Accidental Dural Puncture and Postdural Puncture Headache.pdf

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Accidental Dural Puncture and

Postdural Puncture Headache

Management

Curtis L. Baysinger, MDVanderbilt University School of Medicine, Nashville, Tennessee

Accidental dural puncture (ADP) and the postdural punctureheadache (PDPH) that results from it occur frequently in obstetricalpatients who receive neuraxial blockade. This review summarizescurrent knowledge on the diagnosis and pathophysiology of PDPH,risk factors that affect the incidence of PDPH following meningealpuncture, methods to prevent PDPH following ADP, and the con-servative and invasive treatment of PDPH once the diagnosis isestablished.

Historical Background

Lumbar puncture was introduced into clinical practice in early1890s by Wynter and Quicke for the treatment of infectious meningitisand hydrocephalus. Their initial report included a description of whatwas most probably a PDPH.1 However, it was the introduction of spinalanesthesia by Bier in 1898, followed by rapid expansion of its use overthe next 2 years, that led to widespread recognition of the problem.2Anearly report noted a headache rate of 50%, an incidence that is probablyaccurate given the large bore needles in use at the time; the shortreported duration of 24 hours probably reflects lack of adequate follow-up.3 The association between low cerebrospinal fluid (CSF) pressureand PDPH wasnoted in early work by Sicard4 and Hosemann,5 and thework of Ingvar6 demonstrated a persistent leak in cadavers with duralpuncture, which suggested that altered CSF hydrodynamics was themost probable cause of the headache. Thereport of a persistent hole inthe arachnoid and dura by MacRoberts,7 and the work by Heldt8 that

INTERNATIONAL ANESTHESIOLOGY CLINICS

Volume 52, Number 3, 1839r 2014, Lippincott Williams & Wilkins

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REPRINTS: CURTIS L. BAYSINGER, MD, DEPARTMENT OF ANESTHESIOLOGY, VANDERBILT UNIVERSITY SCHOOL OFMEDICINE, 4202 VUH VUMC, 1211 MEDICAL CENTER DR., NASHVILLE, TN 37232-7580. E-MAIL: [email protected]
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CSF leakage was common after meningeal puncture, added corroborat-ing evidence to the theory. Although the relationship between headacheand low CSF pressure created by drainage of CSF was shown in the1930s and 1940s by Masserman9 and Kunkle et al,10 it was the work ofDripps and Vandam in the 1950s showing the direct relationship

between needle size (and thus the amount of CSF leaked) and theincidence of PDPH that established low intracranial pressure as thepresumed root cause of the pain in PDPH.

Pathophysiology of PDPH

Persistent CSF leak is currently not disputed as the cause ofpersistently lowCSF pressure and reductions in CSF volume in patientswith PDPH.11 CSF leak has been demonstrated with numerousradionuclide studies, during epiduroscopy, and at surgery.12 Loss ofCSF through the meningeal hole has been demonstrated to be greaterthan human CSF production in patients withPDPH13 and most oftenoccurs with cutting needles of 25 G or larger.14

Although the dura has been classicallyheld as the most important layerthat is violated when CSF leak occurs,15 it is the combination of thearachnoid and dural layers that retain CSF.16 The dura consists of multiplelayers of collagen and elastic fibers that do not have a particularorientation,17 whereas the arachnoid is a 5- to 6-cell-thick layer with anorientation along the longitudinal line of the spinal axis.16 Thus, it may bedamage to the arachnoid/dura combination that causes the persistent CSFleak, not the dura per se, and it is the arachnoids longitudinal orientationthat may explain the clinical observation that PDPH is more likely whenorienting a cutting spinal needle perpendicular to the axis of the spine.18,19

The mechanism by which persistent CSF leak, low CSF pressure,and the reductionin CSF volume create the headache associated withPDPH is not clear.1,12,20 The theory of low CSF pressure leading todownward pull on pain-sensitive structures in the upright position issupported by radiographic studies showing downward displacement ofintracranial structures and tension placed on meninges and bloodvessels known to contain stretch pain sensors.20,21 Cranial nerveentrapment by the sagging of the pons in patients with cranial nervepalsies and PDPH has been demonstrated.20,22 These symptoms arerelieved when the patient assumes the supine position.20,22 In analternate theory, CSF lossleads to vasodilation as a consequence of theMonroe-Kellie doctrine.11As the volume of CSF content is constant, thedecrease in CSF volume is accompanied by an increase in blood volumeand intracranial vessel stretching. This theory is supported by ultra-sound and radiographic studies showing increases in intracranial bloodflow in patients with PDPH.22,23 Pain fibers within the arterial system

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may be significant contributors along with those in venous structures. Arecent study that demonstrated a significant correlation between adecrease in the puslatility index of the cerebral circulation and theseverity of PDPH also suggests that arterial vessels are a significantsource for pain.24 Finally, increased hypersensitivity to substance P, lowlevels of which are associated with a substantially increased risk forPDPH, may be an important contributor to headache.25

Further research into the mechanisms that underlie pain expressionis required. Not all patients with significant meningeal rents get aheadache, which may be explained by random variations in lumbardural thickness; individuals with an ADP in an area ofthicker dura may

be less likely to get PDPH because of less CSF leakage.12 In addition, notall patients with headaches have decreased CSF pressure, and the link

between the rate of CSF leak and headache severity is not wellestablished.1

Diagnosis, Presentation, and Natural History of PDPH

The InternationalHeadache Society has established criteria for thediagnosis of PDPH26 (Table 1). Although these criteria will assist aclinician in making the diagnosis, it is often difficult. Headache or neck/shoulder pain, some of the common symptoms of PDPH, occurs withinthe first week of delivery in 40% of women who do not have PDPH.27

Headache ultimately diagnosed as PDPH occurs without dural puncturefrequently as well; van de Velde et al28 noted in a recent largeobservational study that 34 of 89 PDPHs were not accompanied byobvious dural puncture. Although headache that worsens on standing/sitting is the predominant pain expressed by most patients, pain in theshoulders, neck, middle of the back, or upper limbs may be the onlycomplaint.29 Cases presenting with hearing loss and tinnitus only,30

upper extremity pain,31 thoracic back pain without headache,32 andneurological deficits only33,34 have been reported. Clinical maneuversdesigned to increase CSF pressure (firm continuous pressure on theabdomen for 30 s or assumption of the true Trendelenburg position withhips flexed leading to headache relief) have been described,35 althoughthe positive and negative predictive value of those maneuvers have not

been established. Magnetic resonance imaging (MRI) with gadoliniumenhancement to confirm the diagnosis may be useful. Case reports andsmall series describe diffuse meningeal enhancement due to meningealvessel dilation, cerebellar tonsilar descent with crowding of the posteriorfossa, obliteration of the basilar cisterns, and enlargement of thepituitary gland as signs of low CSF pressure3537 (Fig. 1). However,the sensitivity of MRI is reported as low with a low positive predictivevalue.35,38

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Consideration for other serious intracranial pathology should beentertained if headache develops beyond 5 days (van de Velde et als28

study noted that allheadaches presented within 72 h; an observationalstudy by Reynolds39 noted that >90% did as well) or immediately afterdural puncture12 (Table 2). Even if dural puncture preceded the

Table 1. International Headache Society Diagnostic Criteria for Postdural PunctureHeadache

Headache Characteristics Criteria

Headache description Worsens within 15 min of sitting or standingImproves within 15 min of lying down

Headache has at least 1 of thefollowing accompanyingsymptoms

Neck stiffnessTinnitusHypacusiaPhotophobia

Headache timing Follows known or possible dural punctureDevelops within 5 d after dural punctureResolves within 1 wk (occurs in 95% of cases;

if headache persists, consider otherdiagnoses)

Resolves within 48 h of blood patchData from: Headache Classification Committee26 and Gaiser.44

Figure 1. Magnetic resonance image of patient with postdural puncture headache with signs ofintracranial hypotension. A, Meningeal enhancement with gadolinium. B, Movement of cerebellartonsils below the level of foramen magnum.




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headache, the women presenting with headache may have benign orserious intracranial pathology masquerading as PDPH, especially if thedural puncture was made with a small gauge noncutting needle. Onerecent review of venous thrombosis during pregnancy noted that overhalf of the patients in whom the diagnosis was ultimately made presentedwith symptomsof a positional headache and received an epidural bloodpatch (EBP).40 Another review of women who presented followinghospital discharge >24 hours after delivery noted that, although tension/migraine headache was the most common diagnosis (47% of those whopresented), 15 of 95 had abnormal radiologic findings, 10 of whom hadserious intracranial pathology.41 Notably, this report emphasized theimportance of a screening neurological examination in the patientsuspected of having PDPH, as nearly all with serious neurologicalpathology had an abnormality on examination.

The largest follow-up study of PDPH was performed by Vandamand Dripps in 1956.42 They reported that 72% of PDPHs resolvedwithin 7 days and an additional 15% resolved within 6 months,corroborated by later work.43 Cutting needles of 24 to 16 G wereutilized. Theynoted that prolonged headache was associated with largergauge needles,44 a plausible explanation as sealing of the meningeal tearwould be expected to take longerwith the larger holes that large needlesmight create. MacArthur et al45 noted a 23% incidence of headachepersisting >6 weeks in parturients with ADP with large bore needlescompared with a control group incidence of 7.1% with a few patients

with persistent headache after 1 year. That a headache is oftenprolonged following delivery in women who have suffered ADP wascorroborated recently by Webb et al46 who noted a 28% incidence of anyheadache at 18 months compared with a 5% incidence in controls in arecent survey of women after delivery. Epidural blood patching only

Table 2. Differential Diagnosis of Postdural Puncture Headache

Tension/migraine headacheDrug induced (caffeine withdrawal, cocaine, amphetamine)Preeclampsia/eclampsia

MeningitisSubdural/subarachnoid hematomaCerebral venous thrombosisCerebral infarctionStroke (hemorrhagic and ischemic)PneumocephalusSinus headachePituitary apoplexyNeoplasmPosterior leukoencephalopathy

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halved the incidence of chronic headache, despite what was felt to be asuccessful initial therapy.

Risk Factors for Development of PDPH

Parturients are at greater risk for PDPH following dural puncturecompared with other populations because of their younger age, sex, anduse of epidural block for labor analgesia using larger gauge needles. Risk forPDPH is highest in 20- to 30-year-olds, 3 to5 times higher than in patientsgreater than 60 years of age.19,42,47 Wu et als48 recent meta-analysis showedthat women are at greater risk for PDPH compared with men (odds ratio0.55) but this study examined needles of 20 G and smaller (smaller thanthose used for epidural placement) and contained many patients abovechild-bearing age. Whether pregnant women are at greatest risk for PDPHafter ADP compared with nonpregnant women of similar age is unclear.29

The choice of technique and needle type and size used for lumbarpuncture are the factors over which the anesthesiologist has the mostcontrol for reducing the incidence of PDPH44 (Table 3). For Quincke orcutting spinal needles, smaller needles have a lower incidence ofheadache, with an incidence of 2% to12% when 26 G needles are used,increasing to 36% for 22G needles.12,47,4953 The wide range notedinTable 3for some needles reflects study design (incidences are lower inretrospective studies), differences in ages of the patients, and failure tocontrol orientation of the cutting edge of the needle in older studies.

Although use of smaller caliber (18 G) Tuohy epidural needles reducesheadache severity compared with 16 G needles,5456 the incidence of70% to 88% noted with a 16 is not clinically different when an 18 Gneedle is used (incidence 64%).12,49 Laboratory work showing reducedCSF leakage when orienting the bevel of cutting spinal or Tuohy needlesalong the longitudinal axis of the spine57 support the clinical studiesshowing a reduction in incidence of PDPH by half after dural puncture

by Quincke spinal needles18,19 and a comparable reduction in incidencewith Tuohy needles58 oriented along the longitudinal axis. A recentmeta-analysis showed a reduction in PDPH incidence by approximately60% if parallel needle orientation was used with a Tuohy needle.59 Pencilpoint needles carry a substantially reduced risk for headache overcutting needles suggesting that the damage to the arachnoid/duralmembrane is reduced; gauge of needle used is less important inreducing headache when pencil point needles are used. Althoughapplication of this knowledge appears widespread among anesthesiaproviders,60 use of smaller, noncutting needles has been slow to beadopted by other medical specialists.54,61

Both a history of prior PDPH and chronic headache appear toincrease risk for PDPH; higher body mass index (BMI) may be




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protective. Amorim and Valencia21 found that 19% of patients with priorPDPH developed a second PDPH versus 6.9% of patients without aprior PDPH when small needles were used; Lybecker et al19 found that2 of 3 patients with prior PDPH developed another after repeat spinalanesthesia with small needles comparedwith 3 of 114 patients havingtheir first spinal anesthesia. Kuntz et al62 found that a group of patientswith headache 1 week before a dural puncture had an incidence ofPDPH of nearly 70% compared with 30% in those who did not whenlarger bore cutting needles were used for radiologic procedures. One ofthe few benefits of the obesity epidemic in obstetrics may be a lowerincidence of PDPH following ADP or intentional dural puncture.63

Kuntz et al62 and Lavi et al64 found an approximate incidence of PDPHof 25% in patients with higher BMIs (about half of that for all patients),and Faure et al65 noted a headache incidence of 24% in parturients withBMI>30kg/m2 compared with an incidence of 45% in women withBMI less than that of women who underwent an ADP with 18 G epiduralneedles. However, as the overall rate of ADP may be higher in obesewomen because of more frequent need to replace nonfunctioningcatheters,63,65 the overall PDPH rate in the obese population may not begreatly different from nonobese parturients.

A recent review of PDPH by Gaiser44 notes a strong association oflower PDPH rates in women with ADP who deliver by cesarean sectioncompared with thosewith a vaginal delivery. His analysis of data fromwork by Scavone et al66 and Angle et al67 noted an incidence of PDPHfollowing ADP of approximately 11% in women who underwentcesarean section compared with >75% in women who delivered

Table 3. The Incidence of Postdural Puncture Headache: Needle Size and Type

Gauge/Needle Type PDPH Incidence (%)

22 Quincke 36

25 Quincke 20.626 Quincke 0.3-2027 Quincke 1.5-5.629 Quincke 0-232 Quincke 0.424 Sprotte 0-9.620 Whitacre 2-522 Whitacre 0.63-425 Whitacre 0-14.527 Whitacre 026 Atraucan 2.5-4

16 Touhy 70Control for age, sex, bevel orientation of cutting needles vary among studies from which dataare derived. Modified with permission from: Turnbull and Shepard.12 Adaptations arethemselves works protected by copyright. So in order to publish this adaptation, authorizationmust be obtained both from the owner of the copyright in the original work and from theowner of copyright in the translation or adaptation.

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vaginally, with the study by Angle and colleagues noting a strongcorrelation to the length of pushing during the second stage to PDPHdevelopment. He noted that in an additional study by Konrad et al,68

the PDPH rate in women who underwent vaginal delivery was higher(80%) compared with those who underwent cesarean delivery (15%).This suggests that valsalva maneuvers during the second stage of labormight increase the size of dural tear following ADP with Tuohyneedles.44 However, further work to corroborate this hypothesis isneeded as other studies have failed to correlate pushing during thesecond stage to an increase in PDPH incidence.12,43 The studies Gaisercites were designed to answer other questions. A recent survey ofpractitioners reported that limiting pushing after ADP was virtuallynonexistent in the practices of those obstetrical anesthesiologistssurveyed.69 As neuraxial morphine may reduce the incidence of PDPHwhen given after delivery54 and neuraxial morphine is often givenroutinely for postcesarean section analgesia, its administration may also

be an explanation. Gaisers subanalysis of the recent work by Russell,70

which examined the effect of intrathecal catheter placement in reducingthe incidence of PDPH, noted a reduction in PDPH when skilledoperators performed neuraxial anesthesia and corroborates older work

by Reynolds.39 MacArthur et al45 noted a similar correlation, andshowed that the incidence of PDPH dropped from 2.5% in operatorswho had 60placements. As many of these blocks involved anesthesia trainees whomight have been working long hours, Turnbull and Shepard12

suggested that operator fatigue may have been an explanation for thedifference.

Use of either air or saline for the loss-of-resistance technique hasbeen examined. One immediate retrospective observational study of3730 patients by a single chronic pain practitioner showed that whereasthe incidence of ADP was not different when air was used versus saline(2.2% in both groups), the incidence of headache was markedly higherin the air group (34% vs. 10%).71 The character of the headache in theair group was strongly suggestive of that associated with pneumo-cephalus.44 A recent retrospective study of929 epidural blocks failed tocorroborate a difference in headache rate.72 The recent meta-analysis byBradbury et al,73 in which 5 trials of low quality that studied the questionwere evaluated, concluded that the data were not sufficient for funnelplot analysis and that no conclusions could be drawn.

Prevention of PDPH Following ADP

Despite calls for large randomized trials that will help establishpractices that will reduce ADP and PDPH,74 few have been forthcoming.




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A recent meta-analysis concluded that previous studies have not beenrandomized and lack sufficient power, the several small series showing

benefit for the techniques studied lack control groups and thus sufferfrom publication bias, and the wide heterogeneity in results mean thatno technique can be recommended as effective.75 Recent surveys in bothobstetric60 and nonobstetric69 patients show that practitioners useaggressive oral or intravenous hydration (74% to 89% of the time),encourage bed rest (48% to 56% of the time), and prescribe opioid andnonopioid pharmacotherapy (47% to 58% of thetime). None of thesemeasures have been shown to be effective.7375 Prophylactic oral orintravenous caffeine therapy was shown to be effective in 1 smallrandomized trial (an absolute reduction in PDPH of 27%)76 corroborat-ing the good results reported in the 2 much older studies bySechzer.77,78 Caffeine is given frequently by a significant number ofpractitioners of obstetric anesthesia (58%).60 However, a specific meta-analysis addressing its effectiveness79 and the 3 published meta-analyseslooking at the many techniques reported to reduce PDPH show thisintervention to be largely ineffective.7476 The technique is not withoutrisk as maternal cardiac dysrhythmias and central nervous systemtoxicity can accompany its use.12 The survey by Baysinger et al60 showedthat the use of other pharmacotherapies (intravenous adrenocortico-tropin80 or desmopressin81) isinfrequent. Abdominal binders are used

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that the technique offers little benefit, echoed by a recent review ofprophylactic blood patching.94 Both corroborate Scavone et als66 recentrandomized, double-blinded trial showing no reduction in PDPHincidence overall with some reduction in headache duration andseverity of headache of minimal clinical significance. Bradbury et als73

recent meta-analysis concluded that, although all the data minimallysupported the effectiveness of prophylactic EBP, when trials that werepublished only as abstracts were removed there was no significant PDPHreduction.

Placement of an intrathecal catheter is an option following ADP. Arecent survey reported that 76% of respondents would consider use ofan intrathecal catheter because it reduces the rateof PDPH,60 probablyon the basis of the positive reports by Ayad et al95 and Cohen et al96;however, retrospective audits28,97,98 and 1 randomized prospectivestudy71 have failed toshow a reductionin PDPH rate. The reports byNorris and Leighton97 and Rutter et al98 also failed to show a reductionin severity of PDPH as measured by EBP frequency. The recentrandomized, multicentered trial by Russell,70 in which patients wereassigned to either intrathecal placement of a catheter for labor withremoval immediately after delivery or resiting of an epidural catheter,showed no difference in PDPH rate or the frequency of epidural bloodpatching. This study noted that the risk for PDPH was doubled when a16 G needle was used over an 18 G needle. Most notably, the studyreported use of a large proportion of 16 G needles, which is not commonin North America,60 so the negative results could have been influenced

by the predominance of large gauge needles. That use of an intrathecalcatheter for labor analgesia might have other benefits was suggested bythis study as well. Over 1/3 of the women in the epidural group hadfurther complications with epidural placement including an increasedrequirement for 2 or more additional attempts to establish neuraxialanalgesia (41% vs. 12%) and a 9% risk of a second dural puncture.Moreover, catheters were removed immediately; the reports by Ayadand Cohen showed success with PDPH reduction when catheters wereleft in place for 24 hours. Although intrathecal catheter placement doesalso allow for the more rapid establishment of analgesia, loss of CSF andan increased risk for infection are unproven potential complications oftheir placement.

Some recent work shows that a few preventive measures might beeffective. The recent meta-analyses examining PDPH prevention73,75,99

suggest that the administration of neuraxial morphine or systemiccosyntropin might be effective. The effectiveness of both has been shownin 2 small clinical trials utilizing epidural morphine administration and1 small clinical trial of cosyntropin. In Al-Metwallis100 study of 50patients, 3 mg of epidural morphine compared with saline injected atdelivery and 24 hours later reduced the incidence of headache from




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48% to 12% and the number of blood patches from 6 to 0. Cesur et al101

showed similar results with a reduction of PDPH from 58% to 7% whena continuous epidural infusion of local anesthetic and morphine wasused. Other studies of neuraxial narcotic administration are inad-equately controlled. One case report and 1 uncontrolled clinical trialshowed statistical and clinically significant improvement in a smallnumber of patients96,102; intrathecal fentanyl did not affect rates ofPDPHafter dural puncture with small spinal needles in another smallstudy.103 In Hakims104 study of cosyntropin, the incidence of headachewas reduced from 69% to 33% in 90 patients following the admin-istration of 1 mg of cosyntropin. The study has been criticized becausethe definition of PDPHwas unclear and a mechanism for the effect hasnot been postulated.73 There were almost no untoward side effectsnoted from cosyntropin therapy; however, the side effects of nausea,vomiting, and pruritis associated with neuraxial morphine therapy arewell known. Larger prospective trials need to be conducted tocorroborate these findings.

Treatment of PDPH Following ADP

Measures to treat PDPH after ADP vary widely among practicing

anesthesiologists,60,69 probably because good-quality evidence to guidetherapy is scarce. Interpretation of the results from small studies ishampered by failing to recognize that PDPH will resolve in 85% ofpatients over the course of 6 weeks.43,45 Management among anesthesi-ologists in the same practice likely varies widely, and the surveys byBaysinger et al60 and Harrington and Schmitt69 noted that only 14%and 15% of institutions in North America, respectively, have writtenprotocols on ADP and/or PDPH management. Striking is that 23% ofrespondents did not know the rate of ADP in their institution.60 This is

in marked contrast to the United Kingdom where 85% of institutions arereported to have established protocols.105A thorough explanation to themother, whose ability to interact with and care for the newborn is mostlikely interrupted, is essential as well as establishing agreement on thetreatment plan if PDPH occurs.12

Conservative Management of PDPH

Most respondents (90%) to the above-cited survey of ADP/PDPHmanagement practices felt that conservative measures failed themajority of time when used,60 a position supported by the study ofvan Kooten et al106 who noted headache in 86% of patients after 1 weekof conservative therapy following ADP with large bore needles.Conservative measures include the ones cited above for PDPH

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prevention: bed rest, hydration, non-narcotic and narcotic analgesics,caffeine, and other medications.

Bed rest relieves symptoms, but is of no benefit in altering thecourse of PDPH.61,74,99 Hydration,either oral or intravenous, has noevidence to support its routine use.107,108 Nonsteroidal anti-inflamma-tory drugs and oral/systemic opioids may reduce the need for moreaggressive therapy,12 but perhaps only by sedation and mood alterationin the case of opioids.54 The natural course of PDPH appears unalteredwhen analgesics are used.12,47 Patient position while recumbent (pronevs. supine) does not appear to affect the natural history either.12,109

Abdominal binders are ineffective when used for treatment.60

Other pharmacologic interventions are either not effective or havenot undergone enough evaluation to recommend their routine use.Caffeine administration was reported to relieve symptoms in 85% ofpatients who developed PDPH after dural puncture with 22 G Quinckeneedles in older studies by Sechzer.77,78 Interpretation of Sechzers workis difficult as there was lack of proper blinding, no rigorous definition ofPDPH provided, and the patients were not randomized to treatmentand control groups. Another small study by Camman et al110 failed toshow either statistically or clinically significant improvements in eitherpatient pain scores or in the rates of EBP in patients who wererandomized to receive either oral caffeine or placebo. A recent reviewnotes that the proposed mechanism of reducing intracerebral bloodvolume by increasing cerebral vascular resistance through blockade ofadenosine receptors and thus reducing brain blood flow failsto answerhow that improves the pathophysiology underlying PDPH.79 Compen-satory vasodilation, thought by some to accompany the reduction inintracerebral volume and the cause of pain due to pain receptorstretch,111 has not been proven. Moreover, the effects of caffeine oncerebral blood flow are highly variable, and the effects of caffeine may beto merely increasegastrointestinal absorption of concomitantly admin-istered analgesics.79 Caffeine appears in breast milk and may havesignificant neonatal effects if given in large amounts.

Adrenocorticotrophic hormone (ACTH) has been used to treatPDPH. Although Collier112 reported complete headache relief in 14 of20 patients in an observational trial using an infusion of 1.5 mg/kg, thereport lacked a statistical analysis that prevents assessment of itsadequacy. Gupta and Agrawal80 reported complete relief in 40 of 48patients in an observational study of intramuscular ACTH, but theduration of efficacy was not documented. All of these studies lack controlgroups for comparison, so interpretation of the results is difficult.Rucklidge et al,113 in a randomized trial, demonstrated that single-dose

ACTH therapy was not of benefit compared with saline controls. Notsurprisingly, ACTH is used by a vanishingly small number ofclinicians.60 Sumatriptan has been examined as it would be thought to




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cause cerebral vasoconstriction similar to caffeine and thus possibly beeffective, but a recent blinded controlled trial failed to documenteffectiveness,114 and the above-noted criticisms as to the proposedmechanisms of action that apply to caffeine apply to this drug as well. Ofall of the conservative pharmacologicalinterventions proposed to treatPDPH after ADP, only cosyntropin,101 repeated doses of hydrocorti-sone,115 and oral gabapentinoids116,117 have shown enough promise insmall controlled trials to warrant further study.54

Invasive Treatment of PDPH

In patients with PDPH in whom an epidural catheter has been leftafter ADP, saline infusion has beenexamined. Case reports suggest thatlong symptomatic relief may follow118 and that it mightbe tried if othermeasures of treatment, including EBP, have failed.119 Presumably thesaline infusion increases pressure in the area of leak and decreases theoutflow of CSF. The success cited in case reports was not repeated in arecent small prospective trial examining thetechnique. Although reliefwas noted while the infusion was ongoing,120 its effect is not long lastingas the rise in pressure is not sustained after the infusion is stopped.12,121

Although Dextran 40 has beenadvocated by some as likely to have alonger-lasting effect than saline,122 the colloids effect may be similar as itdoes not create an inflammatory response that might hasten duralclosure after puncture.12,122 The use of colloid might be best reservedfor patients in whom the use of blood would be contraindicated for fearof complicating an underlying disease, such as leukemia.123

The prophylactic use of EBP appears largely ineffective; however,injection of autologous bloodinto the epidural space after the diagnosisof PDPH is effective. Gormley124 introduced the technique and reported100% success in 6 patients who received small volumes (2 to 3mL) of

blood. The subsequent work of DiGiovanni and Dunbar125 describedthe efficacy of the modern EBP in a small observational study anddemonstrated its mechanism and safety in a subsequent laboratoryinvestigation and clinical report.126 Safety and efficacy were furtherdemonstrated in an older prospective observational study by Ostheimeret al127 (98.4% success in eliminating headache and no permanentcomplications noted) and a retrospective review by Abouleish et al128

(95% success with no complications). More recent studies have notdemonstrated such high success rates. Safa-Tisseront et als129 prospec-tive observational study of 500 patients noted a complete relief ofsymptoms in 75% of patients, partial relief in 18%, and failure of EBP in7%, with needle size and delay in treatment 90%), subsequent failure is common after ADP with large boreepidural needles, as


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puncture will have no recurrence of symptoms after 1 EBP.130Althoughthe use of EBP for PDPH has been widespread among obstetricanesthesiologists for >40 years, only 1 well-done, prospective, random-ized trial has compared it with conservative therapy. Utilizing anepidural injection of 15 to 20 mL of autologous blood after predom-inantly 20 G cutting needle punctures, 84% of patients who developedPDPH had good relief 7 days after treatment compared withconservative measures.106 Such good results may notoccur in patientswith 16 to 18 G epidural needle puncture. Paech et al131 in a secondaryanalysis of a study evaluating 15 to 30 mL injections of autologous bloodfor EBP failed to show good long-term results. The incidence of partiallong-term relief was noted to be 41% to 51% and total relief 10% to 26%with larger volumes of blood associated with higher rates of success.131

Clearly a success rate of >80%, quoted by 70% of practitioners topatients who are being counseled for EBP in 1 recent survey of obstetricanesthesiologists, indicates that its effectiveness is thought to be greaterthan it probably is.60

The mechanism of acute relief of PDPH with EBP is thought to bethe dislocation of CSF from the lumbar thecal sac due to increasedepidural pressure with an increase in intracranial pressure; longer-termrelief is thought to be due to sealing of the meningealhole.12,44,107,126

Both radiolabeled red cells132 and MRI scanning133 show that theinjected blood moves cephalad and caudally after injection, passes intothe anterior epidural space, and passes through the intervertebralforamina into the paravertebral space. These studies confirm that thethecal sac is compressed by blood with presumed CSF dislocationcephalad, although this effect is not long lived. Collagen formation isextensive at 7 days after injection in animal models, supporting thetheory thatsealing of the meningeal hole against further leakage of CSFis likely.126

The contraindications to EBP are similar to those that apply toepidural placement for anesthesia. Added caution has been suggestedfor patients in whom neuraxial seeding with cancer cells might bepossible.123,134 No significant sequelaehave been reported in patientswith human immunodeficiency virus135 and its use in patients with low

blood viral load should be safe. Although the natural course of PDPHsuggests that most symptoms will clear over time, evidence of cranialnerve involvement (eg, tinnitus, diplopia) would prompt a prudentpractitioner to recommend early EBP to possibly prevent long-termcranial nerve palsy.

Most of the technical aspects of the EBP technique have not beenadequately evaluated. The reports that suggest that delaying EBP by>24 to 48 hours improves efficacy108,129,130 are probably due toselection bias54; however, the retrospective evidence that supportswaiting is substantial and been reported in several studies.136,137 The




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controversy over what volume of bloodismost associated with successmay have been resolved by Paech et als131 recent randomized blindedtrial in which patients were allocated to receive 15, 20, and 30 mL of

blood. The patients who received 30 mL of blood were most likely tostop the injection due to back pain, with complete relief of PDPH at arate similar to that in the 20 mL group. The authors concluded that20 mL of blood is, most probably, the optimal blood volume that should

be used. Although asking the patient to remain supine for 2 hoursafterEBP is supported by the randomized trial of Martin et al,138 theinvestigators failed to follow the patients >24 hours after EBP, and thisaspect of the EBP technique has not been evaluated recently.

Long-term complications after EBP are rare, although short-termback pain occurs in up to 80% of patients.12,44,139 Subarachnoidinjection with long-term neurological deficit has been described,140,141

but it is difficult to determine the relationship between the patientsoutcome and the EBP. One case report of unintentional subdural bloodinjection with long-term nonpostural headache and lower extremityradicular signs exists.141 The effect of EBP on the success of futureepidural success is unknown. One retrospective case-control studyshowed no difference in epidural success in patients who had undergonea previous epidural withan ADP and EBP compared with those who hadnot received an ADP.142 However, recent case reports suggest that EBPmay be associated with extensive epidural space scarring, which mightlimit local anesthetic spread in subsequent epidural blocks.143

Conclusions

ADP with subsequent PDPH is a significant source of patientmorbidity. A better understanding of how CSF leak causes headache andwhy some patients develop PDPH after ADP while others do not isneeded. Although the association of greater risk for PDPH with patientdemographics and needle size is well established, studies of factors thatmight reduce the risk for ADP and thus PDPH have only recently beenundertaken. At present there is no effective way to prevent PDPH after

ADP, although small trials involving neuraxial opioid and systemiccosyntropin use and the observation that vaginal delivery is associatedwith a higher incidence of PDPH than cesarean delivery need furtherinvestigation. Intrathecal catheter use after ADP probably does notreduce PDPH. EBP therapy is effective compared with conservativemeasures. The surveys of obstetric anesthesia providers that show thatmany institutions do not track patients with ADP, do not havestandardized protocols for ADP and PDPH management, and fail tofollow-up patients after EBP are worrisome.

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The author has no conflict of interest to disclose.

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