Doxapram

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Josh L.Ac.

Josh L.Ac.

MSA/LAc & BSN/RN --> AA-S
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I have to give a 10 minute overview of a review article in my physiology class that pertains specifically to the respiratory system. For me, one of the most complicated aspects of the respiratory system is how ventilation is driven and how disease states and medications affect ventilatory drive.

While investigating this topic I came across the drug doxapram. While it looks like it is only used in a limited fashion, I thought that an explanation of how the drug works would be a great way to explain respiratory drive.



Thoughts? Any comments about its use?





http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

CNS Drug Rev. 2006 Fall-Winter;12(3-4):236-49.

A new look at the respiratory stimulant doxapram.

Yost CS.
Department of Anesthesia and Perioperative Care, University of California at San Francisco, San Francisco, California 94143, USA. [email protected]

A number of life-threatening clinical disorders may be amenable to treatment with a drug that can stimulate respiratory drive. These include acute respiratory failure secondary to chronic obstructive pulmonary disease, post-anesthetic respiratory depression, and apnea of prematurity. Doxapram has been available for over forty years for the treatment of these conditions and it has a low side effect profile compared to other available agents. Generally though, the use of doxapram has been limited to these clinical niches involving patients in the intensive care, post-anesthesia care and neonatal intensive care units. Recent basic science studies have made considerable progress in understanding the molecular mechanism of doxapram's respiratory stimulant action. Although it is unlikely that doxapram will undergo a clinical renaissance based on this new understanding, it represents a significant advance in our knowledge of the control of breathing.
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Josh L.Ac. said:
I have to give a 10 minute overview of a review article in my physiology class that pertains specifically to the respiratory system. For me, one of the most complicated aspects of the respiratory system is how ventilation is driven and how disease states and medications affect ventilatory drive.

While investigating this topic I came across the drug doxapram. While it looks like it is only used in a limited fashion, I thought that an explanation of how the drug works would be a great way to explain respiratory drive.



Thoughts? Any comments about its use?





http://www.ncbi.nlm.nih.gov/pubmed/...nel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
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I havent used it since i first started training. However, I will say that there are attendings that swear by it to 'facilitate' waking the pt up faster.

One should be careful about adminstering the med to pts with CNS pathology and h/o seizures.
 
Doxapram

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Doxapram
Systematic (IUPAC) name1-ethyl-4- (2-morpholin-4-ylethyl)- 3,3-diphenyl-pyrrolidin-2-oneIdentifiersCAS number309-29-5ATC codeR07AB01PubChem3156DrugBankAPRD00935Chemical dataFormulaC24H30N2O2 Mol. mass378.507 g/molPharmacokinetic dataBioavailability ?Metabolism ?Half life ?Excretion ?Therapeutic considerationsPregnancy cat.?
Legal statusRoutesIntravenousDoxapram hydrochloride (marketed as Dopram) is a respiratory stimulant. Administered intravenously, doxapram stimulates an increase in tidal volume, and respiratory rate.
Contents

[hide]
[edit] Mode of action

Doxapram stimulates chemoreceptors in the carotid arteries, which in turn, stimulates the respiratory centre in the brain stem.

[edit] Presentation

Doxapram is a white to off-white, odorless, crystalline powder that is stable in light and air. It is soluble in water, sparingly soluble in alcohol and practically insoluble in ether. Injectable products have a pH from 3.5-5. Benzyl alcohol or chlorobutanol is added as a preservative agent in the commercially available injections.

[edit] Uses

Doxapram is used in intensive care settings to stimulate the respiratory rate in patients with respiratory failure. It may be useful for treating respiratory depression in patients who have taken excessive doses of drugs such as buprenorphine which may fail to respond adequately to treatment with naloxone.[1]
It is equally effective as pethidine in suppressing shivering after surgery.[2]

[edit] Side effects

High blood pressure, panic attacks, tachycardia (rapid heart rate), tremor, sweating and vomiting may occur. Convulsions have been reported. It cannot be used in patients with coronary heart disease, epilepsy and high blood pressure. It is also contraindicated in newborns and small children, mainly due to the presence of benzyl alcohol.

[edit] References
 
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The side-effect profile is real. I have seen some real bad cardiac side effects with this drug particularly in the elderly. The majority of time the people using doxapram routinely are giving a high dose narcotic anesthetic. By simply changing your technique doxapram is NOT needed in daily practice. The drug works as described but I highly recommend caution in the elderly and those with preexisting cadiac disease.
 
I didn't realize this was still on the market.

Many years ago, we had a great "real-world" indication for it. Wake-up tests during Harrington Rod placement in kids for scoliosis. This was before the days of all that fancy neurophysiologic monitoring they do now. They put the rods and hooks in and tightened them up. We then turned off all the agents, reversed the NMB's, waited a couple minutes, then gave doxapram. As soon as the patient gave any indication that they were waking up (that would be moving around) we would start yelling at them to move their legs or feet. As soon as they did that, we'd slam in the pentothal and back down they would go, and the surgeons would finish the operation. Not exactly a pretty way of doing it, but that's all we had back then.
 
In my experience, it was a holdover with older anesthesiologists from the days of less soluble volatile agents and, as stated above, when nitrous-narcotic techniques were popular. It is a relic of the past with little to no indication today, side effects notwithstanding (add major anxiety/distress in the awake patient to that list) and if you can find an unopened vial, snatch it an throw it in your locker for that mini-history of anesthesia museum in your study.
 
Thanks for all the responses.


So other than possibly using it if the patient was overly-sedated with a mixed receptor agonist / antagonist (right?), is there any other situation that you can think of where it would be your top choice over any other intervention (pharmacological or otherwise)?


Perhaps power failure + failed backup on the anesthesia machine + failed masked ventilation?


<---------------- grew up watching MacGyver, BTW
 
Josh L.Ac. said:
Thanks for all the responses.


So other than possibly using it if the patient was overly-sedated with a mixed receptor agonist / antagonist (right?), is there any other situation that you can think of where it would be your top choice over any other intervention (pharmacological or otherwise)?


Perhaps power failure + failed backup on the anesthesia machine + failed masked ventilation?


<---------------- grew up watching MacGyver, BTW
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IMO there is no indication for it and you won't find it on the difficult airway algorithm should you choose to review it.
 
Yeah, I definitely didn't see it there.


Sigh. It seemed kinda cool. Guess it's just one of those drugs that are great to highlight mechanisms of action but not very useful in teh real world.
 
Josh L.Ac. said:
Yeah, I definitely didn't see it there.


Sigh. It seemed kinda cool. Guess it's just one of those drugs that are great to highlight mechanisms of action but not very useful in teh real world.
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Josh, it's just an old-fashioned drug that has outlived its usefulness. There really are no good indications for its use any more.
 
proman said:
It has its uses, just not to anesthesiologists. Looks like most of the uses are in the NICU, similar to caffeine.
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Not really used currently in NICU setting due to multiple risks and no real evidence of benefit as first or second line drug. Haven't seen it in many years and doubt it is used in more than a very few places.
 
oldbearprofessor said:
Not really used currently in NICU setting due to multiple risks and no real evidence of benefit as first or second line drug. Haven't seen it in many years and doubt it is used in more than a very few places.
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Interesting. I searched pubmed and found a few recent articles in that population. Maybe international?
 
proman said:
Interesting. I searched pubmed and found a few recent articles in that population. Maybe international?
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and older negative studies that may have been more recently published. The Cochrane reviews are negative as well. The recent data showing that caffeine has long-term positive developmental benefits for very preterm babies and the concern about benzyl alcohol did in doxapram. Also, it needs a dedicated IV for continuous infusion which is a major issue in our population. I had used it in the distant past with some success, but gave up on it quite a few years ago and haven't seen it used recently anywhere.
 
used it when I was a vet... would place a few drops under the tongue of puppies that were just delivered via c-section... haven't found a place where it would be useful in modern anesthesia practice.
 
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