1. Pain/Sedation: Assessment and Management R. Blaine Easley, MD Associate Professor Depts. Of Pediatrics and Anesthesiology

2. Disclosures None.

3. Overview Review the prevalence and nature of common “non-cardiac” pain in children with heart disease. Review relevant studies of Pain and Sedation Assessment issues in PICU. Provide insights into how perioperative pain management may impact outcome from cardiac surgery.

4. Definitions of Pain As defined by the International Association for the Study of Pain (IASP)- "an unpleasant sensory and emotional experience associated with actual or potential damage, or described in terms of such damage" “ Pain is whatever the person says it is and exists whenever he says it does.” Margo McCaffery

5. Prevalence of “Non-Cardiac” Pain Acute and Chronic pain conditions more prevalent in medical populations. 95% of reported pain in children is “non-cardiac” pain “chest pain” accounts for 0.3%-0.6% of pediatric ER visits. Med Clin N Am 94 (2010) 327–347

6. Fig. 2 Journal of Pain and Symptom Management 2006 31, 58-69DOI: (10.1016/j.jpainsymman.2005.06.007) A Comparison of Symptom Prevalence in Far Advanced Cancer, AIDS, Heart Disease, Chronic Obstructive Pulmonary Disease and Renal Disease Journal of Pain and Symptom Management Volume 31, Issue 1, Pages 58-69 (January 2006) DOI: 10.1016/j.jpainsymman.2005.06.007

7. Validation of the Pediatric Cardiac Quality of Life Inventory Marino BS, et al. Pediatrics 2010; 126; 498

8. “Cultural” context of Pediatric Pain Patient Parents Nurses Physicians Surgeons

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11. 2 Nurse Decision Making Regarding the Use of Analgesics and Sedatives in the Pediatric Cardiac ICU*. Staveski, Sandra; RN, PhD; Lincoln, Patricia; RN, MS; Fineman, Lori; RN, MS; Asaro, Lisa; Wypij, David; Curley, Martha; RN, PhD Pediatric Critical Care Medicine. 15(8):691-697, October 2014. Prospective Survey of CVICU nurses 3 institutions 217 patients 1330 surveys 70% of increases in sedative and pain administration were related to hemodynamic issues.

13. Impact on the Stress Response Hyperdynamic circulation Increased O2 consumption Loss of body weight Impaired immune function Cardiovascular strain Positive fluid balance Vascular permeability Hypercoagulability Hyperglycemia Catabolic metabolism (nitrogen loss)

14. Stress Response in Infants Undergoing Cardiac Surgery Anand et al. Anesthesiology 1990; 73: 661-670.

15. Stress Response partially eliminated by IV opioids Anand et al. NEJM 1992; 326: 1-9.

16. Findings: 1) Neonates have a stress response to pain that is partially mitigated by opioids. 2) Mortality was reduced from 20-30% in the non-opioid group to <10% in opioid treatment group. LARGE IMPACT: Changed culture of neonatal pain management. How much is too much?

17. High Dose IV Opioids Positive: Stress reduction Pain elimination Cardiovascular stability Reduce chronic pain? Negative: Ventilatory depression Impair immunity Increased PICU stay Tolerance/withdrawal

18. Current Anesthetic Practice Variation for Norwood Stage 1 (average of 10 recent patients) These graphs represent only OR utilization and not additional administration of opioids or benzodiazepines in the CVICU. Unpublished data courtesy -Gaynor JW, Pediatric Heart Network presentation 4/2012

19. Adjunct Perioperative Pain/Sedation Management Benzodiazepines (midazolam/lorazepam) Alpha-agonist (Dexmedetomidine/clonidine) Acetaminophen NSAIDS (Ketorlac and IV ibuprofen?) Mixed mu receptor agonist/antagonist (tramadol/butorphanol/buprenorphine) Ketamine Propofol

20. Dexmedetomidine: Pediatric Cardiac Surgery Dexmedetomidine: Pediatric Cardiac Surgery Mukhtar AM et al, Anesth Analg 2006;103:52 30 pediatric patients, CPB and surgery for CHD placebo vs. dexmedetomidine – 0.5 µg/kg over 10 minutes → 0.5 µg/kg/hr Dexmedetomidine group – blunting of HR/BP response to skin incision and sternotomy – blunting of catecholamine, cortisol, blood glucose change

21. Perioperative Pain and Sedation in CHD- What’s new at TCH? Protocol-based Pain and Sedation Management – Step based increases in opioid and benzo infusions. Sedation Stewardship Program – Working with pharmacy and nursing to transition off sedatives and analgesics Collaborative Learning Project – Early extubation in TOF and Neonatal Coarc Standardizing intraoperative anesthetic Increased utilization of NCA/PCA

22. Pediatric Anesthesia 24 (2014) 266–274

23. Benzodiazepine Equivalents (mg/kg) Fentanyl Equivalents (mcg/kg) 0.50 0.82 0.68 0.89 0.77 Comparison between OR and ICU Fentanyl and Benzodiazepine exposures for the uninjured group were not different (p=0.1641 and p=0.3945, respectively). There was a difference between OR and ICU Fentanyl Equivalent exposure for the injured group with greater amounts received within the ICU (p=0.0125). There was a difference between OR and ICU Benzodiazepine Equivalent exposure for the injured group with greater amounts received within the ICU (p=0.0309). Pediatric Anesthesia 24 (2014) 266–274

24. Injured p=0.0006* Uninjured p=0.9878 Injured p=0.1757 Uninjured p=0.6660 Injured p=0.0107* Uninjured p=0.7109 Potential Impact on Neurodevelopment CognitiveLanguageMotor 12 month – Bayley Scales of Infant Development III Score Pediatric Anesthesia 24 (2014) 266–274 Conclusion: 1) ICU LOS and new post-OP MRI most predictive of decreased 12-month developmental scores across all domains. 2) VAA exposure had a negative impact on Cognitive scores. Opioids and Benzo had a mildly positive impact

25. Summary Review the prevalence and nature of common “non-cardiac” pain in children with heart disease. Review relevant studies of Pain and Sedation Assessment issues in PICU. Provide insights into how perioperative pain management may impact outcome from cardiac surgery.

26. Questions? rbeasley@texaschildrens.org

28. Management of Mild Pain developmental support parental involvement oral route of administration Acetaminophen-excellent choice for mild post operative pain (hernias, etc) especially in opioid-naïve patients Ibuprofen - analgesic, non-narcotic NSAID; no studies to assess safety in babies less than 3 months old EMLA cream to prevent pain with planned procedures (circumcisions, etc.) recommended in babies >36 weeks GA or > 2 weeks old Sucrose is the most studied treatment to help babies deal with mild or procedural pain, shown to help with LP’s, circumcisions, venipunctures, and ECHO’s –sucrose and sucking each cause the release of endorphins-putting these 2 treatments together has been proven to decrease pain in newborns

29. Management of Moderate Pain developmental support parental involvement oral route first, supplement with IV acetaminophen with oxycodone, given on a scheduled and/or as needed basis –AVOID codeine – 30% unable to metabolize into active analgesic form. ketorolac (torodal) - analgesic, non-narcotic, NSAID; time limited use, works best when given around the clock for 48 hours post op in addition to other analgesics

30. Management of Severe Pain developmental support parental involvement pharmacological management Opioid PCA/NCA - pain is better controlled if medication is given prior to the climax of pain medications given on a prn basis result in peaks and valleys of pain relief continuous drip or regularly scheduled doses maintain a constant level of analgesia Possible IV anxiolytic?

31. Pediatric Pain Assessment Tools Johnson et al. AACN Advanced Critical Care 2012, 4: 415-434

32. Pediatric Sedation Assessment Tools Johnson et al. AACN Advanced Critical Care 2012, 4: 415-434