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Acute Pain Management: An Emergency Department Perspective
Author: Michael A. Cruz, MD, FACEP, Clinical Associate Professor of Surgery, Division of Emergency Medicine, University of Illinois College of Medicine, Peoria; Attending Emergency Physician, OSF Saint Francis Medical Center, Peoria, IL.
Peer Reviewer: Jonathan Glauser, MD, FACEP, Attending Staff Physician, Cleveland Clinic Foundation, Department of Emergency Medicine; Faculty, MetroHealth Medical Center, Cleveland, OH.
Although chronic pain management seems to receive the lion’s share of published literature, acute pain management issues recently have come to the forefront now that regulatory agencies such as the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), American Pain Society (APS), National Committee for Quality Assurance (NCQA), and Center for Medicare/Medicaid Services (CMS) have made this a priority with regard to education, measurement, assessment, and documentation. Since acute pain management is protean in nature, the focus of this report consciously will be to avoid such topics as procedural sedation, alternative nonpharmacologic adjuncts, medication pharmacokinetics, sickle cell pain crisis management, cancer pain management, and physician liability in withholding analgesic treatment.
Prior to the 19th century, pain management was well documented but perhaps not as well understood with regard to the neurobiology of pain. Nevertheless, China’s Xia Dynasty (2140-1711 BC) described pain as the simple disruption of chi—life energy. Ancient Egypt and India were clear in their interpretations that pain was related to demons, gods, and spirits of the dead. Hippocrates first described the four humors (i.e., blood, phlegm, black bile, and yellow bile) and how their imbalance would lead to painful conditions. Plato and Aristotle furthered that notion by stating that there must be a peripheral stimulus to create the imbalance, followed by an internal emotional experience. In addition, Judeo-Christian teachings (through the books of Job and Genesis and the story of the crucifixion) have created an inseparable relationship between pain/suffering and the human condition.1,2
More traditional teachings were first described in the 19th century. Serturner in 1804 first described the importance of the plant extract somniferus opium in alleviating painful conditions. Syringes and medicinal extracts were available widely and were unrestricted. Subsequently, self-medication soon contributed largely to the budding science of addiction, tolerance, dependence, and toxicity. Pharmaceutical companies became very active at the turn of the century, with Bayer making aspirin and morphine analogs available for purchase for purchase by consumers. In 1914 Congress instituted the Narcotic Control Act, mostly in an attempt to gain some control of the narcotic craze.1,3
Livingston in 1943 illustrated that a noxious stimulus needs to be generated peripherally, then transmitted centrally to the spinal cord and, ultimately, to the brain for further processing. In 1950, pain was designated a disease state and soon after Noordenboos described myelinated ("fast system") and unmyelinated ("slow system") nerves. Melzack and Wall in 1965 proposed the gate theory of hyperstimulation, attenuation, and spinal level inhibition. The International Association for the Study of Pain first defined pain in 1986. Issues related to pain and analgesia had an illustrious history and during the past 25-30 years have generated recent renewed interest.1,2,4
Neuroanatomic, Physiologic, and Biologic Considerations
In the acute pain model, a mechanical, chemical, and/or thermal stimulus incites a cascade of events by activating receptors. Following a minor stimulus, an electrical impulse is transmitted and propagated via myelinated A-delta fibers and/or unmyelinated c-fibers. This electrical impulse may dissipate, be attenuated, or be part of a reflex (withdraw) arc. If the stimulus is large enough, a chemical release can occur, creating an "inflammatory soup" consisting of bradykinins, phospholipids, histamine, substance P, endorphins, nitric oxide (NO), serotonin, and other mediators. These chemicals can sustain the stimulation and /or attenuate the impulse depending on receptor regulation, past experiences, concurrent medications, disease states, etc. The electrical impulse travels to the dorsal horn of the spinal cord where further modulation occurs as some of the information is transmitted via the spinothalamic tracts to the cortex. Much facilitation and remodeling occurs at the cortical, subcortical, and spinal levels prior to reflex, peripheral, motor, and/or emotional responses. Neuroplasticity theories describe the nervous system’s capability to fluctuate, adapt, and reset some of these integration processes as one develops and matures. For example, patients exhibit widely different pain thresholds even if the pain stimulus is highly controlled in a laboratory setting.
Locally, sodium (Na) and calcium (Ca) channels affect electrical impulse transmission and this likely is illustrated by the effect that carbamazepine (Na channel blockade) has on neuralgic pain. Endogenous opioids such as enkephalins, dynorphins, and endorphins have affinity for specific receptors (mu, kappa, delta, sigma, and epsilon) located centrally as well as at the spinal cord level. Receptors, and to a lesser degree channels, are extremely dynamic structures that can exert their own control by concentration variability on the end organ, differing affinities for the same ligand depending on their location and their ability to be up- or down-regulated. In addition to local effects, opioids can stimulate the release of more active substances such as serotonin, Norepi, and GABA, which in turn can act locally and systemically. Lastly, the vasoactive substances such as bradykinin, histamine, and prostaglandins also contribute to the pain experience by causing smooth muscle spasm, increasing blood flow, inciting capillary leakage, and ultimately creating inflammation.5-8
Nonallopathic alternative methodologies require specific review that is beyond the scope of this article. They have not been as rigorously studied as the pharmacological agents, but nevertheless have been used clinically for quite some time. These include acupuncture, massage, hypnosis, and manipulation. Other nonpharmacologic methods include ultrasound, transcutaneous electrical nerve stimulation (TENS), and biofeedback.
Adjuvants or coanalgesics are agents that can be used alone or more typically as an aid for providing synergy while employing one of the more traditional analgesics—opioids. These would include the inhalants, nonsteroidal antiinflammatories (NSAIDs), aspirin, acetaminophen, corticosteroids, anticonvulsants, antidepressants, benzodiazepines, and muscle relaxants.
As a group, muscle relaxants afford some efficacy over placebo in multiple clinical trials. The studies are in general somewhat difficult to interpret because of issues involving sample size, uniformity in comparable pain syndromes (acute vs chronic), subjective nature of the syndrome, and measurement standardization (for example, how is muscle spasm defined). The mechanism of action for the muscle relaxants is largely unknown but it is hypothesized that they affect the cortical and subcortical levels to produce sedation. They likely impart decreased muscular response and activity from the alpha and delta neuron inputs that are controlled from the cortex. The prototype comes from the benzodiazepine class—diazepam (Valium). An incomplete list of muscle relaxants includes: carisoprosodol (SOMA), chlozoxazone (Parafon Forte), cyclobenzaprine (Flexeril), metaxolone (Skelaxin), methocarbamol (Robaxin), and orphenadrine (Norflex). Anticholinergic effects and decreased therapeutic indices tend to make some of these agents a bit more difficult to use safely. Orphenadrine and cyclobenzaprine can be used parenterally, which gives them a slight edge for acute management, but their side effect profiles would suggest that perhaps they are not the safest in this class of drugs. One recent trial would suggest what many already believe that adding a muscle relaxant to an NSAID affords no real clinical benefit and definitely exposes the patient to side effects, adverse events, and drug-drug interactions.3,9
Local and regional anesthetic agents play a major role given the sheer volume of lacerations and wounds that are cared for in an acute care setting. They are fairly safe when their respective therapeutic ceilings are respected. The amide family includes lidocaine, mepivacaine, and bupivicaine. Their dosages vary by the specific drug and by the procedure being performed. For instance, top-end dosages for lidocaine vary with a Bier block (1 mg/kg), high volume (3-5 mg/kg), and local infiltration with epinephrine (7 mg/kg). Their toxicities can span from perioral paresthesias and agitation to seizures and cardiovascular collapse. Hepatic microsomes are responsible for their primary degradation.
The esters include procaine and tetracaine. They are metabolized via the RBC cholinesterase and pseudocholinesterase pathways. Over all, the esters have a safer profile than the amides because of their higher therapeutic index. The esters are less available and, hence, tend to be more expensive. They are less likely to cause the toxicities sometimes seen with the amides when accidental toxic doses have been administered.
Nitrous oxide has been used for years in varying concentrations. A 50:50 premixed tank commonly is available, which precludes the need to have an analyzer and mixing apparatus when using the prior method of having two separate tanks that needed mixing at time of administration. Its exact mechanism of action is unknown but it likely exerts its effects as a dissociative agent at the subcortical level. Its primary strength is in procedural sedation because it can be readily turned on and off by the patient and is quickly washed out from the pulmonary circulation. It acts as an amnestic as well as a mild analgesic agent. It has been recommended and used in multiple emergency situations and procedures: prehospital setting, ischemic chest pain, pain crisis, lumbar puncture, foreign body removal, abscess incision and drainage, and arterial puncture to list a few. Self-administration by mask provides both positive and negative features to this modality. Diffusion hypoxemia is unusual with the premixed tanks but a required scavenger unit and the abuse potential make this method a bit more cumbersome from an operational standpoint. Lastly, when used alone, its safety profile is good but once again when used as an adjunct with benzodiazepines and/or narcotics the risk for deep sedation and/or anesthesia is real.3,10,11
Ketamine is a parenteral dissociative agent that exerts itself at the thalamocortical level. It is a phencyclidine (PCP) derivative. Although it has been used widely in veterinary practice for longer, ketamine has been used in human clinical practice for about 30 years. Its strength is for procedural sedation since the IV form has a fairly short half-life. Almost as a rule, patients will be able to maintain their protective reflexes and will be afforded some mild cardiorespiratory stability with this medication. Additionally, via sympathetic stimulation it can provide smooth muscle relaxation that probably explains its utility for bronchospastic patients experiencing acute respiratory failure.
This is a very lipophilic substance and, hence, its therapeutic response is in approximately 5 minutes for IM and 1 min for IV administration. It is water-soluble, and the starting doses are 4 mg/kg IM and 2 mg/kg IV. Atropine or glycopyrrolate can be used for those patients with extra secretions to further guard the respiratory tree during administration. The use of adjuncts such as benzodiazepines, nitrous oxide, and/or narcotics along with ketamine requires a good working knowledge of the additive effects, synergism, and the potential toxicities.
Although it is a fairly safe medication, it too has its relative and absolute contraindications. Since it can increase intraluminal pressure and, therefore, affect intraocular, intracranial, and abdominal pressures, one might have to choose an alternative therapeutic modality. Other side effects and idiosyncratic reactions have been documented. Unpleasant reactions to emergency phenomena can be minimized by educating all caretakers and family members to appropriate recovery. The use of midazolam to emergency phenomena has been proposed, but recent literature would suggest that it is not necessary and probably not worth the risk in coadministering these two agents. Chest wall rigidity is not reversible but can be attenuated by giving the correct IV dose slowly. If it does occur, then time and supplemental oxygen and assisted breathing are very likely the most that will be needed. Laryngospasm is another nonreversible complication but occurs infrequently. By being aware of preprocedure laryngeal secretions and either using an anticholinergic medication or choosing an alternative modality, the physician can minimize this adverse event.
Acetaminophen first was used in 1878 and, other than its excellent antipyretic activity, it also has some mild analgesic properties when used alone. It has a fairly safe therapeutic index when used as intended, but a delay in diagnosing its toxicity can prove fatal. Its primary mechanism of action is via centrally mediated cyclooxygenase inhibition. In addition, it has little peripheral anti-inflammatory activity and has no effect on platelet function. The therapeutic ceiling is about 4 gm/day in a healthy adult. Lastly, tolerance, dependence, and addiction are not issues with acetaminophen.
Acetylsalicylate (ASA) became widely used after 1899. It has equianalgesic and equiantipyretic effects similar to acetaminophen. Its strength comes from its anti-inflammatory and antiplatelet activity. It inhibits prostaglandin synthesis at the cyclooxygenase level at a similar point to where other NSAIDs effect their control. The toxicity profile tends to hinder its wider use in that it decreases mucus secretions, disrupts the gastrointestinal (GI) mucosal barrier, decreases platelet stickiness, decreases glomerular filtration rate (GFR), and can precipitate bronchospasm. Currently, ASA is being widely used for those patients predisposed to atherosclerotic disease or documented atherosclerotic end organ disease states.
NSAIDs exert their effect at the cyclooxygenase level and avoid the lipooxygenase pathway similar to ASA. Some medications within this class have been shown to block at higher levels on the arachidonic pathway, but what clinical significance this bears is unclear. The primary toxicity is related to the cyclooxygenase inhibition that in turn affects the GI mucosa protective barrier and the GFR. The topical preparations have not been well studied and currently are not yet used widely, although the ability for this type of modality with good penetration could have significant clinical impact for acute injuries. Combining NSAIDs with other agents such as narcotics or muscle relaxants for oral use makes sense since effecting analgesia via two separate pathways allows for less total dose of either agent—synergism without toxicity.
The NSAIDs have been grouped based on the acid derivatives—acetic and propionic. Indomethacin (acetic acid prototype) has potent analgesic and anti-inflammatory properties exhibited by its effectiveness with certain arthropathies like gout. Ibuprofen (propionic acid prototype) at higher end doses also can serve as an effective analgesic and anti-inflammatory agent. The pharmacology of most NSAIDs is quite similar except for dosing schedule, therapeutic half-life, and therapeutic ceiling. Ibuprofen has the following characteristics: rapid GI absorption, non-sedating, no respiratory depression, and no dependency or tolerance. Its therapeutic ceiling is about 2400 mg/day for healthy adult patients, but gastropathy can occur at doses above 1800 mg/day. Complications with phenytoin and warfarin also can occur due to the NSAID’s ability to displace those agents from protein binding sites. This displacement could effectively increase each of their therapeutic as well as toxic effects.
Ketorolac is another NSAID agent that can be administered by either parenteral or oral routes. It has become a widely used medication in acute painful conditions in part due to its clinical effectiveness but also due to its relative convenience of administration. It has been studied in the acute care setting for the following diagnoses: renal colic, tension headache, migraine, gout, and skeletomuscular syndromes. Administered at 30 mg either IM or IV, it has been shown to have similar clinical effects as morphine sulfate 10 mg in one study. The pediatric dose is about 0.5 mg/kg but has not been studied well in infants and toddlers. Due to the impact on GFR, the dose needs to be decreased for patients older than 60 years of age, those with known or suspected renal insufficiency, and those with acute or chronic dehydration. Lastly, a rebound pain phenomenon has been documented in patients who receive a parenteral dose but then fail to be treated aggressively prior to ketorolac’s first therapeutic half-life.3,12
The cyclooxygenase-2 (COX-2) inhibitors (rofecoxib/celecoxib) have been a heavily marketed subclass of NSAIDs that act by preferentially inhibiting the COX-2 isoform. This in turn impacts inflammation and pain. This isoform is found throughout the body but its counterpart COX-1 is found in higher concentrations at the GI mucosa, platelet surface, and glomerular apparatus. The premise is that one can selectively inhibit the prostaglandin synthesis that impacts pain while sparing the toxicity typically encountered by the usual NSAIDs. Although the literature does support the use of these COX-2 inhibitors for subacute and chronic inflammatory processes, the emergency medicine literature still is scant in advocating their use in the acute care setting unless otherwise dictated by individual patient characteristics and preferences.
The opioid class of medications originally was isolated from the unripe seed capsules of the opium plant (Papever somniferum). The prototype morphine sulfate receives it name from the Greek god of dreams—Morpheus. Four medicinal isolates have been extracted from the opium plant: morphine, codeine, papaverine, and noscaprine. In 1939 meperidine first was synthesized, and in 1951 nalorphine was the first antagonist identified. The opioid mechanisms of action are protean since they involve multiple receptor sites and can be up- or down-regulated. In treating patients with acute pain crises, this group of medications alone or in synergy with other modalities allows physicians to help in relieving the pain and suffering experienced by so many patients treated in EDs.1,3
The non-therapeutic effects of opioids play a major role in acute care management, especially when safety, toxicity, and monitoring issues are discussed. From a cardiovascular stance, most opioids have little direct cardiovascular effect when given judiciously. Fentanyl has the least direct myocardial depressant effects, at therapeutic doses but all the narcotics when given in toxic doses or administered too rapidly can depress the myocardium as well as cause hypotension. Since some of the medications in this class have different histamine releasing effects such as allergic reactions, local reactions, and bronchospasm, gradual administration is essential during medication delivery and monitoring. The GI adverse reactions usually are related to the dysphoria (sigma receptor mediated) that often is associated with narcotic administration. In addition, the decreased peristalsis affects not only stomach emptying but also constipation. Both the histamine and nausea responses can be alleviated either prophylactically or abortively with the appropriate medications.3
The central nervous system (CNS) is where opiates exert their primary toxic non-therapeutic effects. The miotic pupillary response is due to hyperstimulation of the parasympathetic tracts innervating the iris as well as the ciliary body. The medulla houses the chemotactic trigger zone (CTZ). This area can become over-stimulated and cause nausea as well as hyperemesis. This is the same proposed mechanism of action for apomorphine and ipecac. Lastly, the pons and medulla contain the respiratory drive apparatus that predominantly is influenced by the carbon dioxide (CO2) concentration. Narcotics depress respiratory drive by negatively impacting the CO2-sensing mechanism that in turn allows for hypoventilation, hypoxemia, and CO2 retention (CO2 narcosis).3
The opiates’ primary therapeutic effects are due to their impact on the mu, kappa, and delta receptors at various CNS end organ sites. They exert their control at the primary afferents, dorsal roots, spinothalamic tracts, and medial thalamic nuclei. The mesolimbic system has a complex role in determining mood- and reward-based activity. Dopamine in conjunction with the regulation/sensitization of the mu, kappa, delta, and sigma receptors plays an important role in a patient’s sense of euphoria, dysphoria, and/or possible drug-seeking behavior patterns. The medulla has a cough center that can be inhibited by the antitussives—narcotics and their analogs (dextromethorphan). Basic science pain research constantly is adding to knowledge of receptors and receptor end organ concentrations, plasticity, and regulation as it impacts neurobiology, neurochemistry, and neuroimmunology.3
Morphine sulfate is the prototypical agent in this category and, hence, equianalgesic doses are based on this opiate. Note that MS no longer is an accepted abbreviation due to safety initiatives that have addressed medication errors due to confusion between sound-alike or look-alike medications—magnesium sulfate and morphine sulfate. Several narcotics are administered via multiple routes: IV/IM/PO (additional discouraged abbreviations). The intramuscular route is painful, not very predictable as to time of onset, and poorly titrated. This tends to be the theme with most intramuscular narcotics, although some have the added advantage of being given via a subcutaneous (SC) route. In general, acute pain management usually requires some form of ongoing assessment/reassessment and this factor alone makes intramuscular administration much more challenging, although its convenience makes this route of administration understandable. Patient-controlled analgesia (PCA) allows patients more control of their pain crisis management, but the emergency medicine literature has not convinced clinicians that the inherent risks as well as inconveniences for staff are enough to supplant current practice. Also note that some PCA standing orders primarily generated for postoperative pain management are inadequate for some emergency pain management situations due to the nature of the syndrome being treated. To control a patient’s pain crisis, the physician often can require immediate higher doses than allowed by PCA protocols. Lastly, hydroxyzine (not to be given IV), along with other similar agents, can help blunt or block some of the common narcotic adverse reactions by providing anxiolytic, antihistamine, and antispasmodic properties.
Morphine sulfate has a high volume of distribution and is mostly protein bound in the plasma. Liver glucuronidation provides the initial steps in degrading morphine in that only one-third of this plasma protein-bound products remain functionally active. Both parenteral as well as oral formulations are available and widely prescribed. As in most cases, the intravenous route allows for titration, less pain, access for reversibility, and shorter onset time.
Hydromorphone (Dilaudid) has an earlier onset time and shorter therapeutic half-life than morphine. In addition, due to its high solubility and, hence, concentration, it can be given by a subcutaneous route. This imparts significant advantages to the patient as well as to the staff administering the medication. Patients with strict volume restraints who require repeat dosing of narcotics can be treated more easily when given these small volumes of medication.
Propoxyphene (Darvon) is somewhat of a controversial narcotic since patients are exposed to potentially serious side effects without being provided any significant advantages over what currently is available. Toxicity from an overdose is especially challenging to treat and often requires large amounts of naloxone to reverse.13
Codeine alone has a fairly classic opiate side effect profile with regard to constipation, nausea, and emesis. Despite this, when in combination with acetaminophen (Tylenol with codeine), it has reasonable efficacy for mild to moderate pain syndromes. Its liquid formulation makes it particularly useful for children who are unable to swallow tablets. Similar to other narcotics, it too has reasonable antitussive properties.
Hydrocodone is a semisynthetic derivative of codeine and is a good analgesic for moderate pain crises. It also comes in a myriad of mixed formulations that might include antiemetics, antihistamines, decongestants, and expectorants, to name a few. When hydrocodone is combined with acetaminophen or other NSAIDs, it becomes quite effective because mechanistically the analgesic effects are working through two different pathways. This synergy or coanalgesia also allows for less individual drug toxicity since in theory the patient might receive pain relief at lower doses than if either one drug was used alone.
The effects of Tramadol (Ultram) primarily are mediated via mu receptors. Although some patients believe that it is not a narcotic, it does indeed have some tolerance, dependence, and toxicity profiles consistent with traditional narcotics. It characteristically has under-performed in pain management when compared to combination medications such as NSAIDs and narcotics (hydrocodone/acetaminophen or aspirin/codeine). Lastly, tramadol has to be given special consideration since it also causes monoamine reuptake inhibition. Given its risk profile and less-than-ideal efficacy for moderate or severe pain management, tramadol has not been shown to have a well-defined role in emergency medicine.9
Meperidine (Demerol) first was synthesized in 1939 but has become the most widely used narcotic in the United States. It has one-eighth the potency of morphine and does have oral and parenteral formulations. It has several shortcomings when compared to morphine and other narcotics. From a cardiovascular standpoint, meperidine has atropine-like and negative inotropic effects. It lacks the antitussive effects that are provided by codeine and morphine. In addition, meperidine can have a marked histamine release. Administering meperidine when a patient currently is taking a (MAOI) or a selective serotonin reuptake inhibitor (SSRI) is a recipe for toxicity. Lastly, meperidine is readily metabolized to the not only toxic, but also therapeutic, metabolite normeperidine. Its therapeutic half-life is 30 hours. The CNS toxicity can present with nervousness, hallucinations, psychosis, and status epilepticus.
Fentanyl (Sublimaze) is a near-ideal narcotic for acute pain management for several reasons. It is a highly concentrated substance that has a very similar profile to that of the prototype morphine except that it has a much shorter therapeutic half-life (90 minutes) and is safer. It is almost entirely metabolized by the liver. Fentanyl has no histamine-releasing effects found commonly with other narcotics. In addition, it causes no myocardial depression. Other than the usual narcotic side effects, one of its unique disadvantages is that, if given too rapidly and at higher end initial doses, it can cause muscle rigidity. This side effect is not easily reversed since it does not mechanistically follow the mu receptor pathway. Avoidance is the best way to preventing it from occurring. If it does occur, supportive care and time are the best and only therapies. One other disadvantage is that since it has such a relatively short therapeutic half-life, the clinician needs to recall that rebound pain or having gaps in pain control is a suboptimal method of pain management.
The agonist-antagonist group includes medications such as butorphanol (Stadol) and nalbuphine (Nubain). These agents exercise their therapeutic effect by antagonizing the mu receptors and stimulating the kappa receptors. Their theoretical strengths rest in the fact that respiratory drive and addiction control centers are not directly impacted. Note that although receptor physiology might suggest this to be true, patients are naturally much more complex and abuse potential and toxic overdose still are possible. This class of medications has not been well studied in the emergency medicine literature. One major disadvantage to these agents, in this author’s opinion, is that if a patient is not forthcoming regarding his or her narcotic use or if the medication history was not accurately obtained, then an acute narcotic withdrawal may be precipitated. Lastly, once these medications are used, one is subsequently limited in that using traditional mu receptor narcotics will be rendered ineffective due to the antagonism.
Pediatric pain management deserves some specific discussion, mostly from an educational standpoint. The literature is now replete with evidence about several facts: newborn (neonate) and infant children feel pain; neurological pain pathways have plasticity; toddler and preschool children can describe their pain experience; and children require medication based on weight. Morphine and fentanyl are possibly the narcotics of choice for children. The advantages to IV medication and titration already have been discussed. Synergism or coadjunctive therapy with anxiolytics is powerful but requires vigilance in maintaining skills to optimize therapeutic effects without exposing the child to potentially serious toxicity. Sleep-inducing agents or medications that cause sleepiness are not analgesics and should be used sparingly if at all when administering narcotics.14-17
Pediatric patients have therapeutic as well as toxic responses based on the plasma concentrations of the narcotic administered. This in turn directly is related to the liver degradation and/or plasma clearance properties of the medication. The majority of children being treated for acute painful conditions are not preterm or neonate babies, nor do they have liver or kidney disease. The total plasma clearance is age-dependent and as follows: preterm infants 0.5-3 mL/kg/min; preschool children 20-40 mL/kg/min; and adults 10-20 mL/kg/min. Therefore, other than the neonate, children and adolescent patients have equal or higher plasma clearance rates than adults and hence are at no higher risk for narcotic toxicity. This would suggest that due to plasma clearance, increased cardiac output, decreased circulation time, and increased muscular vascularity, that usual starting doses such as morphine 0.1 mg/kg or fentanyl 2 mcg/kg are possibly low doses for acute pain crisis management.18
Pain Assessment and Response: Patient/Provider
A patient’s pain response is dependent on prior experiences, age, and even gender. A health care provider might find a 27 guage needle puncture to be minor and yet a patient of the same age and gender who is not a health care worker might find it unbearable. In addition, cultural differences, emotional states, and the nature of the injury or illness also play a role in the final pain response. When the patient’s appearance, behavior, and personal characteristics are factored in, there is a very complex and unique pain response. The limbic system plays a significant role in inhibition or heightening of these final responses. Note that patients might find a bladder mini-catheterization and an IV catheterization equally painful but the former causes much more distress—anxiety, embarrassment, and fear. Lastly, physiologic parameters such as heart rate, respiratory rate, skin exam, blood pressure are extremely patient-dependent and can vary further with different injury or illness states.16,19,20
Some patients may be so agitated by their pain crisis that their pain management becomes the center of their emergency department evaluation and treatment. Other patients are reluctant to ask or complain about their pain syndromes. They might, in fact, choose not to bother staff, to accept their pain as a natural part of their condition, to believe that other much sicker patients need care, to be too proud to complain, or to believe that this what they deserve. Furthermore, once analgesic treatment has begun, patients vary even more in their expectations of how and when the medication is supposed to work.
Patient ethnicity and pain management has become a hotbed of research and discussion. Appropriate assessment tools and retrospective analyses probably have made some of these studies less than ideal but nevertheless bring the subject matter to the forefront. Several investigators have described some differences in analgesic treatment patterns among health care workers given differences in patient ethnicity. The striking similarity among several of these studies is that most patients were under-treated for their illness or injury. Once again, the difficulty has been in conducting a study that looks specifically at patient and provider pain assessments before and after treatment. In addition, one would have to account for disparity that exists in language, culture, region, provider characteristics, and patient characteristics.21-23
So how can providers better treat their patients’ painful conditions? The literature is less than forthcoming in stating the "how to?" Patient education should focus on the importance of treatment and that analgesia plays a key role toward their healing, recovery, and overall health. Just as important is for providers to be educated as to safety, monitoring, assessment, and some basic pharmacokinetics of the medications prescribed. Less tangible and yet just as important provider issues would include understanding that there is not one appropriate pain behavior, understanding that providers are likely to underestimate a patient’s pain level, being aware that patients can experience a real emotional component to their painful condition, and discounting statements such as "opiates are inappropriate unless patients are in severe pain."
Pediatric patients have a traditional pain pathway response in that they sequentially go through perception, interpretation, and expression. Within that context their responses vary depending on their developmental level. Recall that behavioral as well as physiologic response has been studied in preterm, neonate, infant, toddler children. Within one week of life, whether premature or not, children can differentiate degrees of invasiveness of procedures. In addition, their behavioral and physiologic responses may or may not be in parallel, depending on the procedure. The literature has not been able to define clearly whether or not normal consciousness and complete myelination occurs simultaneously or even in parallel. Degree of neuroplasticity does exist because some children have reflexive memory (Pavlov) and yet others can alter their pain response positively or negatively if a parent is present or not. Older infants and toddlers have mostly reflexive total body responses that can be stereotypical, anger based, but is most commonly withdrawal. Preschool children keenly recognize strangers, restraint, and separation. They experience guilt, anxiety, and punishment. Older, school-age children need to feel in control, have general body awareness, can fantasize, and are cognitively more developed. Adolescent patients (Piaget) can develop more formal operations such as thought, reason, and socialization. They may lack more mature coping skills, but due to their articulate language skills, can fool the health care provider into believing they are more prepared for the pain crisis.14,17,24-26
Scales and Scores
The available list for pain scales or scores is lengthy. Their reliability and validity have been studied to some degree, depending on the population and scientist testing the scale. The visual analog scale (VAS) is one commonly accepted and utilized scale but others do exist: numerical descriptor scale (NDS), numerical rating scale (NRS), word descriptor scale (WDS), verbal rating scale (VRS), and facial descriptor scale (FDS). Several validation studies have found that independent of adult age, gender, and etiology of painful condition, clinically relevant differences in pain scales occurred with changes in about 16 mm (0-100 mm), 1.6 cm (0-10 cm), or 2 (VAS 0-10). In choosing the right scale, individual patient characteristics and capabilities such as mental status, visual perception, language skills, and literacy will impact the success of the scale in establishing the most correct score. A provider asking the patient for a number between 0-10 and the patient responding in some format seems to have the highest success rate in obtaining what the patients believe to be their current pain score. Children, too, have been evaluated on scales. They require different scales that are developmentally appropriate. Preschool and school age children have the ability to comprehend stair-step or rank scales and, if solicited, can contribute an amazing amount of detail about their pain crisis. In addition, parental VAS or VDS contribute little to the child’s assessment. In fact, their scores tend to overestimate the child’s score. Health care workers, as with adult patients, tend to underestimate a child’s pain score.19,23,26-31
Patient Satisfaction and Pain Control
Several investigators have pursued the link between pain management and patient satisfaction. This is an ambitious undertaking given that pain assessment is fairly subjective and patient satisfaction is very subjective. The latter requires that patients’ perceptions and expectations be addressed in some manner. Although pain relief alone will not dictate a patient's satisfaction with pain management, a moderate linear relationship does exist between pain relief and patient satisfaction. In fact, a threshold change in pain score probably exists that would impact a patient’s satisfaction regardless of the raw score is 2/10, 5/10, or even 7/10 at the start. In other words, some patients can be very satisfied with their pain management even if they are dispositioned from the emergency department in moderate pain—a goal this author would not advocate. Even scripting has a role in patient satisfaction with regard to pain management. Despite patients being in moderate pain they felt that as long as their clinician demonstrated concern in statement and action about the painful condition, they were very satisfied with their overall pain management. It seems likely that pain relief alone is loosely correlated with patient satisfaction but that the concern and action of taking care of a patient's painful condition, even if not very successful, is more important when addressing patient satisfaction.6,27,32
1. Meldrum ML. A capsule history of pain management. JAMA 2003;290:2470-2475.
2. Scarry E. The Body in Pain: The Making and Unmaking of the World. New York, New York: Oxford University Press; 1985:4.
3. Bonica JJ, Loeser JD. History of pain concepts and therapies. In: Loesr JD, ed. Bonica’s Management of Pain, 3rd ed. Baltimore: Lippincott Williams & Wilkins, 2001: 3-17.
4. Melzack R, Wall PD. Pain mechanisms: A new theory. Science 1965;150:971-979.
5. Jones JB. Pathophysiology of acute pain: Implications for clinical management. Emer Med 2001;13:288-292.
6. Ducharme J. Acute pain and pain control: State of the art. Ann Emerg Med 2000; 35:592-603.
7. Pasternak GW. Opiates, enkephalins, and endorphins. Neurology 1981;31:1311-1315.
8. Caillet R. Pain: Mechanisms and Management. Philadelphia, PA: FA Davis Co.; 1993.
9. Turturro MA, Frater CR, D’Amico EJ. Cyclobenzaprine with ibuprofen versus ibuprofen alone in acute myofascial strain: A randomized, double-blind clinical trial. Ann Emerg Med 2003;41:818-826.
10. Kennedy RM, Luhmann JD. The "ouchless emergency department." Ped Clin North Am 1999;46:1215-1247.
11. Principles of Analgesic Use in the Treatment of Acute Pain and Cancer Pain, 4th ed. Glenview, IL: American Pain Society 1999:3-38.
12. Shrestha M, Morgan DL, Moreden JM, et al. Randomized double-blind comparison of the analgesic efficacy of intramuscular ketorolac and oral indomethacin in the treatment of acute gouty arthritis. Ann Emerg Med 1995;26:682-686.
13. Miller RR, Feingold A, Paxinos J. Propoxyphene hydrochloride—A critical review. JAMA 1970;213:996-1006.
14. Jylli L, Olsson GL. Procedural pain in paediatric surgical emergency unit. Acta Paediatr 1995;84:1403-1408.
15. Petrack EM, Christopher NC, Kriwinsky J. Pain management in the emergency department: Patterns of analgesic utilization. Pediatrics 1997;99:711-714.
16. Lambert L. Girls’ and boys’ differing response to pain starts early in their lives. JAMA 1998;280:1035-1036.
17. Friedland LR, Pancioli AM, Duncan KM. Pediatric emergency department analgesic practice. Pediatr Emerg Care 1997;13:103-106.
18. Olkkola KT, Hamunen K, Maunuksela EL. Clinical pharmacokinetics and pharmacodynamics of opioid analgesics in infants and children. Clin Pharmacokinet 1995;28: 385-404.
19. Kelley L, Sklar DP, Johnson DR, et al. Women’s perception of pain and distress during intravenous catheterization and urethral mini-catheterization. Am J Emerg Med 1997; 15:570-572.
20. Krivo S, Reidenberg MM. Assessment of patients’ pain. N Engl J Med 1996;334:59.
21. Todd KH, Lee T, Hoffman JR. The effect of ethnicity on physician estimates of pain severity in patients with isolated extremity trauma. JAMA 1994;271:925-928.
22. Karpman RR, Del Mar N, Bay C. Analgesia for emergency centers’ orthopaedic patients. Clin Orthop 1997;334:270-275.
23. Singer AJ, Richman PR, Kowalska A, et al. Comparison of patient and practitioner assessments of pain from commonly performed emergency department procedures: A randomized trial. Ann Emerg Med 1999;33:652-658.
24. Atherton A. Children’s experiences of pain in an accident and emergency department. Accid Emerg Nurs 1995;3:79-82.
25. Porter FL, Wolf CM, Miller JP. Procedural pain newborn infants: The influence of intensity and development. Pediatrics 1999;104:e13.
26. Harrison A, et al. Arabic children’s pain descriptions. Ped Emerg Care 1991;7:199-203.
27. Stahmer SA, Schofer FS, Marino A, et al. Do quantitative changes in pain intensity correlate with pain relief and satisfaction? Acad Em Med 1998;5:851-857.
28. Berthier F, Potel G, Leconte P, et al. Comparative study of methods of measuring acute pain intensity in an ED. Am J Emerg Med 1998;16:132-136.
29. Chan L, Russell TJ, RobakN. Parental perception of adequacy of pain control in their child after discharge from the emergency department. Pediatr Emerg Care 1998;14: 251-253.
30. Todd KH, Funk JP. The minimum clinically important difference in physician assigned visual analog pain scores. Acad Emerg Med 1996;3:142-146.
31. Todd, KH, Funk KG, Funk JP, et al. Clinical significance of reprted changes in pain severity. Ann Emerg Med 1996;27:485-489.
32. Afilalo M, Tselios C. Pain relief versus satisfaction. Ann Emerg Med 1996;27:436-438.
To help physicians:
Physician CME Questions
1. Which of the following is the most accurate in describing a common pathway for stimulus generation, propagation, and transmission?
A. A chemical reaction occurs peripherally whereby local vasoactive mediators are released and affect their control at the spinal and cortical levels.
B. Following electrical impulses, a cascade of events takes place locally that initiates a fixed response at the spinal cord, cortex, and periphery.
C. A local stimulus almost always relays information to the cortex, requiring some kind of peripheral response.
D. A significant local stimulus not only creates a local chemical reaction but also an electrical impulse that is attenuated/inhibited at multiple levels along the arc thru the central nervous system.
2. Which of the following statements about adjuvants/coanalgesics is most accurate?
A. Nitrous oxide is an excellent adjuvant for pain control because it is easily administered, requires minimal caretaker involvement, and has endorphin agonist properties.
B. The muscle relaxants are widely marketed and prescribed because their mechanism of activity has been elucidated and their side effect profile is very favorable.
C. The use of NSAIDs and opioids makes sense since pain production could involve both arachidonic acid as well as mu receptor pathways.
D. Since xylocaine (Lidocaine) has a proven safety record at multiple doses and has an antidote, it can be administered without much concern for toxicity.
3. Which of the following best describes ketamine’s strengths during procedural sedation?
A. Patients can safely self-administer this agent via a mask and because of its lipophilic characteristic it is readily turned on and off.
B. Its GABA effects make it particularly well suited for alleviating anxiety typically associated with procedures.
C. Rarely will a clinician require an adjunct when employing ketamine because at therapeutic doses it is a very effective dissociative agent.
D. It is a highly titratable substance that mechanistically works similar to propofol.
4. Which of the following statements regarding narcotic opioids is most accurate?
A. Naloxone (Narcan) is the antidote of choice for reversing the histamine effects often seen with narcotic administration.
B. Normeperidine is the toxic metabolite of meperidine (Demerol) that accumulates with repeat dosing.
C. Fentanyl is the prototypical agonist-antagonist agent that has a relatively long therapeutic half-life.
D. Hydromorphone (Dilaudid) is commonly used as an intramuscular narcotic because it is highly concentrated and has mild anesthetic properties.
5. With regard to the clinician’s ability to assess patient’s pain, which of the following is most accurate?
A. In assessing a preschool child’s pain score, it is most accurate to average the scores of the child’s parent(s) and the nurse.
B. Patients who exhibit fear or anger responses to their painful conditions are generally unable to quantify their pain score and hence physiologic indicators become the next best predictors.
C. All health care workers can agree that renal colic is a painful condition and, hence, patients with this condition should receive a standard dose of narcotics early on during their evaluation.
D. With developmentally appropriate scales, clinicians now have fairly reliable and valid tools with which to assess a patient’s pain score.
CME Answer Key: 1. D; 2. C; 3. C; 4. B; 5. D