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: 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.

[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.

PRIS may be diagnosed before ICU period for patients undergoing cardiopulmonary bypass.

There are many published articles on the clinical manifestations of propofol-related infusion syndrome (PRIS), but they are not the same in each case.(1)Moreover, PRIS is only encountered infrequently and, therefore, it may create a diagnostic challenge. Nearly all of the published articles on PRIS are related to the use of long-term (> 48 hour) propofol infusion with a dose range of at least 4-5 mg/kg/h. In this case, not only a short duration, but also a low-dose propofol administration seems to induce PRIS. A 73-year-old male patient under cardiopulmonary bypass (CPB) suffered from some clinical symptoms of PRIS, such as hyperlactatemia and persistent low metabolic acidosis which promptly resolved on the discontinuation of propofol. Therefore, we suggest that any propofol administration (bolus or infusion) may result in such clinical symptoms, which may be the earliest indicators of PRIS. When those symptoms are observed on propofol administration during cardiopulmonary bypass (CPB), the perfusionist must alert both the anaesthesiologist and the surgeon to stop the propofol in order to prevent the patient from further adverse effects of PRIS.

[Fatal hyperpyrexia in an adolescent patient with severe burns after a traffic accident]. / Letale Hyperpyrexie bei einem jugendlichen Schwerbrandverletzten nach Verkehrsunfall.

After a motorcycle accident a 16-year-old patient suffered severe burns to 40.5 % of the total body surface area (TBSA) of which 37 % were deep subdermal burns. After tangential and partly epifascial necrosectomy, Integra® was used as a temporary dermis replacement material for the lower extremities, combined with extensive negative pressure wound therapy (NPWT). In the further course of the treatment the patient developed uncontrollable hyperpyrexia with a fatal outcome. Possible influencing factors, such as the dermis replacement material combined with NPWT over large areas as well as the differential diagnoses propofol infusion syndrome, heatstroke and malignant hyperthermia are discussed.

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.

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.

[Malignant hyperthermia syndrome in the intensive care unit : Differential diagnosis and acute measures]. / Maligne hypertherme Syndrome auf der Intensivstation : Differenzialdiagnostik und Akutmaßnamen.

Malignant hyperthermia is a life-threatening disease caused by derangement of the autonomic nerve system and hypermetabolism of the peripheral musculature. Commonly body core temperatures of more than 40 °C will be found in this disease which is caused mostly by psychopharmacological drugs like antidepressants, neuroleptics but also antibiotics, pain killers, anti-Parkinson drugs, and volatile anesthetics. The inducers of malignant hyperthermia interact with postsynaptic receptors (serotonin, anticholinergics) or muscular intracellular structures responsible for calcium utilization (volatile anesthetics, succinylcholine). Rarely malignant hyperthermia is a consequence of mental stress or vigorous exercise and or heat. Malignant hyperthermic syndromes lead to a severe dysbalance of the autonomic nerve system accompanied by rhabdomyolysis, disseminated intravascular coagulopathy, and finally multi-organ failure. Accordingly, medical management is primarily directed to stabilize vital functions, withdrawal of the causing drug, and if possible antagonizing toxic substances. The leading symptom hyperthermia needs to be treated physically with available cooling systems.

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 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.