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. Conflict of Interest I have nothing to disclose

3. Which of the following is true regarding pain management? 1. Pain management affects wound healing 2. PTSD is not related to acute pain management 3. Neonates don’t feel pain

4. Importance of Effective Pain Control Untreated pain has psychological effects Exacerbates injury and may  mortality Contributes to delayed wound healing Contributes to development of chronic pain and PTSD Bowman et al J of Trauma &Acute Care Surgery 2011

5. Non-pharmacological pain control-audiovisual distraction Decreased pain Increased cooperation Decreased time of procedure Swiss Med Wkly. 2008 Oct 4;138(39-40):579-84. The efficacy of non-pharmacological methods of pain management in school-age children receiving venepuncture in a paediatric department: a randomized controlled trial of audiovisual distraction and routine psychological intervention. Wang ZX, Sun LH, Chen AP. J Prev Med Hyg. 2012 Mar;53(1):44-8. Distraction techniques in children during venipuncture: an Italian experience. Bagnasco A, Pezzi E, Rosa F, Fornonil L, Sasso L.

6. 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

7. <20 years ago common belief was than infants did not feel pain and no anesthesia was used even during surgery In 1992, a trial 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

8. 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.

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. 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

15. 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. ”

16. WHO Golden Rules of Pain Management 1. By the Clock –Regular scheduling ensures steady blood level –PRN results in cycles of pain often leading to increased pain med needs 2. With the child –Regular pain assessment using appropriate scales

17. Scales available on line, standard textbooks or hospital.

18. 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

19. 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

20. 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 8-10mg/kg/dose q 6-8hr PO or PR

21. NSAIDS cont. Naproxen ≥12yo to ≤65yo 200mg q6- 8hr Diclofenac-start in adult 50mg tid All NSAIDS have similar analgesic properties if used in equi-analgesic dose and many of the same side effects

22. ANALGESIA NSAIDS cont. Ketorolac –Only use IV if patient unable to take po NSAID –At equianalgesic dosing no more effective than ibuprofen but has greater side effects –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

23. Codeine Poor analgesic properties Genetic variation means may lead to toxic levels i.e ultra-rapid metabolism can result in toxic accumulation of morphine Don’t use if at all possible

24. Oxycodone Management of moderate-severe pain Comes as immediate and sustained release

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

26. 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 Rectal Morphine also option 0.2 mg/kg/dose

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

28. 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

29. 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

30. 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 –IN-1.5-2.0 mcg/kg

31. 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)

32. Tramadol Non-opioid analgesia but works on opioid receptors w/weak opioid Don’t mix w/strong opoid like morphine or pain make worsen 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)

33. 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

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

35. 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

36. ANALGESIA NALAXONE (NARCAN) Reverses sedation, analgesia, respiratory depression NO agonist activity so NO risk sedation/respiratory depression with overdoses Use has decreased as a reversal agent because of risk of re-sedation 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

37. Naloxone in Low Doses Used to treat itching associated w/narcotics as low-dose continuous infusion Used to Rx nausea unresponsive to anti- emetics Can be given po to treat constipation from narcotics unresponsive to other bowel regimes [(1mg/mL) 4 mL po BID to TID in older children/adults; 1-2mL po BID- TID in younger children]

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

40. 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)

42. 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

43. 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

44. PRESEDATION ASSESSMENT PHYSICAL EXAM Vital signs including baseline SaO 2 General evaluation looking for evidence – illnesses, toxicity – volume depletion – obesity Airway exam –micrognathia/macroglossia, tonsils/adenoids – ability to open mouth well Lung exam –Wheezing, air exchange Cardiac exam –Unrecognized heart disease –Volume status Neurologic status –Ability to protect airway –Ability to cooperate with exam.

45. ASA Physical Status Class I:Healthy patient Class II:Systemic disease-well controlled Class III:Severe systemic disease Class IV:Severe systemic disease that is a constant threat to life Class V:Moribund / not expected to survive without surgery

47. 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

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

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

50. 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

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

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

53. 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

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

56. 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 and if available ET-CO 2 probably better than sat as it picks up changes quicker

57. CONCEPTS Analgesia Sedation Anxiolysis Paralysis

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

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

60. 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 *For IN ideally need Concentrated 5mg/mL

61. 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

62. 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

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

64. 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 Increases pain perception

65. Thiopental Primarily used for induction of anesthesia, seizure control and increased ICP Provides no pain control

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. DEXMEDETOMIDINE Sedation, anxiolysis Analgesia – some but not great Hypertension Bradycardia/hypotension Diuresis Minimal respiratory depression

70. 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!

71. 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)

72. 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)

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

74. 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 –IN-9mg/kg –Suggest adding antisialagogue, benzodiazepine Tsze IN Ketamine for procedural sedation In pediatric laceration repair : a preliminary report Pediatr Emerg Care 2012

75. 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