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. 2020 Mar 3;15(3):e0219722.
doi: 10.1371/journal.pone.0219722. eCollection 2020.

Pre-warming before general anesthesia with isoflurane delays the onset of hypothermia in rats

Maxime Rufiange  1   2 , Vivian S Y Leung  1   2 , Keith Simpson  3 , Daniel S J Pang  1   2
Affiliations

Pre-warming before general anesthesia with isoflurane delays the onset of hypothermia in rats

Maxime Rufiange et al. PLoS One. .

Abstract

General anesthesia causes hypothermia by impairing normal thermoregulatory mechanisms. When using inhalational anesthetic agents, Redistribution of warm blood from the core to the periphery is the primary mechanism in the development of hypothermia and begins following induction of anesthesia. Raising skin temperature before anesthesia reduces the temperature gradient between core and periphery, decreasing the transfer of heat. This prospective, crossover study (n = 17 adult male and female SD rats) compared three treatment groups: PW1% (pre-warming to increase core temperature 1% over baseline), PW40 (pre-warming to increase core temperature to 40°C) and NW (no warming). The PW1% group was completed first to ensure tolerance of pre-warming. Treatment order was then randomized and alternated after a washout period. Once target temperature was achieved, anesthesia was induced and maintained with isoflurane in oxygen without further external temperature support. Pre-warming was effective at delaying the onset of hypothermia, with a significant difference between PW1% (12.4 minutes) and PW40 (19.3 minutes, p = 0.0044 (95%CI -12 to -2.2), PW40 and NW (7.1 minutes, p < 0.0001 (95%CI 8.1 to 16.0) and PW1% and NW (p = 0.003, 95%CI 1.8 to 8.7). The rate of heat loss in the pre-warmed groups exceed that of the NW group: PW1% versus NW (p = 0.005, 95%CI 0.004 to 0.027), PW40 versus NW (p < 0.0001, 95%CI 0.014 to 0.036) and PW1% versus PW40 (p = 0.07, 95%CI -0.021 to 0.00066). Pre-warming alone confers a protective effect against hypothermia during volatile anesthesia; however, longer duration procedures would require additional heating support.

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Conflict of interest statement

The authors have read the journal's policy and have the following conflicts: Author KS is a director at Vetronic Services Ltd., the company that designed and built the heating unit. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Core temperature changes in rats pre-warmed to 40°C (PW40, n = 17), 1% above baseline temperature (PW1%, n = 17) or without warming (NW, n = 17).
Time spent in warming chamber is highlighted in red (time -35 to 0 mins), followed by induction of general anesthesia and removal from warming chamber (green box, time 0 to 50 mins). Area under the curve during temperature reduction was calculated from time 0 to 50 mins. Before time 0, data are plotted every 5 minutes for clarity. Data presented as mean ± SEM.
Fig 2
Fig 2. Time to reach individual hypothermia threshold.
The no-warming (NW, n = 17) group reached their individual hypothermia threshold more quickly than the pre-warming to 1% above baseline core temperature (PW1%, n = 17) (p < 0.01) and pre-warming to 40°C (PW40, n = 17) (p < 0.0001) groups. The PW1% group reached their individual hypothermia threshold more quickly than the PW40 group (p < 0.01). Data presented as mean ± SEM. **p < 0.01. ****p < 0.0001.
Fig 3
Fig 3. Bland-Altman plot of repeated measures comparing rectal and core temperatures.
Rectal temperature underestimates core temperatures by 0.20°C, with 95% limits of agreement ranging from -4.3 to 4.0. Data were pooled from the three treatment groups.
Fig 4
Fig 4. Bland-Altman plot of repeated measures comping fur and core temperatures.
Fur temperature underestimates core temperature by 2.50°C, with 95% limits of agreement ranging from -6.7 to 1.7. Data were pooled from the three treatment groups.
Fig 5
Fig 5. Bland-Altman plot of repeated measures comparing tail and core temperatures.
Tail temperature underestimates core temperature by -7.80°C, with 95% limits of agreement ranging from -15.3 to -0.3. Data were pooled from the three treatment groups.
Fig 6
Fig 6. Percentage of time rats faced the heat source.
The no-warming (NW, n = 17) group spent approximately 50% of the time facing the heat source and this was significantly longer than the pre-warming to 1% above baseline core temperature (PW1%, n = 17) and pre-warming to 40°C (PW40, n = 17) groups during the first and last 3 mins of observation (p < 0.05). During the first three minutes, the PW40 group was more likely to face the heat source than PW1% (p < 0.05). Data presented as median ± 10–90 percentile. *p < 0.05. **p < 0.01. ***p < 0.001.
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Grants and funding

This work was supported by Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (ID: 424022-2013; DSJP), Fondation Lévesque (DSJP), and Vetronic Services Ltd. Author KS received support in the form of a salary from Vetronic Services Ltd. The specific role of this author is articulated in the ‘author contributions’ section. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.