From the Guidelines
Nitrous oxide and ketamine have distinct mechanisms of action, with nitrous oxide being a weaker analgesic and hypnotic compared to ketamine, which is a more potent NMDA receptor antagonist with a longer duration of action. The primary difference in their mechanisms of action lies in their ability to inhibit N-methyl-D-aspartate (NMDA) receptors and activate gamma-aminobutyric acid type A (GABA-A) receptors in the central nervous system. Nitrous oxide produces mild analgesia, anxiolysis, and euphoria, while ketamine creates a dissociative state, profound analgesia, amnesia, and dissociation 1.
Comparison of Nitrous Oxide and Ketamine
- Nitrous oxide has a rapid onset and offset, typically within minutes, due to its gaseous form and elimination through the lungs 1.
- Ketamine, on the other hand, has a longer duration of action, typically 30-60 minutes for IV administration, and undergoes hepatic metabolism 1.
- Nitrous oxide typically produces milder effects, including euphoria and mild analgesia, whereas ketamine creates more profound effects, including analgesia, amnesia, and dissociation 1.
- Both medications can cause cardiovascular effects, but ketamine typically increases heart rate and blood pressure, while nitrous oxide has minimal cardiovascular impact at standard concentrations 1.
Clinical Implications
- The choice between nitrous oxide and ketamine depends on the specific clinical scenario, patient population, and desired level of sedation and analgesia.
- Nitrous oxide may be preferred for procedures requiring mild sedation and analgesia, while ketamine may be preferred for procedures requiring more profound sedation and analgesia 1.
- The use of ketamine should be avoided in patients with ischemic heart disease, cerebrovascular disease, or hypertension due to its potential to increase heart rate and blood pressure 1.
From the Research
Mechanism of Action (MOA) Comparison
- Inhaled nitrous oxide and ketamine are both N-methyl-d-aspartate (NMDA) receptor antagonists, which contributes to their antidepressant effects 2, 3.
- Nitrous oxide acts as a non-competitive inhibitor of NMDA-type glutamate receptors, while ketamine induces complex downstream effects via NMDARs 2, 4.
- Both compounds have been shown to enhance glutamate-mediated synaptic transmission in the hippocampus, although the exact mechanisms may differ 3.
Similarities and Differences
- Nitrous oxide and ketamine have similar effects on hippocampal synaptic function, including persistent enhancement of synaptic responses mediated by both AMPA receptors and NMDA receptors 3.
- However, ketamine's effects are blocked by an AMPA receptor antagonist, while nitrous oxide's effects are not 3.
- The two compounds also differ in their potential for abuse and addiction, with ketamine being a controlled substance and nitrous oxide not being controlled 2, 5.
Neurotoxicity and Sensitivity
- Both nitrous oxide and ketamine have been shown to be neurotoxic, particularly in combination, and the aging brain is more sensitive to their neurotoxic effects 6.
- However, the sensitivity to neurotoxicity induced by nitrous oxide alone is equal in young and old brains, while ketamine alone or in combination with nitrous oxide is more neurotoxic in older brains 6.