Show the model answerAttempt it first — that is what makes it stick
3 marks
Physical properties, manufacture and storage
Three headings. The property that ties them together is the critical temperature: it is why nitrous oxide is a liquid in the cylinder and why the gauge cannot tell you how much is left.
What earns the marks3 marks
| Physical properties | Molecular weight, boiling point, critical temperature and pressure, partition coefficients, MAC, supports combustion |
|---|---|
| Manufacture | Heating ammonium nitrate to 250 °C, the equation, the contaminants and how they are removed |
| Storage | Liquid in blue cylinders at 51 bar; gauge pressure does not show contents; weighed; filling ratio; pin index |
Read the question: Three nouns, three headings. An answer that spends the part on pharmacology, the uses of Entonox or the effects on each organ has answered part (d) early and left manufacture and storage empty.
Physical properties
| Property | Value | What follows from it |
|---|---|---|
| Molecular weight | 44 | |
| Boiling point | −88 °C | A gas at room temperature and pressure |
| Critical temperature | 36.5 °C | Below it, pressure alone liquefies it: a liquid in the cylinder at room temperature. Above it, as can happen in the tropics, the contents are a gas |
| Critical pressure | 72 bar | |
| Saturated vapour pressure at 20 °C | 5200 kPa (52 bar absolute; 51 bar on a gauge) | The cylinder pressure while any liquid remains |
| Blood:gas partition coefficient | 0.46 | Poorly soluble: rapid onset and offset |
| Oil:gas partition coefficient | 1.4 | Very low lipid solubility: low potency |
| MAC | 104% | Above 100%, so 1 MAC cannot be reached at one atmosphere; used as an adjunct at 60 to 70% |
| Combustion | Supports combustion | A risk of fire and explosion if oil or grease meets it at cylinder pressure |
Manufacture
Manufacture of nitrous oxide
Heat
Ammonium nitrate is heated to 250 °C: NH₄NO₃ → N₂O + 2H₂O.
Contaminants
Unless the temperature is carefully controlled, the gas contains ammonia (NH₃), nitrogen (N₂), nitric oxide (NO), nitrogen dioxide (NO₂) and nitric acid (HNO₃).
Purification
The impurities are removed by passage through scrubbers, water and caustic soda.
Storage
Compressed into cylinders, where below 36.5 °C it liquefies.
Storage
| Detail | |
|---|---|
| Cylinder | Blue (French blue in the UK), from size C, 450 L, to size G, 9,000 L. Pin index positions 3 and 5 |
| State | Liquid with vapour above it; filled to 90 to 95% of capacity with liquid, so there is room for expansion |
| Pressure | 51 bar gauge at 20 °C, the saturated vapour pressure, constant for as long as any liquid remains |
| Contents | The gauge does not show how much is left: pressure falls only once the liquid has gone, and then quickly. Contents are found by weighing the cylinder and subtracting the tare weight stamped on it; 1 g of nitrous oxide is about 0.55 L of gas at 20 °C |
| Filling ratio | Mass of nitrous oxide divided by the mass of water the cylinder could hold. Reduced to 0.67 in tropical climates to avoid cylinder explosion |
| In use | Evaporation takes latent heat, so a cylinder in rapid use cools and may frost over the liquid level |
| Handling | Stored indoors, away from extremes of heat and cold; no oil or grease near the valve, because it supports combustion |
3 marks, 1 for each
The concentration effect, the second gas effect and diffusion hypoxia
All three come from the same fact: nitrous oxide is given at 60 to 70%, and although it is poorly soluble it is far more soluble than the nitrogen it replaces, so litres of it move across the alveolus in the first minutes, in one direction at induction and the other at emergence.
What earns the marks3 marks
| (i) Concentration effect | Definition: the higher the inspired concentration, the faster FA approaches FI. Mechanism: concentrating effect and augmented inflow |
|---|---|
| (ii) Second gas effect | Definition: rapid uptake of the first gas speeds the rise of a second gas. Mechanism, and the clinical use |
| (iii) Diffusion hypoxia | Mechanism at the end of anaesthesia, time course, and prevention with oxygen |
Read the question: Each part is one mark, so each needs a definition and one line of mechanism, not a page. Name the gases in (ii): the first gas is nitrous oxide, taken up in volume; the second gas is whatever is given with it, the volatile agent and oxygen.
(i) The concentration effect
Mechanism. At 70%, large volumes of nitrous oxide are taken up into pulmonary capillary blood. Two things follow: the gas that remains is concentrated in a smaller alveolar volume (the concentrating effect), and more inspired gas is drawn in to replace the volume lost (augmented tracheal inflow). Both raise the alveolar fraction faster than uptake alone would allow.
(ii) The second gas effect
Mechanism. It is a direct result of the concentration effect: the second gas is concentrated in the smaller alveolar volume left after nitrous oxide uptake, and more of it arrives in the augmented inflow. Clinical use: a faster rise of the volatile agent, so a shorter inhalational induction.
| Inspired | After half the N₂O is taken up | After the lost volume is refilled | FA/FI for N₂O | |
|---|---|---|---|---|
| 70% nitrous oxide | N₂O 70.0% · O₂ 28.0% · agent 2.0% | N₂O 53.8% · O₂ 43.1% · agent 3.1% | N₂O 59.5% · O₂ 37.8% · agent 2.7% | 0.85 |
| 20% nitrous oxide | N₂O 20.0% · O₂ 78.0% · agent 2.0% | N₂O 11.1% · O₂ 86.7% · agent 2.2% | N₂O 12.0% · O₂ 85.8% · agent 2.2% | 0.60 |
Read across. With 70% nitrous oxide, the same proportional uptake leaves an FA/FI of 0.85, against 0.60 with 20%: the concentration effect. The volatile agent, given at 2%, rises to 2.7% in the alveolus with 70% nitrous oxide, and oxygen from 28% to 37.8%: the second gas effect. The model assumes half the nitrous oxide is taken up in one step and nothing else is, so it shows the direction of each effect, not a patient’s values.
(iii) Diffusion hypoxia
Diffusion hypoxia at the end of a nitrous oxide anaesthetic
Nitrous oxide stopped
The gas mixture is changed to air, so the partial pressure gradient reverses: nitrous oxide leaves the blood for the alveolus.
Unequal exchange
Nitrous oxide is about 33 times more soluble in blood than nitrogen, so far more nitrous oxide enters the alveolus than nitrogen leaves it: several litres per minute over the first 5 to 10 minutes.
Oxygen diluted
Alveolar oxygen partial pressure falls.
CO₂ diluted
Alveolar CO₂ falls, reducing the drive to breathe.
With residual anaesthetic respiratory depression, hypoventilation and desaturation if the patient breathes air.
4 marks
Adverse effects of nitrous oxide
Four marks is four or more distinct effects, each with its mechanism. Group them so none is missed: physical effects of its volume and solubility, biochemical effects on vitamin B12, effects on organs, and effects beyond the patient.
What earns the marks4 marks
| Expansion of closed gas spaces | Mechanism and examples: pneumothorax, bowel, air embolism, middle ear, intraocular gas |
|---|---|
| Vitamin B12 inactivation | Methionine synthase: megaloblastic change, neuropathy, homocysteine; who is at risk |
| Organ effects | Nausea and vomiting, cerebral blood flow, myocardial depression in heart failure, diffusion hypoxia, awareness if used alone |
| Reproductive | Teratogenic in animals |
| Beyond the patient | Occupational exposure, recreational misuse, greenhouse gas and ozone depletion, supports combustion |
Read the question: “Describe” means a mechanism beside each effect. “Megaloblastic anaemia” alone is a word; “oxidises the cobalt in vitamin B12 and inactivates methionine synthase, so DNA synthesis fails” is the mark.
| Effect | Mechanism | Consequence and detail |
|---|---|---|
| Expansion of closed gas spaces | Nitrous oxide (blood:gas 0.46) enters an air-filled space about 33 times faster than nitrogen (0.014) can leave it | Compliant spaces expand: pneumothorax (75% nitrous oxide doubled its volume in 10 minutes in an animal model), bowel, air emboli. Non-compliant spaces rise in pressure: middle ear (tympanic rupture), intraocular gas bubbles after retinal surgery (retinal artery compression and visual loss) |
| Haematological | Irreversibly oxidises the cobalt of vitamin B12, inactivating methionine synthase: less methionine and tetrahydrofolate, so impaired DNA synthesis | Megaloblastic bone marrow change: rare in healthy patients, reported only after more than 12 hours. In the seriously ill or those at risk, shorter or repeated exposures matter, and changes have been induced after 2 to 6 hours. Exposure over days can cause agranulocytosis |
| Neurological | The same inactivation of vitamin B12, impairing myelin synthesis | Subacute combined degeneration of the cord, neuropathy and encephalopathy, mainly with repeated exposure: recreational use, and historically unscavenged dental surgeries |
| Homocysteine | Methionine synthase cannot methylate homocysteine, so it accumulates | Hypothesised to increase vascular risk; a large randomised trial (ENIGMA-II, 7,112 patients) found no difference in myocardial infarction, stroke, pulmonary embolism or cardiac arrest within 30 days |
| Teratogenicity | Linked to the folate pathway: in rats it is prevented by folinic acid | Teratogenic in rats; never shown unequivocally in humans, but often avoided in the first trimester |
| Postoperative nausea and vomiting | Multiple mechanisms; altered middle ear pressure is one proposed contributor | Probably increases the risk, especially in patients with other risk factors |
| Cardiovascular | Mild direct myocardial depression, normally offset by central sympathetic stimulation | Little change in health; cardiac output may fall in heart failure, where sympathetic drive cannot rise |
| Central nervous system | Increases cerebral blood flow | Often avoided when intracranial pressure is raised |
| Respiratory | Outpouring into the alveolus at the end of anaesthesia | Diffusion hypoxia, part (b)(iii) |
| Awareness | MAC-awake (about 0.71 atm) is close to the concentrations used | Used as the sole hypnotic it carries a high risk of awareness |
| Occupational and recreational | Chronic vitamin B12 inactivation in exposed staff and users | No effect on DNA synthesis where scavenging keeps levels below 50 ppm; neurological syndromes after unscavenged chronic exposure and misuse |
| Environmental | Greenhouse gas, and releases oxygen atoms in the stratosphere that break down ozone | Global warming potential over 100 years 298 times that of CO₂, atmospheric lifetime 114 years; now considered the dominant ozone-depleting substance |
| Fire | Supports combustion | Fire and explosion if oil or grease meets it at cylinder pressure |