Narrative Review of Kratom, an Emerging Psychoactive Substance With Perianesthetic Implications

Emily H. Garmon, MD, FASA; Kandice Olson, MD

Anesth Analg. 2022;135(6):1180-1188.

Abstract and Introduction

Abstract

Opioid overprescribing, with resultant overdose and death, has led to a national focus on alternative treatments for pain. With the decline in legal access to opioids, kratom has gained popularity as a legal, "natural," and easily accessible nonprescription analgesic for consumers wishing to self-medicate for pain, opioid use disorder, and other mental health conditions. While implications of kratom use in patients with chronic pain and/or opioid use disorder have been published, information on perianesthetic implications is lacking. Anesthesiologists should be informed about kratom, including the potential for unexpected physiologic derangements and adverse drug interactions resulting from complex pharmacologic activity, cytochrome P450 interactions, and common adulterations of the drug that may result in unpredictable clinical effects. This article explores the relevance of kratom to perioperative anesthetic care, including suggestions for anesthesiologists extrapolated from published information in nonoperative settings that may improve patient safety in individuals using kratom.

Introduction

Opioid overprescribing, with resultant overdose and death, has reached epidemic proportions in the United States. National focus has led to widespread reduction in opioid prescribing, which is at its lowest rate in more than a decade.^[1] With the decline in legal access to opioids, an abundance of legal and illegal novel psychoactive substances have emerged to fill the gap for consumers wishing to self-medicate for somatic and mental health conditions.^[2,3] Kratom has gained popularity as a legal, "natural," and easily accessible alternative to prescription opioids and synthetic psychoactive substances.^[4,5] Anesthesiologists should be informed about the complex pharmacologic activity and perianesthetic implications of kratom, including the potential for unexpected physiologic derangements and adverse drug interactions. While implications of kratom use in patients with chronic pain and/or opioid use disorder have been published, publications relevant to perioperative anesthetic care are limited to a case report detailing a poor patient outcome and a case report with a brief review of literature detailing a favorable patient outcome.^[6–12] This is a narrative review of the relevance of kratom to perioperative anesthetic care, including suggestions for anesthesiologists to consider during preoperative preparation and anesthetic planning for individuals using kratom.

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Next Section

Abstract and Introduction
Kratom Overview
Growing Popularity
Pharmacology
Usage, Clinical Effects, and Adverse Effects
Governmental Regulation
Perianesthetic Considerations
Conclusions
References

Table 1. Comprehensive Summary of Proposed Mechanisms of Action of Kratom at Multiple Receptors and Other Properties
Mechanism of action	Observable effects	Reported reasons for use	Anesthetic considerations
μ-opioid receptor (G-protein--biased agonism)^22,26,27	Low dose: mild stimulant^6,12,18	Increase alertness and productivity^5,17,35–37	Potentiation of opioid drug effects
Delta and kappa opioid receptor antagonism^22,26	High dose: analgesic^6,12,26,27 and euphoric^6,38	Decrease pain, opioid withdrawal, and diarrhea^5,17,35–37	Withdrawal if prolonged abstinence before anesthetic
Cyclooxygenase-2 pathway inhibition²⁹	Anti-inflammatory^2,9,12,29	Decrease pain and inflammation^2,4	Kidney injury with concurrent nonsteroidal anti-inflammatory drug use
Alpha-2 adrenergic receptor agonism (postsynaptic)^30,31	Low dose: anxiolytic^2,18	Increase relaxation^6,17,35–37	Potentiation of vasodilatory and sedative effects of anesthetics
Alpha-2 adrenergic receptor agonism (postsynaptic)^30,31	High dose: analgesic^26,31 and vasodilatory²	Decrease pain, hypertension, and opioid withdrawal^{2,3,6,10,35–37}
Neuronal calcium channel blockade³²	Analgesic^20,32 and vasodilatory^20,32	Increase sexual stamina² and decrease pain⁹	Potentiation of vasodilatory effects of anesthetics
Serotonin receptor antagonism (primarily 5-HT2A)^30,31	Anxiolytic^2,6,12,18 and antidepressant^2,12,20	Decrease anxiety and depression^{5,12,17,35–37}	Potentiation of serotonergic drug effects
Dopamine receptor antagonism (primarily D1)^30,33	Antipsychotic^12,15,33	Decrease substance misuse and posttraumatic stress^5,12,35–37	Potentiation of dopaminergic drug effects
Acetylcholine release inhibition (presynaptic)³⁴	Analgesic²	Decrease pain²	Potentiation of neuromuscular blockade

Observable drug effects that are advertised by proponents and reported by users are correlated with specific receptor site activity, although individual effects may vary. Perianesthetic considerations are extrapolated based on the effects of drugs with similar mechanisms of action.

Table 2. Kratom-Related Adverse Effects
Overdose symptoms	Overdose treatment options
Neurologic	Kratom abstinence
Agitation^36,50,51	Naltrexone^11,54
Drowsiness^{14,50,51,55,56}	Overdose reversal (if indicated)
Confusion^14,51,57	Naloxone^26,56
Hallucinations⁵¹	Supportive care for overdose symptom management
Transient paralysis⁵⁷	Intravenous fluids^55,56
Seizures^14,51,55,58	Anticonvulsants^55,58
Coma⁵¹	Benzodiazepines⁵⁵
Cardiopulmonary	N-acetylcysteine⁴⁹
Tachycardia^36,50,51	Ursodiol⁴⁹
Hypertension^36,50	Life-threatening organ failure management
Prolonged QT_c ^55,59	Advanced cardiac life support
Respiratory depression^51,56	Liver transplantation⁴⁹
Cardiopulmonary arrest^51,53
Gastrointestinal
Nausea^35,36,50
Vomiting^35,36,51
Liver injury or failure^49,60,61
Withdrawal symptoms	Withdrawal treatment options
Neurologic	Kratom abstinence
Irritability^7,14,62–64	Naltrexone^11,54
Insomnia^30,63	Medication-assisted treatment of substance use disorder (if indicated)
Myalgia^14,30,63	Buprenorphine-naloxone^30,55,62
Myoclonus^14,65	Supportive care for withdrawal symptom management
Blurred vision⁵⁴	Intravenous fluids⁷
Cardiopulmonary	Benzodiazepines⁶³
Tachycardia^63,64	Clonidine^11,54,63
Hypertension⁶³	Clomipramine⁶⁴
Hyperhidrosis^54,63,64	Gabapentinoids^54,55,63,64
Gastrointestinal	Haloperidol⁷
Anorexia⁶³	Hydroxyzine^11,54,55
Abdominal pain⁵⁴
Nausea^54,63
Vomiting⁵⁴
Diarrhea⁵⁴

Adverse effects include both overdose and withdrawal symptoms that have been published in case reports, user surveys, and governmental warnings. Possible treatment options (if indicated) are proposed based on kratom pharmacologic activity and/or anecdotal reports of successful treatment.
Abbreviation: QT_c, electrocardiogram corrected QT interval.

Table 3. Anesthesiology Considerations for Patients With Perioperative Kratom Use
Preanesthetic interview
Ask about use of nonprescription vitamin supplements and herbal remedies.⁷⁶
If kratom use is disclosed or suspected, the following information may assist in anesthetic planning:
Usual dose and frequency of kratom use
Kratom-related adverse effects, including history of withdrawal
Use of other prescribed or illicit substances
Selective preanesthetic testing
Routine preanesthetic testing is not indicated.⁷⁷
Selective testing may be helpful for patients with heavy or long-term use and/or unexplained findings on physical exam suggestive of toxicity.
Specific tests that may be indicated based on preanesthetic interview and physical examination include:
Baseline laboratories (electrolyte panel, kidney function testing, liver function testing, and/or thyroid function testing)
Baseline electrocardiogram
Urine drug screen if coexistent illicit substance use is disclosed or suspected
Due to specialized laboratory qualitative and quantitative testing for kratom, day-of-surgery testing is impractical.
Perianesthetic planning
Consider delay of elective surgery if physiologic derangements associated with acute intoxication or chronic use are suspected or discovered during preanesthetic interview or selective preanesthetic testing.
If cancelation is not indicated based on preanesthetic evaluation or not an option (ie, emergency surgery), customize intraoperative balanced anesthetic medications based on individual risk and potential for interaction with kratom based on complex pharmacologic effects.
Hypotension versus hypertension
Prolonged QT_c
Serotonin syndrome
Extrapyramidal symptoms
Prolonged neuromuscular blockade
Prolonged emergence
Potential discussion points that may be relevant to postoperative recovery:
Education regarding potential risks of drug interactions with postoperative pain management regimen (if applicable)
Caution against continued use, especially with other substances
Information about dangers of common additives, including concentrated formulations, bacterial contaminants, and/or heavy metals
Referral of patients interested in treatment