NOTE: Preferred terminology for narcotic analgesics is opioids.

Reasonable starting dose of opioid for neonate who is not mechanically ventilated is 1/4 to 1/3 recommended starting dose for older children. Infant is monitored very closely for respiratory depression. Dose is titrated to effect. Since tolerance can develop rapidly, very large opioid doses may be needed for continued severe pain (American Pain Society, 1992).

Oral - Preferred because of convenience, cost, and relatively steady blood levels, but higher dosages of the oral form of opioid analgesics are required to achieve equivalent analgesia provided by parenteral form. A convenient oral form of acetaminophen is Feverall Sprinkle Caps (80 mg or 160 mg) manufactured by Upsher-Smith Laboratories, Inc. 14905 23rd Ave. N, Minneapolis, MN 55447, 1-800-328-3344.

Sublingual - Highly desirable, more rapid than oral because avoids "first-pass effect;" many drugs can be compounded into a lollipop, posicle, spray, troche or lozenge (Wong and Redding, 1987; Pitorak, 1991).

For information about compounding drugs in troches or suppositories, contact Technical Staff, Professional Compounding Centers of America (PCCA), P.O. Box 368, Sugarland, TX 77487; 800-331-2498; www.thecompounders.com.

Intravenous (bolus) - Provides most rapid onset of effect, usually in about 5 minutes; excellent for immediate relief of pain, such as procedure, trauma, or "breakthrough" pain.

Intravenous (continuous) - Provides steady blood levels, easy to titrate dosage. In case of overdose, medication is stepped immediately and IV access for reversal agents, ie, Noran and Romazicon, is available.

Patient-controlled analgesia (PCA) - Usually administered via a programmable infusion pump that allows patient to self administer predetermined boluses of medication; may be combined with a continuous infusion of opioid as well as intermittent boluses or "rescue doses" for breakthrough pain. PCA can be used with children who understand concept of push button - get pain relief (children as young as 4 years) (Gaukroger and others, 1989; Gureno and Reisinger, 1991). Parents and nurses have successfully used PCA for the child (Reimondy and others, 1991; Webb, Paarlberg, and Sussman, 1991; Ruble and Billett, 1993). Morphine as compared to meperidine (PCA about 37 hrs.) produced better pain relief and fewer side effects (Vetter, 1992).

Intramuscular - readily available but has several disadvantages: painful, wide fluctuation in absorption of drug from muscle, shorter duration than oral drug, expensive, and time consuming for staff.

Subcutaneous (continuous) - May be used when oral and IV routes are not available and child requires continuous pain medication, i.e., terminal disease. Suitable analgesics include morphine and hydromorphone, but not meperidine. Dose is same as IV; needle can remain in place until not patent or signs of irritation occur.

Intradermal - Local anesthetic is injected over area to be accessed, e.g., for lumbar puncture, bone marrow aspiration, or venous or arterial puncture. Warming lidocaine to 37° C (98.6 F) (Davidson and Boom, 1992) and buffering lidocaine with sodium bicarbonate reduces the stinging sensation (McKay, Morris, and Mushlin, 1987; Orlinsky and others, 1992; Wong and Pasero, 1997).

Guidelines for Using Buffered Lidocaine (BL)
Supplies: 8.4% sodium bicarbonate (1 mEq/ml); 1% or 2% lidocaine with or without epinephrine; syringe with removable needle and a 30-gauge needle.

Instructions:
-Use 1 part of sodium bicarbonate to 10 parts of lidocaine (i.e., draw up 1 ml of lidocaine and 0.1 ml of sodium bicarbonate).
-Change needle used to withdraw BL to 30-gauge needle for intradermal injection.
-For venipuncture, inject 0.1 ml or less BL intradermally directly over intended puncture site. Anesthesia occurs almost immediately.
-Suggested maximum dose of lidocaine for local anesthesia is 4.5 mg/kg.
-If buffering lidocaine vial (20 ml lidocaine with 2 ml sodium bicarbonate), use unrefrigerated solution for 7 days or refrigerated solution for 14 days, but preferably when freshly prepared (see sample protocol for buffered lidocaine).

Rectal - Alternative to oral or parenteral routes, but is disliked by children and has variable absorption rates. Many drugs can be compounded into rectal suppositories (Cole and Hanning, 1990).

Topical/transdermal/transmucosal - EMLA - Eutectic mixture of local anesthetics (lidocaine/prilocaine cream) for painless venipunctures, arterial puncture, PICC lines, implanted port access, superficial biopsy, LP, split-thickness skin graft, laser treatment of port-wine stains (Sherwood, 1993), subq or IM injections (Taddio and others, 1992; Himelstein and others, 1996). Thick layer of cream applied under occlusive dressing or as anesthetic disc 1 hour or more before procedure. In U.S approved for children over 1 mo. but has been used successfully for neonatal circumcision (Benini and others, 1993; Law and others, 1996). (See Guidelines for EMLA)

LAT or LET (Lidocaine-Adrenalin/Epinephrine-Tetracaine) - liquid is placed on wounds; anesthesia for suturing occurs in 10-15 minutes. LAT is preferred to TAC (tetracaine-adrenalin-cocaine) because it is safer and less expensive. Neither are used on end-arterioles (ear lobes, penis, digits, or tip of nose) because of vasoconstriction (cocaine, adrenalin) or on mucosa because of increase absorption (cocaine) (see atraumatic suturing).

Coolant (chemical spray or ice) - Ethyl chloride or fluori-methane spray on the site for IM injection (diphtheria-tetanus-pertussis vaccine) numbs the skin (Hagerdorn, 1991; Reis and Houbkov, 1997). Frigiderm (spray refrigerant) can cause rebound burning sensation and possible skin burns; applying ice for 30 seconds to IM site does not sufficiently numb the skin (Gedaly-Duff and Burns, 1992). (See A Cooling Spray [Fluori-Methane] Reduces Immunization Injection Pain)

Fentanyl transdermal patch (Duragesic); peak effect may be from 12 to 24 hours with a duration of up to 72 hours. Usually used for chronic pain; should have order for "rescue doses" of opioid for breakthrough pain. If respiratory depression occurs, several doses of naloxone may be needed (Roberts, 1993).

Transmucosal Fentanyl Oralet (fentanyl in a hard candy base that is attached to a plastic holder) provides nontraumatic preoperative and preprocedural oral sedation. Dose: 5-l5mcg/kg; child <40kg may need 10-l5mcg: if recommended for child <15kg; peak effect in 20-30 minutes if drug is sucked, not chewed and swallowed, effect is delayed. Manufactured by Abbott Laboratories.

Intranasal - Midazolam (Versed) has been used as nasal drops (Theroux and others, 1993); although effective, accurate dosing is difficult and the nasal irritation is distressing to many children; using intranasal lidocaine (4%) can reduce the discomfort (Karl and others, 1991; Lugo and others, 1993). Stadol NS (butorphanol spray) is approved for those over 18 years (Schwesinger and others, 1992). An intranasal form of morphine is under development.

Inhalation - Use of anesthetics, such as nitrous oxide or halothane, can be used to produce partial or complete analgesia for painful procedures (Perin and Frase, 1985; Wattenmaker and others, 1990). Occupational exposure to high levels of nitrous oxide may cause side effects (Baird, 1992; Rowland and others, 1992)
NOTE: Other anesthetic agents - Parenteral or oral ketamine or IV propofol (Deprivan) (short-acting anesthetics) provide excellent pain control for procedures (Bostrom and others, 1993; 1987; Groeneveld and Inkson, 1992; Tobias and others, 1992).

Epidural or intrathecal - May be used postoperatively or in selected terminal care; a catheter is placed into the epidural (or caudal in children) or intrathecal space and a opioid and/or long-acting anesthetic (i.e., ropivacaine orbupivacaine) is instilled via continuous drip or intermittent administration. Analgesia results primarily from drug's direct effect on opiate receptors in the spinal cord, rather than in the brain, which is responsible for undesirable effects, e.g. sedation and respiratory depression (McIvaine, 1990; Sabbe and Yaksh, 1990). Respiratory depression is rare; check child's level of consciousness and respiratory rate and depth hourly for first 24 hours (American Pain Soc., 1992). Itching and urinary retention may occur.

Nerve blocks - Anesthetic, such as long-acting bupivacaine or robivacaine, is injected into site, most commonly at end of surgery, to provide prolonged analgesia postoperatively, e.g., for inguinal herniorrhaphy (Yaster and others, 1994). Dorsal penile nerve block (usually with lidocaine) provides local anesthesia for circumcision (Stang and others, 1988). Shorter-onset chloroprocaine is also effective (Spencer and others, 1992). Another option for circumcision in the penile ring block

• convert half the parenteral dose to a P0 dose
• administer half the parenteral dose and the P0 dose
• assess pain relief
• if pain relief is inadequate, increase the P0 dose as needed
• if sedation occurs, decrease P0 dose
• when the parenteral and P0 doses are effective, discontinue the parenteral dose and give twice the P0 dose

• respiratory depression
• constipation, nausea, diarrhea
• sedation
• agitation, euphoria, hallucinations
• mental clouding
• hallucinations
• orthostatic hypotension
• pruritis, sweating
• miosis (possible sign of toxicity)

If respirations are depressed:

• Stop or reduce infusion by 25% when possible
• Stimulate patient (shake gently, call by name, ask to breathe)
• Administer oxygen as ordered
• Check for or obtain order for naloxone

If patient cannot be aroused or is apneic (American Pain Society, 1992):
-Administer naloxone (Narcan):
-for children less than 40 kg: dilute 0.1 mg of naloxone in 10 ml of sterile saline to make 10 mcg/ml solution and give 0.5 mcg/kg
-for children over 40 kg: dilute 0.4 mg ampule in 10 ml of sterile saline and give 0.5 ml
-administer bolus slow IV push every 2 minutes until effect is obtained
-Closely monitor patient. Naloxone's duration of antagonist action may be shorter than that of opioid, requiring repeated doses of naloxone

Note: Respiratory depression due to benzodiazepines, e.g., diazepam (Valium) or midazolam (Versed) can be reversed with flumazenil (Romazicon). Pediatric dosing experience suggests 0.01 mg/kg (0.1 ml/kg) as loading dose followed by 0.005 mg/kg/min (0.05 ml/kg/min) until awake or to a maximum of 1 mg (10 ml) (Jones and others, 1991). Recommended initial dose for children 20 kg or more is 0.2 mg (2 ml) IV over 15 seconds; if no response after 45 seconds, administer same dose and repeat as needed at 60 second intervals for maximum dose of 1 mg (10 ml).

1. signs of tolerance include:
   • decreasing pain relief
   • decreasing duration of pain relief
2. signs of physical dependence include withdrawal symptoms once the drug is discontinued:
   • initial signs of withdrawal are lacrimation, rhinorrhea, yawning, and sweating;
   • later signs are restlessness irritability, tremors, anorexia, dilated pupils, and gooseflesh.

NOTE: Fears of addiction are unsupported with an incidence of 0.03% among adults (Porter and Jick, 1980). Similar research with children suggests an extremely low risk of addiction in children, including adolescents, receiving opioids (Cole and others, 1986; Schechter, Berrien, and Katz, 1988; Morrison, 1991; Brozovic, 1986).

• Gradually reduce dose (similar to tapering of steroids)
• one-half of previous daily dose given in q6hr doses for first 2 days
• reduce dose by 25% every 2 days
• Continue this schedule until total daily dose of 0.6mg/kg/day of morphine (or equivalent) is reached.
• After 2 days on this dose, discontinue opioid.
• May also switch to oral methadone, using 1/4 of equianalgesic dose as initial weaning dose and proceeding as described above.