CLINICAL PEDIATRIC ANESTHESIOLOGY
From the 45th Annual Clinical Conference in Pediatric Anesthesiology, presented by the Pediatric Anesthesiology
Foundation, Childrens Hospital Los Angeles, CA
| MALIGNANT HYPERTHERMIA (MH)-SUSCEPTIBLE DISEASES: WHO DESERVES A NONTRIGGERING
TECHNIQUE ?—Ronald S. Litman, DO, Associate Professor of Anesthesiology and Pediatrics, University of Pennsylvania
School of Medicine, and Director of Clinical Research, Division of General Anesthesia, Department of Anesthesiology
and Critical Care, The Children’s Hospital of Philadelphia, PA
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| Introduction: difficult to establish causation or association between MH susceptibility (MHS) and particular disease; no
gold standard for MHS diagnosis; determining causation via prospective randomized controlled trials and cohort studies
not feasible; case control studies better, but still difficult; only isolated case reports and series available for study; definitive
diagnosis often in doubt; recently, genetic linkage and pedigree analysis studies have furthered definitive diagnosis
of various syndromes and their link to MHS; majority of MHS patients phenotypically normal
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| Pathophysiology of MH: familial or spontaneous genetic mutation of calcium-regulating structure in muscle cell; several
proteins associated with calcium regulation, but most common ryanodine receptor (gene located on chromosome 19);
autosomal dominant; requires triggering agent (eg, volatile anesthetics, succinylcholine) or condition (eg, stress, extreme
hyperthermia); when muscle cell exposed to triggering agent, ryanodine receptor stays open too long, and allows in excess
calcium; calcium allows actin and myosin cross-bridging; sustained contracture exhausts adenosine triphosphate
(ATP), and muscle cell dies; results in respiratory acidosis from muscle cell CO2 , increased metabolism, rhabdomyolysis,
hyperkalemia, and muscular rigidity (from contracture)
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| Diseases definitely linked to MHS (genetic linkage or overwhelming clinical evidence): central core
myopathy—occurs in infancy or later; not progressive; often associated with kyphoscoliosis (age of onset and severity
variable); mutation also located on chromosome 19; many (but not all) people with central core disease test positive for
MH; assume patient susceptible to MH; multi-minicore disease (congenital myopathy)—rare; autosomal recessive;
ryanodine receptor mutation; congenital myopathy, with hypotonia and proximal weakness in infancy; may present with
joint contracture, torticollis, chest deformity, and cardiac manifestations; Evans myopathy—autosomal dominant; usually
subclinical; baseline creatine kinase (CK) normal or elevated; variable histology; King-Denborough syndrome—
phenotype; characterized by cryptorchidism, pectus carinatum, lumbar lordosis, thoracic kyphosis, ptosis, and strabismus;
elevated CK common; autosomal recessive; genotype unknown
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| Diseases in which triggering agents may cause signs and symptoms similar to MH: Duchenne’s muscular
dystrophy—progressive and fatal muscle wasting disorder; child likely born normal, but loses milestones in first
years of life; x-linked recessive; occurs in boys (1 in 3500 live births); pathophysiology includes absence of dystrophin
protein; beginning of signs and symptoms by 6 yr of age; signs and symptoms include inability to walk, progressive muscle
wasting, and cardiac abnormalities; death at 20 to 30 yr of age; associated anesthetic complications include hyperkalemia
with administration of succinylcholine, rhabdomyolysis with use of volatile anesthetics, and reports of MH; based on
studies, Food and Drug Administration (FDA) originally issued “black box” warning that succinylcholine contraindicated
in children; warning changed and now states succinylcholine indicated for emergency airway management only;
avoid use in boys with developmental delay or hypotonia; development of MH may be coincidental; may have false-positive
contracture test; true genetic association unlikely; recommendations—succinylcholine absolutely contraindicated;
volatile anesthetics relatively contraindicated; screen all boys for occult myopathies by inquiring about motor milestones
(eg, not normal for child to begin walking at ≥15 mo of age); McArdle’s disease—glycogen storage disease; signs and
symptoms include exercise intolerance and myoglobinuria; chromosome 11 mutation; autosomal dominant or recessive;
case reports of positive MH contracture test; treatment essentially same as with Duchenne’s disease (Duchenne’s muscular
dystrophy); channelopathies—include hypo- and hyperkalemic periodic paralysis and myotonia congenita; signs
and symptoms include occasional rigidity of masseter muscle; MH case reports show patients with abnormal contracture
tests; no genetic link to true MHS; prudent to avoid triggering agents; heat stroke—case reports; exercise-induced
rhabdomyolysis—case reports
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| Diseases purportedly linked to MHS: evidence of linkage weak or nonexistent; Noonan’s syndrome—similar
phenotype to King-Denborough syndrome; usually not myopathic; normal CK; no known association with MHS;
arthrogryposis—includes any congenital condition of joint contracture; no association with MHS; osteogenesis
imperfecta—signs and symptoms include easily fractured bones, short stature, and blue sclera; tendency to develop intraoperative
hyperthermia, but not MH; mitochondrial myopathies—no evidence of association with MHS; neuroleptic
malignant syndrome—reaction to antipsychotics; presentation similar to MH (also improves with dantrolene);
contracture test usually negative; no pathophysiologic link with MH
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| MULTIMODAL THERAPY FOR POSTOPERATIVE PAIN IN CHILDREN —Michael H. Joseph, MD, Assistant Professor
of Anesthesiology and Pediatrics, Keck School of Medicine of the University of Southern California, and Associate Director,
Comfort, Pain Management, and Palliative Care Program, Childrens Hospital Los Angeles
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| American Pain Society: on assessment and management of acute pain in infants, children, and adolescents, issued
statement that 1) pediatric acute pain experience involves interaction of physiologic, psychologic, behavioral, developmental,
and situational factors; 2) pain inherently subjective multifactorial experience that should be assessed and treated
accordingly; 3) physicians responsible for eliminating or assuaging pain and suffering of children when possible
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| McCaffery’s definition of pain: nursing origin; “whatever the experiencing person says it is, existing whenever he or
she says it does”
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| Anxiety and fear: can lead to pain, and pain leads to anxiety and fear; anxiety and pain systems internal and external
danger-sensing systems
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 | Regional anesthesia: combining medications—abundant literature on combining different medications with local anesthetic
for single-injection caudal anesthesia; addition of morphine to local anesthetic extends duration of caudal anesthesia;
clonidine also documented to extend duration of caudal anesthesia; morphine provides much denser analgesia,
but side effects significantly greater than with clonidine; some data that ketamine and midazolam also extend duration
of local anesthesia, but unclear whether neurotoxicity an issue; concern that combining nonsteroidal anti-inflammatory
drugs (NSAIDs) with ketorolac (eg, Toradol) for continuous infusion possibly associated with formation of epidural
hematoma; consensus of American Society of Regional Anesthesia and Pain Medicine (2002) that NSAIDs appear to
represent no added significant risk for development of spinal hematoma in patients receiving epidural and/or spinal anesthesia;
studies indicate use of little or no supplemental opioid with this technique; patient-controlled analgesia
(PCA)—used occasionally; regional anesthesia in spinal surgery—intrathecal morphine shown to improve analgesic
outcome in patients having spinal fusion; improves speed of return of gastrointestinal motility and of ambulation;
study data for epidural infusion in posterior and anterior spinal fusion more equivocal; retrospective studies have
shown improvement greater than with PCA alone; at speaker’s institution, most patients being prepared for posterior
spinal fusion receive intrathecal morphine followed by intravenous (IV) opioids
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| Local anesthetics: currently, no good pediatric studies; at speaker’s institution also use local infusion of bupivacaine
through “on-cue” system (greatly decreases need for supplemental morphine); at speaker’s institution, topical anesthesia
placed in all admission care sets; all surgical patients have automatic order for 4% liposomal lidocaine (L-M-X4);
nursing staff should know “that you expect topical anesthesia to be used for IV starts”; lidocaine and tetracaine (Synera)
and other topical anesthetic patches effective in 20 to 30 min
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| Opioids: titration to effect key; maximum safe dose determined by effect and side effect (not true of initial dose; in opioid-naive
patient, starting dose of morphine, 2 mg, and hydromorphone [eg, Dilaudid], 0.2-0.3 mg); fentanyl used
sparingly in postoperative period, except in intensive care unit (ICU), where patient on fentanyl drip; in patient with
normal airway and relatively normally intact neurologic system, if titrating to effect, first side effect sedation, not apnea;
speaker uses morphine as gold standard; evaluate dose given by converting opioid dosage into morphine equivalent;
transdermal fentanyl (patch) only opioid approved by FDA for use in children
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| Dosing: in general, avoid prn (ie, as needed) dosing; initially administer analgesic “around the clock”
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| PCA: reduces fluctuation between sedation and respiratory depression and pain; PCA used in children ≥7 yr of age (understand
concepts of more and less and can use PCA button effectively); children <7 yr of age placed on continuous
infusion, and nurse can administer booster doses through pump; PCA allows child to have control over pain (literature
in adults shows PCA often reduces opioid requirement); low-dose continuous infusion; only patient able to push button;
lockout intervals should be short; no booster doses; if patient injects many doses in 4-hr period, increase dose
(should not need to push >2 times per hour to stay comfortable); opioid choices include morphine and hydromorphone
(meperidine not used for long-standing postoperative pain management because normeperidine [metabolite of meperidine]
central nervous system irritant; can lead to agitation, irritability, and seizures); usual dosing with morphine,
0.02 to 0.04 mg/kg per PCA dose (6- to 10-min lockout); continuous infusion of same dose per hour; maximum starting
dose 2 mg in opioid-naive patient (PCA or continuous); usual dosing for hydromorphone, 3 to 5 µg/kg per PCA
dose, and continuous infusion of same dose per hour; speaker does not generally recommend use of codeine (can have
high nonresponder rate [4%-22% of population cannot convert to morphine] as well as side effects); hydrocodone and
oxycodone better oral choices (cleaner; fewer metabolites; better response; better medications for long-term oral pain
relief and for transition from IV to oral); if pain not adequately controlled, increase medication by 15% to 20% (q12h,
if necessary; calculate appropriate dose based on 24-hr usage); fears about dependence and addiction—in children,
rate of true addiction low; greater the length of time receiving opioid, greater the potential for dependence;
weaning necessary; most wean naturally as pain improves during healing; PCA management involves staff feedback
to patient; must assess situation (eg, is pain not controlled? is patient afraid or anxious? is patient just playing with
button?); psychologic benefits—child in control of pain management, does not have to ask for pain medication, and
free from bothering staff
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| PCA by proxy: analgesic infusion pump activated by someone other than patient; authorized agent-controlled analgesia
(AACA) involves either nurse or caregiver (must be properly educated; important in end-of-life patient and child
with significant neurodevelopmental disorder); study of parent- and/or nurse-controlled analgesia found good pain
control and normal nausea and pruritus, but 1.7% required naloxone for respiratory depression
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| Moderate pain: oxycodone—0.1 mg/kg q4-6h; hydrocodone—0.2 mg/kg (q6h if <2 yr of age, q4h if ≥2 yr of age);
nalbuphine—equipotent to morphine at lower doses; limited analgesic effect; fewer side effects; reverses significant opioid
dependence and opioid-induced side effects (eg, pruritus, nausea); can be used for PCA
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| Management of adverse effects: study of low-dose continuous- infusion naloxone (0.25 µg/kg per hour) vs saline; pruritus
decreased from 77% to 20%, and nausea decreased from 70% to 35%; analgesic properties equivalent; antihistamines
ineffective for reversal of opioid-induced pruritus (merely cause sleepiness and disinterest in itching); some
indication that ondansetron reverses pruritus and nausea, especially with intrathecal opioids; nalbuphine also effective
for pruritus; metoclopramide (eg, Reglan), trimethobenzamide (eg, Tigan), and prochlorperazine (eg, Compazine) also
effective for nausea; treatment for constipation includes corollary orders for bisacodyl (eg, Dulcolax); constipation rate
>90% with opioids given by continuous infusion
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| NSAIDs: beneficial with opioids; data show adding acetaminophen (eg, Tylenol) and/or other NSAIDs (eg, diclofenac,
ketorolac [eg, Toradol]) reduces opioid requirement (fewer side effects; limit ketorolac to 5 days of therapy); data on
bone healing and use of ketorolac “not very strong”; speaker uses standard dosing regimen (despite literature on high-
dose rectal and oral acetaminophen, which speaker considers equivocal)
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| Adjuvant medications: gabapentin—shown effective in reducing analgesic requirements in adult spinal fusion; also shown
to be neuroprotective in spinal muscular atrophy and to prevent and treat phantom limb pain; systemic clonidine—
shown effective in reducing overall opioid requirements in numerous postoperative settings; diazepam (eg, Valium)—
speaker uses for muscle relaxation; fast acting in low doses (0.1 mg/kg to maximum of 5 mg [even for patient >50 kg];
given q8h); use of ketamine in postoperative period equivocal
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| Psychologic strategies: decrease pain and fear by introducing yourself to patient, being friendly, and having “good customer
service”; providing education to family also reduces fear; distraction techniques—eg, bubbles, pinwheels, deep
breathing, toys; music therapy and animal-assisted therapy also effective at reducing pain; positive reinforcement—
important (“most children view their interactions with the health care environment as punitive”); enhances self-esteem
and mastery; encourages similar behavior; facilitates child’s (and parents’) effort to cope; relaxation and imagery —
have patient take 10 slow deep breaths and imagine pain going into lungs and leaving body as he or she breathes out; reduces
acute fear and anxiety; self-hypnosis—using videotape; shown to decrease postoperative pain
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| Physical strategies: acupuncture—more recent studies show benefit of P6 (also known as pericardium 6 or triple
heater 6) acupuncture injections, especially in postoperative nausea; growing body of literature for acupuncture used as
adjunct to analgesia, intra- and perioperatively; auricular acupuncture can also provide anxiolysis for parents;
massage—studies in adults show massage beneficial; positions of comfort—various positions can be used to isolate
extremity (eg, loving embrace or hug, instead of traditional restraining hold); assists patient in being in control
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| Ideal treatment of pain: be aggressive and prevent wind-up; use round-the-clock medication; believe patient; titrate to
effect; employ good cognitive and behavioral intervention
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Suggested Reading
Degotardi PJ et al: Development and evaluation of a cognitive-behavioral intervention for juvenile fibromyalgia. J Pediatr
Psychol 31:714, 2006; Epub 2005 Aug 24; Gold JI et al: Effectiveness of virtual reality for pediatric pain distraction
during i.v. placement. Cyberpsychol Behav 9:207, 2006; Huth MM et al: Imagery reduces children's post-operative pain.
Pain 110:439, 2004; Kotani N et al: Preoperative intradermal acupuncture reduces postoperative pain, nausea and vomiting,
analgesic requirement, and sympathoadrenal responses. Anesthesiology 95:349, 2001; Lambert SA: The effects of
hypnosis/guided imagery on the postoperative course of children. J Dev Behav Pediatr 17:307, 1996; Larach MG et al:
Hyperkalemic cardiac arrest during anesthesia in infants and children with occult myopathies. Clin Pediatr (Phila) 36:9,
1997; Maxwell LG et al: The effects of a small-dose naloxone infusion on opioid-induced side effects and analgesia in
children and adolescents treated with intravenous patient-controlled analgesia: a double-blind, prospective, randomized, controlled
study. Anesth Analg 100:953, 2005; Monitto CL et al: The safety and efficacy of parent-/nurse-controlled analgesia
in patients less than six years of age. Anesth Analg 91:573, 2000; Nathan A et al: Hyperkalemic cardiac arrest after
cardiopulmonary bypass in a child with unsuspected Duchenne muscular dystrophy. Anesth Analg 100:672, 2005; Nilsson U
et al: A comparison of intra-operative or postoperative exposure to music--a controlled trial of the effects on postoperative
pain. Anaesthesia 58:699, 2003; Schmitt HJ et al: Dystrophin deficiency, inhalational anesthetics, and rhabdomyolysis.
Paediatr Anaesth 17:94, 2007; Shenkman Z et al: Acupressure-acupuncture antiemetic prophylaxis in children undergoing
tonsillectomy. Anesthesiology 90:1311, 1999; Sobo EJ et al: Canine visitation (pet) therapy: pilot data on decreases in
child pain perception. J Holist Nurs 24:51, 2006; Tang TT et al: Anesthesia-induced rhabdomyolysis in infants with unsuspected
Duchenne dystrophy. Acta Paediatr 81:716, 1992; Wang SM et al: P6 acupoint injections are as effective as
droperidol in controlling early postoperative nausea and vomiting in children. Anesthesiology 97:359, 2002; Wang SM et
al: Parental auricular acupuncture as an adjunct for parental presence during induction of anesthesia. Anesthesiology
100:1399, 2004.
Educational Objectives
| The goals of this program are to improve management of malignant hyperthermia-susceptible disease in children and to improve
postoperative pediatric pain management. After hearing and assimilating this program, the participant will be better
able to:
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| 1. Recall the pathophysiology of malignant hyperthermia (MH).
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| 2. Identify those diseases definitely linked to MH susceptibility (MHS), those that do not predispose to MHS, and those
purportedly linked to MHS.
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| 3. Evaluate the role of pharmacologic therapy in overall multimodal pain management, focusing especially on regional
anesthesia, opioids, and side-effect management.
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| 4. Describe patient-controlled analgesia and authorized agent-controlled analgesia.
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| 5. Utilize psychologic and physical strategies for multimodal pain management.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose relevant
financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts
were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial
interest. For this program, the faculty reported nothing to disclose.
Acknowledgements
Drs. Litman and Joseph spoke at the 45th Annual Clinical Conference in Pediatric Anesthesiology, held February 9-
11, 2007, in Anaheim, CA, and sponsored by the Pediatric Anesthesiology Foundation, Childrens Hospital Los Angeles.
The Audio-Digest Foundation thanks the speakers and the sponsor for their cooperation in the production of this
program.
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