Key-words:
Antifibrinolytics - fibrinolysis - instrumented spine - intraoperative bleeding -
tranexamic acid
Introduction
The field of instrumented spinal procedures is associated with substantial blood volume
losses, which is one of the major hazards we encounter; this would lead to a greater
need for blood products transfusions. The frequent use of these products can have
negative consequences, such as transmitted infections, acute cerebral or lung edema
due to body fluid shifting, and donor-host rejection.[[1]],[[2]] Thus, it has become mandatory to establish strategies to maintain blood volume
and minimize losses, as encompassed within the concept of “patient blood management.”[[2]] Several strategies have been approved to control the disproportionate blood loss
from the preoperative period by applying blood function monitoring, while intraoperatively,
methods have been established to decrease the need for blood products. Newly promoted
antifibrinolytics agents are also available.[[1]],[[2]],[[3]],[[4]]
In many fields of surgery, recent studies had advocated policies effective in lessening
perioperative bleeding and decreasing the requirements for transfusion of blood products.
Some of these studies are nowadays delving major spine surgeries.[[4]],[[5]],[[6]],[[7]] Here we appraise the efficiency of tranexamic acid as a limiting agent of perioperative
bleeding during our surgeries, while addressing complications associated.
Methods
Patients
In this prospective, retrospective analysis, we gathered data from 153 consecutive
patients treated in the neurosurgical spine unit of King Hussein Hospital, King Hussein
Medical Center, between January 2016 and January 2020. All patients who underwent
instrumented surgery for spinal pathologies at our institute were reviewed. Seventy-nine
patients were enrolled in the final stage study. Thirty-one patients were excluded
after applying the inclusion-exclusion criteria: 13 patients missed the 1 month follow-up,
11 patients had tumours, and 7 patients had posterior cervical instrumented surgery.
Seventy-nine patients with spinal pathologies (namely: degenerative spine disease,
spondylolisthesis, iatrogenic flat back, fractures, and infections) were recruited
from the Spine centre for this study. All surgeries were conducted by a senior neurosurgeon.
A control group (43 patients) was included consisting of our cases who had been previously
operated and had lumbar spinal fusion procedure performed during the 16 months before
tranexamic acid was introduced as an agent. Group I included 79 patients, enrolled
in April 2017. Based on medical records, the intra- and post-operative blood losses
were measured by evaluating the suction volume minus the irrigation fluids at the
intraoperative period and drainage volumes 12, 24, and 48 h postoperatively. In addition,
hemoglobin concentration was reviewed. Furthermore, the complications related to tranexamic
acid administration were considered.
Inclusion/exclusion criteria
Inclusion criteria
-
One or more levels of instrumented spine disease
-
Treatment by posterior interbody fusion and/or reconstructive osteotomies
-
Thoracic and lumbar segments (from T1 to S1)
-
A minimum follow-up of 2 months.
Exclusion criteria were
-
Inadequate documentation of follow up
-
Oncology cases scheme
-
The presence of severe systemic disease (heart disease, thromboembolism, bleeding
tendency, renal malfunction)
-
Age <18 years
-
Cervical spine surgeries
-
Patients with 360° surgical approach.
Demographic features
All adult patients operated by our team at the neurosurgical department from January
2016 to January 2020 were evaluated. The medical reports of patients were retrieved
from our database and reviewed; clinical follow-up data were collected in cooperation
with the investigators.
The mean age of our patient was 54.6 years (27–69 years), and there were 48 men and
31 women. The mean symptom duration before surgery was 1.3 years (range: 1 week to
2.5 years), and patients were monitored for of 12.3 months on an average (range: 2–15
months). The demographic data of Group I are summarized in [[Table 1]] and [[Table 2]].{Table 1}{Table 2}
Table 1: Demographic details of all patients
Table 2: Demographic distribution regarding gender
Our protocol of tranexamic acid includes a loading dose of 20 mg/kg introduced intravenously
on induction, followed by an intravenous infusion of rate 5 mg/kg/h until skin closure.
No added oral doses are given postoperatively, nor intravenous administrations.
Operations/instrumentations
There are many alternative available procedures to address the different spinal pathologies,
such as Posterior lumbar interbody fusion, transforaminal lumbar interbody fusion
with and without osteotomies, either minimally invasive or open. The enrolled patients
underwent open instrumented surgery of thoracic and/or lumbar spine segments, using
a conventional posterior midline approach, while patients operated at the cervical
segment or that had the 360° approach were excluded. All valid options of instrumentations
and techniques were used. There was no preselected method of surgery nor a specific
type of cages, screws, or rods. The surgical technique included subperiosteal discussion
of paraspinal muscles, exposure of posterior neural arches, decompression, spinal
osteotomies, posterolateral fusion techniques utilizing autologous graft, interbody
fusion, and stabilization using pedicle screws. Our technique included inferior facet
partial resection and a foraminotomy in all patients. Procedures were performed by
a senior spine surgeon (Al. R). Subfascial suction drains were inserted and were retained
for at least 48 h postoperatively. The study had 56 patients with one or two instrumented
levels [[Figure 1]]. We also had 23 patients who underwent 3–5 levels instrumentation [[Figure 2]].{Figure 1}{Figure 2}
Figure 1: Single instrumented level
Figure 2: Three instrumented level
Statistical analysis
The main baseline cardinal characteristics of the patients are plotted as means and
standard deviations for definite variables. We compared the baseline characteristics
between the two groups using the analysis of variance method. Correlation analyses
were done using the Pearson correlation coefficient. A value of P < 0.05 was defined
as statistically significant.
Results
During the analysis period, our study included 153 patients who underwent instrumented
spinal interbody fusion. After applying inclusion criteria, the population were allocated
into two groups, 79 patients were recruited for the final stage of study as Group
I, while 43 patients were reviewed as the control group (group II). In Group I, 37
patients had a primary procedure, whereas 42 cases were revision surgeries. The mean
level of instrumented segments was 2.8 (range: 1–5 levels). The demographical data
of patients of both groups analyzed are given in [[Table 3]]. Group I comprised 31 females and 48 males (mean age: 58.6 ± 7.45 years, range:
27–69 years). In group II, 27 males and 16 females were recruited, with a mean age
of 61.4 years. The mean operating time was 212.74 ± 41.85 min for a group I and 208.09
± 42.03 min in the control group.{Table 3}
Table 3: Demographical features of patients recruited in both groups compared
In group I and II, the fluid volumes infused intraoperatively were 2254.40 ± 237.60
ml and 2563.33 ± 782.30 ml, respectively (P = 0.3). The study showed that the mean
drop in the hemoglobin concentration postoperatively was statistically significant
when comparing the two groups, results revealed that the Group I was superior (2.63
g/dl versus 4.27 g/dl) in Group II (P = 0.012). The blood volume in the suction container
was 470 ± 153.06 ml for group I and 1560 ml ± 567.59 ml for the control group (P =
0.002). The drainage volume at 24 h postoperatively was 161.25 ± 111.01 ml in Group
I and 258.75 ± 121.8 ml in the control group (P = 0.002); there was less blood loss
in group I than in Group II. At 12 h postoperatively, we detected no difference in
drainage volumes when comparing groups (P = 0.69).
This review observed minor adverse effects allied with tranexamic acid administration:
three cases of an allergic reaction, there were two cases developed deep-vein thromboses
(DVTs), complications were tackled effectively without any further morbidity by administrating
conventional anticoagulation therapy. There were no major complications in terms of
intracranial embolic infarcts; seizure myocardial infarction or acute renal shut-down.
General outcomes are shown in [[Table 4]].{Table 4}
Table 4: Comparing the perioperative results of the population analyzed
Discussion
Tranexamic acid, as an indirect antifibrinolytic, was developed in Shosuke Okamoto's
lab in the early 1960s. It was initially introduced for patients with heavy menstrual
cycles, then used for cases with hereditary bleeding disorders. Tranexamic acid was
also used for programmed operations because of its blood preservation abilities, and
its contraindications were few, including venous/arterial thrombosis and allergy.[[3]],[[7]]
Such emerging haemostatic agents had a huge impact on controlling perioperative bleeding
necessitating allogenic blood products transfusions. Predominantly, major instrumented
spinal surgeries are associated with massive perioperative bleeding.[[8]],[[9]],[[10]],[[11]],[[12]] The need for transfusions of blood can lead to potential long-term morbidity and
even mortality.[[13]],[[14]] There is an economic burden associated with perioperative blood loss, in terms
of direct costs of the blood products salvage technology and indirectly due to extended
patient hospitalization.[[15]]
Constant efforts have been aimed at achieving healthier perioperative blood preservation.
Prophylactic intravenous administration of antifibrinolytic agents is a principal
method that can be used either before or during major surgery. Currently, intravenous
administration of the low-cost but vastly efficient lysine analogue tranexamic acid
diminishes perioperative hemorrhage and the demand for blood transfusions by one-third
in major surgery, including extensive instrumented spinal surgery.[[16]],[[17]],[[18]],[[19]],[[20]],[[21]],[[22]]
This study was conducted to investigate whether tranexamic acid can diminish perioperative
blood loss in our set-up. Taking into consideration all previously reported data,
we introduced this agent in action with tremendous precautions, registering all available
data. Results were in line and comparable with all studies reported. This might be
subject to bias, as we introduced the tranexamic acid bases on previous studies and
reports. Furthermore, we followed the guidelines strictly. However, during tranexamic
acid usage, many questions were not addressed and remained unanswered, such as when
to start intravenous administration (e.g., 24 h preoperatively, on induction, during
surgery, or just after), the optimal dose, and the route of administration.
Unfortunately, these challenges remain.[[8]] Finally, this was a small-size retrospective analysis; although large studies might
reveal different results, our results indicate that tranexamic acid is a drug of great
value to reduce almost most kinds of bleeding. The efficacious concomitant factors
controlling perioperative bleeding are well-established.
Future studies with larger sample sizes and further evaluating the concomitant parameters
will have higher precision and stronger conclusions in terms of timing, safety, related
complications, patient quality of life, impact on the cost, dosage, and route of administration.
Also, this might help in the development of further treatment strategies.
Conclusion
In synopsis, perioperative bleeding is deemed one of the most important threats for
patients needing extensive surgeries mandating blood transfusion. Tranexamic acid
is proved as a drug of excellent benefit in controlling perioperative bleeding; it
is cheap and convenient to use and has few contraindications.
Among parameters, the cost-effective and applicability are important for broadening
the indications for any treatment. Future studies are now needed to address the remaining
unanswered questions.
Informed consent
Patient's informed consent was waived as this is a retrospective study.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms.
In the form the patients have given their consent for their images and other clinical
information to be reported in the journal. The patients understand that their names
and initials will not be published and due efforts will be made to conceal their identity,
but anonymity cannot be guaranteed.
