SEDATION and ANALGESIA in the PICU

1. SEDATION and ANALGESIA in the PICU

2. GOALS • Analgesia for painful diseases and procedures • Compliance with controlled ventilation and routine intensive care • Amnesia for the periods of sedation • Reduce the physiological responses to stress • Avoid complication

3. SEDATION and ANALGESIA • Inadequate analgesia and postsurgical stress response is a metabolic, humoral, and hemodynamic response following injury or surgery • This neuroendocrine cascade leads to increased oxygen consumption, increased carbon dioxide production, and a generalized catabolic state with a negative nitrogen balance

4. SEDATION/ANALGESIA Sedation (seda/shun) [L. sedatio, to calm, allay]. The act of calming, especially by the administration of a sedative, or the state of being calm. Analgesia (an-al-je/zi-ah) [G. insensibility, from an - privative,negative + algesis, sensation of pain] A condition in which nocioceptive stimuli are perceived but are not interpreted as pain; usually accompanied by sedation without loss of consciousness.

5. IDEAL PICU SEDATIVE/ANALGESIA • Rapid onset • Predictable duration • No active metabolites • Rapid recovery • Multiple routes of delivery • Easy to titrate • Minimal cardiopulmonary effects • Not altered by renal or hepatic disease • No drug interactions • Wide therapeutic index

6. COMMON DRUGS UTILIZED • Opiates (Narcotics) • Benzodiazepines • Chloral hydrate • Barbiturates • Ketamine • Propofol • Neuroleptics • Paralytics

7. SITUATIONS REQUIRING SEDATIVES/ANALGESIA • MECHANICAL VENTILATION • Respiratory failure • Airway • Neurological • POST OPERATIVE • HEAD INJURY • PULMONARY HYPERTENSION • PROCEDURES

8. OPIOIDS • First line drugs • Provide analgesia and sedation, NOT amnesia • Act similarly as a class • Produce delayed gastric emptying, decreased intestinal peristalsis, and urinary retention • Narcotic to be used: • Morphine • Fentanyl • Methadone

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

10. MORPHINE • Gold standard • Hepatic metabolism • Depresses respiration by altering chemoreceptor sensitivity to CO2 • Depresses rate over tidal volume • Decreases sigh frequency • Can cause hypotension due to histamine mediated vasodilation • Can block compensatory catecholamine effect • Prolonged clearance in neonates

11. IV intermittent 0.1 mg/kg q 3 - 4 hrs IV continuous 0.05 mg - 0.1 mg/kg/hr PO scheduled 0.3 mg/kg q 3 - 4 hrs 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 MORPHINE

12. FENTANYL • Synthetic opiate, 100 x more potent than morphine • Rapid onset, highly lipophilic, rapidly crosses BBB, redistributed to fatty tissue • Short distribution t1/2, long elimination t1/2 • Minimal hemodynamic effect • Blunts pulmonary vascular responses • May produce “chest wall rigidity”, reversed with relaxants or naloxone

13. FENTANYL • 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

14. METHADONE • Equipotent to morphine • Minimal hemodynamic effects • Long half life • Sedation and euphoric properties less pronounced than morphine • Useful for pain control and abstinence PO dosing • 0.1 mg/kg q 4-8 hrs • 50 % oral bioavailability • Drug accumulation with repeated doses caused by extensive protein binding

15. MODE OF ADMINISTRATION • Intravenous bolus administration • Common • PRN - as needed • Half-life of drug determines interval • Disadvantage of pain breakthrough

16. IV BOLUS ADMINISTRATION

17. CONTINUOUS INFUSION • Utilized when prolonged analgesia and sedation needed • Less labor intensive • Better analgesia, initial bolus important • Need for dedicated IV site

18. CONTINUOUS INFUSION

19. 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

20. PCA

21. OPIATE SIDE EFFECTS • RESPIRATORY DEPRESSION • Reversal - Nalaxone (Narcan) • Full reversal 0.1 mg/kg • Partial reversal - titrate to effect • Half life is less than narcotics • IV,IM,Sub Q, ETT • Abrupt reversal may result in nausea, vomiting, sweating, tachycardia, increased BP, and tremors

22. OPIATE SIDE EFFECTS • Pruritis • Individual variability and susceptibility, alleviated by Benadryl • 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

23. OPIATE SIDE EFFECTS • DEPENDENCE • Physiological state leading to abstinence syndrome on withdrawal of the drug • 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

24. OPIATE SIDE EFFECTS • DEPENDENCE • In general the longer the period of treatment the longer the period of withdrawal needed • A child is at risk for dependence if they have been on narcotics for a week • Finnegan scoring to monitor adequate weaning dose • Weaning strategies can vary, typically 10% decrease per day • Do not spread the dosing interval beyond the normal dosing interval, rather decrease the dose • Can substitute methadone and wean q 48 hrs over a longer time period

25. BENZODIAZEPINES • First line agents for sedation • Provide hypnosis, anxiolysis, antegrade amnesia, and anticonvulsant activity • NO ANALGESIA • Can cause abstinence syndrome after prolonged use • Mechanism in the limbic system via the inhibitory neurotransmitter, gamma aminobutyric acid (GABA)

26. DIAZEPAM (VALIUM) • Sedating, variable amnesia, anxiolytic • Irritating to veins, pain in PIV • Multiple active metabolites • Advantage for prolonged sedation • Disadvantage for rapid arousal • Not recommended for continuous infusion • Half-life 12-24 hrs • Hepatic metabolism

27. LORAZEPAM (ATIVAN) • 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

28. 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 Less absorption requiring increase dosing MIDAZOLAM (VERSED)

29. MIDAZOLAM • Reports of dystonia and choreoathetosis post infusion, greater risk in neonates • Heparin decreases protein binding, increases free drug • Disadvantage cost • 20 kg patient • 80 $/day compared to Ativan = 30 $/day

30. BENZODIAZEPINES SIDE EFFECTS • RESPIRATORY DEPRESSION • Less than narcotics, but potentiated with narcotics • Dose related • Reversal • Flumazenil - benzodiazepine receptor antagonist • Contraindicated in patients with chronic benzo use for seizures, mixed overdose, TCA’s - may result in seizures

31. BENZODIAZEPINESSIDE EFFECTS • Choreoathetoid movement disorder • Tolerance • As with narcotics may need to increase dose following 2-3 days use • Dependence • Withdrawal carefully and slowly if on greater than 7-10 days • Signs of withdrawal - tremor, tachycardia, hypertension, • Rapid withdrawal may promote seizures

32. 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 • Paradoxical reaction in some older children • Not to exceed 100 mg/kg/day - i.e.: 25mg/kg/q 6 hrs • Caution in children < 3 months or with hepatic dysfunction

33. BARBITURATES • Sedative • Respiratory depression dose dependent • Negative inotropic effects/vasodilation - decreased cardiac output • Decreased cerebral O2 consumption • CBF • ICP • Anticonvulsant

34. BARBITURATES • Useful in patients with increased ICP • Short acting barbiturate useful for sedation for procedure/imaging in hemodynamically stable child • Alkaline solution, often incompatible with TPN or meds.

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

36. KETAMINE • Dissociative IV anesthetic • Good amnesia and somatic analgesia • Anesthetic state classically described as a functional and electrophysiological dissociation between the thalamoneocortical and limbic system • Chemically related to phencyclidine and cyclohexamine • Water and lipid soluble • Quickly crosses blood-brain barrier, < 30 seconds

37. KETAMINE • Redistribution half-life 4.7 minutes • Elimination half-life 2.2 hours • Clinical effects evident within one minute, resolution within 15 - 20 minutes of dose • Bronchodilation • Sialagogue -“promoting the flow of saliva” • Administer with an anticholinergic • Atropine or Robinol • Minimal net hemodynamic effect • Negative inotrope • Central effect - HR, SVR • Good choice in shock or status asthmaticus

38. KETAMINE • Risk of laryngospasm • Risk of emesis/aspiration • Increases ICP , globe pressure • Seizure inducing • Emergent reactions, hallucinations • Improved with administration of a benzodiazepine • IM: 2 - 4 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

39. 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

40. PROPOFOL • Lipid emulsion, reports of anaphylaxis • Soybean oil, egg lecithin, and glycerol • Decreased ICP, may lower CPP • Decreased sympathetic tone • Contraindicated in hemodynamically unstable • Moderate respiratory depression • Pain with injection/infusion site • Improved with use of 1% lidocaine • 0.5 mg/kg

41. PROPOFOL • Neurologic sequela • Opisthotonic posturing • Myoclonic movements • Metabolic acidosis reported with use > 24 hrs • Contraindicated for long term use • Doses • 1 - 3 mg/kg induction • 20 - 100 mcg/kg/min • Increase infusion rate 5-10 mcg/kg/min increments of 5 - 10 minutes