Propofol infusion syndrome

The Propofol infusion syndrome contains a very rarely occurring serious complication during long-term anesthesia with propofol. The syndrome typically manifests itself in cardiac arrhythmias, problems with the striated muscles of the heart, skeleton, and diaphragm, as well as lactic acidosis, an acidosis caused by lactic acid. The exact causes of the propofol infusion syndrome are not (yet) adequately understood, it is probably multifactorial and long-term anesthesia with a dose of propofol of

What is Propofol Infusion Syndrome?

Propofol infusion syndrome usually occurs in the course of long-term sedation or long-term anesthesia, so important cardiovascular parameters are under constant observation.
© chanawit - stock.adobe.com

Propofol (2,6-diisopropylphenol) with the chemical molecular formula C12H18O is a very commonly used intravenous anesthetic. It is used to induce and maintain anesthesia and is also suitable for total intravenous anesthesia (TIVA) and for the long-term sedation of patients.

The remedy has a purely hypnotic effect, i.e. sleep-inducing and has no analgesic (pain-relieving) properties. It usually causes hardly any undesirable side effects and is very well tolerated. Propofol is valued by anesthetists because the depth of the anesthesia can be easily controlled with the agent.

In very rare cases, however, serious reactions can occur that are known as Propofol infusion syndrome (PRIS) can be summarized. Obviously, the likelihood of the syndrome occurring is slightly increased with long-term infusions longer than 24 hours and in children. Relatively high doses of the anesthetic of more than 5 mg / kg / h also favor the propofol infusion syndrome.

causes

The causes of propofol infusion syndrome have not (yet) been adequately clarified. A multifactorial complex of causes that affects the fatty acid metabolism in the mitochondria and the decoupling of the citrate cycle is considered very likely. There is obviously a disturbance in the transport of fatty acids into the matrix of the mitochondria.

This leads to an inadequate energy supply through a disruption of mitochondrial fatty acid oxidation. This thesis is also supported by the symptoms that arise in patients with the very rare genetic deficiency of active acyl-CoA dehydrogenase.

These patients also experience myolysis of the striated muscles (rhabdomyolysis) as well as heart failure, cardiac arrhythmias and metabolic acidosis. The missing enzyme, as the causative agent, leads to a comparable disruption of lipid metabolism as in PRIS.

Symptoms, ailments & signs

The propofol infusion syndrome initially shows itself through various non-specific symptoms. The first signs can be cardiac arrhythmias. These are mostly atrio-ventricular blockages, that is, problems with the conduction of the contraction pulse triggered by the sinus node for the atria 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 other problems arise because of the developing rhabdomyolysis, which leads to the dissolution of the tissue of striated muscles. This means that the heart and skeletal muscles as well as the diaphragm are particularly affected.

Propofol syndrome also causes metabolic lactic acidosis, and a greatly increased excretion of myoglobin in the urine (myoglobinuria) is probably responsible for the development of renal insufficiency. In some cases, pathologically elevated levels of triglycerides in the blood were also found (hypertriglyceridemia).

Diagnosis & course of disease

Propofol infusion syndrome usually occurs in the course of long-term sedation or long-term anesthesia, so important cardiovascular parameters are under constant observation. The first signs of the syndrome are cardiac rhythm problems, especially AV blocks, which can be associated with a very slow heartbeat (brachycardia).

If lactic acidosis is also found in the blood serum and important cardiac enzymes such as creatine kinase (CK), glutamate oxaloacetate transaminase (GOT), glycogen phosphorylase BB (GPBB) and others are abnormally elevated, the suspicion of propofol infusion syndrome is reinforced. If left untreated and if Propofol sedation or Propofol anesthesia is continued, the prognosis is very poor due to the expected cardiac arrest.

Complications

Because of the propofol infusion syndrome, those affected in most cases suffer from heart problems. In the worst case, heart failure can occur if treatment of the propofol infusion syndrome is not initiated in good time. Furthermore, there are also discomforts in the tissue of the diaphragm. Renal failure can also occur if propofol infusion syndrome is not treated.

Those affected are then dependent on dialysis or a kidney transplant. If there is no treatment, the patients usually die. Complications usually only arise if surgery continues and no treatment is initiated. In most cases, this leads to cardiac arrest.

The drug is replaced by another anesthetic, and in most cases there are no particular complications. In severe cases, treatment must then be completely interrupted. If the propofol infusion syndrome is treated successfully, there is also no reduction in life expectancy. With an optimized dosage, these complaints can usually be completely avoided, so that there are no further complications.

When should you go to the doctor?

People who are under the influence of propofol can naturally no longer take care of their own health. Propofol infusion syndrome is a complication during anesthesia. It is an irregularity in long-term anesthesia. Due to an existing disorder, the affected person has already been in a state for a few days, weeks or months in which there are no conscious options for action on his part.

Since the person concerned is already receiving medical treatment, the attending doctors or the nursing team independently take over the necessary steps for health care if irregularities occur. During this time, relatives should have a close communicative exchange with the doctor and the nursing staff.

If there are any abnormalities within the visiting hours, they must be reported to a contact person immediately. In addition, open questions about the patient's state of health should be asked and extensive information should be provided about the existing disease. In many cases, doctors need the consent of relatives in order to carry out necessary treatment steps. Since the affected person cannot decide for himself about his care, relatives or partners should inform themselves sufficiently about the overall situation. In some cases it should be checked whether it is appropriate to obtain a second opinion from another doctor.

Treatment & Therapy

The most important measure to be taken if the propofol syndrome is diagnosed is to stop the propofol infusion immediately. Propofol must be replaced with another narcotic. In addition to stopping the propofol infusion immediately, supportive measures are indicated.

The measures consist of an adequate supply of fluids and the administration of catecholamines, which act as stress hormones to maintain blood pressure and increase the heart rate. If the bradycardia cannot be corrected by drug treatment and AV block persists, pacemaker pacing can be considered.

In addition, adequate electrolytic compensation should be provided for the treatment of lactic acidosis. In some cases, continuous hemofiltration or hemodialysis has proven to be effective because it leads to a massive improvement in symptoms. An early use of hemofiltration as the therapeutic agent of first choice for PRIS is discussed in the specialist literature.

Cases were also reported in which the (too late) application of hemofiltration no longer led to the goal. To compensate for the suspected fatty acid oxidation disorder in the mitochondria, care should also be taken to ensure an adequate intake of calories during therapy.

You can find your medication here

➔ Medicines for pain

prevention

Direct preventive measures to avoid propofol infusion syndrome are not in place because it is not known before the anesthetic is used for long-term sedation or long-term anesthesia whether the patient is suitable for the development of the syndrome. Limiting the dosage of the agent to 4 mg / kg / h can already be seen as one of the most important preventive measures.

Limiting long-term anesthesia or sedation with propofol to a maximum of seven days also includes a precautionary measure to avoid PRIS. As a precautionary measure, propofol should not be used during pregnancy and breastfeeding. There is a strict contraindication for people who are allergic to soy.

Aftercare

Propofol infusion syndrome requires rigorous clinical monitoring during follow-up. Since the metabolic disorder only occurs when propofol has been administered over a long period of time, it is highly recommended to avoid re-use of propofol. The cardiac and renal insufficiency must heal completely and it is especially important to ensure that sufficient fluids are given.

The use of dialysis must be considered in acute treatment. Permanent damage to the heart and kidneys cannot be ruled out and require further treatment and stabilization of the patient's general condition in follow-up care. After the inpatient care, further outpatient check-ups are necessary and the patient must work with an experienced doctor.

Propofol infusion syndrome is no longer present as a disease after discontinuation of propofol and acute treatment, but it takes some time to determine whether the effects on the patient's body have been completely eliminated in time. The patient must be fully and comprehensively informed about the effects of propofol and must not be sedated again with a propofol infusion or be kept under anesthesia for longer. It is therefore essential that the person concerned immediately mentions the complication to an anesthetist in a clarification session.

You can do that yourself

When Propofol Infusion Syndrome (PRIS) has occurred, there is no longer any possibility of self-help. It is a very rare medical emergency after 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.

Hemofiltration or hemodialysis should be considered at an early stage to compensate for kidney failure. The symptoms improve rapidly, especially with hemodialysis. After successful application of these measures, the patient is completely recovered. Neither life expectancy nor quality of life are limited. However, should a situation arise that require anesthesia, it is very important for the patient concerned to discuss alternatives with the doctor. The patient must therefore inform the doctor about the intolerance to normal anesthetics. If PRIS has already occurred, drugs for sedation with propofol should no longer be used in pain patients. Therefore, the patient should discuss alternatives with the doctor in these cases as well.

The only way the patient can reduce the likelihood of PRIS is through diet design. In addition to genetic factors and an excessive dose of propofol, PRIS is also favored by long periods of fasting, ketogenic diets and low-carbohydrate diets.