SGEM#69: Cry Me A River (Early Goal Directed Therapy) ProCESS Trial

Podcast Link: SGEM69
Date:  April 2, 2014

Guest Skeptic: Dr. Suneel Upahdye Suneel is a founding member of the BEEM Team.

Case Scenario: You are working in a rural community emergency department. The next patient you see is a 71 year old man who has been sick for three days with fever, chills and a productive cough.  On arrival, the vital signs were as follows: Temp 38.7C, HR 110, RR 24, BP 95/60 (after a 500cc normal saline bolus by ambulance), oxygen saturations 88% on room air.  Skin looks mottled, and the patient seems to be confused on questioning.

You diagnose the patient to be in septic shock, and administer another IV crystalloid bolus, broad spectrum antibiotics and oxygen by mask.  Your hospital does not have critical care facilities, and if the patient requires intubation or invasive vascular monitoring (eg. CVP, arterial line for MAP), the patient will have to be transferred out to another larger centre.

You are aware that the Early Goal Direct Therapy protocols mandated in the 2013 Surviving Sepsis Campaign guidelines include such  invasive measures.  You are also aware that there have been numerous concerns that such aggressive invasive measures may not be necessary for resuscitating septic patients, and that more conservative measures (intravenous crystalloid boluses, broad spectrum antibiotics, lactate screening) may be just as effective.

Question: Is early goal directed therapy (EGDT) or other protocol-based care superior to usual care for septic shock patients in the ED?

Rivers_20080126_Emanuel Rivers 2007

Dr. E. Rivers

Background: It all started over 10 years ago when Dr. Emmanuel Rivers published in the NEJM his single centre RCT showing EGDT could reduce septic mortality from 47% to 31% (NNT=6).

Dr. River’s “bundle” put emphasis on early recognition, IV fluids, broad spectrum antibiotics. Also included vasopressors, iontropes and blood transusions. Monitoring required placement of a central venous catheter.

  1. Early Recognition – Every 60min delay can increase mortality by 7.5%
  2. IV Fluid – Volume is important (30cc/kg IV bolus)  with crystalloid better than colloids (Cochrane SR 2013)
  3. Normal Saline or Ringers Lactate – ringers lactate will not effect lactate levels
  4. Broad Spectrum Antibiotics – Usual source is respiratory genital urinary

Article: The ProCESS Investigators. NEJM 2014. doi: 10.1056/NEJMoa1401602

  • Population: Adult patients >18 years old with at least 2 systemic inflammatory response syndrome (SIRS) criteria, AND refractory hypotension (systolic BP <90mmHg after fluid challenge or requiring vasopressors) or lactate >4mM. Recruited in 31 US tertiary hospital ED’s.
    • Excluded: acute CVA/ACS/CHF/arrhythmia/seizure/GI bleed/status asthmaticus/overdose/burn/trauma/need for immediate surgery, known CD4 count< 50/mm2, advanced directive against resuscitation, CI to CVP line placement, high likelihood of refusing blood transfusion (ie. Jehovah’s witness), resuscitation deemed futile, pregnancy, transfer from other hospital, or participant in another ongoing study.
  • sepsismanagementchartIntervention: Early Goal Directed Therapy vs other protocol-based care
  • Comparison: “Usual care” (at discretion of MD)
  • Outcome:
    • Primary = In-hospital death any cause at 60 days.
    • Secondary = Any death at 90 days, cumulative death at 90 days and 1 year, duration of CV failure, respiratory failure and acute renal failure, hospital and intensive care unit length of stay, and hospital discharge disposition (eg. home, nursing/other long term care facility)

Authors Conclusions: “In a multicenter trial conducted in the tertiary care setting, protocol-based resuscitation of patients in whom septic shock was diagnosed in emergency departments did not improve outcomes.”

checklist-cartoonQuality Checklist:

  1. Emergency department population – YES
  2. Randomized – YES
  3. Concealed Randomization - YES
  4. Analyzed in their group – YES
  5. Consecutively recruited – Unsure
  6. Patient groups similar at baseline - YES
  7. Unaware of group allocation – YES
  8. Groups treated equally – YES
  9. Follow-up complete – YES
  10. Patient oriented outcomes – YES
  11. Treatment effect was large and precise – It depends (Dr. Worster’s answer to any EBM question)

Key Results: 31 centres screened about 12,000 patients and ultimately included ~10% (n=1,341). There were about 450 patients in each group (EGDT n=439, Protocol-based n=446 and usual care n=456).

All ED physician/resuscitation teams trained in different protocols, ongoing telephone support 24/7, routine site visits and feedback support processes. Baseline characteristics of patients enrolled essentially identical. Sequential recruiting not reported; the primary author reports average  1 patient/month recruited at various sites (D. Yealy, as discussed on ALiEM podcast).

Protocol-based fluid loading was based on CLINICAL findings (jugular venous destention, rales, decreased pulse oxymetry readings), hypoperfusion and CLINICAL features (mottled skin, oliguria, altered sensorium, MAP <65mmHg with systolic BP>100, arterial lactate >4)

  • Outcomes:
    • Primary outcome was in hospital death 60 days: NO DIFFERENCE (EGDT 21%, Protocol 18.2%, Usual care 18.9%)
    • Death 90 days: NO DIFFERENCE (31.9%/30.8%/33.7%)
    • ICU admissions: More EGDT admissions (91.3% vs. 85.4% vs. 86.2%)
    • Hospital LOS: NO DIFFERENCE (11.1 days vs 12.3 vs. 11.3)
    • Adverse organ system failures: NO DIFFERENCE for cardiovascular/respiratory/renal; slight increase in acute renal failure requiring dialysis in Protocol group
    • Adverse Events: NO DIFFERENCE (5.2% vs 4.9% vs 8.1%)
    • Disposition Destinations: NO DIFFERENCES
  • Protocol Performance: The protocol-based algorithm was based on 6 hours of resuscitative care but less aggressive/invasive than EGDT (based on literature review, 2 surveys of ED and ICU physicians worldwide)
    • Adherence to Protocols (0-6hrs): EGDT = 89.1%,  Protocol  = 95.6% and not applicable to Usual care
    • Intravenous Fluids: 96% crystalloid overall (colloids not encouraged/excluded): more fluid given in Protocol arm (3.3L) than EGDT (2.8L) or usual care (2.3L)
    • Intravenous Antibiotics: 97% in all 3 arms
    • CVP line placement: EGDT 94% vs Protocol 56.5% vs Usual care 57.9%; SVO2 rarely measured in latter two groups (4% and 3.5% resp). Those who got CVP lines in latter groups received them much later than the EGDT arm patients who got them right away
    • Vasopressor use: 54.9% EGDT vs 52.2% Protocol vs 44.1% Usual
    • Dobutamine use RARE: 8% EGDT vs 1.1% Protocol vs 0.9% Usual
    • Blood transfusion rate: 14.4% EGDT vs 8.3% Protocol vs 7.5% Usual; transfusion threshold set at Hb <7.5g/dl (4.5mmol/L)
photo-1

Dr. Suneel Upadhye

BEEM Comments: This was a well executed three arm randomized clinical trial looking at three likely resuscitation scenarios.  Block randomization 1:1:1 to ensure adequate numbers in each group.

Blinding was not explicitly described in paper or Supp Appendix; but outcomes data locked until Dec 2013 so clinical investigators unaware of different arm outcomes.  No industry sponsorship. Near perfect follow-up for outcomes.

They did change their sample size part way through the study. The initial sample size was 1950 and based on a power calculation on the difference seen in the Dr. River’s trial. Then they changed the sample size. Initial sample size calculation modified at first planned interim analysis due to less observed mortality in control arm (attributed to the changing trend in improved sepsis care over last decade); reduced from 1950 to 1350 patients with preserved power metrics.  The limitations discussed are appropriate and likely irrelevant to the overall conclusions.  Overall quality was super.

This landmark ED-based study further refines the revolutionary care pioneered in the original Rivers EGDT paper in 2001.  It refutes the need for universal invasive monitoring, which will be welcome for most ED clinicians in smaller/rural settings who may not have the full technical support/expertise to fully execute the original EGDT protocol.

This study also reaffirms the importance of early antibiotics, IV crystalloid resuscitation, and following serial lactates to monitor resuscitation success.  The options outlined here can likely be extrapolated easily to those patients with severe sepsis as well as septic shock.

Importantly, this article does NOT refute the value of bundled care, which has been proven in prior trials/metaanalyses to be of significant benefit to reduce patient mortality/morbidity, but does suggest that an all-or-nothing super-invasive strategy (a la EGDT) is not universally required.  Furthermore, the emphasis on crystalloids for IV resuscitation is congruent with SSC guidelines (update 2013) and a 2013 Cochrane update on fluid resuscitation of critically patients.

Finally, although no vasopressor is specified, the results here again are congruent with use of norepinephrine (NE) vs. dopamine (DA) recommendations from the SSC 2013 update and a recent metaanalysis published supporting NE over DA (De Backer et al. Dopamine versus norepinephrine in the treatment of septic shock: a meta-analysis. Crit Care Med 2012).

Surviving Sepsis Campaign (SSC) Response to ProCESS Trial:Screen Shot 2014-04-05 at 1.59.15 PM

  1. Importance of Early Recognition
  2. 18% mortality rate in “usual” care is much better than the 46% seen in 2001
  3. Because the low mortality rate in the control arm and two other large trials (ARISE and ProMISe) they are not going to revise the bundles at this time
  4. ProCESS does not answer the question about using a protocol to manage patients with severe sepsis without septic shock
  5. Regarding the SSC 6 hour Bundle
    1. Supports MAP target of 65mmHg
    2. Repeat lactate testing no addressed in the ProCESS trial
    3. More than half of the usual care and protocol based care got central lines

Overall, the SSC are a little more reserved in embracing the ProCESS results, but do support overall principles in conjunction with their recent SSC updates. They do refer to a companion paper that supports a target MAP of 65mmHg (NEJM 2014).

The Bottom Line: Effective care for septic shock hinges on early recognition, lactate screening, intravenous crystalloid resuscitation and early broad spectrum antibiotics

Clinical Application: This information is what most ED physicians have been waiting for since the original EGDT paper in 2001, and confirms what most already suspected: generate a protocol based on early recognition, intravenous crystalloids, broad-spectrum antibiotics and lactate screening. This is READY FOR PRIME TIME, NOW!

What do I tell my Patient: It looks like you have a serious infection. We are going to give you intravenous fluids, intravenous antibiotics and admit you to hospital.

Case Resolution: 71 year old man with sepsis probably from a respiratory infection. You have given him 2L of fluid now and intravenous antibiotics. He is looking a little better, his blood pressure is responding and lactate level is going down. You discuss the case with the patient and the family. Ask them if they would like to be transferred to a higher level of care with central monitoring or stay locally. They decide to stay in your rural facility and consider transfer if takes a turn for the worst.

Keener Kontest: Last weeks winner was Jarosław Gucwa from Krakówl. He knew more than five reasons a child would have sinus tachycardia (pain, fever, anxiety, dehydration, malignant hyperthermia, hypovolemia with hypotension/shock and anemia).

If you want to play the Keener Kontest 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.

Additional Reviews of the ProCESS Trail:

Shout_OutSpecial shout out to Lauren Westafer and Jeremy Faust. Both have appeared on previous episodes of the SGEM. Lauren was on SGEM#17: Best of FOAM 2012 and Jeremy was on SGEM#49: Fives Stages of EBM Grief. These two bright FOAMed advocates suggested the theme music for todays podcast “Cry me a River” by Joe Cocker.

Remember to be skeptical of anything you learn,

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

RANThony#2: Pediatric Cough Medications

Check out the latest RANThony on YouTube from Dr. Anthony Crocco on paediatric cough medications. This was recored at the amazing Society of Rural Physicians of Canada (SRPC) Rural and Remote meeting in Banff last week.

We were both invited to the meeting to give the Best of BEEM (BoB) talk. The BoB talk was very well attended and we covered some of the practice changing papers published in the emergency medicine literature in the last few years. SRPC recorded this session and I hope it will be posted soon.

logo-SRPC

I gave two other talks at SRPC. One was on how to create a rural academic centre of excellence. The other talk was on using social media and FOAMed for rural practice. Dr. Crocco gave an additional lecture on paediatric airway emergencies.

Dr. Crocco is the pediatric lead of the BEEM Dream Team . He is also the Medical Director and Pediatric Emergency Medicine Division Head for McMaster University.

Dr. Crocco is know by the residents to rant on various subjects. Pediatric cough medications is one of his favourite rants. The inspiration for these YouTube videos comes from comedian Rick Mercers who does a rant on his TV show.

SGEM#26: Honey, Honey covered the issue of cough medications for children. It reviewed three publications which Dr. Crocco highlights in his latest RANThony. These included:

  • Smith et al. Over-the-counter (OTC) medications for acute cough in children and adults in ambulatory settings. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD001831. DOI: 10.1002/14651858.CD001831.pub4.22895922
  • Oduwole et al. Honey for acute cough in children. Cochrane Database of Systematic Reviews 2012, Issue 3. Art. No.: CD007094. DOI: 10.1002/14651858.CD007094.pub3.22419319
  • Cohen et al. Effect of Honey on Nocturnal Cough and Sleep Quality: A Double-blind, Randomized, Placebo-Controlled Study Pediatrics; originally published online August 6, 2012; DOI: 10.1542/peds.2011-3075 cohen-honey-cough

HARM: There are significant dangers to child cough and cold medicine. Data from 2011 National Poison Data System in the USA documented the following for child over the counter cough and cold medicines:

  • 35,000 calls to poison control centres
  • 3% of all pediatric poison control calls
  • 5 pediatric deaths
  • 10% of all pediatric toxicological deaths

Harm Associated with  Over-the-Counter Child Cough Medication: In 2011 the Food and Drug Administration (FDA) pulled 500 cough/cold/allergy medicines off the market. The FDA sent a specifically advisory warning that OTC cough medicines should not be used in children under 2 years of age.

  • “FDA has completed its review of information about the safety of over-the-counter (OTC) cough and cold medicines in infants and children under 2 years of age.  FDA is recommending that these drugs not be used to treat infants and children under 2 years of age because serious and potentially life-threatening side effects can occur.”

The American Association of Family Physicians(AAFP) in 2012 recommend that these treatment not be used in children under the age of four.

  • “In children, there is a potential for harm and no benefits with over-the-counter cough and cold medications; therefore, they should not be used in children younger than four years.”

The bottom line from Dr. Crocco’s review on child cough medication and honey was“If you have a child with a cough older than 1 year of age try a teaspoon of honey every 6 to 8 hours as needed.”

This information is given with the warning that children under the age of one year should not get honey due to the risk of botulism.

avoid-honey-babies2-270BOTULISM WARNING:

Honey should not be given to children under the age of one year of age due to the risk of botulism.

Please let us know if you like these RANThonys because Dr. Crocco has many more topics he can cover.

Remember to be skeptical of anything you learn,
even if you heard it on the Skeptics’ Guide to Emergency Medicine.

SGEM#68: Sign, Sign Everywhere a Pediatric Vital Sign

Podcast Link: SGEM68
Date:  March 27, 2014

Guest Skeptic: Dr. Anthony Crocco Anthony is the pediatric member of the BEEM Dream Team. Anthony works at McMaster University and is the Medical Director and Division Head for Pediatric Emergency Medicine.

Case Scenario: 18 month old girl presents to the emergency department with viral gastroenteritis. She has vomiting, diarrhea and fever. Her heart rate is 165 beats per minute.

Screen Shot 2014-03-27 at 8.20.08 PMQuestion: What are the normal ranges for heart rate and respiratory rate in children?

Background: There are a number of ways you can assess pediatric vital signs.

  1. Clinical Gestalt
  2. PALS – Pediatric Advanced Life Support
  3. APLS – Advanced Pediatric Life Support
  4. Formula – a variety are available
  5. Apps – ex: PediStat

Article: Fleming S et al. Normal Ranges of Heart Rate and Respiratory Rate in Children from Birth to 18 Years of Age: A Systematic Review of Observational Studies. Lancet 2011; 377: 1011-18.

  • Population: Children 18 years and younger
  • 
Intervention: Observational studies on the normal heart rate or respiratory rate of children
  • Comparison: Reference ranges from existing text books
  • Outcome: No applicable

Authors Conclusions: “evidence-based centile charts for children from birth to 18 years”.

Quality Checklist:

  1. Clinically relevant question with an established criterion standard? Yes.
  2. Search detailed and exhaustive. No. The authors did a search of MEDLINE, EMBASE, CINHAL as well as checking reference lists. There were no language restrictions. The authors do not, however, discuss searching abstracts, conference proceedings or discussing with experts in the field.
  3. The methodological quality of primary studies were assessed for common forms of bias? Unsure. The authors did not address the quality of the studies included.
  4. Assessments of studies were reproducible? Unsure.
  5. Was there low between-study heterogeneity. Unsure.

Key Results: These figures present the summarized data from the 69 studies as well as how the pooled data relate to current norms presented by PALS and APLS.

Screen Shot 2014-03-27 at 8.08.34 PM

 

Screen Shot 2014-03-27 at 8.08.44 PM

 

Screen Shot 2014-03-27 at 8.08.51 PM

BEEM Comments: One of the more challenging aspects of pediatric emergency care is deciding when vital signs fall outside of the normal range. In the past, guidelines from PALS and APLS courses have directed care both at the nursing and physician level.

This well performed systematic review compiles all the data regarding normal heart rates and respiratory rates in children, including over 150,000 data points. The results provide a more accurate reflection of the normal ranges, with percentiles, for children of various ages.

The provided graphs should be used to replace current ‘best guess’ normal values. The implications for this research affect not only the physicians providing care, but also the nurses at triage deciding on level of acuity.

The Bottom Line: This is a well conducted systematic review of the pediatric normal values for heart rate and respiratory rate. The provided graphs should replace existing values from other sources.

Clinical Application: I quote and reference this paper ALL THE TIME!. Triage vitals at my hospital are measured against this graph. It is easy to have a PDF of these charts on your smart phone to use as a reference.

What do I tell my Patient: You daughters has abnormal vitals signs. I am going to treat her symptoms and see if we can make her better.

Case Resolution: 18 month old girl presents to the emergency department with viral gastroenteritis. She has vomiting, diarrhea and fever. Her heart rate is 165 beats per minute. I provide her with oral ondansetron (8-15kg=2mg, 15-30kg=4mg and >30kg=8mg) and oral rehydration therapy based upon our previous podcast SGEM#12: Oh Dance-a-Tron

Screen Shot 2014-03-27 at 8.35.21 PMKeener Kontest: Last weeks winner was Cornelia Härtel. She attended the SweetBEEM conference and saw the presentation on the Valsalva Maneuver. Clearly there must have been some knowledge translation. Cornelia knew that the Valsalva described the maneuver was to test the patency (openness) of the Eustachian tube. He also described the use of this maneuver to expel pus from the middle ear. I will be sending Cornelia the standard skeptical prize but also something special that relates back to Swedish culture.

If you want to play the Keener Kontest 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.

SweetBEEM 2014

The BEEM Dream Team of Drs. Anthony Crocco, Ken Milne and Suneel Upadhye. returned from Stockholm, Sweden this weekend. It was a fantastic trip filled with great experiences and knowledge translation.

Screen Shot 2014-03-19 at 9.27.15 AMThe adventure started with our arrival in the airport wearing Swedish hockey jerseys (while in Rome). This was despite the fact that Dr. Katrin Hruska lost the friendly bet on the Men’s Olympic goal medal game. She was a good sport and wore the Canadian Hockey jersey for the first day of the SweetBEEM course.

Dr. Arin Malkomian who co-organized the conference . He was wise enough not to bet against the Canada. However, we brought a jersey for him to wear as well.

IMG_2709We took a tour of Stockholm before the conference started. The highlight was visiting Stockholm city hall. This is where the Nobel prize reception is held. Suneel and I used the opportunity to waltz in the golden hall. It was the closest we will ever get to a Nobel prize.

IMG_4253Our group also took a tour of their major trauma centre (Karolinska Hospital) and paediatric emergency department (Astrid Lindgrens Hospital). The paediatric hospital is named after the author of the children book series, Pippi Long Stocking.

We appreciated Dr. Pia Malmqvist coming in on her day off to give us a tour. The trauma bay was connected to the surgical theatre on one side and CT scanner on the other. This made us stop and take pictures of the great design.

Then the two day SweetBEEM course began with 7hrs a day of high quality, clinically relevant evidence based medicine. The Scandinavian audience impressed us with their answers to our Turning Point questions. These doctors practice evidence based medicine even if they did not know it.

IMG_0156 IMG_0199The conference ended with a “friendly” game of BEEM Jeopardy. It was a very close competition with the lead changing through the game. Alex Trabek (Ken) had his sparkly coat and Vana White (Katrin) kept track of the questions. The winner was only named after the final jeopardy question. In the end, Norway placed first but everyone tasted sweet victory with a bottle of Canadian Maple Syrup.

The next day the BEEM Dream Team spoke at the Swedish national emergency conference. Suneel had a well attended talk on diving emergencies. His presentation even had video of diving with hundreds of hammer head sharks. Anthony gave a talk on teaching evidence-based medicine at the bedside and paediatric ECGs.

I was invited to debate the evidence for thrombolysis in acute CVA. The challenge was addressed as a scientist considering the null hypothesis that the tPA produces no effect or makes no difference. The burden of proof was upon Dr. Kjell Asplund who was making the positive claim.

Screen Shot 2014-03-24 at 6.12.14 PM

I presented the twelve major randomized control trials. There were four trials stopped due to harm or futility, six showing no difference, and only two showing benefit. This was not enough proof for me to reject the null hypothesis. I remain skeptical of the intervention. None of the arguments were directly addressed by Dr. Asplund. It was up to the audience to decide what to make of the information presented. A video of the presentations will be posted soon.

IMG_0117My favourite picture of the trip was of Katrin on the second day of the SweetBEEM conference. We were both feeling the glow of how well things were going. She is smiling at how it had worked out so well. I am watching the BEEMers in action hoping we will have another opportunity visit Scandinavia.

Five is my favourite number because I can count to it on one hand. Here is my Top Five list of SweetBEEM memories:

  1. Smart Docs: We were so very impressed repeatedly with the quality of evidence based medicine being practiced by the attendees.
  2. Garbage in Garbage Out:  Getting a Swedish translation of this EBM saying was great!
  3. Scooters: They have fancy little scooters to ride with a arrest is called for the resuscitation team to get to patients quickly.
  4. Fika: Canada may have its Double/Double (TIm Horton’s Coffee) and the USA may run on Dunkin Donuts coffee but the Scandinavians take their coffee breaks seriously.
  5. Come A Long Way: Emergency medicine may be a new specialty in Sweden but they have made huge progress in a relatively short time. Clearly it is due to organizations like Sweets, leadership from Drs. Hruska and Malkomian and an enthusiastic group of emergency physicians.

Thank you Sweden for a wonderful trip, great conference and many fabulous memories. Here is a short video to express our appreciation called “You’ve got a friend in BEEM:)” SweetBEEM 2-Medium

Remember to be skeptical of anything you learn, even if you heard it on the Skeptics’ Guide to Emergency Medicine.

SGEM#67: Shock the Monkey Tonight (Valsalva Maneuver for SVT)

Podcast Link: SGEM67
Date:  March 23, 2014

Case Scenario: 30 year old woman presents for the first time with supraventricular tachycardia (SVT). You call the cardiologist after three unsuccessfully attempts to chemically convert her into sinus. The cardiologists asked you why you did not try the valsalva maneuver (VM).

Question: Is the valsalva maneuver effective in converting supra ventricular tachycardia?

Article: Smith et al. Effectiveness of the Valsalva Manoeuvre for reversion of supraventricular tachycardia. Cochrane Database Syst Rev. 2013 Mar 28;3:CD009502. doi: 10.1002/14651858.CD009502.pub2.

Background: Patients with SVT often present to the emergency department. Life in the Fast Lane has a good blog posting about SVT.

Restoring patents back to a sinus rhythm can be done by the VM, drugs (adenosine, calcium channel blockers or beta-blockers) or electricity (synchronized cardioversion).

The VM is a non-invasive way to convert patients from SVT to sinus.It increases myocardial refractory period by increasing intrathoracic pressure thus stimulating baroreceptors in the aortic arch and carotid bodies Increases vagal tone (parasympathetic).

Screen Shot 2014-03-23 at 12.27.49 PMAnother way to convert patients that does not include drugs or electricity uses the mammalian dive reflex. This is used more often in children than in adults. Smith el al also published a review article on this method. The patient puts their face in an ice-cold bath. I have used this one time successfully on a patient who did not want to have adenosine again. I almost picked the mammalian dive reflex as the keener question.

  • Population: 316 patients presenting with SVT from 3 randomized controlled trials from Singapore, England, and Taiwan. 2 studies were done in a controlled arrhythmia lab setting after patients had ceased all medications. One study involved patients presenting undifferentiated to an ED with an episode of SVT.
  • 
Intervention: Valsalva maneuver defined by posture [supine or supine with legs elevated], strain duration [15 to 30 seconds], and pressure [intraoral with range 30 to 50 mm Hg].
  • Comparison: Standard pharmacological therapy for cardioversion of SVT.
  • Outcome: The primary outcome was reversion of SVT to sinus rhythm. Side effects, cardiovascular effects and mortality associated with VM use for SVT were not reported in any of the studies.

Authors Conclusions: “We did not find sufficient evidence to support or refute the effectiveness of the Valsalva Maneuver for termination of SVT. Further research is needed and this should include a standardized approach to performance technique and methodology.”

Quality Checklist: 

BEEM Critical Appraisal forms are available on at the SGEM: Make It So.

  1. Clinically relevant question with an established criterion standard? Yes. The question is clinically relevant but unfocused in terms of exact presentation of SVT (varying etiologies, such as primary or recurrent or artificial i.e. induced).
  2. Search detailed and exhaustive. Yes.
  3. The methodological quality of primary studies were assessed for common forms of bias? Yes. The authors assessed risk of bias using the Cochrane Handbook for Systematic Reviews of Intervention checklist to determine potential selection bias, performance bias, attrition bias, or detection bias. Most patients included were pre-selected, prepared and had lab-induced SVT.
  4. Assessments of studies were reproducible? Yes.
  5. Was there low between-study heterogeneity. No. The studies were very heterogeneous, only 1 included ED patients, and 2/3 included induced SVT with prior exclusions of home medications.

Key Results: With respect to the primary outcome of conversion of SVT, two of the studies provided reversion success rates of 54.3% (19/35) and 45.9% (61/133), respectively, while the third (the ER based study) reported reversion success of only 19.4% (12/62). Results could not be pooled due to heterogeneity.

BEEM Commentary: Only one of the included studies was on ED presentations of spontaneous SVT and not induced SVT (controlling for prior medications and co-morbidities). This grouped comparison is not applicable to the emergency medicine group and does not answer questions with respect to varying VM techniques. The patients with induced SVT in the lab, and who had prior medications held do not represent patients seen in the ED with spontaneous SVT or primary SVT. The authors recognize the fact the included review studies are limited in application to SVT presentations.

Bottom Line: There is no standardized methods to perform a VM to terminate uncomplicated SVT that are evidence based.

Screen Shot 2014-03-23 at 12.26.36 PMClinical Application: VM is a viable technique that is poorly researched for the conversion of SVT and should not be considered essential to attempt prior to chemical cardioversion. It may work in up to 20% of presentations. What do I tell my patient: We can try a valsalva maneuver (pushing air out with your throat, mouth, and nose closed) with reasonable safety while preparing medications for a rapid heartbeat like you have to attempt to correct your palpitations. However, there is no evidence that pushing the air out will be effective and may only work approximately 1 out of every 5 attempts.

Keener Kontest: Last weeks winner was Luis Rubio. He knew that I was going to be away teaching at SweetBEEM this week.

Listen to this weeks podcast for the Keener Question. If you know what the answer send me an email to TheSGEM@gmail.com with keener in the subject line. The first person to correctly answer the keener 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.

SGEM#66: King of Pain (Migraine Headaches)

Podcast Link: SGEM66
Date:  March 14, 2014

Case Scenario: 32yo woman presents with her usual migraine headache.

Questions: Does ketorolac work well for acute migraine headache treatment?

Background: More than 10% of people (6% men and 18% women) suffer from migraines. This condition represents a significant source of both medical costs and lost productivity. Direct costs are estimated at ~17 billion dollars a year. There are also indirect costs of about 15 billion dollars a year mainly due to missed work.

Up to half of patients presenting to the ED with their migraines will “bounce-back” to the ED in a few days. Dexamethasone has been tried in randomized control trials to prevent bounce-backs. Giuliano et al did a good review on this topic in Postgraduate Medicine last year.

SGEM#28: Bang Your Head talked about the paper by Coleman et al in BMJ on the subject of migraine bounce backs. It showed that a single parenteral dose of dexamethasone ≥15mg for successfully aborted migraine will significantly reduce early recurrences (NNT=9) with no significant side effects.

Reference: Taggart E et al. Ketorolac in the Treatment of Acute Migraine: A Systematic Review. Headache 2013; 53: 277-287

  • Population: Eight studies of adult patients (n=321) presenting to the ED with acute severe migraine headache
  • Intervention: Ketorolac parental alone or in combination with other migraine abortive therapies
  • Comparison: Placebo or other standard therapy
  • Outcome: Efficacy (pain relief) and safety

Authors Conclusions: ”Overall, ketorolac is an effective alternative agent for the relief of acute migraine headache in the emergency department. Ketorolac results in similar pain relief, and is less potentially addictive than meperidine and more effective than sumatriptan; however, it may not be as effective as metoclopramide/phenothiazine agents.” 

Quality Check List:

  1. Sensible and answerable – Yes
  2. Detailed and exhaustive search – Yes
  3. High methodological quality – Yes
  4. Studies reproducible – Yes
  5. Outcomes clinically relevant – Yes
  6. Low heterogeneity – Yes
  7. Large and Precise – Yes

Results: Pooled estimates showed no difference in pain relief at 60 minutes between ketorolac alone or in combination compared to placebo or other standard therapy. For meperidine WMD=0.44 (95% CI= – 0.49 to 1.38) and heterogeneity was low (I2=0%).

Only one trial compared ketorolac to sumatriptan and demonstrated significant reduction in migraine pain at 60 minutes (WMD -4.07, 95%CI -6.02—2.12).

Only two trials compared ketorolac to phenothiazine with no significant benefit noted on the summary estimate (WMD 0.82, 95%CI 0.82, 95% CI -1.33- 2.98), though significant heterogeneity was identified (I2 = 70%).

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Commentary: There is a wide variety of practice variations in the treatment of acute migraine. This may be because no single approach has been shown to be clinically superior. This study attempted to review what role ketorolac can play in the treatment of these common and painful presentations to the emergency department.

This SR started with some difficulty because while diagnostic criteria for migraine exist, they are often not used in the emergency department. This made it unclear if patients meet criteria for the diagnosis of migraine. The SR included studies that gave ketorolac IM in 6/8 studies with 5/6 studies using 60mg IM. Giving any medication IM vs. oral increases the placebo effect and could have influenced the results in some of these studies.

The quality of the primary studies was moderate to high quality on the Jadad score (3). However, the bias was either “high” or unclear.

The conclusion of ketorolac being more effective than sumatriptan was based on one RCT from 2003 of only 29 patients and should be viewed with caution.

The discussions of ketorolac +/- meperidine seem a bit irrelevant because most departments no longer have meperidine on their formulary. Ketorolac would be the preferred treatment in the ED due to the potential for abuse and addiction with meperidine.

There was very inconsistent information on rescue medications and no reporting on relapse rates. Previous BEEM review has demonstrated a single dose of dexamethasone can decrease migraine headache recurrence and bounce backs to the ED following an acute migraine (NNT=9).

This SR was of moderate quality, included small studies, high/unclear bias, inconsistent outcome reporting, and lack of data on relapse.

Bottom Line: Ketorolac is a reasonable second-line agent in the treatment of acute migraine.

Clinical Application: Will tend to use ketorolac only as a second-line agent in the treatment of acute migraine.

Screen Shot 2014-03-09 at 11.12.30 AMCase Resolution? I can see you are in pain and that is important to me. We will try some standard treatments first that have been shown to work. I will check back with you in 30-60 minutes to see how you are doing. If your pain is not controlled there is a plan B.

Keener Kontest: Last weeks winner was Jaime Davis from Florida. He correctly answered the riddle of the Sphinx ““What goes on four feet in the morning, two feet at noon, and three feet in the evening?”

Listen to this weeks episode of the SGEM for the Keener Kontest? If you know the answer send an email to TheSGEM@gmail.com with “keener” in the subject line. The first person will receive a skeptical prize.

Remember to be skeptical of anything you learn,

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