Comparison of the hemodynamic response to induction and intubation during a target-controlled infusion of propofol with 2 different pharmacokinetic models. A prospective randomized trial

Abstract

Objective

To determine the best propofol pharmacokinetic model that meets patient requirements and is devoid of major haemodynamic side effects.

Material and methods

Prospective, randomised, open-label, clinical trial was performed on an intention to treat basis. It included 280 patients with ASA physical status I–III, aged 18–80 years and a weight range between 45 and 100 kg, scheduled for surgery under general anaesthesia. They were randomised into two groups according to the pharmacokinetic model: Modified Marsh group and Schnider group. The haemodynamic changes that occurred during the induction and intubation were analysed. A propofol target-controlled infusion was started to achieve and maintain a bispectral index value between 35 and 55. At minute 6, orotracheal intubation was performed and the study finished at minute 11.

Heart rate, mean arterial pressure and their product (HR × MAP) were measured and recorded every minute throughout the study. Every HR × MAP value was compared to its baseline value to determine the minimum value before intubation, the maximum value after intubation, the maximum variation after intubation, and its final value. The GRADIENTE (MIN, MAX) variable (primary endpoint of this study) analyses the difference between maximal and minimal values related to intubation. Propofol doses and calculated concentrations and any hypotensive events were also recorded.

Results

No differences were found between groups regarding haemodynamic performance. GRADIENTE (MIN, MAX) values and the percentage of hypotensive events were: Modified Marsh group median 77.41% vs. Schnider group 84.86% (p = 0.821) and 17.3% vs. 12.8% (p = 0.292), respectively.

Conclusion

The study failed to demonstrate any haemodynamic difference between the two groups, even though the Modified Marsh group received a larger dose of propofol.

Resumen

Objetivo

Determinar qué modelo farmacocinético para propofol proporciona una mayor estabilidad hemodinámica durante la inducción anestésica.

Material y métodos

Ensayo clínico prospectivo, aleatorizado, no ciego y por intención de tratar donde se incluyeron 280 pacientes ASA I–III, 18–80 años de edad y 45–100 kg de peso, programados para cirugía bajo anestesia general. Los pacientes se distribuyeron aleatoriamente en 2 grupos, dependiendo del modelo farmacodinámico para propofol empleado (Marsh Modificado o Schnider), para analizar el comportamiento hemodinámico durante la inducción y la intubación. Se administró una infusión controlada por objetivo de propofol para mantener un índice biespectral de 35–55. En el minuto 6 se realizó la intubación orotraqueal, finalizando el estudio a los 11 min del comienzo.

Fueron recogidos cada minuto la frecuencia cardiaca, la tensión arterial media, las dosis, las concentraciones de propofol y la aparición de hipotensión. El producto de la frecuencia cardiaca y la tensión arterial media (FC × TAM) fue calculado cada minuto y analizado pormenorizadamente, determinando, entre otros, el valor mínimo antes de la intubación, el máximo tras ella, y la relación entre estos 2 valores (GRADIENTE [MÍN, MÁX], variable principal del estudio).

Resultados

No hubo diferencias significativas en el comportamiento hemodinámico entre los grupos del estudio. GRADIENTE (MÍN, MÁX): 77,41 vs. 84,86% (p = 0,821); hipotensión: 17,3 vs. 12,8% (p = 0,292); Marsh Modificado y Schnider, respectivamente.

Conclusión

No se han podido demostrar diferencias en el comportamiento hemodinámico, a pesar de que el grupo del Marsh Modificado recibió una dosis mayor de propofol.