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The Patient Screening Process: Recommendations for Determining Who Is Eligible for Ketamine Infusion

Creating a great customer experience is a valuable marketing strategy when operating a healthcare practice. It increases the likelihood of repeat business and inspires word-of-mouth advertising. The same principle applies to private medical practice.


One of the ways to make an excellent patient experience is by ensuring safety when performing a procedure, and the screening process is crucial. Additionally, careful patient selection is vital for improving the overall patient outcomes and experiences.


This article presents recommendations for determining who is eligible for ketamine infusion therapy.


Who Are the Potential Candidates for IV Ketamine Infusion?


Most ketamine clinics have a patient base that consists of the following:

  • People in need of a surgical or painful procedure

  • Individuals suffering from chronic pain

  • Those with treatment-resistant depressive disorders

  • And those with other refractory mental health disorders

However, experts propose further restrictions for each category.


For Patients Needing Anesthesia During Surgery or a Painful Procedure

You may give ketamine IV infusion for anesthesia under the following circumstances:

  • When severe post-procedural or post-surgical pain is expected. The severity of pain usually depends on the anatomic location of the involved site and the anticipated extent of tissue injury. IV ketamine’s combined sedative and analgesic actions are useful in cases where local anesthesia or nerve blocks will not suffice or are not a viable part of a treatment plan.

  • When the patient is opioid-tolerant or opioid-dependent. The usual clinical doses of morphine and other opioids are far less effective on these patients. A thorough H&P can reveal if a patient has become opioid-tolerant or dependent and if they could benefit from an adjunctive analgesic such as ketamine.

  • When the patient has a higher risk of developing opioid-related respiratory depression. Examples are people with obstructive sleep apnea, morbidly obese patients, and those with severe pulmonary disease. Opioid-induced respiratory depression makes it harder for anesthetized patients to breathe spontaneously and at an adequate rate and depth, proper breathing allows them to exhale off the remaining anesthetic gasses that keep them anesthetized. Ketamine is far less likely to cause respiratory depression than opioids and can lead to faster anesthesia recoveries. It can also improve any hypercarbia or respiratory acidosis situations that can be caused by opioid-induced respiratory depression.

These individuals will get the greatest benefit and lowest side effect risk from having the NMDA receptor blocker for procedural or surgical pain control. You will need the expertise of an anesthesia specialist to identify them accurately (Schwenk et al., 2018).


For Chronic Pain Relief


You may also give ketamine treatment to people suffering from chronic pain, such as those with CRPS or cancer. But you should first consider two things: the presence of neuropathic pain, central sensitization, and if the patient has failed with more traditional pain management treatments (Cohen et al., 2018).

Central sensitization is an important component of neuropathic pain. It is a state wherein neurons are more excitable and efficient at transmitting painful nociceptive impulses. It can make patients hurt even at the slightest pressure or touch at the affected site. NMDA receptors contribute to the pathology of chronic pain, so these individuals may benefit from racemic ketamine infusion therapy (Zhao et al., 2018; Bredlau et al., 2013).


However, many pain medicine experts recommend giving IV ketamine as chronic pain medication only after first-line modalities have failed. First, the drug has cardiopulmonary and other side effects that some people may not tolerate. Second, although rare, it can lead to physiological addiction or ongoing psychological desire for the medication. Third, it is typically ineffective for non-neuropathic cases or even some pain types with mixed etiologies (Cohen et al., 2018).


For the Alleviation of Treatment-Resistant Depression


Ketamine infusion therapy rapidly reduces depressive symptoms and suicidal ideation. But American and European mental health experts recommend it for major depression and similar psychiatric disorders only if traditional treatments do not work or if their side-effects prohibit their usage (Sanacora et al., 2017; Lopez-Diaz et al., 2019).

The reasons for this cautious approach include the following (Sanacora et al., 2017; Lopez-Diaz et al., 2019):

  • Traditional antidepressant treatment’s efficacy and safety have long been established.

  • Clinical trials demonstrating ketamine’s antidepressant effect focus on depressed individuals who have not responded to other modalities.

  • Ketamine’s cardiopulmonary side effects can still be observed even at subanesthetic doses.

  • The benefits and risks of long-term continued ketamine therapy are still largely unknown.

The drug has also demonstrated potential in the treatment of other mental health conditions, including:

  • PTSD (Feder et al., 2014)

  • Anxiety disorder (Glue et al., 2020)

  • Bipolar disorder with depression (Grunebaum et al., 2017)

  • Substance abuse disorder (Jones et al., 2018)

But the evidence on its effects on these mental illnesses is more limited. Clinicians should consider collaborating with a psychiatrist or mental health nurse practitioner to determine which mental health patients are the best candidates for ketamine infusion treatment.


Finding out which individuals can benefit from ketamine therapy is the first step of the screening process. The patients whose benefits outweigh the potential risks of treatment are those who are deemed eligible for IV ketamine infusion therapy, but some of them may still develop unwanted side effects.


Which Patients Should Not Be Given Ketamine?


To answer this question, the ketamine provider must keep the drug’s contraindications in mind.


Active Illicit Substance Abuse


Ketamine is a medication with abuse potential. It can also worsen the symptoms of recent illicit drug intake. Make sure to complete a thorough H&P and screen for a history of drug abuse. Some clinicians who prescribe ketamine for home use also require a negative urine toxicology screen before prescribing ketamine troches for home use.

If you suspect that a patient may have developed signs and symptoms of ketamine abuse or misuse, you may want to inquire from other treatment centers about attempts to get additional sessions or prescriptions (Sanacora et al., 2017). You may also want to consider initiating regular urine toxicology testing.


A History of Psychosis

Some studies show that the risk of aggravating psychosis after ketamine therapy is possible, although the risk is small and the event is short-lived. A thorough review of the literature shows this typically only lasts a few hours post-ketamine administration. However, many clinicians would rather avoid that slippery slope and place a history of psychosis on their exclusion criteria. Animal studies demonstrate that the drug acts on dopaminergic receptors and can trigger a temporary onset of psychotic symptoms (Sanacora et al., 2017; Pennybaker et al., 2017; Schwenk et al., 2018; Cohen et al., 2018; Yang et al., 2018). There are a number of psychiatrists in the US who do not feel that a history of psychosis is an absolute contraindication and will treat those patients on a case-by-case basis. During your H&P you will want to screen your patients for a history of psychosis and other severe mental health disorders.

A History of Increased Intracranial or Intraocular Pressure

Recent clinical research on ketamine’s intracranial and intraocular pressure effects has mostly been done on trauma and pediatric glaucoma patients. The limited information from these studies reveals that ketamine causes only small temporary changes to the pressure inside the head or the eyes (Morgan et al., 2020; Schwenk et al., 2018; Ruiz-Villa et al., 2019)


Still, you must exercise caution in patients at risk of having higher ICPs or IOPs. Earlier studies found that these parameters rise following a single ketamine infusion, likely due to sympathomimetic stimulation (Gregers et al., 2020; Ruiz-Villa et al., 2019).

Pregnancy

Ketamine can cross the placenta because of its lipophilicity, but we know little of its effects on human fetal development. Meanwhile, animal studies show that the drug is toxic to immature neurons (Cheung & Yew, 2019).


It is prudent to withhold IV ketamine from pregnant patients and recommend alternatives. You should also consider administering a pregnancy test when encountering a reproductive-age female patient.


Uncontrolled Hypertension and Acute or Unstable Cardiovascular Disease

Ketamine can increase the blood pressure and heart rate even at a low dose because of its sympathomimetic effects and ability to inhibit the vagus nerve (Cohen et al., 2018; Short et al., 2018).

Hypertensive patients will need effective blood pressure control before starting the treatment. You may exclude individuals with acute or unstable heart disease unless evaluated and cleared by a cardiologist.

Lack of Response to Prior IV Ketamine Infusions

Mental health and pain medicine experts do not have clear-cut criteria for determining if a ketamine treatment course has been futile. But based on limited studies, it may be clear after several infusions which individuals will most likely achieve a sustainable antidepressant response (Sanacora et al., 2017).

For depression and chronic pain patients, you may try increasing the dose before deciding that the treatment has failed. Some people improve only at higher doses due to pharmacokinetic variability (Cohen et al., 2018).

Unresponsiveness to a series of intravenous infusion sessions reduces the odds of subsequent treatment success. Close monitoring may help you determine which patients will benefit from continuing IV ketamine therapy.

A History of Severe Adverse Reactions to Ketamine Treatment

Hypersensitivity and cystitis have been reported following ketamine administration. Urinary tract changes commonly result from repeated, heavy use (Bylund et al., 2017; Short et al., 2018). It is best to withhold the therapy from patients who have experienced these side effects after exposure to the medication.

Liver Disease


The liver is ketamine’s chief metabolic site (Mion & Villevieille, 2013). Advanced liver disease can cause the drug to accumulate in the blood and enhance its toxicity, so it is best to keep it from patients with this condition (Schwenk et al., 2018).


A meticulously done H&P can help you elicit all the information you need to screen patients properly. Additionally, the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments emphasizes the importance of having the patient sign an informed consent form before ketamine treatment (Sanacora et al., 2017).


Taking the patients’ socio-economic circumstances into account is also imperative. Financial barriers and the lack of a reliable caregiver at home can make IV ketamine infusion therapy a less ideal option for some people (Blum & Grey, 2021; Sanacora et al., 2017).


Safety Starts Even Before You Administer the First Ketamine Dose


A good screening process enhances patient safety.


For a Schedule III substance like ketamine, screening starts with choosing the patients for whom its infusion is indicated. From there, you may select the ones who are less likely to experience severe side effects, and for whom the potential benefits outweigh the potential risks.

Ensuring patient safety throughout the procedure helps you create a good patient experience. And this will protect and boost your business in the long run.

 

References


Blum, B. & Grey, J. (2021). Administration of Ketamine for Depression Should Be Limited to Psychiatrists. Current Psychiatry, 20(9), e1-e2. https://doi.org/10.12788/cp.0175


Bredlau, A. L., Thakur, R., Korones, D. N. & Dworkin, R. H. (2013). Ketamine for Pain in Adults and Children with Cancer: A Systematic Review and Synthesis of the Literature. Pain Medicine, 14(10), 1505-1517. https://doi.org/10.1111/pme.12182


Bylund, W., Delahanty, L. & Cooper, M. (2017). The Case of Ketamine Allergy. Clinical Practice and Cases in Emergency Medicine, 1(4), 323-325. https://dx.doi.org/10.5811%2Fcpcem.2017.7.34405


Cheung, H. M. & Yew, D. T. W. (2019). Effects of Perinatal Exposure to Ketamine on the Developing Brain. Frontiers in Neuroscience, 13, 1-12. https://dx.doi.org/10.3389%2Ffnins.2019.00138


Cohen, S. P., Bhatia, A., Buvanendran, A., Schwenk, E. S., Wasan, A. D., Hurley, R. W., Viscusi, E. R., Narouze, S., Davis, F. N., Ritchie, E. C., Lubenow, T. R. & Hooten, W. M. (2018). Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine and the American Society of Anesthesiologists. Chronic and Interventional Pain, 43(5), 521- 546. https://doi.org/10.1097/aap.0000000000000808


Feder, A., Parides, M. K., Murrough, J. W., Perez, A. M., Morgan, J. E., Saxena, S., Kirkwood, K., Rot, M., Lapidus, K. A. B., Wan, L., Iosifescu, D. & Charney, D. S. (2014). Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder A Randomized Clinical Trial. JAMA Psychiatry, 71(6), 681-688. https://doi.org/10.1001/jamapsychiatry.2014.62


Glue, P., Neehoff, S., Sabadel, A., Broughton, L., Le Nedelec, M., Shadli, S., McNaughton, N. & Medlicott, N. J. (2020). Effects of Ketamine in Patients with Treatment-Refractory Generalized Anxiety and Social Anxiety Disorders: Exploratory Double-Blind Psychoactive-Controlled Replication Study. Journal of Psychopharmacology, 34(3), 267-272. https://doi.org/10.1177/0269881119874457


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Grunebaum, M. F., Ellis, S. P., Keilp, J. G., Moitra, V. K., Cooper, T. B., Marver, J. E., Burke, A. K., Milak, M. S., Sublette, M. E., Oquendo, M. A. & Mann, J. J. (2017). Ketamine versus Midazolam in Bipolar Depression with Suicidal Thoughts: A Pilot Midazolam-Controlled Randomized Clinical Trial. Bipolar Disorders, 19(3), 176-183. https://doi.org/10.1111/bdi.12487


Jones, J. L., Mateus, C. F., Malcolm, R. J., Brady, K. T. & Back, S. E. (2018). Efficacy of Ketamine in the Treatment of Substance Use Disorders: A Systematic Review. Frontiers in Psychiatry, 9, 1-10. https://doi.org/10.3389/fpsyt.2018.00277


Lopez-Diaz, A., Murillo-Izquierdo, M. & Moreno-Mellado, E. (2019). Off-Label Use of Ketamine for Treatment-Resistant Depression in Clinical Practice: European Perspective. The British Journal of Psychiatry, 215(2), 447-448. https://doi.org/10.1192/bjp.2019.102


Mion, G. & Villevieille, T. (2013). Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings). CNS Neuroscience and Therapeutics, 19(6), 370-380. https://doi.org/10.1111/cns.12099


Morgan, M. M., Perina, D. G., Acquisto, N. M., Fallat, M. E., Gallagher, J. M., Brown, K. M., Ho, J., Burnett, A., Lairet, J., Rowe, D. & Gestring, M. L. (2020). Ketamine Use in Prehospital and Hospital Treatment of the Acute Trauma Patient: A Joint Position Statement. Prehospital Emergency Care, 25(4), 588-592. https://doi.org/10.1080/10903127.2020.1801920


Pennybaker, S. J., Luckenbaugh, D. A., Park, L. T., Marquardt, C. A. & Zarate, C. A. J. (2017). Ketamine and Psychosis History: Antidepressant Efficacy and Psychotomimetic Effects Posinfusion. Biological Psychiatry, 82(5), e35-e36. https://dx.doi.org/10.1016%2Fj.biopsych.2016.08.041


Ruiz-Villa, J. O., Jaramillo-Rivera, D. A. & Pineda-Gutierrez, L. M. (2019). Ketamine Impact on Intraocular Pressure of Children: A Systematic Review and Qualitative Synthesis of Evidence. Columbian Journal of Anesthesiology, 47(4), 226-235. http://dx.doi.org/10.1097/CJ9.0000000000000141


Sanacora, G., Frye, M. A., McDonald, W., Mathew, S. J., Turner, M. S., Schatzberg, A. F., Summergard, P. & Nemeroff, C. B. (2017). A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry, 74(4), 399-405. https://doi.org/10.1001/jamapsychiatry.2017.0080


Schwenk, E. S., Viscusi, E. R., Buvanendran, A., Hurley, R. W., Wasan, A. D., Narouze, S., Bhatia, A., Davis, F. N., Hooten, W. M. & Cohen, S. P. (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 and Pain Medicine, 43(5), 456-466. https://doi.org/10.1097/aap.0000000000000806


Short, B., Fong, J., Galvez, V., Shelker, W. & Loo, C. K. (2018). Side Effects Associated with Ketamine Use in Depression: A Systematic Review. The Lancet Psychiatry, 5(1), 65-78. https://doi.org/10.1016/s2215-0366(17)30272-9


US Drug Enforcement Administration (2021). Controlled Substances—Alphabetical Order. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf


Yang, C., Kobayashi, S., Nakao, K., Dong, C., Han, M., Qu, Y., Ren, Q., Zhang, J., Ma, M., Toki, H., Yamaguchi, J., Chaki, S., Shirayama, Y., Nakazawa, K., Manabe, T. & Hashimoto, K. (2018). AMPA Receptor Activation-Independent Antidepressant Actions of Ketamine Metabolite (S)-Norketamine. Biological Psychiatry, 84(8), 591-600. https://doi.org/10.1016/j.biopsych.2018.05.007


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