Deepali Dixit, PharmD, BCPS, BCCCP, FCCM

will likely bring a continued focus on COVID-19’s substantial effect on prices and utilization of services.

In its annual report, health care services company Vizient predicts a 3.1% increase in total pharmaceutical spending in 2022. Oncology drugs will account for about 25% of the increase, with continued spending on pharmacotherapy related to COVID-19.

The sustained impact of COVID-19 on health care is due to the continuing emergence of disease variants coupled with vaccine hesitancy, according to Vizient.

The company also predicts that specialty pharmaceutical pricing will grow at a rate of 4.68% in 2022, driven by the likely approval of new therapies as well as price increases for adalimumab, a specialty drug used to treat autoimmune diseases.

Further, Vizient estimates that with recent endorsements from diabetes management guidelines and organizations the cost of influential diabetes agents such as glucagon-like peptide 1 and 2 and insulin, will increase by 2.63% next year. These novel diabetes drugs are gaining diverse indications beyond the management of blood glucose, such as for the prevention of cardiovascular events and other disease complications.

The report states that “when combined with the increasing prevalence of the disease, health systems are expected to see growing use of these products in their patient populations.”

The COVID-19 pandemic brought challenges that overwhelmed the health care system and required greater flexibility in cooperation and responsibilities from all essential health care providers, including pharmacists. In 2022, there will likely be continuing evolvement and expansion of the pharmacist’s role with their recognition as critical frontline workers in the fight against COVID-19. Additionally, pharmacists are extensively involved in education and research, while remaining active members of inpatient and outpatient COVID-19 recovery clinic multidisciplinary teams and vaccination efforts. Moreover, with the increased use of telehealth during the pandemic, health systems are investing more in digital innovation. Pharmacists are taking advantage of virtual postintensive care syndrome clinics, among others, to adjust medications and to counsel and educate patients. The results of a recent study show that in the beginning of 2020, 0.1% of Medicare primary care visits were conducted using telehealth, but this number increased to 43% within 3 months because of the pandemic.

 This growth is expected to continue, and some experts recommend that organizations start aligning their virtual strategies with the evolving needs.

Meanwhile, Amazon’s entry into pharmacy services may have a large impact in 2022. Consumers are so accustomed to using Amazon to order a whole slew of merchandise and it will be interesting to see how the prescription services landscape will be affected.

In 2022, organizations will continue to take a holistic approach to infusion care covering extended sites, including home infusion. Home infusion services had previously existed in health systems but some had stopped providing the service because of increased competition and payor rates. However, the pandemic led to more patients preferring to receive infusion therapy at home, leading to a heightened interest in providing these services.

Over the past decade, more than 500 health system and hospital mergers have occurred. An advantage of this partnership is the availability of large data sets that can guide health care delivery programs, prevention efforts, and wellness with wide-ranging medication management. The pursuit of medication errors prevention and quality improvement has led to a growing interest in artificial intelligence (AI) and precision medicine. An example of AI technology gaining traction in health care is machine learning, which focuses on the development and use of computer systems that can adapt and emulate without following explicit instructions. The systems use algorithms and statistical models to analyze and draw inferences from data patterns.

AI has been hailed as a transformational force in health care. In the past few years, the AI health market has experienced explosive growth, with investments worth billions of dollars, and in 2022, huge investments will likely continue to be made on the digital front. Health care is embracing AI for a range of applications, including clinical research, drug development, and robotic surgery. In addition, AI is being adopted as a practical tool to improve medication safety and patient outcomes, monitor medication adherence, reduce drug costs, replace labor-intensive and repetitive tasks that are prone to error, and streamline prior authorizations. These applications of AI will transform medication management. Thorough digestion and utilization of health care data are crucial, once the data analyses have been completed; equally important is knowing what to do based on the findings. Increasingly, real-time data assessment, models, and predictions are being used to help detect and prevent patient deterioration and manage health care crises. As data sets require the expertise and skills of data scientists, pharmacy departments will need to recruit these scientists to support predictive modeling to drive health care delivery. In 2022, AI will continue to be a priority and will have a positive and profound effect on the delivery of health care and medication management. On a similar front, genetics will continue to play a key role in personalized medication treatment to achieve the desired therapeutic effects.

Another growing trend that will continue to garner attention is the emphasis on gender inequity and sexual harassment in the pharmacy profession. In 2020, a petition titled End Gender Inequality in Clinical Pharmacy led to a response from several major pharmacy organizations. The petition advocates for gender equality, the development of policies against such behavior, and guidance and support for members of the profession who encounter gender bias, harassment, predatory conduct, or other intimidating or threatening behaviors. These organizations stand on values such as a culture that strongly supports diversity, equality, and inclusion. Major underpinning is required to promote gender equity more effectively within the profession, but this work is critical to ensuring future sustained infrastructure. Gender inequity and sexual harassment are widespread in the medical community, the pharmacy profession, and our society. All members of the pharmacy profession should have equal opportunity and support to reach their highest potential. However, major gaps in support of the diverse membership of the pharmacy profession have highlighted a lack of awareness of harassment resulting from gender and gender inequity issues. Fostering greater diversity in the workforce cultivates innovation, decreases health disparities, and improves communication, health care access, patient satisfaction, and problem solving for complex challenges.

 The potential benefits of gender equity are vast, including economic benefits, patient satisfaction, and the cultivation of diversity, innovation, and a unified profession. Women in pharmacy have started the discussion using online platforms and professional networks, but the drivers of continued change will be through organizational leadership and advocacy as well as through awareness by individual pharmacists.

In light of the pandemic’s challenges, the new year will see a continued focus on health care delivery through continued testing, vaccination, and treatment. Other important trends will include rising health care costs and an increase in digital health care. Moreover, it is hoped that progress will be made in addressing gender equity and sexual harassment in the pharmacy profession.

Deepali Dixit, PharmD, BCPS, BCCCP, FCCM, 

is a clinical associate professor at Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway, and a clinical pharmacy specialist in critical care at Robert Wood Johnson University Hospital in New Brunswick, New Jersey.

1. Pharmacy market outlook. Vizient. Accessed October 1, 2021. 

https:/info.vizientinc.com/pharmacy-market-outlook

2. Martin G. Top 10 emerging trends in health care for 2021: the new normal. AHA Trustee Services. Accessed October 1, 2021.https://trustees.aha.org/top-10-emerging-trends-health-care-2021-new-normal

3. Aungst TD, Franzese C, Kim Y. Digital health implications for clinical pharmacists services: a primer on the current landscape and future concerns. 

2021;4(4):514-524. doi.org/10.1002/jac5.1382

4. Institute of Medicine (US) Committee on the Robert Wood Johnson Foundation Initiative on the Future of Nursing, at the Institute of Medicine. 

The Future of Nursing: Leading Change, Advancing Health

5. Bissell BD, Johnston JP, Smith RR, et al. Gender inequity and sexual harassment in the pharmacy profession: evidence and call to action. 

 Published online July 7, 2021. doi:10.1093/ajhp/zxab275

Articles

Trends to watch include increased spending on drugs and treatments, expansion of pharmacists' role, and ongoing interest in home infusion therapy.

COVID-19 Impact Will Continue to Dominate in 2022

Post-Intensive Care Syndrome (PICS) comprises a series of ailments that patients experience upon discharge from the hospital following care for a critical illness.

These ailments may be a new occurrence or worsening of a cognitive, mental, or physical health issue. From pain to anxiety and depression to difficulty concentrating and remembering, the manifestation of PICS varies.

The overall population of critical care patients who experience PICS is unknown; however, with improved survival rates and increased ventilator users, many discharged patients experience at least 1 problem associated with PICS. These patients often have trouble returning to their pre-illness state, with some never fully recovering. Resolution of symptoms is dependent upon both the patient and the symptom, with time frames of a few weeks to several years.

PICS can appear in any patient, regardless of demographics or environment. Severity of symptoms also differs, although some risk factors have been defined. Remaining within the intensive care unit (ICU), especially while intubated and sedated, is a major risk factor for developing PICS, which can also result from dysregulated blood glucose, respiratory distress syndrome, prolonged delirium, and sepsis while in the hospital.

Unfortunately, PICS is not exclusive to the patient and can similarly be experienced by caregivers. The patient’s family can develop anxiety, depression, and post-traumatic stress disorder, and maintenance of their well-being is a crucial objective. PICS can, however, be prevented, or at least managed, through close monitoring and interventions. Caregivers, family, and the medical team, including pharmacists, can involve themselves in the patient’s critical care journey to improve the care and prognosis of PICS.

In terms of prevention, there are many factors to consider. Certain drugs used in the ICU have been found to be associated with PICS.

 Also, blood glucose levels are an important laboratory value to monitor in patients in the ICU because hyperglycemia has been found to be associated with increased morbidity and mortality.

Generally, insulin is used to manage blood glucose levels if they become elevated. The clinical guidelines recommend targeting a glucose goal of approximately 140 mg/dL to 180 mg/dL.

 If glucose levels go beyond the recommended target, that is an indication to optimize the insulin dose.

Medications for the treatment of delirium that are a concern in the development of PICS. Antipsychotics not only have weak evidence in the prevention and treatment of delirium but, when used in the ICU, they also can potentially precipitate effects of delirium or other adverse effects and increase the patient’s chances of developing PICS.

 The best way to prevent delirium is through early mobilization. Another concern is that antipsychotics and other medications initiated in the ICU are often continued erroneously during transitions of care.

In terms of comorbidities, pain and sedation are associated with an increased risk of developing PICS. When an individual is sedated for a long period of time, the likelihood of delirium increases, so light sedation using nonbenzodiazepines for the shortest amount of time is preferable. Also, in terms of pain management, nonopioid analgesics are preferred over opioid analgesics because opioids can also cause central nervous system depression and prolonged immobilization.

Monitoring these conditions closely is vital because any improvement in a patient’s status may warrant a dose reduction. Furthermore, pain should be monitored using validated pain scales, such as the Behavioral Pain Scale and the Critical-Care Pain Observation Tool. Monitoring pain helps improve patient experience and quality of life after discharge because individuals who recall pain in the ICU often develop chronic pain.

 Finally, in terms of monitoring sedation, the Richmond Agitation and Sedation Scale or another validated sedation assessment tool should be used.

Transitions of care (TOC) are an important aspect of prevention because medication errors during TOC are common.

 TOC can get complicated for a patient, especially if they are discharged with many different medications. Pharmacists can help by making sure that the medications prescribed to the patient are appropriate for the outpatient setting. Pharmacists can also screen for and discontinue any unnecessary medications to reduce the pill burden for patients. In addition, pharmacists can educate patients about the importance of medication adherence and how nonadherence can lead to the disease state worsening.

Patients who develop PICS are treated based on their symptoms. If their minds are affected, they can be started on medications and therapy. If their physical states are affected, they may initiate exercise and physical therapy. If quality of life is affected, occupational therapy is an option.

There are many avenues through which patients with PICS can heal, and PICS clinics are a promising way to start. These clinics are a developing idea in North America but are well established in Europe.

Traditionally, the clinics include multidisciplinary teams that support patients who have shown at least 1 risk factor for PICS. These teams often include nurses, occupational and physical therapists, physicians, and social workers, but pharmacists can also play a big role by reviewing medications and counseling on adherence and proper use. Through pharmacists’ efforts, therapies can be optimized and mistakes such as potential interactions or unnecessary medications that fell through the cracks during TOC can be corrected.

PICS clinics provide an invaluable opportunity to comfort and educate patients, continue care, and provide patients the opportunity to comment on and share their ICU and post-ICU experiences, empowering them in their care.

Patients requiring ICU care can experience impairments in normal bodily functions that make it difficult to perform self-care and participate in daily activities. This can have a detrimental effect on mental health and overall well-being, which can lead to a greater risk of hospitalization, institutionalization, and mortality.

It is critical to manage PICS with education, follow-up, and medication to lower the rate of these incidences and provide patients with a better quality of life once discharged from the ICU. Health care providers should participate in TOC to minimize the risks of medication error and discontinue unnecessary medications using proper guidelines and protocols. Health care providers should be aware of the risks of and treatments for PICS, not only to better serve patients, but also to help educate caregivers and family members so that they may continue to provide care outside the health care setting.

Winston Su, Olivia Wierciszewski, Kapil Rawal, 

 are PharmD candidates at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey in Piscataway.

is a clinical associate professor of pharmacy practice and administration at the Ernest Mario School of Pharmacy at Rutgers, The State University of New Jersey.

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Managing transitions of care is vital to discontinue use of unnecessary drugs and minimize medication errors.

Pharmacists Can Help Treat Post-Intensive Care Syndrome

Pain management in the intensive care unit (ICU) is not a one-size-fits-all discipline. There are many factors to consider, including location and type of pain, breakthrough pain despite adequate management, and patient history of opioid use. But preventing pain instead of reacting to it is key. 

It is important to keep in mind that pain management medications are not without the risks of oversedation and, ultimately, respiratory depression. Hence, it is imperative to find a balance in addressing pain by using medications that have different mechanisms of action.

The first class of medication that providers turn to is local anesthetics. Guidelines do not recommend the use of topical anesthetics in ICU patients. However, topical anesthetics can provide great advantages when other routes of administration are not plausible. Lidocaine is a local anesthetic that binds reversibly to sodium channels, blocking nerve depolarization by locking nerves in the open state.

 One study evaluated pretreatment with lidocaine 5% patches in acute potthoracotomy population pain. Results found that lidocaine was effective in reducing pain intensity and total morphine consumption. Therefore, lidocaine 5% patches could be considered as an adjunct treatment to intravenous (IV) morphine to control postthoracotomy pain.

 Nevertheless, the results of another study assessing the efficacy of topical lidocaine 5% patches in ICU patients in poststernotomy or postthoracotomy pain concluded that lidocaine did not reduce acute pain.

Because of their low risk of systemic effects, minimal drug interactions, and safety profiles, lidocaine patches are considered a suitable treatment for the elderly population. However, variable skin properties in individuals may influence absorption and distribution. Additionally, many studies of topical medications lack quality; thus, further studies are needed to analyze effectiveness and long-term effects.

The guidelines also suggest using low-dose ketamine for pain relief in post-operative adults in the ICU.

-aspartate and glutamate receptor antagonist. It is recommended as an adjunct to opioid therapy to reduce opioid consumption in ICU patients with postsurgical pain. Common adverse effects (AEs) include confusion, diplopia, drowsiness, dysphoria, and, in some rare cases, hallucinations.

Although opioids remain the mainstay of therapy in the ICU, the guidelines also recognize the negative effects that opioids pose and encourage the use of multi-modal therapies whenever possible to decrease opioid use.

 Two other classes of medications used in the ICU are nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen, an analgesic, and antipyretic medication. NSAIDs work by inhibiting prostaglandin synthesis through COX-1 and COX-2 inhibition.

 Patients must have stable renal functions and not be on concomitant nephrotoxic medications while receiving NSAIDs. These drugs should also be avoided in patients with gastric ulcers, active gastrointestinal (GI) bleeds, or a history of GI bleeds, and congestive heart failure.

 Additionally, in patients with severe cirrhosis or liver impairment, alternatives should be considered.

Acetaminophen is the preferred initial agent of choice for ICU patients.

 According to the guidelines, IV, oral, or rectal acetaminophen should be used for pain control and to decrease opioid use in the critically ill population.

 Acetaminophen has proved to have comparable effects to opioids and demonstrated an opioid-sparing effect in multiple investigations. In 1 study looking at moderate to severe pain after orthopedic surgery, results showed  that IV acetaminophen at a dose of 1 g, administered over 24 hours, reduced opioid need, and was well tolerated.

 The results of another study showed that the addition of acetaminophen to meperidine provided adequate pain control in patients and reduced their opioid need.

 Results from another trial demonstrated adequate pain control and opioid-sparing effects through the combined use of acetaminophen and tramadol in patients who have cardiac surgery.

Similar opioid-sparing effects can be seen with NSAIDs, such as ibuprofen and ketorolac. Study results showed that using 800 mg of IV ibuprofen every 6 hours in patients who had postabdominal pain effectively controlled their pain and reduced their opioid requirements.

 The results of one controlled, randomized trial comparing IV morphine 4 mg with IV ketorolac 4 mg showed that pain scores were similar after chest tube removal. These results indicated that NSAIDs could be used as an alternative to opioid therapy in the critically ill population for certain procedures.

 When using ketorolac, it is imperative to maintain therapy for no more than 5 days, as prolonged therapy can increase the risk of AEs, particularly GI bleeding.

 Patients should be evaluated to determine whether they are good candidates for either acetaminophen of NSAID therapy alone or in combination with opioids to decrease AEs and opioid burden and help prevent pain.

Neuropathic pain is derived from damaged nerves and is often treated by medications, such as carbamazepine, gabapentin, and pregabalin. Their analgesic properties are exhibited through mechanisms of binding to voltage-gated calcium channels and inhibiting the release of excitatory neurotransmitters.

 Neuropathic agents are recommended as adjuncts to opioids to lower the intensity of neuropathic and postcardiovascular surgery pain in critically ill adults. These agents are also recommended for patients with diabetes who have nerve pain.

 Gabapentin has structural similarities to γ-aminobutyric acid (GABA) but does not bind to GABA receptors and has minimal effect on degradation or uptake of GABA. It has proved to be useful in postherpetic neuralgia, as well as in peripheral nerve injuries.

Because of Pain Agitation Delirium Immobility Sleep guidelines on analagosedation, opioid use remains the mainstay for pain management in most ICU settings because of the greater analgesic effects they produce over acetaminophen and NSAIDs, especially in the setting of mechanical ventilation or postsurgical analgesia.

 Opioids produce analgesia by activating G protein–coupled receptors, particularly μ-opioid receptors, located in the brain and spinal cord regions, which are involved in transmission and modulation of pain. Activation of G protein–coupled receptors alters pain perception, increases pain threshold, and inhibits ascending pain pathways.

The most common opioids used in the ICU setting include fentanyl, hydromorphone, and morphine, because of their titratability as either bolus doses or infusions. With renal failure, morphine is used cautiously because of the significant accumulation of morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide. Morphine is also associated with histamine release, which can lead to vasodilation and decreased blood pressure.

 Fentanyl, a synthetic derivative of morphine, is 100 times more potent than morphine and is not associated with histamine release, making it preferred in the setting of hemodynamic instability.

 Hydromorphone, a semisynthetic derivative or morphine, is 5 to 10 times more potent than morphine and is an appropriate alternative to either fentanyl or morphine.

Although opioids are considered the mainstay of therapy, they are associated with negative AEs.

All opioids carry a risk for fatal, life-threatening, or serious respiratory depression and more common AEs, including constipation, drowsiness, nausea, sedation, and vomiting.

 As a result, the guidelines endorse multimodal analgesia to reduce opioid requirements, as well as bowel regimens to manage constipation in the ICU.

Adequate pain assessment and management in the ICU is a complex process. It is further complicated by patients' unstable health statuses, making them unable to communicate their pain accurately. To overcome these barriers between health care providers and patients, proper identification of pain is important. Universal pain management is not possible in the ICU; therefore, it is critical to find the right drug or combination of drugs for each patient, monitor progress throughout the therapy, and adjust as needed. Each class of medications comes with its own set of indications and AEs, which is why pain must be managed carefully and remain under the supervision of an interprofessional team (see table).

1. Lidocaine (systemic). Drugs.com. Updated October 20, 2020. Accessed April 11, 2021. https://www.drugs.com/ppa/lidocaine-systemic.html

2. Fiorelli A, Pace C, Cascone R, et al. Preventive skin analgesia with lidocaine patch for management of post-thoracotomy pain: results of a randomized, double blind, placebo controlled study. Thorac Cancer. 2019;10(4):631-641. doi:10.1111/1759-7714.12975

3. Liu M, Wai M, Nunez J. Topical lidocaine patch for postthoracotomy and poststernotomy pain in cardiothoracic intensive care unit adult patients. Crit Care Nurse. 2019;39(5):51-57. doi:10.4037/ccn2019849

4. Jorge LL, Feres CC, Teles VE. Topical preparations for pain relief: efficacy and patient adherence. J Pain Res. 2010;4:11-24. doi:10.2147/JPR.S9492

5. Devlin JW, Skrobik Y, Gélinas C, et al. Executive summary: clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):1532-1548. doi:10.1097/CCM.0000000000003259

6. Ketamine. Drugs.com. Updated October 26, 2020. Accessed April 26, 2021. https://www.drugs.com/monograph/ketamine.html

7. Ibuprofen. Drugs.com. Updated November 9, 2020. Accessed April 26, 2021. https://www.drugs.com/monograph/ibuprofen.html

8. Ketorolac (systemic). Drugs.com. Updated November 9, 2020. Accessed April 26, 2021. https://www.drugs.com/monograph/ketorolac-systemic.html

9. Acetaminophen. Drugs.com. Updated January 22, 2021. Accessed April 26, 2021. https://www.drugs.com/acetaminophen.html

10. Shi SB, Wang XB, Song JM, Guo SF, Chen ZX, Wang Y. Efficacy of intravenous acetaminophen in multimodal management for pain relief following total knee arthroplasty: a meta-analysis. J Orthop Surg Res. 2018;13(1):250. doi:10.1186/s13018-018-0950-7

11. Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen-Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology. 2005;102(4):822-831. doi:10.1097/00000542-200504000-00019

12. Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of opioids, extubation time, and opioid-related adverse effects after major surgery in intensive care unit. J Crit Care. 2010;25(3):458-462. doi:10.1016/j.jcrc.2009.12.012

13. Cattabriga I, Pacini D, Lamazza G, et al. Intravenous paracetamol as adjunctive treatment for postoperative pain after cardiac surgery: a double blind randomized controlled trial. Eur J Cardiothorac Surg. 2007;32(3):527-531. doi:10.1016/j.ejcts.2007.05.017

14. Benyamin R, Trescot AM, Datta S, et al. Opioid complications and side effects. Pain Physician. 2008;11(suppl 2):S105-S120.

15. Rose MA, Kam PCA. Gabapentin: pharmacology and its use in pain management. Anaesthesia. 2002;57(5):451-462. doi:10.1046/j.0003-2409.2001.02399.x

16. Backonja M, Glanzman RL. Gabapentin dosing for neuropathic pain: evidence from randomized, placebo-controlled clinical trials. Clin Ther. 2003;25(1):81-104. doi:10.1016/s0149-2918(03)90011-7

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18. Devlin JW, Skrobik Y, Gélinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825-e873 doi:10.1097/CCM.0000000000003299

19. Schumacher MA, Basbaum AI, Naidu RK. Opioid agonists and antagonists. In: Katzung BG, Vanderah TW, eds. Basic and Clinical Pharmacology. 15th ed. McGraw-Hill Professional Publishing: 2021;573-594.

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21. FentaNYL. Drugs.com. Updated March 29, 2021. Accessed April 26, 2021. https://www.drugs.com/monograph/fentanyl.html

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are PharmD candidates at Rutgers University Ernest Mario School of Pharmacy in Piscataway, New Jersey.

Deepali Dixit, PharmD, BCCCP, BCPS, FCCM,

 is a clinical associate professor of pharmacy practice and 

 at Rutgers University Ernest Mario School of Pharmacy.

Finding the right medication or drug combination for individual patients is critical.

Pain Management in the ICU Is Complex

Pain occurs in up to 80% of patients in the intensive care unit (ICU) and is a significant source of fear and stress for the critically ill, varying among many subgroups, such as surgical patients and even those at rest.

If not adequately managed, pain can have many psychological and physiologic consequences, along with increased cost and morbidity.

 Opioids, such as fentanyl, hydromorphone, methadone, and morphine, have long been the mainstay treatment for managing pain in patients in the ICU and are equally effective when titrated to similar pain intensity end points.

However, patients in the ICU often experience many adverse effects (AEs) of opioids, such as constipation, nausea, and vomiting.

Increasing concerns about the opioid crisis is also driving the search for other methods of pain relief. The number of overdose deaths involving opioids was 6 times higher in 2017 than in 1999, according to the CDC.

Taken together, these concerns suggest a greater role for a multimodal approach to acute pain management in the critically ill.

Multimodal analgesia is defined as the use of multiple analgesic medications of different classes to target different areas of the central and/or peripheral nervous system affecting pain. Although there are not much data regarding use in the ICU, studies have shown that a combination of pharmacologic agents may offer additive or synergistic effects and more effective pain relief than single-modality interventions.

 Nonopioid analgesics have been considered for this multi-modal approach because of their ability to help reduce opioid use and AEs.

 ketamine, lidocaine, and nonsteroidal anti-inflammatory drugs (NSAIDs), may play a role in acute pain management.

Acetaminophen is an antipyretic, nonopioid analgesic that is considered a weak inhibitor of prostaglandin synthesis. Studies have shown that intravenous (IV) acetaminophen added to opioid therapy produces superior pain control, with a decrease in opioid-related AEs, such as postoperative nausea or vomiting.

 The benefits of IV administration include its greater central nervous system penetration and shorter onset of action—about 5 to 10 minutes versus 30 to 60 minutes for IV and oral administration, respectively. However, the cost of IV acetaminophen is 400-fold greater than that of oral acetaminophen, posing a significantly larger cost burden.

 The AE profile for both routes of administration is similar, as total daily doses are recommended to not exceed 3 to 4 g per day because of the risk of liver toxicity.

Recent case reports note other AEs, such as IV acetaminophen—induced hypotension, that may be particularly concerning in the critically ill population. Patients in the ICU are often admitted for sepsis/septic shock requiring fluid and vasopressor support, and any change in mean arterial pressure and potential increase in vasopressor requirements following IV acetaminophen administration warrants close monitoring.

 To date, limited evidence supports the use of IV acetaminophen in the ICU, but ongoing trials are further assessing the efficacy and safety of IV acetaminophen.

2-Receptor agonists include drugs such as clonidine and dexmedetomidine. Their analgesic properties come from inhibition of nociceptive neurotransmission and of norepinephrine release, which causes hyperpolarization and impedespain signals to the brain.

Dexmedetomidine has an onset of 5 to 10 minutes, whereas oral clonidine can take up to 60 minutes. Common AEs of this class are bradycardia and hypotension, whereas rebound hypertension is a more common AE with clonidine.

2-receptor agonists has been associated with decreased postoperative opioid consumption, nausea, and pain intensity, which are significant end points for patients in the ICU.

Gabapentinoids include anticonvulsants used for neuropathic pain, such as gabapentin and pregabalin. Their analgesic properties are exhibited through mechanisms of binding to voltage-gated calcium channels and inhibiting release of excitatory neurotransmitters.

Recent trials illustrated that coadministering gabapentin and opioids reduced opioid consumption and demonstrated a modest effect in promoting postoperative opioid cessation.

 Likewise, pregabalin was found to have clinically relevant opioid-sparing effects when given with opioids.

 However, both agents are available only for administration via the enteral route and possess similar AEs of dizziness and sedation.

Although gabapentinoids appear promising, several questions remain regarding adjunctive use, such as the length of therapy, optimal dosage, and timing of therapy.

Ketamine is an N-methyl-D-aspartate receptor antagonist that blocks glutamate and can cause down regulation of central sensitization, which is thought to be involved in inducing pain.

 Ketamine is noted to have an opioid-sparing effect, decreasing patient opioid consumption when used as a continuous IV infusion in the ICU, and has been shown in trial findings to decrease postoperative nausea and vomiting.

IV ketamine has an onset of 30 seconds, and potential AEs include increased blood pressure or psychomimetic effects with higher doses. Although ketamine is excreted primarily in the urine, there is a risk of accumulation of active metabolites in severe disease. Ketamine has a potential role as an adjunct to analgesic therapy and as use for acute pain in opioid-tolerant patients.

Lidocaine is a local anesthetic with analgesic properties thought to occur by reducing sodium ions’ ability to permeate the neuronal membrane, suppressing nerve impulses. It can be given intravenously or topically, with an onset of 45 to 90 seconds and 4 hours, respectively. Because of the 90% hepatic metabolism of the drug, liver function tests should be frequently monitored to prevent accumulation. When used with opioids, continuous IV lidocaine infusion therapy exhibits opioid-sparing effects without a significant increase in serious AEs, though extra caution is still necessary for patients with diseases potentially exacerbated by an antiarrhythmic.

NSAIDs work by inhibiting cyclooxygenase (COX) iso-enzymes, which lead to their anti-inflammatory and anti- platelet mechanisms, because synthesis of prostaglandins and thromboxanes is likewise affected. Agents in this class have varying selectivity of COX enzymes with AEs, such as bleeding and gastrointestinal effects. Examples include celecoxib, diclofenac, ibuprofen, and ketorolac. In the acute setting, NSAID use may be limited for patients with kidney injury. However, NSAIDs have a proven prominent role in providing analgesia and opioid-sparing effects associated with a decrease in opioid-related AEs, such as postoperative nausea and vomiting. 

Although opioids are the mainstay of pain management in the ICU, these agents pose many risks in regard to their AEs and high potential for abuse. The use of nonopioid adjunctive therapies is associated with reducing opioid consumption and the ability to reduce opioid-related AEs. It is important to consider a patient’s comorbidities and provide appropriate monitoring to address AEs, especially when using a multimodal approach. Pharmacists should be aware of the many analgesic options available and the value of nonopioid adjunctive therapies for pain management.

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A Multimodal Analgesic Approach Can Improve the Quality of Analgesia and Reduce Adverse Effects.
 

How Nonopioids Can Be Used More In ICUs

In the United States, opioid use has increased significantly over the past few decades, and according to the results of a 2013 CDC study, opioid abuse, misuse, and overdose cost about $78.5 billion annually.

With the rise of opioid use, there has also been an increase in average opioid prescription duration and in opioid use for chronic pain management.

 Chronic pain is defined as pain that lasts beyond 3 months.

 As of 2009, about 3% of American adults used opioids regularly and about 1 of 4 patients prescribed opioids for chronic pain end up misusing them.

Pharmacists play a vital role in managing regimens and ensuring proper compliance. 