August 2018

Author: Becky Maxwell / Codes: CMP2, HMP2, CAP18, HAP20, HAP25, CC4, CC5, CAP28, HAP14, HAP28, HAP15, CAP17, CAP27 / Published: 01/08/2018

Authors:

Dave McCreary
Andy Neill

Codes:

CMP2, HMP2

Clinical Question:

Does adrenaline actually work for cardiac arrest?

Title of Paper:

A Randomised Trial of Epinephrine in Out-of-Hospital Cardiac Arrest

Journal and Year:

NEJM. July 2018.

Lead Author:

Perkins

Background:

  • We have limited offerings at our disposal for treatment of cardiac arrest. Early CPR and early defibrillation have been shown to improve outcomes, but the evidence for resuscitation drugs such as adrenaline (epinephrine if your across the pond) isnt so convincing.
  • The Theory:
  • Acts on -adrenergic receptors:
  • arteriolar constriction increased aortic diastolic BP during CPR improved coronary blood flow improved change of return of spontaneous circulation (ROSC)
  • also causes platelet activation thrombosis and impairment of cerebral cortex microvascular blood flow increased severity of cerebral ischaemia during CPR and post ROSC
  • Acts on -adrenergic receptors:
  • Increases chance of dysrhythmias
  • Increase myocardial oxygen demand, risking recurrent cardiac arrest
  • Previous studies have looked at standard (1mg) dose adrenaline vs high-dose (5-10mg), vs adrenaline+vasopressin, and vs placebo but not shown better outcomes
  • Generally it has been shown to improve ROSC, but not favourable neurological outcome
  • The previous attempt to perform an RCT (the PACA trial) only recruited 10% target before being stopped early

Study Design:

  • Multicentre, randomised, double-blind, placebo-controlled trial (PARAMEDIC2)
  • 5 NHS ambulance services in the UK

Patients Studied:

  • Adult patients with sustained out-of-hospital cardiac arrest (initial resuscitation with CPR defibrillation unsuccessful)
  • Exclusions:
  • Pregnancy
  • Age <16 years
  • Anaphylaxis & asthma arrests
  • Admin of adrenaline prior to arrival of trial-trained paramedic

Intervention:

  • Parenteral adrenaline (1mg) q3-5 mins

Comparison:

  • Placebo (0.9% saline) q3-5mins

Outcomes:

  • Primary: survival rate at 30 days
  • Secondary:
  • Neuro outcomes at discharge and at 3 months
  • Favourable = modified Rankin score 3 (3 = Moderate disability, requires some assistance but mobilises independently)
  • Survival to hospital admission
  • Hospital & ICU length of stay (LOS)
  • Survival at hospital discharge and at 3 months

Summary of Results:

  • 8014 patients: 4015 got adrenaline, 3999 got placebo
  • Survival at 30 days:
  • Adrenaline 3.2%, placebo 2.4%
  • unadjusted OR for survival 1.39 [95%CI 1.06 – 1.82; p=0.02]
  • NNT 112 to prevent one death at 30 days
  • Favourable neuro outcome at 3 discharge and 3 months:
  • No difference: Adrenaline – 87/4007 (2.2%), Placebo 74/3994 (1.9%)
  • Unadjusted OR 1.18 [95%CI 0.86 – 1.61]
  • Severe neuro impairment (4 or 5 on mRS):
  • More common with adrenaline: 31.0% vs 17.8%
  • Survival to hospital: Adrenaline > placebo
  • ICU admission: Adrenaline > placebo

Authors Conclusion:

The use of adrenaline resulted in a significantly higher rate of survival at 30 days that the use of placebo, but there was no significant difference in the rate of favourable neurological outcome because more survivors have severe neurologic impairment in the adrenaline group.

Clinical Bottom Line:

NNT adrenaline 112
NNT early recognition of cardiac arrest 11
NNT bystander CPR 15
NNT early defibrillation 5
Maybe there are better things we should be concentrating on in cardiac arrest, eh? Around 60% patients had bystander CPR in this study (good on you, UK!). It has also been announced that the government is aiming to have CPR in the school curriculum by 2020, that should help.
There are lots of questions that remain when it comes to adrenaline: Whats the right dose (is <1mg actually the sweet spot?)? Whats the right dose interval? Bolus or infusion? Should it only be for non-shockable rhythms or even just PEA? Should we be chucking it straight in the Aorta (shout out to Prof Manning there)? In the meantime, I have an OSCE approaching so I’ll be toeing the line and giving my 1mg of adrenaline every other cycle until they change the guidelines to say otherwise. Also worth remembering this was a pre-hospital study with pretty long interval from down time to first dose of adrenaline (22 minutes) – so this probably isn’t directly applicable to hospital or even ED practice.
There has been some debate in the twitter sphere about the benefits of ROSC patients making it to the ICU regardless of the neurological sequelae as there is potential for them to become organ donorsI’ll leave that one out there for you to debate amongst yourselves, but I dont think that was in the remit of the trial
Other #FOAMed Resources / References:
As you would expect, the FOAMed world has been all over this:
St.Emlyn’s were straight in with this Journal Club the day the study was released, as always well played Carley
Justin at first10em blogged this review
EMNerd discusses the case of the costly compound
Our old buddies at the resus room covered the paper with an interview with the lead author
RebelEM also have a podcast on this paper here
A few years ago I recorded a podcast at the London Cardiac Arrest Symposium with Prof. Jim Manning on intra-aortic adrenaline in cardiac arrest – have a listen here

Codes:

CAP18

Definition

‘Sport related concussion is a traumatic brain injury induced by biomechanical forces’

All in the history taking:

No macroscopic damage to brain but altered function more research and technology gets better this may be debated. Therefore for an ED perspective it is a functional diagnosis with a normal MRI/CT scan

Head injury/insult

Headache dizziness, nausea, vomiting, no neurology or localizing signs

Functional autonomic symptoms

NOT LOC!!!! Only occurs in approx. 10 %

Previous concussion history is very important!

Short tem complications of Concussion:

  • Functional problems both at school and at work
  • Prone to get another concussion
  • 6 x more likely to get an MS injury
  • Second Impact Syndrome massive cerebral oedema and death
  • Due to altered autoregulation within the brain

Medium complications

  • Recurrent concussions

Long-term complications

  • CTE chronic Traumatic Encephalopathy and possible links with dementia though currently further work is needed

What do we tell patient who have concussion and want to return to sport?

Staged return to life or to play.

Gradually build yourself up to normal wife over a week or so Normal life comes first!!

Followed by gradual return to play

See berlin document

or Sports Scotland Concussion Guidance

for full details

First stage exercise bike if no symptoms the next day light jog slowly progressing to training with team in non contact way before finally starting training again.

By the time you have added up ‘Return to Normal Life’ and ‘Return to sport’

minimum 12 days for adults and under 19 year olds minimum 23 days

This is a minimum time not a target!

If at any stage you get are of symptoms you drop back a level of sporting activity.

Patients who return to ED with ongoing concussion symptoms:

Will need follow up by specialists and MRI as OP find out who your local brain rehabilitation expert is!

Author:

Dave McCreary

Codes:

CAP27, HAP20, HAP25

Nerve agents have been getting a bit of press recently so we thought that was a good opportunity to refresh our memories on what they are and how we should manage poisoned patients in the ED – just in case the next case comes to your shop.

In this segment we go into a little bit of the history of nerve agents so you know your sarin from your VX from your Novichoks, then we look at the symptoms to expect, and finally how the initial management should go.

The jist?

– Nerve agents are organophosphates so treatment is the same – you’ll probably just have to go harder on the dosing.
– Wear PPEdont be that guy.
– Decontaminate patients with soap and water – learn how decontamination would work in your department
– Give atropine to all symptomatic patients
– Atropinisation is what we’re aiming for:
– Clear chest
– HR >80 bpm
– SBP >80 mmHg
– Atropine dosing is big – the regime suggested from the 2012 RCT (see reference below) is:
– 1mg initial dose (toxbase advises 2mg ) – if it works, they probably weren’t that poisoned, and it might be something else altogether
-If it doesn’t – bring out the big guns:
– 1.8-3.0mg, repeat and double the dose every 5 minutes until atropinisation
– Start an infusion at 10-20% the final dose needed
– Titrate as needed (see the trial or talk to your friendly neighbourhood toxicologist for more info)
– Next give pralidoxime 2g over 20-30 minutes (30mg/kg for kiddies)

References:

  1. Abedin, Mohammed Joynal, Abdullah Abu Sayeed, Ariful Basher, Richard J Maude, Gofranul Hoque, and M. A. Faiz. Open-Label Randomized Clinical Trial of Atropine Bolus Injection Versus Incremental Boluses Plus Infusion for Organophosphate Poisoning in Bangladesh. Journal of Medical Toxicology 8, no. 2 (June 2012): 10817.
  2. Gupta, Ramesh C., ed. Handbook of Toxicology of Chemical Warfare Agents. Second edition. Amsterdam; Boston: Elsevier/AP, Academic Press is an imprint of Elsevier, 2015.
  3. Ian Greaves, Paul Hunt. CHAPTER 5 – Chemical Agents, Responding to Terrorism – A Medical Handbook. Churchill Livingstone, 2010, Pages 233-344, ISBN 9780080450438, https://doi.org/10.1016/B978-0-08-045043-8.00005-2.
  4. Toxicology (Oxford Desk Reference). Oxford University Press.

Codes:

CC4, CC5

Nikki Abela catches up with the renowned Damian Roland at the hugely successful #PEMFest (which he organised), to speak about a recent article topic in the BMJ which he wrote together with Edward Snelson entitled ‘So why didnt you think this baby was ill? Decision making in acute paediatrics. Be sure to read the full article linked here, and if you want to think further, why not follow Damian on his site rolobotrambles.com and Edward at gppaedstips.blogspot.com ? RCEMLearning will be delving deeper in this topic in our iBook aimed at induction for PEM, due in September, so keep your eyes peeled for that.

Codes:

CAP28, HAP14, HAP28

Measles:

PHE guidance

So it’s the height of summer and we have decided to talk about measles why I hear you ask, I haven’t seen a measles case in my life I hear you say.

Well if you have seen the news and been watching Public Health Alerts you will know it is back we have had a particular problem with it in Bristol so we thought wed update you on the signs and symptoms and any important things we have learnt down here in the South West to help should measles end up coming your direction

Why should we care? Well its highly infectious inf act the most infectious respiratory bug, with high risk groups being immunocompromised and the very young, it increases the risk of miscarriage and still birth in pregnant people.

Signs/symptoms:

Clinical likely diagnosis you need ALL of the following Cough AND coryzal illness AND conjunctivitis AND temp >39 in absence of antipyretics AND maculopapular rash.

SO identification and isolation really important here otherwise we create a public health nightmare but are now much better at these.

  • Infectious for about 4 days pre rash to 4 days after it develops.
  • Incubation period 7-21 days
  • Droplet spread but really infectious – one of the highest, with a basic reproduction number (R0) estimated around 15 20 (i.e. on average, there will be 15 – 20 individuals infected from a single case in a totally susceptible population) compared to Ebola 1.5-2.5 and flu 2-3!!!!

At risk groups:

  • Immunocompromised
  • Pregnant women premature labour,
  • Unvaccinated

1 MMR 90% effect 2 95% – therefore small subset will still be susceptible despite being vaccinated importance of herd immunity.

If staff are unvaccinated or not immune and come into contact its 21 days off! So we have had to check IGG on staff who OH have no measles records on to ensure they are safe to work in ED.

Why is this so important what are the complications?

  • viral pneumonitis
  • otitis media
  • Interestingly – Measles infection often leads to a temporary reduction in immune responses in the few weeks following infection, which may increase the risk of severe secondary bacterial and viral infections such as Tracheobronchitis (measles croup again never heard of this!!!) and pneumonia
  • Encephalitis occurs more rarely, in about 0.05% to 0.1% of measles cases
  • Subacute sclerosing panencephalitis (SSPE) is a very rare but very severe complication, occurring in about 0.01% of cases presents a few years after measles infection with progressive neuro-cognitive symptoms which in most cases lead to coma and death. The risk of SSPE is increased in children who acquire measles before the age of 1 year.

SO we have now assessed the patient and think they have measles what to we do?

Supportive treatment fluids etc. and

Phone PHE ASAP (you can also email a form)

PHE will send a test to people at home to do oral secretions are tested so no need to do in ED unless admitted. IGM and IgG may not be present in serum forseveral days whereas both can be detected in oral fluid 3 days prior to rash developing for 3 weeks. If stable some good advice and discharge.

SO all in all —— need to be prepared, bit like flu it may well come your way if it hasn’t already, identify and isolate. Protect members of staff now. Very few people need admission so discharge home and contact PHE in most cases with good safety netting advice.

Authors:

Dave McCreary
Andy Neill

Codes:

HAP15

Clinical question:

– Is Levitiracetam a better drug for status epilepticus than good old phenytoin

Title:

– Intravenous levetiracetam vs phenytoin for status epilepticus and cluster seizures: A prospective, randomized study
– https://www.ncbi.nlm.nih.gov/pubmed/28528211

Author:

– Gujjar, Seizure, 2017, from Oman

Background

– Status is common and most algorithms place phenytoin immediately after our benzos have failed. It’s a pain to make up and can cause big issues if infused too fast. It is also not 100% effective. There are lots of other agents available but very little data to support any of it

Methods:

– open label (they say for “patient safety” but i’m not sure i buy that…)
– Allowed a single small dose benzo (4mg loraz) before the study drug
– seems like they were randomised at beginning of seizure and if it was still going they gave a benzo and then study drug and if it had stopped already they just gave study drug
– phenytoin 20/kg v leviteracetam 30/kg both over 30 mins
– Note keppra can probably be safely given over 10-15mins
– if further seizure then an extra 10/kg of the study drug was given and if that failed then the full dose of the alternate study drug was given
– only then were the anaesthetic drugs pulled out
– they acknowledge that 500 probably needed but chose 100 as it was more realistic
– also included cluster seizures (2 or more within 24 hrs but with normality in between)

Results

– in the end they got 52…
– most were standard epilepsy
– 70% needed the benzo before study drug
– 82% control v 70% with phenytoin
– half of the patients here had a poor MRS – which surprises me but also implies they were pretty sick
– had 63 with cluster seizures with 80% resolution with both drugs

Thoughts

– they conclude optimistically that lev might be better and they claim safety but I don’t think they can do any such thing. I don’t think you can make strong claims about anything based on this very flawed study.
– that being said it’s important to be aware that there are alternatives to phenytoin (used largely because we’ve had it for so long) and that you may need additional drugs including levitiracetam and valproate
– we’re currently down to our last dose of phenobarb so we’ve added levitiracetam if needed

Codes:

CAP28, HAP14, HAP28

Measles:

PHE guidance

So it’s the height of summer and we have decided to talk about measles why I hear you ask, I haven’t seen a measles case in my life I hear you say.

Well if you have seen the news and been watching Public Health Alerts you will know it is back we have had a particular problem with it in Bristol so we thought wed update you on the signs and symptoms and any important things we have learnt down here in the South West to help should measles end up coming your direction

Why should we care? Well its highly infectious inf act the most infectious respiratory bug, with high risk groups being immunocompromised and the very young, it increases the risk of miscarriage and still birth in pregnant people.

Signs/symptoms:

Clinical likely diagnosis you need ALL of the following Cough AND coryzal illness AND conjunctivitis AND temp >39 in absence of antipyretics AND maculopapular rash.

SO identification and isolation really important here otherwise we create a public health nightmare but are now much better at these.

  • Infectious for about 4 days pre rash to 4 days after it develops.
  • Incubation period 7-21 days
  • Droplet spread but really infectious – one of the highest, with a basic reproduction number (R0) estimated around 15 20 (i.e. on average, there will be 15 – 20 individuals infected from a single case in a totally susceptible population) compared to Ebola 1.5-2.5 and flu 2-3!!!!

At risk groups:

  • Immunocompromised
  • Pregnant women premature labour,
  • Unvaccinated

1 MMR 90% effect 2 95% – therefore small subset will still be susceptible despite being vaccinated importance of herd immunity.

If staff are unvaccinated or not immune and come into contact its 21 days off! So we have had to check IGG on staff who OH have no measles records on to ensure they are safe to work in ED.

Why is this so important what are the complications?

  • viral pneumonitis
  • otitis media
  • Interestingly – Measles infection often leads to a temporary reduction in immune responses in the few weeks following infection, which may increase the risk of severe secondary bacterial and viral infections such as Tracheobronchitis (measles croup again never heard of this!!!) and pneumonia
  • Encephalitis occurs more rarely, in about 0.05% to 0.1% of measles cases
  • Subacute sclerosing panencephalitis (SSPE) is a very rare but very severe complication, occurring in about 0.01% of cases presents a few years after measles infection with progressive neuro-cognitive symptoms which in most cases lead to coma and death. The risk of SSPE is increased in children who acquire measles before the age of 1 year.

SO we have now assessed the patient and think they have measles what to we do?

Supportive treatment fluids etc. and

Phone PHE ASAP (you can also email a form)

PHE will send a test to people at home to do oral secretions are tested so no need to do in ED unless admitted. IGM and IgG may not be present in serum forseveral days whereas both can be detected in oral fluid 3 days prior to rash developing for 3 weeks. If stable some good advice and discharge.

SO all in all —— need to be prepared, bit like flu it may well come your way if it hasn’t already, identify and isolate. Protect members of staff now. Very few people need admission so discharge home and contact PHE in most cases with good safety netting advice.

Codes:

CAP27, HAP20, HAP25

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