SGEM#83: In Your Eyes (Topical Tetracaine for Corneal Abrasions)

Podcast Link: SGEM83
Date:  July 12th, 2014 

Rebel Skeptics: Dr. Salim Rezaie is an Assistant Professor in the Department of Emergency Medicine and Internal Medicine at the University of Texas at San Antonio. You may better know him from his website REBEL EM or twitter handle @srrezaie.

Case Scenario: 47 year old man is playing Marco Polo in the pool with his daughters. He is accidentally hit in the eye and sustains a uncomplicated corneal abrasion

Question: Is the use of topical 1.0% tetracaine for 24 hours safe and effective for the treatment of uncomplicated corneal abrasions?

Background: Corneal abrasions are very common presentations to the emergency department and very painful. We have all been warned that topical anesthetics to take home should not be given to patients with corneal injuries. The fear is that these drops could delay/decrease healing, prevent recognition of eye foreign bodies, cause keratitis or worsen corneal symptoms.

fact-or-fictionSome of this information comes from animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery:

  • Duffin RM, Olson RJ. Tetracaine toxicity. Ann Ophthalmol. 1984;16(9)836,838. 
  • Judge AJ, et al. Corneal endothelial toxicity of topical anesthesia. Ophthalmology. 1997;104(9):1373–1379.
  • Guzey M, et al. The effects of bupivacaine and lidocaine on the corneal endothelium when applied into the anterior chamber at the concentrations supplied commercially. Ophthalmologica. 2002;216(2):113–117.

Are the dangers of topical anesthetics for simple corneal abrasions fact or fiction?

Article: Waldman N et al.  Topical Tetracaine used for 24 Hours is Safe and Rated Highly Effective by Patients for the Treatment of apain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Acad Emerg Med 2014; 21: 374 – 382.

  • Population: Patients presenting to the ED of Southland Hospital in New Zealand with Corneal Abrasions (N = 116)
  • Intervention: Acetaminophen 500mg plus 1% tetracaine hydrochloride topical eye drops
  • Comparison: Acetaminophen 500mg plus placebo (saline eye drops)
  • Outcome:
    • Primary Outcome Safety: Repeat fluorescein/slit lamp ED examinations at 48 hours, 1-week, and 1-month telephone interviews for corneal complications
    • Secondary Outcomes Pain: 100-mm VAS pain scores recorded every 2 hours while awake for 48 hours and patient perceived overall effectiveness with a numeric rating scale (NRS) of 0 – 10.
  • Exclusions: Injury > 36hrs before presentation, < 18 years of age, previous eye surgery or cataracts, wear contact lenses, injury to both eyes, suffering from infectious or chemical conjunctivitis, grossly contaminated foreign bodies, suffering from an ocular infection, current herpes keratitis, allergy to tetracaine, injury requiring urgent ophthalmologic evaluation (i.e. penetrating eye injuries, large corneal abrasions, or injuries causing a disruption of vision), and unable to attend follow up at 48 hours

Authors Conclusions: ”Topical Tetracaine used for 24 hours is safe, and while there was no significant difference in patient VAS pain ratings over time, patient surveys on overall effectiveness showed that patients perceived tetracaine to be significantly more effective than saline.”

checklist-cartoonQuality Check List for Random Control Trials:

  1. The study population included or focused on those in the ED? Yes
    • Comment: These were all patients presenting to a regional ED in New Zealand
  2. The patients were adequately randomized? Yes 
    • They used numbered sealed envelopes to randomize patients
  3. The randomization process was concealed? Yes

    • Both the authors and the patients were blinded
  4. The patients were analyzed in the groups to which they were randomized? Yes 
    • Two arms 1% tetracaine vs. saline eye drops
  5. The study patients were recruited consecutively (i.e. no selection bias)? Yes 
    • Patient enrollment into the study could occur at any time during the day or night, 7 days a week and was dictated in part by staffing levels and demands on the department
  6. The patients in both groups were similar with respect to prognostic factors. Yes 
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure? 
    • Some patients commented on the fact that the drops they were using burned like the tetracaine used in the ED at their initial evaluation. This may have unblinded some physicians and some patients
  8. All groups were treated equally except for the intervention. Yes 
  9. Follow-up was complete (i.e. at least 80% for both groups). No 
    • Only 70% of patients had 48 hour follow-up
  10. All patient-important outcomes were considered. Yes
    • specifically pain relief and corneal complications
  11. The treatment effect was large enough and precise enough to be clinically significant. No
    • Twenty-three patients were removed from data analysis after 48 hour check up. This was due to retained rust rings, making the study underpowered to detect differences in corneal complications and pain scale evaluation.

Key Results:  

  • Primary:
    • 48 hours: No statistical difference in healing identified by fluorescein uptake between the two groups
      • 20 patients had persistent symptoms (10/46 tetracaine vs. 10/47 placebo)
    • 1 Week: Persistent symptoms in five patients (1 tetracaine and 4 placebo)
    • 1 Month: No complications reported by either group
  • Secondary:
    • No difference in 100mm VAS pain scores at an given time between the two groups
    • Patient perceived effectiveness at 1 week (0- not effective and 10- completely effective)
      • Statistically difference (7.7 for tetracaine vs. 3.8 for saline group)
Dr. Salim Rezaie

Dr. Salim Rezaie

Comments:  This was the largest randomized clinical trial to date (n=116) to evaluate the use of topical anesthetics for corneal abrasions. There was no significant difference in healing between the two groups. However, only 93 patients returned for the primary outcome of follow-up at 48 hours.

Another problem was the large number of patients with retained rust rings (13-tetracaine and 10-placebo). This was unanticipated and made it challenging to analyze the data.

The study was underpowered to detect a difference in efficacy between the two groups both in 100mm-VAS pain scale. This represents a common limitations to randomized control trials. They are powered for the primary outcome not for the secondary outcome. However, their goal was to look at safety and that did not show a difference at 48hrs, 1-week or 1-month.

Patients self rated their pain about 50/100 on the VAS. Within 12 hours both groups had dropped to below 10 and at 24 hours approached zero. This speaks to the amazing healing properties of the cornea and made it nearly impossible to show a clinically significant difference between the two groups at 48 hours.

In addition, the study may have been unblinded. Tetracaine causes some local irritation and patients commented on the drops burning like the tetracaine drops used in the initial ED evaluation. A placebo drop which caused mild local irritation could have been used rather than saline. This potential unblinding may have caused the secondary outcome of patient-perceived overall effectiveness to be inflated. Researchers could have simply asked participants which group they thought they were assigned.

Finally, patient compliance with drops was not recorded. This makes it unclear whether drops were used as instructed.

This data agrees with a couple other smaller studies looking at acute corneal injuries:

  • Ting et al. Management of Ocular Trauma in Emergency (MOTE) Trial: A pilot randomized double-blinded trial comparing topical amethocaine with saline in the outpatient management of corneal trauma. J Emerg Trauma Shock, 2(1):10-14, Jan-April, 2009
  • Ball et al. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM 12(5):389, September 2010

Author’s conclusion compared to our conclusion: One small randomized control trial does not prove safety but it does help chip away at the myth that these drugs are toxic when used correctly.

The Bottom Line: Tetracaine appears safe for uncomplicated corneal abrasions and provides more effective pain relief than saline eye drops.

Dr. Louis Probst

Dr. Louis Probst

Consult Ophthalmology: Dr. Louis Probst from Michigan. He would evaluate the injury and be most concerned about infection. The next step would be to treat the patient symptomatically. This includes:

  • Antibiotic eye drops (4th generation fluroquinolone plus polytrim for gram positive coverage)
  • Bandage contact lens
  • Non-steroidal anti-inflammatory drugs (NSAID) eye drops

These patients would then traditionally be follow-up every 24 hours by ophthalmology until the corneal defect had healed.

Screen Shot 2014-07-11 at 11.26.10 PMCase Resolution: You offer the Marco Polo playing dad some 1% tetracaine drips to use as needed every two hours for the next 24 hours. The drops sting and burn when used but make it much easier to get to sleep that night. He is seen in the emergency department for follow-up in 48 hours. The pain is gone and the abrasion has completely healed.

Clinical Application: Topical anesthetics are better at patient perceived pain relief compared to oral pain medications and saline eye drops. Evidence is not robust, but indicates when topical anesthetics are used appropriately, and for a short duration of time (24 hours) there are no corneal complications.

What do I tell my patients? You have scratched your cornea. Here are some eye drops to help treat the pain. It is safe to use for 24 hours. Your vision is important so we have arranged to see you back in the emergency department in two days. Please come back earlier if you have increased pain, decreased vision or otherwise concerned.

For more on this topic, checkout REBEL EM, where Salim discusses:

  1. Historical case reports, case series, and animal studies (The dogma of topical anesthetics being unsafe for corneal abrasions)
  2. Other trials evaluating the safety and effectiveness of topical anesthetics
  3. My review of the current paper we discussed plus commentary article that was released shortly after this publication
  4. How your pharmacist can make a 1:10 dilution of topical anesthetics
  5. Take home message for safety of topical anesthetics

Keener Kontest: There was no winner from last week. I guess the Swedish Skeptic, Katrin Hruska, came up with a question that was just too hard.

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

BEEM Logo

Upcoming conferences:

  • QueBEEM Quebec City September 29th and 30th
  • EuroBEEM Prague  December 5th and 6th

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

 

SGEM#83: In Your Eyes (Topical Tetracaine for Corneal Abrasions)

Podcast Link: SGEM83
Date:  July 12th, 2014 

Rebel Skeptics: Dr. Salim Rezaie is an Assistant Professor in the Department of Emergency Medicine and Internal Medicine at the University of Texas at San Antonio. You may better know him from his website REBEL EM or twitter handle @srrezaie.

Case Scenario: 47 year old man is playing Marco Polo in the pool with his daughters. He is accidentally hit in the eye and sustains a uncomplicated corneal abrasion

Question: Is the use of topical 1.0% tetracaine for 24 hours safe and effective for the treatment of uncomplicated corneal abrasions?

Background: Corneal abrasions are very common presentations to the emergency department and very painful. We have all been warned that topical anesthetics to take home should not be given to patients with corneal injuries. The fear is that these drops could delay/decrease healing, prevent recognition of eye foreign bodies, cause keratitis or worsen corneal symptoms.

fact-or-fictionSome of this information comes from animal models or local anesthetic injected directly into the anterior chamber of the eye for cataract surgery:

  • Duffin RM, Olson RJ. Tetracaine toxicity. Ann Ophthalmol. 1984;16(9)836,838. 
  • Judge AJ, et al. Corneal endothelial toxicity of topical anesthesia. Ophthalmology. 1997;104(9):1373–1379.
  • Guzey M, et al. The effects of bupivacaine and lidocaine on the corneal endothelium when applied into the anterior chamber at the concentrations supplied commercially. Ophthalmologica. 2002;216(2):113–117.

Are the dangers of topical anesthetics for simple corneal abrasions fact or fiction?

Article: Waldman N et al.  Topical Tetracaine used for 24 Hours is Safe and Rated Highly Effective by Patients for the Treatment of apain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Acad Emerg Med 2014; 21: 374 – 382.

  • Population: Patients presenting to the ED of Southland Hospital in New Zealand with Corneal Abrasions (N = 116)
  • Intervention: Acetaminophen 500mg plus 1% tetracaine hydrochloride topical eye drops
  • Comparison: Acetaminophen 500mg plus placebo (saline eye drops)
  • Outcome:
    • Primary Outcome Safety: Repeat fluorescein/slit lamp ED examinations at 48 hours, 1-week, and 1-month telephone interviews for corneal complications
    • Secondary Outcomes Pain: 100-mm VAS pain scores recorded every 2 hours while awake for 48 hours and patient perceived overall effectiveness with a numeric rating scale (NRS) of 0 – 10.
  • Exclusions: Injury > 36hrs before presentation, < 18 years of age, previous eye surgery or cataracts, wear contact lenses, injury to both eyes, suffering from infectious or chemical conjunctivitis, grossly contaminated foreign bodies, suffering from an ocular infection, current herpes keratitis, allergy to tetracaine, injury requiring urgent ophthalmologic evaluation (i.e. penetrating eye injuries, large corneal abrasions, or injuries causing a disruption of vision), and unable to attend follow up at 48 hours

Authors Conclusions: ”Topical Tetracaine used for 24 hours is safe, and while there was no significant difference in patient VAS pain ratings over time, patient surveys on overall effectiveness showed that patients perceived tetracaine to be significantly more effective than saline.”

checklist-cartoonQuality Check List for Random Control Trials:

  1. The study population included or focused on those in the ED? Yes
    • Comment: These were all patients presenting to a regional ED in New Zealand
  2. The patients were adequately randomized? Yes 
    • They used numbered sealed envelopes to randomize patients
  3. The randomization process was concealed? Yes

    • Both the authors and the patients were blinded
  4. The patients were analyzed in the groups to which they were randomized? Yes 
    • Two arms 1% tetracaine vs. saline eye drops
  5. The study patients were recruited consecutively (i.e. no selection bias)? Yes 
    • Patient enrollment into the study could occur at any time during the day or night, 7 days a week and was dictated in part by staffing levels and demands on the department
  6. The patients in both groups were similar with respect to prognostic factors. Yes 
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure? 
    • Some patients commented on the fact that the drops they were using burned like the tetracaine used in the ED at their initial evaluation. This may have unblinded some physicians and some patients
  8. All groups were treated equally except for the intervention. Yes 
  9. Follow-up was complete (i.e. at least 80% for both groups). No 
    • Only 70% of patients had 48 hour follow-up
  10. All patient-important outcomes were considered. Yes
    • specifically pain relief and corneal complications
  11. The treatment effect was large enough and precise enough to be clinically significant. No
    • Twenty-three patients were removed from data analysis after 48 hour check up. This was due to retained rust rings, making the study underpowered to detect differences in corneal complications and pain scale evaluation.

Key Results:  

  • Primary:
    • 48 hours: No statistical difference in healing identified by fluorescein uptake between the two groups
      • 20 patients had persistent symptoms (10/46 tetracaine vs. 10/47 placebo)
    • 1 Week: Persistent symptoms in five patients (1 tetracaine and 4 placebo)
    • 1 Month: No complications reported by either group
  • Secondary:
    • No difference in 100mm VAS pain scores at an given time between the two groups
    • Patient perceived effectiveness at 1 week (0- not effective and 10- completely effective)
      • Statistically difference (7.7 for tetracaine vs. 3.8 for saline group)
Dr. Salim Rezaie

Dr. Salim Rezaie

Comments:  This was the largest randomized clinical trial to date (n=116) to evaluate the use of topical anesthetics for corneal abrasions. There was no significant difference in healing between the two groups. However, only 93 patients returned for the primary outcome of follow-up at 48 hours.

Another problem was the large number of patients with retained rust rings (13-tetracaine and 10-placebo). This was unanticipated and made it challenging to analyze the data.

The study was underpowered to detect a difference in efficacy between the two groups both in 100mm-VAS pain scale. This represents a common limitations to randomized control trials. They are powered for the primary outcome not for the secondary outcome. However, their goal was to look at safety and that did not show a difference at 48hrs, 1-week or 1-month.

Patients self rated their pain about 50/100 on the VAS. Within 12 hours both groups had dropped to below 10 and at 24 hours approached zero. This speaks to the amazing healing properties of the cornea and made it nearly impossible to show a clinically significant difference between the two groups at 48 hours.

In addition, the study may have been unblinded. Tetracaine causes some local irritation and patients commented on the drops burning like the tetracaine drops used in the initial ED evaluation. A placebo drop which caused mild local irritation could have been used rather than saline. This potential unblinding may have caused the secondary outcome of patient-perceived overall effectiveness to be inflated. Researchers could have simply asked participants which group they thought they were assigned.

Finally, patient compliance with drops was not recorded. This makes it unclear whether drops were used as instructed.

This data agrees with a couple other smaller studies looking at acute corneal injuries:

  • Ting et al. Management of Ocular Trauma in Emergency (MOTE) Trial: A pilot randomized double-blinded trial comparing topical amethocaine with saline in the outpatient management of corneal trauma. J Emerg Trauma Shock, 2(1):10-14, Jan-April, 2009
  • Ball et al. Dilute proparacaine for the management of acute corneal injuries in the emergency department. CJEM 12(5):389, September 2010

Author’s conclusion compared to our conclusion: One small randomized control trial does not prove safety but it does help chip away at the myth that these drugs are toxic when used correctly.

The Bottom Line: Tetracaine appears safe for uncomplicated corneal abrasions and provides more effective pain relief than saline eye drops.

Dr. Louis Probst

Dr. Louis Probst

Consult Ophthalmology: Dr. Louis Probst from Michigan. He would evaluate the injury and be most concerned about infection. The next step would be to treat the patient symptomatically. This includes:

  • Antibiotic eye drops (4th generation fluroquinolone plus polytrim for gram positive coverage)
  • Bandage contact lens
  • Non-steroidal anti-inflammatory drugs (NSAID) eye drops

These patients would then traditionally be follow-up every 24 hours by ophthalmology until the corneal defect had healed.

Screen Shot 2014-07-11 at 11.26.10 PMCase Resolution: You offer the Marco Polo playing dad some 1% tetracaine drips to use as needed every two hours for the next 24 hours. The drops sting and burn when used but make it much easier to get to sleep that night. He is seen in the emergency department for follow-up in 48 hours. The pain is gone and the abrasion has completely healed.

Clinical Application: Topical anesthetics are better at patient perceived pain relief compared to oral pain medications and saline eye drops. Evidence is not robust, but indicates when topical anesthetics are used appropriately, and for a short duration of time (24 hours) there are no corneal complications.

What do I tell my patients? You have scratched your cornea. Here are some eye drops to help treat the pain. It is safe to use for 24 hours. Your vision is important so we have arranged to see you back in the emergency department in two days. Please come back earlier if you have increased pain, decreased vision or otherwise concerned.

For more on this topic, checkout REBEL EM, where Salim discusses:

  1. Historical case reports, case series, and animal studies (The dogma of topical anesthetics being unsafe for corneal abrasions)
  2. Other trials evaluating the safety and effectiveness of topical anesthetics
  3. My review of the current paper we discussed plus commentary article that was released shortly after this publication
  4. How your pharmacist can make a 1:10 dilution of topical anesthetics
  5. Take home message for safety of topical anesthetics

Keener Kontest: There was no winner from last week. I guess the Swedish Skeptic, Katrin Hruska, came up with a question that was just too hard.

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

BEEM Logo

Upcoming conferences:

  • QueBEEM Quebec City September 29th and 30th
  • EuroBEEM Prague  December 5th and 6th

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

 

SGEM#82: Melt with You (Targeted Temperature Management)

Podcast Link: SGEM82
Date:  July 3rd, 2014 

Guest Swedish Skeptics: Katrin Hruska @Akutdok

Case Scenario:  A 72 year old man has witnessed arrest at the Goderich beach. By-standard CPR is started and he shocked out of ventricular fibrillation by emergency medical services but does not regain consciousness. We know from SGEM#54 that cooling in the field does not improve survival. His temperature on arrival to the emergency department is 36°C.

Question: Does cooling to a target temperature of 33°C improve survival to hospital discharge and neurological outcome in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause?

Background: Therapeutic hypothermia post cardiac arrest has received a great deal of attention over the last decade. Two randomized control trials showed that hypothermia post cardiac arrest resuscitation was neuroprotective. One trial (n=273) in NEJM 2002 used cooled air mattress to demonstrate good outcome at 6 months (55% vs. 39%). The smaller Australian study (n=77) also published in NEJM 2002 showed good neurologic outcome at time of hospital discharge (49% vs. 26%).

Screen Shot 2013-01-26 at 4.23.03 PM

Dr. David Newman has calculated the NNT=6 for mild therapeutic hypothermia for neuroprotection following cardiopulmonary resuscitation. The Cochrane Collaboration updated their review on hypothermia for neurporotection in adults after CPR in 2012. They concluded:

  • “Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.”

cartoon_ambulanceThe SGEM was skeptical after it covered the issue in Episode#21: Ice, Ice Baby. We looked at the paper by Bernard SA et al. called Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospital ventricular fibrillation cardiac arrest: a randomized controlled trial, Circulation. 2010;122:737-742. The question was whether pre-hospital therapeutic hypothermia improve patient outcomes after successful resuscitation? The study had 234 patients and used large volumes of ice-cold lactated Ringer’s. The primary outcome was about 50% of patients survived to functional hospital discharge and there was not benefit to cooling.

The SGEM covered the larger pre-hopsital cooling paper by Kim F et al. in JAMA earlier this year. The bottom line was: Scoop and run after cardiac arrest with no cooling required in the field.

Reference: Nielsen N et al. Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest. NEJM 2013

  • Population: 939 patients from 36 intensive care units (ICUs) in Europe and Australia with OHCA with more than 20 consecutive minutes of spontaneous circulation after resuscitation.
  • Intervention: Cooling to 36 degrees celsius for 36 hours, <37.5 for 72 hs post-arrest
  • Control: Active cooling to 33 degrees celsius
  • Outcome:
    • Primary: Mortality at the end of the trial.
    • Secondary: Mortality, Cerebral Performance Category (CPC) 3-5 or Modified Ranking (mRS) 4-6 at 180 days

Screen Shot 2014-07-06 at 9.27.23 PM

Authors’ Conclusions: In conclusion, our trial does not provide evidence that targeting a body temperature of 33°C confers any benefit for unconscious patients admitted to the hospital after out-of-hospital cardiac arrest, as compared with targeting a body temperature of 36°C.

checklist-cartoonQuality Check List:

  1. The study population included or focused on those in the ED. Unsure
    • Comment: These were all out of hospital cardiac arrests. The emergency department was not mentioned. Some countries such as Sweden patients bypass the emergency department and are admitted directly to the hospital. However, it is reasonable to believe that many patients were admitted through the emergency department.
  2. The patients were adequately randomized.  Yes
  3. The randomization process was concealed.  Yes
  4. The patients were analyzed in the groups to which they were randomized.  Yes
  5. The study patients were recruited consecutively (i.e. no selection bias). Yes
  6. The patients in both groups were similar with respect to prognostic factors. Yes
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. 
    • Health care professionals caring for the trial patients were aware of the intervention assignments because of inherent problems with blinding of body temperature. Physicians performing neurologic prognostication, assessors of neurologic follow-up and final outcome, study administrators, statisticians, and the authors were unaware of the intervention assignments and so were the patients and their families. Manuscript written before randomization code was broken.
  8. All groups were treated equally except for the intervention.  Yes
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes, 100%
  10. All patient-important outcomes were considered. Unsure
    • Little focus on disability. Modified Ranking Scale 0-3 slumped together
  11. The treatment effect was large enough and precise enough to be clinically significant.  No

Results: No difference in mortality. No difference in Cerebral Performance Category (CPC), modified Rankin Score (mRS) or mortality at 180 days.

Dr. Katrin Hruska

Dr. Katrin Hruska

Commentary: This is a well conducted multisite randomized controlled trial on targeted temperature management after out-of-hospital cardiac arrest. They excluded very few patients from the trial. The main reasons for exclusion:

  • Interval from return of spontaneous circulation to screening of >4 hours
  • Unwitnessed arrest with asystole as the initial rhythm
  • Suspected or know acute intracranial hemorrhage or stroke
  • Body temperature of <30°C

A strength of the study was the multiple sites where the trial was conducted and the various sizes of hospitals.

Another strong feature of this study was that temperature was managed in different ways depending on the site’s preferences. The different methods of cooling did not seem to influence the results. This makes the result applicable to different practice settings depending on local protocols.

There was a risk of bias because of the inherent difficulty of blinding the treating physician to the intervention, but this is unlikely to affect mortality.

beer-bubbles-copyThree were lots of bubbles in the FOAMed world as a result of the TTM trial. It is not necessary to go into all the details but you can read more about this issue by clicking on the links:

Comment on Author’s Conclusions: Agree with author’s conclusions.

Bottom Line: There is no difference between a targeted temperature of 33°C and 36°C for survival of out-of-hospital cardiac arrest.

Case Resolution: The 72 year old man with the out-of-hospital cardiac arrest who arrived at 36°C. He was actively cooled to maintain this temperature but was not cooled further to 33°C. You plan to check in on him in the intensive care unit on your next shift.

Clinical Application: I will start cooling patients to 36°C and admit them to the intensive care unit for further management based on our own local protocols.

What Do I Tell the Patient: I will tell the patient’s wife that her husband had a cardiac arrest. We were able to bring him back but he is still unconscious. We are going to cool him to improve his chances of survival and a good neurological outcome.

KEENER KONTEST: Last weeks winner was Dr. Neil Dattani from Toronto. He knew cocaine was the first local anesthetic isolated from a plant source?

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

Upcoming conferences:

  • QueBEEM Quebec City September 29th and 30th
  • EuroBEEM Prague  December 5th and 6th

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

SGEM#81: Sore Mouth (Lidocaine for Oral Ulcers)

Podcast Link: SGEM81
Date:  June 24th, 2014 

Guest Skeptics: Meghan Groth (@EMPharmGirl). Meghan is the emergency medicine pharmacy specialist at Fletcher Allen Health Care in Burlington, Vermont and an adjunct professor of pharmacy practice at the Albany College of Pharmacy and Health Sciences. Her professional interests include resuscitation and acute neurologic emergencies. In her free time, you can find her teaching Les Mills BodyPump classes at the local gym.

Case Scenario: Two year old comes to the ER with a rash on his hands and feet. It is associated with painful mouth ulcers. You diagnose the child with hand, foot and mouth disease. The parents are concerned about dehydration. You estimate the child to be mildly dehydrated. You know from SGEM#12 that ondansetron helps hydrate the child with vomiting but this is different.

Question: Does fluid intake improve when 2% viscous lidocaine is applied to oral ulcers?

Background: Children with infected mouth ulcers is a common emergency department presentation. Most of these can be easily diagnosed clinically. The cause is often viral infections like gingivostomatitis, ulcerative pharyngitis, herpangina and hand, foot and mouth disease.

Children usually present because of pain and decreased oral intact. Oligoanalgesia (poor pain management) is a big problem in emergency departments. Children represent a group that is less likely to receive adequate analgesia. (Brown et al, Selbst and Clark).

Goldman et al Pediatrics 2008 published a helpful article describing the degree of dehydration in children ranging from mild, moderate to severe.

Screen Shot 2012-11-15 at 4.45.16 PM

Dehydration can usually be treated effectively with oral rehydration. For more information on visit this site on Oral Rehydration Therapy. The Canadian Pediatric Society also has a algorithm for oral rehydration.

Article:Hooper et al. Topical lidocaine to improve oral intake in children with painful infectious mouth ulcers: a blinded, randomized, placebo-controlled trial. Ann Emerg Med 2014.

  • Population: Pediatric patients aged 6 months to 8 years (n=100) with the mouth ulcers (gingivostomatitis, ulcerative pharyngitis, herpangina or hand, foot and mouth disease) and decreased PO intake (parent/guardian “not drinking well” and <10ml/kg of body fluid in preceding 2 hours).
  • Intervention: A single oral dose of 2% lidocaine (weight based at 0.15 mL/kg), patients instructed to gargle and spit (if able) or swallow if not able to follow instructions
  • Comparison: Placebo arm administered a topical methylcellulose/cherry flavored solution in an identical fashion
  • Outcome: Amount of oral fluid ingested within 60 minutes after study drug administration (mL/kg)
    • Excluded: Hypersensitivity to lidocaine or other amide local anesthetics. Diseases in which elevated levels of lidocaine may be dangerous (epilepsy, impaired cardiac conduction, bradycardia, or impaired hepatic or renal function). Severe dehydration or toxic needing immediate resuscitation. Patients with >2 episodes of vomiting before ED arrival, dental disease, mouth trauma, or malignancy. Patients on cardiac or other drugs with possible interactions with lidocaine. Patients who already had >1 dose of topical anesthetic for the same illness. Pre-existing upper airway obstruction or swallowing difficulties, If they had received analgesia <1hr before enrollment. Non-English speaking.

Authors Conclusions: Viscous lidocaine is not superior to a flavored gel placebo in improving oral intake in otherwise healthy children with painful infectious mouth ulcers. It appears that staff coaching and possibly the coating effect of oral topical agents alone can increase oral intake.”

checklist-cartoonQuality Check List for Systematic Reviews:

  1. The study population included or focused on those in the ED. Yes
    • Comment: These were all pediatric ED patients presenting to the Royal Children;s Hospital in Melbourne, Australia
  2. The patients were adequately randomized. Yes 
    • Block randomization with block sizes of 2 and 4
  3. The randomization process was concealed. Unsure?
    • Numbered bottles by pharmacist independent of the study.
    • Patient given two bottles (A and B)
      • A- contained study drug or placebo
      • B- contained the alternative mixture (lidocaine or placebo)
    • After 60min the treating clinician could give the second bottle if clinically indicated. So all participants int he study had access to lidocaine.
  4. The patients were analyzed in the groups to which they were randomized. Yes 
  5. The study patients were recruited consecutively (i.e. no selection bias). No 
    • Convenience sample when research assistants or investigators were in the ED
  6. The patients in both groups were similar with respect to prognostic factors. Unsure 
  7. All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Unsure? 
  8. All groups were treated equally except for the intervention. Yes 
  9. Follow-up was complete (i.e. at least 80% for both groups). Yes 
    • One patient left the ED before completion of the study
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. No

Key Results:  No difference in the amount of fluid intake at 60 minutes between groups. Lidocaine group 8.5 mL/kg (IQR 4.1-13.8 mL/kg) vs. placebo group 9.3 mL/kg (IQR 3.1-15.2 mL/kg). Difference in medians 0.8 mL/kg (95% CI -2.52 to 3.26 mL/kg)

  • Secondary outcomes: Similar oral intake at multiple time points measured, similar utility of adjunct analgesics. 40% of patients (n=20) in each group required “rescue” treatment. Bottle B 14% (n=7) in lidocaine group, 6% (n=3) in placebo group required admission for fluid administration via either NG or IV route. Longer term outcomes detailed in methods (adverse events, ED LOS) not reported in results section.
Meghan Groth

Meghan Groth

Comments: This is the first study to evaluate the efficacy of topical lidocaine for painful mouth ulcers in children. The randomization was adequate, but patients were enrolled as a convenience sample as research investigators were only present in the ED about 50 hours per week. Additionally, 40% of patients in each arm received the other “treatment” at 60 minutes.

There is concern about the randomization being concealed. The placebo may have looked, tasted and smelled like the lidocaine viscus but it would not have caused oral numbness. If the child starts talking funny and drooling parents/guardians may have figured it out which group their child was in. This information could have been passed along to the research staff even unintentionally.

If there was unblinding the bias would have probably been towards lidocaine treatment. Such that there was no difference between groups this potential unblinding actually strengthens the conclusion to accept the null hypothesis.

One way researchers could have tested for unblinding would have been to ask the parents/guardians and the researchers which group they felt the child was assigned. If they were able to tell more than random chance than randomization was not concealed.

Another issue with this paper was the original intent to report the primary outcome in terms of mean fluid intake at 60 minutes, with the comparison between groups as mean difference. An interim analysis revealed a skewed data set, thus the primary outcome was ultimately reported as a median with an interquartile range instead.

nerd glassesTalk Nerdy to Me? Mean and Median can both be used to describe the “centre” of a dataset. Which one to use depends on the symmetry of the dataset being measured.

A mean is simply the average. You add all the data points up and divide by the number of data points. However, if your data is skewed this can represent a problem. The mean can be highly influences by one or two outliers. It is only representative of the centre if the distribution of the data is symmetric. The mean can be affected by any single change to the data

As an example take the following dataset: 1, 5, 5, 5, 5, 5, 5, 5, 5, 5, 5, 1000

Mean is 1046/11 = 95.1

The median denotes the value lying at the midpoint of the dataset. It is is not influenced by outlying measurements. So for asymmetrical data or skewed data the median might better represent the centre of the data. The median does not change with any single data point change. In the example given the median would be 5. Which do you think better represents the centre of the data?

STOP THE NERDY STUFF

Both groups may not have been equal with prognostic factors. More patients in the placebo group received topical analgesics in the 24 hours prior to being enrolled in the study. The authors did not report a p value, and did not comment on whether or not this was a significant difference. However, it has the potential to introduce bias as patients in the placebo group may have been more “comfortable” at baseline and thus more likely to increase their oral intake during the study period, a difference which would have been attributed to the intervention.

The authors comment that it may have been coaching from the medical staff and/or simply the coating of the ulcers with a liquid preparation that encouraged an increase in oral intake in this study. I think this is a reasonable conclusion. They did however, only study topical lidocaine by itself.

In US EDs, a “magic mouthwash” preparation is commonly prescribed for painful mouth ulcers, with includes diphenhydramine and an antacid along with lidocaine. Many patients in this cohort (50% in the lidocaine group, 44% in the placebo group) required adjunct analgesia; this appears to be a helpful treatment in this condition.

Although adverse events were not reported in this study, there have been serious adverse events associated with oral lidocaine use (see poison center data from Curtis LA, Dolan TS, Seibert HE. Are one or two dangerous? Lidocaine and topical anesthetic exposures in children. J Emerg Med 2009;37:32-39), especially in young children that may not be able to follow instructions to “spit” after gargling.

fda-warningBlack Box Warning FDA June 2014: “oral viscous lidocaine 2 percent solution should not be used to treat infants and children with teething pain.”

Author’s conclusion compared to our conclusion: This study calls into question the routine utility of topical lidocaine for painful mouth ulcers. Even though there are a few methodological flaws to the study, it seems as though the conclusion is reasonable.

The Bottom Line: Viscous lidocaine is not superior to a placebo gel in improving oral intake in children with painful infectious mouth ulcers.

Case Resolution: Educate the parents about the diagnosis of hand, foot and mouth disease. Reassure them it is a common viral illness in children < 5 years of age. It usually is mild in nature with a low grade fever and rash lasting about 1 week. There is no specific treatment but taking over the counter medication for pain and fever may help. Encourage your son to drink liquids is important to prevent dehydrated.

Clinical Application: Given the questionable efficacy over placebo demonstrated in this study, along with the potential to cause harm, it may be time to rethink the use of topical lidocaine for painful mouth ulcers in this population.

What do I tell my patients? There appears to be evidence that topical lidocaine is not better than a placebo for increasing oral intake (and preventing dehydration) in children with painful mouth ulcers. Supportive care with analgesic therapy, along with encouragement by parents and/or ED staff are useful adjuncts.

Keener Kontest: Last weeks winner was Femke Friesema from the Netherlands. Fremke knew the couple who discovered tranexamic acid was Shosuke and Utako Okamoto (husband and wife).

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

BEEM LogoUpcoming conferences:

  • QueBEEM Quebec City September 29th and 30th
  • EuroBEEM Prague  December 5th and 6th

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

 

SGEM#80: CRASH-2 (Classic Paper)

Podcast Link: SGEM80
Date:  June 12th, 2014 

Guest Skeptics: Dr. Anand Swaninathan or Swami as his is better known. He is an assistant program director at NYU/Bellevue Hospital in the Department of Emergency Medicine.

Case Scenario: You’re working in a busy urban trauma center when EMS slams through the doors with a 22-year-old man who was in a major MVC. The patient has significant abdominal and pelvic trauma and is hypotensive and tachycardic. You mobilize your resources and within minutes, the patient is intubated, his pelvis is placed in a binder and blood is being infused through a peripheral intravenous line. Your trauma colleagues are waiting to take the patient to the operating room for an exploratory laparotomy based on your positive FAST exam. Before they leave, one of you bright residents asks if you should start Tranexamic acid on the patient.

Question: Does tranexamic acid (TXA) reduce mortality in patients who have sustained major trauma?

Dr. Anand Swaminathan

Dr. Anand Swaminathan

Background: Injuries are a major cause of death worldwide. Millions of people die every year from traffic injuries. In fact, they are the 9th leading cause of death around the world. Additionally, another 1.5 million people die every year from interpersonal violence. Hemorrhage accounts for about 1/3 of all trauma deaths and as such, it should be our goal to find treatments to decrease death from hemorrhage.

Our bodies have a finely tuned system that allows blood to flow freely and not clot too easily while also allowing the body to form clots when needed. This balance is upset in trauma by loss of blood and factors, acidosis, hypothermia and the inflammatory cascade. Hyperfibrinolysis often occurs making hemostasis extremely challenging.

TXA is a synthetic derivative of lysine that inhibits fibrinolysis and thus stabilizing clots that are formed. TXA has been widely used in elective surgical cases and has shown decreased need for blood transfusion and reduction in mortality. It makes sense, then to apply TXA to the trauma patient to see if we can get similar effects.

five+fingersFive (my favourite number) Reasons for Picking CRASH-2:

  1. Instant classic that everyone providing trauma care should know despite being published only 4 years ago.
  2. It does not involve a fancy new expensive drug (cheap).
  3. It also affects an important patient oriented outcomes like…saving a life.
  4. It is very easy to give (loading dose of 1 g of infused over 10 minutes, followed by an IV infusion of 1 g over 8 h.
  5. It is something I can give in the small/rural hospital setting

Article: Effects of tanexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised placebo-controlled trial. Lancet 2010; 376: 23-32. PMID: 20554319

  • Population: Adult trauma patients within 8-hours of injury with or at risk of significant bleeding, from 274 hospitals in 40 countries. N=20, 211). Significant haemorrhage was defined as systolic blood pressure < 90mm Hg or heart rate > 110 beats per minute or both.
  • Intervention: Loading dose of 1 g of tranexamic acid infused over 10 minutes, followed by an intravenous infusion of 1 g over 8 h (n=10,060).
  • Control: Placebo (0.9% saline) (n=10,067).
  • Outcome:
    • Primary: Death in hospital within 4 weeks of injury.
    • Secondary: Receipt of a blood-products transfusion, number of units of blood products transfused, surgical intervention, occurrence of thromboembolic episodes (stroke, myocardial infarction, pulmonary embolism, clinical evidence of DVT).
  • Exclusion criteria: Patients for whom the responsible doctor considered that there was a clear indication for tranexamic acid were not randomly assigned. Similarly, patients for whom there was considered to be a clear contraindication to tranexamic acid treatment were not randomly assigned.

Authors Conclusions: “TXA safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients.”

checklist-cartoonQuality Check List for Systematic Reviews:

  1. Were these ED patients? Yes
  2. Were the patients adequately randomized? Yes.
    • A computer random number generator was used to allocate blocks
  3. Was the randomization process was concealed? Yes
  4. Were the patients were analyzed in the groups to which they were randomized? Yes, they were.
  5. Were patients recruited consecutively? Yes
    • With the exception of the exclusions we already mentioned.
  6. Were patients in both groups were similar with respect to prognostic factors?  Yes.
    • You can see this in table 1, so why is this important?
  7. Were participants unaware of group allocation? Yes.
    • The placebo was administered just like the TXA.
  8. Were groups treated equally except for the intervention? Yes
  9. Was follow-up was complete? No but it was excellent.
    • A total of 80 patients out of over 20,000 were lost to follow up which is amazing.
  10. Were all patient-important outcomes were considered? Yes
    • The primary outcome is the most important patient centered outcome . . . death.
  11. Was the treatment effect large enough and precise enough to be clinically significant? Yes

Key Results:  All cause mortality was reduced from 16% in the placebo group to 14.5% in the TXA group (RR 0.91, 95% CI 0.85-0.97). This was and absolute risk reduction of 1.5% and was statistically significant. The calculated NNT was 68 (95% CI 0-206) to prevent one death.

Screen Shot 2014-06-05 at 9.28.30 AM

There was no significant difference between any of the secondary outcomes:

  • Receipt of a blood-products transfusion
  • Number of units of blood products transfused
  • Surgical intervention
  • Occurrence of thromboembolic episodes (stroke, myocardial infarction, pulmonary embolism, clinical evidence of DVT)

Tranexamic acid significantly benefited the subset with systolic blood pressure <75mmHg (Fig 3, RR 0.87; 95% CI 0.76- 0.99).

Comments: This is a very pragmatic real world study which includes trauma patients from 247 hospitals in 40 countries. We do not know the breakdown of which patients were seen in various hospital settings, which may make it difficult to establish if these results can be applied to our patients. However, with such large numbers it is likely that the randomization process would help ensure generalizability.

It is refreshing to see a well conducted large clinical trial that looks at an inexpensive drug and measures meaningful outcomes rather than some manufactured combined endpoint that gives a positive result for a new expensive me too drug.

The trials of the mega expensive Factor VIIa did not work in these sick patients and had many concerning adverse effects. Although the mechanism of action of tranexamic acid in bleeding trauma patients remains unexplained, this large trial offers promise for an affordable therapeutic alternative to reduce post-traumatic bleeding and deaths.

The Bottom Line: The use of tranexamic acid in the trauma patient with significant bleeding reduces mortality by 1.5% without increasing thromboembolic events. TXA is a safe and effective treatment in patients with hemorrhagic shock from trauma in reducing mortality. It is an inexpensive therapy, which should be included in the care of these critically injured patients.

Case Resolution: Based on your knowledge of the CRASH2 study, you decide to begin TXA treatment. You give 1 gram of TXA over 10 minutes and hang an infusion of 1 gram over the next 8 hours. The patient goes for an Ex-lap where he’s found to have a grade 5 splenic laceration and a grade 3 liver laceration. The patient also has an angio of the pelvis and has embolization to some bleeding veins in the pelvis. His postoperative course is rocky but he is discharged to rehabilitation 3 weeks later.

Clinical ApplicationIf it hasn’t changed what you do, it should. TXA is an inexpensive drug that is found in most hospitals that have operating rooms since it has been used in this setting for years.

This study did not find an increased rate of clinically significant clotting. TXA should be administered to patients with severe trauma. Additionally, CRASH-2 opened the doors on the use of TXA in bleeding.

We have an article showing great efficacy for epistaxis, there’s a study going on now for the use in post-partum hemorrhage. I’ve used it for intraoral bleeding in patients on agents like clopidogrel and Coumadin and in patients with massive GI bleeding. The indications for this drug continue to expand.

What do I tell patients: You have had serious trauma with significant bleeding. We are going to give you a drug that should help control the bleeding and improve your chances of survival.

Keener Kontest: Last weeks winner was Benjamin Flam from Sweden.  Ben knew that the deaf, dumb and blind kid sure played a mean pinball. 

If you want to play the Keener Kontest this week then listen to the podcast for the question. Email me your answer at TheSGEM@gmail.com with “keener” in the subject line. The first person to correctly answer the question will receive a cool skeptical prize.

Remember to be skeptical of anything you learn,

even if you heard it on the Skeptics’ Guide to Emergency Medicine.

 

I Am Your Father…

Happy Father’s Day to all the SGEM listeners. I hope you have time to enjoy your family and spend time with your children and/or your father. Here are some classic fathers from the movies.