Medical gas

Definition

Medical gases are a unique class of therapeutic agents used in clinical diagnosis, treatment, and anesthesia. These gases, often regulated as medicinal products, include both pure gases (e.g., oxygen, nitrogen, carbon dioxide) and gas mixtures (e.g., Entonox, heliox). Unlike typical drugs, medical gases are administered via inhalation and exert rapid systemic effects, often used in acute care settings such as intensive care units, operating theatres, and emergency response.

Medical gases are essential for oxygenation, ventilation, pain control, anesthesia, respiratory therapy, and diagnostic imaging.

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Classification of Medical Gases

Medical gases can be categorized based on therapeutic function and chemical composition:

1. Respiratory Gases

• Oxygen (O₂) – Primary gas for hypoxia and life support

• Helium/Oxygen mixtures (Heliox) – For obstructive airway diseases

• Carbon dioxide (CO₂) – Used for respiratory stimulation and laparoscopy

2. Anesthetic Gases

• Nitrous oxide (N₂O) – Analgesic and anesthetic agent

• Xenon – Experimental inhalational anesthetic (neuroprotective potential)

3. Diagnostic Gases

• Carbon monoxide (CO) – Used in controlled amounts for pulmonary function tests

• Xenon (Xe-133) – Radioisotope for cerebral blood flow studies (nuclear medicine)

4. Specialty Gases and Mixtures

• Entonox – 50:50 nitrous oxide and oxygen, used for analgesia

• Nitric oxide (NO) – Used in pulmonary hypertension

• Medical air – Filtered, compressed air used in ventilators and nebulizers

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Mechanisms of Action

Medical gases exert their effects through physiochemical interactions, rather than classical receptor-based pharmacology:

• Oxygen: Increases arterial oxygen tension, enhancing tissue oxygenation

• Carbon dioxide: Stimulates respiratory center in medulla oblongata

• Nitric oxide: Activates guanylate cyclase → increases cGMP → smooth muscle relaxation

• Nitrous oxide: Acts on NMDA receptors; analgesic and anesthetic action

• Helium (in Heliox): Low-density gas reduces airway resistance

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Key Medical Gases: Drug Profiles

1. Oxygen (O₂)

• Indications: Hypoxia, ARDS, shock, COPD exacerbation, anesthesia, carbon monoxide poisoning

• Concentration: Administered from 21% (room air) up to 100%

• Routes: Nasal cannula, face mask, non-rebreather, high-flow nasal oxygen, mechanical ventilation

• Adverse Effects:

  • Oxygen toxicity (high FiO₂ > 60% for prolonged periods)

  • Absorption atelectasis

  • CO₂ retention in COPD (hypoventilation risk)

• Contraindications: Relative in paraquat poisoning and certain types of neonatal lung injury

2. Nitrous Oxide (N₂O)

• Indications: Analgesia during minor procedures, labor, dental procedures, as adjunct to general anesthesia

• Mechanism: NMDA receptor inhibition; modulates opioid receptors

• Formulation: Often combined with oxygen (e.g., Entonox)

• Side Effects:

  • Nausea, vomiting, dizziness

  • Diffusion hypoxia if stopped abruptly

  • Bone marrow suppression with chronic use

• Caution: Avoid in pneumothorax, bowel obstruction, middle ear disease

3. Nitric Oxide (NO)

• Indications: Persistent pulmonary hypertension of the newborn (PPHN), ARDS, heart surgery in infants

• Dose: Typically started at 20 ppm and titrated

• Mechanism: Selective pulmonary vasodilator via cGMP pathway

• Side Effects:

  • Methemoglobinemia

  • Rebound pulmonary hypertension upon abrupt withdrawal

• Contraindications: Use caution in neonates with left ventricular dysfunction

4. Carbon Dioxide (CO₂)

• Indications: Respiratory drive stimulation in apnea testing, insufflation during laparoscopic surgery

• Mechanism: Acidifies CSF → stimulates medullary respiratory center

• Caution:

  • Risk of hypercapnia, respiratory acidosis

  • Can exacerbate increased intracranial pressure

5. Heliox (Helium + Oxygen)

• Typical mixture: 70% helium + 30% oxygen

• Indications: Upper airway obstruction, COPD, asthma exacerbation

• Mechanism: Reduces airway resistance due to low gas density

• Advantages:

  • Facilitates laminar flow

  • Enhances delivery of nebulized medications

• Limitations: Requires tight mask seal, specialized equipment

6. Entonox (50% N₂O + 50% O₂)

• Indications: Acute trauma, labor analgesia, burns, dental procedures

• Onset: Within 2–3 minutes; self-administered via demand valve

• Advantages: Rapid analgesia, short recovery time

• Cautions:

  • Avoid in enclosed air spaces (pneumothorax, obstructed bowel)

  • Not for use with vitamin B12 deficiency (interferes with methionine synthase)

7. Medical Air

• Composition: 21% oxygen, 78% nitrogen (same as ambient air), but purified and pressurized

• Use: Ventilators, nebulization, humidification, anesthesia carrier gas

• Not a drug, but regulated due to medical use

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Pharmacokinetics

Gas	Onset	Duration	Metabolism	Elimination
Oxygen	Immediate	Depends on FiO₂	Not metabolized	Exhaled unchanged
Nitrous oxide	2–3 min	Short	Minimal hepatic metabolism	Lungs (exhaled)
Nitric oxide	Seconds	Very short	Rapidly binds hemoglobin	Methemoglobin → urine
CO₂	Seconds	Short	Combines with HCO₃⁻ and hemoglobin	Lungs
Heliox	Immediate	Continuous while inhaled	Inert gas (no metabolism)	Exhaled unchanged

Safety Considerations

• Storage: Cylinders must be clearly labeled, secured upright, and kept away from heat

• Color coding (varies by country, e.g., in the US):

  • Oxygen – green

  • Nitrous oxide – blue

  • Air – yellow

  • Carbon dioxide – gray

  • Nitric oxide – teal

• Hazards:

  • Fire risk with oxygen

  • Gas embolism risk with improper delivery

  • Cryogenic injury with liquid gases

  • Explosion risk if oil/grease contacts high-pressure O₂

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Drug Interactions

• Nitrous oxide + CNS depressants (opioids, benzodiazepines): Enhanced sedation

• Nitric oxide + vasodilators: Additive hypotensive effects

• Long-term N₂O + methotrexate or isoniazid: ↑ neuropathy risk (via B12 inhibition)

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Monitoring Parameters

• Oxygen:

  • Pulse oximetry (SpO₂), arterial blood gases (PaO₂)

  • Watch for signs of oxygen toxicity in high FiO₂ therapy

• Nitric oxide:

  • Monitor methemoglobin levels (>5% is concerning)

  • Rebound effect upon withdrawal; wean slowly

• N₂O:

  • Ensure proper ventilation to prevent accumulation in clinical areas

  • Monitor for nausea, sedation levels

• CO₂:

  • Capnography (EtCO₂) during use

  • Arterial blood gases to assess acidosis risk

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Use in Special Populations

• Neonates:

  • Nitric oxide is approved for PPHN; caution with NO₂ formation

  • Caution with high FiO₂ in premature infants (risk of retinopathy of prematurity)

• Pregnancy:

  • Entonox commonly used in labor

  • Nitrous oxide not teratogenic in short-term use but avoid chronic exposure

• COPD:

  • Oxygen therapy should be titrated carefully to avoid CO₂ retention

• Elderly:

  • Sensitive to sedative effects of N₂O

  • Slower recovery from hypoventilation

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Regulatory and Quality Standards

• United States Pharmacopeia (USP) and European Pharmacopoeia (Ph. Eur.) provide specifications for purity

• Medical gases are regulated under FDA (21 CFR 201) and EMA regulations

• Gases must be labeled as "For Medical Use Only", with batch control, expiration date, and purity standards

• Pharmacovigilance applies as for other drug products

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Examples of Commercial Products

Brand Name	Composition	Manufacturer
Entonox	50% N₂O + 50% O₂	BOC Healthcare, Linde
INOmax	Nitric oxide 800 ppm	Mallinckrodt Pharmaceuticals
Scandinavian Heliox	70% He + 30% O₂	AGA Gas AB
Medical Oxygen USP	>99% O₂	Multiple suppliers
Medical Air	Filtered ambient air	Hospitals’ in-house systems or suppliers

Summary Table: Key Gases

Gas	Main Use	Key Risk	Delivery Mode
Oxygen	Hypoxia, ARDS, CO poisoning	Toxicity at high FiO₂	Mask, cannula, ventilator
Nitrous oxide	Analgesia, anesthesia	B12 inactivation, hypoxia	Mask, demand valve, endotracheal
Nitric oxide	PPHN, ARDS	Methemoglobinemia	Specialized ventilator
Carbon dioxide	Laparoscopy, respiratory stimulation	Hypercapnia	Insufflation, inhalation
Heliox	Airway obstruction	Hypoxia if FiO₂ too low	Mask, non-rebreather
Entonox	Labor pain, minor trauma	Air trapping, nausea	Self-administered inhaler