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EDITORIAL

A Strategy to Improve Endobronchial Drug Administration

Volker Wenzel, MD^*, Andreas W. Prengel, MD, and Karl H. Lindner, MD^*

Department of Anesthesiology and Critical Care Medicine, Knappschafts-Hospital, Ruhr-University, Bochum, Germany *Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens-University, Innsbruck, Austria; and

Address correspondence to Dr. Volker Wenzel, Leopold-Franzens-University, Department of Anesthesiology and Critical Care Medicine, Anichstrasse 35, 6020 Innsbruck, Austria. Address e-mail to volker.wenzel{at}uibk.ac.at Address reprint requests to Dr. Karl H. Lindner, The Leopold-Franzens-University of Innsbruck, Department of Anesthesiology and Critical Care Medicine, Anichstrasse 35, 6020 Innsbruck, Austria.

In this issue of Anesthesia & Analgesia, Naganobu et al. (1) report that, in dogs, 20 µg/kg epinephrine given endobronchially in combination with 2 mL distilled water increased both epinephrine plasma levels and arterial blood pressure significantly more than did 2 mL normal saline as diluent of 20 µg/kg endobronchial epinephrine, indicating that distilled water provided a "solvent drag" for endobronchial epinephrine. Although distilled water administered into the endobronchial tree transiently decreased partial-pressure oxygen more than did normal saline, these changes are acceptable because of the profound benefit of the more rapid and extensive epinephrine effects.

Endobronchial drug administration may be a simple and rapid alternative during cardiopulmonary resuscitation (CPR), when endotracheal intubation is performed before IV cannulation (2), when the time interval to IV access is prolonged, or when attempts to establish IV access are unsuccessful (3). Thus, endobronchial drug delivery may be of advantage whenever intubation is performed before IV access has been obtained. Endobronchial drug administration strategy during CPR is not as simple as during stable cardiocirculatory conditions because of dependence on many factors, including drug conversion or degradation by lung tissue, drug structure and lung permeability, ventilation/perfusion ratio of the lung, drug dilution with saline or water, volume of dilution carrier, and depth of drug administration into the bronchial tree (4–9). The European Resuscitation Council therefore recommends the administration of drugs via an endotracheal tube (with normal saline as diluent) during CPR only as a second-line approach because of impaired absorption and unpredictable pharmacodynamics (10), whereas the American Heart Association CPR guidelines take a more liberal approach and state that endobronchial drugs (with normal saline or distilled water as diluent) should be administered if venous access is delayed (11).

This dichotomy of recommendations is at least partially based on a lack of adequate clinical data and results in frequent and lengthy discussions among advanced cardiac life support providers regarding when to administer endobronchial drugs during CPR: immediately after intubation, or if obtaining IV cannulation after endotracheal intubation takes longer than two, three, or maybe five minutes? This reflects the fact that some parts of the CPR guidelines are based on judgement of experts as a result of the lack of clinical data that could clearly answer these questions. Although the study of Naganobu et al. (1) lacks a dose-response curve, it is an initiation of a step-by-step approach to bring more light into the issue of endobronchial drug administration. Namely, if a rapid and significant blood pressure effect with endobronchial epinephrine given with distilled water can be bought for only a minor decrease in oxygen partial pressure, we might be onto a good approach. Although the results of Naganobu et al. (1) indicate that endobronchial epinephrine with distilled water acts so rapidly that obtaining intravascular access for drug administration would be a complete waste of time, there is doubt whether these conditions in a beating heart model can be extrapolated to the CPR setting without an increase in drug dosage. Accordingly, one of the next steps would be to convert this canine model to a cardiac arrest design and assess whether we can always administer epinephrine with distilled water endobronchially to achieve rapid blood pressure increases or if it is better to wait for IV access during CPR. During CPR, the "equipotent epinephrine dose" administered endobronchially is approximately 3 to 10 times larger than the IV dose (12,13). During CPR, lung perfusion is only approximately 10%–30% of the normal value, resulting in a pulmonary epinephrine depot. When cardiac output is restored after a large dose of endobronchially administered epinephrine, a prolonged reabsorption of epinephrine from the lungs into the pulmonary circulation may occur, resulting in arterial hypertension, malignant arrhythmias, and recurrence of ventricular fibrillation in the immediate postresuscitation phase.

Another question to be resolved is whether the alternative vasopressor for cardiac arrest management, vasopressin, can be used within a similar manner. In a previous experiment, endobronchial vasopressin subsequently resulted in similar blood pressure responses when given endobronchially (14), intraosseously (15), or IV (16). An increase in coronary perfusion pressure was delayed two to three minutes after endobronchial compared with IV vasopressin (14). A more rapid increase in coronary perfusion pressure might have been achieved with distilled water. The fascinating concept with vasopressin is that, based on the absorption kinetics of this drug, the same dose, whether administered IV, intraosseously, or endobronchially, it leads to the same increase in coronary perfusion pressure and successful resuscitation rates, minimizing the risk of a depot effect after CPR.

The desired endpoint of all research efforts would be to enable us to make recommendations such as: "If obtaining IV access after endotracheal intubation takes more than x seconds, administer y drug with z diluent endobronchially." This would make CPR recommendations more straightforward and, most likely, would decrease the duration of vital organ ischemia during CPR, which, in turn, may be beneficial for CPR outcome. Accordingly, IV drug administration remains the first-line strategy during CPR; administration of drugs via an endotracheal tube during CPR is only a second-line approach.

Acknowledgments

Supported, in part, by the Austrian Science Foundation Grant 14169-MED, Vienna, Austria; and a Founder’s grant of the Society of Critical Care Medicine, Chicago, IL.

References

1. Naganobu K, Hasebe Y, Uchiyama Y, et al. Comparison of distilled water and normal saline as diluents for endobronchial administration in the dog. Anesth Analg 2000;91:317–21.[Abstract/Free Full Text]
2. Lindemann R. Endotracheal administration of epinephrine during cardiopulmonary resuscitation [letter]. Am J Dis Child 1982;136:753.[Abstract/Free Full Text]
3. Hähnel J, Lindner KH, Ahnefeld FW. Endobronchial administration of emergency drugs. Resuscitation 1989;17:261–72.[Medline]
4. Prengel AW, Lindner KH, Hähnel J, et al. Endotracheal and endobronchial lidocaine administration: effects on plasma lidocaine concentration and blood gases. Crit Care Med 1991;19:911–5.[Web of Science][Medline]
5. Prengel AW, Lindner KH, Hähnel JH, et al. Pharmacokinetics and technique of endotracheal and deep endobronchial lidocaine administration. Anesth Analg 1993;77:985–9.[Abstract/Free Full Text]
6. Ralston SH, Tacker WA, Showen L, et al. Endotracheal versus intravenous epinephrine during electromechanical dissociation with CPR in dogs. Ann Emerg Med 1985;14:1044–8.[Web of Science][Medline]
7. Hähnel JH, Lindner KH, Schürmann C, et al. Endobronchial drug administration: does deep endobronchial delivery have advantages in comparison with simple injection through the endotracheal tube? Resuscitation 1990;20:193–202.[Web of Science][Medline]
8. Hähnel JH, Lindner KH, Schürmann C, et al. Plasma lidocaine levels and PaO₂ with endobronchial administration: dilution with normal saline or distilled water? Ann Emerg Med 1990;19:1314–7.[Web of Science][Medline]
9. Hähnel JH, Lindner KH, Schürmann C, et al. What is the optimal volume of administration for endobronchial drugs? Am J Emerg Med 1990;8:504–8.[Web of Science][Medline]
10. Robertson C, Steen P, Adgey J, et al. The 1998 European Resuscitation Council guidelines for adult advanced life support: a statement from the Working Group on Advanced Life Support, and approved by the executive committee. Resuscitation 1998;37:81–90.[Web of Science][Medline]
11. Emergency Cardiac Care Committee and Subcommittees, American Heart Association.Guidelines for cardiopulmonary resuscitation and emergency cardiac care. III. Adult advanced life support. J Am Med Assoc 1992;268:2199–241.[Abstract/Free Full Text]
12. Hörnchen U, Schüttler J, Stoeckel H, et al. Endobronchial instillation of epinephrine during cardiopulmonary resuscitation. Crit Care Med 1987;15:1037–9.[Web of Science][Medline]
13. Schüttler J, Bartsch A, Ebeling BJ, et al. Endobronchial administration of adrenaline in preclinical cardiopulmonary resuscitation [German]. Anästh Intensivther Notf Med 1987;22:63–8.
14. Wenzel V, Lindner KH, Prengel AW, et al. Endobronchial vasopressin improves survival during cardiopulmonary resuscitation in pigs. Anesthesiology 1997;86:1375–81.[Web of Science][Medline]
15. Wenzel V, Lindner KH, Augenstein S, et al. Intraosseous vasopressin improves coronary perfusion pressure rapidly during cardiopulmonary resuscitation in pigs. Crit Care Med 1999;27:1565–9.[Web of Science][Medline]
16. Wenzel V, Lindner KH, Prengel AW, et al. Vasopressin improves vital organ blood flow after prolonged cardiac arrest with postcountershock pulseless electrical activity in pigs. Crit Care Med 1999;27:486–92.[Web of Science][Medline]

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