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

Abstract

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^–1 and ketamine 10 mg kg^–1 intramuscularly) and induction [propofol 0.25–0.5 mg kg^–1 intravenously (IV)], anaesthesia was maintained with isoflurane in oxygen, and either GHB 250 mg kg^–1 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 PaO₂ [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 PaCO₂ [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^–1, with volume of distribution 335.3 ± 68.5 mL kg^–1, clearance 77.2 ± 19.12 mL kg^–1 hour^–1 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.