JC: Salt or Sugar? Hypertonic saline for head injury at St.Emlyn’s.

St.Emlyn's - Meducation in Virchester #FOAMed

‘Why did you give Mannitol?’ asked the Registrar. ‘Hypertonic saline was the standard of care for head injury at St.Elsewhere and I was told it reduced mortality’. OK, so that’s a paraphrased recollection from some time ago. Our patient had presented with a GCS of 12: CT scan showed a large subdural haematoma and on […]

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Global Drug Reference Online – Global DRO

The Global Drug Reference Online (Global DRO) provides athletes and support personnel with information about the prohibited status of specific medications based on the current World Anti-Doping Agency (WADA) Prohibited List. Global DRO does not contain information on, or that applies to, any dietary supplements.

The new, updated and readily accessible website for Global DRO is found here:


The Global DRO allows users to search for specific information on products sold in the United Kingdom, Canada, the United States, Japan and Australia. The Global DRO provides the same critical information to athletes and support personnel about the prohibited status of specific substances under the rules of sport, based on the current World Anti-Doping Agency (WADA) Prohibited List. Various ingredients and brands, and more specifically whether they are classified as “Prohibited”, “Not Prohibited”, or “Conditional”.

It is increasingly common for high level and elite athletes to attend emergency departments for management of medical complaints. We are often unaware of the complexity of drug administration in such athletes and blind to the implications of inpatient treatment and outpatient prescribing. Although many of these athletes have a sports physician caring for them in the community – many do not.

Recently one of the athletes I look after attended emergency for management of cellulitis and was discharged with a script for probenecid. A quick search of the Global DRO confirmed this agent to be a prohibited substance for the athlete liable to a 2 year ban without an appropriate therapeutic drug exemption (TUE).

Having a readily accessible, updated database for country of origin medications makes it much easier for athletes and medical professionals to ensure compliance with the WADA code of conduct pertaining to medication administration and ingestion.

probenecid global DRO rugby

The Global DRO directory is updated regularly to include new products entering the marketplace, or to adjust for changes in the Prohibited List status. All data is fully verified by pharmacists experienced in the field of anti-doping.

The data sources for the Global DRO include:

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Research and Reviews in the Fastlane 132

Research and Reviews in the Fastlane

Welcome to the 132nd edition of Research and Reviews in the Fastlane. R&R in the Fastlane is a free resource that harnesses the power of social media to allow some of the best and brightest emergency medicine and critical care clinicians from all over the world tell us what they think is worth reading from the published literature.

This edition contains 6 recommended reads. The R&R Editorial Team includes Jeremy Fried, Nudrat Rashid, Soren Rudolph, Anand Swaminathan and, of course, Chris Nickson. Find more R&R in the Fastlane reviews in the R&R Archive, read more about the R&R project or check out the full list of R&R contributors

This Edition’s R&R Hall of Famer

Research and Critical Appraisal
R&R Hall of Famer - You simply MUST READ this!

Saini P et al. Selective reporting bias of harm outcomes within studies: findings from a cohort of systematic reviews. BMJ  349:g6501. 2014. PMID: 25416499

  • These authors looked at how accurately harms are reported in studies. Looking at a general cohort of studies, the found that the studies either didn’t report harms, or only partially reported harms 76% of the time. It is an important reminder that we tend to minimize our discussions of harm. For most therapies, it is likely that the true harms are greater than those reported in clinical trials.
  • Recommended by: Justin Morgenstern

The Best of the Rest

Emergency Medicine, Urology
Schultz L et al. Top Ten Myths Regarding the Diagnosis and Treatment of Urinary Tract Infections. J Emerg Med 2016. PMID: 27066953

  • Misinterpretation of the urinalysis is a common issue in the Emergency Department. This article reviews 10 myths about the UA and UTIs. A common theme that permeates the article is that an abnormal UA is not diagnostic of a UTI: symptoms must be present as well since a significant portion of patients will have chronic colonization. A good lesson to keep in mind the next time you work clinically.
  • Recommended by: Anand Swaminathan

Emergency Medicine, Neurology
Friedman BW et al. The association between headache and elevated blood pressure among patients presenting to an ED. The American journal of emergency medicine. 32(9):976-81. 2014. PMID: 24993684

  • More data that BP & HA aren’t related. To be fair, the patients with headaches had higher BPs, but lowering BPs didn’t make a difference. One more reason to explain to the patient, the referring doc, the floor staff, etc, that no, their head is not about to explode.
  • Recommended by: Seth Trueger

Education, Psychiatry and Mental Health
R&R Eureka - Revolutionary idea or concept
Konopasek L, Slavin S. Addressing Resident and Fellow Mental Health and Well-Being: What Can You Do in Your Department? J Pediatr. 2015 Dec;167(6):1183-1184.e1. PMID: 26611453

  • Although some of our medical elders laugh about how easy residents have it as compared to the ‘good old days’, residency is still incredibly stressful and residents are at high risk for burnout and depression. We need to look after our own. Some suggestions from this article: try to decrease the stigma around mental health in medicine, role model healthy behaviours, make mental well being an emphasis during orientation, and specifically check in with residents to see how they are coping.
  • Recommended by: Justin Morgenstern

Emergency Medicine, Pediatrics, Gastroenterology
R&R Hot Stuff - Everyone’s going to be talking about thisTseng HJ et al. Imaging Foreign Bodies: Ingested, Aspirated, and Inserted. Ann Emerg Med 2015. PMID: 26320521

  • An excellent, in depth review of finding and managing foreign bodies that are ingested, aspirated or inserted. The authors create some great tables that can act as rapid access guides on your smart device for just in time clinical guidance.
  • Recommended by: Anand Swaminathan

Research and Critical Appraisal
R&R Eureka - Revolutionary idea or concept
Zipkin DA, et al. Evidence-based risk communication: a systematic review. Annals of internal medicine. 161(4):270-80. 2014. PMID: 25133362

  • Statistics are easily gamed and, are increasingly called upon as we engage patients in shared decision making, Communicating with patients – Think the number need to treat (NNT) is the best way? That’s not what this review found. They found that participants most accurately perceived risk when presented with absolute risk reduction but were most swayed by relative risk.
  • Recommended by: Lauren Westafer

The R&R iconoclastic sneak peek icon key

Research and Reviews The list of contributors R&R in the FASTLANE 009 RR Vault 64 The R&R ARCHIVE
R&R in the FASTLANE Hall of Famer R&R Hall of famer You simply MUST READ this! R&R Hot Stuff 64 R&R Hot stuff! Everyone’s going to be talking about this
R&R in the FASTLANELandmark Paper R&R Landmark paper A paper that made a difference R&R Game Changer 64 R&R Game Changer? Might change your clinical practice
R&R Eureka 64 R&R Eureka! Revolutionary idea or concept R&R in the FASTLANE RR Mona Lisa R&R Mona Lisa Brilliant writing or explanation
R&R in the FASTLANE RR Boffin 64 R&R Boffintastic High quality research R&R in the FASTLANE RR Trash 64 R&R Trash Must read, because it is so wrong!
R&R in the FASTLANE 009 RR WTF 64 R&R WTF! Weird, transcendent or funtabulous!

That’s it for this week…

That should keep you busy for a week at least! Thanks to our wonderful group of editors and contributors Leave a comment below if you have any queries, suggestions, or comments about this week’s R&R in the FASTLANE or if you want to tell us what you think is worth reading.

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Funtabulously Frivolous Friday Five 143

Just when you thought your brain could unwind on a Friday, you realise that it would rather be challenged with some good old fashioned medical trivia FFFF…introducing Funtabulously Frivolous Friday Five 143

Question 1

What is Fagan famous for in evidence-based medicine (nothing to do with Oliver Twist)?

  • The Fagan nomogram converts pre-test porbabilities into post-test probabilities using the likelihood ratio for any given test.



Question 2

What do a sloth bear and local people in the Central Indian Highlands get from Madhuca flowers?

  • A hangover.
  • They both eat them when they’ve fermented so as to get drunk.

Question 3

What was Dr Guedel’s dog called and what did he do to it?

  • His dog’s name was Airway.
  • He intubated it of course. He wanted to prove that a cuffed ETT tube would prevent aspiration so he famously submerged his dog with the cuffed ETT while it was anaesthetised. Pulled the dog out of the water and woke them up. “Airway” than ran out of the auditorium thus proving his invention was a success. [Reference]


Question 4

A patient presents one week after having a CTPA with tachycardia, hyper-reflexia, heat intolerance and loose bowel motions, labs indicate hyperthyroidism. What phenomenon has occurred?

  • The Jod-Basedow phenomenon. Jod is the German word for iodine and Karl Adolph von Based was the German physician who first described the effect.
  • It is hyperthyroidism following administration of iodine or iodide either dietary or as contrast medium. It does not occur in those patients with a normal thyroid but in those with Graves, toxic multi nodular loiter or thyroid adenomas as it needs a part of the gland that is not suppressed by the actions of the pituitary.
  • Wolf-Chaikoff effect is the opposite which can occur in patients with a normal or diseased thyroid whereby large quantities of iodine or iodide suppress thyroid function. [Reference]

Question 5

Dying on the throne can be embarrassing, who does the following describe?

    He rose at the usual hour of six o’clock. His German valet de chamber (Schroder) stating he ‘never looked better’ on receiving his cup of chocolate. He threw up at the window and looked onto the South-east gardens. He asked Schroder about the weather and wind direction. Since he received favourable answers he announced his intention of walking in the gardens. At quarter past seven, he retired to “a little closet’ to empty his bowels. After a time there was a “noise louder than the royal wind” followed by a groan and a thud.

tywin toilet

  • King George the Second.
  • He died of a rupture in his right ventricle causing a pericardial tamponade.
  • Blood letting was the done thing and his doctor complained he was not able to perform this due to lack of circulation once he got to the king. Probably was not going to help. [Reference]


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The Heparin Citrate Study


A Randomized Controlled Trial of Regional Citrate Versus Regional Heparin Anticoagulation for Continuous Renal Replacement Therapy in Critically Ill Adults

Gattas DJ. Journal Crit Care Med 2015;43(8):1622-9. doi: 10.1097/CCM.0000000000001004

Clinical Question

  • In critically ill patients requiring continuous renal replacement therapy (CRRT), does regional anticoagulation with citrate prolong circuit life compared to heparin and protamine?


  • Randomised controlled trial
  • Multicenter
  • Randomisation stratified by study site
  • Each site used a randomly generated sequence of numbers in permuted block sizes of 4,6 and 10 to allocated study groups
  • Intention to treat analysis
  • Clinicians unblinded. The statistician was blinded to group allocation until completion of the primary outcome analysis
  • Sample size calculation: 218 study subjects provided 80% power to detect a difference in mean circuit survival of 4 hours


  • Seven ICUs: Six Australian and one New Zealand
    • Four tertiary referral units and three metropolitan
  • May 2010 – January 2013


  • Inclusion: acute renal failure requiring CRRT and suitable for regional anticoagulation of the CRRT circuit; clinical equipoise regarding the method of circuit allocation
  • Exclusion: expected stay in ICU less than 24 hours; age less than 18 years; pregnant or breastfeeding; suspected ischemic hepatitis or liver failure; known allergy to heparin or protamine; suspected or confirmed heparin induced thrombocytopenia (HIT); chronic kidney disease requiring dialysis prior to ICU admission.
  • 212 patients randomised. 857 circuits
  • Baseline characteristics between groups were similar in respect to severity of illness and common renal and haematological laboratory results. More patients were admitted to the ICU from the Emergency Department in the heparin group compared with the citrate group (35.5% vs 22.9%)


  • Regional citrate anticoagulation with maintenance of systemic normocalcemia


  • Regional heparin anticoagulation with protamine reversal to avoid systemic anticoagulation


  • Primary outcome: functional circuit life was longer in the group receiving citrate anticoagulation
    • median circuit life of first circuit: 39.2 hours [95% CI, 32.1–48.0] vs 22.8 hours [95% CI, 13.3–34.0] P=0.0037
    • circuits clotting: 57.9% vs 66.4% P < 0.02
    • median circuit life of clotted circuits: 16.5 hours (IQR 21.1 hours) vs 11.8 hours (IQR 14.3 hours) P =< 0.0001
    • the hazard ratio for a filter clotting in the heparin group (compared to citrate) was 2.03 (95% CI 1.36-3.03) P=<0.005

Circuit stopped if one of following occured: transmembrane pressure across the circuit exceeded 300 mm Hg; visible clot was obstructing flow through the machine; the blood pump was unable to rotate due to clot obstruction; other (free-text entry by bedside staff)

  • Secondary outcomes: No statistical difference between groups
    • change in interleukin-6, interleukin-8, and interleukin-10 between randomsation and 48–72 hours later
    • ICU mortality: 26.7% in citrate group vs 23.4% in the heparin group P=0.58
    • ICU length of stay: 9 days vs 9 days P=0.79
    • hospital mortality: 31.4% vs 29% P=0.7
    • red cells transfused:
      • patients transfused: 52% vs 47% P=0.58
      • mean volume of red cells: 908 vs 872 P=0.83
    • duration of CRRT
      • total patient time on circuit in hours: 8282 vs 8015
      • medial hours per patient on circuit: 55.7 vs 50.6 P=0.6
  • Adverse outcomes: there were more adverse events in the heparin group (11 events, three serious) compared with the citrate group (two events, one serious) although this did not reach statistical significance (P= 0.011 for all events). The most common adverse event was suspected or confirmed HIT, resulting in discontinuation of study treatment

Authors’ Conclusions

  • Regional citrate and calcium anticoagulation prolongs CRRT circuit life compared with regional heparin and protamine anticoagulation, does not affect cytokine levels, and is associated with fewer adverse events


  • RCT
  • Multi-centre (although 74% of the patients were from two centres)
  • Statistician was blinded to group allocation until after primary analysis
  • No patients lost to follow up
  • Large trial compared to previous trials (857 circuits)
  • Examined other factors that could have affected filter life, including coagulation screens, platelet counts, catheter insertion sites, renal replacement modality, blood flow rates and ratio of pre- & post-dilution


  • More patients were admitted to the ICU from the Emergency Department in the heparin group compared with the citrate group (35.5% vs 22.9%)
  • Unblinded
  • Underpowered to detect important patient-centered outcomes such as mortality, time in ICU, time in hospital and renal recovery
  • A cost analysis would have been useful
  • large number of patients excluded from study limits external validity – 1219 patients excluded due to not meeting inclusion critera (these all presumably treated with CRRT)

The Bottom Line

  • In patients needing continuous renal replacement therapy, regional anticoagulation with citrate and calcium extends filter life in comparison with regional heparin and systemic reversal with protamine
  • Given the greater efficiency and safety of citrate, serious consideration should be given to its use as first line anticoagulation in continuous renal replacement.

External Links


Summary author: Phil McGlone
Summary date: 23rd April 2016
Peer-review editor: Steve Mathieu

Declaration of interest: Celia Bradford is an editor for TBL. She is a grant applicant, investigator and an author for this paper. She has not been involved in writing or reviewing this summary and critique