Keywords
adverse allergic reaction - CSF rhinorrhea - intrathecal route - radionuclide cisternography
-
99mTc DTPA
Introduction
The accurate preoperative localization of a cerebrospinal fluid (CSF) leak is an essential
prerequisite to successful surgical repair. This is especially important in cases
where recurrence has occurred following a blind epidural blood patch repair or where
conservative management is unfavorable due to the development of complications such
as bacterial meningitis. Various imaging modalities are available to achieve this
end. Computed tomographic (CT) cisternography with metrizamide contrast is considered
the gold standard for this indication. However, it has a variable detection rate between
40 and 92%.[1]
[2] Other modalities such as a combination of high-resolution CT and magnetic resonance
cisternography and radionuclide cisternography are seldom performed. Radionuclide
cisternography using technetium-99m diethylenetriamine pentaacetate (99mTc DTPA) lends itself as a useful procedure with a high sensitivity for the detection
and localization of the leak site, especially in cases with intermittent symptoms.[3]
[4] However, caution must be exercised as the intrathecal route of administration of
a radiopharmaceutical may result in idiosyncratic reactions requiring urgent care
and further exploration.[5]
[6] Herein, we present an interesting case of spontaneous recurrent CSF rhinorrhea with
a history of failed patch repair where intrathecal administration of 99mTc DTPA was followed by an immediate allergic reaction to one or more of the components
of the radiopharmaceutical preparation.
Case Presentation
A 41-year-old male patient presented with intermittent watery nasal discharge for
1 year, which could not be sniffed back. He was evaluated elsewhere, diagnosed with
spontaneous CSF rhinorrhea, and underwent endoscopic epidural blood patch repair 4
months ago. He developed recurrent CSF rhinorrhea in the immediate postoperative period
and was referred to our institution for further management. Comorbidities included
poorly controlled diabetes mellitus, hypertension, and complex regional pain syndrome
involving the right forearm and arm. He was referred to the Department of Nuclear
Medicine in our institution for radionuclide cisternography to locate the site of
leak. On the day of the scan, 99mTc DTPA was freshly prepared using a predispensed sterile formulated kit under strict
aseptic conditions. The kit contained 35 mg of DTPA and 2 mg of stannous chloride
dihydrate in freeze-dried form. Sterile sodium pertechnetate was freshly eluted from
a molybdenum-technetium generator under aseptic conditions and 99mTc DTPA was prepared by adding two milliliters containing 740 megabecquerels (MBq)
or 20 millicurie (mCi) of sodium pertechnetate to the radiopharmaceutical kit after
attaining room temperature. The reaction vial was then placed in a boiling water bath
for 5 minutes and then cooled to attain room temperature. The tagged 99mTc DTPA was measured as 700 MBq (∼ 19 mCi) by the dose calibrator. Radiochemical purity
was assessed by paper chromatography using saline and acetone as solvents and Whatman
filter paper strips III, and was found to be approximately 99%. Per protocol, he underwent
lumbar puncture in the median portion of L4 to L5 level in a sitting position without
imaging guidance. About 30 milliliters of CSF was drawn into three sterile containers
for analysis following which 220 MBq (∼ 6 mCi) of 99mTc DTPA was injected intrathecally. The patient was instructed to lie down in the
Trendelenburg position. Within 60 seconds, the patient developed a diffuse erythematous
rash over the chest and shoulders, along with profuse sweating. He also complained
of headache and watery discharge from the nose that could not be sniffed back. An
intravenous access was obtained and the patient was administered 200 mg hydrocortisone
immediately. The head end was elevated by 15 degrees. The patient then complained
of pain in the lower limbs and numbness spreading to the level of the nipples (T4
dermatome). On examination, the patient appeared anxious; he had tachypnea but was
able to communicate well. He was also hypertensive and had tachycardia. The lungs
were clear on auscultation and saturation was maintained via high flow nasal cannula
followed by room air after one hour. The erythematous rash and sweating were resolved
within minutes of administration of intravenous cortisone. He was administered a bolus
dose of midazolam and an infusion of dexmedetomidine. The patient was reassured and
Merocel nasal packing of the right naris was performed one hour after injection. The
patient was then shifted to the department of nuclear medicine for delayed static
planar and single-photon emission computed tomography/computed tomography imaging.
CSF leak into the right ethmoid and sphenoid air sinuses, and into the nasal cavity,
was noted ([Fig. 1]). No abnormal tracer distribution was noted at the site of injection that would
suggest extravasation of the tracer. As the patient was stable and the procedure was
complete, he was shifted back to the ward 6 hours after the tracer injection. A few
hours later, it was observed that his peripheral oxygen saturation was in the range
of 90 to 92% and he was tachypnic with a respiratory rate of 30 breaths per minute.
He was shifted back to the intensive care unit and on evaluation he was found to have
high blood pressure in the range of 170/100 mm Hg, decreased ejection fraction, and
B lines on lung ultrasound. Auscultation revealed fine crackles. Accelerated hypertension-related
cardiogenic pulmonary edema was suspected and he was managed with furosemide and noninvasive
positive pressure ventilation. He was observed for 24 hours during which his blood
pressure and ultrasound findings normalized. No other possible delayed reactions were
noted during the rest of his hospital stay.
Fig. 1 Cerebrospinal fluid leak into the right ethmoid and sphenoid air sinuses, and into
the nasal cavity (solid white arrow).
Discussion
Frequency of drug reactions following the administration of radiopharmaceuticals is
generally low and therefore, information regarding the same may be lacking in terms
of crisp data. However, the uncommonly used routes of administration such as intrathecal
route may warrant special attention due to the possibility of rare, but significant
adverse hypersensitivity reactions. Most case reports highlight the occurrence of
aseptic meningitis following radionuclide cisternography.[7]
[8] Vasomotor and skin reactions have been reported with the use of 99mTc DTPA, while its intrathecal administration has been reported to cause neurological
symptoms including paraesthesias due to the formation of neurotoxic trisodium salts.[5]
[9] Animal studies conducted by Verbruggen et al in 1982 suggested that paralysis could
be due to chelation of calcium and magnesium ions in the CSF by the trisodium salts,
thus resulting in their depletion from the spinal cord.[6] In our patient, it was not possible to determine with certainty which component
of the radiopharmaceutical preparation led to the development of an adverse allergic
reaction. Additionally, it was not possible to establish a cause–effect relationship
between administration of radiotracer and the delayed presentation of cardiogenic
pulmonary edema. It is difficult to rule out the possibility of contribution by the
patient's concurrent medical comorbidities and medications. No previous exposure sensitizing
this patient to the contents of the radiopharmaceutical preparation could be traced.
Radionuclide cisternography is not routinely performed in every nuclear medicine facility.
Hence, when performed, it is crucial to be prepared for bizarre adverse drug reactions
while administering 99mTc DTPA intrathecally. We recommend that the patient should have a patent intravenous
cannula in situ prior to the procedure. Additionally, the injection should be performed
with close monitoring of vitals, and resuscitation drugs and equipment close at hand.
Patients should be monitored for 24 hours in the inpatient set-up whenever feasible.
Conclusion
Herein, we report an interesting case of adverse allergic reaction to intrathecal
administration of 99mTc DTPA who later developed cardiogenic pulmonary edema due to accelerated hypertension
and was managed in the critical care unit.
