MADettÔ Educational
Center:
Abstracts: Endotracheal tube medication delivery:
Drug delivery directly into the lung via catheter passed
through the ETT is superior to delivery when the drug is squirted into the
ETT:
1.
Mazkereth R,
Paret G, Ezra D, et al. Epinephrine blood
concentrations after peripheral bronchial versus endotracheal administration of
epinephrine in dogs. Crit Care Med 1992;
20:1582-7.
BACKGROUND AND METHODS: Emergency endotracheal drug administration has become an acceptable route for drug delivery during cardiopulmonary resuscitation. The purpose of the present study was to determine whether the site of endotracheal epinephrine injection is an important factor in its absorption. Epinephrine (1:1000), in a dose of 0.02 mg/kg diluted in 2 mL of saline, was given to ten anesthetized mongrel dogs. Each dog was studied twice: once when the epinephrine was injected into the endotracheal tube, and on another day, through the endotracheal tube via a flexible catheter wedged into a peripheral bronchus. Arterial blood samples for plasma epinephrine concentration determinations were collected, before and at 1, 2, 5, 10, 15, and 30 mins after each intratracheal drug administration. RESULTS: Both routes of epinephrine administration significantly increased plasma concentrations within 1 min of injection. Higher plasma epinephrine concentrations were achieved after peripheral bronchial epinephrine administration (maximal concentration 8.9 +/- 3.2 vs. 2.0 +/- 0.4 ng/mL), and the total dose absorbed was significantly (76.5 +/- 13.5 vs. 36.7 +/- 6.5 ng/min/mL, p < .05) higher. The time interval to reach maximal concentration was significantly shorter with the peripheral bronchial dosing than with the endotracheal route (1.3 +/- 0.2 vs. 2.7 +/- 0.5 min, p < .05). Neither group demonstrated a significant change in heart rate, and both had similar, minor decreases in BP for > 2 to 5 mins. There were no significant differences between the arterial blood gases of the two groups at various stages of the experiment. CONCLUSIONS: In dogs, epinephrine administered via the peripheral bronchial route has a clear pharmacologic advantage over the endotracheal route. This advantage may be more important during cardiopulmonary resuscitation conditions and other low flow states, and may account for the failure observed with the endotracheal route in recently published clinical reports.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1424703&dopt=Abstract
2.
Paret G, Mazkereth R, Sella R, et al. Atropine pharmacokinetics and
pharmacodynamics following endotracheal versus endobronchial administration in
dogs. Resuscitation 1999; 41:57-62.
Emergency endotracheal and endobronchial drug administration provide an effective alternative for intravenous drug delivery during cardiopulmonary resuscitation. The purpose of the present study was to determine the immediate pharmacokinetic and pharmacodynamic properties of atropine following administration by either of these routes. Atropine (0.02 mg/kg) was given to seven anaesthetized mongrel dogs. Each dog was studied twice: once when atropine was injected into the endotracheal tube, and on another day when atropine was given via a flexible catheter wedged into a peripheral bronchus. Plasma atropine concentrations and blood gases were measured during 60 min following drug administration. Both routes of atropine administration differed significantly in three measures: the maximal atropine concentration (Cmax) was significantly higher with the endobronchial administration 40.0 +/- 7.8 ng/ml compared to 23.9 +/- 5 ng/ml endotracheally (P = 0.008); atropine's elimination (t1/2beta) half-life was significantly longer with the endobronchial route (39.3 +/- 5.2 min vs. 28.0 +/- 7.9 min; P = 0.05); Endobronchial administration resulted in an increase of 16% in heart rate, beginning immediately after drug delivery and peaking after 5 min. Other pharmacokinetic parameters were not significantly different. We conclude that endobronchial administration of atropine has a clear advantage over the endotracheal route.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10459593&dopt=Abstract
Drug delivery to the lungs directly through an endotracheal tube results in far higher drug delivery to the lung and circulation than if it is nebulized.
1.
Bressolle F, de
la Coussaye JE, Ayoub R, et
al. Endotracheal and aerosol administrations of ceftazidime in patients with
nosocomial pneumonia: pharmacokinetics and absolute bioavailability. Antimicrob Agents Chemother 1992;
36:1404-11.
Pharmacokinetic studies on ceftazidime, an aminothiazole cephalosporin with a wide spectrum of antibacterial activity, including activity against Pseudomonas aeruginosa, were performed in patients with nosocomial pneumonia. The concentration-time profiles of ceftazidime in plasma, urine, and bronchial secretions of 12 patients were investigated after intravenous (i.v.) (n = 12), endotracheal (n = 10), and aerosol (n = 5) administrations. In all cases a 1-g dose was administered. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with UV detection. The elimination of the drug from the blood followed a biexponential (i.v. administration) or a monoexponential (endotracheal and aerosol administrations) decay, with an elimination half-life of 6 h and a total body clearance of 4.2 liters/h. The apparent volume of distribution was 0.36 liter/kg of body weight. Renal clearance of the drug accounted for 58% of the total clearance; 66% +/- 17.7%, 33.5% +/- 17.3%, and 6.59% +/- 3.45% of the administered dose were eliminated in urine as parent drug after i.v., endotracheal, and aerosol administrations, respectively. The absolute bioavailabilities were 0.47 and 0.08 for endotracheal and aerosol administrations, respectively. Very high concentrations were found in bronchial secretions after local administration. The MICs for 90% of the most important pathogens responsible for nosocomial infections were exceeded by concentrations in bronchial secretion for up to 12 h after i.v. infusion and for up to 24 h after endotracheal and aerosol administrations.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=1510435&dopt=Abstract
A very small percentage of
aerosolized medications actually get into the lungs. Most remain in the
ventilator circuit, ETT or are lost into the air.
1.
Coleman DM, Kelly HW,
OBJECTIVE: To provide an overview of aerosol drug delivery during mechanical ventilation in the pediatric and adult populations. DATA SOURCES: Published articles and abstracts identified in a MEDLINE search (1984-July 1994) were reviewed. STUDY SELECTION: All articles and abstracts found, including review articles, in vivo and in vitro studies, case reports, and case series pertaining to issues involving aerosol delivery during mechanical ventilation, were reviewed. No predetermined selection criteria were used to exclude studies. DATA EXTRACTION: Percent delivery of the starting dose to either the patients or the various in vitro lung models, as well as each variable possibly affecting delivery for each study, were tabulated for each study reviewed. DATA SYNTHESIS: The delivery of therapeutic aerosols to endotracheally intubated and mechanically ventilated patients presents a unique challenge for healthcare providers. Delivery can be affected by the diameter of the endotracheal tube and ventilator circuitry, type of ventilator, ventilator modes, type of delivery device, and how the delivery device is operated and introduced into the ventilator circuitry. The drug being aerosolized may behave differently from one delivery system to another. The proper operation of each device requires attention to positioning in the ventilator circuit as well as the mode of ventilation. CONCLUSIONS: No apparent advantage exists for metered-dose inhalers with a large-volume adapter over jet nebulizers, as each method of delivery is capable of similar efficiency (5-15%). Sufficient attention to detail, including the use of an efficient nebulizer and/or adapter and proper placement and operating method, is required to provide optimal delivery. For bronchodilator administration, careful monitoring of outcomes will provide the most optimal dosing schedule.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8792952
2.
Crogan SJ,
Bishop MJ. Delivery efficiency of metered dose aerosols given via endotracheal
tubes. Anesthesiology 1989; 70:1008-10.
The authors studied the efficiency of delivery of the inhaled bronchodilator metaproterenol when delivered via an endotracheal tube (ETT) using a metered dose inhaler (MDI). They found that the percentage of drug exiting the ETT varied with tube size, ranging from 3.0 +/- 1.9 for a 6.0 mm ETT to 6.5 +/- 4.4 for a 9.0 mm ETT (mean +/- SEM, P less than 0.05). The efficiency of delivery was also affected by whether the MDI was activated before or after initiation of gas flow through the ETT, with activation into a flowing stream significantly more efficient. The authors conclude that an MDI can deliver a dose of drug to the trachea, but delivery efficiency is lower than reported for MDI delivery in spontaneously breathing patients.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2729618
3.
Fuller HD, Dolovich MB,
Turpie FH,
STUDY OBJECTIVE: To compare aerosol delivery to the lungs in ventilated patients from two devices with holding chamber and two devices without holding chamber. DESIGN: A controlled clinical trial with randomization to one of four delivery devices. SETTING: An academic university-affiliated Canadian ICU. PATIENTS: Forty-eight patients undergoing mechanically assisted ventilation for a variety of clinical reasons and each judged to require inhaled bronchodilator therapy by the attending physician. INTERVENTIONS: Patients received 4 puffs of fenoterol labeled with technetium 99m pertechnetate delivered by metered-dose inhaler via 1 of the following: A, a 167-ml chamber device; B, a 700-ml chamber device; C, a nonchamber device (A, B, and C, all in the ventilator inspiratory line); and D, a nonchamber device on the end of the endotracheal tube. MEASUREMENTS AND RESULTS: One-minute images of the thorax were made by a portable gamma camera at the bedside. Deposition of radioactivity in the lungs (uncorrected for tissue absorption and calculated as a percentage of the radioactivity delivered from 4 puffs) was 5.53 +/- 0.72 (mean +/- 1 SEM), 6.33 +/- 1.16, 1.67 +/- 0.43, and 3.89 +/- 0.52 percent for devices A, B, C, and D, respectively (p = 0.004). Subgroup analysis showed a statistically significant difference in delivery between devices A and C and between devices B and C only. CONCLUSION: There were statistically significant differences between delivery from both chamber devices and the inline nonchamber device, but not between delivery from other devices. Further work will be necessary to determine the effect of device position in the ventilator circuit on aerosol delivery.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8275733
4.
MacIntyre NR.
Intratracheal catheters as drug delivery systems. Respir Care 2001; 46:193-7.
Medication delivery into the lungs can be used to provide a high therapeutic index for agents targeted to specific lung diseases. In addition, the lung can be used as a portal of entry for other agents targeted to systemic diseases. Delivery of medications into the lung can be accomplished by either instillation or aerosolization. Instillation approaches are limited by the fluid volume that can be given safely, and instilled liquids distribute according to gravity. In contrast, aerosolization approaches can deliver larger volumes over longer periods and aerosols distribute according to ventilation. In the mechanically ventilated patient, externally generated aerosols have very poor lung delivery because the endotracheal tube functions as a barrier to aerosol passage. Novel aerosol generating systems at the ends of small-diameter catheters that can be placed into the trachea (or beyond) are being developed to address this. In vitro testing has shown these systems to be capable of producing appropriately sized particles, with high rates of lung deposition. These catheters could be coupled with tracheal gas insufflation systems, not only to deliver therapeutic aerosols but also to create water aerosols to supply necessary humidification during tracheal gas insufflation.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11175248