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“Humans Are Not Yeast”: (almost) everything we believe about lactate is a myth. 

5 Ott

4e193a6c-13de-44f2-aabe-2b095321f652_1-8a517f942153f96606ebbde8331f1dc8On September issue of Emergency Medicine News, Paul Marik wrote an article entitled “Humans are not yeast”

This is a game changer article about the current concepts on lactic acid and its clinical meaning in emergency medicine.

The author illustrate simple but well established concepts about lactic acid metabolism that revert most of the common conceptions about its significance in clincal medicine.  

I will resume below some of the most relevant concepts expressed in the article. The italic bullet point text is from the original article.

I really encourage all of you to read the full text of original article to completely understand the whole rationale behind those statements and to access the complete list of references.

It is free open access.

Let’s start with some biochemistry.  

Piruvate, the product of glycolysis, can enter in Krebs cicle to produce energy through aerobic (oxygen driven) process or can take a shorter and faster (x100 times) way to produce energy when is transformed to lactate (the basis of lactic acid) using NADH (so reduced to NAD+ and ready to take another H+) and H+.

  • No hydrogen ions are present in glycolysis. In fact, the conversion of pyruvate to lactate consumes hydrogen ions. It is actually a lactic alkalosis. (J Mol Cell Cardiol 1997;9[11]:867.)
  • Increased lactate may simply occur because of increased production of pyruvate due to in- creased glycolysis there is no oxygen debt. We spoke about the muscles exporting lactate; the same thing happens in shock: lactate is used as a fuel for oxidative metabolism. Lactate is transported into the mitochondrion through specific transport proteins, and then is converted to pyruvate in the mitochondrial intermembrane space. Pyruvate then moves into the mitochondrial matrix and undergoes oxidative metabolism.
    Lactate is, therefore, a fuel for oxidative metabolism. It’s consumed by the brain and heart, and that is absolutely vital to survival when someone is in shock
    .
So why is lactate produced and used for?
Lactate is aerobically producted by muscle and is a more efficient source of energy for the brain and the heart.
  • Lactate is a much more efficient bioenergetic fuel than glucose so as someone exercises, the muscles make lactate to fuel the heart. The heart works much more efficiently with lactate. What happens to the brain? The exact same thing. As someone exercises, brain lactate goes up, and the brain starts using lactate preferentially as a source of fuel. This is a brilliant design: Muscles make lactate aerobically as a source of energy for the brain and heart.
Lactic metabolic acidosis is a biochemical myth! It’s more a lactic alkalosis.
  • The lactic acidosis explanation of metabolic acidosis is not supported by fundamental biochemistry, and has no research basis. Acidosis is caused by reactions other than lactate production.  
  • No hydrogen ions are present in glycolysis. In fact, the conversion of pyruvate to lactate consumes hydrogen ions. It is actually a lactic alkalosis. (J Mol Cell Cardiol 1997;9[11]:867.)
Hypoxia does not induce lactate serum level elevation, and in sepsis oxygen cellular level is not decreased. 
  • There is this pervasive idea that people with sepsis have cellular hypoxia and bioenergetic failure, but this concept was debunked in 1992. Compared with limited infection, the muscle O2 goes up in patients with severe sepsis.
  • Increased lactate may simply occur because of increased production of pyruvate due to increased glycolysis there is no oxygen debt. We spoke about the muscles exporting lactate; the same thing happens in shock: lactate is used as a fuel for oxidative metabolism. Lactate is, therefore, a fuel for oxidative metabolism. It’s consumed by the brain and heart, and that is absolutely vital to survival when someone is in shock. The body makes lactate, which is then used as a metabolic fuel.
Iperlactic state is generated, by epinephrine and not by hypoxia, in case of extreme physiological stress as protective mechanism.
  • The clinical plausibility was that lactate increases during adrenergic states and in the absence of an oxygen debt. Lactate increases with epinephrine infusion; lactate increases with hyperdynamic sepsis. All of the states have a high cardiac output, high oxygen delivery, and not a single trace of hypoxia. It’s driven by epinephrine, not by hypoxia.
  • We do know that lactate is associated with increased mortality because the sicker a patient is, the higher his epinephrine levels. It’s a protective mechanism. The association is related to the fact that lactate is a biomarker of physiological stress. And clearly the greater the physiological stress, the greater the risk of death. But lactate itself is a survival advantage, and it’s not an evolutionary accident that we make lactate.

Credits:

Thanks to the author and to Aidan Baron who originally shared the article.

Reference:

  1. The Science of Emergency Medicine: Humans Are Not Yeast. Emergency Medicine News: September 2016 – Volume 38 – Issue 9 – pp 1,29–30 doi:10.1097/01.EEM.0000499522.28133.48

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2016 NICE Major Trauma Guidelines. The pre-hospital recommendations.

21 Feb

NICE released the 2016 Major trauma Guidelines.

Many interesting recommendations where made for pre-hospital and in hospital providers about several topics

  • Airway management

  • Chest trauma

  • Haemorrage control

  • Circulatory access

  • Volume resuscitation

  • Fluid replacement

  • Pain management

  • Documentation

  • Training

Here is the Excerpt regarding the pre-hospital settings

Download the full guidelines for in-hospital recommendations and full description of Guidelines process and rationale behind every single recommendation

Download the full Guidelines at:

Major trauma: assessment and initial management

NICE guidelines [NG39] Published date: February 2016

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Forget ACLS guidelines if you are dealing with Pulseless Electric Activity. Part 1.

5 Set
ACLS Guidelines are misleading about diagnosis and treatment of pulseless electric activity (PEA)
This takes to conceptual and clinical errors when treating patients in cardiac arrest.
Let’s see why and if there is a better way to follow when dealing with this kind of patients.
First part is about diagnosis and diagnostic tools.

Live your comment below and see you soon for Part 2. The treatment options.

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F.A.R. in E.M. (Focus Assessed Review in Emergency Medicine ) #4: Stroke. Bonus feature, 2015 ACEP Clinical Policy on Use of Intravenous tPA for the Management of Acute Ischemic Stroke in the Emergency Department

27 Gen
MEDEST F.A.RAnd here we are with the 4th episode of the F.A.R. series. If you accidentally lost the first two episodes you can find them here:
#1 Cardiac Arrest
#2 Airway Management
In this episode we’ll explore the best articles of 2014 about:

Stroke

Before starting we have to declare (if you are not aware of) that MEDEST is quite skeptical about the previous studies that are at the basis of thrombolytic therapy (Lo strano caso del trombolitico nell’ictus cerebrale ischemico, Pubblicate le nuove linee guida AHA/ASA sul trattamento precoce dello Stroke: nessuna nuova ed ancora qulache dubbio!, L’uso del trombolitico nello stroke. Stiamo giocando con la salute dei nostri pazienti?, rt-PA e Stroke: IST-3 l’analisi dei risultati). This can represent a potential bias on the choice of the articles. We also think that the actual evidences, and the consequent guidelines, are strongly influenced by commercial interests and not well supported from evidences that demonstrates how benefits outweight harms. We hope that 2015 will be the first year of a new era for stroke management, an era of well done studies producing strong evidences to achieve good neurological targets in all stroke patients.

In the first part we mention the litterature about thrombolytic therapy

And then the articles about endovascular therapy:

And now as anticipated in the title the 2015 ACEP Clinical Policy on Use of Intravenous tPA for the Management of Acute Ischemic Stroke in the Emergency Department. Those freshly published guidelines give answer at two of most recurrent questions on stroke treatment:

  1. Is IV tPA safe and effective for acute ischemic stroke patients if given within 3 hours of symptom onset?
  2. Is IV tPA safe and effective for acute ischemic stroke patients treated between 3 to 4.5 hours after symptom onset?
Download and read the full policy to discover the recommendations made and based on the strength of the available data.
DISCLOSURE: MEDEST strongly encourage AWARNESS reading the propoused articles.
Abstracts are often misleading and articles potentially biased. Even this selection is not immune from potential bias (just human factors not commercial interests).
So download the full text and read it carefully to have a clear and complete opinion of the related topics.


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F.A.R. in E.M. (Focus Assessed Review in Emergency Medicine ) #3: Trauma

10 Gen
MEDEST F.A.RAnd here we are with the 3th episode of the F.A.R. series. If you accidentally lost the first two episodes you can find them here:
#1 Cardiac Arrest
#2 Airway Management
In this episode we’ll explore the best articles of 2014 about:

Trauma

Before approaching specific arguments about trauma here are some fundamental articles to read about new emerging concepts in trauma care. Those are the clinical and physiological bases to understand what is happening in the actual trauma management scene.

And now let’s go to specific area of interest:

  • Spine immobilization

Spine immobilization in trauma is changing.

After years of dogmatic approach to strict spine immobilization for all trauma patients regardless any other factor, is now pretty clear that not all the trauma patients benefits from this all or nothing way of thinking. MEDEST already faced the argument in previous posts (The Death of the Cervical Collar?) as also did some prehospital consensus guidelines (Faculty of Pre-Hospital Care Consensus Statements).

In 2014 many articles treated this topic in a critical and modern way of re-thinking spinal immobilization, in particular the widespread use of cervical collar. The lessons we learned is that:

  1. Widespread use of cervical collar in neck trauma has to be carefully evaluated (and even avoided) due to the low incidence of unstable spinal lesions.
  2. Routine use of cervical collar is of unclear benefit and supported by weak evidences. A new selective approach has to be implemented based on prehospital clearance protocols.

What is “revolution” in clinical practice? We don’t have the answer to this dilemma, but what is happening in fluid resuscitation for trauma patients seems likely to be revolutionary. Restrictive strategies and new blood products are the future for the treatment of trauma patients (read also Fluid resuscitation in bleeding trauma patient: are you aware of wich is the right fluid and the right strategy?).

But much more happened in 2014 about trauma….

Resuscitative throacotomy is now a reality not only “in” but even “out” of hospital, so read all about it

An evergreen topic is TBI but new concepts are arousing so read here the latest updates

New drugs and new protocols for airway and pain management: a rationale guide to choose the right drug for the right patient.

DISCLOSURE: MEDEST strongly encourage AWARNESS reading the propoused articles.
Abstracts are often misleading and articles potentially biased. Even this selection is not immune from potential bias (just human factors not commercial interests).
So download the full text and read it carefully to have a clear and complete opinion of the related topics.


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F.A.R. in E.M. (Focus Assessed Review in Emergency Medicine ) #2

5 Gen
MEDEST F.A.RThe second episode of this focus reviews will deeply assess a topic that is very “hot” for every emergency professional.
Before reading this episode give a look at the first of the series about the best of 2014 literature on  Cardiac Arrest
And now enjoy the very best of 2014 articles on:

Airway Management

Not all is CRASH! Especially when it comes to airway management. RSI is the gold standard when we talk about intubating a spontaneously breathin patient but DSI is becoming a classic. And is recommended by Scott Weingart and Seth Trueger, not properly two “new kids on the block”….
Caution! You are about to perform an invasive maneuver on a previously spontaneously breathing patient. So remember to carefully avoid desaturation and hyper-inflation!
This disclaimer should be written on the handle of every laryngoscope to remember two of the most frequent fault to avoid when managing the airways.
Always rewarded as a nightmare for the emergency professional, surgical airway is most of the time a real no through road for the patient. So here is a complete guide on how to approach in the best way such a difficult skill.
Does the aggressive management of the airways gets benefits on critically ill patients or a more conservative approach gives best results on clinical outcomes? Facts (few) and doubts (many) in this year literature.

 

DISCLOSURE: MEDEST strongly encourage AWARNESS reading the propoused articles.
Abstracts are often misleading and articles potentially biased. Even this selection is not immune from potential bias (just human factors not commercial interests).
So download the full text and read it carefully to have a clear and complete opinion of the related topics.


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F.A.R. in E.M. (Focus Assessed Review in Emergency Medicine ) #1

2 Gen
MEDEST F.A.RThis is the first (of a series) of literature reviews dedicated to a particular topic of Emergency Medicine clinical life.
We tried to give a deep look to all the articles that had a relevance for a particular argument in this year, and made some considerations regarding the emerged evidences . All the articles are full text end ready to be downloaded.
The first edition is focused on the “king argument” for an emergency medicine and critical care professional:

Cardiac Arrest

Chest compressions

This year the importance of chest compressions in CA was confirmed and even emphasized as one of the few (along with defibrillation) really wothy intervention to perform during CPR.

Mechanical Devices

The “black year” for mechanical devices saw 3 major trials finding no difference in outcome between mechanical and (good quality) manual chest compressions. Still remains the subjective (personal) impression that mechanical devices are of some utility for the human resources management and  transport during CPR.

Vasoactive (and other) drugs

Like (and perhaps more) than for mechanical devices, 2014 signed a really bad year for epinephrine.

Lack of evidence on his utility and emerging ones on detrimental effects, accompanied this “historical” drug through the year that preludes to new 2015 CA Guidelines. Will epinephrine still be there at the end of this 2015? Or new emerging trends on use of steroids and vasopressin will prevale at the end?

ECLS

And after interventions that are loosing evidence in the years, new future prospectives for the management of CA patients, comes from Extra-Corporeal Membrane Oxygenation that gives renewed hopes of better survival and good neurological outcome, despite initial difficulties and skepticism.

Outcome and prognostication

Therapeutic Hypothermia

New era for the post-resuscitative care! Less oxygen, lower tidal volume and last, but not least, less cooling. And, while this year will give us some answers about intra-arrest cooling, now we know that 33°C is equally effective as 36°C and is no longer recommended in post ROSC patients! Maybe….

Other

Hypotermia (accidental not therapeutic), highlights from ERC 2014 Congress and decision on non starting CPR: what changes and what remains in our daily practice.

DISCLOSURE: MEDEST strongly encourage AWARNESS reading the propoused articles.
Abstracts are often misleading and articles potentially biased. Even this selection is not immune from potential bias (just human factors not commercial interests).
So download the full text and read it carefully to have a clear and complete opinion of the related topics.

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MEDEST Review 30. One year in Review.

25 Dic

MEDEST-review

 

 

 

DISCLOSURE: MEDEST strongly encourage AWARNESS reading the propoused articles.
Abstracts are often misleading and articles potentially biased. Even this selection is not immune from potential bias (just human factors not commercial interests).
So download the full text and read it carefully to have a clear and complete opinion of the related topics.

The latest Review of the year is dedicated to a collection of the most important (for us) articles of this 2014.

This is MEDEST way to wish you all Merry Xmas.

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Enjoy the reading:

Cardiac Arrest

Chest compression

Mechanical Devices

Vasoactive drugs

ECLS

Outcome and prognostication

Therapeutic Hypothermia

Other

Trauma

Spine immobilization

Fluids and blood products

Other

Airway management

Sepsis

ACS

Stroke

Guidelines

Emergency Pharmacology

Mechanical Ventilation

Other clinical conditions

Non Clinical

 

 

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MEDEST Review : Speciale Trauma

13 Ago

MEDEST-review

 

 

Ancora letteratura ancora articoli ancora novità in medicina d’urgenza.

 

Attenzione! MEDEST incoraggia la lettura completa e responsabile degli articoli proposti. Evitate sgradevoli effetti collaterali!
Scaricate il full text ed approfondite gli argomenti d’interesse con altre fonti per un’informazione consapevole e quanto più possibile completa dei temi trattati.

In questa edizione straordinaria 5 articoli fondamentali che trattano aspetti attualissimi della gestione del trauma in emergenza.

Da leggere attentamente per cogliere i molteplici aspetti d’interesse per tutti i professionisti dell’emergenza sanitaria intra ed extraospedaliera

 

 

Puoi trovare la raccolta di tutti gli articoli citati nelle review di MEDEST a questo link

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MEDEST Review 29. Il meglio della letteratura internazionale.

12 Ago

MEDEST-review

Ancora letteratura ancora articoli ancora novità in medicina d’urgenza.

 

Attenzione! MEDEST incoraggia la lettura completa e responsabile degli articoli proposti. Evitate sgradevoli effetti collaterali!
Scaricate il full text ed approfondite gli argomenti d’interesse con altre fonti per un’informazione consapevole e quanto più possibile completa dei temi trattati.

Questa settimana su MEDEST Review:

Do Mechanical Devices Improve Return of Spontaneous Circulation Over Manual Chest Compressions in Out-of-Hospital Cardiac Arrest

Nessun chiaro beneficio sull’outcome (ma anche nessun peggioramento), molti studi mai pubblicati (anche se menzionati sui siti dei costruttori), fanno dei device per la compressione meccanica del torace degli oggetti controversi ed ancora tutti da scoprire. Nuovi e più rigorosi studi attesi a breve faranno luce sull’argomento.

Steroid-Pressor Cocktail for In-Hospital Cardiac Arrest? – See more at: http://www.jwatch.org/na31719/2013/09/24/steroid-pressor-cocktail-hospital-cardiac-arrest#sthash.qZBir4Aa.dpuf

Gli investigatori dimostrano che non vi è differenza in mortalità tra i pazienti traumatizzati intubati con laringoscopio tradizionale rispetto a quelli intubati con un videolaringoscopio. Ma l’impossibilità a randomizzare almeno il 30% dei pazienti per scelta dell’operatore, che ha preferito il videolaringoscopio per previsione di intubazione difficile, ha sicuramente influenzato positivamente la prestazione della laringoscopia diretta.

The Effect of Ketamine on Intracranial and Cerebral Perfusion Pressure and Health Outcomes- A Systematic Review

E se qualcuno avesse ancora dei residui culturali del passato riguardo all’uso della Ketamina nel trauma, ecco una buona occasione, speriamo quella definitiva, per aggiornare le proprie conoscenze. Review sistematica di tutte le evidenze disponibili che dimostra coem nessun effetto negativo sull’outcome sia collegato all’uso della Ketamina nel paziente critico.

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

Da NINDS a IST 3 il cammino  del trombolitico nello stroke è stato costellato di studi controversi e negativi, più che di evidenze univoche e convincenti (leggi anche: L’uso del trombolitico nello stroke. Stiamo giocando con la salute dei nostri pazienti?, Cronostoria dei trial sulla trombolisi nello stroke ischemico, rt-PA e Stroke: IST-3 l’analisi dei risultati). In questa meta-analisi che prende in considerazione tutti gli studi attualmente disponibili si evidenzia il beneficio del trombolitici se somministrato entro le 4,5 ore in tutte le categorie di pazienti. Fermo restando la serietà del metodo, permettete alcuni dubbi sul confronto tra popolazioni diverse e sul fatto che nell’articolo non sono illustrati i risultati dei singoli studi, ma solo l’aggregato dei dati. A tutti voi l’ardua sentenza.

Does Calcium Administration During Cardiopulmonary Resuscitation Improve Survival for Patients in Cardiac Arrest?

Negli anni e nelle varie edizioni delle Linee Guida ALS il calcio, nelle sue varie forme, ha sempre giocato un ruolo limitato a situazioni di ACR particolari. In questa review si prendono in considerazione tutti gli studi che riguardano la somministrazione del Calcio in ACR ed il suo effetto sull’outcome. Le conclusioni evidenziano come non ci siano evidenze di beneficio sull’outcome ma anche come tutti gli studi disponibili siano stati condotti in modo non uniforme e che quindi questo argomento va ancora esplorato in modo rigoroso in futuro per trarre conclusioni più convincenti.

Tidal Volume and Mortality in Mechanically Ventilated Children- A Systematic Review and Meta-Analysis of Observational Studies

L’avvento della Lung protective ventilation ha da alcuni anni cambiato l’approccio al paziente sottoposto a ventilazione meccanica. In particolare l’utilizzo di bassi volumi correnti si è visto come sia correlata ad una  aumento della sopravvivenza nei pazienti adulti. In questa meta-analisi di studi osservazionali che prende in considerazione i pazienti pediatrici si evidenzia come le evidenze in merito non siano altrattanto solide per l’etereogeneicità dei dati degli studi disponibili. Quindi quello che è un cardine oramai consolidato per l’adulto necessita di ulteriori evidenze prima di diventare tale anche per il paziente pediatrico.

Observational study of the success rates of intubation and failed intubation airway rescue techniques in 7256 attempted intubations of trauma patients by pre-hospital physicians

Il più ampio database di gestione delle vie aeree in ambito preospedaliero esaminato fin’ora. Percentuale di successo dell’intubazione 99,3%. I non anestesisti hanno il doppio della probabilità di utilizzare presidi alternativi (fortunatamente). Questi solo alcuni degli spunti che si possono ricavare dalla lettura di questa fondamentale risorsa.

 

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