Cardiovascular 4: Endotracheal Drug Delivery
The endotracheal (ET) route for drug delivery may be used when a life-threatening or serious condition requires immediate drug intervention, but intravenous or intraosseous access is not readily available. While many medications are absorbed through the endotracheal route, it is uncertain if drug delivery via this route is clinically equivalent to intravenous/intraosseous administration. Blood levels achieved through endotracheal delivery may not be comparable to those produced by IV/IO administration, and optimal doses are unknown.1 Therefore, endotracheal administration of resuscitation drugs should be considered a second-line intervention utilized only if IV and IO access cannot be established in a timely manner.
Endotracheal Drugs
If vascular access is unavailable, the ET route may be used for the administration of certain drugs, including lidocaine, epinephrine, atropine, naloxone, and vasopressin.2-4
| Remember the mnemonic NAVEL: | or LEAN (PEDS) |
|
N-Naloxone
A-Atropine V-Vasopressin (adults only) E-Epinephrine L-Lidocaine |
L-Lidocaine
E-Epinephrine A-Atropine N-Naloxone |
Endotracheal administration of medications other than those on this list may damage airway mucosa and is not recommended.1
Factors that Determine the Effectiveness of Endotracheal Drugs
- Method of Drug Delivery
In intubated patients, the ET delivered drug may be given either by direct injection of the solution down the ET tube or through a 5 French feeding catheter passed 0.5 cm beyond the distal tip of the ET tube. Some controversy exists regarding the degree of physiologic response when delivering a drug past the tip of the ET tube via a catheter placed through the ET tube.5,6 The American Heart Association (AHA) Guidelines recommend administration of the drugs directly down the endotracheal tube in adult and pediatric patients.1 No matter which method is used to deliver the drug, it is essential during resuscitation to stop chest compressions, spray the drug solution (adequately diluted) quickly down the tube, follow immediately with five manual ventilations to create a rapidly absorbed aerosol, and then resume chest compressions if necessary. Aerosolized sprays of drugs have been promoted as delivering the medications more distally and thus providing for more rapid absorption of drugs than solutions delivered in bolus form.7 While this may seem logical, this technique is cumbersome to accomplish in an arrested patient.
- Diluents Used With the Drugs
Various diluents used with an ET-delivered drug can affect the rate of absorption of a drug, the peak serum level attained by the drug, and the duration of therapeutic levels of the drug. Tracheal absorption is greater with distilled water as the diluent than with saline,8 but distilled water has a greater adverse effect on PaO2.9 Therefore, it appears to be safer to use saline as the diluent than to use distilled water.
- Volume
The most appropriate volume for ET drug delivery has not been determined. An insufficient volume may result in inadequate drug delivery and lack of the desired systemic effects. Placing an excess volume of solution into the ET tree may cause hypoxia or respiratory acidosis.2,9 Since many of the emergency drugs now come diluted in pre-filled syringes, this issue is frequently taken care of by the pre-diluted drug solutions that are available. AHA Guidelines1 suggest that in the adult the tracheal administered drug should be in 10 mL of solution and (PEDS) in pediatric patients the drug should be diluted up to 5 mL. The volume of solution (and the optimal drug doses) to give to neonates is unclear,10 but a reasonable volume to use is 2 mL.
- Drug Dosage
The true equivalent dose of drug delivered endotracheally versus intravenously is unknown. This controversy is apparent in the discrepancy in the AHA Guidelines for the drug doses to use for adults as opposed to (PEDS) pediatric or neonatal patients.4 For adults, the recommendation is to give all ET drugs at 2 to 2.5 times the recommended IV dose.1 PEDS: The recommended ET dose of epinephrine for pediatric patients is approximately 10 times the dose given via an IV route (Class IIb).4 The AHA Guidelines go on to state “it is logical to assume that doses of other resuscitation drugs administered tracheally should be increased compared with the IV dose.1"
- Duration of Drug Effect
Many studies2,5,11,12 have indicated that the duration of action of drugs given endotracheally is prolonged (depot effect) compared to the same drug dose given IV. Drugs where this depot effect has been observed include: epinephrine,5 atropine,11 and lidocaine.2
- The amount by which the kinetics of the drug is altered (if at all) when the drug is delivered endotracheally in shock/CPR is unknown.2
- The manner and the degree that accompanying diseases (like CHF, pulmonary edema, severe acidosis, COPD, or pneumonia frequently present in patients preceding cardiac and/or respiratory arrest) affect the absorption and physiologic response to drugs delivered to the respiratory tree is unknown.2
- The time interval from the ET administration of a drug until adequate physiologic response has not been adequately studied for many of the drugs used via the ET tube.2
- The maximum number of doses or the time interval between doses given via the endotracheal route has not been adequately studied.2
Specific Drug Observations and Recommendations:
Lidocaine: Current adult AHA Guidelines recommend4 that an ET-delivered dose of lidocaine of 2 to 4 mg/kg. For this ET dose to reach therapeutic levels takes 5 minutes and to reach peak levels takes 20 minutes. The level remains therapeutic for 30 to 60 minutes.13
Epinephrine: Current AHA Guidelines for ET use of epinephrine in an adult recommend4,14 using 2 to 2.5 times the standard IV dose of 1 mg (ET dose = 2 to 2.5 mg), while suggesting that the (PEDS) pediatric ET dose of epinephrine be increased by approximately 10 times the standard IV dose of 0.1 mL/kg of a 1:10 000 solution (0.01 mg/kg) (ET dose = 1 mL/kg of 1:10 000 solution or 0.1 mg/kg).4 For neonatal resuscitation, ET doses of epinephrine up to 0.1 mg/kg of a 1 to 10 000 (0.1 mg/mL) are suggested.4
Atropine: Current AHA Guidelines4 suggest that the recommended ET delivered dose of atropine be 2 to 2.5 the standard IV dose of 1 mg (ET dose= 2 to 2.5 mg). PEDS: AHA Guidelines4 suggest that the pediatric ET dose should be 0.04 to 0.6 mg/kg with a minimal dose of 0.1 mg.a
Naloxone: Human data on the use of naloxone ET is sparse to nonexistent. Current AHA Guidelines4 do not specifically give an adult dose for naloxone ET, but logic would suggest that the dose should be 2 to 2.5 times the standard IV/IO dose of 0.4 to 2 mg. PEDS: AHA Guidelines do not recommend ET use of naloxone in neonates; for pediatric patients, the AHA states that other routes are preferred.4 If used, a reasonable dose, based on 2 to 10 times the IV/IO dose of 0.1 mg/kg, would be 0.2 to 1 mg/kg. For a single dose, a maximum of 2 mg is consistent with standard dosing recommendations.
Vasopressin: The administration of vasopressin appears to be equally effective by ET and IV routes.3,15 No currently published studies clearly define the optimal dose of ET vasopressin. Therefore, at this time, using the standard IV dose of 40 units of vasopressin diluted with normal saline to 10 mL is reasonable. PEDS: There is no current recommendation for use of vasopressin in pediatric patients.
Conclusion
The administration of drugs via the ET route
is an option in special situations in which IV/IO access cannot be
obtained and critical medications must be given immediately. Continue
to seek intravenous or intraosseous access and use in place of the ET
route as soon as possible.
References
- ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 suppl 3):S742, S881-S882.
- Ward JT Jr. Endotracheal drug therapy. Am J Emerg Med. 1983;1:71-82.
- Babbs CF, Berg RA, Kette F, et al. Use of pressors in the treatment of cardiac arrest. Ann Emerg Med. 2001:37:S152-S162.
- Hazinski MF, Samson R, Schexnayder S, eds. 2010 Handbook of Emergency Cardiovascular Care. Dallas, Tx: American Heart Association, 2010.
- Roberts JR, Greenberg MI, Knaub MA, Kendrick ZV, Baskin SI. Blood levels following intravenous and endotracheal epinephrine administration. JACEP 1979;8:53-56.
- Jasani MS, Nadkarni VM, Finkelstein MS, Mandell GA, Salzman SK, Norman ME. Endotracheal epinephrine administration technique effects in pediatric porcine hypoxic-hypercarbic arrest. Crit Care Med. 1994; 22:1174-1180.
- Beakey JF, Gaensley EA, Segal MS. Pharmacodynamics of pulmonary absorption in man; the influence of various diluents on aerosol and intratracheal penicillin. Ann Intern Med. 1949; 31:805-820.
- Courtice FC, Phipps PJ. The absorption of fluids from the lungs. J Physiol. 1946; 105:186-190.
- Greenberg MI, Baskin SI, Kaplan AM, Urrichio FJ. Effects of endotracheally administered distilled water and normal saline on the arterial blood gases of dogs. Ann Emerg Med. 1982; 11:600-694.
- Kleinman ME, Oh W, Stonestreet BS. Comparison of intravenous and endotracheal epinephrine during cardiopulmonary resuscitation in newborn piglets. Crit Care Med. 1999; 27:2748-2754.
- Elam JO. The intrapulmonary route for CPR drugs. In Safar P, Elam JO, eds. Advances in Cardiopulmonary Resuscitation. New York, NY: Springer Verlag Inc., 1977; 132.
- Kaplan SA, Jack ML, Alexander K, Weinfeld RE. Pharmacokinetic profile of diazepam in man following single intravenous and oral and chronic oral administration. J Pharm Sci. 1973;62:1789-1796.
- Collinsworth KA, Kalman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrhythmic drug. Circulation. 1974;50:1217-1230.
- Aitkenhead AR. Drug administration during CPR: what route? Resuscitation. 1991:22:191-195.
- Wenzel V, Lindner KH, Prengel AW, Lurie KG, Strohmenger HU. Endobronchial vasopressin improves survival during cardiopulmonary resuscitation in pigs. Anesthesiology. 1997:86:1375-81.