Cyanides and their toxicity: A literature review

Summary Cyanide is a potent and rapidly-acting asphyxiant which prevents tissue utilization of oxygen by inhibition of the cellular respiratory enzyme, cytochrome oxidase. Inhalation or ingestion of cyanide produces reactions within a few seconds and death within minutes. Cyanide toxicity of dietary origin has been implicated in acute animal deaths and as major etiologic factors in toxic ataxic neuropathy in man and as a cause of vision failure in humans suffering from tobacco amblyopia and leber's hereditary optic atrophy. Diagnosis of cyanide toxicity may be confirmed by a variety of laboratory procedures, but accurate assay is essential for proper conclusions from analysis of animal tissues several hours after death or from human samples in instances of chronic dietary exposure. Biological detoxification of cyanide is available through several routes, and the application of sodium nitrite with sodium thiosulfate or administration of methylene blue are effective treatment procedure. The environmental availability of cyanide in its various forms necessitates an understanding of its pathophysiology and responsible management of hazardous situations.     

Sodium nitroprusside, a convenient source of dietary cyanide for the study of chronic cyanide toxicity

1. The suitability of sodium nitroprusside (SNP) as a source of dietary cyanide has been tested with growing chicks and with hens by measuring plasma or urinary thiocyanate; the major detoxication product of cyanide. 2. Growth and food intake were depressed and plasma thiocyanate concentration was increased in chicks in a progressive manner as the dietary concentration of SNP was increased from 0 to 0.5 g/kg. 3. In laying hens, urinary excretion of thiocyanate was increased fivefold by including SNP in the diet at 0.3 g/kg. 4. It is concluded that SNP is a suitable and convenient source of dietary cyanide for the investigation of chronic cyanide toxicity.     

Effect of dietary sodium nitroprusside as a source of cyanide on the selenium status of chicks given diets of varying selenium concentration

1. The interaction between dietary cyanide, given in the form of sodium nitroprusside (SNP), and selenium has been studied in two experiments with growing chicks from 14 to 38 d of age.

2. In experiment 1, dietary selenium at 10 mg Se/kg reduced growth, food intake and efficiency of utilisation, and increased relative liver size and selenium content. All of these effects were eliminated by the addition of 0–1 g SNP/kg except for liver selenium content, which progressively declined towards control values as SNP was increased to 0–4 g/kg in increments of 0.1 g/kg. At 0.3 g SNP/kg, cyanide toxicity, as judged by decreased growth, reached significance.

3. In experiment 2, similar effects were observed with selenium at 10 mg Se/kg and SNP at 0.3 g/kg, but selenium deficiency was not evident from growth indicators when selenium supplementation of the diet was omitted completely, nor did these indicators suggest that deficiency was induced by cyanide.

4. In both experiments, plasma and liver glutathione peroxidase activity reflected the dietary selenium content. There was an interaction with dietary SNP content. With selenium intake at a toxic level, SNP increased enzyme activity, further evidence of alleviation of selenium toxicity, but when selenium intake was low and normal, SNP decreased activity in liver, an indication that cyanide could induce deficiency.

5. A possible mechanism for alleviation of selenium toxicity is proposed.     

The acute toxicity of four common poisons to the opossum,Trichosurus vulpecula

Extract

Although a number of poisons are used for the destruction of opossums, Trichosurus vulpecula (Kerr), very little information on their acute toxic effects is available. A study of the toxicity of four poisons was therefore undertaken. Two of these compounds, sodium monofluoroacetate and sodium cyanide, are used as toxins against opossums in New Zealand, and two others, arsenic trioxide and strychnine, alkaloid, are used for the destruction of rabbits. Arsenic trioxide and strychnine were suggested as replacements for sodium monofluoroacetate and sodium cyanide by the Rabbit Destruction Council (pers. comm.). They suggested strychnine as a substitute for cyanide to overcome poison shyness and arsenic as a substitute for sodium monofluoroacetate to circumvent the danger of secondary poisoning to farmers' dogs.     

Cyanide toxicosis in goats after ingestion of California Holly (Heteromeles arbutifolia).

Cyanogenic glycosides are found in many native and naturalized plants throughout North America. The glycosides themselves are not toxic, but they yield hydrogen cyanide (hydrocyanic or prussic acid) when they are hydrolyzed by beta-glycosidases, either as a result of injury to the plant cells or by microbial action in the rumen. Hydrogen cyanide is readily absorbed from the gastrointestinal tract. Cyanide ion binds with iron in cytochrome oxidase, interfering with cellular respiration. The clinical effects are peracute, often resulting in death less than 1 hour after ingestion. This study describes a case that resulted in significant morbidity and mortality in a herd of goats after exposure to California holly (Heteromeles arbutifolia).     

Milk transfer of cyanide and thiocyanate: Cyanide exposure by lactation in goats

The present work was aimed at evaluating the effects of maternal exposure to potassium cyanide (KCN) during lactation in goats. Twenty-seven lactating female goats were orally dosed with 0 (control), 1.0, 2.0, or 3.0 mg KCN/kg body weight/day from lactation days 0 to 90. After this period, all male kids and one mother from each group were killed for a pathological study. Cyanide treatment promoted the clinical signs of maternal toxicity in the highest KCN group but did not affect body weight. Both cyanide and thiocyanate presented increased levels in both dams and kids from the treated groups. Microscopic lesions, but without alterations on the biochemical panel, were found in the brain, thyroid, liver, and kidneys of both dams and kids from the treated groups. These findings suggest that lactating offspring can be indirectly intoxicated by maternal exposure to cyanide.     

Seasonal variations in the cyanide content of Poa aquatica

Abstract

Extract

Sir,—Cattle deaths from cyanide poisoning have resulted from the ingestion of reed sweet-grass, Poa aquatica (Sharman, 1967 Sharman, J. R. 1967. Cyanide poisoning in cattle grazing reed sweet-grass. N.Z. vet. J., 15: 7–7. [Taylor &; Francis Online] , [Google Scholar]). Samples of leaves from this plant, gathered at approximately monthly intervals throughout the year, have now been analysed for their cyanide content.     

木薯及其副产品的营养价值及在动物生产中的应用

木薯耐干旱、耐贫瘠且易管理，其茎叶、块根及工业副产物营养物质含量较高，是一种优质的非常规饲料。木薯叶粗蛋白质、粗脂肪、灰分含量较高，含有丰富的钙、铁、锌、锰。木薯块根是很好的能量来源，其粗蛋白质、粗脂肪、矿物质、维生素含量低于木薯叶。木薯渣主要由木薯的外皮、破碎细胞壁等组成，粗蛋白质含量很低，粗纤维、中性洗涤纤维、酸性洗涤纤维含量较高，矿物质、氨基酸丰富，但钙、磷、氨基酸不平衡。木薯品种、生长条件、收割方式、收获时间、加工工艺等均会影响木薯及其副产品营养物质的含量。木薯中含有氰化物、单宁及植酸等抗营养因子，其中氰化物是限制木薯应用的最主要因素，其可结合细胞色素C氧化酶，阻断线粒体电子传递链，抑制有氧呼吸，导致中枢神经系统抑制和死亡。单宁、植酸与蛋白质结合生成络合物，阻碍营养物质的消化吸收，可通过水煮、烘烤、干燥等物理化学方法，以及发酵、育种等手段对木薯进行脱毒。研究表明，木薯及其副产品可广泛应用于动物生产中，对动物生长性能、肉品质无不良影响。开发与利用非常规饲料有利于缓解饲料资源紧张，降低养殖成本。作者详细介绍了木薯及其副产品的营养价值、抗营养因子及其脱毒方法以及其在动物生产上的应用，以期为木薯在畜禽养殖中的综合利用提供一定的参考。     

Effect of potassium cyanide on behaviour and time to death in possums

AIM: To assess the sickness behaviours of possums after eating a lethal dose of potassium cyanide. METHOD: Spontaneous behaviour and the time to loss of physical responses were examined. RESULTS: Cyanide ingestion caused a short-lasting period of mild respiratory stimulation. There was no salivation, retching or vomiting. Convulsions occurred in 73% of the possums. After the ingestion of cyanide, the average time to onset of ataxia was 3 minutes, the average time to overall loss of consciousness was 6.5 minutes, and the time to cessation of breathing was 18 minutes. CONCLUSION: Cyanide is a rapid-acting toxin with few undesirable signs from the welfare perspective.     

Age at death and cause of death of pet rabbits (Oryctolagus cuniculus) seen at an exotic animal clinic in Tokyo,Japan: a retrospective study of 898 cases (2006–2020)

BackgroundAs the quality of care received by pet rabbits improves, the age at death of these animals is expected to increase; however, reliable data on the age at death of pet rabbits is lacking. The present retrospective study aims to clarify the age at death and cause of death of pet rabbits.Materials and MethodsThe age at death, cause of death, and clinical details of 898 rabbits that died between 2006 and 2020 were obtained by reviewing paper-based medical records, including necropsy and/or biopsy reports, at a referral exotic animal hospital in Japan.ResultsThe median age at death in the 898 rabbits was 7 years (interquartile range: 5to9 years), and 18% of all rabbits lived beyond 9 years. The main causes of death included neoplasia (n = 223; 24.8%), gastrointestinal disease (n = 135; 15.0%), bacterial abscess (n = 90; 10.0%), urinary disease (n = 85; 9.5%), trauma (n = 44; 4.9%), and cardiac disease (n = 27; 3.0%). Gastrointestinal disease was the most common cause of death in younger-aged rabbits (4 years or less), while neoplasia was the most common cause of death in the middle to older-aged rabbits (5 years or more).Clinical significanceThis is one of the largest retrospective studies on the age at death in pet rabbits conducted to date; thus, the findings will serve as a useful reference for veterinarians working with such rabbits. Nevertheless, additional studies are needed to elucidate differences in the age at death of rabbits according to sex and neutering status.     

Mortality related to general anaesthesia and sedation in dogs under UK primary veterinary care

ObjectivesTo quantify and explore risk factors in dogs seen at primary care UK veterinary clinics for general anaesthetic (GA)/sedative-related death overall, in addition to neuter-specific procedures.Study designA nested case-control study within UK primary care veterinary electronic patient record surveillance programme, VetCompass, including over 300 UK veterinary practices.AnimalsA total of 157,318 dogs undergoing GA/sedative events.MethodsCases included dogs undergoing GA/sedative events between January 2010 and December 2013 with GA/sedative-related death recorded within 48 hours or 2 weeks of the event. Controls were randomly selected from dogs undergoing GA/sedation that did not die within these time periods. Risks of GA/sedative-related death for all surgeries and neuter-specific surgeries were estimated. Demographic and clinical associations with GA/sedative-related death were reported as odds ratios following multivariable logistic regression modelling. Statistical significance was set at 5%.ResultsFrom 157,318 dogs with a GA/sedative event, there were 159 (0.10%) within 48 hours and 219 (0.14%) GA/sedative-related deaths within 2 weeks. Within 89,852 dogs that underwent a neuter surgery, there were eight GA/sedative related (0.009%). Greater age, poorer American Society of Anaesthesiologists health status scores and more urgent procedures were associated with greater odds of death. Compared with mixed breeds, Rottweilers and West Highland White Terriers had greater odds and Cocker Spaniels had lower odds of GA/sedative-related death.Conclusions and clinical relevanceThe overall risk for GA/sedative related death was relatively low, particularly among the subset of dogs undergoing castration or ovariohysterectomy surgery. Associations and risk estimates may assist shared decision-making in clinical practice and provide benchmarks for audit.     

The impact of highly concentrated Mo and Cu dietary supplements,fed as a bolus,on the efficacy of chelated versus inorganic Cu in cattle on a low-Cu diet

AIM: To compare the efficacy of chelated versus inorganic forms of dietary Cu supplements, fed as a bolus, when challenged by a daily bolus of dietary Mo in cattle on a low-Cu diet.

METHODS: Forty non-lactating, Friesian dairy cows of adequate Cu status were assigned to four groups and fed a basal diet of baled silage containing 5.3 mg Cu and 0.4 mg Mo/kg DM. The experimental design was a factorial of two chemical forms of supplemental Cu and two levels of Mo intake, provided as pelleted grain supplements made from crushed barley/molasses plus Cu and Mo. The supplements contained 140 mg Cu/kg as Cu sulphate pentahydrate (CS), 140 mg Cu/kg as Cu glycinate (CG), CS plus 38 mg Mo/kg as sodium molybdate (CS+Mo), or CG plus 38 mg Mo/kg (CG+Mo). Commencing on Day 0, supplements were fed once daily (offered 1–1.2 kg/cow) and were completely consumed within 5–10 minutes, which constitutes a bolus type of administration. Liver samples were collected by biopsy at Days ?24, 13, 41 or 47, and 69 for Cu determinations.

RESULTS: The diets fed to the Cu+Mo groups were roughly equivalent to 25 mg Cu and 5.7 mg Mo/kg DM. Mean initial concentration of Cu in liver for all groups was 516 (SE 54) μmol Cu/kg fresh tissue. In cows supplemented with CS and CG, the final (Day 69) concentrations increased (p<0.01) to 939 (SE 166) and 853 (SE 163) μmol Cu/kg, respectively. These values were not different (p=0.72). For groups CS+Mo and CG+Mo, the final concentrations of 535 (SE 122) and 453 (SE 102) μmol Cu/kg were not different from initial values or from each other (p>0.25). The rate of accumulation of Cu in liver following bolus Cu and Mo intake was highly variable but was not affected by initial concentration of Cu in liver (p>0.9) or by the form of Cu (p>0.6). Mean rates of accumulation of Cu in liver were 4.0 (SD 3.8) and 0.65 (SD 2.0) μmol Cu/kg fresh tissue/day for the Cu-only treatments and the Cu+Mo treatments, respectively.

CONCLUSIONS: When fed together as a bolus, high Mo intake negated the effect of supplemental Cu but it did not reduce liver Cu stores. There was no difference in the reaction of dietary Mo with chelated Cu (as glycinate) versus inorganic Cu (as sulphate) dietary supplements.     

Xanthogranulomatous Panniculitis of the Head of an Aquarium-Maintained California Moray

Abstract

An aquarium-maintained male California moray Gymnothorax mordax had a symmetrical enlargement of the soft tissues of the head dorsal to the cranium for 2 years prior to its death. This individual was anesthetized for radiographic and ultrasonographic examination of the lesion, and blood was collected for plasma biochemical analytes and lipid profiles. Radiographs and ultrasound of the lesion demonstrated a symmetrical and homogeneous soft tissue density that was consistent with adipose tissue. Plasma cholesterol and triglyceride values appeared elevated; therefore, the animal's diet was amended to decrease fat consumption. Triglyceride values decreased after dietary changes were made; however, values for cholesterol, high-density lipoproteins, and low-density lipoproteins fluctuated but remained largely unchanged. Histopathological assessment of the lesion revealed localized xanthogranulomatous inflammation of hypodermal adipose tissue. The etiology of the lesion in this animal was never determined. This paper describes the first documented case of localized xanthogranulomatous panniculitis in a California moray and demonstrates the need for additional research on specific dietary requirements, species-specific physiological differences, and lesions involving the adipose tissue of morays in comparison with other teleost species.

Received September 16, 2011; accepted February 9, 2012     

The effect of replacement of 0.30% sodium chloride by 0.43% sodium bicarbonate in rations of fattening pigs on leg weakness,osteochondrosis and growth

Summary

The effect of replacing dietary sodium chloride by sodium bicarbonate on leg weakness, osteochondrosis and growth in young fattening pigs was studied in two experiments using 104 and 126 animals. The experimental pigs were fed 0.43 % dietary sodium bicarbonate, which replaced the sodium chloride (0.30%), was present in the diets of the control groups.

It was found that the clinical symptoms of leg weakness could be improved significantly in the experimental group which received bicarbonate. No positive effects on osteochondrosis, however, could be shown. The treated animals even tended to have more severe osteochondral lesions. Reasons for the negative tendency are discussed. Daily weight gain and food conversion were not influenced by the experimental bicarbonate diet excluding a chloride deficiency. Differences incarcass grading were not significant, although barrows fed the NaHCO₃‐containing diet tended to score better, while the carcass quality of the experimental gilts was slightly less in comparison to the control animals.     

Spirulina as a livestock supplement and animal feed

Summary Spirulina (Athrospira sp.) is an edible microalga and a highly nutritious potential feed resource for many agriculturally important animal species. Research findings have associated Spirulina to improvements in animal growth, fertility, aesthetic and nutritional product quality. Spirulina intake has also been linked to an improvement in animal health and welfare. Its influence over animal development stems from its nutritive and protein‐rich composition, thus leading to an increased commercial production to meet consumer demand. Consequently, Spirulina is emerging as a cost‐effective means of improving animal productivity for a sustainable and viable food security future. However, our present knowledge of animal response to dietary Spirulina supplementation is relatively scanty and largely unknown. Therefore, the primary objective of this paper was to review past and current findings on the utilisation of Spirulina as a feed supplement and its impact on animal productivity and health. Only animals deemed to be of agricultural significance were investigated; hence, only ruminants, poultry, swine and rabbits and their responses to dietary Spirulina supplementation are covered.     

Using sodium molybdate to treat chronic copper toxicity in dairy cows: A practical approach

Abstract

CASE HISTORY: A Jersey herd of 350 cows and 70 heifers located in the Taranaki region of New Zealand ceased milking in June 2011. Ten cows died during the subsequent 14 days. For at least 9 months, the cows had received palm kernel expeller (PKE) and molasses supplements. Additional Cu supplementation was provided through the water system. Total Cu intake was calculated to be 400?mg/day/cow.

CLINICAL AND PATHOLOGICAL FINDINGS: Half of the cows died suddenly while others presented with anorexia, depression and ataxia, which progressed to recumbency and death after 1 to 3 days. Clinical signs were mild dehydration, cyanosis and firm faeces which were covered in dark blood. Mean concentrations of Cu in liver and kidney in three of the dead cows were 3,900 and 440?µmol/kg fresh weight (FW), respectively. Haemorrhages were observed throughout the alimentary tracts and in muscles, and there were ecchymotic haemorrhages on the epi- and endocardia. The livers were swollen and the gall bladder walls were inflamed.

DIAGNOSIS: High concentrations of Cu in the liver and kidney are characteristic findings of chronic Cu toxicity.

TREATMENT: The remaining herd was fed 200?mg Mo, as sodium molybdate, per cow per day and all Cu supplements were removed including those provided by the water supply. This reduced mean concentrations of Cu in liver from 3,100 to 1,320?µmol/kg FW within 26 days in the five live animals that were biopsied. There were no further deaths.

CLINICAL RELEVANCE: In dairy herds where excessive Cu intakes have resulted in high liver Cu concentrations and caused chronic Cu toxicity, the removal of all Cu supplements and provision of high intakes of Mo (200?mg/cow/day) can markedly reduce liver Cu stores within 4 weeks.     

A behaviour study on the potential for direct transmission of tuberculosis from possums (Trichosura vulpecula) to alpacas (Lama pacos), and the converse from alpacas to possums

Aims. To evaluate the potential for the direct transmission of tuberculosis from possums to alpacas, and vice versa.

Methods. A field study was conducted on an alpaca farm in Northland, New Zealand on 7 January 1999. Observations were recorded on the interaction of one group of male alpacas with a simulated dead possum, one male and one female alpaca group with a simulated terminally tuberculous possum, and one group of male alpacas with a normal possum in an enclosure from which the animals could not escape. The possum was sedated with ketamine as hydrochloride to simulate death (inactive; no movement), and terminal illness (active, into-ordinated movement around the paddock). The observations were based on the focal animal sampling technique, they were un-replicated, and recorded visually and manually with intermittent still photography.

Results. Both male and female alpacas showed strongly inquisitive interaction with the possum. They clustered around the possum (focal animal) very soon after it was observed by the first member of the group. The interest of the majority of both sex groups remained high for the observation periods of approximately 30 minutes, and most individuals remained within 5 metres of the possum for that time. Approximately 50% of the alpacas were within possible aerosol transmission distance of 2 metres from the sedated, erratically mobile possum with their heads towards it for approximately 50% of the two observation periods. Aggressive behaviour was recorded for a young male with stamping on the moving possum. Similar, but more vigorous and prolonged stamping behaviour was recorded for a female with a young (<1 week) offspring (cria).The stamping behaviour was accompanied by very close nose to nose contact of the alpaca and possum. At one point the female threw the possum approximately 1.5 metres in the air with her teeth. The group of male alpacas placed in an enclosure with an unsedated normal possum generally moved away from the possum during its rapid active attempts to escape. When it became inactive their approaches were cautious and only once elicited a defence reaction from the possum, from which they recoiled. One male made one attempt to stamp on the active possum. Soon after the possum became inactive in a small loose hay pile, the alpacas lost interest in it.

Conclusions. The alpaca / possum behavioural interactions show there is potential for direct aerosol transmission of tuberculosis from possums to alpacas, but probably not from alpacas to possums.     

Chemical Composition and Energy Value of Different Fat Sources for Growing Pigs

The chemical composition, digestibility and energy value of eight animal and vegetable fat batches was determined (animal fat, soya oil, palm oil, palm oil, palm oil mix and vegetable oil byproduct). To a basal diet, 5, 10, 15, 20, 25 or 30% dietary fat was added, and digestibility and balance experiments with each fat batch were carried out with three litters of six female pigs, weighing 50-75 kg. The digestibility was determined by multiple regression analysis. The content of HCl-extracted fat and the amount of gross energy was nearly equal for all the fat sources and as such not related to the variation in fatty acid composition or digestibility. Inclusion of soya oil, which is high in polyunsaturated fatty acids, enhanced protein digestibility, whereas inclusion of the other fat sources did not influence protein digestibility. A curvilinear function of fat digestibility (% of intake) to dietary fat concentration was found, thus reflecting the significance of the endogenous fat losses on the determined digestibility value. In contrast, the relationship of digested fat (g day     

Toxicity of apolar and polar Lantana camara L. crude extracts in mice

Lantana camara L, widely used in folk medicine, presents toxicity for farm animals. The acute poisoning effects of the apolar and polar L. camara L. extracts in mice were done. The percentage of death during 7 days after treatment, the acute signs of toxicity as well as the general activity observed in open field were assessed. The extracts were administered by i.p. route at 1.5, 3.0 and 5.0 g/kg. Animals were evaluated during the first 2 h after the treatments to assess the acute signs of toxicity and daily observations were done for the presence of death. In the end of the experiment, at day 7, or immediately after death the animals had their organs removed, weighted and observed for macroscopic alterations. ¹H NMR and TLC analysis suggest the presence of triterpenoids in the apolar phase but not in the polar phase. Results showed also that both extracts produced similar percentage of death, mainly after 2 days of treatment; only the apolar extract presented a dose-dependent increased lethality. At necropsy, mice treated by both apolar and polar extracts were severely icteric, dehydrated and constipated, with hepatosis, showed congested heart and lung, and nephrosis; no skin lesions were shown. The main signs of toxicity revealed a decreased spontaneous general activity. In addition, it was observed a decreased duration of locomotion and animal rearing parallel to an increased immobility in the open field. The similarity of the signs related to the acute toxicity for both apolar and polar extracts suggested that the extracts have some of the active toxic principles in common. Data from open field behavior and spontaneous signs of toxicity suggest that the toxic principles have depressive properties on central nervous system.     

An evidence‐based medicine approach to small animal anaesthetic mortality in a referral practice: the influence of initiating three recommendations on subsequent anaesthetic deaths

ObjectiveTo evaluate anaesthetic death after implementation of recommendations and its risk factors in a small animal practice.Study designObservational cohort study.AnimalsAll cats and dogs anaesthetized at the Centre Hospitalier Vétérinaire des Cordeliers during two periods, from April 15th, 2008 to April 15th, 2010 (period 1) and from June 15th, 2010 to August 24th, 2011 (period 2).MethodsDeath occurring during or before full recovery from anaesthesia was recorded. At the end of period 1, a logistic regression model was generated to describe anaesthetic death and identify risk factors. Potential risk factors in our practice setting were identified, and three recommendations, relating to improving physical status and anaesthetic/analgesic regimen implemented for period 2. The relationship between anaesthetic death and recorded variables were analyzed, and where relevant, compared between periods.ResultsSix thousand two hundred and thirty-one animals underwent general anaesthesia. The overall death rate during period 1 was 1.35% (48 in 3546, 95% CI [1.0–1.7%]) and during period 2 was 0.8% (21 in 2685, 95% CI [0.6–1.2%]). For sick animals (ASA status 3 and over), the overall death rate was 4.8% (45 of 944 95% [CI 3.5–6.4%]) during period 1 and 2.2% (18 of 834 95% CI [1.3–3.5%]) during period 2; this represented a significant decrease in death rate in period 2 (p = 0.002). In period 2, the main factors associated with an increased odds ratio of anaesthetic death were poor health status (ASA physical status classification) and old age. Species, gender, anaesthetic regimen, the nature and urgency of the procedure were not associated with risk.Conclusion and clinical relevanceFollowing evidence based recommendations, the death rate related to anaesthesia was significantly decreased during period 2 compared to period 1. Application of evidence-based medicine may contribute to an effective approach to decrease death rates. Other factors, not monitored in this study, may also have had an impact.