The effect of dexmedetomidine on cerebral perfusion and oxygenation in healthy piglets with normal and lowered blood pressure anaesthetized with propofol-remifentanil total intravenous anaesthesia

Abstract

Background: During anaesthesia and surgery, in particular neurosurgery, preservation of cerebral perfusion and oxygenation (CPO) is essential for normal postoperative brain function. The isolated effects on CPO of either individual anaesthetic drugs or entire anaesthetic protocols are of importance in both clinical and research settings. Total intravenous anaesthesia (TIVA) with propofol and remifentanil is widely used in human neuroanaesthesia. In addition, dexmedetomidine is receiving increasing attention as an anaesthetic adjuvant in neurosurgical, intensive care, and paediatric patients. Despite the extensive use of pigs as animal models in neuroscience and the increasing use of both propofol-remifentanil and dexmedetomidine, very little is known about their combined effect on CPO in pigs with uninjured brains. This study investigates the effect of dexmedetomidine on CPO in piglets with normal and lowered blood pressure during background anaesthesia with propofol-remifentanil TIVA. Sixteen healthy female Danish pigs (crossbreeds of Danish Landrace, Yorkshire and Duroc, 25-34 kg) were used. Three animals were subsequently excluded. The animals were randomly allocated into one of two groups with either normal blood pressure (NBP, n = 6) or with induced low blood pressure (LBP, n = 7). Both groups were subjected to the same experimental protocol. Intravenous propofol induction was performed without premedication. Anaesthesia was maintained with propofol-remifentanil TIVA, and later supplemented with continuous infusion of dexmedetomidine. Assessments of cerebral perfusion obtained by laser speckle contrast imaging (LSCI) were related to cerebral oxygenation measures (P_brO₂) obtained by an intracerebral Clark-type Licox probe.

Results: Addition of dexmedetomidine resulted in a 32% reduction in median P_brO₂ values for the LBP group (P = 0.03), but no significant changes in P_brO₂ were observed for the NBP group. No significant changes in LSCI readings were observed in either group between any time points, despite a 28% decrease in the LBP group following dexmedetomidine administration. Caval block resulted in a significant (P = 0.02) reduction in median MAP from 68 mmHg (range 63-85) at PCB to 58 mmHg (range 53-63) in the LBP group, but no significant differences in either P_brO₂ or LSCI were observed due to this intervention (P = 0.6 and P = 0.3 respectively).

Conclusions: Addition of dexmedetomidine to propofol-remifentanil TIVA resulted in a significant decrease in cerebral oxygenation (P_brO₂) measurements in piglets with lowered blood pressure. Cerebral perfusion (LSCI) did not decrease significantly in this group. In piglets with normal blood pressure, no significant changes in cerebral perfusion or oxygenation were seen in response to addition of dexmedetomidine to the background anaesthesia.

Keywords: Cerebral oxygenation; Cerebral perfusion; Dexmedetomidine; Laser speckle contrast imaging; Licox; Propofol; Remifentanil; Swine.

Fig. 1

Experimental design. The experimental flow for the two groups (NBP normal blood pressure group, LBP low blood pressure group), with the median duration of each period (min–max range in brackets). Key time points are marked (arrows), and corresponding time points between groups are joined by dotted lines. PCB Pre-caval Block, PR-1 Propofol-remifentanil experimental start, PR-2 Propofol-remifentanil end–immediately prior to dexmedetomidine infusion, PR-D following dexmedetomidine infusion

Fig. 2

Boxplots of mean arterial blood pressure and end-tidal carbon dioxide at the different timepoints. Box and whisker plots showing median (line), interquartile range (shaded) and outliers (circles) for mean arterial pressure (in mmHg) (a), and end-tidal carbon dioxide (ETCO₂, in mmHg) (b) in the normal blood pressure group (NBP) and low blood pressure group (LBP). Whiskers extend a maximum of 1.5× the interquartile range. The lower mean arterial pressure limit for cerebral autoregulation is shown (dashed line). Experimental timepoints: PCB pre-caval block, PR-1 initial baseline for propofol-remifentanil TIVA, PR-2 immediately before dexmedetomidine administration, PRD following propofol-remifentanil-dexmedetomidine TIVA. Significant differences from either the autoregulation limit (vertical bars) or between timepoints (horizontal bars) are shown

Fig. 3

Boxplots of cerebral perfusion and oxygenation at the different time points. Box and whisker plots showing median (line), interquartile range (shaded) and outliers (circles) for partial pressure of tissue oxygen (P_brO₂, in mmHg) (a) and laser speckle perfusion units (b) in the normal blood pressure group (NBP) and low blood pressure group (LBP). Whiskers extend a maximum of 1.5× the interquartile range. The value for ischaemic threshold is shown (dashed line). Experimental time points: PCB pre-caval block, PR-1 initial baseline for propofol-remifentanil TIVA, PR-2 immediately before dexmedetomidine administration, PRD following propofol–remifentanil–dexmedetomidine TIVA. Significant differences from either the ischaemia limit (vertical bars) or between timepoints (horizontal bars) are shown