Dexmedetomidine Alleviates Propofol Infusion Syndrome-Induced Myocardial Injury through Inhibiting Ferroptosis Associated with Accumulation of Reactive Oxygen Species.

OBJECTIVE: To observe the effect of dexmedetomidine (Dex) on propofol infusion syndrome (PRIS)-induced myocardial injury and explore the roles of ferroptosis and accumulation of reactive oxygen species (ROS). METHODS: Eighteen male Sprague-Dawley rats were evenly divided into the control group, model group and test group (n=6/group) based on a computer-generated random number table. The PRIS-induced myocardial injury model was prepared in the model group and test group through a 12 h-caudal vein infusion of 1% propofol medium and long chain fat emulsion injection at a rate of 20 mg·Kg-1·h-1 for the first 6 h and 40 mg·Kg-1·h--1 for the last 6 h, and meanwhile the test group was treated by Dex. The control group received the same amount of normal saline through the caudal vein. The following indicators were compared between the three groups including myocardial pathological results, enzymatic changes of myocardial injury, ferroptosis of myocardial cells and accumulation of ROS. RESULTS: Dex alleviated the myocardial pathological injury caused by propofol infusion. Propofol infusion caused time-dependent enzymatic changes of myocardial injury and Dex alleviated these enzymatic changes. Dex alleviated the ferroptosis of myocardial cells and accumulation of ROS caused by propofol infusion. CONCLUSIONS: Dex could alleviate PRIS-induced myocardial injury by inhibiting ferroptosis associated with accumulation of ROS. Combined sedation using propofol and Dex might be a potential strategy for the prevention and treatment of PRIS-induced cardiotoxicity.

Propofol Infusion Syndrome Following Endoscopic Tracheoplasty and Jet Ventilation: Case Report.

OBJECTIVE: We present a case of propofol infusion syndrome (PRIS) following jet ventilation. METHOD: Case report and review of literature. RESULTS: A 70-year-old man required CO2 laser endoscopic tracheoplasty for tracheal and subglottic stenosis due to A-frame deformity. Postoperatively, the patient was reintubated for respiratory distress and propofol was resumed. Over the next two days the patient developed acute kidney injury, leukocytosis, acute primary respiratory acidosis with high anion gap metabolic acidosis, multiple end organ damage, elevated cardiac markers, and worsening lactic acidosis. The patient was recognized as having propofol infusion syndrome and propofol was immediately discontinued and replaced with dexmedetomidine. Unfortunately the patient progressed to multi-organ failure complicated by rhabdomyolysis and distributive intravascular coagulopathy. CONCLUSIONS: Propofol is often used as an anesthetic for jet ventilation during otolaryngologic airway surgery. Propofol related infusion syndrome is an uncommon but life-threatening peri-operative complication that should be considered in any patient with an unusual post-operative recovery characterized by metabolic acidosis, ECG changes, end organ damage, and elevated lactate.

Refractory atrial fibrillation with rapid ventricular response as a heralding sign of propofol infusion syndrome in a patient with COVID-19.

A woman in her 40s was transferred to the medical intensive care unit due to severe COVID-19 infection causing respiratory failure. Her respiratory failure worsened rapidly, requiring intubation and continuous sedation with fentanyl and propofol infusions. She required progressive increases in the rates of the propofol infusion, as well as addition of midazolam and cisatracurium due to ventilator dyssynchrony. To support the high sedative doses, norepinephrine was administered as a continuous infusion. She developed atrial fibrillation with rapid ventricular response, with rates ranging between 180 and 200 s which did not respond to intravenous adenosine, metoprolol, synchronised cardioversion or amiodarone. A blood draw revealed lipaemia, and triglyceride levels were noted to be elevated to 2018. The patient developed high-grade fevers up to 105.3 and acute renal failure with severe mixed respiratory and metabolic acidosis, indicating propofol-related infusion syndrome. Propofol was promptly discontinued. An insulin-dextrose infusion was initiated which improved patient's fevers and hypertriglyceridaemia.

Unusual case of propofol-related infusion syndrome complicating severe COVID-19 ARDS.

An elderly man presenting with shortness of breath and hypoxaemia was admitted with acute hypoxic respiratory failure secondary to COVID-19 pneumonia. Due to worsening hypoxaemia, he was transferred to the intensive care unit and required mechanical ventilation. Propofol was infused at 1.5-4 mg/kg/hour. Within 48 hours of initiation, we noticed worsening metabolic acidosis, acute kidney injury, hyperkalaemia, hyperphosphataemia, hypertriglyceridaemia, elevated creatine kinase and elevated myoglobin levels. Suspecting propofol-related infusion syndrome (PRIS), we discontinued his propofol infusion immediately and initiated supportive measures. In 48 hours, there was a significant improvement in metabolic acidosis, hypertriglyceridaemia, rhabdomyolysis and renal function. The propofol infusion rate and cumulative propofol dosage (under 140 mg/kg) were well below levels associated with PRIS. COVID-19's pathogenesis, still under investigation, may have contributed to this presentation. It is imperative for clinicians to maintain a high degree of suspicion once propofol is initiated, regardless of the cumulative dose or rate of infusion.

VA-ECMO rescue therapy in propofol infusion syndrome after cardiac surgery.

INTRODUCTION: Propofol infusion syndrome (PRIS) is a rare entity that could lead to profound cardiogenic shock (CS). Mitochondrial toxicity and sympathetic blockade are the mechanisms leading to CS in PRIS. CASE REPORT: We present a 22-year-old woman who developed refractory CS due to PRIS after aortic valve replacement surgery secondary to Coxiella infective endocarditis. She was rescued with VA-ECMO (veno-arterial extracorporeal membrane oxygenation) and was discharged 2 months later with no cardiac dysfunction. DISCUSSION: PRIS diagnosis is difficult even though propofol is frequently used in critical care units. Abrupt refractory CS in patients with recent use of high doses of propofol (> 4 mg/Kg/h) together with rhabdomyolysis should raise the suspicion. Diagnostic confirmation is based on muscle biopsy and fat enzyme analysis. CONCLUSION: Propofol withdrawal and support therapies-including VA-ECMO-are the treatment of choice in severe PRIS. VA-ECMO could increase survival as a bridge to recovery due to reversibility of PRIS.

The incidence of propofol infusion syndrome in critically-ill patients.

PURPOSE: PRIS is a potentially fatal syndrome characterized by various clinical symptoms and abnormalities. Experts suggest that propofol treatment duration ≥48 h or dose ≥83 µg/kg/min is associated with developing PRIS. We hypothesized PRIS might be underdiagnosed due to the overlap of PRIS clinical manifestations with critical illnesses. MATERIALS AND METHODS: Multihospital, retrospective study of adult patients who received continuous propofol infusion ≥48 h or dose ≥60µg/kg/min for >24 h since admission were assessed for the development of PRIS. RESULTS: The incidence of PRIS was 2.9% with a PRIS-associated mortality rate of 36.8%. In PRIS patients, propofol was administered at a median dose of 36.4 µg/kg/min and over a median duration of 147.0 h. The development of PRIS was observed at a median of 125.0 h post-propofol initiation and a cumulative dose of 276.5 mg/kg. The development of metabolic acidosis (78.9%), cardiac dysfunction (52.6%), hypertriglyceridemia (100%), and rhabdomyolysis (26.3%) were observed in our PRIS patients. CONCLUSION: PRIS can often be overlooked and underdiagnosed. It is important to monitor for early signs of PRIS in patients who are on prolonged propofol infusion. Prompt recognition and interventions can minimize the dangers resulting from PRIS.

Síndrome por infusión de propofol en un adolescente / Syndrome due to propofol infusion in an adolescent

Se describe el caso clínico de un adolescente de 18 años de edad, con antecedente de salud aparente, atendido en el cuerpo de guardia del Hospital General Docente Roberto Rodríguez Fernández de Morón, provincia de Ciego de Ávila, con síntomas sugestivos de apendicitis aguda, por lo que fue intervenido quirúrgicamente. Una vez terminado el proceder tuvo parada cardíaca, lo cual se interpretó como un síndrome por propofol. Se decidió transferirlo a la Unidad de Cuidados Intensivos, donde fue evolucionando favorablemente, con mejoría de todos los parámetros. A los 6 días lo trasladaron a la Unidad de Cuidados Intermedios y posteriormente egresó de la institución hospitalaria sin complicaciones.

The case report of an 18 years adolescent with history of apparent health is described. He was assisted in the emergency service of Roberto Rodríguez Fernández Teaching General Hospital from Morón, Ciego de Ávila, with suggestive symptoms of acute appendicitis, reason why he was surgically intervened. Once finished the procedure he had a cardiac arrest, which was interpreted as a syndrome due to propofol. It was decided to referred him to the Intensive Cares Unit, where he had a favorable clinical course, with improvement of all parameters. Six days later he was transferred to the Intermediate Cares Unit and later on he was discharged from the hospital institution without complications.

[Propofol Infusion Syndrome Treated Successfully by Early Diagnosis].

Propofol infusion syndrome (PRIS) is one of the severe complications which occur during continuous venous infusion of propofol, and has a high mortality rate. It is featured by high fever, oliguria, myogloblin urine, acute renal failure, hepatomegaly, fatty liver, and so on. We have experienced a case of PRIS who was saved by prompt changing of sedatives from propofol to midazolam and dexmedetomidine. The patient was an 82-year-old man, who underwent off-pump coronary bypass grafting due to effort angina pectoris. After the operation, he suffered from continuous high fever over 38 ℃, acute renal impairment, and high level of creatine kinase (CK) without CK-MB increment, suggesting PRIS. We promptly changed sedatives from propofol to midazolam and dexmedetomidine, then the patient recuperated from these abnormalities. It is strongly suggested that meticulous observation is necessary during propofol infusion.

Propofol infusion syndrome; are high doses always required? / Síndrome por infusión de propofol; ¿realmente se requieren altas dosis?

Propofol infusion syndrome is a rare condition that mainly affects critically ill patients who receive high doses of this hypnotic for a long time. We describe the case of a patient who presented hepatotoxicity in the immediate postoperative period of two surgeries in which she had received conventional doses of propofol for a short period of time. After studying the patient and monitoring her evolution, we arrived at a differential diagnosis of propofol infusion syndrome due to increased susceptibility. This syndrome should be considered in patients presenting hepatotoxicity in the immediate postoperative period, even when low doses of propofol have been administered.

Suspected propofol infusion syndrome during normal targeted propofol concentration.

To this day, the pathophysiology and risk factors of propofol infusion syndrome (PRIS) remain unknown. Moreover, there is no widely accepted definition of PRIS, even though it is a potentially fatal condition. While many suspected cases of PRIS have been reported in both pediatric and adult populations, the actual propofol plasma concentration (Cp) has never been clarified. In this clinical report, we described the first suspected PRIS case in which the propofol Cp was measured 25 min after 226 min of propofol infusion (7.2 µg/mL), which was 12 times higher than the predicted value (0.6 µg/mL). In the presented case, we observed gradually progressive uncontrollable hypercapnia and tachycardia, followed by severe lactic acidosis during surgical anesthesia based on the target-controlled infusion of propofol. Levels of liver enzymes were slightly elevated which suggests little or no liver damage though propofol is mainly metabolized by the liver. Meanwhile, renal impairment, a common secondary feature of PRIS, occurred concomitantly when hypercapnia and metabolic acidosis were manifested. In this case, low or delayed propofol clearance might have been a triggering factor causing severe lactic acidosis.

Propofol infusion syndrome: a structured literature review and analysis of published case reports.

Propofol infusion syndrome is a rare, potentially fatal condition first described in children in the 1990s and later reported in adults. We provide a narrative review of what is currently known about propofol infusion syndrome, including a structured analysis of all published case reports; child and adult cases were analysed separately as propofol is no longer used for long-term sedation in children. The review contains an update on current knowledge of the pathophysiology of this condition along with recommendations for its diagnosis, prevention, and management. We reviewed 108 publications documenting 168 cases of propofol infusion syndrome. We evaluated clinical features and analysed factors influencing mortality in child and adult cases using separate multivariate analysis models. We used separate multiple linear regression models to analyse relationships between cumulative dose of propofol and the number of features seen and organ systems involved. Lipidaemia, fever, and hepatomegaly occurred more frequently in children than in adults, whilst rhabdomyolysis and hyperkalaemia were more frequent in adults. 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 >5 mg kg-1 h-1 in adults. The cumulative dose of propofol was associated with an increased number of clinical features and the number of organ systems involved in adult cases only. Clinicians should consider propofol infusion syndrome in cases of unexplained metabolic acidosis, ECG changes, and rhabdomyolysis. We recommend early consideration of continuous haemofiltration in the management of propofol infusion syndrome.

The Effect of Concomitant Sirolimus and Propofol Therapy on Triglyceride Concentrations in Critically Ill Patients.

BACKGROUND: Sirolimus and propofol are both independently associated with the development of hypertriglyceridemia (HTG) during therapy. To date, there are no published reports describing synergistic or additive drug interaction resulting in HTG with concomitant use of these medications. STUDY QUESTION: To identify the occurrence of HTG in patients receiving concomitant sirolimus and propofol infusion therapy. METHODS: Adult patients receiving sirolimus and a continuous propofol infusion for at least 12 hours from January 2005 to August 2009 were retrospectively evaluated. Data included Acute Physiology and Chronic Health Evaluation II score, weight, length of propofol therapy, and baseline triglyceride (TG) concentrations. The major outcome was incidence of HTG (TGs ≥500 mg/dL). Minor outcomes included the change in TG concentration from therapy initiation and manifestations of propofol-related infusion syndrome (PRIS). RESULTS: Sixteen patients were included in the analysis, with 8 (50%) of the patients developing HTG. The patients in this case series had the following mean values: Acute Physiology and Chronic Health Evaluation II score of 20.2 ± 5.3, weight of 76.3 ± 21.2 kg, and baseline TG concentrations of 181.3 ± 89.7 mg/dL. Indications for sirolimus therapy included hematopoietic stem-cell transplantation (n = 15) and heart transplantation (n = 1). Mean length of propofol infusion was 99.8 ± 88.5 hours. The mean TG concentration during infusion was 515.6 ± 468.1 mg/dL. Fourteen (87.5%) patients had an increase of ≥100 mg/dL, 12 (75%) patients had an increase of ≥200 mg/dL, and 6 (37.5%) patients had an increase of ≥300 mg/dL in TG concentrations during therapy. Eleven patients developed one manifestation of PRIS, excluding HTG, and one patient had more than 2 new onset PRIS manifestations during propofol therapy. CONCLUSIONS: Coadministration of propofol and sirolimus can potentially result in HTG, which may warrant more frequent monitoring. Further analysis is needed to examine the mechanism and clinical impact of this interaction.

Propofol Infusion Syndrome: Efficacy of a Prospective Screening Protocol.

Propofol infusion syndrome (PIS) is a potentially lethal complication of propofol marked by rhabdomyolysis, metabolic acidosis, and cardiac arrhythmias or collapse. The objective of this study was to determine the effectiveness of a prospective screening protocol to prevent PIS. All trauma patients admitted who received propofol as a continuous infusion were prospectively screened from November 1, 2013 to December 31, 2015. Variables studied included demographics, injury severity, laboratory values, infusion rates, and mortality. Serum creatine phosphokinase (CPK) and lactate were drawn daily. Propofol was stopped for a positive screen defined as an increase in CPK to greater than 5000 IU/L or lactate greater than 4 mmol/L. Positive and negative cohorts were compared. Two hundred and twenty-five patients met the inclusion criteria and 12 patients (5.3%) had propofol stopped because of elevated CPK. No differences were identified in demographics, transfusions, injury severity, hospital length of stay, or propofol dose. The positive screened group had longer intensive care unit length of stay (20 vs 13 days; P = 0.002) and increased vent days (14.5 vs 10 days; P = 0.008). Max serum osmolality (334 vs 305 mosm/kg; P = 0.049) and max serum CPK (6782 vs 1058 IU/L; P < 0.0001) were higher in the positive cohort. No cases of PIS occurred, and mortality (16.7 vs 15.5%; P = 0.999) was not different between the cohorts. The screening protocol was effective in eliminating PIS. Serial CPK evaluations provided an effective screening tool and serum lactate can be dropped from screening.

[Propofol Infusion Syndrome in a refractory epileptic status case]. / Síndrome por Infusión de Propofol en un caso de estatus epiléptico refractario.

INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.

Síndrome por Infusión de propofol en un caso de estatus epiléptico refractario / Propofol infusion syndrome in a refractory epileptic status case

INTRODUCCIÓN: El síndrome por infusión de propofol (SIP) es una reacción adversa poco frecuente, pero potencialmente letal descrita por la utilización de dicho fármaco en infusión intravenosa (IV) continua. El diagnóstico se basa en la combinación de acidosis metabólica, rabdomiolisis, hiperkalemia, hepatomegalia, insuficiencia renal, hiperlipidemia, arritmias e insuficiencia cardiaca rápida mente progresiva. OBJETIVO: Presentación de un caso clínico de SIP y revisión de literatura. CASO CLÍNICO: Paciente femenino de 6 años de edad con antecedentes de epilepsia secundaria a extensa alteración del desarrollo cortical hemisférico derecho. Presentó estatus epiléptico refractario que requirió ingreso a Unidad de Cuidados Intensivos para soporte vital y tratamiento, el que incluyó como terapia de tercera línea infusión intravenosa continua de propofol en dosis progresivas hasta alcanzar una tasa 10 mg/kg/h. Cursó con compromiso hemodinámico y a las 24 h de iniciado el tratamiento se observó alza de la creatinifosfokinasa (CK), acidosis metabólica y lactacidemia elevada, y luego de descartar otras causas se planteó el diagnóstico de SIP por lo que se suspendió la droga, logrando estabilización hemodinámica a las 24 h. DISCUSIÓN: El diagnóstico de SIP es complejo, se debe considerar en pacientes que estén recibiendo el fármaco y presenten acidosis metabólica o insuficiencia cardiaca. Los factores que más influyen en la mortalidad son la dosis acumulativa de la droga, la presencia de fiebre y lesión encéfalo craneana. En el caso descrito la paciente recibió una dosis mayor a 4 mg/ kg/h que es la dosis máxima recomendada y respondió favorablemente luego de 12 h después de la suspensión del fármaco.

INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.