Midazolam sedation for handling in psittacine birds: does intranasal midazolam vs saline control improve sedation and ease restraint? — POSSIBLE

In psittacine birds, does midazolam (intranasal or intramuscular) vs saline control or manual restraint alone improve sedation quality and ease examination, and how fast is recovery?

Shelf #958 · gate-verified and displayed under the developer's blinded-trial rule

POSSIBLE: Intranasal midazolam sedates psittacine birds for handling in two small controlled crossover studies in two species, one of them randomised and blinded; a third randomised study shows that this sedation does not blunt the plasma corticosterone response to restraint. Doss 2018 (PMID: 30457900; randomized, controlled, blinded, complete crossover in 9 healthy adult cockatiels) found intranasal midazolam 3 mg/kg produced sedation with a median onset of first sedation effects of 85 seconds (range 60 to 120), and that midazolam and midazolam-butorphanol both significantly attenuated the stress-induced increase in respiratory rate during restraint, whereas neither attenuated the increase in cloacal temperature; midazolam-butorphanol resulted in significantly less vigorous struggling during restraint than midazolam alone or saline. Mans 2012 (PMID: 23156974; complete crossover in 9 adult Hispaniolan Amazon parrots) found intranasal midazolam 2 mg/kg produced sedation within 3 minutes, significantly reduced vocalization, flight and defense responses during capture, kept the cloacal temperature rise during 15 minutes of manual restraint significantly slower and lower, and kept respiratory rates significantly lower for up to 12 minutes, all versus saline; intranasal flumazenil 0.05 mg/kg antagonized the effects within 10 minutes. Helms-Pack 2025 (PMID: 41065686; 22 Hispaniolan Amazon parrots allocated by a preset randomized list) found intranasal midazolam-butorphanol did NOT reduce the plasma corticosterone response to 30 minutes of restraint versus saline (P = 0.99) (the treatment made no difference to that outcome) — visible sedation and a blunted hormonal stress response are not the same thing, and this shelf claims only the former. Design class (a): randomisation and blinding are established by the carded Doss 2018 record answering the midazolam-versus-saline comparison in a psittacine species. The stamp is POSSIBLE rather than LIKELY because the controlled evidence is two crossovers of 9 birds each in healthy research birds, sedation scoring is partly subjective, no carded record measures examination success in clinical patients, and the one hormonal stress outcome was null. Scope: intranasal midazolam at single doses of 2-3 mg/kg in cockatiels and Hispaniolan Amazon parrots; other species and midazolam combinations appear only as context in the synthesis. Drafted Nov 10, 2026 (VetMed build, topic #958); all figures from the abstracts fetched and verified at drafting.

Doss 2018: intranasal midazolam 3 mg/kg sedated 9 cockatiels with a median onset of 85 seconds in a randomized blinded crossover, and attenuated the restraint-induced increase in respiratory rate, but not the increase in cloacal temperature

Randomized, controlled, blinded, complete crossover study (record's own wording; publication types: Clinical Trial, Veterinary, Journal Article)

Who: Psittacine birds: 9 healthy adult cockatiels (Nymphicus hollandicus) in a university research setting (Wisconsin, USA). In a randomized, controlled, blinded, complete crossover study, each bird was assigned to 3 treatment groups in turn and received intranasally midazolam (3 mg/kg), midazolam-butorphanol (3 mg/kg of each drug), or sterile saline (0.9% NaCl) solution (control treatment), with treatments repeated after a minimum washout period of 7 days. Sedation quality was assessed at 3 time points using eye and body position, response to visual, auditory and tactile stimulation, and response during manual restraint (eye position and struggling intensity); heart rate, respiratory rate and cloacal temperature were measured over a 15-minute restraint period.

Result: Median onset of first sedation effects was 85 seconds (range 60 to 120 seconds) for midazolam and 90 seconds (range 45 to 180 seconds) for midazolam-butorphanol. Midazolam-butorphanol resulted in significantly less vigorous struggling during restraint than did midazolam or the control treatment. Heart rate did not differ significantly among treatments. The stress-induced increase in respiratory rate was significantly attenuated by midazolam and by midazolam-butorphanol, whereas the increase in cloacal temperature was not attenuated by midazolam or midazolam-butorphanol. The authors conclude that intranasal administration of midazolam and midazolam-butorphanol resulted in a rapid onset of sedation in cockatiels, that the combination resulted in deeper sedation in both restrained and unrestrained birds than midazolam alone, and that both provided safe and effective sedation in cockatiels.

Watch out: Nine healthy research-housed birds, not clinical patients undergoing examination. The abstract does not print sedation-score values for midazolam alone versus saline, so this card claims onset of effect, respiratory-rate attenuation and (for the combination) reduced struggling — not a quantified sedation-score advantage for midazolam alone. The record's MeSH indexes the species as 'Cockatoos' although the birds studied were cockatiels; the MeSH string is reproduced exactly as it appears in the record.

Doss GA, Fink DM, Mans C. Assessment of sedation after intranasal administration of midazolam and midazolam-butorphanol in cockatiels (Nymphicus hollandicus). Am J Vet Res. 2018;79(12):1246-1252. PMID: 30457900. Registry ID: none in the record. MeSH: Administration, Intranasal/veterinary · Anesthesia · Animals · Butorphanol/administration & dosage/pharmacology* · Cockatoos* · Cross-Over Studies · Female · Heart Rate/drug effects · Hypnotics and Sedatives/pharmacology* · Male · Midazolam/administration & dosage/pharmacology* · Respiratory Rate/drug effects · Single-Blind Method

Mans 2012: intranasal midazolam 2 mg/kg sedated Hispaniolan Amazon parrots within 3 minutes and significantly reduced vocalization, flight and defense responses during capture versus saline in a 9-bird complete crossover

Complete crossover study (publication types: Journal Article, Randomized Controlled Trial)

Who: Psittacine birds: 9 adult Hispaniolan Amazon parrots (Amazona ventralis) in a university research setting (Wisconsin, USA). In a complete crossover study, each parrot was administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint. Respiratory rate and sedation scores were recorded before and during capture and during and after restraint; heart rate and cloacal temperature were recorded during restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and recovery time was recorded.

Result: In the birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects of intranasal midazolam or flumazenil administration were observed; the authors state that further studies on safety in this species are warranted. The abstract reports statistical significance but not the underlying sedation-score values, so no absolute scores are printed for this card.

Watch out: The abstract does not itself state that treatment order was randomised or that scorers were blinded, so the design class (a) claim for this shelf rests on Doss 2018, not on this record; this record is carded for its saline-controlled comparison in a second psittacine species. Nine healthy research parrots and a single 2 mg/kg intranasal dose: safety in sick, debilitated or very young birds is not addressed.

Mans C, Guzman DS, Lahner LL, Paul-Murphy J, Sladky KK. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis). J Avian Med Surg. 2012;26(3):130-9. PMID: 23156974. Registry ID: none in the record. MeSH: Administration, Intranasal · Amazona* · Animals · Antidotes/administration & dosage/pharmacology · Behavior, Animal/drug effects · Body Temperature · Cross-Over Studies · Flumazenil/administration & dosage/pharmacology · Hypnotics and Sedatives/administration & dosage/pharmacology* · Midazolam/administration & dosage/pharmacology* · Respiratory Physiological Phenomena/drug effects · Restraint, Physical/veterinary* · Time Factors

Helms-Pack 2025: intranasal midazolam-butorphanol made no difference to the plasma corticosterone response to 30 minutes of restraint in Hispaniolan Amazon parrots versus saline (P = 0.99)

Randomised noncrossover controlled study (record describes allocation by a preset randomized list; publication types: Journal Article, Clinical Trial, Veterinary)

Who: Psittacine birds: 22 Hispaniolan Amazon parrots (Amazona ventralis; 10 male and 12 female, 15-26 years of age, weight range 264-334 g) in a university colony (Louisiana, USA). In this noncrossover study, each parrot was caught and restrained in a towel, a baseline blood sample was collected in under 3 minutes, and the bird was then weighed and given a control (saline solution, n = 11) or sedative (midazolam and butorphanol, n = 11) treatment administered intranasally based on a preset randomized list. Additional blood samples were taken 15 and 30 minutes after administration during a total of three samples per bird, and plasma corticosterone levels were determined using enzyme-linked immunoassays.

Result: The prediction that sedated parrots would have significantly decreased plasma corticosterone responses compared with controls was not supported (P = 0.99) (the treatment made no difference). The authors conclude that even when sedated, psittacines can experience acute stress responses when handled, and that clinicians should be mindful of this stress response to reduce potential adverse effects. The abstract does not print the corticosterone concentrations, so none are given on this card.

Watch out: The test article is the midazolam-butorphanol COMBINATION, not midazolam alone, and the outcome is a hormonal stress marker, not sedation quality: this card limits the shelf's stress wording and does not show the birds were unsedated. Birds were processed according to cage order with treatment assigned from the preset list, and blinding of handlers or of the assay is not stated in the record. Doses of the combination are not given in the abstract and are not stated on this card.

Helms-Pack ML, Tully TN, Freeman BS, Liu CC, Stansberry KR, Tuminello JA, Lattin CR. NO SIGNIFICANT REDUCTION IN THE PLASMA CORTICOSTERONE RESPONSE OF HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS) SEDATED WITH INTRANASAL MIDAZOLAM-BUTORPHANOL DURING PERIODS OF ROUTINE RESTRAINT. J Zoo Wildl Med. 2025;56(3):533-538. PMID: 41065686. Registry ID: none in the record. MeSH: Animals · Butorphanol*/administration & dosage/pharmacology · Amazona*/blood · Corticosterone*/blood · Midazolam*/administration & dosage/pharmacology · Female · Male · Hypnotics and Sedatives*/administration & dosage/pharmacology · Restraint, Physical*/veterinary · Administration, Intranasal · Analgesics, Opioid/administration & dosage/pharmacology

Synthesis: intranasal midazolam sedates small psittacines for restraint in controlled crossovers, but a hormonal stress benefit is unshown — POSSIBLE

Synthesis

Who: Synthesis of the three cards above (Doss 2018, cockatiels; Mans 2012 and Helms-Pack 2025, Hispaniolan Amazon parrots) and of the two context records documented in the result, which were fetched at drafting and deliberately not carded as claim-carriers.

Result: (1) Sedation for handling: two saline-controlled crossovers in two psittacine species agree that intranasal midazolam 2-3 mg/kg sedates within about 1-3 minutes and reduces capture and restraint responses, with flumazenil reversal within 10 minutes where tested (Mans 2012). (2) Uncontrolled corroboration: Schaffer 2017 (PMID: 28891701) gave intranasal midazolam 2 mg/kg to 20 wild-caught blue-fronted Amazon (Amazona aestiva) and orange-winged Amazon (Amazona amazonica) parrots with no control group; onset times were 5.36 +/- 1.16 minutes (blue-fronted) and 5.09 +/- 0.89 minutes (orange-winged) and total sedation times 25.40 +/- 5.72 and 27.10 +/- 3.73 minutes respectively, 15 animals showed absence of vocalization with moderate muscle relaxation, and 2 presented lateral recumbence requiring no restraint — while the record also states that 3 blue-fronted Amazons had no effective sedation, wording in tension with its own 'satisfactory sedation in all birds' statement, so it is used as context only. (3) Combinations are a different question: Abreu 2024 (PMID: 38453494), a randomized crossover study of three subcutaneous midazolam-based protocols in nine budgerigars (Melopsittacus undulatus) and nine black-cheeked lovebirds (Agapornis nigrigenis), found midazolam-medetomidine consistently provided deep sedation with successful radiographic positioning at every attempt and midazolam-butorphanol provided the shortest recovery times, but alfaxalone-midazolam produced mortalities from suspected cardiorespiratory arrest in lovebirds even after the alfaxalone dosage was reduced to 3 mg/kg — combination results do not transfer to midazolam alone. (4) Stress: the only hormonal outcome carded on this shelf (Helms-Pack 2025) was null, so the shelf claims easier handling and visible sedation, not a demonstrated reduction in the physiological stress response. (5) Design class (a): randomisation and blinding are established by Doss 2018 for the midazolam-versus-saline comparison in a psittacine species.

Watch out: One-home check at drafting: none of PMIDs 30457900, 23156974, 41065686, 28891701 or 38453494 appears in any other pack on disk. Records deliberately not carded: Isayama 2026 (PMID: 42528181) — a randomized crossover in 6 cockatiels adding dexmedetomidine to a midazolam-butorphanol control regimen, a combination-versus-combination question rather than midazolam versus control. Practical reading: intranasal midazolam is a handling sedative with fast onset and a reversal agent in the species tested; nothing carded here supports extrapolating the doses or the safety statement to other psittacine species, to intramuscular use, or to birds that are sick.

Synthesis of Doss GA et al. PMID: 30457900; Mans C et al. PMID: 23156974; Helms-Pack ML et al. PMID: 41065686; Schaffer DPH et al. PMID: 28891701; Abreu SA et al. PMID: 38453494. Registry IDs as on the individual cards (none in the records).

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