Intravenous tranexamic acid and intraoperative visualization during functional endoscopic sinus surgery: a doubleblind randomized controlled trial

Intravenous tranexamic acid and intraoperative visualization during functional endoscopic sinus surgery: a double-blind Morgan A. Langille, MD1, Angelo Chiarella, MD2, David W.J. C ˆot ´e, MD1, Graeme Mulholland, BSc1, Leigh J. Sowerby, MD1, Peter T. Dziegielewski, MD1 and Erin D. Wright, MDCM1 Background: Bleeding during endoscopic sinus surgery
included chronic rhinosinusitis without polyposis (n = 5), (ESS) can hinder surgical progress and may be associated chronic rhinosinusitis with polyposis (n = 23). The use of with increased complications. Tranexamic acid is an antifib- the tranexamic acid was not associated with a statistically rinolytic that is known to reduce operative bleeding. The significant decrease in estimated blood loss (201 vs 231 mL; current study was designed to assess the effect of adjunc- p = 0.60) or Wormald grading scale (5.84 vs 5.80; p = 0.93).
tive intravenous tranexamic acid on intraoperative bleed- There were no adverse events or complications during the ing and the quality of the surgical field during ESS.
Methods: Double-blind, randomized, controlled trial. Pa-
Conclusion: Adjunctive intravenous tranexamic acid does
tients undergoing ESS for the primary diagnosis of chronic not appear to result in a clinically meaningful reduction in rhinosinusitis with or without polyposis were included.
blood loss or improve visualization of the surgical field dur- Sample size calculation based on a clinically relevant differ- ence in the Wormald surgical field score yielded a sampleof 28. In addition to standard measures to minimize blood loss, study patients received intravenous tranexamic acid endoscopic surgical procedures; hemorrhage; sinusitis; with control patients receiving intravenous normal saline.
Outcome measures included the Wormald grading scale toassess the intraoperative surgical field and estimated blood How to Cite this Article:
loss based on suction container contents with irrigation Langille MA, Chiarella A, Cˆ
e DWJ, et al. Intravenous
tranexamic acid and intraoperative visualization during
functional endoscopic sinus surgery: a double-blind ran-
Results:
Twenty-eight patients (median age, 45 years; domized controlled trial. Int Forum Allergy Rhinol. 2012;
range, 23–80 years) were included in the study. Diagnoses 00: X-XX.
Functionalendoscopicsinussurgery(FESS)isfrequently inintraoperativevisualizationcanhindersurgicalprogress.
used in the treatment of recalcitrant chronic rhinos- In an effort to reduce bleeding and thus improve visual- inusitis (CRS) and chronic rhinosinusitis with polyposis ization many surgeons use techniques such as hypotensive (CRSwP). Excessive bleeding and the consequent reduction anesthesia or total intravenous anesthesia (TIVA),1 eleva-tion of the head of the bed during surgery, and administra-tion of local vasoconstrictors.
1Division of Otolaryngology–Head and Neck Surgery, University of Tranexamic acid is a medication that can be adminis- Alberta, Edmonton, AB, Canada; 2Department of Anaesthesiology, tered topically or intravenously. In the clotting cascade, University of Alberta, Edmonton, AB, Canada it serves to stabilize the fibrin clot2 and reduces overall Correspondence to: Erin D. Wright, MDCM, Alberta Sinus Centre, Universityof Alberta Hospital, Room 1E4 W.C. Mackenzie Centre, 8440-112 Street, bleeding. Tranexamic acid has been used extensively in Edmonton, AB T6G 2B7, Canada; e-mail: [email protected] certain surgical procedures and has been shown to limit Potential conflict of interest: E.D.W. has received travel and research bleeding with no increase in adverse events. In coronary funding from Medtronic Canada and Stryker Canada; he has served as a artery bypass graft surgery, tranexamic acid was shown to consultant for Johnson & Johnson Medical Products, and has been a paidspeaker for Merck and GlaxoSmithKline. None of the other authors have reduce bleeding and the need for blood transfusions.3 A review of using tranexamic acid in orthopedic surgery has Received: 15 March 2012; Revised: 24 June 2012; Accepted: 17 July 2012 shown it to be safe and decreases perioperative blood loss.4 DOI: 10.1002/alr.21100View this article online at wileyonlinelibrary.com.
For nasal bleeding, tranexamic acid has been suggested to International Forum of Allergy & Rhinology, Vol. 00, No. 0, Month/Month 2012 reduce the frequency of epistaxis in patients with heredi- tary hemorrhagic telangiectasia.5 Furthermore, it improveshemostasis and improves the surgical field when admin- istered topically.6 However, the topical gel would impair visualization of the underlying structures during ESS. Top-ical tranexamic acid can only be effectively applied at the conclusion of the operation and would not serve to reduce bleeding during the surgery when visualization is necessary.
The goal of the current study is to determine if the adjunctive measure of intravenous tranexamic acid has any effect on intraoperative visualization and bleeding 9–10 points of ooze (sphenoid fills in 60 seconds) Mild bleeding/oozing from entire surgical surface with slow accumulation of blood in postnasal space (sphenoid fills in Moderate bleeding from entire surgical surface with moderate Patients who had failed medical management for the di- accumulation of blood in postnasal space (sphenoid fills in30 seconds) agnosis of CRS or CRSwP and were thus undergoing ESS(bilateral complete sphenoethmoidectomies) were eligible Moderately severe bleeding with rapid accumulation of blood in for the study. The patients in this study represent a single- postnasal space (sphenoid fills in 20 seconds) surgeon series from a tertiary care center. Patients were ex- Severe bleeding with nasal cavity filling rapidly (sphenoid fills in cluded from the study if they had a history of hypertension, renal failure, or vascular disease, or if they were AmericanSociety of Anesthesiologists (ASA) class III or greater. Pa-tients undergoing any additional surgical procedures such was responsible for preparing tranexamic acid solution or as a septoplasty were also excluded. Health Research Ethics normal saline solution. This investigator was not involved Board (HREB Protocol #00005621) approval and a Health in data extraction or analysis. The randomization scheme Canada no objection letter was obtained prior to patient was not revealed until data had been collected from all enrolment. The study was registered with clinicaltrials.gov patients. The tranexamic acid or normal saline solutions on September 15, 2009. Informed written consent was ob- were prepared in 100 mL normal saline intravenous bags so that they appeared indistinguishable to the case anesthe-siologist and operating surgeon. The experimental group received tranexamic acid bolus (15 mg/kg) then infusion(1 mg/kg/hour) for the duration of the operation. The con- Sample size calculation was based on a clinically relevant trol group received the equivalent volume of normal saline.
reduction in surgical field bleeding with the intranasal use of All patients received inhalational anesthetic, end-tidal tranexamic acid.6 This previous work utilized the Wormald grading scale (Table 1) to assess the operative field.7 For 2 was maintained between 30 and 35 mmHg, the head of bed was elevated 15 degrees, and mean arterial pressure the purpose of the current study, a difference of 1 on the was maintained between 60 and 70 mmHg. All patients Wormald scale was deemed clinically relevant. The cal- underwent decongestion of the nasal mucosa, initially with culation determined that 28 participants total (14 in the oxymetazoline and subsequently with nasal pledgets soaked tranexamic acid arm and 14 in the placebo arm) would be in 1:1000 epinephrine. A bilateral intranasal injection was required for a study with a power of 0.80 and an alpha of performed in the region of the sphenopalatine artery with 1% lidocaine with 1:100,000 epinephrine. The surgery wasthen carried out in a standard fashion using intraoperative image guidance, mucosal sparing technique, and a com- Continuous variables were compared using the Mann- bination of through-cutting instrumentation and microde- Whitney U test. Categorical variables were compared using brider (Medtronic, Minneapolis, MN).
the Fisher’s exact test. A level of significance was considered The primary outcome measure was the Wormald grading at p < 0.05. Analyses were performed with SPSS Statistics scale. This scale requires an endoscopic video of each pa- tient as described.6 Videos were viewed independently by2 investigators (E.D.W., L.J.S.) who assigned a Wormald grade for each side of each patient (Fig. 1). Secondary Our design was that of a double-blind, randomized, outcome measures included the Peri-Operative Sinus En- placebo-controlled trial with block randomization used to doscopy (POSE) score,8 Lund-Kennedy endoscopic score ensure an even distribution of treatment allotment. Only (assigned on the 1 week postoperative follow-up visit), 1 study investigator (A.C.) knew the randomization and and total estimated blood loss as calculated by measuring International Forum of Allergy & Rhinology, Vol. 00, No. 0, Month/Month 2012 TABLE 3. Outcome comparison between patients undergoing functional endoscopic sinus surgery for TXA 121.5, 24.2 (63–152) 131.5, 26.3 (83–177) 0.14 *Data are reported as: median, standard deviation (range).
a Scores are reported as an average between left and right sides.
FIGURE 1. Surgical field visualization of the tranexamic acid group vs the EBL = estimated blood loss; OR = operating room; POSE = Perioperative Sinus placebo group using the Wormald grading scale.
TABLE 2. Intraoperative variables between patients undergoing functional endoscopic sinus surgery for TXA radiologic grading scores were equivalent for both groups (p = 0.85). The POSE scores are shown in Table 3. Thepreoperative and postoperative POSE score showed no dif- ference between groups. There was no difference in surgicaltime between groups (p = 0.14).
There was no statistically significant difference (p = 0.89) between groups in terms of surgical field visualization as measured by the Wormald grading scale with mean val-ues of 5.84 vs 5.80 for the tranexamic acid and normal saline groups, respectively. There was no difference be- tween groups in terms of estimated blood loss (201 vs231 mL mean blood loss in tranexamic acid and normal saline groups, respectively; p = 0.40).
a Data are reported as: median, standard deviation (range).
All surgical procedures were completed and there was ETCO2 = mean end-tidal CO2 (intraoperatively); MAC = mean minimal alveolarconcentration; MAP = mean arterial pressure (intraoperatively); TXA = tranexamic no limitation of surgical progress by bleeding in any of the cases. There were no operative complications and allpatients were discharged home the same day of surgery.
suction container contents with irrigation fluid subtracted.
Data was also collected regarding preoperative acetylsali-cylic acid (ASA) and oral steroid use.
Blood loss during ESS can present a challenge to surgeons,particularly in cases of massive polyposis or in patients with hypertension. Surgeons and anesthetists have devel- Twenty-eight patients were enrolled between March 2010 oped several methods to minimize blood loss during surgery and November 2011. Fourteen patients were enrolled in such as preparing the nose with local vasoconstrictors, use the tranexamic acid group and 14 were enrolled in the nor- of hypotensive anesthesia, and elevating the head of the mal saline group. Diagnoses included CRS without poly- bed during surgery. Despite these measures, surgeons may posis (n = 5) and CRSwNP (n = 23). Table 2 shows still encounter cases in which bleeding may hinder surgical the intraoperative variables between groups. The median progress. Poor visualization during sinus surgery could the- age of all participants was 45 (range, 23–80), with 17 oretically lead to misidentification of structures and result males and 11 females. There were no statistically significant in complications or incomplete surgery. Surgeons have an differences in age between the study and control groups interest in decreasing bleeding during surgery and tranex- (p = 0.55). No patients in either group used ASA preopera- amic acid has a proven benefit in other surgical procedures.
tively. There was no difference in preoperative oral steroid The current study was developed to determine if tranex- use between groups (p = 0.32). There was no difference amic acid had any impact on intraoperative bleeding or between groups with respect to the mean arterial pressure (p = 0.77) and end-tidal CO2 (p = 0.98). Table 3 shows the The current study employed strict inclusion and exclu- outcome comparison between groups. The Lund-Mackay sion criteria to ensure a homogeneous population. Patients International Forum of Allergy & Rhinology, Vol. 00, No. 0, Month/Month 2012 with hypertension were excluded to ensure that a standard- Any medication or protocol that decreases bleeding may ized anesthetic protocol could be maintained to eliminate help to increase intraoperative visualization and help with intraoperative blood pressure as a confounding variable.
surgical progression and allow for a more complete surgical The strict inclusion criteria led to a relatively long enrol- procedure. Tranexamic acid is generally a safe medication11 ment period, which is a potential weakness of this study.
and there were no adverse events associated with its use in A recent work9 found an improvement of the surgical field our study. However, the current work has employed a rig- using the Boezaart grading scale10 and a nonvalidated sur- orous study design and has shown that intravenous tranex- geon satisfaction scale. For this referenced study a smaller amic acid offers no benefit as an adjunctive measure during dose of tranexamic acid (10 mg/kg bolus with no ongoing ESS. As such, we would not recommend its routine use in infusion) was used. The populations of the present study ESS. However, based on other studies it may have a role and the referenced study are similar in that both patient in select cases wherein intraoperative visualization presents groups were treated for CRS. In the referenced study, how- ever, they did not use any topical vasoconstrictors nor didthey use a microdebrider—thus their study cannot be ap-plied to standard practice in North America. The current study was designed to assess if tranexamic acid is useful Used as an adjunct to standard perioperative techniques, as an adjunct with standard ESS and this work has shown tranexamic acid does not improve intraoperative visualiza- that it is not useful for the purpose of reducing bleeding or tion or result in a clinically meaningful difference in blood loss during ESS for the treatment of CRS or CRSwP.
Previous studies that have shown a difference in bleeding with tranexamic acid have looked at cardiac and orthope-dic surgical procedures with large volumes of blood loss.3,4The blood loss itself during ESS is generally not a major consideration, averaging less than 400 mL in the vast ma- We thank Lori Anderson from the Northern Alberta Clini- jority of cases; rather it is the surgical field visualization that cal Trials and Research Center (NACTRC) for submission is of greater importance for sinus surgeons. There is a good of the Health Canada No Objection Letter and the clinical- rationale regarding the use of tranexamic acid during ESS.
Wormald PJ, van Renen G, Perks J, Jones JA, Langton- Sabba C, Pasculli G, Cirulli A, et al. Rendu-Osler- ing system. Laryngoscope. 2007;117(11 Pt 2 Suppl Hewer CD. The effect of the total intravenous anes- Weber disease: experience with 56 patients. Ann Ital thesia compared with inhalational anesthesia on the Alimian M, Mohseni M. The effect of intravenous surgical field during endoscopic sinus surgery. Am J Athanasiadis T, Beule AG, Wormald PJ. Effects of tranexamic acid on blood loss and surgical field topical antifibrinolytics in endoscopic sinus surgery: quality during endoscopic sinus surgery: a placebo- Dunn CJ, Goa KL. Tranexamic acid: a review of a pilot randomized controlled trial. Am J Rhinol.
controlled clinical trial. J Clin Anesth. 2011;23:611– its use in surgery and other indications. Drugs.
Athanasiadis T, Beule A, Embate J, Steinmeier E, 10. Boezaart AP, van der Merwe J, Coetzee A. Compar- Adler Ma SC, Brindle W, Burton G, et al. Tranex- Field J, Wormald PJ. Standardized video-endoscopy ison of sodium nitroprusside- and esmolol-induced amic acid is associated with less blood transfusion in and surgical field grading scale for endoscopic si- controlled hypotension for functional endoscopic si- off-pump coronary artery bypass graft surgery: a sys- nus surgery: a multi-centre study. Laryngoscope.
nus surgery. Can J Anaesth. 1995;42(5 Pt 1):373– tematic review and meta-analysis. J Cardiothorac Vasc Wright ED, Agrawal S. Impact of perioperative sys- 11. Henry DA, Carless PA, Moxey AJ, et al. Anti- Eubanks JD. Antifibrinolytics in major orthopaedic temic steroids on surgical outcomes in patients with fibrinolytic use for minimising perioperative allo- surgery. J Am Acad Orthop Surg. 2010;18:132– chronic rhinosinusitis with polyposis: evaluation with geneic blood transfusion. Cochrane Database Syst the novel Perioperative Sinus Endoscopy (POSE) scor- International Forum of Allergy & Rhinology, Vol. 00, No. 0, Month/Month 2012

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