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Reader Remarks on:

Happy 50th? Sedation for Colonoscopy in HIV-Infected Patients

• Unboosted ATV dosing
• Use propofol without the fentanyl
• What Dr. Fennerty said...
• titrated to effect, modazolam-ketamine is a good alternative
• Use sedatives with caution in any patient
• Use common sense
• Ask the sailor how to sail not the professor.
• common sense
• Fentanyl and Midazolam
• no nfusions for short procedures
• Similar concern as previously with azoles
• PK principles
• Titration and Post-Procedure Monitoring Are Key

Unboosted ATV dosing

Rob Sandmann, Pharm.D., AAHIVE, 8 Apr 2009 2:17 PM EST

Competing interests: Speaker for Gilead, GSK, and Abbott.

As a pharmacist, I agree with the last two responses which essentially use the drugs at reduced dosing to compensate for the drug interaction, but I disagree with the first response that states dosing unboosted atazanavir is FDA approved with tenofovir. There is a proven drug interaction between atazanavir and tenofovir that requires boosting to overcome and I believe using a suboptimal regimen for a period of two weeks could be clinically significant.

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Use propofol without the fentanyl

Ravpreet S. Gill, 9 Apr 2009 9:07 AM EST

Competing interests: None declared

During my anesthesiology residency I did hundreds of colonoscopies with propofol alone -- you don't necessarily need the fentanyl.

If no practitioner qualified to administer propofol is available, another option is etomidate (a short acting sedative/induction agent). A third option is what the physician in the article stated: titration with small doses of midazolam--you just have to be patient for this option and make sure you have flumazenil available.

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What Dr. Fennerty said...

James E. Carroll, Critical Access Hospital, 9 Apr 2009 9:07 AM EST

Competing interests: None declared

Dr. Fennerty's astute comment captures the clinician's dilemma. Titration of sedation drugs to effect is at the core of what clinicians do. Generalizations may be made about drugs and their effects, but the effect on an individual patient is specific to that patient. Incremental dosing and careful monitoring of effect is essential. The word "contraindication" is often used as a substitute for the word "caution".

Careful study of the patient's drug list is essential, and, armed with the knowledge of the altered pharmacokinetics and dynamics, the clinician chooses appropriate drugs and doses cautiously.

There are no "cookbooks" in this important area of patient care and risk management.

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titrated to effect, modazolam-ketamine is a good alternative

Pinny Halpern, Tel Aviv Medical Center, 9 Apr 2009 9:07 AM EST

Competing interests: None declared

We use midazolam titration until spontaneous eye closure and thenadd ketamine 0.5-1.0 mg/kg to excellent effect in such pts, with esentially no complications.

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Use sedatives with caution in any patient

A. J. Lee, 9 Apr 2009 9:07 AM EST

Competing interests: None declared

Speaking as an anesthesiologist, these sedative drugs are always titrated to effect for individual patients. We are aware that responses are variable and I think it completely unnecessary to alter an HIV patient's drug regimen to allow them to receive the discussed drugs. In my experience, I have never noticed a marked exaggeration in clinical effects in this scenario anyway. Bolus doses should be reduced and given with more caution, in the same manner that we approach any patient with altered metabolism, such as the elderly, or those known to have hepato-renal failure. If there is increased concern for a particular case, monitoring from an Anesthesia Provider should be sought.

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Use common sense

Karen V Williams, Pharm D, Health Partners Specialty Center, St Paul, MN, 9 Apr 2009 9:07 AM EST

Competing interests: None declared

I have queried several gastroenterologists treating HIV patients in Minneapolis and their practice follows Response 3. They feel reduced doses with titration are safe and effective. Modifying the HAART regimen would be confusing to many patients and resistance-risky.

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Ask the sailor how to sail not the professor.

Jonathan C Hausheer, 9 Apr 2009 11:41 AM EST

Competing interests: None declared

Why do you ask people who don't give sedation for colonoscopy how do do it. Clearly the first two responders are extrapolating from the scientific literature and the 3rd is speaking from experience. If you want steer a ship thru dangerous waters who do you ask, the professor at Harvard or an old salt of a sailor.

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common sense

Robert C. Barker, Sparks Hosptal, Ft. Smith, AR, 14 Apr 2009 10:29 AM EST

Competing interests: None declared

Common sense would would seem consistent with Dr. Fennerty's approach.

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Fentanyl and Midazolam

Kevin Parent, Geisinger Clinic, 14 Apr 2009 10:29 AM EST

Competing interests: None declared

I would use fentanyl and Midazolam at low and slow doses to achieve desired effect.

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no nfusions for short procedures

Ramanathan Moorthy, Manipal Hospital, Bangalore, 14 Apr 2009 10:29 AM EST

Competing interests: None declared

By logical thinking, when you are talking about lack of availability for prolonged monitoring, do not use infusions, especially for short procedures.This should hold good for non-HIV patients as well. You can still use the same drugs in smaller doses with titration to clinical response.

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Similar concern as previously with azoles

George R Thompson, UTHSCSA, 14 Apr 2009 10:29 AM EST

Competing interests: None declared

Although admittedly ritonavir is a more potent CYP450 inhibitor, this concern received attention previously early in the AIDS epidemic due to itraconazole and midazolam. No adverse events have been described with the prior combination, and haven't seen anything about ritonavir/midazolam either. Difficult to extrapolate date, but sets a precedent that a one time dose is likely still safe if caution is used.

Varhe, A., K. T. Olkkola, and P. J. Neuvonen. 1994. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 56:601-7.

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PK principles

Cari Brackett, 14 Apr 2009 10:29 AM EST

Competing interests: None declared

An important thing to remember is that IV sedation for a procedure constitutes a SINGLE rather than repeated dosing model. If we eliminate oral bioavailability from the picture by giving sedation IV, we must remember the following: If the net effect of the drug-drug interaction is increased clearance of the sedative agent, the peak concentration (hence sedative effect) will be UNALTERED.....but the duration of effect (as determined by elimination rate constant) will be shorter. If the issue is inhibition of clearance, the peak concentration (and hence effect) will be unaltered, but the duration of effect (sedation) will be prolonged.

It is with repeated dosing that "peaks and trough" are altered and either drug failure or accumulation become relevant. With single doses, these effects should not be operant.

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Titration and Post-Procedure Monitoring Are Key

John K. DesMarteau, MD, 22 Apr 2009 6:27 PM EST

Competing interests: None declared

As someone who happens to be on efavirenz I received midazolam and fentanyl for a colonoscopy without incident at age 57 two years ago. The dosage used of both medications was comparable with that I have given patients many times for short relatively pain-free procedures before I retired from the practice of anesthesiology. And my recovery time was comparable to patients I have treated who were not on either RTV or EFV. Dr. Fennerty's approach is the one my gastroenterologist used and is one that I endorse. Giving sedation is all about titration according to individual response and circumstances. The additional caveat I have to make is that since the patient could have a prolonged response is to make sure that the recovery personnel are aware of that fact and are prepared to keep the patient under observation for as long as necessary. This might mean scheduling the case earlier in the day so there is no time pressure to discharge the patient.

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