Category Archives: Uncategorized

The Lactate Conspiracy: Part 1

What is lactate?  A good medical student will tell you something along the lines of

“Lactate is a byproduct of anaerobic respiration that is produced in response to cellular hypoxia secondary to inadequate oxygen delivery.  It is a marker of tissue hypoperfusion and shock”

They might go on to say high lactates are correlated with high mortality.  They might colloquially refer to lactate being ‘badness’.  You’d probably look at them moderately stunned, and say they were correct.

Oh’s Intensive Care Manual states:

 In critically ill patients, lactic acidosis is often due to shock.  In cardiogenic and hypovoloaemic shock hypoperfusion and tissue hypoxia increase lactic acid production while decreased hepatic perfusion decreases lactic acid metabolism.  In septic shock lactic acidosis is multifactorial.  Contributors include global hypoperfusion, microvascular disruption causing regional hypoperfusion and impaired cellular oxygen utiliisation by mitochondria.

The actual truth is far more complex, and though Oh’s not wrong, it’s waaaaay off right.  You’ll hear critical care peeps talking about optimizing lactate clearance4.  Hopefully after reading these two article you’ll understand that the very concept of lactate clearance makes no sense.

Now it’s important to know what lactate is, and how it affects acid-base balance because it’s seen as a marker of disease severity in every specialty.  The more you read, and the more you learn, the likelihood is that like me, you’ll realize that you’ve been taught convenient white lies about lactate to make quick intuitive leaps about people’s clinical condition.  Now short cuts are all very well, but if we don’t know the full picture we make errors based on incomplete data (more on that later).

People assume lactate is the cause of the acidosis, they are wrong.  People assume that lactate is a poison, they are wrong.

So here it is.  Everything we should know about lactate but were never taught. It’s fully referenced, and I encourage you to delve into those references for even more detail.

History:

Lactate was first discovered in the late 18th century in milk.  It was discovered by a Swedish chemist called Carl Wilhelm Scheele in 1780.  He found samples in sour milk.  This led to it being called lactic acid.  It should be called 2-hydroxypropanoic acid.  It’s existence was verified 30 years later in 18101.  Lactic acid can exist in L and D isomeric forms, and it is the L isomer that we use and produce.  Now because lactic acid was originally found in fermenting products, most of the early research into it was done from that perspective.

Lactic acid is used as a preservative, it is used in the beer industry, to make cheese, and even to ferment sauerkraut.  In 1922 Otto Meyerhoff unpicked most of the glycolytic pathway and demonstrated that lactic acid was produced as a side reaction to glycolysis in the absence of oxygen.  Archibald Hill quantified the energy release from glucose conversion to lactic acid and proposed that glucose oxidation in times of limited oxygen availability or demand/supply imbalances can supply a rapid amount of fuel for muscle contraction.  At the time in-vitro studies had shown muscle contracting in the absence of oxygen, and Hills experimental evidence suggested there had to be another fuel capable of providing up to 8 times the amount of energy that oxidative glycolysis could provide. Hill and Meyeroff didn’t know about mitochondria, or the phosphagen system and they also weren’t aware that weak acids pyruvate and lactate are produced as conjugate bases.  They were also held in very high regard, so when they plotted lactate and pyruvate concentrations against pH and showed a linear relationship, they incorrectly assumed that one caused the other, they weren’t questioned in the same way as others might have been.

Correlational evidence is all very well, but what if lactate is an innocent bystander?  Present in higher quantities during times of absolute clinical badness.  What if lactate was there, hands’ bloodied, but trying to help?

We have to talk about the biochemistry now:

First of some basics.  The molecule produced by the lactate dehydrogenase reaction is a base.  Chemistry at it’s simplest tells you that if you add a base to a solution it become more alkaline, not more acidic. Lactate is a conjugate base, it accepts hydrogen ions and can become a weak acid, it’s pKA is 3.86 (that’s the pH at which 50% of lactic acid exists in its ionized form) therefore in humans nearly all of it will exist as a base.  The only way we would “produce” lactic acid, is if our cellular pH was less than 3.86.  I think we can all agree that if our cellular pH is less than 3.86 we probably aren’t respiring at all.

So how can adding a lot of base to a solution make you more acidotic?

Hold that thought.

If you vaguely remember your A-levels or your physiology bits at first year of med school, you’ll know that cells utilize ATP to make stuff happen.  ATP is constantly recycled, and that recycling of ADP to ATP is what cellular respiration is for.  We have 4 ways of making ATP from ADP.

  1. The mitochondria (aka oxidative phosphorylation)
  2. Lactate Dehydrogenase reaction
  3. Glycolysis
  4. Phophagen system (muscle)

The phosphagen system uses creatinine phosphate as a source of phosphate and creatinine kinase as it’s enzyme.  It eats a proton, makes creatinine and ATP.  It’s super fast, but it’s fuel (the creatinine phosphate) gets used up quickly.  This system only really exists in muscle cells, as they must recycle high volumes of ADP quickly.

Glycolysis is the main respiratory pathway, here we convert either glucose from the blood, or glycogen from our cellular energy stores into 2 pyruvate molecules, 2 or 3 ATPs and produce 1 or two protons, and some water.  We use an enzyme called NAD (nicotinamide adenine dinucleotide), which becomes NADH.  NADH needs to be recycled, and here I think is the clever bit; the lactate dehydrogenase reaction uses the NADH to produce NAD, and converts the glucose or glycogen to pyruvate and onto lactate, and releases 2 or 3 ATPs.  These reactions are linked.  You need to make lactate to help refresh the NADH (though it is recycled in other ways too), the faster you refresh your NADH the more glucose you can convert to pyruvate.  NADH is also needed in the mitochondria for oxidative phosphorylation, so lactate production gives us a bit of energy, and recycles a key enzyme that’s needed in mitochondria, and for basic glycolysis.

Now when you look at the above reactions you can quantify their speed.  The slowest reactions become the rate-limiting step. Look at the maximal rate of mitochondrial respiration compared to the glycolytic pathway1.  If glycolysis goes into overdrive lots of substrate will be provided for the lactate dehydrogenase reaction.  This is rather elegant I think, as it it mitigates the potential acidifying effect of the pyruvate reaction.

So we know that lacate is a base, that it’s production most likely retards cellular acidosis.

The other common belief about lactate is that is is produced in anaerobic conditions.  Now I’m not sure this really matters.  The concept of aerobic and aneorobic conditions is an artificial distinction that was made in the early 1900’s to allow us to more easily understand the complex sea of interconnecting biochemical reactions that allow a cell to function.  Mammallian cells don’t really function that well in the total absence of oxygen, and though I suppose it could be argued that they can survive for very short periods the distinction between one pathway and another, and the idea of a cell switching from one to another is not the case.  I think this is interesting because it probably reflects our understanding at the time.  The pathways were thought of as railway tracks, and we would switch between them based on what was required.  The truth is more complex and harder to pin down.  Mitochondria will continue to work if the oxygen tension is as low at 1 tor (though some studies have shown this critical threshold to be 0.55).  For those of you who don’t know 1 tor = 0.13kpa.

Again I put it to you that if the cytoplasm has an oxygen tension that is as low as 1 tor things stopped going in the right direction some time ago.  As such true anaerobic respiration is unlikely to have a clinical impact, or even really exist, what is a more accurate assessment of events is that as energy demand in the cell exceeds the supply provided by the mitochondria, glycolysis and therefore lactate production becomes upregulated.  Now I think the best analogy here is that the glycolytic pathway is a bit like running your car in first gear.  It will move, but it’s not very efficient and you will quickly run out of fuel (and absolutely knacker your car).

So we now know that lactate is a base, it’s production retards cellular acidosis, and that it isn’t really produced because the cell has switched to an ‘anaerobic pathway’. 

Lactate is produced all the time, (we make 1400mmol/day).  Now considering our normal range for lactate at any point is <2mmol we probably need to know where it is going.  Also if lactate is a poison why we do make so much of it?  Most textbooks say that Lactate is metabolized back into glucose by the liver (this is the Cori cycle).  Why does the Cori cycle switch off when we are acidotic?

Couple of useful things to know.

The lactate dehydrogenase reaction can go forwards and backwards.

There is experimental evidence to show that some cells will use lactate to make pyruvate at times of stress, or just because.  Here is a list of those cells

  • Alveolar Epithelial cells6
  • Cardiac myocytes3
  • Hepatocytes1,2,3
  • Renal Cortex (only uses lactate)8
  • Renal Medulla8
  • Neuron7
  • Astrocyte7

The Cori cycle tends to down regulate or switch off during periods of acidosis.  Adrenaline upregulates the rate of the lactate dehydrogenase reaction.

If lactate is bad – why would these responses evolve in mammalian physiology?

So now we know:

  • Lactate is a base
  • Lactate production retards cellular acidosis
  • Lactate is not produced in anaerobic conditions, and that anaerobic conditions don’t really exist.  Therefore, poor oxygen delivery cannot explain increased lactate production.
  •  Lactate is utilized by cells for energy production, therefore it is a FUEL.

So where does the acid come from?

See Part Two.

 

  1. Biochemistry of exercise-induced metabolic acidosis Robert A. Robergs, Farzenah Ghiasvand, Daryl Parker American Journal of Physiology – Regulatory, Integrative and Comparative Physiology Sep 2004, 287 (3) R502-R516; DOI:10.1152/ajpregu.00114.2004
  2. Lactate efflux from exercising human skeletal muscle: role of intracellular    Russell S. Richardson, Elizabeth A. Noyszewski, John S. Leigh, Peter D.Wagner Journal of Applied Physiology Aug 1998, 85 (2) 627-634;
  3. Gladden LB. Lactate metabolism: a new paradigm for the third millennium. The Journal of Physiology. 2004;558(Pt 1):5-30. doi:10.1113/jphysiol.2003.058701.
  4. Jones AE. Lactate Clearance for Assessing Response to Resuscitation in Severe Sepsis. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2013;20(8):844-847. doi:10.1111/acem.12179.
  5. Lanza IR, Tevald MA, Befroy DE, Kent-Braun JA. Intracellular energetics and critical Po2 in resting ischemic human skeletal muscle in vivo. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology. 2010;299(5):R1415-R1422. doi:10.1152/ajpregu.00225.2010.
  6. Lottes RG, Newton DA, Spyropoulos DD, Baatz JE. Lactate as substrate for mitochondrial respiration in alveolar epithelial type II cells. American Journal of Physiology – Lung Cellular and Molecular Physiology. 2015;308(9):L953-L961. doi:10.1152/ajplung.00335.2014.
  7. Schurr, Avital. “Lactate: the ultimate cerebral oxidative energy substrate?.” Journal of Cerebral Blood Flow & Metabolism1 (2006): 142-152.
  8. Bellomo, Rinaldo. “Bench-to-bedside review: lactate and the kidney.” Critical Care4 (2002): 322.

Should we care if Mavis has crackles?

Presentations to the ED with acute dyspnoea are a bit of challenge.  History, examination and tests are used to decide if people have heart failure, pneumonia, COPD, or something else.  I think diagnosing heart failure in the ED is a particular challenge, as commonly used ED strategies aren’t particularly good tests for LVF.

In a pretty robust study of patients with no cardiovascular disease, normal hearts on ECHO, and normal BNP measurements in 2007 the incidence of bibasal creps in the 80-95 age group was 70%. (CI 58-92% p<0.001).  Incidence increases with age with 11% in 45-64, 34% in 65-79.  The auscultator was the same senior cardiologist who was blinded to patient diagnoses, so someone who is better than your or I at listening with a steth.

Right okay.  So I should get a CXR then right?

Well…. a meta-analysis in 1997 looked at this and pooled data from 29 studies.

Sign Sensitivity Specificity
Venous Redistribution 65% (95 % CI 55-75%) 67% (95% CI 53-79%)
Cardiomegaly 51% (95% CI 43 – 60%) 79%(95% CI 71-85%)

So it’s not an excellent test to rule in or rule out heart failure, however I couldn’t get at the full text for this one, so I don’t know how they were defining a true positive diagnosis of left ventricular failure.

In a subsequent retrospective analysis of the Acute Decompensated Heart Failure National Registry (85 376 patients), 15 937 had CXRs with no signs of congestion on the initial ED XR.  That’s a negative rate of 18.7% (CI 18.4-18.9%).  So nearly 1 in 5 heart failure patients don’t have obvious CXR signs.

Right.  So is there any collection of tests or investigations that have a high sensitivity and specificity for diagnosing say interstitial oedema versus consolidation?

Yup.  Well…maybe…Lung USS.

Comet tail artifact (aka B-lines) on USS appear in heart failure but not generally in COPD.  In 66 consecutive patients with dyspnoea and 80 patients without.  B-lines appeared in all 40 patients with pulmonary oedema.   That gives a sensitivity of 100% and a specificity of 92%.   (1 normal patient had them, and 2 COPD patients had ‘em).

However the gold standard test they were using to diagnose LVF or COPD was a CXR (blinded).  This means that they were not really using a great test to compare the new test to.  Also we’ve not got large trials of lung USS compared to any other tests, so the best I can say with any integrity is that it’s promising.

Really promising; The ETUDES study published in january 2009, compared B-lines and N-type BNP (blood test ‘for heart failure).  They did a prospective blinded, observational study for a convenience sample of patients (bias alert) presenting to the ED with dypsnoea.   They did an 8 zone lung USS, if all 8 zones were positive for B-lines the  positive LR ratio for pulmonary oedema was infinite (diagnostic).  Scanners were USS happy ED physicians or medical students who had had 2.5 hrs training .  USS performed better than BNP, but this was a single centre study, with inherent bias, and a small sample size.

So in summary –

Use the quiet time listening to the back of an old persons’ chest to think about what you are going to do.  The bases will be crackly.

You don’t need a CXR to diagnose LVF as 20% of the time your CXR is going to be clear.

Lung USS is promising.

References:

Kataoka H, Matsuno O. Age-Related Pulmonary Crackles (Rales) in Asymptomatic Cardiovascular Patients. Annals of Family Medicine. 2008;6(3):239-245. doi:10.1370/afm.834. 

 Badgett, Robert G., et al. “How well can the chest radiograph diagnose left ventricular dysfunction?.” Journal of general internal medicine 11.10 (1996): 625-634.

Collins, Sean P., et al. “Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure.” Annals of emergency medicine 47.1 (2006): 13-18.

 Lichtenstein D, Mezière G. A lung ultrasound sign allowing bedside distinction between pulmonary edema and COPD: The comet-tail artifact. Intensive Care Med. 1998 Dec;24(12):1331–4.

Liteplo, Andrew S., et al. “Emergency Thoracic Ultrasound in the Differentiation of the Etiology of Shortness of Breath (ETUDES): Sonographic B‐lines and N‐terminal Pro‐brain‐type Natriuretic Peptide in Diagnosing Congestive Heart Failure.” Academic Emergency Medicine 16.3 (2009): 201-210.

Crispy…

There’s a lady in Resus, she’s 46, she’s got a history of mental health problems.  Her husband tells you she’s been gradually more lethargic over the last few days.  He called the ambulance today because he found her on the sofa in the morning mumbling incoherently.  Her observations are okay.  Her ABC’s are okay, she’s got a normal glucose, but when you go to move her arm to cannulate you notice she’s rigid.  Hypertonic all over.  You do what you can of a neuro exam and find she’s got globally increased reflexes.  Her pupils are fine.  VBG is okay acid base wise but her Na is 154.

Now as we said last week.  Sodium is important, and it’s ubiquitous.  We need it for everything, and every single one of our cells uses a lot of energy to maintain a sodium concentration of between 135-145mmol/l.  When things go wrong with sodium homeostasis, things are very wrong indeed.  Mortality rates are higher for hypernatraemia than hyponatraemia ranging from 45-60% for all patient groups, and can be as high as 80% in the elderly.  Thankfully it is less common than hyponatraemia, and we most often see it in patients as they enter their last phase of life, this adds an ethical dimension to treatment that I’m not going to talk about here (maybe another day).

Features of severe hypernatraemia are hyperthermia, delirium, seizures, and coma.  Patients with milder symptoms can sometimes present with delirium or changes in mental status.  Patients might have features of underlying disease processes (such as Conns or Cushings).

Hypernatreamia is usually caused by combined electrolyte and water loss, it’s just that the water loss is in excess of the electrolyte loss, and is coupled with an inability to replace water via the thirst response (people with low GCS, dementia, mental health problems).  The trick is working out where the water is being lost from.

Net water loss from kidneys

Diabetes insipidus can be neurogenic, or nephrogenic.  Neurogenic is usually due to traumatic brain injury, space occupying lesions or infections.  Nephrogenic can be caused by general renal dysfunction, or electrolyte abnormalities such as hypercalcaemia or hypokalaemia, or HHS.

Net water loss from other sources:

The commonest drug cause of hypernatraemia is Lithium, though other drugs such as amphotericin, diuretics and vasopressin analgoues (demeclocycline) can also contribute to or cause it.  Lithium actually inhibits a protein called GSK3 which is part of how renal cells’ respond to vasopressin.  Colchicine, gentamicin, and rifampicin can also cause diabetes insipidus.  Unreplaced loss from the respiratory system, sweating, burns, GI tract (D+V) or any type of fistulae can also be implicated.

Hypernatraemia from sodium gain

Feeding, or increased oral salt intake (this usually needs to be massive, or Iatrogenic).  Sea water ingestion, hyptertonic enemas, or dialysis.  Primary hyperaldosteronism (Conns), or Cushings syndrome can also cause excess sodium re-absorption.

 

Treatment

As with hyponatraemia the symptoms are vague and wide ranging.  Treatment depends on the speed of onset with those with a rapid onset (<48 hours) likely to have more severe symptoms.

Assessment of volume status again here is key, because disorders of sodium metabolism are also disorders of WATER.

Hypovolaemic hypernatraemia – patients have signs of hypovolaemia, plus a high sodium!  If you check a urinary sodium and it is low it suggests that the the loss of Na is coming from somewhere other than the kidneys (normally GI tract).  The Na in these cases is usually elevated at 150-170mmol/L.  I think this is the most common class of hypernatraemia.

Euvolaemic hypernatraemia – can be caused by either renal or extra-renal loss of water without loss of Na.  These patients usually have an inability to respond to thirst, or one of the diabetes insipiduses? Inspidies?  Urine osmolality will be lower than plasma osmolality in patients with renal losses of water.  Serum Na in these cases is usually higher >170mmol/L.

Hypernatreamia with hypervolaemia – least common, these patients have normally been given more Na+ than they need (hypertonic solutions either NG, IV) OR they may have conditions which compound this such as renal or liver dysfunction.  People in this category have sky high sodiums >190mmol/L.

Acute Ix strategy – send urine and plasma for electrolytes and osmolality.

Urine osmolality

Lower than plasma or <300

[very dilute]

Normal 400-800 High >800

[super concentrated]

Central or nephrogenic diabetes insipidus

 

Incomplete Central or nephrogenic diabetes insipidus

 

 

Lots of water loss (and your patient has just run out of free H20)

OR

Total Na+ gain

OR

Extra-renal losses, D+V, burns etc

The mainstay of emergency treatment is infusion of the right amount of normal saline to bring the sodium back down.  You want to do this slowly in chronic hypernatreamia (drop the Na by no more than 10mmol/day).  I think this is why Normal Saline is suggested in the emergency phase rather than 5% Dextrose.

Most sources suggest we calculate the water deficit, and replace the lost fluid (after initial resuscitation fluids) over 24-48 hours with oral or 5% dextrose.  The formulae are similar but I encountered 3 different ones in the 3 sources I used (BMJ best evidence, Life in the Fast Lane, Mushin article).  Most of them changed either B or the way you calculate the Na excess.  The one below is from BMJ best evidence I found it the easiest to actually use (for me).

Deficit = A x B x ([Serum Na/140]-1)

A = is their weight

B = % water (0.6 for men, 0.4 for women)

Challenges:

Patients with hypervolaemic hypernatraemia might require that dirtiest of treatments;  fluid AND diuretics, as by expanding their intravascular volume with IV fluid you will downregulate vasopressin excretion further, compounding the problem.  This group of patients might benefit from dialysis to remove the volume and improve the sodium (carefully).

Once we’ve corrected this (and unless your bed-state is really really bad) most patients will be out of your department but further diagnostic tests may be done to confirm the cause.

Tests that may be required:

Plasma Aldosterone:Renin ratio: a high PCA:PRA ratio supports the diagnosis of Conns.  The ratio should be >1000 and a random aldosterone level should be >250pmol/L. (requires patient to be K+ replete, and have all diuretics and antihypertensives stopped for a few weeks beforehand  ).  If you get an equivocal result you might need to get a saline infusion test for hyperaldosteronism (this is an outpatient thing).

Dexamethasone suppression test (Cushings).  Patient takes 1mg dexamethasone at 23:00 and at 09:00 has blood taken for plasma cortisol.  A positive result is <50nmol/L.

Water deprivation test (for euvolaemic hypernatraemias)

When everything is back to normal.  Water restriction starts in the early morning, with baseline vasopressin level, with hourly Na checks.  Once the sodium is >148mmol/L another vaspopressin level should be taken.  At this point DDAVP (vasopressin agonist) should be given.  Patients with nephrogenic DI fail to respond to DDAVP, and their urine osmolality increases by <50% or <150mOsm/kg from baseline pointing to another cause.

CT or MRI head for cranial DI

CT or MRI adrenals for primary aldosteronism.

Summary

So just like our hyponatraemia patients, hypernatraemia patients need a serum and urine electrolytes and osmolality.  We need to decide on their volume status.  We need to resuscitate if required with normal saline, or replace slowly with 5% dextrose.  It is possible to calculate their fluid requirements and we should do this too.  In some circumstances we might even need to infuse 5% dextrose while giving diuretics.

The key question to answer is “Where has all the water gone?”

 

Hypernatraemia
Hypovolaemic Euvolemic Hypervolaemic
Causes:

 

Renal Losses

Renal failure

HHS

Post-obstructive diuresis

 

Non Renal Losses (urinary sodium low)

D+V

Burns

Fistulae

Failure to drink (psychological, behavioral, inability)

 

Nephrogenic DI

Drugs, AKI, Electrolytes

 

Neurogenic DI

TBI/CVA/SOL

 

Failure to drink (psychological, behavioral, inability)

 

Iatrogenic infusion/feeding of high Na fluid

 

Co-existing renal or liver dysfunction

 

Cushings

Primary Aldosteronism

Rx
Resuscitate with Normal Saline

 

Calculate deficit and replace losses with 5% dextrose over 48 hours.

 

Aim for <10mmol/day increase in Na

Calculate deficit and replace losses with 5% dextrose over 48 hours.

 

Aim for <10mmol/day increase in Na

Calculate deficit, replace any losses carefully to avoid worsening overload using 5% dextrose.

 

Use IV Furosemide

 

Aim for <10mmol/day increase in Na

PS if you are wondering about that lady, she ended up having neuroleptic malignant syndrome plus a partial neurogenic diabetes insipidus from mass effect from maxillary bone osteomyelitis.  You know, one of those simple diagnoses…

 

References:

BMJ best practice Hypernatraemia (http://bestpractice.bmj.com/best-practice/monograph/58/overview/summary.html) Accessed 24/11/2016

Mushin, A, Mount D Diagnosis and Treatment of Hypernatraemia.  Best Practive and Research Clinical Endocrinology and Metabolism 30;2 March 2016 189-203.  http://www.sciencedirect.com/science/article/pii/S1521690X16000415  [paywall]

Sodium

An old man is wheeled into resus.  His GCS hovers around 10.  No carers have come with him, you find out from the paramedics that the care home staff were alerted to a thump as he fell out of bed.  He’s moving all 4 limbs.  His obs are okay.  His CT head is normal.  His VBG shows a Na of 119, but is otherwise okay.

This, for me, is a frighteningly common scenario.  It’s also generally managed badly and in variable ways.  Do you give normal saline?  How fast?  What are the risks?  Aren’t you meant to fluid restrict?  What about urine tests, don’t’ we need to send that off for something?

The Oxford Handbook of Clinical Medicine (which I credit with allowing me to pass both my undergraduate degree and membership exam) is annoyingly vague in the single page it devotes to this issue, and concentrates more on fluid management than low or high Na.  Now the management of low sodium is important because patients with hyponatraemia are 7x more likely to die in hospital than those with a normal sodium.

  • A normal serum sodium is between 134 – 146 mmol/l.
  • Osmolarity is the number of osmoles per litre of solution
  • Osmolality is the number of osmoles per kilogram of solvent
  • (2 x (NA +K) + Glucose + Urea )  Normal is 280 – 295 mOsm/kg

Sodium is a highly reactive alkali metal that readily donates it’s free outer electron to any and all comers.  It doesn’t exist in it’s pure form naturally anywhere on the planet.  Many of it’s salts are water soluble and it’s that property and it is it’s positive charge that makes it essential to pretty much every cellular process in biology.

The Na/K ATPase is ubiquitous to all animal cells.  It exchanges 3 Na+ ions from inside the cell with 2 K+  against their respective concentration gradients.  Maintaining this gradient uses up at least 20% of most cells energy (nerve cells use more).  What’s particular fascinating about this protein is it seems to have roles in signaling as well as maintaining homeostatic functions and resting potentials., but before I vanish down a Wikipedia fueled rabbit hole talking about ouabain-binding signaling I’ll get back to the point of this post.

The point is, is that the maintenance of Na/K concentration is so vital to cellular processes at a basic level that every cell is spending at least one fifth of it’s energy maintaining it.  Now every single one of us knows how to put potassium back into cells, but Hypo and Hypernatraemia feel complex, and aren’t intuitive.  Na+ itself is responsible for 86% of plasma osmolality, which is why small fluctuations in the amount available have relatively massive (and vague) clinical manifestations.

Sodium and water homeostasis are linked.  Principally because as Sodium is the main osmole water will follow it.  If you excrete more sodium, you excrete more water.

Key point“ Water follows sodium around like an overly-keen medical student with boundary issues “

Sodium is tightly controlled by brain and kidney via ADH release and perception of thirst (water intake).  Aldosterone acts to re-absorb sodium from the collecting ducts (also sweat and salivary glands and the colon), water follows this via osmosis.  Urine osmolality reflects how much sodium is being secreted or absorbed, and varies between 50 (water) to 1400 (more salty than sea water).

If ECF  (extra cellular fluid) osmolality increases by 1-2% (more osmoles in solution, the more concentrated it is), the posterior pituitary makes vasopressin.  Vasopressin works on the distal nephron to open aquaporin-2 channels.  This lets more water back into the circulation.  The sensation of thirst is also triggered.  Reductions in ECF osmolality reduce vasopressin secretion.

Hypovolaemia stimulates renin secretion from the juxtaglomerular apparatus.  Renin converts angiotensinogen to angiotensin I, which via ACE is converted to angiontensin II which stimulates the adrenal cortex to produce aldosterone (aldosterone can also be released directly if the Na+ in the ECF drops).  Aldosterone causes sodium to re-absorbed in the nephron, gut, and sweat and salivary glands.  If we re-absorb sodium water is meant to follow.

Let’s pause a minute and consider the effect of us fiddling with the renin-angiontensin system on a patient.

If you give people an ACEi, or an ARB you are effectively stopping people being able to re-absorb sodium, if you stop them doing that they can’t effectively scavenge water back into their system, this is why these drugs are BAD if for whatever reason you have a low BP.  They can compound a mild problem to a severe one, as there is no compensatory mechanism.  Diuretics change the urine osmolality and Na concentration.  They make making the appropriate diagnosis harder.

How should we manage these patients?  This depends on the type of hyponatraemia.

Hyponatraemia is a disorder of Sodium AND WATER.

Classify or die.

Hyponatraemia  = Na+ <135
Acute <48 hours Mild <135
Chronic >48 hours Moderate 125-130
Severe <125

Symptoms

Subtle Mild Severe
Gait abnormalities

Falls

Decreased concentration

Cognitive deficits

Increased risk of fracture

Nausea

Confusion

Headache

Vomiting

Cardiorespiratory distress

Abnormal and deep sleep

Seizures

Coma

Severe symptoms are more likely to occur in acute hyponatraemia, as compensatory mechanisms kick in to protect the brain from cerebral oedema (it makes intracellular osmotic molecules like glutamine which keep water in the cells), which is the cause of the severe symptoms.

Investigation Strategy

document_2016-11-10_14-30-30-1

You need 4 test results to decide what the cause is (and often you don’t need all four).

  • Serum Osmolality (Estimating the osmolality is a good first step, however you need to measured value for the diagnosis)
  • Urine Osmolality (how concentrated the urine is)
  • Serum U+E (what’s the Na?)
  • Urine Na (how well are the kidney’s scavenging up Na)

You also need to decide if the patient is hypo, hyper, or euvolaemic.  Now this is fraught with difficulty and inconsistency (because clinical examination isn’t accurate).

There are three broad classes based on amount of solute in the serum (hypertonic, isotonic and hypotonic).  Hypotonic is the commonest, and it splits into 3.

Hypertonic hyponatremia occurs when another osmole (normally glucose) is exerting more of an affect than it normally does.  This causes water to leave the cells, causing a relative hyponatraemia that corrects if the offending osmole is put back into line.  Think HHS and DKA.  This is the reason why we correct high glucoses slowly, as rapid shifts cause the cerebral oedema that kills.

Isotonic hyponatraemia (MEASURED Serum Osmolality >275mOsmol/kg) is associated with infusion of dextrose or mannitol, or Iv IG.

Hypotonic hyponatraemia  (MEASURED Serum osmolality <275mOsmol/kg) is Divided into three: hypovolaemic, euvovolaemic, hypervolaemic, and is the commonest class we see in the ED.

Hypovolaemic – Loss of water and Na from ECF causes increased vasopressin secretion, decreased water excretion, causing water retention.

Renal causes – diuretics, osmotic diuresis, renal tubular acidosis, salt wasting nephropathy, mineralocorticoid deficiency, ketones.

Non renal (consider if Urinary Na <10) – vomiting, third spacing (eg pancreatitis + bowel obstruction), diarrhea, bowel prep, sweat, bleeding  If the urinary Na is <10  the kidney is working to scavenge Na back into the ECF.

Euvolaemic (Euvolemic patients will have a normal or low urea and an elevated Urinary Na) SIADH is the most common, also think of Psychogenic polydipsia, hypotonic IVF, adrenal insufficiency, hypothyroidism

Hypervolaemiac

Total body water and Na are both decreased but there is more water than sodium.  Vasopressin release causes water retention.

Hypotonic Hyponatraemia  (dilute serum)
Hypovolaemic

Rx – isotonic fluids

Euvolaemic

Rx – fluid restrict

Hypervolaemic

Rx – fluid restrict

D+V

Diuretics (thiazides)

Primary adrenal insufficiency

Cerebral salt wasting

Renal Disease

Third spacing

Pancreatitis

Sepsis

Bowel Obstruction

Syndrome of inappropriate diuresis

Secondary adrenal insufficiency

Hypothyroidism

High Water intake

Lowe solute intake

Failures:

Renal, Liver, Heart

Nephrotic Syndrome

Drugs that can cause Hyponatraemia (apart from diuretics)

  • Antipsychotics
  • PPI
  • ACEi
  • ARB
  • Anti-eplieptics
  • SSRI
  • MDMA (ecstasy)

The weirdness:

In loads of cases of hyponatraemia you get inappropriate release of vasopressin.  This acts to further decrease serum sodium.

In hypovolaemic patients, the release of vasopressin is in response to their low BP, in an attempt to scavenge water back into the system  to improve BP, but this acts to lower Na concentration further.  This happens in hypervolaemic patients too (as often their intravascular volume is low too).

In the above cases the inappropriate vasopressin release isn’t the primary cause of the hyponatraemia but it compounds the problem.  However you can get inappropriate vasopressin release as the primary cause of the hyponatremia too.  This should be thought of as a diagnosis of exclusion.

SIADH Criteria:  Serum Osmolality <275, Urine Osmol >100, urinary Na > 30 with normal thyroid, renal and pituitary function (and no use of diuretics).
Carcinoma Lung CNS Medications
Lung

Oropharynx

GI Tract

GU Tract

Lymphoma

Sarcoma

Pneumonia

TB

Asthma

CF

Meningitis

Encephalitis

 

Subdural

Extradural

Stroke

SSRI

SNRI

 

Carbamazepine

Sodium valproate

Lamotrigine

 

Phenothiazides

(prochlorperazine)

Butyrophenones

(haloperidol)

Cerebral/Renal salt wasting syndrome

This is relatively rare, and was first described in association with brain tumours and bleeds.  It can occur without them however.  The mechanism is thought to involve the release of a natriuretic factor which causes increased renal excretion of sodium.  As this causes volume depletion (water follows sodium).  ADH is released due to hypovolaemia, and the renin-angiotensin system is activated.  Biochemically these patients have exactly the same kind of findings as SIADH.  However they should be hypovolaemic. 

Management

Guidance for the management of hyponatraemia exist.  They are here and here.  And summarized well here.

document_2016-11-10_14-30-22

The guidelines state that hypertonic saline should be given in the first hour of someone’s presentation if they have features of severe hyponatraemia.   It is entirely possible then to have given two boluses of 3% saline before you’re even thinking about getting your urine results back.

Patients with hypervolaemia or SIAD are best managed with fluid restriction.  If there is no improvement with fluid restriction diuretics or oral NaCl should be started.  Patients with hypovolaemia should be given 0.9% NaCl or another balanced solution at 0.5-1ml/kg/hr (which is really quite slow, a litre in 12 hours or more).  We should not be treating asymptomatic patients aggressively because of the risks of treatment.  If you cannot confirm that this is acute hypernatraemia you should assume it is chronic, and only treat it aggressively if there are severe symptoms.

Interesting points on management I’ve been thinking about:

  • Acute hyponatraemia often doesn’t get managed well in the initial assessment by us in the ED. We often don’t order the serum and urine osmolality until prompted to by medics.  We should do this first line as soon as we realise their sodium is low.
  • We also probably generally do not give hypertonic saline often enough.
  • Catheterisation to assess fluid status, and get that urine to the lab is probably not done quickly enough.
  • I’m not sure if we can run people’s urine through our gas analysers to get a quick urinary sodium off (I think it’d probably work), however I’m not aware of a way to estimate Urine osmolality (if you find one please let me know!).

ODS (Osmotic demyelination syndrome)

This used to be called central pontine myelinolysis, occurs if the Na is corrected too rapidly, causing neuronal cells to dessicate as water follows it’s osmotic gradient out into the ECF.  Symptoms are heterogeneous and similar to symptoms of severe hyponatraemia.  The stand out differences are acute neurological deficits.

Severe symptoms of hyponatraemia Symptoms of ODS
Vomiting

Cardiorespiratory distress

Abnormal and deep sleep

Seizures

Coma

Seizures

Disturbed consciousness

Gait changes

Respiratory depression

Quadraparesis

Dysphagia

Dysarthria

Diplopia

Coma

 

ODS can also be caused by severe liver disease, alcoholism, malnutrition, anorexia, and hyperemesis gravidarum too.

What to do if treatment goes wrong.

If you’ve pushed up someones Na too quickly, the first sign you might get is a massive increase in their urine output.  If Vasopressin activity stops then free water clearance increases resulting in a more rapid increase in sodium than you really want.

If you need to quickly lower Na, then you should stop your IV treatment or diuretics, and give 10ml/kg of 5% dextrose over 1 hour.  It might also be appropriate to give desmopressin IV 2microgrammes, but I’d check with someone first.

Summary

The management of hyponatraemia hinges upon the severity and speed of onset of the imbalance.  The classification depends on investigations of urine and serum.  There are 3 types of hyponatraemia hyper, iso, and hypotonic.  There are 3 classes of hypotonic hyponatraemia (hyper, euvo, and hypovolaemic).

Acute or Severe hypontraemia should be treated by at least one infusion of 3% NaCl over 30 minutes.

Next time Hypernatraemia!

References

European Society of Endocrinology guidelines on the management of Hyponatraemia, European Journal of Endocrinology (March 1 2014). 170-G1G47  Here

Hirst et al The adult patient with hyponatraemia British Journal of Anaesthesia:Education 15(5):248-252(2015).  [pay walled]

Williams et al The clinical management of hyponatraemia Postgraduate Medical Journal 2016;92:407-411 [paywalled]

 

Catheter changes

So an elderly gentleman comes into the department.  He lives in a care home, he has a catheter, and he’s got a mild pyrexia, slightly more muddled than normal and some suprapubic tenderness.  After a full assessment you decide he has a Catheter Associated UTI (CA-UTI).

Your hospital policy suggests treating based on a previous culture growths and discussion with a microbiologist.  After a short discussion you get a code and prescribe an appropriate antibiotic.

You are just preparing to change the catheter when a senior colleague suggests you should also ‘give a shot of Gent’ to cover the change.

Should you?

People who have a long term catheter (LTC) will have asymptomatic bacteriuria.  All catheters become colonised with organisms that produce biofilms.  This biofilm acts as a reservoir for bacteria, and it needs to be removed if someone is symptomatic. You do that by changing the catheter.

In some respects I can understand the rationale for giving gentamicin to someone in this situation.  You want to reduce the amount of bacteria left in the bladder to limit the formation of a new biofilm on your shiny new catheter.

However evidence that this is what we should do is lacking.

SIGNs guidance on suspected bacterial UTI in adults states that “In a hospital setting, when prophylaxis for catheter change is required, consider using a narrow spectrum agent such as gentamicin rather than ciprofloxacin to minimise the risk of C difficile infection”.  It states this is a category C recommendation (low quality).  It has one reference to back it up, which is the 2009 guidelines for CAUTI from the Infectious Diseases Society of America.

These guidelines do not recommend the use of prophylactic antibiotics for catheter change.  They do recommend changing the catheter in CAUTI, but say nothing about the incredibly common situation described above.

Now the evidence they cite does suggest that giving antimicrobials does decrease the number of people with asymptomatic bacteriuria, however that response is transient, and does lead to resistance.  I think you can probably argue either way that in our situation (man with CA UTI) we may want to decrease the amount of free bacteria in the urine as much as possible.  However if you’ve taken appropriate microbiological advice the systemic therapy you have started should be enough to do just that.

They other justification I would suppose would be that instrumentation of the urethra might lead to a transient bacteriuria.  However in the one study of community catheter changes they quote (Jews et al) the bacteraemia was transient, and asymptomatic.  They then go on two discuss 3 RCTS comparing prophylaxis for catheter change and though each one showed a reduction in amount of bacteriuria in the prophylaxis groups the rates if bacteriuria equilibrated after 2 weeks.

I ran through a quick pubmed search for catheter associated UTI and of the 369 papers it threw back at me none seemed to look at this specific issue.  The guidance from SIGN on this specific thing, is based on the Infectious Diseases Society of America guidance, but does seem to draw a slightly different conclusion.  NICE draws its guidance from SIGN and suggests that prophylaxis should only be given if there is trauma during insertion or if the patient has a history of post-change CA-UTI.

So I think I’ll be leaving the Gent in the cupboard on this occasion.

References

SIGN

NICE

Hooton, Thomas M., et al. “Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America.” Clinical infectious diseases 50.5 (2010): 625-663.  [available here]

Beveridge LA, Davey PG, Phillips G, McMurdo ME. Optimal management of urinary tract infections in older people. Clinical Interventions in Aging. 2011;6:173-180. doi:10.2147/CIA.S13423.  [available here]

Missing things: Addisons

Recently missed an Addisonian crisis.  Here’s a brief summary of the case.

61 y o female attended the ED after seeing her GP with vaginal bleeding.  GP sent the patient to the ED for an inappropriate official reason (vaginal bleeding in a post menopausal lady unless torrential should be managed as a two week wait), but the lady looked unwell, and I think that was why the GP fabricated a reason.

This lady had a PMH of psychotic illness, rectal prolapse, and that was pretty much it.  She was seen with a family member who looked after her.  The history was vague.  She wouldn’t talk much, she said she had felt unwell for a few days, tired, and lethargic.  She had noticed the bleeding intermittently for the last few months.  She had a grey waxy sheen to her skin, and her hair was matted and unkempt.  Was this because of her mental health problem?

Systemic examination was unremarkable apart from a large rectal prolapse which I reduced, it was probably also the source of the blood.  Her results were phoned through:

Na 129, K6.9 Urea 17.2 Creat 152.  She had an elevated neutrophilia.  ECG showed sinus tachy with what were on reflection tented t-waves.  Her VBG showed a normal pH, slightly reduced HCO3- 15, and a BE of -5.

She was dry.  She had a high K+.  I started her on insulin/dex.  Started a septic screen and began rehydrating her with normal saline.  I did not giver her steroids but the medical SpR did about 1 hour after I saw her.

So why didn’t I think of Addisons? (apart from me being a bit thick).

The patient arrived in the ED by ambulance.  The history was confused.  The reason for attendance was really ‘unwell ?cause’ that the GP had recognised but then put more emphasis on the symptom of vaginal bleeding.  I think this led me down a strange path.  Possibly slowing my decision making with an anchoring bias.  I’d found a pathology with the rectal prolapse, and solved it (premature closure).  Did I think that this could explain the GI symptoms, AKI and dehydration?  Possibly, given the mental health problems and poor communication, this lady was likely to present late enough to cause these things if she’d avoided nutrition and fluid because toileting was painful.

Did I also fall prey to confirmation bias?  I think so.  I had a theory, I’d found something to confirm this.  I think I stopped looking for or considering differentials, despite the fact that I was thinking renal failure in someone with a normal venous pH, and only slightly disturbed bicarb.  .  I think there was also an element of fundamental attribution error (stereotyping), I probably placed too much emphasis on this woman’s serious mental health problem, as I tried to fit my theory together.

I may have rejected a new diagnosis of Addisons as a form of availability bias – I’ve never diagnosed primary Addisons, which means it’s not an explanation I often examine or reach for.  This is also called Zebra Retreat.  My normal cue for thinking about Hypoadrenalism is if people are on long term steroids and this lady wasn’t.

So how do we mitigate against cognitive errors?

Well there’s a good article on that here, along with a list of other cognitive errors you can make here.  The biggest step is being aware that they can happen, and what they are.

One way I normally work is I try to write down my differential, weighing the relative merits of each one as best I can.  However the time when I do this is when I’m less busy, and I know that when I am juggling a few Resus patients simultaneously I neglect my documentation, but those are probably exactly the times it needs to be done!  Especially as writing my working out is so important to my ‘cognitive process’.

When I miss something I also like to read up on the thing I missed, as well as trying to understand why I missed it.  Sometimes I write a reflection, sometimes (more often) I chat to my wife about it (she’s an ICU doc).  I just wish more time was allowed for this kind of thing at work.

Some notes on Addisons.

Incidence 0.8 per 100 000 of population.  More common in women than men.

The commonest cause of glucocorticoid deficiency is Iatrogenic, this technically isn’t Addisons.  Consider replacement if patients have been on 7.5mg pred/day (30mg Hydrocortisone/day) for longer than one month.  The mechanism here as I’m sure you know is suppression of the adrenal axis by negative feedback, causing adrenal atrophy.

Classically the causes are usually infection (TB, HIV), trauma, anything causing adrenal haemorrhage, and malignancy (mets like the adrenal glands as they are highly vascular).

Clinical Features:

Vague, frustrating and insidious.  Tiredness is the commonest symptom.  Skin hyperpigmentation (secondary to excess ACTH) looks quite subtle to me.  It’s more pronounced in areas of increased friction like palms, knuckles and scars.  GI symptoms can be severe enough to mimic an acute abdomen.

ED presentations are mostly crises, so you get hypotension, alongside the hyperkalaemia and hyponatraemia.  You can also get hypoglycemia.  On reflection I wonder how many potential mild cases we send back to GPs.

In summary

Mistakes and errors are common, especially with rare conditions and vague presentations. The ED environment sometimes feels like it’s designed to cause and not mitigate cognitive error, with multiple distractions and heavy time pressure.  We all need to develop our own strategies for limiting our own cognitive errors as we develop as clinicians.

And.

Don’t miss an Addisonian crisis. [Low Na, High K –> Give steroids]

Muppet.

beaker

Suspicious Histories

Ask any medical student (when they are sober) the clinical features of an Acute Coronary Syndrome they’ll look at you funny for a bit, then talk of  severe, left sided chest pain radiating through to the arm, they might add in diaphoresis, or pulmonary oedema.  If you’ve got a real nugget that might carry on talking about risk factors, relief from GTN and ‘pain like previous MI’ making a cardiac cause more likely.

You’d probably tell them they were right.

I remember hearing the first description of a chest pain history in a big lecture theatre as a first year medical student, and it was pretty much that.

We’ve always been taught that Histories Are Important, we are taught these by rote, by repetition and by  exposure to lots of real world cases.  They are the narrative that gives us the pathology our patients experience. So it’s implicit that the clinical features of those histories are equally important, and give us a sense of the probability of the disease in question.  I doubt I’m alone in labouring to commit ‘red flag symptoms’ to memory for exams, or general day to day work.

Now in my last post I got in a bit of a tiz about the HEART score, and about how the definition of a suspicious history was a little vague.  Now the history component of the HEART score is just worth 0,1, or 2 points out of 10.  So if histories were as important as my old professor said why does the component only make up a maximum of 20% of the score?

Thats because the classical chest pain history is not a very good predictor of ACS.

Let that sink in.  You have been taught that histories are important, they’re the key to finding the pathology.  Sometimes when the diagnosis is essentially a clinical one (eg appendicitis) that still holds true.  However when you have a good quality gold-standard test (eg a Troponin) things become different.  You can test the history, and the chest pain history is not very good at all.

In 2001 Prof Steve Goodacre published a study looking at the clinical features of people with low risk chest pain (normal ECG, no initial trop rise), seeing if any particular features had a predictive effect.  Previous research up to this point suggested left arm pain, diaphoresis, a 3rd heart sound and hypotension predicted acute myocardial infarction, but these studies were done prior to the advent of Troponin.

He conducted a big single centre prospective trial of patients over 25 with chest pain, no known CAD, and a normal initial workup.    He followed his patients up over 6 months looking for AMI and MACE.  He had a ACS rate of 9.1% in his cohort of 893 patients.

If I were to ask you ‘where do most people who have an NSTEMI complain there pain is coming from?’ You’d probably point somewhere over the left side of your chest.

Site Odds Ratio CI P
Both arms 6.0 2.8-12.8 >0.0001
Shoulder 3.4 1.5-7.8 0.004
Right arm 2.5 0.5-11.9 0.24
Throat 2.0 0.4-9.4 0.37
Left arm 1.7 0.9-3.1 0.084
Neck 0.8 0.3-2.5 0.74

Taken from table 4 – Univariate Analysis of Predictors of ACS (Goodacre 2001)

Would you suggest pain in both arms?   What about pain in the right arm being more suggestive of AMI than pain in the left?  That’s what Prof Goodacre found, though his confidence intervals are wide, and some of his findings were not statistically significant.

Now if we look at some his multivariate analysis results we can see that he only really found 3 good predictors.  Pain in both arms, exertional pain and a tender chest wall (this was a good negative predictor).  How many people have you admitted because ‘they had pain at rest’?

LR OR CI P
Pain in both arms 4.07 4.9 1.3-19.4 0.02
Exertional pain 2.35 3.3 1.3-8.4 0.014
Tender chest wall (as negative predictor) 0.3 0.2 0.05-0.97 0.045

He concludes

“We also found no evidence that the site of pain, the presence of nausea, vomiting, or diaphoresis, and the duration of the pain were at all useful in predicting whether the pain was likely to be cardiac or not”

Despite him having a pretty big sample of low risk, non cardiac chest pain he probably still didn’t have a big enough sample to look at what he wanted to look at.  This dataset was taken from another study primarily looking at the feasibility of a rapid chest pain assessment service.  I guess thats why theres no sample size calculation.

Lets look at my next study.  I love this study, it’s come out of manchester.  Prof Body included everyone over 25 who attended with suspected cardiac chest pain, treating clinicians completed a standard form with tick boxes for clinical features.  All patients had a 12 hour troponin and follow up at 48 hours, 30 days and 6 months.  His primary outcome measure was AMI and secondary outcome was MACE at 6 months.  So we’ve got a slightly different risk profile to the Goodacre study.

They analysed the results from 796 patients, and got 100% follow up.  I feel they had a slightly higher AMI rate of 18.6% (n=148) for initial presentation.  At 6 months they had a MACE rate of 22.9% (n=179).

The Odds ratios for AMI for individual clinical features are below.

bodygraph A few things to point out.  Sweating and abdominal pain seemed to be good predictors of AMI, as did reported N+V (which was not predictive in Prof Goodacres cohort).  Pain location that was in both arms predicted AMI more than pain in the left (and pain in the right was slightly better than left).    My favourite one though is that if the pain was described as ‘like their previous MI’ patients were less likely to have AMI.

Body didn’t find any excellent predictors of AMI.  His best ones were observed sweating, both arm/shoulder pain, and hypotension.

Predictor Sensitivity Specificity PPV NPV LR+ LR-
Sweating Observed 36.5 (28.7-44.8) 94.3 (92.2 – 96.0) 59.3 (48.5 – 69.5) 86.7 (83.9 – 89.1) 6.39 (4.38 – 9.33) 0.67 (0.28 – ).46)
Reported Vomiting 16.2 (10.7 – 23.2) 94.8 (92.7 – 96.3) 41.4 (28.6 – 55.1) 83.2 (80.3 – 85.8) 3.09 (1.89 – 5.05) 0.88 (0.82 – 0.95)
Pain in both shoulders 13.5 (8.5 – 20.1) 94.8 (92.7 – 96.3) 37.0 (24.3 – 51.3) 82.8 (79.8-85.4) 2.58 (1.53-4.34) 0.91 (0.85-0.96)
Same as previous ischemia 22.3 (15.9-29.9) 69.4 (65.7 – 73.0) 14.3 (10-19.5) 79.7 (76.1 – 82.3) 0.73 (0.53-1.01) 1.12 (1.01-1.24)
Right arm/shoulder pain 18.9 (13.0 – 26.2) 91.8 (89.4 – 93.8) 34.6 (24.4 -46.0) 83.2 (80.3 – 85.9) 2.31 (1.52 – 3.53) 0.88 (0.81 – 0.96)

Taken from Table 3 of Body (2010)  Characteristics of each predictive clinical feature as a diagnostic test for AMI

So in two good quality studies of chest pain characteristics we get right arm pain more predictive of AMI than left arm pain.  We can’t with any degree of accuracy state that someones epigastric burning pain isn’t cardiac in origin, and a classical heavy central pain radiating to the jaw or arm isn’t predictive of AMI or 6 month MACE at all.

Caveats.  You’ve got lots of hypothesis tests going in both of these studies.  Maybe too many, given the sample size and the rarity of the condition we are looking for.  A bigger sample would increase the accuracy certainly.

So should we stop talking to people about their chest pain?  Of course not, however we need to be very careful at excluding ACS based on the chest pain history alone.  Using something like the HEART score is probably more accurate, safer for your patient and safer for your registration.