Overview and historical pain management
Perioperative pain management is an essential component of surgical care. In the United States, an estimated 360,000–420,000 head and neck surgeries are performed annually. Pain severity tends to differ depending upon the type of otolaryngological procedure performed as well as with the anatomic location of the procedure. Opioid pain medications have been a mainstay in the treatment of acute perioperative pain in head and neck surgery. Early publications from the 1930s demonstrate that pain control was primarily achieved with opioids and salicylates for tonsillectomy and adenoidectomy. In the 1950s, the addition of adjunctive local anesthetics, such as effocaine, to tonsillectomy procedures provided further pain control.
Oncology patients make up a significant proportion of patients requiring pain control, with nearly 50% of cancer patients undergoing treatment reporting pain. In the United States, an estimated 54,000 new oral cavity and pharyngeal cancers, 12,600 new laryngeal cancers, and 44,200 new thyroid cancers will be diagnosed in 2021. Additionally, an estimated 586,000 thyroid, 377,000 lip/oral cavity, 184,000 larynx, 133,000 nasopharynx, 98,000 oropharynx, 84,000 hypopharynx, and 53,000 salivary gland malignancies will be diagnosed in 2020 worldwide. Surgical resection is a mainstay for the treatment of many head and neck cancers, and therefore, a strong understanding of perioperative pain management is essential for the care of head and neck oncology patients.
Pain management continues to evolve in the otolaryngology practice, and several shifts in prescribing patterns have occurred over the past several decades. Notably, an increase in the prevalence of opioid prescription began in the 1990s, which coincided with an increase in opioid dependence, and opioid-related deaths within the United States have brought attention to prescribing practices among physicians. These consequences have been a major driving force in the evolution of pain management within otolaryngology and include the introduction and implementation of multimodal analgesic strategies and enhanced recovery protocols that aim to limit the use of opioid analgesics. Another notable shift in perioperative pain management includes the cessation of codeine-containing analgesia for pediatric patients undergoing adenotonsillectomy as a result of deaths among patients who hypermetabolize the drug into its active opioid.
The first enhanced recovery after surgery (ERAS) protocol specific to otolaryngology was published by Coyle et al. in 2016. Their ERAS protocol was developed specifically for patients undergoing head and neck oncology procedures. Further ERAS protocols have been subsequently tailored to more specific procedures such as head and neck cancer resection with free-flap reconstruction and thyroid/parathyroid surgery. ERAS protocols are multifaceted with an overall goal of improving the perioperative experience for the patient and improving outcomes of major surgeries by decreasing length of hospitalization and reducing postoperative complication rates. Pain control is a key component of all ERAS protocols, and a majority of these protocols involve a multimodal pain management strategy in an effort to decrease the number of opioid analgesics utilized during recovery. These strategies will be further discussed within this chapter. , ,
Typical pain management regimens
A strong understanding of perioperative pain management provides a basis for safe perioperative care in patients undergoing head and neck surgery. Perioperative pain regimens often include a combination of opioid and/or nonopioid medications that are oriented toward decreasing each medication’s side effects and limiting the overall use of opioids. The exact pain management regimen selected is often based on provider preference and patient factors such as medication allergies, renal and liver function, enteral status, the type of procedure performed, and expected pain levels. Care should also be taken for patients who undergo procedures requiring airway manipulation and in patients with obstructive sleep apnea, as opioids pose a risk of sedation and respiratory depression. Several nonopioid analgesics including nonsteroidal anti-inflammatory drugs, acetaminophen, anticonvulsants such as gabapentin, corticosteroids, and locoregional anesthetics may be utilized in an effort to decrease the risks associated with opioid use in patients undergoing head and neck surgery. Medications commonly utilized within the perioperative period are included in Table 1.1 .
| Route of administration | Class | Medication | Dose | Mechanism of action | Special considerations | Side effects | History |
|---|---|---|---|---|---|---|---|
| Oral/Nasogastic tube/Gastrostomy tube | Analgesic/Antipyretic | Acetaminophen | 650 mg Q6h-950 mg Q8h | Activation of descending serotonergic inhibitory pathways in CNS | Hepatic dosing | Hearing loss, skin rash | First used clinically in 1893, did not appear commercially until 1950s in the US |
| NSAID | Ibuprofen | 200–400 mg Q4-6h | Reversibly inhibits COX-1 and 2 resulting in decreased prostaglandin production | Renal dosing or omit in patients with CKD or decreased GFR Cardiovascular considerations | Decreased hemoglobin, increased serum ALT and AST, edema, dyspepsia, nausea, vomiting, prolonged bleeding time, rash | COX genes were characterized in the 1980s and NSAIDs were developed shortly after. | |
| Celecoxib | Preop: 200 mg once Postop: 200 mg BID and continue for 5 days postop | Decreases prostaglandin synthesis by selectively inhibiting the activity of COX-2 | Acute myocardial infarction, angina, palpitations, alopecia, dermatitis, GI symptoms, GERD, anemia, thrombocytopenia, increased liver enzymes, bronchospasm | ||||
| Anticonvulsants | Gabapentin | 300–1200 mg TID | Not well known. Proposed mechanisms include the class being structurally related to GABA, antagonism of calcium channels in CNS, and antagonism of NMDA receptors | Renal dosing or omit in patients with CKD or decreased GFR, need for up-titration based on side effects | Somnolence, dizziness, ataxia, asthenia, hypertension, hyperglycemia, weight gain, skin rash, constipation, nausea, impotence, infection, emotional lability | Gabapentin was originally approved in the United Kingdom in 1993. Pregabalin was approved in Europe in 2014 | |
| Pregabalin | 50–300 mg BID | ||||||
| Opioid | Tramadol | 50 mg Q4-6h PRN | Partial mu agonist, in addition to central GABA, catecholamine, and serotonergic activities. | Renal dosing may interfere with serotonin and norepinephrine | Constipation, nausea, drowsiness, orthostatic hypotension, pruritus, hyperglycemia | It was first synthesized in 1962 and has been available for pain treatment since 1977 | |
| Acetaminophen-hydrocodone | 325-5 mg Q6h PRN | Mu opioid receptor agonist | Hepatic dosing | Sedation, tolerance respiratory depression, constipation, nausea/vomiting, urinary retention, hearing loss, skin rash | Oxycodone has been in clinical use since 1917 | ||
| Oxycodone | 5–10 mg Q4-6h PRN | ||||||
| Intravenous (IV) | Opioid | Morphine | 1–4 mg IV Q1-4h PRN | Mu opioid receptor agonists | Renal dosing | Sedation, tolerance respiratory depression, constipation, nausea/vomiting, urinary retention | Morphine was isolated in 1804 by a German pharmacist |
| Hydromorphone | 0.2–1 mg IV Q2-3h PRN | ||||||
| Analgesic/Antipyretic | Acetaminophen | 650 mg IV Q6H | Activation of descending serotonergic inhibitory pathways in CNS | Hepatic dosing | Nausea, vomiting | ||
| Corticosteroid | Dexamethasone | 8–10 mg IV Q8h | Suppresses neutrophil migration, decreases the production of inflammatory mediators, and reverses increased capillary permeability; suppresses normal immune response | Dose reduction in diabetic patients | Cardiac arrhythmias, bradycardia, depression, euphoria, insomnia, psychosis, acne vulgaris, adrenal suppression, decreased glucose tolerance, growth suppression, hirsutism, weight gain, infection, fractures, osteoporosis, impaired wound healing | Dexamethasone was introduced in the 1950s | |
| NSAIDs | Ketorolac | 15–30 mg IV Q6h PRN | Decreases prostaglandin synthesis by weakly inhibiting both COX-1 and COX-2 | Should be limited to 72 h of use maximum. Consider renal dosing | Dyspepsia, increased liver enzymes, headache, hypertension, pruritus, gastrointestinal ulcer, heartburn, prolonged bleeding time, anemia | ||
| Patient-controlled analgesia (PCA) | Opioid | Morphine | Demand dose: 0.5–2 mg Lockout (min): 6–10 Continuous basal: 0–2 mg/h (not recommended) | Mu opioid receptor agonists | Renal dosing | Sedation, tolerance respiratory depression, constipation, nausea/vomiting, urinary retention | Morphine was isolated in 1804 by a German pharmacist. |
| Hydromorphone | Demand dose: 0.1–0.4 mg Lockout (min): 6–10 Continuous basal: 0.0.4 mg/h (not recommended) | Renal dosing | |||||
| Fentanyl | Demand dose: 5–50 μg Lockout (min): 5–10 Continuous basal: 0–2 mg/h (not recommended) | Preferred opioid for patients with renal or hepatic dysfunction | |||||
| Transdermal | Opioid | Fentanyl | Apply 1 device (40 mcg dose delivered over 10 min; maximum 6 doses per hour). 1 device operates for 24 h or 80 doses. Reapply Q24h for a maximum duration of up to 72 h | Mu opioid receptor agonist | Has a lag time of 6–12 h to onset of action, and typically reaches a steady state in 3–6 days. After removal, a subcutaneous reservoir remains, and drug clearance may take up to 24 h | Peripheral edema, hyperhidrosis, dehydration, hypokalemia, abdominal pain, nausea, vomiting, constipation, anemia, confusion, drowsiness, dyspnea, pneumonia | |
| Local anesthetics (amides and esters) | Lidocaine | 3.5%–4% patch: apply to the affected area for up to 12 h in a 24-h period | Blocks initiation and conduction of nerve impulses by decreasing the neuronal membrane’s permeability to sodium ions, which results in inhibition of depolarization with resultant blockade of conduction | Erythema, petechia, edema, pruritus, nausea, flushing, metallic taste, dermatitis, burning |
Opioids and changes in prescribing habits within otolaryngology
The opioid epidemic remains an important health crisis that continues to shape how prescribers manage perioperative pain. Between 1991 and 2010, the number of opioid prescriptions in the United States nearly tripled as a result of several contributing factors. Routine documentation of patients’ pain levels as a vital sign was recommended in a consensus statement introduced in 1995 by the American Pain Society. The consensus statement also advised frequent pain assessments, prompt pain control, and assessment of pain response to analgesics provided. In the late 1990s, state medical boards reduced restrictions on opioid prescriptions for noncancer patients, and in 2000 the Joint Commission on the Accreditation of Health Care Organizations introduced new inpatient and outpatient pain management standards. Other factors that may have compounded the increase in opioid utilization included an increase in patient awareness of pain control via opioid medication, claims of undertreatment of pain, physician promotion, and marketing by the pharmaceutical industry. , Several misconceptions regarding opioids exist including the belief that they are a uniquely powerful pain reliever, that they are particularly effective for acute pain, and that short-term courses do not pose a risk of long-term use or opioid use disorders. These misconceptions also likely contributed to their overuse. Risks of opioid prescription have long been established and include respiratory depression, constipation, nausea, vomiting, sedation, tolerance, opioid dependence, overdose, and opioid-related death. Additionally, more recent studies suggest that opioids modulate immune function and contribute to delayed wound healing that may further negatively impact postoperative recovery, however, these findings require further investigation. , ,
The increase in opioid prescribing has been correlated with an increase in opioid-related deaths and hospital admissions. , The most recently published cause of mortality data by the Centers for Disease Control and Prevention (CDC) ranges from 1999 to 2019. The age-adjusted death rate in the United States involving all opioids increased from 2.9 per 100,000 population in 1999 to 15.5 per 100,000 population in 2019. Between 2013 and 2019, death from drug overdose increased by 56.5%, with a total of 70,360 opioid-related deaths reported in 2019. Of these opioid-related deaths within the United States, the age-adjusted death rate from synthetic opioids increased from 1.0 (2013) to 11.4 (2019) per 100,000 population, and the prescription opioid-related death rate decreased from 4.4 (2013) to 4.2 (2019) per 100,000 population.
The CDC Annual Surveillance Report of Drug-Related Health Risks was most recently updated for 2019. This report demonstrated that the total volume of opioid prescriptions in the United States peaked in 2012 with an annual dispense rate of 81.3 per 100 persons, accounting for 255 million prescriptions. Additionally, in 2012, surgeons accounted for 9.8% of the total annual opioid prescriptions made and prescribed opioids at a rate of 36.5% of their total prescriptions. A steady decline in prescription dispense rate has occurred between 2012 and 2019, with a dispense rate of 46.7 per 100 persons and 153 million prescriptions written in 2019.
The risk of developing long-term opioid use has been correlated with the duration of the initial prescription. Alam et al. performed a retrospective cohort study to assess long-term opioid use in patients who underwent short stay surgery between 1999 and 2008 and demonstrated patients who received an opioid pain medication within 7 days of an outpatient procedure were 44% more likely to become long term users than those who did not receive an opioid. Long-term use was defined as having filled an opioid prescription greater than 10 months from the initial procedure date. Characteristics that have been proposed to increase the likelihood of long-term opioid use include the duration of the prescription, number of refills provided, and providing second opioid prescriptions. Likelihood of long-term opioid use begins to rise in patients who receive postoperative opioid prescriptions longer than 3 days duration, with the sharpest increase in likelihood at the 10th day and 30th day of a prescription. An estimated one in seven patients who receive opioid refills, or a second opioid prescriptions, remain on opioids 1 year later. Additionally, an estimated 33% of patients who undergo a resection for head and neck cancer continue opioid use >90 days after the procedure, with an increased likelihood in patients with preoperative opioid use.
Otolaryngologists continue to make efforts to transition away from opioid utilization. Nonopioid strategies and strategies that decrease the number of opioids prescribed for postoperative pain management have demonstrated success in many studies and often involve a multimodal approach. These multimodal strategies include the use of local and regional anesthesia, acetaminophen and nonsteroidal antiinflammatory drugs (NSAIDs), γ-aminobutyric acid agonists (i.e., Gabapentin, pregabalin), tramadol, as well as the implementation of advanced recovery after surgery protocols. While many studies demonstrate a reduced opioid requirement with multimodal approaches to analgesia, the true analgesia requirements for various procedures remain poorly understood due to the heterogeneity of the procedures performed by the otolaryngologist. Subsets of procedures have been explored to include head and neck oncologic surgeries, neck dissection, and endocrine surgeries. ,
Additional factors that have facilitated a decrease in opioid prescription by physicians include governmental legislation. While the 2016 opioid prescribing guidelines for chronic pain by the CDC does not specifically address perioperative pain management, the guideline does discuss treatment of acute pain. It states when using opioids for acute pain, the lowest effective dose of immediate-release opioids should be used, and the quantity should be no greater than the expected duration of pain severe enough to require opioids. They conclude that 3 days or less of opioids is often sufficient for acute pain, and rarely is more than 7 days of opioids required. Since its publication in 2016, 49 states have implemented a prescription drug monitoring program (PDMP) and have demonstrated success in the reduction of opioid prescription within otolaryngology. Rubin et al. assessed the effectiveness of Massachusetts’ prescription awareness tool specifically on otolaryngologic procedures and demonstrated a statistically significant reduction in opioid prescriptions for thyroidectomy, tonsillectomy, and parotidectomy since their states program initiation in 2016. Legislation that limits the duration of opioid prescription have also been shown to significantly decrease the duration of opioids prescribed, decrease the proportion of patients receiving an opioid, and decrease the total opioid dose prescribed postoperatively specifically within otolaryngology.
In 2021, the American Academy of Otolaryngology—Head and Neck Surgery published their first clinical practice guidelines addressing opioid prescribing for analgesia after common otolaryngology operations. The guidelines outlined 10 key action statements can be found in Table 1.2 .
| Statement | Action: clinicians should… | Strength |
|---|---|---|
| Statement 1: Expected pain | Preoperatively advise patients and those involved in the postoperative care about expected severity and duration of pain | Recommendation |
| Statement 2: Modifying factors | Preoperatively gather information about specific patient factors that may modulate the severity or duration of pain | Recommendation |
| Statement 3A: Risk factors for opioid use disorder | Preoperatively identify patient-specific risk factors for opioid use disorder when analgesia with opioids is anticipated | Strong recommendation |
| Statement 3B: Patients at risk for opioid use disorder | Preoperative evaluate the need for modification of postoperative pain management plan in patients at risk for opioid use disorder | Recommendation |
| Statement 4: Shared decision making | Encourage shared decision making by informing patients of the benefits and risks of postoperative pain treatments that include nonopioid analgesics, opioid analgesics, and nonpharmacologic interventions | Recommendation |
| Statement 5: Multimodal therapy | Develop a multimodal treatment strategy for the management of postoperative pain | Recommendation |
| Statement 6: Nonopioid analgesia | Advocate for the use of nonopioid medications as the first line for postoperative pain management | Strong recommendation |
| Statement 7: Opioid prescribing | Limit therapy to the lowest effective dose and shortest duration when treating pain with opioids | Recommendation |
| Statement 8A: Patient feedback | Educate patients and caregivers on how to communicate if pain is not controlled, or if side effects are experienced from pain medications | Recommendation |
| Statement 8B: Stopping pain medications | Recommend patients discontinue opioids when pain is controlled with nonopioids, and discontinue all analgesics when pain has resolved. | Recommendation |
| Statement 9: Storage and disposal of opioids | Recommend patients or caregivers securely store opioids, and dispose of unused opioids through take-back programs or other accepted means | Strong recommendation |
| Statement 10: Assessment of pain control with opioids | Inquire within 30 days postoperatively whether a patient has stopped use of opioids, has properly disposed of unused opioids, and was satisfied with their postoperative pain management plan | Recommendation |
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