A Comparison of the Efficacy of Sphenopalatine Ganglion (SPG) Block With 5% Lidocaine Versus Epidural Blood Patch (EBP) for the Treatment of Post-Dural Puncture Headache (PDPH)
Phase: PHASE3
Conditions: Postdural Puncture Headache
Sponsor: Rutgers, The State University of New Jersey

Statistical Analysis Plan 
 
A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural 
Blood Patch (EBP) for the Treatment of Post-Dural Puncture Headache (PDPH) 
 
                                                                                                                              Version 10/5/2021 
INTERVENTIONAL 
RESEARCH PROTOCOL TEMPLATE 
NCT# 03112720 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Statistical Analysis Plan 
TRIAL FULL TITLE 
A Comparison of the Efficacy of Sphenopalatine Ganglion Block 
(SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
SAP VERSION 
1 
SAP VERSION DATE 
10/5/2021 
TRIAL STATISTICIAN 
William R. Grubb, MD 
Protocol Version (SAP 
associated with) 
Version 1 Protocol NCT# 03112720 
TRIAL PRINCIPAL 
INVESTIGATOR 
William R. Grubb, MD 
SAP AUTHOR(s) 
William R. Grubb, MD 
1 SAP Signatures 
I give my approval for the attached SAP A Comparison of the Efficacy of Sphenopalatine 
Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) dated 10/5/2021 
Statistician (Author) 
Name: William R. Grubb, MD 
Signature: 
   
             
Date:  
    10/5/2021                            
Statistician Reviewer (As applicable) 
Name: William R. Grubb, MD 
Signature: 
  
             
Date:  
   10/5/2021                                              
Principal Investigator 
Name: William R. Grubb, MD 
Signature: 
  
                 
Date:  
    10/5/2021                             
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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version 10/5/2021 
 
 
Table of Contents  
Skip To Section: Hold CTRL + Click (Below) To Follow Link in Blue 
 
1.0 
Research Introduction 
 
 
1.1 
Purpose/Specific Aims 
 
 
1.2 
Research Significance 
 
 
1.3 
Research Design and Methods 
 
 
1.4 
Preliminary Data 
 
 
1.5 
Sample Size Justification 
 
 
1.6 
Study Variables 
 
 
1.7 
Drugs/Devices/Biologics 
 
 
1.8 
Primary Specimen Collection 
 
 
1.9 
Interviews, Focus Groups, or Surveys 
 
 
1.10 
Timetable/Schedule of Events 
 
 
2.0 
Project Management 
 
 
2.1 
Research Staff and Qualifications 
 
 
2.2 
Resources Available 
 
 
2.3 
Research Sites 
 
 
3.0 
Multi-Site Research Communication & Coordination 
 
 
3.1 
Outside Research 
 
 
4.0 
Research Data Source/s 
 
 
4.1 
Primary Data – Subjects and Specimens 
 
 
4.2 
Subject Selection and Enrollment Considerations 
 
 
4.3 
Subject Randomization 
 
 
4.4 
Secondary Subjects 
 
 
4.5 
Number of Subjects 
 
 
4.6 
Consent Procedures 
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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4.7 
Special Consent Populations 
 
 
4.8 
Economic Burden and/or Compensation For Subjects 
 
 
4.9 
Risks to Subjects 
 
 
4.10 
Secondary Data – Record/Chart Reviews, Databases, Tissue Banks, Etc. 
 
 
4.11 
Chart/Record Review Selection 
 
 
4.12 
Secondary Specimen Collection 
 
 
5.0 
Special Considerations 
 
 
5.1 
Health Insurance Portability and Accountability Act (HIPAA) 
 
 
5.2 
Family Educational Rights and Privacy Act (FERPA) 
 
 
5.3 
NJ Access to Medical Research Act 
 
 
5.4 
Code of Federal Regulations Title 45 Part 46 (Vulnerable Populations) 
 
 
6.0 
Research Data Protection and Reporting 
 
 
6.1 
Data Management and Confidentiality 
 
 
6.2 
Data Security 
 
 
6.3 
Data Safety And Monitoring 
 
 
6.4 
Reporting Results 
 
 
6.5 
Data Sharing 
 
 
7.0 
Data and/or Specimen Banking 
 
 
8.0 
Other Approvals/Authorizations 
 
 
9.0 
Bibliography 
 
 
1.0 Research Introduction 
 
Title of Project 
A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine 
and Epidural Blood Patch (EBP) for the Treatment of Post-Dural Puncture Headache (PDPH) 
NCT# 03112720 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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version 10/5/2021 
 
Principal Investigator 
William R. Grubb, MD, DDS 
Sub-Investigators 
Shaul Cohen MD, Sagar S. Mungekar MD, Scott Mellender MD, Preet Patel MD 
(Administrative Assistant) 
Funding Source 
Department of Anesthesiology 
1. Purpose 
To compare the sphenopalatine ganglion block (SPGB), a local anesthetic technique that is 
facile to perform and carries fewer potential side effects, to the traditional, more invasive, 
epidural blood patch (EBP) for the treatment of post-dural puncture headache (PDPH). The 
SPGB is experimental while the EBP is considered to be the standard of care. 
1.1. Objectives 
1.1.1. To compare subjects who present with PDPH and are randomized into one of two 
treatment groups whether the SPGB technique is not inferior to the traditional 
EBP in treating their symptoms. 
1.1.2. To follow subjects who initially present with PDPH to determine the efficacy of 
either technique in maintaining a symptom-free period. 
1.1.3. To compare patients’ experiences with the SPGB as compared to the EBP. 
1.2. Hypotheses 
1.2.1. There will be no appreciable difference in the amelioration of PDPH symptoms    
with the SPGB technique as compared to the EBP. 
1.2.2. Both the SPGB and the EBP will maintain similar symptom-free periods. 
1.2.3. The patients will experience less subjective discomfort with the SPGB as 
compared to the traditional EBP. 
 
2. Background and Significance 
Dural punctures may be intended or unintended following instrumentation of the spine when 
administering neuraxial anesthesia or performing diagnostic studies such as lumbar punctures 
and myelograms. As many as 40% of patients may complain of frontal and nuchal headache 
several hours after dural puncture (1). Furthermore, patients complain of diplopia, loss of 
hearing, nausea, and vomiting. Symptoms may be self-limited, though the time range varies. 
Significant morbidity can be observed during this interim as patients remain bed-ridden, 
missing time from work and enjoyment with their families. Conservative treatment measures 
include maintaining a supine posture, hydration with fluids, caffeine intake, and pain control 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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with traditional oral and parenteral medications (2) until the symptoms subside. When an 
unintentional dural puncture occurs during epidural catheter placement, the catheter can be 
left in situ with a low infusion of saline to ameliorate the symptoms partially. 
Several theories exist to explain PDPH. Cerebral spinal fluid surrounds the brain and the 
spinal cord, all of which is surrounded by the dura mater. Traditionally, it was thought that 
following dural puncture, the leakage of cerebral spinal fluid (CSF) causes the brain that is 
usually suspended in this fluid to “sag”, an action that exerts traction on the meninges, which 
in turn causes headache (3-5). Recent studies have questioned this as the sole mechanism 
since any leakage would be slow, and would not explain the stark difference in symptoms 
from the supine to orthostatic positions (6). Instead, these symptoms likely share an etiology 
with other so-called “neurovascular headaches”. In the intact nervous system, CSF and the 
brain tissue exert pressure on the vasculature. This pressure is sufficient to cause collapse of 
the venous side of the circulation, a phenomenon known as “subdural venous collapse”. 
Following dural puncture, CSF pressure, which is normally greater than atmospheric 
pressure, drops as it tends to equalize through this extradural communication. The decreasing 
CSF and tissue pressures release the subdural venous collapse, allowing vasodilation. 
Furthermore, since the dural puncture turns the usually closed system into an open one, CSF 
pressure becomes dependent on the patient’s position, dropping significantly when sitting 
upright or standing. The dura is exquisitely sensitive to pain in the very areas surrounding 
blood vessels. The vasodilation triggers nociceptive nerve endings, which accounts for the 
exquisite pain from neurovascular headaches such as PDPH (6).  
The EBP has traditionally been the definitive mode of treatment in patients with PDPH. This 
intervention involves the autologous transfusion of a patient’s blood from a sterile peripheral 
site into the epidural space.  Several studies have established the EBP as standard of care for 
PDPH. A randomized, controlled clinical trial has showed that EBPs resolve PDPHs after 
one week in 84% of patients compared to 14% with placebo (7). Another prospective, 
randomized, double-blinded trial compared EBP to conservative management (fluid 
replacement, non-steroidal anti-inflammatory drugs, and caffeine) for the treatment of PDPH. 
(8). These authors found that when treated conservatively patients with PDPH noted little to 
no change in headache, as reported on a visual analog scale (VAS). Their headaches rated 8.2 
± 1.4 both before and after treatment. In the group who received an EBP, patients reported a 
decrease in headache from 8.0 ± 1.6 to 0.7 ± 0.16. The authors further state that “The 
epidural blood patch represents the first choice treatment of PDPH no matter the etiology, 
being significantly superior to the conventional treatment which did not affect pain scores” 
(8). These studies have helped establish the EBP as a standard of care for PDPH. It now 
appears as a listed treatment for PDPH in common physician reference resources such as 
UpToDate® (Waltham, MA) (9). 
Originally, the EBP was thought to act through a tamponade effect, plugging the dural defect 
and preventing the further leakage of CSF. As noted above, this is unlikely the true 
mechanism as patients often report immediate relief, which could not be explained by 
cessation of the minute flow of CSF. The more contemporary explanation is that the EBP 
does in fact plug the dural tear, but in doing so, it prevents the equilibration of CSF pressure 
with the atmospheric pressure. Injection of blood into the epidural space immediately raises 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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the CSF pressure within the closed spinal canal space and thus causes reflex cerebral 
vasoconstriction. Consequently, subdural venous collapse is restored and the headache 
subsides. 
Although the EBP has been proven to be one effective treatment for PDPH, it is an invasive 
procedure and carries the same risks as those associated with the inciting event. Infections, 
subdural and epidural hematoma, needle trauma, and back pain have been described (10,11), 
in addition to a possible second dural puncture. Furthermore, the procedure requires the 
physician to be adept at the epidural injection technique, which usually limits treatment to 
anesthesiologists.  
Given the purported neurovascular etiology of PDPHs, patients who suffer from this 
condition have been successfully treated with nerve blocks for immediate relief (12). We had 
proposed targeting the sphenopalatine ganglion based on the success of manipulating the 
trigeminal–autonomic arc for treating cluster headache, a type of neurovascular headache. 
Briefly, this reflex arc describes an afferent limb that includes trigeminal nerve fibers in the 
perivascular area of cerebral circulation. When stimulated, these neurons activate the efferent 
limb, the parasympathetic fibers within the greater superficial petrosal nerve, which in turn 
causes vasodilation (13). In neurovascular headaches, a triggering mechanism causes initial 
vasodilation which irritates the dura and stimulates the afferent limb of this arc. In PDPH, the 
equalization of pressure between the CSF and the atmosphere acts as a trigger. The 
parasympathetic efferent limb of this reflex causes vasodilation, which in this case is 
deleterious since it provides positive feedback to this reflex loop, causing continued 
headache. Blockade of the synaptic communication in the SPG would terminate this loop, 
and is the proposed pathophysiological mechanism by which neurovascular headaches are 
treated. 
Our recent literature review has suggested that there are multiple techniques for performing 
the sphenopalatine ganglion block. A proven method for performing the block involves using 
a cotton tip applicator to place lidocaine gel in the middle posterior pharynx followed by 
administration of 1 mL of 4% lidocaine solution through the plastic channel of the applicator, 
all simply by placing the soft, flexible, cotton-tip applicator into the nares (14). This 
technique of transmucosal application of local anesthetics was proposed by Lebovits et al. 
(15) and others (16). The side effects associated with SPG blocks are minimal, often limited 
to the bitter taste of the anesthetic solution. The theoretical rare risks of anaphylaxis and 
severe epistaxis exist, but have not been described in the literature.  
The SPGB has been described in the literature for the treatment of cluster headaches and is 
recognized as a treatment for this condition when other modalities fail (17-20). A study has 
investigated its use for the treatment of PDPH (21). Twenty-eight patients with PDPH were 
offered a SPG block prior to EBP. Nineteen of 28 patients noted relief and only 9 patients 
eventually needed an epidural blood patch after 1 week. Moreover, most patients (~93%) 
noted relief of headache at and beyond 72 hours following the procedure significantly 
decreasing morbidity during the otherwise symptomatic period. In this pilot study, 
approximately 68% of patients were saved from having to undergo the invasive EBP in favor 
of a more cost-effective and less invasive technique (21). This study has helped establish the 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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sphenopalatine ganglion block as a standard of care for the treatment of PDPH, especially 
when other modalities fail or are not preferred by the patient. The SPGB appears as a 
treatment in the common physician reference resource UpToDate® (Waltham, MA) for the 
treatment of adverse effects of neuraxial anesthesia (22). 
3. Research Design and Methods 
We propose to treat patients suffering from a severe and incapacitating headache resulting 
from dural puncture. Both the EBP and SPGB therapies have been shown to reduce the 
intensity of PDPH. The design of this study seeks to determine the duration of relief 
associated with both therapies and to compare the patient’s satisfaction with both techniques. 
3.1. Subject selection and enrollment considerations 
3.1.1. Subject recruitment 
Patients who suffer from headache following dural puncture may present 
following neuraxial procedures such as epidural anesthesia, diagnostic lumbar 
puncture, diagnostic radiographic studies to physicians in several departments 
(Table 1). 
Table 1. Procedures that may result in PDPH and the respective departments to whom suffering 
patients may present 
Recent procedure 
Presenting department 
Epidural or spinal anesthesia 
Anesthesiology or Pain Medicine (division of Anesthesiology) 
Epidural steroid injection 
Pain Medicine 
Diagnostic lumbar puncture 
Medicine, Pediatrics, Neurology, Emergency Medicine (ER) 
RWJUH 
Myelogram 
Neurology 
 
The members of the respective departments will be informed of this study for 
enrollment of patients. For the purposes of the initial referral, all patients meeting 
minimal criteria for PDPH (Table 2) will be considered. These criteria for referral 
will be published by electronic mail to the members of the aforementioned 
departments. Physicians who seek to make a referral will do so by contacting the 
Pain Medicine physician-on-call. This on-call physician is available continuously 
(24 hours per day, 7 days per week) by mobile telephone. The Pain Medicine 
physician-on-call will receive the demographic information of this patient in the 
hospital and inform the principle investigator or his designee for enrollment 
pursuant to criteria outlined in the next section. 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Table 2. Minimum criteria for initial referral into study 
Criterion 
A neuraxial procedure within the past 7 days 
Postural headache that improves with supine position 
Absence of other more likely etiology of headache 
 
3.1.2. Inclusion Criteria 
We will include patients with a moderate or severe PDPH classification, modified 
from van Kooten et al. (7) Complete inclusion criteria follows (Tables 3–5) 
Table 3. PDPH classification 
Classification 
Definition 
Absent 
no headache 
Mild 
postural headache with some restriction of daily activities but without 
confinement to bed and without associated symptoms 
Moderate 
postural headache with confinement to bed for at least part of the day OR 
postural headache with associated symptoms restricting daily activities 
Severe 
postural headache with confinement to bed for entire day with associated 
symptoms 
 
Table 4. Symptoms associated with PDPH 
Symptoms 
Nausea and/or vomiting 
Dizziness 
Hearing loss, hyperacusis, or tinnitus 
Photophobia, diplopia 
Nuchal pain or stiffness 
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Table 5. Inclusion criteria 
Criteria 
Moderate to severe PDPH (Table 3) for greater than 24 hours, but not more than 7 days after the 
initial procedure 
Men, women, and children ages 13–92 
Consent to participate in this study 
 
3.1.3. Exclusion criteria 
Criteria to exclude patients are listed (Table 6). Urine pregnancy tests are 
standard of care for all women of child bearing age prior to any anesthesia 
procedures. We note that pregnancy is one of our exclusion criteria. Many of the 
patients we seek to enroll in this study will have received neuraxial anesthesia for 
childbirth. Since a urine pregnancy test is not reliable in post-partum women 
owing to residual circulating levels of the beta subunit of human chorionic 
gonadotropin hormone (β-hCG) leading to a false positive result (23), any woman 
who complains of PDPH within 7 days of delivery will be considered not 
pregnant and thus be eligible for our study. All other women of child bearing age 
will require a negative urine pregnancy test result within the last 7 days. If no 
pregnancy test was completed prior to referral to this study, the patient will be 
required to undergo one prior to randomization. Any patient who has a positive 
pregnancy test or refuses to undergo this test will be excluded from the study. The 
pregnancy test will be billed as part of the routine work up involved with the 
standard of care. 
In patients receiving antithrombotic or thrombolytic therapy, we will use the most 
recent guidelines from the American Society of Regional Anesthesia Practice 
Advisory (24) to determine whether the patient may undergo neuraxial anesthesia. 
Any patient who would be unfit for epidural instrumentation will be excluded 
prior to randomization. 
We will exclude non–English-speaking patients in this study. While both 
procedures could potentially be performed in patients regardless of language 
proficiency, this study will specifically assess the patients’ symptoms such as 
pain, nausea, and discomfort among others as listed in (Table 8). These 
assessments would need to be made contemporaneously during the procedure, 
which can be difficult when using a telephone translator. There would be a delay 
in receiving a response; moreover, the patient would not be able to hold a 
telephone handset when assuming the correct posture and position for these sterile 
procedures. 
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Table 6. Exclusion criteria  
Criteria 
Age less than 13 
Non–English-speaking 
Pregnancy 
Allergy to lidocaine or lidocaine-containing ointments or solutions 
Heart disease with New York Heart Association (NYHA) Functional Classification II or greater 
Current treatment with lidocaine patch or other topical or depot vehicle for chronic pain 
Presence of a spinal cord stimulator, intrathecal pump, or other implanted device in the spine 
Platelet count < 100,000/ μL 
Sepsis 
Skin or soft tissue infection overlying lumbar spine 
Sinusitis requiring the current use of antibiotics 
Nasal polyps 
Nasal surgery within the past 7 days 
Neurological event including stroke, intracranial hemorrhage, epidural hematoma, or other 
event causing a focal deficit within the past 30 days 
Current anticoagulant therapy contraindicating epidural injection 
Prior treatment with SPG block or EBP for this presenting condition 
 
All inclusion criteria (table 5) and exclusion criteria (table 6) will be ascertained 
from the patient’s medical chart. 
All patients who are excluded due to one or more criteria listed above will be 
treated for their headache symptoms according to standard clinical practices, 
which may include EBP, SPGB or other block, or medical management as the 
clinical situation dictates. An anesthesiologist or a physician in another 
department may perform these procedures according to institutional practices. 
Exclusion from this study will not in any way prevent a patient with PDPH from 
receiving the treatment he or she would have otherwise received. 
3.1.4. Consent Procedures 
Once a patient is referred for enrollment for this study, only the anesthesiologists listed on this 
study (William Grubb, Shaul Cohen, Shruti Shah, Scott Mellender & Sagar Mungekar) will 
interview the patient to confirm that the minimum criteria listed in Table 2 are met. This 
interview will take place as soon as possible after the Pain Medicine physician-on-call refers the 
patient to the PI or SI. In all cases, this initial consultation will take place within 24 hours of the 
referral as is the standard practice for all consultation requests sent to the Pain Medicine 
physician-on-call. In the rare case that neither the PI nor any SI is available within this period, 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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the patient’s PDPH will be treated according to standard practice. In no instance will treatment 
for PDPH be delayed because of failure of the PI or SI to interview the patient. 
Only the anesthesiologists listed in this study will obtain informed consent 
(William Grubb, Shaul Cohen, Shruti Shah, Scott Mellender & Sagar Mungekar). 
The administrative assistant (Preet Patel) will not obtain informed consent. 
Resident anesthesiologists will not obtain informed consent. Each patient will be 
given the informed consent document to read and consider prior to agreeing to 
participate. The PI or SI will answer all the subjects’ questions and ensure the 
subject has had adequate time to consider participation prior to signing the 
informed consent document. No study assessments, measurements, or 
interventions will occur prior to subject signing the informed consent document. 
In addition, at each new encounter with the subject, the investigator will ask the 
subject if he or she is agreeable to continued study participation. 
We acknowledge that due to the intensity of the headache and any associated 
symptoms, the patient may not be able to give informed consent to participate in 
this study. If the PI or SI determines in such a case that the patient’s 
overwhelming symptomatology prevents decision-making capacity regarding 
participating in this study or if the patient states that he or she cannot make a 
decision regarding participation in this study, then the patient will NOT be 
enrolled in this study. No surrogate decision maker will be allowed to give 
consent. As noted earlier, such patients will be treated for their headache 
symptoms according to standard clinical practices taking the patient’s wishes into 
consideration. Failure to consent for participation in this study will not in any way 
prevent a patient with PDPH from receiving the treatment he or she would have 
otherwise received. 
3.1.5. Subject Costs and Compensation 
The subject will not incur additional costs outside of standard of care costs for 
medication and pregnancy testing that may be performed for routine standard of 
care. There will be no compensation for participation in this study. 
3.1.6. Chart Review Selection 
There will be no retrospective chart review. Below is the “Data Collection List” 
that will be used to gather data at every patient encounter as described previously. 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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3.2. Study Design 
3.2.1. Type 
This is a non-inferiority trial comparing the SPGB to the EBP for the treatment of 
PDPH. The study is not blinded to the subject or investigator. Due to the nature of 
the procedure and the anatomical site of intervention, both will know which 
method they are receiving or delivering. We acknowledge this as a limitation of 
our study but reiterate that blinding one or both parties is not feasible. 
3.2.2. Randomization 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Subjects suffering from PDPH shall be randomized to one of two groups (Table 
7) by a random number generation spreadsheet (Excel, Microsoft, Redmond, 
Washington). 
Table 7. Patients with PDPH to be treated for their symptoms are randomized to one of the two 
groups below 
Group 
Intervention 
1, EBP (control) 
EBP as described below 
2, SPG block (treatment) 
SPG block as described below 
 
3.2.3. Symptoms assessment 
After obtaining informed consent and inclusion in the study, the patient’s 
symptoms will be assessed prior to the intervention. Four headache and associated 
symptoms will be assessed on a visual analog scale of 0 to 10 or in a binary 
manner (Table 8 and Figure 1).  
Table 8. Symptoms that will be assessed prior to and after interventions. VAS: (visual analog scale, 
0–10, Figure 1) 
Symptom 
Description 
Scoring System 
orthostatic headache 
headache that presents or worsens when changing 
from supine to sitting or standing position 
VAS 
supine headache 
headache when supine 
VAS 
nuchal headache 
pain in the back of the neck either when supine or 
sitting 
VAS 
nausea 
nauseated with or without vomiting 
VAS 
auditory disturbances 
tinnitus, hyperacusis, subjective loss or decrease in 
hearing, or worsening of any other symptoms with 
noise 
VAS 
visual disturbances 
photophobia, diplopia, subjective loss or decrease in 
vision, or worsening of any other symptom with light 
VAS 
vomiting 
vomiting that day since the past symptom assessment 
binary (yes or no) 
pruritus 
itching in any part of the body 
VAS 
epistaxis 
bleeding from either naris 
 
numbness 
subjectively decreased sensation 
VAS, location 
 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
Treatment of Post-Dural Puncture Headache (PDPH) 
PI: Grubb 
 
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Figure 1. Visual Analog Scale (VAS) used to grade severity of symptoms. 0 = symptom absent. 10 = 
symptom severity is the worst that can be imagined. Any integer between 0 and 10, inclusive, may be 
chosen by the patient. 
 
 
For patients randomized to group 1 (EBP), the symptoms in Table 8 will be 
assessed and graded 30 and 60 min post-procedure in person by the 
anesthesiologist who performed the procedure. The same symptoms will be 
assessed 24 and 48 hours after the procedure, in person if the patient remains in 
the hospital or by telephone if the patient has since been discharged. In addition, 
at 30 min the patient’s comfort level with the procedure will be assessed using the 
VAS (0 = no discomfort during procedure; 10 = as uncomfortable as could 
possibly be imagined during the procedure). Specifically, the investigator will ask 
the patient how comfortable they were with the procedure irrespective of 
headache relief.  
For patients randomized to group 2 (SPGB), the symptoms in Table 8 will be 
assessed and graded at 30 min post-procedure. If this treatment does not decrease 
the patient’s “orthostatic headache” severity past the pre-treatment score, then the 
SPGB will be performed for a second time. The symptoms will be graded again 
30 min after the second block. If the “orthostatic headache” severity score is still 
unchanged, then a SPGB will be performed for a third time. If the “orthostatic 
headache” severity score remains unchanged at the 30 min mark following the 
third SPGB, the procedure will be considered a failure and conservative measures 
or an EBP will be offered to the patient. 
If the first, second or third SPGB succeeds in decreasing the “orthostatic 
headache” severity score at 30 min post-procedure, the symptoms in Table 8 will 
be assessed and graded again at 60 min post-procedure. In all cases, the same 
symptoms will be assessed at 24 and 48 hours post-procedure in the manner noted 
above. If patients in any group on telephone interview note dissatisfaction with 
the alleviation of the symptoms or if the symptoms return, they will be given the 
option of arriving at the Pain Clinic at the New Jersey Pain Institute during 
normal clinic hours or to the emergency room (ER) after hours. At that time, they 
will be given the option of an EBP, SPGB or medical management. This is the 
same as what would be offered if a patient underwent treatment for a PDPH 
outside of this study and had symptoms return afterward. 

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3.3. Procedures 
3.3.1. Location 
Both procedures, the EBP and the SPGB will take place in the Regional Nerve 
Block Area, a section of the operating room holding (OR holding) suite 
specifically designed for the performance of regional nerve blocks. Patients who 
consent to this study will be transported to this area by the institution’s patient 
transport personnel and any other personnel that the institutional policy dictates. 
This area is accessible by anesthesiologists and includes the requisite monitoring 
and procedure equipment. This private area is the same location used by 
anesthesiologists for other regional nerve blocks; however, only one patient will 
be in any one bed location area at any given time. 
Only the anesthesiologists (William Grubb, Shaul Cohen, Shruti Shah, Scott 
Mellender & Sagar Mungekar) will perform these procedures. Administrative 
assistants (Preet Patel) and residents will not perform any procedures. Ancillary 
staff such as resident physicians, nurses and technicians may be required to assist 
in checking the patient into the area, monitoring, and positioning as institutional 
policy dictates. The pregnancy test is part of the exclusion criteria (section 3.1.3) 
and all details with respect to the pregnancy test can be found in that section. The 
pregnancy test is not a part of the procedures. 
3.3.2. Monitoring 
While either the EBP or SPG block are performed, the patient’s vital signs will be 
monitored by continuous pulse oximetry and five-lead electrocardiography (EKG) 
and a non-invasive blood pressure cuff cycled at least every five minutes. After 
the randomized procedure is assigned, a time-out procedure will be performed 
according to institutional protocol. 
3.3.3. EBP 
Immediately after obtaining informed consent, inclusion in the study, transport to 
the OR holding suite, randomization to the control arm of this study, completion 
of the time-out procedure, and initial symptom assessment, the patient will 
receive an EBP. The EBP involves three separate procedures: epidural access, 
venipuncture, and autologous transfer. Vital-sign monitoring of the patient as 
described above will commence once the patient is checked into this area. 
Symptom assessment will be as described in section 3.2.3. In addition, the 
investigator will assess whether the patient has any adverse effects of this 
procedure. These are rare, but could include pain at the site, a new motor deficit, a 
new sensory deficit and continued bleeding from any puncture site. 
3.3.3.1. 
Epidural Access 
Epidural access will be performed by the anesthesiologist using the Perifix 
FX Epidural Anesthesia Kit (Braun, Bethlehem, Pennsylvania), the same 
kit that is currently used for epidural anesthesia. The subject will be 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
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positioned in either the decubitus or sitting position. The anesthesiologist 
will wear sterile gown and gloves. The patients’ skin over the lumbar area 
will be prepped with povidone-iodine three times and draped in a sterile 
fashion. The appropriate lumbar interspace, one or more interspaces above 
the presumed site of the initial dural puncture, will be identified by 
anatomical landmarks and palpation. Five mL of 2% lidocaine will be 
locally infiltrated with a 25-gauge needle. A 17-gauge Touhy needle will 
be placed into the epidural space using the loss-of-resistance to air 
technique. Once positioned, the sterile stylette will be replaced within the 
needle to maintain the sterility of the epidural space. All of the equipment 
described in this section is included in the aforementioned kit. 
3.3.3.2. 
Venipuncture 
A tourniquet will be applied to either upper extremity to identify a 
peripheral venous site. The intended area of venipuncture will be prepped 
with betadine or chlorhexidine gluconate and isopropyl alcohol 1-mL 
applicator (ChloraPrep, CareFusion, San Diego, California) according to 
the manufacturer’s directions. Venipuncture will be performed with an 18-
guage needle attached to a 20-mL syringe. Twenty mL of blood will be 
aspirated into this sterile system. The tourniquet will be released and the 
needle, removed. Hemostasis will be achieved with manual pressure 
followed by a sterile dressing. 
3.3.3.3. 
Autologous Transfer 
The stylette from the Touhy needle described above will be removed. 
Negative aspiration will confirm that the needle has not pierced the dura or 
vasculature. Using sterile technique, the autologous blood sample will be 
slowly injected into the epidural space through the Touhy needle. 
Following epidural needle removal, pressure dressings will be applied to 
achieve hemostasis. The patient will be returned to the supine position and 
will remain in this position for one hour. 
3.3.4. SPG block 
Immediately after obtaining informed consent, inclusion in the study, transport to 
the OR holding suite, randomization to the treatment arm of this study, 
completion of the time-out procedure and initial symptom assessment, the patient 
will receive an SPG block. Vital-sign monitoring of the patient as described above 
will commence once the patient is checked into this area. 
The subject will be placed in the supine position with the neck extended to the 
extent that he or she can tolerate with the use of a shoulder roll and head-of-the-
bed positioning as appropriate. One cm of 5% lidocaine ointment will be applied 
to the end of each of two sterile 6-inch hollow–plastic-shaft cotton-tip applicator 
(Cardinal Health, Dublin, Ohio). One so-treated applicator will be inserted each of 
the patient’s two both nares, posteriorly directed toward the anatomic location of 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
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the sphenopalatine ganglion. Correct positioning will evidenced by slight 
resistance at the appropriate depth. Four mL of 1% lidocaine solution will then be 
slowly injected into the hollow shaft of the applicator and allowed to anesthetize 
the ganglion topically by gravity flow for 30 minutes. The applicators will be 
removed from the nares and the subject will be returned to the supine position 
with a neutral neck position. 
Symptom assessment, determination of treatment failure, and performance 
subsequent procedures will be as described in section 3.2.3. In addition, the 
investigator will assess whether the patient has any adverse effects of this 
procedure. These are rare, but could include pain in the nares, epistaxis, 
pharyngeal numbness and a bitter taste in the mouth. 
3.4. Duration of Study 
The study will last 8 years in duration. 
3.5. Study Sites 
This is a single-site clinical research study that will be conducted at Robert Wood 
Johnson University Hospital, New Brunswick, NJ 08901 by the PI and SIs of Rutgers 
Robert Wood Johnson Medical School, part of Rutgers, the State University of New 
Jersey. 
3.6. Sample Size Justification 
We derive data for calculation of the sample size from the prior studies noted above. In 
the control group (Table 7, Group 1, EBP) we predict a success rate of 84% as noted by 
van Kooten et al. (7). In the treatment group (Table 7, group 2, SPG block) we predict a 
success rate of 68% based on our pilot study (15).  If therefore there is a true 16% 
(84% - 68%) in favor of the EBP group then 210 subjects are required to be 90% certain 
that the upper limit of a one-sided 95% confidence interval will exclude a difference in 
favor of the EBP group of more than 33%. This calculation was performed using the 
formula below (Table 9 and Equation) using an online calculator 
https://www.sealedenvelope.com/power/binary-noninferior/). 
Our chosen non-inferiority limit d of 33% means that we believed saving 67% 
(100% – 33%) of patients from the invasive EBP in favor of the non-invasive, cost-
effective SPG block would be clinically relevant. 

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Table 9. Values used for determination of sample size 
Variable 
Description 
Value 
n 
sample size 
210 
𝝓−𝟏 
cumulative distribution function of a standardized normal deviate 
n/a 
𝜶 
significance level, alpha 
0.05 
𝜷 
false negative rate, beta, where power (1 −𝜷) = 0.90 
0.10 
𝝅𝒔 
success rate in control group 
0.84 
𝝅𝒆 
success rate in treatment group 
0.68 
𝒅 
non-inferiority limit 
0.33 
 
Equation. Sample size calculation for a binary outcome non-inferiority trial 
𝐧= (𝝓−𝟏(𝜶) + 𝝓−𝟏(𝜷))
𝟐
× 𝝅𝒔× (𝟏𝟎𝟎−𝝅𝒔) + 𝝅𝒆× (𝟏𝟎𝟎−𝝅𝒆)
𝝅𝒔−𝝅𝒆−𝒅𝟐
 
 
4. Study Variables 
4.1. Independent Variables and Interventions 
As described in Section 3.3 “Procedures”, above, the two interventions to be studied are 
the EBP and the SPG block. Though the EBP is the standard of care for definitive 
treatment for PDPH, both procedures are well documented in the literature. Furthermore, 
the SPG block has already been shown in our pilot study to decrease the symptom 
severity in patients with PDPH, thus patients in both arms of this study will receive a 
treatment modality. 
4.1.1. Drug and device Intervention for EBP 
The procedure for the EBP is described in Section 3.3.3 above. All of the drugs 
and equipment required are either part of the kit noted or readily available in the 
Regional Nerve Block area. No equipment or drug described is experimental or 
investigational. The Current Procedural Terminology (CPT®, American Medical 
Association, Chicago, Illinois) code for EBP is 62273, “Injection, epidural, of 
blood or clot patch”. 
4.1.2. Drug and device Intervention for SPG block 
The procedure for the SPG block is described in Section 3.3.4 above. All of the 
drugs and equipment required are readily available in the Regional Nerve Block 
area. No equipment or drug described is experimental or investigational. Though 
a CPT code exists for a SPG block involving an injection (64505), as the 
technique described herein is non-invasive and does not involve injection, and as 
a specific code does not exist for this technique, it will be included in the 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
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appropriate level Evaluation and Management (E/M) code. (AMA 
Knowledgebase #5436). 
4.2. Dependent Variables and Outcome Measures 
Symptom assessment as described in section 3.2.3 will be by personal or telephone 
interview by the PI or SI using a questionnaire (Attachment 1). The laboratory tests 
noted in the exclusion criteria including the pregnancy test and platelet count (Table 6), 
and the medical history interview are not specific to this study, and would be part of 
standard practice if the patient sought intervention for a PDPH outside of this study.  No 
specimens will be taken. 
4.3. Risk of Harm 
As noted earlier, both the EBP and the SPG block are well-established procedures with 
favorable safety profiles. The limited risks of the procedures themselves are listed in the 
procedure sections above, but these are not specific to inclusion in this study. 
Subjects who are enrolled in this study will be randomized to either one of the treatment 
arms whereas patients would otherwise be given the choice of which one they prefer. 
There is a risk of psychological or emotional harm that is intrinsic to any such 
randomized treatment study; however, this risk is minimized since as stated earlier, all 
subjects retain the ability to be excluded from the study and undergo the procedure of 
their choice at any point in the study process. 
This study aims to determine whether there is a difference in the symptom-free period. If 
the study ultimately finds that one treatment maintains a longer symptom-free period, the 
subject in the other arm of the study could face having to undergo a repeated or new 
procedure. Again, this harm is minimal, since symptom-assessment scheme is such that 
in the period that symptoms are likely to relapse after a failed treatment (1–24 hours), 
the patient will be repeatedly assessed. 
The subject may encounter minor inconvenience after receiving two follow-up phone 
calls for symptom assessment instead of the standard one call. This would account for 
approximately 5 minutes of extra time out of the patient’s day. 
4.4. Potential for Benefit 
All patients enrolled in this study will receive one type of treatment for a PDPH. Since 
we seek to enroll all patients who meet the minimum criteria for the diagnosis of PDPH 
(Table 2), all included subjects will potentially be spared pain medications that are often 
given during conservative treatment efforts as well as avoiding having to cope with these 
symptoms while medical management is attempted. 
If one arm treatment is found to be better than the other, the subjects in that group may 
experience a quicker relief of symptoms, and improvement in the overall quality of life. 

Title: A Comparison of the Efficacy of Sphenopalatine Ganglion Block (SPGB) with 5% Lidocaine and Epidural Blood Patch (EBP) for the 
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Following the conclusion of the study, the medical community will gain knowledge 
about the best method by which certain individuals may be treated for PDPH.  
5. Data Handling and Statistical Analysis 
5.1. Safeguarding Data 
All data will be stored in a locked file in the office of the principal investigator with 
limited access.  Once the subject is enrolled, he or she will be assigned a number that 
will both assign the subject to one of the arms as well as serve as the identification 
number for the storage of results. Since this study involves multiple contacts with the 
subject, one set of data will contain demographic information including the patient’s 
name and telephone number, which is recognized as protected health information (PHI). 
The other set of data will only reference the assigned number and will contain the 
symptom assessment data. The link to the protected health information (PHI) will be 
stored separately from the study files and will be destroyed after all the data has been 
collected and analyzed. Up to 500 subjects may sign the informed consent for 
participating in this trial. This number is to ensure 210 subjects complete each study 
group below. Therefore, we will be replacing subjects that do not complete the study as 
designed. 
5.2. Analysis 
Nonparametric data such as those resulting from the VAS assessments from the two 
groups will be compared using the Mann–Whitney U test. The Student’s t-test will be 
used to compare normally distributed continuous variables. A p value of less than or 
equal to 0.05 will be considered statistically significant. 
6. Data and Safety Monitoring 
All subjects enrolled in this study will receive at least one of two types of treatment for 
their PDPH. Both the EBP and SPG block are low-risk procedures that can be and are 
routinely performed in an office setting on outpatients in our pain clinic at the New 
Jersey Pain Institute. Furthermore, neither of these techniques are experimental; rather, 
their methods are well documented in literature and are common procedures in the pain 
medicine field. 
Subjects who undergo the procedures within this study will have additional monitoring 
as opposed to patients who undergo the same procedures outside of this study. Patients 
in this study will receive two follow-up phone calls to assess their symptoms and to 
expedite the availability of any additional procedures that need to be performed. These 
telephone calls will also serve to inform the SIs and PI if the patients are experiencing 
any undue and unexpected harms as a result of this study. As all of the investigators in 
this study are in the department of anesthesia, they are the best equipped to identify 
potential side effects and treatment. 
All subjects enrolled in this study will be given a contact sheet including phone numbers 
by which they may reach the PI, emergency room, the pain clinic, and the Pain Medicine 

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physician-on-call who, as previously stated, is available continuously by mobile 
telephone. 
7. Reporting Results 
7.1. Individual Results 
The only laboratory tests that may be performed are a urine pregnancy test and a platelet 
count as part of the exclusion criteria (Table 6). Both of these tests are frequently 
performed on patients in the hospital. If this test was already performed before the 
patient was enrolled in the study, the physician who ordered the test will be responsible 
for notifying and counseling the patient. If the test is performed after enrollment in the 
study, in the case of an unexpected result, namely a positive pregnancy test or a low 
platelet count, the patient will be notified immediately after the PI or SI views the result. 
The patient will be excluded from the study and counselled about the ramifications of 
the results. These laboratory tests will be performed using the same equipment and 
methods that are used for all patients at Robert Wood Johnson University Hospital. 
7.2. Aggregate Results 
Aggregate results will be available after statistical analysis. Subjects may contact the PI 
to view or learn about the aggregate results after the study has been completed. Subjects 
may be provided with copies of abstracts or directions on how to retrieve the data 
resulting from this study. Any study data so released to the subjects will be anonymized 
such that no protected health information is traceable from those data. 
7.3. Professional Reporting 
The data gathered and conclusions reached from this study will be presented in several 
venues including departmental meetings, abstracts and posters at professional meetings, 
and a manuscript in a peer-reviewed pain medicine journal. 
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