What is Propofol Toxicity?
Propofol is a medicine often used to make patients sleepy or unconscious for surgery. It’s a type of medicine called a phenol, and it’s given through a vein (intravenous or IV). The most common form is a fat-soluble (lipophilic) mixture, which allows it to quickly spread into different parts of the body, including the brain. Propofol is frequently used in Intensive Care Units (ICUs) to keep patients sedated because it works fast and doesn’t stay in the body too long.
The effects of Propofol can vary depending on the dose – higher doses can cause changes in blood pressure and heart rate. Also, it can cause some discomfort at the spot where it’s injected. While Propofol is generally safe and effective, too much of it can harm a patient. Propofol Infusion Syndrome (PRIS) is a condition where the patient’s health deteriorates due to a toxic amount of Propofol in the body.
What Causes Propofol Toxicity?
Propofol infusion syndrome (PRIS) usually appears in those who’ve been given propofol for a very long time at large doses. According to studies, you’re more likely to get PRIS if propofol is given for over 48 hours or at a rate of about 4 mg/kg/hr (which is 67 mcg/kg/minute).
There are also risk factors that make you more prone to get PRIS, like severe illnesses such as blood infections, brain injuries, airway infections, and poor delivery of oxygen in your body. Other things that could increase the chances of getting PRIS include low carbohydrate levels, use of certain medications (like glucocorticoids), instances of unnoticed mitochondrial disease (a disease that affects how our cells produce energy), and carnitine deficiency (lower levels of a substance that our body needs to use fats for energy).
Risk Factors and Frequency for Propofol Toxicity
Pain when being given propofol, a type of anesthesia, usually affects younger people aged from 20 to 40 years and tends to be more common in females. When propofol infusion syndrome was first discovered, it was typically found in children in the ICU who were being heavily sedated with propofol. However, as more cases have been reported, the average age has increased to 58. Around 1.1% of people who are given propofol experience this syndrome, and it is more common in men than in women. The fatality rate has been estimated to be between 18 and 32% based on different studies.
- Propofol-induced pain usually presents in younger patients, aged 20-40 years old.
- It is more common in females and when given in a peripheral IV site.
- Propofol infusion syndrome was initially most common in children in ICU under heavy sedation with propofol.
- However, the average age has increased to around 58 years as more cases are reported.
- The chance of having propofol infusion syndrome is about 1.1% for people given propofol infusions.
- It is more common in men than women.
- The death rate varies between 18% and 32%, according to different studies.
Signs and Symptoms of Propofol Toxicity
Propofol is a medication that is given through an injection into a vein. A common side effect of propofol is pain at the injection site, often described by patients as a burning sensation that lasts up to 20 seconds.
Sometimes, patients might experience a condition called propofol infusion syndrome. Signs of this syndrome can include a number of health issues:
- Metabolic acidosis: an imbalance in the body’s acid-base with high levels of lactic acid.
- Cardiac problems: these can range from low blood pressure, slow heart rate, irregular heart rhythms, or even heart stoppage. Changes may also be seen on an ECG, a test that measures electrical activity of the heart.
- Musculoskeletal injury: this can include rhabdomyolysis (the breakdown of muscle fibers resulting in the release of muscle fiber contents into the bloodstream) and myopathy (any disease that affects the muscles that control voluntary movement in the body).
- Kidney and liver issues: symptoms might include producing less urine than usual or an enlarged liver.
- Changes in the urine: the urine might appear red or green.
Testing for Propofol Toxicity
In cases where a patient is sedated with a drug called propofol, it’s crucial to regularly check for symptoms of organ malfunction that the patient may not communicate due to the sedation. These signs could include producing dark urine – a symptom of a condition called rhabdomyolysis, or having an enlarged liver.
While the drug is being given, lab tests need to be consistently done to catch early signs of Propofol Infusion Syndrome (PRIS), a rare but severe complication of propofol. The lab results might show problems with multiple organ systems. Lab values that could indicate problems include certain types of acidosis, high levels of substances like creatine kinase, myoglobin, urea, potassium, and liver enzymes in the blood. The medication’s fatty (lipemic) nature can also increase levels of triglycerides, a type of fat in your blood, which could lead to pancreatitis, a disease characterized by inflammation of the pancreas.
Besides this, it’s necessary to monitor the patient’s heart closely. Early signs of cardiac irregularities such as arrhythmias (an abnormal heartbeat) may indicate drug toxicity and need further investigation. This is typically done by constant heart-monitoring (telemetry) and repeated electrocardiograms (EKGs) – tests that measure the electrical activity of your heartbeat. A slower than normal heart rate, also known as bradycardia, is often the first indication of heart irregularities.
Treatment Options for Propofol Toxicity
Lidocaine, a type of numbing medication, is commonly used to reduce the pain that can be caused by the injection of a sedative called propofol. The lidocaine can be mixed with the propofol or given before the propofol is administered. Both methods have been shown to be effective.
Propofol-related infusion syndrome (PRIS) is a serious condition that can occur if propofol is used extensively. If doctors suspect PRIS, they need to act quickly. The propofol must be stopped, and if the patient still needs to be sedated, a different type of sedative will be used. The main goal is to stabilize the patient’s heart rate and blood pressure. In extreme cases, advanced support for the heart and lungs might be needed, such as the use of a machine that takes over the function of these organs (extracorporeal membranous oxygenation, or ECMO). If the patient develops a very slow heart rate (severe bradycardia), a device to regulate the heartbeat (a cardiac pacemaker) might be needed. Propofol can also interfere with some heart medications, which can potentially make the heart less responsive to emergency treatments.
After the propofol has been discontinued, doctors then work on reversing any problems caused by it. This might involve correcting any electrolyte imbalances in the patient’s body by either adding or removing certain electrolytes as needed. For instance, high levels of potassium in the blood (hyperkalemia) can happen, and this can be treated with medications like calcium, insulin, beta2 agonists, or potassium-binding drugs. If the propofol caused a harmful increase in acid levels in the body (metabolic acidosis), therapies that filter and clean the blood (like continuous renal replacement therapy, or CRRT) might be needed. These therapies, along with therapeutic plasma exchange, hemodialysis and hemofiltration, can also help to decrease the levels of propofol and other harmful substances in the body. Lastly, providing the patient with carbohydrates can help support the body’s processing of fats, a process that can be affected by propofol.
What else can Propofol Toxicity be?
Healthcare professionals must carefully analyze the array of symptoms that come with PRIS (Propofol Infusion Syndrome), to determine whether they’re actually caused by propofol, a commonly used sedative, or by another health issue. If they don’t consider the use of propofol, they might misdiagnose the patient’s symptoms as signs of serious diseases like shock, sepsis, or kidney disease. They also need to consider other factors that could be involved, such as birth defects (for example, Brugada Syndrome) or other medicines that the patient might be taken at the same time as propofol. This emphasizes the importance of always considering the possibility of PRIS when propofol has been administered to a patient.
What to expect with Propofol Toxicity
PRIS, or Propofol Infusion Syndrome, often has a challenging outcome, especially if it’s not detected quickly. The death rate for this condition can vary, falling anywhere between 18 to 32%. However, the chances of survival can improve if doctors are aware of the risks and can recognize the early symptoms of the syndrome. That’s why it’s crucial to communicate well with your healthcare team and report any concerning symptoms as early as possible.
Possible Complications When Diagnosed with Propofol Toxicity
The main issue with propofol toxicity is that it can develop dangerous conditions that may lead to death. Hypertriglyceridemia, or high levels of triglycerides in the blood, can set the stage for pancreatitis, which is inflammation of the pancreas. Metabolic acidosis is another condition which can develop and trigger additional health problems. Heart failure and rhabdomyolysis, which is a breakdown of muscle tissue that releases damaging proteins into the blood, are significant worries when it comes to propofol toxicity. If Propofol Infusion Syndrome (PRIS) is not addressed in a timely manner, the situation can become fatal. Some complications are closely linked with multifaceted treatment options.
Concerns related to Propofol Toxicity:
- Triggering of fatal conditions
- Hypertriglyceridemia leading to pancreatitis
- Development of metabolic acidosis causing additional health problems
- Cardiac failure
- Rhabdomyolysis or breakdown of muscles
- Fatality if Propofol Infusion Syndrome (PRIS) is not timely addressed
- Complications associated with complex treatment approaches
Preventing Propofol Toxicity
Before a doctor starts using a medicine called propofol, it’s important for them to understand a patient’s full medical history. Patients should feel free to share any information that might not make propofol a good choice for them. For example, if the patient has had bad reactions to propofol in the past, or they have a condition called a mitochondrial disease, this could suggest that there might be a high risk of negative side effects with propofol.
If the doctor is worried that they would need to use a high dose of propofol or that the patient might get too much of it in their system (a condition known as toxicity), they would need to think about using a different medicine to make the patient relaxed and sleepy.
