Hemodynamic and thermoregulatory effects of xylazine-ketamine mixture persist even after the anesthetic stage in rats

Picollo, C.; Serra, Andrey Jorge; Levy, Rozeli Ferreira; Antônio, Ednei Luiz; Santos, Leonardo dos; Tucci, Paulo José Ferreira

doi:10.1590/s0102-09352012000400011

Cited by 22 publications

(20 citation statements)

References 8 publications

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“…Although the combination of KX should therefore not lead to a marked hypotension, BP continuously decreased over a long time to mild hypotensive values almost until the rats had regained their righting reflex. These findings are in accordance with another study, which showed the most prominent hypotension after 150 minutes of KX anaesthesia in rats [ 50 ]. In contrast, MMF had a completely different effect on BP.…”

Section: Discussionsupporting

confidence: 93%

“…With KX, the lowest HR was observed after 30 minutes followed by a continuous, slow increase of HR almost until the end of the measurement. One study described similar findings of alterations in HR during KX anaesthesia in rats and it was suggested that the cardiovascular depressant effect of xylazine overrides the increased sympathetic and reduced vagal tone and the adverse effect of baroreceptor reflex attributed to ketamine [ 50 ]. HR during MMF rapidly decreased after injection and continued to decrease slightly until it was antagonized.…”

Section: Discussionmentioning

confidence: 86%

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Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats

et al. 2014

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BackgroundThis study investigated effects on cardiovascular parameters during anaesthesia with isoflurane (ISO, 2–3 Vol%), ketamine-xylazine (KX, 100 mg•kg−1 + 5 mg•kg−1) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg•kg−1 + 2.0 mg•kg−1 + 0.005 mg•kg−1) in rats throughout induction, maintenance and recovery from anaesthesia. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), heart rate (HR) and core body temperature (BT). The parameters were continuously measured before, during and after each type of anaesthesia. Forty minutes after induction, ISO delivery was terminated and MMF was antagonized with atipamezole-flumazenil-naloxone (AFN, 0.75 mg•kg−1 + 0.2 mg•kg−1 + 0.12 mg•kg−1) whereas KX was not antagonized.ResultsDifferences were observed between anaesthesias with KX (301 min) lasting much longer than MMF (45 min) and ISO (43 min). HR in ISO (truex¯ = 404 ± 25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX (truex¯ = 255 ± 26 bpm) and MMF (truex¯ = 209 ± 24 bpm). In ISO (MAP during time of surgical tolerance: truex¯ = 89 ± 12.3 mmHg) and KX (MAP during wake-up period: truex¯ = 84 ± 8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: truex¯ = 138 ± 9.9 mmHg) increased. Despite keeping animals on a warming pad, a loss of BT of about 1°C was seen in all groups. Additionally, we observed a peaked increase of HR (truex¯ = 445 ± 20 bpm) during the wake-up period with ISO and an increase of PP (truex¯ = 59 ± 8.5 mmHg) in MMF during the time of surgical tolerance.ConclusionThe anaesthesias influenced very differently the cardiovascular parameters measured in Wistar rats. ISO caused mild hypotension and increased HR whereas MMF produced a marked hypertension and a significant decrease of HR. The slightest alterations of BP, HR and BT were observed using KX, but the long wake-up and recovery period suggest the need for prolonged monitoring.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 86%

Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats

et al. 2014

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“…This explanation is further supported by previous literature describing dramatic reductions in mean arterial pressure in rodents after ketamine-xylazine anesthesia; with some papers describing these effects continuing beyond the recovery period. 2,43 Further mechanistic research is necessary to confirm this speculation.…”

Section: Discussionmentioning

confidence: 99%

Effects of General Anesthesia on 2 Urinary Biomarkers of Kidney Injury—Hepatitis A Virus Cellular Receptor 1 and Lipocalin 2—in Male C57BL/6J Mice

Gibbs

Izer

Reeves

et al. 2019

j am assoc lab anim sci

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Urinary biomarkers are used increasingly for sensitive prediction of kidney injury in preclinical and clinical studies. Given the frequent requirement of anesthesia in various animal models of disease, it is important to define the effects of anesthesia on kidney injury biomarkers to guide the appropriate selection of anesthetic agents and to avoid potential confounders in the interpretation of data. Therefore, we performed a prospective study using male C57BL/6J mice (n = 45) exposed to a single anesthetic episode to determine the effects several common anesthesia regimens on the urinary excretion of 2 commonly used kidney injury biomarkers: hepatitis A virus cellular receptor 1 (HAVCR1, also known as KIM1) and lipocalin 2 (LCN2, also known as NGAL). We evaluated 3 injectable regimens (ketamine-xylazine, tiletamine-zolazepam, and pentobarbital) and 2 inhalational agents (isoflurane and sevoflurane). Concentrations of HAVCR1 and LCN2 in urine collected at various time points after anesthesia were measured by using ELISA. Administration of ketamine-xylazine resulted in a significant increase in HAVCR1 levels at 6 h after anesthesia but a decrease in LCN2 levels compared with baseline. LCN2 levels steadily increased over the first 24 h after inhalant anesthesia, with a significant increase at 24 h after sevoflurane. These results suggest that injectable anesthesia had early effects on HAVCR1 and LCN2 levels, whereas inhalational agents increased these biomarkers over prolonged time.

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“…Rats in our experiments were left spontaneously breathing, without intubation and without accessory oxygen as described several times for KX narcosis [14–16]. We observed unsustainable high mortality rates during the first 7 postoperative days but not during or immediately after surgery.…”

Section: Introductionmentioning

confidence: 98%

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

et al. 2019

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ObjectiveA 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 designObservational study.AnimalsTwenty-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.MethodsIntolerable 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.ResultsThe 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 relevanceIn 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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Hemodynamic and thermoregulatory effects of xylazine-ketamine mixture persist even after the anesthetic stage in rats

Cited by 22 publications

References 8 publications

Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats

Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats

Effects of General Anesthesia on 2 Urinary Biomarkers of Kidney Injury—Hepatitis A Virus Cellular Receptor 1 and Lipocalin 2—in Male C57BL/6J Mice

Oxygen inhalation improves postoperative survival in ketamine-xylazine anaesthetised rats: An observational study

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