The hypoxic drive myth

It was difficult to go through any single month in medical school without being reminded that giving oxygen to chronic CO2 retainers abolishes their respiratory drive (which in these patients is apparently dependent on hypoxia).

This is taught with similar vigour in nursing schools.

There is one small problem with this elegant concept. To quote Blackadder; “it is complete bollocks”.

The concept was developed in 1949 and we have held onto it with fervour ever since. I would not wish to minimise the efforts of physicians who precede us, but for context the year 1949 predates the invention of CPR.

co2

This graph (1) from 1980 shows what happens when patients with COPD and acute respiratory failure are given uncontrolled high flow oxygen for 15 minutes. The first thing to note is that the ventilatory drive (minute ventilation – VE) is supranormal to begin with (normal is about 5L/min). The graph is produced here with no permission whatsoever.

The second thing is that after a brief, not particularly significant, drop in the minute ventilation in the first few minutes, it pretty much returns to baseline. The last is the lack of correlation between minute ventilation and the rise in CO2 (which has been confirmed in subsequent studies).

So how does uncontrolled oxygen result in worsening hypercapnia in chronic CO2 retainers? It seems two main mechanisms are at play. The first is that oxygen displaces CO2 off of haemoglobin- the Haldane effect. The second is that usually the blood flow in the lungs is directed away from crappy hypoxic alveoli to healthy alveoli where the CO2 can be properly eliminated (hypoxic pulmonary vasoconstriction). Supplying crappy alveoli with excess oxygen reverses this process.

So, yes, uncontrolled oxygen can make respiratory failure worse, but it will not make your patient stop breathing. Which is important to know. If the patient has a respiratory arrest it is likely because they were tiring out and heading there anyway, not because you weren’t stingy enough with the oxygen.

It is also important to realise that the patient saturations give a good indication of how much oxygen their alveoli are seeing (it is this that determines how much hypoxic pulmonary vasoconstriction goes on). People obsess about the flow rate on the wall, but really the flow rate does not tell you how much oxygen is getting into crappy alveoli. As long as you are hitting a more conservative oxygen saturation target of 88-92%, you are fine.

References:

  1. Crit Care. 2012; 16(5): 323. Published online 2012 Oct 29. doi: 10.1186/cc11475. PMCID: PMC3682248 PMID: 23106947. Oxygen-induced hypercapnia in COPD: myths and facts. Wilson F Abdo  and Leo MA Heunks

Why is hypoxia not part of the Wells Criteria?

Whether you have done medical or surgical runs you will have spent plenty of time trying to figure out whether a patient has a pulmonary embolism. Many clinicians will hang their hat on the presence or absence of hypoxia. You may then wonder why hypoxia is not actually part of the esteemed Wells criteria.

Well, it turns out the presence of hypoxia in PE is quite variable. In fact, not uncommonly patients with massive PE may have normal oxygen saturations, a phenomenon confirmed both by the literature (1) and my own observations. To understand why, we have to understand why hypoxia might occur in the first place.

It has actually taken a while for people to figure out why hypoxia occurs in PE, although it is still not 100% transparent. Many people assume that the problem is V (ventilation)/Q (perfusion) mismatching, where Q is decreased due to the obstruction. This is not quite correct. V > Q results in hypercarbia, but not hypoxia. The problem is that Q is redistributed to other lung units, without a matching rise in V. This results in regions of lung with low V/Q, away from the embolism (2,3). This seems to be the most likely cause of hypoxia.

This explains why massive pulmonary embolism may not cause hypoxia. Remember that massive pulmonary embolism is defined by the presence of RV strain and cardiogenic shock. If most of the pulmonary arterial tree is obstructed there is nowhere for the blood to be redistributed, minimizing the ability for areas of low V/Q to form. Additionally, if the patient has cardiogenic shock, low cardiac output reduces Q, reducing the inequality. Therefore, paradoxically, improving oxygen saturations may be a sign of worsening shock (4).

Hypoxia is therefore not correlated with the severity of pulmonary embolism. Patients with severe PE may not be hypoxic. If your patient appears shocked, or just looks terrible, you cannot use the absence of hypoxia to rule out PE.

On the other hand, small PEs may also not cause hypoxia, if they are too small for significant redistribution of pulmonary blood flow to occur.

All of this leads onto the next point, which is the utility of ABGs when you suspect PE. No doubt at some point you will have been asked to obtain an ABG in a patient where PE is suspected. The origins of this were some small, flawed studies suggesting that a normal A-a gradient on an ABG could rule out PE in combination with other features. This has been proven false in a more rigorous study (5) – a normal A-a gradient is equally likely in patients with or without PE initially suspected of having PE. This study concluded that ABGs had limited diagnostic value in the investigation of PE. Hopefully now you understand why.

Additionally most of these ABGs are requested on patients in whom it is clearly obvious from the end of the bed that there is an elevated A-a gradient. If you are on 5L of oxygen to maintain normal saturations and there is no clinical reason for hypoventilation, then you will have an elevated A-a gradient.

Till next time…

 

  1. Intensive Care Medicine. June 1977, Volume 3, Issue 2, pp 77–80| Cite as Massive pulmonary embolism without arterial hypoxaemia Pathophysiology in two cases. F. Jardin, J. Bardet, A. Sanchez, F. Blanchet, J. P. Bourdarias, A. Margairaz.
  2. Pulmonary Circulation. Gas Exchange and Pulmonary Hypertension following Acute Pulmonary Thromboembolism: Has the Emperor Got Some New Clothes Yet? John Y. C. Tsang, James C. Hogg First Published June 1, 2014 Review Article.
  3. Journal of Applied Physiology. Pulmonary embolization causes hypoxemia by redistributing regional blood flow without changing ventilation. William A. Altemeier, H. Thomas Robertson, Steve McKinney, and Robb W. Glenny. 01 DEC 1998https://doi.org/10.1152/jappl.1998.85.6.2337
  4. Hemodynamic Factors Influencing Arterial Hypoxemia in Massive Pulmonary Embolism with Circulatory Failure FRAN(OIS JARDIN, M.D., FRANCIS GURDJIAN, M.D., PIERRE DESFONDS, M.D., JEAN-LUC FOUILLADIEU, M.D., AND ANDRI MARGAIRAZ, M.D. Circulation 59, No. 5, 1979.
  5. Diagnostic Value of Arterial Blood Gas Measurement in Suspected Pulmonary Embolism. MARC A. RODGER , MARC CARRIER , GWYNNE N. JONES , PASTEUR RASULI , FRANÇOIS RAYMOND , HELENE DJUNAEDI , and PHILIP S. WELLS. https://doi.org/10.1164/ajrccm.162.6.2004204   PubMed: 1111212 Received: April 24, 2000

How to properly interpret the creatinine (Cr)

The house officer wades through a swamp of daily creatinines. Unfortunately there is poor example setting on what to do with these. The classic example is the 90 year old with a “normal” creatinine of 90.

Nobody likes formulae, but it is important to refer to a couple here in order to understand what is to come.

Cr Clearance = (Urine volume x urine concentration of Cr) / Plasma Cr

The exact formula is irrelevant for your purposes but it is important to take home the concept that from this formula we can say that Cr clearance is inversely proportional to serum Cr.

Of course we don’t calculate Cr clearance by taking samples of everybody’s piss. That would be far too unwieldy. Instead we estimate Cr clearance using formulae, such as Cockgrauft- Gault, which takes sex, age and weight and spits out a result.

Of course it would be foolish to think we can accurately determine someone’s muscle mass and rate of Cr production even with fancy maths, so these formulae are estimates only, especially at the extremes of age and weight.

What this really boils down to is that I’m more likely to win the lottery than a 90 year old is to have “normal” renal function with a Cr of 90. This, at least, is commonly accepted, although commonly ignored, probably because we all have a habit of only looking at the exact number if it appears in red.

The nephron deepens

There are more interesting conclusions we can come to just from looking at the Cr clearance formula. Consider the graph that plots the function y = 1/x (CrCl being proportional to 1 / Cr)

inverse

If the y axis is Cr clearance and the x axis is Cr, what you can see is that

  • On the first part of the graph a fairly significant fall in Cr clearance is accompanied by only a small increase in Cr
  • Towards the end of the graph a fairly small drop off in Cr clearance is accompanied by a large increase in Cr

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Why it’s important to question authority, even in medicine

Last night I was watching one of those air crash disaster shows. For 60 minutes it followed the case of Comair flight 3272, which crashed in 1997 on its approach to the airport, killing all 29 aboard. While I get bored of the constant analogies drawn between medicine and the aviation industry, I found that this case imparted a powerful lesson.

For those of you who are regular readers (hopefully there are some!) you may have noticed a pattern in my blog posts- they often advocate challenging commonly held wisdom that may come from your seniors. It has not escaped my attention that this is one of those ‘easier said than done situations’. Comair flight 3272 will help me expound why I think this is important, and how to go about it.

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