Caring for the Critically Ill Patient with Cerebral Palsy - Sauer_CP_04172018.pdfASSESSMENT QUESTION 1 Which of the following represents a true statement about critically ill adult

©2015 MFMER | slide-1

Caring for the Critically Ill Patient with Cerebral Palsy

Hannah Sauer, PharmDPGY1 Pediatric Pharmacy Resident

Mayo Clinic Children’s Center


Objectives• Describe challenges in acute medical

management of patients with cerebral palsy (CP)

• List special considerations for drug therapy in patients with CP

• Identify the optimal approach to pain and sedation in patients with CP







Cerebral Palsy (CP)• Occurs in 205 per 1000 live births• Permanent disorder of the development of

movement and posture resulting in activity limitation

• Caused by non-progressive disturbances that occurred in the developing fetal or infant brain

Novak, I. J Child Neurol, 2914; 29(8):1141-1156.


Morbidity and Mortality• Most have normal life expectancy

• 5-10% mortality during childhood• Comorbid epilepsy and intellectual disability

predictive of premature death• Deterioration of function occurs due

musculoskeletal impairments• Medical interventions do not improve overall

gross motor function

Taft, LT. Pediatrics in Review, 1995; 16(11):411-418.Novak, I. J Child Neurol, 2914; 29(8):1141-1156.


Classification by Severity

I - Indepdently ambulates

II - Indepdently ambulates withlimitations

III - Ambulates with walking aids

IV - Independently mobilizes withpowered mobility

V - Dependent for all mobility


Most patients with CP will walk

I - Indepdently ambulates

II - Indepdently ambulates withlimitations

III - Ambulates with walking aids

IV - Independently mobilizes withpowered mobility

V - Dependent for all mobility


CP Subtypes

SpasticDyskineticAtaxic


ComorbiditiesNeurologic/Psychiatric

• Intellectual disability (50%)• Behavior disorder (25%)• Non-verbal (25%)• Epilepsy (25%)• Bladder incontinence (25%)• Sleep disorder (20%)

Musculoskeletal• Chronic pain (75%)• Hip displacement (33%)

Sensory• Blindness (10%)• Deafness (4%)

Other• Chronic lung disease (33%)• Gastroesophageal reflux• Hyper-salivation


“Chronic Critical Illness”• Complex disease state with multiple

comorbidities• Common reasons for ICU admission

• Orthopedic surgeries• Acute infections (pneumonia)• Refractory epilepsy



Challenges in Cerebral Palsy

•Pediatric features•Limited literature

• Polypharmacy• Medication

sensitivity?

• Communication barriers

• Emotional burden• Low rates of

confidence• Consult overload

Provider Factors

Patient Factors

Disease Factors

Medication Factors







Common Medications

• Anti-epileptics• Anti-spasticity • Anti-spasmodics• Analgesics• Antacids

• Laxatives• Anti-sialogogues• Prophylactic

antibiotics• Bisphosphonates


Assess for drug interactions.


Drug Sensitivity • May be more sensitive to dose changes• Comorbid intellectual disability associated with

idiosyncratic reactions• Increased risk for medication withdrawal?

Nolan, J, et al. Anaesthsia, 2000; 55(32-41).


Intrathecal Baclofen Withdrawal• If pump must be removed oral baclofen should

be started 2-3 days beforehand• Monitor for withdrawal

• Tachycardia, labile pressures, hypothermia• Delirium, hallucinations, seizures• Muscle rigidity, paresthesis

• Symptom-directed treatment

Ross, JC, et al. Neurocrit Care, 2011; 14:103-108.


Paralytic Agents• Up-regulation of ACh receptors in CP patients

(30%)• Increased risk of hyperkalemia following

succinylcholine?• Increased sensitivity to non-depolarizing

agents?

Prosser, DP and Sharma, N. Anaesthsia, 2010; 10(3):72-76.


Paralytic Agents• Up-regulation of ACh receptors in CP patients

(30%)• Increased risk of hyperkalemia following succinylcholine?• Increased sensitivity to non-depolarizing agents?

Clinically… • Succinycholine is not contraindicated• Non-depolarizing agents are less potent and

have shorter duration

Prosser, DP and Sharma, N. Anaesthsia, 2010; 10(3):72-76.


Dosing Considerations• Increased body surface area to body weight

ratio (“giant neonates”)• Low body weight relative to non-CP individuals• Poor nutritional status

• Altered absorption• Dehydration and hypovolemia common

• Consider appropriate assessments of renal function

Taft, LT. Pediatrics in Review, 1995; 16(11):411-418.Novak, I. J Child Neurol, 2914; 29(8):1141-1156.


ASSESSMENT QUESTION 1Which of the following represents a true statement about critically ill adult patients with CP?

a) Serum creatinine is a reliable indicator of renal function

b) Succinylcholine is an appropriate paralytic agent for rapid sequence intubation

c) Intrathecal baclofen can be safely held for 48 hours

d) Pediatric weight-based dosing should be avoided in anyone over 18 years


General Principles of Medication Management• Use appropriate weight-based dosing, even in

adult patients• Keep medication withdrawal on differential• Consider unpredicted responses to medications• Re-start home medications as soon as possible







Audience Poll: True or False“Individuals with cerebral palsy are desensitized to pain and therefore have increased pain tolerance.”

A. TrueB. False


Pain in CP• Increased sensitivity to pain stimuli due to

altered excitability in the somatosensory cortex• Heterogeneous pain experiences both inter-

and intra-personally • Typical and atypical physical manifestations• Significant emotional and spiritual burden

Riquelme I, et al. Pain Med, 2011; 12(4):535-545.Warlow and Hain. Children 2018; 5(13).


Warlow and Hain. Children 2018; 5(13).

PainMusculoskeletal

Hypertonia

Muscle fatigue, immobility

Constipation

Gastrointestinal dysmotility

Baseline Pain Burden• 75% of patients experience pain at least weekly• 50% have episodes of pain that last >9 hours


Post-Operative Pain Management• Post-operative analgesia should be continuous

rather than on demand regimens• Options:

• Continuous intravenous opioids • Intermittent intravenous and oral opioids• Epidural opioids• Epidural opioids + local anesthetic


Epidural v. Systemic Analgesia ProtocolsMoore, et al.

Study design Retrospective comparison of post-operative analgesia protocols

Population Pediatric patients with cerebral palsy undergoing selective dorsal rhizotomy

Efficacy Outcomes Difference in age-appropriate pain scale scoreFrequency of severe pain episode (pain ≥5)

Safety Outcomes Treated nausea or pruritisHypoxia, supplemental O2 requirements

Moore, et al. Pediatric Anesthesia, 2013; 23(720-725).



Systemic Protocol

Epidural Protocol

• Continuous infusion fentanyl

• 1 mcg/kg/h x12 hours followed by

• 0.5 mcg/kg/h until noon POD2

• Diazepam 0.1 mg/kg q4h scheduled x6 doses, then q6h x4 doses

• Gabapentin added D2 for kids ≥ 10 years

• Ropivicaine 0.2%/ hydromorphone 2.5 mcg/mL

• Rate of 0.2 mL/kg/h until 6 am POD3

• Ketorolac 0.5 mg/kg q6h (total of 8 doses)

• Methocarbamol 15 mg/kg q8h prn for breakthrough spasm


POD1 POD2 POD3

Fentanyl @1 Fentanyl @0.5

Midazolam

Ropivacaine/hydromorphone epidural

Ketorolac

Methocarbamol as needed

Gabapentin if age-appropriate

Study Protocols

Systemic ProtocolEpidural Protocol


Patient Characteristics

Epidural (n=31) Systemic (n=41)

Age (years) 6.06 (±3.78) 6.63 (±4.02)

Weight (kg) 21.43 (±9.53) 24.9 (±14.12)

Male 64.5% 61%

Diplegia 93.5% 92.6%



Post-Operative Pain Scores

0

1

2

3

4

5

6EpiduralSystemic

*p<0.05Moore, et al. Pediatric Anesthesia, 2013; 23(720-725).


ResultsEpidural (n=31) Systemic (n=41) OR p-value

Episodes of severe pain (POD 0-1)

9.6% 68.3% 20.1 <0.001

Episodes of severe pain (POD 0-1)

5 episodes 74 episodes NR NR

Respiratorydepression 6.5% 41% 10.3 <0.001

POD=post-op dayMoore, et al. Pediatric Anesthesia, 2013; 23(720-725).


Epidural v. Systemic Analgesia ProtocolsStudy Conclusions• Multimodal approach to

pain control is ideal

• Epidural may be preferred route of analgesia in post-operative setting

Study Limitations• Study design

• Cause of improved pain control?

• Other medications not reported

• Pain assessment tools



Validated Pain Assessment Tools

Pediatric Pain Profile (PPP)

• Twenty item behavioral scale (4

points each)• Designed for non-verbal children with severe neurological

impairment (SNI)• Highly sensitive and

specific

Face Legs Activity Cry Consolability

(FLACC)• Five item behavior scale (3 points each)• Quick assessment

• Only validated in post-operative settings for

SNI

Non-Communication Children’s Pain

Checklist—Revised • Thirty item behavior scale (4 points each)

• Two hours of observation required

• Highly sensitive and specific

• Weak correlation to parent scores

Warlow and Hain. Children 2018; 5(13).


ASSESSMENT QUESTION 2:Which of the following may be a sign of pain in a non-verbal patient with cerebral palsy?a) Flushing and/or pallorb) Tachycardiac) Sudden stillnessd) Self-harme) All of the above


Procedural Sedation in CP • Preferred agents

• Historically propofol, benzodiazepines• No sedative agents contraindicated

• Consider co-morbidities• Seizures• Respiratory status

• Optimal doses and general approaches remain controversial…


Sedation in Patients with CP• Disability associated with risk for respiratory

depression and delayed awakening• Review of intravenous sedation in patients with

disabilities revealed cerebral palsy:• Independently associated with SpO2 <90%

(OR 1.642, p=0.018)• Not independently associated with delayed

awakening

Yoshikawa, et al. Anesth Prog, 2013; 153-161.


General Anesthesia in CP • Patients with cerebral palsy require lower doses

of propofol for anesthesia induction• Target bispectral index (BIS™) 35-45• 3.29 mg/kg versus 3.6 mg/kg (p=0.03)

• Decreased minimum alveolar concentration (MAC) of halothane

• Levels 20% lower compared to healthy controls (p<0.05)

• Delayed emergence? Saricaoglu F, et al. Pediatric Anesthesia, 2005; 15:1048-1052.Frei, FJ, et al. Anaesthesia, 1997; 52(11):1056-1060.


Optimal Propofol Dose for MRIKim, et al.

Study PopulationCerebral palsy Age 6 months to 5 yearsScheduled for brain MRI under sedation

Intervention

Propofol started at 2 mg/kg and modified for sequential patients• If unsuccessful, dose increased by 0.5 mg/kg for

next child• If successful, decreased by 0.5 mg/kg for next child

Efficacy OutcomesSuccessful sedation (UMSS* score ≥3 after 1 minute)ED50 and ED95 determined by modified up-and-down method

Kim EJ, et al. Korean J Anesthesiol, 2011; 61(3):216-19.*University of Michigan Sedation Scale


Patient CharacteristicsN=20

Age 28.7 months ± 17.8

Weight 10.3 kg ± 4.6

Male 80%

MRI scanning time 26.3 minutes

Co-morbid behavior disturbances 16

On anti-epileptic medications 4

Kim EJ, et al. Korean J Anesthesiol, 2011; 61(3):216-19.


Results• Successful completion of all MRI scans

• Ten received 2 mg/kg (50% success)• Five received 1.5 mg/kg (0% success)• Five received 2.5 mg/kg (80% success)

• Desaturation in 5 patients with successful sedation

• Proposed therapeutic index:• ED50 = 2.07 mg/kg (CI 1.69-2.56)• ED95 = 2.69 mg/kg (CI 2.35-5.95)*

• Mean total dose 3.2 mg/kg ± 0.9 mg/kg*Up-down method used



Study Summary and Conclusions• Typical starting procedural sedation 1-2 mg/kg• CP alone may not be a compelling indication to

give lower doses of procedural sedation• Lingering questions

• What subgroups of patients are worth exploring?• Is desaturation in 25% of patients significant?• What is the appropriate starting dose of propofol for

procedural sedation?



The Bottom Line for Pain and Sedation• Assess and treat anxiety related to disease and

hospitalization• Multimodal approaches to pain are ideal (don’t

forget about baseline pain factors)• Continuous pain control > on demand pain control• Use appropriate pain assessment tools and rely

on caregiver assessments• Start with low end of sedative dose ranges and

titrate slowly


ASSESSMENT QUESTION 3:A 24 yoM (30 kg) with cerebral palsy s/p orthopedic surgery is being admitted to your ICU. Which of the following standard post-operative orders is your priority for re-assessment prior to his arrival to the unit?

a) Morphine PCA 2 mg load, followed by (level 1) 1 mg IV every 10 minutes 20 mg LO q4h

b) Ketorolac 15 mg IV q6h x 4 dosesc) Cefazolin 1 g q8h x2 dosesd) Senna 17.2 mg PO QHS


Summary• A lack of published experience in managing CP

patients in ICU settings makes it a challenging population

• Patients with CP should be assessed for appropriate weight-based dosing, drug interactions and medication withdrawal

• CP does not permit a “one size fits all” approach to optimal pain and sedation


Questions & Discussion

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Caring for the Critically Ill Patient with Cerebral Palsy - Sauer_CP_04172018.pdfASSESSMENT QUESTION 1 Which of the following represents a true statement about critically ill adult