CO, cyanide and methaemoglobin: why SpO₂ and PaO₂ fool you
CO, cyanide and methaemoglobin can all starve tissue of oxygen while the pulse oximeter or the arterial PaO₂ looks reassuring. Each poison leaves a different fingerprint.
Distinguish carbon monoxide poisoning, cyanide toxicity and methaemoglobinaemia by mechanism, PaO₂, SpO₂ and oxygen content.
The short version
- Oxygen content depends on usable haemoglobin, its saturation and a little dissolved oxygen, and a poison can attack each part.
- Carbon monoxide: normal PaO₂, a falsely normal SpO₂ and a low oxygen content; confirm with a co-oximeter.
- Methaemoglobin: normal PaO₂, an oximeter reading that settles near 85 percent once methaemoglobin is significant and that supplemental oxygen does not move, chocolate-brown blood and a low content.
- Cyanide: normal arterial PaO₂, SpO₂ and oxygen content, but high venous oxygen because the cells cannot use it.
- Treatments differ: oxygen for carbon monoxide, methylene blue for methaemoglobin, hydroxocobalamin for cyanide.
A normal SpO₂ does not mean the tissue has oxygen
A woman is found confused in a closed garage beside a running car. The paramedic clips on a pulse oximeter and it reads 99 percent. She is not safe: the oximeter is fooled. CO, cyanide and methaemoglobin can each starve tissue of oxygen, and each leaves a different pattern of PaO₂, SpO₂ and oxygen content.[1][3]
To tell them apart, start from what oxygen content is made of.
mL O₂/dL; Hb in g/dL; 0.003 × PaO₂ is the small dissolved fraction. Sources quote the haemoglobin constant between 1.31 and 1.39; this lesson uses 1.34.
So oxygen content depends on usable haemoglobin, its saturation and a little dissolved oxygen. A poison can attack each part.[1][2]
Carbon monoxide: a falsely normal SpO₂
Carbon monoxide takes the haem sites that oxygen needs, binding with about 200 to 250 times the affinity of oxygen.[1][3]
It also shifts the curve of the remaining haemoglobin to the left, so the oxygen that is left is released poorly.[4][7]
Dissolved oxygen is untouched, so the PaO₂ is normal.[3][4] A standard pulse oximeter cannot tell carboxyhaemoglobin from oxyhaemoglobin, so the SpO₂ reads falsely normal.[4]
The test is a co-oximeter, which measures carboxyhaemoglobin directly.[3]
Worked example: oxygen content with carbon monoxide
Take haemoglobin 15 g/dL and carboxyhaemoglobin 40 percent. This assumes normal oxygen pressure saturates all the usable haemoglobin, so oxyhaemoglobin is about 98 − 40 = 58 percent.
- 1.34 × 15 × 0.58 ≈ 11.7
- 11.7 + 0.3 (dissolved oxygen, 0.003 × a PaO₂ of about 100) ≈ 12 mL/dL
- Nothing blocking it: 1.34 × 15 × 0.98 ≈ 19.7, plus 0.3 ≈ 20 mL/dL
That is the woman in the garage: a normal oximeter and a normal PaO₂, but little usable haemoglobin. Her oxygen content is about 12 against about 20 for the same haemoglobin when nothing blocks it.[1]
Treatment is 100 percent oxygen, which cuts the half-life of carbon monoxide from 4 to 5 hours on room air to about 1 hour to 90 minutes. Hyperbaric oxygen cuts it to 20 to 30 minutes.[3][4]
Methaemoglobinaemia: the mid-eighties oximeter
In methaemoglobinaemia the iron in haem is oxidised from ferrous (Fe²⁺) to ferric (Fe³⁺), and ferric iron cannot bind oxygen.[5][8]
Causes include dapsone, prilocaine and nitrites.[5][9] The remaining haem also holds oxygen tighter, so the curve shifts left.[7][9]
- The PaO₂ is normal.[5]
- The blood looks chocolate brown.[5][8]
- The pulse oximeter falls and then settles near 85 percent once methaemoglobin is significant, and supplemental oxygen does not move it.[5][8][9]
- The oxygen content is low.
Treatment is methylene blue, with caution or avoided in G6PD deficiency, because it can cause haemolysis.[5][8]
Cyanide: oxygen arrives but the cell cannot use it
Cyanide does not touch haemoglobin. It blocks cytochrome oxidase inside mitochondria. Oxygen arrives, but the cell cannot use it.[1][6][8]
So classically the PaO₂, the SpO₂ and the arterial oxygen content are normal, and the venous blood stays rich in oxygen.[6][8][9]
The treatment is hydroxocobalamin.[6][8] The older nitrite regimen makes methaemoglobin on purpose, which lowers oxygen-carrying capacity; that is dangerous when carbon monoxide has already lowered it. In smoke inhalation, where carbon monoxide may be present, hydroxocobalamin is preferred.[6][8]
Comparing CO, cyanide and methaemoglobin
| Poison | PaO₂ | SpO₂ | Arterial oxygen content | Other clue |
|---|---|---|---|---|
| Carbon monoxide | Normal | Falsely normal | Low | Co-oximeter shows carboxyhaemoglobin |
| Methaemoglobin | Normal | Mid-eighties, about 85 percent | Low | Chocolate-brown blood; no response to oxygen |
| Cyanide | Normal | Normal | Normal | High venous oxygen |
Anaemia and pulmonary embolism can also cause hypoxia, but they do not fit these fingerprints. Anaemia alone leaves saturation and arterial PaO₂ normal with a low content, and an embolism lowers arterial PaO₂ and does not turn blood brown.[1][9]
Practice question
Original · USMLE styleA 36-year-old man is seen after a dental procedure in which topical prilocaine was applied. He is short of breath with bluish skin, and a drawn blood sample is chocolate brown. The pulse oximeter reads 86 percent and does not improve when oxygen is given by mask. An arterial sample drawn on room air has a PO₂ of 96 mmHg; haemoglobin is 13 g/dL.
Common questions
Why is SpO₂ falsely normal in carbon monoxide poisoning?
A standard pulse oximeter cannot tell carboxyhaemoglobin from oxyhaemoglobin, so it reads falsely normal. A co-oximeter measures carboxyhaemoglobin directly.
What SpO₂ does methaemoglobinaemia give?
The pulse oximeter falls and then settles near 85 percent once methaemoglobin is significant, and supplemental oxygen does not move it. The PaO₂ is normal and the blood looks chocolate brown.
Why are PaO₂ and SpO₂ normal in cyanide poisoning?
Cyanide does not touch haemoglobin. It blocks cytochrome oxidase inside mitochondria, so oxygen arrives but the cell cannot use it, and the venous blood stays rich in oxygen.
What is the treatment for each of the three poisons?
Carbon monoxide: 100 percent oxygen, or hyperbaric oxygen. Methaemoglobinaemia: methylene blue, with caution or avoided in G6PD deficiency. Cyanide: hydroxocobalamin, which is preferred in smoke inhalation.
Transcript
Read the full narration, by chapter641 words
0:00The case: normal SpO2 and PaO2, but starving
A 35-year-old woman is found confused in a closed garage beside a running car. The paramedic clips on a pulse oximeter. It reads 99%. Is she safe? The oximeter is fooled. Three poisons can starve tissue of oxygen, and each leaves a different fingerprint. Today: tell carbon monoxide, methaemoglobin and cyanide apart by mechanism, PaO2, SpO2 and oxygen content.
0:30The oxygen content equation, and where poisons attack it
Remember the content equation. Oxygen content is 1.34 times haemoglobin times saturation, plus 0.003 times the PaO2, in mL per decilitre. So it depends on usable haemoglobin, its saturation and a little dissolved oxygen. A poison can attack each part.
0:53Carbon monoxide: affinity, left shift, a normal PaO2
First, carbon monoxide. It takes the haem sites oxygen needs, binding with about 200 to 250 times the affinity. It also shifts the curve of the remaining haemoglobin to the left, so the oxygen that is left is released poorly.
1:11Dissolved O2 and PaO2 stay normal; the pulse oximeter is fooled
Dissolved oxygen is untouched, so the PaO2 is normal. And a standard pulse oximeter cannot tell carboxyhaemoglobin from oxyhaemoglobin, so the SpO2 reads falsely normal. The test is a co-oximeter, which measures carboxyhaemoglobin directly.
1:30Worked example: Hb 15, COHb 40 %, content about 12 vs about 20
Take haemoglobin 15 and carboxyhaemoglobin 40%. The oxyhaemoglobin is about 58%. This assumes normal oxygen pressure saturates all the usable haemoglobin. 1.34 times 15 times 0.58 is about 11.7; plus 0.3, about 12 mL per decilitre, against about 20 with nothing blocking it. That is the woman in the garage: a normal oximeter and a normal PaO2, but little usable haemoglobin.
2:03Treatment: CO half-life on room air, 100 % oxygen, hyperbaric
Treatment is 100% oxygen, which cuts the half-life of carbon monoxide from 4 to 5 hours to about an hour to 90 minutes; hyperbaric oxygen, to 20 to 30 minutes.
2:16Methaemoglobinaemia: Fe2+ to Fe3+, causes, mid-80s SpO2, methylene blue
Second, methaemoglobin. Here the iron in haem is oxidised from ferrous to ferric, and ferric iron cannot bind oxygen. Causes include dapsone, prilocaine and nitrites. The remaining haem also holds oxygen tighter, so the curve shifts left. The PaO2 is normal, the blood looks chocolate brown, and supplemental oxygen does not fix it. The pulse oximeter usually reads in the mid-eighties, drifting toward about 85% as methaemoglobin rises. Treatment is methylene blue, with caution or avoided in G6PD deficiency, because it can cause haemolysis.
2:58Cyanide: the block at cytochrome oxidase, high venous O2
Third, cyanide. Cyanide does not touch haemoglobin. It blocks cytochrome oxidase inside mitochondria. Oxygen arrives, but the cell cannot use it. So classically the PaO2, the SpO2 and the arterial oxygen content are normal, and the venous blood stays rich in oxygen. The treatment is hydroxocobalamin. The older nitrite regimen makes methaemoglobin on purpose, lowering oxygen-carrying capacity further. In smoke inhalation, where carbon monoxide may be present, hydroxocobalamin is preferred.
3:37Your turn: a practice question
Your turn. A 36-year-old man is seen after a dental procedure in which topical prilocaine was applied. He is short of breath with bluish skin, and a drawn blood sample is chocolate brown. The pulse oximeter reads 86%, and it does not improve when oxygen is given by mask. An arterial sample drawn on room air has a PaO2 of 96 mm Hg, and the haemoglobin is 13 grams per decilitre. Which of the following is the most likely diagnosis? A, methaemoglobinaemia. B, carbon monoxide poisoning. C, cyanide poisoning. D, pulmonary embolism. E, severe anaemia. Pause here and decide.
4:30The answer, one option at a time
B is out: carbon monoxide would give a falsely normal pulse oximeter reading, not 86. C is out: cyanide leaves the oximeter and the arterial PaO2 normal. D is out: an embolism would lower the arterial PaO2, and it does not turn blood brown. E is out: his haemoglobin is 13, and anaemia alone leaves saturation and arterial PaO2 normal. So the answer is A. Prilocaine oxidises haem iron: mid-eighties oximeter, normal arterial PaO2, chocolate-brown blood.
5:09Recap pocket card
Three things to keep. One: carbon monoxide gives a falsely normal oximeter and a low oxygen content. Two: methaemoglobin gives an oximeter in the mid-eighties and a low content. Three: cyanide gives a normal arterial oxygen content with high venous oxygen. That is the end of this lesson.
Sources
Numbers in the text, e.g. [1], point here- LITFL Part One. Hypoxia. partone.litfl.com/hypoxia.html
- OpenAnesthesia. Oxygen delivery vs PaO2. openanesthesia.org/o2_delivery_vs-_pao2/
- LITFL. Carbon monoxide poisoning. litfl.com/carbon-monoxide-poisoning/
- MSD Manual Professional Version. Carbon monoxide poisoning. msdmanuals.com/professional/injuries-poisoning/poisoning/carbon-monoxide-poisoning
- LITFL. Methaemoglobinaemia. litfl.com/methaemoglobinaemia/
- MSD Manual Professional Version. Systemic asphyxiant chemical warfare agents (cyanide). msdmanuals.com/professional/injuries-poisoning/mass-casualty-weapons/systemic-asphyxiant-chemical-warfare-agents
- Deranged Physiology. Factors which influence the affinity of haemoglobin for oxygen. derangedphysiology.com/main/cicm-primary-exam/respiratory-system/Chapter-113/factors-which-influence-affinity-haemoglobin-oxygen
- University of Maryland EM, Educational Pearls (methaemoglobinaemia, id 2781; cyanide, id 4924). medschool.umaryland.edu/em/cme/umem-educational-pearls/?id=2781 · medschool.umaryland.edu/em/cme/umem-educational-pearls/?id=4924
- PubMed Central: methaemoglobinaemia reviews (PMC9291883, PMC10332666), cyanide toxicity (PMC13589660, PMC12702631), mechanisms of hypoxaemia (PMC5234199). pmc.ncbi.nlm.nih.gov/articles/PMC9291883/ · pmc.ncbi.nlm.nih.gov/articles/PMC10332666/ · pmc.ncbi.nlm.nih.gov/articles/PMC13589660/ · pmc.ncbi.nlm.nih.gov/articles/PMC12702631/ · pmc.ncbi.nlm.nih.gov/articles/PMC5234199/
The practice question is original and its patient is synthetic. Every fact is checked against the sources above in independent accuracy reviews. Always follow your local guidelines and your own laboratory’s ranges.
Image credits. Illustrations: Servier Medical Art (smart.servier.com), CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/), adapted (recoloured, outlined, resized): woman, red blood cell, tooth, syringe, blood tube, mitochondrion. Oxygen cylinder icon: Health Icons (CC0). The garage, car, haem ring, curves, bars, dial, slip, cards and all handwriting are drawn in code (original). No AI-generated teaching images.
Corrections. None so far. Spotted an error? Email info@medservatory.com with the lesson code MS-S1-RESP-010.
For exam study only, not medical advice. Read the medical disclaimer.
In this series
Playlist on YouTube- EP 01Lung volumes and capacities, explained5:26
- EP 02Obstructive vs restrictive lung disease: FEV1/FVC and loops5:23
- EP 03Lung compliance, Laplace and surfactant: why alveoli stay open5:23
- EP 04V/Q mismatch: shunt, dead space and the oxygen test5:18
- EP 05A-a gradient: the alveolar gas equation and the causes of hypoxaemia5:39
- EP 06Oxygen-hemoglobin dissociation curve: P50, shifts and content5:19
- EP 07CO₂ transport: bicarbonate, the chloride shift, Bohr vs Haldane5:29
- EP 08Central vs peripheral chemoreceptors and oxygen-induced hypercapnia5:27
- EP 09Hypoxic pulmonary vasoconstriction and cor pulmonale5:41
- EP 10CO, cyanide and methaemoglobin: why SpO₂ and PaO₂ fool you5:34