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A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine.

ABSTRACT: BACKGROUND:General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory effects of propofol-ketamine-dexmedetomidine and alfaxalone-ketamine-dexmedetomidine in pigs. Sixteen pigs premedicated with ketamine 15 mg/kg and midazolam 1 mg/kg intramuscularly were anaesthetised with propofol or alfaxalone to allow endotracheal intubation, followed by propofol 8 mg/kg/h or alfaxalone 5 mg/kg/h in combination with ketamine 5 mg/kg/h and dexmedetomidine 4 µg/kg/h given as a continuous infusion for 60 min. The pigs breathed spontaneously with an FIO2 of 0.21. Oxygen saturation (SpO2), end-tidal CO2 concentration (PE'CO2), respiratory rate (fR) and inspired tidal volume (VT) were measured, and statistically compared between treatments. If the SpO2 dropped below 80% or if PE'CO2 increased above 10.0 kPa, the pigs were recorded as failing to complete the study, and time to failure was statistically compared between treatments. RESULTS:Alfaxalone treated pigs had significantly higher respiratory rates and lower PE'CO2 than propofol treated pigs, with a fR being 7.3 /min higher (P?=?0.01) and PE'CO2 0.8 kPa lower (P?=?0.05). SpO2 decreased by 0.6% and fR by 1.0 /min per kg increase in body weight in both treatment groups. Three of eight propofol treated and two of eight alfaxalone treated pigs failed to complete the study, and times to failure were not significantly different between treatments (P?=?0.75). CONCLUSIONS:No major differences in respiratory variables were found when comparing treatments. Respiratory supportive measures must be available when using both protocols.

SUBMITTER: Lervik A

PROVIDER: S-EPMC7066810 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine.

Lervik Andreas A Toverud Simen Forr SF Krontveit Randi R Haga Henning Andreas HA

Acta veterinaria Scandinavica 20200312 1

<h4>Background</h4>General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory effects of propofol-ketamine-dexmedetomidine and alfaxalone-ketamine-dexmedetomidine in pigs. Sixteen pigs premedicated with ketamine 15 mg/kg and midazolam 1 mg/kg intramuscularly were anaesthetised with propofol or alfaxalone to allow ...[more]

PMID: 32164761

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Project description:BackgroundThis exploratory study aimed to investigate whether dexmedetomidine, propofol, sevoflurane, and S-ketamine affect oxylipins and bile acids, which are functionally diverse molecules with possible connections to cellular bioenergetics, immune modulation, and organ protection.MethodsIn this randomised, open-label, controlled, parallel group, Phase IV clinical drug trial, healthy male subjects (n=160) received equipotent doses (EC50 for verbal command) of dexmedetomidine (1.5 ng ml-1; n=40), propofol (1.7 μg ml-1; n=40), sevoflurane (0.9% end-tidal; n=40), S-ketamine (0.75 μg ml-1; n=20), or placebo (n=20). Blood samples for tandem mass spectrometry were obtained at baseline, after study drug administration at 60 and 130 min from baseline; 40 metabolites were analysed.ResultsStatistically significant changes vs placebo were observed in 62.5%, 12.5%, 5.0%, and 2.5% of analytes in dexmedetomidine, propofol, sevoflurane, and S-ketamine groups, respectively. Data are presented as standard deviation score, 95% confidence interval, and P-value. Dexmedetomidine induced wide-ranging decreases in oxylipins and bile acids. Amongst others, 9,10-dihydroxyoctadecenoic acid (DiHOME) -1.19 (-1.6; -0.78), P<0.001 and 12,13-DiHOME -1.22 (-1.66; -0.77), P<0.001 were affected. Propofol elevated 9,10-DiHOME 2.29 (1.62; 2.96), P<0.001 and 12,13-DiHOME 2.13 (1.42; 2.84), P<0.001. Analytes were mostly unaffected by S-ketamine. Sevoflurane decreased tauroursodeoxycholic acid (TUDCA) -2.7 (-3.84; -1.55), P=0.015.ConclusionsDexmedetomidine-induced oxylipin alterations may be connected to pathways associated with organ protection. In contrast to dexmedetomidine, propofol emulsion elevated DiHOMEs, oxylipins associated with acute respiratory distress syndrome, and mitochondrial dysfunction in high concentrations. Further research is needed to establish the behaviour of DIHOMEs during prolonged propofol/dexmedetomidine infusions and to verify the sevoflurane-induced reduction in TUDCA, a suggested neuroprotective agent.Clinical trial registrationNCT02624401.

Project description:BackgroundMedetomidine-ketamine (MK) and dexmedetomidine-ketamine (DK) are widely used to provide general anaesthesia in laboratory animals, but have not been compared directly in many of these species, including rodents. This study aimed to compare the onset and depth of anaesthesia, and changes in vital signs, after intraperitoneal (IP) or subcutaneous (SC) administration of ketamine (75 mg kg(-1)) combined with medetomidine (1 mg kg(-1)) or dexmedetomidine (0.5 mg kg(-1)) using a randomised semi-crossover design with ? 48 hours between treatments in 10 male and 10 female mice. Each mouse was anaesthetised twice using the same administration route (IP or SC): once with each drug-ketamine combination. Anaesthetised mice were monitored on a heating pad without supplemental oxygen for 89 minutes; atipamezole was administered for reversal. The times that the righting reflex was lost post-injection and returned post-reversal were analysed using general linear models. Tail-pinch and pedal reflexes were examined using binomial generalized linear models. Pulse rate (PR), respiratory rate (fr), and arterial haemoglobin saturation (S(p)O2) were compared using generalized additive mixed models.ResultsThere were no significant differences among treatments for the times taken for loss and return of the righting reflex, or response of the tail-pinch reflex. The pedal withdrawal reflex was abolished more frequently with MK than DK over time (P = 0.021). The response of PR and S(p)O2 were similar among treatments, but fr was significantly higher with MK than DK (P ? 0.0005). Markedly low S(p)O2 concentrations occurred within 5 minutes post-injection (83.8 ± 6.7%) in all treatment groups and were most severe after 89 minutes lapsed (66.7 ± 7.5%). No statistical differences were detected in regards to administration route (P ? 0.94).ConclusionsThis study failed to demonstrate clinical advantages of the enantiomer dexmedetomidine over medetomidine when combined with ketamine to produce general anaesthesia in mice. At the doses administered, deep surgical anaesthesia was not consistently produced with either combination; therefore, anaesthetic depth must be assessed before performing surgical procedures. Supplemental oxygen should always be provided during anaesthesia to prevent hypoxaemia.

Project description:OBJECTIVE:A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and without airway management. However, there are important pitfalls to be avoided by special precautions and monitoring, as shown subsequently. STUDY DESIGN:Observational study. ANIMALS:Twenty-four anaesthetic procedures for bile duct ligation, sham operation or carotid artery dilatation in 20 male Sprague-Dawley rats, preoperatively weighing between 440 and 550 g. METHODS:Intolerable high mortality rates occurred in the first 7 postoperative days while establishing a new experimental model in rats using ketamine-xylazine anaesthesia. Rats were spontaneously breathing ambient air during the first 12 surgeries without airway management. An observed high mortality rate in these animals led to a change in the trial protocol: the insufflation of 2 litres of oxygen per minute via nose cone during the following 12 rat surgeries. Retrospective comparison of the outcome (without oxygen vs. with oxygen insufflation) was conducted. RESULTS:The perioperative mortality rate could be significantly reduced from 58% (7/12) to 17% (2/12) (p = 0.036) by oxygen insufflation via nose cone. Significantly different levels of intraoperative oxygen saturation (SpO2; 89 ± 4% [without oxygen] vs. 97 ± 0.5% [with oxygen], p < 0.0001), but no significant differences in heart rate (HR; 267 ± 7 beats minute-1 [bpm] [without oxygen] vs. 266 ± 6 bpm [with oxygen], p = 0.955) were observed. CONCLUSIONS AND CLINICAL RELEVANCE:In summary, rats under ketamine-xylazine anaesthesia are susceptible to hypoxia. This may lead to increased delayed mortality related to hypoxia induced lung failure. Apparently, this is an underestimated problem. We highly recommend using additional oxygen insufflation in spontaneously breathing rats under ketamine-xylazine anaesthesia with basic monitoring such as measurement of oxygen saturation.

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A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine.

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A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine.

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