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Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e

Chapter 35: Acute Pain Management James Ducharme

INTRODUCTION

Pain is the most common presenting symptom for patients coming to the ED, with 75% to 80% of all patients

having pain as their primary complaint.1 Despite increasing research and information about pain

management, oligoanalgesia, or the under treatment of pain, persists.2,3,4,5 While all patients are susceptibleto oligoanalgesia, certain subgroups, such as ethnic minorities, the aged, the very young, and those with

diminished cognitive function, are more at risk (Table 35-1).6,7,8,9 Pain management is further influenced byconcerns of prescription opioid misuse, a rising concern in all age groups but most notably in adolescents

and young adults. Pain and addiction are not mutually exclusive,10 and appropriate treatment of acute painshould not be withheld for fear of facilitating drug misuse.

TABLE 35-1

Barriers to Adequate ED Pain Control

Patient Related Provider Related System Related

Ethnicity, gender, age (very

young, very old)

Diminished cognitive function

Fear of medications: addiction,

side e�ects

Acceptance of pain as being

inevitable

Unwillingness to bother

healthcare providers

Inadequate education

No objective measuring tool for pain

Accepting only pain reports that conform

to our expectations

Perception of addiction and drug-seeking

behavior

Lack of clearly articulated

standards

Paucity of treatment

guidelines

Fear of regulatory sanctions

Lack of healthcare provider

accountability

Specific measures to treat pain should occur in addition to, and at the same time as, treatment of theunderlying illness or injury. It is not possible to generalize the extent and quality of pain control needed for aspecific patient. For example, pain is an indicator of ongoing cardiac ischemia, and the goal should be toeliminate all pain. On the other hand, a patient with a traumatic injury may choose to endure more pain out

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of personal or cultural beliefs. Physicians may limit analgesics in those with head injuries to perform serialneurologic examinations. Whenever possible, medications that act on specific sites that initiate the painsignal—a mechanistic approach—are preferred to agents such as opioids that mask pain, which is asymptomatic approach. Current migraine treatment is an excellent example of the mechanistic approach;

preferred treatment includes a serotonin agonist (triptan)11 or a dopamine antagonist (phenothiazine),12

rather than opiates.13,14

PATHOPHYSIOLOGY

Pain is the physiologic response to a noxious stimulus, whereas su�ering—the expression of pain—ismodified by the complex interaction of cognitive, behavioral, and sociocultural dimensions. Individual painexperience is therefore not static, but varies depending on current and past medical history, physical andemotional maturity, cognitive state, meaning of pain, family attitudes, culture, and environment. Emotionscan modify pain either negatively or positively: fear and anxiety may accentuate pain, or pain can besuppressed completely if an essential task must be performed or if there is acute concern about a loved one.

The peripheral nervous system (e.g., nociceptors, C fibers, A-δ fibers, and free nerve endings) initiates thesensation of somatic pain by responding to a noxious stimulus and sending a neuronal discharge to the

dorsal horn of the spinal cord.15 Neurons in the dorsal horn of the spinal cord integrate and modulate inputfrom multiple peripheral nerves and other sensory stimuli. Transmission then proceeds up the spinal cord tothe CNS (e.g., hypothalamus, thalamic nuclei, limbic system, and reticular activating system) where furtherintegration and processing generate the perception of pain. Identification and localization of pain, cognitiveinterpretation, and triggering of emotional and physiologic reactions also occur at these central sites. Unlikesomatic pain, which is easily localized, visceral pain pathways are more complex and di�er in structure fromsomatic pain pathways, which may explain the poor localization of visceral pain.

Opioid analgesics work by binding to receptors in the spinal cord and brain. There are four types of opioidreceptors: three classic families (delta, kappa, and mu, each with identified subtypes) and nociceptin, areceptor with significant structural homology. These receptors are found in the brain, spinal cord, and GItract where their physiologic function is to interact with endogenous dynorphins, enkephalins,endomorphins, endorphins, and nociceptin. Opioid analgesics interact with these receptors in varyingdegrees, accounting for the di�erence in desired and adverse e�ects among the drugs in this class.Stimulation of the mu-1 (μ1) receptor produces supraspinal analgesia. Stimulation of the mu-2 (μ2) receptor

results in euphoria, miosis, respiratory depression, and depressed GI motility. Stimulation of the delta (δ)receptor produces analgesia, but less than the μ1 receptor, and also exerts an antidepressant e�ect.

Stimulation of the kappa (κ) receptor produces dysphoria, along with dissociation, delirium, and diuresis byinhibiting antidiuretic hormone release.

EVALUATION

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Document the degree of pain on initial assessment. This process serves to identify patients with severe pain,facilitates treatment, and meets the mandates of regulatory agencies that promote assessing and treatingpain. ED pain assessment should determine duration, location, quality, severity, and exacerbating andrelieving factors. The patient's subjective reporting of pain, not the physician's impression, is the basis forpain assessment and treatment. There is at best a weak correlation between nonverbal signs, such astachycardia, tachypnea, and changes in patient expression and movements, and the patient's report of pain,

so do not rely on these to determine the severity of a patient's pain16,17 or response to treatment.18 Becausepain is dynamic and changes with time, periodic pain reassessment is needed.

Although standardized scales for measuring reported pain are commonly used, their impact on e�ective pain

control is uncertain.19,20 The primary value of pain scales is their essential role in research enablingreproducible comparisons of interventions. Some studies have suggested that the use of pain scales mayactually decrease the provision of analgesics. Given the subjectivity both of pain reporting and the provider'sinterpretation of such reporting, the use of simple descriptors such as "a little" or "an awful lot" is equallyvalid in the clinical setting. What is important is that the patient's subjective reporting should be the basis forassessment and management. For most, but not all, painful conditions, the goal is to control pain to the levelthe patient desires. Asking if the patient requires more analgesic may even be simpler and accomplish more

than using any standardized pain evaluation tool.21,22

PAIN SCALES

The purpose of pain scales is to quantitate pain severity, guide the selection and administration of ananalgesic agent, and reassess the pain response to determine the need for repeated doses or more e�ectiveanalgesics. Several self-report instruments are valid in patients with acute pain, and some require only averbal response (Table 35-2). Each tool has advantages and specific limitations. ED personnel in any onelocation should use the same tool so information collected is standardized. A value assigned by a patient is

not an absolute value but rather a reference point based on past personal experience.23

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TABLE 35-2

Pain Scales29A

Scale Method Comments

Adjective

rating scale

(Figure 35-

1)

Patient rates pain by choosing from an

ordered list of pain descriptors, ranging

from no pain to worst possible pain, with

allowance for marks between discrete

labels.

Easy to administer.

Visual

analog

scale (VAS)

(Figure 35-

2)

Patient places a mark that best describes

pain intensity along a 10-cm linear scale

marked at one end with a term such as no

pain and at the other end with worst

imaginable pain.

Pain intensity measured in millimeters from

the no-pain end.

A di�erence of 13 mm is the minimum

clinically significant change noticeable by

patients, whereas an average decrease of 30

mm appears to be the minimum acceptable

change for pain control.*

Numeric

rating scale

(Figure 35-

3)

The patient is asked to self-report pain on

a scale of 0 to 10 with descriptors.

Can be used in patients with visual, speech, or

manual dexterity di�iculties by using upheld

fingers.

Not as discriminating as the VAS.

5-Point

global scale

Patient rates pain as:

0 = none

1 = a little

2 = some

3 = a lot

4 = worst possible

A decrease of 1 point is a large change; scales

with more choices allow monitoring of small

changes in pain and may be more sensitive to

changes.

Verbal

quantitative

scale

The patient is asked to self-report pain on

a scale of 0 to 10 without descriptors.

Most commonly used scale; easy to administer.

FIGURE 35-1.

Pain scale: Adjective rating scale.

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FIGURE 35-2.

Pain scale: Visual analog scale (VAS).

FIGURE 35-3.

Pain scale: Numeric rating scale.

PAIN SCALE PERFORMANCE IN SPECIAL PATIENT POPULATIONS

The elderly o�en report pain di�erently from younger patients because of physiologic, psychological, andcultural changes associated with aging. Visual, hearing, motor, and cognitive impairments can be barriers toe�ective pain assessment. Using a numerical pain scale, the elderly may also experience a decrease in the

minimum clinically significant noticeable di�erence in acute pain over time.24,25 Family members andcaregivers are o�en able to judge nonverbal actions of the patient as representing pain or distress, so theyshould be used if available to help with pain assessment in the noncommunicating elderly patient.

Trauma patients and those with acute intoxication do not perform as well on pain scales.26 Women are more

likely to express pain and to actively seek treatment for pain,27,28 yet there is a tendency to underestimateand undertreat pain in women. Ethnicity of both the patient and the physician has a bearing on di�erent

cultural concepts of pain and on the characteristics of culturally appropriate pain-related behaviors.7

Translators and family members should be asked to provide assistance. There is also interplay between the

ethnicity of the patient and that of the physician.7 When there are language di�iculties or cross-cultural

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Abbreviations: NRS = numeric rating scale; VAS = visual analog scale.

di�erences, the visual analog scale is the preferred pain assessment tool because it is the least a�ected bythese factors.

PHARMACOLOGIC PAIN TREATMENT

The administration of pharmacologic agents is the mainstay of acute pain management. The key to e�ectivepharmacologic pain management in the ED is selection of an agent appropriate for the intensity of pain and

it's time to onset of analgesic activity, ease of administration, safety, and e�icacy.29 Acute pain is usuallyaccompanied by anxiety and feelings of loss of control. If verbal reassurance combined with an analgesicdoes not su�ice, an anxiolytic may be useful.

The "tiered approach" to pain management starts with an agent of low potency regardless of pain intensity,assesses the response a�er a clinically relevant period, and sequentially changes to agents of higher potencyif pain persists. The tiered approach for acute pain management unnecessarily subjects the patient to moreprolonged su�ering. It is preferable to select initial analgesics that are appropriate to treat the intensity(mild, moderate, or severe) of the patient's pain. Agents such as nonsteroidal anti-inflammatory drugsshould be considered for mild to moderate pain, and systemic opioids for moderate to severe pain (Table 35-3). In specific instances such as renal and biliary colic, a parenteral nonsteroidal anti-inflammatory drug maycontrol severe pain, although combination therapy with an opioid is usually superior.

TABLE 35-3

Pain Severity with VAS or NRS

Pain Severity VAS (0 to 100 mm) or NRS (0 to 10)

Mild VAS: 0 to 30–40 mm or NRS: 0 to 3–4

Moderate VAS: 40 to 60–70 mm or NRS: 4 to 6–7

Severe VAS: >60–70 mm or NRS: >6–7

When possible, local anesthesia is a useful adjunct (Table 35-4). Peripheral nerve blockade for pain controland for procedures is a useful option, especially if guided by US (see chapter 36, Local and Regional

Anesthesia).30,31

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TABLE 35-4

Pain Treatment: Comparison of Pharmacologic Classes

Class Route Advantages Disadvantages

Nonsteroidal anti-

inflammatory

drugs

PO Mild/moderate somatic

pain plus severe colicky

pain

Use caution in the elderly and in those

with renal, GI, and hematologic disorders

Parenteral Does not require GI

absorption

No more e�ective than PO

More costly

Opioids PO Can be e�ective if

adequately dosed

Variable absorption, somewhat slower

onset

IM No IV access required Painful injections

Unreliable absorption

IV Ideal for titrated dosing Need for IV access

Local anesthetics Infiltration Technical ease Limited duration of action

Peripheral

nerve

block

Opioid sparing Technically di�icult at some sites

Facilitated with use of US guidance

OPIOID ANALGESICS

Opioid analgesics are the cornerstone of pharmacologic management of moderate to severe acute pain(Table 35-5). The term opiate refers to agents that are structurally related to natural alkaloids found in opium,the dried resin of the opium poppy. The term opioid describes any compound with pharmacologic activitysimilar to an opiate, regardless of chemical structure. Opioid use in the ED is o�en a�ected by concern for theprecipitation of adverse events, such as respiratory depression or hypotension, or for facilitating drug-seeking behavior. As noted, a greater concern is oligoanalgesia and inadequate dosing of opioids when used.Considerations for use of opioids include (1) desired onset of action, (2) available routes of administration,(3) achievable frequency of administration, (4) concurrent use of nonopioid analgesics and adjunctiveagents, (5) possible incidence and severity of side e�ects, and (6) continuation of the agent in an inpatient orambulatory setting

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TABLE 35-5

Pain Treatment: Initial Opioid Dosing

Drug [Class]Typical Initial

Adult DosePharmacokinetics Comments

Morphine

[natural

alkaloid]

0.1

milligram/kg

IV

Onset: 1–2 min

(IV) and 10–15

min (IM/SC)

Histamine release may produce transient

hypotension or nausea and emesis; neither

require routine adjunctive treatment.

10 milligrams

IM/SC

Peak e�ect: 3–5

min (IV) and 15–

30 min (IM)

 

0.3

milligram/kg

PO

Duration: 1–2 h

(IV) and 3–4 h

(IM/SC)

 

Hydromorphone

[semi-synthetic

alkaloid]

0.015

milligram/kg

IV

Onset: 3–5 min

(IV)

More euphoria inducing than morphine.

1–2

milligrams IM

Peak e�ect: 7–10

min (IV)

Duration: 2–4 h

(IV)

Fentanyl

[synthetic

piperidine]

1.0

microgram/kg

IV

Onset: <1 min (IV) Less cardiovascular depression than morphine.

High doses can cause chest wall rigidity (>5

micrograms/kg IV).Peak e�ect: 2–5

min (IV)

Duration: 30–60

min (IV)

100-

microgram

nasal spray in

1 nostril

  Used for breakthrough pain in opioid-tolerant

cancer patients.

Wait >2 h before treating another episode.

May increase dose by 100 micrograms per

episode.

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Drug [Class]Typical Initial

Adult DosePharmacokinetics Comments

100-

microgram

buccal

mucosa tablet

  Used for breakthrough pain in opioid-tolerant

cancer patients.

May repeat a�er 30 min.

Wait >4 h before treating another episode.

May increase dose by 100 micrograms per

episode.

Available transmucosal forms not bioequivalent.

Meperidine

(pethidine)

[synthetic

piperidine]

1.0–1.5

milligrams/kg

IV/IM

Onset: 5 min (IV) Contraindicated when patient is taking a

monoamine oxidase inhibitor.

Neurotoxicity may occur when multiple doses

are given in the presence of renal failure.

Peak e�ect: 5–10

min (IV)

Duration: 2–3 h

(IV)

Oxycodone

[semi-synthetic

alkaloid]

5–10

milligrams PO

OR

0.125

milligram/kg

PO

Onset: 10–15 min

(PO)

Lower incidence of nausea.

Possible inadvertent acetaminophen overdose

with combination agents.

30 milligrams

PR

Duration: 3–6 h

(PO)

Hydrocodone

[semi-synthetic

alkaloid]

5–10

milligrams PO

Onset: 30–60 min

(PO)

Lower incidence of nausea.

Possible inadvertent acetaminophen overdose

with combination agents.Duration: 4–6 h

(PO)

Codeine [natural

alkaloid]

30–60

milligrams PO

Onset: 30–60 min

(PO)

High incidence of GI side e�ects.

Some patients cannot convert to codeine-6-

glucuronide and morphine.

Possible inadvertent acetaminophen overdose

with combination agents.

30–100

milligrams IM

Duration: 4–6 h

(PO)

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Drug [Class]Typical Initial

Adult DosePharmacokinetics Comments

Tramadol [other] 50–100

milligrams PO

Onset: 10–15 min

(PO)

CNS side e�ects common.

Duration: 4–6 h

(PO)

Opioids need to be titrated to e�ect; patients di�er greatly in their response to opioid analgesics.32,33,34

Variation in pain reduction is related to age, initial pain severity, and previous or chronic exposure to opioids,

but not body mass35,36 or gender.37 Relative potency estimates provide a rational basis for selecting the

appropriate starting dose to initiate analgesic therapy,38 changing the route of administration (e.g., fromparenteral to PO), or switching to another opioid (Table 35-6), but undue reliance on these ratios is an

oversimplification with potential for over- or underdosing.39

TABLE 35-6

Equipotent Opioid Doses

DrugEquipotent IV Dose

(milligrams)

Equipotent PO Dose

(milligrams)

Equipotent IM Dose

(milligrams)

Morphine 10 60 (acute) and 30 (chronic) 10

Hydromorphone 1.5 7.5 1.5

Fentanyl 0.1 0.2 (transmucosal) 0.1

Meperidine

(pethidine)

75 300 75

Oxycodone 15 30 15

Hydrocodone — 30 —

Codeine 130 200 130

Tramadol — 350 —

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Opioid hypersensitivity is uncommon, and true allergic reactions are extremely rare. There is minimalevidence of clinical cross-sensitivity within opioid classes, with the possible exception that cross-sensitivityhas been suggested among the piperidines (fentanyl, alfentanil, sufentanil, and meperidine). Until more isknown, it would be prudent to switch to a drug from a di�erent opioid class if a patient develops ahypersensitivity reaction. When used in equianalgesic doses, there is no compelling evidence to recommendone opioid over another. As much as possible, avoid using multiple agents, and titrate a single drug to thedesired e�ect.

The use of meperidine is discouraged for several reasons: it is o�en underdosed; meperidine can interactwith many drugs to precipitate a serotonin syndrome; and the parent drug is metabolized to normeperidine,

which has neuroexcitatory properties and a long elimination half-life (24 to 48 hours).40 Normeperidine canaccumulate and produce toxicity in the elderly and those with renal failure, although this is a rare event.

Codeine is not a reliable analgesic, and it produces more nausea, vomiting, and dysphoria than otheropioids. The analgesic e�ect of codeine is highly dependent on the metabolic conversion to the activemetabolites codeine-6-glucuronide and morphine. Up to 10% of the U.S. population is deficient in therelevant enzymes for this conversion and, therefore, has an inadequate analgesic response to codeine.Conversely, there are case reports of neonatal deaths as a result of breastfeeding from mothers who werehypermetabolizers of codeine. In addition, the standard PO dose of 30 to 60 milligrams produces little

analgesic e�ect above that of acetaminophen or nonsteroidal anti-inflammatory drugs.41

Tramadol binds to mu-receptors and weakly inhibits the reuptake of norepinephrine and serotoninproducing a central opioid analgesic e�ect. Common side e�ects include dizziness, nausea, constipation andheadache. Tramadol can induce the serotonin syndrome. Severe toxicity can include agitation and seizures.

It is one of the many substances that can produce a false-positive result on the urine phencyclidine screen.42

Adverse e�ects of opioids include nausea, vomiting, constipation, pruritus, urinary retention, confusion, andrespiratory depression. Pruritus, urinary retention, confusion, and respiratory depression are more commonwith IV, transmucosal, and epidural administrations as opposed to PO administration.

Adjuncts are sometimes used to enhance the analgesic e�ect, reduce the amount of opioid required, andprevent side e�ects (Table 35-7). Depending on the agent, amount, route, and setting, a beneficial e�ect canbe seen. However, appropriate titration with opioids in the ED is highly e�ective, and there are few data to

support the routine use of adjuncts with opioids in the ED.43 Pretreatment with antiemetics is not necessary

given the low risk of emesis,44 but symptom-targeted therapy is sometimes necessary.

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TABLE 35-7

Pain Management: Adjunctive Medications

Drug Initial Dosing Pharmacokinetics Comments

Prochlorperazine 5–10 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Promethazine 25–50 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Metoclopramide 5–10 milligrams IV/IM Duration: 4–6 h Can cause extrapyramidal reactions

Transdermal formulations are not useful for acute pain treatment because of delayed onset and prolongedduration of action. Transdermal fentanyl and transdermal buprenorphine preparations are used for chronicpain, particularly in cancer patients. When such patients are treated for acute pain in the ED, it is best toremove the delayed-release transdermal opioid patches to better titrate the acute opioid dose and tominimize adverse reactions from the combination of agents.

OPIOID AGONISTS-ANTAGONISTS

Opioid agonists-antagonists are used to minimize some of the adverse e�ects of pure opioid agonists (Table35-8). The major benefit claimed is a ceiling on respiratory depression (no further reduction in respirationwith increasing doses past a set amount). It is not clear if there is a ceiling e�ect for analgesia. The variabilityin e�icacy relates to each particular agent's a�inity for the various central opioid receptors. Because of theantagonistic e�ects, these agents should be used with extreme caution in patients with opioid addiction asthey may precipitate withdrawal symptoms.

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TABLE 35-8

Pain Management: Initial Opioid Agonist-Antagonist Dosing

Drug [Class] Initial Dosing Pharmacokinetics Comments

Buprenorphine [synthetic

oripavine]

0.3 milligram IV/IM every

6 h

Onset: rapid

Duration: 4–10 h

Sedation, dizziness,

nausea

0.4 milligram

sublingually every 6-8 h

Butorphanol [synthetic

morphinan]

0.5–2.0 milligrams IV

every 3–4 h

Onset: <1 min

Duration: 2–4 h

Sedation, dizziness,

nausea

1–4 milligrams IM every

3–4 h

Dezocine [synthetic

benzomorphan]

2.5–10.0 milligrams IV

every 4 h

Onset: 15 min (IV) and 30

min (IM)

Duration: 4–6 h

Dizziness, respiratory

depression

5–20 milligrams IM every

6 h

Nalbuphine [synthetic

morphinan]

10–20 milligrams

IV/IM/SC every 3–6 h

Onset: 2–3 min (IV) and

30 min (IM)

Duration: 3–6 h

Sedation, headache,

dizziness

Pentazocine [synthetic

benzomorphan]

30 milligrams IV/IM/SC

every 3–6 h

Onset: 2–3 min (IV) and

15–20 min (IM)

Duration: 2–3 h

CNS side e�ects

NONOPIOID AGENTS

Acetaminophen (paracetamol) is an e�ective analgesic for mild to moderate pain (Table 35-9).45

Acetaminophen does not a�ect platelet aggregation and does not have anti-inflammatory properties. Nochange is required for renal or mild hepatic impairment (see chapter 190, Acetaminophen).

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TABLE 35-9

Pain Management: Nonopioid Analgesics

Drug Adult Dosage Comments

Acetaminophen

(paracetamol)

325–1000 milligrams PO every 4–6 h Liver dysfunction and necrosis.

Maximum oral dose is 3.9 grams per day when

using the 325-milligram oral preparation and 3

grams per day when using the 500-milligram oral

preparation.

Maximum IV dose is 4 g per day.

325–650 milligrams PR every 4–6 h

If >50 kg: 1 gram IV every 6 h

If <50 kg: 15 milligrams/kg IV every 6

h

Aspirin 325–650 milligrams PO every 4 h GI irritation and mucosal bleeding.

Platelet dysfunction.

Tinnitus, CNS toxicity, metabolic acidosis.

Maximum dose is 4 g per day.300–600 milligrams PR every 4–6 h

Ibuprofen 400–800 milligrams PO every 4–6 h GI upset, platelet dysfunction, renal dysfunction,

bronchospasm.

Maximum dose is 2400 milligrams per day.400–800 milligrams IV every 6 h

Naproxen 250–500 milligrams PO every 8–12 h GI upset, platelet dysfunction, renal dysfunction,

bronchospasm.

Maximum dose is 1250 milligrams per day for

acute therapy.

Indomethacin 25–50 milligrams PO every 8 h GI upset, platelet dysfunction, renal dysfunction,

bronchospasm.

Maximum dose is 200 milligrams per day.50 milligrams PR every 6 h

Ketorolac Multiple dose therapy: 30 milligrams

IV/IM every 6 h, 15 milligrams IV/IM

every 6 h if age >65 y or weight <50 kg

GI upset, platelet dysfunction, renal dysfunction,

bronchospasm.

Greater risk of GI bleeding than ibuprofen.

Use limited to 3 d IV and 5 d PO.

Maximum IV/IM dose is 120 milligrams per day,

but if age >65 y or weight <50 kg, then maximum

dose is 60 milligrams per day.

Maximum PO dose is 40 milligrams per day.

Single dose therapy: 60 milligrams IM

or 30 milligrams IV, 30 milligrams IM

or 15 milligrams IV if age >65 y or

weight <50 kg

10 milligrams PO every 4-6 h

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Drug Adult Dosage Comments

Ketamine 0.15–0.4 milligrams/kg IV over 10

min; can follow by IV infusion 0.1–0.2

milligrams/kg/h

No renal or hepatic adjustment; adverse e�ects

uncommon with single doses; dizziness,

agitation, hallucinations possible with higher

doses.

Aspirin and the nonsteroidal anti-inflammatory drugs are both anti-inflammatory agents and analgesics. Asanti-inflammatory agents, aspirin and nonsteroidal anti-inflammatory drugs decrease the production ofprostanoids and arachidonic acid–mediated inflammatory peptides generated at the site of tissue injury,diminishing the inflammatory response seen with some noxious stimuli. As analgesics, inhibition of thecyclooxygenase-2 enzyme in the spinal cord decreases the excitability of dorsal horn neurons that producehyperalgesia and allodynia. These agents do not cause sedation or respiratory depression or interfere withbowel or bladder function. Nonsteroidal anti-inflammatory drugs have significant opioid dose-sparinge�ects.

Adverse e�ects of nonsteroidal anti-inflammatory drugs include platelet dysfunction, GI irritation andmucosal bleeding, nephropathy, headaches, and dizziness. All nonsteroidal anti-inflammatory drugs

increase the risk of cardiac death in patients with ischemic heart disease,46,47 although the cyclooxygenase-

2–specific agents appear to carry higher risk than the nonselective agents.48,49 Nonsteroidal anti-inflammatory drug–induced acute renal failure is more common in elderly patients and in those who arevolume depleted, have preexisting renal or cardiac disease, or are taking loop diuretics.

OTHER PHARMACOLOGIC AGENTS

Ketamine

A phencyclidine derivative, ketamine produces analgesia and/or dissociative anesthesia with the advantageof causing minimal respiratory depression with usual doses (see chapter 37, Procedural Sedation). Low-dose(subdissociative) infusions of ketamine are e�ective in combination with opioids for patients in severe

pain.50,51,52 Ketamine dosing for analgesia is typically a loading dose of 0.15 to 0.4 milligrams/kg IV over 10minutes followed by an infusion if desired. Ketamine can be used in trauma patients, resulting in a loweropioid requirement for pain control, and is also e�ective in controlling acute flare-ups of neuropathic pain.Ketamine is also useful as an SC infusion in palliative care patients. Adverse e�ects include hypersalivationand reemergence phenomena (disagreeable dreams or hallucinations upon awakening), especially whenlarger induction doses are used (1.5 milligrams/kg IV).

Nitrous Oxide

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Nitrous oxide is a fast-onset, short-acting analgesic and sedative inhalational agent useful for brief, minor

procedures (see chapter 37) and for prehospital analgesia.53 The primary adverse e�ects are nausea andvomiting. Nitrous oxide is usually supplied as a preblended 50% mixture with oxygen and administered tothe patient by face mask, but if available, the 70/30 nitrous oxide/oxygen mixture is more e�ective. Barriersto ED use of nitrous oxide include the need for patient cooperation and an e�ective scavenging system. Inaddition, nitrous oxide is contraindicated in patients with altered mental status, head injury, suspectedpneumothorax, or perforated abdominal viscus. Severe pulmonary disease also may alter the respiratoryelimination of nitrous oxide.

Cyclic Antidepressants and Anticonvulsants

Patients with acute-onset neuropathic pain, such as postherpetic or trigeminal neuralgia, are di�icult to treatwith short-acting opioid analgesics. It may be di�icult to identify neuropathic causes of pain in ED patients,but if suspected, more specific therapy and follow-up instructions are needed. Long-acting opioids, cyclicantidepressants, serotonin-norepinephrine reuptake inhibitors, and anticonvulsants are e�ective forneuropathic pain (Table 35-10). When initiating an agent for patients with new-onset neuropathic pain, close

follow-up with the primary care physician is important so that titration to e�ect may continue.54,55 Patientsalready taking one of these agents for chronic neuropathic pain may require either titration upward of theirmedication or addition of a second agent; this should be discussed with the patient's regular physician.

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TABLE 35-10

Pain Management: Neuropathic Pain Syndromes

Drug UseInitial

DosageTitrate

Typical E�ective Dosage (Maximum

Daily Dose)

Amitriptyline or

nortriptyline

Chronic pain 0.1

milligram/kg

PO once in

the evening

Increase over

2–3 wk

0.5–2.0 milligrams/kg per day PO

(maximum 150 milligrams per day)

Carbamazepine Trigeminal

neuralgia

100

milligrams

PO twice per

day

Increase 100–

200 milligrams

per day

200–400 milligrams PO twice per day

(1200 milligrams per day)

Oxcarbazepine Trigeminal

neuralgia

300

milligrams

PO twice per

day

Increase 300–

600 milligrams

per day every

week

450–1200 milligrams PO twice per day

Duloxetine Diabetic

neuropathic

pain

30

milligrams

PO once per

day

Increase a�er 1

wk on initial

dose

60 milligrams PO once per day

(maximum 120 milligrams per day)

Gabapentin Neuropathic

pain,

postherpetic

neuralgia

300

milligrams

PO per day

Increase up to

300 milligrams

per day

300–1200 milligrams PO three times

per day (maximum 3600 milligrams

per day)

Pregabalin Neuropathic

pain,

postherpetic

neuralgia

50

milligrams

PO three

times per

day

Increase over 1

wk

150 milligrams PO twice per day to

100 milligrams PO three times per

day (maximum 600 milligrams per

day)

Topical Medications

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Topical administration of medications at the site of injury or inflammation can provide pain relief with

reduced systemic drug absorption and a lower risk of adverse drug reactions (Table 35-11).56 This approachdi�ers from the transdermal drug administration to achieve systemic e�ects, typically with opioids (seeRoute of Administration). Topical nonsteroidal anti-inflammatory drugs are e�ective for treating acute so�tissue injuries such as sprains and strains and also for chronic joint pain from osteoarthritis. Topical lidocainetherapy is e�ective for patients with postherpetic neuralgia and diabetic neuropathy. Topical capsaicin hasproduced variable results depending on the treatment population and dose applied; regular use appearsnecessary for prolonged pain relief. A single 60-minute application of a high-dose preparation (8% capsaicintopical patch) is e�ective for postherpetic neuralgia but requires professional application and removal tominimize side e�ects.

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*Not available in the United States.

TABLE 35-11

Pain Management: Topical Analgesic Agents

Agent Preparation Comments

Diclofenac 1% gel

1.3%

topical

patch

Gel: apply using dosing card—4 grams for knees, ankles, and feet, and 2 grams

for elbows, wrists, and hands. Lightly rub until absorbed. Use up to 4 times a

day. Maximum total daily dose 32 grams.

Patch: apply to intact skin at most painful site twice a day.

Ibuprofen* 5% gel Squeeze 50–125 milligrams (4–10 cm) of the gel from the tube and lightly rub

into the a�ected area until absorbed. Apply up to 4 times per day.

Ketoprofen* 2.5% gel Squeeze 2–4 grams (5–10 cm) of the gel from the tube and lightly rub into the

a�ected area until absorbed. Apply 2–4 times per day.

Lidocaine 5% gel

5% topical

patch

Gel: apply a moderately thick layer to the a�ected area (approximately 1/8

inch thick). Allow time for numbness to develop. Best results obtained 20 min

to 1 hour a�er application.

Patch: apply to intact skin to cover the most painful area. Use only once for up

to 12 h within a 24-h period.

Capsaicin 0.025%

cream

0.075%

cream

0.1% gel

8% patch

Cream and gel: apply to a�ected area not more than 3–4 times daily. Massage

into area until thoroughly absorbed.

Patch: only for postherpetic neuralgia. Requires physician or healthcare

professional application. Applied for 60 min. Treatment may be repeated

every 3 months.

The primary adverse reaction of topical medications is local burning, particularly seen with capsaicin, whichis derived from chili peppers. Rare cases of localized burns have been reported with topical muscle and joint

pain relievers.57 Most of the serious burns were associated with agents containing menthol (>3%concentration) and/or methyl salicylate (>10% concentration).

ROUTE OF ADMINISTRATION

Systemic pain medications can be given by multiple routes (Table 35-12). Oral administration is convenient,inexpensive, and appropriate once the patient can tolerate oral intake; it is a mainstay of pain management

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in the ambulatory ED population.

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TABLE 35-12

Delivery Routes of Systemic Analgesia

Method Advantages Disadvantages

PO Ease

Painless

Minimal cost

No technical skill

required

Patient acceptability

Unreliable GI absorption

Requires gastric motility

Slow onset

Titration less reliable

IV Rapid onset

Titratable

Usually easier to reverse

Venous access required

Potential for overdose

IM or SC Convenient Painful

Titration di�icult and requires repeated injections

Absorption variable

More expensive than PO route

PR (transmucosal) No first-pass hepatic

metabolism

No reliance on gastric

motility

Requires patient acceptance and cooperation

Variable absorption

Buccal/nasal

(transmucosal)

Ease

Painless

Di�icult to control dose

Can irritate nasal mucosa

Available buccal mucosal fentanyl preparations are no

bioequivalent

Transdermal Ease

Painless

Variable dose and duration

Di�icult to titrate

Slow onset

Prolonged duration a�er removal

Inhalational Rapid onset and o�set Requires patient cooperation

Scavenger equipment required

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Method Advantages Disadvantages

Intra-articular Direct action

No systemic side e�ects

Can last up to 48 h

Only in major joints

Risk of joint infection

IV opioids are suitable for bolus administration or continuous infusion and are preferred to intermittent IMinjections. IM injections are painful, do not allow for easy titration, and have no clinically relevant advantageover PO medications. Absorption can be variable, especially in sickle cell patients (due to scarring) andhypotensive or volume-depleted patients. Patient-controlled IV analgesic systems are particularly e�ectivefor ED patients with acute abdominal pain and in addicts with pain when compared with the usual approach

of intermittent nurse-administered parenteral medications.58,59,60 Intra-articular analgesia using opioids orbupivacaine can provide sustained relief during the immediate postoperative period following hip and knee

surgery.61,62,63 Nasal and buccal preparations of fentanyl are available primarily for breakthrough pain inopioid-tolerant cancer patients, and these routes may have a role in prehospital and ED acute pain

management.64 Sublingual buprenorphine is described as e�ective for ED management of acute pain from

fractures.65

DOSAGE AND PRECAUTIONS

Safe and e�ective use of opioids is facilitated by choosing an appropriate initial dose66 and subsequentlytitrating additional doses toward the desired e�ect, thus avoiding overmedication and minimizing unwantede�ects. In unmonitored opioid-naïve patients, excessive doses of opioids can result in respiratory depressionand decreased levels of consciousness. Hypotension is infrequent, is almost always due to histamine releasewith the first dose of medication, and is usually of short duration. With comorbidities, such as altered mentalstatus, hemodynamic instability, respiratory dysfunction, or multisystem trauma, initial dosing should bedecreased, and dose titration is important for achieving satisfactory pain relief.

The Elderly

Acute pain management for the elderly can be a challenge; these patients may have more than one source of

pain and/or multiple comorbidities and are at increased risk for drug–drug and drug–disease interactions.67

Opioid-naïve elderly patients are more sensitive to the analgesic e�ects of opioid drugs, because theyexperience a higher peak and longer duration of pain relief. Moreover, they are more sensitive to sedation,respiratory depression, and cognitive and neuropsychiatric dysfunction. Initial IV opioid doses in the elderlyare typically half those used in younger adults (e.g., morphine 0.05 milligram/kg and hydromorphone 0.0075milligram/kg), although single doses may not achieve adequate pain control for elderly patients with acute

severe pain.68

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Addiction and Dependence

Addiction is the misuse of a medication or drug to the detriment of the patient's well-being. Dependenceinfers that abrupt cessation of a medication will result in acute withdrawal symptoms. Dependence onopioids requires regular daily usage for 4 to 6 weeks in most patients, whereas addiction may occur a�er oneuse of heroin. Care should be taken to assess a patient's risk for addiction or diversion of prescriptionmedications, but when uncertainty exists, the general approach is to err on the side of acute pain control,

although management in opioid-tolerant patients can be a challenge.69 Contemporary and rigorous

evidence is that dependence and addiction occur in up to one-third of patients on chronic opioid therapy,70

but there is little knowledge regarding the risk of short-term (<2 weeks) opioid therapy following an ED visitfor an acute injury or temporary illness. Although EDs are not where most cases of opioid abuse originate,

they are perceived as a potential perpetuator of misuse.71 Distinguishing patient requests for medicationsbecause of oligoanalgesia from addiction o�en requires multiple patient assessments over time; subjectiveassessment in the ED during a single visit is usually inaccurate for identifying addiction versus aberrant

behavior due to oligoanalgesia.72 Use of an assessment tool such as the Drug Abuse Screening Test may

provide a more objective means of screening for addiction.73

Renal and Hepatic Dysfunction

Because most analgesics are metabolized by the liver or kidney, take care when using opioids in patientswith impaired hepatic or renal function. Renal excretion is a major route of elimination for suchpharmacologically active opioid metabolites such as norpropoxyphene, normeperidine, morphine-6-glucuronide, and dihydrocodeine. Mild renal failure can impede excretion of the metabolites of manyopioids, resulting in clinically significant narcosis and respiratory depression. In patients with renal failure,hydromorphone and fentanyl are the preferred opioids. Mild hepatic dysfunction has little e�ect on opioidmetabolism. In patients with severe hepatic dysfunction, titration with low doses of analgesics will minimizethe risk of overdose.

Respiratory Insu�iciency

Patients with respiratory insu�iciency and those with chronic obstructive pulmonary disease, cystic fibrosis,and neuromuscular disorders a�ecting respiratory e�ort (e.g., muscular dystrophy and myasthenia gravis)are particularly vulnerable to the respiratory depressant e�ects of opioids and nitrous oxide. Careful dosetitration and monitoring of oxygenation and ventilation are necessary. Ketamine may be a useful alternativeagent in such cases.

Drug Interactions

Opioids may have adverse synergistic sedative e�ects in patients with psychiatric illnesses taking anxiolyticsor other psychoactive drugs. The use of monoamine oxidase inhibitors with meperidine is associated withsevere adverse reactions, including death as the result of precipitating a serotonin syndrome (see chapter

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178, Atypical and Serotonergic Antidepressants). The cyclic antidepressants clomipramine and amitriptylinemay increase morphine levels and potentiate the opioid e�ects.

NONPHARMACOLOGIC MODALITIES

Traditionally, nonpharmacologic techniques of pain management in the ED have been limited to applicationof heat or cold and immobilization and elevation of injured extremities. Other techniques may be useful inthe ED and a�er discharge. Cognitive-behavioral techniques can be e�ective in reducing pain and anxiety,may control mild pain when used alone, and can enhance patient satisfaction. Such techniques includereassurance, explanation, relaxation, music, psychoprophylaxis, biofeedback, guided imagery, hypnosis, anddistraction. They are a useful adjunct to pharmacologic management of moderate to severe pain. Successfulapplication of these therapies requires a cognitively intact patient and skilled personnel, but many of thetechniques require only a few minutes to teach the patient.

Physical nonpharmacologic agents are becoming increasingly relevant to acute pain management. Inaddition to the traditional techniques noted above, less commonly used physical modalities, such astranscutaneous electrical nerve stimulation and acupuncture, may have some potential role in the ED.Although specific technical skills and equipment are required, there is no need for IV access, and there is nosystemic e�ect such as respiratory depression or altered mental status.

SPECIFIC SITUATIONS

ABDOMINAL PAIN

Early administration of IV opioids is safe for the treatment of acute abdominal pain in the ED and does not

a�ect the accuracy of the evaluation, diagnosis, or management.74,75,76,77 The dogma against the use ofopioids for patients with acute abdominal pain stated in previous editions of Cope's Early Diagnosis of the

Acute Abdomen was revised in 2000.78 The one valid concern regarding analgesia and abdominal pain is thatreduction in pain does not indicate improvement in pathophysiology. Analgesia without proper evaluation isas inappropriate as proper evaluation without analgesia.

MIGRAINE

There is no one, consistent, best analgesic agent for the management of a patient with migraine headache in

the ED.11,12,14 Opioid use for acute migraine treatment has lost favor due to poor performance in clinical

trials, but can be considered if other agents have been ine�ective.14 The high success rates withpromethazine, chlorpromazine, and prochlorperazine are tempered by the extrapyramidal side e�ects, seen

in as many as 45% of patients, and occasional intense dysphoria (see chapter 165, Headache).13

TRAUMA

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1. 

2. 

Patients in shock and those with trauma, burns, and hemodynamic or respiratory instability need judicious

use of opioids.2 Fentanyl, first as a bolus and then as an infusion, may be the opioid of choice due to its lesser

impact on hemodynamic function. Use of regional analgesia is encouraged.29 Nonsteroidal anti-inflammatory drugs should not be given to patients with major trauma due to the risks of excessive bleedingfrom platelet dysfunction and gastric stress ulcers and the potential for acute renal failure in a volume-depleted patient.

DISPOSITION

Although rare, intractable acute pain can be a primary reason for hospital admission. Otherwise, mostpatients may be safely discharged with a plan for pain management that includes instructions for use ofshort-acting analgesics (i.e., those with a duration of action of up to 6 hours). Persistent pain a�er ED

discharge is common.79,80,81 Prescriptions for long-acting agents (e.g., methadone, controlled-releasepreparations of morphine or oxycodone) are generally avoided upon ED discharge but are sometimes usedfor special patients, such as those with cancer in whom short-acting agents are no longer e�ective (seechapter 38, Chronic Pain).

Patients should be counseled to take subsequent doses on a regular basis or when their pain begins toreturn, rather than when it approaches its peak. Patients with recurrence of severe pain or changes in thequality of pain should be told to return to the ED for reassessment. It is best to prescribe only a few days'worth of analgesics, because conditions with a longer duration of pain require follow-up with the primarycare physician. If opioids are prescribed to the elderly or those naïve to narcotics, home observation by aresponsible adult is recommended so that adverse e�ects can be quickly recognized. Discharge instructionsfor those given opioids should include instructions to avoid making important decisions while medicatedand to avoid driving, operating machinery, climbing or working from heights, and so on, and should alsoinclude instructions for treatment of constipation. Education about securing opioid prescriptions isimportant because up to 85% of prescription opioids misused by adolescents come from their parents'medication cabinet.

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