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https://www.infirmiere-canadienne.com/blogs/ic-contenu/2022/09/06/ketamine-a-faible-dose-surmonter-les-stigmates

Non-opioid drug a viable alternative to improve patient experience

By Heather Ead
September 6, 2022

Providing adequate postoperative pain management to patients with underlying chronic pain conditions while avoiding over sedation can be challenging. Following surgery, acute surgical pain on top of a chronic pain condition (e.g., spinal nerve compression) must be adequately addressed to facilitate recovery (Pendi, Field, Farhan, Eichler, & Bederman, 2019). However, lengthy wait times for elective surgery and delays and cancellations in surgery related to COVID-19 can lead to more complex surgical cases, including deconditioned and opioid-tolerant patients. Nursing staff can have concerns about administering higher doses of opioids when required where opioid tolerance has developed during delays to surgical treatment.

Internationally, there is a concerted effort to decrease the amount of opioids being prescribed due to the ongoing opioid crisis (George & Johns, 2020). At our hospital, to help reduce opioid prescribing and opioid-related complications, low-dose ketamine is an adjunct used along with other multimodal pharmacological and non-pharmacological strategies. This aligns with best practices, such as the Registered Nurses’ Association’s Assessment and Management of Pain best practice guideline (RNAO, 2013). This guideline supports the use of multimodal analgesia such as non-steroidal anti-inflammatory drugs, acetaminophen and other non-opioid adjuncts to safely and effectively reduce acute pain and prevent the development of chronic pain. Multimodal analgesia is the practice whereby two or more medications from different classifications are used, allowing lower doses of each agent to be used, with fewer adverse effects (Velasco, Simonovich, Krawczyk, & Roche, 2019).

Low-dose ketamine

Ketamine was introduced as an induction agent for general anesthesia in 1970. Over the past 20 years, the indications for ketamine have widely expanded due to its unique pharmacological effects (Moon & Smith, 2021). It is increasingly being used in acute, chronic and palliative pain management. Ketamine can effectively reduce pain by working centrally and blocking N-methyl-d-aspartate (NMDA) receptors. This inhibits glutamate, which is an excitatory neurotransmitter involved in pain signal transmission. Ketamine blocks other pathways that are important for treatment of chronic pain, opioid tolerance, hyperalgesia and neuropathic pain (Moon & Smith, 2021). Ketamine provides analgesia through several pathways, but the majority of its effects for acute pain are via the NMDA receptor (Caruso, Tyler & Lyden, 2021). The current formulation of ketamine used today allows for lower dosing with similar effects compared to previous research on isomers. This enables beneficial analgesia effects while avoiding psychoactive effects, such as hallucinations (Gales & Maxwell, 2020).

It is important to note that ketamine does not bind to opioid receptors or cause opioid-related side effects, such as depressed respiratory drive, constipation and urinary retention (Caruso et al., 2021). In fact, ketamine reduces the hypotension associated with anesthesia and opioids and has bronchodilating effects. The latter effect makes it a desirable choice for patients with asthma (Gales & Maxwell, 2020).

Despite ketamine having numerous indications beyond anesthesia and sedation, it is still classified as an anesthetic. With this classification, it is not uncommon for nurses to have some hesitation about its use. Even though ketamine is a versatile drug with an excellent safety profile, it is not used as frequently as opioid adjuncts because of its association with emergence delirium, which can occur with high dosing for general anesthesia (Gales & Maxwell, 2020). Furthermore, concerns regarding using ketamine as a recreational drug can add to negative stigmas (Moon & Smith, 2021). Staff may expect that a medication that is used illegally will cause a profound, negative patient response. However, through education and continued safe use, there is an opportunity to expand the use of low-dose ketamine appropriately to secure numerous benefits in patient care (Velasco et al., 2019).

Staff survey

Qualitative research has found that barriers exist among some health-care providers around administration of opioid alternatives. Some of the barriers are based on the understanding that opioids are overall the best analgesics and that staff are more comfortable administering them; another major barrier is that there is a knowledge gap regarding non-opioids, largely because information sources tend to be anecdotal (Velasco et al., 2019). To help identify barriers to application of ketamine orders, we shared an anonymous survey with nursing staff. Three questions were posed to encourage staff to share their knowledge and comfort level and any concerns they may have regarding low-dose ketamine. Overall, the findings showed that a lack of experience with this non-opioid was creating some hesitancy about administering it. Staff stated that they would feel more comfortable if an educator, an acute pain service nurse or another experienced staff member were available to assist with drug administration and monitoring. See the appendix.

Ketamine is a good option to include for patients who are elderly, opioid naïve, dependent on alcohol or have a history of opioid-misuse disorder.

Benefits

The benefits of administering ketamine are as follows:

• Decreased opioid requirements (an average decrease of 14.38 mg of intravenous [IV] morphine equivalents in 24 hours) (Brinck et al., 2018)
• Improved pain scores following abdominal, spinal and other major orthopaedic surgery (Brinck et al., 2018)
•  Reduction in opioid-related side effects such as respiratory sedation and postoperative nausea and vomiting (Brinck et al., 2018).
• Improved participation in postoperative physiotherapy and other activities essential to recovery (Pendi et al., 2018)

Indications for low-dose ketamine for pain management

Guidelines for the use of ketamine for acute pain treatment have been published. The American Society of Anesthesiologists supports the use of ketamine as an adjunct for pain management following surgeries that are associated with high pain levels (Schwenk et al., 2018). This includes spine, thoracic and orthopaedic surgery; patients who are opioid dependent or tolerant or have chronic pain issues (e.g., sickle cell disease); or where risk factors exist and opioids are best avoided. Such risk factors may include obstructive sleep apnea and chronic obstructive pulmonary disease (Wang, Yang, Shan, Cao, & Wang, 2020). Additionally, ketamine is a good option to include for patients who are elderly, opioid naïve, dependent on alcohol or have a history of opioid-misuse disorder (Moon & Smith, 2021).

Administration

The analgesic effects of ketamine occur at much lower doses than with dosing used for general anesthesia or procedural sedation. This dosing is termed “subanesthetic” or “sub-dissociative” (Schwenk et al., 2018). At our facility, ketamine is ordered as an intermittent, as-needed dose of 10 mg IV (in 100 cc normal saline) and is given over 30 minutes. Compared to anesthesia doses of 2 mg/kg, this is a significantly lower dose, which avoids the adverse effects seen at anesthetic dosing while allowing for improved pain management and hemodynamic stability (Caruso et al., 2021). Ketamine is shown to desensitize central pain pathways and modulate opioid receptors and provides potent analgesic (Gales & Maxwell, 2020). Brief elevations in blood pressure can be observed, which are typically clinically insignificant while helping to support hemodynamic stability if postoperative hypotension presents (Schwenk et al., 2018). Other adverse effects to monitor for following low-dose use include transient tachycardia, nausea, increased salivation, dizziness and blurred vision (Schwenk et al., 2018).

Contraindications

As with any medication, one must consider the presence of contraindications prior to administration. For low-dose ketamine, the contraindications are related to the small risk of visual hallucinations and increased blood pressure. Thus, ketamine is not recommended for use in patients with poorly controlled hypertension or elevated intracranial or intraocular pressures, in pregnant patients or in the presence of a delirium or psychosis (Schwenk et al., 2018).

Next steps

With staffing challenges, many organizations have higher ratios of novice nursing staff to experienced nurses. At a time when reducing opioid administration has become increasingly important, adjuncts for pain management are timely and advantageous tools to use. With increased awareness and education, we can help staff feel comfortable in using alternatives to opioids that help prevent side effects and unnecessary pain. Optimizing pain management can help avoid the negative outcomes of undermanaged pain, such as hemodynamic instability, chronic pain syndrome and patient dissatisfaction (Pendi et al., 2018). Supporting effective pain management is one of the many ways we advocate for our patients and make a stressful surgical event as comfortable and complication free as possible.

Summary

Overall, ketamine is a versatile drug that can be safely used as an adjunct for analgesia. At low dosing, it provides potent analgesia and avoids the adverse psychoactive effects seen with anesthesia dosing (Gales & Maxwell, 2020). By continuing to share information with health-care providers, we can support appropriate use of low-dose ketamine as part of a multimodal pain management plan. By advancing our knowledge of non-opioid adjuncts, we are promoting best practices, advocating for our patients and reducing the risk of chronic pain and long-term opioid use (Velasco et al., 2019).

Appendix: nursing staff survey on postoperative ketamine administration

Question 1: On a scale of 1-5, how knowledgeable do you feel around the benefits of low-dose ketamine post-spine surgery for pain management?
Responses
23.08% (n=6): I have little to no knowledge of low-dose ketamine for analgesia
53.85% (n=14): I have some knowledge, but haven’t administered this adjunct agent yet
23.08% (n=6): I have a good understanding of how this can reduce pain; it has less side-effects than morphine at this dose

Question 2: Describe what (if any) concerns you have around low-dose ketamine for analgesia
Responses
0% (n=0): I am extremely concerned this medication could trigger postop complications.
23.08% (n=6): I have a bit of concern this medication may be too strong for some patients.
42.31% (n=11): I would prefer the first time I administer this, that I have support of someone from the acute pain services (APS) team, an educator, or other staff member
34.6% (n=9): I don’t have concerns at this time, but will contact APS/anesthesia/educator if I have any questions.

Question 3: What complications do you anticipate will most often occur following low-dose ketamine administration?
Responses
16% (n=4): Brief elevation in BP
16% (n=4): Complaints of visual disturbance/hallucinations
48% (n=12): Complaints of mild symptoms: nausea, headache, feeling like in a daydream
0% (n=0): Concerns around addiction
20% (n=5): Concerns around continued pain (we are using a lower dose than other organizations)

References

Brinck, E., Tiippana, E., Heesen, M., Bell, R., Straube, S., Moore, R., & Kontinen, V. (2018). Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database of Systematic Reviews, 12(12), CD012033. doi:10.1002/14651858.CD012033.pub4

Caruso, K., Tyler, D., & Lyden, A.  (2021). Ketamine for pain management. A review of literature and clinical application. Orthopaedic Nursing, 40(3), 189-193. doi:10.1097/NOR.0000000000000759

Gales, A., & Maxwell, S. (2020). Ketamine: Recent evidence and current uses. Update in Anaesthesia, 35, 43-48.

George, S., & Johns, M. (2020). Review of nonopioid multimodal analgesia for surgical and trauma patients. American Journal of Health System Pharmacy, 77(24), 2052-2063. doi:10.1093/ajhp/zxaa301

Moon, T., & Smith, K. (2021). Ketamine use in the surgical patient: A literature review. Current Pain and Headache Reports, 25(3), 17. doi:10.1007/s11916-020-00930-3

Pendi, A., Field, R., Farhan, S.-D., Eichler, M., & Bederman, S.S. (2018). Perioperative ketamine for analgesia in spine surgery: A meta-analysis of randomized controlled trials. Spine, 43(5), E299-E307.

Registered Nurses’ Association of Ontario. (2013). Assessment and management of pain (3rd ed.). Toronto: Author.

Schwenk, E., Viscusi, E., Buvanendran, A., Hurley, R., Wasan, A., Narouze, S., Bhatia, A., Cohen, S. (2018). Consensus guidelines on the use of intravenous ketamine infusions for acute pain management from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Regional Anesthesia & Pain Medicine, 43(5), 456-466. doi:10.1097/AAP.000000000000080.

Velasco, D., Simonovich, S. D., Krawczyk, S., & Roche, B. (2019). Barriers and facilitators to intraoperative alternatives to opioids: Examining CRNA perspectives and practices. AANA Journal, 87(6), 459-467.

Wang , P., Yang, Z., Shan, S., Cao, Z., & Wang, Z. (2020). Analgesic effect of perioperative ketamine for total hip arthroplasties and total knee arthroplasties. Medicine, 99(42), e22809. doi:10.1097/MD.0000000000022809

Heather Ead, RN, MHS is a clinical educator at Trillium Health Partners in Mississauga, Ont. She can be reached by email at: Heather.Ead@thp.ca