Question:In children undergoing long-segment posterior spinal
fusion, does the use of aprotinin reduce blood loss?
Design: Randomized (unclear allocation concealment), blinded
(clinicians and patients), placebo-controlled trial with follow-up to
discharge.
Setting: 2 children's hospitals in St. Louis, Missouri.
Patients: 44 children and adolescents (mean age, 13 yr) who required
long-segment posterior spinal fusion (=7 segments) for spinal deformities
and who were at high risk for blood loss because of neuromuscular scoliosis or
an underlying medical condition or because the procedure was a reoperation.
Follow-up was complete.
Intervention: Patients were allocated to aprotinin (n = 21), a
broad-based, nonspecific serine protease inhibitor, or placebo (n = 23).
Aprotinin was given as a 240-mg/m2 load (maximum 280 mg if patient
was >1 m2 of body surface area) for 30 minutes before incision
and then as a continuous infusion of 56 mg/m2/h during the
procedure and for 4 hours after surgery. Placebo was given as a saline
infusion at a similar load and infusion rate as aprotinin.
Main outcome measures: Blood loss and blood transfusion during
hospitalization.
Main results: Patients who received aprotinin had less blood loss (p
= 0.039) and fewer blood transfusions (p = 0.016) than did patients who
received placebo (Table).
Conclusions: In children undergoing long-segment posterior spinal
fusion, the use of aprotinin reduced blood loss and blood transfusions.
This investigation is a randomized, blinded study of 44 patients who had a
condition (cerebral palsy, myelomeningocele, spinal muscular atrophy, muscular
dystrophy, or a reoperation) that put them at greater risk for operative blood
loss during surgery for spinal deformity. The hypothesis of the investigators
was that intraoperative aprotinin significantly reduces blood loss in this
difficult patient group. The results of this trial cannot be generalized to
other patient groups.
The clinical benefits of reducing blood loss from a mean (and standard
deviation) of 930 mL (±771.7 mL) to a mean of 545 mL (±311.9 mL)
were not discussed but are certainly implied. Although the prevalence of
hypotension, end-organ ischemia, and acidosis was not described, surgeons with
experience in treating pediatric spinal deformities would generally agree that
a reduction of blood loss from 33% to 20% of total blood volume (assuming 72.5
mL/kg blood volume) would probably reduce morbidity and mortality in such
high-risk patients. Confidence intervals (not provided) would have been useful
so that orthopaedists might know what to expect in their practices.
The primary pediatric usage of aprotinin has been in cardiac surgery.
Published studies as well as product literature discuss the risks of
intraoperative thromboses and anaphylactoid reactions. A PubMed search
indicates that there are 111 citations for aprotinin and complications in
children from 0 to 18 years of age and 81 citations for aprotinin and
anaphylaxis. Although the authors reported no anaphylactic complications, they
acknowledged that sensitization may occur and that it would preclude
subsequent usage of the drug.
Before aprotinin is adopted for this specific group of high-risk patients,
a risk-to-benefit analysis should be performed to compare blood loss with
anaphylaxis and other complications.