Author: Aaron Dora-Laskey, MD, Central Michigan University College of Medicine, Saginaw, Michigan

Case

“This hurts so bad! Please help me!” An otherwise healthy 29 year-old man arrives by private car with severe ankle pain after being thrown from a mechanical bull at a local bar. His right ankle is deformed and the PT and DP pulses are palpable but diminished. He is alert and oriented, but estimates that he’s had about nine 12 oz. beers in the past three hours. His vital signs are: BP 160/90, HR 120, RR 18, T 98.8F, SaO2 96% on room air, and he weighs 100 kg. The EM resident orders 4 mg of morphine IM. The attending cancels this and orders 2 mg of hydromorphone (Dilaudid®) IV. His nurse worries about giving any pain medication to this intoxicated patient, and asks your opinion. What do you think is the best choice for this patient?

Objectives

Upon completion of this self-study module, you should be able to:

• List the common classes of analgesics used in the ED and describe their mechanisms of action
• Discuss the advantages and disadvantages of different analgesics and their routes of administration
• Be familiar with commonly used local anesthetics and their characteristics
• Describe the necessary safety precautions when performing procedural sedation and be familiar with commonly used agents
  

Introduction

Pain is the most common reason patients seek care in the ED. While we may be focused on rapidly identifying life-and limb-threatening conditions, patients’ first priority is often pain relief. We may not always know the precise cause of their chest pain, abdominal discomfort, or cephalgia, but we can always help alleviate their suffering.

Treating pain has many benefits. In some cases (like acute MI and aortic dissection) analgesics can decrease pain-related tachycardia. Patients in pain (e.g., from a kidney stone or perforated duodenal ulcer) are often so uncomfortable that examinations may be rendered more reliable after their pain is treated. Patients who get better pain relief tend to have greater satisfaction. This is important for many reasons, including the fact that satisfied patients are more likely to return to you for care after discharge if their condition worsens.

Analgesics

There are no absolute contraindications to providing analgesics to patients in pain. Several factors should be considered when choosing an analgesic agent, including the severity of the pain, its suspected cause, and the patient’s age, weight, medical history (including drug allergies) and vital signs.

For patients with acute severe pain, parenteral opioids are the first-line therapy. Opioids act on specific receptors in the central and peripheral nervous systems that modify perceptions and responses to painful stimuli. They should be administered initially as a bolus dose estimated by the patient’s weight, and titrated every 5-15 minutes following reassessment of the patient’s subjective description of their pain.

All opioids share nausea (to varying degrees) as a possible side effect, however routine co-administration of antiemetics is not necessary. Parenteral opioids may also cause pruritus and/or urticaria. This is the result of mast cell destabilization, and it is important to explain to the patient that this response does not represent an allergic reaction. Symptomatic side effects respond well to antihistamines or antiemetics. The most serious complication of opioid analgesics is respiratory depression, which is more common if other sedative-hypnotics are used simultaneously. This rarely requires reversal (with naloxone).

Elderly patients are at greater risk of developing constipation, sedation, and confusion when treated with opioids, and it is reasonable to adjust doses to account for age-related changes in pharmacokinetics. However, when “starting low and going slow,” don’t forget to go—studies have shown that elderly patients’ pain is undertreated in the ED.

The first choice of parenteral opioids is often morphine. (Fentanyl and hydromorphone are alternatives.) A safe starting dose of morphine is 0.1 mg/kg, and should be given intravenously. (Subcutaneous administration can be used if IV access is not an option, however IM injection is more painful and takes longer to work.) It is reasonable to consider a lower dose (e.g., 0.05 mg/kg) in patients who are older or sicker. Because different patients will require different doses to relieve their pain, morphine can be safely titrated using doses of 0.025-0.05 mg/kg every 5-15 minutes following the initial bolus.

Hydromorphone can be given intravenously at a starting dose of 0.015 mg/kg. It is reported to cause less nausea, vomiting, and pruritus than morphine, however it is often associated with a greater risk of respiratory depression. This may be in part because providers don’t recognize how much more potent it is (on a milligram per milligram basis). For this reason, larger initial (e.g., 2 mg) doses are best avoided, especially in those who are naïve to opioids. (Patients with sickle cell pain crises or cancer pain are important exceptions. These patients are often in severe pain, and they are rarely opioid naive.) As with morphine, hydromorphone can be titrated after the initial bolus every 5-15 minutes at doses of 0.0075 mg/kg.

Fentanyl has the advantage of acting rapidly (within 1-2 minutes) and having a shorter half-life, allowing for serial reexaminations (e.g., of the head-injured patient). It can be given intravenously with an initial dose of 1-1.5 μg/kg. Fentanyl can be safely repeated every 15 minutes at doses of 0.25-0.5 μg/kg. “Rigid chest syndrome” is a rare complication with dosages used in the ED.

For patients with less severe pain, oral opioids are a good option. These include oxycodone and hydrocodone, which are often combined with acetaminophen (which limits the maximum daily dosage). They are both given as 0.05-0.15 mg/kg of the opioid component, and can be repeated every 4-6 hours. Codeine—while commonly prescribed—is best avoided, as it is a weak opioid receptor agonist and provides poor pain control. Further, genetic differences among patients may increase the likelihood of certain side effects.

For mild to moderate pain, non-opioid analgesics are a good first choice. In some cases, they may act synergistically with opioids, lowering the total required dose of these medications (which may decrease the risk of side effects). Non-narcotic analgesics include the non-steroidal anti-inflammatory medications (NSAIDs) and acetaminophen.

The safest of these is acetaminophen, which is available in oral and intravenous formulations. It acts centrally, though its precise mechanism is unknown. It can be given at doses of 10-15 mg/kg with a maximum single dose limit of 1000 mg. Acetaminophen can be repeated every 6 hours. The maximum daily safe dose of 75 mg/kg/day (maximum of 4000 mg/day) includes all sources, so be sure to ask patients if they’re taking any other prescription or over-the-counter medications containing acetaminophen. Its most worrisome toxic effect is liver injury, however this occurs very rarely in adults receiving doses less than 10 g/day (with the possible exceptions of people with liver disease or alcohol dependence).

NSAIDs act by blocking prostaglandin-mediated inflammation via inhibition of cyclooxygenase (COX). Most of the serious complications of NSAIDs (e.g., GI bleeding, renal injury) result from chronic use. That said they should be avoided in elderly patients and those with renal disease or heart failure, as their inhibition of prostaglandin synthesis may adversely affect the kidneys’ ability to maintain salt and water balance. Their potential for toxicity is increased in patients who are acutely dehydrated or hypovolemic. While there is controversy regarding the effect of NSAIDs on bone healing, there is no convincing evidence that their short-term use is harmful to patients with acute fractures. No oral NSAID has been shown to be superior to ibuprofen, which can be given at doses of 5-10 mg/kg, with a maximum dose of 600 mg every 6 hours.

Ketorolac is the only parenteral NSAID available in the U.S. While studies have questioned whether it is more effective than ibuprofen for most conditions, it does appear to have synergy with morphine in treating renal colic. It can be given as an IM or IV injection at 0.5 mg/kg with a maximum dose of 30 mg IM or 15 mg IV, but should not be repeated more than every 6 hours or continued more than 5 days.

Table 2. Non-opioid Analgesics

Local anesthesia

Local anesthetics prevent transmission of pain signals by reversibly blocking sodium channels in the membranes of sensory nerves. They are commonly used for painful procedures (like laceration repair or lumbar puncture) and regional blocks (e.g., femoral nerve blocks for hip fractures). The most commonly used local anesthetic in the ED is lidocaine, prepared with or without epinephrine, which helps with hemostasis and increases the duration of the anesthetic effect. Longer-acting agents like bupivacaine are usually used for regional anesthesia.

Systemic toxicity can occur at large doses, and may manifest with seizures or dysrhythmias. The maximum dose of lidocaine is 4 mg/kg (without epinephrine) and 7 mg/kg with epinephrine. While local anesthetics with epinephrine have traditionally been avoided in end organs like the penis, ears, nose, and fingers, digital anesthesia with dilute concentrations of epinephrine (1:200,000 or less) has been shown to be safe. The pain of local anesthetic injection can be reduced by slowing the rate of injection, buffering it with bicarbonate, or by prior application of a topical anesthetic.

The most commonly used topical agent for open skin lesions is LET (lidocaine, epinephrine, and tetracaine), and is applied in 5-10 mL aliquots and held in place with a dressing for 10-20 minutes. It is more effective on the scalp and face than the extremities, but should be avoided on mucosal surfaces.

Procedural Sedation

Sedation is often a useful adjunct to pain relief, and can be necessary to relieve anxiety and enhance patient cooperation. Similar to providing safe and effective treatment for patients in pain, there are several principles you should understand when sedating patients for painful procedures.

Examples of cases where procedural sedation and analgesia (PSA) might be used include:

• Reduction of a dislocated prosthetic hip
• Incision and drainage of a large subcutaneous abscess
• Complex facial laceration repair in a wiggly toddler
• Lumbar puncture in an agitated patient with altered mental status
• Cardioversion of a patient with chest pain and a wide complex tachycardia

The goal of procedural sedation in the ED is to provide a level of sedation and analgesia in which the patient is able to maintain a patent airway and spontaneous ventilation without intervention, and retain the ability to respond purposefully to tactile or verbal stimulation. (The exception is dissociative sedation, unique to ketamine, which will be discussed below.) A variety of medications are used in the ED to achieve this goal, depending on the indication for the procedure as well as the patient’s age, medical history, allergies, and vital signs.

Before initiating PSA in the ED, the patient should be assessed for signs of predicted airway difficulty in the event that bag-valve-mask ventilation or intubation is required (e.g., facial hair, missing teeth, facial/neck surgery or decreased neck mobility). A history and physical should be performed that identifies any underlying cardiac disease, lung disease, or the presence of obesity or sleep apnea that may compromise the patient’s respiratory status during sedation. Attention should be paid to vital signs, as some medications may make preexisting abnormalities worse (for example, propofol aggravating hypotension). The patient’s baseline mental status should be documented, as well as the presence of any known or suspected intoxication with alcohol or other sedatives at the time of the assessment.

Fasting prior to ED procedural sedation is controversial, and has never been shown to decrease complications from aspiration. However, as with all decisions about patient care in the ED, it should be informed by an assessment of the predicted risks and benefits.

It is important to have another person (e.g., a nurse or respiratory therapist) who is not directly involved in administering medications available to monitor the patient continuously. Monitoring must be continued until the procedure is completed and the patient has recovered from sedation and is spontaneously awake.

Equipment necessary to safely perform PSA in the ED includes:

• Cardiac monitoring (including pulse oximetry and capnography)
• High-flow oxygen source
• Suction
• Bag-valve mask
• Airway equipment (including oral airways and nasal trumpets)
• IV access
• Defibrillator
• Reversal agents
• Resuscitation medications
  

Sedative Agents

There is no “ideal” medication for PSA (i.e., one that would safely provide analgesia, amnesia, anxiolysis, and somnolence simultaneously). For some procedures, like lumbar puncture or foreign body removal in children, an anxiolytic like midazolam may be preferable. In patients who require abscess drainage or burn debridement, the combination of a sedative and an analgesic might be used (e.g., fentanyl and propofol). For adult patients (and most pediatric patients), intravenous agents titrated to sedation are the safest, most rapid, and most predictable means of administration.

Opioids alone are not safe or adequate for procedural sedation, but they should be given when using sedatives without analgesic effect (e.g., propofol or etomidate). Fentanyl, which is short acting and has a rapid onset, may be used with benzodiazepines like midazolam to produce moderate sedation. It can be given IV at 1-1.5 μg/kg. Its most serious complication is respiratory depression, which is more common at higher doses and in the presence of other CNS depressants (like ethanol).

Benzodiazepines like midazolam provide anxiolysis and amnesia. The recommended starting dose is 0.05 mg/kg. It has an onset of 1-2 minutes and lasts 30-60 minutes. (It can also be given intramuscularly at 0.1-0.15 mg/kg.) Intranasal administration is an alternative, however it can be irritating. Respiratory depression and hypotension are dose-related and occur more frequently with simultaneous opioid use.

Ketamine, a derivative of phencyclidine (PCP), is a dissociative agent that that blocks painful stimuli by disrupting signals between the thalamo-neocortical and limbic systems. Unlike most sedatives, it does not produce unconsciousness. Rather, patients experience a trancelike state characterized by nystagmus and roving eye movements. Its major advantages are that is provides excellent analgesia while preserving airway reflexes and without causing respiratory depression. It has both fast onset (1 minute) and fast offset.

Ketamine is administered IV in doses of 1-2 mg/kg, and lasts about 15 minutes. It can be given IM in children (4-5 mg/kg) and takes about 5 minutes to work. 15% of patients will awake with unpleasant dreams or hallucinations (the so-called emergence phenomenon), however only a few of these patients will be significantly agitated. Nausea upon wakening is fairly common, and responds well to antiemetics if it persists. Ketamine is contraindicated in patients with elevated intraocular pressure.

Etomidate is a short-acting agent that acts by potentiating GABA receptor neurotransmission. It has no analgesic properties. It has a rapid onset (1 minute) and lasts 5-10 minutes. It is given at initial doses of 0.1 mg/kg intravenously, and may be repeated every 2-3 minutes at 0.05-0.1 mg/kg until adequate sedation is achieved. It typically causes little respiratory or cardiovascular depression. Although rare, apnea may occur in older patients and after rapid administration. Its use is sometimes associated with myoclonus, however this is usually brief. Etomidate has been shown to suppress adrenal function, however this is rarely associated with a single sedating dose in the ED.

Propofol is a very short-acting, rapid-onset sedative that acts by enhancing the inhibitory function of GABA through GABAA receptors. It is easy to titrate, and has the added benefits of being antiemetic. Like etomidate, it has no analgesic properties. Propofol can be administered by initial IV bolus dose of 0.5-1 mg/kg and repeated every 1-3 minutes in 0.25-0.5 mg/kg doses. Onset is less than 1 minute, and lasts about 10 minutes. Lower doses should be used in the elderly (0.25-0.5 mg/kg) and in the presence of other CNS depressants. Downsides include respiratory depression and hypotension, both of which are dose-dependent. Hypoxia or transient apnea may necessitate a brief period of assisted ventilation.

Table 3. Procedural Sedation and Analgesia (PSA) Agents

Case Resolution

Given the obvious painful ankle deformity and diminished pulses, emergent reduction is indicated. The patient is placed on a cardiac monitor (including oxygen saturation and capnography) and an IV is established. A trauma survey and AMPLE history are completed, and he is given 100 μg of fentanyl IV. High flow oxygen, bag valve mask, suction, and airway equipment (including adjuncts) are prepared, and the patient is evaluated for predictors of airway difficulty. He is given a propofol bolus of 50 mg, followed by 25 mg boluses every 2 minutes until sedation is achieved. The dislocated ankle is successfully reduced and immobilized, post-reduction radiographs are ordered, and he is monitored closely until sedation resolves. On waking the patient reports that his pain has dramatically improved, and thanks you for your care.

Bibliography

• Mace SE, Ducharme J, and Murphy MF. Pain Management and Sedation. New York: McGraw Hill, 2006.
• Miner JR, Paris PM, and Yealy DM. “Pain Management.” In Rosen’s Emergency Medicine: Concepts and Clinical Practice, edited by Marx, Hockberger, and Walls (7th Ed.). Philadelphia: Mosby, 2010.
• Thomas, S. “Management of Pain in the Emergency Department.” ISRN Emergency Medicine, vol. 2013, article ID 583132. http://dx.doi.org/10.1155/2013/583132.