Chapter 9. Endotracheal Medication Administration

Healthcare providers are charged with the primary goal of optimizing the oxygenation, ventilation, and the hemodynamic status of the patient during a resuscitation. In most cases, the first definitive intervention is to secure the airway through endotracheal (ET) intubation. The establishment of access to the systemic circulation soon follows. Vascular access in certain patients can be problematic. In such cases, the ability to administer medications endotracheally can be life saving.

Bernard first reported the ET route of medication administration in 1857, describing the alveolar absorption of curare in dogs. This discovery was followed by the observation that ET instilled salicylates appeared in the urine (Peiper 1884). In 1897, Washitzky studied the ET application of strychnine, atropine, chloral hydrate, and potassium iodide.1

The first suggestion for using the ET route for the therapy of pulmonary disease was in 1915.2 This idea evolved, culminating in a study in 1937, which recommended the use of inhaled epinephrine in asthmatics.3 The rapidity of pulmonary absorption was eventually utilized for resuscitation purposes 1967. This study demonstrated the equality of the intratracheal, intravenous (IV), and intracardiac routes of epinephrine administration in resuscitating hypoxia-induced cardiorespiratory arrest in dogs. This study began the utilization of the ET route for medication administration in emergent clinical situations.

Most experiments involving ET medication administration are conducted on subjects with normal cardiovascular function. Thus, there are still many questions remaining about the utility of this route in patients with cardiopulmonary arrest. While the alveolar-capillary membrane is a highly absorptive surface, numerous factors can undermine this potential. These include reduced pulmonary blood flow (less than 30% of normal during CPR), ventilation–perfusion mismatch, and compromised alveolar absorption (e.g., pulmonary edema and pneumonia) in cardiopulmonary arrest.5–7

During a cardiopulmonary arrest, ET administered medications are absorbed in a protracted manner. This phenomenon, termed the “depot effect”, is observed in laboratory and clinical experiments.5 Studying ET administered lidocaine (2 mg/kg) in nonarrest patients revealed a biphasic pattern of absorption, an initial immediate peak, and a second higher peak approximately 24 minutes later.8 Plasma lidocaine levels were still measurable 120 minutes postinstillation.8 In addition to the altered physiologic conditions of cardiopulmonary arrest as described above, local vasoconstriction induced by epinephrine may contribute to this “depot effect.”9 The relatively low initial plasma medication levels and then the subsequent extended plateau of plasma medication levels are also exhibited by the ET administration of atropine, epinephrine, and vasopressin.5,10

Medication Dose

The American Heart Association (AHA) suggests an ET medication dose of 2 to 2.5 times the recommended IV dose (Table 9-1).11 The optimal dose of ET administered medications is unknown. While there is a consensus that IV doses given endotracheally result in subtherapeutic plasma levels, the equipotent dose ranges from 3 to 10 times the IV dose in the literature.12–42

Many studies have noted the inadequacy of the currently recommended dose of epinephrine and atropine in cardiopulmonary arrest models.27,31,36 Niemann and Stratton retrospectively reviewed 136 adult medical arrests, both primary and secondary asystole, with less than 10 minutes to definitive care. The rates of response (positive rhythm) and return of spontaneous circulation were significantly greater in the IV medication group than both the ET medication group and the no therapy group.27

A recent discussion in the literature has drawn attention to the behavior of epinephrine when given at suboptimal doses. Epinephrine is used in arrest situations for its α-adrenergic effects. The β-adrenergic effects predominate when epinephrine is administered in small doses. This can transiently result in potentially harmful hypotension, decreased coronary perfusion pressure, and the diminished likelihood of return of spontaneous circulation.11 Manisterski et al. documented an early drop in mean arterial blood pressure with prolonged tachycardia after ET epinephrine at doses of 0.02, 0.035, 0.1, and 0.2 mg/kg in healthy dogs.28 Only the 0.3 mg/kg dose was effective in achieving an increase in blood pressure without a transient drop.28 Findings such as this have prompted investigations on pretreatment with β-blockers (e.g., propranolol) prior to ET epinephrine administration, which does blunt the early β-effects.29,30 Although more research is needed in this area, these studies do question the efficacy of the current recommended ET epinephrine dose, calling for higher ET doses.

Despite these results, concerns regarding the “depot effect” have kept the current ET medication dose recommendation at 2 to 2.5 times the IV dose. This is to avoid the prolonged side effects in the critical postresuscitation period.5 This compromise leads to many uncertainties regarding the effectiveness and reliability of the ET route for medication administration.9,31,32

Diluent

A primary goal in administering ET medications is to achieve rapid absorption. This goal can be reached with larger volumes of diluent, but is tempered by the potentially detrimental effects on pulmonary function.4 The current recommended volumes for ET instillation of each medication are dilution to a total volume of 10 mL in adults, 5 mL for children, and 1 mL for neonates.11,26

Another controversy arises with respect to the type of diluent used. Distilled water and 0.9% saline have been utilized for ET medication administration and are currently recommended by the AHA.11 In theory, water creates a greater osmotic gradient to potentially speed up medication absorption. This could also lead to a greater disruption of pulmonary surfactant, thereby hindering gas exchange.5 This has been confirmed in nonarrest experiments using dogs.33 It was later disputed utilizing much smaller volumes (2 and 10 mL) of instilled medication.34,35 These studies found that distilled water provides more rapid and more effective absorption (higher peak serum medication levels) than 0.9% saline without a physiologically significant drop in PaO2.

Pediatric Considerations

Much of the debate regarding ET medication administration still exists in pediatrics. While approximately half of pediatric arrests are resuscitated without the use of medications, resuscitation drugs may be required to achieve return of spontaneous circulation. Obtaining vascular access in children, especially in neonates, can be extremely difficult. This makes the ET medication administration route a possible option for early resuscitative efforts.37 There are no published pediatric or neonatal studies examining the type or volume of diluent, only consensus recommendations.11,26

A major difference between adults and children in arrest is the absorptive capacity of the immature lung. In particular, the surface area is smaller, the diffusion coefficient is larger, and there exists the potential for right to left shunts in children.9,38 These conditions greatly affect an already unreliable absorptive process.

The indications, procedures, and complications are considered to be much the same in pediatrics as in adults. There are very few published studies focused on ET medication administration in pediatrics. Those that studied epinephrine in pediatric arrest agree that it seems to take 10 times the IV medication dose to achieve appropriate serum epinephrine levels and responses in the heart rate and blood pressure.26,38,39 A retrospective study of neonates who received epinephrine in the delivery room underscores the difficulty of obtaining vascular access.40 Almost all the neonates (94%, n = 52) received their first dose of epinephrine via the ET route. Of these, 32% obtained return of spontaneous circulation while the rest required additional epinephrine through their IV line once it was established. The authors concluded that the currently recommended ET epinephrine dose of 0.01 to 0.03 mg/kg is ineffective.

The ET administration of medications is reserved for resuscitations in which vascular access (i.e., IV or intraosseous (IO)) is delayed.11 This may apply to the resuscitation of any patient with cardiovascular collapse. The ET route may be more frequently encountered in certain patient populations traditionally associated with difficult vascular access such as neonates, the obese, cancer patients, sickle cell patients, IV drug abusers, burn patients, and dialysis patients.12 The goal is to increase the probability of successful resuscitation despite a delay in obtaining definitive systemic vascular access.

The ET route is recommended for the administration of lidocaine, epinephrine, atropine, naloxone, and vasopressin.11 Other medications that can be administered but are not widely used include flumazenil, diazepam, midazolam, penicillins, sulfonamides, and aminoglycosides.13–17

The absorption of medications given through an ET tube is unpredictable during a cardiopulmonary arrest. The only contraindication to ET medication administration is the patient having IV or IO access. The ET route may be used initially until IV or IO access is established.

• ET tube, standard or specialty ET tube
• Bag-valve device
• Medication to be administered
• Diluent, 0.9% normal saline or distilled water
• 10 mL syringe
• 18 gauge needle
• IV adapter lock
• Water-soluble lubricant
• Optional catheters (suction, feeding, or central venous)

The patient may be intubated with a standard ET tube, an ET tube with a monitoring lumen, or a specialty ET tube with a medication injection port.18 The EDGAR ET tube (endobronchial drug and gas application during resuscitation, Rusch, Germany) has a separate injection channel that terminates at the tip of the ET tube. This ET tube is currently available in Europe, but not in the United States. The Stat-Med ET tube (Hudson RCI, Temecula, CA) has a separate injection port and channel that terminates distal to the inflated cuff (Figure 9-1). These two ET tubes allow the ET administration of medications without interrupting CPR compressions or ventilation.

The LITA ET tube (Hudson RCI, Temecula, CA) is a modification of the Stat-Med ET tube. Like the Stat-Med, it has a separate injection port and channel. The channel has eight openings above the cuff and two below the cuff. This ET tube was designed for use with local anesthetic solutions to anesthetize the tracheal mucosa. It should not be used to administer resuscitation medications. They will mostly pool above the cuff in the trachea and not get properly absorbed.

Other, optional, equipment may be used depending on the technique used to administer the medications. A catheter may be used to administer the medication. A suction, feeding, or central venous catheter may be introduced into the ET tube to administer medications more distally. An IV adapter lock is required on the proximal end of these catheters to allow the syringe to attach to the catheter. There are no formal guidelines regarding proper catheter size. There are recommendations to use a 16 French (Fr) suction catheter in adults,19 an 8 Fr feeding catheter in children,20 and a 5 Fr feeding catheter in neonates.21

The administration of drugs through laryngeal mask airways (LMAs, Chapter 19) and combitubes (Chapter 20) as compared with ET tubes has been studied. Medication instilled through a catheter inserted through an LMA and into the trachea achieved the equivalent blood concentrations as through an ET tube.43 Unfortunately, it is often difficult to successfully pass a catheter through an LMA and into the trachea.22 Administration of lidocaine through LMAs was unreliable (4 out of 10 reached therapeutic plasma levels) as compared with ET tubes (10 out of 10 reached therapeutic plasma levels) in nonarrest patients.22 Subtherapeutic plasma medication levels were noted when comparing lidocaine administration via combitubes (placed in the esophagus) versus ET tubes.23

The intubating LMA (ILMA) is a modification of an LMA. It is designed to allow the blind passage of an ET tube through it and into the trachea. Insertion of a catheter through an ILMA was only successful in 92% of the attempts.44 It also required a mean time of 20 seconds (range 11–44 seconds), which is too long by AHA guidelines to discontinue CPR.11

An interesting device is the MADett™ or mucosal atomizer device (Wolfe Tory Medical, Salt Lake City, UT, Figure 9-2). This device allows ET medication administration without stopping compressions and ventilations of CPR, and no splash back into the face of the person administering the medication. The MADett™ must be used only with an ET tube size greater or equal to 7.0 mm inner diameter and a length of at least 28 cm.

Proximal Medication Instillation

The simplest method for ET medication administration is direct instillation. Prepare the medication or use a prefilled syringe with a needleless adapter. If drawing your own medications, use a syringe with an 18 gauge needle to draw up the medication into the syringe. Draw up sterile water or 0.9% normal saline to dilute the medication to the appropriate volume. Remove the bag-valve-mask device from the ET tube. Briefly interrupt external chest compressions. Remove the 18 gauge needle from the syringe. Inject the diluted medication in the syringe or from the prefilled syringe into the proximal end of the ET tube. Replace the bag-valve-mask device and manually ventilate five times in quick succession. The forced hyperventilation results in bilateral and distal distribution of the medication.12 Resume chest compressions.

Always remove the needle from the syringe when injecting medication into the ET tube. Some medical personnel may choose to leave the needle attached to the syringe for convenience or to decrease any delays in medication administration. The needle, if loose, can fall off the syringe and into the ET tube. It will then “ride the tube” and can become an airway foreign body in the distal trachea or main bronchus. The needle also slows down medication injection into the ET tube, delaying restarting CPR.

Proximal Needle Injection of Medication into the ET Tube

An alternative approach is to piercing the proximal end of the ET tube with an 18 gauge needle attached to the medication-filled syringe.24 Care must be taken to assure that the needle does not damage the ET cuff inflation tube and the tip of the needle is completely within the lumen of the ET tube. Instill the medication during inspiration, when the bag is squeezed. Detach the syringe from the needle. Attach a new medication-filled syringe or refill the used syringe to instill other medications without removing the needle from the ET tube. The remaining hole in the ET tube after the resuscitation and the needle is removed results in a negligible air leak that may be closed with a piece of tape.

Distal Medication Instillation

Medications may be administered deeper through a catheter inserted into the ET tube. This technique minimizes medication adherence to the walls of the ET tube. Prepare the medication and catheter. Draw up the appropriate medication and diluent into a syringe or use a prefilled syringe. Choose the appropriate type and size of catheter. Attach an IV adapter lock to the proximal end of the catheter. The proximal end of the catheter may have to be cut off if it is flared, tapered, or too big for the IV adapter lock to fit.25 After cutting the proximal end, attach the IV adapter lock.

Remove the bag-valve-mask device from the ET tube. Briefly interrupt external chest compressions. Lightly lubricate the catheter with a water-soluble lubricant, so that it will advance easily through the ET tube. Insert the catheter (feeding, venous, and suction) into the ET tube until its tip extends just beyond the distal end of the ET tube by approximately 1 to 2 cm. Attach the medication-filled syringe to the IV catheter lock if using a feeding or suction tube, or the leur lock if using a central venous catheter. Inject the medication into the catheter followed by 5 mL of air to clear the tube of any residual medication. Replace the bag-valve-mask device and manually ventilate five times in quick succession. The forced hyperventilation results in bilateral and distal distribution of the medication.12 Resume chest compressions.

Techniques to Minimize Interruption of Ventilations and Compressions

The goal of CPR is to minimize interruptions of chest compression and ventilation. This can be accomplished using one of the specialized ET tubes discussed in the “Equipment” section of this chapter. These ET tubes may be placed initially in a patient with a cardiopulmonary arrest. If a standard ET tube is initially placed, it can be exchanged for one of these specialized ET tubes. Prepare the medication. Attach the medication-filled syringe to the injection port of the ET tube. Inject the medication into the ET tube injection port during inspiration with the bag-valve-mask device. The diluted drug solution may be followed by the injection of 5 mL of air to clear the tube of any residual medication.

An alternative to using these specialty ET tubes is to attach the MADett™ to a standard ET tube. The MADett™ is quick, simple, and easy to use (Figure 9-3). The patient should already be intubated. Stop ventilations, but not compressions, and remove the bag-valve device from the ET tube. Attach the MADett™ adapter onto the ET tube (Figure 9-3A). Resume ventilations by attaching the bag-valve device to the side port of the adapter. Advance the MADett™ catheter into the ET tube until the black mark on the catheter lines up with the 26 cm mark on the ET tube (Figure 9-3B). Tighten the lock nut on the MADett™ adapter to hold the catheter in place, so that it will not be advanced or withdrawn. Attach the medication-containing syringe to the luer lock attachment and inject the medication while ventilating the patient (Figure 9-3C). Inject the medication while bagging the patient to allow the atomized medication (Figure 9-3D) to penetrate deeply into the respiratory tract.

Which Is the Best Technique?

Mielke et al. studied the time involved to perform each technique by Paramedics and Emergency Physicians.25 These included direct injection into the ET tube, via suction catheter, via central venous catheter, and use of an EDGAR tube with an injection channel. Overall, both direct injection into the ET tube and use of the EDGAR tube were significantly faster (median 7 and 8 seconds, respectively) than the catheter techniques (median 26 and 30 seconds). In their discussion, a theoretical disadvantage of using a catheter was the instillation of medication unilaterally down one of the mainstem bronchi if the catheter was advanced too far down the ET tube. This would thereby decrease the potential absorptive surface by half. This potential negative was offset, however, by the use of larger volumes of medication and the application of postinstillation hyperventilation.25

Studying the same three techniques (direct ET instillation, via a suction catheter, and use of an EDGAR tube) in nonarrest patients, no difference was found in the pharmacokinetic response to lidocaine administration.19 Specifically, there was no significant difference in serum lidocaine concentration, heart rate, blood pressure, end-tidal PCO2, and oxygen saturation among the three groups. These findings disputed any previous assertion that using a catheter provided an advantage by instilling medications more peripherally (therefore closer to the absorptive surface). They also reported that catheter use led to a significantly longer interruption in ventilation (10.2 seconds) compared to the direct ET instillation group (3.6 seconds).19

These techniques were evaluated in a porcine model representing pediatric respiratory arrests.20 Epinephrine was instilled through an ET tube, a feeding catheter, and an ET tube with a monitoring lumen. There was no significant difference in hemodynamic response or in the rate of successful resuscitation. Interestingly, by using radiolabeled epinephrine, they were also able to show that medication adherence to the ET tube was minimal and that there was no difference in bilateral pulmonary distribution among the three groups.

There are no specific assessments related to the procedure of endotracheal medication administration. Medications instilled through the ET tube enter the respiratory tract. Large volumes of fluid in the lung may interfere with oxygen exchange, cause a pneumonitis, or cause pulmonary edema. The assessment is related to the resuscitation itself (chest compression, positive pressure ventilation, defibrillation, etc.). There is no method to determine plasma medication levels of endotracheally administered medications in a timely manner to impact clinical care.

After a successful resuscitation, there is no indication to remove one of the specialty ET tubes if used. These can be left in place and used similar to a standard ET tube. Place a piece of tape over the needle hole in the ET tube if the needle injection technique was used. Otherwise, no aftercare specific to the procedure of endotracheal medication administration is required.

The main complication of administering medications by the ET route arises from the “depot effect.” Epinephrine, atropine, vasopressin, and lidocaine have been observed to be absorbed in a prolonged fashion, much like a continuous intravenous infusion. This phenomenon has been attributed to local vasoconstriction (epinephrine), poor lung perfusion, vascular congestion due to markedly diminished cardiac output, and comorbid conditions (e.g., pulmonary edema, atelectasis, COPD, etc.) present at the time of the arrest. However, this sustained drug effect has also been observed in nonarrest patients.8 The result, in the case of epinephrine, is prolonged hypertension, malignant arrhythmias, and tachycardia in the postresuscitative period.36,41 Endotracheal atropine can cause sustained tachycardia.5,42 Endotracheal vasopressin can cause sustained bradycardia, prompting experiments with prophylactic atropine.10 These prolonged effects may hinder both cerebral and cardiac recovery once return of spontaneous circulation is established.42

Another drawback to ET medication administration is the transient impairment of gas exchange. Many studies describe an early reduction in PaO2, which is directly correlated with the volume of liquid instilled. There is a greater drop in PaO2 after instilling water than after saline. In nonarrest dogs using large volumes of diluent (2 mL/kg), there was a decrease in PaO2 to 61% of baseline with distilled water as opposed to 75% of baseline with saline.33 In nonarrest humans with instilled volumes of 10 mL through the ET tube, there was a drop in PaO2 from 157 to 95 mmHg with saline and from 157 to 103 mmHg with water.34 Hypoxia, to a much greater extent than hypercarbia, has been reported in nonarrest models. Alterations in pulmonary gas exchange in arrest are less well understood. However, adherence to recommended volumes and the use of hyperventilation postinstillation has the potential to offset this complication.

Despite concerns regarding the efficacy of ET medication administration, this route remains second line for instances when vascular access (IV or IO) is not available for the instillation of resuscitation medications. When IV or IO access is delayed, the ET route should be considered to increase the chances of successful return of spontaneous circulation. Attempts at vascular access should be continued during the administration of ET medications. The use of the ET route should be discontinued once vascular access is achieved. Despite its inherent issues, knowledge of the ET medication administration procedure can be life saving.