Co-induction in dogs: does midazolam reduce the propofol induction dose and improve induction quality? — POSSIBLE

In dogs, does midazolam co-induction vs propofol alone reduce induction dose and improve induction quality?

Shelf #530 · gate-verified and displayed under the developer's blinded-trial rule

POSSIBLE: In dogs, midazolam co-induction can reduce the propofol dose needed for intubation, but the effect depends on the midazolam dose, the sequence of administration and the population, and it does not reliably improve induction quality — in several trials it caused excitement and a poorer induction score. In the largest trial (Robinson 2013, 90 client-owned dogs, prospective randomised blinded placebo-controlled), midazolam at all doses combined significantly reduced propofol dose requirement compared with saline (p < 0.001) and compared with diazepam (p = 0.008), but of the individual doses only 0.4 mg/kg reached significance against saline (p = 0.014). At the commonly used 0.2 mg/kg dose, Covey-Crump 2008 (66 dogs, randomized controlled blinded) found no sparing at all — midazolam–propofol 3.58 mg kg(-1) versus control–propofol 3.51 mg kg(-1) — with a significantly higher activity (excitement) score and a significantly poorer quality of induction score (both p = 0.0001). Sánchez 2013 (33 dogs, randomized controlled) found propofol requirements decreased whether midazolam was given before or after propofol (p < 0.001 against control), with quality of sedation and induction and ease of intubation similar in all groups but more excitement when midazolam came first. In critically ill dogs, Aguilera 2020 (19 dogs, prospective randomized blinded) found a lower induction dose with midazolam (1.1 ± 0.5 versus 1.9 ± 0.5 mg kg-1) and a significantly better induction/intubation score. Design class (a): randomisation and blinding are both established by carded records' own wording — Robinson 2013 ('Prospective, randomised, blinded placebo controlled clinical trial') and Covey-Crump 2008 ('Randomized, controlled, blinded clinical study'). The honest limits: premedication, midazolam dose (0.2–0.5 mg/kg) and propofol administration technique differ across trials, which is the likely source of the inconsistency; induction-quality scores are subjective; excitement after midazolam is a recurrent finding in healthy/sedated dogs; and no carded record addresses patient outcomes beyond induction. One-home note: intranasal midazolam versus rectal diazepam for status epilepticus is a different indication, carded on shelf #294 (PMID: 28543780), and is not carded here. Drafted Nov 10, 2026 (VetMed build, topic #530); all figures from the abstract fetched and verified at drafting.

Robinson 2013: midazolam (all doses combined) significantly reduced propofol dose requirement versus saline (p < 0.001) in 90 dogs, but only the 0.4 mg/kg dose was individually significant (p = 0.014)

Randomised, blinded, placebo-controlled clinical trial (record's own wording: 'Prospective, randomised, blinded placebo controlled clinical trial'; publication type: Randomized Controlled Trial)

Who: Dogs: 90 client-owned dogs (ASA I-III, median body mass 21.5 kg (IQR 10-33)) presented for anaesthesia for a variety of procedures in a clinical setting. Dogs were randomised to receive saline 0.1 mL kg(-1), or midazolam or diazepam at 0.2, 0.3, 0.4 or 0.5 mg kg(-1). All dogs received 0.01 mg kg(-1) acepromazine and 0.2 mg kg(-1) methadone intravenously; 15 minutes later sedation was scored, propofol 1 mg kg(-1) was administered IV followed by the treatment drug, and further propofol was given until endotracheal intubation was possible. Recorded data included signalment, sedation score, propofol dosage and any adverse reactions.

Result: Midazolam (all groups combined) significantly reduced propofol dose requirement compared to saline (p < 0.001) and diazepam (p = 0.008). Midazolam 0.4 mg kg(-1) significantly reduced propofol dose requirement (p = 0.014) compared to saline; other midazolam doses failed to reach statistical significance individually. Diazepam did not significantly reduce propofol dose requirement compared to saline (p = 0.089). Dogs weighing <5 kg required a greater propofol dose than those weighing 5-40 kg (p = 0.002) and those >40 kg (p = 0.008), and profoundly sedated dogs required less propofol than mildly sedated (p < 0.001) or adequately sedated (p = 0.003) dogs. The record gives no mean propofol doses per group in its abstract and reports no induction-quality comparison for midazolam in its abstract.

Watch out: The headline significance is for all midazolam doses pooled; at the individual-dose level only 0.4 mg/kg separated from saline, so this record does not establish sparing at 0.2 mg/kg. The abstract reports P values without the actual propofol doses, so the size of the sparing cannot be stated from this record. Premedication (acepromazine plus methadone IV) and the fixed 1 mg/kg propofol first bolus are part of the protocol and may not match other practices.

Robinson R, Borer-Weir K. 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. Vet Anaesth Analg. 2013;40(5):455-63. PMID: 23750585. Registry ID: none in the record. MeSH: Anesthesia, General/veterinary* · Anesthetics, Intravenous/administration & dosage, pharmacology* · Animals · Diazepam/administration & dosage, pharmacology* · Dogs · Dose-Response Relationship, Drug · Drug Interactions · Drug Therapy, Combination · Midazolam/administration & dosage, pharmacology* · Propofol/administration & dosage, pharmacology*

Covey-Crump 2008: midazolam 0.2 mg/kg did not reduce propofol requirement (3.58 vs 3.51 mg kg(-1) control) and gave a poorer induction quality score (p = 0.0001) in 66 dogs

Randomized, controlled, blinded clinical study (record's own wording: 'Randomized, controlled, blinded clinical study'; publication type: Randomized Controlled Trial)

Who: Dogs: 66 client-owned dogs (35 male, 31 female, ASA I-II, age 6-120 months, body mass 4.7-48.0 kg) in a clinical setting, premedicated intramuscularly with acepromazine (0.025 mg kg(-1)) and morphine (0.25 mg kg(-1)). After 30 minutes, group fentanyl–propofol received fentanyl (2 microg kg(-1)), group midazolam–propofol (MP) received midazolam (0.2 mg kg(-1)) injected over 30 seconds via a cephalic catheter, and group control–propofol had the catheter flushed with an equivalent volume of heparinized saline; anaesthesia was induced 2 minutes later with propofol (4 mg kg(-1) minute(-1)) to effect. Pulse rate, respiratory rate and mean arterial pressure were recorded; apnoea of at least 30 seconds was recorded and treated; sedation, activity after the co-induction agent, quality of anaesthetic induction and endotracheal intubation were scored.

Result: Propofol dose requirement was significantly reduced in the fentanyl group [2.90 mg kg(-1) (0.57)] compared to control [3.51 mg kg(-1) (0.74)] and midazolam [3.58 mg kg(-1) (0.49)] — that is, midazolam did not reduce the dose versus control. Mean pulse rate was higher in MP than in control or fentanyl groups (p = 0.003). No statistically significant difference was found between groups in mean respiratory rate, mean arterial pressure or incidence of apnoea. Activity score was significantly higher (more excited) (p = 0.0001) and quality of induction score was significantly poorer (p = 0.0001) in MP compared to control or fentanyl groups. Intubation score was similar in all groups. The record's conclusion: midazolam did not reduce propofol requirements and caused excitement in some animals.

Watch out: This is the direct counterweight to the dose-sparing claim at 0.2 mg/kg midazolam, with the actual doses printed — midazolam dogs needed numerically slightly more propofol than controls. The fentanyl arm answers a different co-induction question and is not relied on for this shelf. Induction quality and activity are scored, subjective outcomes, though the study was blinded.

Covey-Crump GL, Murison PJ. Fentanyl or midazolam for co-induction of anaesthesia with propofol in dogs. Vet Anaesth Analg. 2008;35(6):463-72. PMID: 18565204. Registry ID: none in the record. MeSH: Anesthesia/veterinary · Anesthetics, Intravenous/administration & dosage, pharmacology* · Animals · Dogs* · Drug Therapy, Combination · Female · Fentanyl/administration & dosage, pharmacology* · Male · Midazolam/administration & dosage, pharmacology* · Propofol/administration & dosage, pharmacology*

Sánchez 2013: propofol requirements fell whether midazolam was given before or after propofol (both p < 0.001 vs control), induction quality was similar in all groups, and excitement was higher when midazolam came first

Randomized, controlled, clinical study (record's own wording: 'Randomized, controlled, clinical study'; publication type: Randomized Controlled Trial) — blinding not stated in the record

Who: Dogs: 33 client-owned dogs (ASA I-III, 0.5-10 years, 5-30 kg) in a clinical setting, premedicated with acepromazine (0.02 mg kg(-1)) and morphine (0.4 mg kg(-1)) intramuscularly. After 30 minutes, group midazolam–propofol (MP) received midazolam (0.25 mg kg(-1)) intravenously before propofol (1 mg kg(-1)) IV, group propofol–midazolam (PM) received propofol before midazolam at the same doses, and the control group received saline IV instead of midazolam before propofol; supplementary propofol boluses (0.5 mg kg(-1)) were given to effect until orotracheal intubation. Behaviour after midazolam, quality of sedation and induction, and ease of intubation were scored; heart rate, respiratory rate and systolic arterial blood pressure were recorded at set time points, and end-tidal CO2 and oxygen saturation after intubation.

Result: Quality of sedation and induction, and ease of intubation were similar in all groups. Incidence of excitement was higher in MP compared to control (p = 0.014) and PM (p = 0.026) groups. Propofol requirements were decreased in MP and PM groups with respect to control (p < 0.001), and in PM compared to MP (p = 0.022). Heart rate decreased after premedication in all groups and increased after midazolam and subsequently in MP (p = 0.019) and PM (p = 0.001) groups. Incidence of apnoea and paddling was higher in control (p = 0.005) and MP (p = 0.031) groups than in PM. The record gives no absolute propofol doses in its abstract. The record's conclusion is that midazolam before propofol reduced requirements but caused mild excitement in some dogs, while propofol before midazolam produced less excitatory phenomena and a greater reduction in requirements.

Watch out: Small (33 dogs, about 11 per group), no blinding stated, and the abstract reports P values without absolute propofol doses. The midazolam dose was 0.25 mg/kg and the sequence comparison is this study's real subject: sparing was greatest in the propofol-first sequence, which is not the classic give-midazolam-first co-induction routine.

Sánchez A, Belda E, Escobar M, Agut A, Soler M, Laredo FG. Effects of altering the sequence of midazolam and propofol during co-induction of anaesthesia. Vet Anaesth Analg. 2013;40(4):359-66. PMID: 23570259. Registry ID: none in the record. MeSH: Anesthesia, General/veterinary* · Anesthetics, Intravenous/administration & dosage, pharmacology* · Animals · Dogs/physiology* · Drug Administration Schedule · Female · Male · Midazolam/administration & dosage, adverse effects, pharmacology* · Propofol/administration & dosage, adverse effects, pharmacology*

Aguilera 2020: in critically ill dogs, midazolam co-induction lowered the propofol induction dose (1.1 ± 0.5 vs 1.9 ± 0.5 mg kg-1) and gave a significantly better induction/intubation score

Prospective, randomized, blinded, clinical trial (record's own wording: 'Prospective, randomized, blinded, clinical trial'; MeSH includes Single-Blind Method; publication type: Randomized Controlled Trial, Veterinary)

Who: Dogs: 19 client-owned dogs of ASA status at least III requiring emergency abdominal surgery, in a critical-care clinical setting. Dogs were sedated with fentanyl (2 μg kg-1) intravenously for instrumentation (heart rate, arterial blood pressure, cardiac index, systemic vascular resistance index, arterial blood gases, respiratory rate, rectal temperature); after additional IV fentanyl (3 μg kg-1), sedation quality was scored and variables recorded. Induction was with IV propofol (1 mg kg-1) and saline (0.06 mL kg-1; group PS, nine dogs) or midazolam (0.3 mg kg-1; group PM, 10 dogs), with additional propofol (0.25 mg kg-1) IV every 6 seconds until endotracheal intubation; induction/intubation quality was scored and anaesthesia maintained with isoflurane.

Result: There were no differences in group demographics, temperature or cardiopulmonary variables between groups or within groups before or after induction. The propofol doses for induction of anesthesia were significantly different between groups, 1.9 ± 0.5 and 1.1 ± 0.5 mg kg-1 for groups PS and PM respectively — an absolute difference of 0.8 mg kg-1, a 42% relative reduction on midazolam — and the induction/intubation score was significantly better for group PM. The record's conclusion: midazolam co-induction reduced the propofol induction dose and improved the quality of induction in critically ill dogs without an improvement in cardiopulmonary variables.

Watch out: Only 19 dogs, and the population is specifically critically ill (ASA at least III) dogs for emergency abdominal surgery after fentanyl sedation — the better induction score here does not overturn the poorer or unchanged quality scores in healthy-dog trials. Blinding is single-blind per the record's MeSH. The midazolam dose was 0.3 mg/kg, given with a 1 mg/kg propofol bolus, not as a stand-alone pre-induction agent.

Aguilera R, Sinclair M, Valverde A, Bateman S, Hanna B. Dose and cardiopulmonary effects of propofol alone or with midazolam for induction of anesthesia in critically ill dogs. Vet Anaesth Analg. 2020;47(4):472-480. PMID: 32402602. Registry ID: none in the record. MeSH: Anesthesia/veterinary* · Anesthetics, Combined* · Anesthetics, Intravenous · Animals · Critical Illness · Dog Diseases* · Dogs/surgery* · Female · Male · Midazolam* · Propofol* · Prospective Studies · Single-Blind Method

Synthesis: midazolam co-induction spares propofol in some protocols, but at 0.2 mg/kg one blinded trial found no sparing and worse induction quality

Synthesis

Who: Synthesis of the cards above: Robinson 2013 (90 dogs, randomised blinded placebo-controlled dose titration, midazolam 0.2–0.5 mg/kg), Covey-Crump 2008 (66 dogs, randomized blinded, midazolam 0.2 mg/kg), Sánchez 2013 (33 dogs, randomized, midazolam 0.25 mg/kg before or after propofol) and Aguilera 2020 (19 critically ill dogs, prospective randomized blinded, midazolam 0.3 mg/kg). Premedications were acepromazine-based (with methadone or morphine) in the healthy-dog trials and fentanyl in the critically ill trial.

Result: (1) Dose: sparing is real but conditional — pooled midazolam doses beat saline in Robinson (p < 0.001) with only 0.4 mg/kg individually significant; both administration sequences spared propofol in Sánchez (p < 0.001 vs control); critically ill dogs needed 1.1 ± 0.5 versus 1.9 ± 0.5 mg kg-1 in Aguilera. Against that, at 0.2 mg/kg Covey-Crump measured 3.58 mg kg(-1) on midazolam versus 3.51 mg kg(-1) on control — no sparing. (2) Quality: not improved in healthy dogs — induction quality was similar in all Sánchez groups, and significantly poorer with more excitement in Covey-Crump (both p = 0.0001); the only better induction/intubation score is in the small critically ill trial. (3) Excitement after midazolam recurs across the healthy-dog trials, especially when midazolam is given before propofol.

Watch out: Two further randomised records were not carded: a 17-dog pilot of midazolam 0.2 mg/kg (PMID: 24118993; significantly less propofol, excitement in 5 of 9 midazolam dogs, lower systolic pressure — small pilot, no doses in its abstract) and a target-controlled-infusion trial (PMID: 26833994) whose endpoint is a propofol target concentration rather than an induction dose in mg/kg; neither changes the conditional picture above. This shelf does not address midazolam for seizures (shelf #294), midazolam premedication/sedation combinations, or alfaxalone co-induction.

Synthesis of Robinson R et al. PMID: 23750585; Covey-Crump GL et al. PMID: 18565204; Sánchez A et al. PMID: 23570259; Aguilera R et al. PMID: 32402602. Registry IDs as on the individual cards.

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