Cardiopulmonary Bypass for A Patient with Systemic
Mastocytosis
Nickolas Trubov, Patrick Kelly, Peggy J. Clark, Rodrigo Miranda, and Bechara F. Akl
USVA Hospital
Albuquerque, NM
Key words: systemic mastocytosis, histamine release, mast cells
Abstract _ _ _ _ _ _ _ _ _ _ _ __
A patient with systemic mastocytosis was seen in our
practice for coronary revascularization. Systemic mastocytosis is a disease characterized by proliferation of
mast cells which, under stress, are likely to release
vasoactive substances. Coronary artery bypass grafting,
utilizing cardiopulmonary bypass with moderate hypothermia, resulted in no clinical problems attributable to
this rare pathology. Steps to lessen or eliminate stresses
likely to precipitate problems associated with histamine
release are discussed.
Introduction _ _ _ _ _ _ _ _ _ _ __
Systemic mastocytosis (SM) is a relatively uncommon disease 1·6 with features that can have serious
consequences during general anesthesia. 7 SM is a disease of mast cell proliferation. Mast cells are connective tissue cells whose specific physiologic function
remains unknown. 1·5·6 These cells are capable of producing cytoplasmic granules which contain histamine
and heparin. 3 ·6 ·8 Small quantities of hyaluronic acid and
serotonin may also be present, 5 · 6 ·9 as well as prostaglandin D 2 . 7 · 10 The name "mast cell" is derived from the
German "mastzellen," or "well fed cell," coined by
Paul Ehrlich in 1877, because of the large number of
these granules in the cell.
Mastocytosis falls into two clinical forms. The
benign or juvenile form, sometimes called urticaria
Direct communications to: Nickolas Trubov, C.C.P., USVA
Hospital (112), 2100 Ridgecrest Rd., S.E., Albuquerque,
NM 87108
2 The Journal of Extra-Corporeal Technology
pigmentosa, is seen in infancy or early childhood and is
generally limited to mast cell infiltration of the skin.
The malignant or adult form of SM is more severe and
involves widespread involvement of other organs, particularly the reticuloendothelial system. 1. 9 - 11 - 12
The clinical feature of SM with which the perfusionist should be concerned is the degranulation of
mast cells releasing histamine, heparin, and prostaglandin D 2 • This release may be triggered by pharmacological, physical or psychological stimuli. Curare and
morphine trigger histamine release, and so may many
other compounds. Heat and cold may also lead to
histamine release. Care should be taken not to administer cold intravascular solutions, especially blood. 1
Electrocautery pads must have adequate electrolyte
jelly to prevent burns. The patient should be kept
calm. 1
Liver and gut involvement are commonly seen in
SM. In severe cases there may be significant depression
of clotting factors synthesized by the liver. 1·5 ·6 ·9 Combined with a potential for the release of unknown
quantities of heparin it may be difficult to interpret the
dose-response relationship to exogenous heparin used
to ensure adequate anticoagulation before and during
cardiopulmonary bypass (CPB). 1 A patient with SM
may have increased metabolic or excretory mechanisms
for dealing with the excess heparin found in this disease. Consequently, the use of a dose response curve 13
and frequent determination of the activated clotting
time (ACT) is crucial for the management of anticoagulation. Allergic reactions may also be encountered
wh~n giving protamine sulphate to reverse the effects of
heparin.
Volume 18, Number 1, Spring 1986
Case Report _ _ _ _ _ _ _ _ _ _ __
A 51-year old white male initially came to our attention as a candidate for cardiac surgery. He had a history
of substernal chest pain radiating into his neck and left
arm leading to a diagnosis of coronary artery disease.
He also presented with a thirty year history of symptoms of SM, including recurring multiple macular
eruptions over his entire body and generalized "bone
pain" described by the patient as arthritis and back
pain. The patient denied prior episodes of syncope,
nausea, or diarrhea. In 1974 a positive skin biopsy
confirmed SM (more than five mast cells in a high
power field).
In the days preceding his surgery we sought to determine what drug sensitivities, if any, he might have as a
result of his SM. Small intradermal aliquots of
butorphanol (0.2 mg) and dopamine (0.04 mg) resulted
in no reddening or swelling. Fentanyl (0.005 mg),
pancuronium (0.2 mg), protamine (1.0 mg), nitroprusside (1.0 mg), isoproterenol (0.02 mg), dobutamine
(25 micrograms), atropine (0.08 mg), and diazepam
(0.1 mg) elicited either very mild or questionable reactions. Because we definitely foresaw its use, protamine
was subsequently tested intravenously (10 mg). No
reaction was elicited. The patient had been receiving
the antihistamine, diphenhydramine, prophylactically
for years obviating the need to test this drug.
On the evening before surgery the patient received
chlorpheniramine (9 mg) and diphenhydramine (25
mg) orally. On the morning of his surgery the patient
received cimetidine (300 mg) orally, diphenhydramine
(50 mg) intramuscularly and methylprednisolone (100
mg) intramuscularly.
His ACT was 144 seconds, which is in our range of
normal. Systemic heparinization was achieved with 370
units/Kg. which brought his ACT to 638 seconds.
Additional heparin, however, was needed frequently
during CPB to maintain the ACT above 480 seconds.
This additional need for heparin was notably greater
than average, for our practice. He required approximately 5,000 units of heparin every thirty minutes
during CPB. This need doubled during the rewarming
period. No allergic reaction was seen using the calculated protamine dose to return the patient's ACT to its
baseline level.
Moderate hypothermia (25 oc measured in the nasopharynx) was reached after eighteen minutes of cooling
with ice water. Four cross clamp periods of 10 to 12
minutes each allowed the three distal anastamoses and
Volume 18, Number 1, Spring 1986
one of the proximal anastamoses to be made, the final
proximal anastamosis being made with partial cross
clamping of the aorta. Total pump time was two hours
and twenty minutes. Vasoactive drugs were not
required during CPB since the patient's blood pressure
(measured at the radial artery) remained between 55-85
mmHg at flow rates ranging from 1.6-2.5 L/M 2 /min.
The patient weighed 95 Kg. with a body surface area of
2.03 M 2 • Rewarming to 38 oc required 43 minutes with
a water to blood temperature gradient not exceeding
eight degrees centigrade. This relatively slower
rewarming phase was accomplished uneventfully. Lactated Ringers was used for volume replacement during
CPB. The pump was primed with lactated Ringers
solution and 100 cc of 25 percent albumin and 100 meq
of sodium bicarbonate which is our normal protocol.
No blood was used during CPB since the patient's
hematocrit never fell below 25 percent. After CPB the
patient did receive two units of packed red cells which
had been rewarmed to 37 oc. This addition was for the
purpose of raising the patient's hematocrit to 30 percent. Again, no problems were seen.
Conclusion _____________
We found that cardiac surgery, using CPB, may be
performed successfully on a patient with SM, but
special care should be exercised to avoid histamine
release as well as the other potential problems which
have been reported to appear in patients with this
disease. Antihistamines may be used prophylactically,
but they may occasionally provoke the release of histamine.1 Cromolyn sodium, discovered in 1965 and used
to treat asthma, is a drug which may possibly stabilize
the mast cell before it can fragment. However, the
mechanism by which it operates is not clear. 9 Cromolyn
sodium is still classified as an experimental drug for
use in patients with SM and as such was unavailable for
our use with this patient at our hospital.
This patient recovered from surgery for coronary
artery bypass grafting and was released from the hospital without complications attributable to SM.
References ____________________
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4 The Journal of Extra-Corporeal Technology
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Volume 18, Number 1, Spring 1986