Alpha-Chloralose Toxicosis

https://journals.sagepub.com/doi/full/10.1177/1098612X221107787

Alpha-Chloralose

氯醛糖

氯醛缩葡萄糖

Abstract 摘要

Objectives 目的

The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning.

- 猫α氯醛糖的中毒临床表现

- 血清α氯醛糖

Methods 方法

Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat’s intoxication severity score.

2014年1月至2020年2月，
在一家小型动物大学医院的病历中发现疑似α氯醛糖中毒的病例。

收集各自记录中描述的中毒临床症状，
将猫分为四个中毒严重程度评分，
并记录住院时间和死亡率。

对2019年底和2020年初选定病例的剩余血清进行分析，
采用定量超高高效液相色谱串联质谱分析（quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis）检测α氯醛糖，
并将α氯醛糖浓度与各猫的中毒严重程度评分进行比较。

Results 结果

Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score.

25例猫血清分析，均为α氯醛糖中毒。

此外，
在病患记录中发现了78例临床怀疑α氯醛糖中毒的猫，
其中大多数是在9月至4月期间出现的。

中毒最常见的症状有
共济失调 ataxia、
震颤 tremors、
脑神经缺陷 cranial nerve deficits 
和感觉过敏 hyperaesthesia。

临床症状和中毒严重程度的流行程度与先前报道的不同，
此报道的群体出现的症状较轻，
没有因中毒而死亡的病例。

无论中毒严重程度评分如何，
大多数病患住院时间<48小时。

Conclusions and relevance 结论和相关性

This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia.

本研究描述了猫α氯醛糖中毒的临床症状和预后。

确诊病例中没有死亡病例，
这表明如果及时治疗，
α氯醛糖中毒猫的预后很好。

在可能接触α氯醛糖的地区，
将α氯醛糖中毒作为急性发作的神经症状的鉴别诊断可能会影响临床决策，
并有助于避免过度的诊断检查。

严重的临床表现可能被误解会出现严重的预后，
对α氯醛糖中毒的认识可以避免不必要的安乐死。

Introduction 引文

Alpha-chloralose (AC) is a compound with both excitatory and depressive effects on the central nervous system, in low and high doses, respectively. It is used as a rodenticide, avicide and as an anaesthetic for laboratory animals.1–10 AC-based rodenticides are approved in many countries and cause death by central nervous affection, leading to an inability to maintain homeostasis.1,2 For outdoor pets, accidental poisoning is a risk in areas where these products are used for pest control. Clinical signs of AC intoxication in several species have previously been reported,1–11 but publications on AC poisoning in companion animals are scarce.12–15 AC intoxication in the clinical setting is a presumptive diagnosis based on history, clinical signs and exclusion of other diseases with a similar presentation. Poisoning can be confirmed by demonstrating AC or its metabolites in blood or urine;1,6,11–13,16 however, the availability of commercial tests has so far been limited. As there is no antidote or otherwise specific treatment for AC intoxication, treatment is supportive and symptomatic, including monitoring and maintaining a normal body temperature, minimising external stimuli and, when indicated, anticonvulsants.1,5,9

α氯醛糖

    - 中枢神经系统

        - 兴奋性 - 低剂量
        - 抑制性 - 高剂量

    - 灭鼠剂 rodenticide
    - 杀鸟剂 avicide
    - 实验室动物麻醉剂  an anaesthetic for laboratory animals

    - 户外宠物意外摄入

    - 中毒确认
        - 血液，尿液 - α氯醛糖及其代谢产物

    - 无解毒剂/其他特异性治疗

    - 支持性治疗
    - 对症性治疗

    - 监测 
        - 维持体温
        - 减少外部刺激
        - 必要时使用抗惊厥药物

Following the approval of use of AC rodenticides in Sweden in 2013, suspected cases of AC poisoning in outdoor cats have been anecdotally communicated within the veterinary community. In the autumn of 2019, there was a surge in suspected cases admitted to the University Animal Hospital, Small Animal Clinic (UDS) at the Swedish University of Agricultural Sciences in Uppsala and other small animal hospitals and clinics across the country. A collaboration between UDS and the Swedish National Veterinary Institute was initiated, leading to the development and validation of a novel quantitative ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) analysis for the detection of AC in feline blood.16

The objectives of this study were to describe clinical signs of feline AC poisoning, confirm intoxication through chemical analysis of blood samples from admitted cats and to investigate the association between the severity of intoxication and AC serum concentrations.

Materials and methods

The UDS patient record database from January 2014 to February 2020 was reviewed to identify suspected cases of AC poisoning in client-owned cats presenting to the emergency clinic. The database did not include AC intoxication as a specific diagnosis, and the search was based on the following primary and/or secondary diagnoses: unspecified poisoning; rodenticide poisoning; signs of poisoning or intoxication; and signs of neurological disease. In most cases, the attending clinician had noted AC intoxication as the main differential diagnosis. Cats were included if the following criteria were fulfilled: (1) outdoor cat with possible exposure to AC according to history; (2) a clinical suspicion of AC intoxication; and (3) the presence of at least two signs of AC intoxication from a clinical case definition based on previous publications on AC poisoning.1,2,9,12–15 Signs included coma; stupor; somnolence; seizures; cranial nerve deficits, including vision impairment; ataxia; tremor; hyperaesthesia; hypothermia; bradycardia; bradypnoea or other respiratory alteration; hypotension and behavioural changes (see supplementary material for definitions of signs). Cats were excluded if there was a history of trauma, no possible risk of exposure (ie, indoor cats) or a previous diagnosis of neurological disease.

For each cat, clinical signs of intoxication were noted as either absent or present based on the patient record. Signs noted by the caregiver were also included, regardless of whether the sign was seen at presentation or during stationary care. A score of the overall clinical severity of intoxication was assigned to each cat and mortalities were noted. Ambulatory cats with few or mild signs were given scores of 1 or 2 and non-ambulatory cats with several and/or more severe signs were scored as 3 or 4 (Table 1). The identification of cases, documentation of signs and scoring of each case was performed by one clinician.

Table 1 Description of clinical signs with respect to intoxication severity score assigned to cats with suspected alpha-chloralose poisoning in 2014–2020 admitted to the University Animal Hospital, Small Animal Clinic, Uppsala, Sweden

表1 2014-2020年瑞典乌普萨拉大学动物医院小动物诊所疑似α氯醛糖中毒猫的中毒严重程度评分临床症状描述

Available surplus serum samples from 25 cats that had presented from October 2019 to February 2020 were analysed in order to detect AC. The cats were aged 5 months to 15 years (median 5 years). All but one (Maine Coon mixed-breed) were domestic shorthair or domestic longhair cats. Six cats were male castrated, seven male entire, nine female spayed and three female entire. There was no standardised treatment protocol, and treatment was dependent on the attending clinician. All patients in this group had been provided with supportive care with intravenous crystalloid fluids, warming when hypothermic and reduction of external stimuli (ie, dark and silent environment with minimal handling). Some patients had also been given a constant rate infusion (CRI) of intralipid (200 mg/ml; Fresenius Kabi) lipid emulsion to help bind circulating toxins, and patients with seizures had been treated with anticonvulsants as needed.

A novel validated UHPLC–MS/MS method with a lowest detection limit of 30 ng/ml was used.16 For each cat, the association between serum concentration of AC and intoxication severity score (1–4) was calculated using Spearman’s correlation. The duration of hospitalisation for each cat was noted and the median and range described for each severity score group. Outdoor cats admitted to the clinic with (n = 9) and without (n = 10) neurological signs but no clinical suspicion of AC poisoning were used as controls.

Results 结果

A total of 103 cases were extracted from patient records and 44 surplus serum samples from 25 cats with suspected AC poisoning were available for chemical analysis. AC was detected in all samples in a concentration range of 386–17,500 ng/ml and was not detected in any of the 19 controls. All samples had been stored at −20°C prior to analysis.

In the 25 confirmed cases, the most common clinical signs were ataxia and tremor, described in all cats (n = 25). Cranial nerve deficits (mainly vision impairment), hyperaesthesia, bradycardia, somnolence and behavioural changes were all described in ⩾60% of the cases (Table 2). Median duration of hospitalisation was 24 h (range 13–75) with no difference between severity scores. All but one cat (severity score 4) were hospitalised for <48 h, and all cats survived to discharge.

Table 2 Prevalence of clinical signs in 25 cats with confirmed alpha-chloralose poisoning admitted to the University Animal Hospital, Small Animal Clinic, Uppsala, Sweden in October 2019 and February 2020

表2 2019年10月至2020年2月，瑞典乌普萨拉大学动物医院小动物诊所收治的25例确诊为α氯醛糖中毒的猫的临床症状发生率

With regard to intoxication severity scores, five cats were scored as mild (1), five as moderate (2), 11 as severe (3) and four as very severe (4). The intoxication severity score correlated with the detected AC concentration (r = 0.74; P <0.0001 [Figure 1]). When several samples from the same individual were analysed, the sample with the highest AC concentration was used in the comparison.

Seventy-eight additional suspected cases were extracted from the UDS patient medical record database. With regard to intoxication severity, 15 were classified as mild (1), 24 as moderate (2), 22 as severe (3) and 17 as very severe (4). The prevalence of clinical signs was, overall, in agreement with the confirmed cases of AC poisoning. However, seizures were notably more common in this group, with 22% of suspected case records noting seizures vs 8% of confirmed cases (see Tables 2 and 3). There were no mortalities due to poisoning; however, nine of the cats in this group (11%) were euthanased at presentation, at the owners’ request.

从UDS病患病历数据库中提取了另外78例疑似病例。

根据中毒严重程度，15例为轻度(1)，24例为中度(2)，22例为重度(3)，17例为极重度(4)。

总的来说，临床症状的发生率与确诊的ACα氯醛糖中毒病例一致。

然而，抽搐发作在这一组中明显更常见，
22%的疑似病例记录显示出现了抽搐发作，
而确诊病例的比例为8%(见表2和3)。

然而，这组猫中有9例(11%)在主人的要求下被安乐死。

Of all cases (n = 103), two presented in 2014, four in 2015, three in 2016, four in 2017, seven in 2018, 74 in 2019 (Figure 2) and nine in the first two months of 2020. In the years 2014–2019, 84/94 cats (89%) were admitted from September to April each year.

Table 3 Prevalence of clinical signs in 78 cats presenting with suspected alpha-chloralose poisoning admitted to University Animal Hospital, Small Animal Clinic, Uppsala, Sweden, between January 2014 and February 2020

Discussion 讨论

The present study aimed to contribute to the knowledge about AC intoxication in cats by describing the clinical presentation of a large group of cats with suspected AC poisoning admitted to a small animal university hospital.

AC poisoning was confirmed in 25 cats where blood samples were available for chemical analysis. The prevalence of clinical signs differed somewhat from what was previously reported by Segev et al,12 who reported a series of AC intoxication in both dogs and cats. The most common clinical signs observed by Segev et al in 13 cats were hypothermia, seizures, coma, hyperaesthesia, miosis and tremor.12 The clinical presentation was overall more severe in the report by Segev et al,12 with 46% of patients presenting comatose, and seizures noted in 54% of cats. This could reflect a difference in the definition of coma between studies. Clinically, severe hyperaesthesia may be very similar to partial seizures, with an overlap in the appearance and interpretation of the two, both between studies and between clinicians in the present study.（在临床上，严重的感觉过敏可能与部分性抽搐发作非常相似，在多个研究之间和本研究中多个临床医生之间，两者在外在表现和判读上都有重叠。）Furthermore, while Segev et al reported an overall mortality of 15%, there were no mortalities in the cats with confirmed AC poisoning in the present study. Increasing public awareness about AC poisoning in cats in Sweden in 2019 may have influenced caregivers to seek veterinary care for cats with few or minor signs. This may have decreased the mortality and severity of signs of intoxication in this population as a result of receiving supportive care early in the progression of intoxication. However, the duration of hospitalisation in surviving cats was similar between our study and that which has been previously reported.12

Bradycardia 心动过缓 was not reported by Segev et al,12 but was noted in 80% of our cats with confirmed poisoning. Tremor and ataxia 震颤和共济失调, which were noted in all our cats with confirmed intoxication, was noted in 15% and 0%, respectively, in the study by Segev et al.12 At UDS, hypothermia 低体温 has been considered a very common sign of AC poisoning. When normal endothermia is impaired, the ambient temperature will greatly influence body temperature. In mice, ambient temperatures below 15.6°C were shown to be associated with higher mortalities after AC bait ingestion.1,2 As most cats in the present study presented to the clinic in the colder months (September–April), hypothermia is potentially a lethal consequence of poisoning. However, only 40% of confirmed cats presented with hypothermia (ie, fewer than expected). In the report by Segev et al, hypothermia was the most common sign of intoxication, seen in 91% of the cats.12 It is possible that the normothermic cats in the present study were admitted prior to the development of hypothermia, and that it was prevented by the supportive care provided. Regardless, these findings illustrate the importance of not excluding AC poisoning based on normothermia.（基于正常体温不能排除α氯醛糖中毒）

Cats are more sensitive to AC than both dogs and humans, with a minimum lethal dose of 100 mg/kg vs 600–1000 mg/kg for dogs and >1000 mg/kg for humans（猫对α氯醛糖比犬和人都更敏感，最低致死剂量为100 mg/kg，犬为600-1000 mg/kg，人为1000 mg/kg）.2,8,9 Hanriot and Richet (1893, cited in Balis and Monroe)2 reported the LD50 for cats and dogs to be 400–600 mg/kg orally, but injecting as little as 40 mg/kg could lead to convulsions（Hanriot和Richet(1893年，Balis和Monroe引用)2报告猫和犬口服的LD50为400 - 600 mg/kg，但注射仅40mg/kg就可能导致惊厥。）. In an experimental model, a 5 mg/kg/h CRI maintained a stable level of surgical anaesthesia（在实验模型中，5mg/kg/h的CRI维持了稳定的手术麻醉水平）.4 To our knowledge, there have been no publications on the amount of intake, or AC serum concentration, where the first signs of intoxication can be expected in cats.

In the present study, it was not possible to determine with certainty how the cats had been exposed to AC. Several caregivers reported known baiting with AC either on their own property or in the vicinity（α氯醛糖诱饵）. Many observed the onset of neurological signs shortly after the cat had eaten a rodent（猫捕食了啮齿类）. Ingested rodent carcasses（吞食啮齿类尸体） were occasionally detected radiographically in the stomach at the time of presentation and one of the confirmed poisoned cats vomited a mouse carcass at the clinic. Many bird species are also very sensitive to AC and secondary poisoning through ingestion of intoxicated birds cannot be excluded（许多鸟类对α氯醛糖也非常敏感，不能排除通过摄入已中毒的鸟类而继发中毒的可能性。）.9 Cats are also known dietary neophobes（猫也是出了名的饮食恐新者。）. A pilot study on the use of AC as a poison for feral cat control showed that the AC-containing bait palatability was low, and the cats were very reluctant to eat it, even when it contained low concentrations of AC（一项关于使用α氯醛糖作为野猫对照中毒的初步研究表明，含有α氯醛糖的诱饵的适口性很低，野猫非常不愿意吃这种诱饵，即使诱饵中含有的α氯醛糖浓度低）.17  Cornwell reported that cats did not eat AC bait, even when fasted for 36 h（Cornwell报告说，即使禁食了36小时，猫也不吃α氯醛糖的诱饵）.8 This could indicate that the cats in the present study were secondarily poisoned, rather than having eaten bait directly（这可能表明，本研究中的猫是二次中毒，而不是直接吃了诱饵。）. However, hazard analysis of AC deemed the risk for secondary poisoning to mammal predators as ‘negligible’（然而，α氯醛糖的公害分析认为，对哺乳动物捕食者的二次中毒风险是“可以忽略不计的”）.18 In summary, with the available data, it was not possible to know how the cats were exposed to AC（总之，根据现有的数据，不可能知道猫是如何接触到α氯醛糖的。）.

Owing to its retrospective nature there are weaknesses in this study. Samples were obtained opportunistically, and blood sampling was performed at different points in time in relation to the progression of intoxication. This limitation likely influenced the measured concentrations in each sample. Our data show a clear correlation between clinical severity and AC concentration, which is expected with a dose-dependent toxin. Some individual differences between cats’ ability to metabolise and excrete the toxin may however, influence the clinical severity in relation to AC concentration. Although all signs of intoxication were registered, including those reliably reported from the caretaker, the study was dependent on the extent of the history-taking by the attending clinicians upon admission, as well as during stationary care. As the study population consisted of outdoor cats, some clinical signs may also have gone unobserved by the caregiver. Furthermore, the confirmed cases in this study were all sampled in 2019 and 2020, when the clinical records generally included more detailed descriptions about which signs were present or absent due to increased awareness. Earlier records (2014–2018) are often less elaborate, and some signs may therefore be under-reported in the unconfirmed cases. As a direct, quantitative method of AC detection was not used in the study by Segev et al,12 a comparison between differences in blood concentrations of AC – and its impact on the prevalence of clinical signs and intoxication severity – was not possible.

In the present study, mortality and duration of hospitalisation was not dependent on the severity of clinical signs, indicating that intoxication severity is not indicative of prognosis. Our data suggest that cats with AC poisoning will rarely succumb when given proper supportive care in a timely manner.

在本研究中，死亡率和住院时间与临床症状的严重程度无关，这表明中毒严重程度并不能预示预后如何。

我们的数据表明，如果及时给予适当的支持性护理，α氯醛糖中毒的猫很少会出现死亡。

Conclusions 结论

This study provides a clinical description of AC intoxication in cats, describing 25 confirmed and 78 suspected cases of AC poisoning. Cats with AC intoxication have an excellent prognosis for complete recovery, providing that supportive care is given in a timely manner. When admitting an outdoor cat with acute onset of described neurological signs, no history of trauma and possible AC exposure, intoxication should be included in the list of differential diagnoses. This may influence both clinical decision-making, diagnostic work-up and client communication. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and both clinical and client awareness about AC poisoning may avoid unnecessary euthanasia.

本研究提供了猫α氯醛糖中毒的临床描述，描述了25例确诊病例和78例疑似α氯醛糖中毒病例。猫α氯醛糖中毒有很好的预后完全恢复，提供及时的支持护理。当收治有急性神经症状、无外伤史和可能接触α氯醛糖的户外猫时，中毒应列入鉴别诊断列表中。这可能会影响临床决策、诊断检查和与宠主沟通。严重的临床表现可能被误解为严重的预后，临床环境和宠主对α氯醛糖中毒的认识可以避免不必要的安乐死。

Acknowledgments

Preliminary results from this study were communicated to the Swedish Chemicals Agency. We would like to thank them for taking our data into consideration, resulting in rapid action and a ban of layman use of AC rodenticides in Sweden in December of 2019.19 Following the ban, the number of cases decreased rapidly and substantially.

Ethical approval

The work described in this manuscript involved the use of non-experimental (owned or unowned) animals. Established internationally recognised high standards (‘best practice’) of veterinary clinical care for the individual patient were always followed and/or this work involved the use of cadavers. Ethical approval from a committee was therefore not specifically required for publication in JFMS. Although not required, where ethical approval was still obtained, it is stated in the manuscript.

Informed consent

Informed consent (verbal or written) was obtained from the owner or legal custodian of all animal(s) described in this work (experimental or non-experimental animals, including cadavers) for all procedure(s) undertaken (prospective or retrospective studies). No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required.

Conflict of interest

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The Swedish Environmental Protection Agency and Djurvännernas Förening, Stockholm, funded the chemical analyses in this study.

ORCID iD

Cecilia Tegner https://orcid.org/0000-0003-4015-1228

Footnote

Accepted: 25 May 2022

References 参考文献

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4. Kullmann FA, et al. Stability of the acetic acid-induced bladder irritation model in alpha chloralose-anesthetized female cats. PLoS One 2013; 8: e73771.

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16. Windahl U, et al. Development and validation of a quantitative UHPLC-MS-MS method for the determination of alpha-chloralose in feline blood and application on blood samples collected from cats with symptoms of alpha-chloralose poisoning. J Anal Toxicol. Epub ahead of print 6 August 2021.

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18. Standing Committee on Biocidal Products. Directive 98/8/EC concerning the placing biocidal products on the market, alphachloralose product-type 14 (rodenticide). https://circabc.europa.eu/sd/a/0a566792-98a3-4b34-8c6f-62bb51d23af8/Alphachloralose_final%20AR.pdf (2008, accessed June 7, 2022).

19. Swedish Chemicals Agency. Användningvillkoren skärps för musmedel med alfakloralos. https://www.kemi.se/arkiv/nyhetsarkiv/nyheter/2019-12-18-anvandningsvillkoren-skarps-for-musmedel-med-alfakloralos (2019, accessed 17 September, 2021).

Supplementary Material

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• Definitions of clinical signs.

Summary

The following file is available online:

Definitions of clinical signs.

Resources 资源

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Clinical definitions 临床定义

Coma - non-ambulatory, obtunded, unconscious and unresponsive including to nociceptive stimuli.

昏迷 - 不能行动，迟钝，无意识和无反应，包括对伤害性刺激无反应。

Stupor - non-ambulatory, obtunded, unresponsive to external stimuli except nociceptive stimuli. May have some degree of consciousness.

木僵/昏睡 - 不能行动，迟钝，对外部刺激无反应，除了对伤害性刺激有反应。可能有一定程度的意识反应。

Somnolence - impaired reactions to external stimuli and reduced awareness.、

嗜睡 - 对外部刺激的反应变差和意识水平下降。

Seizures - tonic/clonic or tonic epileptiform seizures in unconscious, non-ambulatory patient.

抽搐发作 - 昏迷、不可行动的病患的强直性/阵挛性或强直性癫痫样抽搐发作。

Cranial nerve affection - including miosis, mydriasis, anisocoria, impairment of pupil light reflex, dazzle or menace, facial nerve paralysis, vestibular syndromes, ptyalism, Horner’s syndrome etc.

脑神经的影响 - 包括瞳孔缩小、瞳孔散大、瞳孔大小不一、瞳孔对光反射障碍、炫目或威胁反应变差、面神经麻痹、前庭综合征、过度流涎、霍纳氏综合征等。

Vision impairment - signs indicating reduced/impaired ability to process visual stimuli. These patients are also noted as cranial nerve affection.

视觉障碍 - 表明处理视觉刺激的能力下降或受损的迹象。这些病患还会出现脑神经的影响的相关症状。

Ataxia - decreased ability to coordinate movements, including proprioceptive, cerebellar and vestibular ataxia.

共济失调 - 协调运动的能力下降，包括本体感觉性、小脑性共济失调和前庭性共济失调。

Hypotension - average systolic pressure ≤100 mmHg or mean arterial pressure ≤80 mmHg.

低血压 - 平均收缩压≤100mmHg 或 平均动脉压≤80mmHg。

Hypothermia - body temperature ≤37℃.

低体温 - 体温≤37℃.

Bradycardia - heart rate ≤140/min.

心动过缓 - 心率≤140次/min。

Bradypnea - respiratory rate ≤15/min.

呼吸过缓 - 呼吸速率 ≤15次/min.

Other respiratory alteration - choppy breathing pattern, intermittent apnoea or other abnormal breathing patterns.

其他呼吸改变 - 深起伏的呼吸模式，间歇性呼吸暂停或其他异常呼吸模式。

Hyperesthesia - exaggerated reactions to external stimuli such as sound, light or touch.

感觉过敏 - 对声音、光线或触觉等外界刺激的过度反应。

Tremor - rhythmic oscillating movement generalised or localised, especially involving ears, whiskers and muzzle.

震颤 - 有节奏的振荡运动，全身或局部，特别是涉及耳朵，胡须和吻部。

Behavioural changes - in patients with normal consciousness. Includes signs of hallucinations, extreme polyphagia, desorientation, euphoria, dysphoria, hypervigilance, compulsive behaviour or aggression in a patient who is normally calm/timid

行为改变 - 在意识正常的病患身上。包括幻觉、极度食欲亢进、定向障碍、兴奋、不安、高度警惕、强迫行为或攻击的迹象，通常是平静/胆小的病患

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