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Veterinarian Technician August 2013 (Vol 34, No 8)

Case Study: Baclofen Toxicosis

by Jerzy Kotlowski, CVT, VTS (ECC)

    Gizmo—a 3-year-old, 12.1-lb (5.5-kg), neutered Shih Tzu mix—was found lying on the floor, vocalizing, and vomiting. Before the owner rushed Gizmo to the emergency hospital, he found a chewed bottle of Ritalin (Novartis; methylphenidate hydrochloride), which is used for treating attention-deficit/hyperactivity disorder in humans. Gizmo was suspected to have ingested 15 to 25 5-mg tablets. On triage, his vital parameters were as follows:

    Attitude: hyperactive and vocalizing

    Temperature: 99.3°F (37.4°C; normal range: 100.5°F to 102.5°F)

    Pulse: 94 bpm (normal range: 60 to 140 bpm)

    Respiration: 120 breaths/min (panting; normal range: 1 to 30 breaths/min)

    Mucous membranes: pink

    Capillary refill time: <2 seconds (normal range: 1 to 2 seconds)

    Systolic blood pressure (BP): 156 mm Hg (normal range: 100 to 160 mm Hg)

    Neurologic status: recumbent, hypesthesic, vocalizing, mydriasis, convulsions

    After 1.5 hours, Gizmo became more hypothermic (95.7°F; 35.4°C) and hypotensive (systolic BP: 70 mm Hg). He was constantly drooling, regurgitating, and breathing irregularly.

    Glossary

    Hypesthesia—abnormally high sensitivity to stimuli of the senses
    Lipophilicity—affinity for fat
    Mydriasis—excessive dilation of the pupil(s) due to disease, trauma, or drug use
    Ptyalism—excessive flow of saliva

    Diagnosis

    Complete blood work, imaging, and neurologic consultation were performed. The results of the complete blood count were normal. A serum biochemistry profile showed high levels of alanine aminotransferase (102 IU/L; normal range: 5 to 95 IU/L) and creatine kinase (416 IU/L; normal range: 5 to 235 IU/L) and low levels of potassium (3.3 mmol/L; normal range: 5.9 to 5.7 mmol/L), chloride (106 mmol/L; normal range: 107 to 123 mmol/L), and pH (7.3; normal range: 7.35 to 7.45). Thoracic radiography was performed to rule out aspiration pneumonia due to irregular breathing, drooling, and occasional regurgitation. The full mental status and neurologic examinations found depression, delirium, stupor, mydriasis, and ptyalism.

    Therapy

    When Ritalin toxicosis was suspected, we called an animal poison control helpline, which recommended treatment using chlorpromazine, acepromazine, or methocarbamol. If seizures occurred, administration of phenobarbital was recommended; if this did not resolve the seizures, intubation and maintenance of anesthesia using isoflurane were also recommended. Arrhythmias could be treated with lidocaine or propanolol. None of these treatments was needed. Instead, advanced monitoring and oxygen supplementation (100%) via flow-by mask were implemented. For toxin absorption, activated charcoal was given via a nasogastric tube. Gizmo was then transferred to the intensive care unit.

    Soon after nasogastric medical therapy finished, Gizmo had periods of apnea and respiratory arrest, so he was intubated and supported with manual intermittent breathing by Ambu bag and oxygen supplementation for the first 24 hours. Hypothermia was controlled using a Bair Hugger (Arizant Healthcare). A 5-French urinary catheter with a closed collection system was placed to measure urine output. Nursing care was performed every 4 hours and included urinary catheter care, oral care using mouthwash to prevent bacterial growth, and application of lubricant to the eyes. The patient and endotracheal tube were repositioned every 6 hours. Continuous multiparameter monitoring included electrocardiography, oxygen saturation (Spo2), the end-tidal carbon dioxide level, body temperature, direct BP (via a 22-gauge arterial catheter in the pedal artery), and indirect BP (via Doppler ultrasonography).

    Hypotension was initially treated with two crystalloid fluid (Plasma-Lyte, Abbott Animal Health) boluses at a shock rate of 80 mL/kg for 15 minutes and two boluses of the plasma volume expander Pentaspan (Bristol-Myers Squibb; 2 to 3 mL/kg/d). Hypotension was finally corrected with vasopressor therapy: dopamine at 5 to 10 µg/kg/min CRI. This treatment was provided at the end of the first day.

    The following day, the owner reported that Gizmo had ingested baclofen (20 10-mg tablets; 38 mg/kg) instead of Ritalin. Baclofen is a muscle relaxant with toxicity known to cause respiratory arrest, dyspnea, vomiting, seizures, vocalization, and tremors. We called the helpline, which recommended administration of Intralipid 20% (Baxter Healthcare), along with IV fluid and advanced vital monitoring for novel treatment of baclofen toxicosis. A second small-bore, 22-gauge, 1.14-inch intravenous catheter was placed, and a bolus of Intralipid 20% (1.5 mL/kg over 10 min) was administered, followed by a second infusion (18 mL/kg over 1 h). After this treatment, Gizmo’s mental status immediately improved. Although not ambulatory, Gizmo was partially responsive and was breathing independently. Advanced monitoring and all supportive treatment for BP were discontinued. After 70 minutes, Gizmo was ambulatory but not completely coordinated. During the next 3 hours, he began walking outside and eating on his own. During the next 8 hours, his neurologic function continued to improve with the infusion of Intralipid 20% (0.5 mL/kg) and crystalloid Plasma-Lyte (3 mL/h), which were continued for the day and discontinued overnight. Gizmo recovered completely, without neurologic abnormalities, and was discharged the next day.

    Discussion

    Baclofen is a skeletal muscle relaxant that affects γ-aminobutyric acid–agonist receptors in the spinal cord. In people, baclofen is used for treating multiple sclerosis; a clinical trial is assessing whether the drug could be used to treat alcohol addiction. In dogs, the drug is used off label for urine retention. The drug’s inhibitory effect on reflex activity reduces muscle tension, causing flaccid paralysis of skeletal muscle. However, in the toxic dose range, baclofen penetrates the blood-brain barrier, stimulating protein P, reducing secretion of epinephrine and norepinephrine, and leading to central nervous system dysfunction, respiratory distress, or bradycardia. The toxic signs (e.g., ataxia, coma, bradycardia, thoracic muscle paralysis, pulmonary edema, death) can occur within 15 minutes of ingestion. The half-life of the drug can be a few hours to several days, depending on the dose. Baclofen is mainly metabolized in the liver and the kidneys and is lipophilic (lipid soluble). This is the main reason why Intralipid 20% was recommended as an antidote in Gizmo’s treatment. Intralipid 20% is known as a high-calorie (1 mL = 2 kcal) component of total parenteral nutrition for patients in intensive care. Intralipid 20% is a white emulsion made of purified soya bean oil, egg phospholipids, purified water, and glycerin. The mixture, consisting of fatty acids with equal numbers of medium- and long-chain triglycerides, is a strong colloid with an osmolality of 260 mOsm/L and a good source of energy (adenosine triphosphate). When Intralipid 20% is rapidly infused into patients that have ingested lipid-soluble drugs, the lipophilic components of the drugs bind with long-chain triglycerides of Intralipid, altering the kinetic activity of the drug and greatly diminishing its diffusion into cells, thereby preventing cell damage. Infusion of the drug results in a high level of free fatty acids (FFAs) in the plasma, creating the “lipid sink” phenomenon, which is due to a concentration gradient between the plasma and the extracellular fluid. FFAs can attract the toxin and create a weak chemical bond in the mitochondrial inner membrane, neutralizing and moving the toxin from affected cells into the intravascular space, from which FFAs are excreted like other lipids. This process allows the body to recuperate quickly from intoxication. Treatment success and patient recovery depend on the form of the drug and its lipophilicity. This therapy can be used to treat other drug toxicities.

    Acknowledgment

    The author thanks Monica Rosati, BSc, DVM, DVSc, DACVA, for her help.

    Suggested Reading

    Fernandez AL, Lee J, Rahilly L, et al. The use of intravenous lipid emulsion as an antidote in veterinary toxicology. J Vet Emerg Crit Care 2011;21(4):309-319.

    Lee J. Advances in toxicology: the use of intra-lipid therapy & high dose insulin therapy. Proc ACVIM Forum 2010:674-676.

    Rothchild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med 2010;18:51.

    Wismer T. Toxicology brief: baclofen overdose in dogs. Vet Med 2004:406-410.

    NEXT: Equine Essentials: Case Report: Rehabilitating a Foal After Trauma

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