What is chronic rhinosinusitis?
Chronic rhinosinusitis is an inflammation of the sinuses that has lasted for at least 12 weeks. People with chronic rhinosinusitis can experience symptoms such as a blocked or runny nose, a feeling of facial pain or pressure, or a reduction or loss of the sense of smell. Some people may also have polyps in their nose, which can worsen the symptoms.
How is chronic rhinosinusitis treated?
Chronic rhinosinusitis is usually treated with medicines such as saline sprays or rinses, anti-inflammatory sprays/drops (steroids), antibiotics or anti-inflammatory steroid tablets. If the symptoms continue despite this treatment, surgery can be performed.
What did we want to find out?
We wanted to see if tranexamic acid, a medicine used to improve blood clotting, could be effective during endoscopic sinus surgery by reducing bleeding, which then potentially reduces the risk of complications. Less bleeding means that surgeons have a better view of the sinuses when they are operating.
What did we do?
We searched for studies that investigated tranexamic acid (either given in the vein or directly applied in the nose by sprays or drops) compared with a placebo (dummy treatment) or no tranexamic acid. We were interested in both children and adults. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 14 studies, with a total of 942 participants, which compared tranexamic acid to normal saline (placebo - dummy treatment) in patients having endoscopic sinus surgery. In 10 studies the treatment was given in a vein and in three it was applied in the nose. All studies used different amounts of the drug.
We found that tranexamic acid probably greatly improves the view of the surgeon (based on 13 studies), may slightly reduce total blood loss during surgery (12 studies) and likely does not cause any serious side effects within 24 hours of surgery (i.e. blood clot formation in the brain or seizures - there were no such events in either the treatment or placebo groups) (eight studies). Unfortunately, there is no evidence with respect to serious side effects at a longer duration of follow-up.
The duration of the surgery was investigated in 10 studies. The duration of surgery is probably slightly lower with tranexamic acid.
Only two studies investigated complications related to surgery and difficulty completing the surgery as planned. In these studies no difference was seen between the tranexamic acid and placebo groups. However, because these complications are rare no conclusions can be drawn based on these studies.
Nosebleeds after surgery that required intervention (placing of nasal tampons or further surgery) were investigated in six studies. Only two studies reported a patient treated with saline solution (placebo) who experienced a nosebleed after surgery. Tranexamic acid may not make a difference to the likelihood of postoperative bleeding.
Based on the evidence in the studies we cannot conclude whether tranexamic acid given either in a vein or applied in the nose is better. We also cannot conclude whether a particular dose of tranexamic acid is better.
What are the limitations of the evidence?
We are moderately confident about the evidence for the improvement of the view of the surgeon during surgery, but further research may have an impact on the estimate of the effect. We have less confidence in the evidence for lower blood loss during surgery, meaning that the true effect could be very different after more research. For the occurrence of serious side effects within 24 hours after surgery (blood clot formation in the brain or seizures) we are confident that more research would probably not change our findings.
How up-to-date is the evidence?
The evidence is up-to-date to February 2022.
There is moderate-certainty evidence to support the beneficial value of topical or intravenous tranexamic acid during endoscopic sinus surgery with respect to surgical field bleeding score. Low- to moderate-certainty evidence suggests a slight decrease in total blood loss during surgery and duration of surgery. Whilst there is moderate-certainty evidence that tranexamic acid does not lead to more immediate significant adverse events compared to placebo, there is no evidence regarding the risk of serious adverse events more than 24 hours after surgery. There is low-certainty evidence that tranexamic acid may not change postoperative bleeding. There is not enough evidence available to draw robust conclusions about incomplete surgery or surgical complications.
Chronic rhinosinusitis, with or without nasal polyps, can have a major impact on a person's quality of life. Treatment is usually conservative and may include nasal saline, intranasal corticosteroids, antibiotics or systemic corticosteroids. If these treatments fail endoscopic sinus surgery can be considered. During surgery, visibility of the surgical field is important for the identification of important anatomic landmarks and structures that contribute to safety. Impaired visualisation can lead to complications during surgery, inability to complete the operation or a longer duration of surgery. Different methods are used to decrease intraoperative bleeding, including induced hypotension, topical or systemic vasoconstrictors or total intravenous anaesthesia. Another option is tranexamic acid, an antifibrinolytic agent, which can be administered topically or intravenously.
To assess the effects of peri-operative tranexamic acid versus no therapy or placebo on operative parameters in patients with chronic rhinosinusitis (with or without nasal polyps) who are undergoing functional endoscopic sinus surgery (FESS).
The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 10 February 2022.
Randomised controlled trials (RCTs) comparing intravenous, oral or topical tranexamic acid with no therapy or placebo in the treatment of patients (adults and children) with chronic rhinosinusitis, with or without nasal polyps, undergoing FESS.
We used the standard methodological procedures expected by Cochrane. Primary outcome measures were surgical field bleeding score (e.g. Wormald or Boezaart grading system), intraoperative blood loss and significant adverse effects (seizures or thromboembolism within 12 weeks of surgery). Secondary outcomes were duration of surgery, incomplete surgery, surgical complications and postoperative bleeding (placing of packing or revision surgery) in the first two weeks after surgery. We performed subgroup analyses for methods of administration, different dosages, different forms of anaesthesia, use of thromboembolic prophylaxis and children versus adults. We evaluated each included study for risk of bias and used GRADE to assess the certainty of the evidence.
We included 14 studies in the review, with a total of 942 participants. Sample sizes in the included studies ranged from 10 to 170. All but two studies included adult patients (≥ 18 years). Two studies included children. Most studies had more male patients (range 46.6% to 80%). All studies were placebo-controlled and four studies had three treatment arms. Three studies investigated topical tranexamic acid; the other studies reported the use of intravenous tranexamic acid.
For our primary outcome, surgical field bleeding score measured with the Boezaart or Wormald grading score, we pooled data from 13 studies. The pooled result demonstrated that tranexamic acid probably reduces the surgical field bleeding score, with a standardised mean difference (SMD) of -0.87 (95% confidence interval (CI) -1.23 to -0.51; 13 studies, 772 participants; moderate-certainty evidence). A SMD below -0.70 represents a large effect (in either direction).
Tranexamic acid may result in a slight reduction in blood loss during surgery compared to placebo with a mean difference (MD) of -70.32 mL (95% CI -92.28 to -48.35 mL; 12 studies, 802 participants; low-certainty evidence).
Tranexamic acid probably has little to no effect on the development of significant adverse events (seizures or thromboembolism) within 24 hours of surgery, with no events in either group and a risk difference (RD) of 0.00 (95% CI -0.02 to 0.02; 8 studies, 664 participants; moderate-certainty evidence). However, there were no studies reporting significant adverse event data with a longer duration of follow-up.
Tranexamic acid probably results in little difference in the duration of surgery with a MD of -13.04 minutes (95% CI -19.27 to -6.81; 10 studies, 666 participants; moderate-certainty evidence). Tranexamic acid probably results in little to no difference in the incidence of incomplete surgery, with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence) and likely results in little to no difference in surgical complications, again with no events in either group and a RD of 0.00 (95% CI -0.09 to 0.09; 2 studies, 58 participants; moderate-certainty evidence), although these numbers are too small to draw robust conclusions. Tranexamic acid may result in little to no difference in the likelihood of postoperative bleeding (placement of packing or revision surgery within three days of surgery) (RD -0.01, 95% CI -0.04 to 0.02; 6 studies, 404 participants; low-certainty evidence). There were no studies with longer follow-up.