Entonox Summary

Drug Profile

  • Name: Nitrous Oxide (Entonox®)
  • Type: Inhalational analgesic/anaesthetic
  • Mixture: 50% N₂O + 50% O₂
  • Color Code: Blue/white cylinders

Clinical Uses

  • Anaesthesia: 50-66% with other agents
  • Analgesia: 50% Entonox for pain relief
  • Obstetric analgesia
  • Emergency analgesia
  • Dressing changes
  • Post-operative physiotherapy

Absolute Contraindications

  • Pneumothorax
  • Intracranial air
  • Recent diving (air embolism risk)
  • Intraocular gas injection
  • Intestinal obstruction
  • Raised ICP

Key Adverse Effects

  • Post-administration hypoxia
  • Megaloblastic anemia
  • Neurological toxicity
  • Leukocyte depression
  • Vitamin B12 inactivation

Safety Precautions

  • Always administer oxygen post-use
  • Limit prolonged exposure
  • Monitor for hematological changes
  • Avoid in closed air spaces
  • Use demand valve for self-administration

Administration Notes

  • Not potent enough as sole anaesthetic
  • Allows reduction of other agent doses
  • Rapid onset and offset
  • Self-administered via demand valve

Mechanism of Action

  • NMDA receptor antagonism
  • Opioid receptor activation
  • GABAergic effects
  • Diffusion into closed spaces

Nitrous Oxide (Entonox) Pharmacology

Inhalational analgesic and anaesthetic agent for acute pain management

Overview

Nitrous oxide is used for maintenance of anaesthesia and, in sub-anaesthetic concentrations, for analgesia. It is commonly administered as Entonox®, a 50:50 mixture with oxygen.

Identification: Entonox cylinders are blue or blue/white in colour and should have a blue/white quartered collar for easy recognition.

Clinical Uses

Anaesthetic Use

  • Concentration: 50-66% in oxygen
  • Administration: With other inhalational or intravenous agents
  • Role: Allows reduction in dosage of other anaesthetic agents
  • Limitation: Cannot be used as sole anaesthetic agent due to lack of potency

Analgesic Use (Entonox®)

  • Concentration: 50% nitrous oxide + 50% oxygen
  • Administration: Self-administration using demand valve
  • Onset: Rapid (2-3 minutes)
  • Duration: Short-acting

Common Clinical Applications

Obstetric Practice

  • Labour analgesia
  • Perineal repair
  • Manual removal of placenta

Emergency Medicine

  • Emergency ambulance use
  • Fracture reduction
  • Burn dressing changes
  • Trauma analgesia

Hospital Settings

  • Painful dressing changes
  • Post-operative physiotherapy
  • Minor procedures
  • Diagnostic procedures

Contraindications

Critical Warning: Nitrous oxide must not be used in patients with an air-containing closed space as nitrous oxide diffuses into these spaces with a resulting increase in pressure.

Absolute Contraindications

  • Pneumothorax (undrained)
  • Intracranial air after head injury or surgery
  • Entrapped air following recent underwater diving
  • Recent intraocular gas injection
  • Intestinal obstruction with gas-filled loops
  • Raised intracranial pressure or risk thereof

Relative Contraindications

  • Chronic respiratory disease
  • Severe cardiac disease
  • First trimester pregnancy
  • Vitamin B12 deficiency
  • History of substance abuse

Mechanism of Contraindication

Nitrous oxide is 35 times more soluble than nitrogen in blood. When administered, it rapidly diffuses into air-filled cavities faster than nitrogen can diffuse out, causing expansion of the cavity and increased pressure.

Adverse Effects

Immediate Risk: Hypoxia can occur immediately following the administration of nitrous oxide. Additional oxygen should always be given for several minutes after stopping the flow of nitrous oxide.

Acute Adverse Effects

Effect Mechanism Management
Diffusion hypoxia Rapid diffusion of N₂O from blood to alveoli displacing oxygen Administer 100% oxygen for 5-10 minutes post-use
Nausea & vomiting Direct effect on chemoreceptor trigger zone Antiemetics if prolonged use
Dizziness/euphoria CNS effects Supervision during use
Expansion of air spaces High solubility in blood Avoid in contraindicated conditions

Chronic Adverse Effects

Hematological Effects

  • Megaloblastic anaemia
    • Due to interference with vitamin B12 metabolism
    • Inactivates methionine synthase
    • Impairs DNA synthesis
  • Leukocyte depression
  • Thrombocytopenia (rare)

Neurological Effects

  • Peripheral neuropathy
  • Myelopathy
  • Encephalopathy
  • Can occur without preceding hematological changes

Occupational Hazard: Healthcare workers chronically exposed to trace amounts of nitrous oxide may develop similar hematological and neurological complications. Proper scavenging systems are essential.

Pharmacology & Mechanism of Action

Pharmacokinetics

  • Blood:Gas partition coefficient: 0.47
  • MAC: 104% (weak anaesthetic)
  • Onset: 2-3 minutes
  • Elimination: Primarily pulmonary (unchanged)
  • Metabolism: Minimal (0.004%)

Mechanisms of Action

  • NMDA receptor antagonism
  • Opioid receptor activation (κ and μ receptors)
  • GABAA receptor potentiation
  • Two-pore domain potassium channel activation

Physical Properties

Property Value Clinical Significance
Molecular weight 44 g/mol Heavier than air
Boiling point -88°C Stored as liquid under pressure
Blood:Gas solubility 0.47 Rapid onset and offset
Oil:Gas solubility 1.4 Low potency

Practical Administration

Entonox Administration Protocol
  1. Check contraindications - especially pneumothorax, intracranial air
  2. Verify cylinder - blue/white, properly labeled Entonox
  3. Explain procedure to patient
  4. Instruct patient on demand valve use
  5. Monitor patient throughout administration
  6. Administer oxygen for 5-10 minutes after discontinuation
  7. Document administration and effects

Special Populations

Obstetric Patients

  • Excellent safety profile in labour
  • No effect on uterine contractions
  • Minimal effect on neonate
  • Maternal cooperation maintained

Pediatric Patients

  • Use with caution
  • Appropriate supervision required
  • Consider reduced duration of use
  • Monitor for excessive sedation

Elderly Patients

  • Increased sensitivity possible
  • Monitor for excessive sedation
  • Consider comorbidities
  • Shorter duration recommended

Drug Interactions

Drug Class Interaction Clinical Significance
Other anaesthetics Additive CNS depression Allows reduction of other agent doses
Opioids Enhanced analgesia Synergistic effect
Benzodiazepines Increased sedation Risk of excessive CNS depression
Methotrexate Enhanced bone marrow suppression Avoid combination
Vitamin B12 Functional deficiency Supplement if prolonged use