Hypercalcaemia Refresher

 (From http://www.chem4kids.com/files/elements/020_shells.html

(From http://www.chem4kids.com/files/elements/020_shells.html

Basic physiology:

Hypercalcaemia is a common electrolyte disturbance in both cats and dogs. The differential diagnosis list is vast for both species with several options for both acute and chronic causes. 

Three forms of circulating calcium exist:

  • Ionised/free (biologically active)
  • Protein-bound
  • Complexed (to phosphate, bicarbonate, lactate, citrate and oxalate)

From a clinical standpoint, the ionised form is the most useful. Ideally it should be used to help guide treatment in these patients as it is considered to indicate functional calcium levels. 

Calcium regulation is complex and divided into both short-term/minute-to-minute control and long-term control. Parathyroid hormone (PTH) is synthesised in and secreted from the parathyroid glands in response to hypocalcaemia or low levels of calcitriol. PTH is secreted constantly to help maintain tight calcium control. It acts to increase calcium via increased tubular resorption in the kidneys; increased osteoclastic bone resorption; and increased calcitriol. 

Unlike humans, dogs and cats cannot synthesise vitamin D and require it in their diet. Vitamin D levels are inherently tied to calcium levels. Small animal veterinarians are seeing more frequent cases of vitamin D toxicosis related to ingestion of multivitamin supplements. Once ingested, vitamin D is converted to calcidiol in the liver and further converted to calcitriol in the kidneys. Calcitriol acts to:

  • Increase absorption of calcium in the intestines
  • Increase healthy bone formation
  • Promote renal calcium and phosphorus resorption
  • Inhibit PTH synthesis in the parathyroid gland 

As previously discussed, ionised calcium is the preferred parameter for interpretation in animals suspected of being hypo- or hypercalcaemic. Total calcium is often more available for many veterinarians. However in a sick patient, this parameter is often a sub-optimal indicator of ionised calcium. Formulae to convert total calcium into ionised calcium have been recommended in the past. However they are no longer considered valid and reliable. 

Clinical signs:

Common clinical signs of hypercalcaemia include polyuria/polydipsia (more common in dogs), anorexia, constipation, lethargy and weakness.
In severely affected animals, neurological signs including obtundation, twitching and seizures are possible but rare.
Cardiac abnormalities including certain bradydysrhythmias (especially atrioventricular block) are possible but also not commonly seen.

Clinical hypercalcaemia is diagnosed by measured ionised hypercalcaemia (> 5-6 mg/dl or 1.4-1.5 mmol/l) in the face of suitable clinical signs.


Hypercalcaemia causes table.png

The most common cause of hypercalcaemia in dogs is neoplasia with lymphoma being the most common followed by apocrine anal gland adenocarcinoma.

In cats the idiopathic form is most common followed by renal failure and neoplasia.

Lymphoma is believed to cause hypercalcaemia due to release of PTHrp which acts in a similar way to PTH. There is an assay which can be used to measured PTH and PTHrp levels in dogs to help differentiate hypercalcaemia of malignancy from non-neoplastic causes.


Acute therapy for hypercalcaemia usually includes:

  • Diuresis with intravenous fluids and diuretics
  • Glucocorticoids
  • Bisphosphonates
  • Calcitonin

The fluid of choice is 0.9% sodium chloride (NaCl, ‘normal’saline). Sodium competes with calcium in the renal tubules allowing increased calcium loss into the urine. A typical fluid rate would be 1.5-2 times the patient’s maintenance fluid rate.

In additional to fluids, loop diuretics like furosemide can be used although they may need to be used cautiously in azotaemic animals. Furosemide given as a continuous rate infusion may promote more rapid diuresis and less potassium loss versus intermittent bolus administration. Thiazide diuretics are contraindicated as they promote calcium retention.

Glucocorticoids reduce bone resorption and intestinal calcium resorption and increase renal excretion. They need to be used cautiously in the absence of a definitive diagnosis as they may impede accurate diagnosis of certain types of neoplasia, especially lymphoma and multiple myeloma.

Calcitonin can act rapidly to reduce calcium levels, sometimes causing a profound hypocalcaemia. In certain countries the cost of this agent is preclusively expensive. Furthermore, the patient can grow tolerant to its affects reducing its utility for long-term calcium control.

In contrast to calcitonin, bisphosphonates take longer to reduce calcium levels (typically 2-3 days) but can have long-lasting effects (1-3 weeks). Pamidronate is the most common bisphosphonate used in veterinary medicine. It does need to be used carefully in dehydrated patients or those who are azotaemic as there are reports of nephrotoxicity in people – although this is usually seen when the drug is administered rapidly over a 1-2 hour period. Oral forms of bisphosphonate (alendronate) offer another long-term solution albeit it can cause gastrointestinal side-effects in some patients.

Hypercalcaemia treatment table.png

Carbon Monoxide Poisoning and Smoke Inhalation

By Lisa Murphy DACVECC

Carbon Monoxide Poisoning

Carbon monoxide (CO) is a colourless, odourless gas which is produced by combustion of hydrocarbons from fires, car exhausts, charcoal grills and also endogenously via erythrocyte and haem catabolism. A normal carboxyhaemoglobin (COHb) level in dogs and cats is approximately 1-3%. In the normal environment, CO has a concentration of 0.001%; however inhalation of air containing 0.1% CO can result in COHb levels > 50%. The most common routes of exposure to CO in small animal patients include smoke inhalation, gas heaters and running generators. 

Following inhalation, CO is absorbed rapidly at the level of the alveoli. The amount of CO absorbed will depend on several factors including the patient’s minute ventilation (respiratory rate x tidal volume), duration of exposure and the concentration of CO in the environment. Once absorbed, a small amount will be oxidised into carbon dioxide and the remainder is bound to haem proteins. 

Carbon monoxide interacts with haemoglobin. It has 200x the affinity for haemoglobin when compared to oxygen. It, therefore, displaces oxygen from haemoglobin affecting normal haemoglobin release of oxygen to the tissues. Carbon monoxide binds 2/4 of the available haem groups within each molecule of haemoglobin. This reduces the oxygen-carrying capacity of the haemoglobin by 50% shifting the oxyhaemoglobin dissociation curve, see below. Furthermore, any oxygen which is bound by haemoglobin finds it more difficult to dissociate due to changes in the chemical equilibrium following CO binding. This leads to subsequent tissue hypoxia and cellular shock.


Carbon monoxide also has direct toxic effects on cells. In the case of cardiac and skeletal muscle, CO binds to myoglobin and reduces the contractile functions. In the case of cardiac cells, this can decrease cardiac output worsening tissue hypoxia. Finally, CO may also cause:

  • sequestration of white blood cells
  • increased nitric oxide production (which can affect blood pressure regulation)
  • reperfusion injury
  • lipid peroxidation (which leads to damaged cell membranes), and
  • direct neurotoxicity as it can act as a stimulatory neurotransmitter

Clinical signs of CO poisoning will depend on the amount inhaled but can include lethargy, depression, disorientation, seizures, tachypneic, nausea and vomiting. Severe poisoning in people may also cherry-coloured mucous membranes. Veterinary retrospective studies have reported hyperaemic mucous membranes in a minority of dogs and cats.

Diagnosis of CO poisoning requires measurement of COHb levels via a co-oximetry machine. Pulse oximetry is inaccurate and will falsely elevate SpO2 levels in these cases. Pulse oximetry is based on the ratio of light absorbed by tissues at two different wavelengths (660nm to 940nm) and only measures oxyhaemoglobin and deoxyhaemoglobin. Carboxyhaemoglobin and oxyhaemoglobin have similar light absorption and are indistinguishable via a pulse oximeter. In contrast, a co-oximetry machine can give specific levels of oxyhaemoglobin, COHb and methaemoglobin. Venous samples are adequate for measurement of COHb although arterial samples will give more information regarding the patient’s oxygenation status. 

The most important aspect of treatment in these cases is oxygen supplementation. Elimination of COHb depends on minute ventilation and the fraction of inspired oxygen (FiO2). Increasing FiO2 will decrease the half-life of COHb as dissolved oxygen competes with CO for binding sites on haemoglobin. Once displaced from haemoglobin, CO is exhaled via the lungs.

In a patient breathing room air with a FiO2 of 21%, the half-life of CO is 4-6 hours. This decreases to 40-80 min at a FiO2 of 100% which can only be achieved with mechanical ventilation. Less invasive options for oxygen therapy include oxygen cages, nasal prongs and nasal cannulas among others. In animals with concurrent airway damage from smoke inhalation, the half-life may be slightly longer due to reduced efficiency of gas exchange. Hyperbaric oxygen chambers, which are not commonly available in veterinary medicine, can further reduce the CO half-life to 15-30 minutes. Human studies have not conclusively proven however that hyperbaric oxygen therapy offers significantly improved outcomes when compared to normobaric oxygen therapy. 

Care of the Smoke Inhalation Patient 

Regardless of whether or not they have significant CO poisoning, smoke inhalation patients may be dyspnoeic for multiple reasons. Reduced lung compliance from atelectasis and impaired lung surfactant function is common and leads to significant pulmonary oedema. The normal mucociliary escalator which acts to aid in the removal of irritant substances from the airway is impaired. This can lead to mucosal oedema, sloughing and damage to the tracheal and bronchial epithelium in the ensuing hours.

It is important to note that while these patients may be at risk of secondary bacterial pneumonia, signs of infection will not be seen for at least 12-24 hours; moreover, the risk of clinically significant infection is thought to be low. The empirical use of antibiotics in similar human patients has not been conclusively shown to improve outcomes so prophylactic antibiotics are not recommended for these patients. 

Other important treatment considerations include:

  • Judicious intravenous fluid therapy especially in patients with severe dermal burn injuries.
  • Steroid use has been associated with an increased incidence of bacterial pneumonia and is not recommended.
  • Diuretics are also controversial. While diuretics are of benefit in hydrostatic oedema associated with congestive heart failure, there is less evidence supporting their use in cases of oedema due to increased permeability as in the case of smoke inhalation injury. They should be avoided in hypovolaemic or dehydrated patients.
  • Bronchodilators including the methylxanthines (aminophylline, theophylline) and beta-adrenergic agonists (terbutaline) can also be used. Many human studies recommend nebulised bronchodilators, see below.
  • N-Acetylcysteine (NAC) is used for its mucolytic properties and as a free radical (reactive oxygen species) scavenger, it may reduce reperfusion injury. Several human studies have shown benefit to using it in nebulised form to attenuate the lung injury associated with smoke inhalation and burns. 

Several drugs can be administered in aerosolised form. Most notably, bronchodilators like albuterol are recommended in human patients. Furthermore, several adult and paediatric human studies have reported benefit of aerosolised heparin which has anti-inflammatory effects. One veterinary study evaluating aerosolised heparin in research dogs did not report any benefit. While N-acetylcysteine can be administered in nebulised form, it can be irritant to the airways and cause bronchospasm when given via this route. It is important to note that dyspnoeic veterinary patients are easily stressed, and some could worsen with the restraint involved in administering aerosolised medications. 

In addition to the above, some of these patients can sustain corneal injuries from exposure to high temperatures and will require ophthalmic medications to promote healing.  

Delayed Neurological Sequelae

Delayed neuropsychiatric syndrome (DNS) has been described in humans who have experienced significant CO toxicity. Typically, signs develop within 3-240 days post exposure and can lead to cognitive dysfunction, personality changes, ataxia and deafness. The risk of DNS is highest with COHb levels > 25%. The exact mechanism of DNS is not known but it is not believed to be solely from hypoxia.

In a retrospective evaluation of dogs who had experienced CO poisoning, neurological dysfunction was noted to occur 2-6 days following exposure in 5/11 dogs evaluated. Anecdotally, in the author’s experience, 2 dogs who had been treated for CO poisoning following house fires developed suspect DNS with one dog developing behavioural changes and aggression and the other developing seizures. While seizures in these cases can be managed with standard anticonvulsive medications, therapy for behavioural changes is more difficult to recommend at this time. 


Beasley, V.R., 1990. Smoke inhalation. Veterinary Clinics of North America: Small Animal Practice, 20(2), pp.545-556.

Vaughn, L., Beckel, N. and Walters, P., 2012. Severe burn injury, burn shock, and smoke inhalation injury in small animals. Part 2: diagnosis, therapy, complications, and prognosis. Journal of Veterinary Emergency and Critical Care, 22(2), pp.187-200.

Berent, A.C., Todd, J., Sergeeff, J. and Powell, L.L., 2005. Carbon monoxide toxicity: a case series. Journal of veterinary emergency and critical care, 15(2), pp.128-135.

Mariani, C.L., 2003. Full recovery following delayed neurologic signs after smoke inhalation in a dog. Journal of Veterinary Emergency and Critical Care, 13(4), pp.235-239.

Norkool, D.M. and Kirkpatrick, J.N., 1985. Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: a review of 115 cases. Annals of emergency medicine, 14(12), pp.1168-1171.

Weaver, L.K., Hopkins, R.O., Chan, K.J., Churchill, S., Elliott, C.G., Clemmer, T.P., Orme Jr, J.F., Thomas, F.O. and Morris, A.H., 2002. Hyperbaric oxygen for acute carbon monoxide poisoning. New England Journal of Medicine, 347(14), pp.1057-1067.

Weaver, L.K., 2009. Carbon monoxide poisoning. New England Journal of Medicine, 360(12), pp.1217-1225.

Monthly Journal Round-Up - April 2018

Thanks as always to Lara Brunori DVM CertAVP MRCVS

Clinical studies:


  • Bhalla, R.J. et al. (2018) ‘Comparison of intramuscular butorphanol and buprenorphine combined with dexmedetomidine for sedation in cats’. Journal of Feline Medicine and Surgery, 20(4), pp.325-331
  • Sylvane, B. et al. (2018) ‘Effect of cross-match on packed cell volume after transfusion of packed red blood cells in transfusion-naïve anemic cats’. Journal of Veterinary Internal Medicine, doi: 10.1111/jvim.15120 (Early view)
  • Ateca, L.B. et al (2018) ‘Evaluation of the relationship between peripheral pulse palpation and Doppler systolic blood pressure in dogs presenting to an emergency service’. Journal of Veterinary Emergency and Critical Care, doi: 10.1111/vec.12718 (Early view)


  • Lux, C.N. et al. (2018) ‘Perioperative mortality rate and risk factors for death in dogs undergoing surgery for treatment of thoracic trauma: 157 cases (1990-2014)’. Journal of the American Veterinary Medical Association, 252(9), pp.1090-1097. 
  • Gremillion, C.L. et al. (2018) ‘Radiographic findings and clinical factors in dogs with surgically confirmed or presumed colonic torsion’. Veterinary Radiology & Ultrasound, doi: 10.1111/vru.12595 (Early view)


  • Ash, K. et al. (2018) ‘Performance evaluation and validation of the animal trauma triage score and modified Glasgow Coma Scale with suggested category adjustment in dogs: A VetCOT registry study’. Journal of Veterinary Emergency and Critical Care, doi: 10.1111/vec.12717 (Early view)
  • Reminga, C.L. et al. (2018) ‘Evaluation of the placement and maintenance of central venous jugular catheters in critically ill dogs and cats’. Journal of Veterinary Emergency and Critical Care, doi: 10.1111/vec.12714 (Early view) 

Case report:

  • Scagnelli, A.M. et al. (2018) ‘Effects of therapeutic plasma exchange on serum immunoglobulin concentrations in a dog with refractory immune-mediated hemolytic anemia’. Journal of the American Veterinary Medical Association, 252(9), pp. 1097-1108
  • Ueda, Y. Et al. (2018) ‘Severe lactic acidosis and hypoglycemia due to acute metformin intoxication in a dog’. Journal of Veterinary Emergency and Critical Care, doi: 10.1111/vec.12711 (Early view)

For a copy of any of the papers mentioned in this post (personal education purposes only), please email lara.brunori@gmail.com.

Pick of the Month

‘Evaluation of the relationship between peripheral pulse palpation and Doppler systolic blood pressure in dogs presenting to an emergency service’
Ateca, L.B. et al. (2018) Journal of Emergency and Critical Care, doi: 10.111/vec.12718

Peripheral pulse palpation is considered a key parameter of the emergency patient’s triage. Its evaluation is relevant for the identification of cardiovascular abnormalities like hypotension, dysrhythmias, hyperdynamic states, decreased cardiac output and peripheral vasoconstriction. 

Pulse quality is closely related to stroke volume, arterial wall compliance and intrathoracic pressure and it is determined by the difference between systolic and diastolic blood pressure. It is, therefore, a common assumption that a strong peripheral pulse is indicative of a normal/high systolic blood pressure, while a weak one represents a low systolic blood pressure or an arterial clot. 

However, recent publications in the human medical literature are no longer supportive of this assumption. Several studies demonstrated that measured arterial blood pressure was significantly lower than expected from the peripheral pulse palpation alone. 

The evidence in veterinary medicine is lacking and this prospective observational study is aimed at filling the gap evaluating the relationship between pulse quality and measured blood pressure in dogs. 

Ninety-three canine patients presented to the Emergency Department of the University of Pennsylvania Veterinary Teaching Hospital between February 2012 and December 2013 were enrolled. Inclusion criteria consisted of a complete physical examination and systemic blood pressure measurement prior to any other intervention. Dogs with suspected arterial thromboembolism were excluded from the study. 

Pulse quality of both femoral and dorsal metatarsal arteries was assessed by digital palpation. Normal pulses were defined as easily palpable, while weak or absent pulses were difficult to find or not found at all. 

Systolic blood pressure was measured via Doppler flow detector. The cuff was appropriately chosen and at least 3 measurements were obtained. The average value was then recorded.

The study’s results are clearly summarised in a table within the text (Table 1), which shows a noticeable trend for both femoral and dorsal metatarsal pulses: when quality weakens, median systolic blood pressure decreases and heart rate increases. However, the differences were only statistically significant for blood pressure values in relation to dorsal metatarsal pulse quality and for heart rate values in relation to femoral pulse quality.

Sensitivity, specificity and relative confidence interval values were calculated for the reliability of metatarsal pulse palpation to detect hypotension. A specificity of 93% vs a sensitivity of 33% was found. This means that a dog with an absent metatarsal pulse is very likely to be hypotensive, but a palpable dorsal metatarsal pulse is not enough to rule out a hypotensive status. 

This study, although generally well designed, presents several limitations. The main ones refer to the variability in the assessors’ clinical experience and the fact that they were not blinded to the systemic blood pressure measurements, nor assessed for inter-rater or intra-rater reliability. Inconsistencies in patients’ sizes and body condition scores were taken into consideration by the authors and deemed not significant in the assessment of pulse quality; nevertheless, a more homogeneous sample would have been preferable.

Ultimately the choice to use Doppler blood pressure measurement instead of more invasive methods could be justified in terms of study feasibility and patient welfare. However, it has previously been demonstrated that Doppler flow tends to underestimate systolic blood pressure values.


In conclusion, this study demonstrates that an absent dorsal metatarsal pulse is very specific for hypotension and should trigger prompt interventions to re-establish adequate perfusion and blood pressure values. Nevertheless, it is not advisable to rely on a single parameter when evaluating the emergency patient’s cardiovascular status. The presence of dorsal metatarsal pulse alone does not rule out hypotension and evaluation of other indicators of poor perfusion like mucous membrane colour, capillary refill time, heart rate, mental status and systolic blood pressure should always be performed.

For a copy of any of the papers mentioned in this post (personal education purposes only), please email lara.brunori@gmail.com.

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