A member of the coffee family, kratom has been used for centuries in parts of Asia for its energizing and pain-relieving effects. It is used as a treatment for fever, malaria, cough, diarrhea, and pain, and to improve stamina and elevate mood.1,2 Kratom leaves can be chewed, brewed in tea, smoked, and ingested as a compressed tablet or filled capsule.
More than 20 active compounds and over 40 alkaloids have been isolated from kratom.3,4 Mitragynine and 7-hydroxymitragynine are responsible for the main effects, which include analgesic, anti-inflammatory, and antidepressant activity.4 Mitragynine has been shown to be a μ-opioid receptor agonist and a δ- and κ-opioid receptor antagonist.3,5 It also stimulates postsynaptic α-2 adrenergic receptors, activates descending noradrenergic and serotonergic pathways, and inhibits cyclooxygenase-2 expression and prostaglandin E2 production.4–6 The complete pharmacology is yet to be discovered. Discontinuation after chronic use has been associated with withdrawal symptoms.6
Individuals in the United States are increasingly using kratom as a recreational drug and for self-medication for the treatment of chronic pain and opioid withdrawal.1 Throughout the United States, kratom is widely available for sale in smoke shops and on the Internet. It is illegal in 6 states and the District of Columbia. In August 2016, the US Drug Enforcement Agency announced that it would temporarily reclassify kratom as a schedule 1 drug.7 Outcry from groups such as the American Kratom Association led to the withdrawal of the Drug Enforcement Agency’s notice of intent of rescheduling. Recently, the US Food and Drug Administration used a computational model to analyze the 25 most prevalent compounds in kratom and determined that 22 of these compounds bind to μ-opioid receptors, comparable to scheduled opioid drugs.8 The agency warned of side effects from kratom, such as respiratory depression, dependence, and withdrawal. There have been 44 deaths associated with the use of kratom when taken in combination with other drugs.8
In our search of the literature, we found no reported cases of general anesthesia in a patient chronically using kratom. Written Health Insurance Portability and Accountability Act authorization to use/disclose existing protected health information was obtained from the patient and parent.
A 15-year-old boy presented with 3-month history of significant lower back pain after an injury while playing basketball. The patient walked using a cane and was unable to attend school secondary to pain. A lumbar spine radiograph showed significant central stenosis and bilateral lateral recess compromise at L2–L3. He was scheduled for a lumbar laminectomy. His airway, cardiac, and pulmonary examinations were unremarkable. His weight was 100 kg. The patient’s blood pressure and pulse rate were within normal limits for his age. He exhibited diminished reflexes at L4, normal plantar reflexes, and normal motor strength in his lower extremities. His medication list included gabapentin 400 mg 3 times daily and naproxen 500 mg twice a day. During the preoperative interview, it was revealed by the patient’s mother that he had been using kratom, ½ teaspoon, 3–4 times daily for the previous 3 months. His last kratom use was the immediate preoperative evening. Routine laboratory values included normal electrolytes, blood urea nitrogen, serum creatinine, urinalysis, coagulation studies, and a slightly decreased hemoglobin and hematocrit with normal platelet count. The patient had a history of snoring; a preoperative Stop-Bang questionnaire was negative.
The patient was premedicated with gabapentin and midazolam. Induction of anesthesia was with propofol, 1% lidocaine, and fentanyl. No muscle relaxation was used. An endotracheal tube was placed. Maintenance of anesthesia was with sevoflurane and fentanyl. He received 100 mg of ketamine, 1000 mg of intravenous acetaminophen, 30 mg of ketorolac, 250 μg of fentanyl, 12 mg of decadron, and 4 mg of ondansetron during the 3-hour procedure. The patient exhibited pulse rate, blood pressure, and temperature readings all within normal limits throughout the case. At the end of the procedure, he was extubated and taken to the recovery room in stable condition. The patient required intermittent jaw thrust until fully awake. The first postoperative night, the patient was prescribed hydromorphone intravenous patient-controlled analgesia (IVPCA) with a demand dose of 0.3 mg. Gabapentin 400 mg 3 times a day, naproxen 500 mg twice a day, and acetaminophen 1000 mg 3 times a day were also prescribed for pain management. As per institutional protocol for patients receiving IVPCA narcotics, continuous electrocardiogram, end-tidal carbon dioxide, and pulse oximetry monitoring were used. His IVPCA was discontinued the morning of postoperative day 1; the total usage was 5.4 mg over 18 hours. The patient had elevated end-tidal carbon dioxide via nasal cannula monitor during the first postoperative night, but remained easily arousable. On discontinuation of the IVPCA, he was prescribed oxycodone up to 10 mg every 4 hours as needed for pain. The patient required 3 doses of 5 mg of oxycodone on the first day postoperative and 1 dose of 5 mg the morning of postoperative day 2. His blood pressure and heart rate were within normal ranges throughout his stay. He successfully reached his physical therapy goals and was discharged home on postoperative day 2. The patient exhibited no signs or symptoms of withdrawal throughout his hospital stay. His discharge medications included gabapentin 400 mg 3 times a day, naproxen 500 mg twice a day, and oxycodone 10 mg every 4 hours as needed.
Advocacy groups claim that there are 4–5 million users of kratom in the United States.9 Currently, no controlled experimental studies in humans exist. Human surveys and animal studies demonstrate that mitragynine and 7-hydroxymitragynine possess both opioid and psychostimulant-like effects.3,10 Evidence exists for the development of tolerance, dependence, and withdrawal. Routine drug screens do not detect kratom; it can be detected by gas chromatography-mass spectrometry.11 It stands to reason that with kratom’s popularity and ready availability, an increasing number of kratom users will present as patients seeking routine medical care.
Mitragynine is a lipophilic opioid whose pharmacokinetics suggest an oral 2-compartment model.4 The maximum plasma concentration is reached in 90 minutes with a terminal half-life of 23 ± 16 hours.4 In animal studies and human case reports, kratom use has been associated with hepatotoxicity, cholestasis, nephrotoxicity, cardiotoxicity, tachycardia, hypertension, hypotension, seizures, hypothyroidism, polyuria, constipation, dry mouth, increased sweating, pruritus, hyperpigmentation, impaired working memory, insomnia, nausea, vomiting, and weight loss.4,6,8,10,12 These side effects appear to be dose dependent, duration of use dependent, and dependent on which strain of alkaloid is predominant in the mixture.
In 1 study, all regular users of kratom reported to be dependent on kratom with over half reporting severe dependence problems.13 Physical withdrawal symptoms include muscle spasms, myalgia, sleeping difficulty, watery eyes and nose, hot flashes, fever, abdominal cramps, decreased appetite, and diarrhea.6,13 Withdrawal symptoms may appear within 12 hours of cessation and continue for up to 14 days.6,13 Kratom withdrawal has been successfully treated with clonidine, hydroxyzine, and naltrexone.14
Currently, there have been 44 deaths attributed to the use of kratom in combination with other drugs. These drugs include benzodiazepines, modafinil, O-desmethyltramadol, alcohol, paroxetine, lamotrigine, antidepressants, dextromethorphan, diphenhydramine, morphine, acetaminophen, and propylhexedrine.4,9,14 Given this polypharmacy, it is difficult to determine what role, if any, kratom played in these fatalities.
Our patient had used kratom for 3 months before surgery. He had taken 4 doses of kratom the immediate preoperative day. Routine preoperative laboratory values were collected before our knowledge of the kratom use. Given the potential toxicities of chronic kratom intake, a liver function panel, thyroid function tests, and electrocardiogram would have provided valuable information. Due to kratom’s known interaction at the α-2 receptor, there was discussion of adding clonidine to our patient’s medication regimen to prevent possible withdrawal. The decision was made to observe the patient, with the nursing staff fully aware of withdrawal signs and symptoms, such as agitation, hallucinations, hypertension, tachycardia, and seizures. On discharge home, the patient and parents were counseled about the risks of using kratom in conjunction with narcotics. Risks include those for narcotic overdose with both drugs acting at opiate receptors. The family stated that they preferred to use kratom instead of narcotics and would continue with kratom.
It is important to note that this is a single case report. Because it is a single case, it does not offer general advice for all patients on kratom but offers new information that may guide others in their medical decision making.
With kratom’s popularity, it is clear that human studies are needed to elucidate the interactions of kratom with commonly used medications, to explore its potential as an alternative pain therapy, and to develop a routine screening test.
Name: Deborah J. Vermaire, MD.
Contribution: This author helped prepare the manuscript.
Name: Deborah Skaer, BS Pharm.
Contribution: This author helped prepare the manuscript.
Name: William Tippets, DO.
Contribution: This author helped prepare the manuscript.
This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.
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