Long‐term Treatment with Methylene Blue in a Dog with Hereditary Methemoglobinemia Caused by Cytochrome b5 Reductase Deficiency

A juvenile male mixed breed dog was presented for lethargy, exercise intolerance, and aggression when touched on the head. Cyanosis, tachycardia, and tachypnea were observed and persisted during oxygen supplementation. Arterial blood gas analysis by co‐oximetry identified an increased methemoglobin concentration (27%; normal, <2%) with normal arterial oxygen tension. The methemoglobinemia and associated clinical signs resolved after administration of methylene blue (1 mg/kg) IV, and the dog was discharged. The affected dog's whole‐genome sequence contained 2 potentially causal heterozygous CYB5R3 missense mutations suggesting that cytochrome b5 reductase deficiency was responsible for the methemoglobinemia. This hypothesis was confirmed by enzyme analysis that identified cytochrome b5 reductase activity in the affected dog's erythrocytes to only approximately 6% of that in a control sample. Clinical signs recurred 11 days after discharge but normalized and the methemoglobin concentration decreased with methylene blue administration PO (1.5 mg/kg, initially daily and then every other day).     

Duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in clinically normal cats

OBJECTIVE: To determine duration of corneal anesthesia following topical administration of 0.5% proparacaine hydrochloride solution in domestic shorthair (DSH) cats. ANIMALS: 20 clinically normal DSH cats. PROCEDURES: Baseline corneal touch threshold (CCT) was established by use of a Cochet-Bonnet aesthesiometer. Treatment consisted of a single 50-microL topical application of an ophthalmic preparation of 0.5% proparacaine solution to a randomly selected eye of each cat. The corneal touch threshold was assessed 1 and 5 minutes after application to the cornea and at 5- minute intervals thereafter for 60 minutes. RESULTS: Corneal sensitivity, as determined by Cochet-Bonnet aesthesiometry, was significantly reduced from baseline for 25 minutes following topical administration of ophthalmic proparacaine. Maximal anesthetic effect lasted 5 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: As determined by Cochet-Bonnet aesthesiometry, duration of anesthetic effects on the cornea induced by a single topical application of an ophthalmic preparation of 0.5% proparacaine solution in DSH cats is considerably shorter than the reported duration of corneal anesthesia in dogs.     

A comparison of polychromasia and reticulocyte counts in assessing erythrocytic regenerative response in the cat.

Three staining techniques were evaluated for use in assessing the erythrocytic regenerative responses in the cat. Using new methylene blue as a vital stain, the aggregate reticulocyte count closely corresponded to the reticulocyte count on air-dried smears stained with new methylene blue and to the polychromatophilic erythrocyte count on Wright's stained smears.     

Methylene blue: effects and disposition in sheep

The disposition and urinary excretion pharmacokinetics of methylene blue were determined after its intravenous administration at 15 mg/kg to mature female sheep. Comparisons were made between methylene blue administered alone or subsequent to 50 mg/kg sodium nitrite. The overall elimination rate constant (beta) of methylene blue, 0.0076 +/- 0.0016 min-1, was not influenced by prior administration of sodium nitrite. However, the distribution rate was significantly altered by sodium nitrite. Very little of the methylene blue was eliminated in the urine either intact or as leucomethylene blue in spite of its relatively short half life. Toxicologic assessment was carried out using LD50 determination, methemoglobin production and hematologic effects as evaluation parameters. Methemoglobin production was minimal with doses as high as 50 mg/kg and no significant hematologic changes were seen up to 4 weeks after a total dose of 30 mg/kg methylene blue. The 24 h LD50 for intravenous methylene blue administered as a 3% solution was 42.3 mg/kg with 95% confidence interval limits of 37.3 to 47.9 mg/kg. From these data it appears that as conditions may warrant, the dosage of methylene blue may be safely increased up to at least 15 mg/kg in therapy of severe methemoglobinemias.     

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.     

COMPARATIVE EFFICACY OF DIFFERENT ANTIDOTES AGAINST EXPERIMENTAL NITRATE INTOXICATION IN RABBITS

The antidotal efficacy of aqueous garlic extract, methylene blue, and velenium (Vitamin E + sodium selenite) was compared against experimental nitrate intoxication in rabbits. Forty-two, albino rabbits of identical age, gender, and body weight were randomly divided into 7 groups (A to G) and subjected to experimental treatments for a period of 40 days. Rabbits of group A were offered only normal feed and served as negative control, while, rabbits of group B constituted the positive control group and received feed supplemented with sodium nitrate at 400 mg/kg body weight. Sodium nitrate-containing feed and intraperitoneal injection of 1% methylene blue solution at 2 mg/kg body weight were administered to group C. Rabbits of group D were given sodium nitrate-supplemented feed and aqueous garlic extract at 500 mg/kg body weight through oral route. Group E was treated with sodium nitrate-added feed, intraperitoneal injection of 1% methylene blue solution at 2 mg/kg body weight, and oral administration of garlic extract at 500 mg/kg. Velenium (25 mg of Vitamin E + 2.2 mg of sodium selenite per ml) was intraperitoneally injected at 1 ml/kg body weight to rabbits of group F along with the provision of sodium nitrate-supplemented feed. In addition to being fed with sodium nitrate-containing feed, group G obtained intraperitoneal injection of velenium at 1 ml/kg body weight and oral administration of garlic extract at 500 mg/kg body weight. The efficacy of antidotes was assessed on the basis of changes in blood nitrite level, biochemical profile, and gross pathological lesions manifested by the treated rabbits. The combination of methylene blue and garlic extract was highly effective in treating nitrate toxicity followed by methylene blue, garlic extract, and velenium, respectively. Whereas, the concurrent administration of garlic extract and velenium was least efficacious in terms of antidotal efficacy. In conclusion, aqueous garlic extract can be effectively used either alone or in combination with methylene blue when treating rabbits diagnosed with nitrate toxicity.     

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.     

Cardiorespiratory Effects of the Intravenous Administration of Tiletamine-zolazepam to Cats

The hemodynamic and respiratory effects of three doses (9.7, 15.8, and 23.7 mg/kg intravenous [IV]) of a 1:1 combination of tiletamine and zolazepam were studied after isoflurane anesthesia in cats instrumented for the recording of hemodynamic data. Systolic, mean, and diastolic arterial blood pressures were decreased 1 minute after drug administration but then increased above baseline with all three doses. Cardiac output was decreased briefly at 1 minute with the 15.8 and 23.7 mg/kg doses. The rate of development of left ventricular pressure and peripheral vascular resistance decreased at 1 minute but returned to baseline or above by 10 minutes. There were no significant changes in heart rate, central venous pressure, or left ventricular end diastolic pressure. The arterial pH and blood gas measurements reflected the development of respiratory acidosis after administration of 23.7 mg/kg. These results support the conclusions that tiletamine-zolazepam administered intravenously is a useful and comparatively safe anesthetic agent in the cat.     

Assessment of methadone as an anaesthetic premedicant in cats

Ninety cats scheduled to undergo surgical procedures requiring the provision of postoperative analgesia were premedicated with either 0·1, 0·3 or 0·5 mgl/kg of racemic methadone by intramuscular injection. Each cat was assessed on three behavioural criteria before administration and again 20 minutes later. In a further 20 cats a specific assessment was made of the respiratory rate, heart rate and intraoperative minute volume during ovariohysterectomy following premedication with methadone (0·5 mgl/kg intramuscularly). In these cats an assessment of duration of analgesia was attempted. There was no significant change in behavioural scores following premedication with methadone. No cat vomited or became excited. No evidence of serious respiratory depression was found in the 20 cats monitored in detail. Duration of analgesia in cats receiving methadone (0·5 mgl/kg intramuscularly) before ovariohysterectomy varied from 1·5 to over 6·5 hours. Methadone may be used at dose rates of up to 0·5 mg/kg as a premedicant for cats without significant risk of undesirable behavioural changes or serious intraoperative respiratory depression when combined with the anaesthetic protocol described.     

Efficacy of lidocaine hydrochloride for laryngeal desensitization: a clinical comparison of techniques in the cat

Assessment of laryngeal relaxation and ease of intubation in cats was made after preanesthetic medication with acepromazine/meperidine/atropine (IM) and induction of anesthesia 20 minutes later by thiopental administration (IV). Healthy cats (n = 32) scheduled for elective surgery were randomly assigned to 1 of 4 treatment groups to be provided with laryngeal desensitization: group 1, 2% lidocaine HCl (2 mg/kg of body weight) given IV 30 seconds before thiopental induction; group 2, 2% lidocaine HCl (2 mg/kg) topically applied to the larynx; group 3, 10% lidocaine HCl (10 mg) as a topical aerosol; and group 4, no treatment before intubation. A significant (P less than 0.05; ANOVA) difference between groups in the reaction to intubation attempts was apparent. Cats receiving 2% lidocaine IV or no treatment for desensitization had a greater response to intubation than did those receiving 2% or 10% lidocaine topically. The number of attempts required to intubate cats was significantly (P less than 0.05) greater in cats with no treatment than in cats treated topically with 2% or 10% lidocaine. Response to IV administration of 2% lidocaine HCl was not significantly different from the response to other treatments, indicating little advantage over no laryngeal desensitization. It was concluded that topical application of 2% lidocaine (2 mg/kg) or 10% lidocaine aerosol 1 1/2 minutes before intubation provides effective laryngeal desensitization in the cat.     

Ultrasound-guided transversus abdominis plane block in the dog: an anatomical evaluation

Objective To describe the ultrasound‐guided technique to the transversus abdominis plane (TAP) block in the dog and evaluate the spread of a local anesthetic/methylene blue solution. Study design Prospective experimental trial. Animals Ten adult Beagle cadavers weighing 11.1 ± 1.1 kg (mean ± SD). Methods Transversus abdominis plane (TAP) blocks were performed bilaterally by a single trained individual on unpreserved cadaver dogs using 10 mL of methylene blue/bupivacaine solution per site. Dissection of the abdominal wall was performed within 15–55 minutes of block to determine distribution of injectate and nerve involvement in the transversus abdominis fascial plane. Results The transversus abdominis fascial plane was adequately visualized via ultrasound and injected in twenty hemi‐abdominal walls. Segmental branches of T11, T12, T13, L1, L2, and L3 were adequately stained in 20%, 60%, 100%, 100%, 90%, and 30% of injections, respectively. Conclusions and clinical relevance This anatomical study suggests that the transversus abdominis plane (TAP) block would provide adequate regional anesthesia of the abdomen, potentially extending to the cranial and caudal limits of the abdomen. This supports the clinical potential of this block in veterinary medicine.     

Pulmonary oedema as a suspected adverse drug reaction following vincristine administration to a cat: a case report

This report describes recurrent respiratory distress following vincristine administration to a cat with chronic lymphocytic leukaemia. The cat was treated with a combination of vincristine, chlorambucil and prednisolone with initial success. After approximately 4 months, dyspnoea developed within 6 h of vincristine administration. Emergency therapy was instituted resulting in a full recovery. Further vincristine was administered; dyspnoea was similarly noted after all but one of these treatments. Dyspnoeic episodes were not attributable to alterations in vincristine dose or method of administration. The repeated temporal association was consistent with a suspected adverse drug reaction to vincristine.     

Heinz-body hemolytic anemia associated with ingestion of methylene blue in a river otter

Heinz-body hemolytic anemia and nephrosis associated with hemoglobinuria were diagnosed in a North American river otter. Fluids were administered, and the signs of renal failure improved immediately. Severe anemia developed, and the otter received a semisynthetic hemoglobin product to maintain the oxygen-carrying capacity of the blood until a blood transfusion could be given. Immediate clinical improvement was observed following hemoglobin administration, and adverse effects were not seen. Six days after admission, the otter began to produce its own RBC and recovered without complications. The Heinz-body anemia was determined to be caused by methylene blue that was in the water of minnows consumed by the otter the night before it became ill. Methylene blue is a common ingredient in products used to extend the life of bait fish. Bait fish kept in water treated with methylene blue should not be used as food for fish-eating animals.     

Cardiovascular changes associated with anaesthesia induced by medetomidine combined with ketamine in cats

SUMMARY Fifteen cats had anaesthesia induced by intramuscular injection of medetomidine combined with ketamine. By five minutes after drug administration, heart rate had decreased by 31 per cent, respiratory rate had decreased by 70 per cent and systolic blood pressure had increased by 69 per cent. Atipamezole administration was associated with a decrease in systolic blood pressure and an increase in heart and respiratory rates. Time to first head lift was eight minutes and to sternal recumbency 12 minutes after atipamezole administration. Postoperative analgesia was provided by methadone, administered when the cats adopted sternal recumbency.     

The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats

Acetaminophen (APAP) overdose in most species is associated with hepatotoxicity because of the metabolite N -acetyl- p -benzoquinoneimine (NAPQI). In dogs and cats, APAP overdose primarily causes methemoglobinemia and hemolysis. Although NAPQI has been proposed as the responsible intermediate in dogs and cats, it lacks chemical or pharmacokinetic characteristics that favor methemoglobin formation. We hypothesized that para -aminophenol (PAP) rather than NAPQI induces methemoglobinemia and that deficient arylamine N -acetyltransferase (NAT) activity in dogs and cats contributes to this species-dependent methemoglobinemia. Erythrocytes from dogs, cats, mice, and rats were exposed in vitro to APAP, NAPQI, and PAP. Only PAP induced methemoglobin and it induced more methemoglobin formation in dog and cat than rat and mouse erythrocytes. PAP also induced more methemoglobin in erythrocytes from Nat1/Nat2 knockout mice than wildtype (WT) mouse erythrocytes ( P  <   0.05), but less than in dog and cat erythrocytes ( P  <   0.01). APAP and PAP toxicity were compared in vivo in WT and Nat1/Nat2 knockout mice. APAP caused no hematotoxicity while PAP induced more methemoglobin in NAT1/NAT2 knockout mice than in WT mice ( P  <   0.05). These results support the hypothesis that PAP is the metabolite responsible for APAP-induced methemoglobinemia and that deficient NAT activity in dogs and cats contributes to this species-dependent toxicity.     

Eugenol for anesthesia of African clawed frogs (Xenopus laevis)

OBJECTIVE: To determine the level of anesthesia attained in Xenopus laevis frogs with eugenol at different doses and by different routes of administration. STUDY DESIGN: Prospective experimental trial. ANIMALS: Sixty X. laevis nonbreeding female frogs weighing between 90 and 140 g. METHODS: Three different routes of administration were tested - subcutaneous injections into the dorsal lymph sacs, topical administration using a gauze patch, and immersion in a bath containing eugenol. Following the determination of the best route of administration, the acetic acid test, the withdrawal reflex, righting reflex, heart rate, and respiratory frequency were used to evaluate central nervous system depression following eugenol bath administration. In an additional group, the response to a surgical incision of the abdominal wall was evaluated. The pharmacokinetics of eugenol were determined following bath immersion administration, and pharmacokinetic parameters were calculated following blood concentration determination by tandem liquid chromatography/mass spectrometry analyses. RESULTS: It was not possible to induce anethesia with subcutaneous and patch administration, independent of the eugenol dose administered. The immersion bath was the only efficacious route for anesthesia inducing surgical anesthesia for at least 30 minutes with postoperative analgesia. Histopathology of selected tissues (heart, lung, liver, kidneys, eyes) showed no evidence of lesions 24 hours following bath immersion. The elimination half-life (T(1/2)) was 4 hours. CONCLUSIONS: When administered as a single-bath immersion (dose 350 mg L(-1)) for 15 minutes, eugenol may serve as an effective anesthetic in X. laevis frogs for short surgical procedures.     

Intra‐operative hyperthermia in a cat with a fatal outcome

HistoryA four year old male neutered Domestic Short Hair cat presented for general anaesthesia for hind limb orthopaedic surgery. The cat had been anaesthetized four days previously with propofol and isoflurane and made an uneventful recovery.Physical Examination and ManagementOn pre-anaesthetic examination the cat had a temperature of 38.9 °C and was otherwise healthy. After a premedication of acepromazine and pethidine, anaesthesia was induced with thiopental and maintained with isoflurane in oxygen 50% and nitrous oxide 50%. Increases in heart rate, respiratory rate, end tidal carbon dioxide tension and temperature were observed, occurring sequentially, from 110 to 175 minutes after anaesthetic induction. Despite ceasing all warming measures and attempting to cool the patient, body temperature continued to rapidly rise, reaching 42.5 °C and limb rigidity was observed. Isoflurane administration was stopped and esmolol was administered. Cardiac arrest occurred. Cardio-pulmonary cerebral resuscitation was commenced and a lateral thoracotomy was performed to allow cardiac compressions and internal defibrillation. Atropine, adrenaline, glucose and dopamine were administered and cold saline was instilled into the thoracic cavity.Follow-upResuscitation was unsuccessful and the cat died.ConclusionsA presumptive diagnosis of malignant hyperthermia was made. Malignant hyperthermia should be considered, even if prior exposure to volatile inhalational anaesthesia was uneventful, and prompt and aggressive therapy instituted.     

Eosinophilic conjunctivitis, herpes virus and mast cell tumor of the third eyelid in a cat

A 3-year-old Himalayan cat was diagnosed with concurrent eosinophilic conjunctivitis, herpes virus, and a conjunctival mast cell tumor. Eosinophilic conjunctivitis was verified via cytology from a conjunctival scraping, which revealed 50% eosinophils and 50% neutrophils. Herpes virus was verified via a positive polymerase chain reaction (PCR). Conjunctival scrapings for chlamydia immmunofluorescent antibody (IFA) and herpes IFA were negative. A mycoplasma was detected by a general mycoplasma PCR but the organism did not grow on the available mycoplasma media. The mass was excised and microscopic evaluation revealed a histiocytic mast cell tumor. The mast cell did not recur following local excision (at 1 year follow-up). The eosinophilic conjunctivitis was treated with both topical steroids and systemic megesterol acetate (Ovaban). When topical steroids were used, the herpes virus flared up and resulted in dendritic and geographic corneal ulceration. Therefore, the cat was treated with megesterol acetate and the eosinophilic conjunctivitis was well controlled. Treatment of eosinophilic conjunctivitis in the cat with megesterol acetate may be the treatement of choice due to the possibility of herpes virus.     

Effect of xylazine and ketamine on intraocular pressure in horses

Intraocular pressure was measured with a MacKay-Marg tonometer in eight horses following auriculopalpebral nerve block and topical application of lignocaine. Measurements were recorded before and after xylazine, 1.1 mg/kg intravenously, every two minutes for 16 minutes after administration of ketamine, 2.2 mg/kg intravenously, and after recovery from anaesthesia. Before xylazine, intraocular pressure was 17.1 +/- 3.9 and 18.4 +/- 2.2 mm Hg in the left and right eyes, respectively. Intraocular pressure tended to decrease after administration of xylazine and ketamine, with a significant decrease in one eye six minutes after injection of ketamine.     

Systemic absorption of amitriptyline and buspirone after oral and transdermal administration to healthy cats

A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzyme-linked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.