Management of breakthrough pain in children with cancer

Figures & data

Table 1 Opioid analgesics: usual starting doses (calculated rescue [breakthrough] dose for morphine, hydromorphone, and oxycodone: 10% of 24-hour opioid dose to be given every 1–2 hours as needed)

Drug (route of administration)	Equianalgesic dose (parenteral)	Starting dose (IV)	IV:PO ratio	Starting dose PO (transdermal)	Starting dose controlled releasea
Morphine (PO, SL, IV, SC, PR)	10 mg	Bolus dose: 50–100 μg/kg every 2–4 hours Continuous infusion: 10–30 μg/kg/hour	1:3	0.15–0.3 mg/kg every 4 hours	0.45–0.9 mg every 12 hours
Fentanyl (IV, SC, SL, transdermal, buccal)	100–250 μg	Bolus dose: 1–3 μg/kg (slowly over 3–5 minutes; fast bolus may cause thorax rigidity) Continuous infusion: 1–2 μg/kg/hour	1:1 (IV to transdermalZ)	12 μg/hour patch (must be the equivalent of at least 30 mg oral morphine/24 hours before switching patch)	NA
Hydromorphone (PO, SL, IV, SC, PR)	1.5 mg	Bolus dose: 15–20 μg/kg every 4 hours Continuous infusion: 5 μg/kg/hour	1:5	60 μg/kg every 3–4 hours	180 μg/kg every 12 hours; currently not available in US
Oxycodone (PO, SL, PR)	5–10 mg	NA	NA	0.1–0.2 mg/kg every 4–6 hours	0.3–0.9 mg/kg every 12 hours
Tramadol (PO, PR)	100 mg	IV not available in US Bolus dose: 1 mg/kg every 3–4 hours Continuous infusion: 0.25 mg/kg/hour	1:1	1–2 mg/kg every 3–4 hours, maximum of 8 mg/kg/day (>50 kg: maximum of 400 mg/day)	2–4 mg/kg every 12 hours

Note:

a Doses are for children >6 months of age, and are capped at 50 kg body weight.

Abbreviations: IV, intravenous; PO, per os (by mouth); SL, sublingual; SC, subcutaneous; PR, per rectum; NA, not applicable.

Table 2 Usual starting doses for patient- or nurse-controlled analgesia pumps

	Continuous infusion (μg/kg/hour)	PCA bolus (μg)	Lockout time (minutes)	Maximum number of boluses/hour
Morphine	20 (maximum 1,000)	20 (maximum 1,000)	5–10	4–6
Hydromorphone	3–5 (maximum 250)	3–5 (maximum 250)	5–10	4–6
Fentanyl	1 (maximum 50)	1 (maximum 50)	5	4–6

Notes: Doses are for children >6 months of age, and are capped at 50 kg body weight. Dose escalation is usually calculated in 50% increments, both for continuous and PCA/NCA bolus doses.

Abbreviations: PCA, patient-controlled analgesia; NCA, nurse-controlled analgesia.

Figure 1 Managing children in acute cancer pain: multimodal “opioid-sparing” analgesia.

Notes: Blue circles show the standard approach; yellow circles show an advanced management approach in select cases.
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; WHO, World Health Organization; NMDA, N-methyl-D-aspartate.

Table 3 Adjuvant analgesia in neuropathic pediatric cancer pain management

Class	Medication	Dose	Route of administration	Comments/side effects
Tricyclic antidepressants (TCAs)	Amitriptyline	Starting dose 0.1 mg/kg QHS, usually slowly titrated up to 0.5 mg/kg (maximum 1–2 mg/kg)	PO	Tertiary amine TCA; stronger anticholinergic side effects (including sedation) than nortriptyline
	Nortriptyline	Starting dose 0.1 mg/kg QHS, usually titrated up to 0.5 mg/kg (maximum 1 mg/kg)	PO	Secondary amine TCA; anticholinergic side effects
Gabapentinoids	Gabapentin	Starting dose 2 mg/kg QHS, usually slowly titrated up to initial target dose of 6 mg/kg/dose TID (maximum 300 mg/dose TID). Maximum dose escalation to 24 mg/kg/dose TID (maximum 1,200 mg/dose TID)	PO	Slow dose increase required. Side effects ataxia, nystagmus, myalgia, hallucination, dizziness, somnolence, aggressive behaviors, hyperactivity, thought disorder, peripheral edema
	Pregabalin	Starting dose 0.3 mg/kg QHS, usually slowly titrated up to initial target dose of 1.5 mg/kg/dose BID (maximum 75 mg/dose BID). Maximum dose escalation to 6 mg/kg/dose BID (maximum 300 mg/dose BID)	PO	Switch from gabapentin if distressing side effects or inadequate analgesia Side effects ataxia, nystagmus, myalgia, hallucinations, dizziness, somnolence, aggressive behaviors, hyperactivity, thought disorder, peripheral edema; associated with weight gain
Sodium-channel blocker/local anesthetic	Lidocaine 5%	Maximum of four patches (in patients >50 kg) 12 hours on/12 hours off	Transdermal patch	Not for severe hepatic dysfunction
Glucocorticoid	Dexamethasone	0.1–1.5 mg/kg (maximum 10 mg) starting dose, then 0.1–0.25 mg/kg × 2/day (for <14 days) (Malignant spinal cord compression [adult dose]: dexamethasone 16–96 mg/day or equivalent)	PO, IV	Add gastroprotective agent
NMDA-receptor antagonist	Ketamine (racemic mixture of S^+/R^− enantiomers)	IV 0.06–0.3 mg/kg/hour PO 0.2–0.5 mg/kg TID–QID and PRN	IV, PO, (SC, SL, intranasal, spinally)	Typical side effects rare at low dose, but would require benzodiazepine administration

Abbreviations: QHS, quaque hora somni (every night at bedtime); TID, ter in die (three times a day); BID, bis in die (twice a day); QID, quater in die (four times a day); IV, intravenous; PO, per os (by mouth); SL, sublingual; SC, subcutaneous; NMDA, N-methyl-D-aspartate; PRN, pro re nata (as needed).