Jacksonville talk

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Sedation and Pain Management in Children
Christina M. Pabelick, M.D. Assistant Professor
of Anesthesiology Department of
Anesthesiology Mayo Clinic College of
Medicine Rochester, MN
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Introduction

• Remarkable growth over past 20 yrs in management
  of pediatric pain and sedation management
• Recognition of need for pediatric sedation and
  comfort (procedures pediatric intensive care
  unit (PICU))
• Controversies in field now focused on how best to
  treat pain
• Failure to provide adequate sedation and
  analgesia to control stress response associated
  with increased morbidity and mortality

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Reasons for Sedation/Analgesia in PICU

• Pain perception in children as much as in adults
• Inability of child to understand purpose of
  procedure or cause of pain
• Protection against tremendous stress response
• Adequate sedation/pain management
• Reduces child and parent anxiety
• Increases compliance and cooperation
• Reduces burden on medical staff and resources
• Long-term negative effects of pain/stress more
  apparent
• Increased complications
• Increased morbidity and mortality
• Possible negative impact on development

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Goals of Sedation in Critically Ill Children

• Comfort control in strange and unpredictable PICU
  environment
• Improve patient cooperation
• Reduce injury to surgical site (e.g. LTR, tenuous
  closure, ICP)
• Prevent accidental dislodgement of
  lines/catheters
• Prevent patients from harming themselves
• Enable successful completion of procedures

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Sedation/Analgesia in PICU -Depending on
Situation

• Noninvasive procedures
• e.g. imaging studies (CT, MRI etc)
• GOAL motion control and anxiolysis
• Invasive procedures
• e.g. CVP and/or arterial line placement, chest
  tube placement
• GOAL sedation, anxiolysis, amnesia, motion
  control
• Long-term sedation/analgesia most difficult
• e.g. postoperatively, respiratory and/or
  cardiovascular failure etc.
• GOAL sedation, anxiolysis, pain control

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Definition of Sedation(ASA Guidelines)

• Minimal sedation (anxiolysis)
• Drug-induced state
• Patients respond normally to verbal commands
• Cognitive function and coordination may be
  impaired
• Ventilatory and cardiovascular command unaffected
• Moderate sedation/analgesia (conscious
  sedation)
• Drug-induced depression of consciousness
• Patients respond purposefully to verbal commands,
  with or without tactile stimulation
• Patent airway maintained with adequate
  spontaneous ventilation
• Cardiovascular function usually maintained

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Definition of Sedation(ASA Guidelines)

• Deep sedation/analgesia
• Drug-induced depression of consciousness
• Patients cannot be easily aroused but respond
  purposefully to repeated or painful stimulation
• Ability to independently maintain ventilatory
  function may be impaired
• Assistance required in maintaining patent airway
• Inadequate spontaneous ventilation
• Cardiovascular function usually maintained
• General anesthesia
• Drug-induced loss of consciousness
• Patients not arousable, even by painful stimuli
• Ability to independently maintain patient airway
  and ventilatory function often impaired
• Cardiovascular function may be impaired

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Definition of Sedation - Summary

• Sedation should be viewed as a continuum, ranging
  from conscious to deep sedation
• Difficult to predict a patients response to any
  medication
• Level of sedation required depends on situation
• Multiple scales to assess sedation however, only
  comfort scale studied in pediatric patients
• Comfort scale
• Demonstrated validity and reliability in
  critically ill, ventilated children
• Observational scale
• Scoring of 0 to 5 for each of eight dimensions
  used to measure general distress (including pain,
  anxiety, and fear)
• Does not require arousability as criterion

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Preparation for Sedation/Analgesia

• Preprocedural evaluation and assessment
• History and physical, including age, weight,
  baseline vital signs
• Current medications
• Known drug allergies
• Review of systems
• Fasting guidelines (2,4,6 rule)
• ASA status assigned - higher incidence of oxygen
  desaturation and failed sedation in children with
  ASA status 3 and 4 compared with those who are
  ASA 1 to 2
• Need a plan What are you trying to accomplish?

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Preparation for Sedation/Analgesia - Child
Specific

• Childrens fears focus on
• Unfamiliar environment
• Pain
• Mutilation
• Separation from parents
• Parents also likely to experience stress,
  anxiety, and apprehension which heightens fears
  of child
• Age-appropriate explanations for children and
  parents frequently lower anxiety levels and
  enhance coping mechanisms
• Nonpharmacologic interventions
• Decrease pain perception
• Reduce fears and anxieties
• Facilitate co-operation

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Preparation for Sedation/Analgesia - Child
Specific

• Separation of children from their parents often
  accentuates anxiety and results in uncooperative
  behavior
• Delaying the separation until the onset of
  sedation significantly reduces problem
• Parental presence actually may reduce amount of
  sedation/analgesia needed

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Monitoring

• Early recognition of adverse events and prompt
  interventions key components in minimizing risks
  for child receiving sedation
• Due to variable response of patients, all
  patients should undergo basic physiologic
  monitoring throughout procedure and recovery
  period, regardless of intended depth of sedation
• Monitors include
• Pulse oximetry (continuously)
• Blood pressure, heart rate, respiratory rate
• Level of consciousness
• Parameters documented at least every 5 min
• Presence of functioning suction
• Ambu bag, mask in appropriate sizes, Oxygen
• Ability to resuscitate

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Drug Selection for Sedation/Procedures

• Sedatives - e.g. chloral hydrate,
  benzodiazepines, barbiturates, propofol,
  dexmedetomidine
• Analgesics - e.g. opioids, NSAIDs
• Anesthetics - e.g. dissociative agent (ketamine)

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Drug Selection - Chloral Hydrate

• Long track record and safety profile
• Often used as sedative for imaging studies
• Potential for liver toxicity - avoid in patients
  with significant hepatic and renal disease
• Avoid in patients with severe cardiac dysfunction
  - reduces myocardial contractility
• Most effective in children younger than 3 years
• No analgesic properties
• No effective reversal agents
• Often useful as adjunct with e.g. benzodiazepines
  for longer term sedation

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Drug Selection - Benzodiazepines

• Benzodiazepines commonly used as sedatives for
  anxiolysis, sedation, and amnesia, and in
  combination with opioids for painful procedures
• Potent anticonvulsants
• Midazolam most frequently used agent
• Advantages
• Short-acting
• Multiple routes of administration
• Easily titratable and useful as infusion
• Mechanism of action through central nervous
  system ?-aminobutyric acid (GABA-A) receptors
• Effects of benzodiazepines reversible with
  antagonist flumazenil

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Drug Selection - Barbiturates

• Commonly used in children undergoing imaging
  studies
• Pentobarbital intermediate-acting agent in
  contrast to methohexital and thiopental (both
  ultra-short acting)
• Avoid rapid iv administration in patients with
  hypovolemia and cardiac dysfunction since
  barbiturates potent vasodilators and decrease
  myocardial function
• Barbiturates contraindicated in patients with
  porphyria (induce ?-aminolevulinic acid)
• Barbiturates act at GABA-A receptor
• No analgesic effect
• Non reversible
• May be used for resistant patient as adjunct to
  other medication

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Drug Selection - Propofol

• Propofol is not indicated in pediatric patients
  for monitored anesthesia care (MAC) sedation or
  for sedation in the intensive care unit.
  (Micromedex)
• Produces dose-dependent levels of altered
  consciousness, ranging from sedation quickly to
  general anesthesia
• Due to its profound respiratory depression its
  use should be restricted to anesthesia personnel
• May be useful for 2-4 h prior to extubation as
  infusion in experienced hands need to monitor
  pH
• Adverse effects development of metabolic
  acidosis even after induction dose

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Drug Selection - Dexmedetomidine

• Dexmedetomidine IV is a specific and selective
  alpha-2 adrenoceptor agonist
• Produces clinical actions similar to those of
  clonidine
• Sedation
• Reduced salivation
• Decreased blood pressure and heart rate
• Appropriate studies on the relationship of age
  and to the effects of dexmedetomidine have not
  been performed in pediatric patients below 18
  years of age (Micromedex)
• Safety and efficacy have not been established
  (Micromedex)
• 3 citations on Pubmed for dexmedetomidine use in
  children
• 2 case reports
• 1 study looking at the effects of dexmedetomidine
  on reduction of agitation after sevoflurane
  anesthesia in children

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Drug Selection - Dissociative Agent (Ketamine)

• Ketamine being classified as dissociative agent,
  since it can rapidly induce a trancelike,
  cataleptic condition
• Causes profound analgesia, sedation, amnesia, and
  immobilization
• This unique state allows painful procedures to be
  performed with preservation of upper airway tone
  and protective airway reflexes
• Adverse reactions
• Hypersalivation - concurrent use of
  anticholinergic agent recommended (e.g.
  glycopyrrolate - benefit good bronchodilator
• Laryngospasm
• Mild cardiovascular stimulation
• Musculoskeletal effects (e.g. myoclonus)
• Increased intracranial and intraocular pressure
• Nightmares - always combine with benzodiazepine

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Definition of Pain

• Standard definition of Pain (International
  Association for the Study of Pain)
• Pain is an unpleasant sensory and emotional
  experience associated with actual or potential
  tissue damage or described in terms of such
  damage
• Pain is always subjective and learned through
  experience related to injury early in life
• Discrepancy of definition in relation to
  pediatric pain especially in the newborn
• Revision of definition (suggested)
• Pain is an inherent quality of life that appears
  early in development and serves as signal for
  tissue damage

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Pain Management - Strategy

• Multimodal approach
• Prevention or diminution of all elements of
  nociception
• Inhibition of peripheral response to tissue
  injury (NSAIDS)
• Neural blockade of transmission of pain impulses
  (regional anesthesia)
• Enhancement of descending inhibitory pathways
  (neuraxial administration of opioids or
  alpha-adrenergic agonists)
• Prevention and management of anxiety (preop
  teaching and postop anxiolysis)

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Pain Assessment

• Pain assessment key to good pain management
• Pain often underestimated in children because of
  inability of caretakers to assess pain
• Although physiologic parameters and parental
  observations helpful in assessing pain,
  self-report gold standard
• lt3 years, more difficult
• Between 3-8 years self-assessment with
  developmentally appropriate tools
• cartoon faces
• photographs of people in pain
• colors quantifying degree of pain
• gt8 years use visual analog scale (VAS) commonly
  used in adults

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WHO Pain Ladder

• Appropriate for pediatric population
• Obviously less clear cut since pain assessment
  may not be as accurate as in self-reporting
  adults
• Opioid use more likely starting point in many
  postoperative situations

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Drug Selection - Acetaminophen (Paracetamol)

• Very effective for management of mild to moderate
  pain or in combination with opioids for more
  severe pain
• Blocks prostaglandin synthesis centrally
• Acts as antipyretic and analgesic
• No effects on gastric mucosa and platelet
  aggregation
• Subject to ceiling effect, in which a maximum
  dose is achieved, after which no additional
  analgesic benefit is derived

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Drug Selection - NSAIDS

• Ibuprofen (8 mg/kg PO q6h) Naproxen (5 mg/kg PO
  q8-12h)
• More potent analgesic effect than acetaminophen
• Very effective for management of mild to moderate
  pain or in combination with opioids for more
  severe pain
• Potent inhibitors of cyclooxygenase (COX) pathway
  preventing formation of mediators of pain,
  inflammation, and fever
• Subject to ceiling effect
• Significant side effect profile gastritis,
  gastric or duodenal ulcerations, painless bleeding

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Drug Selection - Other NSAIDS

• Ketorolac (0.5 mg/kg IV q6h) and diclofenac two
  other NSAIDS non-approved by FDA in children
• Advantage of ketorolac is IV administration in
  NPO patient non-sedating and appropriate
  alternative for opioid therapy
• Reserved for patients with intolerance to generic
  NSAIDS, chronic pain syndromes or rheumatologic
  disease requiring long-term NSAIDS (limited
  duration for ketorolac)
• Avoid use in patients with renal dysfunction

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Drug Selection Opioids

• Choice of opioid dictated by clinical situation
• Parenteral opioids that have moderate duration of
  action, such as morphine or hydromorphone, used
  for patient suffering from acute pain
• For procedural pain control, short-acting opioid
  such as fentanyl may be appropriate
• Oral opioids, in some cases in combination with
  NSAID, more appropriate for mild to moderate pain
• Meperidine (Demerol) rarely used for pain control

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Drug Therapy Opioid Infusions

• Patient-controlled analgesia (PCA)
• Primary mode for management of moderate-severe
  pain in older children
• Less total analgesic use and less severe pain in
  older children and adolescents
• Continuous IV opioid infusions
• Largely reserved for neonates, infants, and older
  children (no PCA)
• Significant co-morbidities likely (e.g.
  disordered control of ventilation with increased
  risk of respiratory depression)
• Estimate likely degree of pain to determine
  amount of required opioid
• Bolus dosing to initially reach therapeutic blood
  level often necessary
• Caveats
• Children on chronic opioid therapy require 3X
  increase in opioid dosing following surgical
  intervention
• In neonates, opioids can produce apnea and
  seizures at safe doses
• Neonates lt2 months should be initially placed in
  monitored setting

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Drug Therapy Novel Techniques for Opioid
Administration

• Lipophilic nature of fentanyl allows various
  routes of administration
• Fentanyl Oralet (lollipop) transmucosal
  absorption within 10-20 min for premedication or
  short procedure-related pain
• Fentanyl patch transdermal absorption for
  chronic pain or in opioid tolerance (onset of
  action 16 h with continued absorption for almost
  24h after patch is removed)

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Drug Selection Opioids Adverse Effects

• Predictable adverse effects (to be anticipated)
• Pruritis treat with antihistamines, alternate
  opioid, or low-dose naloxone infusion
  (hospitalized patient)
• Constipation treat aggressively with laxative
• Sedation and Respiratory depression careful
  monitoring and judicious use of opioid antagonist
  
• Dysphoria judicious selection of opioid

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Adjuvant Therapies

• Epidural analgesia allows children to be alert
  and pain free, and interact with parents and
  staff
• For continued significant fear and anxiety low
  dose benzodiazepines useful
• Antiemetics, anti-pruritic medications, and low
  dose opioid antagonists may also be helpful
• In patients with inflammatory or neuropathic pain
  syndromes, consideration should be given to
  anti-convulsant therapies (e.g. gabapentin)

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Customizing

• Variety of long- and short-acting sedatives and
  analgesics available
• Multiple routes of administration
• Consideration given to
• Anticipated level of anxiety and/or pain
• Individual patients needs
• Type and length of procedure

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Reassessment

• Why does patient have pain needs sedation?
• Are we contributing to patients agitation
  through
• Mode of ventilation
• Dressing too tight causing ulcers
• NPO with gastritis
• CO2 ?, O2 ?, ? temperature

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Outcomes

• Even with goals for pediatric sedation and pain
  control in mind failure rates vary between 3-20
• Success rates not only depend on setting
  (including provider) and type of procedure being
  performed, but also definition used for adequate
  or successful sedation and pain control
• Failed sedation/pain control
• Unwanted stress in child and family
• Adverse procedure outcomes
• Care generally less effective
• 54 of children undergoing stressful
  sedation/anesthesia have postoperative
  maladaptive behaviors

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Conclusions

• Sedation and analgesia critical components of
  critical care in children
• Pediatric sedation and pain management is not
  challenging
• Emphasis should be placed on accurate assessment,
  and multimodal approach
• Parental involvement is important
• For pharmacologic approach, combination of
  medications as well as techniques allows for
  greater flexibility and greater likelihood of
  successful sedation and pain control
• Even in the absence of quantifiable pain, patient
  anxiety should be considered (hospital
  environment, surgical stress)