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Observational Study
. 2019 Dec 13;14(12):e0226430.
doi: 10.1371/journal.pone.0226430. eCollection 2019.

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

Mare Mechelinck  1   2 , Carolin Kupp  1 , Johanne C Krüger  2 , Moriz A Habigt  1 , Marius J Helmedag  3 , René H Tolba  2 , Rolf Rossaint  1 , Marc Hein  1
Affiliations
Observational Study

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

Mare Mechelinck et al. PLoS One. .

Abstract

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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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. 28-day survival of rats after KX anaesthesia with (O2 group) or without (AA group) additional oxygen insufflation.
The survival curve (Kaplan-Meier analysis) revealed that the survival rate during the follow-up period of 28 days was significantly higher in rats who received additional oxygen insufflation intra- and postoperatively (O2 group) compared to rats who only breathed ambient air peri- and intraoperatively (AA group) (p = 0.036).
Fig 2
Fig 2. Intraoperative time course of (A) respiratory rate (RR), (B) oxygen saturation (SpO2) and (C) heart rate (HR) of male Sprague Dawley rats under KX anaesthesia depending on the additional oxygen supply.
Rats in the ambient air (AA) group only breathed ambient air whereas rats in the oxygen (O2) group had an increased oxygen supply intra- and postoperatively. The graphs show significantly increased saturation values in the O2 group and significantly higher respiratory rates after 40 minutes of anaesthesia compared to the AA group. No group differences are visible in heart rate. Symbols mark significant differences between groups at the time points (*<0.05; **<0.005; ***<0.0005; ****<0.0001).
Fig 3
Fig 3. Postoperative weight and score development of male rats during the follow-up period of 28 days after KX anaesthesia with (O2 group) or without (AA group) additional intra- and postoperative oxygen insufflation.
Course of (A) postoperative, in relation to preoperative body weight (BW) and (B) the postoperative score values illustrated for ambient air (AA) and oxygen (O2) group. A score value of altogether 5 to 9 points was defined as low, 10 to 19 points as medium and equal or greater than 20 points as high distress. There are no significant group differences in weight (p = 0.521) or score values (p = 0.259). However, the average weight in rats that only received ambient air tends to be slightly lower on the second and third postoperative day and the score value from the second to the fourth day slightly higher than in animals with additional oxygen.
Fig 4
Fig 4. Exemplary histological images of lung tissue from both hypoxic and normoxic rats in 40x and 100x magnifications.
The images of the hypoxic lung show intra-alveolar fibrin depositions and increased interstitial erythrocytes. Both changes indicate increased vascular permeability in hypoxic rats.
See this image and copyright information in PMC

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