Effect of predosing versus slow administration of propofol on the dose required for anaesthetic induction and on physiologic variables in healthy dogs

Abstract

Objective

To investigate the effects of the timing of propofol administration on the dose required for induction of anaesthesia and commonly measured physiological effects.

Study design

Randomized, investigator-blinded clinical study.

Animals

A group of 32 healthy dogs aged 6–144 months and weighing 3.5–47.2 kg.

Methods

Premedication was intramuscular acepromazine (0.025 mg kg⁻¹) and methadone (0.25 mg kg⁻¹). After 30 minutes, one of three treatments was administered to the dogs: propofol (0.5 mg kg⁻¹; group PP), an equivalent volume of saline (group CP) or a propofol infusion (1.3 mg kg⁻¹ minute⁻¹; group SI). Two minutes later, a propofol infusion (4 mg kg⁻¹ minute⁻¹) was started in PP and CP, whereas the propofol infusion was continued in SI. At this stage an investigator, blinded to the group assignments, entered the room and decided when each animal was ready for intubation and stopped the propofol infusion. After intubation, management of anaesthesia was standardized. Pulse rate (PR), respiratory rate (f_R) and mean arterial pressure (MAP) were recorded before induction, 2 minutes later and 0, 2 and 5 minutes after intubation. Apnoea >30 seconds was recorded and managed. Sedation, quality of induction and endotracheal intubation were scored using simple descriptive scales. Data are presented as mean ± standard deviation.

Results

Propofol dose requirement was lower in SI (3.5 ± 1.2 mg kg⁻¹) compared with PP and CP (5.0 ± 0.9 and 4.8 ± 0.6 mg kg⁻¹; p = 0.002 and 0.012), respectively. No statistically significant differences were found among groups for PR, f_R, MAP or incidence of apnoea. Sedation score and quality of induction were similar among groups.

Conclusions

Slow administration of propofol reduced the anaesthetic induction dose required compared with predosing and control groups. Effects on PR, f_R, MAP and apnoea were similar among groups.

Clinical relevance

Slower injection of propofol reduces the dose required for induction of anaesthesia.

Introduction

Propofol is commonly used to induce anaesthesia in dogs and can cause adverse cardiovascular and respiratory effects (Berry 2015). Co-induction is defined as the administration of two or more agents together to induce anaesthesia. It has been proposed as a possible way to reduce dose and side effects of drugs coadministered (Whitwam 1995). The effects of different drugs administered with propofol for induction of anaesthesia in dogs have been documented, including midazolam and diazepam (Covey-Crump and Murison, 2008, Fayyaz et al., 2009, Hopkins et al., 2013, Robinson and Borer-Weir, 2013, Sánchez et al., 2013, Minghella et al., 2016), fentanyl, alfentanil and remifentanil (Musk and Flaherty, 2007, Auckburally et al., 2008, Covey-Crump and Murison, 2008), lidocaine (Braun et al., 2007, Jolliffe et al., 2007, Panti et al., 2015, Thompson and Rioja, 2015, Cerasoli et al., 2016, Minghella et al., 2016) and ketamine (Lerche et al., 2000, Mair et al., 2009, Henao-Guerrero and Riccó, 2014, Martinez-Taboada and Leece, 2014). A reduction in propofol dose was demonstrated in some studies. The sequence of co-induction drugs appears to influence the results. For example, in one study intravenous (IV) administration of midazolam before propofol resulted in signs of excitement and no reduction in propofol dose, whereas in another study, administration of a bolus of propofol before midazolam resulted in a lower requirement for propofol and less excitable behaviour (Covey-Crump and Murison, 2008, Robinson and Borer-Weir, 2013, Sánchez et al., 2013).

Predosing with propofol has been reported in human anaesthesia. The technique involves the administration of a fixed dose of propofol 2 minutes before induction of anaesthesia with propofol (Anderson and Robb, 1998, Djaiani and Ribes-Pastor, 1999). It reduces the propofol dose required for induction of anaesthesia (Anderson and Robb, 1998, Djaiani and Ribes-Pastor, 1999, Srivastava et al., 2006, Kataria et al., 2010), with variable effects on heart rate and blood pressure but possibly improved haemodynamic stability (Djaiani and Ribes-Pastor, 1999, Kataria et al., 2010). One study reported a decreased incidence of apnoea at induction following propofol predosing compared with propofol-midazolam co-induction (Djaiani & Ribes-Pastor 1999). To our knowledge, the effects of propofol predosing in dogs have not been reported. In sheep the peak in anaesthesia depth is reached 2–3 minutes after the interruption of propofol administration (Ludbrook & Upton 1997), so it is possible that the dose reduction observed with the propofol predosing originates from the longer time propofol has to exert its effects.

The aim of this study was to investigate the effects of propofol predosing in dogs on the total dose of propofol required for endotracheal intubation and the cardiovascular and respiratory effects in the absence of other co-induction agents. Our hypothesis was that propofol predosing or slower administration of propofol in dogs would reduce the amount of propofol necessary to induce anaesthesia and reduce adverse cardiovascular and respiratory effects.