Short Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double Blind Randomised Clinical Trial

Shipman S et al. Ann Emerg Med. 2021; 77:338-344. doi:xxx]

Clinical Question

• In adults presenting to the ED with a corneal abrasion is topical tetracaine more effective than placebo to control pain at a 24-48 hour follow up appointment?

Background

• Corneal abrasions are examined in ED after immediately alleviating pain with a topical anaesthetic, but patients are sent home with none after fears of complications
• Complications have been mainly reported in case reports and series and include corneal ulcerations, keratitis, hypopyon and delayed healing
• Despite this, various studies have suggested safety in topical anaesthetic use for 24-48hours
• No high quality studies looking at efficacy of corneal local anaesthetic use

Design

• Prospective randomised double blind, placebo controlled trial
• Randomisation in a 1:1 ratio to receive tetracaine or placebo
• Concealed allocation by computer generated random number generator then sequentially numbered opaque sealed envelopes
• 60 patients per group would have a 95% power to detect a minimum clinical difference in pain scores of 1.5cm on a 10cm numeric rating scale (NRS)

Setting

• Single centre urban community ED in Oklahoma City (USA), that sees 86,000 patients a year
• Data collected Jan 2015- Sep 2017

Population

• Inclusion:
  • 18-80yrs old presenting with a corneal abrasion
• Exclusion:
  • Contact lens wearers
  • Previous corneal surgery on affected eye
  • >36 hrs post injury
  • Grossly contaminated FB/co-existing ocular infection
  • Retained FB
  • Penetrating eye injury
  • Immunosuppression
  • Allergy to study medications
  • Inability to attend follow up
  • Injury requiring urgent ophthalmology evaluation (large or complicated abrasions with visual loss, corneal ulcers or lacerations)
  • Inability to speak fluent English or Spanish
• Baseline clinical and demographic characteristics (Tetracaine vs Placebo)
  • Male: 61% vs 58%
  • Median Age: 35 vs 38
  • Baseline NRS pain rating: 7 vs 7
  • Mechanism:
    • Metalic FB: 14% vs 9%
    • Other FB: 29% vs 25%
    • Direct trauma: 17% vs 34%
    • Unknown: 40% vs 32%
  • Language spoken
    • English: 97% vs 97%
    • Spanish: 3% vs 3%

Intervention

• Tetracaine 0.5%
  • 1 drop every 30mins PRN for maximum 24 hours
  • A single 2ml bottle

Control

• A balanced artificial tear solution
  • Trade name: Systane
  • 1 drop every 30mins PN for maximum 24 hours
  • 4 separate 0.5ml ampules

Management common to both groups

• All patients also given:
  • Antibiotic drops mixture of polymyxin B/trimethoprim 2 drops 4 hourly
  • A prescription for hydrocodone/paracetamol 7.5/325mg PRN for breakthrough pain
• Patients asked to record:
  • Pain measurements on NRS before and 2mins after use of study drops
  • Amount of hydrocodone taken between discharge and ED follow up
• All patients followed up at 24-48 hours by a blinded EM physician who:
  • Examined under slit lamp looking for persistence/delayed healing or complications- if present referred to blinded study ophthalmologist
  • Asked for an overall NRS score after using study drops
  • Collected study drops at this appointment to prevent prolonged use
• All patients were asked to then be followed up with a blinded study ophthalmologist at 1 week

Outcome

• Primary outcome: Overall NRS pain score measured at the patient’s initial ED follow up at 24-48hours was significantly lower in the tetracaine group
  • NRS score 1 vs 8; difference of 7; CI 6-8; P<.001
  • Change to NRS from baseline score:
    • Tetracaine 6; 95% CI 5-7
    • Placebo 0; 95% CI 0-0
• Secondary outcomes: Patients in tetracaine group ingested less hydrocodone then in placebo group
  • 1 in tetracaine group vs 7 in placebo. Difference 6; CI 4-6

• Adverse effects between groups were non significant
  • 3.6% in tetracaine group vs 11% in placebo. CI -2.9 to 18
• Number of patients with small residual corneal abraision at 24-48 hour follow up – no significant difference
  • 18% in tetracaine group vs 11% in placebo. CI -6.4 to 20.4

Authors’ Conclusions

• Short term topical tetracaine is safe and efficacious as an analgesic for corneal abrasions, is associated with less hydrocodone use compared with placebo

Strengths

• Randomised controlled
• Reasonable attempts to blind both patients and physicians involved
• Intention to treat methodology
• Despite single centre still has external validity

Weaknesses

• No mention of how they selected patients, all physicians where trained to recruit which was possible 24/7 but no mention of whether all were assessed for eligibility i.e. likely convenience sample
• Blinding is limited given:
  • Physician enrolling – tetracaine and placebo arm had different number of ampoules/bottles in envelopes ( 1 in tetracaine vs 4 in placebo). Envelope unlikely to fully mask this
  • Patient- will be able to calculate if they had been allocated study group given they will recognise that tetracaine stings when first applied
• Only 20% in study arm and 18% in control attended 1wk follow up with ophthalmologist. Despite this:
  • They did attempt to contact all that didn’t attend by either phone or searching local electronic records or both
  • 95% in the study arm and 93% control arm did attend the 24-48hr ED follow up where the necessary primary outcome data was collected
• Secondary endpoint of adverse effects:
  • May lack reliability as description of healing corneal abrasion is subjective.  Physician initially assessing is likely to be different to physician reviewing at ED follow up
  • No standardised approach thus difficult to ensure consistency of results.
  • This study is not powered for safety
• Registered on clinicaltrials.gov only after study had been completed

The Bottom Line

• This study indicates tetracaine is more effective in providing analgesia compared to commonly used alternative- artificial tears with a significant difference in NRS scores at 24-48hours. This specific study has not been powered for safety and should not be used for this. Other studies have however shown safety for short term use
• As a result of this combined information I will selectively start prescribing topical tetracaine for patients with simple uncomplicated corneal abrasions that I am confident will follow advice on use being short term only

External Links

• [article] Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial
• [further reading] Waldman: Topical Tetracaine Used for 24 Hours Is Safe and Rated Highly Effective by Patients for the Treatment of Pain Caused by Corneal Abrasions: A Double-blind, Randomized Clinical Trial
• [further reading] A Prospective, Randomized, Double-masked Trial to Evaluate the Role of Topical Anesthetics in Controlling Pain after Photorefractive Keratectomy
• [further reading] REBELEM: Corneal Abrasions and Short-Term Topical Tetracaine

Metadata

Summary author: Halah Zareian @DocHZ
Summary date: 3/3/21
Peer-review editor: David Slessor

Image by: Rudy and Peter Skitterians from Pixabay