Interaktion von Nimodipin und Propofol beim HundHämodynamik und Kardiodynamik

Zusammenfassung

Hintergrund: Da Propofol und Nimodipin bei neurochirurgischen Eingriffen häufig zusammen verwendet werden, und Propofol auf Kalziumkanäle wirkt, wird in dieser Studie eine mögliche hämodynamische Interaktion zwischen beiden Substanzen untersucht.

Methodik: Fünf Hunde wurden chronisch instrumentiert zur Messung von Herzfrequenz, aortalem Druck, LV-dp/dt, koronarer Blutflußgeschwindigkeit (CBFV), Herzzeitvolumen, systemvaskulärem Widerstand und myokardialer Wanddicke. Alle Tiere erhielten an verschiedenen Tagen Propofol (30 mg/kg/h) (P), Nimodipin (N) (1 und 2 µg/kg/min für je 40 min) und die Kombination von N und P (N+P).

Ergebnisse: Es bestand für keinen Parameter ein signifikanter Unterschied zwischen N und N+P und zwischen beiden Nimodipindosierungen. Die Herzfrequenz war unter N signifikant höher als in der Kontrolle. Nimodipin führte zu einer signifikanten Zunahme der CBFV.

Schlußfolgerungen: Propofol verändert nicht die kardiovaskulären Wirkungen einer Nimodipininfusion von 1 bzw. 2 µg/kg/min im chronisch instrumentierten Hund.

Abstract

Nimodipine is frequently used for treatment of cerebral vasospasm in patients undergoing intracerebral vascular surgery and during intensive care therapy of patients with subarachnoid haemorrhage. Propofol is being increasingly used as a hypnotic drug in neuroanaesthesia and for sedation in critically ill patients. There is evidence of a propofol effect on voltage-dependent calcium channels; hence, the administration of propofol may interact with the haemodynamic effects of nimodipine. We investigated the haemodynamic interactions of both compounds in chronically instrumented dogs. Methods: Five mongrel dogs were chronically instrumented for measurement of heart rate (HR), left atrial (LAP), aortic (ABP), and left ventricular pressure (LVP), LV dP/dt, cardiac output (CO), systemic vascular resistance (SVR), coronary blood flow velocity (CBFV), and myodardial wall-thickening fraction (WTF). After complete recovery from surgery and assessment of normal resting blood gas values and temperature, all animals received on separate days either propofol 30 mg/kg · h (P), nimodipine in two maintenance doses in the awake state (N), or the combination of nimodipine and propofol (N+P). The maintenance doses of nimodipine in N and N+P were 1 and 2 µg/kg · min for 40 min each after a bolus of either 10 or 20 µg/kg · min over 2 min. Measurements were performed as controls, in the middle (20 min), and at the end (40 min) of each maintenance infusion of nimodipine or at equivalent points in time in group P (Fig. 1). Animals receiving propofol were mechanically ventilated after endotracheal intubation. Blood gas values were kept within the normal range. All data were analysed with repeated measures of ANOVA followed by student’s t-test with Bonferroni correction. Results: There was no statistically significant difference for any of the measured parameters between N and N+P or between the two maintenance doses of nimodipine (Table 1). HR was significantly higher with both doses of nimodipine in the awake state compared to the control values (123±7.1 and 146±6.4 vs 78±2.4/min). The administration of nimodipine with and without propofol led to a significant increase in CBFV (Fig. 2). However, there was no difference in CBFV between nimodipine in the awake state and in combination with propofol (Fig. 2).Conclusions:

We conclude that administration of propofol does not alter the systemic haemodynamic and regional myocardial effects of a nimodipine infusion in a dose of 1 or 2 µg/kg · min in chronically instrumented dogs.