Justine A. Lee

The use of intravenous lipid emulsion as an antidote in veterinary toxicology

OBJECTIVE To review the use of IV lipid emulsion (ILE) for the treatment of toxicities related to fat-soluble agents; evaluate current human and veterinary literature; and to provide proposed guidelines for the use of this emerging therapy in veterinary medicine and toxicology. DATA SOURCES Human and veterinary medical literature. HUMAN DATA SYNTHESIS Human data are composed mostly of case reports describing the response to treatment with ILE as variant from mild improvement to complete resolution of clinical signs, which is suspected to be due to the variability of lipid solubility of the drugs. The use of ILE therapy has been advocated as an antidote in cases of local anesthetic and other lipophilic drug toxicoses, particularly in the face of cardiopulmonary arrest and unsuccessful cardiopulmonary cerebral resuscitation. VETERINARY DATA SYNTHESIS The use of ILE therapy in veterinary medicine has recently been advocated by animal poison control centers for toxicoses associated with fat-soluble agents, but there are only few clinical reports documenting successful use of this therapy. Evidence for the use of ILE in both human and veterinary medicine is composed primarily from experimental animal data. CONCLUSIONS The use of ILE appears to be a safe therapy for the poisoned animal patient, but is warranted only with certain toxicoses. Adverse events associated with ILE in veterinary medicine are rare and anecdotal. Standard resuscitation protocols should be exhausted before considering this therapy and the potential side effects should be evaluated before administration of ILE as a potential antidote in cases of lipophilic drug toxicoses. Further research is waranted.

Use of intravenous lipid emulsion to treat ivermectin toxicosis in a Border Collie.

CASE DESCRIPTION A 2-year-old spayed female Border Collie was treated with IV lipid emulsion (ILE) after ingesting 6 mg/kg (2.73 mg/lb) of an equine ivermectin anthelmintic paste 8 hours prior to examination. CLINICAL FINDINGS On initial examination, the dog had stable cardiovascular signs but had diffuse muscle tremors and was hyperthermic. Neurologic evaluation revealed that the dog was ataxic and had mydriasis with bilaterally absent menace responses and pupillary light reflexes. The remaining physical examination findings were unremarkable. Results of CBC, serum biochemical analysis, venous blood gas analysis, and measurement of plasma lactate concentration were also within reference limits. TREATMENT AND OUTCOME The dog was treated with ILE in addition to supportive care with IV fluid therapy and cardiovascular, respiratory, and neurologic monitoring. The use of ILE treatment was initiated in this patient on the basis of previous clinical and experimental evidence supporting its use for toxicosis resulting from lipid-soluble agents. An initial bolus of 1.5 mL/kg (0.68 mL/lb) of a 20% sterile lipid solution was administered IV over 10 minutes, followed by a constant rate infusion of 0.25 mL/kg/min (0.11 mL/lb/min) over 60 minutes that was administered twice to treat clinical signs of ivermectin toxicosis. The dog was discharged from the hospital 48 hours after admission and was clinically normal within 4 days after ivermectin ingestion. Further diagnostic evaluation subsequently revealed that this dog was unaffected by the multidrug resistance gene (MDR-1) deletion, known as the ATP-binding cassette polymorphism. CLINICAL RELEVANCE Ivermectin toxicosis in veterinary patients can result in death without aggressive treatment, and severe toxicosis often requires mechanical ventilation and intensive supportive care. This is particularly true in dogs affected by the ATP-binding cassette polymorphism. Novel ILE treatment has been shown to be effective in human patients with lipid-soluble drug toxicoses, although the exact mechanism is unknown. In the patient in the present report, ILE was used successfully to treat ivermectin toxicosis, and results of serial measurement of serum ivermectin concentration supported the proposed lipid sink mechanism of action.

Potential risks, prognostic indicators, and diagnostic and treatment modalities affecting survival in dogs with presumptive aspiration pneumonia: 125 cases (2005–2008)

OBJECTIVE To evaluate a clinical population of dogs diagnosed with presumptive aspiration pneumonia (AP) and determine diagnostic and treatment modalities contributing to survival. DESIGN Retrospective study. SETTING A university veterinary teaching hospital in an urban setting. ANIMALS One hundred and twenty-five dogs with presumed AP treated from 2005 to 2008. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Dogs with presumptive AP identified by a review of medical records had an overall survival of 81.6% (102/125). Male large-breed dogs (mean 24.9 kg; 82/125) were overrepresented and were more likely to develop AP in this study population. Recent anesthesia had been performed in 16% (20/125), and vomiting was reported in 64% (80/125). The most common radiographic findings were a predominantly alveolar pattern (187/272, [68.8%] total lung lobes) in the right middle lung lobe (80/115, [69.6%]). A mean of 2 lung lobes were involved radiographically, and the relationship between survival and the number of lung lobes affected was statistically significant (P=0.04). Neutrophilia with a left shift was common with no significant change on consecutive daily evaluations. The mean PaO(2) was 77.7 mm Hg (SD, 17.5 mm Hg) (range, 40.7-100 mm Hg) with a median alveolar-arterial gradient of 41.1 mm Hg (range, 8.1-81.8 mm Hg). In this study population, 37.6% (47/125) of dogs had microbial cultures performed and of these, 76.6% (36/47) were positive for growth; Escherichia coli (38.8%), Mycoplasma spp. (21.3%), Pasturella spp. (19.1%), and Staphylococcus spp. (17%) were the most common isolates in either single or multiagent infections. No treatment modality was statistically associated with increased survival. Colloid therapy was a negative prognostic indicator. CONCLUSIONS In this study the overall prognosis for AP was good. Patients with only 1 affected lung lobe appeared more likely to survive. Supportive treatment modalities are warranted for the hospitalized patient, although no individual treatment method was found to be clearly superior to others.

Comparison of two anesthetic protocols for feline blood donation

OBJECTIVE To compare hemodynamic variables during, and recovery quality following, anesthesia for feline blood donation using intramuscular ketamine-midazolam-butorphanol (KMB) versus inhaled sevoflurane in oxygen (SEV). STUDY DESIGN Prospective blinded, randomized, crossover study. ANIMALS Twenty healthy, client-owned, mixed breed cats, aged 4-8 years, weighing 5.2-6.4 kg. METHODS Cats were anesthetized with KMB for one donation and SEV for another. Heart rate (HR), respiratory rate (f(R)), pulse quality, mucous membrane color, capillary refill time, arterial hemoglobin saturation with oxygen (SpO(2)), and noninvasive arterial blood pressure (Doppler) were assessed by a blinded observer every 1 minute during collection. A nonblinded anesthesiologist delivered drugs and responded to hemodynamic changes. Each donation consisted of 55 mL of whole blood drawn via jugular puncture over 5-22 minutes. Donors received 60 mL subcutaneous lactated Ringers solution before recovery. Donors were monitored for a minimum of 4 hours post-donation, before returning home. Owners, unaware of anesthetic protocol, completed a questionnaire regarding their cats behavior during the 24 hours following donation. RESULTS Both protocols provided adequate restraint but were complicated by significant hypotension, requiring intervention in 16 (84%) SEV cats, and eight (42%) KMB cats. KMB cats experienced post-procedure hyperthermia, with body temperatures >103.5 degrees F. All animals responded to symptomatic therapy within 2 hours. Owners noted a significantly faster return to normal behavior at home following SEV. CONCLUSION All cats experienced hypotension, with many animals requiring intervention. There was no significant difference between protocols in incidence and severity of hypotension. The primary post-procedure complication was hyperthermia with KMB. CLINICAL RELEVANCE As a result of the potential for hypotension during blood donation, intravenous (IV) access and blood pressure monitoring are recommended for all anesthetized donor cats, regardless of the anesthetic protocol. Post-procedure hyperthermia is a risk with KMB, so temperature monitoring is recommended. Return to normal behavior is faster with SEV.

Retrospective evaluation of toxicosis from selective serotonin reuptake inhibitor antidepressants: 313 dogs (2005-2010)

Objective To evaluate a clinical population of dogs exposed to selective serotonin reuptake inhibitor (SSRI) antidepressant medications and describe the clinical findings, epidemiological characteristics, outcome, and prognosis. Design Retrospective study (February 1, 2005–August 31, 2010). Setting Animal poison control helpline. Animals Three hundred thirteen dogs with presumed SSRI toxicosis. Interventions None. Measurements and Main Results Dogs with presumptive SSRI medication toxicosis identified by a review of the electronic database of Pet Poison Helpline, an animal poison control center, were evaluated. No clinical signs were reported in 76.3% (239/313) of cases. The remaining 23.6% (74/313) of cases demonstrated the following clinical signs: neurological 79.7% (59/74), gastrointestinal 25.6% (19/74), cardiovascular 9.5% (7/74), respiratory 8.2% (6/74), and thermoregulatory 6.7% (5/74). Of the dogs exhibiting neurological signs, 62.7% (37/59) showed depression, 37.2% (22/59) showed hyperactivity, 10.1% (6/59) exhibited ataxia, and 1.7% (1/59) showed other miscellaneous signs (eg, hyperesthesia). There was a significant difference between the dose ingested by symptomatic and asymptomatic dogs for fluoxetine (P = 0.0039), but not with any other SSRI. Ninety-four patients were confirmed to have received veterinary care. In cases where duration of veterinary care was determined (55/313), 67.2% (37/55) of dogs were hospitalized and 32.7% (18/55) treated as outpatients. The average duration of hospitalization was 18.5 hours, excluding outpatient visits. Of those patients that had complete follow-up information available (136/313), overall survival was 100%. Conclusions The overall prognosis for animals with SSRI toxicosis is excellent with veterinary attention. Central nervous system depression was the most common clinical sign associated with SSRI toxicosis.OBJECTIVE To evaluate a clinical population of dogs exposed to selective serotonin reuptake inhibitor (SSRI) antidepressant medications and describe the clinical findings, epidemiological characteristics, outcome, and prognosis. DESIGN Retrospective study (February 1, 2005-August 31, 2010). SETTING Animal poison control helpline. ANIMALS Three hundred thirteen dogs with presumed SSRI toxicosis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Dogs with presumptive SSRI medication toxicosis identified by a review of the electronic database of Pet Poison Helpline, an animal poison control center, were evaluated. No clinical signs were reported in 76.3% (239/313) of cases. The remaining 23.6% (74/313) of cases demonstrated the following clinical signs: neurological 79.7% (59/74), gastrointestinal 25.6% (19/74), cardiovascular 9.5% (7/74), respiratory 8.2% (6/74), and thermoregulatory 6.7% (5/74). Of the dogs exhibiting neurological signs, 62.7% (37/59) showed depression, 37.2% (22/59) showed hyperactivity, 10.1% (6/59) exhibited ataxia, and 1.7% (1/59) showed other miscellaneous signs (eg, hyperesthesia). There was a significant difference between the dose ingested by symptomatic and asymptomatic dogs for fluoxetine (P = 0.0039), but not with any other SSRI. Ninety-four patients were confirmed to have received veterinary care. In cases where duration of veterinary care was determined (55/313), 67.2% (37/55) of dogs were hospitalized and 32.7% (18/55) treated as outpatients. The average duration of hospitalization was 18.5 hours, excluding outpatient visits. Of those patients that had complete follow-up information available (136/313), overall survival was 100%. CONCLUSIONS The overall prognosis for animals with SSRI toxicosis is excellent with veterinary attention. Central nervous system depression was the most common clinical sign associated with SSRI toxicosis.

The effect of noncardiac disease on plasma brain natriuretic peptide concentration in dogs.

OBJECTIVE To evaluate the effects of noncardiac disease on c-terminal brain natriuretic peptide (cBNP) concentrations in dogs. DESIGN Prospective observational study. SETTING Urban university veterinary hospital. ANIMALS Thirty-eight apparently healthy dogs, 28 dogs with cardiac disease (14 CHF, 14 non-CHF), and 81 dogs with primary noncardiac diseases. INTERVENTIONS none. MATERIALS AND METHODS Plasma was collected from each dog and analyzed for active (cBNP) B-type natriuretic peptide using an assay that is being investigated for commercial use (Biosite). MEASUREMENTS AND MAIN RESULTS Dogs with CHF had significantly higher plasma cBNP concentrations than dogs with subclinical cardiac disease, apparently healthy dogs, or dogs with primary noncardiac disease. However, 21% (28/133) of dogs without CHF (including healthy dogs, dogs with primary noncardiac disease, and dogs with subclinical cardiac disease) had cBNP concentrations above previously identified diagnostic thresholds for CHF, reiterating the importance of reestablishing new diagnostic cutoffs when considering comorbidities affecting B-type natriuretic peptide levels. CONCLUSIONS A clinically relevant proportion of nondyspneic dogs with primary noncardiac diseases have increased cBNP concentrations that exceed previously identified diagnostic thresholds, potentially limiting the ability of this test to identify CHF when noncardiac comorbidities exist. Interpretation of increased cBNP concentrations in such cases must be appropriately interpreted with further diagnostic investigation.

Immune‐mediated hemolytic anemia and severe thrombocytopenia in dogs: 12 cases (2001–2008)

OBJECTIVE To identify and characterize the syndrome of immune-mediated hemolytic anemia (IMHA) with concurrent severe thrombocytopenia (<or=15.0 x 10(9) platelets/L; [15.0 x 10(3) platelets/microL]), and to evaluate prognostic factors, clinicopathologic findings, complications, treatment, outcome, and survival of dogs with this hematologic disorder. DESIGN Retrospective, observational study. SETTING Veterinary teaching hospital. ANIMALS Twelve client-owned dogs with IMHA and severe thrombocytopenia (<or=15.0 x 10(9) platelets/L; [15.0 x 10(3) platelets/microL]), without evidence of overt disseminated intravascular coagulation. INTERVENTIONS The following data were recorded and analyzed from the electronic medical record: signalment, history, concurrent diseases, clinical signs at presentation, clinicopathologic data, diagnostic testing, radiographic findings, treatment modalities, length of hospitalization, complications, and clinical outcome. All dogs were treated with immunosuppressive doses of corticosteroids. MEASUREMENTS AND MAIN RESULTS Twelve dogs were identified with the diagnosis of IMHA and severe thrombocytopenia; of these, 9 (75%) survived, 3 (25%) were euthanized, and none died. Dogs that survived were significantly younger than nonsurvivors (P=0.03). There were no specific clinical signs or therapies associated with survival. CONCLUSIONS Dogs in this study had a mortality rate similar to reported rates for dogs with either disease alone. Overall, younger dogs were more likely to survive. No association between different treatment modalities and overall survival was identified.

Selective serotonin reuptake inhibitor (SSRI) toxicosis in cats: 33 cases (2004–2010)

OBJECTIVE To evaluate a population of cats with selective-serotonin reuptake inhibitor (SSRI) toxicosis and characterize the population affected, list products ingested, the clinical signs observed, treatments performed, length of hospitalization, patient outcome, and overall prognosis. DESIGN Retrospective study from 2004 to 2010. SETTING Referral veterinary center. ANIMALS Thirty-three witnessed cat SSRI ingestions. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The medical records of cats with a witnessed SSRI ingestion identified by review of an animal poison control center electronic database were evaluated. The most common SSRIs ingested were venlafaxine (Effexor; 12/33; 36%), fluoxetine (Prozac; 12/33; 36%), citalopram (Celexa; 6/33; 18%), and escitalopram (Lexapro; 3/33; 9%). Overall, 24% of cats (8/33) became symptomatic, while 76% (25/33) remained asymptomatic. Of the symptomatic cats, sedation was the most common clinical sign (6/8; 75%), followed by gastrointestinal signs (4/8; 50%), central nervous system stimulation (1/8; 13%), cardiovascular signs (1/8; 13%), and hyperthermia (1/8; 13%). Veterinary care was sought in 20 cats (20/33; 61%). Sixteen cats (16/20; 80%) were hospitalized, while 4 cats (4/20; 20%) were treated as outpatients. Treatment for hospitalized patients included administration of IV fluid therapy (14/16; 88%), activated charcoal (12/16; 75%), anti-arrhythmic agents (7/16; 44%), methocarbamol (6/16; 38%), cyproheptadine (6/16; 38%), anti-emetics (5/16; 31%), and sedation (5/16; 31%). Diagnostics included blood work (7/16; 44%), blood pressure measurement (3/16; 19%), and electrocardiogram monitoring (2/16; 13%). Mean hospitalization time for all cases of SSRI ingestion was 14.6 ± 7.8 hours (n = 16). All symptomatic cats in this study (8/8; 100%) had resolution of clinical signs and survived to discharge. CONCLUSIONS The prognosis for SSRI ingestion in this population of cats was excellent. Decontamination and supportive care for at least 12-24 hours can be considered in cats with SSRI ingestion, particularly venlafaxine to monitor resolution of clinical signs.

Baclofen toxicosis in dogs and cats: 145 cases (2004-2010).

OBJECTIVE To identify dogs and cats with baclofen toxicosis and characterize the patient population, clinical signs, and outcome. DESIGN Retrospective case series. ANIMALS 140 dogs and 5 cats with baclofen toxicosis. PROCEDURES An animal poison control center electronic database was reviewed from November 2004 through April 2010 to identify dogs and cats with baclofen toxicosis. Information on signalment, clinical signs, and amount of baclofen ingested was obtained. Clinical signs were categorized as CNS, gastrointestinal, general malaise, cardiovascular, respiratory, or urogenital. Follow-up communications were performed to determine overall outcome. RESULTS Dogs had a median age of 0.67 years (range, 0.1 to 15 years) and cats of 1 year (range, 0.7 to 16 years). Of 145 patients, 133 (92%) developed clinical signs of baclofen toxicosis. A total of 259 signs fell within defined categories: CNS (121/259 [46.7%]), gastrointestinal (69/259 [26.6%]), general malaise (27/259 [10.4%]), cardiovascular (23/259 [8.9%]), respiratory (14/259 [5.4%]), and urogenital (5/259 [1.9%]). For 68 dogs with known survival status, survival rate was 83.8% (57/68); of these dogs, the amount of baclofen ingested was known for 53 (46 survivors and 7 nonsurvivors). Amount of baclofen ingested was significantly lower in survivor dogs (median, 4.2 mg/kg [1.91 mg/lb]; range, 0.61 to 61 mg/kg [0.28 to 27.7 mg/lb]), compared with nonsurvivor dogs (median, 14 mg/kg [6.4 mg/lb]; range, 2.3 to 52.3 mg/kg [1.04 to 23.77 mg/lb]. Of 5 cats, 2 survived, 1 died, and 2 had unknown outcomes. CONCLUSIONS AND CLINICAL RELEVANCE Clinical signs of baclofen toxicosis occurred in most patients, with the CNS being the system most commonly affected.

Sleep aid toxicosis in dogs: 317 cases (2004-2010).

OBJECTIVE To summarize the signalment, clinical signs observed, time to onset of clinical signs, duration of clinical signs, and the outcome in a large case series of nonbenzodiazepine sleep aid ingestions in dogs, including 2 sleep aids that have not been previously described in the veterinary literature. DESIGN Retrospective study conducted between 2004 and 2010. SETTING An animal poison control center based out of Bloomington, MN. ANIMALS During this time frame, 453 cases were identified involving 467 dogs. Of these cases, 150 cases were excluded due to incomplete medical records, multipet households, or the inability to calculate a dose exposure. A total of 317 dogs with presumed sleep aid medication toxicosis were included. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Records of dogs with sleep aid medication toxicosis identified by a review of an animal poison control center electronic database were evaluated. The most common sleep aid medications ingested were zolpidem (240/317 [75.7%]), eszopiclone (62/317 [19.5%]), and zaleplon (15/317 [4.7%]). Overall, clinical signs developed in 36% of patients (115/317), while 64% (202/317) remained asymptomatic. The most common organ systems affected and clinical signs seen involved the central nervous system (eg, agitation, sedation) and gastrointestinal tract (eg, anorexia, hypersalivation, vomiting). CONCLUSIONS Overall, the prognosis for dogs with sleep aid medication toxicosis was excellent, and no fatalities were reported in this clinical population. As significant clinical signs can still be seen with ingestion, appropriate decontamination is warranted in asymptomatic patients via emesis or gastric lavage, followed by activated charcoal administration. Symptomatic patients should be hospitalized for monitoring and supportive care for a minimum of 12 hours or until clinical signs resolve.