CHAPTER 3: Analgesia and Sedation

ANALGESIA IS THE DIMINUTION OR ELIMINATION OF PAIN IN THE CONSCIOUS PATIENT.

• Even neonates demonstrate behavioral and hormonal changes in response to painful procedures

• Children do not have to understand the meaning of pain nor do they have to communicate pain to experience pain

• Preemptive analgesia may decrease post-injury opioid requirements

• Observational-behavioral measures

  • ✓ Useful in infants and toddlers (who do have physiologic and behavioral responses to pain, such as increased heart rate, blood pressure, respiratory rate, crying, flushing, facial expressions, and body movements)

  • ✓ Example: FLACC (Face, Leg, Activity, Cry, Consolability) Behavioral Pain Scale (Merkel SI, et al. The FLACC: A behavioral scale for scoring postoperative pain in young children. Pediatr Nurs. 1997;23(3):293–297)

• Self-report

  • ✓ OUCHER scale combines numeric and faces scales, making it appropriate for young children (available at http://www.oucher.org)

  • ✓ Faces scale: The child is asked to point to the face that best describes his/her own pain (available at http://www.wongbakerfaces.org)

  • ✓ Verbal numeric pain rating: Useful in developmentally normal children 6–7 years of age (or older). Pain is rated from 0 to 10 (0 is no pain and 10 is the worst pain imaginable)

EUTECTIC MIXTURE OF LOCAL ANESTHETICS (EMLA)

• 2.5% Lidocaine/2.5% Prilocaine

• Apply to intact skin; complete anesthesia in 60–90 minutes

• Use for blood drawing/IV placement, bone marrow aspiration, lumbar puncture in non-emergent settings

• May use liposomal lidocaine (LMX) for faster onset; topical lidocaine only; anesthesia in 30 minutes

• Contraindications: Methemoglobinemia, age less than 1 month

LIDOCAINE, EPINEPHRINE, TETRACAINE (LET)

• Used for dermal lacerations; apply to open wound

• Contraindicated in areas supplied by end-arteries (digits, pinna, nose, penis)

VISCOUS LIDOCAINE

• For older children who can expectorate

• Combine with diphenhydramine and Maalox in equal parts (1:1:1) to create “magic mouthwash” (can also exclude lidocaine if mouth sores create a concern for systemic absorption)

• Usual dose: 15 mL of undiluted mixture to “swish and spit” (not swallow); maximum dose is 4.5 mg/kg or 300 mg of lidocaine component (up to every 3 hours). Smaller amounts work well

LIDOCAINE JELLY

• Used for nasogastric tube placement and urethral catheterizations

INJECTABLE LOCAL ANESTHETIC

• Buffer with 1 mL (1 mEq/mL) sodium bicarbonate (NaHCO₃) per 9 mL lidocaine or 0.1 mL NaHCO₃ per 10 mL bupivacaine to reduce pain associated with injection

• Enhance efficacy and duration by using in combination with epinephrine

• Contraindicated in areas supplied by end arteries (digits, pinna, nose, penis)

• All doses referred to here are equianalgesic doses

• All opioids can be reversed with naloxone hydrochloride (Narcan) 0.01 mg/kg IV/IM/SC/ETT; naloxone can be repeated every 2 minutes as needed to maximum of 10 mg

• All narcotics may have side effects of sedation, nausea, vomiting, pruritus, and constipation

CODEINE

• Codeine is metabolized into morphine by cytochrome P450 2D6, but this enzyme is absent in up to 10% of the population

• No longer recommended for use in children due to variable metabolism where non-metabolizers will have minimal to no analgesia, and ultra-rapid metabolizers will be at risk for excessive sedation, respiratory depression, and death

FENTANYL

• 0.001 mg/kg/dose IV with onset in 1–2 minutes; duration: 0.5–1 hour (repeat or higher dosing may result in increased context-sensitive half-life)

• 0.01 mg/kg/dose transmucosal with onset in 15 minutes (FDA approved for cancer pain only)

• The transdermal patch is used in chronic pain management for opioid tolerant patients with expected pain management needs of several weeks

• Caution: Chest wall rigidity may occur with high doses and rapid IV push; reversible with naloxone or neuromuscular paralysis/endotracheal intubation

HYDROMORPHONE

• 0.015 mg/kg/dose IV/SC (usual adult dose 0.4–0.8 mg) with onset in 5–10 minutes; duration: 3–4 hours

• 0.02–0.08 mg/kg/dose PO with onset in 30–60 minutes (usual adult dose 2–4 mg); duration: 3–4 hours

• Has no active metabolites

MEPERIDINE

• Rarely used for analgesic purposes due to severe drug interactions (MAO inhibitors)

• Occasionally used to treat postoperative shivering or medication-induced shaking (e.g., amphotericin-related rigors)

• Side effects: Tachycardia, seizures, worsens bronchospasm, serotonin syndrome

• Active metabolite, normeperidine, may accumulate and induce seizures

METHADONE

• 0.1 mg/kg/dose IV with onset in 15–30 minutes; duration: 12–24 hours

• 0.1 mg/kg/dose PO with onset in 30–60 minutes; duration: 12–24 hours

• Commonly used as an opioid taper

• Due to drug accumulation with long half-life, respiratory side effects may not appear until days after drug initiation

• Baseline ECG is necessary as methadone may prolong QT interval

MORPHINE

• 0.1 mg/kg/dose IV (usual adult dose 2–4 mg) with onset in 5–10 minutes; duration: 3–4 hours

• 0.1–0.2 mg/kg/dose SC with onset in 10–30 minutes; duration: 4–5 hours

• 0.3–0.5 mg/kg/dose PO with onset in 30–60 minutes; duration: 4–5 hours

• Side effects: Nausea, sedation, pruritus, constipation, seizures (in neonates—due to decreased elimination of active metabolite morphine-3-glucuronide)

• Contraindications: Renal failure (active metabolites may accumulate to cause profound sedation and/or respiratory depression)

NALBUPHINE

• 0.1 mg/kg/dose (usual adult dose 5 mg) with onset in 5–10 minutes; duration: 6 hours

• Partial opioid agonist, resulting in plateau of analgesic effects but also minimizing risk of respiratory depression

• May be used to treat opioid-related side effects (e.g., pruritus, nausea/vomiting) by the partial opioid antagonism at the mu receptor

• Relatively contraindicated in patients on chronic opioids as nalbuphine may precipitate acute opioid withdrawal

OXYCODONE

• 0.1 mg/kg/dose PO with onset in 30–60 minutes; duration: 4–6 hours

• Active metabolite, oxymorphone, can accumulate in renal failure

• When oxycodone is made with acetaminophen, this limits its utility in young children due to the toxicity of acetaminophen

ACETAMINOPHEN

• Antipyretic; weak analgesic

• Side effects: Hepatic necrosis (overdosage)

• Usual dose: 10–15 mg/kg PO or rectally every 4–6 hours; adult dose: 325 mg⁻¹g/dose

• Maximum dose: 4g/day (adults); 90 mg/kg/day (children)

• Acetaminophen should be administered in a separate formulation from an opioid to reduce the toxic potential of an acetaminophen overdose

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS

• Useful for inflammatory pain

• Side effects: Platelet inhibition, gastrointestinal irritation, nephrotoxicity

• Ibuprofen: 5–10 mg/kg PO every 6–8 hours with a maximum of 40 mg/kg/day; adult dose 200–400 mg/dose, maximum 1.2g/day

• Ketorolac: 0.5 mg/kg/dose IV/IM every 6 hours with maximum 30 mg every 6 hours which is usual adult dose (avoid if post conceptual age <44 weeks versus <6 months depending on institutional protocol)

• Naproxen: 5–10 mg/kg/dose PO every 8–12 hours with maximum 1000 mg/day; adult dose 250–500 mg/dose; maximum 1000 mg/day

ASPIRIN

• No longer routinely used for analgesia due to side effects, but continues to be utilized for anti-platelet effects in specific situations (e.g., Kawasaki disease, vascular shunts, etc.)

• Side effects: Reye’s syndrome (avoid in children with varicella or influenza)

KETAMINE

• Low dose infusions of 0.1–0.2 mg/kg/h may utilized for analgesia (especially in patients on chronic opioids as part of a weaning regimen) and higher dose infusions (e.g., 0.5–2 mg/kg/h) or boluses (2 mg/kg IV or 4 mg/kg IM) may be used for sedation

• Side effects: Excess salivary secretions (prevent with glycopyrrolate pretreatment), nystagmus, increased ICP (though cerebral perfusion pressure maintained given increased mean arterial pressure), emergence delirium

DIAZEPAM

• 0.05–0.1 mg/kg/dose IV every 6–8 hours for muscle spasms and anxiolysis

• 0.1–0.2 mg/kg/dose PO every 6–8 hours (usual adult dosing 2–10 mg)

• Prolonged half-life can lead to late onset of side effects which are sedation, respiratory depression, and hypotension and can be worsened by coadministration of opioids

• Distraction, music, play

• Acupuncture, massage, and hypnosis are other methods of analgesia usually requiring trained practitioners

• Indicated for acute/chronic pain of known etiology as well as preemptive pain management. Cardiorespiratory monitoring is required. Six or 7 years is minimum age to control a Patient-Controlled Analgesia (PCA). Parents and nurses can also be trained to administer a PCA for younger patients or those with developmental delay

• Minimum developmental age of about 7 years to self-administer PCA

  • ✓ Parents and nurses can also be trained to administer PCA to younger patients and those with developmental delay

• Route: IV or rarely SC

• Dosing for PCA:

  • ✓ Morphine: Basal dose 10–20 μg/kg/h; bolus dose 10–20 μg/kg; lockout 8–10 minutes, four to six boluses per hour; maximum dose per hour: 100–150 μg/kg

  • ✓ Hydromorphone: Basal dose 3–4 μg/kg/h; bolus dose 3–4 μg/kg/h; lockout 8–10 minutes, four to six boluses per hour; maximum dose per hour: 15–20 μg/kg

  • ✓ Fentanyl: Basal dose 0.25–1 μg/kg/h; bolus dose 0.25–1 μg/kg; lockout 8–10 minutes, two to three boluses per hour; maximum dose per hour: 2 μg/kg

SEDATION IS A CONTINUUM

• Minimal Sedation (anxiolysis): A drug-induced state in which cognitive function and coordination may be impaired. Patients respond normally to verbal commands. Protective airway reflexes are maintained. Ventilatory and cardiovascular functions are unaffected

• Moderate Sedation: A drug-induced state of depressed consciousness. Patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. There is significant loss of orientation to environment, with moderate impairment of gross motor function. Protective airway reflexes are maintained. Ability to maintain patient airway and cardiovascular function are usually maintained. There may be mild alterations in ventilatory responsiveness

• Deep Sedation: A drug-induced state of depressed consciousness or unconsciousness from which a patient is not easily aroused. Patients may respond purposefully to painful stimulation. May be accompanied by a partial or complete loss of protective reflexes, which may include the inability to maintain a patent airway independently and respond purposefully to physical stimulation or verbal command. Spontaneous ventilation may be inadequate. Cardiovascular function is usually maintained

• General Anesthesia: Drug-induced loss of consciousness with loss of protective reflexes, inability to maintain patent airway, and loss of purposeful response. Cardiovascular function may be impaired

PATIENT-RELATED FACTORS

• Pre-sedation Assessment (Table 3-1 and Figure 3-1): Essential to identify high-risk patient populations to both anticipate and reduce adverse sedation events

• NPO Guidelines (American Society of Anesthesiology [ASA]):

  • ✓ No clear liquids for 2 hours before sedation

  • ✓ No breast milk for 4 hours prior to sedation

  • ✓ No formula for 6 hours prior to sedation

  • ✓ No solids/milk for 8 hours prior to sedation

  • ✓ In an emergency situation: Delay sedation if possible or use lightest possible level of sedation. Consider elective intubation for airway protection

• ASA Classification:

  • I: Normal healthy patient

  • II: Mild systemic disease

  • III: Severe systemic disease

  • IV: Severe systemic disease associated with significant dysfunction and potential threat to life

  • V: Critical medical condition where operative intervention is critical to survival

PROCEDURAL CONSIDERATIONS

• Duration of procedure

• Painful versus nonpainful

• Position for procedure

• Need for immobility

• Age and ability to cooperate with instructions

PROVIDER-RELATED FACTORS

• Dedicated sedation providers. Require at least two providers—one to administer sedation and one to monitor the sedation

  • ✓ Providers require airway skills, advanced life support skills, experience managing complications, and ability to rescue patient from a level of sedation which is deeper than anticipated

  • ✓ Traditionally administered by anesthesiologists, intensivists, and emergency medicine physicians with RN, CRNA, NP, or PA support

  • ✓ Increasing number of pediatric hospitalists performing sedation within a dedicated sedation program and with similar outcomes and complication rates

• Equipment (can use SOAPME acronym)

  • ✓ Suction—Apparatus including catheters (Tonsil, Yankauer)

  • ✓ Oxygen—Supply and age-appropriately sized positive pressure oxygen delivery system

  • ✓ Airway—Size-appropriate equipment (nasopharyngeal and oropharyngeal airways, facemask, bag-valve-mask, etc.)

  • ✓ Pharmacy—Medications for sedation, sedative antagonists and resuscitation, intravenous fluids

  • ✓ Monitors—Pulse oximeter, blood pressure, end-tidal CO₂ detector, stethoscope

  • ✓ Extra equipment—Special equipment or drugs for the given case

• Monitoring:

  • ✓ Continuous pulse oximetry, heart rate, and end-tidal monitoring

  • ✓ Vital signs with blood pressure monitored every 15 minutes for minimal sedation and every 5 minutes for moderate or deep sedation

  • ✓ Consider full cardiorespiratory monitoring for specific cases (e.g., ketamine)

  • ✓ Backup system for emergencies: Highly trained and reliable (e.g., code team, 911)

• Anxiolytics—Make patients more comfortable

  • ✓ Benzodiazepines (e.g., diazepam, midazolam, lorazepam): Provide anxiolysis and amnesia. Often used as premedication or as adjunct with analgesics. Administered PO, IV, IN, IM, or PR

  • ✓ Nitrous oxide: Anxiolytic with some analgesia effect. Administered via inhaled delivery system

• Analgesics—Achieve pain control

  • ✓ Lidocaine (e.g., LMX): Local analgesia at the procedure site. Administered topically or SQ

  • ✓ Opioid agonists (e.g., fentanyl, morphine): Dose-dependent analgesia and sedation. Often used in conjunction with anxiolytics or hypnotics. Administered PO, IV, or IN

  • ✓ Ketamine: Dissociative sedative with analgesic and amnestic properties. Administered PO, IV, or IM

• Hypnotics—Achieve sleep/immobility, especially useful for noninvasive procedures

  • ✓ Chloral hydrate: Produces sleep with mild to moderate respiratory depression. Currently with limited manufacturing resources. Administered PO or PR

  • ✓ Barbiturates (e.g., pentobarbital): Potent sedative, hypnotic and anesthetic properties. Administered PO, IV, or PR

  • ✓ Central α2 adrenergic agonists (e.g., clonidine, dexmedetomidine): Sedative, anxiolytic, and sometimes analgesic properties. Administered PO, IN, or IV

  • ✓ Etomidate: Short-acting anesthetic and amnestic. Especially useful in settings of hemodynamic instability. Administered IV

  • ✓ Propofol: Sedative, hypnotic, and anesthetic properties. Administered IV

• Sedative antagonists

  • ✓ Flumazenil: Short-acting agent that reverses benzodiazepine-induced sedation (use cautiously in patients with seizure disorders, as benzodiazepine reversal can induce seizures)

  • ✓ Naloxone: Short-active agent that reverses opiate-induced sedation

• Airway obstruction

• Laryngospasm

• Hypoventilation and apnea

• Vomiting/Aspiration

• Cardiovascular instability

• Patient recovery should be monitored with vital signs at regular intervals until patient is awake and interactive

• Patients should only be discharged once specific criteria have been met: Stable vital signs, adequate pain control, return to level of consciousness that is similar to baseline for that patient, adequate head control and muscle strength to maintain patent airway, adequate hydration (tolerates oral challenge), and nausea/vomiting should be controlled

COMPUTED TOMOGRAPHY (CT) SCAN

• Need for relative immobility but not analgesia

• Young infants often can be swaddled and may not require sedation. Patients 6 weeks–3 years old are the most likely age group to require sedation

• Option 1: PO Pentobarbital 2–4 mg/kg PO 30 minutes before procedure; repeat ½ dose 20–30 minutes after initial dose if patient still moving. Maximum dose: 100 mg or 8 mg/kg. Works well in infants <10kg who do not require an IV for the procedure. Can use in conjunction with IN versed or fentanyl if need additional sedation

• Option 2: IV Pentobarbital 2–3 mg/kg slow IV push with titration to response. Give in increments of 1–3 mg/kg IV. Time to sedation is 2–5 minutes and time to recovery is 1–2 hours. Maximum 100 mg/dose or about 10 mg/kg

• Midazolam and fentanyl are unreliable in producing sedation with immobility but can be used as an adjunct to hypnotics to decrease total dose of longer acting medications

MAGNETIC RESONANCE IMAGING (MRI)

• Need for relative immobility but not analgesia. Study typically lasts >45 minutes

• Young infants can often be swaddled or placed in an immobilizer device and may not require sedation. Children often require sedation until 6–8 years of age but older children, especially those with developmental delays, claustrophobia, ADHD, and/or anxiety, may require sedation as teenagers

• IV Pentobarbital 2–3 mg/kg; maximum dose 100 mg/dose with titration to response. Give in increments of 1–3 mg/kg. Can use in conjunction with IV midazolam (0.05–0.1 mg/kg with maximum of 2.5 mg max/dose) and fentanyl (1 μg/kg with maximum of 100 μg/dose) to reduce total pentobarbital dose required

LUMBAR PUNCTURE

• Infants younger than 2 months are not routinely sedated for this procedure

• Midazolam 0.05–0.1 mg/kg IV given 3–5 minutes before lumbar puncture significantly decreases anxiety in older children. Repeat 0.1 mg/kg IV doses as needed to achieve adequate sedation. Maximum 2.5 mg/dose

• Fentanyl 1–2 μg/kg IV given via slow push over 3–5 minutes can provide analgesia. Repeat 1 μg/kg IV doses as needed to achieve adequate sedation. Maximum dose 100 μg/dose

• Can use midazolam and fentanyl together to achieve moderate to deep sedation as indicated. Can consider adding ketamine or pentobarbital as needed, depending on patient-specific characteristics (see options below)

PAINFUL PROCEDURES SUCH AS FRACTURE REDUCTION/INCISION AND DRAINAGE/BURN DEBRIDEMENT/CENTRAL VENOUS LINE

• Option 1: Midazolam IV (0.05–0.1 mg/kg with maximum of 2.5 mg/dose) plus fentanyl (1–2 μg/kg with maximum dose of 100 μg/dose). Titrate additional doses as needed to achieve adequate sedation

• Option 2: Ketamine (0.5–2 mg/kg with maximum of 100 mg/dose) slow IV push. Titrate additional doses as needed to achieve adequate sedation. Consider atropine or glycopyrrolate premedication to decrease secretions. Can use midazolam and fentanyl adjuncts if needed to reduce total ketamine dose

• Option 3 (for longer procedures, ≥30 minutes): Midazolam IV (0.05–0.1 mg/kg with maximum of 2.5 mg/dose) plus fentanyl (1 μg/kg with maximum dose of 100 μg/dose) plus pentobarbital IV (2–3 mg/kg with maximum dose of 100 mg/dose)

• When using combination of sedatives/analgesics, start with lowest dose possible and give additional doses as needed to achieve desired depth of sedation. The rate of complications increases with polypharmacy