The International Convention Centre (ICC),

Birmingham11 – 12

September 2017

British Thoracic Society

Acute Oxygen Guideline

What’s new in 2017?

Birmingham

11-12 September 2017

Dr Ronan O’DriscollConsultant Respiratory Physician

Salford Royal Foundation NHS TrustSalford M6 8 HD

ronan.o.driscoll@srft.nhs.ukNo conflict of interests to declare

Oxygen is probably the most

commonly used drug

in emergency medicine

• 34% of emergency ambulance

patients receive oxygen1

• 14% of UK hospital patients were

using oxygen during BTS audits2

Approx 2-4 million people per year in UK

UK Emergency Oxygen

Guideline published 2008

Endorsed or

supported

by 21 other

Societies and

Colleges

• Aim at a lower level for those at risk from hypercapnia (Target 88-92% or patient-specific target range)

• Aim for a normal or near-normal oxygen

saturation level for most patients (94-98%)

• Oxygen is a treatment for Hypoxemia

Key Principles

of the Guideline

•Doctors prescribe a “Target Range” and Nurses

adjust equipment and flow rates to achieve this

Giving oxygen does not relieve breathlessness or increase the oxygen

supply to vital organs if the patient’s oxygen level is normal to start with

*The target saturation range will guide NEWS oximetry scores in future*

Why do we use oxygen?

Risks of hypoxaemia

Hypoxaemia is associated with

increased mortality in many studies

• Acute Medical Admissions1

• Post Resuscitation2,3

• Ventilated ICU Patients4,5

• Traumatic Brain Injury6

• Chronic conditions e.g. COPD7

Oxygen saturation on air and survival

for 37,593 acute medical admissionsSmith GB et al. Resuscitation 2012 ;83:1201-5

Oxygen Saturation

Mortality (%)With 95% CI bars

…but those who die are

older and sicker and thus

more likely to have a

lower oxygen level

Tachycardia is also associated with mortality risk

………but beta blockers do not reduce mortality

for most sick patients with tachycardia

Risks of

hyperoxaemia

…too much of a good thing!

Pulmonary Oxygen Toxicity

Lorrain-Smith EffectJL Smith J Physiology 1899 Vol 24 p19-35

Fatal pneumonia was observed in rats

after breathing 73% oxygen for 4 days

Human experiments found evidence of “leaky airways”

in healthy subjects after inhaling 30% oxygen for 45 hours

Griffith DE et al Am Rev Respir Disease 1986 ; 134: 233-237

Critical Illness Requiring High Levels of Oxygen Supplementation

Serious Illness Requiring Moderate Levels of Oxygen if the Patient is Hypoxaemic

COPD and Other Conditions Requiring Controlled or low-dose Oxygen Therapy

Conditions for which patients should be monitored closely but oxygen therapy is not required unless the patient is hypoxaemic

Pre

scrib

e to targ

et

BTS Recommendations

Year2008 2009 2010 2011 2012 2013 2015

Hospitals 99 47 90 156 145 151 180

Wards 712 300 1,026 1919 1733 2074 2473

Patients 14,830 7,113 22,017 41,009 38,094 45,032 55,208

Percent

on Oxygen 17.5% 18.4% 15.5% 13.7% 14.0% 13.8% 14.0%

BTS Oxygen audits 2008-2015

Prescription of oxygen

Percent of patients using oxygen who had a prescription or other written order for oxygen use

• 32% in 2008

• 48% in 2011

• 55.1% in 2013

• 57.5% in 2015

Observations Rounds for 4083 patients

on Oxygen with a Target Range 2015• 69% of patients within the target range

• 31% of patients outside the target range

Below

Target Range

Above

Target Range

By 1% 3% 6%

By 2% 3% 7%

By >2% 3% 9%*

Total 9% Below target range

22% Above target range

*It is not possible to be >2% above target range if target range is 94-98% Therefore, all patients who are >2% above target are at risk of hypercapnic respiratory failure

New evidence contradicting

2008 BTS Guideline advice

None that we know of

The 2015 Thoracic Society of Australia and New Zealand

recommends a saturation target range of 92-96% for most

patients based on the same evidence review.

- otherwise it is based on the BTS Guideline

New evidence supporting

2008 BTS Oxygen Guideline

• Controlled oxygen therapy in exacerbated COPD1

• Aim for normal saturation in myocardial infarction2,3

• Increasing evidence of harm from hyperoxaemia in

critical care settings4-6

Risk to COPD patients50 years or anectotes, now good evidence

• Mortality in acute COPD was 9% V 4% when high concentration oxygen was compared with controlled oxygen (target 88-92%)1

• Mortality in acute COPD was 11% V 7% comparing >35% oxygen with lower doses2

• Need for ventilatory support; 22% V 9%2

1. Austin MA, et al. BMJ. 2010 Oct 18;341:c5462. doi: 10.1136/bmj.c5462

2. Roberts CM et al. Thorax 2011: 66: 43

Care Bundles in acute COPD

Turner AM et al Thorax 2015; 70: 992-994

Mortality was reduced by correct use of oxygen

OR 0.22 95% CI 0.05-0.88 p=0.03

2008

Guideline

Non-COPD patients who may be at

risk from hyperoxaemia

• Other hypercapnia risk (Morbid Obesity, Muscle disease, Scoliosis etc)

• Myocardial Infarction1 (AVOID study… but no harms seen in DETO2X)

• ? Stroke Increased mortality in non-hypoxic patients with mild-moderate stroke randomised to oxygen in Ronning study but not in the Stroke Oxygen studies 2,3

Increased mortality in ventilated stroke patients if hyperoxic4

• Post Resuscitation Hyperoxaemia was associated with increased mortality in survivors of cardiac arrest but controversy remains 5-7

• Ventilated ICU Patients Hyperoxaemia was associated with increased mortality in most retrospective studies (see meta analyses in later slides).

• Traumatic Brain Injury Hyperoxaemia was associated with increased mortality in patients with severe traumatic brain injury12,13

AVOID Study: Oxygen in STEMI

2016;102:444-51

2015

55% increase

in infarct size

on Cardiac MR

Scans

Recurrent MI

5.5% V 0.9%

26% increase

in peak CK

on oxygen

2015

Average 21% increase in infarct size based on troponin biomarker with dose-response

No difference in

• peak troponin level

• mortality at one year

• repeat MI in 1 year

DETO2X Study

NEJM 2017

AVOID Study

Circulation 2015

Number of patients 6629 441

Diagnosis Suspected MI with ECG changes or

troponin rise

24% did not have MI

76% had confirmed MI

including 44% with STEMI

All had confirmed STEMI

Eligible saturation range ≥90%Patients with SpO2 of 90-93% who might benefit from

oxygen were included in the DETO2X study

≥94%

Recruitment location(s) Ambulance/ ED/CCU/Cath Lab Ambulance only

Time from onset of

symptoms to

randomisation

245-250 minutes 150 minutes

Oxygen therapy 6 l/min via face mask for 6-12 hours 8 l/min via face mask until transfer

from catheter lab to general ward

Outcome No difference in troponin or other outcomes

CK not measured

Higher CK in the group randomised

to oxygen. This group had bigger

infarcts and more re-admissionsTroponin was not significantly higher in the

oxygen group but did show a dose response

with the amount of oxygen given

• Several observational studies reported optimal survival with

normoxaemia and increased mortality for ICU patients with

either hypoxaemia or hyperoxaemia

OXYGEN USE IN CRITICAL CARE UNITS

Oxygen was used generously on a

“precautionary basis” in most

Critical Care Units since the mid 20th century

Is there any evidence that this saved lives?

• In some studies the effects of hyperoxaemia

were no longer significant after multi-variate analysis

“After multi-variate analysis to adjust for hypotension, blood loss, tachycardia and

tachypnoea, there was no remaining association between knife wounds and mortality.”

Mortality

“Normoxia” 45%

“Hypoxia” 57%

Hyperoxia 63%(PaO2 >300mm Hg/ 40 kPa)

• Hyperoxia may be associated with increased mortality in patients with stroke,

traumatic brain injury, in those resuscitated from cardiac arrest and in general

critical care patients

• However, these results are limited by the heterogeneity of the included studies

Hyperoxia and CCU Mortality: Systematic Reviews/Meta Analysis

Girardis et al JAMA 2016 First RCT

Implementation of normoxaemia on CCU

Target range 94-98% V standard practice

11.6% V 20.2% ICU Mortality

Mean PaO2 11.2 kPa in conservative group versus 13.6 kPa in standard group

HYPERS2S StudyAsfar P et al Lancet Respir Med 2017;5:180-90

• 442 ventilated patients with septic shock

• First 24 hours

• Randomised to FIO2 1.0 or range 88-92%

• Also randomised to normal saline V 3% saline

• Trial stopped early for safety reasons

• Mortality at 28 days 43% V 35% p=0.12• Serious adverse events 85% V 76% p=0.02

• ICU weakness 11% V 6% p=0.06

Declining prevalence of hyperoxaemia on two Critical Care Units

(CCU)

Percent of blood gas samples in Salford and Truro with SaO2 >98%

What’s new in the 2016 Guideline?

• Postoperative and perioperative care

• Endoscopy and other procedures requiring sedation

• Use of helium-oxygen and nitrous oxide/O2 mixtures (Heliox & Entonox)

• Use of CPAP (continuous positive airway pressure)

• High flow nasal cannulae

• Use of oxygen by health care professionals in patients’ homes

• Use of oxygen by voluntary rescue organisations and other non-NHS first

responders

• Use of oxygen in palliative care settings including hospices

Use of helium-oxygen and nitrous

oxide/oxygen mixtures (Heliox & Entonox)

• L1. There is insufficient evidence to support the use of Heliox either as an

inhaled gas or as the driving gas for nebuliser therapy in adult patients with

acute exacerbations of asthma or COPD except as part of randomised clinical

trials or in exceptional circumstances. (Grade D)

• L2. A therapeutic trial of Heliox is reasonable in patients with mechanical

upper airway obstruction or postoperative stridor. (Grade D)

Heliox (Helium and oxygen mixture; 79:21%, 70:30% of 60:40%)

Entonox (50% Nitrous Oxide; 50% Oxygen “Laughing Gas”)

• M1. The use of Entonox gas mixture for analgesia should be avoided

if possible in patients at risk of type 2 respiratory failure. [Grade D]

Use of CPAP for Pulmonary Oedema

(continuous positive airway pressure)

• N2. CPAP with entrained oxygen to maintain saturation 94-98%

should be considered as an adjunctive treatment to improve gas

exchange in patients with cardiogenic pulmonary oedema who are not

responding to standard treatment in hospital care or in pre-hospital

care. [Grade B]

High flow nasal cannulae in acute

hypoxaemic respiratory failure

Good Practice Point, High Flow Nasal oxygen

• High flow nasal oxygen should be considered as a potentially superior

alternative to reservoir mask treatment in patients with acute hypoxaemic

(type 1) respiratory failure

Reported benefits compared with conventional high concentration oxygen:

• Patient preference (Roca and Cuquemelle)

• Reduced risk of re-intubation (Hernandez) and NIV (Parke)

• Increased number of ventilator free days and reduced 90 day mortality (Frat)

History of the hypothesis that moderate oxygen

therapy is likely to be safer than uncontrolled

high dose oxygen thearpy

1899

1986

2008 and 2017

Take away messages

• Oxygen is a drug with a “therapeutic range” which varies

between patients (usual target range 94-98% or 88-92%)

• There is increasing evidence that the 20th century fashion

for iatrogenic hyperoxaemia was harmful

• Best practice is to prescribe a target saturation range for

all patients on admission to hospital. The target

saturation range will influence Early Warning Scores in

the updated NEWS bedside observation charts (Patients at risk of hypercapnia will score up to 3 NEWS points if

their saturation is below target range or if above range on oxygen)

Joseph Priestley (Co-discoverer of oxygen) Experiments and Observations on Different Kinds of Air 1776

“From the greater strength and vivacity of the flame of a candle, in this pure air, it may be

conjectured, that it might be particularly salutary to the lungs in certain morbid cases,

when the common air would not be sufficient to carry off the phlogistic putrid effluvium

fast enough.

But, perhaps, we may also infer from these experiments, that though pure

dephlogisticated air might be useful as a medicine, it might not be so proper for us in the

usually healthy state of the body; for as a candle burns out much faster in

dephlogisiticated than in common air, so we might, as may be said, live out too fast, and

the animal powers be too soon exhausted in this pure kind of air.

A moralist, at least, may say, that the air which nature has provided for us is as good as

we deserve.”

JS Haldane 1917“The probable risks of prolonged administration of pure oxygen must be

borne in mind, and if necessary balanced against the risks of allowing the

oxygen want to continue. No fixed rule can be given.

The proper course to pursue must be determined by the physician after

careful observation of the patient, and in the light of experience and knowledge”.