KNOWLEDGE SUMMARY

Keywords: ANAESTHESIA; APNOEA; CANINE; PHARMACOLOGY; PROPOFOL INFUSION RATE; RESPIRATORY DISTRESS

Appearance of post-induction respiratory apnoea in dogs following slow or fast administration of propofol

Alexandra Fraser, DVM Student^1*
Eduardo Uquillas, BVM DVM DACVAA¹

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¹ School of Veterinary Science, The University of Sydney, Sydney, Australia
* Corresponding author email: alexandra.y.fraser@gmail.com

Vol 11, Issue 1 (2026)
Submitted 25 Oct 2024; Published: 09 Jan 2026
DOI: https://doi.org/10.18849/ve.v11i1.729

PICO question

In healthy dogs undergoing general anaesthesia is rapid infusion of propofol compared to slow infusion of propofol associated with a greater incidence or duration of post-induction apnoea?

Clinical bottom line

Category of research

Treatment.

Number and type of study designs reviewed

Four prospective, randomised, controlled clinical trials.

Strength of evidence

Weak.

Outcomes reported

The studies have produced inconsistent findings regarding the relationship between propofol infusion speed and post-induction apnoea appearance in dogs. While two studies have found that increasing the speed of administration increases the incidence or duration of post-induction apnoea, other studies have not found a significant correlation.

Conclusion

Based on available evidence, administering propofol at a slow rate is unlikely to lower the incidence or duration of post-induction apnoea compared with faster propofol infusion where the total dose is kept constant. However, administering propofol slowly is recommended when titrating to effect, since slow administration reduces the total dose required to induce anaesthesia, thereby reducing the risk of apnoea.

How to apply this evidence in practice

The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.

Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Clinical scenario

You work in a suburban small animal clinic and are planning anaesthesia for a dog with a history of epileptic seizures. You choose propofol as the induction drug but are concerned by the manufacturer’s warning regarding rapid administration and respiratory effects. To address this concern, you decide to investigate the relationship between propofol infusion rate and the occurrence or duration of post-induction apnoea in dogs.

The evidence

Four randomised controlled clinical trials (Bigby et al., 2017a; Murison, 2001; Raillard et al., 2018; Walters et al., 2022) were found to address whether rapid infusion of propofol, compared with slow infusion of propofol, to induce anaesthesia in healthy dogs was associated with a greater incidence or duration of post-induction apnoea. Each study had methodological limitations and together produced inconsistent findings, providing strong evidence that high doses of propofol increased the incidence and duration of post-induction apnoea, but weak evidence that these findings can be attributed to rapid delivery if dose is kept constant. Overall, the evidence supporting a causative link between propofol administration speed and respiratory apnoea incidence in canines is weak, and further research is required to improve anaesthetic management for canine patients in this regard.

Summary of the evidence

Bigby et al. (2017a)

Effect of rate of administration of propofol or alfaxalone on induction dose requirements and occurrence of apnea in dogs

Aim: To determine how induction dose requirements, in addition to incidence and duration of post-induction apnoea, are influenced by the rate of administration of alfaxalone or propofol in healthy adult dogs premedicated with methadone and dexmedetomidine.

 

Murison (2001)

Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog

Aim: To quantify and compare the incidence and duration of apnoea following endotracheal intubation in dogs induced with either thiopentone or propofol, and assess the effect of propofol induction speed on respiratory depression.

 

Raillard et al. (2018)

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

Aim: To evaluate the effects of propofol predosing compared with slow administration on total induction dose and associated cardiorespiratory effects in healthy dogs.

 

Walters et al. (2022)

Determining an optimum propofol infusion rate for induction of anaesthesia in healthy dogs: a randomized clinical trial

Aim: To elucidate the optimal infusion rate of propofol for induction of anaesthesia in healthy dogs by comparing intubation time and duration of post-induction apnoea between several infusion rates.

 

Appraisal, application and reflection

Propofol, the most widely used intravenous induction agent in both human and veterinary medical fields, is relatively well understood in both its action and potential to produce adverse effects (Bigby 2018; Smith et al., 1993). Propofol acts on the central nervous system via direct and indirect effects on GABA_A receptors to produce either anaesthesia or hypnotic sedation depending on administration protocol, and may also affect the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, the inhibition of which further contributes to the ability of propofol to induce anaesthesia (Bigby, 2018; Orser et al., 1995). Propofol has a number of notable advantages over other induction agents including its ability to be administered intravenously without significant cumulative effects upon repeat administration, produce rapid induction and smooth recovery without an excitatory phase, and, importantly, be used in canine and feline patients with pre-existing status epilepticus, hepatic and renal disease (Cochrane, 2007; Glowaski & Wetmore, 1999; Muir & Gadawski, 1998). However, propofol also has a number of limitations, reportedly producing high rates of post-induction apnoea, cardiorespiratory depression, and hypotension (Cattai et al., 2018; Muir & Gadawski, 1998). The clinical implications of prolonged respiratory apnoea for small animal patients involve simultaneous decreases in alveolar gas exchange and gaseous anaesthetic intake, thereby increasing the risk of life-threatening respiratory complications and producing a more challenging environment for safe and effective anaesthetic management of the patient (Keates & Whittem, 2012).

The four studies identified in the literature search strived to identify causative links between rate of propofol administration and the incidence or duration of post-induction apnoea in healthy dogs, and all followed a prospective clinical trial study design. Randomised controlled trials are among the most rigorous study designs, and are particularly valuable when research objectives involve investigating clinical problems pertaining to intervention effects on measurable outcomes, and offering readers applicable solutions to improve patient outcomes (Bhide et al., 2018; Hariton & Locascio, 2018; Sargeant et al., 2014). The Murison (2001), Bigby et al. (2017a), and Raillard (2018) studies may be assigned Evidence Action Ratings (EARs) of B3, B4, and B3 respectively in regard to apnoea incidence if faster propofol infusion is considered as the treatment intervention and slower propofol infusion as standard treatment. Walters et al. (2022) considered propofol duration as an intervention outcome following anaesthetic induction using one of five propofol infusion speeds, making EAR assignment impractical. Very similar study populations were used across the four studies, with brachycephalic breeds and dogs on concurrent medications consistently excluded. However, there are a number of methodological differences between the studies, and each has a number of internal limitations.

Murison (2001) used halothane as the volatile agent during maintenance of anaesthesia whereas Bigby et al. (2017a), Walters et al. (2022), and Raillard et al. (2018) used isoflurane. For measurements of time-to-first-breath these differences will not have impacted results since no gaseous anaesthetic uptake has occurred prior to respiration. However, these differences may contribute to future apnoea phases which occur after breathing circuit connection and the first spontaneous breath, as measured in the Murison (2001), Bigby et al. (2017a), and Raillard et al. (2018) studies. The apnoeic index of halothane is approximately 60% higher than the apnoeic index of isoflurane, meaning that halothane causes greater respiratory depression than isoflurane if given at the same gas concentration (Dunlop, 2014). This difference may have caused a higher overall apnoea incidence in the Murison (2001) study population, since respiratory depression can cause hypoventilation eventually leading to complete cessation of spontaneous respiration (Taenzer & Havidich, 2018).

There is also a possibility that study outcomes were influenced by the choice of premedication drugs in each study. Murison (2001) and Raillard et al. (2018) utilised acepromazine whilst Bigby et al. (2017a) and Walters et al. (2022) used dexmedetomidine in their premedication protocols. Raillard et al. (2018), Bigby et al. (2017a), and Walters et al. (2022) also used methadone. These drugs and drug combinations have been found to have no significant impact on the incidence or duration of apnoea following induction with propofol in dogs (Bigby et al., 2017b; Bigby, 2018). However, Murison (2001) utilised morphine, which is known to cause respiratory depression and upper airway collapse, as a second premedication drug (Freire et al., 2022). Whilst this is possibly a confounding factor in the Murison (2001) study, some research has suggested that morphine is a less potent cardio-pulmonary depressor than methadone in dogs (Maiante et al., 2009). Together, existing evidence suggests that premedication selection is unlikely to have introduced significant variability to findings across the four appraised studies (Bigby et al., 2017a; Murison, 2001; Raillard, 2018; Walters et al., 2022).

Additionally, propofol was administered intravenously using a syringe-driver in the Bigby et al. (2017a), Walters et al. (2022), and Raillard et al. (2018) studies, compared with manual syringe depression by Murison (2001). This means that administration speeds were less consistent within the Murison (2001) study than in the other two papers, potentially introducing variability and creating a comparative limitation. Additionally, both administration speeds used in the Murison (2001) paper are rapid relative to the manufacturer-recommended administration speed, meaning that the study did not investigate the effects of a true ‘slow’ rate, as might be used in clinical practice (Zoetis, 2022). This creates an important limitation to the applicability and reliability of conclusions drawn from the Murison (2001) paper. In the Raillard et al. (2018) study, too, even the fastest propofol administration speed was set at the low end of manufacturer recommended administration rates. This may have resulted in expected differences in apnoea incidence between fast and slow groups not being observed and makes it challenging to compare findings with those reported by Murison (2001).

A further difference between the studies was in relation to the definition of apnoea used. Murison (2001), Bigby et al. (2017a), and Raillard et al. (2018) defined apnoea in terms of time elapsed under anaesthesia with no spontaneous respiration. By contrast, Walters et al. (2022) defined apnoea in terms of time from intubation to commencement of either spontaneous breathing or manual ventilation. These differences in apnoea definition are not study limitations per se, but must be taken into account when comparing study findings and drawing conclusions to improve evidence-based clinical decisions. Finally, Bigby et al. (2017a) and Raillard et al. (2018) both used a sample size of 32 dogs, which is relatively small compared with the Murison (2001) and Walters et al. (2022) studies. In the Bigby et al. (2017a) paper, sample size and power calculations were performed prior to study commencement and statistically significant results were identified, suggesting that sample size is unlikely to have created a true limitation. In the Raillard et al. (2018) study, however, post hoc statistical tests revealed that this sample size has insufficient power to accurately identify significant differences in independent variables between the control and fast administration groups. This may have compromised the accuracy of findings reported by the paper.

The first finding identified by both Bigby et al. (2017a) and Walters et al. (2022) relates to the effect of total propofol dose on the incidence of post-induction apnoea. Though this finding does not directly relate to the PICO question, it is a notable confounding factor when investigating the effects of administration speed for a drug that is commonly titrated to effect in clinical practice. The dose-dependent cardiopulmonary depression caused by propofol has been extensively studied in both veterinary and human medical literature, and there is strong evidence linking high propofol doses with a higher incidence of respiratory apnoea in dogs (Muir & Gadawski, 1998). In a canine dose-escalation study, Keates and Whittem (2012) confirmed the positive correlation between propofol dose and apnoea incidence identified by Bigby et al. (2017a) and Walters et al. (2022), and a human paediatric medicine study has indicated this dose-dependent increase is non-linear, instead involving a plateau or decrease in apnoea incidence for certain dose ranges before the increase continues (Aun et al., 1992). Walters et al. (2022) also discovered that apnoea duration significantly increases with increasing propofol dose, a finding which too reflects existing evidence of this correlation in human anaesthesiology (Park et al., 1997). Bigby et al. (2017a) accounts for differences in apnoea incidence between slow infusion of propofol (P-Slow) and fast infusion of propofol (P-Fast) groups by suggesting that rapid administration of drugs causes accumulation in the plasma before penetrating the central nervous system (CNS), due to a constant equilibration rate of the drug concentration between plasma and CNS. Once the entire induction dose has been transferred to the CNS, the drug is in relative excess, causing increased respiratory and nervous depression and an elevated risk of apnoea (Bigby et al., 2017a). Bigby et al. (2017a) linked this finding to one of the study hypotheses, which was that the induction dose of propofol required to induce anaesthesia is higher when the drug is administered quickly, compared with the required dose when propofol is administered slowly. They concluded that reducing the administration speed of propofol lowers the risk of a relative overdose, thereby minimising apnoea incidence (Bigby et al., 2017a). Similar findings were identified by Raillard et al. (2018), where slow propofol administration was found to reduce induction dose requirements, compared to the other two treatment groups, fast propofol administration, and placebo, respectively. However, unlike Bigby et al. (2017a) and Walters et al. (2022), Raillard et al. (2018) found no significant difference in apnoea incidence between the predosed and slow infusion groups. A similar relationship has also been found between propofol concentration and dose required to induce anaesthesia, where diluted propofol significantly lowers the dose required to induce anaesthesia (Rögels & Martinez-Taboada, 2021). By contrast, Murison (2001) kept the total dose, in mg/kg, of propofol administered to each dog consistent, only varying the speed at which this dose was administered.

A further objective of the studies was to measure the effect that speed of propofol administration has on the generation and appearance of post-induction apnoea, closely reflecting the PICO question. Murison (2001) aimed to quantify the incidence and duration of post-induction apnoea in canine subjects in response to a faster or slower propofol infusion. Their findings suggest that a slower propofol infusion rate is associated with a higher incidence and duration of post-induction apnoea though this difference was not statistically significant (Murison, 2001). Significant differences were found, however, between the slow and fast administration groups in time elapsed before first breath (Murison, 2001). Although time elapsed before first spontaneous breath was not included in the Murison (2001) definition of respiratory apnoea, this metric was included in the Walters et al. (2022) definition. As such, the significant difference in time to first breath identified between fast and slow propofol infusion groups by Murison (2001), with slow propofol administration resulting in a longer time to first breath, directly contradicts the findings of Walters et al. (2022). Importantly, the Murison (2001) study kept the propofol dose, in mg/kg, constant for all subjects. By contrast, in the Bigby et al. (2017a) and Walters et al. (2022) studies, there were significant differences in total induction agent dose between propofol administration groups, as well as a strong positive correlation between propofol dose and both apnoea incidence and duration. Raillard et al. (2018) found no significant difference in apnoea incidence between slow infusion and predosed groups. This makes it challenging to determine whether the effect on the appearance of apnoea in some studies was caused by speed of administration, by dose, or by a combination of both factors. As such, the association between administration speed and apnoea incidence is more clearly characterised in the Murison (2001) study, where administration speed was the only independent variable, than in the Bigby et al. (2017a), Walters et al. (2022), or Raillard et al. (2018) studies where both administration speed and propofol dose varied significantly between intervention groups. Despite this, study outcomes from both Bigby et al. (2017a) and Walters et al. (2022) agree that faster speeds of propofol administration were associated with both significantly higher rates of apnoea incidence, as well as significantly higher propofol doses. Hence, considering the key findings from each of the four studies, current evidence inconsistently characterises the relationship between speed of propofol administration and the appearance of respiratory apnoea in dogs. Cuniberti et al. (2023) compared target-controlled propofol infusion with continuous rate infusion. While the study reported incidental findings regarding administration speed and apnoea incidence, which were consistent with Raillard et al. (2018), it was excluded from this Knowledge Summary as its primary research aims and methodological framework were not aligned with the defined PICO question.

Similarly, Khojasteh & Vesal (2023) found that apnoea incidence was not influenced by a significant difference in propofol infusion rate between two intervention groups, as part of a reflex assessment study in anaesthetised dogs where propofol was utilised for anaesthetic induction and maintenance. As for Cuniberti et al. (2023), Khojasteh & Vesal (2023) was excluded from this Knowledge Summary since their research objectives and study design did not aim to elucidate the effect of propofol infusion speed on apnoea in dogs.

In conclusion, the evidence that a higher propofol dose is associated with greater post-induction apnoea incidence in dogs is strong, supported by findings from two out of four studies, alongside reasonable evidence to suggest that higher doses are also associated with longer apnoea duration (Bigby et al., 2017a; Walters et al., 2022). However, evidence suggesting that slow administration of propofol lowers respiratory apnoea incidence when compared with fast administration of propofol if total propofol dose is kept constant remains weak, since findings from the four examined studies inconsistently supported this (Bigby et al., 2017a; Murison, 2001; Raillard et al., 2018; Walters et al., 2022). It follows, however, from the Bigby et al. (2017a) and Walters et al. (2022) studies, that rapid intravenous administration of propofol during anaesthetic induction when titrating to effect consistently leads to administration of a higher total dose when compared with a slower injection speed, due to both practical limitations of this method – such as waiting to observe clinical effects before ceasing propofol infusion – as well as altered dose requirements depending on administration speed (Raillard et al., 2018). As such, a clinical takeaway from these studies is that administering propofol slowly is likely to minimise effects associated with high doses, including the incidence and duration of apnoea.

Future research may choose to investigate whether similar findings are established if brachycephalic breeds are included in studies of apnoea appearance and the effects of propofol administration speed. At present, no studies have examined whether these breeds demonstrate different outcomes compared with those described by Murison (2001), Bigby et al. (2017a), and Walters et al. (2022), despite having significant anatomical deviations from non-brachycephalic dogs that may exacerbate respiratory complications when under anaesthesia (Gruenheid et al., 2018). Additionally, a small number of studies have examined the relationship between propofol administration methods and intra-anaesthetic hypotension incidence, and this remains an area for further research – in particular, the effect of propofol administration speed on hypotension incidence and severity. Measurement of hypotension, and its occurrence relative to plasma concentration targets during propofol infusion, was one study outcome of the Cuniberti et al. (2023) study. A similar study was conducted by Musk et al. (2005) to analyse anaesthetic induction targets and apnoea incidence in response to increased plasma concentration of propofol. This association also warrants further investigation. Finally, Walters et al. (2022) identified a need for further research to identify propofol bolus administration rates that minimise adverse effects, including apnoea.

Methodology

Search Strategy

 

Exclusion / Inclusion Criteria

 

Search Outcome

 

Acknowledgements

Thank you to Dr Eduardo Uquillas, (BVM, DVM, DACVAA) for supervising the preparation of this Knowledge Summary and providing a wealth of experience, knowledge and guidance.

Author contributions

Alexandra Fraser: Project administration, Conceptualisation, Methodology, Investigation, Writing - Original Draft, Writing - Review and Editing, Visualisation. Eduardo Uquillas: Supervision, Conceptualisation, Methodology, Validation, Writing - Review and Editing.

ORCiD

Alexandra Fraser: https://orcid.org/0009-0001-9585-0360
Eduardo Uquillas: https://orcid.org/0000-0002-4227-2173

Conflict of Interest

The author declares no conflicts of interest.

References

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