SAMBA Talks eNewsletter - September, 2006

Volume 6, Issue 4

S A M B A T A L K S - PAGE 2

September, 2006

JOIN THE DISCUSSION - TOP

Need advice about a problem case in ambulatory anesthesia? Want suggestions about a difficult situation in your ambulatory surgery center? Have a reply to questions others have raised about ambulatory anesthesia issues?

If you answered "yes" to any of these questions, or would like to share with other professionals a comment or opinion on a topic related to ambulatory anesthesia then please "Join the Discussion" here.

To enter the Discussion with a question, reply, or other comment, please contact us. Your submission will be published in this section of the next available issue of SAMBA TALKS. Include your name (or initials), city, and state, if you would like these published. Please note that because of the high volume of questions we receive, there is often a delay of 1 to 2 months before the questions can be published.

Questions and responses from previous months are now available at the eNewsletter Discussion Archive. If you have any comments regarding the previous questions, please submit them to SAMBA Discussion, and they will be published here next month.

Please note: The information presented in the replies below does not represent SAMBA policy. The replies are solely the opinions of the individuals who wrote them.

?? - LAST MONTH'S QUESTION WITH REPLY - ?? - TOP

Duloxetine(Cymbalta) and Drug Interactions

Part of the action of Duloxitine (Cymbalta) is the inhibition of norepinephrine reuptake. Because it is relatively new to the market, there has been some concern regarding this effect, but little opportunity for large-scale study of its potential interaction with anesthetics. Is it reasonable to admit patients on this drug for surgery in an ASC or office setting where vasoactive drugs and monitoring are limited?

-- Paul Berghuis, M.D., Mount Vernon, WA

Answer:

You are correct in that duloxetine, one of two serotonin (5-HT) and norepinephrine reuptake inhibitors (SNRI) available as an antidepressant (there are other SNRIs such as sibutramine used for weight control), is a relatively new drug, introduced in August 2004. However, the other SNRI antidepressant, venlafaxine, better known as Effexor has been on the market since 1993 with very little overall side effects.

Mechanism of Action:

The SNRIs were developed as a drug that would provide improved efficacy in managing depression over the selective serotonin reuptake inhibitors (SSRIs) but without the toxic effects associated with the monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs).

The SNRIs block the reuptake of 5-HT, norepinephrine (NE), and dopamine (DA) in a dose dependent fashion. This is the unique property of these drugs. In contrast, TCAs block 5-HT and NE in a fixed ratio, irrespective of dosage, with no significant DA reuptake inhibition. Beyond this distinction, TCAs block cholinergic, histaminic and adrenergic receptors causing uncomfortable effects. Patients taking SNRIs are essentially spared these side effects.

Serotonin Syndrome:

The only reported adverse event associated with the use of the SNRI antidepressants and anesthetics, more specifically, venlafaxine is serotonin syndrome (SS). No adverse events with anesthetics have been reported with duloxetine. SS is due to overstimulation of the 5-HT receptor (more specifically, 5-HT1A and possibly 5-HT2) and is characterized by a triad of neuro-excitatory features including mental, autonomic and neurological events. SS is usually associated with the use of multiple agents that contribute to the increased availability of 5-HT in any manner: excess precursors, increased release, reduced reuptake or decreased metabolism of 5-HT. The onset of toxicity is usually rapid, occurring once the “second” drug reaches effective blood levels.

Some opioids can inhibit 5-HT re-uptake and may act as the “second” drug. Meperidine, tramadol, methadone, dextromethorphan, and propoxyphene appear to be weak 5-HT re-uptake inhibitors and have all been involved in 5-HT toxicity reactions with MAOIs and many with the SSRIs. Additionally, even though oxycodone does not inhibit serotonin reuptake there have been few case reports linking its usage to SS.

To date, no reports of SS have been described with the use of duloxetine. As anesthetics are concerned, only tramadol has been associated with SS when added to venlafaxine. There is one report of SS induced by the combination of amitriptyline, venlafaxine and meperidine but it is unclear whether meperidine was “necessary” for this to occur. However, because of the theoretical concerns, it is prudent to avoid opioids that may inhibit the re-uptake of serotonin in patients at risk for SS.

Other Side Effects

Some patients taking venlafaxine develop a noticeably sustained increase in diastolic blood pressure and heart rate as outpatients. Because of this, care should be taken when vasoconstrictors are used. Similar caution is prudent for patients taking duloxetine.
As outpatients, clinical experience suggests patients taking duloxetine (compared to venlafaxine) have more difficulties with urinary retention. It is unclear what clinical significance this may have in the ambulatory surgical setting but should be taken into consideration, particularly during cases that may lead to delayed bladder emptying and discharge home.

Post-marketing case reports of duloxetine have noted that patients with pre-existing liver disease may be at an increased risk for additional liver damage. Prescribing information has been expanded to discourage use of duloxetine in patients with evidence of chronic liver disease.

Furthermore, abrupt discontinuation prior to surgery should be discouraged in light of possible withdrawal symptoms.

Other general guidelines for its usage and drug interactions can be found in a variety of standard references.

To Answer Your Question:

I think it is perfectly reasonable and safe to provide care for patients on these “new” SNRIs in an ambulatory setting as long as the appropriate precautions are taken as reviewed above.

Food For Thought

One interesting thought is: Are patients taking SSRIs or SNRIs at higher risk for PONV? The obvious connection is that since we are using 5-HT3 receptor blocking agents to prevent PONV are patients with higher levels of 5-HT prone for PONV? I am not aware of any studies, comments or conversation amongst our peers in regards to this topic. Time will tell. If anyone has thoughts on this, please e-mail me at jahana@ccf.org.

-- Ali Jahan, MD, Cleveland, OH

?? -- THIS MONTH'S QUESTION -- ?? - TOP

“I am a bit confused on the role of NSAIDs; where I practice, we tell our patients not to use NSAIDs for at least 7days prior to their scheduled surgery (I think that is due to the bleeding concerns). At the same time I understand that other places use NSAIDs (or at least advocate it usage) as part of the pain management regimen by administering the drug either preoperatively, intraoperatively and/or postoperatively.

What is the best way to use NSAIDs and do we have to worry about bleeding? Thanks.”

-- Anonymous

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