• DOI:10.7326/0003-4819-132-10-200005160-00007
• Corpus ID: 12713291

Absorption and Hemodynamic Effects of Airway Administration of Adrenaline in Patients with Severe Cardiac Disease

@article{Raymondos2000AbsorptionAH,
  title={Absorption and Hemodynamic Effects of Airway Administration of Adrenaline in Patients with Severe Cardiac Disease},
  author={Konstantinos Raymondos and Bernhard Panning and Martin Leuwer and G Brechelt and Thomas Korte and Michael Niehaus and Jürgen Tebbenjohanns and Siegfried Piepenbrock},
  journal={Annals of Internal Medicine},
  year={2000},
  volume={132},
  pages={800-803}
}

• K. Raymondos, B. Panning, +5 authors S. Piepenbrock
• Published 16 May 2000
• Medicine, Biology
• Annals of Internal Medicine

Endotracheal administration of at least 2 mg of adrenaline is recommended in adults if intravenous access cannot be attained during resuscitation (1). It is an accepted and frequently used alternative to intravenous administration. Studies in animals have suggested that endotracheal doses of adrenaline must be at least 10 times greater than intravenous doses (2, 3). However, three previous studies failed to show any effects after endotracheal administration of 0.03 to 1 mg of adrenaline in adults (4-6). These authors concluded that the endotracheal route should not be used for administration of adrenaline during resuscitation (6), thereby contradicting international recommendations (1). We hypothesized that the doses of endotracheal adrenaline used in these studies (4-6) were too low to have any effect. Therefore, we investigated the effect of 100 times the effective central intravenous dose of adrenaline on adrenaline plasma levels and hemodynamic variables in patients with cardiac disease who received implantable cardioverter defibrillators under general anesthesia. Methods The study group consisted of 34 patients (5 women, 29 men) who received implantable cardioverter defibrillators for the first time (n =8) or had them replaced (n =26) under general anesthesia. The mean (SD) patient age was 63 10 years (range, 38 to 77 years). All patients had coronary artery disease, dilated cardiomyopathy, or other cardiac diseases, and most had an ejection fraction that was less than 40% (mean ejection fraction SD, 34.5% 14.9% [range, 15% to 70%]). All patients were at high risk for cardiac arrest because of ventricular arrhythmia, and 18 patients had been resuscitated before study entry. Eighteen patients were receiving angiotensin-converting enzyme inhibitors, 15 patients were receiving sotalol, 7 patients were receiving amiodarone, 4 patients were receiving verapamil, and 3 patients were receiving -blockers. A polygraph recorder continuously recorded 5-lead electrocardiography, pulse oximetry, capnometry, central intravenous pressure, and radial artery pressure. All hemodynamic data were abstracted from these continuous recordings. Anesthesia was induced with midazolam, 0.05 to 0.2 mg/kg of body weight; etomidate, 0.3 mg/kg; and propofol, 0.5 to 3 mg/kg. Atracurium, 0.5 mg/kg, was used for muscle relaxation. After endotracheal intubation, the lungs were ventilated with 100% oxygen. Anesthesia was maintained with 1.3 to 8 mg/kg of propofol per hour (mean SD, 4.1 1.9 mg/kg per hour) and 0.4 to 8.7 g/kg of remifentanil per hour (4.0 2.16 g/kg per hour). While adequate anesthesia was maintained, the volume status was adjusted to keep the mean arterial pressure above 80 mm Hg. If mean arterial pressure decreased below 80 mm Hg, adrenaline was given. To standardize the adrenaline dose according to effectiveness, we determined the central intravenous dose necessary to increase mean arterial pressure by at least 10 mm Hg. We started with 0.1 g/kg of adrenaline (5) and increased the dose until the mean arterial pressure increased sufficiently. When mean arterial pressure decreased below 80 mm Hg, 100 times the effective intravenous dose of adrenaline (mean SD, 1.3 0.6 mg [range, 0.7 to 3 mg]) was diluted in 10 mL of saline and administered slowly over 5 seconds into the airways, followed by 10 forced ventilations. In the first 17 patients, adrenaline was administered into the peripheral airways through a bronchial catheter; in the remaining 17 patients, adrenaline was administered directly into the endotracheal tube. The patients' clinical characteristics did not differ between groups (data not shown). For application into the peripheral airways, a central intravenous catheter was inserted using radiologic imaging until wedge position was achieved (23.2 3.1 cm [range, 18.5 to 27.0 cm] distal to the end of the endotracheal tube). When mean arterial pressure increased to 120 mm Hg after adrenaline administration, nitroglycerin was given. To determine adrenaline and noradrenaline levels, plasma samples were collected from the second lumen of the central intravenous line immediately before adrenaline administration; 0.5, 2, 3, and 5 minutes after intravenous administration; and 0.5, 2, 3, 5, 10, and 20 minutes after airway administration. Samples were recovered in chilled EDTA test tubes, stored on ice, and centrifuged at 4 C within 30 minutes. Separated plasma was frozen at 20 C until analysis. Catecholamines were electrochemically detected by high-pressure liquid chromatography with a commercially available analysis kit (7). Results are expressed as the mean SD (range). We used the MannWhitney U test to determine differences between the two patient groups and the Wilcoxon rank test for comparison within groups. The ethics committee at Medical School Hannover, Hannover, Germany, approved the study. Each patient gave informed consent before study entry. Institutional funding was obtained for catecholamine analysis. Results Airway administration of adrenaline significantly increased adrenaline plasma levels and arterial blood pressure in all patients (Figure). Adrenaline plasma levels increased more than 200-foldfrom 0.26 0.21 nmol/L (range, 0.05 to 0.71 nmol/L) to 57.9 56.8 nmol/L (range, 8.2 to 205.8 nmol/L) (P =0.0015). Mean arterial pressure increased almost 100% (P <0.001), and heart rate increased from 64.0 12.6 beats/min (range, 40 to 100 beats/min) to a maximum of 79.7 20.5 beats/min (range, 50 to 140 beats/min) (P <0.001). Twenty minutes after airway administration, 30.8% 18.6% (range, 8.4% to 76.1%) of the peak adrenaline plasma concentration was still detected. Noradrenaline plasma levels did not increase during the observation period but decreased 2 minutes after airway administration, from 1.95 1.0 nmol/L (range, 0.77 to 4.32 nmol/L) to 1.60 0.65 nmol/L (range, 0.35 to 2.36 nmol/L) (P <0.01). Baseline values and effects did not differ between groups (Figure, Table) or between patients in whom catecholamines were measured and those in whom they were not (data not shown). Figure. Effect of adrenaline on mean arterial blood pressure. Top. CV ET Bottom. PB Table. Adrenaline Doses, Plasma Levels, and Hemodynamic Variables Airway administration of adrenaline resulted in higher adrenaline plasma levels and greater mean arterial pressurebut not higher heart ratesthan central intravenous adrenaline. A delayed response was seen when adrenaline was administered through the airways (Table). Twenty-one patients received nitroglycerin to counteract blood pressure increases after receiving airway adrenaline (total dose per patient, 1.15 1.14 mg [range, 0.1 to 3.6 mg]). Nitroglycerin doses did not differ between groups. Myocardial perfusion, as reflected by electrocardiography, was not impaired after adrenaline administration, but five patients had short bursts of ventricular tachycardia with up to eight consecutive beats. No patient developed sustained ventricular tachycardia or fibrillation. Six patients died of cardiac failure 2 to 16 months after study entry. Discussion This is the first prospective study to demonstrate that administration of adrenaline into the airways is hemodynamically effective and increases plasma adrenaline levels in adults. In contrast to studies in animals, previous studies in adult patients have not shown any effects with adrenaline (4-6). In our study, however, all patients responded. Standard recommendations state that in adults, at least 2 mg of adrenaline should be administered endotracheally if intravenous access cannot be attained during resuscitation (1). We administered approximately 70% of the recommended dose through the airways. This dose was higher than doses used in previous studies (4-6), which may explain the substantial effects we observed. Our observations support the recommendation to consider the airways as an alternate route for adrenaline administration during resuscitation. In our study, a general endogenous release of catecholamines after adrenaline administration was avoided by maintaining sufficient anesthesia, as indicated by the course of noradrenaline plasma concentrations. In contrast to observations in animals (8), we found that both airway routes were equally effective. This may be because slower injection distributed fluids to a smaller lung surface and more forced manual ventilation allowed a more peripheral distribution of fluids (9). Peripheral bronchial administration of adrenaline through a catheter, which is cumbersome and time-consuming, seems unnecessary. In animals, equal hemodynamic responses were seen after airway administration of 10 times the intravenous dose (2, 3). We administered 100 times the effective central intravenous dose through the airways, which resulted in adrenaline plasma levels that were three times higher and mean arterial blood pressure that was 1.3 times compared with central intravenous administration. Because 21 of 34 patients required nitroglycerin to counteract blood pressure responses, 100 times the effective intravenous dose may be excessive. However, after airway administration of adrenaline, maximum heart rate responses did not differ compared with central venous administration. This may indicate a reduced cardiac sensibility to higher adrenaline levels because of cardiac disease and long-term medications; it could also be related to pressoreceptor reflexes. In contrast to data from animals (2, 3), we observed a delayed response after airway administration of adrenaline compared with central intravenous administration. Furthermore, plasma adrenaline levels and blood pressure responses varied considerably after airway administration. In patients experiencing cardiac arrest, a more pronounced delay, greater variation, and less effectiveness can be expected because low pulmonary blood flow reduces drug absorption from the lungs. Therefore, the extrapolation of our observations to patients in cardiac arrest is limited. In addition, pati