Cardiology

Interventional Pharmacology: Procedural Sedation

General (including evidence of efficacy)

The ability to deliver safe and effective moderate sedation is important in the performance of cardiac catheterization. The goals of procedural sedation are to ease anxiety and discomfort without compromising patient cooperation and ventilation.

Moderate sedation in the catheterization laboratory is most commonly achieved with a combination of a short-acting sedative and analgesic medications. When benzodiazepines are combined with opiates their individual effects are potentiated. Dosages should be individually titrated to achieve the desired level of sedation and pain control.

A serious consequence of over sedation is dose-dependent respiratory depression. Extra care should be exercised when administering sedatives and analgesics in elderly patients and those with significant comorbidities.

Differences between drugs within the class

Anxiolytics

Benzodiazepines, such as midazolam and diazepam, are effective for mild or moderate sedation. These agents produce anxiolysis and antegrade amnesia, but have no analgesic properties. Most invasive cardiologists favor midazolam because of its rapid onset of action, short duration of effect, and high amnestic properties. Benzodiazepines are often coadministered with short-acting opioids for analgesia and enhanced sedation.

Analgesics

Short-acting opioids, such as morphine sulfate, fentanyl, and hydromorphone hydrochloride, are often given alone or in combination with anxiolytics for procedural sedation. They are primarily used to provide analgesia, but they also produce a degree of anxiety relief. All of the opioids have similar analgesic and sedative properties when administered in equipotent doses.

Administration

Anxiolytics

Midazolam is usually given in IV doses of 0.5 to 1 mg and may be repeated every 3 to 5 minutes as necessary to achieve the desired effect. Lower doses and/or longer dosing intervals should be used in patients at risk of prolonged sedation, such as the elderly, obese, and those with renal or hepatic dysfunction.

Diazepam: The usual initial dose is 2.5 to 5 mg IV, which can be repeated after 5 minutes to achieve adequate sedation.

Analgesics

Fentanyl: The usual initial dose of fentanly is 25 to 50 mcg IV. Doses may be repeated every 3 to 5 minutes until adequate analgesia and sedation are achieved.

Morphine: Morphine is commonly given at a dose of 2 to 4 mg IV and repeated as required.

Hydromorphone: Hydromorphone is typically administered in doses of 0.5 to 1 mg IV and titrated to effect.

Pharmacologic action

Anxiolytics

Midazolam: Midazolam is highly lipophilic resulting in rapid penetration across the blood-brain barrier. Its onset of action is within 2 to 3 minutes and its effects can last up to an hour. With high and/or repeated doses midazolam accumulates in adipose tissue, which can considerably prolong sedation. It is eliminated by both hepatic and renal routes.

Diazepam: Diazepam is also lipophilic and has an almost immediate onset of action (1 to 5 minutes for IV administration and 15 to 30 minutes for IM administration). It may cause prolonged sedation with repeated dosing because it has a large volume of distribution and has two active metabolites.

Analgesics

Fentanyl: Fentanyl is a synthetic opioid. It has an almost immediate onset of action with a duration of effect of 30 to 60 minutes. Unlike morphine, fentanyl does not cause histamine release, and thus rarely causes hypotension. It is primarily metabolized in the liver.

Morphine: Morphine is the prototype opiate. It has a rapid onset of analgesia with a duration of action up to 240 minutes. It is hepatically metabolized and renally eliminated. Morphine stimulates histamine release, which may result in hypotension, flushing, and bronchospasm.

Hydromorphone hydrochloride (Dilaudid): Hydromorphone is a semisynthetic opiate agonist. It has a rapid onset of analgesic effect (10 to 15 minutes) and lasts for 120 to 240 minutes. Hydromorphone is primarily metabolized in the liver and excreted in urine.

Undesirable effects

Anxiolytics

The major risk associated with benzodiazepines is depression of the respiratory system, especially with higher doses and when coadministered with opiates. These agents may also produce a slight drop in blood pressure and cardiac output. Therefore, close monitoring of the patients oxygen saturation, blood pressure, and heart rate is mandatory.

The benzodiazepine antagonist, flumazenil, can be used to reverse the sedative effects of benzodiazepines, but it has limited efficacy for reversing respiratory depression. Flumazenil is given as an initial dose of 0.1 to 0.3 mg IV. Repeated doses may be required because the half-life of flumazenil is shorter than that of the midazolam or diazepam. Flumazenil should be used cautiously in patients taking chronic benzodiazepines because it may induce seizures or withdrawal.

Analgesics

The major risk associated with opiates is respiratory depression, which can be potentiated when they are combined with sedatives. Lower total doses and longer dosing intervals should be used in the elderly, and in patients with hepatic or renal impairment.

The respiratory depression and sedation induced by opiates can be reversed with the opiate antagonist naloxone. The usual dose of naloxone is 0.4 to 2 mg IV. It is shorter acting than most narcotics, and thus serial doses may be required.

Morphine and hydromorphone act directly on blood and tissue cells to release histamine, which can produce hypotension, flushing, pruritus, and bronchospasm.

Other adverse effects associated with opiates include nausea and vomiting, depressed consciousness, hallucinations, and urinary retention.

Alternative approaches

Analgesics

Occasionally deep sedation or even general anesthesia may be required, particularly for longer and more complex procedures such as structural heart interventions.

  • Propofol: Propofol is a phenol derivative that acts as a sedative and amnestic but provides no analgesia. It has a very rapid onset of action (<1 min) and its duration of action is 5 to 10 minutes. An initial loading dose of 1 mg/kg IV is followed by 0.5 mg/kg doses every 3 to 5 minutes as needed to enhance or prolong sedation. The dose should be reduced in elderly patients. Adverse effects include hypotension (due to myocardial depression), respiratory depression, and pain during injection. Propofol is not reversible. It is contraindicated in patients with egg or soy allergies.

  • Etomidate: Etomidate, an imidazole derivative, is a sedative that is commonly used for rapid sequence intubation but can also be used at lower doses for procedural sedation. An important benefit of etomidate is that it does not cause myocardial depression. Like propofol, it has no analgesic effects and is irreversible. For sedation 0.1 mg/kg IV etomidate is given over 30 seconds and can be repeated every 3 to-5 minutes if there is an inadequate response. It has an almost immediate onset of action and its duration of effect is 5-10 minutes. Lower doses should be administered to the elderly and those patients with significant renal or hepatic impairment. Side effects include respiratory depression, myoclonus, nausea/vomiting, and rarely transient adrenocortical suppression.

What's the Evidence?

"Practice guidelines for sedation and analgesia by non-anesthesiologists". Anesthesiology. vol. 96. 2002. pp. 1004-17.

(This is a comprehensive, relatively concise and authoritative document on the use of procedural sedation, written for the nonanesthesiologists.)

Gan, TJ. "Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation". Clin Pharmacokinet. vol. 45. 2006. pp. 855-69.

(Article provides a nice overview of commonly used drugs for sedation during invasive procedures.)
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