SGEM#87: Let Your Back Bone Slide (Paracetamol for Low-Back Pain)

Podcast Link: SGEM87
Date:  September 17th, 2014 

Guest Skeptics: Dr. Pal Ager-Wick is from Norway. Consultant at Legevakten in Drammen, which is a GP run ED handling most things except major trauma. Keen interest in everything evidence based especially ultrasound. Pal is bringing Matt and Mike from the Ultrasound podcast to Norway.

Case Scenario: 35 year old man presents to ED with mechanical back pain after doing some heavy lifting on the weekend. He has not “red flags”.

Question: Does paracetamol improve time to recovery from pain compared to placebo in patients with low-back pain?

Background: The leading cause of disability worldwide is low-back pain. Guidelines recommend paracetamol (acetaminophen) as the first-line agent. There have been no randomized control trials comparing paracetamol vs. placebo for low-back pain.

rred-flags

1) Cancer Related Red Flags with Low Back Pain

  • History of cancer
  • Unexplained weight loss >10 kg within 6 months
  • Age over 50 years or under 18 years old
  • Failure to improve with therapy
  • Pain persists for more than 4 to 6 weeks
  • Night pain or pain at rest

2) Infection Related Red Flags with Low Back Pain

  • Persistent fever
  • History of intravenous drug abuse
  • Severe Pain
  • Lumbar spine surgery within the last year
  • Recent bacterial infection
  • Immunocompromised states

3) Cauda Equina Syndrome Related Red Flags with Low Back Pain

  • Urinary Incontinence or retention
  • Saddle anesthesia
  • Anal sphincter tone decreased or Fecal Incontinence
  • Bilateral lower extremity weakness or numbness
  • Progressive neurologic deficit

4) Significant Herniated Nucleus Pulposus

  • Major Muscle Weakness (strength 3 of 5 or less)
  • Foot drop

5) Vertebral Fracture Related Red Flags with Low Back Pain

  • Prolonged use of Corticosteroids
  • Age greater than 70 years
  • History of Osteoporosis
  • Mild trauma over age 50 years (or with Osteoporosis)
  • Recent significant trauma at any age

6)  Abdominal Aortic Aneurysm Red Flags with Low Back Pain

  • Abdominal pulsating mass
  • Atherosclerotic vascular disease
  • Pain at rest or nocturnal pain
  • Age greater than 60 years

Article: Williams CW et al. Efficacy of paracetamol for acute low-back pain:
a double-blind, randomized controlled trial. Lancet Published online July 24, 2014

  • Population: 1,652 patients from Australia and New Zealand
    • Inclusion: adults who sought care for low-back pain directly or in response to a community advertisement. New episode with pain between 12th rib and buttock. Shorter than 6 weeks duration with the month prior having no pain. No leg pain. Pain had to be of at least moderate intensity (measured by a evaluation tool)
    • Exclusions: Suspected serious spinal pathology, current use of full, regular does of analgesics, spinal surgery in last 6 months, contraindications to paracetamol, psychotropic drugs, pregnancy or planned to get pregnant.
  • Intervention: Paracetamol as needed and paracetamol as regimen
  • Comparison: Placebo
  • Outcome:
    • Primary outcome was time to pain free (VAS 0 or 1) maintained for 7 days
    • Secondary outcomes were pain intensity, disability, function, global rating of symptom change, sleep quality, and quality of life. Process measures consisted of adherence to drug (daily and at 4 weeks); concomitant treatment use and work absenteeism (at 4 and 12 weeks); adverse events (at 1, 2, 4, and 12 weeks); and treatment satisfaction and patient masking (at 12 weeks).

Authors Conclusions: Our findings suggest that regular or as-needed dosing with paracetamol does not affect recovery time compared with placebo in low-back pain, and question the universal endorsement of paracetamol in this patient group.

checklist-cartoonQuality Check List for Random Control Trials:

  1. The study population included or focused on those in the ED? NO 
    • 235 primary care clinicians (181 general practitioners, 50 pharmacists, and four physiotherapists) across Sydney, Australia, screened consecutive patients who sought care for low-back pain directly or in response to a community advertisement
  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? YES
  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
  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:

  • 550 regular paracetamol group
  • 549 to the as-needed paracetamol group
  • 553 to the placebo group

Was there a difference in their primary outcome of time to recovery from low-back pain? Just to remind everyone that was defined as self-reporting 0-1 on a pain VAS (pain free) for 7 days.

There was no difference in median time to recovery between the three groups. Regular 17 days (95%CI 14-19), As-needed 17 days (95% CI 15-20) and placebo 16 days (95% CI 14-20).

Ok, so there was not a difference in their primary outcome. It took a median time of between two and three weeks for all groups to be “pain free” for their low-back pain.

They also expressed this as a hazard ratio (HR):

  • Regular vs. Placebo HR 0.99 (95%CI; 0.87-1.14)
  • As-Needed vs. Placebo HR 1.05 (95% CI 0.92-1.19)
  • Regular vs. As-Needed HR 1.05 (95% CI; 0.92-1.20)

What about secondary outcomes? They looked at pain intensity, disability, function, global rating of symptom change, sleep quality, and quality of life, adherence to drug, concomitant treatment use and work absenteeism, adverse events, treatment satisfaction and patient masking. Surely there must have been some differences in these parameters?

Short answer is NO. Table 3 in the manuscript details the change in secondary outcomes. They did longitudinal mixed models and did not demonstrate any differences between groups for any of the secondary outcomes.

Pal

Pal Ager-Wick

Commentary: This is a large and well designed study which aims to see if paracetamol is an efficacious treatment for uncomplicated lower back pain with no red flags. It is important to note that the time to self reported VAS 0-1 for one week was the primary outcomes. Both as needed and a regular dosing of paracetamol does not seem to make for a more speedy recovery.

It was a very well done study but I have some concerns that 1/3 of the patients approached declined to participate. There are also issues with external validity to the ED setting. Are people who mainly present to the General Practitioners office different from those that present to the ED in Australia and New Zealand?

In addition, how is low-back pain perceived in Australia and New Zealand? There can be differences perceptions, approaches, management between counties when it comes to various conditions. It would be interesting hear from someone down under. If you are a SGEM listener from Australia or New Zealand send me an email (TheSGEM@Gmail.com) I would love to hear and share your thougths.

Naproxen was used as a rescue medication, and as this study was industry sponsored this study might later be used as support for naproxen as standard for lower back pain.

So you are not just a skeptic but you are also a cynic. But the drug company that sponsored this trial makes paracetamol so you would think the bias would be towards finding an effect?

Anybody who had read Ben Goldacre’s book Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients would become cynical towards the pharmaceutical industry.

I think the lack of effect says more about the complex nature of low back pain in our society than the treatment. When there are multiple modalities all claiming to have great effect for the same condition I am skeptical that anything really works well (medical, manipulative, non-science based, etc).

I would interpret the data saying the natural history of acute low back pain with no underlying serious pathology is a self-limiting condition. We should not expect acetaminophen to effect time to recovery in this type of situation.

There is a strong placebo effect involved in the treatment of low back pain. If the placebo effect is large and the active treatment effect is small it may be hard to distinguish the signal (treatment) from the noise (placebo). Patients who believe in the treatment modality will more likely get benefit. So I think when it comes to treating non-serious low back pain, it all depends…

Comment on authors conclusion compared to our conclusion: Agree with their conclusions based on the data presented and encourage being skeptical of the universal endorsement of paracetamol for these types of patients.

Bottom Line: It appears that paracetamol does not improve time to recovery compared to placebo for out-patients with low-back pain.

Clinical Application: This is just one randomized clinical trial looking into the issue and is not strong enough evidence for me to abandon recommending this treatment modality. I would like to see the study replicated in my practice environment. Specifically, a study looking at consecutive patients presenting to the emergency department with low-back pain.

What do I tell my patient? You appear to have a mechanical injury to your low-back. There are no “red flags” to suggest anything more serious is going on right now. The natural history of this condition is for it to resolve with or without treatment. Has anything worked well for you in the past? Different treatments have different potential benefits and harms. Taking paracetamol has not been shown to speed up how fast you get better.  Most people get better within a few weeks. You should try to stay active and see your primary care doctor in a couple of weeks if the pain is not resolving. Please return to the emergency department if your pain is getting worse, you develop any of those red flags we discussed or are otherwise concerned.

Keener Kontest: Last weeks winner was Loice Swisher from Philadelphia. They knew the name of the ECG manifestation of pericarditis named after Dave Spodick? Spodick’s Sign is downward sloping of the TP segment is suggestive of pericarditis and reported to occur in as much as 80% of the patients.  It can be essentially the entire QRST segment and lead II has been reported to be usually the best lead to see this in.

Listen to the podcast to hear this weeks keener question. If you know the answer send an email to 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

Remember to be skeptical of anything you learn,

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

 

SGEM#86: Achy Breaky Heart (Colchicine for Acute Pericarditis)

Podcast Link: SGEM86
Date:  August 26th, 2014 

Guest Skeptics: Dr. Chris Bond. Chris is a clinical lecturer and emergency physician at the University of Calgary, #FOAM blogger, dogma basher, wine and food supergeek. Chris has a blog called SOCMOB, is part of the REBEL-EM Alliance and did a blog entry on colchicine for pericarditis.

Case Scenario: 33 year old woman presents to ED with sharp RSCP which is pleuritic in nature. Well’s low and PERC negative. ECG consistent with acute pericarditis. Other lab investigations normal.

Question: Is colchicine more effective in combination than standard anti-inflammatory therapy for acute pericarditis, than standard anti-inflammatory therapy alone?

Background: Pericarditis is inflammation of the pericardium, most often from an infectious or idiopathic cause.  There are also other less common etiologies like neoplastic, autoimmune, drugs, trauma and radiation.

The classic history is positional, pleuritic chest pain radiating to the trapezius muscles.  The pain is worsened by lying flat and relieved sitting forward.  Other historical clues would be concurrent or recent infectious symptoms, eg. low grade fever, cough, general weakness.

On exam there are two important diagnostic findings: a pericardial friction rub, and a pericardial effusion on bedside U/S.Screen Shot 2014-08-28 at 11.29.32 AM

For investigations, the ECG is the diagnostic test of choice, which should show widespread ST elevation, and PR depression inferiorly and PR elevation in aVR.  However, this is a very simplified description of the pericarditis ECG, and I would highly recommend listeners check out Amal Mattu’s pericarditis EKG videos.

For blood tests, the WBC and CRP are insensitive and non-specific.  The troponin is used to look for myocardial involvement (myopericarditis), however, with the new high-sensitivity troponins, we may be calling myopericarditis more in the future.Screen Shot 2014-08-28 at 11.30.29 AM

To summarize, there are generally 4 consensus diagnostic criteria:

  1. Classic Chest Pain
  2. Friction Rub
  3. Effusion on Ultrasound
  4. ECG Changes

Colchicine is a plant derived alkaloid that functions as a microtubule inhibitor.  It comes from the autumn crocus or meadow saffron plant.  It is one of the oldest anti-inflammatories and has been used to treat rheumatic diseases for about 2500 years.  Traditional uses include treatment of familial Mediterranean fever, Behcet’s disease and gout.

Unfortunately, colchicine also has a pretty narrow therapeutic window, so you can imagine that there was quite a bit of colchicine toxicity back in the day.

For some good information as background material check out Controversial Issues in the Management of Pericardial Disease. Imazio et al Circulation 2010;121:916-928

Article: Imazio, et al. A Randomized Trial of Colchicine for Acute Pericarditis. NEJM 2013;369:1522-8. PubMed ID: 23992557

  • Population: 240 adult patients were enrolled from from five general hospitals in Northern Italy. All were diagnosed with a first episode of acute pericarditis. This was defined as at least two of the following; typical chest pain (pleuritic, improved sitting up and forward), pericardial friction rub, ST elevation or PR depression, new or worsening pericardial effusion.
  • Intervention: Colchicine (0.5 – 1.0 mg) daily for 3 months in conjunction with conventional anti-inflammatories.
  • Comparison:
    • ASA 800 mg or ibuprofen 600 mg every 8 hours for 7 to 10 days, followed by a taper for 4 weeks.
    • Prednisone (0.2-0.5 mg/kg) daily was given to patients with contraindications to aspirin therapy (allergy, peptic ulcer disease, anticoagulant use i.e patient’s with high risk of bleeding).
    • All patients in both groups received gastroduodenal prophylaxis with proton-pump inhibitors.
  • Outcome:
    • Primary Outcome:  Incessant or recurrent pericarditis.  Recurrent pericarditis was defined by symptom-free interval of 6 weeks or longer after the initial episode of pericarditis.  Recurrence was documented by recurrent pain and one or more of the following signs:  pericardial friction rub; ECG changes; pericardial effusion on echocardiography; or elevation in WBC or ESR or C-reactive protein.
    • Secondary Outcome: Symptom persistence at 72 hours, remission within 1 week, number of recurrences, the time to first recurrence, disease-related hospitalization, cardiac tamponade, and constrictive pericarditis.
  • Exclusions:TB, neoplastic, or purulent pericarditis; severe liver disease or current aminotransferase levels >1.5x upper limit of normal; serum creatinine >2.5 mg/dL; skeletal myopathy or serum creatinine kinase level above the upper limit of the normal range; blood dyscrasia; inflammatory bowel disease; hypersensitivity to colchicines or other contraindication to its use; current treatment with colchicines; life expectancy of 18 months or less; pregnant or lactating women. Also patients with evidence of myopericarditis, as indicated by an elevation in the serum troponin level.

Authors Conclusions: The use of colchicine in addition to standard anti-inflammatory therapy with GI prophylaxis in the treatment of acute pericarditis reduced the rate of refractory or recurrent episodes and increased the time to recurrence when compared to placebo.

checklist-cartoonQuality Check List for Random Control Trials:

  1. The study population included or focused on those in the ED? Unsure

    • Comment: Comment: Patients were recruited consecutively through 5 major hospitals but it was not clear how they presented (through the ED, clinic, ward). There were many exclusion criteria.
  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. Yes 
  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
  10. All patient-important outcomes were considered. Yes
  11. The treatment effect was large enough and precise enough to be clinically significant. Yes

Pericarditis NEJM curve Key Results: Based upon the data presented the NNT for the primary outcome to prevent the one case of recurrent or incessant pericarditis was 4.8 (95% CI 3-11). Figure2 in the manuscript showed the Kaplan-Meier Survival Curves for freedom from incessant or recurrent pericarditis.

nerd glasses

Talk Nerdy To Me

 

 

 

Kaplan-Meier survival curve is the probability of surviving in a given length of time while considering small time intervals. It is a standard way of expressing the number of subjects living for a certain amount of time after treatment from clinical trials.

Screen Shot 2014-08-28 at 11.32.11 AM

  • Secondary Outcomes:
    • Symptom persistance 72hrs (ARR 20.8%, NNT=5)
    • Recurrence frequency (ARR 31%, NNT=3)
    • Hospitalizations (ARR 9.2%, NNT=11)
    • Remission 1 week (ARR 26.7%, NNT=4)
    • Prolonged time to first recurrence (24.7 weeks vs. 17.7 weeks)
Dr. Chris Bond

Dr. Chris Bond

Comments: This was a well done RCT with excellent adherence to drug regimens (95%) and no losses to follow-up. The effects of colchicine was seen early and the benefits were sustained out to 18 months. Benefits were seen both in the primary and secondary outcomes.

The authors reported a NNT of 4 but recomputed the NNT is 4.8 with 95% CI 3-11, so actual applied NNT is 5.

This paper was funded by the pharmaceutical industry, as disclosed via a non-influence statement in the article.

As with many RCT the study was powered to show benefit but underpowered to detect rare adverse effects.

The main side effects in both groups were gastrointestinal (GI) disturbances, and were statistically insignificant between groups (9.2% in the colchicine group, compared to 8.3% in the placebo group, P=0.67). It is possible the side effects were caused by the standard therapies (ASA, ibuprofen, corticosteroids) all despite prophylactic GI protection with proton pump inhibitor.

The Bottom Line: Adding colchicine to usual anti-inflammatory management with GI prophylaxis prevents recurrence or refractory pericarditis symptoms with a NNT of 5. The most common side effect being diarrhea. Strict exclusion criteria limits application to uncomplicated pericarditis without systemic manifestations or evidence of elevated cardiac biomarkers (including non-specific troponitis).

Case Resolution: This 33year old woman diagnosed with pericarditis was given a prescription for ibuprofen 600mg TID for 7 days followed by a tapering dose over 1 month, colchicine 0.5mg daily for three months and proton pump inhibitor for 3 months. She was also referred to cardiology for on-going follow-up.

Clinical Application: Colchicine (0.5-1.0mg) daily for three months in conjunction with conventional anti-inflammatories and GI prophylaxis can be used for acute non-suppurative pericarditis to prevent recurrence or refractory symptoms.

What do I tell patients: You have inflammation around your heart called pericarditis. Anti-infammatory drugs like ibuprofen and ASA can help treat your symptoms. An additional medicine called colchicine has been shown to prevent prolonged symptoms. Colchicine has also been shown to prevent pericarditis from happening again. These two type of medications can be hard on the stomach so we are going to give you something to protect your gut. The most common side effect to these effective pericarditis treatments is diarrhea.

Keener Kontest: Marcus Prescott knew that Sussman and Fitch published the first study on thrombolysis in stroke in 1958. Thrombolysis with fibrinolysin in cerebral arterial occlusion. JAMA. 1958 Aug 2;167(14):1705–1709.

Listen to the podcast to hear this weeks keener question. If you know the answer send an email to 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#85: Won’t Get Fooled Again (tPA for CVA)

Podcast Link: SGEM85
Date:  September 5th, 2014 

Guest Skeptics: Dr. Ryan Radecki is an Assistant Professor of Emergency Medicine – The University of Texas Medical School at Houston. He has an amazing blog called Emergency Medicine Literature of Note. It is billed as musings on publications and studies relevant to EM & otherwise. You can follow Ryan on Twitter @EMLitofNote.

This is the first episode of season#3 of the Skeptics’ Guide to Emergency Medicine. The goal continues to be to cut the knowledge translation window from 10 years down to 1 year. The SGEM does this by using social media to provide you with high quality, clinically relevant, critically appraised, evidence based information. It is all part of the Free Open Access to Meducation movement. FOAM – Medical education for anyone, anywhere, anytime.

Fonzie Jumps the Shark

I was warned by Jeremy Faust and Lauren Westafer of FOAMCast that season threes can be dangerous. Let me assure the SGEM listeners there will be no jumping of the shark.

We will continue to provide a weekly podcast critically reviewing a recent publication. The validated and reliable Best Evidence in Emergency Medicine (BEEM) appraisal tool will be used to review the manuscripts. Guest skeptics will be invited on to help and give a variety of opinions. There will be more SGEM Classics with the Swami on historic, must know emergency medicine papers. Cheesy theme music mostly from the 1980’s will be selected to help with the edumatainment factor. And of course, cool skeptical prizes will be awarded to the keenest listener who answers the trivia question at the end of each podcast.

I am also working on an exciting new segment for the SGEM tentatively called “Hot Off the Press”. Can’t provide details right now but I hope it will help cut the KT window to less than one week.

So let us start season#3 by addressing one of the most hotly debated issues in emergency medicine, thrombolysis for acute CVA. The SGEM does not shy away from controversial issues it just follows the data.

Thrombolytic therapy for acute ischemic stroke does remains widely controversial.  A “pro/con” debate in the BMJ was accompanied by a non-scientific poll with results split nearly 50/50 regarding whether the benefits of tPA were adequately proven.  Many professional organizations have recommended thrombolytic therapy, with treatment under 3 hours preferred, but treatment up to 4.5 hours accepted.  Other professional societies, primarily in Emergency Medicine, have been less enthusiastic about tPA.

The Australasian College of Emergency Medicine suggests additional evidence is necessary, and the Council of the American College of Emergency Physicians recently voted to revise a pro-tPA Clinical Policy statement.  Alternatively, many stroke neurologists feel tPA to be beneficial in many patients currently excluded from treatment.  This includes the very elderly (>80 years), mild strokes (NIHSS < 5), and time windows up to six hours from onset.

Active clinical trials are underway addressing each of these questions, as well as trials evaluating the utility of advanced imaging to select patients even further from the onset of symptoms.

Case Scenario: 78 year old man presents to ED with right leg and arm for the last 4 hours.  He has a history of hypertension and dyslipidemia. His vitals are unremarkable except for a blood pressure of 165/95. A non-contrast CT head is performed that shows no acute intracranial pathology. Your stroke team asks you to administer thrombolysis and admit.

Question: Is thrombolysis safe and effective treatment in patients who present with signs of an ischemic stroke of less than 6 hours duration?

Background: Acute ischemic strokes represent the leading cause of disability in our society and the third most common cause of death. There have been many studies performed looking at thrombolysis for acute CVA.

We have covered the original 1995 NINDS article on Episode#70. The bottom line from that manuscript was I was skeptical that thrombolysis has benefit for acute stroke.

I presented 12 major trials for thrombolysis in CVA at the Swedish National Emergency conference early this year at SweetBEEM. To summarize there were four trials stopped due to harm or futility, six showing no benefit, and only two showing benefit. This was not enough proof for me to reject the null hypothesis.

Screen Shot 2014-03-26 at 8.40.10 PM

Citation: Wardlaw JM et al. Thrombolysis for Acute Ischemic Stroke (Review).  Cochrane Database Syst Rev. 2014 Jul 29;7:CD000213. doi: 10.1002/14651858.CD000213.pub3. PubMed ID: 25072528

  • Population: 27 randomised trials, involving 10,187 patients, with definite ischemic stroke.
    Intervention: Any thrombolytic agent – urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase.
  • Comparison: Placebo.
  • Outcome: Functional independence at long-term follow up, with safety outcomes of spontaneous intracerebral hemorrhage and death.

Authors Conclusions: Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up).

checklist-cartoonQuality Checklist for Systematic Reviews:

  1. The clinical question is sensible and answerable. Agree.
  2. The search for studies was detailed and exhaustive.  Agree. 
  3. The primary studies were of high methodological quality. Uncertain.
  4. The assessments of studies were reproducible. Disagree.
  5. The outcomes were clinically relevant.  Agree.
  6. There was low statistical heterogeneity for the primary outcome. Disagree.
  7. The treatment effect was large enough and precise enough to be clinically significant. No.

Key Results: In evaluating 27 trials, the authors perform 39 analyses, some with multiple sub-analyses.  They also tend to focus primarily on those involving rt-PA, or alteplase, as the approved and guideline-recommended therapy.

  • Thrombolytic therapy, up to six hours, dead or dependent – 23 trials, 9,318 participants
    • 2679/4891 (54.7%) allocated thrombolysis vs. 2608/4427 (58.9%) allocated control
    • OR 0.85 (95% CI 0.78 to 0.93), with significant heterogeneity (I2 = 39%, P = 0.03)
  • Thrombolytic therapy, up to six hours, risk of symptomatic intracranial hemorrhage – 25 trials, 10,186 participants:
    • 402/5372 (7.4%) allocated thrombolysis vs. 84/4814 (1.7%) allocated control
    • OR 3.75 (95% CI 3.11 to 4.51), without heterogeneity (I2 = 7%)
  • Thrombolytic therapy, up to six hours, risk of death from all causes – 28 trials, 10,187 patients
    • 1043/5372 (19.4%) allocated thrombolysis vs. 856/4815 (17.7%) allocated control
    • OR 1.18 (95% CI 1.06 to 1.30), with significant heterogeneity (I2 = 48%, P = 0.003)

These trials included urokinase, streptokinase, and desmoteplase – and modern thrombolytic therapy is typically undertaken with alteplase, or rt-PA. How about the results for just the rt-PA trials?

  • rt-PA, up to six hours, dead or dependent – 8 trials, 6729 participants
    • 1830/3372 (54.2%) allocated rt-PA vs. 1947/3357 (57.9%) allocated control
    • OR 0.85 (95% CI 0.77 to 0.93), with significant heterogeneity (I2 = 45%, p = 0.04)
  • rt-PA, within 3 hours, dead or dependent – 6 trials, 1779 participants
    • 531/896 (59.2%) allocated rt-PA vs. 603/883 (68.3%) allocated control
    • OR 0.65 (95% CI 0.54 to 0.80), without heterogeneity

The authors therefore lead their published abstract conclusion with the sentence:  Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people.”

Dr. Ryan Radecki

Dr. Ryan Radecki

Commentary: This Cochrane Review update the 2009 version through the addition of the Third International Stroke Trial (IST-3), the largest stroke trial to date.  To remind listeners, IST-3 enrolled patients up to six hours, and specifically enrolled those who were not eligible for tPA under the current European license, but where the treating clinician believed tPA was promising therapy.

A minimal initial number were enrolled double-blind, but following the approval of tPA in Europe, Boehringer Ingelheim ceased supply of the study medication.  This resulted in transition to an open-label design, in which both the treating clinician and the patient were aware of treatment allocation.

This introduces several forms of bias, including alteration of the type or intensity of other initial treatment based on allocation, a placebo effect after being given the “promising” therapy, and a nocebo effect if randomized to no additional treatment.

Outcome assessments at 6 months were blinded to allocation, but many occurred via telephone or postal mail, relying on un-blinded patients or family members to report functional status.  This trial is subject to substantial limitations to internal validity, and its inclusion in this updated Cochrane Review – comprising over half the total number of patients treated with thrombolytic therapy – diminishes the reliability of the analysis as a result of bias in favour of thrombolytics.

There were a number of problems with IST-3:

  • Pragmatic, open-label (blinding)
  • Small blinded (300) favored control
  • Only patients doctors thought would benefit (bias)
  • Missed target by ~50% for enrollment
  • After 7 years they seemed to move the goal post
  • Another statistician was brought in to “persuade”
  • Came up with secondary outcome with ordinal logistic regression analysis
  • Primary end point was NEGATIVE
  • Reported as a positive study -  “despite the early hazards, thrombolysis within 6h improved functional outcome. Benefit did not seem to be diminished in elderly patients.

The SGEM did a critical review of IST-3 on Episode#29. The bottom line from that review was treatment with tPA harmed (death) 1 in 25 early, the fatal and non-fatal bleed rate when up significantly and there was no benefit seen at 6 months in the primary outcome.

The authors appropriately note many of these threats in their reporting of potential sources of bias.  Only 14 of 27 included trials met criteria for high-grade concealment.  Other than IST-3, most were double-blind, placebo-controlled trials – although, the authors note saline placebo is not identical in appearance to tPA, and prolonged incidental bleeding from venipuncture or gingiva in tPA patients could serve to un-blind patients or clinicians.  Blinding of follow-up assessment was only explicitly declared in seven trials, which may have resulted in clinicians aware of acute phase events performing the follow-up assessment.

We mentioned earlier that several trials were stopped prematurely as a result of safety, futility, or enrolment issues.  ATLANTIS A was stopped after 142 patients due to an excess of symptomatic intracranial haemorrhage.  ATLANTIS B was stopped after 619 patients due to futility, and the authors note data has only been publicly presented on 547 of them.

ASK, MAST-E, MAST-I, and MELT were stopped early by their data monitoring committees.  AUST was discontinued after slow recruitment.  The authors do not acknowledge the distorting effect of early termination when weighting results for pooled analysis.

The authors also downplay the potential bias resulted to trial funding and author affiliation.  They note “8/27 trials were run by companies that make the clot-dissolving drugs”, but go on to state most participants come from trials funded by Government or charity sources.  However, this statement is only true based on the inclusion of IST-3.  The majority of trials comprising the remaining participants, including most trials evaluating tPA, were funded by Genentech and Boehringer Ingelheim.  All tPA trial reports were co-authored by individuals declaring conflict-of-interest with one of the two manufacturers.

All trials were performed in specialized stroke centers, and patients were assessed by expert neurologists prior to enrolment and treatment.  The generalizability of any of these findings to many practice settings is limited, and observational studies show mixed results regarding safety and rate of treatment of stroke mimics.

The simple summary of this review boils down to the reliability of the evidence, rather than the analyses of the authors.  However, after nearly two decades of tPA, most clinicians’ opinions are fully crystalized.  Regardless of the conclusions or analyses in this article, few will change practice.

Comment on authors conclusion compared to our conclusion: The authors write:Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment.

In fact, those treated with tPA after three hours derived NO benefit, according to their analyses.  Analysis 1.19 reports death or dependency at follow-up with an OR of 0.93 (95% CI 0.83 to 1.04) versus control.  Therefore, even accepting the data at face value, the authors present a misleading conclusion through inappropriate partitioning of data.

Screen Shot 2014-09-05 at 2.17.34 PM

The remaining author conclusions, regarding a definite increase in symptomatic intracranial hemorrhage, deaths at 7 to 10 days, and deaths at final follow-up, accurately reflect consistent harms present across all trials.

The authors also call for additional trials aimed at identifying the latest time window, treatment population, reduction in harms from intracranial hemorrhage, and the appropriate environment for practice.  However, it may be more appropriate to perform additional studies to narrow the treatment population to maximize benefit, rather than expand the treatment population to the very limits of risk/benefit balance.

Screen Shot 2014-04-08 at 2.57.04 PMThe Bottom Line: No true believers – on either side of the issue – are harmed by this publication. Thrombolysis for CVA…I remain skeptical

Case Resolution:  You reassess the patient and he seems to be improving clinically. You discuss the potential benefits and risk of thrombolysis. By now it is now over 4.5hrs and the treatment window has closed. The patient is not given tPA and admitted for further care.

This is a challenging case and we are clearly in a realm of uncertainty. There are few risk stratification and prognostic tools out there to predict outcome with tPA. But this patient is far from that idea patient population. His age, hypertension and dyslipidemia are clinical features likely increasing his chance of intracranial hemorrhage.

In these trials in a typically younger population the symptomatic intracranial hemorrhage rate was 7.4%. Just roughly estimating his chance of ICH after tPA is probably 10-12% or even higher with a corresponding increase in mortality.

His unilateral weakness is improving. Is this a transient event? It is difficulty to say so close to the onset of symptoms. Stroke mimics and TIAs also do great with tPA but they also do great without treatment. The level of disability is an important consideration. A patient with some weakness might be reasonable to expect to regain some function with rehabilitation, whereas profound hemiparesis is almost certain to be completely disabled for the remained of his life.

Many individuals will actually make the decision to take that substantial risk of bleeding in order to gain an even smaller chance of independent living. Assessment of pre-stroke functional status is also an important consideration. Then as you say this patient’s presents near the end of this proposed therapeutic window. In general, and in this specific case, I would say the risks even exceed the theoretical benefits.

Clinical Application: I will continue to offer tPA, as recommended by the American Heart Association guidelines, and tacitly mandated by medicolegal consequences if not offered.  The manner in which patients are provided informed consent for this therapy dramatically influences their likelihood of electing to receive treatment.

What do I tell my patient? Thrombolytic therapy for acute ischemic stroke is controversial.  The risks – severe bleeding and with neurologic worsening – are consistent and known, occurring in about 1 in 12 patients.  The benefits are uncertain, and most studies suggestive of benefit were sponsored by drug companies or otherwise biased.  Other trials showing harm or no benefit were stopped early when hoped-for results did not materialize.  However, a number of patients in all trials using tPA – about 1 in 10 – received noticeable functional benefit from this therapy when given quickly after a stroke.  Doubts persist about the reliability of this data, and, unfortunately, it is unclear which patients have the greatest chances of benefit or harm from this therapy.  The choice to receive this therapy remains an individual patient decision.

Keener Kontest: Who did the first study for thrombolysis is stroke and when was it published?

If you know the answer than send me an email to 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

Thank you to Dr. Ryan Radecki for being the first guest skeptic on Season3 of the SGEM. I hope this was a good way to launch Season#3. You can look forward to a weekly skeptical review of the EM literature. As mentioned, Swami will be back with some Classic papers, expect more great skeptical guests, I will be recording SGEM Journal Club at Queen’s University next month, there will be the occasional 10,000 foot view of an EM/MedEd/EBM issue and a brand new SGEM segment coming soon.

Remember to be skeptical of anything you learn,

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

 

SGEM Special: O Captain! My Captain

Podcast Link: SGEM O Captain
Date:  August 18th, 2014 

As many of you know actor and comedian Robin Williams died last week. I am having difficulties processing the loss. There are feelings of anger, sadness and disbelief.

It is weird; a person I have only known through movies has had a profound effect on me.

Robin Williams made a huge impact on my desire to teach, the way I teach and the goal to inspire independent critical/skeptical thinking students.

It must be affecting others in the EM community too. A SGEM listener emailed asking if there would be an episode dedicated to Robin Williams. I was not sure if it would be respectful or appropriate.

As always, when I am not sure of things I check with people I hold in high regard. So I contacted Rob Rogers (I Teach EM) and Rob Orman (ER Cast). They thought it was a good idea and felt it may help all of us and other SGEM listeners heal.

Rob Rogers and Rob Orman

Rob Rogers and Rob Orman

In true SGEM fashion we are going to cover Five of Robin Williams movies. These are must see movies and part of any EM core training. We will discuss why the movie was important to us and to our practice and teaching of EM.

Before we start I think it would be appropriate to read the poem that was to be read at the start of every Dead Poets’ Society gathering.

  • “I went to the woods because I wished to live deliberately, to front only the essential facts of life, and see if I could not learn what it had to teach, and not, when I came to die, discover that I had not lived. I did not wish to live what was not life, living is so dear; nor did I wish to practise resignation, unless it was quite necessary. I wanted to live deep and suck out all the marrow of life, to live so sturdily and Spartan-like as to put to rout all that was not life, to cut a broad swath and shave close, to drive life into a corner, and reduce it to its lowest terms.” Henry David Thoreau, Walden: Or, Life in the Woods

patch adams

1) Patch Adams (1998): I learned a lot from this movie as a young doctor. One of the most important lessons I learned was to be myself. I started wearing bright red shoes on shift. Nurses call them my Dorothy slippers. Click my heels twice and say; “there is no place like emerg”. Wearing these crazy red shoes seems to make kids less scared of me. The only contact they may have had with doctors involves needles.

I also learned from Patch Adams that if I just follow my passions and act in the patients best interest things will be OK.

  • “You treat a disease, you win, you lose. You treat a person, I guarantee you, you’ll win, no matter what the outcome.”
  •  “Our job is improving the quality of life, not just delaying death.”
  •  “But you can’t control my spirit, gentlemen. You can’t keep me from learning, you can’t keep me from studying. So you have a choice: you can have me as a professional colleague, passionate, or you can have me as an outspoken outsider, still adamant. Either way I’ll probably still be viewed as a thorn. But I promise you one thing: I am a thorn that will not go away”

Aladdin2) Aladdin (1992): EM docs are like the Genie in Aladdin… “Poof! What do you need, “Poof! What do you need, Poof! What do you need?”  Patients often expect us to grant them wishes and perform miracles.

  • Night shifts “Oi! Ten thousand years will give you such a crick in the neck.”
  • Call/Sleep Rooms “ Phenomenal cosmic powers! Itty bitty living space!”
  • ACLS for Asystole “I can’t bring people back from the dead. It’s not a pretty picture”
  • Writing Narcotic prescriptions “There are a few, uh, provisos. Ah, a couple of quid pro quo.”
  • People I work with so hard in the ED on a daily basis. Treating critically ill patients. Seeing so much suffering and pain. Sharing these incredibly difficult emotional situations. These are my friends not co-workers. Special kinds of friends who give so much. To them I say “You ain’t never had a friend like me”

2a) Good Morning Vietnam (1987): (Rob Orman’s 2nd choice). Gooooooooood Morning SGEM Listener.

Good Will Hunting3) Good Will Hunting (1997): The story was similar to how I my wife Barb and just knew she was the one.

  • “You’re not perfect, sport, and let me save you the suspense: this girl you’ve met, she’s not perfect either. But the question is whether or not you’re perfect for each other.”
  • “Real loss is only possible when you love something more than you love yourself.”
  • “Sorry, guys; I gotta see about a girl.”

mrs-doubtfire24) Mrs. Doubtfire (1993): Since having kids there is nothing I would not do to be part of their lives. Robin Williams showed everyone the importance of family, that life was not perfect, parents got divorced, parents make mistake, don’t worry about what other people think and sadness is temporary.

  • “There are all sorts of different families, Katie. Some families have one mommy, some families have one daddy, or two families. And some children live with their uncle or aunt. Some live with their grandparents, and some children live with foster parents. And some live in separate homes, in separate neighborhoods, in different areas of the country – and they may not see each other for days, or weeks, months… even years at a time. But if there’s love, dear… those are the ties that bind, and you’ll have a family in your heart, forever.”

4a) Awakenings (1990): This was Rob Orman’s 4th pick. “What we do know is that, as the chemical window closed, another awakening took place; that the human spirit is more powerful than any drug – and THAT is what needs to be nourished: with work, play, friendship, family. THESE are the things that matter. This is what we’d forgotten – the simplest things.”

Mr. Keating5) Dead Poets’ Society (1989): This movie had the most impact upon me. I identified with both the students and Mr. Keating. There were so many great lines. Encourage students not to conform, find their own voice and be critical/skeptical thinkers.

  • “Medicine, law, business, engineering, these are noble pursuits and necessary to sustain life. But poetry, beauty, romance, love, these are what we stay alive for.”
  • “A powerful play goes on and you may contribute a verse. That the powerful play *goes on* and you may contribute a verse. What will your verse be?”
  • “Boys, you must strive to find your own voice. Because the longer you wait to begin, the less likely you are to find it at all. Thoreau said, “Most men lead lives of quiet desperation.” Don’t be resigned to that. Break out!”
  • “No matter what anybody tells you, words and ideas can change the world.”
  • “There’s a time for daring and there’s a time for caution, and a wise man understands which is called for.”
  •  “Now we all have a great need for acceptance, but you must trust that your beliefs are unique, your own, even though others may think them odd or unpopular.”

Screen Shot 2014-08-16 at 12.34.17 PMPhysicians and Mental Health: Studies have demonstrated and increased suicide rate among physicians. This can be seen as early as medical school. Physicians are also more likely to be successfully in their suicide attempts compared to non-physicians. Many factors are felt to be involved in the increased suicide rate including the professional burden. (Eve Schemhammer NEJM 2005)

Various resources are available to physicians. In Ontario, Canada if you are concerned about your own well being/mental health or that of a colleague you can call 1-800-851-6606 (Ontario only).

There are also suicide prevention resources are available across Canada. You can access crisis centres 24hrs a day. There is also a Centre for Suicide Prevention for more information.

In the United States there is a national suicide prevention lifeline. 1-800-271-TALK (8255). They list a number of warning signs for which may mean someone is at risk for suicide.

  • Screen Shot 2014-08-16 at 12.36.28 PMTalking about wanting to die or to kill oneself.
  • Looking for a way to kill oneself, such as searching online or buying a gun.
  • Talking about feeling hopeless or having no reason to live.
  • Talking about feeling trapped or in unbearable pain.
  • Talking about being a burden to others.
  • Increasing the use of alcohol or drugs.
  • Acting anxious or agitated; behaving recklessly.
  • Sleeping too little or too much.
  • Withdrawing or feeling isolated.
  • Showing rage or talking about seeking revenge.
  • Displaying extreme mood swings.

Remember, you are not alone and many people have felt suicidal at some point in their lives. Suicide crises are almost always temporary – this too shall pass. Problems look big at first but are seldom as great as they appear at first glance. Don’t loose sight of all the reasons to live. No matter how big the problems seem, how much you are hurting, suicide is not the answer. Help is available so don’t keep suicidal thoughts to yourself.

A Few Final Thoughts:

  • “Carpe Diem”: Seize the day
  • “Sucking the marrow out of life doesn’t mean choking on the bone”
  •  “We are not now that strength which in old days, moved earth and heaven, that which we are, we are; One equal temper of heroic hearts, Made weak by time and fate, but strong in will, To strive, to seek, to find, and not to yield.” Lord Alfred Tennyson -Ulysses

Screen Shot 2014-08-18 at 10.01.22 PMListen to Robin Williams speak about death and grieving. This is from a 1996 movie called Jack. It is about a person born with a disorder causing him to age 4 times faster than normal. Click on the picture to see a Youtube video put together by ModernGreen. It has video clips from Robin Williams movies and the audio clip from the movie Jack.

“Please, don’t worry so much. Because in the end, none of us have very long on this Earth. Life is fleeting. And if you’re ever distressed, cast your eyes to the summer sky when the stars are strung across the velvety night. And when a shooting star streaks through the blackness, turning night into day… make a wish and think of me. Make your life spectacular. I know I did.”

I am skeptical about a lot of things but one thing I am not skeptical about is that Robin Williams, a man I never met, made a difference and changed my life.

RIP O Captain! My Captain!

Two robs and a Ken

Remember to be skeptical of anything you learn,

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

SGEM#84: Season Two Finale (Don’t You Forget About Me)

Podcast Link: SGEM84
Date:  July 26th, 2014 

This is the 42nd podcast of for this year and the last for Season#2. Why only 42 episodes? Keeping with the hitchhiker’s Guide to the Galaxy 42 seems like the right number. But don’t panic, the SGEM will be back in the fall with new episodes.

The goal of the SGEM has always being to cut the knowledge translation window down from 10 years to 1 year. It does this by using social media to provide you with high quality, clinically relevant, critically appraised, evidence based information. The SGEM wants you to have the best evidence so you can provide your patients with the best care.

Much of the SGEM content is a result of the Best Evidence in Emergency Medicine (BEEM) process. The BEEM process is a reliable and validated method of selecting relevant emergency medicine articles. BEEM is evidence based medicine worth spreading.

Screen Shot 2013-06-03 at 1.48.37 PMYou can get the BEEM critical appraisal tools as part of the Free Open Access to Meducation movement. FOAM – Medical education for anyone, anywhere, anytime.

Season#2 has been very successful. The numbers of subscribers grew substantially. The program also improved significantly with the edition of the SGEM Journal Club and SGEM Classics.

The SGEM Classics was an excellent suggestion by Dr. Anand Swaminathan (Swami) who pointed out there are practice changing papers that were published before the SGEM started in 2012.

Swami and I did three classic papers this year including OPALSNINDS and CRASH-2. If you have a suggestion for a SGEM Classic paper then send it to me (TheSGEM@gmail.com) to consider for Season#3.

Five Highlights from Season#2:five+fingers

  1. Dr. Jeff Perry, lead author of the new Ottawa Subarachnoid Hemorrhage TOOL (SGEM#48)
  2. Dr. David Newman discussed Presidential Care (SGEM#47).
  3. SGEM Journal Club at McGill University (SGEM#50) and McMaster University (SGEM#55)
  4. Interviewing the Godfather of FOAM, Dr. Joe Lex (SGEM#77)
  5. Presenting thrombolysis for acute embolic stroke controversey in Sweden

The SGEM had many guest skeptics who helped make the show much better. There were students, consultants, physiotherapist, pharmacist, nurse, residents, and a ranting paediatrician (Dr. Anthony Crocco).

Many of my guest skeptics are involved in their own knowledge translation projects. I asked a few of them to send me a audio clip of why you should listen to the SGEM and what was their favourite Season#2 episode.

Eve Purdy

Eve Purdy

Eve Purdy (The Student):

  • Third year medical student from Queen’s University in Kingston, Ontario
  • Guest Skeptic SGEM#63 Goldfinger (More Dogma of Wound Care) dispelling the myth about the golden time period for laceration repair
  • FOAM project Manu et Corde. “The doctor works by hand and heart.”
  • Eve’s pick SGEM#68: Sign, Sign Everywhere a Pediatric Vital Sign
Dr. Jeremy Faust

Dr. Jeremy Faust

Jeremy Faust (The NYC Resident):

  • Emergency medicine resident, Mount Sinai in New York City
  • Guest Skeptic SGEM#49: Five Stages of Evidence Based Medicine Grief and SGEM#79: Tommy Can you Hear Me (Steroids for Bacterial Meningitis)
  • FOAM project FOAMCast
  • Jeremy’s pick SGEM#72: Tiny Bubbles (#FOAMed and #MedEd)

Lauren Westafer (The Short Coat):

Dr. Lauren Westafer

Dr. Lauren Westafer

  • Emergency medicine resident, Baystate Medical Center in Northampton, Massachusetts
  • Guest Skeptic SGEM#17: The Best FOAM/#FOAMed of 2012 and SGEM#20: Hit Me with your BEST Shot (Flu Shot for Healthcare Workers)
  • FOAM project The Short Coat and FOAMCast
  • Lauren’s pick SGEM#77: Take the Hashtag, Leave the Classroom (Pro #FOAMed Argument)

Brent Thoma (The Boring EM):

Dr. Brent Thoma

Dr. Brent Thoma

  • 2013 Canadian Emergency Medicine Resident of the Year
  • Guest Skeptic SGEM#56: BEEM Me Up (Impact Factor in the Age of Social Media)
  • FOAM project BoringEM
  • Brent picked the Classics Series SGEM#64: OPALS, SGEM#70: NINDS and SGEM#80: CRASH-2

 

Erich Hanel (The BEEM Team):

Dr. Erich Hanel

Dr. Erich Hanel

  • Assistant Clinical Professor, Division of Emergency Medicine, Department of Family Medicine and Department of Pediatrics, McMaster University
  • Guest Skeptic SGEM#53: Sunday, Bloody Sunday (Epistaxis and Tranexamic Acid)
  • Erich’s pick SGEM#51: Home (Discharging Patients with Acute Pulmonary Emboli Home from the Emergency Department)

Katrin Hruska (The Swede):

Dr. Katrin Hruska

Dr. Katrin Hruska

  • A Swedish doctor, interested in patients and trying to figure out how to improve emergency care, with a fair amount of skeptisism.She organized the amazing SweetBEEM conference this year.
  • Guest Skeptic SGEM#82: Melt with You (Targeted Temperature Management)
  • Katrin really did not have a pick:)

Salim Raziae (The Rebel):

Dr. Salim Rezaie

Dr. Salim Rezaie

  • Assistant Professor in the Department of Emergency Medicine and Internal Medicine at the University of Texas at San Antonio
  • Guest Skeptic SGEM#76: And the Beat Goes On (Azithromycin and Risk of Cardiovascular Death) and SGEM#83: In Your Eyes (Topical Tetracaine for Corneal Abrasions)
  • FOAM Project REBEL EM (Rezaie’s Evidence Based Evaluation of Literature in Emergency Medicine)
  • Salim’s pick SGEM#54: Baby It’s Cold Outside (Pre-Hospital Therapeutic Hypothermia in Out of Hospital Cardiac Arrest)
Dr. Anand Swaminathan

Dr. Anand Swaminathan

Anand Swaminathan (The Swami):

  • Assistant Program Director at NYU/Bellevue Hospital in the Department of Emergency Medicine, New York City
  • Guest Skeptic on all the Classic Episodes SGEM#64: OPALS, SGEM#70: NINDS and SGEM#80: CRASH-2
  • FOAM Project REBEL Cast
  • Swami’s pick SGEM#56: BEEM Me Up (Impact Factor in the Age of Social Media)
Dr. Steve Carroll

Dr. Steve Carroll

Steve Carroll (The EM Basic):

  • Active duty Emergency Medicine Physician with the US Army
  • Guest Skeptic SGEM#75: Video Killed Direct Laryngoscopy?
  • FOAM project EMBasic (Your Boot Camp Guide to Emergency Medicine)
  • Steve’s pick SGEM#57: Should I Stay or Should I Go (Biphasic Anaphylactic Response)

Chris Carpenter (The Brain):

Dr. Chris Carpenter

Dr. Chris Carpenter

  • Associate Professor, Emergency Medicine, Director, Evidence Based Medicine, Washington University Division of Emergency Medicine, St. Louis
  • Guest Skeptic SGEM#56: BEEM Me Up (Impact Factor in the Age of Social Media)
  • FOAM project WashU EM Journal Cub
  • Chris’ picks SGEM#72: Tiny Bubbles (#FOAMed and #MedEd) and SGEM#77: Take the Hashtag, Leave the Classroom (Pro #FOAMed Argument)

I will be taking the summer off to reflect, recharge and improve the SGEM for Season#3. Jeremy and Lauren I promise there will be no jumping of sharks.

Shark with Frick'n laser pointer.

Shark with Frick’n laser pointer.

The SGEM will return this fall with more critical reviews and classic papers. I hope to get a few new guest skeptics on the program including Rob Orman from ERCast.

I am also working on some exciting new projects that will make the SGEM even FOAMyer and cut that knowledge translation window down even further.

If you are in the northern hemisphere enjoy the rest of the summer. If you are listening in the southern hemisphere I hope you have a great winter.

Keener Kontest: There was no winner from last week. I guess the questions have been just too hard lately.

If you want to play the last Keener Kontest of this season 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 provide the correct answer will be sent 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.