Changes

June 2023 — reviewed. A literature search was conducted in May 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. The clinical recommendations have been updated to reflect the latest guidelines, sections about potential differential diagnoses and managing self-harm have also been added.

Update

Goals

To support primary healthcare professionals to:

• Recognise possible carbon monoxide poisoning.
• Make a working diagnosis and provide an assessment.
• Provide appropriate treatment and advice.
• Refer to secondary care or a specialist service, when appropriate.

Outcome measures

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

QIPP - Options for local implementation

NICE quality standards

What is carbon monoxide?

• Carbon monoxide is a colourless, odourless, tasteless, non-irritant gas produced by incomplete combustion of fuels — this occurs when insufficient oxygen is present.
• Carbon monoxide has a much greater affinity for haemoglobin than oxygen.
• It is important to note that leaks of domestic gas do not involve carbon monoxide.

[TOXBASE, 2021; Gentile, 2022; UKHSA, 2022a; UKHSA, 2022b; BMJ Best Practice, 2023]

How does carbon monoxide cause harm?

• Exposure to carbon monoxide causes tissue hypoxia, because:
  • Carbon monoxide binds to haemoglobin with about 240 times the affinity of oxygen and forms carboxyhaemoglobin.
  • Once bound, carbon monoxide takes several hours to dissociate from haemoglobin, during which time the oxygen-carrying capacity of the blood is reduced. 
• Tissue hypoxia impairs cell function and, when severe, may cause tissue damage.
  • The cardiovascular system and central nervous system are particularly sensitive to carbon monoxide-induced hypoxia due to their high oxygen requirements. 
• Carbon monoxide may also cause tissue injury directly through non-hypoxic mechanisms as it is also transported dissolved in plasma where it may form oxygen free radicals or bind to intracellular myoglobin, guanylyl cyclase and mitochondrial cytochrome enzymes, resulting in impaired cellular function.
• The severity of carbon monoxide poisoning is largely related to the amount of carbon monoxide inhaled.
  • As exposure to a constant concentration of carbon monoxide is maintained, the carboxyhaemoglobin level increases until an equilibrium is reached with the ambient air. This level is dependent on the duration of exposure, the concentration of carbon monoxide, and breathing volumes relating to respiratory rate and depth.

[Jüttner, 2021; TOXBASE, 2021; UKHSA, 2022b; BMJ Best Practice, 2023]

How common is it?

• Carbon monoxide poisoning is an underdiagnosed problem.
  • The signs and symptoms of low-level carbon monoxide toxicity are often non-specific and simulate other common conditions, such as flu-like illness, food poisoning, or depression. As a result, carbon monoxide poisoning may be misdiagnosed.
  • It is estimated that there are approximately 4000 attendances at accident and emergency departments in England each year for treatment of carbon monoxide poisoning.
  • There are approximately 440 hospital admissions per year in England due to carbon monoxide poisoning.
    • Approximately 51% of these admissions are due to accidental exposure, and 40% are due to intentional self-harm (undetermined in the remaining 9%).
  • In England and Wales, approximately 40 deaths are reported each year due to carbon monoxide poisoning.
    • Studies have consistently shown that approximately 80% of accidental, non-fire related, carbon monoxide poisoning fatalities in England are among males.
    • Poisonings in residential locations, due to faulty piped gas appliances with inadequate ventilation were the place, source, and underlying reason for most accidental, non-fire related, carbon monoxide poisoning fatalities in England and Wales (1998 to 2019).
  • Poisoning is more prevalent in the winter months, likely related to the increased indoor use of heating and other devices which are common sources of carbon monoxide.
  • Although the risk of carbon monoxide poisoning is virtually identical in adult males and females, the mortality rate in men is nearly double that of women in accidental poisoning.
    • This may be due to sex-related differences in carbon monoxide elimination, which may be faster in females.
    • It may also be related to males being more likely to be poisoned in industrial or occupational settings than females, which likely presents an increased risk of severe poisoning.
  • Carbon monoxide poisoning may also be more common among the socio-economically deprived.
    • Approximately 50% of unintentional non-fire related carbon monoxide poisoning fatalities in England and Wales between 1998 and 2019 occurred in people from the two most deprived quintiles of the population.

[DH 2013; Zavorsky, 2014; Eichhorn, 2018; Roca-Barceló, 2020; Close, 2022; Gentile, 2022; ONS, 2022]

Who is most at risk of harm?

• Those most at risk of harm from carbon monoxide poisoning include:
  • Older people — who may have existing co-morbidities, such as heart disease or respiratory disease, and a reduced compensatory response to hypoxic situations.
    • Those aged over 80 years have the highest rate of mortality following carbon monoxide poisoning.
  • Children — more likely to be sensitive to the harmful effects of carbon monoxide.
  • Women who are pregnant
    • During pregnancy a woman's endogenous carbon monoxide levels are typically 20% higher than non-pregnant values and the elimination half-life of carbon monoxide in the fetus is up to 4–5 times longer than in the mother as its blood has a higher affinity for carbon monoxide — maternal levels may not accurately reflect fetal levels.
    • Maternal exposure to high levels of carbon monoxide, which results in moderate to severe toxicity may cause fetal or neonatal death, congenital malformations, or neurological effects.
    • Less severe toxicity or exposure to chronic low levels of carbon monoxide may be associated with pre-term delivery, low birth weight, congenital malformations (including heart defects), sudden infant death and neurodevelopmental problems.
  • People with respiratory disease — there is inconclusive evidence for an association between increasing ambient air concentrations of carbon monoxide and respiratory complications (for example, exacerbation of asthma, hospitalisations and emergency room visits related to respiratory complaints).
  • People with cardiovascular disease — the cardiovascular system is particularly sensitive to carbon monoxide-induced hypoxia.
  • People with anaemia — the oxygen-carrying capacity of the blood is already compromised in this group of people, making them more sensitive to the effects of carbon monoxide.
  • Adult males — although the risk of carbon monoxide poisoning is virtually identical in adult males and females, the mortality rate in men is nearly double that of women in accidental poisoning. This may be due to sex-related differences in carbon monoxide elimination, which may be faster in females. It may also be related to males being more likely to be poisoned in industrial or occupational settings than females, which likely presents an increased risk of severe poisoning.
  • Socio-economically deprived — 51% of unintentional non-fire related carbon monoxide poisoning fatalities in England and Wales between 1998 and 2019 occurred in people from the two most deprived quintiles of the population.

[DH 2013; Zavorsky, 2014; UKTIS, 2017; Eichhorn, 2018; Mattiuzzi, 2020; Close, 2022; UKHSA, 2022a]

What are the potential sources of carbon monoxide?

• Exposure to carbon monoxide may occur:
  • When fuel-burning appliances are poorly installed, faulty, not maintained, or used inappropriately.
    • Chimneys or flues are blocked.
    • There is a lack of ventilation in the room.
    • Gas ovens are used inappropriately for heating.
    • Barbecues are used inside homes, caravans or tents for cooking or heating.
    • Oversized pots are used on gas cooker rings.
  • If shisha/hookah water pipes are used in poorly ventilated rooms.
  • If petrol or diesel engine exhaust gases are retained in an enclosed space, for example, from vehicles or portable generators.
• Other sources of carbon monoxide include:
  • Smoke in burning buildings.
  • Paint removers and industrial degreasers (containing methylene chloride).
  • Aerosol propellants.
  • Neighbouring property with an appliance which is producing carbon monoxide.
  • Cigarette smoke.
  • Liquid petroleum gas (LPG) powered industrial equipment and recreational vehicles (particularly in enclosed spaces).
  • Industrial compressed carbon monoxide gas cylinders.
• Note — Accidental exposure in industrial facilities can result in significantly higher carbon monoxide concentrations compared to residential environments.
• Signs that indicate incomplete combustion may be taking place, releasing carbon monoxide, include:
  • Yellow or orange rather than blue flames (except fuel effect fires or flueless appliances which display this colour flame).
  • Soot or yellow/brown staining around or on appliances.
  • Pilot lights which frequently blow out.
  • Increased condensation inside windows.
• Be aware that there may be more than one source of carbon monoxide and that carbon monoxide can leak into attached dwellings (semi-detached/terraced house or flat).
• Intentional self-harm is a common cause of carbon monoxide poisoning. Carefully consider any exposure scenario details which may indicate that poisoning was an act of intentional self-harm.
  • Concomitant exposures may be present in these cases, including alcohol or other sedative hypnotics.

[DH 2013; TOXBASE, 2021; Jüttner, 2021; UKHSA, 2022a; UKHSA, 2022b; BMJ Best Practice, 2023]

What are the complications of carbon monoxide poisoning?

• The majority of people exposed to carbon monoxide recover, however, some people develop neuropsychiatric features — this is more likely in people who have been severely poisoned, exposed to carbon monoxide over a long period of time, or who become unconscious during a poisoning episode. The onset of complications may be delayed by up to 40 days. 
  • Neurological complications may persist in up to half of those with symptomatic acute exposure.
• Complications include:
  • Apathy and inability to concentrate.
  • Apraxia.
  • Chorea.
  • Dementia and parkinsonism.
  • Disorientation.
  • Emotional lability, irritability and personality change.
  • Incontinence.
  • Insomnia.
  • Lethargy.
  • Memory impairment.
  • Mutism.
  • Neuropathy.
  • Parosmia.
  • Psychosis.
  • Vision problems.

[Eichhorn, 2018; TOXBASE, 2021; UKHSA, 2022b; BMJ Best Practice, 2023]

When should I suspect carbon monoxide poisoning?

• Ask people with possible symptoms of carbon monoxide poisoning about:
  • C — co-occupants and if anyone else in the house is affected. This should include pets, as animals are often the first to display symptoms of carbon monoxide poisoning due to their smaller size.
  • O — outdoors. If symptoms improve when they are out of the building.
  • M — maintenance. If their fuel-burning appliances and vents are properly maintained.  
  • A — alarm. If they have a carbon monoxide alarm.
• If suspicious of carbon monoxide poisoning, also ask the person if they:
  • Have recently had a heating or cooking appliance installed.
  • Ever use the oven or gas stove for heating purposes as well as for cooking.
  • Have had any ventilation changes in the home recently (for example, double glazing has been fitted).
  • Have noticed any sooty stains around appliances or an increase in condensation. 
  • Do work which involves possible exposure to smoke, fumes or motor vehicle exhaust at work.
• Suspect carbon monoxide poisoning when:
  • Clinical features of poisoning are present.
  • Exposure to a potential source of carbon monoxide has occurred.
  • Symptoms correlate with exposure:
    • Symptoms develop following exposure and improve slowly when exposure stops.
    • Other people (or pets) exposed to the same possible source develop similar symptoms correlating with exposure.

What are the clinical features of carbon monoxide poisoning?

• Brief exposure to low levels of carbon monoxide may cause:
  • Dizziness.
  • Flushing.
  • Headache — the most common symptom, reported by 90% of people poisoned with carbon monoxide.
  • Muscle pain.
  • Nausea, vomiting.
  • Personality changes.
  • Vertigo.
• Exposure to higher levels of carbon monoxide may cause:
  • Confusion.
  • Hypotension.
  • Loss of consciousness and death.
  • Movement problems.
  • Myocardial infarction.
  • Respiratory failure.
  • Weakness.
  • Seizures, cerebral oedema and metabolic acidosis in severe poisoning.
• Chronic exposure to low levels of carbon monoxide may cause:
  • Cardiovascular problems.
  • Dementia.
  • Dizziness.
  • Flu-like symptoms with tiredness.
  • Headache.
  • Lethargy.
  • Loss of vision.
  • Memory problems.
  • Nausea.
  • Neuropsychological problems (for example, anxiety, psychomotor dysfunction, loss of balance, changes in sleep, memory, vision, and smell).
  • Personality changes.
• Less common symptoms of carbon monoxide poisoning include:
  • Acute renal failure.
  • Choreoathetosis.
  • Compartment syndrome.
  • Cortical blindness
  • Dysrhythmias.
  • Hearing loss.
  • Mutism.
  • Myocardial infarction.
  • Pulmonary oedema.
  • Retinal haemorrhages.
  • Rhabdomyolysis.
  • Skin blisters.
• Due to the considerable overlap in symptomatology, it is not usually possible to determine whether poisoning is a result of acute or chronic carbon monoxide exposure.

What else might it be?

Many of the clinical features of carbon monoxide poisoning are non-specific. Care should be taken not to exclude the possibility of carbon monoxide poisoning in people with non-specific symptoms. 

• In cases where the exposure scenario details do not clearly indicate that carbon monoxide poisoning should be suspected, other conditions may need to be excluded, including:
  • Viral infection — Many of the features of carbon monoxide poisoning are also experienced by people with viral infections.
  • Migraine — Headache associated with symptoms such as photophobia (sensitivity to light), phonophobia (sensitivity to sound), or transient focal neurological symptoms (aura) may indicate migraine. For more information, see the CKS topic on Migraine.
  • Tension headache — Although headache is the most common symptom among people with carbon monoxide poisoning, it is a highly common non-specific symptom associated with many conditions. For more information, see the CKS topic on Headache - tension-type.
  • Depression — Symptoms of lethargy and some of the neuropsychological features associated with carbon monoxide poisoning (such as anxiety, mood/personality changes, sleep disorders) may be experienced by people with depression. For more information, see the CKS topic on Depression.
  • Chronic fatigue syndrome — Symptoms of lethargy may be indicative of chronic fatigue syndrome. For more information, see the CKS topic on Tiredness/fatigue in adults.
  • Diabetic ketoacidosis — A serious complication of diabetes characterized by hyperglycaemia (or a diagnosis of diabetes), metabolic acidosis, and ketonaemia. For more information, see the CKS topic on Diabetes -  type 2.

Scenario: Management of carbon monoxide poisoning

From birth onwards.

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of carbon monoxide poisoning.

Search dates

July 2018 - May 2023

Key search terms

Various combinations of searches were carried out. The terms listed below are the core search terms that were used for EBSCO Medline.

• (MH "Carbon Monoxide Poisoning") 
• AB ( (carbon monoxide N3 (poison* or toxicity)) ) OR TI ( (carbon monoxide N3 (poison* or toxicity)) ) 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• UK Teratology Information Service (UKTIS)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.