1. THE USE OF ANALGESICS, SEDATIVE MEDICATIONS PAIN, SEDATION IN CHILDREN Compiled by Tina M. Slusher, MD University of Minnesota Contributions from: JOHN BERKENBOSH, M.D. University of Louisville CHERI LANDERS, M.D. University of Kentucky LYNNE W. COULE, M.D. Medical College of Georgia DAVID ROSEN, M.D. West Virginia University STEVE BARNES, M.D. STEVE BARNES, M.D. Rush University

2. Add oxycotin Add rectal morphine Scheduled versus prn

3. Conflict of Interest I have nothing to disclose

4. Children especially neonates feel less pain than adults w/similar painful stimuli 1.True 2.False

5. Anesthesia Myths cont. Wrong!! Children do feel pain and neonates likely feel even more pain Pain transmission begins @2weeks gestation w/development of skin and mouth sensory neurons Appearance of pain inhibitory apparatus begins at about 32 wks gestation

6. <20 years ago common belief was than infants did not feel pain and no anesthesia was used even during surgery In 1992, a trial2 showed deep anesthesia during cardiac surgery ↓ physiologic stress responses and mortality & gave convincing evidence of importance of adequate analgesia for newborn infants Untreated pain may have undesirable long- term consequences, even after fairly minor procedures Nelson ’ s textbook

7. Analgesia/Sedation Myths Concerns about respiratory depression make pain control impossible in children Wrong again!!! –Need to titrate and Need to monitor –Easy to overshoot in < 6 months –Caveat in the < 6 month old infant Opioids can cause apnea prior to pain relief Neonates may not get good pain relief from morphine but is commonly used in neonates- more studies needed.

8. Concerns about addiction should limit appropriate pain control 1.True 2.False

9. Analgesia/Sedation Myths True addiction rarely happens with appropriate pain control “ Addiction ” –Addiction vs. Tolerance vs. Dependance

10. Addiction A common fear voiced by health care workers Includes a psychological “ need ” or craving along with physical withdrawal symptoms if medication is discontinued People in real pain DON ’ T become addicted as long as medication titrated to pain

11. Tolerance The same dose of medication no longer has the same effect as when first started More commonly occurs in patients on long term continuous infusions of sedatives or analgesics rather than intermittent dosing especially if not titrated to the clinical situation There are currently NO medications to which tolerance will not develop

12. Dependence Removing medication results in withdrawal symptoms To avoid withdrawal, may need to wean sedative or analgesic or change to long acting agents such as methadone or clonidine when patient has been on the medication for 1 week or more

13. ASSESSING PAIN JCAHO – pain as 5 th vital sign (mandate) Developmental and cultural barriers –Ability to verbalize –Cultural attitudes to pain coping/treatment Non-painful contributors to “ pain-like ” behaviors

14. VAS-can be used in  8yo Faces scale  4yo

15. Assessing Pain cont. Autonomic measures –Heart rate –Blood pressure Behavioral or combined behavioral- physiologic scales (e.g. facial expression, limb movement ± heart rate & blood pressure

16. What is Analgesia? “ Relief of the perception of pain without intentional production of a sedated state. Altered mental status may be a secondary effect of medications administered for this purpose. ”

17. MANAGING PAIN 1990 – WHO pain management ladder –Stepwise approach, based on anticipated severity –1° developed for cancer pain, adapted for all acute pain Outpatient and inpatient applications Enteral and intravenous routes encouraged

18. WHO LADDER MILD PAIN: –NSAIDS, Acetaminophen ± adjuvants MODERATE PAIN: –NSAID or acetaminophen ± weak opioid (oxy, hydro, codeine) ± adjuvants –IV opioids with scheduled NSAID or acetamin PCA vs CI vs intermittent –Regional Anesthetic techniques SEVERE PAIN: –IV opioids (PCA/CI) ± adjuvants –Regional Anesthetic techniques ± adjuvants

19. ANALGESIA NSAIDS Ibuprofen: –Onset – 60-90 min –Peak – 2-4 hrs –Duration – 6-8 hrs –80% oral bioavailability –Hepatic metabolism via oxidation, excreted in urine

20. ANALGESIA NSAIDS Ketorolac –0.5-1 mg/kg q6h, po/IV/IM –Onset – 10/30 min, peak – 40-60/90-180 min –Duration – ~6 hrs –Similar kinetics in infants, children, adolescents –Time limited regimen

21. ANALGESIA NSAIDS Ketorolac –0.9 mg/kg equipotent to 0.1 mg/kg morphine >5 y.o. –Munro (2002) – morphine PCA ± q6h ketorolacPSF 0.2 mg/kg ketorolac Sustained  morphine, diazepam requirements –Surgical concerns re impaired wound healing –Some of our orthopedic surgeons (KCH) DO NOT allow in in scoliosis surgery –Limited data in <6 mo

22. Morphine Opioid Advantages –Analgesia –Less expensive than fentanyl Disadvantages –no amnesia, anxiolysis –Histamine release - wheezing, hypotension –Urinary retention –Longer onset than fentanyl

23. ANALGESIA MORPHINE Dose/route –IV/IM - 0.05-0.1mg/kg/dose - onset 2-3 min, duration 3-4 hr infusion 0.01-0.04 mg/kg/hr –po - 0.2-0.5 mg/kg - slow - onset 30-60 minutes –onset – <5 min/1 hr –Peak – 20 min/1-2 hr –Duration – 3-5 hr

24. ANALGESIA MORPHINE More widely available than fentanyl Advantages: -Cheap Disadvantages: –pruritus, hypotension, bronchospasm, sedation, urinary retention

25. ANALGESIA FENTANYL Synthetic opioid, ~ 100X more potent than morphine More “ hemodynamically friendly ” than morphine –100x more potent than morphine –shorter duration than morphine onset in 2-3 min, lasts 30-60 min –less histamine release than morphine

26. Fentanyl Disadvantages: –no amnesia –“ Steel chest ” or “ rigid chest ” phenomenon more likely with large bolus dose Treat with reversal of fentanyl or paralyzation or midazolam

27. Fentanyl cont. Dose/route: –IV - sedation/analgesia - 1-3 mcg/kg/dose - anaesthesia - 5-10 mcg/kg/dose - infusion - 3-5 mcg/kg/hr –Oral - 5-10 mcg/kg

28. ANALGESIA FENTANYL IV/transmucosal –onset – <2 min/5-15 min –Peak – <5 min/20 min –Duration – 30-60 min/1-2 hr –Transmucosal – 25% buccal (rapid), 75% GI (slow)

29. Tramadol Non-opioid analgesia Central inhibition of seroton and non- epinephrine Causes some inhibition of ascending pain pathway PO Dose 1-2 mg/kg/dose q 4-6 hours (max 400mg/day)

30. Pethidine Bad choice but sometimes only one available Agonist-Antagonist Metabolite can build up and cause respiratory depression w/out adequate pain control Often underdosed Dose 0.3-1mg/kg/dose q6hours

31. Ketamine Low dose ketamine may be alternative for pain control See latter section on ketamine for more information

32. Sucrose/Breastfeeding in Neonates Sucrose with or without a pacifier can be used for both pain and stress control in the neonate Breastfeeding + sucrose or glucose may be best alternative? However, recent article in Lancet questions whether oral sucrose actually does reduce pain because although pain score was lower there was no difference in nociceptive or spinal withdrawal activity (Slater R et al, Lancet. 2010;376:1225-1232

33. ANALGESIA NALAXONE (NARCAN) Reverses sedation, analgesia, respiratory depression NO agonist activity so NO risk sedation/respiratory depression with overdoses Dose: 0.1 mg/kg IV/IM –use incremental doses (0.005-0.01 mg/kg) to avoid adverse Adverse: –short half-life, resedation/depression –opioid withdrawal (infants of addicted mothers) –agitation, seizures, N+V

34. Tina M. Slusher, MD Associate Professor of Pediatrics

36. SEDATION RATIONALE Anxiety –underlying illness –separation from parents –transport environment and transfers Ability to perform procedure –Safety - risks of motion (invasive) –Motion interference (i.e. radiologic)

38. PRESEDATION ASSESSMENT HISTORY Brief and Targeted: –Procedure being done and why –Pertinent past history underlying medical conditions prior sedations/anaesthetics and reactions to them Underlying airway issues –Present medications - consider possible interactions –Allergies - get specifics - not all reactions are allergies-include food allergies as well –Family history of anaesthetic reactions –NPO Status –Determine specific sources of anxiety

39. Patient ’ s NPO status –<6 mo 2 hours for clears and 4 hours for breast milk and 6 hours for formula or food –>6 mo 2 hours for clears and 6 hours for food unless diabetic or GER or other situations at increased risk for delayed emptying

40. PRESEDATION ASSESSMENT PHYSICAL EXAM Complete vitals, including room air SaO 2 Airway - micrognathia/macroglossia, tonsils/adenoids obesity (compliance) Underlying lung disease - need to pretreat wheezing etc. Evidence of hypovolemia Neurologic status - relates to ability to protect airway many of these patients are on other CNS-altering medications

41. Precautions Include Airway –Critical Airway: trauma, anatomic abnormality, neonate, full stomach, loose tooth Ventilation –Risk for hypoventilation neonate, debilitated, mentally compromised patient, hx of apnea

42. SEDATION EFFECTS CARDIOVASCULAR CONSIDERATIONS Primary concern is hypotension –vasodilation (esp. venous) (most agents) beware of patient with hypovolemia (presedation fasting) drugs may be synergistic –myocardial suppression (barbiturates, propofol) Precipitation of dysrhythmias –include contribution of relative bradycardia as some drugs (opioids) blunt the normal compensatory HR response to vasodilation/hypovolemia

43. Volume Depletion/Hypotension (Hemodynamic issues) IF intravascularly volume depleted or hypotensive may have a  in BP if administered sedatives IF intravascularly volume depleted or hypotensive should be appropriately fluid resuscitated & hemodynamically stable PRIOR to receiving sedation!

45. AGENT DETERMINATION Relative need for anxiolysis vs analgesia Depth of sedation desired/required Duration of procedure Degree of patient/family anxiety –prior experiences with procedures  sedation Underlying medical conditions –include family history of reactions to anaesthetics –airway - obstruction, oral anatomy, CLDz –hemodynamic - volume status, cardiac function

46. Sedation and Pain Control are synonymous. 1.True 2.False

47. Some drugs like barbiturates actually increase pain by inhibiting neural pathways 

48. SEDATION DEFINTIONS Mild (Conscious) Sedation minimally depressed level of consciousness ability to independently maintain airway patency retained respond appropriately to physical or verbal stimulation Deep (Unconscious) Sedation controlled state of decreased or lost consciousness risk of partial/complete loss of airway protection/patency partial/complete inability to respond appropriately General Anaesthesia medically controlled state of unconsciousness complete loss of airway protection and responsiveness

49. Continuum of Consciousness Awake, baseline General anesthesia Drowsy Conscious sedation Deep sedation

50. ALL SEDATION CAN PROGRESS TO DEEP SEDATION REGARDLESS OF THE DRUG OR DOSE EMPLOYED!

51. Equipment Check your equipment & make sure it ’ s the right size for your patient and in working condition Must have equipment for –Securing airway –Assisting ventilation –Supporting circulation –Suctioning equipment/supplies PPV (ambu) bag, appropriate mask, IV supplies, & suctioning equipment are the basic minimum

52. What is the Best Monitoring Tool 1. Pulse oximeter 2. Blood pressure 3. Cardiac monitor 4. Eyeballs

54. MONITORING Absolute MINIMUM: –(after Two eyeballs looking at the patient) –Continuous HR, SaO 2 –Intermittent (q5-15 min) BP –DOCUMENTATION – frequent HR, RR, BP, SaO 2 Consider: –EKG –ET-CO 2 Hypercarbia and hypoxemia not always simultaneous

55. CONCEPTS Analgesia Sedation Anxiolysis Paralysis

56. DRUG CLASSES Sedatives benzodiazepines barbiturates chloral hydrate  2 receptor agonists Analgesics opioids ketamine Anaesthetics ketamine propofol

57. Benzodiazepines Amnesia –Antegrade and retrograde Anxiolysis Respiratory Depression Skeletal muscle relaxation

58. Midazolam (Versed) Advantages: –anxiolysis, sedation, some motion control –retrograde amnesia –PO, IV, IM, IN, PR dosing routes –onset 2-6 min after IV administration, 45-60 min duration –available reversal agent Flumazenil

59. Midazolam (Versed) Disadvantages –No analgesia –Paradoxical reactions –More than additive risk of respiratory compromise when added to opiate –Neonates: bradycardia, hypotension and seizures with rapid injection –Peak serum level increased with itraconazole, erythromycin and clarithromycin

60. Diazepam Advantages: Similar to other benzo ’ s except longer acting, metabolites can accumulate over time causing toxicity especially w/larger doses Dosage for sedation: –0.04-0.2mg/kg/dose IV/IM q2-4 hours (maximum 8 mg in 24 hours) –0.12-0.8 mg/kg/24 hours PO divided q6hours

61. Barbiturates General CNS depressants Induction of anesthesia Hypnosis Sedation Respiratory depression

62. Pentobarbital (Nembutal) Advantages: –Fairly safe –Sedation, motion control, anxiolysis –Short onset (3-5 min. given IV) and duration (15-45 min.) –Alternative to chloral hydrate in older children –PO, IV, IM, PR dosing routes longer time to onset and longer duration with routes other than IV

63. Pentobarbital Disadvantages –Enhances pain perception –No reversal agent

64. Chloral Hydrate Advantages –PO, PR dosing initial 25-100 mg/kg repeat after 30 min if need 25-50 mg/kg –Anxiolysis, sedation, motion control –Single dose toxicity is low –Successful in younger patients (< 2-3 yrs) –Many practitioners familiar with its use –Just as good as bourbon

65. Chloral Hydrate Disadvantages –15-30 min to onset, lasts 1-2 hours –Less successful in older children –High doses can cause respiratory depression and dysrhythmias –No pain control –Not reversible –Repetitive doses cause metabolites to accumulate with unknown toxicities

66. Propofol Sedative/hypnotic anesthetic Increased popularity for procedural sedation –Rapid onset and recovery –Lack of agitation –Anti-emetic properties Deep sedation for short procedures –Consider concomitant analgesic or local anaesthetic NO significant Analgesic Properties

67. PROPOFOL Administration: –1-2 mg/kg/dose – slowly and titrate –Infusion (3-5 mg/kg/hr) or frequent small boluses Onset/Duration: –Rapid onset (1-2 minutes) –Rapid recovery - baseline in 10-15 minutes Adverse: –Respiratory depression/airway protection Dose-dependent Smaller therapeutic window than ketamine –Hypotension/bradycardia –Pain at injection site – lidocaine helps~I mix 1mg/kg in first 10cc syringe of propofol ~less problematic w/larger IV ’ s

68. Propofol cont. Adverse: –Respiratory depression/airway protection Dose-dependent Smaller therapeutic window than ketamine –Hypotension/bradycardia –Pain at injection site - lidocaine

69. Narcotics Plus Benzo ’ s Monitor closely for respiratory depression esp. when used in combination w/benzodiazepines! Remember that narcotics plus benzo ’ s = more respiratory depression than either alone!

70. Ketamine Dissociative anesthetic Advantages –provides both analgesia and amnesia –less alteration of upper airway tone and reflexes than benzo ’ s or narcotics –preserves upper airway tone and reflexes –causes bronchodilatation Although studies don ’ t all agree ketamine likely reduces the dose of morphine when used together. (Carstensen & Moller, BMJ, 2010, 401-6)

71. Ketamine Disadvantages –increases intracranial pressure –laryngospasm –hypersecretory response (can lessen with use of glycopyrrolate-best or atropine) –emergence phenomenon/agitation (can lessen with benzo ’ s)

72. Ketamine Relative contraindications –head injury –airway abnormalities –procedures where posterior pharynx will be stimulated –glaucoma, acute globe injury –psychosis –thyroid disorder –uncontrolled hypertension

73. KETAMINE Dose: –IV - 1-2 mg/kg initially repeat 0.5-1 mg/kg as needed –IM - 3-6 mg/kg –PO – 5-10 mg/kg –Suggest adding antisialagogue, benzodiazepine

74. Ketamine cont Onset/Duration: –rapid onset (<1 min IV, 5-10 minutes IM, 10-15 PO) –dissociation lasts 15-30 minutes, return to baseline usually by 30-60 minutes after last dose