Propofol infusion syndrome | |
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Propofol |
Propofol infusion syndrome (PRIS) is a rare syndrome which affects patients undergoing long-term treatment with high doses of the anaesthetic and sedative drug propofol. It can lead to cardiac failure, rhabdomyolysis, metabolic acidosis, and kidney failure, and is often fatal. [1] [2] [3] High blood potassium, high blood triglycerides, and liver enlargement, proposed to be caused by either "a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism" [4] are also key features. It is associated with high doses and long-term use of propofol (> 4 mg/kg/h for more than 24 hours). It occurs more commonly in children, and critically ill patients receiving catecholamines and glucocorticoids are at high risk. Treatment is supportive. Early recognition of the syndrome and discontinuation of the propofol infusion reduces morbidity and mortality. Metabolic acidosis is a primary feature and may be the first laboratory evidence of the syndrome.
The syndrome clinically presents as acute refractory bradycardia that leads to asystole, in the presence of one or more of the following conditions: metabolic acidosis, rhabdomyolysis, hyperlipidemia, and enlarged liver. The association between PRIS and propofol infusions is generally noted at infusions higher than 4 mg/kg per hour for greater than 48 hours. [4]
The mechanism of action is poorly understood but may involve the impairment of mitochondrial fatty acid metabolism by propofol. [4]
PRIS is a rare complication of propofol infusion. It is generally associated with high doses (>4 mg/kg per hour or >67 mcg/kg per minute) and prolonged use (>48 hours) [5] [6] [7] [8] though it has been reported with high-dose short-term infusions. [9] [10]
Additional proposed risk factors include a young age, critical illness, high fat and low carbohydrate intake, inborn errors of mitochondrial fatty acid oxidation, and concomitant catecholamine infusion or steroid therapy. [9] Characteristics of PRIS include acute refractory bradycardia, severe metabolic acidosis, cardiovascular collapse, rhabdomyolysis, hyperlipidemia, renal failure, and hepatomegaly. [7] [11]
The incidence of PRIS is unknown, but it is probably less than 1 percent. [12] Mortality is variable but high (33 to 66 percent). [13] [14] [7] Treatment involves discontinuation of the propofol infusion and supportive care. [9]
Predisposing factors seem to include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. [4]
Treatment options are limited and are usually supportive, including hemodialysis with cardiorespiratory support. [4]
Sodium thiopental, also known as Sodium Pentothal, thiopental, thiopentone, or Trapanal, is a rapid-onset short-acting barbiturate general anesthetic. It is the thiobarbiturate analog of pentobarbital, and an analog of thiobarbital. Sodium thiopental was a core medicine in the World Health Organization's List of Essential Medicines, but was supplanted by propofol. Despite this, thiopental is listed as an acceptable alternative to propofol, depending on local availability and cost of these agents. It was the first of three drugs administered during most lethal injections in the United States until the US division of Hospira objected and stopped manufacturing the drug in 2011, and the European Union banned the export of the drug for this purpose. Although thiopental abuse carries a dependency risk, its recreational use is rare.
Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes mellitus. Signs and symptoms may include vomiting, abdominal pain, deep gasping breathing, increased urination, weakness, confusion and occasionally loss of consciousness. A person's breath may develop a specific "fruity" smell. The onset of symptoms is usually rapid. People without a previous diagnosis of diabetes may develop DKA as the first obvious symptom.
Ketosis is a metabolic state characterized by elevated levels of ketone bodies in the blood or urine. Physiological ketosis is a normal response to low glucose availability. In physiological ketosis, ketones in the blood are elevated above baseline levels, but the body's acid–base homeostasis is maintained. This contrasts with ketoacidosis, an uncontrolled production of ketones that occurs in pathologic states and causes a metabolic acidosis, which is a medical emergency. Ketoacidosis is most commonly the result of complete insulin deficiency in type 1 diabetes or late-stage type 2 diabetes. Ketone levels can be measured in blood, urine or breath and are generally between 0.5 and 3.0 millimolar (mM) in physiological ketosis, while ketoacidosis may cause blood concentrations greater than 10 mM.
Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly, often due to high intensity exercise over a short period. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of the muscle breakdown products, such as the protein myoglobin, are harmful to the kidneys and can cause acute kidney injury.
Lactic Acidosis refers to the process leading to the production of lactate by anaerobic metabolism. It increases hydrogen ion concentration tending to the state of acidemia or low pH. The result can be detected with high levels of lactate and low levels of bicarbonate. This is usually considered the result of illness but also results from strenuous exercise. The effect on pH is moderated by the presence of respiratory compensation.
Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Numerous generic versions have since been released. Intravenous administration is used to induce unconsciousness after which anesthesia may be maintained using a combination of medications. It is manufactured as part of a sterile injectable emulsion formulation using soybean oil and lecithin, giving it a white milky coloration.
Ketoacidosis is a metabolic state caused by uncontrolled production of ketone bodies that cause a metabolic acidosis. While ketosis refers to any elevation of blood ketones, ketoacidosis is a specific pathologic condition that results in changes in blood pH and requires medical attention. The most common cause of ketoacidosis is diabetic ketoacidosis but can also be caused by alcohol, medications, toxins, and rarely, starvation.
Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat severe agitation. It induces sleepiness, decreases anxiety, and causes anterograde amnesia.
Malignant hyperthermia (MH) is a type of severe reaction that occurs in response to particular medications used during general anesthesia, among those who are susceptible. Symptoms include muscle rigidity, fever, and a fast heart rate. Complications can include muscle breakdown and high blood potassium. Most people who are susceptible to MH are generally unaffected when not exposed to triggering agents.
Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.
An induced coma – also known as a medically induced coma (MIC), barbiturate-induced coma, or drug-induced coma – is a temporary coma brought on by a controlled dose of an anesthetic drug, often a barbiturate such as pentobarbital or thiopental. Other intravenous anesthetic drugs such as midazolam or propofol may be used.
Metabolic acidosis is a serious electrolyte disorder characterized by an imbalance in the body's acid-base balance. Metabolic acidosis has three main root causes: increased acid production, loss of bicarbonate, and a reduced ability of the kidneys to excrete excess acids. Metabolic acidosis can lead to acidemia, which is defined as arterial blood pH that is lower than 7.35. Acidemia and acidosis are not mutually exclusive – pH and hydrogen ion concentrations also depend on the coexistence of other acid-base disorders; therefore, pH levels in people with metabolic acidosis can range from low to high.
In anaesthesia and advanced airway management, rapid sequence induction (RSI) – also referred to as rapid sequence intubation or as rapid sequence induction and intubation (RSII) or as crash induction – is a special process for endotracheal intubation that is used where the patient is at a high risk of pulmonary aspiration. It differs from other techniques for inducing general anesthesia in that several extra precautions are taken to minimize the time between giving the induction drugs and securing the tube, during which period the patient's airway is essentially unprotected.
Mitochondrial myopathies are types of myopathies associated with mitochondrial disease. Adenosine triphosphate (ATP), the chemical used to provide energy for the cell, cannot be produced sufficiently by oxidative phosphorylation when the mitochondrion is either damaged or missing necessary enzymes or transport proteins. With ATP production deficient in mitochondria, there is an over-reliance on anaerobic glycolysis which leads to lactic acidosis either at rest or exercise-induced.
Etomidate is a short-acting intravenous anaesthetic agent used for the induction of general anaesthesia and sedation for short procedures such as reduction of dislocated joints, tracheal intubation, cardioversion and electroconvulsive therapy. It was developed at Janssen Pharmaceutica in 1964 and was introduced as an intravenous agent in 1972 in Europe and in 1983 in the United States.
Dexmedetomidine, sold under the trade name Precedex among others, is a drug used in humans for sedation. Veterinarians use dexmedetomidine for similar purposes in treating cats, dogs, and horses. It is also used in humans to treat acute agitation associated with schizophrenia or bipolar disorder. It is administered as an injection or intravenous solution or as a buccal or sublingual film.
Critical illness–related corticosteroid insufficiency is a form of adrenal insufficiency in critically ill patients who have blood corticosteroid levels which are inadequate for the severe stress response they experience. Combined with decreased glucocorticoid receptor sensitivity and tissue response to corticosteroids, this adrenal insufficiency constitutes a negative prognostic factor for intensive care patients.
Target-controlled infusion (TCI) automates the dosing of intravenous drugs during surgery. After the anesthetist sets the desired parameters in a computer and presses the start button, the system controls the infusion pump, while being monitored by the anesthetist. TCI is as safe and effective as manually controlled infusion.
Vasodilatory shock, vasogenic shock, or vasoplegic shock is a medical emergency belonging to shock along with cardiogenic shock, septic shock, allergen-induced shock and hypovolemic shock. When the blood vessels suddenly relax, it results in vasodilation. In vasodilatory shock, the blood vessels are too relaxed leading to extreme vasodilation and blood pressure drops and blood flow becomes very low. Without enough blood pressure, blood and oxygen will not be pushed to reach the body's organs. If vasodilatory shock lasts more than a few minutes, the lack of oxygen starts to damage the body's organs. Vasodilatory shock like other types of shock should be treated quickly, otherwise it can cause permanent organ damage or death as a result of multiple organ dysfunction.
Total intravenous anesthesia (TIVA) refers to the intravenous administration of anesthetic agents to induce a temporary loss of sensation or awareness. The first study of TIVA was done in 1872 using chloral hydrate, and the common anesthetic agent propofol was licensed in 1986. TIVA is currently employed in various procedures as an alternative technique of general anesthesia in order to improve post-operative recovery.