Leveron&Nexovas
Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 4416  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Search
 
  
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (981 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

 
  In this Article
 »  Abstract
 » Methods
 » Results
 » Discussion
 » Conclusion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed1322    
    Printed92    
    Emailed0    
    PDF Downloaded41    
    Comments [Add]    

Recommend this journal

 


 
Table of Contents    
ORIGINAL ARTICLE
Year : 2022  |  Volume : 70  |  Issue : 3  |  Page : 960-964

Effect of Tranexamic Acid on Blood Loss and the Quality of Surgical Field in Transsphenoidal Pituitary Surgeries: Double-Blind Placebo-Controlled Randomized Control Trial


Department of Anaesthesia and Intensive Care, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India

Date of Submission02-Apr-2019
Date of Decision16-May-2019
Date of Acceptance23-Apr-2020
Date of Web Publication1-Jul-2022

Correspondence Address:
Ritesh Lamsal
Department of Anaesthesiology, Institute of Medicine, Tribhuvan University, Kathmandu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.349622

Rights and Permissions

 » Abstract 


Background and Aims: Pituitary adenomas are common intracranial neoplasms and several cases require surgery, radiotherapy or radiosurgery. Transsphenoidal access to the pituitary gland is the commonest surgical approach. In microscopic or endoscopic approach to the pituitary, even modest bleeding can significantly worsen the surgical field for the neurosurgeon, lengthen intra-operative time and lead to potentially catastrophic complications.
Methods: The investigators hypothesized that administration of tranexamic acid (TXA) would improve the quality of the surgical field and reduce bleeding during transsphenoidal surgery (TSS) of pituitary tumors. Fifty American Society of Anesthesiologists (ASA) physical-status 1 or 2 patients undergoing TSS were randomized into two groups: T and P. Patients in Group T received 25 mg/kg bolus of TXA followed by intraoperative infusion of 1 mg/kg/hour, while those in Group P received a matching saline infusion. The operating neurosurgeon, and the anesthesiologist, who managed the patient and collected data, were blinded to the test drug. Surgical field quality was assessed using the Boezaart scale. A single neurosurgeon performed all the surgeries to ensure consistency in estimating the quality of the surgical field.
Results: The median Boezaart score (interquartile range) was 3 (1.0) in Group T and 3.0 (1.5) in Group P (P = 0.03). There was an absolute blood loss reduction of nearly 32% with TXA use. Blood loss in Group T was 334 ± 101 mL, compared to 495 ± 226 mL in Group P (P = 0.002).
Conclusion: The administration of TXA significantly improved the quality of surgical field and reduced blood loss in patients undergoing TSS.


Keywords: Boezaart score, pituitary surgery, quality of surgical field, tranexamic acid, transsphenoidal surgery
Key Message: Intraoperative administration of tranexamic acid improves the quality of the surgical field and decreases blood loss in patients undergoing transsphenoidal pituitary surgeries.


How to cite this article:
Lamsal R, Panda NB, Wig J. Effect of Tranexamic Acid on Blood Loss and the Quality of Surgical Field in Transsphenoidal Pituitary Surgeries: Double-Blind Placebo-Controlled Randomized Control Trial. Neurol India 2022;70:960-4

How to cite this URL:
Lamsal R, Panda NB, Wig J. Effect of Tranexamic Acid on Blood Loss and the Quality of Surgical Field in Transsphenoidal Pituitary Surgeries: Double-Blind Placebo-Controlled Randomized Control Trial. Neurol India [serial online] 2022 [cited 2023 Mar 26];70:960-4. Available from: https://www.neurologyindia.com/text.asp?2022/70/3/960/349622




Pituitary adenomas are common, diverse group of tumors of the pituitary gland. Transsphenoidal route is the most common neurosurgical approach of resection of these adenomas. This route is preferred for all but the largest of tumors, as it has the advantage of rapid midline access to the sella with minimal risk of brain trauma.[1],[2] The goal of neuroanesthesia in these surgeries is to provide stable hemodynamics, a clear surgical field, adequate cerebral oxygenation, and rapid emergence to facilitate early neurological assessment.[3]

Risk of bleeding is usually modest in transsphenoidal pituitary surgeries.[4] However, even slight bleeding can cause considerable difficulties for the surgeon by obscuring the view of the surgical field through the operating microscope or endoscope. With increased bleeding, the neurosurgeon can lose the anatomic landmark of the fossa and might have difficulty differentiating normal tissue from tumor. This can lead to catastrophic complications, such as injury to the neighboring structures. These surgeries have the potential for massive intraoperative bleeding because of the proximity of the pituitary gland to the carotid arteries.[5] Profound blood loss can also occur from continuous oozing from the cavernous sinus and nearby capillaries.[6]

There are very few studies that have focused on minimizing blood loss in endoscopic or microscopic intracranial procedures. The use of antifibrinolytics such as tranexamic acid to reduce bleeding and transfusion requirement is widespread in cardiac, pediatric, orthopedic, and spinal surgeries.[7],[8],[9],[10] Tranexamic acid is a synthetic derivative of the amino acid lysine that competitively blocks the breakdown of fibrin by binding to sites on plasminogen and plasmin, thereby stabilizing blood clots and reducing blood loss.[11] Even though TXA use has shown to reduce intraoperative blood loss in various surgeries, including skull base, cranial vault, sinus and open intracranial tumor surgeries, it has never been used in a randomized study for pituitary surgeries.


 » Methods Top


After the Institute's Ethics Committee approval, a randomized, double blind, placebo-controlled study was conducted in 50 patients undergoing elective transsphenoidal pituitary surgery. Patients aged 18-75 years, American Society of Anesthesiologists physical status I and II, of either sex were included in the study. Exclusion criteria included patients with pituitary apoplexy, impaired renal function (creatinine >1.5 mg/dl), preoperative hemoglobin less than 8 gm/dl, patients on anticoagulant or antiplatelet medications and those who had a previous pituitary surgery. Intraoperative blood transfusion was guided by our institutional practice like measured hemoglobin less than 8 gm/dl and sudden massive bleeding with hemodynamic instability. Written informed consent was obtained from all the patients before enrolment in the study.

Simple random allocation rule was followed for randomization. Patients were randomly recruited into either Group T or Group P by a computer-generated random number table. The random numbers were then kept in opaque, sealed envelopes and numbered sequentially. The anesthesiologist who prepared the study drug did not participate in anesthetizing the patient or collecting the data. The anesthesiologist managing the patient and collecting the data along with the operating neurosurgeon were blinded to the study drug. A single blinded neurosurgeon performed all the surgeries to ensure consistency in estimating the quality of the surgical field.

An identical standard anesthesia protocol was followed for all patients. All patients were kept nil per oral for 8 hours. Intravenous fentanyl 2 μg/kg, propofol 1-2 mg/kg and vecuronium 0.1 mg/kg were used at induction of anesthesia. Anesthesia was maintained by a titrated infusion of propofol and intermittent doses of vecuronium and fentanyl as required. The patients were ventilated to maintain end-tidal CO2 at 35 to 38 mmHg. Positive end-expiratory pressure (PEEP) was not used in any patient. After tracheal intubation, an arterial line was established in the radial artery.

In order to correct the fasting fluid deficit for baseline hematocrit estimation, 10 ml/kg of normal saline was first administered to all the patients in 15-20 minutes. After 10 minutes of completion of fluid administration, a blood sample was sent to the laboratory for hematocrit estimation. This hematocrit value was considered as “Initial hematocrit (Hi)”. Patients in group T then received a bolus dose of tranexamic acid 25 mg/kg over 10 minutes before the start of surgery, and then a continuous infusion of 1 mg/kg/hour through an infusion pump till the end of the surgery. Patients in group P received a corresponding volume of normal saline in an identical fashion. At all times, mean arterial pressure was maintained within 20% of the baseline value. The infusion of tranexamic acid was stopped at the end of the surgery. The second blood sample was then sent for “Final hematocrit (Hf)” estimation. At the end of the surgery, the neurosurgeon rated the quality of the surgical field according to the Boezaart Scale [Table 1].[12] Blood loss was calculated using the Modified Gross Formula: [predicted blood loss = blood volume x (Hi - Hf)]. Blood volume was estimated as the product of body weight and 0.75 (or 0.70 for females).
Table 1: Bleeding score (Boezaart)

Click here to view


Sample size

Prior to conducting this study, a pilot study was carried out in 10 patients undergoing transsphenoidal surgery of pituitary tumors. The same anesthesia protocol was followed in all these cases. None of the patients were given the test drug. The mean intraoperative blood loss was found to be 470 ± 137 ml. In order to reduce the mean intraoperative blood loss satisfactorily by a factor of 30% using the test drug with an alpha error of 0.05 and a power of 80%, a sample size of 22 patients in each group was required. Considering the possibility of unforeseen circumstances, we chose a sample size of 25 in each group with a total sample size of 50 patients.

Statistical analysis

Statistical analysis was carried out using IBM SPSS, version 21 for Windows. Variables such as age, weight, total duration of surgery and anesthesia, total intravenous fluids administered, and requirement of anesthetic agents were compared using the t-test. Categorical variables such as sex, ASA physical status, number of patients with hypertension or diabetes, and the type of pituitary pathology were compared among the two groups using Chi Square test. The difference in the quality of the surgical field (Boezaart score) between groups was analyzed using the Mann Whitney U test. Total blood loss difference between groups was analyzed using the independent sample t-test.


 » Results Top


A total of 63 patients were assessed for eligibility [Figure 1], out of which 13 patients were not enrolled because of meeting exclusion criteria, leaving 50 patients who were randomized into two groups of 25 each. The patients in the two groups were comparable in terms of age, body weight, gender, ASA physical status, total duration of surgery, total duration of anesthesia, and administered intravenous fluids [Table 2]. Other baseline characteristics such as the type of pituitary adenoma (broadly classified as functional and non-functional) and the presence of comorbid conditions like diabetes mellitus and hypertension were also similar in the two groups [Table 3].
Figure 1: CONSORT diagram

Click here to view
Table 2: Patient characteristics

Click here to view
Table 3: Other baseline characteristics

Click here to view


Most patients who had a good surgical field (corresponding to a lower Boezaart score of 2 and 3) were in Group T. Six patients in Group P had a Boezaart score of 2, compared to 11 patients in Group T. On the other hand, 8 patients who received placebo had a high score of 4 (indicating moderate bleeding and a poor surgical field), compared to only 2 patients who received TXA [Figure 2]. The median (interquartile range) Boezaart score in Group T was 3 (1.0), compared to 3 (1.5) in Group P. This difference was statistically significant (P = 0.03) [Table 4]. None of our patients required intraoperative blood transfusion. The mean blood loss in Group T was 334 ± 101 ml, whereas it was 495 ± 226 ml Group P. This difference of approximately 32% was also statistically significant (P = 0.002, [Table 4]).
Figure 2: Frequency distribution of Boezaart scores in the two groups

Click here to view
Table 4: Bleeding characteristics

Click here to view



 » Discussion Top


Numerous surgical complications have been reported during transsphenoidal resection of pituitary adenomas. Some of these complications such as injury to the internal carotid artery can have immediate life-threatening consequences. Even modest bleeding can significantly worsen the surgical field under the magnification of the operating microscope or endoscope, potentially leading to serious complications. Furthermore, minimizing intraoperative bleeding also reduces the need for blood transfusion, even though blood transfusion is uncommon in transsphenoidal resection of pituitary adenomas. There are serious concerns of blood transfusion such as transmission of infectious diseases, increased postoperative infection, dyselectrolytemia, allergic reactions, volume overload as well as immune modulation effects.[13],[14] Thus, it is important for the neuroanesthesiologist to maintain hemodynamic stability, adopt strategies to reduce intraoperative bleeding, and provide a clear surgical field to facilitate complete and uncomplicated resection of the pituitary adenoma.

Antifibrinolytic agents, which inhibit the enzymatic breakdown of fibrin, are commonly used to reduce intraoperative bleeding. Fibrinolysis is an important physiologic process to maintain the patency of blood vessels and coexists with the coagulation system through an intricate network of feedback loops in the body. During trauma and surgery, where there is tissue destruction, this equilibrium shifts to promote fibrinolysis and thus, antifibrinolytic drugs are believed to exert their protective effect by decreasing bleeding. However, published literature on the use of TXA in neurosurgeries is scarce. Two recently published studies showed a significant decrease in blood loss with the use of tranexamic acid in patients undergoing craniotomy for tumor excision.[15],[16]

Several methods and formulas have been designed to estimate blood loss, but accurate estimation isn't easy in the operating room setup. Estimation by visual inspection of the suction canister, wet sponges, pads, drapes and sheets is widely practised, but has a wide inter-observer variation and can often be very misleading. Many quantitative methods such as photo spectrometry, radioisotope dilution, platelet function analysis and accurate gravimetric methods are generally expensive, require special equipment, are time-consuming, and are either impractical or unavailable in most operating room setups.[17],[18],[19],[20],[21] The technique used in our study suggested by Gross et al.[22] is easy to perform and doesn't consume much time or expense. This cost-effective method has been used in several studies to assess blood loss.[23],[24],[25],[26],[27],[28] In our study, the mean blood loss in Group T was less compared to Group P (P = 0.002). Although there was no need for transfusion in both groups, there was a significant absolute reduction of blood loss with TXA use, amounting to 32%.

Assessment of the view of the surgical field is subjective and mostly based on the qualitative assessment of the anesthesiologists or the surgeons. Various rating scales have been devised to assess the quality of the surgical field. The most commonly used is the one designed by Boezaart et al.[29],[30],[31],[32] This is a pre-determined, objective category scale with six grades from 0 to 5: 0 (no bleeding) to 5 (severe bleeding requiring constant suctioning). In our study, more patients in Group T had a lower Boezaart score (score: 3 or less) compared to Group P. Similarly, a poor surgical field (score: 4 or more) was present in more patients receiving placebo compared to TXA. Similar findings were obtained by Alimian and colleagues[33] in endoscopic sinus surgeries. In our study, the median Boezaart score was statistically better in those receiving TXA. This finding may be very useful from neurosurgical point of view.

There are a few limitations of this study. Dose-response study for tranexamic acid was not done. Similarly, the bolus and infusion doses of TXA were based on the review of similar studies carried out previously. However, these may not be the optimal doses in neurosurgical patients because large-scale studies on tranexamic acid in intracranial surgeries are lacking. Though there were no immediate complications seen in any of the patient in the study group, long-term potential adverse effects of the drug such as seizures and thromboembolic events, albeit rare, were not assessed. We did not use any other laboratory method of estimating blood loss due to logistical reasons. All the patients in the study had a normal platelet count and coagulation profile, and it is not known whether TXA remains equally effective in those with deranged coagulation profile or platelet abnormalities. Stratification of patients on the basis of tumor-size was not possible because of heterogeneity in the modality and reporting of the radiological scans, as well as significant time-lag between the scan and the surgery in some cases. Lastly, this is a single-center randomized study and larger multicentric studies are warranted for broad generalizations of these study findings.


 » Conclusion Top


This study not only shows a significantly better surgical field with the use of tranexamic acid but also a significantly lesser blood loss. In the doses administered, intraoperative complications were not encountered. Despite widespread use in other surgical specialties, tranexamic acid is not commonly used in pituitary surgeries. Routine use of this inexpensive drug can be considered in all transsphenoidal pituitary surgeries, unless a specific contraindication for its use exists.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/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.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Wilson CB. Role of surgery in the management of pituitary tumors. Neurosurg Clin N Am 1990;1:139-59.  Back to cited text no. 1
    
2.
Jho HD. Endoscopic transsphenoidal surgery. J Neurooncol 2001;54:187-95.  Back to cited text no. 2
    
3.
Smith M, Hirsch NP. Pituitary disease and anaesthesia. Br J Anaesth 2000;85:3-14.  Back to cited text no. 3
    
4.
Raymond J, Hardy J, Czepko R, Roy D. Arterial injuries in transsphenoidal surgery for pituitary adenoma; the role of angiography and endovascular treatment. AJNR Am J Neuroradiol 1997;18:655-65.  Back to cited text no. 4
    
5.
Gadhinglajkar SV, Sreedhar R, Bhattacharya RN. Carotid artery injury during transsphenoidal resection of pituitary tumor: Anesthesia perspective. J Neurosurg Anesthesiol 2003;15:323-6.  Back to cited text no. 5
    
6.
Nemergut EC, Dumont AS, Barry UT, Laws ER. Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg 2005;101:1170-81.  Back to cited text no. 6
    
7.
Sethna NF, Zurakowski D, Brustowicz RM, Bacsik J, Sullivan LJ, Shapiro F. Tranexamic acid reduces intraoperative blood loss in pediatric patients undergoing scoliosis surgery. Anesthesiology 2005;102:727-32.  Back to cited text no. 7
    
8.
Fiechtner BK, Nuttall GA, Johnson ME, Dong Y, Sujirattanawimol N, Oliver WC Jr, et al. Plasma tranexamic acid concentrations during cardiopulmonary bypass. Anesth Analg 2001;92:1131-6.  Back to cited text no. 8
    
9.
Collaborators CI. Effect of tranexamic acid in traumatic brain injury: A nested randomised, placebo controlled trial (CRASH-2 Intracranial Bleeding Study). BMJ 2011;343:d3795.  Back to cited text no. 9
    
10.
Li ZJ, Fu X, Xing D, Zhang HF, Zang JC, Ma XL. Is tranexamic acid effective and safe in spinal surgery? A meta-analysis of randomized controlled trials. Eur Spine J 2013;22:1950-7.  Back to cited text no. 10
    
11.
Dunn CJ, Goa KL. Tranexamic acid: A review of its use in surgery and other indications. Drugs 1999;57:1005-32.  Back to cited text no. 11
    
12.
Boezaart AP, van der Merwe J, Coetzee A. Comparison of sodium nitroprusside- and esmolol-induced controlled hypotension for functional endoscopic sinus surgery. Can J Anaesth 1995;42:373-6.  Back to cited text no. 12
    
13.
Triulzi DJ, Vanek K, Ryan DH, Blumberg N. A clinical and immunologic study of blood transfusion and postoperative bacterial infection in spinal surgery. Transfusion 1992;32:517-24.  Back to cited text no. 13
    
14.
Vamvakas EC, Blajchman MA. Deleterious clinical effects of transfusion-associated immunomodulation: Fact or fiction? Blood 2001;97:1180-95.  Back to cited text no. 14
    
15.
Vel R, Udupi BP, Satya Prakash MV, Adinarayanan S, Mishra S, Babu L. Effect of low dose tranexamic acid on intra-operative blood loss in neurosurgical patients. Saudi J Anaesth 2015;9:42-8.  Back to cited text no. 15
    
16.
Hooda B, Chouhan RS, Rath GP, Bithal PK, Suri A, Lamsal R. Effect of tranexamic acid on intraoperative blood loss and transfusion requirements in patients undergoing excision of intracranial meningioma. J Clin Neurosci 2017;41:132-8.  Back to cited text no. 16
    
17.
Chua S, Ho LM, Vanaja K, Nordstrom L, Roy AC, Arulkumaran S. Validation of a laboratory method of measuring postpartum blood loss. Gynecol Obstet Invest 1998;46:31-3.  Back to cited text no. 17
    
18.
Quinlivan WL, Brock JA. Blood volume changes and blood loss associated with labor. I. Correlation of changes in blood volume measured by I-131 albumin and Evans blue dye, with measured blood loss. Am J Obstet Gynecol 1970;106:843-9.  Back to cited text no. 18
    
19.
Nelson GH, Ashford C, Williamson R, Amburn SD. Method for calculating blood loss at vaginal delivery. South Med J 1981;74:550-2.  Back to cited text no. 19
    
20.
Cammerer U, Dietrich W, Rampf T, Braun SL, Richter JA. The predictive value of modified computerized thromboelastography and platelet function analysis for postoperative blood loss in routine cardiac surgery. Anesth Analg 2003;96:51-7.  Back to cited text no. 20
    
21.
Karkouti K, McCluskey SA, Syed S, Pazaratz C, Poonawala H, Crowther MA. The influence of perioperative coagulation status on postoperative blood loss in complex cardiac surgery: A prospective observational study. Anesth Analg 2010;110:1533-40.  Back to cited text no. 21
    
22.
Gross JB. Estimating allowable blood loss: Corrected for dilution. Anesthesiology 1983;58:277-80.  Back to cited text no. 22
    
23.
Ishii Y, Matsuda Y. Perioperative blood loss in cementless or hybrid total knee arthroplasty without patellar resurfacing: A prospective, randomized study. J Arthroplasty 2005;20:972-6.  Back to cited text no. 23
    
24.
Levy O, Martinowitz U, Oran A, Tauber C, Horoszowski H. The use of fibrin tissue adhesive to reduce blood loss and the need for blood transfusion after total knee arthroplasty. A prospective, randomized, multicenter study. J Bone Joint Surg Am 1999;81:1580-8.  Back to cited text no. 24
    
25.
Prasad N, Padmanabhan V, Mullaji A. Blood loss in total knee arthroplasty: An analysis of risk factors. Int Orthop 2007;31:39-44.  Back to cited text no. 25
    
26.
Tanaka N, Sakahashi H, Sato E, Hirose K, Ishima T, Ishii S. Timing of the administration of tranexamic acid for maximum reduction in blood loss in arthroplasty of the knee. J Bone Joint Surg Br 2001;83:702-5.  Back to cited text no. 26
    
27.
Goodnough LT, Despotis GJ, Merkel K, Monk TG. A randomized trial comparing acute normovolemic hemodilution and preoperative autologous blood donation in total hip arthroplasty. Transfusion 2000;40:1054-7.  Back to cited text no. 27
    
28.
Jans O, Grevstad U, Mandoe H, Kehlet H, Johansson PI. A randomized trial of the effect of low dose epinephrine infusion in addition to tranexamic acid on blood loss during total hip arthroplasty. Br J Anaesth 2016;116:357-62.  Back to cited text no. 28
    
29.
Jacobi KE, Bohm BE, Rickauer AJ, Jacobi C, Hemmerling TM. Moderate controlled hypotension with sodium nitroprusside does not improve surgical conditions or decrease blood loss in endoscopic sinus surgery. J Clin Anesth 2000;12:202-7.  Back to cited text no. 29
    
30.
Ayoglu H, Yapakci O, Ugur MB, Uzun L, Altunkaya H, Ozer Y, et al. Effectiveness of dexmedetomidine in reducing bleeding during septoplasty and tympanoplasty operations. J Clin Anesth 2008;20:437-41.  Back to cited text no. 30
    
31.
Hathorn IF, Habib AR, Manji J, Javer AR. Comparing the reverse Trendelenburg and horizontal position for endoscopic sinus surgery: A randomized controlled trial. Otolaryngol Head Neck Surg 2013;148:308-13.  Back to cited text no. 31
    
32.
Wormald PJ, van Renen G, Perks J, Jones JA, Langton-Hewer CD. The effect of the total intravenous anesthesia compared with inhalational anesthesia on the surgical field during endoscopic sinus surgery. Am J Rhinol 2005;19:514-20.  Back to cited text no. 32
    
33.
Alimian M, Mohseni M. The effect of intravenous tranexamic acid on blood loss and surgical field quality during endoscopic sinus surgery: A placebo-controlled clinical trial. J Clin Anesth 2011;23:611-5.  Back to cited text no. 33
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
Print this article  Email this article
   
Online since 20th March '04
Published by Wolters Kluwer - Medknow