COMMENTARY
Dogma Challenged: Tetracaine for Corneal Abrasions?
T
he longer one practices emergency medicine, the more it becomes clear that many common practices are driven by dogma, untested conventional wisdom, and opinions of both actual and self-proclaimed experts. Working with residents and students on a day-to-day basis is often the only thing that slows down busy clinicians long enough to consider the lack of evidence supporting many common practices. Seemingly innocuous questions such as “Do I need to wear sterile gloves to repair this simple laceration?” or “Do I really need to pack this abscess?” are enough to send a seasoned attending physician running to the literature after almost every shift. Dogma is easy—it gets us through the day without feeling silly about how little we truly know to be fact. It fills many of the voids in our collective knowledge and persists in our clinical practices until someone challenges it with real-world clinical evidence. It is very likely that much of the conventional wisdom taught in medical school and residency, and reiterated in lectures and textbooks, is actually valid. However, it has been shown several times over the past few decades that at least some of the core beliefs that pervade the daily practice of medicine are eventually proven wrong. Some notable examples include the discovery that peptic ulcer disease was not caused simply by an overproduction of gastric acid, and the discovery of the positive effects of beta-blockers in congestive heart failure. Often, ill-informed conventional wisdom persists because investigators are unable to persuade local institutional review boards that a putative “standard of care” merits reconsideration. Equipoise is a guiding principal of ethical clinical trials. As traditionally interpreted, equipoise exists when there is no expert consensus that one treatment alternative is superior to another. Clinical trials can move forward only when experts agree that proposed treatment options appear equally efficacious and none pose an increased risk of harm to the patient. This principle is intended to protect human subjects from being assigned to treatments that are reasonably likely to be less effective or more harmful than current standards of care.
The authors have no relevant financial information or potential conflicts of interest to disclose. A related article appears on page 374.
© 2014 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12359
The concept of clinical equipoise has been challenged in the medical literature.1 The standard-of-care treatment option may itself be based on poor evidence. It is often unclear when an individual or committee is qualified to render the “expert” opinion regarding the efficacy of treatment options. It is very possible that one investigator may be able to persuade his institutional review board that treatment standards merit reconsideration, while another investigator would find his local board unmoved by the same argument. Clearly, the definition of standard of care is subject to divergent interpretation, and many clinical practices go unchallenged because of the hurdle presented by need to demonstrate therapeutic equipoise, however well intended. Emergency physicians have been taught that topical anesthetic use is associated with poor healing and recurrent trauma in the management of corneal abrasions.2 These fears are grounded in laboratory-based studies and case reports that described the prolonged, unsupervised use (or abuse) of topical anesthetics. However, studies published in the 1990s have demonstrated the safety and efficacy of topical anesthetics in postphotorefractive keratectomy patients.3,4 We suspect that many an emergency physician would take home a bottle of topical anesthetic if he or she personally sustained a corneal abrasion and would use it without too much hesitation. Yet we deny our patients this same courtesy, discharging them instead with prescriptions for oral pain medications, which have their own possible adverse consequences.5 In this issue of Academic Emergency Medicine, Dr. Waldman and colleagues6 report the results of a study examining the safety and efficacy of topical tetracaine in the treatment of corneal abrasions. This is the largest ED-based study to date on this topic. We applaud the authors for challenging common wisdom through this double-blind, randomized trial. We also applaud their institutional review board for finding the clinical equipoise to allow this trial to proceed despite the frequently stated opinion that the use of topical anesthetics deviates from the standard of care. The study demonstrated no complications specifically attributable to topical anesthetic use among the 59 patients in the tetracaine group, yielding a 95% confidence interval (CI) of a topical anesthetic–induced complication between zero and 6.1%. Additionally, there was no significant difference in healing between the groups as measured by persistent fluorescein uptake at
ISSN 1069-6563 PII ISSN 1069-6563583
467 467
468
the 48-hour recheck. At least one follow-up encounter was completed on each study patient. While median visual analog scale (VAS) pain scores were lower in the tetracaine group at all study time points after presentation, the mixed-model analysis did not demonstrate a clinically significant difference in pain scores between the two groups. However, patients rated the study drug to be significantly more effective on a global rating scale (7.7 vs. 3.8 on the numeric 0 to 10 rating scale, p < 0.0005). The reason for the dichotomous findings related to pain control efficacy is not entirely clear, and the authors proffer several possible explanations. Whether or not to start using tetracaine routinely in the treatment of simple corneal abrasions remains up to the reader. While this study found no complications, the width of the 95% CI may cause some to consider waiting for further study. Additionally, the seemingly conflicting results of the mixed-model VAS score analysis and the analysis of the global effectiveness ratings may lead some to question the efficacy of topical anesthetics. What is clear is that these authors have, at the very least, opened the door to the use of a promising, inexpensive medication once considered off-limits to our patients after ED discharge. Future trials will likely answer any remaining questions regarding safety and efficacy, but the investigators hoping to conduct those trials can thank the authors of this manuscript for paving the road to institutional review board approval. Jacob W. Ufberg, MD ([email protected]) David J. Karras, MD Department of Emergency Medicine Temple University School of Medicine Philadelphia, PA
Supervising Editor: David C. Cone, MD.
Ufberg and Karras • TETRACAINE FOR CORNEAL ABRASIONS
References 1. Miller FG, Joffe S. Equipoise and the dilemma of randomized clinical trials. N Engl J Med 2011;364:476– 480. 2. Walker RA, Adhikari S. Eye emergencies. In: Tintinalli JE, Stapczynski S, Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York, NY: McGraw-Hill, 2011. 3. Verma S, Corbett MC, Marshall J. A prospective, randomized double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy. Ophthalmology 1995;102: 1918–24. 4. Verma S, Corbett MC, Patmore G, Marshall J. A comparative study of the duration and efficacy of tetracaine 1% and bupivacaine 0.75% in controlling pain following photorefractive keratectomy (PRK). Eur J Ophthalmol 1997;7:327–33. 5. Perrone J, Mycyk M. A challenging crossroad for emergency medicine: the epidemics of pain and pain medication deaths [commentary]. Acad Emerg Med 2014;21:334–36. 6. Waldman N, Densie IK, Herbison P. 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. Acad Emerg Med 2014;21:374–82.
Dogma Challenged: Tetracaine for Corneal Abrasions?
T
he longer one practices emergency medicine, the more it becomes clear that many common practices are driven by dogma, untested conventional wisdom, and opinions of both actual and self-proclaimed experts. Working with residents and students on a day-to-day basis is often the only thing that slows down busy clinicians long enough to consider the lack of evidence supporting many common practices. Seemingly innocuous questions such as “Do I need to wear sterile gloves to repair this simple laceration?” or “Do I really need to pack this abscess?” are enough to send a seasoned attending physician running to the literature after almost every shift. Dogma is easy—it gets us through the day without feeling silly about how little we truly know to be fact. It fills many of the voids in our collective knowledge and persists in our clinical practices until someone challenges it with real-world clinical evidence. It is very likely that much of the conventional wisdom taught in medical school and residency, and reiterated in lectures and textbooks, is actually valid. However, it has been shown several times over the past few decades that at least some of the core beliefs that pervade the daily practice of medicine are eventually proven wrong. Some notable examples include the discovery that peptic ulcer disease was not caused simply by an overproduction of gastric acid, and the discovery of the positive effects of beta-blockers in congestive heart failure. Often, ill-informed conventional wisdom persists because investigators are unable to persuade local institutional review boards that a putative “standard of care” merits reconsideration. Equipoise is a guiding principal of ethical clinical trials. As traditionally interpreted, equipoise exists when there is no expert consensus that one treatment alternative is superior to another. Clinical trials can move forward only when experts agree that proposed treatment options appear equally efficacious and none pose an increased risk of harm to the patient. This principle is intended to protect human subjects from being assigned to treatments that are reasonably likely to be less effective or more harmful than current standards of care.
The authors have no relevant financial information or potential conflicts of interest to disclose. A related article appears on page 374.
© 2014 by the Society for Academic Emergency Medicine doi: 10.1111/acem.12359
The concept of clinical equipoise has been challenged in the medical literature.1 The standard-of-care treatment option may itself be based on poor evidence. It is often unclear when an individual or committee is qualified to render the “expert” opinion regarding the efficacy of treatment options. It is very possible that one investigator may be able to persuade his institutional review board that treatment standards merit reconsideration, while another investigator would find his local board unmoved by the same argument. Clearly, the definition of standard of care is subject to divergent interpretation, and many clinical practices go unchallenged because of the hurdle presented by need to demonstrate therapeutic equipoise, however well intended. Emergency physicians have been taught that topical anesthetic use is associated with poor healing and recurrent trauma in the management of corneal abrasions.2 These fears are grounded in laboratory-based studies and case reports that described the prolonged, unsupervised use (or abuse) of topical anesthetics. However, studies published in the 1990s have demonstrated the safety and efficacy of topical anesthetics in postphotorefractive keratectomy patients.3,4 We suspect that many an emergency physician would take home a bottle of topical anesthetic if he or she personally sustained a corneal abrasion and would use it without too much hesitation. Yet we deny our patients this same courtesy, discharging them instead with prescriptions for oral pain medications, which have their own possible adverse consequences.5 In this issue of Academic Emergency Medicine, Dr. Waldman and colleagues6 report the results of a study examining the safety and efficacy of topical tetracaine in the treatment of corneal abrasions. This is the largest ED-based study to date on this topic. We applaud the authors for challenging common wisdom through this double-blind, randomized trial. We also applaud their institutional review board for finding the clinical equipoise to allow this trial to proceed despite the frequently stated opinion that the use of topical anesthetics deviates from the standard of care. The study demonstrated no complications specifically attributable to topical anesthetic use among the 59 patients in the tetracaine group, yielding a 95% confidence interval (CI) of a topical anesthetic–induced complication between zero and 6.1%. Additionally, there was no significant difference in healing between the groups as measured by persistent fluorescein uptake at
ISSN 1069-6563 PII ISSN 1069-6563583
467 467
468
the 48-hour recheck. At least one follow-up encounter was completed on each study patient. While median visual analog scale (VAS) pain scores were lower in the tetracaine group at all study time points after presentation, the mixed-model analysis did not demonstrate a clinically significant difference in pain scores between the two groups. However, patients rated the study drug to be significantly more effective on a global rating scale (7.7 vs. 3.8 on the numeric 0 to 10 rating scale, p < 0.0005). The reason for the dichotomous findings related to pain control efficacy is not entirely clear, and the authors proffer several possible explanations. Whether or not to start using tetracaine routinely in the treatment of simple corneal abrasions remains up to the reader. While this study found no complications, the width of the 95% CI may cause some to consider waiting for further study. Additionally, the seemingly conflicting results of the mixed-model VAS score analysis and the analysis of the global effectiveness ratings may lead some to question the efficacy of topical anesthetics. What is clear is that these authors have, at the very least, opened the door to the use of a promising, inexpensive medication once considered off-limits to our patients after ED discharge. Future trials will likely answer any remaining questions regarding safety and efficacy, but the investigators hoping to conduct those trials can thank the authors of this manuscript for paving the road to institutional review board approval. Jacob W. Ufberg, MD ([email protected]) David J. Karras, MD Department of Emergency Medicine Temple University School of Medicine Philadelphia, PA
Supervising Editor: David C. Cone, MD.
Ufberg and Karras • TETRACAINE FOR CORNEAL ABRASIONS
References 1. Miller FG, Joffe S. Equipoise and the dilemma of randomized clinical trials. N Engl J Med 2011;364:476– 480. 2. Walker RA, Adhikari S. Eye emergencies. In: Tintinalli JE, Stapczynski S, Cline DM, Ma OJ, Cydulka RK, Meckler GD, eds. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 7th ed. New York, NY: McGraw-Hill, 2011. 3. Verma S, Corbett MC, Marshall J. A prospective, randomized double-masked trial to evaluate the role of topical anesthetics in controlling pain after photorefractive keratectomy. Ophthalmology 1995;102: 1918–24. 4. Verma S, Corbett MC, Patmore G, Marshall J. A comparative study of the duration and efficacy of tetracaine 1% and bupivacaine 0.75% in controlling pain following photorefractive keratectomy (PRK). Eur J Ophthalmol 1997;7:327–33. 5. Perrone J, Mycyk M. A challenging crossroad for emergency medicine: the epidemics of pain and pain medication deaths [commentary]. Acad Emerg Med 2014;21:334–36. 6. Waldman N, Densie IK, Herbison P. 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. Acad Emerg Med 2014;21:374–82.
