Cardiorespiratory effects of gamma-hydroxybutyric acid during isoflurane anaesthesia in pigs.

Objective: To investigate the haemodynamic effects of gamma-hydroxybutyric acid (GHB) in isoflurane-anaesthetized pigs.

Study Design: Experimental, randomized, nonblinded, crossover study.

Animals: A group of six stress-resistant Landrace pigs (approximately 3 months old; three male, three female; bodyweight 39.2 ± 4 kg, mean ± standard deviation).

Methods: After premedication (midazolam 0.5 mg kg and ketamine 10 mg kg intramuscularly) and induction [propofol 0.25-0.5 mg kg intravenously (IV)], anaesthesia was maintained with isoflurane in oxygen, and either GHB 250 mg kg IV or an equal volume of saline was administered (minimum washout period 1 week). Systolic (SAP), diastolic (DAP) and mean (MAP) arterial pressures, heart rate and rhythm and respiratory rate were recorded every 5 minutes for 2 hours. Arterial samples were collected for blood gas and pharmacokinetic analyses. Relative changes from baseline were calculated and compared between treatments using a mixed model with time, period and treatment as variables (α < 0.05).

Results: Changes from baseline differed significantly between treatments (p < 0.001) for SAP (GHB -1.6 ± 10.7; saline -5.9 ± 14.8 mmHg), DAP (GHB +2.9 ± 9.6; saline -6.5 ± 10.7 mmHg) and MAP (GHB +2.2 ± 10.5; saline -5.7 ± 9.6 mmHg). Statistical analysis of secondary outcomes suggested effects on PaO [GHB -45.2 ± 29.8 mmHg (-6.03 ± 3.97 kPa); saline +24.5 ± 32.4 mmHg (+3.27 ± 4.32 kPa); p < 0.001] and PaCO [GHB -2 ± 10 mmHg (-0.27 ± 1.33 kPa); saline -9 ± 8 mmHg (-1.20 ± 1.07 kPa); p < 0.001]. Mean maximum blood concentration of GHB was 1171.1 ± 229.3 μg mL, with volume of distribution 335.3 ± 68.5 mL kg, clearance 77.2 ± 19.12 mL kg hour and elimination half-life 3.10 ± 0.80 hours.

Conclusions And Clinical Relevance: GHB did not cause severe physiological side effects and may reduce cardiovascular depression.