Pain management in the emergency department: a clinical review

Indications

Opioid analgesics provide rapid and effective pain relief to patients presenting to the ED with a variety of acute painful syndromes, several chronic painful syndromes, and cancer-related pain syndromes (Table 1) [11]. Opioids should be used in the ED as a part of multimodal analgesia in conjunction with non-pharmacological and non-opioid therapies when the likelihood of their analgesic benefit is judged to exceed the likelihood of harm [12]. Opioids should not be used as first-line analgesics in the ED or at discharge in patients with acute back pain [14], acute headache [15-17], acute MSK pain (with the exception of fractures) [7], and acute dental pain [18] as the risks associated with their use (misuse, overdose, addiction) are significantly higher than the marginal, if any, pain relief provided.

Table 1.

Indications for opioid administration in the ED

Data supporting the use of opioids in the ED for treatment of acute exacerbation of chronic, non-cancer pain demonstrates higher likelihood of harm rather than benefit [19]. Opioid analgesics should not be routinely used in the ED for chronic non-cancer pain with a notable exception of vaso-occlusive crisis of sickle cell disease [20].

Choice of opioids

ED clinicians must recognize that commonly used opioids in the ED significantly differ from each other with respect to their ability to induce euphoria potentially leading to addiction (Table 2) [21]. Based on the available evidence, morphine sulfate administered either parenterally or orally in the ED and at discharge provides better balance of adequate analgesia and reduced euphoria and should be considered as the opioid of choice. In the situation when morphine is contraindicated and opioid analgesia is still warranted, parenteral fentanyl and oral hydrocodone are suitable alternatives in the ED and at discharge [11,12]. Parenteral and oral hydromorphone should be avoided as a first line opioid in the ED due to increased rates of respiratory and central nervous system depression (compared to morphine) as well as due to severe euphorigenic properties [22,23]. Oxycodone should not be used in the ED or at discharge due to greater potential for misuse, diversion, overdose, and the development of addiction with a lack of analgesic superiority to morphine and hydrocodone [21,24]. Similarly, tramadol should not be used in the ED and at discharge due to its modest, at best, analgesic efficacy, high potential for misuse, and host of numerous adverse effects (e.g., hypoglycemia, hyponatremia, seizures, serotonergic syndrome) [11,21]. Lastly, codeine plays no role in managing pain in the ED as it provides sub-optimal pain relief with significant genetic variability in analgesic response [11,21].

Table 2.

Dosing, routes, and clinical properties of commonly used opioids in the ED

Dosing ranges and routes of administration

Pure mu-receptor agonists lack an analgesic ceiling, and their doses can be titrated upwards until pain is controlled, or side effects become intolerable or dangerous [11]. Parenteral opioid administration via an intravenous (IV) route achieves rapid, titratable, and effective pain relief in the ED and serves as a preferred route of opioid delivery [3,11]. When intravascular access is not readily available, ED clinicians should consider administration of opioids via intranasal (IN) route (fentanyl, hydromorphone), inhalation (via nebulizer) route (fentanyl, morphine), subcutaneous injection (morphine, hydromorphone), or transmucosal route (rapidly dissolvable fentanyl tablets) [3]. Intramuscular (IM) delivery of opioids in the ED should be avoided as it is associated with severe pain at the injection site, unpredictable absorption rates, soft tissue infection, and myofibrosis leading to a dose escalation and higher rates of adverse effects [3]. The oral route of opioid administration in the ED should be considered when feasible, even though it results in poor oral bioavailability (with the exception of oxycodone) and delayed onset of analgesia in the ED limiting its utility for rapid pain control [2,3,25].

Nitrous oxide

Nitrous oxide is a tasteless colorless gas administered in combination with oxygen via inhalation and is used as an anxiolytic, analgesic, and sedative agent. The mechanism of action involves NMDA receptor antagonism and release of endogenous opioid via opioid receptor agonism in the central nervous system [36]. Nitrous oxide is administered via facemask or nasal hood, is easily titratable, and has rapid onset and elimination making it an ideal agent for pain control in the ED [37]. The most common concentration is 50% to 70% nitrous oxide (30%–50% oxygen) via an on demand inhalation mechanism or continuous flow device [37,38]. Nitrous oxide is a potent, safe, effective inhalational anesthetic that provides quick and titratable pain relief for a variety of acutely painful complaints or procedures performed in the pediatric and adult ED population [37,38] (Table 4). Administration of nitrous oxide in concentrations higher than 70% or in combinations with opioids or benzodiazepines requires full cardiopulmonary monitoring. There are no fasting requirements or restrictions postadministration when nitrous oxide is given as a single agent in the ED [39].

Table 4.

Indications and contraindications for emergency medicine nitrous oxide use

Intravenous (IV) lidocaine

Lidocaine non-competitively blocks voltage-gated sodium channels as well as NMDA receptors and reduces hyperalgesia and central sensitization [40]. When administered IV at 1 to 1.5 mg/kg dose over 10 to 15 minutes, lidocaine causes minimal adverse effects (dizziness, tinnitus, periorbital and perioral numbness) that are transient and rapidly reversible [40,41]. Despite promising data from the earlier studies for renal colic [41], subsequent studies demonstrated analgesic inferiority of IV lidocaine to IV ketorolac alone and to IV ketorolac/lidocaine combination [42]. Similarly, IV lidocaine failed to demonstrate significant pain relief in ED patients presenting with acute headache [43], acute low back pain [44], and abdominal pain [45]. A recent systematic review found no definitive evidence to recommend IV lidocaine use and recommended further research within a larger and older population to assess the efficacy and safety in specific painful syndromes [46]. At present, IV lidocaine cannot be recommended for routine use in the ED and its administration should be based on a case by case basis.

Neuroleptics (antidopaminergic medications)

Haloperidol is a butyrophenone derivative that exerts its effects through dopamine receptor blockade (D2-R antagonist). Additionally, haloperidol binds to the histamine receptors, alpha-2 adrenergic receptors, 5HT-2 receptors and NMDA receptors and decreases hyperalgesia produced by chronic opioid use [47]. Droperidol is a butyrophenone derivative with potent dopamine D2 antagonist actions with additional actions such as A2 adrenoceptor agonist and 5HT-3, muscarinic and nicotinic receptors antagonist [48].

Haloperidol and droperidol have been used in the ED as an adjunct in treatment of headache [49], abdominal pain associated with cannabinoid hyperemesis syndrome [50], gastroparesis and cyclic vomiting syndrome [51], and chronic pain not responsive to opioids [52]. Traditional dosing regimens and routes include haloperidol: 2.5–5 mg IV, 5–10 mg IM; droperidol: 1.25–2.5 mg IV, 2.5–5 mg IM.

Ultrasound-guided regional anesthesia

The most common ultrasound-guided regional anesthesia (UGRA) application in the ED is for management of patients presenting with hip/femur/upper extremity fractures followed by truncal and cervico-cranial applications (Table 5). UGRA provides significant pain reduction, alleviates the need for rescue opioid analgesia, and decreases the length of stay in the ED when compared to procedural sedation with no appreciable differences in analgesic efficacy and patient’s satisfaction. Furthermore, the utilization of UGRA in geriatric patients and patients with substance use disorder may eliminate any untoward side effects of parenteral opioid medications and reduce the dose of opioids [53,54]. Ultrasound guidance, calculation of maximum/lowest effective dose, aspiration before injection of 3 to 5 mL aliquots of local anesthetic of choice, and hydrolocation of structures with sterile saline at the start of infiltration are recommendations to prevent UGRA-related complications including local anesthetic systemic toxicity (LAST) [55].

Table 5.

Commonly performed ultrasound-guided nerve blocks in the emergency department

An IV lipid emulsion (intralipid) therapy should be readily available when using UGRA to manage a LAST. Symptoms of LAST are typically progressive, from minor (tongue, perioral numbness, restlessness, muscle fasciculations, hypertension, tachycardia) to moderate (seizures, global central nervous system depression/confusion) to signs of impending cardiovascular collapse (bradycardia, conduction block, hypotension) [56].

If the patient is above 70 kg, an initial bolus of 100 mL 20% lipid emulsion should be administered over 2 to 3 minutes followed by a 20% lipid emulsion infusion of 200 to 250 mL over 15 to 20 minutes. For patients below 70 kg, the bolus dose is a weight-based 1.5 mL/kg followed by a 0.25 mL/kg/min infusion. If circulatory stability is not attained, rebolusing up to two further times and increasing the infusion to 0.5 mL/kg/min is suggested. The maximum recommended dose of lipid emulsion is 12 mL/kg [57].

Cryotherapy

Multiple mechanisms have been proposed to explain the physiological basis for cryotherapy effectiveness, including inhibition of nociceptors, reducing the metabolic enzymatic activity of the injured tissue, and decreasing the nerve conduction velocity [64]. Cryotherapy is frequently used for managing acute MSK and soft tissue painful syndromes [65-68]. A common ED practice of applying a cold pack or ice pack to the skin with 10 minutes on, 10 minutes off can result in rapid analgesia in the ED and outpatient setting [66]. Another technique such as intensive targeted cryotherapy (wetted crushed ice in the plastic bag) was found to produce lower skin temperature than the application of the cold pack [67] and recently, has demonstrated more effective analgesia than chemical cold packs for acute MSK injuries in the ED [66]. Cryotherapy has been shown to be effective in the treatment of low back pain, neck pain, and a multitude of other sports-related injuries [66-69].

Heat therapy

When used in the context of a multimodal pain management, application of heat has shown moderate benefit in improving pain associated with acute neck and back strain in the ED [70]. Use of heat packs for treatment of chronic neck pain in the elderly population has been shown to decrease pain and improve range of motion [71]. Use of superficial heat was shown to be beneficial for the treatment of pain associated with temporomandibular disorders [72].

A systematic review provided tentative evidence that transcutaneous electrical nerve stimulation (TENS) provided mild to moderate improvement in acute pain (back pain, fractures, headache, MSK pain, and procedural pain) as a stand-alone treatment modality in adult patients. The evidence suffered from high risk of bias and inadequate sample sizes [73]. Specifically to the ED, in a single center pilot study, TENS was found to be effective (average pain relief by 40% from the baseline) in 99% of patients with a variety of acute and chronic painful conditions, and to result in functional improvement in 83% of patients [74]. At present, however, robust data is lacking to support widespread use of TENS in the ED setting.

Acupuncture

The evidence for acupuncture is markedly heterogeneous, with a dearth of large, well designed, randomized controlled trials primarily supporting its use for chronic painful syndromes (back pain, osteoarthritis, and headache) [75]. Data on utilization of acupuncture (battlefield acupuncture) in the ED is limited with preliminary case series and smaller pilot studies showing promising results for pain control [76] but with larger, randomized studies demonstrating markedly mixed outcomes [77,78] that do not support widespread use of acupuncture in the ED.

Osteopathic manipulative treatment

Osteopathic manipulative treatment (OMT) is therapeutic maneuvers employed by osteopathic physicians to address dysfunctions in the MSK, myofascial, lymphatic, vascular or neurological structures. Studies looking at the application of OMT in the ED demonstrate analgesic improvement in MSK painful syndrome, reduction in the amount of parenteral analgesia [79,80] and decrease in length of stay [81]. However, there is a significant lack of large, randomized controlled trials. OMT is reimbursable as a procedure via five distinct codes in the American Medical Associations Current Procedural Terminology, making the utilization of this low risk [79], non-pharmacologic intervention more palatable in the hands of an OMT trained emergency physicians.