Here's how NIV benefits CO2-retaining COPD patients

I often tell my patients that nothing I do cures any ailment.  To the contrary, I tell them that the procedures I perform treat acute symptoms, while the doctor and nurse do other things that will provide the cure.

A perfect example of this is with noninvasive ventilation (NIV) for treatment of acute respiratory distress due to chronic obstructive pulmonary disease (COPD). Savi et al, 2014, notes the following:

Noninvasive ventilation benefits patients with COPD, and it seems reasonable to expect that NIV would increase tidal volume and improve CO2 elimination, and thus reduce respiratory drive.

The note the studies have proven that NIV results in the following when used on COPD patient's presenting to the emergency room with flare-ups:

• Reduction of treatment failure
• Lower mortality
• Fewer complications
• Lower Intubation rates

However, the studies also conclude that:  "In these patients CO2 elimination is increased but overall ventilation-perfusion mismatch is not changed during NIV. 

What does improve ventilation, the authors note, are the following:

• Treating precipitating factors (eg, infection with antibiotics)
• Increase expiratory flow (eg, with beta agonists)
• Reduce pulmonary inflammation (eg, with corticosteroids)
• Manage gas exchange (eg, improve oxygenation)

Without NIV, studies have shown, patient's who have COPD with CO2 retainers should receive an FiO2 just enough to maintain an SpO2 of 88-92%, as higher FiO2s (either due to the loss of hypoxic drive, or V/Q mismatching) have been shown to cause a rise in PaCO2.  

However, this effect is negated with NIV.  Savi et al concludes:

During NIV with an FiO2 sufficient to maintain a normal PaO2, a further increase in FiO2 does not result in an increase in PaCO2 in CO2-rataining COPD patients, since no changes occur in (minute ventilation).

Crossley et al had similar results, concluding, that "CO2-retaining COPD patients following a period of mechanical ventilation with PaO2 in the normal range can safely receive supplemental oxygen without retaining CO2 or a depression of respiratory drive.  A new ventilation-perfusion relationship is established during ventilation to normoxia, and it is not altered by further increasing FiO2," Savi et all reports.

Since NIV helps COPD patients take deeper breaths, thus improving their ventilation (allowing them to blow off CO2), high levels of oxygen do not cause rising PaCO2 levels while a patient is receiving NIV therapy.  However, we often find that, while using NIV, many patients require less oxygen compared to prior to the NIV start.

Bottom line:  NIV is beneficial to CO2-retaining COPD patients because it increases their tidal volume, increases CO2 elimination, and reduces their drive to breathe.  By treating these symptoms, caregivers are provided an opportunity to do whatever is necessary to treat the cause of the exacerbation (even if that means utilizing higher oxygen levels).

References:

1. Savi, Augusto, Jucara Gasparetto Maccari, Tulio Frederico Tonietto, Ana Carolina Pecanha Antonio, Roselaine Pinheiro de Oliveira, Marcelo de Mello Rieder, Evelyn Cristina Zignani, Emerson Boschi da Silva, and Cassiano Teixeira, "Influence of FiO2 on PaCO2 During Noninvasive Ventilation in Patients With COPD," Respiratory Care, March, 2014, volume 59, number 3, pages 383-387

Hypoxic Drive Theory: Here are the evidence that disproves it

The hypoxic drive theory was established in 1960.  Since then many studies have shed doubt on this theory, in favor of the Haldane Effect and ventilation-perfusion mismatching.  Listed here is all the evidence that either proves or disproves these theories.

1. Hoyt, John. W., "Debunking the Myths of Chronic Obstructive Pulmonary Disease", Critical Care Medicine, 1997, Volume 25, Number 9, pages 1450-1451 (you'll have to obtain a prescription to view article)
2. Campbell, E.J.M, "Respiratory Failure,"  The British Medical Journal,  June 1965, 1451-1460 (article provided by link)
3. Arnottt, W.M, "Respiratory Failure,"  Lancet,  January 1960, Volume 25, Issue 7114, pages 1-7 (you'll have to subscribe to view article)
4. Campbell, E.J.M, "The J. Burns Amberson Lecture - Management of Acute Respiratory Failure in Chronic Bronchitis and Emphysema," The Journal of Occupational and Environmental Medicine, June 1968,  Volume 10, issue 6, pages 329-332  (You'll have to become a member to veiw article)
5. Campbell, E.J.M, "The J. Burns Amberson Lecture - Management of Acute Respiratory Failure in Chronic Bronchitis and Emphysema," American Review of Respiratory Diseases, October 1967, Volume 96, Issue 4 (no link available)
6. Scano,G, A. Spinelli,  R. Duranti, M. Gorini, F. Gigliott i, P. Goti, J. Milic-Emili, "Carbon dioxide responsiveness in COPD patients with and without chronic hypercapnia," Europe Respiratory Journal, 1995, Volume 8, pages 78-85 (full pdf provided by link)
7. Robinson, Tracy D  David B. Freiberg, Jeff A. Regnis and Iven H. Young, "The Role of Hypoventilation and Ventilation-Perfusion Redistribution in Oxygen-induced Hypercapnea during Acute Exacerbation of Chronic Obstructive Pulmonary Disease," American Journal of Respiratory and Critical Care Medicine, 2000, volume 161, pages 1524-1529 (full pdf provided by link)
8. Aubier, M, et al, "Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure", American Review of Respiratory Diseases,  1980, Volume 122, pages 747-754 (abstract available by link)
9. Hanson, et all, "Causes of hypercapnia with Oxygen Therapy in patients with Chronic Obstructive Pulmonary Disease," Critical Care medicine, 1996, volume 24, pages 23-28 (abstract available by link)
10. Lazic, D, et al, "The influence of oxygen therapy on the hypercapnia in patients with chronic obstructive pulmonary disease,"  July 2008, Volume 65, Issue 7, pages 521-524 (abstract available by link)
11. Sassoon, C.S., et al, "Hyperoxic-induced Hypercapnea in Stable Chronic Obstructive Pulmonary Disease," American Review of Respiratory Disease, 1987, 144, pages526-530 (abstract available by link)
12. Chien, et al, "Uncontrolled Oxygen Administration and Respiratory Failure in Acute Asthma," Chest, March 2000, Volume 117, Issue 3, pages728-733 (abstract available by link, or pdf here)
13. Caruana-Montaldo, et al, "The Control of Breathing in Clinical Practice," January 2000, 117/1, pages 205-225 (Article available by link)
14. Dunn, et al, "Oxygen-Induced Hypercarbia in Obstructive Pulmonary Disease," American Review of Respiratory Disease, 1991, 144, pages 526-530
15. Gosselink, R, H, Stam editors, Lung Function Testing, 2000 chapter 3, "Control of Breathing," , page 51 (chapter 5 provided for viewing only, supports Campbell)
16. Rudolf, et al, "(Hypothesis) Hypercapnea During Oxygen Therapy in Acute Exacerbation of Chronic Respiratory Failure," Lancet, September 3, 1977, pages 4483-486 (Abstract available by link, prescription needed to view article)
17. Stradling, J.R, "(Editorial) Hypercapnia during oxygen therapy in airways obstruction: a reappraisal," Thorax, December 1986, 41(12) pages 897-90202 (have to subscribe to veiw article)
18. Siafakas, N. M, editor, Mitrouska, I, N. Tzanakis, N.M. Siafakas, Management of Chronic Obstructive Pulmonary Disease, Chapter 18,  "Oxygen Therapy in Chronic Obstructive Pulmonary Disease," 2006, pages 302-308
19. Crossley, et al, "Influence of inspired oxygen concentration on deadspace, respiratory drive, and paCO2 in intubated patients with chronic obstructive pulmonary disease," Critical Care Medicine, 1997, volume 25, Number 9, pages 1522-1526 (abstract available by link)
20. Plantt, et al, "One year prevalence study of respiratory acidosis in acute exacerbations of COPD:  implications for the provision of non-invasive ventilation and O2 administration," Thorax, 2000, 55, pages 550-554 (full pdf available by link, for abstract click here).
21. Molfino, et al, "respiratory arrest in Near-Fatal Asthma," New England Journal of Medicine, 1991, 324: pages 285-288 (abstract available by link,  another abstract available here or full pdf available here)  Correspondence to this article from pages 205-206 here.
22. McFadden, "(Editorial) Fatal and Near Fatal Asthma," New England Journal of Medicine, 1991, 324: pages 409-411
23. Burnell, et al, "(Case Report) Extreme Obesity Associated with Alveolar Hypoventilation- A Pickwickian Syndrome," , American Journal of Medicine, 1956, 21:811-818 (abstract available by link)
24. Wagner, et al, "Ventilation-perfusion inequality in chronic obstructive pulmonary disease," The Journal of Clinical investigations, February 1977, Volume 59, pages 203-216 (full article available by link)
25. Dick, et al, "O2-Induced changes in Ventilation and Ventilatory Drive in COPD," American Journal of Critical Care Medicine, 1997, Volume 115, pages 609-614 (abstract available by link)
26. Gasparini, et al, "Inter-Individual Variability of the Response to Oxygen Administration in Hypercapneic Patients," European Journal of Respiratory Disease,  1986, 69 (suppl 146) 427-443 (no abstract or pdf availaable)
27. Schiavi, "Acute Respiratory Failure in Chronic Obstructive Pulmonary Disease," Clinical Pulmonary Medicine, May 1998
28. Gomersall, Charles D, et al, "Oxygen therapy for hypercapnic patients with chronic obstructive pulmonary disease and acute respiratory failure: A randomized, controlled pilot study," Critical Care Medicine, January 2002, 1: 113-116 (abstract available by link)
29. Simpson, Stephen Q, "(Editorial) Oxygen-induced acute hypercapnia in chronic obstructive pulmonary disease: What's the problem?" Critical Care Medicine, January 2002, 1, page 258
30. Day, Rene A, Beverly Williams, Brunner and Suddarth's Textbook of Canadian Medical-Surgical Nursing, 2009, page 654
31. French, William A, "The Hypoxic Drive Theory Revisited," RT:  For Decision Makers in Respiratory Care, " February/ March, 2000
32. "Hypoxic Drive Theory: A Myth -- the why and how," Myparamedicblog.wordpress.com, 2009, http://paramedicblog.wordpress.com/2009/11/19/hypoxic-drive-theory-myth-the-why-and-how/
33. Siobal, Mark, "Hypoxic Drive in Chronic Obstructive Lung Disease: Is the fear of oxygen therapy based on fact or myth," UCSF San Fransisco General Hospital," power point presentation: PPT
34.  Beachey, Will, "Breathing Control in Chronic Hypercapnia," RT:  For Decision Makers in Respiratory Care, " June/ July, 2000
35. "Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients prehospital setting: randomized controlled trial," British Medical Journal, 2010, page 341, C5462
36. Correspondence (Aubier and Stradling regarding study cited in #8 above), American Review of Respiratory Disease, Oct. 16, 1986
37. Aubier, et al, "Central Respiratory Drive in Acute Respiratory Failure of Patients with Chronic Obstructive Pulmonary Disease," American Review of Respiratory Disease, 1980, Volume 122, pages 191-99
38. Grief, Robert, et al, "Supplemental perioperative oxygen to reduce the incidence of surgical wound infection," The New England Journal of Medicine, Jan. 20, 2000, volume 342, no. 3
39. Jonnson K, et al, "Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients," Ann Surg, Nov. 1991, 214 (5), pages 605-13
40. La Van, FB, TK Hunt, "Oxygen and wound healing," Clin Plast Surg, July, 1990, 17 (3), pages 463-72
41. Bartells, Matthew N., John M. Gonzales, Woojin Kim, Ronald E. De Meersman, "Oxygen Supplementation and Cardiac-Autonomic Modulation in COPD, Chest, 2000, 118, pages 691-6
42. Noriaki, et al, "the relationship between chronic hypoxemia and activation of the tumor necrosis factor-x- system in Patients with Chronic Obstructive Pulmonary Disease, American Journal of Respiratory and Critical Care Medicine, April, 2000, Vol. 161, Number 4, pages 1179-1184
43. Mannix, ET, F. Manifredi, MO Farb er, "Elevated O2 cost of ventilation contributes to tissue wasting in COPD," Chest, March, 1999, volume 115, no. 3, pages 708-13
44. Macnee, Skwarski, "The pathogenisis of peripheral edema in Chronic Obstructive Pulmonary Disease," Clinical Pulmonary Medicine, Nov., 1997
45. "Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema.  Report of the Medical Research Council Working Party, Lancet, 1981, 1(8222), pages 681-6
46. Plywaczewski, et al, "Incidence of nocturnal desaturation while breathing oxygen in COPD patients undergoing long-term oxygen therapy," Chest, 2000, 117, pages 679-83
47. Burnell, et al, "(Case Report) Extreme obesity associated with aleolar hypoventilation -- a pickwickian syndrome," American Journal of Medicine, 1956, 21, pages 811-18
48. Steven M., Scharf, Michael R. Pinsky, Sheldon Magder, ed., "Respiratory-circulatory interactions in health and disease," 2005, New York, pages 656-658.  This provides a great review of all the evidence that disproves the hypoxic drive theory up to this date.  Great read for those interested. 
49. Cooper, Nicola, Kirsty Forrest, Paul Cramp, "Essential guide to acute care," 2nd edition, 2006, Massachusettes, page 24
50. Moulton, Chris, David W. Yates, "Lecture notes:  Emergency Medicine," 3rd ed., 2006, pages 215-16
51. Savi, Augusto, et al, "Influence of FiO2 During Noninvasive Ventilation in Patients with COPD," Respiratory Care, March, 2014, Volume 59, Number 3, pages 383-387
52. Young

Note:  Various individuals contributed to this list, most notably Jeffrey Whitnack and Dana Oachs. 

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What is the hypoxic drive theory?

The hypoxic drive theory was born in the 1950s, was given credulity in 1960, and was first disproved in 1987.  (1)  Since then the theory, known to some as the myth or the hoax, has become one of the most hotly debated theories in all of medicine.

The crux of the theory is that the main drive to breath comes from neurons in the medulla oblongata at the base of the brain.  These neurons receive signals from central chemoreceptors on the medulla and peripheral chemoreceptors located in the bifurcations of the aortic arteries and the aortic arch.

Respiratory rate is adjusted to maintain a normal acid base balance (pH) throughout the body.  The majority of the times, the central chemo receptors send signals to the brain that control breathing. They monitor carbon dioxide (CO2) levels.  When CO2 levels are high a signal is sent to speed up the drive to breathe to blow off the excess CO2.  In this way, CO2 is our main drive to breathe.

The peripheral chemo receptors send a signal to breathe when the partial pressure of oxygen in the arteries (PaO2) is less than 60. This is referred to as the hypoxic drive.  This hypoxic response is far slower than signals sent by central chemoreceptors, and therefore the hypoxic drive has only a minor role in breathing.

In COPD patients, chronic airway obstruction due to bronchospasm and increased mucus secretion blocks air passages, and as a result many alveoli become ineffective at ventilating (CO2 cannot get out and oxygen cannot get in).  For these patients, this results in a chronically elevated CO2 (greater than 50), and lowered oxygen levels (SpO2 less than 90 and Po2 less than 60). (2)

As CO2 rises, bicarbonate (HCO3) falls in order to compensate and prevent acidosis (a drop in pH, or a pH less than 7.35).  The result here is that many of these patients normally live with something like a PaCO2 of 50, a PaO2 of 50, and a Bicarb of 30.  These patients are aptly referred to as CO2 retainers, or simply retainers.

In many instances students are incorrectly taught that all COPD patients are retainers who breathe under influence of the hypoxic drive.  The truth is that less than 25 percent of chronic CO2 retainers use the hypoxic drive to breathe, (4) and it's not as significant as once believed.

In fact, of patients who present to hospitals in respiratory distress, half will have reversible CO2 retention, and half will be chronic CO2 retainers.  (5)

The hypoxic drive theory has it that the high CO2 may make the chemoreceptors tolerant of the high CO2, and thus CO2 ceases to be that person's drive to breath.  These patients are your prototypical CO2 retainers. The hypoxic drive theory, thus, states that many of them are hypoxic drive breathers.

Those who believe in the theory believe if you give these patients too much oxygen, enough to drive their PO2 above 70, then you will blunt their hypoxic drive and knock out their drive to breathe.  Their respiratory rare will slow, their CO2 will therefore rise even more, acidosis will occur, the patient will become lethargic (very sleepy or somnolent), and ultimately they will stop breathing.

It is for this reason that most medical experts champion for never over-oxygenating patients who are CO2 retainers. The experts recommend using a nasal cannula set at 2-4lpm, and never higher.  Or, if their respiratory rate is sporadic, to use a venturi mask set no higher than 40% FiO2.

These experts say that if the CO2 rises, that the FiO2 should be lowered.  This has resulted in many physicians accepting PO2s in the lower 80s and even the upper 70s in certain patients.

Yet this often results in the ire of caregivers taking care of these patients, because they are the ones who have to watch them suffer from dyspnea, or air hunger, or the feeling they can't catch their breath.

It has also resulted in ire because many of these patients are placed on 100% oxygen with no ill effect.  Many of these patents have been given breathing treatments using oxygen, estimated to be about 60%, and have never seen any patient drop dead during a breathing treatment.

It was evidence like this that made clinicians second guess the hypoxic drive theory.  It was from here that various studies were done to show, once and for all, whether the hypoxic drive theory is a fact, or whether it's nothing more than a medical myth.

What in turn happened was that, even though most studies proved the theory was in fact a myth, the subject became even more controversial.

References:

1. Schmidt, Greggory A., Jesse B. Hall M.D "Oxygen Therapy and Hypoxic Drive to Breath:  Is There Danger in the patient with COPD?" Critical Care Digest, 1989, 8, pages 52-53
2. Wilkins, Robert L, James K. Stoller, ed. "Egan's Fundamentals of Respiratory Care," 2009, pages 309-310
3. Caruana-Montaldo, Brendan, et al, "The Control of Breathing in Clinical Practice," Chest, 2000, 117, pages 205-225 (This article also provides a good review of the central and peripheral chemoreceptors and the drive to breathe)
4. Wojciechowski, William V., "Entry Level Exam Review for Respiratory Care:  Guidelines for success," 3rd edition, 2011, U.S., page 487?
5. Cooper, Nicola, Kirsty Forrest, Paul Cramp, "Essential guide to acute care," 2nd edition, 2006, Massachusettes, page 24

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