Drug-to-drug interaction. New evidences on Morphine and delayed onset of action of antiplatelet agents.

11 mag Logo MEDEST2

A recently published article entitled  “Chest pain relief in patients with acute myocardial infarction” (European Heart Journal: Acute Cardiovascular Care April 22, 2015) address in a very well documentrd way the topic about drug-to-drug interactiono between morfine and antiplatelets agents in STEMI patients.

Guido Parodi, a lead interventional cardiologist in Cardiovascular and Thoracic Department of Careggi Hospital in Florence, (Italy) author of the article, highlights the fact that “despite the complete absence of rigorous studies designed to assess the impact of morphine administration in patients with AMI, clinical practice guidelines for the management of patients with STEMI strongly recommend the use of morphine for analgesia.”

As indicated in the article recent literature indicates an increased risk of mortality in STEMI patients treated with Morphine.

The analysis of CRUSADE registry in 2005 has shown how patients treated with morphine had a higher adjusted risk of death than patients not treated with morphine even after using a propensity score matching method. This is a non randomized trial and so influenced from potential bias, and the hypothesis that morphine was administered to higher-risk patients is also to be considered. But an additional potential explanation of morphine’s negative impact on AMI outcome may be related to drug-to-drug interactions.

Biologically a cause effect relation can be explained, because morphine inhibits gastric emptying, delaying absorption and so decreasing peak plasma levels of orally administered drugs in general and antiplatelet agents in this particular case.
This was very well demonstrated in a 2015 study from the same author “Morphine is associated with a delayed activity of oral antiplatelet agents in patients with ST elevation acute myocardial infarction undergoing primary PCI” (Parodi G, Bellandi B, Xanthopoulou I, et al. Circ Cardiovasc Interv Epub ahead of print January 2015) in whom the negative impact of morphine on platelet inhibition was not only limited to patients who vomited (patients with vomiting were excluded), but morphine-treated patients clearly showed higher residual platelet reactivity compared with patients who did not receive morphine.

In ATLANTIC Trial (Montalescot G, van ‘t Hof AW, Lapostolle F, et al.; ATLANTIC Investigators. Prehospital ticagrelor in ST-elevation myocardial infarction. New Engl J Med 2014; 371: 1016–1027), STEMI patients who did not receive morphine had a significant improvement in the ECG-based primary end point (ST-segment resolution), reflecting better myocardial reperfusion,with a significant “p” value for interaction between morphine use and time of ticagrelor administration. Professor Montalescot one of the lead authors of this Trial noted:“Co-administration of morphine in the ambulance may have delayed ticagrelor’s onset of action. To what extent this interaction may have affected our results remains unknown at this stage.”

So what to do with analgesia strategy in STEMI patients?

Given the key importance of platelet inhibition in patients treated by PPCI for STEMI and the absence of data that may support a potential clinical benefit of morphine in patients with acute myocardial infarction, more caution should be used regarding morphine administration in STEMI patients, and a restricted morphine use seems to be reasonably recommended.

Morphine administration has to be reserved, as suggested in the article, just for level of pain ≥ 7 on the base of a numerical rating scale (NRS) related value.

Courtesely from Dott. Guido Parodi

Courtesely from Dott. Guido Parodi

For lower chest pain intensity (NRS ≤ 7) alternative strategies has to be persecuted.
The author indicates paracetamol (1 g) or aspirin (≥300 mg) as alternative of choice to reduce chest pain as well demonstrated in letterature.
It has also to be considered how first line agents, currently indicated from STEMI guidelines, as Beta- blocker and Nitrates are able to reduce AMI-related chest pain until the definitive pain relief effect obtained with myocardial mechanical reperfusion.

Bottom Line

The first impact to reduce chest pain has to be reserved to Nitrates or B-blockers (where all contraindications are excluded).

After this NRS has to be evaluated and the use of Morphine is indicated only for values above 7. For lower values Paracetamol or Aspirin are the agents of choice.



  • Parodi G. Chest pain relief in patients with acute myocardial infarction. Eur Heart J Acute Cardiovasc Care. 2015 Apr 22. pii: 2048872615584078. [Epub ahead of print] Review.PMID:25904757

  • Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: Results from the CRUSADE Quality Improvement Initiative. Am Heart J 2005; 149: 1043–1049.

  • Parodi G,Valenti R, Bellandi B, et al. Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation
    myocardial infarction patients: RAPID (Rapid Activity of Platelet Inhibitor Drugs) primary PCI study. J Am Coll Cardiol 2013; 61: 1601–1606
  • Parodi G, Bellandi B, Valenti R, et al. Comparison of double (360 mg) ticagrelor loading dose with standard (60 mg) prasugrel loading dose in STEMI patients: The Rapid Activity of Platelet Inhibitor Drugs (RAPID) primary PCI 2 study.
    Am Heart J 2014; 167: 909–914.
  • Nimmo WS, Heading RC, Wilson J, et al. Inhibition of gastric emptying and drug absorption by narcotic analgesics. Br J Clin Pharmacol 1975; 2: 509–513.
  • Parodi G, Xanthopoulou I, Bellandi B, et al. Ticagrelor crushed tablets administration in STEMI patients: The MOJITO study. J Am Coll Cardiol 2015; 65: 511–512.
  • Montalescot G, van ‘t Hof AW, Lapostolle F, et al.; ATLANTIC Investigators. Prehospital ticagrelor in ST-elevation myocardial infarction. New Engl J Med 2014; 371: 1016–1027
  • Duggan ST and Scott LJ. Intravenous paracetamol (acetaminophen). Drugs 2009; 69: 101–113.
  • Zijlstra F, Ernst N, de Boer MJ, et al. Influence of prehospital administration of aspirin and heparin on initial patency of
    the infarct-related artery in patients with acute ST elevation myocardial infarction. J Am Coll Cardiol 2002; 39: 1733–1737
  • Yusuf S, Sleigh P, Rossi P, et al. Reduction in infarct size and chest pain by early intravenous beta blockade in suspected
    acute myocardial infarction. Circulation 1983; 67: 132–141.
  • Kim YI and Williams JF Jr. Large dose sublingual nitroglycerin in acute myocardial infarction: Relief of chest pain and reduction of Q wave evolution. Am J Cardiol 1982; 49: 842–848.

HEMS vs GEMS. By ground or by air: which is the best way to take care of traumatized patients

1 mag
Amb vs HEMS22 years old male hit from a car on the roadside of an urban area.
The ground EMS ambulance (physician, nurse staffed), dispatched on scene, find the patient alert, oriented and spontaneously breathing. His vitals are:
GCS 15 , RR 20, SaO2 95, HR 85, SBP 110
No mention of head trauma.
Chest no sign of trauma, bilateral and equal expansion and air entry.
Pulse is strong.
He has a profound laceration with loss of substance but not evisceration on left flank and no external bleeding from the wound.
The abdomen is painful and resistant to palpation in left flank.
There is an open fracture to left tibia (VNS 9).
The ground team, after the primary survey, activates the local medical helicopter.
The place is 10 k from a level 1 Trauma Center on a local road in an urban area and the helicopter is at 10 minutes flight distance. There is a safe landing space at 500 mt from the point of the accident.
A Level 2 hospital (general surgery, orthopedics, anesthesiologist, radiology and laboratory 24/7) is at 2 km distance from the scene.
Is this a proper activation for HEMS?
What international litterature says about advantages of air medical service vs ground medical service?


So what about the case?

Comparative effectiveness of helicopter emergency medical services compared to ground emergency medical services






Severity: The patient is slightly tachycardic, and the mechanism of trauma give us some clue on possible abdominal injuries, so he need a quick transport to an hospital with a general surgery (and orthopedics naturally for the tibial fracture)
Speed: non simultaneous activation. This kind of missions become competitive on long distances (45 miles) from Level 1 Trauma center (or the appropriate hospital). So GEMS is faster anyway.
Trauma center access: no difference between HEMS and GEMS and even there is doubt on the fact that this patient really need a Level 1 Trauma Center
Crew: this patient does not need an over skilled staff for some particular procedure.
We can conclude that for the standard HEMS activation criteria, this is not an appropriate activation and the best way to reach the hospital for this patient is a ground ambulance.
Any suggestion on the theme treated is, as usual, very welcome



Canadian Association of Emergency Physicians Position Statement on Acute Ischemic Stroke

12 apr CJEM CJO masthead9

CJEM CJO masthead9Has been published in March 2015 on Canadian Journal of Emergency Medicine (CJEM), the Canadian Association of Emergency Physicians Position Statement on Acute Ischemic Stroke.

Let’s see what they say about thrombolitic therapy and administration timing.


Summary of Evidence

Seven trials either specifically addressed the efficacy of rt-PA in stroke within three hours of symptom onset or provided data on a subgroup of patients receiving therapy within three hours of symptom onset.
Fibrinolytic therapy administered within three hours of symptom onset increases the probability of survival with a favourable neurologic outcome (NNT 10).
This favourable effect appears to be independent of age, including patients aged 80 and older.
Pooled data from several clinical trials suggest an important relationship between time from symptom onset to treatment and outcome. Patients treated with rt-PA within 90 minutes to symptom onset were more likely to have a favourable neurologic outcome compared to those treated from 90 – 180 minutes to treatment onset.



1. Patients with acute ischemic stroke whose neuroimaging excludes contraindications, and who can be treated within three hours of symptom onset, should be offered rt-PA with the goal of improving functional outcome (STRONG RECOMMENDATION, HIGH QUALITY EVIDENCE)
2. Stroke patients meeting eligibility criteria for thrombolytic therapy should be treated as rapidly as possible, with a target door-to-needle time of less than 60 minutes (STRONG RECOMMENDATION, MODERATE QUALITY EVIDENCE)
3. Due to limited resources and practical constraints, the administration of thrombolytic therapy within 3 hours in rural hospital may not be feasible and hence not recommended in all of these settings but should fall to the discretion of the local decision making team (WEAK RECOMMENDATION, LOW QUALITY EVIDENCE)


The statement is fair enough. The 3 hrs time window, even with the controversy that all the 7 available studies evidenced, is pretty condivisible. I love the great emphasis on ” target door-to-needle time of less than 60 minutes” that has to be the real target of all Emergency Systems. Is also well thought the flexibility on rural hospital and the assumption that treatment in those situations is discretional. Very well done i feel to subscribe everything!

CJEM CJO masthead9


Summary of Evidence

A pooled analysis of all trials involving acute ischemic stroke patients treated in the 3.0 to 4.5 hour time window was published by Emberson et al. in 2014. Combing data from 7 studies that included 2768 patients, the likelihood of a favorable outcome was higher if patients were randomized to rt-PA. (Emberson J, Lees KR, Lyden P, et al; for the StrokeThrombolysis Trialists’ Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet 2014;384(9958):1929-35)(.……) the latter figure (of the meta-analysis) showing significant imprecision and no difference in mortality, but a direction of effect towards a mortality increase with rt-PA in a dose-response relationship between time to treatment and 90-day mortality, suggesting a potential for increased mortality in those treated beyond 3 hours.
Included in this most recent systematic review is patient-level data from the IST-3 trial.

IST-3 suggested a 7-fold increase in symptomatic ICH associated with thrombolytic use (7% vs. 1%) as well as an expected increase in early mortality but no difference in disability or mortality at 6 months for those treated at 3–4.5 hours.



1. Thrombolytic therapy for acute ischemic stroke patients should not be routinely offered for the treatment of acute ischemic stroke for patients if administered beyond three hours of stroke symptom onset (WEAK RECOMMENDATION, MODERATE QUALITY EVIDENCE).
2. The administration of thrombolytic therapy for acute ischemic stroke beyond 3 hours from stroke symptom onset should be restricted to specialized stroke centers with advanced imaging capabilities or as part of a research protocol (WEAK RECOMMENDATION, LOW QUALITY EVIDENCE).


Even for this part of the statement my agreement is total.
IST 3 that is, at the moment, the largest study on thrombolytic therapy for ischemic stroke is a total contradiction in terms of evidence about benefit and major bleeding events.
Good outcome in the first 3 hrs, a majority of adverse events between 3 and 4,5 hrs and again beneficial between 4,5 and 6 hrs. Just one consideration: the results are not suitable for clinical practice.
So Thrombolytic therapy for acute ischemic stroke patients should not be routinely offered for the treatment of acute ischemic stroke for patients if administered beyond three hours of stroke symptom onset.

This is in contrast with the 2013 AHA/ASA Guidelines for the Early Management of Patients With Acute Ischemic Stroke that states:

Intravenous rtPA (0.9 mg/kg, maximum dose 90 mg) is recommended for administration to eligible patients who can be treated in the time period of 3 to 4.5 hours after stroke onset (Class I; Level of Evidence B). The eligibility criteria for treatment in this time period are similar to those for people treated at earlier time periods within 3 hours, with the following additional exclusion criteria: patients >80 years old, those taking oral anticoagulants regardless of INR, those with a baseline NIHSS score >25, those with imaging evidence of ischemic injury involving more than one third of the MCA territory, or those with a history of both stroke and diabetes mellitus.

Bottom line:

I really like this Statement and think that is one of best available policy  about thrombolytic therapy and ischemic stroke.





Cricoid Pressure in DAS 2015 Intubation Guidelines: an update.

10 apr

Below you can read the answer to my question (Cricoid pressure in new DAS (Difficult Airway Society) Guidelines: still on?) from Chris Frerk, Chair of DAS guidelines group:




Thanks for your thoughtful comments

The website posting is necessarily brief and there will be more detail in the developing paper.

Your point is well made re cricoid pressure vs BURP and external laryngeal manipulation.

The paper is predominantly aimed at anaesthesia for surgery in the UK though we recognise that the existing 2004 guidelines are referred to in ED and ITU settings. Current UK practice does endorse cricoid pressure for RSI (which includes most ED intubations) though we are aware this is not the case in other countries – we’ve taken the stance so far that this paper isn’t the place to debate RSI techniques but we do have a developing section on RSI.

 I think we do need to be more explicit about when cricoid pressure would be expected to be applied – we are already clear in the paper  that if it is applied and laryngoscopy is difficult the pressure should be removed (with suction at hand). In the elective scenario (with no cricoid pressure) then we say BURP / external laryngeal pressure (different from cricoid pressure) should be tried to see if view improves.

The group meet again soon and we’ll be discussing your thoughts in more detail then.

Thanks for taking the time to contribute”

Chris Frerk

Chair of DAS guidelines group

Now is only a matter of time.
We wait for the release of the new DAS Guidelines on intubation and, as Chris anticipated, on RSI.

Stay tuned on MEDEST and all the FOAMED community to be up to date on this and all the news from the Emergency Medicine World


Cricoid pressure in new DAS (Difficult Airway Society) Guidelines: still on?

9 apr

DAS Difficult Airway Society

Background story:

This is the post I wrote about the DAS April 2015 draft on intubation Guidelines:

DAS (Difficult Airway Society) released a draft of its intubating Guidelines for evaluation and comment before definitive update.

Previuos 2007 Guidelines are available here DAS Intubation Guidelines

This is the link to download the Update (April 2015) on DAS intubation guidelines 2015

What’s new on this draft:

Plan A (face mask ventilation and intubation)

  • Preoxygeneation is now included (to mantain even during the intubation, O2 nasal cannula).
  • VL is considered as standard approach (same leve than DL).
  • Cricoid pressure is no longer mentioned and replaced with BURP.
  • BURP has to be released if difficult intubation(laryngoscopy is predicted.

The authors invite all to send suggestions and comments to intubation@das.uk.com.

Last night (Italy time at least) on Twitter a debate about the presence on less of cricoid pressure aroused:

23:06 @MyEmergencyMed: Difficult Airway Society 2015
 intubating Guidelines http://t.co/3I82OaQEhV vía
 23:12 @MDaware: cc @ketaminh MT @MyEmergencyMed: DAS
 2015 intubating Guidelines http://t.co/qmIQLonSTQ vía


23:13 @ketaminh: @MDaware @MyEmergencyMed
 @MEDEST118 have u checked original source
 23:13 @MDaware: @ketaminh @MyEmergencyMed
 @MEDEST118 nope in a meeting
23:18 @ketaminh: @MDaware @MyEmergencyMed
 @MEDEST118 ok let me help you then
 23:22 @MDaware: @ketaminh @myemergencymed @medest118
 interestingly the guidelines say "Remove cricoid
 pressure" — not use it! http://t.co/3mAGwKRKoj
 23:23 @ketaminh: @MDaware @MyEmergencyMed
 @MEDEST118 stick to social media, editor! cricoid
 pressure still advocated by DAS as far as I can tell .
 remove prn
 23:29 @ketaminh: @MDaware @MyEmergencyMed
 @MEDEST118 well…you have to use it if you are to
 remove it

So let’s see what the released material from DAS says about cricoid pressure?

On the algorithm:


And then on the Highlights:


Pretty controversial.

So let’s ask directly to DAS wich is their position on cricoid pressure.

Screen Shot 2015-04-09 at 09.41.06And let’s wait for their answer.

Stay in touch!


Difficult Airway Society 2015 intubating Guidelines

6 apr Logo MEDEST2

DAS Difficult Airway Society

DAS (Difficult Airway Society) released a draft of its intubating Guidelines for evaluation and comment before definitive update.

Previuos 2007 Guidelines are available here DAS Intubation Guidelines

This is the link to download the Update (April 2015) on DAS intubation guidelines 2015

What’s new on this draft:

Plan A (face mask ventilation and intubation)

  • Preoxygeneation is now included (to mantain even during the intubation, O2 nasal cannula).
  • VL is considered as standard approach (same leve than DL).
  • Cricoid pressure is no longer mentioned and replaced with BURP.
  • BURP has to be released if difficult intubation(laryngoscopy is predicted.

Plan B (Oxygenation/ventilation with Supraglottic Airway Devices)

  • ILMA is no longer mentioned as preferred device
  • 2nd generation SAD is suggested as default devices

Plan C (Think and revert to face mask oxygenation/ventilation before surgical approach)

  • No main changes
  • Focus on reverting neuromuscolar blockade action

Plan D (surgical approach)

  • Scalpel Bougie Tube (finger????) technique suggested as standard approach
  • Cannula techniques only for skilled operators

The authors invite all to send suggestions and comments to intubation@das.uk.com.


VL tecnique in suspect intracranial bleeding

31 mar

62 yrs old male found unconscious GCS 6 (E1,V1, P4). Sign of vomiting and inhalation. Profoundly hypoxic, hypertensive (BP 200 over 110). Pupils were miotic with anisocoria dx>sx.

The team, after aspiration of gastric material from the airway, decided for airway control, before transport. The patient is overweight with a “taurine” neck so VL was chosen as first choice for airway management.

RSI (Fentanyl. Midazolam, Sux) performed. In the video you can see a detailed explanation of the VL technique that is slightly different from DL technique.

 Post-intubation management included ventilation optimization (EtCO2 35-38 mmHg in suspected intracranial hypertension) oxygenation and haemodynamic management.



A Day in Milan

16 mar Featured Image -- 4755


Not just Emergency Medicine! If you planned to visit Italy for the great EXPO follow this amazing Blog.
Linda Sorgiovanni guide you through the most exciting travel experience.
Food, wine, art and much more from real italian culture.
Don’t miss it!

Originally posted on Italy Travel Designer:

With the expo just around the corner all eyes on on Milan. Typically known as the business hub of Italy not as romantic or as charming as its famous neighbours to visit.  Although Milan is actually a fabulous city to visit with historical and contemporary charm and probably the best restaurants in the entire country!

I was there a couple of weeks ago to meet up with our friends and collaborators. Heres is how I spent my day:
Just a short ride from Florence on Italo to arrive at the Porta Garibaldi Train Station a short walk over the road to Feltrinelli Cafe and Book Shop in Piazza Sigmund Fraud. This business district is known as Centro Direzione situated north west of the city centre.  After our cappuccino and introduction in to the business district we took a cab in the historical centre for lunch at L’Arte  an exceptional restaurant…

View original 346 altre parole

RSI Basics Podcast with Minh Le Cong (@ketaminh on twitter)

16 mar


A Podcast with Minh Le Cong on beginner RSI. Recorded for my own personal reference but its such a great resource for Paramedics, Paramedic Students and a good all round touch up on the subject with a person much more knowledgeable than I.

If your not listening to Minh I highly suggest you start! His podcast was my first step into #FOAMed, so its an absolute honor to have him on my own.

You can find the Podcast over on I-Tunes:  https://itunes.apple.com/au/podcast/downstairs-care-outthere-podcast/id876296199c (please take time to leave a review or rating!!)

Below you will find some of the papers, trial and websites that we mention throughout, all are a good read. There’s also a number of different checklist ideas.

PHARM Podcast 61:

The Original RSII Article;


The study protocol for the Head Injury Retrieval Trial (HIRT): a single centre randomised controlled trial of physician prehospital management of severe…

View original 41 altre parole

Let’s be clear! Not all trauma patients must be treated with spinal immobilization during prehospital resuscitation and transport.

9 mar

ems-backboardsSpinal immobilization is performed in all trauma patients from the rescuers in EMS systems all over the world, regardless the mechanism of injury and the clinical signs.
This kind of approach is nowadays been rebutted from the recents evidences and the actual guidelines.
ACEP, in Jan 2015, released a policy statement entitled :”EMS Management of Patients with Potential Spinal Injury” clarifying the right indications, and contraindications, for spinal immobilization in prehospital setting.
The lack of evidence of beneficial use of devices such as spinal backboards, cervical collars etc… is in contrast with the demonstrated detrimental effects of such instruments: airway compromise, respiratory impairment, aspiration, tissue ischemia,increased intracranial pressure, and pain, consequent to spinal immobilization tools, can result in increased use of diagnostic imaging and mortality.

Already in 2009 a Cochrane review demonstrated the lack of evidences on use of spinal restriction strategies in trauma.

Recently the out of hospital validation of Nexus criteria and Canadian C-spine rules, strongly driven to a revisited approach to spinal immobilization.

So in 2013 American Association of Neurological Surgeons and the Congress of Neurological Surgeons Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injurie”  and Faculty of Pre-Hospital Care “Pre-hospital Spinal Immobilisation: An Initial Consensus Statement” stated those changes.

Based on this statements:

  1. Spinal immobilization should not be used for patients with penetrating trauma without evidence of spinal injury.
  2. Spinal immobilization should be considered in all trauma patients with a cervical spine or spinal cord injury or with a mechanism of injury having the potential to cause cervical spinal injury.
  3. Spinal motion restriction should not be considered for patients with plausible blunt mechanism of injury and any of the following:
    • The patient is GCS 15 (normal lev el of alertness)
    • There is no posterior mid-line tenderness
    • There is no distracting injury (other painful injury)
    • There is no focal neurological signs and /or symptoms (e.g., numbness and/or motor weakness)
    • There is no anatomic deformity of the spine
    • There is no intoxication (alcohol or drugs, including iatrogenic)
  4. The long spinal board is an extrication device solely.
  5. Backboards should not be used as a therapeutic intervention or as a precautionary measure either inside or outside the hospital or for inter-facility transfers. For this purpose, a scoop stretch or vacuum mattress should be used.
  6. EMS providers ahs to be properly educated on assessing risk for spinal injury and neurologic assessment, as well as on performing patient movement in a manner that limits additional spinal movement in patients with potential spinal injury.


  1. 2015 ACEP Policy statements: EMS Management of Patients with Potential Spinal Injury
  2. Totten VY, Sugarman DB. Respiratory effects of spinal immobilization. Prehosp Emerg Care. Oct-Dec 1999;3(4):347-352.
  3. Cochrane Rewiev Spinal immobilisation for trauma patients
  4. Test performance of the individual NEXUS low-risk clinical screening criteria for cervical spine injury.
  5. The Out-of-Hospital Validation of the Canadian C-Spine Rule by Paramedics
  6. Evaluation of the Safety of C-Spine Clearance by Paramedics
  7. 2013 American Association of Neurological Surgeons and the Congress of Neurological Surgeons Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injurie
  8. Faculty of Pre-Hospital Care “Pre-hospital Spinal Immobilisation: An Initial Consensus Statement”


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