Propofol Infusion Syndrome

What Is Propofol Infusion Syndrome?

Propofol Infusion Syndrome can be defined as the acute medical condition leads to refractory bradycardia (slow heart rate), and further cause cardiac asystole (cessation of heart beat) with other associated conditions like metabolic acidosis, hyperlipidemia, rhabdomyolysis and fatty or enlarged liver. Propofol infusion syndrome arises due to its number of serious adverse effects, including metabolic acidosis, cardiac asystole, myocardial failure, rhabdomyolysis, and death.

Propofol Infusion Syndrome is common in children, but the recent medical report stated that adult also gets affected with the adverse effect of propofol and Propofol Infusion Syndrome arises¹.

What is Propofol?

Propofol is an anesthetic drug but also used as a short-term sedative agent in ICU (intensive care unit) due to its favorable pharmacokinetic properties and fast reversible sedation effect³.

Mechanism

Dose and duration of infusion are important criteria for initiation of Propofol Infusion Syndrome (PRIS). A higher dose like 4 mg/kg/hour of more than 48 hours extended period usually cause PRIS.

The exact mechanism is unknown in PRIS development. But possible involve mechanism which established through in vitro study is due to mitochondrial function become impaired through a higher dose of propofol infusion through prolonged period. The impairment of mitochondrial function is not described properly in the medical literature, but it may occur due to an inhibitory effect on mitochondrial respiratory chain or impairment metabolism of mitochondrial fatty acid^2,3,4.

History

The reporting of incidence of Propofol Infusion Syndrome has not very old history. Danish medical committee had been first raised an issue about the using of propofol in the pediatric population after serious adverse effect (death) was reported in 1990.

BMJ published articles in 1992, which highlighted the safety concerns of propofol usage in children and that also indicated caution must be taken care for adult usability. First Propofol Infusion Syndrome in adult was reported in 1996 after using propofol in adult intensive care unit (ICU) after using of propofol for median 3 days .

Considering general Propofol Infusion Syndrome, almost 1.1% incidence rate observed per year in ICU. The total death rate due to PRIS was almost 18% in comparison with a total incidence of Propofol Infusion Syndrome previously. But currently, the death rate become decreased due increase awareness about the adverse effects of propofol^5,6.

Symptoms of PIS

The following are the most common symptoms of propofol infusion syndrome:

• Metabolic acidosis
• Cardiac dysfunction
• Destruction of skeletal muscles (rhabdomyolysis). Rhabdomyolysis develops due to necrosis of muscular tissues. Destruction of muscular tissue develops in all striated muscles including cardiac myocytes, which leads to enhanced discharge of creatinine kinase (CK) and myoglobin.
• Elevated levels of triglycerides (hypertriglyceridemia),
• Renal failure and occurs due to excessive release of myoglobin⁷.

Other included symptoms are

• Hepatomegaly
• Hyperkalemia
• Lipemia; This may occur due to sympathetic stimulation, elevated levels of cortisol and growth hormone, obstructive oxidation of mitochondrial fatty acid and lipid metabolism impairment. Thus non-esterified fatty acids level become high in blood circulation and clinical presentation shows as is clinically manifested as raised serum triglyceride.
• Arrhythmic symptoms like atrial fibrillation, ventricular tachycardias, including or supraventricular tachycardias, blocking of a bundle of his, sequential bradycardia, and ultimately asystole⁸.

Risk Factors

Certain risk factors may responsible for development of the PRIS, which include

• Severe head injuries
• Sepsis
• Exogenous or endogenous catecholamine level enhancement
• Increased level of glucocorticoid levels
• Low carbohydrate consumption with high lipid intake,
• Congenital defects of fatty acid oxidation⁹.

Diagnosis

Following are the different diagnostic criteria for PRIS:

• The early clinical presentation is lactate production enhancement, which leads to lactic acidosis and renal failure. Both these conditions sequentially lead to metabolic acidosis. Different case report description illustrated that lactate measurement was not conducted in most of the cases. Therefore, it is an important diagnostic criterion to understand the onset of PRIS.
• ECG or electrocardiogram can detect cardiac dysfunction. The specific characteristic of ECG has coved-type ST elevations in V1–V3, which clinically termed as Brugada-like ECG alterations.
• Serum samples are analysis for estimating lipaemia in PRIS patients.
• Creatinine kinase (CK) is also elevated in a blood sample (>10 000 units litre−1) for PRIS patients^7,8,9.

Treatment

The most important management criteria for PRIs patient is the rapid identification of clinical signs through performing the different diagnostic test. The vulnerable persons are most cautiously handled with propofol infusion. The following observation is required to manage PRIs patients

• Daily monitoring of Creatinine kinase (CK) and triglyceride levels after 48 hours administration of propofol infusion. Any elevated level of CK without the involvement of other pathologic condition of muscles need to immediate stoppage of propofol and alternative sedative drugs like midazolam can be used to maintain the patient treatment requirement.
• The treatment of PRIS is difficult. Cardiovascular support with haemofiltration and cardiac pacing required for management of the patient. Cardiac pacing or Electrical pacing can be provided either through a temporary wire or transcutaneously. It has some degree of relief from the bradycardia.
• Rapid elimination of propofol and its metabolite can be obtained by giving renal therapy. Lactic acidosis can be controlled by giving renal replacement therapy.
• Extracorporeal membrane oxygenation provides maximum cardiovascular support of PRIS^7,8,9.

Prevention

Some preventive measure of PRIS include

• The dose and duration are very crucial for PRIS. Therefore, it has been preferred that dose should not increase 4 mg kg−1 h−1 for long-term use (more than 48 hours).
• Frequent monitoring of serum lactate, arterial blood gasses and CK are required to prevent PRIS, specifically if the patient requires a higher dose of propofol for more than 48 hours.
• Carbohydrate intake or glucose infusion require to reduce the risk of lipolysis, specifically when high energy demands in periods of starvation period.
• Routine monitoring of Ck and triglyceride require The patients who have high-risk factors to prevent PRIS^8,9,10.

References

1. Kam PC, Cardone D. ; Propofol infusion syndrome; Anaesthesia. 2007 Jul;62(7):690-701.
2. Jose Orsini; Abhijeet Nadkarni; Julie Chen; Nina Cohen; Propofol Infusion Syndrome: Case Report and Literature Review; Am J Health Syst Pharm. 2009;66(10):908-915.
3. Chris Nickson; Propofol-related Infusion Syndrome (PRIS); Online available at http://lifeinthefastlane.com/ccc/propofol-infusion-syndrome/
4. Parke TJ, Stevens JE, Rice ASC, Greenway CL, Bray RJ, Smith PJ, Waldmann CS, Verghese C. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. British Medical Journal 1992; 305: 613–6.
5. Cremer OL, Moons KGM, Bouman EAC, Kruijswijk JE, De Smet AMGA, Kalkman CJ. Long term propofol infusion and cardiac failure in adult head-injured patients. Lancet 2001; 357: 117–8.
6. Parke TJ, Stevens JE, Rice ASC, et al. Metabolic acidosis and fatal myocardial failure after propofol infusion in children: five case reports. Br Med J1992;305:613-6. doi:10.1136/bmj.305.6854.613.
7. Roberts R, Barletta J,  Fong J, et al. Incidence of propofol-related infusion syndrome in critically ill adults: a prospective, multicenter study. Crit Care2009;13:R169. doi:10.1186/cc8145.
8. Fodale V,  La Monaca E. Propofol infusion syndrome: an overview of a perplexing disease. Drug Saf 2008;31:293-303. doi:10.2165/00002018-200831040-00003.
9. Priya Nair, Propofol infusion syndrome; Contin Educ Anaesth Crit Care Pain (2013)doi: 10.1093/bjaceaccp/mkt007
10. Cremer OL,  Moons KGM,  Bouman EAC, et al. Long term propofol infusion and cardiac failure in adult head injured patients. Lancet 2001;357:117-8.