Pediatric pain management in surgical and diseases state: Pharmacological approach

Assoc Prof Vimolluck Sanansilp, MD Assist Prof Duenpen Horatanaruang, MD Assist Prof Kattiya Manomayangkul, MD

Case discussion A 6-y-o boy presented with abdominal mass and severe abdominal pain. After thorough investigation and tumor biopsy, neuroblastoma stage III was diagnosed. His body weight was 20 kg.  Pain service was consulted for management of severe cancer pain 

Case discussion 

Pain assessment ◦ Characteristics  Dull aching pain all day, night pain  No radiation  No colicky pain

Case discussion 

Pain assessment ◦ Intensity  Self-report: FPS-R  Rest = 6  Activity = 10

Dx: Visceral pain from tumor Severe cancer pain  Goal of Rx: mild pain 

Cancer Pain Management Comprehensive management of CA pain in children ◦ Active treatment of the disease ◦ Pharmacological and non-pharmacological interventions to reduce pain and suffering  Discuss with patients and family ◦ Treatment options ◦ Goal of treatment 

 Improve quality of life  Acceptable pain intensity

Pharmacological therapy  Considered

the mainstay of treatment  Key concepts “By the ladder” “By the clock” “By the appropriate route” “By the child”

By the ladder

WHO 3-steps approach (1998) WHO 2-steps approach (2012)

By the clock Regular schedule rather than pro re nata (prn) basis  With additional “rescue” dose 

Example: Morphine …. mg IV q 4 hr Morphine …. mg IV prn for breakthrough pain q 1-2 hr (rescue dose  10% of total daily dose)

By the appropriate route oral

transdermal

intravenous

•painless

•painless

•Rapid pain control

•Preferred by children

•Restricted to fentanyl

•Easiest to titrate and adjust to changing pain levels

•Not indicated for acute pain

•Useful for intermittent bolus and continuous infusion

•Not indicated for escalating pain

•Appropriate for PCA

•Can be used if pain has been stabilized

By the appropriate route subcutaneous

intramuscular

rectal

•Avoids need for IV line

•painful

•Generally disliked by children

•Useful for home setting

•Not recommended

•Wide variability in therapeutic blood levels

•Useful of continuous •Wide variability in infusion therapeutic blood levels

•Variable absorption

•Appropriate for PCA

•Can be used if there is transient vomiting

WHO. Cancer Pain Relief and Palliative Care in Children, Geneva: WHO, 1998.

By the child Based upon each child‟s circumstances  No single regimen that will be appropriate for all children 

Morphine parenteral: oral conversion ratio

1:3 IV Mo 10 mg = oral Mo 30 mg

Analgesic drugs Non-opioid analgesics ◦ For mild to moderate pain  Opioid analgesics ◦ For moderate to severe pain  Adjuvant analgesics ◦ e.g. gabapentin start 10-15 mg/kg/day up to 50 mg/kg/day ◦ Antidepressants ◦ Ketamine 

Strong opioid dosage ชนิดยา Morphine

รูปแบบการบริหารยา

ขนาดเริ่มต้ น

Oral (immediate release) 1-2 ปี : 200-400 มคก./กก. ทุก 4 ชม. 2-12 ปี : 200-500 มคก./กก. ทุก 4 ชม. (ไม่เกิน 5 มก.) Oral (prolonged release) 200-800 มคก./กก. ทุก 12 ชม. IV injection

SC injection

1-2 ปี : 100 มคก./กก. ทุก 4 ชม. 2-12 ปี : 100-200 มคก./กก. ทุก 4 ชม. (ไม่เกิน 2.5 มก.)

IV infusion

100-200 มคก./กก. จากนั ้น 20-30 มคก./กก./ชม.

SC infusion

20 มคก./กก./ชม.

Strong opioid dosage ชนิดยา Fentanyl

รูปแบบการบริหารยา

ขนาดเริ่มต้ น

IV injection

1-2 มคก./กก. ทุก 30-60 นาที

IV infusion

1-2 มคก./กก. จากนั ้น 1 มคก./กก./ชม.

Methadone Oral (immediate release) 100-200 มคก./กก. ทุก 4 ชม. สาหรับ 2-3 ครัง้ แรก จากนั ้น ทุก 6-12 ชม. (เริ่มต้ นไม่เกิน 5 มก. ต่อครัง้ ) Oxycodone Oral (immediate release) 125-200 มคก./กก. ทุก 4 ชม. (ไม่เกิน 5 มก./ครัง้ ) Oral (prolonged release) 5 มก. ทุก 12 ชม.

Opioid side effects

Pediatr Clin N Am 2005;52:995-1027

Opioid side effects

Pediatr Clin N Am 2005;52:995-1027

Case discussion Dx: Visceral pain from tumor Severe cancer pain  Goal of Rx: mild pain  Rx: BW 20 kg. 

◦ Mo syr. (2 mg/ml) 2 ml oral q 4 hr Then switch to ◦ MST (10) 1 tab oral q 12 hr (8:00, 20:00) ◦ Mo syr. 1 ml oral prn for breakthrough pain q 2 hr ◦ MOM 10 ml oral hs

Case discussion 

Then after 6 cycles of chemotherapy, patient was scheduled for surgery: Explor lap. with tumor removal

Perioperative pain management 

General or regional anesthesia can be appropriate for patients undergoing abdominal surgery



Low thoracic epidural remains the „gold standard‟ for the delivery of postoperative analgesia after abdominal surgery

Perioperative pain management Continuous epidural analgesia is beneficial for children undergoing complex abdominal tumor surgery:  



central blockade of pain transmission reduced pain levels overcome surgical stress through blockade of nociceptive signalsdiminish stress hormones releasing (cortisol, catecholamines) improve postoperative recovery

Caution! The majority of regional anesthesia in children and infants is performed under either deep sedation or general anesthesia   Inability to recognize paresthesia  Difficult to identify accidental intravascular injection of local anesthetics

Pediatric epidural dosing guidelines Medication

Initial bolus

Infusion solution

Infusion limits

Bupivacaine

≤2.5–3 mg/kg

0.0625–0.1%

≤0.4 mg/kg/h

Ropivacaine

≤2.5–3 mg/kg

0.1–0.2%

≤0.4–0.5 mg/kg/h

Fentanyl

1–2 µg/kg

2–5 µg/ml

0.5–2 µg/kg/h

Morphine

10–30 µg/kg

5–10 µg/ml

1–5 µg/kg/h

Hydromorphone 2–6 µg/kg

2–5 µg/ml

1–2.5 µg/kg/h

Clonidine

0.5–1 µg/ml

0.5–1 µg/kg/h

1–2 µg/kg

Pediatric epidural analgesia Pharmacokinetic studies of bupivacaine in children

> 6 months: infusion rates < 0.4 mg/kg/hr with plasma bupivacaine levels in a safe range of 2-3 µg/ml have reported good safety  < 4-6 months: infusion rates 0.2 mg/kg/hr 

Case discussion Then after 6 cycles of chemotherapy, patient was scheduled for surgery: Explor lap. with tumor removal  Rx: BW 20 kg 

Epidural block was performed at T11-T12 level and catheter was threaded 2.5 cm. into space  0.25% Bupivacaine bolus 10 ml (B 25 mg)  0.1% Bupivacaine + Fentanyl 2 µg/ml drip 4-6 ml/hr (B 4-6 mg/hr, F 8-12 µg/hr) 

Postoperative analgesia

Postoperative analgesia

Hierachy of postop. analgesia

Epid. analg. Contin. Ep. Analg.; Patient-Controlled Ep. Analg.

Intermittent Ep.Opioid Analg.

Postoperative analgesia

Hierachy of postop. analgesia

IV-PCA IV-cont. infusion IV-algorithm

Postoperative analgesia

Epidural analgesia (1) Appropriate level of blockade – near the incision if LA is used  Proper length in epidural space – exc. still unable to walk >> measure the length  Spreading of LA in epidural space  Maintain the analgesic level 

Postoperative analgesia

Epidural analgesia (2) Maintain the analgesic level  0.0625% Bupivacaine + Morphine (0.01-0.02 mg/mL) or 0.1% B + Fentanyl (1-2 mcg/mL)  Rate of infusion: adequate to cover pain 

Postoperative analgesia

Epidural analgesia (3) Continue or adjust rate of infusion  1-3 days  Start oral analgesics ASAP  Overlap  24 h with previous technique 

Postoperative analgesia

IV technique (1) IV-PCA - initial loading to MEAC - explain when to press PCA button - small PCA dose (opioid naïve) - by the child only - no need for basal rate except ...e.g. previous use of opioid  Adjust setting daily, if needed 

Postoperative analgesia

IV technique (2.1) 

IV-continuous infusion - initial loading to MEAC - small rate per hour (opioid naïve) (MO 0.01-0.03 mg/kg/h)

Postoperative analgesia

IV technique (2.2) IV-continuous infusion  Nurse purges extra dose for pain PRN q 1 h (< the same dose of infusion rate)  2 consecutive extra dose increase rate incrementally (1/2 of infused rate) x 2-3  SS 2 reduce rate incrementally (the same dose as the increase rate) & notify MD 

**Nurse can purge med & adjust the rate after assessment**

Postoperative analgesia

IV technique (3) IV-algorithm - dose  age group - 2 extra doses (1/2 of initial dose) PRN q 30 min by nurse, after assessment  Assess: SS, RR, PS 

Postoperative analgesia

IV technique (4) Add IV NSAIDs, if needed - Ketorolac (0.5 mg/kg/dose) IV q 8-12 h  Start oral analgesics ASAP  Overlap  24 h with previous technique 

Postoperative analgesia

Oral analgesics Strong opioids :- Morphine (opioid naïve) - 0.1 mg/kg around the clock q 4 h - 0.05 mg/kg PRN q 1-2 h - In this case – resume previous dosage  Non-opioids - Paracetamol (40 mg/kg/day - Thai) - NSAIDs, if no C/I :Ibuprofen (6-10 mg/kg/dose) x 3 

Postoperative analgesia

Follow-up every day 

Whether pain is under control - assess type of pain  nociceptive/neuropathic pain (How to differentiate it in children?) - adjust the dose for nociceptive pain - add anticonvulsants for neuropathic pain :- gabapentin start 3-5 mg/kg/dose, q 8 h



If new pain occur... assess its type & Rx

Case discussion 6-y-o boy, BW 20 kg  Dx - Neuroblastoma  Op - Explor lap.with partial tumor removal  Intraoperative finding: tumor with pelvic invasion  Optimum postoperative pain control  Postop.on day 3: left leg pain...

Neuropathic pain in children Less well studied in children than adult  Neuropathic pain is a pain arising as a direct consequence of a lesion or disease affecting the somatosensory system 

** Pain that is not nociceptive **

Neuropathic pain in children 

Neuropathic condition in children and adolescents ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦ ◦

complex regional pain syndromes (CRPSs) phantom limb pain spinal cord injury trauma and postoperative neuropathic pain autoimmune and degenerative neuropathies (eg, GuillainBarre syndrome, Charcot-Marie-Tooth disease) effects of cancer disease processes and treatment toxic and metabolic neuropathies (eg, lead, mercury, alcohol, infection) hereditary neurodegenerative disorders (eg, Fabry disease) mitochondrial disorders primary erythromelalgia etc.

Neuropathic pain in children 

Diagnosis ◦ Hx and Physical exam ◦ Quantitative sensory testing (QST)

Neuropathic pain in children Common features of neuropathic pain condition Pain descriptors Sensory disturbances Motor finding

Autonomic disturbances

Burning, electrical, stabbing, shooting, spontaneous and evoked Allodynia, hyperpathia/hyperalgesia, dysesthesia, paresthesia, focal sensory deficit, hypersensitivity to cold Spasm, dystonia, tremor, fasciculations, weakness, atrophy Cyanosis, erythema, mottling, increased sweating, swelling, poor capillary refill Pain in Infants Children and Adolescents, 2003

Neuropathic pain in children 

Treatment

Pain Res Manag Vol 19 No 6 November/December 2014

Neuropathic pain in children 

Treatment ◦ Psychologic/cognitive-behavioral treatment ◦ Physical therapy

Neuropathic pain in children 

Neuropathic pain in children with cancer ◦ Surveyed in a referral center in Australia ◦ Patients with NP  significantly greater mean number of pain visits per consult ◦ The most common cause of NP  cancer treatment ◦ Nonpharmacological approaches used for 57.6% of NP referrals Pain Manag Nurs. Author manuscript; available in PMC 2015 March 01

Case discussion 6-y-o boy, BW 20 kg  Dx - Neuroblastoma  Op - Explor lap.with partial tumor removal  Intraoperative finding: tumor with pelvic invasion  Optimum postoperative pain control NEUROPATHIC PAIN  Postop.on day 3: left leg pain...

Case discussion 6-y-o boy, BW 20 kg  Dx - Neuroblastoma  Op - Explor lap.with partial tumor removal  Postop.on day 3: left leg pain... ◦ Dx. Neuropathic pain ◦ Rx. Add gabapentin 100 mg tid. amitriptyline 5 mg hs.

Summary Knowledge of the pathophysiology of disease and the type of pain (nociceptive, neuropathic, visceral, or combination) will help us to decide the method of pharmacological pain management.