Propofol infusion syndrome involves a very rare serious complication that occurs during long-term anesthesia with propofol. The syndrome typically manifests as cardiac arrhythmias; problems with striated cardiac, skeletal, and diaphragmatic muscles; and lactic acidosis, an acidosis caused by lactic acid. The exact causes of propofol infusion syndrome are not (yet) well understood; it is probably multifactorial in origin, and long-term anesthesia with a dosage of propofol of
What is propofol infusion syndrome?
Propofol (2,6-diisopropylphenol), with the chemical molecular formula C12H18Ois a very commonly used intravenous anesthetic. It is used for induction and maintenance of anesthesia and is also suitable for total intravenous anesthesia (TIVA) and for permanent sedation of patients. The drug has a purely hypnotic, or soporific, effect and has no analgesic (pain-relieving) properties. It usually causes few undesirable side effects and is very well tolerated. Among anesthesiologists, propofol is valued because the depth of anesthesia can be well controlled with the drug. However, in very rare cases, serious reactions can still occur, collectively known as propofol infusion syndrome (PRIS). The likelihood of the syndrome occurring is obviously somewhat increased with long-term infusions of more than 24 hours and in children. Similarly, relatively high doses of the anesthetic above 5 mg/kg/h favor propofol infusion syndrome.
Causes
The causes for the occurrence of propofol infusion syndrome are not (yet) adequately understood. A multifactorial complex of causes is considered very likely, involving fatty acid metabolism in the mitochondria along with uncoupling of the citrate cycle. Obviously, there is a disturbance of the transport of fatty acids into the matrix of the mitochondria. This leads to a disturbance of the mitochondrial fatty acid oxidation and thus to a deficient energy supply. This hypothesis is also supported by the symptoms that occur in patients with the very rare genetic deficiency of active acyl-CoA dehydrogenase. These patients also present with myolysis of the striated muscles (rhabdomyolysis), heart failure, cardiac arrhythmias and metabolic acidosis. As a causative agent, the missing enzyme leads to a comparable disturbance of lipid metabolism as in PRIS.
Symptoms, complaints, and signs
Propofol infusion syndrome initially presents with a variety of nonspecific symptoms. The first signs may be cardiac arrhythmias. These are usually atrio-ventricular block, that is, conduction problems of the contraction impulse for the atria triggered by the sinus node through the AV node to the ventricles. Typically, the ECG shows a widening of the QRS complex or the contraction signal is completely blocked by the AV node, so that at best the very slow ventricular replacement rhythm can step in. Serious further problems arise because of developing rhabdomyolysis, which leads to dissolution of the tissue of striated muscle. This means that the cardiac and skeletal muscles and the diaphragm are particularly affected. Propofol syndrome also triggers metabolic lactic acidosis, and greatly increased excretion of myoglobin in the urine (myoglobinuria) is probably causally responsible for the development of renal insufficiency. In some cases, pathologically elevated levels of triglycerides in the blood have also been found (hypertriglyceridemia).
Diagnosis and course of the disease
Propofol infusion syndrome usually occurs during the course of long-term sedation or anesthesia, so important cardiovascular parameters are under continuous observation. Initial signs of the syndrome are manifested by cardiac rhythm problems, particularly AV block, which may be associated with very slow heartbeat (brachycardia). If, in addition, lactic acidosis is detected in the blood serum and important cardiac enzymes such as creatine kinase (CK), glutamate oxaloacetate transaminase (GOT), glycogen phosphorylase BB (GPBB) and others are pathologically elevated, the suspicion of propofol infusion syndrome is strengthened.If left untreated and propofol sedation or propofol anesthesia is continued, the prognosis is very poor because of the expected cardiac arrest.
Complications
Due to propofol infusion syndrome, in most cases, the affected person suffers from cardiac discomfort. In the worst case, this can also lead to heart failure if no treatment for propofol infusion syndrome is initiated in time. Furthermore, there is also discomfort to the tissues of the diaphragm. Renal failure may also occur if propofol infusion syndrome is not treated. Those affected are then dependent on dialysis or on a kidney transplant. If this does not result in treatment, patients usually die. Complications usually only occur if the operation continues and no treatment is initiated. In most cases, cardiac arrest occurs. The drug is replaced by another anesthetic, and in most cases there are no particular complications. In severe cases, treatment must then be stopped completely. With successful treatment of propofol infusion syndrome, there is also no reduction in life expectancy. With optimized dosing, these complaints can usually be avoided completely, so that no further complications occur.
When should you see a doctor?
By their very nature, people who are under the influence of propofol can no longer take care of their own health. Propofol infusion syndrome is a complication during anesthesia. It is an irregularity of long-term anesthesia. Due to an existing disorder, the affected person is therefore already in a state for several days, weeks or months in which there are no conscious possibilities for action on his part. Since the patient is already undergoing medical treatment, the attending physicians or the nursing team independently take over necessary steps of health care in case of irregularities. During this time, relatives should maintain close communication with the physician and the nursing staff. If any abnormalities occur during visiting hours, they should be reported immediately to a contact person. In addition, open questions should be asked about the patient’s state of health and a comprehensive explanation of the existing illness should be provided. In many cases, physicians require the consent of relatives to carry out necessary treatment steps. Since the affected person cannot decide on his or her own care, relatives or partners should be adequately informed about the overall situation. In some cases, consideration should be given to whether obtaining a second opinion from another physician is indicated.
Treatment and therapy
The most important measure for a diagnosed propofol syndrome is immediate discontinuation of the propofol infusion. Propofol must be replaced with another narcotic. In addition to immediate interruption of the propofol infusion, supportive measures are indicated. These measures consist of an adequate supply of fluids and administration of catecholamines, which are stress hormones that maintain blood pressure and increase heart rate. If bradycardia cannot be resolved by drug treatment in the presence of persistent AV block, pacing may be considered. In addition, appropriate electrolyte compensation should be provided to treat lactic acidosis. In some cases, continuous hemofiltration or hemodialysis has been shown to be beneficial because it resulted in massive improvement of symptoms. Early use of hemofiltration as the first-line treatment for PRIS has been discussed in the literature. Cases have also been reported in which the (too late) use of hemofiltration failed to achieve its goal. To compensate for the presumed fatty acid oxidation disorder in mitochondria, adequate caloric intake should also be ensured during therapy.
Prevention
Direct preventive measures to avoid propofol infusion syndrome are nonexistent because it is not known before the use of the anesthetic for long-term sedation or long-term anesthesia whether the patient has preconditions for the development of the syndrome.Limiting the dosage of the drug to 4 mg/kg/h can already be considered one of the most important preventive measures. Limiting continuous anesthesia or sedation with propofol to a maximum of seven days also includes a precautionary measure to prevent PRIS. As a precaution, propofol should not be used during pregnancy or while breastfeeding. A strict contraindication exists for individuals suffering from soy allergy.
Follow-up
Propofol infusion syndrome requires consistent clinical monitoring during follow-up. Because the metabolic disturbance occurs only when propofol was given in prolonged doses, it is strongly recommended to avoid reuse of propofol. Cardiac and renal insufficiency must be completely cured and attention must be paid to the administration of sufficient fluids. In acute treatment, the use of dialysis must be considered. Permanent damage to the heart and kidneys cannot be ruled out and requires further treatment and stabilization of the patient’s general condition during follow-up care. Further follow-up examinations on an outpatient basis are necessary after inpatient care, as well as the patient’s cooperation with an experienced physician. Although propofol infusion syndrome is no longer present as a condition after discontinuation of propofol and acute treatment, it takes time to determine whether the effects on the patient’s body have been completely resolved in a timely manner. The patient must be thoroughly and completely educated about the effects of propofol and must not be sedated again with a propofol infusion or even kept under anesthesia for a longer period of time. Therefore, it is essential that the affected person immediately mention the complication to an anesthesiologist during an educational interview.
Here’s what you can do yourself
Once propofol infusion syndrome (PRIS) has occurred, there is no self-help option. It is a very rare medical emergency following administration of the anesthetic propofol. The infusion of propofol must be stopped immediately. In addition, supportive measures are often necessary to protect against circulatory collapse and metabolic acidosis. To compensate for renal failure, hemofiltration or hemodialysis should be considered early. Hemodialysis in particular rapidly improves symptoms. After successful application of these measures, the patient recovers completely. Neither life expectancy nor quality of life is reduced. However, should a situation arise again that makes anesthesia necessary, it is very important for the patient concerned to discuss alternatives with the physician. The physician must therefore be informed by the patient of the intolerance to normal anesthetics. If PRIS has already occurred once, no more drugs for sedation with propofol may be used in pain patients. Therefore, the patient should discuss alternatives with the physician in these cases as well. The only way for the patient to decrease the likelihood of PRIS is through dietary design. Thus, in addition to genetic factors and excessive dosing of propofol, PRIS is also favored by long periods of fasting, ketogenic diets, and low-carbohydrate diets.