Eclampsia is an acute, life-threatening condition that usually occurs at peak lactation, 2–3 weeks after whelping. Small-breed bitches with large litters are most often affected. Hypocalcemia may also occur during parturition and may precipitate dystocia.
Etiology and Pathogenesis of Eclampsia in Small Animals
Hypocalcemia most likely results from loss of calcium into the milk and from inadequate dietary calcium intake. This imbalance in calcium metabolism occurs because calcium mobilization from bone into the serum pool is insufficient to compensate for the efflux of calcium via the mammary glands during lactation. Heavy lactational demands from large puppies or a large litter are often noted. The incidence is higher in small breeds of dogs, although eclampsia can occur in any breed, with any size of litter, and at any time during lactation. Rarely, it occurs during late gestation in bitches. Although uncommon in queens, hypocalcemia may occur during early lactation. In dogs, supplementation with oral calcium during pregnancy may predispose the animal to eclampsia during peak lactation, because excessive calcium intake during pregnancy causes downregulation of the calcium regulatory system and subsequent clinical hypocalcemia when calcium demand is high.
Inadequate production of parathyroid hormone (PTH) during the hypocalcemic crisis is not responsible for eclampsia in dogs. In dairy cows with a similar condition, parturient paresis Parturient Paresis in Cows Parturient paresis (milk fever, hypocalcemia, paresis puerperalis, parturient apoplexy) is a disease of adult dairy cows in which acute hypocalcemia causes acute to peracute, afebrile, flaccid... read more , production of PTH is adequate; however, the pool of osteoclasts for PTH to stimulate is not. The small osteoclast pool results from feeding a high concentration of dietary calcium during the nonlactating period, which suppresses secretion of PTH by the parathyroid gland and stimulates secretion of calcitonin by parafollicular C cells. Hypocalcemia at parturition interferes with the release of acetylcholine at the neuromuscular junction, which is normally mediated by extracellular calcium entering presynaptic nerve terminals through voltage-gated calcium channels and triggering the fusion of acetylcholine-filled synaptic vesicles with the presynaptic nerve terminus. The paresis observed in cattle, rather than the tetany evident in dogs, is probably results from a combination of factors. Cows often have concurrent mild hypermagnesemia. Magnesium is a calcium-channel antagonist and plays a key role in modulating any activity governed by intracellular calcium fluxes. Cows also have increased volatile fatty acids (which are inhibitory at neuromuscular synapses), and the threshold potential at neuromuscular junctions is higher in cows than in dogs.
In dogs with hypocalcemia, unlike cows, excitation-secretion coupling is maintained at the neuromuscular junction. The low concentration of calcium in the extracellular fluid has an excitatory effect on nerve and muscle cells because it lowers the threshold potential (voltage level at which sodium channels become activated) so that it is closer to the resting membrane potential. With hypocalcemia, sodium channels become activated (opened) by very little increase in membrane potential from their normal, negative level. Therefore, the nerve fiber becomes highly excitable, sometimes discharging repetitively without provocation rather than remaining in the resting state. The probable way that calcium ions affect sodium channels is that calcium ions bind to the exterior surfaces of the channels. The positive charge of these calcium ions alters the electrical state of the sodium-channel protein, thus altering the voltage level required to open the channel. Because of the loss of stabilizing membrane-bound calcium ions, nerve membranes become more permeable to sodium ions and require a stimulus of lesser magnitude to depolarize. Tetany occurs as a result of spontaneous repetitive firing of motor nerve fibers. Hypoglycemia can occur concurrently.
Clinical Findings of Eclampsia in Small Animals
Panting and restlessness are early clinical signs of eclampsia. Mild tremors, twitching, muscle spasms, and gait changes (stiffness and ataxia) result from increased neuromuscular excitability. Behavioral changes such as aggression, whining, salivation, pacing, hypersensitivity to stimuli, and disorientation are common. Severe tremors, tetany, generalized seizure activity, and finally coma and death may occur. Hyperthermia may occur in severe cases. Prolonged seizure activity may cause cerebral edema. Tachycardia, hyperthermia, polyuria, polydipsia, and vomiting sometimes occur. Historically, the bitch has been otherwise healthy and the neonates have been thriving.
Although hypocalcemia usually occurs postpartum, clinical signs can appear prepartum or at parturition. Mild hypocalcemia may contribute to ineffective myometrial contractions and slow the progression of labor without causing other clinical signs.
Heavy panting may produce a respiratory alkalosis. Ionized calcium is the physiologically available fraction of calcium; it is affected by protein concentration, acid-base status (alkalosis favors protein binding of serum calcium and will decrease blood concentrations of the biologically important ionized calcium, thus exacerbating hypocalcemia), and other electrolyte imbalances. Thus, the severity of clinical signs may not correlate with total calcium concentration.
Diagnosis of Eclampsia in Small Animals
Presumptive diagnosis based on signalment and clinical signs
Confirmatory diagnosis based on results of measurement of serum calcium concentration
Diagnosis is often based on signalment, history, clinical signs, and response to treatment. A pretreatment total serum calcium concentration of <7 mg/dL in dogs or < 6 mg/dL in cats confirms the diagnosis; noting that reference values vary between laboratories. However, in many cases IV treatment with calcium is started before serum calcium concentration is known. A serum biochemical analysis is useful to exclude concurrent hypoglycemia and other electrolyte imbalances. Prolongation of the Q–T interval and ventricular premature contractions may be evident on an ECG.
Differential diagnoses include other causes of seizures, such as hypoglycemia, toxicoses, and primary neurologic disorders such as idiopathic epilepsy Congenital and Inherited Cerebral Disorders in Animals Anencephaly means that the brain is largely absent at birth. It is a rare disorder but is seen sporadically in calves; the cause is unknown. Because the pituitary gland may also be absent, prolonged... read more or meningoencephalitis Meningitis, Encephalitis, and Encephalomyelitis in Animals Meningitis, encephalitis, and encephalomyelitis are terms used to describe inflammatory conditions of the meninges, brain, or brain and spinal cord, respectively. These inflammatory processes... read more . Other causes of irritability and hyperthermia, such as metritis Metritis in Small Animals Metritis is defined as a uterine infection. Inflammation of the endometrium and myometrium characterized by postpartum vaginal discharge is a classic sign of metritis. However, due to the serious... read more and mastitis Mastitis in Small Animals Mastitis is most commonly seen in postpartum lactating bitches. It can, however, occur in nonpregnant dogs with galactorrhea. It may involve only one or multiple glands and it can be chronic... read more , should also be excluded. If the parathyroid glands are functioning normally, serum PTH will be increased in the face of hypocalcemia. Low or undetectable serum PTH concentration in a hypocalcemic animal is strongly suggestive of primary hypoparathyroidism Hypoparathyroidism in Dogs Hypoparathyroidism of various causes is primarily recognized in dogs and is characterized by insufficient PTH secretion by parathyroid glands. Deficiency of PTH results in an inability to adequately... read more . A commercially available human intact-PTH assay has been validated in both cats and dogs; PTH-calcium curves are also similar in cats and dogs.
Treatment and Prevention of Eclampsia in Small Animals
Guided by the severity of neurologic signs
Administration of IV calcium gluconate with appropriate monitoring
Slow intravenous administration of 10% calcium gluconate—0.5–1.5 mL/kg over 10–30 minutes (5–20 mL is a typical dose)—is an effective treatment for eclampsia, usually resulting in clinical improvement within 15 minutes. Muscle relaxation should be immediate.
During administration of calcium, heart rate should be carefully monitored by auscultation or ECG for bradycardia or arrhythmias. Adverse effects resulting from too rapid administration of calcium include bradycardia, shortening of the Q–T interval, and premature ventricular complexes. If an arrhythmia develops, calcium administration should be discontinued until the heart rate and rhythm are normal; then administration can be resumed at half the original infusion rate.
It is important to base the dosage of calcium on a calculation of elemental calcium because different products vary in the amount of calcium available. The dosage of elemental calcium for hypocalcemia is 5–15 mg/kg, IV, slowly over 10 minutes. Calcium gluconate, 10%, contains 9.3 mg of elemental calcium/mL. Calcium chloride, 10%, contains 27.2 mg of elemental calcium/mL. Thus, for calcium gluconate, 10%, the dosage is ~0.5–1.5 mL/kg, IV, slowly over 10 minutes; and for calcium chloride, 10%, the dosage is ~0.18–0.55 mL/kg, IV, slowly over 10 minutes. Calcium gluconate solution may be preferred over calcium chloride because the former is perceived to carry a lower risk of tissue injury if inadvertent extravasation occurs.
Once the animal is stable, the dose of calcium gluconate needed for initial control of tetany may be diluted in an equal volume of normal (0.9%) saline and given subcutaneously every 8 hours to control clinical signs. (Calcium chloride cannot be given subcutaneously.) Alternatively, 5–15 mg of elemental calcium/kg per hour can be continued intravenously. This protocol effectively supports serum calcium concentrations while waiting for oral vitamin D and calcium treatment to have effect. Ideally, serum calcium concentrations should be maintained at>8 mg/dL. Serum calcium concentrations of <8 mg/dL indicate the need to increase the dosage of parenteral calcium, whereas concentrations of>9 mg/dL suggest that it be decreased. The aim of longterm treatment is to maintain the serum calcium concentration at mildly low to low-normal concentrations (8–9.5 mg/dL).
The bitch may remain nonresponsive after correction of hypocalcemia if cerebral edema has developed. Cerebral edema, hyperthermia, and hypoglycemia should be treated, if present. Fever usually resolves rapidly with control of tetany, and specific treatment for fever may result in hypothermia.
It is best not to let puppies or kittens nurse for 12–24 hours after the bitch or queen is treated for hypocalcemia. During this period, they should be fed a milk substitute or other appropriate diet; if mature enough, they should be weaned. If tetany recurs during the same lactation, the litter should be removed from the bitch or queen and either hand-raised (<4 weeks old) or weaned (>4 weeks old).
After the acute crisis, elemental calcium at 25–50 mg/kg per day orally in three or four divided doses is given for the remainder of lactation. Again, the dose of calcium is based on the amount of elemental calcium in the product (eg, calcium carbonate tablets contain 295 mg elemental calcium/1-g tablet). In dogs, the dosage is usually 1–4 g/day, in divided doses. In cats, the dosage of calcium is ~0.5–1 g/day, in divided doses. Longterm maintenance treatment with oral vitamin D and oral calcium supplementation usually requires a minimum of 24–96 hours before an effect is achieved. Hypocalcemic animals should, therefore, receive parenteral calcium support during the initial posttetany period. Calcium carbonate is a good choice because of its high percentage of elemental calcium, general availability in drugstores in the form of antacids, low cost, and lack of gastric irritation. The dosage of calcium can be gradually tapered to avoid unnecessary treatment; commercial pet food usually contains sufficient calcium to meet the needs of dogs and cats. However, to avoid acute problems of hypocalcemic tetany, oral calcium supplementation should continue throughout lactation.
Vitamin D supplementation is used to increase calcium absorption from the intestines. The concentration of serum calcium should be monitored weekly. The dosage of 1,25-dihydroxyvitamin D3 (calcitriol) is 0.03–0.06 mcg/kg per day. Calcitriol has a rapid onset of action (1–4 days) and a short half-life (<1 day). Iatrogenic hypercalcemia is a common complication of this treatment. If hypercalcemia results from overdosage, it can be rapidly corrected by discontinuing calcitriol. The toxic effects resolve in 1–14 days. This is a much briefer period than that observed with the use of dihydrotachysterol (1–3 weeks) or ergocalciferol (vitamin D2; 1–18 weeks).
Corticosteroids lower serum calcium and, therefore, are contraindicated. They may interfere with intestinal calcium transport and increase urinary loss of calcium.
Owners should be warned that eclampsia is likely to recur with future pregnancies. Preventive steps to consider in the bitch include feeding a high-quality, nutritionally balanced, and appropriate diet during pregnancy and lactation; providing food and water ad lib during lactation; and supplementing feeding of the puppies with milk replacer early in lactation and with solid food after 3–4 weeks of age. Oral calcium supplementation during gestation is not indicated and may cause rather than prevent postpartum hypocalcemia. Calcium administration during peak lactation may be helpful in bitches with a history of eclampsia.
Signalment is key to the diagnosis of eclampsia; typically a small-breed dog nursing a large litter at peak lactation
IV administration of 10% calcium gluconate to control neurologic signs is usually required for treatment.
For More Information
Membrane potentials and action potentials. In: Hall JE, ed. Guyton and Hall Textbook of Medical Physiology, 14th ed. Elsevier; 2021:63–78.
Gonzales K. Periparturient Diseases in the Dam. Vet Clin North Am: Sm Anim Pract. 48(4):663–681. https://doi.org/10.1016/j.cvsm.2018.02.010
Also see pet health content regarding disorders of calcium metabolism in dogs Disorders of Calcium Metabolism in Dogs Calcium is an essential component of the skeleton, and it has important functions in muscle contraction, blood clotting, enzyme activity, the nervous system, and hormone release, among others... read more and cats Disorders of Calcium Metabolism in Cats Calcium is an essential component of the skeleton, and it has important functions in muscle contraction, blood clotting, enzyme activity, the nervous system, and hormone release, among others... read more .