apneic threshold

[jok200]

confused on the concept? I understand that it is the an arbitrary point that changes, above which respiration ensues, and below which respiration ceases, am I correct so far? So for instance whitney houston, had possession of benzo's, that drug should cause cessation of respiration that leads to accumulation of pCO2 in the arterial blood, correct? Here comes my confusion, if the level of pCO2 accumulates to a high enough level why doesn't respiration suddenly begin? Also what affect would this have on her apneic threshold?


thanks-

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[pgg]

confused on the concept? I understand that it is the an arbitrary point that changes, above which respiration ensues, and below which respiration ceases, am I correct so far? So for instance whitney houston, had possession of benzo's, that drug should cause cessation of respiration that leads to accumulation of pCO2 in the arterial blood, correct? Here comes my confusion, if the level of pCO2 accumulates to a high enough level why doesn't respiration suddenly begin? Also what affect would this have on her apneic threshold?


thanks-

Yes, hypercarbia is a powerful pro-breathing influence, but -

1) Ventilation is only 1/2 the story. If you're apneic or hypopneic long enough to get your CO2 way up there, odds are you have a bigger and more immediate problem, hypoxia. Oxygenation and ventilation are different. Oxygenation = getting enough O2. Ventilation = getting rid of CO2. You CAN have one without the other. Hypercarbia and respiratory acidosis in a controlled setting is (usually) pretty well tolerated provided oxygenation is maintained. Absent stuff like pulm HTN, head injuries, etc which have non-respiratory reasons to dislike hypercarbia.

2) Hypercarbia has physiologic effects. There comes a CO2 level at which the CO2 itself has sedating effects and can cause other non-resp-drive breathing-related difficulties - like airway obstruction or drowning if you happen to be in a bathtub.

"Insufficient drive" is only one reason why people might not breath enough to support life.

 

[jok200]

Okay... I understand that respiratory drive is not the only part of the problem. Saying oxygenation is not impaired in any way and the only problem is that she isn't breathing because of the respiratory depression abilities of the benzo overdose. The pCO2 accumulates and in such a situation as overdose like you said hypoxia would be a huge problem enough to affect the brain in such a way that the receptors within the brainstem probably would not be able to read the levels of co2 well enough to cause respiration to increase? What I am confused about is that, I know that the apneic threshold once exceeded should stimulate the respiratory center to cause increase respiration but, why does respiration not ensue when the levels have accumulated excessively because of benzo overdose? that is my first question, secondly how and why does the apneic threshold increase in this patient?

thanks again-

 

[G0S2]

Okay... I understand that respiratory drive is not the only part of the problem. Saying oxygenation is not impaired in any way and the only problem is that she isn't breathing because of the respiratory depression abilities of the benzo overdose. The pCO2 accumulates and in such a situation as overdose like you said hypoxia would be a huge problem enough to affect the brain in such a way that the receptors within the brainstem probably would not be able to read the levels of co2 well enough to cause respiration to increase? What I am confused about is that, I know that the apneic threshold once exceeded should stimulate the respiratory center to cause increase respiration but, why does respiration not ensue when the levels have accumulated excessively because of benzo overdose? that is my first question, secondly how and why does the apneic threshold increase in this patient?

thanks again-

Right shift in the PCO2 response curve due to benzo. Hypoxemia eventually due to Alveolar gas equation Fi (Fb-Fw)-PaCO2/R and pCO2 100 is 0.5 MAC, PCO2 200 is 1 MAC, which further shifts your curve.

 

[MTGas2B]

Tolerance plays a part as well. I like to think of it using the therapeutic index idea from pharm. As tolerance develops, higher plasma levels are required to reach the desired effect. The plasma levels required to cause unwanted side effects (apnea) don't go up as fast, and the therapeutic index gets smaller. So, as tolerance develops the dose to keep you happy becomes closer to the make you stop breathing dose. With a narrower margin for safety, its easy for someone to load up past their apneic threshold while trying to get the desired anxiolytic/pain relief/high they want.

 

[proman]

Right shift in the PCO2 response curve due to benzo. Hypoxemia eventually due to Alveolar gas equation Fi (Fb-Fw)-PaCO2/R and pCO2 100 is 0.5 MAC, PCO2 200 is 1 MAC, which further shifts your curve.

I don't think benzos cause a rightward shift of the response curve like opioids do. Instead, they cause a decrease in the slope of the curve. The result is less respiratory depression when compared to opioids. The effect is synergistic when combined with opioids or other respiratory depressants like alcohol.

 

[partydoc]

Tolerance plays a part as well. I like to think of it using the therapeutic index idea from pharm. As tolerance develops, higher plasma levels are required to reach the desired effect. The plasma levels required to cause unwanted side effects (apnea) don't go up as fast, and the therapeutic index gets smaller. So, as tolerance develops the dose to keep you happy becomes closer to the make you stop breathing dose. With a narrower margin for safety, its easy for someone to load up past their apneic threshold while trying to get the desired anxiolytic/pain relief/high they want.

Just making sure, tolerance would be seen in chronic CO2 retainers, right? Such as somebody with COPD?

 

[MTGas2B]

Just making sure, tolerance would be seen in chronic CO2 retainers, right? Such as somebody with COPD?

Same idea, rightward shift of their CO2 response curve, however it is being reset due to a physiologic increase in CO2 (ie obstructive lung disease) as opposed to pharmacologic in chronic opiates.

 

[MTGas2B]

I don't think benzos cause a rightward shift of the response curve like opioids do. Instead, they cause a decrease in the slope of the curve. The result is less respiratory depression when compared to opioids. The effect is synergistic when combined with opioids or other respiratory depressants like alcohol.

No, I should have clarified, what I was referring to was opiates. But as you mentioned benzos just have a synergistic effect on the whole process. I have no clue what the proposed tox screen on Whitney Houston had in it. I generally don't read that part of the paper. I just assume high profile overdose usually involves some amount of opiates. Especially in the time of pain as the 5th vital sign.

 

[jok200]

Okay.. no offense but nobody has answered my question yet, simply you have reiterated what I already know by using the co2 dissociation curve but that doesn't help me to understand:

1- Why does respiration not ensue when the levels have accumulated excessively because of benzo overdose?
2 Secondly how and why does the apneic threshold increase in this patient?

 

[pgg]

Okay.. no offense but nobody has answered my question yet, simply you have reiterated what I already know by using the co2 dissociation curve but that doesn't help me to understand:

1- Why does respiration not ensue when the levels have accumulated excessively because of benzo overdose?
2 Secondly how and why does the apneic threshold increase in this patient?

1 Respiration may not ensue because hypoventilation may lead to hypoxia and death first, or the sedation/hypercarbia may cause airway obstruction (also causing hypoxia and death).

2 Drugs shift/alter the CO2 response curve, raising the apneic threshold, it's what opiates and benzos and some other drugs do. What are you looking for, the molecular mechanism by which these drugs affect CO2 sensitivity and respiratory drive?

 

[Gern Blansten]

Okay.. no offense but nobody has answered my question yet, simply you have reiterated what I already know by using the co2 dissociation curve but that doesn't help me to understand:

1- Why does respiration not ensue when the levels have accumulated excessively because of benzo overdose?
2 Secondly how and why does the apneic threshold increase in this patient?

As PGG stated, sometimes you die of hypoxia first. What is the question behind the question?

 

[jok200]

hey pgg, thanks for the response that definitely helped to clear a lot up. So...

1- Respiration hasn't started even though the CO2 levels have increased tremendously because hypoxia from an overdose could have caused enough "brain death" that the receptors in the brainstem wouldn't be able to respond to the increase amounts anyway because they would be "dead", is that correct?

2-Co2 accumulation causes the dissociation curve to shift meaning that a greater amount of co2 retention is needed to stimulate breathing, is that correct? If it is correct what is the mechanism, I mean co2 accumulates acutely and what... the body senses this increase and says.. I have to change my set point now, how does that mechanism occur?

... sorry for all the questions but this is annoying me. I NEED to know how this works, and for that to occur I have to keep asking myself questions on the mechanism.

-Either way thanks again for the help, Lange anesthesia is definitely a life saver at this point.

 

[Per4mer8]

hey pgg, thanks for the response that definitely helped to clear a lot up. So...

1- Respiration hasn't started even though the CO2 levels have increased tremendously because hypoxia from an overdose could have caused enough "brain death" that the receptors in the brainstem wouldn't be able to respond to the increase amounts anyway because they would be "dead", is that correct?

2-Co2 accumulation causes the dissociation curve to shift meaning that a greater amount of co2 retention is needed to stimulate breathing, is that correct? If it is correct what is the mechanism, I mean co2 accumulates acutely and what... the body senses this increase and says.. I have to change my set point now, how does that mechanism occur?

... sorry for all the questions but this is annoying me. I NEED to know how this works, and for that to occur I have to keep asking myself questions on the mechanism.

-Either way thanks again for the help, Lange anesthesia is definitely a life saver at this point.

I'll give it a go. The set point itself increases slowly over time in COPD, whereas in Benzo OD/Toxicity it's a direct agonist action. Increased inhibitory effect (GABA) at the receptor level on the neurons of the medullary respiratory center. Therefore increased stimulus (higher CO2) is required to get response from neurons.

My .02

 

[pgg]

2-Co2 accumulation causes the dissociation curve to shift meaning that a greater amount of co2 retention is needed to stimulate breathing, is that correct?

No

You're mixng up concepts here, back up. Hypercarbia does in fact affect the oxyhemoglobin dissociation curve but that's really only tangentially related here. The curve of interest is the CO2 response curve, which has CO2 on the x-axis and minute ventilation (drive) on the y-axis. Hypercarbia doesn't shift this curve; the relationship between CO2 and MV define the curve. Many of the drugs we use shift this curve, usually to the right, meaning a higher CO2 level is needed to stimulate the same MV.

As for the molecular "how" it's chemoreceptors and drug receptors and 2nd messengers and all that Step 1 biochem that I used to know better than I do now.

 

[jok200]

Got it completely thanks for the help, sorry it took me a while. I love this forum.

thanks again-

 

[Idiopathic]

Okay.. no offense but nobody has answered my question yet, simply you have reiterated what I already know by using the co2 dissociation curve but that doesn't help me to understand:

1- Why does respiration not ensue when the levels have accumulated excessively because of benzo overdose?
2 Secondly how and why does the apneic threshold increase in this patient?

at a certain point, hypercarbia/respiratory acidosis may become narcotizing, and inhibit respiratory drive on its own. Where you may be able to breathe spontaneously from a PaCO2 of 30-80, a chronic CO2 retainer or opiate-treated individual may do so from 45-85, highlighting differences in therapeutic index between patients

thats my understanding at least