see: [RCH Nitrous Oxide Oxygen Mix](x-devonthink-item://A8575F8D-29A2-4CBF-83D5-2E2B42698C17) [Austin - nitrous oxide toxicity](x-devonthink-item://A8B1FF54-123F-4101-8CA4-A62ECB63D607) #paeds #anaesthetics #toxicology **contraindications in ED** - gas-filled space: [[pneumothorax]], [[Bowel obstruction]], severe head injuries or recent brain surgery - airway or breathing compromise: severe COPD or current asthma exacerbation - [[Diving injuries and Dysbarism|Decompression illness]] or recent dive - patient requiring > 50% oxygen - intoxication or depressed conscious state - pregnancy (relative) - pulmonary hypertension - ↑ risk of N2O-induced bone marrow suppression (eg methionine synthase deficency, homocystinuria, methylmalonic academia) ## Nitrous oxide toxicity see also: [[Solvents|chroming]] see: [RCH - Nitrous oxide misuse](https://www.rch.org.au/clinicalguide/guideline_index/Nitrous_Oxide_Misuse/), [Nangs, balloons and crackers: Recreational nitrous oxide neurotoxicity](https://www1.racgp.org.au/ajgp/2021/november/recreational-nitrous-oxide-neurotoxicity) - [bookends](bookends://sonnysoftware.com/ref/DL/132988) Antidote:: B12 injections, methionine. rarely folic acid ### Pathology - Chronic exposure leads to inactivation of vitamin B12 and reduction of available methionine, leading to demyelination in the peripheral +/- central nervous system - Reduction in tetrahydrofolate may lead to bone marrow suppression ![[Pasted image 20260213141826.png]] ![[Pasted image 20260213141931.png]] > [!caption] B12 is a cofactor for methionine synthase (transfers CH3 groups as methylcobalamin) and methylmalonyl-CoA mutase. Important for DNA synthesis. see [[Anaemia#from Goljan lecture notes|Goljan notes]] for more information ![[Pasted image 20260213142658.png]] source: [AJGP - recreational nitrous oxide neurotoxicity](https://www1.racgp.org.au/ajgp/2021/november/recreational-nitrous-oxide-neurotoxicity) > [!pearl]+ Why does N2O tox affect spinal columns? > [Subacute combined degeneration of spinal cord](https://en.wikipedia.org/wiki/Subacute_combined_degeneration_of_spinal_cord) is due to preferential degeneration of white matter tracts of posterior and lateral column of lower cervical and upper thoracic cord segments. Histologically the first event seen in posterolateral column is myelin oedema followed by collection of small foci of tissue destruction into larger ones, giving vacuolated appearance of the tissue. Similar changes are seen in AIDS myelopathy and rarely in systemic lupus erythrematosus. Early on there is little gliosis of tissue but later in the chronic state, gliosis is prominent > > - Posterior column dysfunction decreases vibratory sensation and proprioception. > - Lateral corticospinal tract dysfunction produces spasticity > - Dorsal spinocerebellar tract dysfunction causes ataxia ### Symptoms - Initial features often consistent with sub-acute degeneration of the spinal cord with sensory changes, gait disturbance and impaired joint position sense - Progression, motor and bladder dysfunction may occur - psychological: depression - haematological: [[Anaemia#macrocytic anaemia|macrocytic anaemia]](uncommon), bone marrow suppression ### Examination see also: [[Neuro - upper limb]] and [[Neuro - lower limb]] - Sensory deficits, may be dermatomal but can be patchy (akin to findings in multiple sclerosis) - Impaired **proprioception** and **coordination** (affects [[Neck and spine trauma#Spinal Cord Injury|dorsal columns]] first) - Sensory ataxia  - Reduced power in limbs - Reduced reflexes ### Investigations - Total B12 and active B12 (holotranscobalamin): may be low-normal or normal - MRI: may demonstrate demyelination in either the central or peripheral nervous system > ***DDxs to consider with B12 tox symptoms*** (see also: [[Weakness]]) > - folic acid def > - copper def > - CNS demyelination (eg [[Multiple Sclerosis]] > - [[Guillain-Barré syndrome|GBS]] > - compressive spinal cord tumour > - several others ### Management Vitamin B12 and methionine should be administered *even if B12 concentration is normal* ***Vitamin B12 (Hydroxocobalamin):*** - Administer 1mg daily IM for 2 weeks, weekly for four weeks then monthly until maximal recovery ***Methionine:*** - Administer 1g TDS orally for 2 weeks. ***Folinic acid:*** - Administer 30 mg of intravenous folinic acid if there is ==evidence of bone marrow suppression== > Consider the presence of other nutritional deficiencies ### Disposition - If unable to safely mobilise or other significant N20 related toxicity is present, admit for treatment until clinical improvement - Referral to alcohol and drug service should be considered