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\begin{document}

\title{Neostigmine and atropine as a treatment for Postdural Puncture Headache
after spinal anesthesia in cesarean section: A Case Report}



\author[1]{Indra Shrestha}%
\author[1]{Rupak Chalise}%
\author[1]{Saroj Poudel}%
\author[1]{Ashim Regmi}%
\author[1]{Anup Ghimire}%
\author[1]{Bikash Khadka}%
\author[1]{Kishor Khanal}%
\affil[1]{Nepal Mediciti}%


\vspace{-1em}



  
  \date{May 23, 2024}


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\textbf{INTRODUCTION}

An unpleasant experience for both the patient and the anesthetist,
post-dural puncture headache (PDPH) is a complication of spinal
anesthesia or lumbar puncture. It is believed to be caused by cerebral
vasodilation, which is an indirect consequence of low cerebrospinal
fluid (CSF) pressure, or meningeal traction linked to low CSF
pressure.\textsuperscript{\textbf{1}} PDPH incidence varies, although it
is generally thought to be 36\% or more after lumbar puncture, 0\%-10\%
after spinal anesthesia, and 81\% after an unintentional dural puncture
during epidural insertion.\textsuperscript{\textbf{2, 3}} Although PDPH
typically resolves on its own, it can make it difficult for mothers to
care for their infants and lengthen hospital stays. Serious side effects
such as subdural hematoma, convulsions, sagittal sinus thrombosis, and
cranial nerve palsies are more infrequently linked to PDPH.

\textbf{CASE PRESENTATION}

We report a case of a 31-year-old female who had a cesarean section
under spinal anesthesia with a history of gestational hypertension and
presented with severe positional headache, blurring of vision on the
5\textsuperscript{th} postoperative day (POD) to a local hospital where
she had done her cesarean section. The headache was postural, mainly in
the front-occipital area, and worsened with upright posture.
Conservative management for headache was done in primary hospital but
couldn't subside. So, she was referred to our hospital.

On the 7\textsuperscript{th} POD, she was admitted to our hospital with
a worsening headache despite conservative and Non-steroidal
anti-inflammatory drug (NSAID) treatment. During the presentation, she
had difficulty speaking, and diplopia, and her Glasgow Coma Scale (GCS)
was E4V5M6.

On the 8\textsuperscript{th} POD, the headache was persistent with
self-reporting NRS score of 7/10 even though she was on intravenous
fluids, NSAIDs, and opioids. A Sphenopalatine ganglion block was tried
but that helped only for a few minutes. The patient was planned for
epidural blood patch but refused to have the procedure because of her
bad prior experience with spinal anesthesia.

As an alternative to EBP, on the next day, intravenous neostigmine (20
mcg/kg) along with atropine (10 mcg/kg) was given over a period of 10
minutes. After 30 minutes of injection, her pain scoring (NRS) was 1/10,
and she did not require any forms of pain medication for 24 hours.

\textbf{DISCUSSION}

A thorough history and physical examination, as well as the clinical
presentation (with documented Dural puncture and acute postural headache
being the most distinctive features), are used to make the diagnosis of
PDPH. An intracranial pathology such as an intracranial subdural
hematoma and posterior reversible encephalopathy syndrome are included
in the differential diagnosis of PDPH in an obstetric patient, along
with caffeine withdrawal, headaches, meningitis, sinus-related
conditions, preeclampsia, pneumocephalus, and
meningitis.\textsuperscript{\textbf{4}}

The International Headache Society (IHS) defines PDPH as a headache
occurring within 5 days of a lumbar puncture, caused by cerebrospinal
fluid (CSF) leakage through the dural puncture. It is usually
accompanied by neck stiffness and/or subjective hearing symptoms within
two weeks; the PDPH typically goes away on its own or after the leak has
been sealed with an autologous epidural lumbar
patch.\textsuperscript{\textbf{5}}

Treatment options can be divided into conservative, pharmacological, and
epidural blood patch (EBP). Conservative management has traditionally
involved bed rest and fluids, though there is little evidence to support
either of these measures.

Numerous other reports exist in the literature with promising results
for a variety of other pharmacological agents, including 5HT agonists
(e.g., Sumatriptan), gabapentin, DDAVP, theophylline, and
hydrocortisone. To date, there is insufficient evidence to support their
use. A recent Cochrane review has concluded that therapeutic EBP is
beneficial compared with conservative treatment for
PDPH.\textsuperscript{\textbf{6}} Even though it is considered the gold
standard of treatment, but the success rate is 50\%, and the need for a
second EBP may be 40\%.\textsuperscript{\textbf{7}} Early complications
include backache during injection, fever, bradycardia, and seizures.
Late complications include meningitis, subdural hematoma, arachnoiditis,
and radicular pain.\textsuperscript{\textbf{8}} In this case, we have
tried pharmacological means such as Neostigmine (20 mcg/kg) and atropine
(10 mcg/kg) after conservative management
failed.\textsuperscript{\textbf{9}} The numeric Rating Scale was 1/10
after 30 minutes of injection. She did not require any pain medications
after a single dose of neostigmine and atropine. A single dose of
neostigmine and atropine was enough, although this can be given every 8
hours if the headache has not subsided.

Systemic neostigmine does not cross the blood-brain barrier. However, it
can enter the CSF because the BBB and Blood --CSF barriers are
anatomically distinct. Neostigmine increases the level of acetylcholine
in CSF and in the brain through inhibition of cholinesterase, resulting
in cerebral vasoconstriction. The central effects of both drugs
influence both cerebrospinal fluid secretion and cerebral vascular tone,
which are the primary pathophysiological changes in PDPH
(figure.1).\textsuperscript{\textbf{10, 13}}

As described by Ahmed et al in a randomized controlled trial of
involving 85 patients, use of neostigmine/atropine for PDPD treatment
when compared with conservative treatment of hydration and analgesic had
significantly better outcome. However side effects such as abdominal
cramps, muscle twitches and urinary bladder hyperactivity occurred in
the treatment group. Although the study was designed to administer the
interventional drug eight hourly for a duration of 72 hours, the authors
report not needing more than 2 subsequent dosages of the treatment drug
for symptomatic relief. In our case, a single dose was sufficient to
achieve excellent symptomatic relief with no reported side
effects.\textsuperscript{\textbf{14}}

\textbf{CONCLUSION}

In the context of severe headache not subsiding with conservative
management and intensity of headache persistently worsening, one must
have a neurologic examination followed by neuroimaging for timely
diagnosis and treatment. Neostigmine/atropine is a choice drug for the
management of severe headaches in post-dural puncture headaches after
spinal anesthesia. Neostigmine/atropine was effective in treating PDPH
after only a single dose. Although lacking robust evidence, use of a
novel and non-invasive treatment when compared to an invasive procedure
like an epidural blood patch certainly warrants more attention and
future research.

\textbf{ABBREVIATIONS}

PDPH Post Dural puncture headache

EBP Epidural blood patch

CSF Cerebrospinal fluid

GCS Glasgow Coma Scale

NRS Numerical Rating Scale

VC Vasoconstriction

VD Vasodilation

BL-CSF Blood cerebrospinal fluid barrier

CSG Cervical sympathetic ganglia

\textbf{AUTHOR CONTRIBUTIONS}

\textbf{Indra Kumar Shrestha:} Conceptualization; data curation;
methodology; writing - original draft; writing -- review and
editing.\textbf{Rupak Chalise:} Data curation; methodology; writing --
original draft; writing -- review and editing\textbf{. Saroj Poudel:}
Data curation; methodology; writing - original draft; writing -- review
and editing. \textbf{Ashim Regmi:} Supervision; writing -- original
draft; writing -- review and editing. \textbf{Anup Ghimire:}
Supervision; writing -- review and editing. \textbf{Bikash Khadka:}
Supervision; writing -- review and editing. \textbf{Kishor}
\textbf{Khanal:}Supervision; writing -- review and editing.

\textbf{ACKNOWLEDGMENTS}

We would like to express our sincere gratitude to the patient, clinical
team and Intensive care unit department for their valuable
contributions.

\textbf{FUNDING INFORMATION}

None

\textbf{CONFLICTS OF INTEREST STATEMENT}

No potential conflict of interest relevant to this article was reported.

\textbf{ETHICAL CONSIDERATIONS}

This case report did not require the approval of any Ethical Committee.

\textbf{INFORMED CONSENT}

Written informed consent was taken from the patient.

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\end{enumerate}\selectlanguage{english}
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