CHRONIC PAIN/CPR UPDATE
| CURRENT TRENDS AND NEW DEVELOPMENTS IN CHRONIC PAIN MANAGEMENT—Mark S. Wallace, MD,
Professor of Clinical Anesthesiology, and Director, Center for Pain and Palliative Medicine, University of California, San
Diego, School of Medicine
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| Pain treatment continuum: moves from least invasive to most invasive; not necessarily related to efficacy of treatment;
begin with psychologic and physical approaches (insurance companies do not pay or only pay for limited number
of treatments), followed by topical medications, systemic medications, and, finally, interventional therapies (after more
conservative therapies have failed)
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| Primary care physician as coordinator: heads-up multidisciplinary team (rather than pain specialist); several medical
specialties help manage patient; pain specialist now consultant to primary care physician; unfortunately, primary care
physicians sometimes do not take responsibility for these patients
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| Pain assessment scales: multiple assessment scales used to determine intensity of pain; 11-point Likert scale used in
clinic (other scales more for research); 2-point change equal to large improvement in overall satisfaction; 4-point change
(50% reduction in pain intensity) indicates even greater improvement
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| Diagnosis of neuropathic pain: no measures or tests available to indicate patient has neuropathic pain; often based on
physical examination and history; questionnaire developed by Backonja determined that presence of numbness, tingling,
and increased pain due to touch had high correlation with neuropathic pain; also look at pain distribution (eg, sock-and-
glove distribution may indicate peripheral neuropathy)
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| Diagnostic studies and limitations: studies such as nerve conduction velocity [NCV], x-ray, or electromyography
[EMG] not helpful if negative; positive studies helpful, but have limitations; eg, nerve conduction study only provides information
about large myelinated fibers (but nothing about small myelinated fibers; disease in these fibers may lead to
ongoing pain); functional magnetic resonance imaging shows changes in brain chemical composition or fluid flow; appears
to respond to placebo
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| Approach to treatment: diagnose underlying problem first, then treat underlying condition; if unable to determine underlying
condition or if pain persists, provide symptomatic treatment; goal to reduce pain, and beyond that, reduce psychologic
distress, improve quality of life, and improve overall physical functioning; “there is the thought that we can
prevent many of these pain syndromes with early treatment”
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| Components of pain management: biologic—pharmacologic and/or nonpharmacologic therapies; psychologic—
mood disturbances; anxiety disorders; sleep disturbances; rehabilitative—family and social relations; work; physical
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| Nonpharmacologic options: biofeedback; relaxation therapy; acupuncture; meditation
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| Pharmacotherapeutic considerations: efficacy of treatment (eg, multicenter randomized double-blind placebo-controlled
trials?); clinical experience (eg, widely used?); safety; ease-of-use; cost
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| Treatments approved by Food and Drug Administration (FDA) for neuropathic pain: pregabalin (approved
for peripheral diabetic neuropathy [PDN] and postherpetic neuralgia [PHN]); duloxetine (antidepressant; for
PDN); lidocaine patch (5%; for PHN); gabapentin (for PHN); carbamazepine (for trigeminal neuralgia)
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| Lidocaine patch (5%): pliable; ≤3 patches applied once daily (12 hr on, 12 hr off); efficacy demonstrated in 3 randomized
controlled trials; minimal systemic absorption; no drug interactions; mechanical barrier decreases allodynia; acts
through blockade of peripheral sodium channels
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| Gabapentin: calcium channel modulator; limited intestinal absorption; difficult to titrate; delayed onset (9-14 days required to
reach peak effectiveness); nonlinear pharmacokinetics (“the more you give, the less it’s absorbed”); usually well tolerated (dizziness
and sedation can occur); FDA-approved for ≤1800 mg daily
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| Pregabalin: similar in mechanism to gabapentin; also calcium channel modulator; but linear pharmacokinetics; rapid onset
of action; easy to titrate; robust efficacy confirmed in 6 multicenter randomized placebo-controlled trials; favorable safety
and tolerability trials; effective dose, 150 mg daily; effective for patients refractory to other therapies and vice-versa;
schedule V controlled substance (equivalent to guaifenesin [eg, Robitussin] with codeine)
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| Antidepressants: tricyclic antidepressants (TCAs)—efficacious in treatment of neuropathic pain, but selective serotonin
reuptake inhibitors (SSRIs) inconsistent; problems with TCAs include possible severe side effects and delayed onset (4-
8 wk; high rate of noncompliance); selective norepinephrine reuptake inhibitors (SNRIs)—duloxetine shown to have
good analgesic properties, rapid onset, and good side effect profile (contraindicated in preexisting hepatic dysfunction); venlafaxine
also has delayed onset of action, but side effect profile “much better” than TCAs
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| Opioid therapy: should be titrated for therapeutic efficacy; fixed-dose regimens generally preferred over as-needed regimens
(for long-term noncancerous patients); document treatment plans and outcomes; consider use of opioid written
care agreement; can be effective in neuropathic pain; fewer side effects than TCAs or anticonvulsant drugs; prophylactic
bowel regimen necessary for constipation; understand difference between addiction, tolerance (greater amount of drug
needed to maintain therapeutic effect), physical dependence, and pseudoaddiction (behavior suggestive of addiction;
caused by undertreatment of pain); mu-opioid receptor polymorphisms appear to increase risk for drug abuse, protect
against opioid side effects, and alter response to opioid analgesia
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Interventional Therapies
| Evidentiary challenges of surgical or minimally invasive procedures: ethical limitations of blinding surgical
techniques; placebo use that prolongs suffering and yet exposes to surgical risk; cost prohibition; difficulties of blinding
studies; ability to recruit adequate numbers of patients for sham procedures
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| Epidural steroid injections: nucleus pulposus rich in phospholipase A; ruptured disc spills contents on nerve, producing
intense inflammatory response; localized placement of steroids reduces inflammation; injection techniques include
interlaminar, transforaminal, and caudal; speaker uses interlaminar approach first; if no response, switches to transforaminal;
minimal complications with lumbar interlaminar epidural steroid injection (eg, dural puncture headache); more serious
complications with cervical and thoracic steroid injections (eg, stroke with cervical transforaminal approach);
transforaminal approach in cervical or thoracic region should use nonparticulate steroids (eg, dexamethasone [Decadron]);
also risk for spinal cord injury with cervical epidural steroid injection using interlaminar approach
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| Radiofrequency ablation techniques: high temperature ablates all nerve fibers; low temperature (pulsing) appears
to stimulate gene expression in central nervous system and leads to ongoing pain relief; studies show efficacy with radiofrequency
neurotomy; minimal safety concerns (possible neuritis or cutaneous dysesthesia)
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| Intradiscal electrothermal (IDET) annuloplasty: weakened disc results in leakage of nucleus pulposus, causing
inflammation of outer layers; heating melts collagen fibers and results in remodeling of disc and neurolysis of C fibers;
one study demonstrated significant improvement in pain; major safety complications include discitis, nerve root trauma,
increasing back pain, catheter breakage, post-IDET disc herniation, and cauda equina syndrome
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| Percutaneous disc decompression: multiple techniques, including nucleoplasty, laser-assisted saphenous endoablation,
and Dekompressor (percutaneous lumbar disc decompression); limited evidence of effectiveness
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| Epidural adhesiolysis: method to “break up” scarring in epidural space after surgery; infusions of hypertonic saline
and steroids; limited evidence of effectiveness
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| Sympathetic blockade: limited efficacy data in complex regional pain syndrome; expert panel recommendations in
2002 stated it should be considered in refractory patient and should be part of comprehensive pain treatment program, not
as single modality; good evidence that it relieves pain of herpes zoster; some evidence suggests it decreases PHN, but no
evidence of relief of pain associated with PHN
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| Celiac and hypogastric plexus blocks: efficacy in pancreatic cancer and upper abdominal cancer, but almost no role
in treatment of chronic abdominal noncancerous pain
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More Invasive Therapies
| Intraspinal drug therapy: problems with efficacy studies (and inherent to therapy)—include difficulty blinding
studies, psychologic screening methods not described, no description of screening methods used to determine if implanted infusion
pump indicated, no control groups, and no randomization; ziconotide (Prialt)—blocks calcium channel; decreases
neurotransmitter release; blocks pain conduction in spinothalamic tract; precautions include cognitive impairment, memory
impairment, and serum creatine kinase (CK) elevation (titrate slowly)
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| Drug mixtures: problems include drug compatibility, drug precipitation at high concentrations, and granuloma formation
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| Spinal cord stimulation: 2 delivery methods; constant voltage—increased resistance leads to decreased current; decreased
resistance leads to increased current; constant current —changes voltage to maintain constant current, eg, with increased
resistance, voltage increases
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| CARDIOPULMONARY RESUSCITATION (CPR) UPDATE—Benjamin S. Abella, MD, Assistant Professor of Emergency
Medicine, and Associate Director, Center for Resuscitation Science, University of Pennsylvania School of Medicine,
Philadelphia
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 | Epidemiology: 300,000 to 400,000 arrests annually in United States; majority of patients relatively healthy and ambulatory
before cardiac arrest (3 in 4 occur outside hospital; 1%-5% survival in out-of-hospital setting; greater survival for
in-hospital)
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| Fundamentals of therapy: CPR mainstay of initial therapy; public increasingly aware of cardiac arrest partly due to automatic
external defibrillator (AED; beginning to make impact on initial survival)
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| Mortality: majority of patients die during resuscitation efforts; fraction of patients achieve return-of-spontaneous-circulation;
many patients die before leaving hospital; majority die 24 to 48 hr after initial survival
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| Guidelines process: every 5 yr American Heart Association (AHA) convenes conference; several hundred experts in resuscitation
from emergency medicine, cardiology, anesthesiology, and critical care; review data to see if any changes
warranted; new guidelines published in November 2005 for CPR, basic life support, and advanced cardiac life support
(ACLS)
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| Changes in CPR guidelines
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| Chest compressions: Hallstrom study found improved survival in group that received chest compression alone (ie, no
gaps in compression for rescue breaths), compared to standard CPR (≈15% vs ≈10%); results may be due to easier mechanics
rather than gaps in chest compression; another study indicates that details of CPR important for hemodynamics
and ultimately survival; 2 recent studies have shown that CPR may actually be more important than defibrillation under
certain circumstances (survival improved when defibrillation delayed to give CPR first); speaker’s study recommended
chest compression rate of 100/min; common deficiencies in CPR performance include frequent pauses,
shallow compressions, and hyperventilation
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| Impact on guidelines: recommended CPR ratio (compressions/ventilations) 30:2, not 15:2; minimize pauses; do not emphasize
ventilation; emphasize chest compressions; monitor performance; improve quality of resuscitation care (eg,
avoid hyperventilation)
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| Defibrillation waveform: standard defibrillators gave unipolar shock (“monophasic,” usually 200 or 300 J); with newer
defibrillators, polarity reverses during mid shock (“biphasic,” usually 150 or 200 J); impact on guidelines—biphasic
defibrillator has equivalent or higher efficacy for termination of ventricular fibrillation (VF) than monophasic defibrillator
(class IIa recommendation)
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| Changes in drug recommendations: no supporting data for majority of currently used ACLS medications; clinical
studies difficult to perform; animal studies not always predictive of clinical setting; vast majority show no differences
in outcome; sodium bicarbonate and calcium not recommended for routine use in cardiac arrest (specific subsets in
which helpful); amiodarone helpful, but no difference in hospital discharge rates; AHA has endorsed amiodarone (vs
lidocaine) for VF and ventricular tachycardia arrest; 300 mg intravenous bolus recommended; AHA down-graded vasopressin
to class indeterminate (no data supporting use over epinephrine)
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| Reasons for drug study failures: none of clinical studies take into account CPR quality (eg, soon-to-be-published study
shows that in “real-world CPR,” epinephrine never entered central circulation); in future, more emphasis on studies
that rigorously look at quality of care
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| Changes in postresuscitation care
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| Therapeutic hypothermia: mechanisms of hypothermia—ischemia can cause reactive O2 species regeneration, inflammatory
cascades, and mitochondrial dysfunction; uncontrolled reperfusion seems to amplify processes at cellular level; leads
to clinical problems, including vascular dysfunction, cerebral edema, cell death, and organ dysfunction; hypothermia
eliminates these problems; practical issues—cooling at 32° to 34°C for 12 to 24 hr; questions include how to cool?
when to start cooling? how deep to cool? when and how to rewarm? other hypothermia applications—cooling as brain
protection (eg, traumatic brain injury; subarachnoid hemorrhage; cerebrovascular accident; fever control); website—
www.med.upenn.edu/resuscitation/hypothermia/
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| Impact on CPR guidelines: recommend hypothermia after out-of-hospital VF arrest (class IIa recommendation); recommend
cooling after in-hospital arrest or other rhythms (weaker recommendation ([class IIb]); National Registry of CPR
(NRCPR) in-hospital registry of cardiac arrest; variety of possible solutions to improve CPR quality, especially before
shock, include improve ACLS training, better filtering software to remove compressions, mechanical compression devices,
and AEDs for in-hospital arrest
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Suggested Reading
Abella BS et al: Quality of cardiopulmonary resuscitation during in-hospital cardiac arrest. JAMA 293:305, 2005;
Aung K et al: Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med 165:17, 2005;
Backonja M et al: Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus:
a randomized controlled trial. JAMA 280:1831, 1998; Backonja MM et al: Neuropathic pain questionnaire--short
form. Clin J Pain 19:315, 2003; Berg RA et al: Adverse hemodynamic effects of interrupting chest compressions for
rescue breathing during cardiopulmonary resuscitation for ventricular fibrillation cardiac arrest. Circulation 104:2465,
2001; Cobb LA et al: Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital
ventricular fibrillation. JAMA 281:1182, 1999; Hallstrom AP: Dispatcher-assisted "phone" cardiopulmonary resuscitation
by chest compression alone or with mouth-to-mouth ventilation. Crit Care Med 28:N190, 2000; Krause SJ
et al: Development of a neuropathic pain questionnaire. Clin J Pain 19:306, 2003; Kudenchuk PJ et al: Transthoracic
incremental monophasic versus biphasic defibrillation by emergency responders (TIMBER): a randomized comparison
of monophasic with biphasic waveform ascending energy defibrillation for the resuscitation of out-of-hospital
cardiac arrest due to ventricular fibrillation. Circulation 114:2010, 2006; Maihofner C et al: Neural activation during
experimental allodynia: a functional magnetic resonance imaging study. Eur J Neurosci 19:3211, 2004; Peberdy
MA et al: Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National
Registry of Cardiopulmonary Resuscitation. Resuscitation 58:297, 2003; Rowbotham MC et al: Lidocaine patch:
double-blind controlled study of a new treatment method for post-herpetic neuralgia. Pain 65:39, 1996; Smith TJ et
al: Randomized clinical trial of an implantable drug delivery system compared with comprehensive medical management
for refractory cancer pain: impact on pain, drug-related toxicity, and survival. J Clin Oncol 20:4040, 2002; Turk
DC: Are pain syndromes acute or chronic diseases? Clin J Pain 16:279, 2000; Wik L et al: Delaying defibrillation to
give basic cardiopulmonary resuscitation to patients with out-of-hospital ventricular fibrillation: a randomized trial.
JAMA 289:1389, 2003.
Educational Objectives
| The goals of this program are to improve clinical outcomes in patients with neuropathic pain, and to update physicians on
the latest recommendations in cardiopulmonary resuscitation (CPR) so as to improve survival in cardiac arrest. After hearing
and assimilating this program, the clinician will be better able to:
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| Review the diagnosis of neuropathic pain.
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| Examine the components of pain management.
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| Compare treatments approved by the Food and Drug Administration for neuropathic pain.
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| List the interventional therapies for neuropathic pain.
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| Examine the latest changes in cardiopulmonary resuscitation guidelines, drug recommendations, and postresuscitation
care.
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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 following has been disclosed: Dr. Abella has received research funding
from Philips Medical Systems, Laerdal Medical Corp, and the National Institutes of Health, and speaking honoraria
from Philips, Laerdal, Zoll Medical Corp, and Alsius Corp.
Acknowledgements
Dr. Wallace spoke at Anesthesiology Update 2007, held January 3-6, 2007, in San Diego, CA, and sponsored by the
University of California, San Diego, School of Medicine, Department of Anesthesiology; Dr. Abella, at Challenges for
Clinicians, held December 1-3, 2006, in Chicago, IL, and sponsored by the University of Chicago Pritzker School of
Medicine, Department of Anesthesia and Critical Care. The Audio-Digest Foundation thanks the speakers and the sponsors
for their cooperation in the production of this program.
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