Adjunct terlipressin effect on vital organ perfusion during advanced life support in a porcine model of ventricular fibrillation

Introduction

Drug administration is an integral part of advanced life support (ALS). The coronary perfusion pressure (CorPP) during cardiopulmonary resuscitation (CPR) predicts the probability of return of spontaneous circulation, while the cerebral perfusion pressure (CPP) affects brain damage. Guidelines for cardiac arrest treatment recommend giving adrenaline (ADR) although there is no evidence showing long-term benefit from any medication. Vaso-pressin was probably the most effective alternative studied in both experimental and clinical trails. As vasopressin has never been available in Europe, we evaluated the effect of its synthetic analogue, terlipressin (TER), on vital organ perfusion in an animal model of ventricular fibrillation (VF) (Terlipressin in Cardiac Arrest (TERCA) study). The use of TER in VF has never been studied before.

Methods

A prospective, experimental study in 14 domestic pigs (30 to 35 kg) randomly assigned into two groups: A (ADR + TER; n = 7) and B (ADR + NaCl; n = 7). CorPP and CPP were calculated from right atrial, aortic and intracerebral pressures. VF was induced using an intracardiac pacing electrode. After 5 minutes of untreated arrest, chest compressions were started using the AutoPulse system (Zoll Circulation, Sunnyvale, CA, USA) simulating hands-only CPR. At a time of 15 minutes after onset of VF, ALS was started for the next 45 minutes. ADR 30 μg/kg and TER 30 μg/kg were administered intravenously 19 minutes after induction of VF in group A, while ADR and NaCl were given in group B. Equal doses of ADR were then repeated every 3 minutes in both groups. The design of the study reflected the real-life time intervals achieved in clinical trials. The primary endpoint was to compare CorPP and CPP between groups A and B. Data were analysed using SigmaStat. P < 0.05 was considered statistically significant.

Results

CorPP (mean ± SD) measured 35, 40 and 45 minutes after the onset of VF was 12 ± 4, 13 ± 4 and 11 ± 6 mmHg in group A (with adjunct TER), and 6 ± 4, 2 ± 7 and 1 ± 5 mmHg in control group B (P < 0.05, P < 0.01 and P < 0.01). CPP at the same times was 23 ± 7, 24 ± 8 and 20 ± 7 mmHg in group A, and 13 ± 7, 8 ± 6 and 6 ± 5 mmHg in control group B (P < 0.05, P < 0.01 and P < 0.01).

Conclusion

Our results suggest a significant increase of CorPP and CPP after early adjunct treatment of VF with TER added to standard doses of ADR during prolonged CPR in pigs.