Primary Sedative - Analgesic Drugs
Drugs used for painful procedures. “Make sure that pain is treated promptly and adequately.” (Parent’s wish list for children with cancer, Durbin, 1997.)
Nonsteroidal Anti-Inflammatory Agents (Not a Sedative)
Use:
- Postoperative pain in children: Ketorolac 0.5/kg IV vs. MSO4
- Postoperative pain in critically ill children: Ketorolac 0.6/kg IV vs. MSO4 (Crit Care Med 1999;27:2786)
| Reaction to Treatment | Morphine (n=48) | Ketorolac (n=54) |
|---|---|---|
| Pain relief in first hour | 27 (56%) | 31 (57%) |
| Pain relief in first 2 hrs | 28 (58%) | 37 (68%) |
| Maximum pain relief in first 2 hrs | 21 (44%) | 27 (50%) |
| Required remedication within the first 4 hrs | 30 (63%) | 31 (58%) |
| Treatment failure (never achieved pain relief) | 7 (14%) | 2 (3.7%) |
Opioid Agonists
Morphine, Fentanyl, Meperidine, Methadone, Hydromorphone, Codeine, Alfentanil
Pharmacodynamic Features
Opioid agonists bind to specific opioid receptors (primarily µ receptors) distributed throughout the neuraxis. Opioids inhibit spontaneous neuronal firing and excitatory neurotransmitter release.
Basics
Clinical onset and duration distinguish morphine from fentanyl, despite similar half-lives.
| Opioid Agonist | Lipid Solubility* | Protein Binding (%) | Volume of distribution (L/kg) | Clearance (mL/kg/min) | Elimination half-life (hours) | Active Metabolites |
|---|---|---|---|---|---|---|
| Morphine | + | 30% (adults, children) 18-22% (neonates) |
3.2-4.7 | 12.4-15.2 | 2-4 (adults, children) 6-7 (infants) |
Morphine-3-glucuronide (excitatory) Morphine-6-glucuronide (active) |
| Fentanyl | ++++ | 80%-85% | 3.2-4.2 | 11.2-13.3 | 2.7 |
- |
| Alfentanil | +++ | 92% | 0.86 | 6.4 | 1-1.6 |
- |
| Methadone | +++ | 80%-85% | 7.1 | 5.4 | 15-30 | - |
*Lipid Solubility: (+) low, (++) medium, (+++) moderate, (++++) high
Notes:
- Morphine is much less protein-bound than fentanyl.
- Fentanyl does not have active metabolites.
- Morphine and fentanyl have similar elimination half-lives and much different lipid solubility.
| Opioid Agonist | Dose | Repeat Dose | Onset | Duration |
|---|---|---|---|---|
| Morphine | 0.05-0.2 mg/kg | 0.05 mg/kg q 10 min |
5-10 min | 3-4 hours |
| Fentanyl | *0.5-2 µg/kg | 0.5 mg/kg q 2-3 min |
2-3 min | 30-60 min |
*Administer over ~2 min
Clinical Use
Procedures associated with moderate to severe discomfort (pain), categories (3) and (4). BNZs augment opioid effects and provide amnesia.
Ketamine
Phencyclidine derivative withdissociative sedative, analgesic and amnestic properties.
Pharmacokinetic Features
Ketamine noncompetitively blocks the N-methyl-D aspartate (NMDA) receptor, part of a class of glutamate receptors mediating excitatory neurotransmission. Ion fluxes and subsequent excitatory neurotransmission are inhibited.
Basics
Clinically effective by a number of different routes. Administer with BNZ to attenuate neuropsychiatric effects and antisialagogue to reduce secretions. Ketamine is relatively contraindicated in any child with perceptual problems (visual, auditory, psychiatric). The single most severe adverse effect occurring in a healthy child is laryngospasm.
| NMDA Receptor Antagonist | Protein Binding (%) | Volume of distribution (L/kg) | Clearance (mL/kg/min) | Elimination half-life (hours) | Active Metabolites |
|---|---|---|---|---|---|
| Ketamine | 12% |
3 | 18 | 2-3 |
Norketamine* |
*Predominates after enteral administration
| Administer | Dose | Repeat Dose | Clinical Onset | Clinical Peak | Clinical Duration |
|---|---|---|---|---|---|
| IV | 0.5-1 mg/kg* | 0.5 mg/kg (every 2-3 min) |
<60 sec | 1-2 min | 10-15 min |
| IM | 2-4 mg/kg | 2-4 mg/kg | 1-2 min | 2-4 min | 30-60 min |
| Oral | 6-10 mg/kg** | 6-10 mg/kg | ~10-15 min (variable) |
~20-45 min | 2-3 hours |
| Rectal | 6-8 mg/kg** | 6-8 mg/kg | ~5-10 min (variable) |
10-20 min | 2-3 hours |
*Midazolam 0.1 mg/kg (IV)
**Midazolam 0.2-0.3 mg/kg (p.o., p.v.)
Clinical Use
Procedures associated with moderate to severe discomfort and pain. Avoid in individuals with intracranial hypertension, systemic hypertension, or neuropsychiatric disorders and any child with visual or auditory problems (perceptual disorders) (Pediatrics 1992;90:537, Pediatrics 1997;99:427, Pediatrics 1998;102:956).