Influence of xylazine on the function of the LiDCO sensor in isoflurane anaesthetized horses

ObjectivePrevious studies showed an influence of xylazine on the LiDCO sensor in vitro and in standing horses, but did not prove that this interaction caused error in LiDCO measurements. Therefore, agreement of cardiac output (CO) measurements by LiDCO and bolus-thermodilution (BTD) was determined in horses receiving xylazine infusions.Study designProspective, experimental study.AnimalsEight Warmblood horses.MethodsAll horses were premedicated with xylazine. Anaesthesia was induced with midazolam and ketamine and was maintained with isoflurane in oxygen. During six hours of anaesthesia CO measurements and blood samples were taken before, during and after a 60 minute period of xylazine infusion. Pairs of LiDCO and bolus thermo-dilution (BTD) measurements of CO were performed. Sensor voltages exposed to blood and saline were measured before, during and after xylazine infusion and compared using Bland-Altman method of agreement with corrections for repeated measures.ResultsThe CO values (mean ± SD) before xylazine were 34.8 ± 7.3 and 36.4 ± 8.1 L minute⁻¹ for BTD and LiDCO, respectively. After starting the xylazine infusion, the CO values for BTD decreased to 27.5 ± 6.1 L minute⁻¹ whereas CO values measured by LiDCO increased to 54.7 ± 18.4 L minute⁻¹. One hour after discontinuing xylazine infusion, CO values were 33 ± 6.7 and 36.5 ±11.9 L minute⁻¹ for BTD and LiDCO, respectively. The difference between saline and blood exposed sensor voltages decreased during xylazine infusion and these differences were positive numbers before but negative during the infusion. There were correlations between xylazine plasma concentrations, CO differences and sensor voltage differences (saline – blood).Conclusions and clinical relevanceThis study proved that xylazine infusion caused concentration dependent bias in LiDCO measurements leading to an overestimation of readings. Sensor voltage differences (saline – blood) may become valuable clinical tool to predict drug-sensor interactions.     

Evaluation of a minimally invasive non-calibrated pulse contour cardiac output monitor (FloTrac/Vigileo) in anaesthetized dogs

ObjectiveTo evaluate the accuracy of a new cardiac output monitor (FloTrac/Vigileo), originally designed for humans, in dogs. This pulse contour cardiac output monitoring system cannot be calibrated and measures cardiac output (

t) from a standard arterial catheter.Study designProspective experimental trial.AnimalsEight adult Beagle dogs weighing 13.1 (9.8–17.1) kg [median (range)].MethodsAnaesthesia in the dogs was maintained using isoflurane. A pulmonary artery catheter and a metatarsal arterial catheter (22 gauge) were placed. Cardiac output was measured simultaneously 331 times by thermodilution and FloTrac technique. A broad spectrum of

t measurements was achieved through alterations of isoflurane concentration, administration of propofol boluses and dobutamine infusions. Agreement between the methods was quantified with Bland Altman analysis and disagreement was assessed with linear mixed models.ResultsMedian (10th and 90th percentile) cardiac output as measured with thermodilution was 2.54 (1.47 and 5.15) L minute^?1 and as measured with FloTrac 8.6 (3.9 and 17.3) L minute^?1. FloTrac measurements were consistently higher with a mean bias of 7 L minute^?1 and limits of agreement of ?3.15 to 17.17 L minute^?1. Difference between the methods was most pronounced in high

t measurements. Linear mixed models showed an estimated difference between the two methods of 8.05 (standard error 1.18) L minute^?1 and a significant interaction between mean arterial pressure and method. Standard deviation (4.45 higher) with the FloTrac method compared to thermodilution was increased.ConclusionCompared to thermodilution measurements, the FloTrac system was influenced to a higher degree by arterial blood pressure, resulting in consistent overestimation of cardiac output.Clinical RelevanceThe FloTrac monitor, whose algorithms were developed based on human data, cannot be used as an alternative for thermodilution in dogs.     

Comparison of noninvasive cardiac output measurements by transthoracic bioimpedance, partial carbon dioxide rebreathing, and transesophageal echocardiography with the thermodilution technique in beagle dogs

Most methods for determining cardiac output (CO) have limited application in clinical practice due to the invasive techniques required. This study compared the thermodilution technique (TDCO) with three noninvasive methods for determining CO in anesthetized dogs: transthoracic bioimpedance (BICO), partial CO₂ rebreathing (NICO), and transesophageal echocardiography (TEECO). TDCO was compared to BICO, NICO, and TEECO in six adult sevoflurane anesthetized beagle dogs (9.1–13.0 kg). All dogs were administered midazolam [0.3 mg kg^?1, intravenously (IV)] and butorphanol (0.1 mg kg^?1 IV), followed by ketamine (5.0 mg kg^–1 IV) and sevoflurane in nitrous oxide (1 L minute^–1) and oxygen (1 L minute^–1) and mechanically ventilated. Dogs were maintained at 2.2% end‐tidal sevoflurane (ETsev) concentration for instrumentation and baseline measurements. Low (5.0% ETsev), intermediate (3.3% ETsev), and high cardiac output values were achieved by varying the end‐tidal sevoflurane concentration and the administration of dobutamine (3–10 g kg^–1 minute^–1 and 2.2% ETsev). A minimum of thirty data sets was obtained for each comparison. The correlation coefficients when compared to TDCO were 0.684 for BICO (p < 0.0001), 0.883 for NICO (p < 0.0001), and 0.991 for TEECO (p < 0.0001). Cardiac output values ranged 50–444 mL kg^–1 minute^–1 for TDCO, 100–253 mL kg^–1 minute^–1 for BICO, 64–214 mL kg^–1 minute^–1 for NICO, and 52–401 mL kg^–1 minute^–1 for TEECO. The differences when compared to TDCO ranged – 62–235 mL kg^?1minute^?1 for BICO, 18–220 mL kg^?1 minute^?1 for NICO, and – 35–32 mL kg^–1 minute^–1 for TEECO. Differences were maximum at the highest CO in BICO and NICO. In conclusion, this study demonstrated that BICO and NICO underestimate CO in sevoflurane anesthetized dogs. TEECO is a viable noninvasive method for determining CO in sevoflurane anesthetized dogs.     

RESEARCH PAPER: Comparison between two methods for cardiac output measurement in propofol‐anesthetized dogs: thermodilution and Doppler

ObjectiveTo compare cardiac output (CO) measured by Doppler echocardiography and thermodilution techniques in spontaneously breathing dogs during continuous infusion of propofol. To do so, CO was obtained using the thermodilution method (CO_TD) and Doppler evaluation of pulmonary flow (CO_DP) and aortic flow (CO_DA).Study designProspective cohort study.AnimalsEight adult dogs weighing 8.3 ± 2.0 kg.MethodsPropofol was used for induction (7.5 ± 1.9 mg kg^?1 IV) followed by a continuous rate infusion at 0.7 mg kg^?1 minute^?1. The animals were positioned in left lateral recumbency on an echocardiography table that allowed for positioning of the transducer at the 3rd and 5th intercostal spaces of the left hemithorax for Doppler evaluation of pulmonary and aortic valves, respectively. CO_DP and CO_DA were calculated from pulmonary and aortic velocity spectra, respectively. A pulmonary artery catheter was inserted via the jugular vein and positioned inside the lumen of the pulmonary artery in order to evaluate CO_TD. The first measurement of CO_TD, CO_DP and CO_DA was performed 30 minutes after beginning continuous infusion (T0) and then at 15‐minute intervals (T15, T30, T45 and T60). Numeric data were submitted to two‐way anova for repeated measurements, Pearson’s correlation coefficient and Bland &; Altman analysis. Data are presented as mean ± SD.ResultsAt T0, CO_TD was lower than CO_DA. CO_DA was higher than CO_TD and CO_DP at T30, T45 and T60. The difference between the CO_TD and CO_DP, when all data were included, was ?0.04 ± 0.22 L minute^?1 and Pearson’s correlation coefficient (r) was 0.86. The difference between the CO_TD and CO_DA was ?0.87 ± 0.54 L minute^?1 and r = 0.69. For CO_TD and CO_DP, the difference was ?0.82 ± 0.59 L minute^?1 and r = 0.61.ConclusionDoppler evaluation of pulmonary flow was a clinically acceptable method for assessing the CO in propofol‐anesthetized dogs.     

The effects of halothane and isoflurane on cardiovascular function in dorsally recumbent horses undergoing surgery

ObjectiveTo determine the haemodynamic effects of halothane and isoflurane with spontaneous and controlled ventilation in dorsally recumbent horses undergoing elective surgery.Study designProspective randomized clinical trial.AnimalsTwenty-five adult horses, body mass 487 kg (range: 267–690).MethodsHorses undergoing elective surgery in dorsal recumbency were randomly assigned to one of four treatment groups, isoflurane (I) or halothane (H) anaesthesia, each with spontaneous (SB) or controlled ventilation (IPPV). Indices of cardiac function and femoral arterial blood flow (ABF) and resistance were measured using transoesophageal and transcutaneous Doppler echocardiography, respectively. Arterial blood pressure was measured directly.ResultsFour horses assigned to receive isoflurane and spontaneous ventilation (SBI) required IPPV, leaving only three groups for analysis: SBH, IPPVH and IPPVI. Two horses were excluded from the halothane groups because dobutamine was infused to maintain arterial blood pressure. Cardiac index (CI) was significantly greater, and pre-ejection period (PEP) shorter, during isoflurane compared with halothane anaesthesia with both spontaneous (p = 0.04, p = 0.0006, respectively) or controlled ventilation (p = 0.04, p = 0.008, respectively). There was an association between CI and PaCO₂ (p = 0.04) such that CI increased by 0.45 L minute⁻¹m⁻² for every kPa increase in PaCO₂. Femoral ABF was only significantly higher during isoflurane compared with halothane anaesthesia during IPPV (p = 0.0006). There was a significant temporal decrease in CI, but not femoral arterial flow.ConclusionThe previously reported superior cardiovascular function during isoflurane compared with halothane anaesthesia was maintained in horses undergoing surgery. However, in these clinical subjects, a progressive decrease in CI, which was independent of ventilatory mode, was observed with both anaesthetic agents.Clinical relevanceCardiovascular function may deteriorate progressively in horses anaesthetized for brief (<2 hours) surgical procedures in dorsal recumbency. Although cardiovascular function is superior with isoflurane in dorsally recumbent horses, the need for IPPV may be greater.     

Cardiovascular effects of increasing dosages of norepinephrine in healthy isoflurane-anesthetized New Zealand White rabbits

ObjectiveTo characterize the cardiovascular effects of increasing dosages of norepinephrine (NE) in healthy isoflurane-anesthetized rabbits.Study designProspective experimental study.AnimalsA total of nine female ovariohysterectomized New Zealand White rabbits weighing 3.4 ± 0.2 kg (mean ± standard deviation).MethodsRabbits were premedicated intramuscularly with buprenorphine (0.05 mg kg^–1) and midazolam (0.5 mg kg^–1). Anesthesia was induced with intravenous propofol and maintained with a 1.1 × minimum alveolar concentration of isoflurane for this species to induce hypotension. Rabbits were administered NE infusions at three doses: low, 0.1 μg kg^–1 minute^–1; medium, 0.5 μg kg^–1 minute^–1; and high doses, 1 μg kg^–1 minute^–1 for 10 minutes each in that order. Cardiovascular variables including heart rate (HR), cardiac output (CO) by lithium dilution technique and systolic (SAP), mean (MAP) and diastolic (DAP) invasive arterial blood pressures measured in the auricular artery were recorded at baseline, 10 minutes after the start of the infusion of each NE treatment and 10 minutes after NE was discontinued. A linear mixed model and a type III anova with Tukey’s post hoc comparison was performed (p < 0.05).ResultsSignificant increases in SAP (28% and 90%), MAP (27% and 90%) and DAP (33% and 97%) were measured with medium and high dose treatments, respectively (p < 0.001), with no changes in CO. HR decreased and stroke volume increased significantly with high dose treatment (by 17% and 15%, respectively; p < 0.05). No arrhythmias were noticed with NE treatments.Conclusions and clinical relevanceThe infusion of NE at 0.5–1.0 μg kg^–1 minute^–1 is a potentially effective treatment for hypotension in healthy isoflurane-anesthetized New Zealand White rabbits.     

Cardiovascular effects following epidural injection of romifidine in isoflurane‐anaesthetized dogs

ObjectiveTo investigate the cardiovascular effects of epidural romifidine in isoflurane-anaesthetized dogs.Study designProspective, randomized, blinded experiment.AnimalsA total of six healthy adult female Beagles aged 1.25 ± 0.08 years and weighing 12.46 ± 1.48 (10.25–14.50) kg.MethodsAnaesthesia was induced with propofol (6–9 mg kg^?1) and maintained with 1.8–1.9% end-tidal isoflurane in oxygen. End-tidal CO₂ was kept between 35 and 45 mmHg (4.7–6.0 kPa) using intermittent positive pressure ventilation. Heart rate (HR), arterial blood pressure and cardiac output (CO) were monitored. Cardiac output was determined using a LiDCO monitor and the derived parameters were calculated. After baseline measurements, either 10 μg kg^?1 romifidine or saline (total volume 1 mL 4.5 kg^?1) was injected into the lumbosacral epidural space. Data were recorded for 1 hour after epidural injection. A minimum of 1 week elapsed between treatments.ResultsAfter epidural injection, the overall means (± standard deviation, SD) of HR (95 ± 20 bpm), mean arterial blood pressure (MAP) (81 ± 19 mmHg), CO (1.63 ± 0.66 L minute^?1), cardiac index (CI) (2.97 ± 1.1 L minute^?1 m^?2) and stroke volume index (SI) (1.38 ± 0.21 mL beat^?1 kg^?1) were significantly lower in the romifidine treatment compared with the overall means in the saline treatment [HR (129 ± 24 bpm), MAP (89 ± 17 mmHg), CO (3.35 ± 0.86 L minute^?1), CI (6.17 ± 1.4 L minute^?1 m^?2) and SI (2.21 ± 0.21 mL beat^?1 kg^?1)]. The overall mean of systemic vascular resistance index (SVRI) (7202 ± 2656 dynes seconds cm^?5 m^?2) after epidural romifidine injection was significantly higher than the overall mean of SVRI (3315 ± 1167 dynes seconds cm^?5 m^?2) after epidural saline injection.ConclusionEpidural romifidine in isoflurane-anaesthetized dogs caused significant cardiovascular effects similar to those reportedly produced by systemic romifidine administration.Clinical relevanceSimilar cardiovascular monitoring is required after epidural and systemically administered romifidine. Further studies are required to evaluate the analgesic effects of epidural romifidine.     

Cardiovascular,respiratory, electrolyte and acid–base balance during continuous dexmedetomidine infusion in anesthetized dogs

ObjectiveTo evaluate the cardiovascular, respiratory, electrolyte and acid–base effects of a continuous infusion of dexmedetomidine during propofol–isoflurane anesthesia following premedication with dexmedetomidine.Study designProspective experimental study.AnimalsFive adult male Walker Hound dogs 1–2 years of age averaging 25.4 ± 3.6 kg.MethodsDogs were sedated with dexmedetomidine 10 μg kg^?1 IM, 78 ± 2.3 minutes (mean ± SD) before general anesthesia. Anesthesia was induced with propofol (2.5 ± 0.5 mg kg^?1) IV and maintained with 1.5% isoflurane. Thirty minutes later dexmedetomidine 0.5 μg kg^?1 IV was administered over 5 minutes followed by an infusion of 0.5 μg kg^?1 hour^?1. Cardiac output (CO), heart rate (HR), ECG, direct blood pressure, body temperature, respiratory parameters, acid–base and arterial blood gases and electrolytes were measured 30 and 60 minutes after the infusion started. Data were analyzed via multiple linear regression modeling of individual variables over time, compared to anesthetized baseline values. Data are presented as mean ± SD.ResultsNo statistical difference from baseline for any parameter was measured at any time point. Baseline CO, HR and mean arterial blood pressure (MAP) before infusion were 3.11 ± 0.9 L minute^?1, 78 ± 18 beats minute^?1 and 96 ± 10 mmHg, respectively. During infusion CO, HR and MAP were 3.20 ± 0.83 L minute^?1, 78 ± 14 beats minute^?1 and 89 ± 16 mmHg, respectively. No differences were found in respiratory rates, PaO₂, PaCO₂, pH, base excess, bicarbonate, sodium, potassium, chloride, calcium or lactate measurements before or during infusion.Conclusions and clinical relevanceDexmedetomidine infusion using a loading dose of 0.5 μg kg^?1 IV followed by a constant rate infusion of 0.5 μg kg^?1 hour^?1 does not cause any significant changes beyond those associated with an IM premedication dose of 10 μg kg^?1, in propofol–isoflurane anesthetized dogs. IM dexmedetomidine given 108 ± 2 minutes before onset of infusion showed typical significant effects on cardiovascular parameters.     

The effect of high doses of remifentanil in brain near‐infrared spectroscopy and in electroencephalographic parameters in pigs

ObjectiveTo study the effects of a high remifentanil bolus dose on pig’s electroencephalographic indices and on brain regional and global oxygenation.Study designProspective experimental study.AnimalsTwelve healthy Large-White male pigs, age 3 months and weight 26.2 ± 3.6 kg.MethodsAnaesthesia was induced with intravenous propofol 4 mg kg^?1, then maintained with constant rate infusions of propofol (15 mg kg^?1 hour^?1) and remifentanil (0.3 μg kg^?1 minute^?1). Following instrumentation, all pigs received a 5 μg kg^?1 remifentanil bolus. The responses of jugular venous oxygen saturation, cardiac output and cerebral oxygen saturation to the remifentanil bolus were studied. The Bispectral index, spectral edge frequency 95%, total power, approximate entropy and permutation entropy were also studied. Repeated measures anova and Pearson correlation were used to analyze the effect of remifentanil bolus on these variables until 5 minutes after the bolus.ResultsCardiac output and cerebral oxygen saturation decreased significantly after the remifentanil bolus from 4.6 ± 0.9 to 3.8 ± 1.0 L minute^?1 and from 65 ± 6 to 62 ± 1% (p < 0.05), respectively. No significant changes were observed in the jugular venous oxygen saturation (p > 0.05) nor in any of the electroencephalogram derived indices (p > 0.05). Correlation analysis revealed strong positive significant correlations between cerebral oxygen saturation and cardiac output (r = 0.82, p < 0.001) and between cerebral oxygen saturation and approximate entropy (r = 0.65, p < 0.001).Conclusions and Clinical RelevanceThe effect caused by the remifentanil bolus on the brain oxygenation seems to be better reflected by the cerebral oxygen saturation than the jugular venous oxygen saturation. The effect of remifentanil on the electroencephalogram may not be reflected in indices derived from the electroencephalogram, but the potential of the approximate entropy in reflecting changes caused by opioids on the electroencephalogram should be further investigated.     

Effect of ephedrine and phenylephrine on cardiopulmonary parameters in horses undergoing elective surgery

ObjectiveTo assess the cardiopulmonary effects of ephedrine and phenylephrine for management of isoflurane‐induced hypotension in horses.Study designProspective randomized clinical study.AnimalsFourteen isoflurane‐anesthetized horses undergoing digital palmar neurectomy.MethodsEphedrine (EPH group; 0.02 mg kg^?1 minute^?1; n = 7) or phenylephrine (PHE group; 0.002 mg kg^?1 minute^?1; n = 7) was administered to all horses when mean arterial pressure (MAP) was <60 mmHg. The infusions were ended when the target MAP was achieved, corresponding to a 50% increase over the pre‐infusion MAP (baseline). The horses were instrumented with an arterial catheter to measure blood pressure and allow the collection of blood for pH and blood‐gas analysis and a Swan‐Ganz catheter for measurement of cardiac output using thermodilution. Cardiopulmonary parameters were recorded at baseline and at 5, 30, 60 and 90 minutes after achieving the target MAP.ResultsIn both groups, the MAP and systemic vascular resistance (SVR) increased significantly at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05). The EPH group had a significant increase in cardiac index (CI) and systemic oxygen delivery index at 5, 30, 60 and 90 minutes post infusion compared to baseline (p < 0.05) and compared to the PHE group (p < 0.05). The PHE group had significantly higher SVR and no decrease in oxygen extraction compared with the EPH group at 30, 60 and 90 minutes post infusion (p < 0.05). No significant differences in ventilatory parameters were observed between groups after the infusion.ConclusionsEphedrine increased the MAP by increasing CI and SVR. Phenylephrine increased MAP by increasing SVR but cardiac index decreased. Ephedrine resulted in better tissue oxygenation than phenylephrine.Clinical relevanceEphedrine would be preferable to phenylephrine to treat isoflurane‐induced hypotension in horses since it increases blood flow and pressure.     

Volumetric evaluation of fluid responsiveness using a modified passive leg raise maneuver during experimental induction and correction of hypovolemia in anesthetized dogs

ObjectiveTo demonstrate if modified passive leg raise (PLR_M) maneuver can be used for volumetric evaluation of fluid responsiveness (FR) by inducing cardiac output (CO) changes during experimental induction and correction of hypovolemia in healthy anesthetized dogs. The effects of PLR_M on plethysmographic variability index (PVI) and pulse pressure variation (PPV) were also investigated.Study designProspective, crossover study.AnimalsA total of six healthy anesthetized Beagle dogs.MethodsDogs were anesthetized with propofol and isoflurane. They were mechanically ventilated under neuromuscular blockade, and normothermia was maintained. After instrumentation, all dogs were subjected to four stages: 1, baseline; 2, removal of 27 mL kg^–1 circulating blood volume; 3, after blood re-transfusion; and 4, after 20 mL kg^–1 hetastarch infusion over 20 minutes. A 10 minute stabilization period was allowed after induction of each stage and before data collection. At each stage, CO via pulmonary artery thermodilution, PVI, PPV and cardiopulmonary variables were measured before, during and after the PLR_M maneuver. Stages were sequential, not randomized. Statistical analysis included repeated measures anova and Tukey’s post hoc test, considering p < 0.05 as significant.ResultsDuring stage 2, PLR_M at a 30° angle significantly increased CO (mean ± standard deviation, 1.0 ± 0.1 to 1.3 ± 0.1 L minute^–1; p < 0.001), with a simultaneous significant reduction in PVI (38 ± 4% to 21 ± 4%; p < 0.001) and PPV (27 ± 2% to 18 ± 2%; p < 0.001). The PLR_M did not affect CO, PPV and PVI during stages 1, 3 and 4.Conclusions and clinical relevanceIn anesthetized dogs, PLR_M at a 30° angle successfully detected FR during hypovolemia, and identified fluid nonresponsiveness during normovolemia and hypervolemia. Also, in hypovolemic dogs, significant decreases in PVI and PPV occurred in response to PLR_M maneuver.     

Hypnotic effects and pharmacokinetics of a single bolus dose of propofol in Japanese macaques (Macaca fuscata fuscata). [corrected

ObjectiveTo describe the hypnotic effects of a single bolus dose of propofol in Japanese macaques, and to develop a pharmacokinetic model.Study designProspective experimental trial.AnimalsFour male macaques (5-6 years old, 8.0-11.2 kg).MethodsThe macaque was restrained and 8 mg kg^?1 of propofol was administrated intravenously at 6 mg kg^?1 minute^?1. Behavioural changes without stimuli (first experiment) then responses to external stimuli (the second experiment) were assessed every 2 minutes for 20 minutes. Venous blood samples were collected before and at 1, 5, 15, 30, 60, 120 and 210 minutes after drug administration, and plasma concentrations of propofol were measured (third experiment). Pharmacokinetic modelling was performed using NONMEM VI.ResultsMacaques were recumbent without voluntary movement for a mean 14.0 ± 2.7 SD (range 10.5-16.2) or 10.0 ± 3.4 (7.2-14.5) minutes and recovered to behave as pre-administration by 25.1 ± 3.6 (22.1-30.1) or 22.2 ± 1.5 (21.1-24.3) minutes after the end of propofol administration without or with stimuli, respectively. Respiratory and heart rates were stable throughout the experiments (28-68 breaths minute^?1 and 72-144 beats minute^?1, respectively). Our final pharmacokinetic model included three compartments and well described the plasma concentration of propofol. The population pharmacokinetic parameters were: V₁ = 10.4 L, V₂=8.38 L, V₃=72.7 L, CL₁= 0.442 L minute^?1, CL₂= 1.14 L minute^?1, CL₃= 0.313 L minute^?1, (the volumes of distribution and the clearances for the central, rapid and slow peripheral compartments, respectively).ConclusionsIntravenous administration of propofol (8 mg kg^?1) at 6 mg kg^?1 minute^?1 to Japanese macaques had a hypnotic effect lasting more than 7 minutes. A three-compartment model described propofol plasma concentrations over more than 3 hours.Clinical relevanceThe developed pharmacokinetic parameters may enable simulations of administration protocols to maintain adequate plasma concentration of propofol.     

The effect of midazolam on the end-tidal concentration of isoflurane necessary to prevent movement in dogs

ObjectiveTo determine the possible additive effect of midazolam, a GABA_A agonist, on the end-tidal concentration of isoflurane that prevents movement (MAC_NM) in response to noxious stimulation.Study designRandomized cross-over experimental study.AnimalsSix healthy, adult intact male, mixed-breed dogs.MethodsAfter baseline isoflurane MAC_NM (MAC_NM-B) determination, midazolam was administered as a low (LDS), medium (MDS) or high (HDS) dose series of midazolam. Each series consisted of two dose levels, low and high. The LDS was a loading dose (Ld) of 0.2 mg kg^?1 and constant rate infusion (CRI) (2.5 μg kg^?1 minute^?1) (LDL), followed by an Ld (0.4 mg kg^?1) and CRI (5 μg kg^?1 minute^?1) (LDH). The MDS was an Ld (0.8 mg kg^?1) and CRI (10 μg kg^?1 minute^?1) (MDL) followed by an Ld (1.6 mg kg^?1) and CRI (20 μg kg^?1 minute^?1) (MDH). The HDS was an Ld (3.2 mg kg^?1) and CRI (40 μg kg^?1 minute^?1) (HDL) followed by an Ld (6.4 mg kg^?1) and CRI (80 μg kg^?1 minute^?1) (HDH). MAC_NM was re-determined after each dose in each series (MAC_NM-T).ResultsThe median MAC_NM-B was 1.42. MAC_NM-B did not differ among groups (p >0.05). Percentage reduction in MAC_NM was significantly less in the LDS (11 ± 5%) compared with MDS (30 ± 5%) and HDS (32 ± 5%). There was a weak correlation between the plasma midazolam concentration and percentage MAC_NM reduction (r = 0.36).Conclusion and clinical relevanceMidazolam doses in the range of 10–80 μg kg^?1 minute^?1 significantly reduced the isoflurane MAC_NM. However, doses greater than 10 μg kg^?1 minute^?1 did not further decrease MAC_NM indicating a ceiling effect.     

Anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in isoflurane‐anaesthetized sheep

ObjectiveTo determine the anaesthetic and cardiorespiratory effects of a constant rate infusion of fentanyl in sheep anaesthetized with isoflurane and undergoing orthopaedic surgery.Study designProspective, randomised, ‘blinded’ controlled study.AnimalsTwenty healthy sheep (weight mean 41.1 ± SD 4.5 kg).MethodsSheep were sedated with intravenous (IV) dexmedetomidine (4 μg kg⁻¹) and morphine (0.2 mg kg⁻¹). Anaesthesia was induced with propofol (1 mg kg⁻¹ minute⁻¹ to effect IV) and maintained with isoflurane in oxygen and a continuous rate infusion (CRI) of fentanyl 10 μg kg⁻¹ hour⁻¹ (group F) or saline (group P) for 100 minutes. The anaesthetic induction dose of propofol, isoflurane expiratory fraction (Fe’iso) required for maintenance and cardiorespiratory measurements were recorded and blood gases analyzed at predetermined intervals. The quality of recovery was assessed. Results were compared between groups using t-tests or Mann–Whitney as relevant.ResultsThe propofol induction dose was 4.7 ± 2.4 mg kg⁻¹. Fe’iso was significantly lower (by 22.6%) in group F sheep than group P (p = 0). Cardiac index (mean ± SD mL kg⁻¹ minute⁻¹) was significantly (p = 0.012) lower in group F (90 ± 15) than group P (102 ± 35). Other measured cardiorespiratory parameters did not differ statistically significantly between groups. Recovery times and recovery quality were statistically similar in both groups.Conclusions and clinical relevanceFentanyl reduced isoflurane requirements without clinically affecting the cardiorespiratory stability or post-operative recovery in anaesthetized sheep undergoing orthopaedic surgery.     

Cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in healthy Beagle dogs

ObjectiveTo determine the cardiovascular effects of a proprietary l-methadone/fenpipramide combination (Polamivet) alone and in addition to acepromazine in dogs.Study designProspective, randomized, experimental crossover study.AnimalsFive adult healthy Beagle dogs (one male and four females, weighing 12.8–16.4 kg).MethodsDogs were instrumented for haemodynamic measurements whilst anaesthetized with isoflurane. Three hours after recovery dogs received 0.025 mg kg^?1 acepromazine (AP) or saline (SP) IM followed by 0.5 mg kg^?1L-methadone/ 0.025 mg kg^?1 fenpipramide IV after 30 minutes. Cardiac output using thermodilution, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), mean pulmonary artery pressure (MPAP), pulmonary artery occlusion pressure (PAOP), haemoglobin concentration, arterial and mixed-venous blood gas analysis were measured and sedation evaluated at baseline (BL), 30 minutes after acepromazine or saline IM (A/S), 5 minutes after L-methadone/fenpipramide IV application (35), every 15 minutes for 1 hour (50, 65, 80, 95 minutes) and every hour until baseline cardiac output was regained. Standard cardiovascular parameters were calculated. Data were analyzed by repeated measures anova and paired t-tests with p < 0.05 considered significant.ResultsBaseline measurements did not differ. Cardiac index decreased after acepromazine administration in treatment AP (p = 0.027), but was not significantly influenced after l-methadone/fenpipramide injection in either treatment. In both treatments heart rate did not change significantly over time. Stroke volume index increased after A/S in both treatments (p = 0.049). Systemic vascular resistance index, MAP, CVP, MPAP, and pulmonary vascular resistance index did not change significantly after either treatment and did not differ between treatments. Dogs were deeply sedated in both treatments with a longer duration in treatment AP.Conclusions and clinical relevanceIn healthy dogs the dose of l-methadone/fenpipramide used in this study alone and in combination with acepromazine induced deep sedation without significant cardiovascular changes.     

Evaluation of cardiovascular effects of intramuscular medetomidine and a medetomidine–vatinoxan combination in Beagle dogs: A randomized blinded crossover laboratory study

ObjectiveTo compare the cardiovascular effects of a combination of medetomidine and vatinoxan (MVX) versus medetomidine (MED) alone administered intramuscularly (IM) and to determine whether heart rate (HR) can be used as a surrogate for cardiac output (CO) after the use of medetomidine with or without vatinoxan.Study designA randomized, blinded, experimental, crossover study.AnimalsA group of eight healthy Beagle dogs aged 4.6 (2.3–9.4) years and weighing 12.9 (9–14.7) kg, median (range).MethodsEach dog was injected with 1 mg m^–2 medetomidine with or without 20 mg m^–2 vatinoxan IM with a washout period of 7 days. Cardiovascular data and arterial and mixed venous blood gas samples were collected at baseline, 5, 10, 15, 20, 35, 45, 60, 90 and 120 minutes after treatment administration. CO was measured at all time points via thermodilution. Differences between treatments, period and sequence were evaluated with repeated measures analysis of covariance and the relationship between HR and CO was assessed with a repeated measures analysis of variance; p values < 0.05 were deemed significant.ResultsThe CO was 47–96% lower after MED than after MVX (p < 0.0001). Increases in systemic, pulmonary arterial and right atrial pressures and oxygen extraction ratio were significantly higher after MED than after MVX (all p < 0.0001). HR was significantly lower after MED and the linear relationship to CO was significant (p < 0.0001).Conclusions and clinical relevanceOverall, MED affected the cardiovascular system more negatively than MVX, and the difference in cardiovascular function between the treatments can be considered clinically relevant. HR was linearly related to CO, and decreases in HR reflected cardiac performance for dogs sedated with medetomidine with or without vatinoxan.     

Comparison of cardiopulmonary effects of etorphine and thiafentanil administered as sole agents for immobilization of impala (Aepyceros melampus)

ObjectiveTo compare the cardiopulmonary effects of the opioids etorphine and thiafentanil for immobilization of impala.Study designTwo-way crossover, randomized study.AnimalsA group of eight adult female impala.MethodsImpala were given two treatments: 0.09 mg kg^–1 etorphine or 0.09 mg kg^–1 thiafentanil via remote dart injection. Time to recumbency, quality of immobilization and recovery were assessed. Respiratory rate, heart rate (HR), mean arterial blood pressure (MAP) and arterial blood gases were measured. A linear mixed model was used to analyse the effects of treatments, treatments over time and interactions of treatment and time (p < 0.05).ResultsTime to recumbency was significantly faster with thiafentanil (2.0 ± 0.8 minutes) than with etorphine (3.9 ± 1.6 minutes; p = 0.007). Both treatments produced bradypnoea, which was more severe at 5 minutes with thiafentanil (7 ± 4 breaths minute^–1) than with etorphine (13 ± 12 breaths minute^–1; p = 0.004). HR increased with both treatments but significantly decreased over time when etorphine (132 ± 17 to 82 ± 11 beats minute^–1) was compared with thiafentanil (113 ± 22 to 107 ± 36 beats minute^–1; p < 0.001). Both treatments caused hypertension which was more profound with thiafentanil (mean overall MAP = 140 ± 14 mmHg; p < 0.001). Hypoxaemia occurred with both treatments but was greater with thiafentanil [PaO₂ 37 ± 13 mmHg (4.9 kPa)] than with etorphine [45 ± 16 mmHg (6.0 kPa)] 5 minutes after recumbency (p < 0.001). After 30 minutes, PaO₂ increased to 59 ± 10 mmHg (7.9 kPa) with both treatments (p < 0.001).Conclusions and clinical relevanceThe shorter time to recumbency with thiafentanil may allow easier and faster retrieval in the field. However, thiafentanil caused greater hypertension, and ventilatory effects during the first 10 minutes, after administration.     

Assessing the influence of mechanical ventilation on blood gases and blood pressure in rattlesnakes

ObjectiveTo characterize the impact of mechanical positive pressure ventilation on heart rate (HR), arterial blood pressure, blood gases, lactate, glucose, sodium, potassium and calcium concentrations in rattlesnakes during anesthesia and the subsequent recovery period.Study designProspective, randomized trial.AnimalsTwenty one fasted adult South American rattlesnakes (Crotalus durissus terrificus).MethodsSnakes were anesthetized with propofol (15 mg kg⁻¹) intravenously, endotracheally intubated and assigned to one of four ventilation regimens: Spontaneous ventilation, or mechanical ventilation at a tidal volume of 30 mL kg⁻¹ at 1 breath every 90 seconds, 5 breaths minute⁻¹, or 15 breaths minute⁻¹. Arterial blood was collected from indwelling catheters at 30, 40, and 60 minutes and 2, 6, and 24 hours following induction of anesthesia and analyzed for pH, PaO₂, PaCO₂, and selected variables. Mean arterial blood pressure (MAP) and HR were recorded at 30, 40, 60 minutes and 24 hours.ResultsSpontaneous ventilation and 1 breath every 90 seconds resulted in a mild hypercapnia (PaCO₂ 22.4 ± 4.3 mmHg [3.0 ± 0.6 kPa] and 24.5 ± 1.6 mmHg [3.3 ± 0.2 kPa], respectively), 5 breaths minute⁻¹ resulted in normocapnia (14.2 ± 2.7 mmHg [1.9 ± 0.4 kPa]), while 15 breaths minute⁻¹ caused marked hypocapnia (8.2 ± 2.5 mmHg [1.1 ± 0.3 kPa]). Following recovery, blood gases of the four groups were similar from 2 hours. Anesthesia, independent of ventilation was associated with significantly elevated glucose, lactate and potassium concentrations compared to values at 24 hours (p < 0.0001). MAP increased significantly with increasing ventilation frequency (p < 0.001). HR did not vary among regimens.Conclusions and clinical relevanceMechanical ventilation had a profound impact on blood gases and blood pressure. The results support the use of mechanical ventilation with a frequency of 1–2 breaths minute⁻¹ at a tidal volume of 30 mL kg⁻¹ during anesthesia in fasted snakes.