NAVEL Contemplation: Part II - @

NAVEL Contemplation: Part II

All About ET Drug Delivery


Howard Rodenberg, MD, MPH, Dip(FM) | | Monday, December 3, 2007

(Continued from last week.)

I think the solution is literally in the palm of our hands. It's called the nebulizer, a device we use every day in the care of patients with asthma and COPD. If we place a nebulizer into the respiratory circuit of a patient who is intubated, it seems to meet our needs quite well. You can deliver a volume of drug in fluid effectively into the respiratory tree. The solution is nebulized to form microdroplets that easily penetrate into the deeper reaches of the lung. The nebulizer is a low-pressure device, and the droplets are delivered by the act of inspiration itself (in this case, as driven by the bag or transport ventilator).

I need to note that the nebulizer as the solution is an idea, and not a fact. I've seen no studies that address its use in an ACLS or cardiac arrest setting. I have a feeling that the effective use of a nebulizer for ACLS agents would require some significant changes in drug dosing, airflow, and drug volume strategies. But it does seem, from the standpoint of physics, to be the best way to surmount the problem. I look forward to someone much brighter than I doing this research (Volker Wenzel and Ahamed Idris, are you listening?).

Can we avoid the issue of nebulization by simply injecting the drug farther into the respiratory tree? Possibly, but don't count on it. The 2000 ACLS Guidelines briefly mention this issue. In adult patients, ACLS advises that drugs be placed into the pulmonary tree via a flexible catheter placed beyond the tip of the endotracheal tube. Drugs are to be sprayed down this catheter, followed by breaths to create an aerosol (at least I think that's what they mean. The text itself says to pass the catheter, but then spray the drug down the ET tube, which seems inconsistent). In contrast, Pediatric Guidelines note that diluting a drug in 5 cc of fluid and then giving it down the endotracheal tube is pharmacologically equivalent, and technically easier, than administering a drug through a separate catheter or feeding tube. It's another honest difference of opinion as we all fish in the darkness.

The procedure for endobronchial administration of ACLS agents is relatively simple. Once an ET tube has been placed, a smaller flexible catheter of longer length than the tube is inserted through the channel. The distal end of this catheter presumably ends up in one of the mainstem bronchi, and the drug (in fluid) is administered through this tube. On the surface, this would seem to be a valuable adjunct to the use of ET agents. However, reality speaks otherwise. While mainstem bronchi are indeed closer to the sites of gas exchange and drug absorption than the tip of the typical ET tube, it is still fairly proximal considering the respiratory tree as a whole. In addition, the use of the catheter limits the potential area of contact between the drug and the respiratory mucosa, and limits the blood flow that might potentially pick up the agent and carry it to the heart and to the vascular segments serving that specific area of lung.

The literature finds mixed results from this procedure. Some reports indicate that endobronchial epinephrine and atropine administration is superior to endotracheal dosing in dogs; two other works indicate that lidocaine is less effective when administered to human patients via the endobronchial route. It's unknown what role differences in the drugs and species studied, as well as the physiologic issues related above, may have played in these conflicting results. Capitalizing on the positive results, Wolfe-Tory Medical is marketing an atomizer (MADett) to be inserted through the endotracheal tube into the carina and mainstem bronchi. When drug in fluid is pushed through the device, the resulting spray of microdroplets theoretically attains better pulmonary penetration. As of yet, however, the efficacy of this technique in enhancing drug levels or patient outcomes in the ACLS setting has not been documented. Once efficacy has been established, this route may prove as beneficial as nebulization.

What about the issue of fluid volume? Can you actually drown a patient with ET drugs? I don't think so, but I can't prove it. My hypothesis is based on an exploration of lung capacities. The total lung capacity of the average adult is 5800 cc. The vital capacity, which represents all the air we can fully inspire, as well as all the air we can forcibly expire, is 4600 cc (this value includes the 150 cc of anatomic dead space noted above). The remaining 1200 cc of total lung capacity is the residual volume, or the air help within the lung at the end of expiration to prevent alveolar collapse.

Assuming we are able to open the majority of airways and alveoli with positive pressure ventilation, we have a potential space of over 4 liters for fluids. I don't know what the critical mass of fluid is that's required to "drown" someone. The drowning literature is actually not very helpful in this regard. Many drowning victims asphyxiate due to laryngospasm and not pulmonary edema ("dry drowning"). Autopsy work shows that most drowning victims aspirate less than 4cc/kg of fluid. If we extrapolate this value to the mean 70 kg patient, 280 cc of aspirated pulmonary fluid would be required to "drown" someone.

However, the intubated ACLS patient is different than the drowning victim. In the patient who drowns, the initial aspiration leads to laryngospasm, which in turn leads to hypoxia, unconsciousness, and further aspiration. The intubated patient does not have to worry about laryngospasm, as the ET tube provides a fixed passage for air.

A better model for our investigation may be the patient with cardiogenic pulmonary edema, where the airway itself is not anatomically compromised. It is worth noting that patients in pulmonary edema may have up to 2 liters of fluid in the lungs. The pulmonary parenchyma can clearly hold a lot of liquid. The bigger question to me is if you have someone in pulmonary edema, how effective are nebulized agents in getting through the edema fluid to the actual sites of gas exchange?

I'll defer to someone who has more knowledge of such things, but I think "drowning" someone with ET fluids is an extremely remote possibility (I suppose if you wanted to push the issue you actually could drown someone using ET fluids, but it would take a special effort). I think this is probably true in children as well, given smaller and more concentrated doses of medications, although my assertion hedges a bit on this due to their relatively smaller lung volumes. The only way to prove this hypothesis as right or wrong is, of course, to give someone fluid down the ET tube until they actually drown. While there is virtually no limit to what medical students will subject themselves to in the name of science and $20, even in my worst collegiate two-Whoppers-for-99-cents days I would have backed out of this one.

Ryland, thanks for your question. It's good to be occasionally forced to think, research, experiment, and then think again. But it's also painful. Please don't make me do this again soon.

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Related Topics: Industry News, Airway and Respiratory, Medical Emergencies, Research

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