Puerperal eclampsia, also called puerperal tetany, hypocalcaemia or milk fever, is an acute, potentially fatal disorder that affects dogs and cats. It is due to a state of hypocalcaemia, which can develop before but, more frequently, after delivery because of a depletion of calcium from the blood in order for this element to be used in the production of milk.
SIGNALMENT AND HISTORY
Puerperal eclampsia may affect bitches of any size, although small animals seem to be predisposed, as do primiparas. The size of the litter does not appear to be a risk factor, even though the pathology is more often observed in small bitches (Fig. 1) with large litters. Although eclampsia can occur before delivery (after more than 40 days of gestation), it more often develops post-partum – in the bitch mainly in the first 2-4 weeks following delivery, contemporaneously with the maximum requirement for milk to feed the puppies (Fig. 2). In cats the condition has been reported in queens aged between 14 months and 5 years, with a higher frequency in multiparas with litters of more than 5-7 kittens.
PATHOGENESIS
The pathogenesis of puerperal eclampsia in bitches is different from that of the post-partum hypocalcaemic collapse occurring in cows, in which a block in the transmission of acetylcholine, due to a deficiency in calcium, leads to a flaccid paralysis. In the bitch, the transmission of acetylcholine is not blocked, but has a different effect on the neuromuscular junction. In bitches, the hypocalcaemia develops because of a contemporaneous increased requirement and decreased availability following reduced intake or reduced absorption. Hypocalcaemia leads to an increase in the permeability of neuronal cell membranes and a reduction in the threshold of depolarisation, which is followed by continuous and repeated depolarisation of the neurones responsible for the onset of the neurological signs. In bovine species, the tetany may, in some cases, be due to altered levels of magnesium, which, like the levels of phosphorus, are normal in bitches. In bitches with eclampsia, hyperpnoea can be associated with alkalosis, which may further lower the concentration of calcium ions in the blood, worsening the neuromuscular dysfunction. The pathogenesis in the queen is still very unclear.
SIGNS
In the post-partum form of eclampsia in the bitch the first signs are restlessness, irritability, panting, lack of interest in the puppies, stiffness, facial pruritus, followed after a few minutes or hours by muscle tremors, uncertain gait and disorientation, mydriasis, dry oral mucosae and sclera or sialorrhoea, vomiting, polyuria and polydipsia, tetany, clonic spasms, laboured breathing, convulsions and hyperthermia >40°C due to the tetany, collapse and, sometimes, death. Both bradycardia and tachycardia can be observed during hypocalcaemia and an electrocardiogram shows wide, deep T waves, a long Q-T interval and relatively high R waves.
The post-partum signs in the cat include incoordination, stiffness and vomiting, followed by muscle fasciculation, tonic-clonic spasms, extensor hypertonus, hyperthermia, hyperpnoea, mydriasis and convulsions. In some queens with antenatal eclampsia, the signs include rapid onset of lethargy and anorexia, muscle fasciculations, weakness, hypothermia, pallor, tachypnoea, bradycardia and breathlessness.
DIAGNOSIS
The diagnosis is based on the clinical examination, supported by the level of calcium in the blood: in bitches with eclampsia the total calcium concentration is <6.5-7 mg/dl, while the ionic calcium concentration is <3.2 mg/dl (<0.8 mmol/L), considering that calcium ions account for 55% of the total calcium and that normal values in the dog range between 8.7 and 12.0 mg/dl, depending on the laboratory. In the queen, the total calcium level indicating hypocalcaemia is <6-8 mg/dl, given that normal calcium levels in the cat range between 8.7 and 11.7 mg/dl. Although it is ionic calcium that is involved in neuromuscular function and its levels are, therefore, more indicative for diagnostic purposes (at least in the bitch), the greater availability of diagnostic tests for assaying total calcium makes this the parameter more widely used.
However, in cases refractory to treatment it is to be hoped that the more appropriate measurement of calcium ions can be performed. In conditions of hypoproteinaemia, when the amount of calcium bound to proteins decreases, the total concentration of calcium can be calculated precisely using the following formula:
CTCa=(TCa-Talb)+4 or CTCa=(TCa-[0.4xTTp])+3.3
where CTCa is the concentration of total calcium, TCa is the concentration of calcium in mg/dl, Talb is the concentration of albumin in g/dl and TTp is the concentration of total proteins in g/dl. Blood glucose levels can be normal or decreased, raising the differential diagnoses of hypoglycaemia and gestational toxaemia. The presence of convulsions raises the differential diagnosis of epilepsy, meningoencephalitis and poisoning.
TREATMENT
The treatment of acute hypocalcaemia is immediate, slow intravenous infusion of calcium when symptoms occur, in many cases before the results of the calcium assays are known. There are various formulations: from among these, calcium gluconate 10% can be administered intravenously at a dose of 0.22-0.44 ml/kg over 10-30 minutes and usually produces a rapid improvement in signs in about 15 minutes.
The management includes checking the patient’s response to calcium and continuous electrocardiographic monitoring of the patients, because of the possible onset of cardiac arrhythmias. If these occur, the administration must be slowed or suspended until the neurological signs disappear.
It should be noted that the concentrations of calcium in the blood can fluctuate depending on various factors, including the concentration of proteins, acid-base status, other electrolyte disorders and possible concomitant hypoglycaemia.
Convulsions are controlled by diazepam, at a dose of 1-5 mg/kg intravenously; hypoglycaemia and cerebral oedema are managed with their respective specific treatments. In the bitch, once the neurological symptoms have resolved, calcium administration (5-15 mg/kg/hour of elemental calcium or 0.5-1.5 ml/kg/hour of calcium gluconate) should be continued by slow intravenous infusion (in 10-30 minutes). The dose is calculated on the basis of elemental calcium, taking into account that calcium gluconate 10% contains 9.3 mg of elemental calcium/ml and that calcium chloride 27% contains 27.2 mg of elemental calcium/ml.
The treatment after the patient has been stabilised should be continued with calcium gluconate (not with calcium chloride), diluted 1:1 in physiological saline 0.9%, and administered subcutaneously three times a day, monitoring the calcium levels in the blood once or twice a day in order to adjust the treatment appropriately. Queens should be given 60-90 mg/kg/die of elemental calcium or 2.5 ml/kg of calcium gluconate 10% every 6-8 hours. Subsequently the treatment is continued by administering oral calcium for about 1 month to prevent relapses: in the bitch, calcium carbonate, calcium gluconate (1-3 g) or elemental calcium (25-50 mg/kg/die) can be used, divided in several doses; in the queen, the oral continuation therapy is elemental calcium (50-100 mg/kg/die) or calcium gluconate 10% (250-500 mg/die) in three or four daily administrations.
When this treatment is ineffective at relieving the signs and/or restoring normal levels of calcium in the blood, vitamin D, at a dose of 10,000-20,000 IU/die, can be administered. At the same time, the newly born puppies or kittens must be removed from the mother, for at least the first 24-48 hours, in order to reduce the loss of calcium with breastfeeding. The litter can be returned gradually, only if necessary, after the mother’s condition has been stabilised and during integration with dietary calcium and under close clinical monitoring. It is worth remembering that, in some cases, convulsions can recur even some weeks after the first episode and even after effective treatment.
Glucocorticoid treatement, used in the past, is not therapeutically justified and should not be given because it can worsen the calcium deficiency both by reducing intestinal absorption of calcium and by increasing its renal excretion. In the prenatal forms of eclampsia in cats, once the patient has been stabilised the treatment is oral elemental calcium 100 mg/kg every 12 hours until 1 month after delivery, allowing normal breastfeeding.
PROGNOSIS
The prognosis with regards to survival of the patient depends on the clinical condition of the animal; the pathology can be fatal if neglected. Contrariwise, the prognosis is favourable when the condition is recognized and treated promptly.
PREVENTION
The role of prenatal diet in the prevention of puerperal hypocalcaemia has been extensively studied in cows, but not equally well investigated in bitches. However, a balanced diet with a calcium:phosphorus ratio of 1:1 or 1.2:1 in pregnancy can be useful prophylaxis against eclampsia, as can encouraging hyperprotective parturients to eat if they tend to renounce food in the immediate post-partum period in order to remain with the whelps.
During breast feeding, a balanced, high quality diet can be useful for preventing the condition, particularly in bitches at risk. Since a personal predisposition has been noted, with recurrent eclampsia at each subsequent delivery, it is advisable to prevent affected bitches from reproducing.
Suggested readings
- WiebeVJ, Pharm D, HowardJP (2009) Pharmacologic Advances in Canine and Feline Reproduction. Top Companion Anim Med, 24:71-99.
- JohnstonSD, Kustritz MVR, Olson PNS (2001) Periparturient disorders in the bitch. In: Johnston SD, Kustritz MVR, Olson PNS (Eds.) Canine and Feline Theriogenology. Saunders 3rd edition.Philadelphia: 129-145.
- JohnstonSD, Kustritz MVR, Olson PNS (2001) The postpartum period in the cat. In: Johnston SD, Kustritz MVR, Olson PNS (Eds.) Canine and Feline Theriogenology. Saunders 3rd edition.Philadelphia: 445-446.
- Biddle D, Macintire DK (2000) Obstetrical emergencies. Clin Tech Small Anim Pract, 15: 88-93.
- Mosier JE (1980) Disorders in the postparturient bitch. In: Morrow DA (ed): Current therapy in theriogenology. WB Saunders. Philadelphia: 608-614.