Episode #57 Perioperative Management for Patients with Methamphetamine SUD

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel and I am your host. Thank you for joining us for another show. Have you taken care of a patient with a history of methamphetamine substance use disorder recently? These patients may be complicated and challenging to manage during anesthesia care. It is important to understand the implications of methamphetamine substance use disorder and how it relates to medications and monitoring in order to help keep these patients safe.

Before we dive into today’s episode, we’d like to recognize Medtronic, a major corporate supporter of APSF. Medtronic has generously provided unrestricted support as well as research and educational grants to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Medtronic- we wouldn’t be able to do all that we do without you!”

Have you checked out the June 2021 APSF Newsletter yet? We have reviewed a couple of the articles on this podcast over the past couple of months, but there is still more to talk about…including our featured article today. We will be talking about “Practice Considerations for the Anesthesia Professional for Methamphetamine Substance Use Disorder Patients” by Krogh (pronounced Crow) and colleagues. To follow along with us, click on the Newsletter heading and then the first one down is the Current Issue. Then, scroll down looking in the right-sided column until you see the featured article. I will include a link in the show notes as well.

Before we get into the article, I reached out to the authors to help introduce this topic and share some insight. Jennifer Krogh submitted a couple of clips that we are going to listen to today. Krogh is a certified registered nurse anesthetist working in California. First up, I asked her what got her interested in this topic. Let’s take a listen to her response:

[Krogh] “My family and I are military which causes us to change locations frequently and working in various parts of the United States, I saw a common thread concerning methamphetamine substance use disorder patients. There were conflicting recommendations and frequent misinformation. Searching for answers, I found no comprehensive practice considerations. This inspired me to pursue my doctorate in nursing practice at Yale University so that I could help provide answers to my colleagues who may be asking the same questions.”

[Bechtel] Thank you so much to Krogh for helping to open the show today. Today, we are going to discuss some questions that may come up while caring for patients with methamphetamine substance use disorder and hopefully provide some answers. Here we go!

The authors kick off the article by outlining the scope of the problem of substance use disorders. In 2014 in the United States with a population of 329.9 million people, 21.5 million people were diagnosed with substance use disorders. If we look at that data a little closer, we can see that methamphetamine use occurs in about 1.6 million of the 21.5 million people in the United States. In addition, the National Institute on Drug Abuse reported that about 0.6% of the population is admits to using methamphetamines, but keep in mind that this may not be an accurate representation of the methamphetamine use due to under-reporting given the legal implications and stigma related to substance use disorder diseases. A survey study by Levy and colleagues published in 2018 revealed that about 81% of patients do not provide accurate and true information related to substance use and abuse to their healthcare providers. The most likely reason for providing false information according to the study was patients desire to avoid being “judged” if they disclosed substance use. Anesthesia professionals need to be aware of this since patients presenting to the OR for surgery may provide false information regarding illicit substance use during the preoperative evaluation. Another important consideration is that due to the COVID-19 pandemic, you may be more likely to take care of a patient with substance use disorders. Patients may be more likely to relapse as a result of the increased stress, social isolation, and economic burden that has occurred during the pandemic. The epidemic of substance use disorders has persisted throughout the pandemic with the use of illicit substances increasing in frequency. Methamphetamine use prior to coming to the OR for surgery puts patients at risk for hypertensive crisis, hypotension and cardiovascular collapse, and death.

Before we talk about the steps that anesthesia professionals can take to help keep patients with methamphetamine substance use disorder safe during anesthesia care, we are going to do a dive into the pharmacology and pharmacokinetics of methamphetamine.

Check out the article for a figure that helps to show the mechanism of action of methamphetamine which includes the release of endogenous monoamines including dopamine, norepinephrine, and serotonin. The downstream effects include monoamines binding to their respective postsynaptic receptors. Dopamine release into the nucleus accumbens follows the same pathway for natural rewards such as eating and exercise, but with an exaggerated response since methamphetamine stimulation leads to 2-10 times more dopamine release from endogenous stores than natural rewards. This can lead to dopamine release levels that are 1000% over basal levels. Another affect involves interaction with the endogenous opioid system to further increase endorphins in the nucleus accumbens which activates the reward pathway as well. Following the dramatic release of monoamines from storage vesicles and the resultant decreased dopamine, patients experience depression and withdrawal which can activate drug-seeking behaviors.

Now, what about the peripheral actions of the monoamine release? The signs and symptoms of methamphetamine use include the following and I will break it into categories. First, in the central nervous system, signs may include:

• Agitation
• Restlessness
• Mydriasis
• Seizures
• Hyperthermia
• Anxiety
• Increased alertness
• Hallucinations
• And Psychosis.

In the cardiovascular and thoracic systems, you may see the following:

• Diaphoresis
• Hypertension
• Tachycardia
• Dysrhythmia
• Malignant arrhythmia
• Myocardial Infarction
• Coronary vasospasm
• Aortic Dissection
• Bronchodilation
• Acute Respiratory Distress Syndrome
• Pulmonary arterial hypertension
• Right heart Failure
• Sudden cardiac arrest
• And Death.

Musculoskeletal signs may include Rhabdomyolysis and severe muscle spasms.

Other signs may include ischemic colitis, metabolic acidosis, and for pregnant patients with methamphetamine substance use disorders, placental abruption leading to fetal death.

The hyperthermia associated with methamphetamine use occurs due to muscular activity and as a result, antipyretics are ineffective as a treatment. Another complication is cardiac arrest after a physical altercation. The muscular activity including isovolumetric muscle contractions can have significant complications including severe acidosis, rhabdomyolysis, hyperkalemia, and sudden asystolic cardiac arrest.

Now, it’s time to review the pharmacokinetics. Keep in mind that there are variable pharmacokinetics and metabolism depending on the route of administration, dose, and repeat dosing. Elimination of methamphetamine occurs by the cytochrome CYP2D6 in the liver as well as some renal pathways. Excretion occurs over the first 20 hours, but does depend on the pH of the urine so that when the urine is alkaline excretion will be lower and in acidic urine the excretion will be considerably higher. The duration of action of methamphetamine is about 24 hours, but patients may experience withdrawal symptoms for up to 10 days following use. Laboratory detection of methamphetamine may include serum levels or urinalysis and patients may test positive for methamphetamine or amphetamine which is the metabolized drug. Lab tests are not quantitative and cannot be used to determine clinical intoxication level or how a patient will react under anesthesia. So, if a patient tests positive for methamphetamine use in the preoperative time period, it is difficult to quantify the level of associated risks under anesthesia.

Now, it’s the moment you have all been waiting for, we are going to review the guidelines and precautions under anesthesia care. Let’s start with the scenario of an acutely intoxicated patient who requires emergent surgery. Considerations include the following:

Avoid physically restraints which may lead to severe muscle contractions followed by cardiovascular collapse.

Consider benzodiazepine therapy for chemical restraint by sedating the patient. Therapy may include Midazolam 2mg IV every 8-10 minutes until the patient is appropriately sedated. The required dose may be up to 20mg, but is highly variable.

For patients with psychosis and inadequate treatment with benzodiazepines, Haloperidol may be considered as a secondary agent. Remember, benzodiazepines and haloperidol antagonize dopamine effects in the central nervous system.

The next scenario includes hypertensive patients. Blood pressure may decrease back to baseline following adequate sedation, but treatment may be required for persistent hypertension. Have you heard the phrase of “unopposed alpha stimulation” with beta-blockers in the setting of methamphetamine use? The authors report that this is becoming increasingly controversial. There are published systemic reviews with no observed adverse outcomes following nonselective beta-blocking agent administration, including Labetalol. Evidence from another disease state, thyrotoxicosis, reveals that beta-blockers may be used for treatment, but we also need to review the 2014 executive summary from the American College of Cardiology Foundation and the American Heart Association. The summary recommends avoidance of beta blockers for patients with acute intoxication to avoid coronary vasospasm. Remember, benzodiazepine therapy is the first line treatment for hypertension for patients with methamphetamine hypertension.

Now, let’s move into the operating room. It is important to monitor blood pressure closely and these patients may require an arterial line. Patients may develop hypotension due to catecholamine depletion. Treatment of hypotension includes direct-acting vasopressors including norepinephrine, epinephrine, dopamine, or phenylephrine. Considerations for spinal or epidural anesthesia involves close monitoring of blood pressure. Be on the look-out for persistent hypotension especially with the sympathectomy that may be difficult to treat even with direct-acting vasopressors.

Another intraoperative consideration is the development of rhabdomyolysis. This may occur due to decreased fluid intake while intoxicated, decreased perfusion leading to vasoconstriction, and the direct effect on skeletal muscles. Succinylcholine administration is relatively contraindicated due to the increased risk for rhabdomyolysis. Rocuronium and vecuronium may be used with Sugammadex available for reversal if needed. Treatment for rhabdomyolysis may include IV fluid boluses depending on the patient’s volume status and heart function.

What about patients who need to take chronic amphetamines to treat attention deficit hyperactivity disorder? These patients are not at risk for labile blood pressures during anesthesia and they should continue to take their medication throughout the perioperative time period.

Let’s move up to the Labor and Delivery Unit? What are the considerations for parturients with methamphetamine substance use disorder? These patients are at risk for hypertension, premature rupture of membranes, hemorrhage, or placental abruption. Benzodiazepine therapy remains the first line therapy for acute agitation in parturiants, especially in the 2^nd and 3^rd trimester. Recent data has revealed that there are no correlations between most benzodiazepine administration and congenital malformations prior to surgery and during pregnancy. Another concern with benzodiazepine administration is drug-trapping in the newborn leading to significantly increased benzodiazepine levels compared to the mother. At midazolam doses of 0.02-0.025 mg/kg in the mother pre-cesarean, there were no differences in Apgar scores in the newborn. In the first trimester, haloperidol administration may be considered for the acute agitated patients with methamphetamine use. Avoidance of ketamine may be considered to avoid the catecholamine surge and resultant hypertension. Just like non-pregnant patients, acutely intoxicated pregnant patients are at risk for intense muscle contraction following physical restraint leading to cardiovascular collapse, so chemical restraint may be necessary with respiratory support for the newborn after delivery.

Another consideration for methamphetamine use is serotonin toxicity or serotonin syndrome. Serotonin syndrome occurs following excess serotonergic activity leading to agitation, hypertension, tachycardia, and diaphoresis. This may occur following a single ingestion of methamphetamine. Other medications that may precipitate serotonin syndrome include tramadol, meperidine, opioids such as Fentanyl, and methylene blue. Perioperative management for patients with methamphetamine substance use disorder and serotonin toxicity include benzodiazepine therapy as well. Additional treatment for serotonin syndrome includes non-selective serotonin antagonists such as cyproheptadine and risperidone and a postsynaptic dopamine blocking agent such as chlorpromazine.

The authors conclude by highlighting the vital considerations for perioperative management of patients with methamphetamine substance use disorder:

Chemical restraint should be used instead of physical restraint.

Direct-acting vasopressors should be used to treat hypotension, which may be refractory.

For hypertension, beta-blocks should only be used with caution to avoid coronary vasospasm.

These patients are at risk for rhabdomyolysis and serotonin toxicity so it is important to avoid triggering medications.

Before we wrap up the show today, we are going to hear from Krogh again. This time, I asked her what she hopes to see going forward related to methamphetamine substance use disorder. She provides a wonderful response and conclusion to our show today. Let’s take a listen.

[Krogh] “Going forward, I hope that anesthesia professionals are able to see methamphetamine substance use disorder patients as people with complex disease processes. With this understanding, we will not only be able to provide better care to these patients but may also recognize any bias one might have as a provider that may impact care of these individuals.”

[Bechtel] If you have any questions or comments from today’s show, please email us at [email protected] or connect with us on Twitter, Instagram, Facebook, or LinkedIn.

Visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.  Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. Whether you are listening to the podcast on our website or have subscribed on iTunes or Spotify or where ever you get your podcasts, thanks for listening!! Please take a minute to rate us and leave us a review! This helps others to be able to find our podcast and learn more about perioperative patient safety.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

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