated using a χ2 test (that is, not accounting for pairwise comparisons), required 360 per group (n = 1080) to detect a complete response in 50% rather than 40% (α = 0.05, β = 0.8). A published randomized trial of epidural blood patch volume, involving only 33 obstetric patients, took 7 years to complete.22 We argue that design based on selection theory was justified, given that it took >5 years to recruit sufficient patients in 10 busy maternity units. Another important criterion to be met in applying this statistical approach is that choosing the wrong arm should not have unacceptable consequences. This criterion applies to this study, because all study volumes are currently used clinically. We considered that between-groups differences were likely to be modest and that even modest benefit or disadvantage of one particular volume could be acknowledged as clinically relevant.
Although the optimum volume of blood remains to be determined, we believe that these findings support an attempt to administer 20 mL of autologous blood when treating postdural puncture headache in obstetric patients after unintentional dural puncture.
Cynthia Wong is the section Editor for Obstetric Anesthesiology for the Journal. This manuscript was handled by Steve Shafer, Editor-in-Chief, and Dr. Wong was not involved in any way with the editorial process or decision.
Name: Michael J. Paech, DM.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Michael J. Paech has seen the original study data, reviewed the analysis of the data, approved the final manuscript, and is the author responsible for archiving the study files.
Name: Dorota A. Doherty, PhD.
Contribution: This author helped design the study, analyze the data, and write the manuscript.
Attestation: Dorota A. Doherty has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Tracey Christmas, FRCA.
Contribution: This author helped conduct the study and write the manuscript.
Attestation: Tracey Christmas has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Cynthia A. Wong, MD.
Contribution: This author helped design the study, conduct the study, and write the manuscript.
Attestation: Cynthia A. Wong has seen the original study data, reviewed the analysis of the data, and approved the final manuscript.
Name: Epidural Blood Patch Trial group (see Table 1).
Contribution: These authors helped design the study and conduct the study.
Attestation: Epidural Blood Patch Trial group approved the final manuscript.
We wish to thank all the research personnel involved in the conduct of this study, in particular Mrs. Desiree Cavill and Tracy Bingham, the study coordinators, and Research Fellows Drs. Raymond Goy, Jane Turner, Sarah Berridge, Karen Clarke, Sebastian Chua, Nolan McDonnell, Roger Browning, Melanie Thew, Neil Muchatuta, and Aneeta Sinha, who also helped. Special thanks also to Angela Jacques, statistician with the Women and Infants Research Foundation.
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