Propofol-Induced Myocardial Depression: Does This Really Exist?

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Author: Sandeep Devabhakthuni, PharmD, BCPS-AQ Cardiology

Propofol is extensively used in the intensive care setting as a sedative for mechanically ventilated patients. Propofol is an appealing option for sedation in this population due to its rapid onset, short duration of action, minimal accumulation, and relatively low cost. Propofol is considered a superior option to benzodiazepines due to shorter time to extubation and time to light sedation (1). Additionally, three randomized controlled trials have demonstrated that there was no difference in time to extubation when comparing propofol and dexmedetomidine (2-4). Thus, the 2018 Society of Critical Care Medicine Clinical Practice Guidelines for Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the Intensive Care Unit (ICU) suggests to use either propofol or dexmedetomidine over benzodiazepines for sedation in critically ill, mechanically ventilated adults (5).

Dexmedetomidine is becoming increasingly popular in the cardiac intensive care setting due to concerns regarding cardiovascular safety with propofol. Propofol has been known to cause severe hemodynamic instability such as bradycardia and hypotension even at therapeutic doses (6). However, both propofol and dexmedetomidine are associated with a similar incidence of bradycardia and hypotension (2-4). Additionally, several publications have described a propofol-induced decrease in cardiac output after induction of anesthesia or with use of a continuous infusion for sedation (7-9). Many use this as an argument to avoid propofol in patients with reduced ejection fraction or hemodynamic instability.

Although propofol has both negative inotropic effects and vasodilatory properties, the effects on myocardial contractility at clinical concentrations are thought to be minimal (10). In fact, propofol protects the myocardium against ischemia/reperfusion injury due to its antioxidant and free-radical scavenging properties. The major hemodynamic consequence of propofol is the reduction of preload due to venodilation, which can cause hypotension in a hypovolemic patient. However, this reduction in preload could be beneficial in a patient with heart failure, who has elevated preload due to volume overload. Propofol may also be antiarrhythmogenic by inducing pharmacological preconditioning of the myocardium (11).

Despite the concerns listed above, there are three important considerations before accepting propofol-induced myocardial depression as clinically significant:

1. Data are primarily derived from animal studies.
The studies that have demonstrated propofol-induced myocardial depression were actually conducted in rats and dogs (12,13). There are limited data investigating the cardiovascular effects of propofol in humans; however, the indication for propofol in these studies was induction of anesthesia (7,14,15). When used for this indication, propofol is administered at significantly higher doses (2-2.5 mg/kg for induction and 50-100 mcg/kg/min for maintenance of general anesthesia). For ICU sedation in mechanically ventilated patients, the dosing range that is commonly used is 5-60 mcg/kg/min. Thus, the studies investigating the effects of propofol when used at general anesthesia doses should not be extrapolated to the management of ICU sedation in mechanically ventilated adults.

2. The decreased cardiac output observed with propofol is likely a result of decreased preload.
Previous studies have determined that propofol at doses used for general anesthesia is associated with decreased mean arterial pressure and systemic vascular resistance, but the effect on cardiac output varied from no effect to a significant decrease (16-19).

A study published in 2016 investigated the effect of propofol on hemodynamics including cardiac output, venous return, mean systemic filling pressure, and vascular resistances (20). The authors hypothesized that propofol decreases vascular capacitance, resulting in decreased stressed volume (volume that stretches the walls in the arteries and veins). The investigators measured hemodynamic parameters in 17 adult patients after upper abdominal surgery. The measurements were performed at three different levels of blood propofol concentrations (low, middle, and high). As the propofol concentration increased, the mean arterial pressure, central venous pressure, mean systemic filling pressure, and systemic arterial and venous resistance decreased. However, the cardiac output was not significantly affected by increased propofol concentrations. As such, it is unclear if the reduced preload demonstrated with propofol leads to a clinically significant myocardial depression in euvolemic patients. However, in those patients who are hypovolemic, propofol could cause marked decrease in cardiac output secondary to decreases preload.

3. Propofol-induced hypotension is likely due to a reduction in systemic vascular resistance, not decreased cardiac output.
Several publications have suggested negative inotropic effects as the mechanism for propofol-induced hypotension. However, the study previously described above used objective hemodynamic parameters for a wide range of blood propofol concentrations to determine if there are negative inotropic effects. Based on the results, the mechanism for hypotension appears to be a decrease in stressed volume, which is likely due to a decrease in systemic vascular resistance. This decrease in stressed volume associated with propofol infusion suggests that hypovolemic patients would have a more pronounced decrease in mean arterial pressure. This reduction in mean arterial pressure could then lead to myocardial depression, particularly in those patients with diminished intravascular volume (20). Patients admitted to the cardiac ICU often have increased systemic vascular resistance due to cardiogenic shock or acute decompensated heart failure; therefore, propofol may offer a clinical advantage in improving cardiac output by reducing afterload in these patients.

So what does this mean for clinical practice?
Propofol appears to produce a dose-dependent decrease in mean arterial pressure due to a decrease in both preload and afterload but without a change in cardiac output. However, in a hypovolemic patient, this decrease in mean arterial pressure could indirectly increase the risk of myocardial depression. Therefore, careful assessment of a patient’s volume status is warranted when considering the use of propofol for ICU sedation. In hypovolemic patients with preserved left ventricular function, clinicians should consider the administration of intravenous fluids to optimize preload as a means of avoiding propofol-induced hypotension. This strategy is not needed in heart failure patients with significant volume overload. Indeed, in those patients, a propofol-induced decrease in preload and afterload may actually enhance cardiac output and reduce filling pressures.

In addition to assessing the patient’s volume status, judicious titration of propofol is recommended. The study results appear to demonstrate a dose-dependent decrease in mean arterial pressure. Therefore, propofol should be titrated carefully while monitoring the patient’s vital signs to avoid any precipitous drop in blood pressure or heart rate. Clinicians might consider the use of alternatives to avoid these adverse effects; however, dexmedetomidine has been shown to have a similar incidence of hypotension and bradycardia when compared to propofol (21). Since benzodiazepines are not routinely used due to increased risk of delirium, there are no other alternative sedatives that would be safer than propofol.

Bottom Line
Propofol should not be avoided in the cardiac intensive care setting in patients with reduced left ventricular function or hemodynamic instability simply due to concerns for myocardial depression. The data suggesting that propofol causes myocardial infarction due to a negative inotropic effect are not convincing. Propofol likely causes myocardial depression indirectly through venous and arterial vasodilation that leads to a reduction in stroke volume. This can be corrected by intravascular volume repletion and cautious dose titration in hypovolemic patients and may even be of benefit in patients with acute decompensated heart failure.

Sandeep Devabhakthuni, PharmD, BCPS-AQ Cardiology

Sandeep Devabhakthuni is an assistant professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist in advanced heart failure at the University of Maryland Medical Center in Baltimore, MD. Follow him on Twitter @deepdev511