Evidence-Based Case Management

Beyond Spinal Headache: Prophylaxis and

Treatment of Low-Pressure Headache Syndromes
Wendy I. Warwick, M.D., and Joseph M. Neal, M.D.
Objective: This Evidence-Based Case Management article evaluates and grades the evidence for two anesthesiology-related interventions: prophylaxis after unintentional meningeal puncture and treatment of spontaneous intracranial hypotension (SIH).
Methods: A search was made of relevant English language clinical studies or reports pertinent to the topic of
low-pressure headache, but excluding the treatment of meningeal puncture headache.
Results: Thirty-seven case reports, case series, and clinical trials were included to develop the best available
evidence-based recommendations for the prophylaxis of unintentional meningeal puncture and for the treatment of SIH.
Conclusion: The highest quality randomized controlled trials suggest that prophylactic epidural blood patch
(EBP) does not reduce the incidence of headache after unintentional meningeal puncture. The weight of existing
literature supports EBP as an initial treatment of SIH, although its effectiveness does not approach that seen
when EBP is used to treat meningeal puncture headache. Reg Anesth Pain Med 2007;32:455-461.

nesthesiologists frequently manage low-pressure headache syndromes. Patients with these

conditions most commonly suffer meningeal puncture headache (MPH) as a direct consequence of
anesthesia-related subarachnoid or epidural block,
or from diagnostic and therapeutic neuraxial procedures performed by other specialists. The anesthesiologist is less frequently presented with two
other low-pressure headache scenarios. The first
involves whether to offer prophylactic intervention in
the setting of unintentional meningeal puncture
sustained during attempted needle placement into
the epidural space. The second involves spontaneous
intracranial hypotensionwherein a patient presents
with symptoms consistent with MPH, but without a
history of meningeal puncture. Various treatment
strategies have been proposed for these conditions,
but the evidence for selecting the best regimen is
equivocal. This evidence-based case management
article will assess those studies that deal with these
From the Department of Anesthesiology, Virginia Mason Medical Center, Seattle, WA.
Accepted for publication January 25, 2007.
James P. Rathmell, M.D. acted as Editor-in-Chief for this
manuscript.
Reprints are not available.
2007 by the American Society of Regional Anesthesia and
Pain Medicine.
1098-7339/07/3205-0015$32.00/0
doi:10.1016/j.rapm.2007.01.008

2 conditions; it will not address the treatment of

MPH, which has recently been extensively reviewed.1,2

Search Procedure
The literature search for this evidence-based case
management article was performed September

2006 using MEDLINE , a comprehensive electronic

database of indexed medical literature. The search
was applied to all English literature, regardless of
specialty. The following key words and their combinations were searched: headache, postdural
puncture headache, spinal headache, spinal
puncture/adverse effects, caffeine, corticosteroids, spontaneous intracranial hypotension,
subarachnoid cysts, Tarlov cysts, Schaltenbrand syndrome, headache: postural, post lumbar puncture headache, epidural saline, and
epidural blood patch. Animal studies, articles that
did not study treatment, and letters to the editor
were excluded from consideration. After applying
these exclusionary criteria, 37 articles remained for
critical evaluation.

Evaluation of the Evidence

Most of the evidence for prophylaxis and treatment strategies for these conditions is derived from
small nonrandomized trials, small case series, or

Regional Anesthesia and Pain Medicine, Vol 32, No 5 (SeptemberOctober), 2007: pp 455461

455

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Regional Anesthesia and Pain Medicine Vol. 32 No. 5 SeptemberOctober 2007

Table 1. Key to Evidence Statements and Grades of Recommendations

Statements of Evidence
Ia Evidence obtained from meta-analysis of randomized controlled trials.
Ib Evidence obtained from at least one randomized controlled trial.
IIa Evidence obtained from at least one well designed controlled study without randomization.
IIb Evidence obtained from at least one other type of well designed quasi experimental study.
III Evidence obtained from well designed nonexperimental descriptive studies, such as comparative studies, correlation studies, and
case reports.
IV Evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities.
Grades of Recommendations
A Requires at least one prospective, randomized, controlled trial as part of a body of literature of overall good quality and
consistency addressing the specific recommendation (Evidence Levels Ia and Ib).
B Requires the availability of well conducted clinical studies, but no prospective, randomized clinical trials on the topic of
recommendation (Evidence Levels IIa, IIb, III).
C Requires evidence obtained from expert committee reports or opinions and/or clinical experiences of respected authorities.
Indicates an absence of directly applicable clinical studies of good quality (Evidence Level IV).
NOTE. Source: United States Agency for Health Care Policy and Research.3

from case reports that may be biased by their reporting of positive results. When randomized controlled trials (RCTs) do exist, they are often limited
by methodological inadequacies, most commonly
the absence of proper blinding or insufficient number of patients from which to ensure statistical
power to show meaningful differences between
treatment modalities.
Evidence-based medicine ideally weighs the
strength of medical recommendations based upon
the scientific soundness of existing studies on the
topic. A recognized schema for such assessment is
based on the United States Agency for Health Care
Policys Statements of Evidence and Grades of Recommendations3 (Table 1). Statements of evidence,
from strongest to weakest, are based on randomized
controlled trials, nonrandomized controlled trials, observational studies, comparative and/or case studies,
and finally, expert opinion. From these statements of
evidence, one can derive grades of recommendations
that are rated A (good quality RCTs), B (good quality,
but nonrandomized controlled trials), or C (absence of
directly applicable clinical studies).
Case 1: Prophylaxis After Unintentional
Meningeal Puncture
A 23-year-old woman requested epidural analgesia for elective cesarean delivery. The anesthesiologists attempt to place a 19-gauge Tuohy epidural
needle was complicated by an unintentional meningeal puncture. The anesthesiologist must now
consider whether to offer the patient a prophylactic
intervention intended to reduce the subsequent risk
of MPH.
Prophylactic epidural blood patch. The decision of whether to offer prophylactic epidural
blood patch (EBP) is not straightforward, particularly in the obstetrical setting where unintentional
large-gauge needle punctures may lead to MPH in

50% to 80% of parturients.4,5 Surveys note that

obstetrical anesthesiologists may be recommending
prophylactic EBP less frequently. The intervention
was offered to 50% of patients in North America
during the mid 1990s,6 but to only 26% of patients
in Great Britain during the early 2000s.7 This decline may reflect practitioner awareness that not
every accidental meningeal puncture will result in
MPH, that not every MPH will require an EBP, and
that not every EBP will be effective; and to balance
that knowledge with the absence of definitive data
supporting the effectiveness of prophylactic EBP.
Furthermore, anesthesiologists who routinely orient the epidural needle so that its bevel is in a
cephalad to caudad configuration may not recommend prophylactic EBP on the basis that the odds of
developing MPH is 3 tenths that of when the needle
is oriented transverse to the spinal axis.8 Rare case
reports cite the potential for prophylactic EBP to
result in intrathecal hematoma and arachnoiditis.9
The practice of prophylactic EBP can be traced to
the observation that a small amount of blood deposited across the meninges upon withdrawal of a
large-gauge spinal needle decreased the incidence
of MPH.10 Subsequent small, nonrandomized studies and case series have demonstrated conflicting
results regarding the effectiveness of prophylactic
EBP.11-13 Various combinations of retrospective
design, small patient numbers, nonrandomization,
and/or the use of small volumes of blood for the
blood patch procedure compromise the results of
most of these studies.
Three randomized studies have shown conflicting
results regarding the effectiveness of prophylactic
EBP. A prospective trial (n 21) in which the
observer was blinded only during portions of patient assessment noted a significant reduction in
MPH in those parturients randomized to receive
prophylactic EBP (10% vs. 64% in the control

Low-Pressure Headache

Warwick and Neal

457

Table 2. Evidence-Based Strategies: Strength of Evidence and Recommendation Grade

Prophylaxis or Treatment Strategy
Prophylactic epidural blood patch
Epidural blood patch
Effectiveness not supported by the best RCTs
Intrathecal or epidural saline infusion
Intrathecal catheter
If used, catheter should be kept in place for 24 hours or more
Spontaneous intracranial hypotension
Epidural or intrathecal saline infusion
Alternative therapy if EBP is contraindicated
Epidural blood patch
Especially effective if placed at level of CSF leak
Percutaneous fibrin sealant or surgical repair
Consider when EBP has failed

Level of Evidence

Recommendation Grade

Ib

III
III

B
B

III

III

III

Abbreviations: CSF, cerebrospinal fluid; EBP, epidural blood patch; RCT, randomized controlled trial.

group).14 Another prospective, but nonblinded

study of 39 patients noted MPH reduction from
80% (16 of 20; control group) to 21% (4 of 19) in
parturients. The eventual need for a therapeutic
EBP did not statistically differ between groups (44%
in controls vs. 75% in those receiving prophylactic
EBP).15 In contrast to the 2 previous studies, the
strongest study of prophylactic EBP was randomized, double blind, used sham EBPs, and rigorously
defined criteria for intervention (placement of
prophylactic EBP and/or therapeutic EBP). Scavone
et al.5 found no difference in the incidence of MPH,
although there was a small decrease in symptom
duration of MPH in those patients who had received a prophylactic EBP. This study provides further credence to an earlier Cochrane Database of
Systematic Reviews report that found insufficient
evidence to support prophylactic EBP.16 Based on
the superior methodology of the Scavone et al.
study5 (Level Ib) and the Cochrane Database of Systematic Reviews report,16 we therefore recommend
that prophylactic EBP not be routinely considered
in patients who sustain accidental meningeal puncture with an epidural needle (grade A recommendation; Table 2).
Prophylactic intrathecal or epidural saline.
The practice of replacing CSF volume with normal
saline to treat or prevent MPH dates well before17
Gormleys original description of the EBP.18 Decreased incidence and/or severity of MPH has been
described using continuous intrathecal analgesic solution infusion in parturients19 or using single injection of intrathecal saline after unintentional
meningeal puncture.20 A retrospective observational survey of 241 parturients noted that the incidence of MPH after unintentional meningeal
puncture decreased from 86% to 70% in those
patients who received 24 hours to 36 hours of
crystalloid infusion into the epidural space.21 Onetime prophylactic 40 mL to 60 mL epidural saline

bolus has been reported to provide a similar decrease in the incidence of MPH.13 In summary,
administering intrathecal or epidural saline is a resource-intensive practice supported by a very limited number of studies that contain small numbers
of patients and have significant methodological limitations. The use of these interventions qualifies for
a weak (Level III) grade B recommendation.
Intrathecal catheters. A recent survey of
United Kingdom obstetric anesthesiologists reported that up to 28% will place an intrathecal
catheter after unintentional meningeal puncture,7 a
practice that offers the advantages of reliable labor
analgesia and avoidance of a second procedure to
re-site an epidural catheter. Evidence from surgical
and obstetrical procedures suggests that leaving an
intrathecal catheter in place for up to 24 hours after
accidental meningeal puncture may reduce the
likelihood of subsequent MPH, but discontinuing
the catheter immediately after delivery does not
affect the incidence of MPH.22 The mechanism for
this benefit is unclear and may involve generation
of inflammatory cells and/or edema, which seal the
meningeal defect.23,24 A small series reported that
only 1 of 7 parturients developed MPH when an
intrathecal catheter was threaded immediately after
unintentional meningeal puncture and subsequently bolused and infused with analgesic mixtures of local anesthetic and opioid for 12 hours to
20 hours.25 A retrospective study of 115 obstetrical
patients with accidental 18-gauge meningeal puncture showed that using an intrathecal infusion until
delivery reduced MPH from 91% to 51%, which
was further reduced to 6% if the catheter was left in
place for 24 hours.26 A retrospective study of 13
obstetric patients confirmed that MPH was less frequent if the catheter was left in place for 24 hours
or more.19 Although the risk of MPH is already
quite low in the elderly population, a prospective
study of continuous spinal anesthesia in older or-

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Regional Anesthesia and Pain Medicine Vol. 32 No. 5 SeptemberOctober 2007

thopedic surgery patients noted no difference in

MPH when catheters were left in place for 12 hours
to 24 hours.23 No studies have directly compared
the effectiveness of intrathecal catheters relative to
other methods of MPH prophylaxis. Therefore, the
use of an intrathecal catheter to reduce the incidence of MPH after accidental meningeal puncture
with an epidural needle is given a weak grade B
recommendation based on limited Level III Evidence. The practice may be most effective when the
intrathecal catheter remains in place for 24 hours or
more in younger patients (obstetrical population).
Case 2: Spontaneous Intracranial Hypotension
A 42-year-old woman was lifting weights when
she felt a popping sensation near her lower thoracic
spine. Within several minutes she became aware of
a generalized headache that was clearly worsened
by sitting or standing. After 3 weeks with no symptomatic resolution, the patient sought neurological
consultation. A neurologist diagnosed spontaneous
intracranial hypotension after obtaining a computerized tomography myelogram that showed a cerebrospinal fluid (CSF) leak at T9. The patient was
referred to the anesthesiology service for treatment.
The diagnosis of spontaneous intracranial hypotension (SIH) is made in patients presenting with a
postural headache that occurs in the absence of
meningeal puncture. Similar to MPH, SIH may be
associated with other symptoms such as tinnitus,
hypacusia, nausea and vomiting, and neck stiffness.
Visual changes including diplopia, photophobia,
and nystagmus are also common.27 Less than 100
cases of SIH were reported between Schaltenbrands original 1938 description and 2001.28,29
Due largely to improvements in diagnostic imaging,
awareness of SIH as a cause of orthostatic headache
has increased substantially in the past decade.30
Presentation of SIH typically occurs during the
third to fifth decade of life, with an approximately 2
to 1 preponderance in women.31 The estimated frequency of SIH is 5 per 100,000 patients per year.30
The etiology of this syndrome is the spontaneous or
trauma-related rupture of a meningeal diverticula
or cyst (Tarlov cyst32), or the tear or dehiscence of a
nerve root sleeve, which then results in CSF leakage similar to that seen with MPH. These cysts or
torn nerve root sleeves are typically found near the
cervicothoracic and thoracolumbar junctions, although they can occur anywhere along the spine as
single or multiple defects.33 The presence of SIH is
often associated with patients who have connective
tissue disease, such as joint hypermobility, Marfan
or Ehlers-Danlos syndromes, or polycystic kidney
disease.34 Associated trauma, which may be present

in one third30 to one half35 of patients, can be

minor, as from exercise or chiropractic manipulation.36
Computed tomography and magnetic resonance
imaging classically demonstrate meningeal enhancement with gadolinium,31 but do not identify
the exact location of the ruptured diverticula. Additional features of magnetic resonance imaging examination include subdural fluid collection, venous
engorgement, pituitary hyperemia, and brain sagging.30 Localization of the leak is best accomplished
with computed tomography myelography (more so
than magnetic resonance) or, less effectively, with
radionuclide cisternography.30,35,37
Similar to MPH, most SIH will resolve spontaneously over time, albeit some cases may persist for
years.31 Schievink reports that approximately 10%
of patients report recurrence of SIH,30 a finding that
is corroborated by long-term (4-5 year) follow-up
studies.38,39 There is no sound experimental evidence that symptomatic treatments such as steroids,40 bed rest, abdominal binders, or caffeine are
effective in treating SIH. When symptoms persist,
patients may be referred to an anesthesiologist for
invasive treatment.
Epidural or intrathecal saline infusion.
Based on its limited success in the treatment of
MPH,41 some practitioners have used epidural saline infusion as a treatment modality for SIH.33,42-45
Two individual case reports document successful
treatment of SIH after 48 hours44 or 5 days45 of
epidural saline infusion. Intrathecal saline infusion
has also been reported as a bridging therapy in an
obtunded patient in whom lumbar EBP failed and
no CSF leak could be identified. The saline infusion
restored the patients neurologic function; repeated
imaging identified the leak source, and subsequent
thoracic EBP permanently resolved the SIH.46 This
practice qualifies for a weak grade B recommendation, based on limited level III evidence (Table 2).
Epidural blood patch. Because epidural blood
patch offers the greatest likelihood of successfully
treating MPH,47 it is commonly recommended for
treating SIH, yet the evidence to support this practice is conflicting and RCTs are absent. The evidence
for effectiveness of EBP for SIH comes primarily
from case series and reports,48-50 most of which
have been summarized in 3 reviews of cases reported through 2001.29,31,51 Teng and Papatheodorou51 reviewed the first 31 reported cases of SIH,
wherein no patient received an EBP (which was not
reported as a treatment until 198348). Moayeri et
al.31 reviewed the next 47 reported cases of SIH. Of
these patients, 7 were treated with a lumbar EBP;
an additional 4 were initially treated with a lumbar
EBP, followed by a thoracic EBP. Epidural blood

Low-Pressure Headache

patch was successful in all reported cases in the

Moayeri et al. review.27,29,31,33,43,48,49,52 Diaz29 reviewed through 1996 an additional 22 cases (level
of presumed CSF leak was known in 6 cases). Sixteen of those 22 patients received an EBP, but not
all were successful. Of these 16 patients, 3 had no
resolution with EBP, 5 had only short-term symptomatic improvement, and 3 required repeat EBP
(with relief of headache).
Four small case series provide further detail regarding SIH treatment. The first,33 which was included in the review by Moayeri et al.,31 described
11 patients who underwent various noncomparative treatments (3 received successful EBP, 3 received successful epidural saline, 1 received steroids, and 3 of 4 underwent successful surgical
ligation). A series of 8 patients (reported in Diaz
review29) underwent successful EBP.53 Sencakova
et al. reported a series of 16 patients who underwent 49 EBPs; only 17 of these EBPs resulted in
sustained headache relief.54 Most recently, Hannerz
et al. reviewed 12 consecutive patients with SIH
who collectively underwent 15 lumbar EBPs and 4
cervicothoracic EBPs. Three of 4 cervicothoracic
EBPs resulted in long-term (4 months or more)
headache relief, while only 2 of 15 lumbar EBPs
resulted in sustained relief. Two of 8 patients initially treated with prednisolone experienced full
SIH resolution.40
It thus remains difficult to calculate an overall
success rate for EBP when used to treat SIH, but
success appears to be less frequent than that observed when the cause involves a known meningeal puncture. This observation is explained in part
by the typically larger, more complex meningeal
defects associated with SIH, their tendency to be
located in the anterior portion of the dural tube or
the nerve root sleeves, and the frequent absence of
knowledge regarding the exact location of the CSF
leak.55 Nevertheless, limited case series have associated a higher likelihood of long-term (5 year)
resolution of SIH symptoms if patients are treated
with EBP rather than conservative measures.39
Based on case reports and case series (Level III
Evidence), EBP appears to be a reasonable initial
option, albeit not universally successful, for treating
SIH (grade B recommendation).
An important consideration when using EBP to
treat SIH involves determining the optimal level to
inject blood into the epidural space. Because many
CSF leaks occur in the higher thoracic or cervicothoracic regions, it is reasonable to postulate that
blood placed at a lumbar level may not ascend to
the cervicothoracic levels,56 thereby biasing EBP to
failure. Several small series or case reports describe
patients in whom a subsequent thoracic29,31,40,57 or

Warwick and Neal

459

cervical EBP58,59 was successful after the failure of

an initial lumbar EBP. Consideration might therefore be given to placing a thoracic EBP if the CSF
leak is known to occur at a thoracic level; if the leak
level is unknown, consider a thoracolumbar EBP as
initial therapy or as second line therapy if a previous lumbar EBP has failed (grade B recommendation). Because epidural space volume is significantly smaller at the thoracic and thoracocervical
levels as compared with that at the lumbar level, it
is prudent to anticipate that less blood will be required and that injection should be terminated at
the first patient complaint of pain, back pressure, or
headache.2 This recommendation is expert opinion
based on theory alone, and thus is grade C.
When EBP is inappropriate or unsuccessful after
2 or more attempts, consideration may be given to
radiologic-guided percutaneous placement of fibrin
sealant at the known level of CSF leak. This practice
has been reported in several case reports60,61 and is
successful in approximately one third of patients.30
In recalcitrant cases, surgical ligation of meningeal
diverticula or epidural space packing is required, although this approach is technically difficult and only
variably successful (8 of 13 patients experienced complete resolution in the largest published series of surgical treatment)55 (grade B recommendation).

Conclusion
When patients experience an unintentional meningeal puncture with an epidural needle, prophylactic EBP is not recommended (grade A recommendation). In parturients, less robust (grade B)
evidence suggests that placing an intrathecal catheter after unintended meningeal puncture and
keeping it in place for at least 24 hours may reduce
the risk of MPH. For SIH, the preponderance of
evidence (grade B recommendation) suggests that
EBP is a reasonable therapy, especially if placed at
the level of the CSF leak. If this fails, consideration
can be given to radiologic-guided percutaneous
placement of fibrin sealant or surgical repair. Particularly in the case of SIH, scientific evidence is
limited by the absence of randomized clinical trials of therapeutic modalities, which in turn is
limited by the relatively infrequent occurrence of
SIH itself.

Acknowledgment
The authors express their appreciation to Brian
E. Harrington, M.D. for his critical review of this
manuscript.

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