Ketamine Toxicity

What is Ketamine Toxicity?

Ketamine is a drug that is similar to the anesthetic drug phencyclidine (PCP). Like PCP, ketamine reduces pain and causes memory loss, but it doesn’t affect breathing or heart functions like other anesthetics might. The original name of Ketamine was CI-581, and it is less potent than PCP and causes less significant unease and hallucinations.

Ketamine was first produced by a chemist named Calvin Stevens in 1962, and it was tested in clinical trials on children and adults undergoing surgery. The Food and Drug Administration (FDA) approved it for use in people in 1970. Ketamine was widely used as an anesthetic during the Vietnam War. It’s commonly used in the form of injections into muscle or vein to anesthetize children, particularly those who are high-risk or in areas with limited resources. In surgical settings, it is often used together with a drug class known as benzodiazepines, which can decrease the negative psychological effects when waking up from anesthesia. Moreover, it is also used unofficially in lower doses for managing acute and chronic pain, for sedation, and for treating severe depression.

Like PCP, ketamine’s effects on the mind have made it popular as a recreational drug. In small doses, it can cause a state of euphoria and feeling of being detached from one’s surroundings, commonly referred to as “k-land.” In higher doses, it causes immobilization and hallucinogenic effects that users describe as being in a “k-hole.” As a street drug, it goes by several names including “K,” “vitamin K,” “super K,” “special K,” “super C,” “special LA coke,” “jet,” “superacid,” and “green.”

Ketamine can potentially be harmful and cause a variety of symptoms related to the nervous system, heart, mental health, urinary system, and stomach. These side effects depend on the dose and whether the drug was used medically or illicitly. For example, there’s a higher chance of developing a type of bladder inflammation called ulcerative cystitis in people who use ketamine recreationally, possibly due to other substances mixed with the drug. Emergency healthcare providers should be informed about the different ways to treat the harmful effects of ketamine and how to prevent acute complications, like muscle breakdown (rhabdomyolysis), seizures, and long-term complications like mental health disturbances and ulcerative cystitis.

What Causes Ketamine Toxicity?

Ketamine is a medication that can be used safely under medical supervision. However, people can experience harmful effects from it if it’s used improperly – medically or recreationally. These harmful effects are known as “ketamine toxicity.”

Ketamine can be given by doctors through a shot into a vein or muscle, or by spraying it into the nose. Recreationally, it can be misused in several ways, such as injecting it into a vein or muscle, snorting it, swallowing it, or even smoking it.

Risk Factors and Frequency for Ketamine Toxicity

Ketamine, categorized as a recreational drug worldwide, is reported to be misused illicitly in 58 countries. However, its misuse scope isn’t too large, with new psychoactive substances derived from PCP (ketamine is one such substance) making up only 1% as reported to the United Nations Office of Drugs and Crime. Additionally, when misused, ketamine is often combined with other substances like alcohol, amphetamines, MDMA, cocaine, and caffeine.

In the US, ketamine has been a controlled substance since 1999. Its misuse has grown since the 1980s, although not as much as opioids and illicit cannabis. In 2005, ketamine was involved in only 0.033% of emergency department visits related to illicit drugs, a slight increase to 0.12% by 2011. Ketamine-related visits often involve alcohol misuse, resulting in 71.5% of such cases in 2011. However, a survey points out a decline in ketamine use among 12th graders and college students between 2002 and 2012.

Similarly, in the UK, where ketamine is a Class C drug since 2006, misuse has reduced in the 21st century. As per the World Health Organisation, adult and young adult ketamine use dropped between 2011 and 2013.

However, in Southeast Asia, including Taiwan, Malaysia, and China, there’s a rise in recreational ketamine use. For instance, in Hong Kong, where ketamine is a Schedule 1 drug, it became the most commonly misused drug in the early 2000s. Studies even found that 9% of drug-related fatal motor vehicle collisions involved ketamine, a significant number compared to fatalities resulting from alcohol and opioid misuse. Surveys indicate that ketamine misuse is notably more prevalent in Southeast China than in other parts of the country.

Signs and Symptoms of Ketamine Toxicity

If someone overdoses on ketamine, a drug often used recreationally but also in anesthesia, the symptoms can be pretty alarming. The severity is typically dependent on the dosage and duration of ketamine use and may even result in a loss of consciousness. It can be hard to determine the cause of these symptoms as the person affected may not be able to give an accurate account due to their altered mental state. It’s important to remember that ketamine goes by various street names, so medical professionals should be familiar with these.

Ketamine intoxication can result in the following symptoms:

• General feelings of sedation and impaired consciousness
• Issues with the head and senses such as involuntary eye movement, dilated pupils, and excessive saliva production
• Cardiovascular problems like high blood pressure, increased heart rate, heart palpitations, irregular heartbeat, and chest pain
• Abdominal discomfort including pain, tenderness, nausea, and vomiting
• Neurological issues like confusion, paranoia, anxiety, slurred speech, difficulty with coordination, muscle stiffness, and altered sensations
• Genitourinary symptoms related to the lower urinary tract
• Possible signs of trauma due to the diminished pain perception caused by ketamine.

Signs of a severe ketamine overdose, extremely rapid drug infusion, or mixing with other drugs include:

• Respiratory issues such as slowed or stopped breathing
• Cardiovascular issues including low blood pressure, slowed heart rate, or even a heart attack
• Neurological problems like seizures, a state of near-unconsciousness (stupor), or even coma

Finally, medical-related issues tied to injecting ketamine include:

• Difficulty in breathing or spasms in the larynx (voice box)

Testing for Ketamine Toxicity

If your doctor suspects that there may be issues with your body’s metabolic processes or cellular functions, they may order several tests. Here’s what each test measures:

• Blood tests for PCP, acetaminophin, and salicylate levels to check if you have accidentally ingested something harmful.
• An electrocardiogram (ECG), which records the electrical signals in your heart to check for heart rhythm problems and other heart conditions.
• Urine myoglobin and blood creatine kinase tests to rule out rhabdomyolysis, a severe condition witnessed when your muscle breaks down, releasing muscle fiber into the blood, which can damage your kidneys.
• Imaging tests like CT scans or MRIs to check for other causes of confusion or changes in behavior, such as bleeding in the brain or physical injuries.
• Cerebrospinal fluid (CSF) test, a procedure where a sample of the fluid surrounding your brain and spinal cord is removed for testing. This is done to check for any infections in the central nervous system, such as meningitis that could be causing your symptoms.
• A complete blood count (CBC), to check for leukocytosis, a condition characterized by high levels of white blood cells indicative of an infection, inflammation or other medical conditions.
• A comprehensive metabolic panel (CMP), which measures your blood sugar level, electrolyte and fluid balance, and kidney and liver function. This is done to look for issues with your kidneys (renal compromise) or liver (hepatotoxicity) or to see if you have high levels of blood urea nitrogen and creatinine.
• A fingerstick blood glucose test, which checks your blood sugar levels. Low blood sugar (hypoglycemia) could be the primary cause of altered mental status, or it could be secondary to ketamine toxicity.

Treatment Options for Ketamine Toxicity

If a person has consumed too much ketamine—an animal tranquilizer often misused as a recreational drug—the primary approach is to manage the symptoms. The effects of ketamine intoxication can last between 15 minutes to several hours, varying based on the amount consumed, how it was taken, the individual’s metabolism, and other factors. Even if a person initially appears fine after taking ketamine, they should be observed for about six hours. After the symptoms have resolved, they should still be monitored for 1 to 2 hours.

Important things to keep an eye on include the person’s airway, breathing, and blood circulation, as ketamine can cause difficulties especially when mixed with other drugs. If the person throws up, they should either lean forward or lie on their left side with their head turned down. This helps prevent choking. In case of breathing problems, inserting a tube to aid breathing may be required. The person’s vital signs, such as temperature, should be regularly checked, as the drug can cause other symptoms including overheating. People showing severe symptoms should be connected to monitoring equipment and admitted to the hospital for further observation.

If someone has consumed ketamine, particularly in large amounts or alongside other drugs, activated charcoal could be administered. Activated charcoal can help remove the drug from the gastrointestinal system. However, it should not be used if the person’s airway isn’t protected or if their intestines aren’t audible. In some cases, activated charcoal can prevent the need for a procedure called gastric lavage that would otherwise be used to flush out the stomach.

Currently, there isn’t any specific medication approved to treat a ketamine overdose. However, other drugs can manage effects like restlessness and hallucinations. For instance, benzodiazepines—medicines often used to treat anxiety and insomnia—can help with many symptoms caused by ketamine. Butyrophenones, a type of antipsychotic, can help manage hallucinations and agitation. Having a quiet and dim environment and limiting unnecessary stimulation can be beneficial. In severe cases, the health care team may need to use physical restraints to ensure the patient’s safety.

Other medications can also be used to manage specific symptoms. Alpha-2 agonists are drugs that can help manage the psychosis-like side effects of ketamine, decrease blood pressure, and enhance the pain-decreasing effects of ketamine. To deal with excessive saliva production related to ketamine use, drugs like atropine or glycopyrrolate can be used. Medications like physostigmine can help with vision problems. Giving fluids can help with dehydration.

What else can Ketamine Toxicity be?

The symptoms of ketamine intoxication can look like those of many other conditions or drugs. The physicians need to check for:

• Intoxication from drugs like PCP, methoxetamine, dextromethorphan (which can all bind to the same receptor as ketamine), alcohol, amphetamine, cocaine, LSD, MDMA, and salicylate
• Alcohol withdrawal (also known as delirium tremens)
• Malignant hyperthermia, a condition that can develop after the use of certain anesthetics
• Side effects from antihistamines like diphenhydramine and anticholinergics like benztropine

In addition to these, they may also have to rule out various psychiatric illnesses and their treatments, such as:

• Bipolar disorder and schizophrenia
• Complications from treatments like serotonin syndrome from SSRIs (a type of antidepressant), neuroleptic malignant syndrome from antipsychotics, and side effects from other types of antidepressants

Other medical conditions that could cause symptoms similar to ketamine intoxication include:

• CNS (central nervous system) infections like meningitis and encephalitis
• CNS malignancies (cancer)
• Acute conditions like brain trauma or bleeding in the brain
• Systemic conditions such as low oxygen levels, low blood sugar, sepsis, overactive thyroid, and problems with electrolyte levels, like low sodium

What to expect with Ketamine Toxicity

Ketamine overdose is quite rare, and not much information is available about survival rates. Addiction to ketamine is also less common, and we don’t have enough data about relapse rates and outcome. However, we know that complications from ketamine are very low, occurring in less than 1% of cases.

The risk of death in accidents when under the influence of ketamine is one of the leading causes of mortality linked to this drug. In a study, within a year, two ketamine users died – one drowned in a bath, and the other died from hypothermia.

Ketamine could have severe effects on patients with other heart conditions, as this drug stimulates the nervous system causing increased heart rate and blood pressure. This could make intoxicated patients with severe heart disease or high blood pressure more prone to conditions like stroke, heart attacks, or increased pressure in the brain. Some reports have shown ketamine triggering unstable chest pain and heart rhythm problems.

Rarely, using ketamine may cause brain-related syndromes, seizures, or even coma. It can also lead to immediate kidney problems, imbalance of minerals in the blood, liver failure, and muscle injury.

Regular misuse of ketamine is linked with a condition that leads to ulcers in the bladder. This can reduce bladder size and increase the size of the tube carrying urine from the kidneys to the bladder, leading to kidney swelling. People misusing ketamine may also experience pain in the stomach or lower abdomen, blood in urine, painful urination, and increased need to urinate. Chronic usage may be connected with liver issues.

Some temporary mental effects of ketamine, like hallucinations and vivid dreams, may re-appear days or weeks after using ketamine. However, long-term use can lead to more severe issues such as depression and problems with memory and concentration. Reports suggest that chronic users of Ketamine or a similar drug – PCP – have experienced psychological symptoms, including anxiety, irritability, depression, and changes in sleep and energy levels a day after stopping the use of ketamine. However, there isn’t any concrete evidence pointing towards physical dependence or withdrawal symptoms.

Interestingly, there is a version of ketamine that is snorted, which has recently been approved as a treatment for depression. It has also gained attention as a treatment for stubborn posttraumatic stress disorder, and it’s being actively researched for reducing alcohol, cocaine, and opioid dependency.

Possible Complications When Diagnosed with Ketamine Toxicity

Ketamine usage can bring about several negative effects which include:

• Mental disturbances (Psychosis)
• Addiction to the drug
• Memory loss (Amnesia)
• Heightened blood pressure
• Difficulty in movement (Impaired motor function)
• Seizure episodes
• Complications associated with breathing (Respiratory complications)
• Issues with balance and decision-making (Impaired coordination and judgment)
• Potential for feeling down or upset (Risk of depression)
• Painful inflammation of the bladder walls (Ketamine-induced ulcerative cystitis)

Preventing Ketamine Toxicity

Patients need to be educated about the effect of being disconnected from reality that can be caused by ketamine. This effect may result in significant changes to your consciousness level that could potentially lead to accidental harm to yourself or others. Ketamine can impact your physical performance related to coordinated movements such as coordination, balance, and coordinating what you see with the movement of your hands.

This impaired coordination might end up increasing the number of deaths caused by car accidents if patients decide to drive while under the influence of ketamine. Since ketamine has a high risk of being abused and is classified by the U.S Drug Enforcement Agency as a schedule-III controlled substance – meaning it has a moderate to low potential for physical and psychological dependence but high potential for misuse – patients who are given ketamine for long-term pain or depression should be educated about the risk of becoming addicted. They should be evaluated in a similar way to those being considered for long-term opioid therapy.

Abusing ketamine could result in long-term health issues that can be difficult and expensive to treat. Ulcerative cystitis, a common side effect caused by the misuse of ketamine, often resists standard treatments. This condition is when your bladder becomes inflamed and forms ulcers. Being diagnosed with this type of cystitis due to ketamine misuse often leads to repeated bladder exams and symptomatic relief through bladder catheter placement. Patients diagnosed with this may need treatment for their whole lives.