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

The folly of chasing urine output with fluid in sepsis

Through medical school and house office years it is easy to develop many ‘reflex’ responses to certain conditions. Treating low urine output with fluid is one of these.

This makes sense in certain conditions. Hypovolemia leads to reduced renal perfusion. Correcting hypovolemia is therefore a good thing. Aggressive fluid resuscitation to restore renal perfusion makes sense in conditions where the patient is significantly fluid deplete, like enteritis or DKA, or where diuresis is helpful to prevent nephrotoxicity such as rhabdomyolysis or tumour lysis syndrome.

Unfortunately this has been extrapolated to every condition associated with AKI, resulting in massive fluid volumes being given to patients in the hope that the fluid will somehow drive the kidneys to work better. This is entirely devoid of physiological sense. This is most apparent in septic conditions. I particularly recall patients on the surgical ward with pancreatitis, who were given fluids for their oliguria and renal failure until they were swollen like the Michelin Man.

Chest Journal has published an article this month (1) addressing fluid management in acute kidney injury. This narrative is supported by a 2017 article of the same name. There are a few things to note.

Firstly, there is really no scientific evidence that macrovascular renal blood flow is routinely compromised in sepsis. Septic patients may be hypovolemic due to fluid shifts into the extracellular space but generally the problem is one of vasodilatation. The pathophysiology of acute kidney injury in sepsis is complex and involves tubular apoptosis and dysfunction at the cellular level.

river

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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

You’re taking the piss

Urinary tract infections are the scapegoat of the medical world. They make us lose our common sense, because once you find something that is easy to treat, you stop looking for anything else. This is termed satisfaction of search.

Let us look at two examples where a positive urine sample may lead the ward house officer astray, related to the domain of surgery.

Firstly, you have a patient who is POD4 after an anterior resection. You are called because they have become febrile. There is no obvious source on examination. You take cultures, and the mid stream urine comes back with a high number of white cells. You start the patient on cefuroxime for a presumed UTI. This is a frequent occurrence.

Unfortunately this decision neglects the basic rule of general surgery. This rule states that the main differentials in a febrile patient after abdominal surgery are as follows; anastomotic leak, anastomotic leak,  anastomotic leak and also anastomotic leak.

“But the urine is positive!”

Unfortunately pyuria is common in intraabdominal sepsis, presumably due to the infection rubbing up against the wall of the bladder and causing inflammation. The rate of sterile pyuria in appendicitis and diverticulitis for example can be anywhere from 25% to 70-80%, depending what literature you read (1,2).

This phenomenon is not even confined to intra-abdominal infection. 30% of patients presenting with pneumonia, sepsis, intra-abdominal infection, or enteritis have pyuria (3). Of these urine samples, only 30% were culture positive. Note that culture positivity does not imply a UTI- there will be a significant proportion of asymptomatic bacteriuria.

The second situation will be when you are not on general surgery, but convincing the surgical registrar to review your patient who has abdominal pain and a clinical presentation concerning for something surgical.

“But the urine is positive, why don’t you just treat the UTI?”

Take home message? Pyuria is common in patients with other serious sources of infection and you should remind yourself and others of this.

Till next time….

  1. Ther Adv Urol. 2015 Oct; 7(5): 295–298. Sterile pyuria: a forgotten entity. Sanchia Goonewardene and Raj Persad
  2. 09 Sterile Pyuria an Indication of Acute Appendicitis in Children. S. Lewis1, C. St. Laurent1, A. Ruiz-Elizalde1 1University Of Oklahoma College Of Medicine,Oklahoma City, OK, USA
  3. Sterile Pyuria in Patients Admitted to the Hospital With Infections Outside of the Urinary Tract. Jared B. Hooker, MS2, James W. Mold, MD, MPH, and Satish Kumar. JABFM March 2013:97-103

 

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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Why shock is not all about the blood pressure

shock

When calling the surgical or gastro registrar on the phone, one of the surefire questions you will be asked is ‘is the patient hemodynamically stable?’ This is no doubt an important question but unfortunately hemodynamic stability means different things to different people. There is generally a lack of willingness to look beyond a ‘normal’ vs ‘low’ blood pressure.

It should be made clear that hypotension is a sign of ‘decompensated’ shock. The idea that hypotension is a late sign of shock has been long recognized in the trauma literature where 18% of penetrating abdominal trauma can have over 750ml of blood in the abdomen despite normal vital signs (including 7% who had over 1500ml). In the majority of patients evidence of tissue hypoperfusion precedes the development of hypotension (1).

Why is this? Well, it is all about the concept that pressure does not equal flow. The body is quite adept at trying to maintain a normal blood pressure through various compensatory mechanism, chief amongst which is the sympathetic response. But this does not tell us whether perfusion at the tissue level is adequate- inadequacy of this is after all the definition of shock. This is especially true in young patients where the compensatory mechanisms are quite strong and blood pressure may be preserved till late in the piece, as illustrated by the graph at the top, of my creation (credit to MS paint).

This phenomenon is true in all situations- not just trauma- so it is relevant to the patients you will be seeing on ward calls. For example ‘normotensive shock’ is recognized in sepsis (2), cardiogenic shock (3), and just generally (4). What then are the signs of ‘normotensive shock’ you should look out for? Well, these are simply the signs of inadequate tissue perfusion- cool and clammy skin, oliguria, mental state changes and elevated lactate. Other signs which may accompany this that are not necessarily indicative of hypoperfusion but that do indicate a compensatory response are tachycardia and tachypnea.

It is also important to note two slightly related things. Firstly, a systolic blood pressure of 110 may be normal for a 20 year old but grossly hypotensive for a 70 year old with chronic hypertension. Secondly, it is sometimes difficult to tell whether a ‘soft’ blood pressure in a young person is just normal for them or whether they are actually hypotensive- a normal heart rate cannot be used to reassure you in this instance because not uncommonly shocked patients may have paradoxically increased parasympathetic tone (1) the exact mechanism for which is unclear. Older patients may also be on Beta Blockers.

The conclusion in all of this- next time you call the gastro reg with a patient who has vomited blood and is clammy with a lactate of 4 but has a normal blood pressure, the answer to the question ‘is the patient hemodynamically stable?’ is a ‘HELL NAH”.

Today’s post may sound basic but it is all about fundamentals- a fundamental which is often simply not done. Rather than spending 10 minutes documenting dual heart sounds, look and feel for the signs of shock!

Till next time.

 

 

  1. Identification and Resuscitation of the Trauma Patient in Shock Michael N. Cocchi, MDa , Edward Kimlin, MDa , Mark Walsh, MDb , Michael W. Donnino, MD. Emerg Med Clin N Am 25 (2007) 623–642
  2. Septic Shock. Advances in Diagnosis and Treatment. Christopher W. Seymour, MD, MSc and Matthew R. Rosengart, MD, MPH. JAMA. 2015 Aug 18; 314(7): 708–717.
  3. Menon V et al. Acute myocardial infarction complicated by systemic hypoperfusion without hypotension: Report of the SHOCK trial registry. Am J Med 2000 Apr 1 108 374380
  4. Approach to Hemodynamic Shock and Vasopressors. Stefan Herget-Rosenthal, Fuat Saner and Lakhmir S. Chawla. CJASN March 2008, 3 (2) 546-553; DOI:https://doi.org/10.2215/CJN.01820407