title: Cafedrine/theodrenaline in anaesthesia: influencing factors in restoring arterial blood pressure.
abstract: BACKGROUND
  Hypotensive states that require fast stabilisation of blood pressure can occur during anaesthesia. In 1963, the 20:1 mixture of cafedrine/theodrenaline (Akrinor) was introduced in Germany for use in anaesthesia and emergency medicine in the first-line management of hypotensive states. Though on the market for many years, few pharmacodynamic data are available on this combination net beta-mimetic agent.
  
  
  OBJECTIVE
  This study aimed to examine the drug combination in real-life clinical practice and recorded time to 10 % mean arterial blood pressure (MAP) increase and heart rate. Furthermore, potential factors that influence drug effectiveness under anaesthesia were assessed.
  
  
  METHODS
  Data were collected within a standardised anaesthesia protocol. A total of 353 consecutive patients (female/male = 149/204) who received cafedrine/theodrenaline after a drop in MAP ≥ 5% were included in the study. The time to 10 % increase in MAP, dosage of cafedrine/theodrenaline, volume loading, blood pressure and heart rate were monitored over time.
  
  
  RESULTS
  Patients were a mean (standard deviation) of 64.4 ± 15.1 years old with a baseline MAP of 82 ± 14 mmHg, which dropped to a mean of 63 ± 10 mmHg during anaesthesia without gender differences. Cafedrine/theodrenaline (1.27 ± 1.0 mg/kg; 64 ± 50 µg/kg) significantly increased MAP (p < 0.001) by 11 ± 16 mmHg within 5 min, reaching peak values within 17.4 ± 9.0 min. Heart rate was not affected in a clinically significant manner. Cafedrine/theodrenaline induced a 10% MAP increase after 7.2 ± 4.6 min (women) and after 8.6 ± 6.3 min (men) (p = 0.018). Independent of gender, the dose of cafedrine/theodrenaline required to achieve the observed MAP increase of 14 ± 16 mmHg at 15 min was significantly different in patients with heart failure [1.78 ± 1.67 mg/kg (cafedrine)/89.0 ± 83.5 µg/kg (theodrenaline)] compared with healthy patients [1.16 ± 0.77 mg/kg (cafedrine)/58.0 ± 38.5 µg/kg (theodrenaline)] (p = 0.005). Concomitant medication with beta-blocking agents significantly prolonged the time to 10 % MAP increase [9.0 ± 7.0 vs. 7.3 ± 4.3 min (p = 0.008)].
  
  
  CONCLUSIONS
  Cafedrine/theodrenaline quickly restores MAP during anaesthesia. Female gender is associated with higher effectiveness, while heart failure and beta-blocker administration lower the anti-hypotonic effect. Prospective studies in defined patient populations are warranted to further characterise the effect of cafedrine/theodrenaline.
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, Department of Anesthesiology and Critical Care Medicine, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany, axel.heller@uniklinkum-dresden.de.
authors.forename: A R
authors.initials: AR
authors.lastname: Heller
authors.forename: J
authors.initials: J
authors.lastname: Heger
authors.forename: M
authors.initials: M
authors.lastname: Gama de Abreu
authors.forename: M P
authors.initials: MP
authors.lastname: Müller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000758:Anesthesia / Q000379:methods*; D001794:Blood Pressure / Q000187:drug effects; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D004338:Drug Combinations; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000150:complications; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000517:prevention & control*; D007430:Intraoperative Care / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012727:Sex Characteristics; D013806:Theophylline / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000319:Adrenergic beta-Antagonists; D002317:Cardiovascular Agents; D004338:Drug Combinations; C000147:cafedrine, theodrenaline drug combination; D013806:Theophylline