University of Edinburgh



RESEARCH PAPERRunning head (Authors): M Raillard et al.Running head (short title): Propofol predosing in dogsEffect of predosing versus slow administration of propofol on the dose required for anaesthetic induction and on physiologic variables in healthy dogsMathieu Raillarda, Emma J Lovea & Pamela J MurisonbaBristol Veterinary School, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UKbRoyal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, Nr Roslin, Midlothian EH25 9RG, UKCorrespondence: Mathieu Raillard, Institute of Anaesthesiology and Pain Therapy, Vetsuisse Faculty, University of Bern, L?nggassstrasse 124, CH-3012 Bern, Switzerland. E-mail: mathieu_raillard@yahoo.itAbstractObjective To investigate 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 Thirty-two healthy dogs (18 male, 13 female, one intersex, 6–144 months, 3.5–47.2 kg). Methods Premedication was intramuscular acepromazine (0.025 mg kg?1) and methadone (0.25 mg kg?1). Thirty minutes later 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 (fR) 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, fR, 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, fR, MAP and apnoea were similar among groups.Clinical relevance Slower injection of propofol reduces the dose required for induction of anaesthesia. Keywords anaesthesia, co-induction, dogs, induction, predosing, propofol.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 co-administered (Whitwam 1995). 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Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Alastair</firstName><middleNames>R</middleNames><lastName>Mair</lastName></author><author><firstName>Patricia</firstName><lastName>Pawson</lastName></author><author><firstName>Emily</firstName><lastName>Courcier</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication></publications><cites></cites></citation>(Lerche et al. 2000; Mair et al. 2009; Henao-Guerrero & Ricco 2014; Martinez-Taboada & Leece 2014). A reduction in propofol dose was demonstrated in some studies. The sequence order 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 ADDIN PAPERS2_CITATIONS <citation><uuid>F089C9F4-745D-4E54-9496-BF8366192998</uuid><priority>0</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication></publications><cites></cites></citation>(Covey-Crump & Murison 2008; ADDIN PAPERS2_CITATIONS <citation><uuid>D428AFF1-067D-4222-8EC0-277BED167793</uuid><priority>5</priority><publications><publication><uuid>917D2B63-EDB6-4887-9E36-557A69019AC7</uuid><volume>40</volume><doi>10.1111/vaa.12038</doi><startpage>359</startpage><publication_date>99201304091200000000222000</publication_date><url> of altering the sequence of midazolam and propofol during co-induction of anaesthesia</title><number>4</number><subtype>400</subtype><endpage>366</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Andrea</firstName><lastName>Sánchez</lastName></author><author><firstName>Eliseo</firstName><lastName>Belda</lastName></author><author><firstName>Mayte</firstName><lastName>Escobar</lastName></author><author><firstName>Amalia</firstName><lastName>Agut</lastName></author><author><firstName>Marta</firstName><lastName>Soler</lastName></author><author><firstName>Francisco</firstName><middleNames>G</middleNames><lastName>Laredo</lastName></author></authors></publication><publication><publication_date>99201306101200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12052</doi><title>A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs, premedicated with methadone and acepromazine</title><uuid>F22B64E1-96D9-4C35-99C7-0C83292EAACF</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><citekey>Robinson:2013hu</citekey><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Rebecca</firstName><lastName>Robinson</lastName></author><author><firstName>Kate</firstName><lastName>Borer-Weir</lastName></author></authors></publication></publications><cites></cites></citation>Robinson & Borer-Weir 2013; Sánchez et al. 2013).Predosing with propofol has been reported in human anaesthesia. The technique is described as the administration of a fixed dose of propofol 2 minutes before induction of anaesthesia with propofol ADDIN PAPERS2_CITATIONS <citation><uuid>B66E1C43-C1B3-4AED-8158-B8ACB6E5634B</uuid><priority>6</priority><publications><publication><volume>53</volume><publication_date>99199811001200000000220000</publication_date><number>11</number><institution>Department of Anaesthetics, Falkirk and District Royal Infirmary, UK.</institution><startpage>1117</startpage><title>A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia.</title><uuid>CD9C99E3-3B08-42B5-8BB6-78B4A6E9A1CE</uuid><subtype>400</subtype><endpage>1120</endpage><type>400</type><url> Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>L</firstName><lastName>Anderson</lastName></author><author><firstName>H</firstName><lastName>Robb</lastName></author></authors></publication><publication><startpage>51</startpage><title>Forum Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery</title><uuid>DC03FCF8-9364-45C6-89E2-957C207879EB</uuid><subtype>400</subtype><endpage>85</endpage><type>400</type><publication_date>99199900001200000000200000</publication_date><bundle><publication><publisher>Blackwell Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>G</firstName><lastName>Djaiani</lastName></author><author><firstName>MP</firstName><lastName>Ribes-Pastor</lastName></author></authors></publication></publications><cites></cites></citation>(Anderson & Robb 1998; Djaiani & Ribes-Pastor 1999). It reduces the propofol dose required for induction of anaesthesia ADDIN PAPERS2_CITATIONS <citation><uuid>52A089D8-5F67-441E-81D3-F0F00A94F2EA</uuid><priority>7</priority><publications><publication><volume>53</volume><publication_date>99199811001200000000220000</publication_date><number>11</number><institution>Department of Anaesthetics, Falkirk and District Royal Infirmary, UK.</institution><startpage>1117</startpage><title>A comparison of midazolam co-induction with propofol predosing for induction of anaesthesia.</title><uuid>CD9C99E3-3B08-42B5-8BB6-78B4A6E9A1CE</uuid><subtype>400</subtype><endpage>1120</endpage><type>400</type><url> Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>L</firstName><lastName>Anderson</lastName></author><author><firstName>H</firstName><lastName>Robb</lastName></author></authors></publication><publication><startpage>51</startpage><title>Forum Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery</title><uuid>DC03FCF8-9364-45C6-89E2-957C207879EB</uuid><subtype>400</subtype><endpage>85</endpage><type>400</type><publication_date>99199900001200000000200000</publication_date><bundle><publication><publisher>Blackwell Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>G</firstName><lastName>Djaiani</lastName></author><author><firstName>MP</firstName><lastName>Ribes-Pastor</lastName></author></authors></publication><publication><volume>50</volume><publication_date>99200600001200000000200000</publication_date><number>2</number><startpage>112</startpage><title>Small dose propofol or Ketamine as an alternative to midazolam co-induction to propofol</title><uuid>1C26413A-4C18-4937-BFA7-3C88FB8ECEA1</uuid><subtype>400</subtype><endpage>114</endpage><type>400</type><citekey>Srivastava:2006wd</citekey><url> J Anaesth</title><type>-100</type><subtype>-100</subtype><uuid>4EF5925C-DB32-4932-B6D9-C358F8A6A046</uuid></publication></bundle><authors><author><firstName>U.</firstName><lastName>Srivastava</lastName></author><author><firstName>DN</firstName><lastName>Sharma</lastName></author><author><firstName>A.</firstName><lastName>Kumar</lastName></author><author><firstName>S.</firstName><lastName>Saxsena</lastName></author></authors></publication><publication><volume>54</volume><publication_date>99201000001200000000200000</publication_date><number>6</number><doi>10.4103/0019-5049.72647</doi><startpage>558</startpage><title>A comparative study of efficacy of propofol auto-co-induction versus midazolam propofol co-induction using the priming principle</title><uuid>C8F86330-4831-472E-BF3B-A2C69A444033</uuid><subtype>400</subtype><publisher>Medknow Publications</publisher><type>400</type><url> journal of anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>31A8CF53-CE2B-4764-8469-B9519567003D</uuid></publication></bundle><authors><author><firstName>R.</firstName><lastName>Kataria</lastName></author><author><firstName>A.</firstName><lastName>Singhal</lastName></author><author><firstName>S.</firstName><lastName>Prakash</lastName></author><author><firstName>I.</firstName><lastName>Singh</lastName></author></authors></publication></publications><cites></cites></citation>(Anderson & Robb 1998; Djaiani & 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 ADDIN PAPERS2_CITATIONS <citation><uuid>913D1474-C0D9-44A2-A3C7-A23239BD1915</uuid><priority>8</priority><publications><publication><startpage>51</startpage><title>Forum Propofol auto-co-induction as an alternative to midazolam co-induction for ambulatory surgery</title><uuid>DC03FCF8-9364-45C6-89E2-957C207879EB</uuid><subtype>400</subtype><endpage>85</endpage><type>400</type><publication_date>99199900001200000000200000</publication_date><bundle><publication><publisher>Blackwell Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>G</firstName><lastName>Djaiani</lastName></author><author><firstName>MP</firstName><lastName>Ribes-Pastor</lastName></author></authors></publication><publication><volume>54</volume><publication_date>99201000001200000000200000</publication_date><number>6</number><doi>10.4103/0019-5049.72647</doi><startpage>558</startpage><title>A comparative study of efficacy of propofol auto-co-induction versus midazolam propofol co-induction using the priming principle</title><uuid>C8F86330-4831-472E-BF3B-A2C69A444033</uuid><subtype>400</subtype><publisher>Medknow Publications</publisher><type>400</type><url> journal of anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>31A8CF53-CE2B-4764-8469-B9519567003D</uuid></publication></bundle><authors><author><firstName>R.</firstName><lastName>Kataria</lastName></author><author><firstName>A.</firstName><lastName>Singhal</lastName></author><author><firstName>S.</firstName><lastName>Prakash</lastName></author><author><firstName>I.</firstName><lastName>Singh</lastName></author></authors></publication></publications><cites></cites></citation>(Djaiani & 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 two to three minutes after the interruption of propofol administration ADDIN PAPERS2_CITATIONS <citation><uuid>7BCB4B43-C118-4AD2-B1EE-1727A279AD97</uuid><priority>0</priority><publications><publication><volume>79</volume><publication_date>99199710001200000000220000</publication_date><number>4</number><institution>Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, SA, Australia.</institution><startpage>505</startpage><title>A physiological model of induction of anaesthesia with propofol in sheep .2. Model analysis and implications for dose requirements</title><uuid>35D7B8A6-0661-4930-A5D4-03F628E89C95</uuid><subtype>400</subtype><endpage>513</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>G</firstName><middleNames>L</middleNames><lastName>Ludbrook</lastName></author><author><firstName>R</firstName><middleNames>N</middleNames><lastName>Upton</lastName></author></authors></publication></publications><cites></cites></citation>(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 hypotheses were 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.Material and methodsHealthy adult dogs in American Society of Anesthesiologists (ASA) categories I and II undergoing elective procedures, and for which a standardized anaesthetic protocol was appropriate, were considered for inclusion in the study. Exclusion criteria included brachycephalic and giant breeds of dog, dogs at high risk for regurgitation during induction of anaesthesia, nervous or aggressive dogs, dogs suffering from systemic illness or trauma, and dogs receiving drug treatment that could potentially affect the action of the sedative and anaesthetic agents. Informed owner consent was obtained and the study was conducted with institutional ethical committee approval (VIN/14/012). Dogs were allocated to one of three groups (propofol predosing, control propofol and slow injection of propofol) by block randomization using . A sample size calculation was performed using data from a published study in which a difference in propofol requirement of 1 mg kg?1 was considered clinically relevant with an estimated standard deviation of 0.75 mg kg?1 ADDIN PAPERS2_CITATIONS <citation><uuid>129148FB-BF21-445C-AA98-621E5760D979</uuid><priority>0</priority><publications><publication><publication_date>99201306101200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12052</doi><title>A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs, premedicated with methadone and acepromazine</title><uuid>F22B64E1-96D9-4C35-99C7-0C83292EAACF</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><citekey>Robinson:2013hu</citekey><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Rebecca</firstName><lastName>Robinson</lastName></author><author><firstName>Kate</firstName><lastName>Borer-Weir</lastName></author></authors></publication></publications><cites></cites></citation>(Robinson & Borer-Weir 2013). The estimated sample size was nine animals per group with a study power of 0.8 and an alpha of 0.05. The same syringe driver (IVAC P7000; Alaris Medical Systems, UK) was used for propofol administration in all cases. Its calibration was regularly checked during the study period by filling a syringe and infusion line identical to the ones used in this study with water and placing the syringe in the syringe driver; different infusion rates and different intervals were set and the amount of water coming out was weighed on an electronic balance and compared with the expected output. The study syringe driver consistently provided the expected output throughout the study. Before any treatment, pulse rate (PR) (palpation of a femoral or a peripheral pulse) and respiratory rate (fR) (observation of thoracic excursions) were measured. Sedation was scored using a simple descriptive scale: 0, no sedation; 1, mild sedation (quieter than before injection but still bright and active); 2, moderate sedation (quiet, reluctant to move, possibly slightly ataxic but able to walk); 3, profound sedation (unable to walk unaided) ADDIN PAPERS2_CITATIONS <citation><uuid>5754B2AA-F713-4752-92F9-C7F2D28E69A1</uuid><priority>0</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication></publications><cites></cites></citation>(Covey-Crump & Murison 2008; Table 1). Activity was scored using a simple descriptive scale: 0, sedation (more sedated than before co-induction?agent injection); 1, no change (compared with before injection); 2, excitement (more activity than before injection) (Covey-Crump ADDIN PAPERS2_CITATIONS <citation><uuid>772F736E-CFE1-404A-8DEE-F2A7BFDAE798</uuid><priority>0</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication></publications><cites></cites></citation> & Murison 2008). The activity score was included in case some excitement occurred during induction of anaesthesia. Acepromazine (0.025 mg kg?1; ACP 2 mg mL?1, Novartis, UK) and methadone (0.25 mg kg?1, Comfortan; 10 mg mL?1 solution for injection; Dechra, UK) were combined in the same syringe and administered into the cervical epaxial musculature. After administration of preanaesthetic medication the dogs were kept in a kennel in a quiet area next to the anaesthetic induction suite. Thirty minutes later, sedation and activity were scored and PR and fR measured (Table 1). When the dog appeared to be relaxed, a catheter was inserted into a cephalic vein and the dog was transferred into the anaesthesia induction suite and positioned in sternal recumbency on a table. Immediately before induction of anaesthesia, PR and fR were measured. Mean arterial pressure (MAP) was recorded using an appropriately sized cuff on the thoracic limb opposite to the IV catheter (width of 35–40 % of the circumference of the measuring site, on the thoracic limb above the carpus) (Cardell model 9401; Midmark Animal Health, FL, USA). Propofol (0.5 mg kg?1; PropoFlo 28; Abbott Animal Health, UK) was injected by hand over 1–3 seconds to dogs in the predosing group (group PP, n = 11) two minutes before commencing administration of propofol (4 mg kg?1 minute?1) IV using the syringe driver (T0) (Table 1). In the control group (group CP, n = 10) saline (equivalent volume to 0.5 mg kg?1 of propofol) was injected IV manually as a rapid bolus two minutes before commencing administration of propofol (4 mg kg?1 minute?1) IV (T0). The third induction protocol was considered to be slow-induction (group SI, n = 10) and propofol (1.3 mg kg?1 minute?1) was administered to the dogs using the syringe driver from the beginning of the induction phase (T0) until intubation. An anaesthetist who was aware of the treatment group started the process of induction of anaesthesia by administering the propofol in PP, saline in CP or commencing the propofol infusion in SI. At 2 minutes (T2), this same anaesthetist started the propofol infusion for dogs in PP and CP; the infusion rate to dogs in SI was unchanged. The infusion rate information on the syringe driver was covered. Then, another investigator (MR) who was unaware of group assignments entered at two minutes after commencing induction of anaesthesia to assess adequacy for tracheal intubation. Depth of anaesthesia was continuously assessed using muscular tone, palpebral reflexes, eye rotation and jaw tone. The dog was considered sufficiently relaxed to allow intubation when it attained lateral recumbency with no spontaneous head, jaw or tongue movement in response to the anaesthetist opening its mouth, and jaw tone was mild to absent. Propofol administration was stopped at that point and the trachea was intubated with a cuffed endotracheal tube (T3). The cuff was initially inflated until the pressure in the pilot balloon assessed by palpation felt subjectively appropriate to the anaesthetist; at the end of data collection the cuff was deflated and re-inflated whilst manual breaths were administered to the animal with the adjustable pressure limiting valve closed until no leak could be detected at a pressure of 20 cm H2O. If a dog became apnoeic within 2 minutes of propofol administration, the anaesthetist aware of the treatment and in charge of anaesthesia was instructed to stop drug administration, if appropriate, and manage the airway as necessary. The dog would have then been excluded from the study.Anaesthesia was maintained with isoflurane vaporized in oxygen delivered via a breathing system appropriate for the size of the dog. PR, fR and MAP were recorded before the induction process was started (T0), 2 minutes later (when the primary investigator re-entered the room; T2) and 0 (T3), 2 and 5 minutes after intubation (P1 and P2) (Table 1). Dogs were positioned in lateral recumbency for 5 minutes after intubation of the trachea. Apnoea >30 seconds was recorded and managed (lungs were inflated manually twice a minute until return of spontaneous ventilation). Quality of induction and endotracheal intubation were scored using simple descriptive scales: Intubation score: 0, smooth (no swallowing, coughing, tongue or jaw ?movement); 1, fair (some tongue movement, slight cough); 2, poor (marked tongue or jaw movement and swallowing?or coughing]; 3, very poor (as 2 but requiring additional propofol?dose and second attempt at intubation) (Covey-Crump ADDIN PAPERS2_CITATIONS <citation><uuid>1345E8B8-1EAC-489D-ABAD-A9E4E6B2BCB9</uuid><priority>0</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication></publications><cites></cites></citation> & Murison 2008). Quality score: 0, smooth (without excitement); 1, fair (slight excitement, muscle twitching or movement?of limbs); 2, poor (marked excitement, muscle twitching, paddling?of limbs, head movements) (Covey-Crump ADDIN PAPERS2_CITATIONS <citation><uuid>1345E8B8-1EAC-489D-ABAD-A9E4E6B2BCB9</uuid><priority>0</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication></publications><cites></cites></citation> & Murison 2008). Once data collection was complete, the dogs were prepared for surgery or underwent the procedure for which they were anaesthetized. Anaesthetic management was adjusted individually at the discretion of the main investigator.Statistical analysisData were analysed using SPSS for Windows (SPSS 14.0, IL, USA) though SigmaPlot for Windows Version 10.0 (Systat Software Inc, CA, USA) was used for re-analysis of the data on propofol. Normal distribution of the data was checked using the Shapiro-Wilk test. One-way analysis of variance (anova) was used for the propofol dose and Bonferroni post hoc test where appropriate; repeated measures anova for PR, fR and MAP; Chi squared exact test for sedation and activity and quality scores; Normal chi squared for the incidence of apnoea. Significance level was set at p < 0.05 and, unless stated differently, data are presented as mean standard deviation.ResultsA total of 32 client-owned dogs (18 male, 13 female and one intersex, ASA I-II, aged 6–144 months and weighing 3.5–47.2 kg) were recruited between August 2014 and March 2015. Demographic data were similar among groups (Table 2). Breed distribution was uneven among the groups, involving 10 crossbreeds, four Springer Spaniels, three Cocker Spaniels and three Labrador Retrievers, and one each of Collie, Flat Coated Retriever, German Shepherd, Miniature Schnauzer, Patterdale, Rhodesian Ridgeback, Rottweiler, Staffordshire Bull Terrier, West Highland White Terrier, Wire-haired Dachshund and Yorkshire Terrier. One dog in PP was excluded due to perivascular propofol administration. Analysis was carried out on 11 dogs in PP and 10 each in CP and SI. Sedation and activity scores did not differ among groups (Table 3). No dog became apnoeic within the first 2 minutes of induction (between T0 and T2). Propofol dose requirement was lower in SI (3.7 1.1 mg kg?1) compared with PP (5.0 1.0 mg kg?1) and CP (4.8 0.6 mg kg?1) (p = 0.002, p = 0.012, respectively; Fig. 1). Quality of induction was smooth in all cases and similar among groups (Table 3). Median time (range) from T0 to T3 was 3.1 (2.9-3.6) minutes in PP, 3.2 (3.0-3.4) minutes in CP and 2.6 (2.2-4.5) minutes in SI.No statistically significant difference was found among groups for mean PR, fR, MAP or incidence of apnoea. Haemodynamic and respiratory variables were not different among groups (Table 4). Between 1 and 4 dogs per group were apnoeic after induction of anaesthesia (χ2 2.14, p = 0.340). Apnoea occurred in four dogs in PP, two in CP and one dog in SI.DiscussionThe main finding of this study was that the speed of injection of propofol had an effect on the dose requirement, with a slower injection of propofol reducing the dose required for endotracheal intubation in dogs. Early animal studies indicated that the rate of administration had an impact on the dosage necessary to induce anaesthesia ADDIN PAPERS2_CITATIONS <citation><uuid>D5E9C3BD-571B-433E-875B-0CCEC300C2D6</uuid><priority>0</priority><publications><publication><volume>52</volume><publication_date>99198000001200000000200000</publication_date><number>8</number><doi>10.1523/JNEUROSCI.1006-04.2004</doi><startpage>731</startpage><title>Animal Studies of the Anesthetic Activity of Ici 35-868</title><uuid>76A8EDC0-8951-4B63-B79C-2C89699E257B</uuid><subtype>400</subtype><endpage>742</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>J</firstName><middleNames>B</middleNames><lastName>GLEN</lastName></author></authors></publication></publications><cites></cites></citation>(Glen 1980). In the original study, faster rates (administration over 1 second) were associated with lower dosages when compared with administration over 10 seconds in mice ADDIN PAPERS2_CITATIONS <citation><uuid>C6EF02D5-C693-4505-A09B-85CD22ADF73E</uuid><priority>0</priority><publications><publication><volume>52</volume><publication_date>99198000001200000000200000</publication_date><number>8</number><doi>10.1523/JNEUROSCI.1006-04.2004</doi><startpage>731</startpage><title>Animal Studies of the Anesthetic Activity of Ici 35-868</title><uuid>76A8EDC0-8951-4B63-B79C-2C89699E257B</uuid><subtype>400</subtype><endpage>742</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>J</firstName><middleNames>B</middleNames><lastName>GLEN</lastName></author></authors></publication></publications><cites></cites></citation>(Glen 1980). This is in contrast to later human studies ADDIN PAPERS2_CITATIONS <citation><uuid>1AC3C449-A4F1-471F-AE6A-77DB045DDA94</uuid><priority>0</priority><publications><publication><volume>72</volume><publication_date>99199105011200000000222000</publication_date><number>5</number><startpage>578</startpage><title>Rate-Dependent Induction Phenomena With Propofol: Implications for the Relative Potency of Intravenous Anesthetics.</title><uuid>63B1A4BF-93F0-4E5F-A510-38A7A22FCBE6</uuid><subtype>400</subtype><type>400</type><url> &amp; Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>8D6171B6-F5E9-4004-828B-BB3DCB988166</uuid></publication></bundle><authors><author><firstName>D</firstName><middleNames>N</middleNames><lastName>Stokes</lastName></author><author><firstName>P</firstName><lastName>Hutton</lastName></author></authors></publication></publications><cites></cites></citation>(Stokes & Hutton 1991) where slower administrations of propofol resulted in lower dosages necessary to lose verbal command. It is difficult to compare human and veterinary studies as the goals and end point of induction of anaesthesia are different. In both cases propofol should facilitate the transition from a conscious to an unconscious state, but in dogs propofol is also used to induce a state suitable for airway management, such as laryngeal mask insertion or tracheal intubation (Berry 2015). As in humans, slower administration of propofol in experimental sheep resulted in lower dosages necessary to induce anaesthesia ADDIN PAPERS2_CITATIONS <citation><uuid>B65D5CFF-7DA6-43F7-993F-BA37634E445D</uuid><priority>0</priority><publications><publication><volume>79</volume><publication_date>99199710001200000000220000</publication_date><number>4</number><institution>Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, SA, Australia.</institution><startpage>505</startpage><title>A physiological model of induction of anaesthesia with propofol in sheep .2. Model analysis and implications for dose requirements</title><uuid>35D7B8A6-0661-4930-A5D4-03F628E89C95</uuid><subtype>400</subtype><endpage>513</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>G</firstName><middleNames>L</middleNames><lastName>Ludbrook</lastName></author><author><firstName>R</firstName><middleNames>N</middleNames><lastName>Upton</lastName></author></authors></publication></publications><cites></cites></citation>(Ludbrook & Upton 1997). When using clinically relevant rates of administration of propofol in dogs in the present study, a slower injection also resulted, as expected, in a lower total dose administered. Similar findings have recently been reported in cats in a pilot study ADDIN PAPERS2_CITATIONS <citation><uuid>335CCF3C-CC3F-40C1-B105-13D40830940B</uuid><priority>0</priority><publications><publication><publication_date>99201700001200000000200000</publication_date><startpage>1098612X1668917</startpage><doi>10.1177/1098612X16689175</doi><title>Influence of two administration rates of propofol at induction of anaesthesia on its relative potency in cats: a pilot study</title><uuid>7CEB2AA2-2B6B-428F-9234-64899C24D016</uuid><subtype>400</subtype><type>400</type><url> of Feline …</title><type>-100</type><subtype>-100</subtype><uuid>B52C3C43-8AA2-4D80-A270-C824B8D55F67</uuid></publication></bundle><authors><author><firstName>S</firstName><middleNames>H</middleNames><lastName>Bauquier</lastName></author><author><firstName>W</firstName><lastName>Bayldon</lastName></author><author><firstName>L</firstName><middleNames>N</middleNames><lastName>Warne</lastName></author></authors></publication></publications><cites></cites></citation>(Bauquier et al. 2017).Modes, dosages and speed of injection of propofol for co-induction of anaesthesia in dogs are extremely variable in the literature. Target-controlled infusion (TCI) has been used in several studies ADDIN PAPERS2_CITATIONS <citation><uuid>2624697B-209D-4356-A3D8-8D9BC65EFE81</uuid><priority>18</priority><publications><publication><uuid>50DB4DDD-C08C-4DD0-A62E-FB3A316BD253</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00395.x</doi><version>Wiley Online Library</version><startpage>319</startpage><publication_date>99200807001200000000220000</publication_date><url> comparison of induction of anaesthesia using a target-controlled infusion device in dogs with propofol or a propofol and alfentanil admixture</title><number>4</number><subtype>400</subtype><endpage>325</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Adam</firstName><lastName>Auckburally</lastName></author><author><firstName>Pat</firstName><lastName>Pawson</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication><publication><uuid>97914D95-DFC5-4067-8019-7DBBC346A879</uuid><volume>36</volume><doi>10.1111/j.1467-2995.2009.00500.x</doi><startpage>532</startpage><publication_date>99200900001200000000200000</publication_date><url> comparison of the effects of two different doses of ketamine used for co-induction of anaesthesia with a target-controlled infusion of propofol in dogs</title><publisher>Wiley Online Library</publisher><number>6</number><subtype>400</subtype><endpage>538</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Alastair</firstName><middleNames>R</middleNames><lastName>Mair</lastName></author><author><firstName>Patricia</firstName><lastName>Pawson</lastName></author><author><firstName>Emily</firstName><lastName>Courcier</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication><publication><volume>34</volume><publication_date>99200709001200000000220000</publication_date><number>5</number><doi>10.1111/j.1467-2995.2006.00332.x</doi><startpage>359</startpage><title>Target-controlled infusion of propofol combined with variable rate infusion of remifentanil for anaesthesia of a dog with patent ductus arteriosus</title><uuid>5733C658-D2C5-41FE-AE69-360059CE68FF</uuid><subtype>400</subtype><endpage>364</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gabrielle</firstName><middleNames>C</middleNames><lastName>Musk</lastName></author><author><firstName>Derek</firstName><middleNames>A</middleNames><lastName>Flaherty</lastName></author></authors></publication><publication><publication_date>99201602021200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12336</doi><title>Clinical effects of midazolam or lidocaine co-induction with a propofol target-controlled infusion (TCI) in dogs</title><uuid>6EB18FB1-1847-4843-A0DB-B3F30587CC4D</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Enzo</firstName><lastName>Minghella</lastName></author><author><firstName>Adam</firstName><lastName>Auckburally</lastName></author><author><firstName>Patricia</firstName><lastName>Pawson</lastName></author><author><firstName>Marian</firstName><middleNames>E</middleNames><lastName>Scott</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication></publications><cites></cites></citation>(Musk & Flaherty 2007; Auckburally et al. 2008; Mair et al. 2009; Minghella et al. 2016). Hand injection has also been proposed with variable rates of administration: 4 mg kg?1 as rapid boluses ADDIN PAPERS2_CITATIONS <citation><uuid>F5315EB4-E413-4A42-BB22-9186658C5773</uuid><priority>0</priority><publications><publication><volume>146</volume><publication_date>99200000001200000000200000</publication_date><number>20</number><startpage>571</startpage><title>Comparative study of propofol or propofol and ketamine for the induction of anaesthesia in dogs</title><uuid>16FD9306-9CE0-4409-BC7F-E85A38200213</uuid><subtype>400</subtype><publisher>BMJ Publishing Group Limited</publisher><type>400</type><endpage>574</endpage><url> Record</title><type>-100</type><subtype>-100</subtype><uuid>B525FB3D-6B4D-42C9-87C2-1163FE93722C</uuid></publication></bundle><authors><author><firstName>P.</firstName><lastName>Lerche</lastName></author><author><firstName>J.</firstName><lastName>Reid</lastName></author><author><firstName>AM</firstName><lastName>Nolan</lastName></author></authors></publication></publications><cites></cites></citation>(Lerche et al. 2000), 4 mg kg minute?1 ADDIN PAPERS2_CITATIONS <citation><uuid>8D42FC99-52BD-4D82-83CB-66F7C820EC59</uuid><priority>20</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication><publication><publication_date>99201306101200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12052</doi><title>A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs, premedicated with methadone and acepromazine</title><uuid>F22B64E1-96D9-4C35-99C7-0C83292EAACF</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><citekey>Robinson:2013hu</citekey><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Rebecca</firstName><lastName>Robinson</lastName></author><author><firstName>Kate</firstName><lastName>Borer-Weir</lastName></author></authors></publication></publications><cites></cites></citation>(Covey-Crump & Murison 2008; Robinson & Borer-Weir 2013), up to 6.5 mg kg?1 over approximately 40 seconds ADDIN PAPERS2_CITATIONS <citation><uuid>9AECB8A0-469E-4EA8-888F-F73A80F86D70</uuid><priority>0</priority><publications><publication><volume>34</volume><publication_date>99200709001200000000220000</publication_date><number>5</number><doi>10.1111/j.1467-2995.2006.00330.x</doi><startpage>322</startpage><title>Effect of intravenous lidocaine on heart rate, systolic arterial blood pressure and cough responses to endotracheal intubation in propofol-anaesthetized dogs</title><uuid>377CCA28-F459-4CED-8348-A29ED64EEC83</uuid><subtype>400</subtype><endpage>330</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Colette</firstName><middleNames>T</middleNames><lastName>Jolliffe</lastName></author><author><firstName>Elizabeth</firstName><middleNames>A</middleNames><lastName>Leece</lastName></author><author><firstName>Vicki</firstName><lastName>Adams</lastName></author><author><firstName>David</firstName><middleNames>J</middleNames><lastName>Marlin</lastName></author></authors></publication></publications><cites></cites></citation>(Jolliffe et al. 2007), 1 to 2 mg kg?1 over 30-40 seconds followed by incremental boluses of 0.5 mg kg?1 every 15 seconds ADDIN PAPERS2_CITATIONS <citation><uuid>0D645B74-E0D3-4E56-A74E-B1CF34B54094</uuid><priority>23</priority><publications><publication><uuid>917D2B63-EDB6-4887-9E36-557A69019AC7</uuid><volume>40</volume><doi>10.1111/vaa.12038</doi><startpage>359</startpage><publication_date>99201304091200000000222000</publication_date><url> of altering the sequence of midazolam and propofol during co-induction of anaesthesia</title><number>4</number><subtype>400</subtype><endpage>366</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Andrea</firstName><lastName>Sánchez</lastName></author><author><firstName>Eliseo</firstName><lastName>Belda</lastName></author><author><firstName>Mayte</firstName><lastName>Escobar</lastName></author><author><firstName>Amalia</firstName><lastName>Agut</lastName></author><author><firstName>Marta</firstName><lastName>Soler</lastName></author><author><firstName>Francisco</firstName><middleNames>G</middleNames><lastName>Laredo</lastName></author></authors></publication><publication><volume>43</volume><publication_date>99201512161200000000222000</publication_date><number>4</number><doi>10.1111/vaa.12332</doi><startpage>405</startpage><title>Effect of intravenous lidocaine on cough response to endotracheal intubation in propofol-anaesthetized dogs</title><uuid>04152CC9-6694-4C3C-A58D-EFC4B4309276</uuid><subtype>400</subtype><endpage>411</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Ambra</firstName><lastName>Panti</lastName></author><author><firstName>Ioana</firstName><middleNames>C</middleNames><lastName>Cafrita</lastName></author><author><firstName>Louise</firstName><lastName>Clark</lastName></author></authors></publication></publications><cites></cites></citation>(Sánchez et al. 2013; Panti et al. 2015). This variability confounds comparisons between studies. In this study, a syringe driver was used for all the inductions to standardize the speed of injection and to maintain the blinding of the principal investigator. The speed of injection in the PP and CP groups was chosen to be at the lowest end of the manufacturer’s recommendation (4 mg kg minute?1). For the SI group, the speed was selected to provide an estimated induction requirement (4 mg kg?1) over a period of 3 minutes, designed to be an equivalent duration to our estimates of duration of the induction in PP group i.e. 2 minutes predosing and 1 minute titration to effect).Given the clinical end points for endotracheal intubation and the number of clinical measurements during the induction process, it is possible that administering propofol via syringe driver meant that larger doses were administered compared with intermittent injection techniques. In fact, dosages of propofol used in the present study were higher than reported in other co-induction studies with comparable premedications ADDIN PAPERS2_CITATIONS <citation><uuid>2B7E2FC2-52EA-4F80-9166-1F9ACF2EA7E5</uuid><priority>23</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication><publication><publication_date>99201306101200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12052</doi><title>A dose titration study into the effects of diazepam or midazolam on the propofol dose requirements for induction of general anaesthesia in client owned dogs, premedicated with methadone and acepromazine</title><uuid>F22B64E1-96D9-4C35-99C7-0C83292EAACF</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><citekey>Robinson:2013hu</citekey><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Rebecca</firstName><lastName>Robinson</lastName></author><author><firstName>Kate</firstName><lastName>Borer-Weir</lastName></author></authors></publication><publication><uuid>917D2B63-EDB6-4887-9E36-557A69019AC7</uuid><volume>40</volume><doi>10.1111/vaa.12038</doi><startpage>359</startpage><publication_date>99201304091200000000222000</publication_date><url> of altering the sequence of midazolam and propofol during co-induction of anaesthesia</title><number>4</number><subtype>400</subtype><endpage>366</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Andrea</firstName><lastName>Sánchez</lastName></author><author><firstName>Eliseo</firstName><lastName>Belda</lastName></author><author><firstName>Mayte</firstName><lastName>Escobar</lastName></author><author><firstName>Amalia</firstName><lastName>Agut</lastName></author><author><firstName>Marta</firstName><lastName>Soler</lastName></author><author><firstName>Francisco</firstName><middleNames>G</middleNames><lastName>Laredo</lastName></author></authors></publication></publications><cites></cites></citation>(Covey-Crump & Murison 2008; Robinson & Borer-Weir 2013; Sánchez et al. 2013). In experimental sheep, it was shown that the peak in anaesthesia depth was reached 2 to 3 minutes after cessation of propofol administration ADDIN PAPERS2_CITATIONS <citation><uuid>7BCB4B43-C118-4AD2-B1EE-1727A279AD97</uuid><priority>0</priority><publications><publication><volume>79</volume><publication_date>99199710001200000000220000</publication_date><number>4</number><institution>Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, SA, Australia.</institution><startpage>505</startpage><title>A physiological model of induction of anaesthesia with propofol in sheep .2. Model analysis and implications for dose requirements</title><uuid>35D7B8A6-0661-4930-A5D4-03F628E89C95</uuid><subtype>400</subtype><endpage>513</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>G</firstName><middleNames>L</middleNames><lastName>Ludbrook</lastName></author><author><firstName>R</firstName><middleNames>N</middleNames><lastName>Upton</lastName></author></authors></publication></publications><cites></cites></citation>(Ludbrook & Upton 1997). The hypothesis that predosing would reduce propofol requirement was not supported at the dose rates of administration used in this study. This could be a consequence of the technique used for induction of anaesthesia. Another limitation is that the method of assessment of anaesthetic depth was not very precise. Propofol was administered rapidly to dogs in PP and CP, and a further 1 mg kg?1 of propofol would have been administered during 15 seconds of assessment of anaesthetic depth. Since it takes propofol some minutes to reach peak effect after the infusion is stopped, the animals in these groups would be more deeply anaesthetized than in the SI group where the rate of propofol administration was slower ADDIN PAPERS2_CITATIONS <citation><uuid>7BCB4B43-C118-4AD2-B1EE-1727A279AD97</uuid><priority>0</priority><publications><publication><volume>79</volume><publication_date>99199710001200000000220000</publication_date><number>4</number><institution>Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, University of Adelaide, North Terrace, SA, Australia.</institution><startpage>505</startpage><title>A physiological model of induction of anaesthesia with propofol in sheep .2. Model analysis and implications for dose requirements</title><uuid>35D7B8A6-0661-4930-A5D4-03F628E89C95</uuid><subtype>400</subtype><endpage>513</endpage><type>400</type><url> Journal of Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>84618B0A-48DD-4B06-9E7D-224F0040AB4E</uuid></publication></bundle><authors><author><firstName>G</firstName><middleNames>L</middleNames><lastName>Ludbrook</lastName></author><author><firstName>R</firstName><middleNames>N</middleNames><lastName>Upton</lastName></author></authors></publication></publications><cites></cites></citation>(Ludbrook & Upton 1997). With hindsight, rather than continuous administration, incremental boluses of propofol at predefined intervals may have been more appropriate. Many co-induction studies in dogs (excepting those involving ketamine) report a reduction in the propofol dose necessary to induce anaesthesia but, in common with this study, no clinically relevant differences in the cardiovascular and respiratory effects have been captured with the noninvasive ways used to measure the variables ADDIN PAPERS2_CITATIONS <citation><uuid>A6D40C49-D985-472F-B11F-9B68A2F6DCEE</uuid><priority>25</priority><publications><publication><uuid>DA2A6604-AF00-4962-B8F0-C51500767EA8</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00408.x</doi><version>Wiley Online Library</version><startpage>463</startpage><publication_date>99200800001200000000200000</publication_date><url> or midazolam for co-induction of anaesthesia with propofol in dogs</title><number>6</number><subtype>400</subtype><endpage>472</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Gwen</firstName><middleNames>L</middleNames><lastName>Covey-Crump</lastName></author><author><firstName>Pamela</firstName><middleNames>J</middleNames><lastName>Murison</lastName></author></authors></publication><publication><uuid>50DB4DDD-C08C-4DD0-A62E-FB3A316BD253</uuid><volume>35</volume><doi>10.1111/j.1467-2995.2008.00395.x</doi><version>Wiley Online Library</version><startpage>319</startpage><publication_date>99200807001200000000220000</publication_date><url> comparison of induction of anaesthesia using a target-controlled infusion device in dogs with propofol or a propofol and alfentanil admixture</title><number>4</number><subtype>400</subtype><endpage>325</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Adam</firstName><lastName>Auckburally</lastName></author><author><firstName>Pat</firstName><lastName>Pawson</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication><publication><uuid>917D2B63-EDB6-4887-9E36-557A69019AC7</uuid><volume>40</volume><doi>10.1111/vaa.12038</doi><startpage>359</startpage><publication_date>99201304091200000000222000</publication_date><url> of altering the sequence of midazolam and propofol during co-induction of anaesthesia</title><number>4</number><subtype>400</subtype><endpage>366</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Andrea</firstName><lastName>Sánchez</lastName></author><author><firstName>Eliseo</firstName><lastName>Belda</lastName></author><author><firstName>Mayte</firstName><lastName>Escobar</lastName></author><author><firstName>Amalia</firstName><lastName>Agut</lastName></author><author><firstName>Marta</firstName><lastName>Soler</lastName></author><author><firstName>Francisco</firstName><middleNames>G</middleNames><lastName>Laredo</lastName></author></authors></publication><publication><volume>41</volume><publication_date>99201310071200000000222000</publication_date><number>1</number><doi>10.1111/vaa.12088</doi><startpage>64</startpage><title>Midazolam, as a co-induction agent, has propofol sparing effects but also decreases systolic blood pressure in healthy dogs</title><uuid>B2A204DF-FAFA-4F4C-B401-AB046082A2B6</uuid><subtype>400</subtype><endpage>72</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Amber</firstName><lastName>Hopkins</lastName></author><author><firstName>Michelle</firstName><lastName>Giuffrida</lastName></author><author><firstName>Maria</firstName><middleNames>Paula</middleNames><lastName>Larenza</lastName></author></authors></publication><publication><publication_date>99201602021200000000222000</publication_date><startpage>n/a</startpage><doi>10.1111/vaa.12336</doi><title>Clinical effects of midazolam or lidocaine co-induction with a propofol target-controlled infusion (TCI) in dogs</title><uuid>6EB18FB1-1847-4843-A0DB-B3F30587CC4D</uuid><subtype>400</subtype><endpage>n/a</endpage><type>400</type><url> Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Enzo</firstName><lastName>Minghella</lastName></author><author><firstName>Adam</firstName><lastName>Auckburally</lastName></author><author><firstName>Patricia</firstName><lastName>Pawson</lastName></author><author><firstName>Marian</firstName><middleNames>E</middleNames><lastName>Scott</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author></authors></publication><publication><publication_date>99201606011200000000222000</publication_date><subtitle>The effects of intravenous lidocaine before propofol induction</subtitle><doi>10.1111/jsap.12502</doi><title>The effects of intravenous lidocaine before propofol induction in premedicated dogs</title><uuid>D2392878-9B59-4C59-BAE3-9661775F9DAF</uuid><subtype>400</subtype><type>400</type><url> of Small Animal Practice</title><type>-100</type><subtype>-100</subtype><uuid>BB7CA6E6-B4A7-4AA7-A9C1-C1A9E0123BEA</uuid></publication></bundle><authors><author><firstName>I</firstName><lastName>Cerasoli</lastName></author><author><firstName>S</firstName><lastName>Nannarone</lastName></author><author><firstName>S</firstName><lastName>SCHAUVLIEGE</lastName></author><author><firstName>L</firstName><lastName>Duchateau</lastName></author><author><firstName>A</firstName><lastName>Bufalari</lastName></author></authors></publication></publications><cites></cites></citation>(Auckburally et al. 2008; Covey-Crump & Murison 2008; Hopkins et al. 2013; Sánchez et al. 2013; Cerasoli et al. 2016; Minghella et al. 2016). Invasive monitoring of additional variables, such as arterial pressure, cardiac output and arterial blood gas analysis, might show relevant differences but would not reflect common anaesthetic practice in healthy animals undergoing procedures within a clinical environment. In the absence of clinically evident effects on the cardiovascular and respiratory systems in healthy animals, the value of dose reduction of propofol is questionable. In human patients, some evidence suggests no correlation between speed of injection of propofol and physiological effects ADDIN PAPERS2_CITATIONS <citation><uuid>9A174AC9-EEB7-4A10-B12E-96DD38463A0F</uuid><priority>26</priority><publications><publication><uuid>48A46E76-B108-4E44-99D0-8E18E89AA6DE</uuid><volume>46</volume><doi>10.1111/j.1365-2044.1991.tb09781.x</doi><startpage>783</startpage><publication_date>99199109011200000000222000</publication_date><url> effects of propofol in children</title><publisher>Blackwell Publishing Ltd</publisher><number>9</number><subtype>400</subtype><endpage>785</endpage><bundle><publication><publisher>Blackwell Publishing Ltd</publisher><title>Anaesthesia</title><type>-100</type><subtype>-100</subtype><uuid>52EBC137-FFC5-4940-A690-4BB9F05186C4</uuid></publication></bundle><authors><author><firstName>S</firstName><middleNames>M</middleNames><lastName>Short</lastName></author><author><firstName>C</firstName><middleNames>S T</middleNames><lastName>Aun</lastName></author></authors></publication><publication><uuid>AC9204B7-9F1C-4CEA-ADA3-56EB5E4C01B8</uuid><volume>51</volume><doi>10.1016/j.aat.2013.06.009</doi><startpage>53</startpage><publication_date>99201306011200000000222000</publication_date><url> dosing regimens for propofol induction in obese patients</title><publisher>Elsevier Taiwan LLC</publisher><number>2</number><subtype>400</subtype><endpage>57</endpage><bundle><publication><publisher>Elsevier Taiwan LLC</publisher><title>Acta Anaesthesiologica Taiwanica</title><type>-100</type><subtype>-100</subtype><uuid>4AB8E553-7106-4AE2-9BFF-C370C74181CE</uuid></publication></bundle><authors><author><firstName>Fai</firstName><lastName>Lam</lastName></author><author><firstName>Chien-Chang</firstName><lastName>Liao</lastName></author><author><firstName>Yi-Jui</firstName><lastName>Lee</lastName></author><author><firstName>Weu</firstName><lastName>Wang</lastName></author><author><firstName>Chien-Ju</firstName><lastName>Kuo</lastName></author><author><firstName>Chao-Shun</firstName><lastName>Lin</lastName></author></authors></publication></publications><cites></cites></citation>(Short & Aun 1991; Lam et al. 2013), and prolonged induction time actually may increase the risk of complications such as desaturation ADDIN PAPERS2_CITATIONS <citation><uuid>B4CCC456-37D4-4956-8ABC-174E653F4ADC</uuid><priority>27</priority><publications><publication><uuid>A1B6CDC4-5403-405A-A013-0E929CCE91E7</uuid><volume>70</volume><doi>10.2460/ajvr.70.11.1333</doi><startpage>1333</startpage><publication_date>99200911001200000000220000</publication_date><url> of time to desaturation between preoxygenated and nonpreoxygenated dogs following sedation with acepromazine maleate and morphine and induction of anesthesia with propofol.</title><location>200,9,29.6452956,-82.3471907</location><institution>Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. mcnallye@</institution><number>11</number><subtype>400</subtype><endpage>1338</endpage><bundle><publication><title>American journal of veterinary research</title><type>-100</type><subtype>-100</subtype><uuid>991EC5F6-B440-400F-844E-947991BFDC2E</uuid></publication></bundle><authors><author><firstName>Erin</firstName><middleNames>M</middleNames><lastName>McNally</lastName></author><author><firstName>Sheilah</firstName><middleNames>A</middleNames><lastName>Robertson</lastName></author><author><firstName>Luisito</firstName><middleNames>S</middleNames><lastName>Pablo</lastName></author></authors></publication><publication><volume>123</volume><publication_date>99201607001200000000220000</publication_date><number>1</number><doi>10.1213/ANE.0000000000001347</doi><startpage>82</startpage><title>The Myth of Rescue Reversal in “Can’t Intubate, Can’t Ventilate” Scenarios</title><uuid>025D0652-BEF1-44DE-87BE-87B628AB3A11</uuid><subtype>400</subtype><endpage>92</endpage><type>400</type><url> &amp; Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>8D6171B6-F5E9-4004-828B-BB3DCB988166</uuid></publication></bundle><authors><author><firstName>Mohamed</firstName><lastName>Naguib</lastName></author><author><firstName>Lara</firstName><lastName>Brewer</lastName></author><author><firstName>Cristen</firstName><lastName>LaPierre</lastName></author><author><firstName>Aaron</firstName><middleNames>F</middleNames><lastName>Kopman</lastName></author><author><firstName>Ken</firstName><middleNames>B</middleNames><lastName>Johnson</lastName></author></authors></publication></publications><cites></cites></citation>(McNally et al. 2009; Naguib et al. 2016) or aspiration (Sellick 1961). There are limits to how slow the propofol injection can be given, both practically (time taken to induce anaesthesia) and clinically (the animal would never be anaesthetized if the clearance rate equals the infusion rate). In dogs, rapid sequence induction provides suitable conditions for orotracheal intubation, frequent apnoea and a decrease in arterial pressure comparable to that observed with slow TCI propofol inductions ADDIN PAPERS2_CITATIONS <citation><uuid>029A065C-1D66-4B6B-81E4-D8DFFC41A424</uuid><priority>0</priority><publications><publication><uuid>06062218-B235-49C7-9DAF-8E8175C16FD7</uuid><volume>40</volume><doi>10.1111/j.1467-2995.2012.00747.x</doi><subtitle>Propofol or alfaxalone for rapid anaesthetic induction</subtitle><startpage>115</startpage><publication_date>99201207131200000000222000</publication_date><url> evaluation of anaesthetic induction in healthy dogs using rapid intravenous injection of propofol or alfaxalone</title><number>2</number><subtype>400</subtype><endpage>123</endpage><bundle><publication><publisher>Elsevier Ltd</publisher><title>Veterinary Anaesthesia and Analgesia</title><type>-100</type><subtype>-100</subtype><uuid>CC021AF9-AD0F-4965-B32D-9E1FC6D68870</uuid></publication></bundle><authors><author><firstName>Maria</firstName><lastName>Amengual</lastName></author><author><firstName>Derek</firstName><lastName>Flaherty</lastName></author><author><firstName>Adam</firstName><lastName>Auckburally</lastName></author><author><firstName>Andrew</firstName><middleNames>M</middleNames><lastName>Bell</lastName></author><author><firstName>E</firstName><middleNames>Marian</middleNames><lastName>Scott</lastName></author><author><firstName>Patricia</firstName><lastName>Pawson</lastName></author></authors></publication></publications><cites></cites></citation>(Musk et al. 2005; Amengual et al. 2012). Apnoea and decrease in arterial pressure could be expected with any induction technique. It is possible that in sick or debilitated animals reducing the dose of propofol required for induction may have beneficial effects on the cardiovascular and respiratory systems. However, in these cases it may be inappropriate to extrapolate the results of the majority of co-induction studies which are performed with healthy subjects (to standardise the population), where responses to the drugs and doses may be very different. A low number of dogs was included in the study. Whereas the study was appropriately powered to show difference between the control and the slow induction groups, a post hoc power calculation revealed that 66 dogs per group would have been necessary to show significant difference in the propofol dose between control and predosing. A larger number of dogs was not recruited as the investigators had concerns that the induction technique was not clinically useful and thus there was limited benefit to collecting more data. Cardiovascular and respiratory data were also highly variable meaning that a higher number of animals would have been necessary to show significant differences.In dogs premedicated with acepromazine and methadone, anaesthesia was induced with propofol at the rate recommended by the manufacturer, preceded (predosing group) or not (control group) by propofol predosing or at a slower rate (slow induction group) corresponding to the expected dose of the control group over the duration of the predosing group. Although this study failed to show any beneficial effect of the propofol predosing, a slower injection of propofol reduced the dose required to allow endotracheal intubation in healthy dogs. This reinforces data previously reported in other species. The speed of injection is of particular importance in studies focusing on the anaesthesia induction dose of propofol.AcknowledgementsThe authors thank the anaesthesia team at Langford Veterinary Services, University of Bristol for their assistance, the surgery clinicians for help with dog enrolment, Prof Toby Knowles, University of Bristol, and Dr Olivier Levionnois, University of Bern, for statistical advice and Dr Gwen Covey-Crump, University of Bristol, for contributions to project development.Authors’ contributionsMR: study design, data management, interpretation and statistical analysis, preparation of the manuscript; EJL: study design, data management, interpretation and statistical analysis, preparation and revision of the manuscript; PJM: study design, data management, interpretation and statistical analysis, revision of the manuscript.Conflict of interest statementAuthors declare no conflict of interest.References ADDIN PAPERS2_CITATIONS <papers2_bibliography/>Amengual M, Flaherty D, Auckburally A et al. 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Indian J Anaesth 50, 112–114.Stokes DN, Hutton P (1991) Rate-dependent induction phenomena with propofol: implications for the relative potency of intravenous anesthetics. Anesth Analg 72, 578–583.Thompson KR, Rioja E (2015) Effects of intravenous and topical laryngeal lidocaine on heart rate, mean arterial pressure and cough response to endotracheal intubation in dogs. Vet Anaesth Analg 43, 371–378.Whitwam JG (1995) Co-induction of anaesthesia: day-case surgery. Eur J Anaesthesiol Suppl 12, 25–34. Table 1 Timeline for evaluation of three propofol protocols for intravenous induction of anesthesia (time points T0–T3) in dogs sedated with acepromazine and methadone: group PP, propofol (0.5 mg kg?1) injected over 3 seconds at T0 and an infusion (4 mg kg?1 minute?1) starting 2 minutes later at T2; group CP, saline (0.05 mL kg?1) injected at T0 and an infusion of propofol (4 mg kg?1 minute?1) starting at T2; and group SI, propofol infusion (1.3 mg kg?1 minute?1) starting at T0. All propofol infusions were discontinued at the time of tracheal intubation (T3).MeasurementsTime pointBaselinePremedicationInduction of anesthesiaTime after intubationT0T2T3P1P2PhysiologicalPRPRPRPRPRPRPRfRfRfRfRfRfRfRMAPMAPMAPMAPMAPScoringSedationSedationActivityActivityActivityIntubation qualityBaseline, no drugs; Premedication, 30 minutes after intramuscular acepromazine and methadone; T0, immediately before induction of anaesthesia; T2, two minutes of protocol administration; T3, tracheal intubation and discontinuation of propofol infusion; P1, 2 minutes after intubation; P2, 5 minutes after intubation; PR, pulse rate; fR, respiratory rate; MAP, mean arterial pressure.Table 2 Details of 31 dogs anaesthetized with 3 protocols, control-propofol (CP), propofol pre-dosing (PP) and propofol slow induction (SI).DemographicGroupCPPPSISex (m:f:i)5(2N):5(1N):07(0N):3(1N):15(4N):5(0N):0ASA (I:II)3:75:63:7Age (months)48.9 (6–122)38.1 (6–103)56.2 (6–144)Body weight (kg)25.2 (4.5–47.2)14.3 (3.5–20.1)21.8 (7.4–41.0)m, male; f, female; i, intersex; N, neutered; ASA (I:II), American Society of Anesthesiologists Class I or II. Table 3 Scores of sedation before and 30 minutes after premedication, activity before induction of anaesthesia, quality of induction and intubation and number of apnoeic animals after induction in dogs that were administered one of three induction protocols: control–propofol (CP), propofol–predosing (PP) and propofol slow induction (SI). Data are median (range).Scoring systemGroupResultsSedation score at baseline(0–3)CP0 (0-0)PP0 (0-0)SI0 (0-0)Sedation score at 30 minutes after premedication(0–3)CP2 (1-2)PP2 (1-3)SI2 (1-3)Activity score at 30 minutes after premedication(0–2)CP0 (0-0)PP0 (0-0)SI0 (0-0)Intubation score(0–3)CP0 (0-0)PP0 (0-1)SI0 (0-1)Quality score(0–2)CP0 (0-0)PP0 (0-0)SI0 (0-0)Apnoea after induction(number of dogs)CP2PP4SI1Sedation score: 0, no sedation; activity score: 0, sedation and 2, excitement; intubation score: 0, best conditions for intubation; quality score: 0, best quality of induction.Table 4 Pulse rate (PR), mean arterial pressure (MAP), and respiratory rate (fR) before and 30 minutes after premedication, during induction of anaesthesia (T0-T2), immediately after endotracheal intubation (T3) and at 2 (P1) and 5 minutes (P2) after endotracheal intubation in 31 dogs assigned to one of three induction protocols: control–propofol (CP), propofol–predosing (PP) and propofol slow induction (SI). Data are mean ± standard deviation.VariableGroupTime pointsBaselinePremedicationT0T2T3P1P2PR(beats minute?1)CP117 ± 19100 ± 1997 ± 2199 ± 29123 ± 37113 ± 33113 ± 33PP117 ± 2272 ± 1380 ± 1983 ± 1994 ± 2086 ± 2086 ± 18SI104 ± 1576 ± 1481 ± 1795 ± 1990 ± 2587 ± 2382 ± 27MAP(mmHg)CP105 ± 1791 ± 2595 ± 1786 ± 1289 ± 14PP108 ± 2199 ± 3385 ± 2180 ± 1081 ± 9SI107 ± 17102 ± 29102 ± 1791 ± 1593 ± 18fR (breaths minute?1)CP 52 ± 4675 ± 7553 ± 3849 ± 5510 ± 1114 ± 1319 ± 14PP59 ± 5955 ± 3657 ± 5147 ± 407 ± 810 ± 721 ± 18SI118 ± 9358 ± 6850 ± 3735 ± 2724 ± 2127 ± 2131 ± 37Figure 1 Propofol dose requirement for induction of anaesthesia in healthy dogs premedicated with acepromazine (0.025 mg kg?1) and methadone (0.25 mg kg?1) intramuscularly 30 minutes before induction of anaesthesia with intravenous propofol (4 mg kg?1 minute?1; group CP, n = 10), administration of propofol (0.5 mg kg?1) 2 minutes before propofol (4 mg kg?1 minute?1; group PP, n = 11) or propofol (1.3 mg kg?1 minute?1; group SI, n = 10). Propofol was discontinued at the time of endotracheal intubation. Data are mean ± standard deviation.*Significantly different from PP (p = 0.002) and CP (p = 0.012). ................
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