Limitations of O2 Therapy

Dr. Ahmet U. Demir

Hacettepe University Dept. of Chest Diseases

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

Therapy…

COPD Mortality COPD is the only

major disease with increased mortality during the last ~30 years

Mannino DM, Kiriz VA. Int J Chron Obstruct Pulmon Dis. 2006;1(3):219-33. Review.

Benefits O2: decreases pulmonary hypertension,

decreases the eryhtrocyte mass, improves exertional capacity

1980’s: NOTT (Nocturnal Oxygen Therapy Trial) and MRC (Medical Research Council) studies showed that LTOT was the only treatment with survival benefit in COPD and respiratory failure.

Patients were receiving O2 for at least 18 hours a day.

MRC: in hypoxemic COPD, the major benefit among those using O2 >19 h/day

Nocturnal Oxygen Therapy Trial Group

Ann Inter Med 1981, 93:391–8; 1981.

Lancet, 1980:681–5. Abbreviations: MRC,

Medical Research Council; NIH, National Institutes of Health;

NOTT, Nocturnal Oxygen Therapy Trial.

Other Treatments

None of them has a demonstrated effect on mortality! Chest. 2008;133(6):1451-62

This finding has been supported by other studies Other benefits: o Stabilizing the progression of Pulmonary hypertenson

o Decreased rate of arrythmia and myocardial

ischaemiao Increased exertional capacity o Improvement in neuropsychiatric function o Improvement in quality of life o Decreased exacerbation and hospitalizationo Improvement in hypoxemia benefits: depend on compliance and length of

administartion

Most of the patients in the trials are COPD, but other chronic lung diseases are also included

Eur Respir J. 2007 Nov;30(5):993-1013

References 169 Miyamoto K, Aida A, Nishimura M, et al. Gender effect on prognosis of patients receiving long-term home oxygen therapy. Am J Respir Crit Care Med 1996; 152: 972–976. 170 Waterhouse JC, Nichol J, Howard P. Survey on domiciliary oxygen by concentrator in England and Wales. Eur Respir J 1994; 7: 2021–2025. 171 Chailleux E, Fauroux B, Binet F, Dautzenberg B, Polu JM. Predictors of survival in patients receiving domiciliary oxygen therapy or mechanical ventilation. A 10-year analysis of ANTADIR Observatory. Chest 1996; 109: 741–749. 172 Neri M, Melani AS, Miorelli AM, et al. Long-term oxygen therapy in chronic respiratory failure: a Multicenter Italian Study on Oxygen Therapy Adherence (MISOTA). Respir Med 2006; 100: 795–806.

Exertional capacity Meta-analysis of RCT’S comparing

ambulatory O2 treatment with breathing roo air (crossover)

O2: 3-7 L/min, 30%-75% Dyspnea has improved

Exertional capacity short term

O2 arm: ~25 m increase in the distance

Exertional capacity short term

O2 arm: ~2.5 min increase in duration

Exertional capacity short term

O2 arm: maximum duration of exercise increased by ~1 min

Exertional capacity short term

O2 arm: maximum exercise distance increased by ~32 m

Exertion COPD patients without severe exertional

hypoxemia vere enrolled to an exercise program with O2 therapy (7 weeks, 21 times) those with O2 could do more intense exercise and increased perfomance after the program

Long term effect? Proc Am Thorac Soc 2007 Oct 1;4(7):549-

53.

Cost effectiveness Cost effectiveness: ICER (incremental cost-

effectiveness ratios) ICER: in compariosns cost/quality adjusted life

year (QALY) ICER <50, 000 dolar >>> Cost effective Survival data of trials were used to construct a

model QALY estimated according to FEV1 No adjustment for exacerbation O2 equipment: 198$/mo, concentator (continuous): 30$/mo, nocturnal: 11

$/mo

Continuous O2 therapy (16 h/d)

Cost effective

Nocturnal O2 therapy (9 h/d)

Not Cost effective (PaO2: 56-65 mmHg, Sao2<% 90 for >30% of total sleep

time or < %90 + minimum %85)

Other treatments

Am J Manag Care. 2009 Feb;15(2):97-104. Nocturnal O2 is expensive than the other treatments except for alfa1 antitrypsin

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

Addiction No previous finding related to addiction!

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

O2 Harm… Retinal blood flow : influenced by O2 pressure

and blood pressure Hyperoxia>>> retinal vasoconstriction (adult and

newbırn) In the newborn choroidal vessels do not consrict

like in adults >>> increased toxic level of O2 in the retina

Hyperoxygenization >>> peroxidation >>> microvascular injury >>> ischeamia >>> vasoproliferative retinopati

VEGF-A has a major role Pharmacol Rep. 2005;57 Suppl:169-90.

O2 Harm… 100% O2 breathing >>> coronary blood flow decrease by

20%-30%, vascular resistance increases by 23%-40% Large conduit arteries’ dimaters do not change Effect on coronary vascular endothelium:reactive O2

species, rapid degradation of NO Production of free O2 radicals >>> reperfusion injury in

heart Reperfusion provided by thrombolytic therapy and

percutaneous coronary plasty is relevant for thşs effect Wijesinghe M, Perrin K, Ranchord A, Simmonds M,

Weatherall M, Beasley R. Heart. 2009 Mar;95(3):198-202

O2 Harm… 6 studies from 4 publications that met the inclusion criteria,

with 6 healthy subjects and 61 subjects with cardiac disease.

high-concentration oxygen therapy resulted in hyperoxia, with a range in mean Pao(2) of 273 to 425 mm Hg.

Hyperoxia caused a significant reduction in coronary blood flow (mean change -7.9% to -28.9%, n = 6 studies).

Hyperoxia caused a significant increase in coronary vascular resistance (mean change 21.5% to 40.9%, n = 4 studies) and a significant reduction in myocardial oxygen consumption (mean change -15.3% to -26.9%, n = 3 studies).

Farquhar H, Weatherall M, Wijesinghe M, Perrin K, Ranchord A, Simmonds M, Beasley R. Am Heart J. 2009;158(3):371-7.

O2 Harm… O2 >>> hypercapnia Hypoventilation (abolishing hypoxemic

stimulus from peripheral chemoreceptors)) Ventilation perfusion changes (abolishing

hypoxic pulmonary vasokonstriction, perfusion of hypoventialted lung regions)

Haldane effect (O2 binding to Hb releases CO2)

Sleep and Respiration

Due to alveolar hypoventilation PaCO2 increase by 3-7

mmHg, PaO2 decrease by 3.5-

9.4 mmHg, SaO2 decreases by

~2%

These changes are not clinically significant

However individuals with compromised lung funciton during the day have difficulty during sleep (COPD) especially during REM sleep

Sleep and Respiration Decreased Tidal volume, changes in the

ventilation perfusion due to lying, decreased mucocilliary clearance azalma >>> aggrevated hypoventilation

Sleep and Respiration Sleep hypercapnia was observed in a high

percentage of COPD patients, 43% and 59%, respectively,

was likely due to the oxygen therapy. Tárrega J, Güell R, Antón A, et al. Respir

Care 2002., 47:882–6. O´Donoghue F, Catcheside P, Ellis E, et al..

Eur Respir J 2003;21:977–84.

Sleep and Respiration Nocturnal flow rate was increased by 1

liter and this induced sleep hypercapnia and respiratory acidosis in a significant number of patients (34.2% vs. 23.7% of patients)

Samolski D, Tárrega J, Antón A, Mayos M, Martí S, Farrero E, Güell R. Respirology. 2010 Feb;15(2):283-8

Sleep and Respiration If patients present with sleep hypercapnia

then: o early mornig PaO2 o test for the presence of OSAS. o Once OSAS is ruled out, the best way to

treat thesepatients with SH under oxygen therapy may be to use the

o Venturi mask or noninvasive ventilation. Pulmon Dis. 2008;3(2):231-7.

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

Early Treatment Twenty-seven patients completed blinded N-of-1 RCTs,

each comprising three pairs of 2-week home treatment periods, with oxygen provided during one period of each pair and a placebo mixture during the other.

Patients: COPD, limited their daily activities due to dyspnea, 2 consecutive minutes with SaO2 88% or less in 6 minute walk test

O2 treatment: no effect on quality of life 5 minute walk test significant improvement with O2: 427 vs

412 steps 2 patients responded (improvement in chronic respiratory

questionnaire compared to placebo in all 3 pairs) Nonoyama ML, Brooks D, Guyatt GH, Goldstein RS. Am J

Respir Crit Care Med 2007; 176: 343–349

None of the QOL scores (dyspnea, fatigue, emotion and mastery) changed significantly

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

Prescribing… In many European

countries patients are tested in supine rather than sitting position

target SaO2 varies from 90% to 92%

not all countries measure arterial blood gases or test SaO2 during sleep.

Lack of standardization

Questions to consider in practical life Do you give this to treat? Does it cause addiction? Does it have a harmful effect? If it is so beneficial why don’t we

recommend it earlier? Is arterial blood gas analysis required to

prescribe long term oxygen treatment? Is there problems related to the use of

oxygen?

Treatment Compliance and Problems Adherence: 45%-70%* concentrator: suspicions about their

efficacy** Compliance rate could be lower than

estimated ** Control visits could improve the

compliance** *: Chron Respir Dis. 2006;3(4):217-22. **: Respir Care. 2000 Feb;45(2):223-8

Treatment Compliance and Problems Early studies were performed before

portable systems were widely used COPD patients: limited by slight exertion

(eating etc) and have dyspnea Data is scanty about 24 h use

International Journal of COPD 2008:3(2) 231–237

Treatment Compliance and Problems meta-synthesis of qualitative studies of O2 treatrment formulated four themes : adapting oxygen to life's

circumstances, living in a restricted world, self-management is fostered by oxygen

two major results: persons prescribed oxygen rationalize its use while negotiating lifestyle interference and physical restrictions and the drive to care for one's self is conflicted.

Patient develops dependency to O2 each oxygen user faces tremendous physical,

psychological, and emotional challenges. They strive to adapt and maintain mastery but eventually

oxygen dependency results. These challenges affect the patient's ability to adhere to

their treatment guidelines. These barriers and challenges are seldom addressed and are under-treated.

J Adv Nurs 2009 Mar;65(3):634-41

Increase Nocturnal O2? Thirty eight patients (63% men) of mean (SD) age

73.5 (8.04) years and mean (SD) forced expiratory volume in 1 second 0.77 (0.35) l were evaluated.

Overnight desaturation occurred in six (16%; 95% CI 4 to 27).

Desaturators had mean (SD) resting oxygen saturation on room air of 88 (4.2)% compared with 90 (4.1)% in non-desaturators

HRQL and sleep quality were poor but did not differ between desaturators and non-desaturators.

Thorax 2006;61(9):779-82.

Conclusions The following should be addressed in

further studies: o Compliance with O2 treatment o O2 treatment to improve exertional

capacity o Usage of O2 during sleep o Long term effects of O2 treatment