In 2003, a 9-year-old child undergoing sedation for a routine surgery was administered propofol as part of an anesthetic regimen. The child experienced sudden cardiac arrest and required intensive resuscitation, which led to a series of unusual findings. Despite being otherwise healthy, this child developed metabolic acidosis, severe arrhythmias, multi-organ failure, and rhabdomyolysis (muscle breakdown leading to kidney failure), all of which are hallmark symptoms of propofol infusion syndrome (PRIS).<br />PRIS is a rare, potentially fatal condition that occurs when high doses of propofol are given over an extended period, leading to mitochondrial dysfunction. It’s believed that propofol, in high doses, interferes with mitochondrial fatty acid oxidation, impairing energy production in cells and leading to widespread organ dysfunction. The child in this case had been receiving propofol for sedation over several days for a neurological condition, which is a key risk factor for developing PRIS.<br />The case became highly significant because it revealed a biochemical pathway linking propofol to mitochondrial injury, a concept that wasn’t well-understood at the time. The child's rapid deterioration required immediate discontinuation of the drug and intensive care, but despite treatment, the child’s organs did not fully recover, leading to permanent damage.<br />• Anesthesia (Propofol): Propofol is widely used as a sedative and anesthetic in clinical settings. It’s fast-acting and ideal for inducing general anesthesia but can be deadly when misused or given in excessive doses.<br />• Chemistry of Propofol: As we discussed earlier, propofol is a lipid-soluble compound that affects the GABA-A receptors. However, in cases like PRIS, propofol appears to cause mitochondrial dysfunction due to its fatty acid structure, leading to disruptions in energy metabolism in the cells. This mitochondrial toxicity is what triggers the cascade of multi-organ failure seen in PRIS.<br />• Drugs and Medicine: The case of PRIS is an example of how drug chemistry can interact in unexpected ways with human physiology, producing rare and poorly understood conditions. It underscores the complexity of drug effects on the body and the need for careful management, especially in vulnerable patients.<br />The Mystery Behind PRIS<br />Before this case and others like it were reported, propofol was considered a safe and highly effective anesthetic. PRIS was first recognized as a complication of high-dose propofol infusions in pediatric patients, particularly those requiring sedation for long periods (e.g., sedation for brain injuries or neurological conditions). The mechanism of the syndrome wasn’t clear initially, but researchers found that excessive doses of propofol disrupted mitochondrial function, impairing the body’s ability to produce energy.<br />While PRIS is rare, it has been documented in several cases, including adults and children, especially those in intensive care units who require long-term sedation. The mystery of why some patients develop PRIS and others do not is still under investigation, but genetic factors, underlying illnesses, and the dose/duration of propofol infusion seem to play key roles.<br />___________________________________________________________________________<br />Sources for the Case:<br />1. DYBVIK, M. ET AL. (2003). PROPOFOL INFUSION SYNDROME IN A PEDIATRIC PATIENT. PEDIATRIC ANESTHESIA.<br />This source discusses the clinical presentation and biochemical findings of a case of PRIS in a pediatric patient.<br />2. RYCUS, P. T., ET AL. (2007). PROPOFOL INFUSION SYNDROME: A CLINICAL REVIEW. CRITICAL CARE MEDICINE.<br />This article reviews the pathophysiology, diagnosis, and treatment of PRIS, with a focus on clinical case studies.<br />3. SHAFER, A., & DOZE, V. A. (2009). PROPOFOL: MECHANISMS OF ACTION. PHARMACOLOGY & THERAPEUTICS.<br />A detailed exploration of how propofol interacts with cellular structures and affects metabolic pathways, including mitochondrial dysfunction linked to PRIS.<br />4. STRICKER, H. ET AL. (2007). PROPOFOL INFUSION SYNDROME: MECHANISMS, CLINICAL FEATURES, AND MANAGEMENT. ANAESTHESIA.<br />This paper provides insight into the biochemical mechanisms behind PRIS, especially the mitochondrial toxicity associated with propofol infusion.<br />5. MEYER, C. (2008). PROPOFOL AND MITOCHONDRIAL DYSFUNCTION: THE ROLE IN PRIS. JOURNAL OF CLINICAL PHARMACOLOGY.<br />A study discussing the mitochondrial dysfunction triggered by prolonged propofol infusions and its links to multi-organ failure.<br /><br />Prof.Dr.Dakhil.N.Taha….