Palliative Medicine Case Rounds

Objectives

• case review
• targeted therapy options
• when to consider spinal options

71 male

• Referred to SPH PCU for pain crisis management
• Dx with metastatic lung cancer in September 2017
• pmhx of gout/hypothyroidism
• 1-2 alcoholic drinks per day
• Married with 4 kids
• Very active prior to diagnosis. Remote ex-smoker

Consolidated recent history

• Initially thought to have had bronchitis + L hip bursitis.
• Initial tx with T3, inhalers, then fentanyl patch (no imaging).
• Pain necessitated visit to local ED, found R lung lesion and lytic area in L acetabulum.
• Bx + for NSCLCA

Antineoplastic Course

• XRT: 5 fractions to left hip, femur. Further tx to RUL mass
• 2 cycles of carboplatin and pacitaxel.
• Consideration of Nivolumab in near future.

Pain crisis

• Admitted to regional outside hospital in pain crisis (acute palliative complex unit).
• Did have some initial sustained (hours) response to Ketamine infusion in ED.
• Transferred to unit on TD Fentanyl 350 mcg. Rotated to Methadone basal and Sufentanil prn.
• Trial of Lidocaine at 5-12.5 mg/kg without success.
• Started on Dexmetetomidine at 0.2 mcg/kg/hr for analgesia and sedation, which led to hypotension.
• Transfer for interventionist consideration.

SPH

• Dexmedetomidine 64mcg/hr
• Ketamine 15mg/hr
• Fentanyl TD 50 mcg/hr
• Methadone 18 mg q 8h
• Sufentanil BT 100 mcg q 15 PRN

Despite this, pain crisis, requests sedation

• Acute Pain Services places Epidural catheter at L34 under PSA (100mg Ketamine)
• 10 cc 2% lidocaine in catheter, then epi-morphine 5 mg

What next?

What has been tried?

Opiates
Refractory?

Methadone
NMDA antagonism benefits
Long half life
Limited by route/QTC/Med interactions

Ketamine
NMDA antagonism
Multiple routes
Limited by SE?
Poor oral bioavailability for discharge planning

Ketamine for Palliation

• likely decreases opiate use
• effective for neuropathic pain
• consider subanesthetic doses (0.25-0.5 mg per kg IV)
• may help with end stage inschemia
• may cause urothelial damage with sustained dosing?
• higher dosing limited by adverse fx (drowsiness, hallucinations, dysphoria).
• can use for depression/suicidality acutely

Dexmedetomidine
Alpha 2 agonist and NE reuptake inhibition in brainstem

Sedation Meds

• Dex usually not first line.
• Midazolam
• Methotrimeprazine
• Phenobarbitol
• Propofol

Dexmedetomidine

• exact mxm not known
• presumably increases activity in monoamine-dependent endogenous pain modulating pathways in the spinal cord and brain.
• SE: dry mouth, hypotension (orthostatic).
• starting dose for pain 0.2 mcg/kg IV per hour.

Dexmedetomidine & Palliative Care

• 7-8 more receptor potency vs. clonidine.
• produces analgesia without respiratory depression.
• major risks include hypotension and bradycardia (5%-which can lead to PEA/asystole*).
• can use dilute naloxone (1-2 ml of 0.4mg in 10ml of NS) for respiratory depression
• can consider in treatment-refractory delirium

more invasive?

Intrathecal Device

• An example of a neuroaxial technique with the target of providing analgesia without the side effects of systemic pharmacotherapy.
• Main disadvantages include cost, risk of infection, and mechanical failure.
• Consider when patient has cancer-related pain and is refractory or intolerant of systemic pharmacotherapy

Epidural?

• space before CSF
• permits analgesia to be restricted to a few dermatomes
• 10x dose of intrathecal thus increasing risk of systemic side effects

ITP

• catheter typically placed below L1 and tip advanced to target level under fluoro.
• typically expect more than 3 months to live for it to be considered.
• single shot trial is usually trialled first

Pump agents

• opiates (morphine, hydromorphone, fentanyl)
• local anesthetics (bupivicaine)
• Ziconitide
• clonidine
• baclofen

ZICONITIDE
from snails
N-type calcium channel blocker only for intrathecal use
Canada?

ITP outcomes

• Smith et. al 2002
• Randomized clinical trial of an implantable drug delivery system with comprehensive medical management for refractory pain: impact on pain, drug-related toxicity, and survival.
• J Clin Oncol. 2002;20(19): 4040

findings

• IT patients had >20% pain reduction in VAS
• less treatment toxicity (58 vs. 38%) esp. with fatigue and LOC
• trend towards longer six month survival (54 vs. 37 %)
• n=202 patients

complications

• resp depression
• tip granuloma
• urinary retention, paresthesias,gait (bupivicaine)
• orthostatic hypotension
• infection
• bleeding

What if this does not work?

other options

• cannabis
• rhizotomy
• cordotomy
• nerve stimulator
• palliative sedation
• MAiD