What IV options exist for a patient with neuropathic and nociplastic (nociceptive plasticity) pain who is Nil Per Os (NPO)?

IV Options for Neuropathic and Nociplastic Pain in NPO Patients

For NPO patients with neuropathic and nociplastic pain, IV ketamine is the primary evidence-based option, with IV lidocaine as an alternative for neuropathic pain specifically, while IV opioids serve as adjunctive therapy rather than first-line treatment for these pain types. 1

Primary IV Option: Ketamine

IV ketamine is the most effective intravenous medication for severe neuropathic pain, particularly when oral medications cannot be administered. 1

Dosing Protocol for Ketamine

• Initial bolus: 1-3 mg/kg administered over 20-30 minutes 1
• Continuous infusion: 0.5-2 mg/kg/hr (maximum 100 mg/hour) if the bolus is effective and tolerated 1
• Alternative maintenance dosing: 0.1-0.5 mg/minute via slow microdrip infusion technique 2
• For induction purposes: 1-4.5 mg/kg IV, with 2 mg/kg producing 5-10 minutes of effect within 30 seconds (though this is anesthetic dosing, not analgesic) 2

Mechanism and Evidence

• Ketamine blocks glutamate through N-methyl-D-aspartate (NMDA) receptor antagonism, which limits central sensitization, hyperalgesia, and opioid tolerance 1
• Meta-analysis demonstrates significant short-term analgesic benefit with a mean difference of -1.83 points on a 0-10 pain scale (95% CI: -2.35 to -1.31) up to 2 weeks post-infusion 3
• Higher total doses and prolonged infusion durations are associated with increased duration of pain relief 4
• Responder rates favor ketamine over placebo (51.3% vs 19.4%; relative risk 2.43) 3

Important Monitoring and Side Effects

• Continuous vital sign monitoring is mandatory during ketamine administration 2
• Emergency airway equipment must be immediately available 2
• Common self-limiting side effects include tinnitus, perioral numbness, sedation, lightheadedness, and headache 1
• Consider coadministration of midazolam to mitigate psychomimetic side effects 4
• Use with caution in patients with cardiac conditions due to potential arrhythmias 1
• Administer slowly over 60 seconds to avoid respiratory depression and enhanced vasopressor response 2

Alternative IV Option: Lidocaine

IV lidocaine is particularly effective for cancer-related neuropathic pain and can reduce opioid requirements. 1

Dosing Protocol for Lidocaine

• Initial bolus: 1-3 mg/kg over 20-30 minutes 1
• Continuous infusion: 0.5-2 mg/kg/hr (maximum 100 mg/hour) if effective and tolerated 1

Clinical Considerations

• Produces faster onset (peak at 15 minutes) compared to oral medications (peak at 60 minutes) 1
• Requires cardiac monitoring due to potential arrhythmias 1
• Side effects are generally self-limiting and include tinnitus, perioral numbness, sedation, lightheadedness, and headache 1

Adjunctive IV Option: Opioids

IV opioids are recommended as first-line for non-neuropathic pain but serve only as adjunctive therapy for neuropathic and nociplastic pain. 5

Key Limitations

• Neuropathic pain is generally less sensitive to opioids than other pain pathophysiologies 6
• Nociplastic pain responds poorly to traditional opioid therapy 7
• All IV opioids show similar efficacy when titrated to similar pain endpoints 5
• Should be used at the smallest effective dose as a salvage option only 8

Clinical Context

• The Critical Care Medicine guidelines recommend IV opioids as first-line for non-neuropathic pain in ICU patients 5
• For neuropathic pain specifically, IV opioids plus oral gabapentin or carbamazepine provide superior relief in mechanically ventilated patients, but this requires enteral access 5

Treatment Algorithm for NPO Patients

1. First attempt: IV ketamine bolus (1-3 mg/kg over 20-30 minutes), followed by continuous infusion (0.5-2 mg/kg/hr) if effective and tolerated 1

2. If ketamine is contraindicated or ineffective: Consider IV lidocaine using the same dosing protocol 1

3. Adjunctive therapy: Add IV opioids at the lowest effective dose if ketamine or lidocaine provide only partial relief 8, 1

4. Transition planning: When oral intake resumes, transition to oral gabapentinoids (pregabalin or gabapentin) combined with antidepressants (duloxetine or TCAs) as first-line oral therapy 6

Critical Pitfalls to Avoid

• Do not use the 100 mg/mL concentration of ketamine IV without proper dilution 2
• Do not rely solely on IV opioids for neuropathic or nociplastic pain, as these pain types are relatively opioid-resistant 6, 7
• Do not administer ketamine rapidly (must be given over 60 seconds minimum) to avoid respiratory depression 2
• Do not use ketamine without continuous monitoring and immediately available airway equipment 2
• Nociplastic pain is often mistaken for central sensitization and requires specific recognition, as traditional nociceptive and neuropathic pain treatments are not entirely suitable 7