Why the Hypoxic Drive Theory Sucks Wind……..

 

          As an RT student I never could quite resolve my understanding of the CO2 retainer/hypoxic drive theory.  The more I tried, the less sense it seemed to make.  Finally the theory's armor started chipping away, eventually collapsing into a sea of absurdity.  One day I looked at this whole issue and could say to myself that this is one emperor who is indeed butt naked. This is an issue I feel strongly about and would therefore like to make a post regarding this issue--- to see where others stand and ask where we should go from here. 

          It is my experienced opinion that one of the causes of an overabundance of both clinical silliness and suffering is the persistence of the CO2 Retainer/Hypoxic Drive theory.  This is the theory  maintaining that any patient with a compensated chronic respiratory acidosis must rely on the hypoxic drive for a stimulus to ventilate----that somehow the CO2 sensors have become blunted or useless.  The theory further maintains that if you give one of these patients "too much oxygen" they will "stop breathing".

          I feel this theory is essentially garbage.  There may be patients who do have a defunct hypercarbic drive.  Some of them may even be CO2 retainers.  The regulation of ventilation is certainly complicated and vies with that of blood pressure in complexity.  Indeed now I am fantasizing two physiologists at a divided chalkboard, each with chalk in hand.  Each physiologist takes a progressively revved up turn diagramming either blood pressure or ventilation as dueling banjoes plays in the background (from the movie "Deliverance").

          If this CO2 Retainer/hypoxic drive theory had any real merit, then where are the legions of patients arriving in ERs whom have turned up their home O2?  Where are the episodes on "Murder She Wrote", as then home oxygen would be the perfect murder weapon (the evidence would disappear after the heinous crime) for any greedy relatives of a CO2 retainer?  Has any malpractice suit ever been won on the grounds of giving a CO2 retainer too much oxygen?  If so then that case should now be reviewed/reversed in light of recent studies and a newer approach which actually makes some sense. 

 

          I would refer anyone interested in this subject to the following articles…..

 

"_Debunking myths of chronic obstructive lung disease [editorial; comment]_ AUTHOR: Hoyt JW SOURCE: Crit Care Med 1997 Sep;25(9):1450-1 NLM CIT. ID: 97441579

 

__O2-induced change in ventilation and ventilatory drive in COPD._ AUTHOR: Dick CR; Liu Z; Sassoon CS; Berry RB; Mahutte CK AUTHOR AFFILIATION: Department of Medicine, University of California, Irvine, USA. SOURCE: Am J Respir Crit Care Med 1997 Feb;155(2):609-14 NLM CIT. ID: 97184400

 

__Influence of inspired oxygen concentration on deadspace, respiratory drive, and PaCO2 in intubated patients with chronic obstructive pulmonary disease [see comments]_ AUTHOR: Crossley DJ; McGuire GP; Barrow PM; Houston PL AUTHOR AFFILIATION: Department of Anaesthesia, Toronto Hospital, ON, Canada. SOURCE: Crit Care Med 1997 Sep;25(9):1522-6 NLM CIT. ID: 97441594

 

 

 

And there is the Critical Care Medicine article,1996 Vol. 24, No1 by Hanson, Marshall, Frasch, Marshall, entitled, "Causes of hypercarbia with oxygen therapy in patients with chronic obstructive pulmonary disease".  To quote the ending paragraph, "The development of Haldane deadspace and loss of the mitigating effects of hypoxic pulmonary vasoconstriction are sufficient to account predominately for the changes in PaCO2 seen in patients with severe COPD when treated with oxygen.".

          And for more discussion of this issue, look at pages 838-9 in Martin  Tobin's book, "Principles and Practice of Mechanical Ventilation".  The chapter is by Robert Lodato. 

          As the article and chapter may be confusing to some, I would like to try my hand in explaining the mechanisms here.....

          .

V/Q MISTMATCH--.  Picture the alveolar air equation as a form of a battle plan whereby an army of O2 soldiers know they will take certain losses on their way to link up with the Hgb.  760 torr minus the water vapor = 713.  Times .21 = 150.  Then minus 1.2 times the PaCO2.  Well if the PaCO2 is 40, then that's 150 minus 48 = 102.  Now imagine one real poorly ventilated alveoli where the PaCO2 has built up to 120 torr in that unit.  Now,with an RE of .8 that O2 army is fighting an effective back pressure of 144 torr so the PAO2 is only 6 in that alveoli.  Well when the pulmonary circulation gets exposed to that low of an oxygen level (below 60 torr) in it's venous circulation it constricts.  Blood is then sent to better ventilated(and thereby oxygenated also) lung units. 

          But if the patient is on 100% O2 then the PAO2 would be 569.  The pulmonary circulation wouldn't constrict (unless the CO2 climbed to about 6-700), and the resultant CO2 would backwash into the systemic circulation. This phenomenom can also affect the V/Q matching of asthmatics whom are placed on a NRB mask, or on 100% O2 as initial ventilator settings.

 

          HADANE EFFECT--. The Haldane effect is where increasing oxygen levels drive CO2 off the RBC—increasing O2 levels decrease the affinity of Hgb for CO2.  This is so O2 from the alveoli will drive CO2 off the RBCs and it will be then ventilated.  The opposite is the Bohr effect at the tissue level where increasing CO2 levels drive O2 off the RBC (or more correctly put—decrease the affinity of Hgb for O2). .

           Remember that stereotypical "blue bloater" with a chronic PaO2 of 50, SpO2 of 85%, and a compensated PaCO2 of say 70.  Usually those patients had a fairly high Hct, let's say 50%. What is attached to the Hgb more now with a lower PaO2?  It's CO2.  Their blood carries a chronic CO2 reservoir  .And the patient has more blood to boot also.  So if that patient has their FIO2 increased then that CO2 will be driven off the blood and into the circulation.  Your or I would just breathe a little deeper and faster, no big deal.   But the compromised COPDpatient's ventilatory ability can't handle it, especially now when they've arrived in the ER with an increased temp and a rapid RR. 

.         When hypercarbia associated with hyperoxemia is seen, it's not so much that you've knocked out the patient's hypoxic drive.  Rather you've driven in a hypercarbic potential. 

          Some may say, "what does it matter the mechanism if the result is still increased respiratory acidosis with O2 administration?".  To the extent that V/Q mismatch is the culprit, now we can be safe with a SpO2 of 97 as opposed to trying to hover in the high 80's to very low 90's.  To the extent that the Haldane effect is the culprit....well if the patient comes in with a PaO2 of 32 on RA with a PaCO2 of 80 with a pH of 7.34 and a RR of 48, just get that ET tube or Bipap ready.  For every SpO2 increase with O2 therapy you will be driving moreCO2 out and challenging further a ventilatory system already on the verge of collapse.  But if that same patient is at home and resting while watching the ball game on TV as their O2 accidentally gets turned up by 1 l/m---- well they won't stop breathing and that's why I've never met an ambulance with such a patient on board.  . 

 

                   And some people say, "but I've seen it happen....No you didn't really see all that theory happen.  You witnessed a series of clinical events interspersed with some lab data and then  chose to invoke a certain theory to tie it all together.  For eons people have believed that they've seen various unscientific superstitions come true and "happen" as lightning, thunder,and earthquakes have wreaked havoc with our psyche and compelled people to come up with some explanation for what they witnessed.

                   Where is the RT report room where stories don't echo off the walls--- telling the tale of the "stupid nurse who almost killed the COPD patient by turning up his oxygen"(notice that the patient is always "almost" killed).  Or one of my favorites, "I couldn't wake him up after his O2 was turned up".  Why did you need to wake him up?  Perhaps his hypoxemia was finally relieved so the patient could get a good rest?  Was it time for a sleeping pill?

          Picture that COPDer whom arrives in the ER SOB with a RR 45 and initial PaO2 44, PaCO2 66, pH 7.35 on RA.  So someone places them on a 8 l/m simple mask and draws another ABG---now they are PaO2 110 PaCO2 80, pH 7.25  The patient's RR is now 26 and the patient's respiratory effort is much less labored.  Did we really knock out that patient's drive to breathe?  Or did we relieve the patient's hypoxemia sufficient that the patient could practice their own form of permissive hypercapnea?  If we intubated that patient and considered his auto-peep we may be happy with the latter ABGs also.  Why should the patient suck anymore than we now blow?

          When I bring up my arguments against the hypoxic drive,often I feel as if I am arguing religion and not science.  To walk into a report room of old-timer RTs and challenge this theory is akin to walking into a group of holy-rollers on good Friday and announcing that Easter has been cancelled as they've found the body. Sadly enough, for too many, this hypoxic drive theory represents the high water mark of their theoretical RT development.

          It may be hard for some to let go of this theory.  After all, some of us have been berating others for years.  It made us the keepers of the O2 Black Art, especially when oxygen was a lucrative ancillary service.  The essence of groupthink.

          I may offend some by opening up against this outdated theory with both barrels.  But I feel this assault is exactly what is needed in order to flush this issue out of the obscure corners where it is presently being debated. The damage is happening daily everywhere.

          I have asked local RT instructors their opinion.  One said, "I don't believe in it (CO2 retainer/hypoxic drive theory), but I've got to teach it". 

          This theory causes clinical silliness as we try with oximetry to maintain CO2 retainers in some magic SpO2 range of 88-90%. 

          This theory causes clinical suffering as hypoxemic patients are often denied the very oxygen which would relieve their dyspnea.

          The hypoxic drive theory is already dead.   It's ghost still lives on in clinical practice. But the body is beginning to smell.  Our profession was instrumental in bringing this theory to life.  It is now our responsibility to drive the nails in the coffin, say a few words, and bury it.

         

 

 

 

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          It seems everyone has about 1 or 2 clinical stories where the hypoxic drive theory has happened.  I have my own, but the patient was not a COPDer.

          Let’s consider the typical patient whom is alleged to have had their hypoxic drive suppressed.

          She was in borderline respiratory failure, fatigued, then when the NRB 100% was put on her, her hypoxemia was relieved(especially if her SpO2 on NRB mask was still only 92%).  Perhaps she rested her muscles. Perhaps she was practicing Patient Permissive Hypercapnea?   If she were then intubated and mechanically ventilated, given her emphyzematic obstructive lung mechanics and auto-peep potential, would we settle for a PaCO2 around 90 and the resultant pH?

          Was she policythemic?  If so then the O2 drove off that CO2 reservoir normally carried on her arterial and venous Hgb.  Her CO2 load was then increased, perhaps at the very time she was having trouble handling her normal load (and was her temp increased already also?   had she had a big bowl of pasta before admission?)

          Was there a significant component of increased airway resistance/bronchospasm to her pre-NRB clinical presentation?  If so then the NRB O2 may have released hypoxic pulmonary vasoconstriction in the most poorly ventilated lung units.  That's another problem of the CO2 Retainer/Hypoxic drive theory---it tends to blind us to the real danger of giving severe asthmatics 100% O2 needlessly.  As a counterpoint though, in that asthmatic setting, perhaps the extra O2 prevents a kind of reverse absorption atelectasis and resultant mucous plugging which must occur in the face of widespread pulmonary vasoconstriction ----decreased perfusion, decreased ventilation, decreased alveolar gas of any kind from either the atmosphere or the circulation.  Just a thought.

          Perhaps this patient actually had a compromised hypercapneic drive?   If so, was it related to her chronic PaCO2 level in the 50s?  Patients with lung disease have various degrees of blunted drives and responses of dyspnea.  This all gets complicated real fast.  I just think we need to replace a new, better theory for an older outdated one which causes so much harm and needless work.

          For my story,....

          Years ago in one of the worst hospitals and RT Depts...

          This patient had abdominal surgery, was extubated and re-intubated several times.  I came on the night shift after she had been re-tubed her second time.   I looked at her pre-admission ABG.  It was something like pH 7.38/PaCO2 54/PaO2 58.  She had no lung disease.  She was rather obese, and had a lot of upper airway tissue.  She probably had sleep apnea contributing to her ABG portfolio and respiratory drive.  As I worked the night shift others told me that when they turned down her SIMV rate she just "wouldn't breathe". 

          So that night I got the only oximeter we had(which, at that time everyone was afraid to use so it was kept in a closet).  As I slowly turned down her FIO2 until her SpO2 reached 89% I watched her then start to spontaneously ventilate.  Her post extubation/pre-reintubation ABGs all showed PaO2s into the 100s with a respiratory acidosis.  I returned her to her previous FIO2 and mentioned all this to the young intern on duty that night.  He asked, "What's an oximeter". 

          Later the next day I heard they put her on CPAP on the same FIO2 after someone had accidentally turned off her Cardiac Monitor alarms.   She arrested in the ICU with an unknown down time.  I heard there was a lawsuit going on...Dah...

          Ironic and sad.  The only known time where perhaps the suppression of the hypoxic drive resulted in a fatal outcome and the patient was ....

on a ventilator

not a COPDer.

 

 

 

                   How can we bridge the gap between complicated studies appearing in Critical Care involving computerized models of compartmental systems and the present wholesale clinical belief structure?

          My objective in posting my opinion is to call for an overhaul of the present pervasive belief in the hypoxic drive as the cause of the hypercapnea which may be associated with oxygen therapy.

          The hypoxic drive is still on the exams and believed as gospel by many RTs and treated as an occult phenomenom by many RNs. 

          I am not suggesting that we just give O2 with wanton disregard, rather that we make some effort to eradicate the pervasive belief that any hypoxic drive suppression is the culprit. 

          I mentioned a SpO2 of 97 as, all things(pH,temp,etc) being equal, a  SpO2 of 97 is usually about a PaO2 of 97.  So if for every 10 torr rise in PaO2 a PaCO2 will rise 1-5 torr, then a rise of PaO2 60 to 97(let's round off to 100) will cause the PaCO2 to climb 4-20 torr. So if the patient looks worse with a PaCO2 of 97, back off to 94%.  But do they need to be 88%?  I just think that in most cases we can have our cake and eat it too (relieve hypoxemia and not raise PaCO2 through worsening V/Q mismatch and/or Haldane effect).  It's when the patient is on really high FIO2 with a SpO2 99-100 (and in crisis) that I would get worried.  And again, let's worry a little about that asthmatic also. (Does high FIO2s for asthmatics, especially children, contribute to the RML atelectasis syndrome through absorption atelectasis combined with decreased collateral ventilation?)

          For a patient to have a chronic compensated PaCO2 level shouldn't be a sentence for hypoxemia.  And let's face it, if we settle for a PaO2 of 60 then they're gonna be far lower a lot of the time.  When you consider all the variables in low flow O2 (and how many patients at home or in the hospital will really chronically wear a Venti-mask), the changes in patient position and activity levels, plus the time for ventilation and perfusion to equilibrate in response to any change in FIO2 (even IF the patient is stable during that time frame), then it really becomes an impossible task to keep a patients PaO2 just above the hypoxemic boundary. To even try is silly. We have to chose---over a little or under alot. 

          I don't think just putting a NRB mask flush on a COPD patient in crisis is a benign thing to do.  But I also don't think they need to cruise the hypoxic boundary to maintain a drive to breathe. 

          The question is.......what can we do about the current theory being so pervasive, so wrong, and so harmful? 

          Is our profession mature enough to make a widespread change in such an entrenched belief structure?  Is there a good enough educational background among the vast numbers of RTs in this country to understand how V/Q mismatch and the Haldane effect could be causing this phenomenon when it does occur?  Can we pull the tablecloth off without breaking too many dishes? 

          For those 30% of patients who, with uncontrolled O2 therapy, became unconscious and had their PaCO2 rise over 30/torr in one hour..........weren't they in trouble already handling their CO2 load?  How policythemic were they?  Were their respiratory muscles already fatigued?

 

Let me relate some clinical stories about how this hypoxic drive theory is causing needless harm to patients and silliness among clinicians....

 

1) Many years ago I worked a night registry shift at a hospital across the bay.  In the middle of report we were summoned stat to a med/surg ward.  By the time we arrived the MD was in the patients room having a conversation with her.  The patient was alert, appeared to have respirations slightly labored and appeared slightly cyanotic from the doorway.  We told the charge RN to call us back after the MD had ordered therapy. (Hey, this was in the old days, before protocols and such).  I went back to shift report, got oriented to the hospital quickly and did my first round of treatments. 

          I then stopped by the med/surg ward to see how the patient was doing.  "She's asleep now, we did an ABG" (the regular staff RT did the ABG). 

          Later on in the early AM I again inquired as to how that patient was doing.  "Oh here's the ABG results we got back before"  The patient was on 4l/m nc O2..pH 7.40/PaCO2 44/PaO2 48.  "What did you do", I asked the RN.  "Oh we found out she is a COPDer,so we turned her O2 down to 2l/m and we're doing another ABG in the morning."

          Ahhhhh..........I begged her to turn up the O2 and let me adjust her with an oximeter.  She didn't know what an oximeter was (this was awhile ago and they were just coming out).  I went to the ICU and related the story to the staff RT who was working in the ICU with their only oximeter.

          "Don't tell them about the oximeter, then they'll want it all the time".

Ahhhh........

 

          Report was coming up in a half an hour.  I quickly related to the oncoming therapist my concerns and urged her to quickly do the am ABG, etc.

          The next night I returned.  During my first rounds of treatments I answered a code blue to ICU.  It was that same patient whom was now on a ventilator FIO2 .70.  She didn't make it.  I doubt that she had her hypoxic drive knocked out.

 

2)  I answer a stat call to the floor for a patient in respiratory distress.  He was one of those patients who, by many perspectives, should have been a no-code but wasn't.  He was in distress, cyanotic, rapid RR with audible ronchi, clearly needing NT sx to relieve his struggling discomfort.  I asked one of the RNs to turn up the O2 from 1 l/m to 6 as I went to get the suction catheter and lubricant.

          "NO!  He's a CO2 retainer and the doctor wants him only on 1 l/m"

          I grabbed a bag/mask and hand ventilated him with O2 before successfully NT sxing him. 

          He was a COPDer, but not even a retainer.

          I asked the RN if she planned to bag the patient during a code with compressed air?         

          Later on, when it was less busy, I came by and tried to explain the phenomenon of hyperoxic induced V/Q mismatch and the Haldane effect.  I can still remember the paper with my bizarre scrawlings of pulmonary circulation and little Hgbs.  She got a migraine. 

 

3)  While working on a burn unit, I went to give a HHN tx and check the O2 of a burn patient.  She was a smoker, indeed she smoked her way into the hospital in a literal sense.  In the Progress Notes it said "probable COPD" as she had a long smoking hx.  But she had had no previous hospital admissions for lung trouble or evidence of CO2 retention per ABGs. 

          On 2l/m her SpO2 was 92%, but her RR was 28 and she said she felt slightly SOB.  As often a respiratory alkalosis may raise the SpO2 via hyperventilation, I raised her O2 from 1 l/m to 3.  Her RR dropped to 18 and she no longer complained of SOB.  Her SpO2 was now 96%.  After the HHN tx I told the RN about how I had raised her FIO2.  The RN was concerned as "she is a COPDer".

          I find this doubly ironic given recent discoveries of how O2 is vital to wound healing through incorporation directly into collagen (studies by Hunt).  In this concern it's the PaO2 that's important more than the SpO2, as tissue O2 levels allow increased collagen formation and wound healing.

          Maybe after checking out of the hospital, she could then go to an oxygen bar to augment wound healing?  Just leave those smokes and that Vaseline at home!

          But we don't want to knock out that hypoxic drive!

4)  We had a real live CO2 retainer come in for a lung resection.  His chronic compensated PaCO2 was in the high 70s.  The previous RT had adjusted his O2 to 2/m via oxymizer for a SpO2 of 89% while he was on his left side.  He had left lower lobe atelectasis.  He was on a continuous oximeter.  In the middle of the night I looked in on him.  He was now laying on his right side (bad lung up now), still on the 2l/m O2, RR 20, with a SpO2 of 98%. I changed nothing.  I didn't try to wake him up.  In the morning I stopped by and the patient told me that he had gotten a good night's sleep. 

          So in this situation, if the hypoxic drive theory was real, I guess we'd have to servo the O2 flowmeter to the oximeter to compensate for his body position changes as well as changes in his ventilation and perfusion? Otherwise he'd stop breathing.

          And in closing-----when hypercapnea occurs with oxygen therapy---it's not because you've knocked out their hypoxic drive.  You've driven in a hypercarbic potential. 

         

It's an important distinction.

 

Jeff Whitnack RRT/RPFT

whitnack@pacbell.net

 

Post script……………

 

    As obstuction worsens, the lungs are filled with areas of both increased deadspace and increased compensatory hyper-ventilation.  The result is always that a higher mixed venous PvCO2 then becomes a lower mixed arterial PaCO2 after traversing the pulmonary circulation.   But in between, the vascular bed that this CO2 load must traverse will constrict if subjected to a PaO2 of less than 60 torr.  So, depending on both the level of the FIO2 and the various differences in deadspace and hyperventilatory compensation going on, at a certain level of PvCO2/FIO2 a crossover point will be reached whereby certain lung units, those with the most deadspace and resultant high PACO2 plus a lower PAO2 dropping below 60, will be subjected to pulmonary vasoconstriction.  And meanwhile, those lung units with less deadspace will have a higher than 60 PAO2 and remain unconstricted.  This will help to facilitate better ventilation/perfusion matching.  The pulmonary circulation will be sent to those areas with both the best oxygenation and ventilation.  Unless uncontrolled hyperoxia completely overides this compensatory mechanism. 

    At room air, the adjusted RE PACO2 at which this starts to occur is 90 torr (150-90 =60) or a PvCO2 of 72. Thus, for every bit of extra oxygen we provide to an obstructed patient in severe distress whose CO2 load is climbing over 70 torr (be they an asthmatic or a COPDer), the level of PACO2 necessary to maintain the hypoxic pulmonary vasoconstriction in those worst ventilated lung units is also raised. 

    Or more to the point,....as the combination of deadspace and CO2 load increases,  the dilemna of the tradeoff between adequate oxygenation and the effect of worsening V/Q matching secondary to the release of pulmonary hypoxic vasoconstriction also increases.  Add to this, in patients chronically hypoxemic with elevated Hgb's, the additional effect of a further increased CO2 load secondary to O2 administration, and the drama continues.  What's a poor therapist to do?

    In the midst of this dilemna we must remember that hypoxia kills, hypercarbia by itself does not.

    From a practical standpoint what this means is that..

1) this issue pertains to the patient in distress in the ER.  Not the CO2 retainer whom is home and stable while eating and watching a ball game on TV.  At all costs we must first relieve the hypoxemia.  Ideally we will do so without increasing hypercarbia needlessly.  But it is bound to happen to a degree anyway.  If the level of PaCO2 becomes a clinical problem, your local RCP should be there to assist ventilation, either in a non-invasive fashion or with a secure airway. 

2)  It's not so much that our goal should be to cruise some lower level of normal oxygenation, even in these distressed patients.  It's not so much that a PaO2 of 60 is the goal as much as it is that a PaO2 of 240 secondary to a NRB mask will worsen V/Q matching needlessly. 

3) the whole issue isn't about the drive to breath at all!!  It is about how oxygen therapy affects the real effective CO2 load that the patient is confronted with. 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

         

 

 

 

 

 

 

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