Is carbon dioxide (CO<sub>2</sub>) a useful short acting anaesthetic for small laboratory animals?

Kohler, I.; Meier, R.; Busato, André; Neiger‐Aeschbacher, Gina; Schatzmann, U.

doi:10.1258/002367799780578390

Cited by 67 publications

(46 citation statements)

References 16 publications

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“…Behaviors chosen for welfare assessment included those associated with physiological distress, such as open-mouth breathing (Forslid, 1987;Martoft et al, 2002;Mota-Rojas et al, 2012), or psychological distress, such as escape (Blackshaw et al, 1988;Velarde et al, 2007), righting response (Grandin, 1998;Kohler et al, 1999;AVMA, 2013), defecation, and urination.…”

Section: Discussionmentioning

confidence: 99%

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Sadler

Hagen²,

Wang

et al. 2014

Journal of Animal Science

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The objectives of this study were to assess efficacy and welfare implications of gas euthanasia when applied to weaned and neonate pigs. Parameters associated with welfare, which were measured before loss of consciousness, included open-mouth breathing, ataxia, righting response, and escape attempts. Two age groups (weaned and neonate) were assessed in 9 gas treatments arranged in a 2 × 4 factorial design, with 2 gas types (CO 2 = 100% CO 2 and 50:50 = 50:50 CO 2 :argon) and 4 flow rates (box volume exchange/min: slow = 20%; medium = 35%; fast = 50%; prefill = prefilled followed by 20%) and a control treatment in which ambient air was passed through the box. Pig pairs (10/treatment) were placed in a modified Euthanex AgPro system (Euthanex Corp., Palmer, PA). Behavioral and physiological responses were observed directly and from video recordings for latency, duration, prevalence (percent of pigs affected), and frequency (number of occurrences/pig). Data were analyzed as linear mixed models or with a Cox proportional hazard model as appropriate. Piglet pair was the experimental unit. For the weaned pig, welfare was superior with CO 2 relative to 50:50 within 1 or more flow rates on the basis of reduced duration of open-mouth breathing, duration of ataxia, frequency of escape attempts, and duration and frequency of righting response (P < 0.05). No measured parameters indicated superior welfare with the use of 50:50, whereas latencies to loss of posture and last movement favored CO 2 (P < 0.05). Faster flow rates were associated with reduced (P < 0.05) duration or frequency of open-mouth breathing, ataxia, and righting response, as well as superior (P< 0.05) indicators of efficacy, including latencies to loss of posture, gasping, and last movement, relative to slower flow rates. Weaned pigs were more likely to defecate (P < 0.01), display nasal discharge (P < 0.05), and display longer (P < 0.001) latencies to loss of posture and last movement than neonates. Duration of ataxia was the only parameter for which neonates were superior (P < 0.01) to weaned pigs during euthanasia. As such, a 50:50 CO 2 :argon gas mixture and slower flow rates should be avoided when euthanizing weaned or neonate pigs with gas methods. Neonate pigs succumb to the effects of gas euthanasia quicker than weaned pigs and display fewer signs of distress. This is a manuscript of an article that is not peer-reviewed from Journal of Animal Science 92 (2014): 793, doi:10.2527/jas.2013-6598. ABSTRACT:The objectives of this study were to assess efficacy and welfare implications of gas euthanasia when applied to weaned and neonate pigs. Parameters associated with welfare, which were measured prior to loss of consciousness, included open-mouth breathing, ataxia, righting response, and escape attempts. Two age groups (weaned and neonate) were assessed in 9 gas treatments arranged in a 2 × 4 factorial design, with 2 gas types (CO 2 = 100% CO 2 or 50:50 = 50:50 CO 2 :argon) and 4 flow rates (box volume exchange/min: slow = 20%; medium = 35%; fast...

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Section: Discussionmentioning

confidence: 99%

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Sadler

Hagen²,

Wang

et al. 2014

Journal of Animal Science

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“…2 and 3. Other sources of time-dependent alterations in hypercapnic ventilatory characteristics may include the activation of GABAergic pathways (1), CO 2 -induced narcosis (21), and fatigue.…”

Section: Discussionmentioning

confidence: 99%

Differential CO₂-induced c-fosgene expression in the nucleus tractus solitarii of inbred mouse strains

Tankersley

Haxhiu

Gauda

2002

Journal of Applied Physiology

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. Differential CO2-induced c-fos gene expression in the nucleus tractus solitarii of inbred mouse strains. J Appl Physiol 92: 1277-1284, 2002. First published November 16, 2001 10.1152/japplphysiol.00609.2001.-Genetic determinants confer variation between inbred mouse strains with respect to the magnitude and pattern of ventilation during hypercapnic challenge. Specifically, inheritance patterns derived from low-responsive C3H/HeJ (C3) and high-responsive C57BL/6J (B6) mouse strains suggest that differential hypercapnic ventilatory sensitivity (HCVS) is controlled by two independent genes. The present study also tests whether differential neuronal activity in respiratory control regions of the brain is positively associated with strain variation in HCVS. With the use of whole body plethysmography, ventilation was assessed in C3 and B6 strains at baseline and during 30 min of hypercapnia (inspired CO2 fraction ϭ 0.15, inspired O 2 fraction ϭ 0.21 in N2). Subsequently, in situ hybridization histochemistry was performed to determine changes in c-fos gene expression in the commissural subnucleus of the nucleus tractus solitarius (NTS). During hypercapnia, breathing frequency and tidal volume were significantly (P Ͻ 0.01) different between strains: C3 mice showed a slow, deep-breathing pattern relative to a rapid, shallow phenotype of B6 mice. CO 2-induced increase in c-fos gene expression was significantly (P Ͻ 0.01) greater in NTS regions of B6 compared with C3 mice. In this genetic model of differential HCVS, the results suggest that a genomic basis for varied hypercapnic chemoreception or transduction confers greater afferent neuronal activity in the caudal NTS for high-responsive B6 mice compared with low-responsive C3 mice.C3H/HeJ; C57BL/6J; hypoventilation; hypercapnic ventilation; control of breathing HYPERCAPNIC VENTILATORY SENSITIVITY (HCVS) among human volunteers has been shown to vary across a continuum from low-to high-responsive subgroups. For example, Hirshman et al. (19) demonstrated a sixfold difference between low-and high-responsive human volunteers. Although phenotypes in these subjects varied positively with height, weight, and the ventilatory response to hypoxia, the feature of bimodality in HCVS distributions suggested that a major genetic determinant conferred individual variation in HCVS.Our laboratory has demonstrated a similar continuum among many inbred mouse strains (34). This implies that genetic diversity, which determines differential HCVS, may be conserved across species and is the basis for comparative mapping studies (31). The C3H/HeJ (C3) and C57BL/6J (B6) inbred strains occupy the extremes of a strain distribution pattern for hypercapnic ventilatory traits (34); that is, with inspirate challenges from 3-8% CO 2 in normoxia, C3 mice are characterized with a blunted HCVS phenotype (i.e., low gain) relative to the B6 phenotype (i.e., high gain) for HCVS (34,35). With the use of quantitative genetic approaches, our studies further demonstrate that hypercapnic ventilatory traits, lik...

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“…Smith & Harrap 1997, Leach et al 2002a, times to anaesthesia and death (Blackshaw et al 1988, Danneman et al 1997, Kohler et al 1999, EEG activity (Thurauf et al 1991), histology (Britt 1986, Danneman et al 1997) and blood pH (Hewett et al 1993).…”

Section: Relevant Human Datamentioning

confidence: 99%

“…A range of authors have measured a variety of behavioural and physiological responses as indicators of pain and distress in studies of CO 2 , such as behavioural signs of asphyxia (Coenen et al 1995), hyperventilation (e.g. Britt 1986, Kohler et al 1999, escape behaviours (Britt 1986, Leach et al 2002a, tail thrashing (Britt 1986), disturbance behaviours such as washing (Britt 1986) and physiological signs of nociception (Anton et al 1992). The interpretation of such behavioural measures can be difficult if the association between the behaviour and an underlying state has not been validated, or where behaviours are poorly described, or where quantitative measures are not used and the reliability of observational recordings confirmed (see Martin and Bateson (1993) for a discussion).…”

Section: Pain and Distress: Considerationsmentioning

confidence: 99%

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

et al. 2005

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SummaryCarbon dioxide (CO 2 ) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO 2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO 2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO 2 flow rate and final concentration, presence of oxygen, and prefilled chambers (the animal is added to the chamber once a predetermined concentration and flow rate have been reached) versus gradual induction (the animal is put into an empty chamber and the gas agent(s) is gradually introduced at a fixed rate). Internationally, animal research standards specify that any procedure that would cause pain or distress in humans should be assumed to do so in non-human animals as well (Public Health Service 1986, US Department of Agriculture 1997, Organization for Economic Cooperation and Development 2000). European Union guidelines, however, specify a certain threshold of pain or distress, such as 'skilled insertion of a hypodermic needle', as the starting point at which regulation of the use of animals in experimental or other scientific procedures begins (Biotechnology Regulatory Atlas n.d.). There is clear evidence in the human literature that CO 2 exposure is painful and distressful, while the non-human literature is equivocal. However, the fact that a number of studies do conclude that CO 2 causes pain and distress in animals indicates a need for careful reconsideration of its use. Finally, this review offers recommendations for alternatives to the use of CO 2 as a euthanasia agent.Keywords Carbon dioxide; euthanasia; pain; distress; anaesthesia; welfare; rodents Carbon dioxide (CO 2 ) is commonly used for euthanasia and anaesthesia of laboratory rodents, largely because of its ease of use, relative safety, and low cost, as well as its capacity to euthanize large numbers of animals in a short time span (Ambrose et al. 2000). In large institutions and those with significant rodent-breeding programmes, large numbers of rodents are often euthanized in a short time (Kline et al. 1963) and an appropriate gas agent is often the best way to approach such a challenge. However, CO 2 is not physiologically inert and the published evidence on whether or not CO 2 administration causes pain or distress in animals raises questions about its routine use. This paper reviews this published evidence and includes information on the effects of CO 2 in both humans and nonhumans. Methodological details are included when possible in order to provide a clear

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Is carbon dioxide (CO₂) a useful short acting anaesthetic for small laboratory animals?

Cited by 67 publications

References 16 publications

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Differential CO₂-induced c-fosgene expression in the nucleus tractus solitarii of inbred mouse strains

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

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Is carbon dioxide (CO2) a useful short acting anaesthetic for small laboratory animals?

Cited by 67 publications

References 16 publications

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Effects of flow rate and gas mixture on the welfare of weaned and neonate pigs during gas euthanasia1

Differential CO2-induced c-fosgene expression in the nucleus tractus solitarii of inbred mouse strains

Carbon dioxide for euthanasia: concerns regarding pain and distress, with special reference to mice and rats

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Is carbon dioxide (CO₂) a useful short acting anaesthetic for small laboratory animals?

Differential CO₂-induced c-fosgene expression in the nucleus tractus solitarii of inbred mouse strains