Determination of midazolam dose for co-induction with alfaxalone in sedated cats

Lagos-Carvajal, A.; Queiroz‐Williams, Patricia; Cunha, Anderson da; Liu, Chin‐Chi

doi:10.1016/j.vaa.2019.01.006

Cited by 10 publications

(4 citation statements)

References 32 publications

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“…The up-and-down method only uses each animal once during testing, so as not to bias the data, and is ceased when a given number of crossover events (sequential trials in which animals displays contradictory results) occur (Dixon, 1965). This method, however, had not been used in amphibian species and is typically used in small mammal and avian medicine (Mercado et al ., 2008; Brandão et al ., 2015; Barletta et al ., 2016; DiGeronimo et al ., 2017; Lagos-Carvajal, 2019). It is also only used to find ED 50 values, not ED 99 values, which requires a statistical estimation using nonlinear regression.…”

Section: Discussionmentioning

confidence: 99%

Intramuscular Alfaxalone Effective Dose (ED) Determination and Cardiopulmonary Effects of ED99 in Sonoran Desert Toads (Incilius alvarius)

Spitznagel

Sadar

Willis

et al. 2023

Journal of Herpetological Medicine and Surgery

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There is limited knowledge on amphibian sedation, and drug doses appear to be species-specific and affected by the administration route. Alfaxalone, a neuroactive steroid, has gained popularity in veterinary medicine and has been evaluated in some amphibian species. Previous studies in amphibians have demonstrated a sedative dose range of 10-30 mg/kg IM. No peer-review publication has investigated this drug in Sonoran Desert toads specifically. Therefore, the purpose of this study was to 1) determine the effective dose 50 (ED50) of IM alfaxalone for sedation and 2) determine the cardiopulmonary effects of the effective dose 99 (ED99) in 13 Sonoran Desert toads. Using the Dixon’s Up-and-Down method, the ED50 was calculated as 9.02 mg/kg while using a non-linear regression, the calculated ED50 was 9.65 mg/kg, and the ED99 was 9.91 mg/kg. Based on these results, 10 mg/kg IM was administered, and its cardiovascular effects were determined for 120 mins post-injection. The 10 mg/kg IM dose resulted in significant transient cardiorespiratory depression in all toads, with most toads (11/13) showing signs of sedation (recumbency and/or loss of righting reflex) within 30–40-minutes post-injection. There was no associated mortality with this study, and the side effects associated with this dosage (cardiorespiratory depression, ventral erythema, dysphoric behavior such as rolling and head pressing) resolved in all toads prior to the end of the 120-minute observation window. This study hopes to increase the understanding of the clinical application and limitations of this drug for sedation of Sonoran Desert toads.

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Section: Discussionmentioning

confidence: 99%

Intramuscular Alfaxalone Effective Dose (ED) Determination and Cardiopulmonary Effects of ED99 in Sonoran Desert Toads (Incilius alvarius)

Spitznagel

Sadar

Willis

et al. 2023

Journal of Herpetological Medicine and Surgery

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“…The rationale for using fixed dosages of alfaxalone alone and in combination with medetomidine or midazolam has been outlined in earlier studies. 4,19,20 Figure 6-Mean ± SD plasma nonesterified fatty acid concentration (µEq/L) immediately before premedication (baseline), during isoflurane anesthesia, and after discontinuation of isoflurane for the cats described in Figure 1 grouped by whether they underwent castration (A) or ovariohysterectomy (B). *Results differed significantly (P < .05) from those of baseline.…”

Section: Discussionmentioning

confidence: 99%

A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery

Kamohara

Hikasa

2022

ajvr

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OBJECTIVE To evaluate the effects of IM and IV administration of alfaxalone alone and in combination with medetomidine, midazolam, or both on key stress-related neurohormonal and metabolic changes in isoflurane-anesthetized cats undergoing ovariohysterectomy or castration. ANIMALS 72 client-owned mixed-breed cats undergoing ovariohysterectomy or castration between October 4, 2018, and January 10, 2020. PROCEDURES For each type of surgery, cats were assigned to 1 of 6 premedication protocols groups, with 6 cats/group: physiologic saline (0.9% NaCl) solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IV); physiologic saline solution (0.5 mL, IM) and alfaxalone (5 mg/kg, IM); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IV); medetomidine (50 μg/kg, IM) and alfaxalone (5 mg/kg, IM); midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IV); or midazolam (0.5 mg/kg, IM), medetomidine (50 μg/kg, IM), and alfaxalone (5 mg/kg, IM). Venous blood was taken before pretreatment, pre- and postoperatively during anesthesia with isoflurane and oxygen, and during early and complete recovery. RESULTS Compared with baseline concentrations, plasma adrenaline and noradrenaline concentrations decreased during anesthesia in cats premedicated with alfaxalone alone and in combination with medetomidine. The combination of medetomidine, midazolam, and alfaxalone prevented an excessive increase in catecholamines during anesthesia and surgery in cats. Postoperative plasma cortisol concentration after ovariohysterectomy was lower for cats premedicated with the combination of medetomidine and alfaxalone or the combination of medetomidine, midazolam, and alfaxalone, compared with cats premedicated with alfaxalone alone. Cats treated with combinations that included medetomidine and midazolam had hyperglycemia during anesthesia. Cats treated with medetomidine or medetomidine and midazolam in combination with alfaxalone, compared with alfaxalone alone, had lower concentrations of nonesterified fatty acids during anesthesia. Behavioral recovery scores were lower (better) for cats that received medetomidine in addition to alfaxalone, compared with alfaxalone alone. CLINICAL RELEVANCE Results indicated that pretreatments with medetomidine and alfaxalone or with medetomidine, midazolam, and alfaxalone were useful for preventing stress-related hormonal and metabolic responses, other than hyperglycemia, during isoflurane anesthesia and surgery in cats.

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“…Midazolam, belonging to the benzodiazepine class, acts by enhancing the activity of the neurotransmitter GABA, the main inhibitory neurotransmitter of the central nervous system (CNS). The inclusion of this drug in the sedation protocol increases the sedative effect and provides greater intensity of muscle relaxation, with minimal interference in the cardiovascular system, when administered to dogs and cats [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of Dexmedetomidine Low Doses with or without Midazolam in Cats: Clinical, Hemodynamic, Blood Gas Analysis, and Echocardiographic Effects

Castro

Câmara

Barreto

et al. 2022

Anesthesiology Research and Practice

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Objectives. The aim of the study is to compare the sedative, cardiorespiratory, echocardiographic, and blood gas effects of dexmedetomidine and methadone associated or not with midazolam for restraint chemistry in cats. Methods. Eighteen healthy young cats (4.06 ± 0.48 kg) were randomly sedated with two protocols, through the intramuscular route: dexmedetomidine (5 µg.kg−1), methadone (0.3 mg. kg−1) and midazolam (0.3 mg. kg−1) (DMTM, n = 9), or dexmedetomidine (7.5 µg.kg−1) and methadone (0.3 mg. kg−1) (DMT, n = 9). The cardiorespiratory parameters were measured at baseline, 5 and 10 minutes after pharmacological latency. The sedation, analgesia, and muscle relaxation scores were assessed before and 5 minutes after pharmacological latency, while arterial blood gas analysis and echocardiography were assessed before and after 10 or 15 minutes, respectively. Results. There was no difference between the protocols regarding the cardiorespiratory, blood gas, and echocardiographic parameters used. The scores for sedation, analgesia, and muscle relaxation also did not differ between the protocols, with the degree of sedation, analgesia, and myorelaxation considered satisfactory in both groups. A significant decrease in heart rate (HR) was observed after administration of the sedative protocols, reaching a maximum reduction at T10 (46% and 53% reduction in the DMT and DMTM groups, respectively). The reduction in HR had an impact on echocardiographic parameters such as CO, which decreased 53% and 56% in the DMT and DMTM groups, respectively. There was a significant reduction in PaO2, SaO2, ejection fraction, and fractional shortening in both protocols. SpO2 decreased significantly after 5 minutes of sedation in the DMT group, but with a minimum mean SpO2 of 92% in T5. The respiratory rate decreased significantly at 5 and 10 minutes in the DMTM group, while PaCO2 increased in both groups, indicating respiratory depression caused by the drugs. Conclusions and Relevance. The study pointed out that both sedative protocols can be recommended for clinical sedation of young and healthy cats in the doses used. However, both protocols resulted in cardiorespiratory depression in cats and also the particularities of the animals should be evaluated regarding reducing cardiac output by more than 50%.

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Determination of midazolam dose for co-induction with alfaxalone in sedated cats

Cited by 10 publications

References 32 publications

Intramuscular Alfaxalone Effective Dose (ED) Determination and Cardiopulmonary Effects of ED99 in Sonoran Desert Toads (Incilius alvarius)

Intramuscular Alfaxalone Effective Dose (ED) Determination and Cardiopulmonary Effects of ED99 in Sonoran Desert Toads (Incilius alvarius)

A randomized clinical trial on effects of alfaxalone combined with medetomidine and midazolam in preventing stress-related neurohormonal and metabolic responses of isoflurane-anesthetized cats undergoing surgery

Effect of Dexmedetomidine Low Doses with or without Midazolam in Cats: Clinical, Hemodynamic, Blood Gas Analysis, and Echocardiographic Effects

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