Hypoglycemia in sick and moribund farmed elk calves

Abstract

Blood glucose was found to be below the reference range in most farmed elk calves examined at the Western College of Veterinary Medicine teaching hospital. Hypoglycemia was associated with diarrhea, sepsis, and malnutrition. Blood glucose analysis and, when indicated, intravenous dextrose administration are recommended when treating moribund farmed elk calves.

The commercial elk (wapiti) industry has become an important agricultural enterprise in Canada. As of December 2001, more than 74 000 domestic elk (Cervus elaphus) were being farmed in the country, with almost 69 000 (93%) located in Alberta, Saskatchewan, and Manitoba. In Saskatchewan, the number of farmed elk has risen each year since 1987, when there were 400. Currently, there are an estimated 28 500 domestic elk in the province, despite the destruction of about 7500 animals during 2000 and 2001 in attempts to control the spread of chronic wasting disease (CWD) (personal communication, Saskatchewan Agriculture and Food). As a result of the dramatic growth in the elk industry, veterinarians, including those at the Western College of Veterinary Medicine (WCVM), increasingly are being asked to provide health care and diagnostic services for these animals.

Sick and moribund elk calves presented for examination to the Veterinary Teaching Hospital (VTH) of the WCVM, often died during the period of initial clinical assessment and preliminary stages of treatment. This was especially true when the animals were physically stressed, such as when they were restrained during the placement of an IV catheter. Evaluation of the clinical and postmortem information could not explain the death of these calves. Therefore, it was decided to measure the blood glucose levels of the elk calves at admission and to monitor the levels throughout their hospital stay. The purpose of this article is to share with veterinarians our observations regarding blood glucose levels in sick and moribund neonatal elk calves.

Hypoglycemia refers to a lower than normal blood glucose concentration. Ideally, a diagnosis of hypoglycemia would be based on the level of blood glucose at which specific metabolic responses are triggered, neurologic function is affected, or clinical signs become apparent. However, such data is rarely available and is often confounded by several factors, such as the source of the blood sample; the assay method used; and whether blood, plasma, or serum glucose concentration is to be or has been determined. For these reasons, hypoglycemia is usually defined statistically and, like other normally distributed biochemical variables, is any value 1.96 standard deviations or more below the mean of a healthy population (1).

Different species of animals are reported to have different normal ranges of blood glucose. Animals of the same species may have different blood levels depending on their age and physiologic state (2). Elk and red deer (Cervus elaphus) have been found to have a wide range of blood glucose concentrations (Table 1), which may be influenced by nutritional status, level of domestication, and method of restraint (3,4,5,6,7,8).

Table 1.

A reference range for blood glucose values in neonatal elk has not been published. However, unpublished hematological and biochemical data from domesticated elk raised in Saskatchewan exists (McIssac A, cited in Haigh (9)) and the reported blood glucose concentrations are similar to those reported by others (Table 1). These data were obtained from 89 healthy, farmed, male and female elk of unspecified ages that were restrained in a chute for blood collection. Based on this information, we define hypoglycemia in neonatal elk as a blood or serum glucose concentration ≤ 4.2 mmol/L.

Between July 1, 1996, and June 30, 2001, 180 elk were examined at the VTH, WCVM. Of these, 39 were calves ≤ 30 d of age. Thirty-four of the 39 calves had either their blood glucose concentrations measured with a hand-held blood glucose meter (One Touch Basic; LifeScan Canada, Burnaby, British Columbia) or had their serum glucose measured with an automated clinical chemistry analyzer (Spectrum II; Abbott Diagnostics, Abbott Park, Illinois, USA or Hitachi 912; Roche Diagnostics, Laval, Quebec) at least once. Blood glucose was determined using blood collected from the jugular vein immediately prior to analysis. Serum glucose was determined using serum separated from the blood cells within 30 min of collection and analyzed within 2 h. Of these 34 calves, 13 were found to have blood or serum glucose concentrations of ≤ 4.2 mmol/L during the initial clinical assessment, prior to any therapy. Details of these cases are summarized in Table 2.

Table 2.

Although not formally evaluated, hand-held glucose meters appear very useful in assessing the glucose status of neonatal farm animals (10). In our experience, which includes neonatal elk, blood glucose levels determined by hand-held meters have been good predictors of serum glucose levels measured with an automated analyzer, when samples are taken from the same animal at the same time (C. Clark, unpublished).

Blood glucose concentration is normally maintained within a relatively narrow range and regulated primarily by insulin and glucagon, while influenced by a variety of other factors. Simply, the blood glucose concentration at a given moment is the net result of the rate of movement of glucose into and out of the circulation. Glucose enters the circulation by means of intestinal absorption of dietary glucose and by hepatic glucose production (glycogenolysis and gluconeogenesis).

Glucose is the primary source of energy for all mammalian cells. Furthermore, neurons, which are insensitive to insulin, require a concentration gradient sufficient to diffuse glucose. While the brain can use ketone bodies as an alternate energy source, it may take hours, or even days, before ketones accumulate at concentrations high enough to pass the blood-brain barrier. Thus, hypoglycemia has the potential to cause irreversible brain damage and death (1,2,10).

Neonates are particularly susceptible to hypoglycemia. After birth, the newborn must immediately make a transition from a continuous supply of maternal glucose to endogenous glucose production and intermittent, albeit frequent, exogenous intake. Between feedings, glycogen stores are mobilized to meet the neonate's glucose needs. However, these stores are limited in neonates and can quickly become depleted if feeding is delayed. The newborn then becomes dependent on gluconeogenesis to provide glucose. Due to its smaller muscle mass and limited fat stores, the neonate has fewer gluconeogenetic precursors than the adult. In addition, the newborn may have inefficient hepatic gluconeogenesis due to a delay in enzymatic induction. The neonate may also have an inefficient system of counterregulatory hormones (epinephrine, glucagon, growth hormone, cortisol) that antagonize insulin levels and increase the rate of glycolysis, gluconeogenesis, and lipolysis.

More than half (19 of 34) of neonatal elk calves admitted to the WCVM VTH were determined to be hypoglycemic at some point during their hospitalization. Most of the calves suffered from undifferentiated diarrhea. However, diarrhea can also be a symptom of severe sepsis (10,11).

In bovine calves, hypoglycemia is thought to occur in a very small percentage of cases of acute diarrhea and, if present, is not marked (10,11). Several studies have shown that sepsis results in transient hyperglycemia, which is followed by hypoglycemia, especially if the disease is severe, prolonged, or both (11). The pathogenesis of hypoglycemia during sepsis is not fully understood. Possible mechanisms leading to hypoglycemia include (i) impaired glycogenolysis and gluconeogenesis in the liver, (ii) the presence of endotoxin or cytokines that have insulinlike activity, (iii) increased catabolism of glucose by the animal, and (iv) excessive utilization of glucose by bacteria and leukocytes.

Most adult animals can maintain normal blood glucose levels during prolonged periods of starvation, and it has been reported that some neonatal animals (lambs, bovine calves, and foals) can resist starvation hypoglycemia for over a week (2). However, immature neonates and neonates of other species rapidly become hypoglycemic because of underdeveloped gluconeogenic mechanisms, if they do not ingest adequate amounts of colostrum and milk. Naturally occurring conditions leading to inadequate food intake by newborn animals include agalactia; maternal rejection; physical separation; and any congenital defect, injury, or disease present in the newborn that limits or prevents suckling or results in inappetence (10). Neonates dying of starvation and hypoglycemia will have no visible lesions but will have an absence of ingested milk and limited hepatic glycogen (11).

In a retrospective study of neonatal elk calves submitted to the diagnostic laboratory at the WCVM, Pople et al (12) found that starvation accounted for 9.9% of mortality. In addition, due to a lack of lesions, no diagnosis could be made at postmortem in 41.4% of the calves in the study. Therefore, some of the calves reported in Pople's study could have died of hypoglycemia associated with diarrhea, sepsis, or malnutrition.

While the mechanisms leading to hypoglycemia in sick and moribund elk calves can only be extrapolated from studies in other species, it appears that hypoglycemia was a common and life-threatening problem in calves examined at the WCVM VTH during the study period. Based on these observations, as well as those of Carmalt et al (13), the current protocol for elk calves admitted to the WCVM VTH includes collecting heparinized blood and testing for blood glucose and blood gases. If blood glucose is < 3 mmol/L, an IV bolus of 50% dextrose at 0.4 mL/kg body weight (BW) is administered. An IV catheter is placed and the calf is given IV fluids. If acidosis is present and considered severe (a negative base excess ≥ 10 mEq/L), 13 g of NaHCO₃ added to 1 L of 5% dextrose to make an isotonic 1.3% bicarbonate solution is administered. If acidosis is present but not considered severe (a negative base excess < 10 mEq/L), 110 mL of 50% dextrose added to 1 L of physiologic saline is administered. The rate of IV fluid administration is 1 to 2 L/d, equivalent to 2 to 8 mL/kg BW/h, depending on the severity of acidosis and weight of the animal. The blood glucose level is monitored periodically, and when calves are septic or at risk for bacterial infections, antibiotics are also given. CVJ