Alpha-chloralose poisoning in cats in three Nordic countries - the importance of secondary poisoning.

BACKGROUND: Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. METHODS: Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. RESULTS: In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. CONCLUSIONS: Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways.

Alpha-chloralose poisoning in 25 cats: clinical picture and evaluation of treatment with intravenous lipid emulsion.

OBJECTIVES: The aims of this study were to describe the clinical picture and progression in cats with alpha-chloralose (AC) intoxication and to determine if treatment with intravenous (IV) lipid emulsion (ILE) influenced either the serum concentration of AC or the clinical signs. METHODS: Cats with suspected AC poisoning admitted to a university small animal hospital were included. The cats were randomised into two groups: one receiving 20% ILE at a dose of 300 mg/kg as a 2 min bolus, followed by a 1500 mg/kg continuous rate infusion over 30 mins (IL+ group) and the other receiving IV fluid therapy with Ringer's acetate (IL- group). Serum samples were drawn at 0, 2, 12 and 24 h after admission. Samples were tested for AC with a novel validated, quantitative, ultra-high-performance liquid chromatography-tandem mass spectrometry method. Vital and predefined clinical signs were noted at the times of sampling and patients were scored using a previously described intoxication severity score. Telephone interviews were conducted after discharge to assess outcome. RESULTS: A total of 25 cats were enrolled: 13 cats in the IL+ group and 12 in the IL- group. The most common clinical signs at presentation were tremor (n = 22, 88.0%), cranial nerve deficits (n = 20, 80.0%) and bradycardia (n = 19, 76.0%). No significant difference in AC concentration or change in intoxication score over time was found between the IL+ and IL- groups at any time point (P >0.05). All cats recovered within 72 h. CONCLUSIONS AND RELEVANCE: ILE did not have any effect on the AC serum concentration or clinical signs in AC-poisoned cats. All cats survived until follow-up. In cats with an acute onset of the described neurological signs, AC intoxication is an important differential diagnosis with an excellent prognosis.

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS AND RELEVANCE: 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.

Concentration of carprofen in the milk of lactating bitches after cesarean section and during inflammatory conditions.

Pain treatment of lactating bitches is a clinically relevant, but complicated issue. Published scientific studies regarding the excretion of drugs in canine milk are scarce. When considering the risk of side effects in their offspring, lactating bitches have traditionally received very restricted analgesic and anti-inflammatory therapy. Our aim was to quantify the concentrations of carprofen in milk from lactating bitches and relate those to potential risks for the puppies. A second aim was to evaluate the impact mastitis may have on the concentration of carprofen in milk. A population of 100 bitches was enrolled in the study, among which 88 were bitches treated with carprofen after cesarean section (Group CS), eight were bitches with painful inflammatory conditions (Group I) and four were bitches with mastitis (Group M). The patients enrolled in the study received carprofen 4 mg/kg sc at day 1 followed by 2 mg/kg po every 12 h for the following 2-5 days. Owners were instructed to collect milk once a day for five days. The concentration of carprofen in the milk was quantified with ultra-performance liquid chromatography-tandem mass spectrometry. The data obtained were statistically analyzed as repeated-measures data with a mixed-model approach. Data were used to calculate the theoretical maximum total daily intake of carprofen by the puppies in order to perform a computerized simulation of the plasma concentration of carprofen in the puppies. Follow-up telephone interviews to check the status of the enrolled bitches and their litters occurred at one week and three-six months after treatment with carprofen. The major finding of the study was that the concentration of carprofen in the milk was <700 ng/mL from bitches undergoing CS or suffering painful conditions other than mastitis. In comparison, administration of 2 mg/kg of carprofen sc or po to adult dogs, results in mean maximal plasma concentrations of 19480 ± 5420 ng/mL (mean ± SD). Moreover, data suggests that inflammation of the mammary gland results in a higher concentration of carprofen in milk (up to 1300 ng/mL). In the computerized simulation, the plasma concentrations of carprofen in puppies in group CS and in group I are one tenth of the concentration in adult dogs receiving carprofen at standard doses. Considering the low excretion into milk, carprofen provides an analgesic alternative to lactating bitches without mastitis.

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.

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative ultra high performance liquid chromatography--tandem mass spectrometry (UHPLC--MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats.

A measure of neurobehavioral functioning after coma. Part I: Theory, reliability, and validity of Disorders of Consciousness Scale.

This is longitudinal validation study describes the psychometric properties of the Disorders of Consciousness Scale (DOCS). This is Part I of a two-part series. Part II illustrates and describes the clinical and scientific implementation of the DOCS measure. The study was conducted at one intensive care unit, two acute rehabilitation hospitals, and one long-term acute chronic care hospital. Participants were unconscious after severe brain injury (BI). We conducted interrater reliability analyses using ratings from interdisciplinary pairs. Results indicated a higher-than-expected level of agreement and no significant difference between any pairs ( chi-square = 8(5df), p = 0.15) (df = degrees of freedom). Examinations of ratings by discipline groups indicated that the DOCS is impacted minimally by discipline. Validity analyses demonstrate that 23 of 34 test stimuli remain stable over time with no floor or ceiling effect. DOCS measures obtained within 94 days of injury predicted recovery of consciousness up to 1 year after injury (c-indices of 0.70 and 0.86). Positive (0.71) and negative (0.68) predictive values indicate that the DOCS predicts recovery and lack of recovery. Twenty-three of the DOCS test stimuli produce a reliable, valid, and stable measure of neurobehavioral recovery after severe BI that predicts recovery and lack of recovery of consciousness 1 year after injury.

Predicting levels of independence with expressing needs and ideas 1 year after severe brain injury.

PURPOSE/OBJECTIVE: Severe brain injury (BI) is a catastrophic event often evolving into a complex chronic and severely disabling condition making activity participation possible only with sustained caregiving. One aspect of building sustainable caregiving is early provision of information about expected outcomes germane to patients and their caregivers. An analysis was conducted to determine whether 2 levels of independence with expressing needs and ideas 1-year after severe BI could be predicted using variables available early after injury. METHOD: The authors examined a subsample (n = 79) of participants of an outcome study who received repeated neurobehavioral evaluations with the Disorders of Consciousness Scale (DOCS) and who were assessed 1 year after injury with the Functional Independence Measures (FIM). Explanatory variables included DOCS measures, patient characteristics, coexisting conditions, and interventions. The outcome is measured with the FIM Expression item. Optimal data analysis was used to construct multivariate classification tree models. RESULTS: The 2nd (p = .004) DOCS visual measure and seizure (p = .004) entered the final model providing 79% accuracy in classifying more or less independence with expressing needs and ideas at 1 year. The model will correctly identify 78% of future severe BI survivors who will have more independence and 82% of persons who will have less independence. CONCLUSIONS: For persons incurring severe BI, it is possible to predict, early after injury, more and less independence with expressing needs and ideas 1-year after injury. This evidence is 1 contribution to a larger body of evidence needed to enable early caregiver education about recovery expectations in terms of patient functioning relative to caregiving needs, which in turn will help build sustainable caregiving for this population.

Predictive value of the Disorders of Consciousness Scale (DOCS).

OBJECTIVE: To examine the predictive validity of measures of neurobehavioral change derived from the Disorders of Consciousness Scale (DOCS) for predicting return to consciousness 4, 8, and 12 months after severe brain injury (BI). DESIGN: Prospective observational predictive validity study SETTING: Inpatient rehabilitation hospitals and postrehabilitation residence PARTICIPANTS: A total of 113 persons with a mean age of 38 +/- 17.8 years who were unconscious for >28 days consecutively after severe BI; 73% (83/113) with traumatic BI and 27% (30/113) with other BI. INDEPENDENT VARIABLES: Baseline DOCS, DOCS average, change from baseline DOCS to subsequent DOCS (DOCS2, DOCS3, DOCS4, DOCS5, DOCS6), and injury type (traumatic BI vs. other BI) MAIN OUTCOME MEASURE: Time to consciousness at 4, 8, and 12 months after injury RESULTS: When controlling for injury type, the DOCS average as well as DOCS change between the first and second DOCS (DOCS1-2), first and fifth DOCS (DOCS1-5) and first and last DOCS (DOCStotalchg) significantly (P < or = .05) contributed to predicting recovery and lack of recovery of consciousness at 4, 8, and/or 12 months after injury. DOCS1-5 manifested the most balanced accuracy in predictions, where predicting recovery of consciousness is accurate 87% of the time and predicting lack of recovery of consciousness is accurate 88% of the time. CONCLUSION: For persons with prolonged disorders of consciousness, the findings indicate that evidence-based prognostication for individual patients is possible. The implications for research are that the DOCS can be used as a meaningful, reliable, and valid primary outcome to measure treatment effects in clinical trials. The evidence indicates further that DOCS measures merit inclusion in future research that aims to develop multivariate prognostication models.

Establishing a prognosis for functional outcome during coma recovery.

PRIMARY OBJECTIVE: One of the most challenging tasks for clinicians caring for survivors of severe brain injury (BI) is establishing a prognosis, for long-term functional outcome, while the patient is unconscious. The objective of this article is to report findings regarding the prediction of functional outcomes 1-year after severe BI using data available when the patient is unconscious. RESEARCH DESIGN: Longitudinal prognostication study. METHODS AND PROCEDURES: Persons unconscious after severe BI who present to inpatient (IP) rehabilitation hospitals in the Midwestern US are enrolled in an ongoing study. Each subject is followed for 1-year and the final outcome interview includes approximately 70 questions; 32 of these questions are from the Craig Handicap Assessment and Reporting Technique (CHART). A sample of 63 persons was abstracted from the study database to examine the predictability of 42 independent variables and 16 dichotomous outcomes. MAIN OUTCOMES AND RESULTS: Twelve of the 16 dichotomous outcomes were found to be significantly predictable (p < 0.05). These involve activity, participation, environment and quality of life outcomes. Ten predictors were found to be significant (p < 0.05): aetiology (Closed Head Injury vs. Other BI), presence of urinary tract infection (UTI), seizure, hypertension during IP rehabilitation, veteran benefit eligibility, health insurance, marital status at injury, whether or not recovery of consciousness occurred within 1 year, the number of days between injury and admission to acute rehabilitation and the average length of IP rehabilitation stay. Eight of the 10 variables are available early after injury or when the patient is unconscious.