Short-term propofol infusion syndrome (PRIS): fact or fiction? A systematic review on early PRIS in intensive care and anesthesia

Vandenbrande, Jeroen

doi:10.1186/cc14560

Cited by 5 publications

(4 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PRIS can be lethal, and multiple studies suggest caution when using prolonged ( > 48 h) propofol sedation at doses higher than 5 mg/kg/h, particularly in patients with inflammatory illnesses 5,6,36 . The results from our findings demonstrate that propofol-induced pyroptosis not only triggers macrophage death but also mediates the release of IL-1β and IL-18, leading to an exaggerated proinflammatory process and multiple-organ dysfunction in the clinic.…”

Section: Discussionmentioning

confidence: 99%

Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome

et al. 2019

View full text Add to dashboard Cite

Propofol infusion syndrome (PRIS) is an uncommon life-threatening complication observed most often in patients receiving high-dose propofol. High-dose propofol treatment with a prolonged duration can damage the immune system. However, the associated molecular mechanisms remain unclear. An increasing number of clinical and experimental observations have demonstrated that tissue-resident macrophages play a critical role in immune regulation during anaesthesia and procedural sedation. Since the inflammatory response is essential for mediating propofol-induced cell death and proinflammatory reactions, we hypothesised that propofol overdose induces macrophage pyroptosis through inflammasomes. Using primary cultured bone marrow-derived macrophages, murine macrophage cell lines (RAW264.7, RAW-asc and J774) and a mouse model, we investigated the role of NLRP3 inflammasome activation and secondary pyroptosis in propofol-induced cell death. We found that high-dose propofol strongly cleaved caspase-1 but not caspase-11 and biosynthesis of downstream interleukin (IL)-1β and IL-18. Inhibition of caspase-1 activity blocks IL-1β production. Moreover, NLRP3 deletion moderately suppressed cleaved caspase-1 as well as the proportion of pyroptosis, while levels of AIM2 were increased, triggering a compensatory pathway to pyroptosis in NLRP3 -/- macrophages. Here, we show that propofol-induced mitochondrial reactive oxygen species (ROS) can trigger NLRP3 inflammasome activation. Furthermore, apoptosis-associated speck-like protein (ASC) was found to mediate NLRP3 and AIM2 signalling and contribute to propofol-induced macrophage pyroptosis. In addition, our work shows that propofol-induced apoptotic initiator caspase (caspase-9) subsequently cleaved effector caspases (caspase-3 and 7), indicating that both apoptotic and pyroptotic cellular death pathways are activated after propofol exposure. Our studies suggest, for the first time, that propofol-induced pyroptosis might be restricted to macrophage through an NLRP3/ASC/caspase-1 pathway, which provides potential targets for limiting adverse reactions during propofol application. These findings demonstrate that propofol overdose can trigger cell death through caspase-1 activation and offer new insights into the use of anaesthetic drugs.

show abstract

Section: Discussionmentioning

confidence: 99%

Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The usage of corticosteroids is another risk factor [19]. The mechanism behind steroids leading to PRIS lies in the activation of the ubiquitin-proteasome pathway that causes muscle rupture because of myofilament disturbance [20].…”

Section: Usage Of Corticosteroidsmentioning

confidence: 99%

Propofol-Related Infusion Syndrome: A Clinical Review

Singh¹,

Anjankar²

2022

Cureus

View full text Add to dashboard Cite

Propofol-related infusion syndrome (PRIS) is a lethal condition characterized by multiple organ system failures. It can occur due to prolonged administration of propofol (an anesthetic) in mechanically intubated patients. The main presenting features of this condition include cardiovascular dysfunction with particular emphasis on impairment of cardiovascular contractility, metabolic acidosis, lactic acidosis, rhabdomyolysis, hyperkalaemia, lipidaemia, hepatomegaly, acute renal failure, and eventually mortality in most cases. The significant risk factors that predispose one to PRIS are: critical illnesses, increased serum catecholamines, steroid therapy, obesity, young age (significantly below three years), depleted carbohydrate stores in the body, increased serum lipids, and most importantly, heavy or extended dosage of propofol. The primary pathophysiology behind PRIS is the disruption of the mitochondrial respiratory chain that causes inhibition of adenosine triphosphate (ATP) synthesis and cellular hypoxia. Further, excess lipolysis of adipose tissue occurs, especially in critically ill patients where the energy source is lipid breakdown instead of carbohydrates. This process generates excess free fatty acids (FFAs) that cannot undergo adequate betaoxidation. These FFAs contribute to the clinical pathology of PRIS. It requires prompt management as it is a fatal condition. The clinicians must observe the patient's electrocardiogram (ECG), serum creatine kinase, lipase, amylase, lactate, liver enzymes, and myoglobin levels in urine, under propofol sedation. Doctors should immediately stop propofol infusion upon noticing any abnormality in these parameters. The other essentials of management of various manifestations of PRIS will be discussed in this article, along with a detailed explanation of the condition, its risk factors, diagnosis, pathophysiology, and presenting features. This article aims to make clinicians more aware of the occurrence of this syndrome so that better ways to manage and treat this condition can be formulated in the future.

show abstract

“…Continuous infusion of Propofol is associated with Propofol infusion syndrome (PRIS), which is characterized by the onset of metabolic acidosis, rhabdomyolysis, acute renal failure, cardiac dysthythmias and hyperlipidemia [ 37 , 38 ]. Although there is evidence that continuous Propofol infusion <4 mg/kg/h for periods >48 h can be safe [ 39 , 40 ], the cost-of-error is deemed so great that the FDA recommends withholding from continuous Propofol infusion in paediatric TBI [ 41 ]. As for bolus medication, Propofol is sometimes briefly used as an adjuvant for procedural sedation.…”

Section: Pitfallsmentioning

confidence: 99%

Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities

et al. 2017

View full text Add to dashboard Cite

Analgosedation is a fundamental part of traumatic brain injury (TBI) treatment guidelines, encompassing both first and second tier supportive strategies. Worldwide analgosedation practices continue to be heterogeneous due to the low level of evidence in treatment guidelines (level III) and the choice of analgosedative drugs is made by the treating clinician. Current practice is thus empirical and may result in unfavourable (often hemodynamic) side effects. This article presents an overview of current analgosedation practices in the paediatric intensive care unit (PICU) and addresses pitfalls both in the short and long term. We discuss innovative (pre-)clinical research that can provide the framework for initiatives to improve our pharmacological understanding of analgesic and sedative drugs used in paediatric severe TBI and ultimately facilitate steps towards evidence-based and precision pharmacotherapy in this vulnerable patient group.

show abstract

Short-term propofol infusion syndrome (PRIS): fact or fiction? A systematic review on early PRIS in intensive care and anesthesia

Cited by 5 publications

References 1 publication

Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome

Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome

Propofol-Related Infusion Syndrome: A Clinical Review

Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities

Contact Info

Product

Resources

About