The Case of the Missing History – Albuterol ToxicosisAugust 13, 2019

The Case of the Missing History - Albuterol Toxicosis

Shelley Smith, DVM, DACVECC

The below case highlights the importance of a thorough work-up and avoiding jumping to conclusions prior to having all the facts.

Presentation:

Lily, a 5-year old SF English Shepherd presented to our emergency room at 9am on a Wednesday morning in early spring after being found unable to rise from her crate. The owners immediately rushed her to the hospital and she was gurneyed to the ICU for evaluation.

History:

The owners report that she had been limping on the right hind limb for the past two weeks. Additionally, they live in a region with a high incidence of ticks and had pulled several off her recently. There was no other pertinent history and she is not on medications at home. The owners report no exposure to toxins.

Physical examination:

On physical examination, she was 28.9kg, had a temperature of 102.4F, HR 132, RR 80 with clear lungs, CRT 2 seconds, pink, moist gums. No other pertinent findings on her physical examination however, neurologic examination revealed Lily to be holding her head down, tetraparetic with decreased withdrawal x4, knuckling x4, normal to increased patellar reflexes x4, intact panniculus, and normal mentation.  She had no neck or back pain. Over the next hour, her motor skills declined rapidly and she was unable to lift her head or move her limbs.

Differential diagnoses:

For the first hour of my evaluation with Lily, I was grappling with the differential diagnoses. Intervertebral disc disease (cervical) was my first thought based on her knuckling and falling forward, however the lack of pain and poor hind limb withdrawal reflex made this mostly impossible. Lower motor neuron diseases such as tick paralysis, polyradiculoneuritis, botulism, and myasthenia gravis or toxins (ciguatera/tropical fish toxicity, etc) seemed more appropriate yet the normal patellar reflex did not fit the picture.  At this point I was planning on shaving Lily down to look for a tick and considering an MRI. I even considered administering neostigmine to test for myasthenia Dog_1gravis. Something felt very wrong about this diagnosis, however, due to the inconsistent neurologic localization – severely decreased withdrawal with normal patellar reflex? Minute by minute she was becoming weaker.

Diagnosis:

Thankfully, the owners were willing to dig deeper and perform labwork, which held the answer. At times, when faced with a rapidly decompensating patient, owners can become overwhelmed and even suggest euthanasia for fear their loved one is suffering. In these times, it is extremely important to slow down and obtain as much information as reasonably possible before allowing the owners to make such rash decisions. Our baseline labwork showed that Lily was suffering from severe hypokalemia at 1.8mmol/L (3.7-5.8mmol/L). Further, her phosphorus was found to be 2.4mg/dL (2.9-6.6mg/dL). When the owner was asked directly about exposure to albuterol, he admitted that, yes, he is on albuterol and has several vials on the kitchen table currently, but she cannot reach the vials. In the owner’s mind, Lily had no access to this medication as it was on the tabletop and therefore did not mention it earlier. After a thorough search of the home, a chewed albuterol vial was discovered hidden in the dog crate as if she took it there as her treat to enjoy.

When asked if Lily was on medications the answer was “no”.  So often we as veterinarians do not make the leap to asking if the owner is on medications since we do not like to pry into the owner’s medical life, however, we need to remember we are advocates for the cats and dogs and this dog_2information may be crucial.When directly asked on presentation if she had exposure to any toxins, the answer was no since an owner would not consider his own albuterol inhaler a “toxin”, as a result it didn’t come up in the discussion of the history around this case.  Aha!

I felt it prudent to bring this case to the attention of the veterinary community as this was an otherwise healthy dog with seemingly progressive paresis and plenty of tick exposure. Without chronic concurrent metabolic disease (DKA, chronic renal failure, hyperaldosteronism, etc), low potassium did not fit the clinical picture unless, of course, exposure to a beta-agonist is a factor.

This was an unusually severe presentation of albuterol toxicosis, but case reports from the literature describe cases this dire. We, as veterinarians, are often not given the full truth from the owner either as an intentional or accidental omission and can jump to incorrect conclusions. Sometimes this may end with just a bad haircut but could be as catastrophic as a euthanasia. Thankfully this particular owner was able to financially and emotionally continue to search for the answer.

Treatment:

Albuterol is a common medication used to treat asthma in people and animals. Overdose in dogs occur when the inhaler or vials are chewed or the tablets ingested. The medication is a beta-2 agonist used for its bronchodilatory effects on bronchial smooth muscle by production of cyclic AMP.  Via actions on Na+/K+ ATPase, potassium and phosphorus are moved intracellularly. The action on potassium is not clinically relevant at prescribed doses, however, with an overdose via inhalation or ingestion, this can be catastrophic. Albuterol has minimal beta-1 agonism, however, with overdose, tachycardia and increased cardiac contractility will occur. This in turn causes a higher myocardial oxygen demand and can results in dysrhythmias and heart failure. Signs of toxicity can occur within 30 minutes of exposure but may take up to 4-6 hours to show themselves.

There are two main avenues of attack for treatment of albuterol toxicosis: beta-blockade and potassium supplementation. Care should be taken as over-supplementation and HYPERkalemia can occur rapidly.

1. Beta-blockage:

Propranolol at 0.02mg/kg IV slowly over 5 minutes and monitor the heart rate. Heart rate reduction is a great sign that this medication is working.   Repeat this dose as needed until a heart rate reduction (goal is less than 180) and improvement in clinical signs is seen. Repeated doses up to 0.1mg/kg are considered safe if given slowly. Bradycardia and hypotension are side effects of overdosage, so go slow and monitor the ECG and blood pressure closely. Care should be used with underlying systolic dysfunction. The half life of IV propranolol is less than one hour. Albuterol can linger and cause side effects for up to 24 hours, so the patient should be closely monitored for recurrence of clinical signs.

If injectable propranolol if not stocked and referral to an emergency clinic not possible, oral propranolol can be administered at 0.1-0.2mg/kg PO up to a max of 1.5mg/kg every 8 hours.  The oral formulation can take 2 hours to start to take effect and therefore is not easily titratable or ideal.

2. Potassium supplementation

Start at 0.25mEQ K+/kg/hr for the first 2-4 hours: For example in a 10 kg dog, add 10 mEQ (5mL) KCL to 35mL balanced isotonic crystalloid (LRS, 0.9% NaCL, Plyte, NormR) and run at 10ml/hr on a syringe pump.  Potassium can be mixed into a larger volume if this is easier, but know the K+ requirements will change rapidly supplementation may be needed only for a short time. Monitor K+ every 30-60 minutes. The 2 mEQ/mL KCL has an osmolarity of 4000 mOsm/L and should be diluted at least 1:4 prior to IV administration.   This fluid can NEVER be flushed as rapid administration of potassium causes severe bradycardia and cardiac arrest. Do not exceed dog_30.5mEQ K+/kg/hr. Due to the half-life of albuterol and concurrent supplementation with propranolol, potassium supplementation is rapidly weaned and discontinued as the patient clinically improves. I strongly encourage blood work every 30 -60 minutes as oversupplementation with potassium can occur leading to catastrophic results if not careful. Once the potassium reaches over 3mmol/L, weaning or discontinuing the supplementation while monitoring K+ should be performed. Potassium should be monitor for 2-4 hours after normalization to watch for any lingering albuterol.

Lily’s treatment:

Lily required 3 doses of propranolol for a total dosage of 0.06mg/kg within the first hour. Her potassium supplementation was started at 0.25mEQ K/kg/hr. Her solution was made by adding 50 mEQ (25mL) to one liter of LRS and run at 140ml/hr. I started with 2 doses of propranolol in rapid succession due to lack of heart rate reduction after the first dose and then rechecked the electrolytes at 30 minutes and the potassium had only increased to 2.17mmol/L.  I administered another dose of propranolol and the heart rate reduced to 160bpm. Thirty minutes later the potassium was found to be 3.9 mmol/L.  At that point, her fluids were reduced by 50% to supplement K+ at 0.125mEQ K+/kg/hr. One hour later, the potassium was 5.01mmol/L and the KCL discontinued. One hour later the potassium was found to be 5.8mmol/L.  This was monitored and 6 hours later leveled out at 4.3mmol/L. After that first hour of treatment, she slowly became stronger and within 4 hours was able to walk, albeit slowly and with ataxia. By 12 hours after ingestion, Lily was back to herself!

Conclusion:

The two take-home points I hope to get across with this article are 1) Go with your gut. If the diagnosis (tick paralysis?) doesn’t feel right, push for more testing, ask more questions; it will be worth it.  And 2) Be very careful with potassium supplementation. Unfortunately I have seen patients go into cardiac arrest secondary to overzealous potassium supplementation. When preparing the infusion, care must be taken to inform all staff members of the risks of too rapid infusion and signs posted on the pump and line/catheter stating “DO NOT FLUSH”. Larger, more dilute bags of potassium can be prepared to  reduce the risk of this occurrence such as adding 100 mEQ KCL to 1000mL of crystalloid such as LRS, running at 50ml/hr for a 20 kg patient (0.25mEQ K/kg/hr). Along the same lines and very worth repeating, once treatment is initiated with the appropriate dose of propranolol, the potassium will respond accordingly. This potassium was never “lost” from the body; it moved intracellularly and with the help of propranolol will move extracellularly once again. Therefore, if a high amount of supplemental K+ is administered intravenously and then the already present intracellular K+ returns to its original location, severe hyperkalemia can occur. My advice is to place a continuous ECG on the patient and set a timer to go off every 30 minutes for a potassium recheck so the patient is not forgotten in the busy veterinary setting.

References:

Sobczak, B. Albuterol Toxicosis in a Pit Bull Terrier. Vet Med DVM 360March 2015; 110 (3): 69-70.

McCown J, et al. Suspected albuterol toxicosis in a dog. J Am Vet Med Assoc April 2008;232(8):1168-71.

About our Team

Shelley Smith, DVM, DACVECC

Dr. Shelley Smith received her degree in veterinary medicine from Tufts University in 2007. After graduation, she completed a one-year rotating internship at Angell Animal Medical Center in Boston, MA, followed by a one-year emergency and critical care specialty internship and a three-year emergency and critical care residency at VCA Veterinary Referral Associates in Gaithersburg, MD. During her residency, she published one article on spontaneous pneumothorax and a second on intra-abdominal hypertension, she received the resident teaching award in 2011.

Dr. Smith is board certified by the American College of Veterinary Emergency and Critical Care. Following her residency, Dr. Smith worked as a criticalist at the VCA Shelley Smith, DVM, DACVECCShoreline Veterinary Referral and Emergency Center in Shelton, CT until 2015 and The Center of Veterinary Expertise in Suffolk, VA. She joined Capital District Veterinary Referral Hospital in June 2017.

Dr. Smith’s interests include metabolic emergencies, sepsis, and polytrauma. She has become proficient in the utilization of thoracic and abdominal ultrasound in triage and monitoring of these patients.

In her free time, she enjoys spending time with husband, daughter, and collection of pets. She also enjoys relaxing with a good book and outdoor activities such as trail running.

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