Effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats.

OBJECTIVE: To investigate the effects of a priming dose of alfaxalone on the total anesthetic induction dose for and cardiorespiratory function of sedated healthy cats. ANIMALS: 8 healthy adult cats. PROCEDURES: For this crossover study, cats were sedated with dexmedetomidine and methadone administered IM. Cats next received a priming induction dose of alfaxalone (0.25 mg/kg, IV) or saline (0.9% NaCl) solution (0.025 mL/kg, IV) over 60 seconds and then an induction dose of alfaxalone (0.5 mg/kg/min, IV) until orotracheal intubation was achieved. Cardiorespiratory variables were recorded at baseline (immediately prior to priming agent administration), immediately after priming agent administration, after orotracheal intubation, and every 2 minutes until extubation. The total induction dose of alfaxalone was compared between the 2 priming agents. RESULTS: Mean ± SD total anesthetic induction dose of alfaxalone was significantly lower when cats received a priming dose of alfaxalone (0.98 ± 0.28 mg/kg), compared with when cats received a priming dose of saline solution (1.41 ± 0.17 mg/kg). Mean arterial blood pressure was significantly higher when alfaxalone was used as the priming dose. No cats became apneic or had a hemoglobin oxygen saturation of < 90%. Expired volume per minute was not significantly different between the 2 priming agents. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a priming dose of alfaxalone to healthy sedated cats reduced the total dose of alfaxalone needed to achieve orotracheal intubation, maintained mean arterial blood pressure, and did not adversely impact the measured respiratory variables.

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

OBJECTIVE: To investigate the median effective dose 50 (ED50) of midazolam required for endotracheal intubation when used for co-induction of anesthesia with a low dose of alfaxalone in sedated cats. STUDY DESIGN: Randomized up-and-down study. ANIMALS: A group of 14 mixed-breed cats (eight males, six females), aged 5-12 years and weighing 4.4-6.8 kg. METHODS: The cats were randomly assigned in a sequential allocation numbers from one to 14. Cats were sedated with dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) intramuscularly. After 15 minutes, the quality of sedation was subjectively evaluated. Anesthesia induction was performed by intravenous (IV) administration of alfaxalone (0.25 mg kg-1) over a 60 second interval, followed by another 60 second interval, and then an IV dose of midazolam was administered over a 5 second interval. The initial midazolam dose was 0.3 mg kg-1; then, the midazolam dose was adjusted by ±0.1 mg kg-1 for each consecutive cat based on successful or unsuccessful endotracheal intubation of the previous animal following an up-and-down method. This sequence was followed until six nonsequential crossovers were observed. Crossover was defined as two opposite outcomes in two sequential animals. Data were analyzed using isotonic regression with bootstrapping for determination of midazolam ED50 and logistic regression for correlations (p < 0.05). RESULTS: Overall, six independent crossovers were found, and ED50 of midazolam was 0.08 ± 0.04 mg kg-1. Sedation score and successful tracheal intubation had a strong positive correlation (p = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: This study determined that 0.08 ± 0.04 mg kg-1 of midazolam co-administered with 0.25 mg kg-1 of alfaxalone IV allowed smooth endotracheal intubation in half of the cats sedated with methadone and dexmedetomidine at the doses used in this study.

Comparison of two species-specific oscillometric blood pressure monitors with direct blood pressure measurement in anesthetized cats.

OBJECTIVE: To compare the performance of 2 species-specific oscillometric blood pressure (OBP) monitors (petMAPclassic and petMAPgraphic ) with direct blood pressure measurement in anesthetized cats. DESIGN: Prospective, experimental study. SETTING: Veterinary teaching hospital. ANIMALS: Eight adult cats (3.2-5.5 kg). INTERVENTIONS: During isoflurane anesthesia, OBP cuffs were placed on the thoracic limb and on the base of the tail while invasive blood pressure (IBP) was recorded from a dorsal pedal artery. End-tidal isoflurane concentrations, with or without intravenous dopamine (n = 8), norepinephrine (n = 1), or phenylephrine (n = 1) were adjusted to change invasive mean arterial pressure (MAP) between 40 to 100 mm Hg. Data were analyzed by the Bland-Altman method and 4-quadrant plots. MEASUREMENTS AND MAIN RESULTS: Mean biases and limits of agreement (LOA: ± 1.96 SD) (mm Hg) recorded between the petMAPclassic (thoracic limb) and IBP for systolic arterial pressure (SAP), diastolic arterial pressure (DAP), and MAP were 4.2 ± 28.5, -6.1 ± 13.2, and -1.9 ± 14.6, respectively; mean biases and LOA (mm Hg) recorded with the tail cuff were 7.2 ± 31.3 (SAP), -6.1 ± 11.6 (DAP), and -1.1 ± 11.7 (MAP). Mean biases and LOA (mm Hg) between petMAPgraphic (thoracic limb) and IBP were 7.7 ± 27.0 (SAP), -4.3 ± 11.5 (DAP), 0.2 ± 13.0 (MAP); values recorded with the tail cuff were 10.9 ± 29.6 (SAP), -4.4 ± 11.7 (DAP), and -0.1 ± 12.1 (MAP). Concordance rates after excluding arterial pressure changes ≤ 5 mm Hg was ≥ 93% for both devices. CONCLUSIONS: Although both OBP monitors provide unacceptable SAP estimations, MAP values derived from both monitors and DAP measured by the petMAPgraphic result in acceptable agreement with the reference method according to the Association for the Advancement of Medical Instrumentation (mean bias ≤ 5 mm Hg with LOA ≤ ± 16 mm Hg). Both monitors provide acceptable trending ability for SAP, DAP, and MAP.

Changes in pulse pressure variation and plethysmographic variability index caused by hypotension-inducing hemorrhage followed by volume replacement in isoflurane-anesthetized dogs.

OBJECTIVE: To compare changes in pulse pressure variation (PPV) and plethysmographic variability index (PVI) induced by hemorrhage followed by volume replacement (VR) in isoflurane-anesthetized dogs. ANIMALS: 7 healthy adult dogs. PROCEDURE: Each dog was anesthetized with isoflurane and mechanically ventilated. End-tidal isoflurane concentration was adjusted to maintain mean arterial pressure (MAP) at 60 to 70 mm Hg before hemorrhage. Controlled hemorrhage was initiated and continued until the MAP decreased to 40 to 50 mm Hg, then autologous blood removed during hemorrhage was retransfused during VR. Various physiologic variables including PPV and PVI were recorded immediately before (baseline) and after controlled hemorrhage and immediately after VR. RESULTS: Mean ± SD PPV and PVI were significantly increased from baseline after hemorrhage (PPV, 20 ± 6%; PVI, 18 ± 4%). After VR, the mean PPV (7 ± 3%) returned to a value similar to baseline, whereas the mean PVI (10 ± 3%) was significantly lower than that at baseline. Cardiac index (CI) and stroke index (SI) were significantly decreased from baseline after hemorrhage (CI, 2.07 ± 0.26 L/min/m(2); SI, 20 ± 3 mL/beat/m(2)) and returned to values similar to baseline after VR (CI, 4.25 ± 0.63 L/min/m(2); SI, 36 ± 6 mL/beat/m(2)). There was a significant positive correlation (r(2) = 0.77) between PPV and PVI after hemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that both PPV and PVI may be useful for identification of dogs that respond to VR with increases in SI and CI (ie, dogs in the preload-dependent limb of the Frank-Starling curve).

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism.

AIMS: The pulmonary vasodilation induced by adrenomedullin may be beneficial in the acute pulmonary embolism (APE) setting. This study examined effects of adrenomedullin in sheep with microsphere-induced APE. MAIN METHODS: Twenty four anesthetized, mechanically ventilated sheep were randomly assigned into 3 groups (n=8 per group): animals not subjected to any intervention (Sham), animals with APE induced by microspheres (500 mg, intravenously) treated 30 min later by intravenous physiological saline (Emb group) or intravenous adrenomedullin (50 ng/kg/min) during 30 min (Emb+Adm group). Plasma concentrations of cyclic adenosine (cAMP) and guanosine monophosphate (cGMP) were determined by enzyme immunoassay. KEY FINDINGS: Variables did not change over time in sham animals. In both embolized groups, microsphere injection significantly (P<0.05) increased pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (MPAP) from baseline by 181% and 111-142%, respectively (% change in mean values). Adrenomedullin significantly decreased PVRI (18%-25%) and significantly increased cardiac index (22%-25%) from values recorded 30 min after APE (E30), without modifying MPAP. Adrenomedullin decreased mean arterial pressure (18%-24%) and systemic vascular resistance index (32%-40%). Embolization significantly increased arterial-to-end tidal CO2 gradient, alveolar-to-arterial O2 gradient, and pulmonary shunt fraction from baseline, but these variables were unaffected by adrenomedullin. While adrenomedullin significantly increased plasma cAMP, cGMP levels were unaltered. SIGNIFICANCE: Adrenomedullin induces systemic and pulmonary vasodilation, possibly via a cAMP mediated mechanism, without modifying the gas exchange impairment associated with APE. The pulmonary anti-hypertensive effect of adrenomedullin may be offset by increases in cardiac index.

Effects of different inspired oxygen fractions on sildenafil-induced pulmonary anti-hypertensive effects in a sheep model of acute pulmonary embolism.

AIMS: Sildenafil is a pulmonary anti-hypertensive agent whose action could be modified by different fractions of inspired oxygen (FiO2). We compared the effects of pure oxygen (FiO2 > 90%) or room air (21% FiO2) on the cardiopulmonary actions of sildenafil in sheep with acute pulmonary embolism (APE). MAIN METHODS: Thirty-two anesthetized, mechanically ventilated sheep (34.9 ± 5.4 kg), were randomly distributed into four groups (n = 8 per group): FiO2 > 90% without intervention; APE induced by microspheres with FiO2 > 90%, followed 30 min later by placebo (Emb90); or APE followed 30 min later by intravenous sildenafil (0.7 mg/kg over 30 min) with FiO2 > 90% (Emb + Sild90) or 21% FiO2 (Emb + Sild21) [Corrected]. Variables were recorded until 30 min after the end of treatment administration. KEY FINDINGS: Microsphere injection increased (P < 0.05) mean pulmonary artery pressure (MPAP) in all embolized groups (111-140% higher than that of baseline). Compared with values recorded 30 min after induction of APE (E30), sildenafil induced greater decreases in MPAP in the Emb + Sil90 group than in the Emb + Sil21 group (23% and 14% lower than E30, respectively). Hypotension (mean arterial pressure < 60 mm Hg) was precipitated by sildenafil due to systemic vasodilation in the Emb + Sil21 group. Embolization lowered the PaO2/FiO2 ratio and increased venous admixture, but sildenafil did not alter the oxygenation impairment induced by APE. SIGNIFICANCE: Sildenafil induces a more consistent pulmonary anti-hypertensive effect and causes less interference with the systemic circulation with the concomitant use of pure oxygen than that with room air in the APE setting.