Methaemoglobinaemia and carbon monoxide poisoning

• Methaemoglobinaemia is a state in which the iron in haemoglobin has been oxidised from its normal ferrous form (Fe2+) to the ferric form (Fe3+). Ferric haemoglobin, called methaemoglobin (MetHb), cannot carry oxygen, so the patient becomes progressively more anaemic in a functional sense as the proportion rises.
• The patient looks cyanosed, yet the partial pressure of oxygen in arterial blood (PaO2) is normal or high and the calculated arterial oxygen saturation (SaO2) on an arterial blood gas (ABG) can appear falsely normal. Pulse oximetry (SpO2) is also unreliable and often fixes near 85 percent. Only co-oximetry measures MetHb accurately. ^[1]
• Three mechanisms dominate: an inherited deficiency of the enzyme cytochrome b5 reductase (CytB5R), mutations in the globin genes producing Haemoglobin M (HbM), and exposure to oxidising agents. ^[1]
• Intravenous methylene blue is the first-line treatment for symptomatic methaemoglobinaemia, at 1 to 2 mg per kg given over 5 to 10 minutes, unless the patient has glucose-6-phosphate dehydrogenase (G6PD) deficiency. ^[1]
• Carbon monoxide (CO) poisoning is a separate but related emergency: CO binds haemoglobin with an affinity up to 200 to 250 times that of oxygen, tissue hypoxia follows from a leftward shift of the oxygen-haemoglobin dissociation curve, and treatment is oxygen rather than any antidote. About 50,000 people in the United States attend an emergency department with CO poisoning each year, and up to 500 die. ^[2]

By the end of this page you should be able to:

1. Explain why oxidised haemoglobin cannot carry oxygen and why the condition looks like cyanosis with a normal PaO2.
2. Name the three main causes and give examples of drugs and toxins that produce acquired methaemoglobinaemia.
3. Interpret the difference between an ABG, a pulse oximeter and a co-oximeter in these patients.
4. State the methylene blue dose, when it is indicated, when it must be avoided, and what to do instead.
5. Recognise CO poisoning, describe its mechanism and list the criteria that prompt consideration of hyperbaric oxygen.
6. Apply immediate management of a poisoned patient, including oxygen, hyperbaric oxygen, pregnancy and follow-up.

Carbon monoxide poisoning is the disorder in which tissue hypoxia results from CO binding haemoglobin, direct cellular toxicity, and a leftward shift of the oxygen-haemoglobin dissociation curve. Both conditions present with hypoxaemia or cyanosis that may be disproportionate to, or unresponsive to, supplemental oxygen. ^[1][2]

Methaemoglobinaemia is rare, and full population data are limited because reporting is incomplete. Recreational and non-prescribed exposures, especially volatile nitrites and sodium nitrite, have become increasingly prominent in recent case series. ^[1]

In the United States, roughly 50,000 people visit an emergency department with CO poisoning each year and up to 500 die annually. ^[2] In Poland, the 2023/2024 heating season saw 53 deaths and 1,468 non-fatal incidents; across the European Union the annual burden is approaching 20,000 hospitalisations. ^[3] In smokers, blood levels of carboxyhaemoglobin (COHb) can reach 10 to 12 percent in heavy smokers, so a history of smoking is essential when interpreting CO levels. ^[2]

Methaemoglobinaemia. Three mechanisms account for almost all cases: inherited cytochrome b5 reductase (CytB5R) deficiency, mutations in the globin genes producing Haemoglobin M (HbM), and exposure to oxidising agents. ^[1] Heterozygous carriers of CytB5R deficiency are usually clinically well but should avoid known oxidant exposures; testing first-degree relatives of patients with homozygous deficiency has been recommended. ^[1][4]

CO poisoning. The gas arises from incomplete combustion of carbon-containing material and spreads insidiously in confined or poorly ventilated spaces. ^[2] Domestic risks include faulty heating systems, blocked chimneys, and car exhaust in enclosed garages; occupational risks include garages, workshops, tunnels, and firefighters. Fire victims are at particular risk because CO acts together with other combustion products, including hydrogen cyanide. ^[2]

Normal haemoglobin (HbFe2+) contains a haem pocket with two key histidine residues, a protoporphyrin ring and central ferrous (Fe2+) iron. The pocket allows reversible oxygen binding and protects the iron from oxidation. Nevertheless, auto-oxidation of Fe2+ in oxyhaemoglobin to Fe3+ occurs at a rate of about 3 percent per day. ^[1]

In methaemoglobinaemia the oxidation is excessive, or the reduction back to Hb is impaired. Once iron is ferric (Fe3+), it has no electron available for oxygen and that haem group cannot carry oxygen. At the same time, ferric haem increases the oxygen affinity of the remaining ferrous haems, shifting the oxygen dissociation curve to the left and impairing release of oxygen to tissues. The result is a functional anaemia that is, weight for weight, more damaging than an equivalent degree of true anaemia. ^[1]

Physiological mechanisms keep the normal MetHb concentration below 1 percent. ^[1] CytB5R is responsible for the majority of MetHb reduction. Two forms exist: an erythrocyte-restricted water-soluble form and a global membrane-bound form. A minor pathway, NADPH-diaphorase, accounts for less than 5 percent of reduction in health but is massively potentiated by methylene blue. ^[1]

Methylene blue exploits the second pathway. Glucose is metabolised along the pentose phosphate pathway to produce NADPH, which reduces methylene blue; reduced methylene blue then transfers electrons to MetHb and restores Hb. This is why maintenance dextrose is given during treatment and why methylene blue is ineffective in G6PD deficiency, where NADPH production is impaired. ^[1]

As the MetHb proportion increases, oxygen-carrying capacity falls. Patients are typically asymptomatic at MetHb concentrations under 10 percent, with cyanosis usually the first sign as levels rise. Symptoms progress through confusion, headache, tachycardia and arrhythmias, coma and death, though the rate of rise matters as much as the absolute level, because slowly rising levels are better tolerated. Patients with anaemia or circulatory impairment develop signs at lower proportions. ^[1]

A systematic review of cases reported between 1980 and 2020 found local anaesthetics (the "-caine" drugs) and dapsone to be the most frequently implicated agents. ^[1] More recent data from a large urban toxicology centre suggest volatile nitrites are emerging as the commonest cause, likely reflecting increasing recreational and non-prescribed use. ^[1]

• Local anaesthetics. Benzocaine and prilocaine are the agents most often responsible. Methaemoglobinaemia usually follows mucosal application, for example during intubation or transoesophageal echocardiography. ^[1]
• Dapsone. A 2024 review found dapsone responsible for the majority of clinically significant acquired cases. Dapsone is metabolised by cytochrome P450 to two hydroxylamine metabolites, dapsone hydroxylamine (DDS-NOH) and monoacetyldapsone hydroxylamine (MADDS-NOH), which oxidise haemoglobin directly. Because these metabolites can be recycled by NADPH after each oxidation, MetHb may fall transiently with treatment then rise again: this explains the higher rate of repeat methylene blue doses in dapsone cases. Charcoal decontamination and, in principle, cytochrome P450 inhibition have been considered, and cimetidine has shown promise in preventing formation of the hydroxylamine metabolite during long-term therapy. ^[1]
• Volatile and alkyl nitrites ("poppers") and sodium nitrite. These are a growing cause. Ingestion of as little as 1 g of sodium nitrite, widely sold as a meat preservative and easily bought online, can cause life-threatening methaemoglobinaemia. Fatalities have also followed volatile nitrites. ^[1]
• Local anaesthetic adulterants in cocaine, producing very high MetHb levels reported up to 90 percent, and nitrous oxide through oxidising contaminants. ^[1]
• Rasburicase, used for tumour lysis syndrome, generates hydrogen peroxide during uric acid metabolism and has been linked to methaemoglobinaemia, particularly in G6PD deficiency. Screening for G6PD deficiency before use, or careful monitoring if testing is not possible in an emergency, has been advised. ^[1]
• Other drugs include glyceryl trinitrate, nitric oxide, primaquine, silver nitrate, sulphadiazine, co-trimoxazole and sulphasalazine. ^[1]
• Environmental and infant exposure. Nitrates in well water can produce high MetHb, most often in neonates or in people with low CytB5R activity, in whom nitrate reductase in gut bacteria converts nitrate to nitrite. ^[1]

Hydroxylamine-containing agents are especially troublesome because they generate oxidants long after the parent drug has left the circulation, and they cannot be neutralised simply by removing the offending agent.

RCM is a rare autosomal recessive disorder caused by deficiency of NADH-cytochrome b5 reductase, coded by the CYB5R3 gene. ^[4] It presents in two forms:

• Type 1 is an erythrocyte-restricted enzyme deficiency, usually from missense mutations leading to structural instability. Patients are visibly cyanosed, with MetHb concentrations around 15 to 30 percent, but are otherwise well. ^[1][4]
• Type 2 is a global enzyme deficiency, usually from deletions or premature stop codons. In addition to cyanosis, patients develop severe progressive neurological and cognitive impairment, reflecting loss of the membrane-bound enzyme in tissues including the central nervous system, with abnormal lipid metabolism. ^[1][4]

In type 1, health is generally good apart from the visible cyanosis, and lifespan is not usually shortened, whereas type 2 is serious and treatment directed at the neurological disease is not established. ^[1][4]

HbM disease arises from single amino acid substitutions in the haem pocket, most often one of the key histidine residues, that stabilise iron in the Fe3+ state and prevent reduction by CytB5R. ^[1] All reported cases are heterozygous and dominant, so less than half of total haemoglobin is abnormal; homozygous disease is thought to be lethal and has not been described. ^[1] Patients tolerate the defect surprisingly well after adaptation, and generally do not require treatment for cyanosis unless they become symptomatic. ^[1]

The genotype determines the clinical timeline because fetal haemoglobin (HbF) is replaced by adult haemoglobin (HbA) shortly after birth. Mutations in the alpha-globin chain are symptomatic from birth and throughout life; gamma-globin variants affect fetuses and newborns and improve over the first 6 months; beta-globin variants cause cyanosis from about 3 months of age. ^[1]

Two practical pitfalls follow from the structure of the haem pocket. HbM variants can interfere with co-oximetry, with some alpha-chain variants mimicking sulfhaemoglobin and others (such as HbM Saskatoon) giving unreliable or uninterpretable MetHb readings. HbM variants can also be electrophoretically silent, so diagnosis depends on DNA analysis of the globin genes. Recognising these patterns prevents unnecessary antidotal treatment and directs appropriate family counselling. ^[1]

The hallmark is cyanosis that does not improve with oxygen. ^[1] Beyond cyanosis, rising levels produce headache, weakness, tachycardia, tachypnoea, confusion, acidosis, arrhythmias, seizures and ultimately coma and death. ^[1] Congenital forms usually present in the newborn with cyanosis; oxygen-unresponsive cyanosis presenting after infancy is likely to be acquired. ^[1]

Because the clinical picture is non-specific, the diagnosis is easily missed. A useful bedside clue is the gap between clinical cyanosis and the calculated SaO2 on ABG, which tends to be high, contrasted with a much lower SpO2 when MetHb exceeds about 15 to 20 percent. ^[1]

The patient may be anxious, tachypnoeic and cyanosed around the lips and fingertips. Blood withdrawn for laboratory testing is often chocolate-brown in these cases, which is a simple diagnostic pointer in an emergency. ^[1]

CO poisoning is a great imitator. Symptoms are non-specific and easily mistaken for viral illness, food poisoning, headache, gastroenteritis, depression, hypoglycaemia, other intoxications, or, more seriously, acute cerebrovascular disease. ^[2] The gas is odourless, colourless and non-irritating, so people may not know they have been exposed. ^[2]

Symptoms range from headache, dizziness, weakness, nausea and vomiting at lower exposures, through tachycardia, breathlessness, confusional states and ataxia, to syncope, seizures, coma and death. Patients exposed together may present with similar symptoms. Survivors may develop delayed neurological sequelae weeks later, including cognitive and motor deficits, Parkinsonian features and psychiatric symptoms. ^[2][3]

Severity of symptoms does not track COHb concentration reliably, because CO also binds mitochondrial cytochrome oxidase and produces oxidative stress, inflammation and direct cellular injury beyond the haemoglobin effect. ^[2] Consequently a normal COHb concentration does not exclude clinically significant poisoning, particularly if the blood was drawn after the patient left the contaminated environment, because COHb falls rapidly with oxygen. ^[2][3]

The main differential for cyanosis or apparent hypoxaemia is broad.

In practice, the single most useful distinction is the gap between a normal PaO2 and low measured oxygen saturations, pointing to a haemoglobin problem rather than a lung problem. ^[1]

• Arterial blood gas with co-oximetry. PaO2 is normal or high, and the calculated SaO2 can be falsely normal. ^[1]
• Pulse oximetry. SpO2 falls to a plateau of about 85 percent once MetHb exceeds roughly 15 to 20 percent, because MetHb absorbs the two wavelengths 660 and 940 nm equally and the ratio sits at 1 to 1. With a ratio of 1 to 1 the oximeter reads 85 percent saturation. ^[1] A large multicentre study found the saturation-gap concept supportive but not universal, so co-oximetry is mandatory when MetHb is suspected. ^[1]
• Co-oximetry. The gold standard. It uses 4 or more wavelengths to measure MetHb directly and is accurate when confirmed by potassium cyanide, which converts MetHb to bright-red cyanomethaemoglobin. Sulfhaemoglobin does not react with potassium cyanide and so stays chocolate-brown with unchanged readings. ^[1] MetHb has peak absorbance at 635 nm. ^[1]
• COHb. Measured directly by co-oximetry in suspected CO poisoning. ^[2]
• Blood appearance. Chocolate-brown blood is a simple pointer. ^[1]
• Screening for G6PD deficiency. Important before rasburicase and essential to the safety of methylene blue. ^[1]
• Echocardiography, chest imaging and cultures are used only to exclude alternative causes such as cardiac septal defects or endocarditis where the clinical picture demands.

A suggested diagnostic sequence when faced with new cyanosis is: consider tissue hypoperfusion and airway disease; obtain an ABG and co-oximetry if available; if MetHb is elevated, look for the likely oxidant exposure; if the picture suggests CO, take a direct COHb level. Throughout, remember that treatment must not wait for absolute confirmation if the patient is unstable.

There are no widely agreed severity scores or staging systems for either condition; management follows the proportion of abnormal haemoglobin together with symptoms, exposure, and the clinical picture. ^[1][2]

Remove the patient from the offending exposure, stop the implicated drug, and give high-flow oxygen. Oxygen alone does not reduce MetHb but improves delivery and is safe, and it does not reverse the problem because the haem itself is oxidised. ^[1] Maintain the airway, preserve perfusion and assess for G6PD deficiency or recent oxidant exposure. ^[1]

Methylene blue remains the first-line therapy for symptomatic patients without G6PD deficiency. ^[1]

• Dose: 1 to 2 mg per kg, as a 1 percent solution, given intravenously over 5 to 10 minutes. ^[1]
• Response: A current review of a toxicology cohort of 185 patients found clinical improvement in 98 percent of cases, most patients responding to a single dose within the 1 to 2 mg per kg range; repeat dosing was needed in about 11 percent, most often with dapsone or volatile nitrite exposure. ^[1]
• Cautions: repeated or excessive dosing can be harmful. Doses above 7 mg per kg can themselves cause cyanosis and haemolytic anaemia, and methylene blue overdose can be disguised as methaemoglobinaemia, prompting further unnecessary doses. Improvement should be followed by co-oximetry, not by the clinical picture alone. ^[1]
• Adjuncts: maintenance dextrose should be provided to all patients receiving methylene blue to feed the pentose phosphate pathway. ^[1]
• Special cautions: use with caution in pregnancy, in severe renal impairment, with a history of severe allergy to thiazine dyes, and with serotonergic drugs including fluoxetine and other antidepressants, tramadol and linezolid. ^[1]
• Ineffectiveness: in HbM disease methylene blue does not resolve the cyanosis because the problem is structural stabilisation of Fe3+ rather than a redox pathway; bone marrow transplantation has been considered in very severe cases. ^[1]

Methylene blue is contraindicated in G6PD deficiency: it is ineffective because the pentose phosphate pathway is already compromised, and it can precipitate haemolytic anaemia. ^[1] In such patients, or when methylene blue is unavailable or fails, the alternatives are:

• High-dose vitamin C, effective but slow, taking up to 24 hours to lower MetHb levels. In RCM, therapeutic dosing is sometimes given over the long term. Advantages are low cost and availability, which matters greatly in low-resource settings. ^[1][4]
• Exchange transfusion, a safe and effective option for adult methaemoglobinaemia, reserved for severe, refractory or life-threatening cases, particularly at MetHb proportions around 60 to 70 percent, or when methylene blue is contraindicated. ^[1]
• Hyperbaric oxygen, reported to be effective in refractory cases, though the evidence is largely observational. ^[1]
• Riboflavin has been described as an adjunct in chronic management at 20 to 30 mg per day, based mainly on case reports. ^[1]

• Dapsone exposure: remove the drug, decontaminate with charcoal, and expect rebound oxidation; repeat methylene blue cautiously and follow MetHb by co-oximetry. ^[1]
• Neonates and infants with methaemoglobinaemia: suspect rasburicase, well-water nitrates, or a congenital enzyme defect. Avoid benzocaine and other local anaesthetics in infants, in whom they are a common precipitant. ^[1]
• HbM disease: the patient usually needs no treatment for cyanosis; reassurance and family counselling are central, with DNA testing offered. ^[1]

Remove the patient from the contaminated environment and, if necessary, apply resuscitation. Rescuers should wear appropriate respiratory equipment and avoid introducing ignition sources where CO has accumulated. ^[2] As CO disperses rapidly and a normal COHb concentration can be found once the patient leaves the source, diagnosis needs a careful history and index of suspicion more than a single laboratory measurement. ^[2][3]

The antidote to CO is oxygen, given in pure (100 percent) form. There is broad agreement that normobaric oxygen should be administered immediately, either high-flow oxygen or 100 percent via a non-rebreather mask, and it should be continued until the COHb falls to about 3 percent, or for at least 6 hours. ^[3] A longer duration is needed in pregnancy, because fetal elimination of CO is slower; a commonly cited estimate in the same source is about five times longer. ^[3]

Normobaric oxygen reduces the half-life of COHb from severe exposure levels to roughly one hour. ^[2] Delivery via a one-way valve device is preferred, starting at emergency care. ^[2]

Always accompany oxygen with symptomatic treatment: correction of acid-base disturbance, airway intervention, haemodynamic support and intensive care as required. ^[2]

Hyperbaric oxygen (HBO) has a coherent rationale beyond simply displacing CO from haemoglobin: it reduces binding to other haem proteins such as cytochrome c oxidase, improves tissue oxygenation, improves tissue oxygenation, limits oxidative stress and inflammation. ^[2] At 2.5 atmospheres absolute, the half-life of COHb falls to 20 minutes. ^[2]

The Undersea and Hyperbaric Medical Society recommends hyperbaric oxygen for patients with severe CO poisoning, particularly those with transient or prolonged unconsciousness, neurological abnormalities, cardiovascular dysfunction or severe acidosis. Patients older than 36, those exposed for 24 hours or more (including intermittent exposures), or with carboxyhaemoglobin levels of 25 percent or more should also receive it. ^[2]

Most current guidance, however, is more selective than that list implies. The 2025 Polish Medical Society position statement, which explicitly compares American Heart Association (2022) and European Committee for Hyperbaric Medicine (2023) guidance and finds them conflicting on both thresholds and treatment windows, recommends that HBO be considered rather than given routinely, primarily for persistent neurological or cardiac symptoms or metabolic acidosis despite normobaric oxygen, regardless of COHb concentration. ^[3] It notes observational evidence that HBO started within 200 minutes of exposure is associated with a roughly 20-fold reduction in delayed neurological sequelae. ^[3]

In pregnancy, the same source recommends that HBO is always indicated, irrespective of COHb concentration or clinical presentation, ideally within 6 hours of exposure. Children should also be referred to a centre equipped for hyperbaric chamber treatment when there are cardiac or neurological features. ^[2][3]

Follow-up for CO poisoning should continue for 6 months. ^[2] Patients should be assessed for neurological and cardiac sequelae before returning to work, and counselled that delayed neurocognitive problems may appear weeks after exposure. There is no specific therapy for established sequelae. ^[2]

Methaemoglobinaemia: cardiovascular collapse, arrhythmias, neurological injury and death with very high proportions; haemolysis with excess methylene blue or in G6PD deficiency; and the downstream problem of repeated oxidation in dapsone poisoning. ^[1]

CO poisoning: myocardial ischaemia, myocardial infarction, arrhythmias, cerebral oedema, and delayed neurological sequelae appearing weeks after exposure. ^[2]

Methaemoglobinaemia carries a good prognosis if recognised promptly. Type 1 congenital disease is compatible with a normal lifespan apart from the visible cyanosis; type 2 is life-limiting because of neurological disease. ^[1][4] Acute acquired cases generally recover well once the oxidant is removed and methylene blue is given, although rebound oxidation is common with dapsone. ^[1]

CO poisoning carries a more guarded prognosis. The extent and rate of recovery is variable, sequelae may persist from the time of exposure or develop weeks later, and they may be permanent. ^[2]

• Methaemoglobinaemia: avoid oxidant drugs in known CytB5R deficiency or G6PD deficiency; screen for G6PD before rasburicase where possible; use benzocaine and other "-caine" anaesthetics with caution in infants and avoid mucosal application in patients at risk. ^[1]
• CO poisoning: install and maintain carbon monoxide alarms, service heating appliances annually, ensure adequate ventilation in garages and workshops, and remove people from environments where multiple occupants have headache or flu-like symptoms. ^[2]
• Genetic and family screening: offer genetic testing and clinical follow-up to first-degree relatives of someone with recessive congenital methaemoglobinaemia, and test at-risk relatives if a CYB5R3 mutation is identified. ^[1][4]

Pregnancy. In methaemoglobinaemia, methylene blue should be used with caution; high-dose vitamin C or exchange transfusion may be preferred if treatment is needed, although evidence is limited. ^[1] In CO poisoning, oxygen is prolonged (roughly five times longer is cited in the Polish position statement highlights) because fetal elimination is slower, and hyperbaric oxygen is always indicated. ^[3]

Children. RCM type 2 presents with neurological disease; rhabdomyoma is not relevant here. CO poisoning in children warrants low-threshold referral for hyperbaric evaluation if neurological or cardiac features are present. ^[2][4]

Older adults and cognitive impairment. CO toxicity falls harder on the brain and the heart; delayed sequelae are more likely, so follow-up should be systematic. ^[2]

G6PD deficiency. This is not a separate disease group but a critical precaution: methylene blue is contraindicated and haemolysis is the risk. ^[1]

• The single most important diagnostic test is co-oximetry; where it is unavailable, the diagnosis depends on a high index of suspicion and the chocolate-brown appearance of blood, and local hospitals should have a pathway for urgent measurement. ^[1]
• A traditional teaching clue, the saturation gap, is only supportive and may not be present, so it should not be relied on to exclude the condition. ^[1]
• Methylene blue, the essential antidote, is not universally available, particularly in rural settings; high-dose vitamin C is cheaper and slower, and exchange transfusion requires blood banking capacity. ^[1]
• For CO poisoning, the answer is oxygen: a non-rebreather mask with 100 percent oxygen can be started anywhere and continued for at least 6 hours; hyperbaric oxygen requires referral. ^[3]

• Methaemoglobin is haemoglobin with ferric (Fe3+) iron that cannot carry oxygen; normal levels are kept below 1 percent. ^[1]
• PaO2 stays normal, calculated SaO2 can be falsely normal, SpO2 often plateaus around 85 percent when MetHb exceeds about 15 to 20 percent, and co-oximetry is the gold standard. ^[1]
• Causes: RCM and HbM disease (inherited), and oxidising drugs and toxins (acquired), especially "-caine" anaesthetics, dapsone, volatile and alkyl nitrites, sodium nitrite and rasburicase. ^[1]
• Patients are usually asymptomatic with MetHb under 10 percent; treatment is generally indicated when levels exceed 20 percent with symptoms, or 30 percent even without symptoms. ^[1]
• Methylene blue 1 to 2 mg per kg intravenously over 5 to 10 minutes is first-line; it is contraindicated in G6PD deficiency, and doses above 7 mg per kg can cause cyanosis and haemolysis. ^[1]
• When methylene blue is unsafe or unavailable, use high-dose vitamin C, exchange transfusion or, in refractory cases, hyperbaric oxygen. ^[1]
• CO binds haemoglobin with an affinity up to 200 to 250 times that of oxygen, producing a leftward shift and tissue hypoxia; the gas also poisons mitochondria directly. ^[2]
• CO affects roughly 50,000 Americans attending emergency departments each year and kills up to 500. ^[2]
• CO poisoning is treated with 100 percent oxygen, continued until COHb reaches about 3 percent or for at least 6 hours, with much longer durations in pregnancy. ^[3]
• Hyperbaric oxygen is indicated in severe CO poisoning; its broader criteria include unconsciousness, neurological or cardiovascular abnormalities, severe acidosis, age above 36, exposure of 24 hours or more, or COHb of 25 percent or more, though many current guidelines use it more selectively. ^[2][3]
• Delayed neurological sequelae may appear weeks after CO exposure; follow-up should last 6 months. ^[2]

Haematology and emergency medicine topics covering approach to cyanosis, arterial blood gas and co-oximetry interpretation, G6PD deficiency, tumour lysis syndrome and rasburicase, dapsone, transfusion and exchange transfusion, and hyperbaric oxygen medicine.