My 75 year old patient has an arterial oxygen tension (Pa02) less than 90 mmHg on room air. Does age affect PaO2?

Short answer: Yes! Most studies of blood gas concentrations have demonstrated a decrease in oxygen tension with age.1

Earlier studies have demonstrated a linear decrease in oxygen tension based on observations that included relatively small number of patients over the age of 60. 1 More recently, however, in a study of 532 consecutive patients admitted for elective surgery without overt cardiac, pulmonary, or metabolic disease, obesity or smoking, the mean PaO2 differed by age group as follows:

  • <30 years: 98.4 mmHg
  • 30-50 years: 88.7 mmHg
  • 51-70 years: 81.0 mmHg
  • >70 years: 76.5 mmHg

After age 70 years, decline in Pa02 may slow down or actually reverse, likely related to the “survival of the fittest” in more advanced years. 1,2 Some have suggested accepting a PaO2 80-85 mmHg as normal for subjects > 65 years of age. 3

The decrease in PaO2 with age is a result of increased heterogeneity of ventilation/perfusion ratio, especially reduced ventilation in the dependent parts of the lung. 3 Aging is also associated with a decrease in chest wall compliance, muscle (including the diaphragm) strength, forced expiratory volume in 1 second (FEV1), vital capacity, and diffusing capacity of carbon monoxide (DLC0)/alveolar volume.  

In addition, aging is associated with a reduction in response to hypoxia and hypercarbia, making older patients particularly vulnerable to complications from  heart failure and pneumonia4, especially in the current Covid-19 era.

Bonus Pearl: Did you know that poor response to hypoxic or hypercarbic states in the elderly is likely related to an age-related decline in efferent neural output to respiratory muscles?4

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References

  1. Blom H, Mulder M, Verwej W. Arterial oxygen tension and saturation in hospital patients: effect of age and activity. BMJ 1988;297:720-2. Doi:10.1136/bmj.297.6650.720 https://www.bmj.com/content/297/6650/720   
  2. Delclaux B, Orcel B, Housset B, et al. Arterial blood gases in elderly persons with chronic obstructive pulmonary disease (COPD). Eur Respir J 1994;7:856-61. https://www.researchgate.net/publication/15147788_Arterial_blood_gases_in_elderly_persons_with_chronic_obstructive_pulmonary_disease_COPD
  3. Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Respir J 1999;13:197-205. https://www.researchgate.net/publication/12689073_Physiological_changes_in_respiratory_function_associated_with_ageing
  4. Sharma G, Goodwin J. Effect of aging on respiratory system physiology and immunology. Clin Interventions in Aging 2006;1:253-60. https://pubmed.ncbi.nlm.nih.gov/18046878/

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

My 75 year old patient has an arterial oxygen tension (Pa02) less than 90 mmHg on room air. Does age affect PaO2?

My 65 year old patient on chronic warfarin happens to have diffuse tracheobronchial calcification on her chest X-ray. Could warfarin be the culprit?

Absolutely! Although tracheobronchial calcification (TBC) is often found as part of normal aging process in the elderly, especially women, long-term warfarin use has also been implicated as a cause of TBC, even among those with less advanced age (1-4).

In a cohort of patients 60 years of age or older, radiographic evidence of trachea and bronchi calcification was found in 47% of patients on warfarin (mean age 64 years, mean duration of treatment 6 years) compared to 19% of controls (1). A positive correlation between the duration of warfarin therapy and increased levels of calcification was also found.  Fortunately, TBC is a benign finding and has no health consequences.

As for the mechanism for this rather intriguing phenomenon, the inhibition of a vitamin K-dependent protein that prevents calcification of cartilaginous tissue seems to be the most plausible (1). Although we often think of vitamin-K dependent factors in relation to the coagulation cascade, several vitamin K-dependent proteins also play an important role in the inhibition of calcification in soft tissues and blood vessels (eg, matrix Gla protein-MGP) (5,6).

In fact, rats maintained on warfarin undergo calcification of cartilage and elastic connective tissue, while exposure of the fetus to warfarin during pregnancy is associated with calcifications in and around joints, airway and nasal cartilages (4,7). These observations further support a causative role of warfarin in inducing TBC.

 

Bonus Pearl: Did you know that MGP deficiency in humans is known as the Keutel syndrome, a rare autosomal recessive disease characterized by several characteristic physical features, including severe cartilage calcifications and depressed nasal bridge?

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References

  1. Moncada RM, Venta LA, Venta ER, et al. Tracheal and bronchial cartilaginous rings: warfarin sodium-induced calcification. Radiology 1992;184:437-39. https://pubs.rsna.org/doi/10.1148/radiology.184.2.1620843
  2. Thoongsuwan N, Stern EJ. Warfarin-induced tracheobronchial calcification. J thoracic Imaging 2003;18:110-12. https://journals.lww.com/thoracicimaging/Abstract/2003/04000/Warfarin_Induced_Tracheobronchial_Calcification.12.aspx
  3. Nour SA, Nour HA, Mehta J, et al. Tracheobronchial calcification due to warfarin therapy. Am J Respir Crit Care Med 2014;189:e73. https://www.atsjournals.org/doi/full/10.1164/rccm.201305-0975IM
  4. Joshi A, Berdon WE, Ruzal-Shapiro C, et al. CT detection of the tracheobronchial calcification in an 18 year-old on maintenance warfarin sodium therapy. AJR Am J Roentgenol 2000;175:921-22. https://www.ajronline.org/doi/full/10.2214/ajr.175.3.1750921
  5. Wen L, Chen J, Duan L, et al. Vitamin K-dependent proteins involved in bone and cardiovascular health (review). Molecular Medicine Reports 2018;18:3-15. https://www.spandidos-publications.com/mmr/18/1/3/abstract \
  6. Theuwissen E, Smit E, Vermeer C. The role of vitamin K in soft-tissue calcification. Adv Nutr 2012; 3:166-173. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648717/pdf/166.pdf

7.      Price PA, Williamson MK, Haba T, et al. Excessive mineralization with growth plate closure in rats on chronic warfarin treatment. Proc Natl Acad Sci  U.S.A 1982;79:7734-8. https://www.ncbi.nlm.nih.gov/pubmed/6984192

My 65 year old patient on chronic warfarin happens to have diffuse tracheobronchial calcification on her chest X-ray. Could warfarin be the culprit?

My elderly nursing home patient is admitted with recent poor oral intake, falls and oral temperatures of 99.1°-99.3° F(37.3°-37.4°C). Is she considered febrile at these temperatures?

Yes! Even though we often think of temperatures of 100.4°F (38° C) or greater as fever, older people often fail to mount an appropriate febrile response despite having a serious infection. 1

Infectious Diseases Society of America (IDSA) guideline on evaluation of fever in older adult residents of long-term care facilities has defined fever in this population as:2

  • Single oral temperature >100° F (>37.8° C) OR
  • Repeated oral temperatures >99° F (>37.2° C) OR
  • Rectal temperatures >99.5° F (>37.5° C) OR
  • Increase in temperature of >2° F (>1.1° C) over the baseline temperature

Even at these lower than traditional thresholds for defining fever, remember that many infected elderly patients may still lack fever. In a study involving bacteremic patients, nearly 40% of those 80 years of age or older did not have fever (defined as maximum temperature over 24 hrs 100° F [37.8°C] or greater).3  

So our patient meets the criteria for fever as suggested by IDSA guidelines and, particularly in light of her recent poor intake and falls, may need evaluation for a systemic source of infection.

Bonus Pearl: Did you know that blunted febrile response of the aged to infections may be related to the inability of cytokines (eg, IL-1) to reach the central nervous system?1

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References 

  1. Norman DC. Fever in the elderly. Clin Infect Dis 2000;31:148-51. https://academic.oup.com/cid/article/31/1/148/318030
  2. High KP, Bradley SF, Gravenstein S, et al. Clinical practice guidelines for the evaluation of fever and infection in older adult residents of long-term care facilities: 2008 update by the Infectious Disease Society of America. Clin Infect Dis 2009;48:149-71. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/Fever%20and%20Long%20Term%20Care.pdf
  3. Manian FA. Fever, abnormal white blood cell count, neutrophilia, and elevated serum C-reactive protein in adult hospitalized patients with bacteremia. South Med J 2012;105;474-78. http://europepmc.org/abstract/med/22948327

 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis or its affiliate healthcare centers, Mass General Hospital, Harvard Medical School or its affiliated institutions. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

My elderly nursing home patient is admitted with recent poor oral intake, falls and oral temperatures of 99.1°-99.3° F(37.3°-37.4°C). Is she considered febrile at these temperatures?