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.

Aim: 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)].

Conclusion: 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.

Fig. 1

Effects of cafedrine/theodrenaline on mean arterial pressure (MAP, mean ± SE) injected at time point 0 (reference value) in male and female patients. Both MAP drop and increase were statistically significant (p < 0.001, paired t-test), as was the between-group comparison with general linear model (GLM) according to two-way analysis of variance (ANOVA) (p = 0.04)

Fig. 2

Effects of cafedrine/theodrenaline on heart rate (mean ± SE) injected at time point 0 (reference value) in male and female patients. The difference between genders was not significant (p = 0.668), while the heart rate difference over time was statistically significant (p < 0.001)

Fig. 3

Kaplan–Meier analysis of the time to 10 % mean arterial pressure (MAP) increase in male (dotted line) and female (solid line) patients after cafedrine/theodrenaline injection at time point 0 (p = 0.018, log-rank test)

Fig. 4

Kaplan–Meier analysis of the time to highest mean arterial pressure (MAP) after cafedrine/theodrenaline injection at time point 0 in patients with heart failure (NYHA ≥ 1, dotted line) and healthy patients (solid line) (p = 0.007, log-rank test). Cases not reaching a MAP increase of 20 % within 30 min were censored

Fig. 5

Kaplan–Meier analysis of the time to 10 % mean arterial pressure (MAP) increase after cafedrine/theodrenaline injection at time point 0 in patients with (dotted line) and without (solid line) current beta-blocker therapy (p = 0.008, log-rank test)