Evaluation of the efficacy of tranexamic acid on blood loss in orthognathic surgery. A prospective, randomized clinical study

Abstract

The purpose of this prospective, randomized, double blind study was to assess the effect of tranexamic acid on blood loss, quality of surgical field and duration of surgery in adolescent orthognathic surgery patients. 50 consecutive patients, scheduled for orthognathic surgery were included. The study group ( n = 25) received tranexamic acid 10 mg/kg as a bolus preoperatively followed by 1 mg/kg as a maintenance dose intra operatively; the control group ( n = 25) received placebo (normal saline). All patients received moderate hypotensive anaesthesia with nitroglycerin and had surgery according to a standard protocol. Intra operative blood loss, duration of surgery, quality of surgical field, blood transfusion and complications, if any, were recorded. The mean total blood loss was 166.1 ± 65.49 ml in the study group and 256.4 ± 77.80 ml in the control group. The results showed statistically significant reduction in blood loss ( p < 0.001) and improved quality of surgical field ( p < 0.001) in the study group. There was no significant difference in duration of surgery and transfusion requirements between the two groups. In conclusion, preoperative and intra operative administration of the antifibrinolytic agent, tranexamic acid, is effective in controlling blood loss and improving the quality of the surgical field.

Blood is a finite resource with a limited shelf life and is associated with considerable processing costs. Utilization of this resource needs critical review to reduce the risks of transmission of various blood borne diseases, infections and transfusion related complications. Conservation of blood is now recognized as a priority in all forms of surgery.

Yu et al. reported that 72.4% of orthognathic patients require double jaw surgeries and that blood loss during simple Le Fort I osteotomies is about half that of multiple segmentalized osteotomies. 27–30% of patients undergoing bimaxillary osteotomy procedures require a blood transfusion. Various preoperative and intra operative measures have been developed to conserve blood, including acute normovolemic hemodilution, induced hypotension, positioning the surgical field above the level of the heart, cell saving, and preoperative autologous blood donation. These techniques require special knowledge, training and skill in the procedure and intensive monitoring of the patients. The cost of autologous blood donation and cell salvage is high.

The pharmacological approach to reducing bleeding and transfusion has recently emerged as an additional complementary approach to conserve blood. Kovesi and Royston reviewed the clinical efficacy of various pharmacological agents and reported that the antifibrinolytic agents, aprotinin and tranexamic acid, were effective in reducing red blood cell transfusion. The lysine analogue inhibitor tranexamic acid is particularly effective in reducing perioperative blood loss in various types of surgery, such as cardiac, knee replacement, caesarian, tonsillectomy and prostatic, with no adverse effects. Studies on the use of tranexamic acid during orthognathic surgery are limited. In this prospective, randomized, double blind study, the effect of tranexamic acid on blood loss, quality of surgical field and duration of surgery was evaluated and compared to the effect of nitroglycerin induced moderate hypotension alone.

Materials and methods

This study was approved by the Ragas dental college and hospital institutional ethical committee and informed consent was obtained from all the patients. All ASA I patients aged 17–30 years scheduled for orthognathic surgery were included in the study consecutively. Subjects included had congenital or acquired skeletal deformities corrected using conventional orthognathic operations. Patients who had bone diseases, cleft lip and palate, craniofacial syndromes, patients requiring palatal expansion surgery, distraction osteogenesis, simultaneous rhinoplasty, TMJ surgery, bone graft or implant placement and endoscopically assisted surgeries were excluded from the study.

Patients were randomized by computerized random allotment to receive study drug (tranexamic acid) or placebo (0.9% normal saline). The tranexamic acid drug or placebo was titrated and preloaded in a syringe, preoperatively. They were then blinded and kept in an envelope. After randomization the specific envelope was transferred to the theatre nurse for administration according to the prescribed schedule. None of the members of the surgical team, nursing staff or the anaesthesiologist were aware of the allocation.

After routine history taking and clinical examination, a blood sample was taken for haemoglobin and hematocrit, coagulation screen, liver function tests, renal function test, random blood glucose, grouping and cross matching. Fitness for general anaesthesia was obtained prior to surgery and one unit of blood was reserved. Three measurements of blood pressure were taken at different time points after admission and the average of these values was used to determine the baseline preoperative blood pressure.

Pre medication comprised pentazocine 30 mg, promethazine 25 mg and glycopyrrolate 0.2 mg. They were given as intramuscular injections 30 min before surgery. Anaesthesia was induced by intravenous thiopentone sodium and succinyl choline. Nasoendotracheal intubation was done. Anaesthesia was maintained with N 2 O and O 2 (60:40 ratio) and 0.5% halothane and incremental doses of the muscle relaxants vecuronium bromide, midazolam and fentanyl. Patients were given moderate hypotensive anaesthesia with intravenous nitroglycerin (3–10 μg/kg/min) titrated to maintain a mean arterial pressure (MAP) of 70–75 mmHg until the osteotomy fragments were fixed. The tranexamic acid or placebo was administered intravenously as an initial bolus dosage of 10 mg/kg before the skin incision was made over a period of 20 min, followed by 1 mg/kg intra operatively for every 1 h until the end of the surgery. Ampicillin 1 g, metronidazole 500 mg, dexamethasone 8 mg were given intravenously intra operatively.

Intra operative monitoring consisted of pulse oximetry, electrocardiography and systolic, diastolic and MAP using noninvasive blood pressure monitoring. Blood pressure was measured every 5 min during surgery. Preoperative body weight, haemoglobin concentration, hematocrit, intra operative blood loss, quality of surgical field, duration of surgery, amount of blood or blood products transfused, and complications, if any, were recorded. Haemoglobin concentration and hematocrit were measured again 48 h postoperatively.

The surgeon, who was unaware to which group the patient had been allocated, rated the surgical field every 15 min using the ordinal scale developed by Fromme et al. ( Table 1 ). The numerical values reported throughout the surgery were averaged and recorded.

Table 1
Fromme’s ordinal scale for assessing quality of surgical field.
Massive bleeding, cannot carry out dissection 5
Severe bleeding; significantly compromises dissection 4
Moderate bleeding; slightly compromises dissection 3
Mild bleeding, a nuisance but does not compromise dissection 2
Minimal bleeding; not a surgical nuisance 1
No bleeding, virtually bloodless field 0

Study variables

The primary predictor variables that would affect the outcome of the study were intra operative patient positioning, anaesthetic techniques, vasoconstrictor use and fixation of osteotomy segments. All the patients were positioned 15° head up and received hypotensive anaesthesia, defined as the anaesthetic technique in which systolic blood pressure was kept under 100 mmHg and MAP below 20–30% of the baseline value for more than 50% of surgery. In all patients, about 5 ml of 2% lignocaine with 1:80,000 adrenalin was infiltrated at the surgical site prior to making the incision. Electrocautery was used in all patients to make the incision. All surgical procedures were performed using standard osteotomy techniques by the same experienced surgical team. All patients received semi rigid internal fixation using miniplates and screws. Surgical procedures were categorized as maxillary, mandibular or bimaxillary. Maxillary procedures included: anterior maxillary osteotomy (Cupar’s technique); Le Fort I osteotomy (Bell’s technique); and Le Fort I osteotomy with anterior maxillary osteotomy (2 segments). Mandibular procedures included: bilateral sagittal split osteotomy (Epker modification); anterior subapical osteotomy (Hofer); and genioplasty.

The duration of anaesthesia was calculated from induction to extubation and the duration of surgery from incision to the last suture. At the end of fixation, nitroglycerin was slowly reduced, to bring the MAP to normal levels. Haemostasis was checked. Estimated blood loss was calculated by volumetric (difference between volume of fluid in the suction bottle and volume of saline used for irrigation) and gravimetric methods (difference in weight between blood soaked gauze and dry gauze). Blood loss up to allowable blood loss was replaced with crystalloid solutions (1:3 ratio). When blood loss was more than the allowable blood loss, it was replaced with blood, but the need to transfuse blood perioperatively was decided by the anaesthesiologist.

Estimated blood volume was calculated as 70 ml/kg for adult patients. Allowable blood loss was calculated using the following formula :

<SPAN role=presentation tabIndex=0 id=MathJax-Element-1-Frame class=MathJax style="POSITION: relative" data-mathml='Allowablebloodloss=Estimatedbloodvolume×(PreoperativeHb−LowestacceptableHb)AverageofpreoperativeandlowestacceptableHb’>Allowablebloodloss=Estimatedbloodvolume×(PreoperativeHbLowestacceptableHb)AverageofpreoperativeandlowestacceptableHbAllowablebloodloss=Estimatedbloodvolume×(PreoperativeHb−LowestacceptableHb)AverageofpreoperativeandlowestacceptableHb
Allowable blood loss = Estimated blood volume × ( Preoperative Hb − Lowest acceptable Hb ) Average of preoperative and lowest acceptable Hb

where Hb is haemoglobin.

Data analysis

The sample size to test the difference between two means is (per group) calculated based on the following formula with power calculation of 80%.

<SPAN role=presentation tabIndex=0 id=MathJax-Element-2-Frame class=MathJax style="POSITION: relative" data-mathml='Samplesizen=2(Zα+Z1−β)2(S12+S22)(m1−m2)2′>Samplesizen=2(Zα+Z1β)2(S21+S22)(m1m2)2Samplesizen=2(Zα+Z1−β)2(S12+S22)(m1−m2)2
Sample size n = 2 ( Z α + Z 1 − β ) 2 ( S 1 2 + S 2 2 ) ( m 1 − m 2 ) 2
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Jan 26, 2018 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Evaluation of the efficacy of tranexamic acid on blood loss in orthognathic surgery. A prospective, randomized clinical study
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