Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

Propofol use in newborns and children: is it safe? A systematic review / Utilização do propofol em recém-nascidos e crianças: é segura? Uma revisão sistemática

Abstract Objectives: To determine the main indications and assess the most common adverse events with the administration of hypnotic propofol in most pediatric clinical scenarios. Sources: A systematic review of PubMed, SciELO, Cochrane, and EMBASE was performed, using filters such as a maximum of five years post-publication, and/or references or articles of importance, with emphasis on clinical trials using propofol. All articles of major relevance were blind-reviewed by both authors according to the PRISMA statement, looking for possible bias and limitations or the quality of the articles. Summary of the findings: Through the search criterion applied, 417 articles were found, and their abstracts evaluated. A total of 69 papers were thoroughly studied. Articles about propofol use in children are increasing, including in neonates, with the majority being cohort studies and clinical trials in two main scenarios: upper digestive endoscopy and magnetic resonance imaging. A huge list of adverse events has been published, but most articles considered them of low risk. Conclusions: Propofol is a hypnotic drug with a safe profile of efficacy and adverse events. Indeed, when administered by non-anesthesiologists, quick access to emergency care must be provided, especially in airway events. The use of propofol in other scenarios must be better studied, aiming to reduce the limitations of its administration by general pediatricians.

Resumo Objetivos: Determinar as principais indicações e examinar os eventos adversos mais comuns com uso do hipnótico propofol na maioria dos cenários clínicos pediátricos. Fontes: Realizada revisão sistemática da literatura nas bases de dados PubMed, Scielo, Cochrane e EMBASE, aplicando-se filtros como máximo de cinco anos de publicação e/ou referências ou publicações relevantes em outras hipóteses com enfoque em ensaios clínicos envolvendo o propofol. Todos os artigos de maior relevância foram avaliados cegamente pelos dois autores, de acordo com o PRISMA Statement, observando os riscos de vieses e qualidades ou limitações dos estudos. Resumo dos achados: Através dos mecanismos de pesquisa, 417 artigos foram encontrados e separados logo após, de acordo com os critérios de inclusão. Um total de 69 artigos foram estudados. Destacam-se a produção científica crescente sobre o propofol em crianças, incluindo recém-nascidos, sendo a grande maioria dos trabalhos coortes retrospectivos ou prospectivos, bem como ensaios clínicos com o propofol nos principais cenários: endoscopia digestiva alta e ressonância magnética. Ampla gama de eventos adversos foi citada, mas a maioria dos trabalhos não as consideraram significativas. Conclusões: O propofol apresenta um seguro perfil de eficácia e segurança. Quando administrado por médicos não anestesistas, deve-se redobrar o cuidado para ação rápida em emergências, especialmente de vias aéreas. A aplicação do fármaco em outros contextos deve ser estudada em maior profundidade, a fim de dirimir a dificuldade do uso por pediatras.

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.

Síndrome de infusión por propofol en el adulto / Propofol infusion syndrome

Propofol infusion syndrome is a rare but lethal complication of propofol administration. The most common clinical presentation is high anion-gap metabolic acidosis, heart failure, rhabdomyolysis and hyperkalemia in patients receiving a prolonged propofol infusion. It has an estimated incidence of 1,1% in patients receiving propofol and its mortality varies between 18 and 81%. The most important risk factor is an infusion over 4 mg/kg/h of propofol and a critically sick patient. Management of a diagnosed PRIS is based on immediate discontinuation of propofol and support therapy.

El síndrome de infusión de propofol es una complicación rara, pero posiblemente letal de la administración de propofol (Propofol Infusion Syndrome, PRIS) Generalmente, se presenta como una acidosis metabólica con anion Gap aumentado, falla cardiaca rápidamente progresiva, rabdomiólisis e hiperkalemia, junto con el antecedente claro de una infusión prolongada de la droga. La incidencia se estima en un 1,1% en los pacientes que reciben propofol y su mortalidad varía entre el 18 al 81%. Los factores de riesgo son: una infusión de propofol mayor a 4 mg/kg/h y pacientes críticos. El tratamiento se basa en la suspensión de la droga y medidas de soporte hemodinámico.

Síndrome por infusión de propofol: reporte de un caso / Propofol infusion syndrome: a case report

El propofol es un anestésico ampliamente utilizado en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente pero extremadamente grave, conocido como síndrome por infusión de propofol (SIP), caracterizado por inestabilidad hemodinámica, rabdomiólisis, acidosis láctica y disfunción multiorgánica. Presentamos un caso de SIP con desenlace fatal, discutiendo su fisiopatología, clínica y consideraciones a tener en cuenta al emplear propofol.

Propofol is a widely used anesthetic in the Intensive Care Unit. At times it may cause rather an unusual adverse reaction known as propofol infusion syndrome (PRIS), characterized by hemodynamic instability, rhabdomyolysis, lactic acidosis, and multiple-organ dysfunction. The study presents a case of PRIS with fatal outcome, including a discussion of its physiopathology, clinical aspects and considerations to be borne in mind when using propofol.

O propofol é um anestésico amplamente utilizado nas Unidades de Cuidados Intensivos. Sua utilização pode provocar um efeito adverso pouco frequente mas extremamente grave conhecido como síndrome por infusão de propofol (SIP), caracterizado por instabilidade hemodinâmica, rabdomiólise, acidose lática e disfunção múltipla de órgãos. Apresentamos um caso fatal de SIP e discutimos a fisiopatologia, clínica e os aspectos que devem ser considerados quando se utiliza esta droga.

Propofol-Related Infusion Syndrome in an Adult Patient Using Propofol Coma Therapy to Control Intracranial Pressure / 대한구급학회지

Propofol-related infusion syndrome (PRIS) is a rare but fatal complication. Unexplained metabolic acidosis, rhabdomyolysis, hyperkalemia, myocardial dysfunction, cardiovascular collapse and acute kidney injury are the main characteristics of PRIS. Herein, we report a case of PRIS in a neurosurgical adult patient, who had received high-dose propofol continuous infusion in order to control intracranial pressure in an intensive care unit. She manifested severe metabolic acidosis, rhabdomyolysis, acute kidney injury and myocardial dysfunction. As soon as PRIS was diagnosed, propofol infusion was stopped. Conservative treatments, such as vasopressors and inotropics, continuous renal replacement therapy and extracorporeal membrane oxygenation were used to treat PRIS. However, she finally expired. This case report suggests that a great caution to PRIS is needed in a situation with high-dose propofol continuous infusion.

Propofol Infusion Syndrome in a Patient with Epilepsia Partialis Continua / 대한간질학회지

Propofol has been used for the treatment of refractory status epilepticus, but propofol can cause propofol infusion syndrome (PRIS). PRIS is rarely developed and often fatal. The syndrome is characterized by metabolic acidosis, rhadomyolysis, and cardiac failure. Most reports were described in critically ill patients undergoing long-term propofol infusion at high doses. But many systemic confounding factors are mixed with the fatality of PRIS and there are no report on epilepsia partialis continua which has stable systemic conditions. We report PRIS in a patient with epilepsia partialis continua.

Is There a Relationship between Hyperkalemia and Propofol?

This is a case of a sudden cardio-pulmonary arrest in a 29 year-old female, which occurred immediately after a large bolus infusion of propofol (100 mg) intravenously during dilatation and curettage. The arrest suddenly occurred, and the patient was eventually transferred to our emergency room (ER) on cardiopulmonary resuscitation. At that time, severe hyperkalemia up to 9.1 mEq/L and ventricular fibrillation were noted. Resuscitation in ER worked successfully with conversion of electrocardiograph to sinus rhythm, but this patient expired unfortunately. On view of this acute event immediately after the bolus injection of propofol accompanied without other identified causes, severe hyperkalemia induced by propofol was strongly assumed to be the cause of death. To our understanding with the literature survey, propofol as a cause of hyperkalemia has not been well described yet. Through this case, the relationship as a cause and an effect between propofol and hyperkalemia is suggested.

Propofol Infusion Syndrome in a Patient with Epilepsia Partialis Continua

Propofol has been used for the treatment of refractory status epilepticus, but propofol can cause propofol infusion syndrome (PRIS). PRIS is rarely developed and often fatal. The syndrome is characterized by metabolic acidosis, rhadomyolysis, and cardiac failure. Most reports were described in critically ill patients undergoing long-term propofol infusion at high doses. But many systemic confounding factors are mixed with the fatality of PRIS and there are no report on epilepsia partialis continua which has stable systemic conditions. We report PRIS in a patient with epilepsia partialis continua.

Síndrome da infusão do propofol / Propofol infusion syndrome

JUSTIFICATIVA E OBJETIVOS: A síndrome da infusão do propofol tem sido descrita como uma síndrome rara e quase sempre fatal que ocorre após infusão prolongada desse fármaco. Ela pode resultar em acidose metabólica grave, rabdomiólise, colapso cardiovascular e morte. O objetivo deste artigo foi mostrar aspectos relacionados com a síndrome da infusão do propofol por meio da revisão de literatura. CONTEUDO: Estão definidas as características da síndrome da infusão do propofol quanto à fisiopatologia, características clínicas, tratamento e recomendações de dose para pacientes gravemente enfermos. CONCLUSÕES: O propofol deve ser usado com cautela quando se planeja seu uso sob regime de infusão contínua por períodos prolongados. O surgimento de sinais sugestivos da síndrome da infusão do propofol indica a suspensão imediata do fármaco e início de medidas de suporte.

BACKGROUND AND OBJECTIVES: Propofol infusion syndrome has been described as a rare, and frequently fatal, syndrome that occurs after prolonged infusion of this drug. It might result in severe metabolic acidosis, rhabdomyolysis, cardiovascular failure, and death. The objective of this report was to review the literature to present aspects related to the propofol infusion syndrome. CONTENTS: The physiopathology, clinical characteristics, and treatment, of the propofol infusion syndrome as well as dose recommendations for severely ill patients are presented here. CONCLUSIONS: Propofol should be used with caution when it is administered as continuous infusion for prolonged periods of time. The development of signs suggestive of the propofol infusion syndrome indicates the drug should be discontinued immediately and support measures instituted.

JUSIFICATIVA Y OBJETIVOS: El síndrome de la infusión del propofol ha sido descrito como un síndrome raro y frecuentemente fatal que ocurre después de la infusión prolongada de ese fármaco. Puede resultar en acidez metabólica grave, rabdomiólisis, colapso cardiovascular y deceso. El objetivo de este artículo fue mostrar aspectos relacionados al síndrome de la infusión del propofol a través de la revisión de la literatura. CONTENIDO: Están definidas las características del síndrome de la infusión del propofol en cuanto a la fisiopatología, características clínicas, tratamiento y recomendaciones de dosis para pacientes gravemente enfermos. CONCLUSIONES: El propofol debe ser usado con cautela cuando se planea su uso bajo el régimen de infusión continua por períodos prolongados. El aparecimiento de señales sugestivas del síndrome de la infusión del propofol indica la suspensión inmediata del fármaco y el inicio de medidas de soporte.

Experience of Suspected Propofol Infusion Syndrome in a Status Epilepticus Patient: A case report / 대한마취과학회지

Propofol is used for the treatment of refractory status epilepticus. When given as a long-term infusion, in combination with catecholamines and/or steroids, propofol rarely causes the fatal complication, known a propofol infusion syndrome. Herein, the case of a previously healthy 8-years-old boy with status epilepticus is reported. He was treated with propofol, in doses ranging from 8.6 to 10.9 mg/kg/h, for 43 hours. The propofol resulted in multiple organ failure, with rhabdomyolysis, which caused the death of the patient. This case fulfills all the criteria of propofol infusion syndrome.