Would reducing the total volume per minute of propofol (sedative/hypnotic agent) infusion affect blood pressure, potentially leading to hypotension, after initiating a fentanyl (synthetic opioid analgesic) infusion in a patient?

From the Guidelines

Reducing the total volume per minute of propofol infusion is likely to improve blood pressure, rather than cause hypotension, after initiating a fentanyl infusion in a patient, as propofol is a more potent vasodilator than fentanyl. Generally, propofol causes dose-dependent respiratory depression and hypotension due to systemic vasodilation, as noted in the clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit 1. Fentanyl at standard analgesic doses (0.5-2 mcg/kg/hr) typically causes minimal cardiovascular depression compared to propofol. However, several factors could explain hypotension in this scenario: the patient may have developed tolerance to propofol's vasodilatory effects, the fentanyl dose might be excessive (>2-3 mcg/kg/hr), the patient could be hypovolemic, or there might be synergistic effects between the medications.

Some key points to consider when managing these medications include:

• The incidence and severity of hypotension will depend on patient factors, such as age, comorbidities, medication history, individual pharmacokinetics, and pharmacodynamic responses to the drugs administered 1.
• Certain drugs and drug combinations are more likely to cause hypotension than others, with propofol being a notable example due to its potent vasodilatory effects.
• A recent retrospective analysis of haemodynamic data from several studies, including patients undergoing colonoscopy, showed that more than a third of patients undergoing moderate to deep sedation with propofol experienced hypotension defined as systolic arterial pressure <90 mm Hg 1.
• Management should include reducing the fentanyl infusion rate, administering IV fluids if the patient is hypovolemic, considering vasopressors if needed, and thoroughly assessing for other causes of hypotension, with the timing of hypotension relative to medication changes being crucial for determining causality.

In terms of specific management strategies, it is essential to:

• Monitor blood pressure closely when adjusting propofol and fentanyl infusion rates.
• Be aware of the potential for synergistic effects between these medications and other factors that could contribute to hypotension.
• Consider alternative sedation strategies or adjust the doses of these medications based on individual patient responses and the clinical context.

From the FDA Drug Label

As with other general anesthetics and sedation drugs, propofol injectable emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole) The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates. When propofol injectable emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia). The induction dose requirements of propofol injectable emulsion may be reduced in patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., morphine, meperidine, and fentanyl, etc.) and combinations of opioids and sedatives (e.g., benzodiazepines, barbiturates, chloral hydrate, droperidol, etc.) These agents may increase the anesthetic or sedative effects of propofol injectable emulsion and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output

Reducing the total volume per minute of propofol infusion may affect blood pressure, potentially leading to hypotension, after initiating a fentanyl infusion in a patient.

• The magnitude of the changes in blood pressure is proportional to the blood and effect site concentrations achieved, which depend on the dose and speed of the induction and maintenance infusion rates.
• Using high-dose opioid technique with propofol may increase the likelihood of hypotension.
• Fentanyl and other narcotics may increase the anesthetic or sedative effects of propofol and result in more pronounced decreases in blood pressure. The administration of propofol should be adjusted according to the desired level of anesthesia or sedation and may be reduced in the presence of supplemental analgesic agents 2, 2, 2.

From the Research

Effect of Reducing Propofol Infusion Volume on Blood Pressure

• Reducing the total volume per minute of propofol infusion may affect blood pressure, potentially leading to hypotension, after initiating a fentanyl infusion in a patient 3, 4, 5, 6, 7.
• The use of propofol for induction of anesthesia is a statistically significant multivariate predictor of hypotension 3.
• Propofol is associated with a dose-dependent decrease in blood pressure and heart rate, and bolus administration may cause transient hypotension 4.
• The combination of propofol and fentanyl may intensify the fall in mean arterial pressure (MAP) after propofol administration 5.
• Increasing the time between fentanyl and propofol administration may result in greater hypotension in patients over 55 years 6.
• Administering fentanyl 5 minutes prior to propofol can cause a marked reduction in the dose requirement of propofol and a significantly decreased incidence of hypotension during induction 7.

Hemodynamic Impact of Propofol and Fentanyl Administration

• The hemodynamic response to propofol and fentanyl administration can be improved by increasing the time between their administration and reducing the dose of propofol 6, 7.
• The incidence of hypotension during induction can be significantly lower when fentanyl is administered 5 minutes prior to propofol 7.
• The dose of propofol required for induction of anesthesia can be reduced by administering fentanyl prior to propofol 7.
• The time to reach hypnosis is not significantly different between groups with different time intervals between fentanyl and propofol administration 6, 7.