Challenges with PCA Management in Kids: Tips, Tricks, and Adjuvants

Shobha Malviya, MD FAAP Professor of Anesthesiology

Disclosure

• Research funding from Cadence Pharmaceuticals – manufacturer of IV acetaminophen in the U.S.

• Developed pain assessment teaching video

to standardize pain assessment across study sites in current clinical trial

Objectives

• Review opioid and non-opioid agents used via PCA

• Discuss the use of patient-, parent- and nurse-controlled analgesia in children

• Identify pitfalls associated with PCA use and

strategies to mitigate risks from PCA

Patient Controlled Analgesia (PCA)

• First studied in adults in 1965 as a research tool

• Clinical use – early 1970s in adults, late 1980’s in children

• Allows titration of small doses of opioids

• Puts patient in control – autonomy, tailor opioid dose to extent of pain

• Decreased workload/avoids delays

• Basal infusions - improved sleep, better pain scores, need for monitoring

PCA pumps

PCA Pump Settings

Options: • Choice of drug • Drug concentration • Bolus dose only • Bolus + Basal infusion • Lockout interval • 4 hr limit, 1 hr limit or doses/hr

PCA - Choice of Opioids

• Morphine most commonly used • Meperidine – no longer recommended • Hydromorphone

- 5-10 times as potent as morphine (Collins J 1996) - Potential for drug error

• Fentanyl - limited experience, more tolerance • Tramadol - European, Chinese studies (Chu Y

2006)

PCA- Opioid Dosing

Drug Bolus Dose

(µg/kg)

Lockout Interval (min)

CBI (µg/kg/hour)

4-hr. limit (µg/kg)

Morphine 10-20 8-15 0-20 250-400

Hydromorphone 2-4 8-15 0-4 50-80

Fentanyl 0.5 5-10 0-0.5 7-10

Reproduced from Malviya S, Polaner DM, Berde CB. AcutePain in Cote CJ, Lerman J, Anderson B eds

A Practice of Anesthesia for Infants and Children. Elsevier Inc 2013 pp 928-933

Initial dosing recommendations in opioid-naïve children

Morphine consumption in children with sickle-cell disease undergoing lap-cholecystectomy

SCD (n=12) Non-SCD (n=10)

Total postop morphine use (mg/kg)

1.58 ± 0.78 0.65 ± 0.32

Pain scores 1st 24 hr. 5.3 ± 1.5 3.9 ± 1.5 Duration of PCA use (hr.) 51 ± 25 h 21 ± 11 h % children needing adjuvant drugs

75 20

Days in hospital 3.4 ± 1.6 1.5 ± 0.5

Crawford M. et al Pediatric Anesthesia 2006 16: 152

Continuous Basal Infusions (CBI)

Proposed benefits: • Maintain therapeutic plasma opioid concentrations • Decreased nocturnal awakenings due to pain • Improved restfulness and sleep • Improved analgesic effectiveness • Reduced total opioid consumption • Fewer adverse effects Potential risks: • Commits the child to receiving a fixed dose of opioid regardless

of sedation depth • Overrides an inherent safety feature of PCA

PCA – Basal Infusions

Hypoventilation

Analgesia

Pain

PCA Plus Basal Infusion Permitting Rapid Catch-Up Upon Awakening from Sleep

Time

Hypoventilation

Analgesia

Pain

PCA Plus Basal Infusion with Delayed Narcotization During Sleep

Time

Hyperventilation

Analgesia

Pain

PCA Without Basal Infusion Resulting in Delayed Catch-Up Following Sleep

Time

CBI – The Evidence - Pro • Berde CB J Peds 1991; 118:460 - Orthopedic surgery - 3 groups: IM morphine, PCA bolus only, PCA bolus + CBI - Similar morphine use, side effects in all groups - Lowest pain scores in CBI group • Skues MA Ped Anesth 1993; 3:223 - Abdominal surgery - Similar morphine use in Bolus only and Bolus +CBI - Improved sleep in CBI group

CBI – The Evidence - Pro

• Yildiz K. Ped Anesth 2003; 13:427 - Appendectomy - Higher Demerol consumption in PCA bolus only group - Trend toward improved pain scores in Bolus + CBI group - Similar side effects in both groups • Doyle E. BJA 1993; 71:818 - Appendectomy - 3 groups: Bolus only, Bolus + 4 mcg/kg/hr, Bolus + 10 mcg/kg/hr - Similar pain scores in all groups - Improved sleep in both CBI groups - 4 mcg/kg/hr : least number of hypoxemic episodes (SpO2 < 94%) - 10 mcg/kg/hr : greatest morphine use, PONV and hypoxemia

CBI – The Evidence - Con • Doyle E. BJA 1993; 71: 670 - Appendectomy - Bolus vs. Bolus + 20 mcg/kg/hr CBI - CBI group – Increased morphine use, sedation, PONV, hypoxemic

episodes, better sleep • McNeely J. J Pain Symptom Manage 1997; 13: 268 - Lower extremity surgery - Bolus vs. Bolus + Nighttime CBI - Increased morphine use and hypoxemic episodes ( SpO2 < 90%) in

CBI group

CBI - Recommendations

• Studies in favor of CBI reduced the bolus dose by 30 -50% in the CBI group or used low background infusion

• Use of CBI is recommended for: - cancer pain, mucositis - pain related to sickle cell disease - children undergoing major surgery – thoracotomy, spine

fusion after assessment in PACU for hypoventilation/ somnolence

• Careful dosing. continuous SpO2 monitoring and frequent

assessment of respiratory status and sedation depth

PCA – Adjuvant Drugs

• Tramadol • Ketamine • Acetaminophen

PCA – Morphine vs.Tramadol

Cardiac Surgery: Chu Y-C Anesth Analg 2006;102:1668

Morphine Tramadol

Loading dose 0.2 mg/kg 2 mg/kg PCA bolus 0.02 mg/kg 0.2 mg/kg CBI 0.015 mg/kg/hr 0.15 mg/kg/hr 4 hr limit 0.3 mg 3 mg

• Similar pain scores • Tramadol group: Earlier awakening and extubation, less sedation

Tonsillectomy: Ozalevli M Ped Anesth 2005 15: 979 • Lower pain scores but more frequent PONV in morphine group

PCA – Ketamine

• Ketamine is believed to prevent the development of central sensitization and opioid resistance by blocking NMDA receptors

• RCT compared the efficacy and side effects of PCA

fentanyl + ketamine with PCA fentanyl alone in children following the Nuss procedure

• Fentanyl + ketamine group experienced

- lower pain scores - reduced fentanyl use and need for ketorolac rescue - reduced PONV and need for antiemetics - No respiratory depression or psychomimetic effects Cha MH Yonsei Med J 2012; 53:427

PCA – Acetaminophen

• RCT in children undergoing ureteroneocystostomy • PCA fentanyl alone vs. fentanyl + acetaminophen • PCA settings - Load : 0.5 µg/kg fent ± 15mg/kg acetaminophen - Bolus : 0.25 µg/kg fent ± 1.5 mg/kg acetaminophen - CBI : 0.25 µg/kg/hr fent ± 1.5 mg/kg/hr acetaminophen - Max dose in 6 hr : 2.5 µg/kg fent and 15 mg/kg acetaminophen • Fentanyl + acetaminophen group had - lower fentanyl usage by 50% - lower incidence of vomiting and excessive sedation Hong JY Anesthesiology 2010; 113:672

PCA - Management

• Dedicated multidisciplinary pediatric pain service vs. individual service ordering PCA

• Twice daily rounds • Adjust PCA settings based on patient/nursing

reports of pain relief, side effects and failed demand doses

• Caution: “phone management” • Training and in-services of nursing staff re: pump

setup • Availability of “Super Users”

PCA - Who Should Push the Button?

• Ideally, the patients themselves

• Lower age limit in most cases is 7 years

• Nurse controlled • ? Parent controlled (only in

specific situations)

Nurse/Caregiver-controlled Analgesia (NCA/CCA)

• Useful in children who lack physical or cognitive skills to push the button

• Clinician vs. non-clinician caregivers • “Surrogate PCA” • “PCA by proxy”

The Safety and Efficacy of Parent/Nurse Controlled Analgesia in Patients Less than Six

Years of Age

• Observational study (n=212) • Mean age = 2.3 years • PCA drugs - fentanyl, morphine,

hydromorphone • Acute postoperative pain in 90% of

cases • Effective pain relief in >80%

Monitto et al, Anesth Analg 2000;91:573

Parent/Nurse Controlled Analgesia

• Adverse effects n % – Vomiting 57 24 – Pruritus 31 14 – Supplemental O2* 54 25 – Naloxone use* 9 4 – Drug overdose 1 0.5 – Apnea* 4 1.8

*underlying medical disease, prematurity, supplemental sedatives

Monitto et al, Anesth Analg 2000;91:573

NCA vs. PCA in Children

• Retrospective chart review • PCA 157, NCA 145 • Adverse events - 24% PCA, 22% NCA • PCA group – Supplemental O2, stimulation, decrease

in opioid dose • NCA group – opioid reversal, airway management,

escalation of care • Opioid dose on POD1 and C.I. predicted adverse

events Voepel-Lewis et al Anesth Analg 2008

NCA/CCA in Prescholers and in Developmentally Delayed Children

• Naloxone required in 2/107 (1.9%) children <4 yr - Infant - CBI 50 µg/kg/hr and bolus 30 µg/kg - 2 y.o. - CBI 40 µg/kg/hr and bolus 40 µg/kg + multiple

doses of lorazepam Czarnecki ML Clin J Pain 2011; 27:102 • Naloxone required in 2/71 (2.8%) developmental delayed

0-19 y.o. children - opioid consumption of 45 µg/kg/hr and multiple adjuvant

sedatives (diazepam, droperidol, CH, benadryl) - child who received average opioid dose of 16 µg/kg/hr but

was progressively more somnolent requiring naloxone on day 4

Czarnecki ML Clin J Pain 2008; 24:817

NCA in 10,000 Patients

• Prospective study of 10,000 children following major surgery over a 12 yr period

• NCA with strict observation of CPG • Inadequate analgesia in 1.8% - switched to

alternative technique • Average duration of NCA - 44 hr • PONV in 25% and Pruritus in 9.4% • Respiratory depression and sedation in 4.5% • SAE in 0.4%

Howard RF Ped Anesth 2010;20:126

NCA in 10,000 Patients

• SAE’s requiring resuscitation and naloxone in 39 (0.4%) - 13 in neonates including 4 premature infants - Highest risk in neonates (2.5% vs. 0.27%, RR = 9.4) - Children > 11 yr. at > risk than those 1-36 months • Respiratory depression/oversedation in 455 (4.5%) - 39 required naloxone and NCA was stopped - Highest risk at 11-15 yr. of age, many with neurological

disabilities - Least risk in plastic surgery patients Howard RF Ped Anesth 2010;20:126

Joint Commission Sentinel Event Alert 2008

• 15 medical errors resulting in harm or death caused by NCA/CCA

- 12 family member, 2 nurse, 1 pharmacist • Specific policies and procedures for activation of PCA by

individuals other than the patient - patient selection – chronic pain, palliative care - process to identify caregivers - communication among health care team – team meetings - education of providers - education of caregivers – when NOT to push button - monitoring protocols – responsibility remains with nurse - only authorized caregivers may push the button

PCA Disasters in Lay Press

Young Woman's Death Sheds Light on Dangers of PCA Pumps When 18 yr-old Amanda Abbiehl's parents kissed her goodnight on July 16, 2010, they never imagined it would be for the last time. "Maybe if she had been on a monitor, she would still be here with us today" – Brian Abbiehl father Physician-Patient Alliance for Health & Safety. “The group says between 2005 and 2009, more than 700 patient deaths and 56,000 adverse events have been linked to PCA pumps.”

PCA Disasters - Swiss Cheese Model

• 8 yr old girl arrived in PACU at 10 pm after abdominal surgery

• PCA hydromorphone ordered • Ready for discharge at change of shift • PACU nurses volunteered to complete patient’s

care rather than call in the midnight shift • PACU nurses decided PCA will be initiated on

floor

PCA Disasters - Swiss Cheese Model

• PACU nurse obtained wrong concentration of hydromorphone

• New night nurse initiated PCA

• Left the room to call 2nd nurse for double check

• PCA tubing had been incorrectly set up and patient received PCA dose without ever activating button

• Respiratory arrest

Pitfalls/ Risks with PCA Use

• Effects of opioid drugs • Co-administration of other sedatives • Patient conditions – Obesity, OSA, C.I. • Human error - incorrect prescription - incorrect dispensing - incorrect administration - inadequate monitoring - failure to rescue • Equipment failure

PCA - Monitoring recommendations

• APSF suggests continuous pulse oximetry and continuous measure of respiratory rate preferably with reliable alerting methods such as alarms, central stations, pagers

• CMS proposed quality measure #3040 calls for respiratory rate, pulse oximetry, and sedation scores for patients on PCA for > 2.5 hr

Monitoring the Child on PCA

• No consensus regarding appropriate monitoring of a child receiving PCA

• Considerable variability in practice among

major children’s hospitals and among different services within the same institution

Monitoring the Child on PCA - UMHS

• CPOE using order sets developed by APS including parameters for when to alert MD

• Continuous pulse oximetry for all children on PCA except during ambulation throughout PCA use

• Pulse oximetry alarms generate automated nurse call light notification after 15 sec, a page to the nurse and charge nurse after 1 min and an emergency group nurse page after 3 min of sustained alarm condition

Assessment of Sedation Depth

• Respiratory pattern, rate, depth • Ease of arousal - UMSS • Alertness, orientation • Speech - slurred

- ability to complete conversation • Other signs - size of pupils - ptosis, glazed eyes - relaxation of facial muscles

Opioid Induced Respiratory Depression

Clinical Picture • Somnolence, small pupils • ↓ RR • ↓ Tidal volume • Apnea • Patient may not exhibit signs of air hunger • Agitation

Incorrect prescription

• Increased risk in children due to weight based dosing, calculation and decimal point errors

• CPOE developed and managed by Acute Pain

Services have been found to reduce the occurrence of incorrect prescriptions and improve compliance with monitoring orders

(Wrona S Ped Anesth17:1083)

Incorrect Pump Programming

• Smart PCA-pumps with barcode readers and remote programming capabilities

• Programmable libraries with hard stops and soft stops

• Implementation of smart pump technology was shown to eliminate incorrect concentration errors

• Review of hard and soft alerts that led to a change in programming showed that 159 potential pump programming errors were averted over a 6 month period in a single institution study.

Tran M. Jt Comm J Qual Patient Saf 2012; 38:112

Case Scenario: 2 yr old child following exploratory laparotomy on PCA bolus + continuous infusion has decreasing O2 saturation on night of surgery

• Verbal order for O2 2 l/min by N/C, and re-evaluate in a.m.

• 0.01 mg/kg naloxone stat • Stimulate pt, assess sedation depth, adequacy

of ventilation • Evaluate opioid dosing, adjust as needed • D/C all opioids and start IV Ketorolac ATC

Summary

• PCA/NCA is an excellent method of pain control in children of all ages

• CCA is useful in selected cases with specific processes in place

• Use of non-opioid adjuvants/multimodal analgesia should be used for opioid-sparing effect whenever possible

• Potential risks of opioid related respiratory depression can be minimized with carefully consideration of dosing, appropriate monitoring, frequent assessment and use of new innovative technology

Agitation - Differential Diagnosis

• Pain • Fear/anxiety/separation/hunger • Hypoxia/hypercarbia/air hunger • Hemodynamic compromise • Urinary retention • Drug induced - paradoxical reactions • Dysphoria from excessive opioids/sedatives • Metabolic changes - electrolytes, glucose • Tight cast

Assessing Agitation

• Respiratory Assessment - pulse oximetry - RR and pattern • Observation of behaviors • Interpretation of lab values

– blood gas-oxygenation – metabolic changes – electrolyte changes

• Patient/parent reports • Neurological assessment

Malviya S et al Anesthesiology 78:1076, 1993

Opioid Equipotency Table

Agonist Equipotent IVdose (mg/kg)

Duration (h)

Morphine 0.1 3-4Meperidine 1.0 3-4Methadone 0.1 6-24Fentanyl 0.001 0.5-1Codeine 1.2 3-4

Hydromorphone 0.015-0.02 3-4Oxycodone 0.15 3-4

Tramadol Hydrochloride

• Centrally acting synthetic analgesic • Low affinity for opioid receptors • Inhibits noradrenaline and serotonin uptake • Low incidence of side effects - minimal respiratory

depression, abuse and addiction • Very effective for pain after abdominal, urologic and

orthopedic surgery in children • Pediatric studies found benefits with IV tramadol

compared to opioids in children undergoing T&A and heart surgery

Arterial oxygen saturation (SaO2) after single doses of IV morphine or tramadol for postoperative pain

management

0

5

10

15

20

25

Morphine 5mgTramadol 50mg

%

SaO2 (%) 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100

Radbruch et al Drug Safety 1996;15:8

50 -

40 -

30 -

20 -

10 -

0 - 30 40 50 60 70

Alveolar PCO2 (mmHg)

Alv

eola

r Ven

tilat

ion

(I / m

in)

Relationship Between Ventilation and CO2

Combination of sedatives and opioids produces most profound effect. , normal, awake; , opioids;

, sedatives; , sedatives + opioids.