Alternative Methods of Drug Administration

Historical Perspective

ET drug administration dates to 1857, when Bernard demonstrated that the lung could rapidly absorb a solution of curare. In this historical experiment, he instilled a fatal solution into the upper respiratory tract of dogs by way of a tracheostomy. Over the following decades, other investigators expanded this work and demonstrated that solutions containing salicylates, atropine, potassium iodide, strychnine, and chloral hydrate were also rapidly absorbed from the lung and excreted in the urine after injecting aqueous solutions into the tracheas of experimental animals. The use of intrapulmonary medication for the treatment of lung disease gained further acceptance when studies demonstrated that inhaling epinephrine mist dramatically relieved the symptoms of asthma.

In the late 1930s and 1940s, several important observations were made concerning ET drug therapy: (1) penicillin delivered by the ET route demonstrated a depot effect, which resulted in therapeutic blood levels that lasted twice as long as those with intramuscular (IM) injection ; (2) various diluents mixed with penicillin affected both the rate and the degree of absorption from the lungs; and (3) higher serum drug levels were attained with direct ET drug administration than with aerosolized administration. In the 1950s it was noted that drugs delivered endotracheally were absorbed much more rapidly than those applied to the posterior part of the pharynx. Drugs applied locally to the larynx and trachea were absorbed rapidly and even resulted in blood levels significant enough to cause adverse anesthetic reactions.

In 1967, Redding and coworkers studied the use of ET administration as a route of drug delivery in a canine model of cardiopulmonary arrest. They administered epinephrine by the IV, intracardiac, and intratracheal routes to resuscitate dogs that had undergone both respiratory and circulatory arrest secondary to hypoxia. They then evaluated the effectiveness of the epinephrine after administration of the drug by all three of these routes. Their study revealed that all three routes of drug administration were equally effective in restoring the circulation of dogs in hypoxia-induced cardiac arrest, again demonstrating that the ET route of drug delivery provides effective access to the systemic circulation.

In the late 1970s, Roberts, Greenberg, and colleagues studied ET drug delivery in a series of laboratory experiments and clinical applications of ET epinephrine. Since that time, a number of important animal and human studies, as well as case reports, have been published in which the various aspects of ET drug administration were investigated. These studies have addressed (1) the appropriate dose of drug to administer; (2) the effect of the drug solution's volume; (3) the effect of different diluent solutions; (4) the role of different ET drug delivery techniques; and (5) the effects of hypoxia, hypotension, shock, and cardiopulmonary arrest on the absorption, distribution, and efficacy of endotracheally administered drugs.

Recommendations for ET Drug Delivery

ET drug delivery is not the delivery method of choice if other routes are available. The American Heart Association (AHA) recommends that if IV access is not available, IO access should be obtained. The AHA makes specific recommendations regarding the use of ET drug delivery for cardiac resuscitation ( Table 26.1 ).

Indications

ET drug therapy is indicated when emergency pharmacologic intervention is needed and other access, either IV or IO, is not available. Specific indications for the delivery of a drug endotracheally are the same as those for IV and IO administration. However, only a limited number of emergency drugs can be given safely by the ET route. Medications that are appropriate for ET administration based on animal and human studies include epinephrine, atropine, lidocaine, and naloxone. Diazepam has also been shown to be effective, but with the possibility of a medication (or diluent) induced pneumonitis. The AHA has removed diazepam from its list of medications that can be given safely via the ET route.

Experimental studies of vasopressin, midazolam, flumazenil, and propranolol, in animal models suggest that these medications may also be effective when administered endotracheally, but no clinical studies in humans have been conducted to verify these findings. Based on a study by Wenzel and colleagues, the 2010 ACLS guidelines added vasopressin to the list of cardiac resuscitation drugs that can be administered via the ET route. However, vasopressin was removed from the 2015 ACLS out-of-hospital cardiac arrest guidelines due to equivalency of response to epinephrine and a want to simplify arrest algorithms. As midazolam is approved for IM use, it seems unlikely that ET administration would be frequently used. Palmer demonstrated that therapeutic blood levels of flumazenil were obtained within 1 minute after ET delivery of 1 mg of the drug diluted in 10 mL of saline, which is 10 times the recommended IV dose of 0.1- to 0.2-mg aliquots.

Contraindications

At present, the only true contraindication to the ET delivery of an appropriate drug is the presence of another form of access to the systemic circulation through which the needed drug can be delivered rapidly and effectively. Specific medications have been shown to be ineffective or unsafe when given via the ET route. Sodium bicarbonate and amiodarone have direct deleterious effects on the lungs. Bretylium and isoproterenol have not been shown to attain adequate serum levels despite high ET doses given.

Equipment

The patient must first be endotracheally intubated. In studies in which the recommended ET tube doses of medications were administered by Combitube (Kendall-Sheridan, Argyle, NY) or laryngeal mask airway (LMA North America, San Diego, CA), absorption of drugs was found to be subtherapeutic. A Combitube, when placed in the esophagus (requiring medications to travel out the side holes to reach the trachea), needs 10 times more epinephrine than that used with an ET tube to obtain the same serum concentration and hemodynamic effects. Presumably, a Combitube that enters the trachea directly would function equivalently to an ET tube, but no studies have been done to support this assumption.

The equipment listed here is that required to perform any of the four different techniques described. This equipment is suggested for the ideal situation; at no time should drug delivery be delayed while searching for the “perfect” piece of equipment.

• 1.

  Manual bag ventilation device capable of delivering a fraction of inspiratory oxygen (Fi o ₂ ) of at least 50%. When ET drug delivery is indicated, the patient's condition almost always warrants supplemental oxygen. Although the technique may not result in any significant deterioration in respiratory function, it is still advisable to administer additional oxygen after drug delivery. Use the bag ventilation device to also deliver several rapid insufflations immediately after drug delivery to assist in delivery of the drug distally, where it may be absorbed more rapidly and effectively. The priorities of drug administration via the ET route must be balanced against the potential deleterious effects that such rapid insufflation might have on hemodynamics and cerebral perfusion. Excessive hyperventilation of victims of out-of-hospital cardiac arrest is common and associated with poor outcomes.

• 2.

  A fine-bore catheter or special ET tube designed to deliver the drug at or beyond the distal end of the ET tube. For adults, select a catheter that is at least 8 Fr in size and 35 cm (14 inches) in length. It should be long enough to protrude past the distal end of the ET tube. The diameter of the catheter should be large enough to allow rapid delivery of 10 mL of solution. In children, the distance to the end of the ET tube is usually equal to three times the circumference of the tube in centimeters measuring from the lip. So for example, in a child intubated with a 4.0 ET tube, make sure the catheter tip lies at least 12 cm distal to where the ET tube enters the mouth. Several different types of tubes and catheters commonly available in the emergency department (ED) can be used for this purpose:

  • a.

    A 16-gauge central venous pressure or cutdown catheter. Because most are only 30 cm in length, the proximal end of the ET tube should be shortened so that the catheter can protrude past the end.

  • b.

    An 8- or 10-Fr polyethylene pediatric feeding tube (e.g., Argyle, St. Louis). These tubes are much longer than needed, so cut them to reduce dead space. Luer-Lok ends fit onto the proximal end of the tube. For neonates, use a 5-Fr feeding tube with a syringe and an IV adapter.

  • c.

    An 8-Fr (or larger) pediatric pulmonary suction catheter without the control port. Because this catheter is designed to extend past the tip of the ET tube, it is an ideal length. However, with some brands it is difficult to attach a syringe or IV adapter lock after the suction control port is removed.

    Alternatively, some ET tubes are made with built-in ports that allow the instillation of drugs without removing the bag ventilation device.

• 3.

  An IV adapter lock. This can be placed as needed onto the proximal end of the irrigation lumen of the Hi-Lo Jet Tracheal Tube (Nellcor, Pleasanton, CA) or on the catheters described previously to convert them for use with prefilled syringes. This adapter is generally unnecessary if a standard syringe is used.

• 4.

  A 10 to 20 mL syringe, preferably a Luer-Lok type, large enough to deliver the desired volume of drug solution plus an additional 5 mL of air. Most of the medications now prescribed for emergency situations come in prefilled syringes. This type of apparatus does not usually allow one to draw up diluent or an additional volume of air to empty the syringe of solution. In addition, depending on the manufacturer and model, some prefilled syringes have either needles or a needleless system that may require an IV adapter lock to use them for ET injection.

• 5.

  Diluent solution. Keep an adequate volume of diluent available, such as normal saline or distilled water.

• 6.

  Medication to be instilled.

• 7.

  An 18- or 19-gauge needle to draw up the medication and inject it. Use an 18-gauge, 8.9-cm (3.5-inch) spinal needle for direct instillation of medications into the proximal end of the ET tube.

• 8.

  Alcohol wipes to clean the vials and injection ports.

• 9.

  Gloves, mask, and eye protection. After instillation, the solution often refluxes out of the ET tube, which makes blood and body fluid precautions critical.

Procedure

The procedure of choice is one that will deliver the medication to the patient in the least amount of time. Secure the ET tube before instilling medications endotracheally to prevent the tube from being expelled if the patient coughs. Inflate the cuff of the tube, if present.

Direct Instillation Into the ET Tube

While the patient is being ventilated, draw up the desired drug into a syringe (or use a prefilled syringe) ( Fig. 26.1 , step 1 ). Dilute the drug to a final volume of 10 mL (adults), 5 mL (children), or 1 mL (neonates) with normal saline or distilled water. Attach an 18- or 19-gauge needle. Some authors recommend using an 8.9-cm (3.5-inch) spinal needle. If using a prefilled syringe, draw up an appropriate volume of diluent in a second syringe so that the total instillation volume (drug plus diluent) equals 10 mL (adults), 5 mL (children), or 1 mL (neonates). Attach an 18- or 19-gauge needle which will be used to flush the ET tube after instillation of the drug.

Interrupt the connection between the proximal end of the ET tube and the bag ventilation device. Insert the needle of the syringe into the proximal opening of the ET tube (see Fig. 26.1 , step 2 ). Hold the proximal end of the needle with one hand to prevent loss of the needle into the tube. Inject the drug solution rapidly and forcefully. If using a prefilled syringe, flush the tube immediately with the diluent in a second syringe. If the patient makes an effort to cough, place a thumb over the opening of the ET tube to prevent expulsion of the solution. Reattach the bag ventilation device and deliver five rapid insufflations.

Use of the ET Atomizer

The Mucosal Atomizer Device-Endotracheal Tube (MADett, LMA North America, San Diego, CA) is an L-shaped port that attaches to both the ventilator bag and the ET tube ( Fig. 26.3 ; see also Fig. 26.1 , step 7 ). A catheter is inserted into the adapter and a mark is aligned at the 26-cm line of the ET tube. The catheter is then locked into place in the adapter. The L shape allows ventilation of the patient to be uninterrupted while medication is administered via the catheter and atomized into the patient's lung mucosa at the distal tip that protrudes from the end of the ET tube. This device can be used only with ET tubes 7.0 mm or larger and longer than 28 cm.

Complications

Reported complications of ET drug therapy are rare, in part because of the infrequent use of this technique. Because most patients who receive ET drug therapy are in cardiopulmonary arrest or are otherwise critically ill, it is difficult to ascertain whether an adverse outcome is the result of the therapy.

With regard to the techniques of ET drug administration, no serious complications have been reported. A theoretical complication is loss of a needle or catheter down the ET tube, which can be prevented by holding the catheter or needle while instilling the drug.

After ET drug administration, the well-described systemic effects of drugs administered in emergency situations may produce adverse effects. Administration of epinephrine during cardiopulmonary resuscitation (CPR) has been noted in case reports to produce prolonged hypertension, tachycardia, and arrhythmias after the return of a perfusing rhythm. It appears that these side effects are related to the depot effect, in which larger doses of drugs administered endotracheally are released slowly over time. In addition to epinephrine, atropine and lidocaine also exhibit a depot effect when administered endotracheally. No serious long-term sequelae, however, have been reported to result from this effect.

A potential concern with ET drug therapy is a transient decrease in arterial oxygen content during or after drug delivery. If total volumes are maintained between 5 and 10 mL in adults, the effect on pulmonary function appears to be minimal. Supplemental oxygen should always be administered to improve oxygenation and offset any transient drop in arterial oxygen content that might develop.

One unusual complication of ET epinephrine is that, during CPR, some of the instilled medication may be expelled and enter the eye. This will produce a fixed dilated pupil, simulating brain death or, if unilateral, brain herniation.