Sedation and analgesia after pediatric cardiac surgery

1. Sedation and analgesia after pediatric cardiac surgery By Mai Mohsen Abdel Aziz, MD

2. In recent years, the importance of appropriate intraoperative anesthesia and analgesia during cardiac surgery has become recognized as an important factor in postoperative recovery • However little attention has been focused on postoperative sedation and analgesia in the pediatric ICU

3. Causes of anxiety in PICU • Separation from parents • Invasive procedures • Disruption of usual day-night cycle • Unfamiliar people and machines Physiological causes of agitation have to be excluded ; • Hypoxemia • Hypercapnia • Cerebral hypoperfusion due to reduced COP

4. Why do we need to address pain ? • Inadequate analgesia and postsurgical stress response metabolic, humoral, and hemodynamic response following injury or surgery. • Neuroendocrine cascade leads to increased oxygen consumption, increased carbon dioxide production, generalized catabolic state with a negative nitrogen balance. • Recent studies have concluded that inadequate pain control causes long term dysregulation of nociceptive mechanisms which may change behavior and responses to future pain stimuli.

5. Decision to be made should take into account • Agent to be used • Mode of administration • Route of delivery

6. Suggested properties of the ideal agent for sedation/analgesia in PICU • Rapid onset • Predictable duration of activity • Effects dissipate rapidly when agent discontinued • Easy to titrate by continuous infusion • Limited effects on cardiorespiratory function • Effects and duration not altered by renal or hepatic disease • Wide therapeutic index • No interference with effect or metabolism by other drugs

7. Most commonly used agents • Benzodiazepines • Opioids • Ketamine • Propofol • Chloral hydrate • Phenothiazines • Barbiturates • NSAID • Acetaminophen • α-2 agonists • Most drugs can have deleterious effects on cardiorespiratory function therefore close monitoring of patient’s cardiorespiratory status in accordance with guidelines of the American Academy of Pediatrics

8. Sedatives and analgesics should not be administered strictly on a per Kg basis • Dosage recommendations are meant as guidelines for starting doses • Actual amount administered should be titrated to achieve the desired level of sedation or analgesia • Significant interpatient variability in infusion requirements

9. Sedation • A broad term that facilitate several goals; Unconsciousness or reduction in conscious level Reduced awareness Loss of explicit and implicit memory Compliance with the need to lie attached to monitors and invasive lines Prevention of distress

10. SEDATION LEVELS Continuous monitoring is mandatory; • SpO2 • ECG • RR • BP • +/- etCO2 Risk of Adverse Event Moderate Sedation Mild Sedation No Sedation

11. Sedation scale

12. Comfort scale • Range (8-40) • Excessive (8-16) • Adequate (17-26) • Insufficient (27-40)

13. Common properties 1- All sedative drugs suppress the CNS 2- Respiratory depression: the most significant adverse effect following sedative drug administration a. Impaired airway control - the single most serious adverse event b. Hypoventilation 3- Depth of sedation is a continuum mild sedation general anesthesia 4- The greater depth of sedation the greater risk

14. IX X inhibition Pharyngeal Segment Nasal Segment Tracheal Segment P(-) P(O) THE UPPER AIRWAY Pharyngeal collapse during sedation

15. sedation Minute ventilation (l/min) pCO2 VENTILATION HYPOVENTILATION DURING SEDATION

16. benzodiazepines First line agents hypnosis NO analgesia action in the limbic anxiolysis system via inhibitory GABA antegrade amnesia Abstinence syndrome anticonvulsant effect after prolonged use • May produce hypotension with decrease in COP>20% in postcardiac surgical patients • Decreased central sympathetic output which may decrease systemic vascular resistance

17. Mechanism of action of benzodiazepines

18. diazepam • Sedating, variable amnesia, anxiolytic • Irritating to veins, pain in injection(propylen glycol) • Highly lipid soluble, rapid onset • Multiple active metabolites • Advantage for prolonged sedation • Disadvantage for rapid arousal • Not recommended for continuous infusion • Half-life 12-24 hrs • Hepatic metabolism

19. lorazepam • Improved amnesia • No active metabolites • Half life 4-12 hours • Metabolized by glucuronyl transferase • Less influence from other drugs • Better preserved in patients with liver disease

20. midazolam • Rapid onset • Rapid metabolism • Good amnesia • Water soluble, no pain with injection • Half life 2 -4 hours • Hepatic metabolism with renal excretion • Active hydroxy-metabolite may accumulate • Other routes of administration • Oral,Nasal,Rectal,Sublingual • Reports of dystonia and choreoathetosis post infusion, greater risk in neonates • Heparin decreases protein binding, increases free drug • Dosing ranging from 0.05-0.2 mg/kg/hr

21. Adverse effects • RESPIRATORY DEPRESSION • Less than narcotics, but potentiated with narcotics • Dose related • Reversal • Flumazenil - benzodiazepine receptor antagonist • Choreoathetoid movement disorder • Tolerance • Dependence • Withdrawal carefully and slowly if administered > 7-10 days • Signs of withdrawal - tremor, tachycardia, hypertension, • Rapid withdrawal may promote seizures

22. Opioids First line analgesia sedation no amnesia delayed gastric emptying decreased intestinal peristalsis urinary retention • Commonly used narcotics: • Morphine • Fentanyl • Methadone

24. ROUTE OF ADMINISTRATION • IV • Oral • Transmucosal • Transdermal MODE OF ADMINISTRATION • Intermittent/on demand (as necessary) • Fixed interval • Continuous infusion • PCA

25. Intravenous bolus administration • Common though antiquated • PRN - as needed • Half-life of drug determines interval • Disadvantage of pain breakthrough

26. Iv bolus method

27. CONTINUOUS INFUSION • Utilized when prolonged analgesia and sedation needed • Better analgesia, initial accurate bolus important • Need for dedicated IV site

28. Continuous infusion method

29. pca • Patient controlled analgesia • Allows patient to administer a preset amount of narcotic at preselected intervals • Improved analgesia with decreased narcotic use • Option to include low basal rate • Nurse controlled analgesia • Eliminates delay • Allows delivery via a closed system

30. Pain Scales in icu

31. Photographic/Numeric Pain Scale(Oucher scale)

32. MORPHINE Gold standard hepatic metabolism depresses respiration depresses rate over tidal volume histamine mediated hypotension esp in hypovolemic • Can block compensatory catecholamine effect • Prolonged clearance in neonates

33. dosing • IV intermittent • 0.1 mg/kg q 3 - 4 hrs • IV continuous • 0.05 mg - 0.1 mg/kg/hr • PCA dosing • Initial dosing: 50 mcg/kg q 10 minutes until comfortable • Demand dose: 20 - 40 mcg/kg • Lock-out period: 10 minutes • 4-hour limit: 0.25 mg/kg

34. FENTANYL Synthetic opiate, 100 x morphine rapid onset highly lipophilic hepatic metabolism minimal hemodynamic effect chest wall rigidity • Short distribution t1/2, long elimination t1/2, • Blunts pulmonary vascular responses

35. dosing • IV intermittent dosing • 1-2 mcg/kg q 1-2 hrs • IV continuous dosing • 1-2 mcg/kg/hr • Transdermal delivery system available • Not recommended in children less than 12 yrs • 25,50,75,100 mcg/hr • 25 mcg/hr is equivalent to 15 mg morphine in a 24 hr period

37. methadone • Potency equivalent to morphine • Half life 12-24 hrs • Prolonged duration of action abolishes the need for continuous infusion

38. Opioid side effects • RESPIRATORY DEPRESSION • Reversal - Nalaxone (Narcan) • Full reversal 0.1 mg/kg • Half life is less than narcotics • IV,IM,Sub Q, ETT • Abrupt reversal may result in nausea, vomiting, sweating, tachycardia, increased BP, and tremors • Pruritis • Individual variability and susceptibility, alleviated by Benadryl

39. Tolerance • Need for increase in dose to achieve the same effect • Generally develops after 2-3 days of frequent/continuous use • Greater with fentanyl • Treated by increasing the dose as needed • DEPENDENCE • Physiological state leading to abstinence syndrome on withdrawal of the drug, rare • Generally develops after 7-10 days of sustained use • Symptoms include: mydriasis, tachycardia, goose bumps, muscle jerks, vomiting, diarrhea, seizures, fever, hypertension • Treated with gradual withdrawal of the drug

40. KETAMINE Dissociative IV anesthetic good amnesia analgesia water and lipid soluble crosses BBB<30 s effect resolves 15-20min

41. Redistribution half-life 4.7 minutes • Elimination half-life 2.2 hours • Bronchodilation • Sialagogue • Administer with an anticholinergic • Atropine or Robinol • Minimal net hemodynamic effect • Negative inotrope • Central effect - HR, SVR • Good choice in shock or status asthmaticus

42. Side effects • Risk of laryngospasm • Risk of emesis/aspiration • Increases ICP , globe pressure • Seizure inducing • Emergent reactions, hallucinations • Improved with administration of a benzodiazepine

43. Dosing • IM: 2 - 5 mg/kg dose q 30 minutes - 1 hour • IV • Intermittent dosing • 1 -2 mg/kg dose q 30 minutes to 1 hr • Continuous dosing • 1 - 3 mg/kg/hr

44. PROPOFOL • Sedative/hypnotic • Dose dependent - conscious sedation to general anesthesia • Rapid onset (20-50 seconds) • Quick recovery ( within 30 minutes of d/c) • Lack of active metabolites • Metabolized in liver • Excreted in urine • Lipid emulsion, reports of anaphylaxis • Decreased ICP, may lower CPP • Decreased sympathetic tone • Contraindicated in hemodynamically unstable • Moderate respiratory depression

45. Side effects • Pain with injection/infusion site • Improved with use of 1% lidocaine • Neurologic sequela • Opisthotonic posturing • Myoclonic movements • Metabolic acidosis reported with use > 24 hrs • Contraindicated for long term use Dosing • 1 - 3 mg/kg induction • 20 - 100 mcg/kg/min • Increase infusion rate 5-10 mcg/kg/min increments of 5 - 10 minutes

46. CHLORAL HYDRATE • Sedative hypnotic agent • Metabolized in the liver to its active form, trichlorethanol • Half life 8-12 hours • Oral or rectal administration • Onset of action delayed • Not to exceed 100 mg/kg/day - i.e.: 25mg/kg/q 6 hrs • Caution in children < 3 months or with hepatic dysfunction

47. BARBITURATES • Sedative • Respiratory depression dose dependent • Negative inotropic effects/vasodilation - decreased cardiac output • Decreased cerebral O2 consumption • CBF • ICP • Anticonvulsant, Useful in patients with increased ICP • Alkaline solution, often incompatible with TPN or meds.

48. MAJOR TRANQUILIZERS • Phenothiazine • Thorazine • Butyrophenones • Droperidol • Haloperidol • Common in adult ICU, uncommon in PICU • Side effects hypotension due to alpha blockade and extrapyramidal effects • May be useful in the difficult to sedate child

49. Alpha-2 agonists

50. Clonidine • Selectivity: 2:1250:1 • t1/2  10 hrs • Antihypertensive • PO, patch, epidural • In opioid withdrawal Dexmedetomidine • Selectivity: 2:1 1620:1 • t1/2  2 hrs • Eliminated by liver/kidney • Sedative • Only available in IV form • Precedex 200 ug/vial others: apraclonidine, detomidine, medetomidine