propofol infusion syndrome

[8,9] Even though many cases … However, the specificity of the latter symptoms for propofol infusion syndrome is questionable. Rhabdomyolysis and cardiac and hepatic failure then develop in these patients.133 Case reports have shown some metabolic abnormalities that may be the cause of the cardiac failure and acidosis. In 2001, Cremer and colleagues proposed the following revised criteria for adult (ages 18-55) propofol infusion syndrome 4: P rogressive myocardial failure status post propofol administration, associated with with metabolic acidosis, hyperkalemia, or evidence of muscle cell destruction. This results in an inadequate energy production state, prompting anaerobic respiration, leading to peripheral muscle necrosis and lactic acid production.8. The authors concluded that some adult deaths and a large number of children’s deaths reported in the post-marketing drug safety database of the FDA have a striking similarity in clinical characteristics, course of illness, and propofol dose and duration to published reports and studies of the propofol infusion syndrome. It probably should not be used as a solo agent because in those cases tolerance appears to develop more rapidly. Although PRIS is rare, it is frequently fatal if not identified early. The serious flaws of this work were outlined in a letter (63r). The propofol infusion syndrome was defined as metabolic acidosis and/or rhabdomyolysis with progressive myocardial failure. The critically ill patient has many reasons to develop the same clinical features. In review, the case reports were not as simple or as complete in their reporting, with several published letters125 from physicians involved with these patients showing incomplete data in the reporting. A case of suspected propofol infusion syndrome after abdominal aortic aneurysm surgery. [1,3,7] After thorough review of these two cases, propofol metabo-lite seemed to be the main cause of green discoloration of urine. The pharmacology of propofol in a more general sense is explored in a chapter dedicated to that substance. Propofol was withdrawn, but she developed acute renal insufficiency and required dialysis. Propofol infusion syndrome. After 3 days he developed a fever, severe hemodynamic instability, and multiorgan dysfunction. Propofol infusion syndrome has not only been observed in patients undergoing long-term sedation with propofol, but also during propofol anesthesia lasting 5 h. J Trauma Nurs. Click on the image (or right click) to open the source website in a new browser window. It has been suggested that the pathological mechanism of PRIS involves mitochondrial disorder caused by propofol. (2013;3:21-27) Key words: Propofol infusion syndrome, Status Epilepticus, Anesthetics Introduction The operational definition of status epilepticus is based on the length of time. These images are a random sampling from a Bing search on the term "Propofol Infusion Syndrome." Four protons and electrons reduce oxygen to water. NLM Supportive Care : [ Diedrich, 2011 ] It has been estimated that a study to show a significant increase in death would require 7000 patients, which would be difficult to accomplish. An autopsy showed normal cerebral hemispheres with no ischemic changes. “Propofol bashing” became popular.129 There are few drugs that are licensed specifically for the PICU, however, and proper trials are needed to avoid drugs being condemned as hearsay. A. Several other case reports of an apparently similar clinical course were then subsequently described in the literature, which was enough evidence for the Committee on Safety of Medicines in the United Kingdom to issue a warning on propofol and its use in pediatric patients. PRIS = propofol infusion syndrome; Refractory bradycardia and cardiovascular collapse; Poorly understood mechanism; Risk factors High doses of (> 4mg/kg/hr or 67 mcg/kg/min) Long duration (> 48 hrs) Younger age (PRIS first recognized in pediatric population) Critical illness; … It is proposed that the syndrome may be caused by either a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism mediated by propofol. They had all received propofol at an average rate of about 8 mg/kg/h for more than 70 hours. The authors hypothesized that total suppression of cerebral activity by any sedative drug could lead to physiological compromise and development of a lethal syndrome resembling the propofol infusion syndrome. Prolonged infusion of propofol at high doses has been associated with the propofol infusion syndrome, a syndrome associated with unexplained metabolic acidosis, rhabdomyolysis and death (60c). 2 Bray et al. Methods. Intensive Care Med 29:1417–1425, 2003. The clinical symptoms that led to this patient’s death mimicked propofol infusion syndrome. The predicted outcome from these scores is shown in Table 123-13. Heard, James E. Fletcher, in, This reaction to propofol came to be known as the, Journal of Cardiothoracic and Vascular Anesthesia. This finding led to a letter from AstraZeneca reminding health care workers that propofol was not approved for sedation of pediatric patients.131. A 36-year-old white woman developed intractable epilepsy 2 weeks post-partum. The propofol infusion syndrome is the commonest cause of death directly related to the use of propofol, and deaths associated with the use of propofol for sedation have been reviewed (46M). It would appear from the reports of PRIS in the neurosurgical population that the desire for rapid awakening has propagated the use of propofol coma, rather than using barbiturates. The use of pacing and extracorporeal membrane oxygenation has been reported. Children have lower glycogen stores and often require higher doses of sedative agents; thus the syndrome is more likely to occur in pediatric patients. Between 1989 and April 2005, the Adverse Event Reporting System of the FDA received reports of 21 patients aged 16 years or under and 68 patients aged over 16 years who died after administration of propofol for non-procedural sedation. Propofol metabolites such as the 4-sulfate and 1- or 4-glucuronide conjugates of 2, 6-diisopropyl-1, 4-quinol are excreted in the urine after glucoconjugation in the liver. Patients at greatest risk are those with acute neurologic illnesses, inflammatory conditions, or post-major trauma or those receiving concomitant steroids or catecholamines. Propofol Infusion Is a Feasible Bridge to Extubation in General Pediatric Intensive Care Unit. An 18-year-old man with a severe head injury after a high-speed road traffic accident was given an infusion of propofol 7.5 mg/kg/hour for more than 72 hours to control intracranial pressure. The propofol infusion syndrome has been reported in a young patient with traumatic brain injury, which is a susceptibility factor, as high doses are often required to achieve a satisfactory degree of sedation and/or to control raised intracerebral pressure (48A). Copyright © 2020 Elsevier B.V. or its licensors or contributors. Propofol is a short-acting intravenous anesthetic agent … The final case of PRIS is reported in a patient with Leber hereditary optic neuropathy (LHON) who was being managed for a traumatic brain injury [92A]. In addition, the use of intravenous inotropes may aggravate lactic acidosis or even trigger the propofol infusion syndrome. Five young patients from different ICUs had croup and went on to have a refractory cardiac failure, bradycardia, and acidosis. Propofol (Diprivan) is an intravenous sedative hypnotic that is used in the induction and maintenance of anesthesia and sedation. This report raises concerns about high-dose, short-term propofol use in the PICU. In addition to the individual features, there were several additional scores depending on a combination of features (see Table 123-12). Endogenous uncoupling proteins in the inner mitochondrial membrane also exist and are regulated by hormones. 2010 May;29(5):377-86. doi: 10.1016/j.annfar.2010.02.030. Heard, James E. Fletcher, in Pediatric Critical Care (Fourth Edition), 2011. This reaction to propofol came to be known as the propofol infusion syndrome (PRIS).126 It is the sudden or relatively sudden onset of a marked bradycardia resistant to treatment with a least one of the following signs: lipemia, enlarged liver, severe metabolic acidosis, or rhabdomyolysis. A steady number of case reports of this syndrome have appeared in the literature since the initial description, as well as a couple of studies involving several hundred patients127,128 who have not shown any problem with propofol in the PICU. Trip Database; TrendMD; Ontology: Propofol infusion syndrome (C1328409) Concepts: Finding (T033) Italian: Sindrome da infusione di propofol : Japanese: プロポ … In a report on the use of propofol for two cases of refractory status epilepticus, patients aged 7 and 17 years had features similar to the PRIS.139 Status epilepticus itself can result in neurologic deficit, hypoxia, rhabdomyolysis, cardiac arrhythmias, hyperthermia, metabolic acidosis, acute renal failure, and death. To decrease the potential for PRIS, propofol should not exceed doses of 5 mg/kg/h (83 μg/kg/min). Tell your caregiver right away if you have: Inhalation sedation for postoperative patients in the intensive care unit: initial sevoflurane concentration and comparison of opioid use with propofol sedation. These findings are consistent with impaired fatty acid oxidation due to impaired entry of long chain fatty acids into the mitochondria and a failure of the respiratory chain. 2020 Aug;35(3):197-204. doi: 10.4266/acc.2020.00213. impaired … The pathophysiologic cause of PRIS is still poorly understood, but it appears to mimic mitochondrial myopathies. The propofol infusion syndrome was defined as metabolic acidosis and/or rhabdomyolysis with progressive myocardial failure. During the procedure, the propofol infusion was discontinued and the lactic acidosis improved. The authors concluded that some adult deaths and a large number of children's deaths reported in the post-marketing drug safety database of the FDA have a striking similarity in clinical characteristics, course of illness, and propofol dose and duration to published reports and studies of the propofol infusion syndrome. The mechanism of propofol infusion syndrome is unknown. An echocardiogram showed severe left ventricular dysfunction and cardiomyopathy, which resolved within 19 days. Uncouplers transport protons into the mitochondrion, dissipating the proton gradient. Propofol is still frequently used for procedural and short-term sedation,137 but in a recent case report, researchers describe a patient who had PRIS.138 The patient had received a propofol infusion for 15 hours at 20 mg/kg/h. Doses of propofol should be kept as low as effectively possible, and regular hemodynamic and blood gas monitoring is necessary in patients who are sedated with propofol, in order to detect early signs of cardiovascular failure and lactic acidosis. In light of the reports now appearing in the adult neurointensive care literature with the development of a propofol infusionlike syndrome in adult neurosurgical patients,140 it would appear that propofol is not the best choice for prolonged sedation for patients with intracranial hypertension. 3 formulated criteria for PRIS: occurrence of bradycardia combined with one of the following conditions: (1) clinically enlarged liver, or fatty infiltration at … The first death associated with PRIS was reported in 1990, a Danish medical committee issued a warning about the use of propofol in the paediatric population.2 In 1992, a case series published in the BMJ highlighted the dangers of high doses of propofol infusions in children and urged caution in adults.3 Adult case reports of PRIS started to appear in publications by 1996. A syndrome with striking similarities to propofol infusion syndrome has been reported in association with thiopental [23]. The dose of propofol was increased to 7.2 mg/kg/hour to achieve burst suppression for 19 hours, and then reduced to 4.8 mg/kg/hour. The most frequent symptoms were progressive cardiac dysfunction/failure (bradycardia, cardiac failure, “cardiovascular collapse”, dysrhythmias, and cardiac arrest), metabolic acidosis, hypotension, and rhabdomyolysis. In a retrospective analysis of the case notes of 301 patients who underwent non-invasive radiofrequency ablation for atrial dysrhythmias, 55 had had arterial blood gas measurements during the procedure. Christopher M.B. The main features consist of cardiac failure (sudden onset of bradycardia), rhabdomyolysis, severe metabolic acidosis, and renal failure. Rhabdomyolysis and cardiac failure developed in both patients. Surg Case Rep. 2020 Jul 31;6(1):188. doi: 10.1186/s40792-020-00946-2. This is thought to be secondary to a combination of increased metabolic demand in critical illness (priming factor) coupled with catecholamine use, reduced glycogen reserve, and impaired fatty acid oxidation (triggering factors).7 The pathophysiology of PRIS is not very well understood, but one of the hypotheses surrounding PRIS relates to the inhibitory process propofol may have on fatty acid oxidation, leading to impaired energy production in a catabolic state such as critical illness. Seven of these patients (four paediatric and three adult patients) developed PRIS during anaesthesia. Some have described effects of high-dose propofol on mitochondria, with changes in electron and calcium transport and oxidative phosphorylation. We use cookies to help provide and enhance our service and tailor content and ads. Although the exact patho-physiology of PRIS remains to be determined, impaired tissue … A case report highlights T-wave inversion on ECG occurring 29 hours before the more classical signs (metabolic acidosis, hyperkalaemia, circulatory failure) of PRIS [90A]. While some reports of propofol infusion syndrome have described elevated serum lactate, until the etiology of the syndrome is better understood, elevated lactate should be considered suggestive rather than a requirement for the diagnosis of the syndrome. Epub 2008 Apr 30. ScienceDirect ® is a registered trademark of Elsevier B.V. ScienceDirect ® is a registered trademark of Elsevier B.V. URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, URL:, Meyler's Side Effects of Drugs (Sixteenth Edition), General anesthetics and therapeutic gases, A worldwide yearly survey of new data in adverse drug reactions, Brian T. Marden PharmD, Jill A. Rebuck PharmD, BCPS, in, Jerry J. Zimmerman, ... Jerry McLaughlin, in, Propofol is a frequently used anesthetic in the PICU and the operating room. One report describes a 10-month-old child who had the syndrome and was successfully treated with hemofiltration and plasmapheresis.134 Muscle and liver biopsy specimens showed changes consistent with a toxic insult. Four additional protons are pumped out of the matrix. 2020 May 28;8:255. doi: 10.3389/fped.2020.00255. However, this article does highlight the variability in features of the PRIS and accounts for the differences in the reported mortality. Exploratory abdominal laparotomy showed no traumatic injury. In this case, early diagnosis and immediate withdrawal of propofol may have contributed to the complete reversal of symptoms and the favorable outcome. There are further case reports of propofol-related infusion syndrome (PRIS) associated with fatal outcome. I.D. Intravenous midazolam was ineffective and he was mechanically ventilated and given high-dose thiopental with continuous electroencephalographic monitoring. Propofol infusion syndrome (PRIS) was first described in 1992 in a case series of five children (1). eCollection 2020. Get the latest research from NIH: Recent many trials were introduced, but 9-30% of status epilepticus remains to be refractory to treatment.1-3 Time- dependent … Others show inhibition of enzymes along the electron transport chain. She developed a fever and hypotension requiring inotropic support. Analysis also showed a reduction in the cytochrome C oxidase activity in the muscle, with a normal activity in skin fibroblasts, excluding an underlying respiratory chain defect. 1 Since 1990, a syndrome associated with propofol sedation has been recognized, which received the name propofol infusion syndrome (PRIS). After 5 days, thiopental and midazolam were withdrawn. High-dose infusions have been associated with several serious adverse effects and, when combined, they are known as propofol infusion syndrome (PRIS). A 59-year-old man with a history of epileptic convulsions developed status epilepticus. No monitoring of lipid status or acid base was performed, and propofol was used as the sole agent by practitioners with limited experience with this drug. Propofol infusion syndrome: update of clinical manifestation and pathophysiology.  |  Get emergency medical help if you have any signs of an allergic reaction to propofol: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Romero P C, Morales R M, Donaire R L, Llanos V O, Cornejo R R, Gálvez A R, Castro O J. Rev Med Chil. There was acute skeletal muscle aseptic necrosis, rhabdomyolysis and myoglobin casts in the renal tubules. The authors did not report sodium, chloride, or bicarbonate concentrations, but they commented that there was no relation between rate of fluid administration and the maximal negative base excess in these patients. Vasile, B, Rasulo F, Candiani A, Latronico N: The pathophysiology of propofol infusion syndrome: A simple name for a complex syndrome. Mortality from propofol infusion syndrome is independently associated with fever and hepatomegaly in children, and electrocardiogram changes, hypotension, hyperkalaemia, traumatic brain injury, and a mean propofol infusion rate >5mgkg1h1in adults. The peak arterial lactate concentration occurred 160 minutes after withdrawal of propofol (lactate 9.2 mmol/l, bicarbonate 16 mmol/l, base deficit 8.3 mmol/l). An American prospective mixed adult intensive care unit (ICU) multicentre study examining the incidence of PRIS showed it to be 1.1% and to … Propofol Infusion Syndrome is a diagnosis of exclusion! This patient was also treated successfully with hemofiltration. Propofol was thought to be the culprit and anesthesia was switched to thiopental; over the next 5 hours the acidosis resolved, although on the next day she developed myoglobinuria with a rising creatine kinase (6966 U/l). Although long-term propofol infusions are no longer used in children because of its risk, much of the literature is based on these cases. A review of the pathophysiologic function of the syndrome136 suggested that propofol increases the activity of malonyl coenzyme A, which inhibits the carnitine palmityl transferase I, so long chain fatty acids cannot enter the mitochondria. Introduction: Propofol is a commonly used sedative agent in ICU due to its rapid onset of action and recovery. The authors concluded that in adults propofol can occasionally produce cytopathic hypoxia by impairing the electron transport chain or fatty acid oxidation. The syndrome is not well understood but appears to be related to long-term (>48 hours), high-dose (>5 mg/kg/h) propofol infusion. The first published case report in adults of PRIS was published in 2000; since then, >15 cases have been reported, many of them fatal. Subsequently, a randomized, controlled trial of propofol was begun, and after its use in 327 patients, it was reviewed by the FDA.130 The study was never published, but researchers found that, despite similar pediatric risk of mortality scores, patients who had received either 1% or 2% propofol preparations had a two to three times greater risk of death compared with the control sedative group. Laquay N, Prieur S, Greff B, Meyer P, Orliaguet G. Ann Fr Anesth Reanim. Author information: (1)Department of Critical Care Medicine, Democritus University of Thrace, Alexandroupolis Teaching Hospital, Greece. The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit > 10 mmol.l −1), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. This site needs JavaScript to work properly. A 29-year-old woman with a severe head injury from a fall and an intracranial pressure of 28 mmHg was given high-dose propofol 4–12 mg/kg/hour for 5 days. Minerva Anestesiol. PRIS is charac-terized by severe unexplained metabolic acidosis, arrhythmias, acute renal failure, rhabdomyolysis, hyperkalemia, and cardiovascular collapse. Regular monitoring of the cardiac function, ECG, and CPK are warranted; lipid profile and acid base status may help in early detection. Long-term use of propofol can lead to a syndrome called Propfol Infusion Syndrome, which may result in death. Further cases have been reported (61A, 62A). All reports of deaths after sedation with propofol in children and adults submitted to the Food and Drug Administration (FDA) and entered into its post-marketing drug safety database were considered, as were published reports and studies. The hypothesized pathogenetic mechanism involves propofol's impairment of free fatty acid use and mitochondrial activity resulting in cardiac and peripheral muscle necrosis. Hemodialysis or hemofiltration have been reported as having some success. Propofol-related Infusion Syndrome (PRIS) is a life-threatening condition characterised by acute refractory bradycardia progressing to asystole and one or more of: metabolic acidosis; rhabdomyolysis; hyperlipidaemia; enlarged or fatty liver; MECHANISM. Echocardiography showed global biventricular dysfunction without four-chamber dilatation and she progressed to bradycardia and eventually asystole. However, later reports suggested that it can occur even after short-term use and low-dose administration [133]. Epub 2020 Jul 24. Refractory bradycardia, unexplained metabolic acidosis, electrocardiogram changes and rhabdomyolysis are consistent features. Propofol remains a useful agent for procedural sedation in the PICU. Once PRIS is suspected, propofol infusion should be stopped and an alternative sedative agent should be used.8 Cardiovascular support and hemodialysis are paramount in helping decrease the levels of circulating metabolic acids. It is therefore difficult to draw any conclusions from this study. Predisposing factors 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. A 21-year-old man with traumatic brain injury was given high doses of propofol for sedation and control of intracranial pressure, combined with vasopressor therapy to maintain a cerebral perfusion pressure above 60 mmHg. 2009 May;75(5):339-44. The clinical features of propofol infusion syndrome (PRIS) are acute refractory bradycardia leading to asystole, in the presence of one or more of the following: metabolic acidosis (base deficit >10 mmol.l)1), rhabdomyolysis, hyperlipidaemia, and enlarged or fatty liver. Question 13.1 from the first paper of 2015 and Question 20 from the first paper of 2010 interrogated the candidate's understanding of propofol infusion syndrome. An early indicator of the cardiac instability from PRIS may be changes in the ECG. Hall, M. Leuwer, in Side Effects of Drugs Annual, 2010. The constituents of the syndrome have changed since first … Propofol infusion syndrome is a rare but potentially fatal condition first described in the paediatric population and subsequently reported in adult intensive care, particularly in neurointensive care. Despite infusion of high-dose propofol (4.2 mg/kg/hour), her myoclonic jerks and electroencephalographic epileptiform activity continued. 2008;31(4):293-303. doi: 10.2165/00002018-200831040-00003. Prolonged infusion of propofol at high doses has been associated with the propofol infusion syndrome, a syndrome associated with unexplained metabolic acidosis, rhabdomyolysis and death (60c). He died after 2 weeks with persistent cardiac failure, severe rhabdomyolysis, renal insufficiency, metabolic acidosis, and fulminant hepatic failure. There is an associ- Acute Crit Care. Clipboard, Search History, and several other advanced features are temporarily unavailable. Elevated levels of malonylcarnitine and C5-acyl carnitine were found in a patient with PRIS. In Meyler's Side Effects of Drugs (Sixteenth Edition), 2016. Propofol infusion syndrome: an overview of a perplexing disease. Postmortem he was identifies to have a deficiency of complex I of the oxidative phosphorylation system related to his LHON and this deficiency was identified as playing a causative role in the development of PRIS in this case.

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