Management of a severe peripartum hemorrhage following cesarean section in a dog

Abstract

This report describes the intensive blood pressure management and transfusion of a peripartum intrauterine hemorrhage following a cesarean section in a dog. The impact of pregnancy-associated physiologic changes and anesthesia on hemodynamic parameters along with potential alternate management techniques are discussed.

Peripartum hemorrhage (PPH) is a possible complication following cesarean section in dogs and cats (1). Oxygen delivery in the body is dependent on cardiac output (Q), hemoglobin concentration, and the saturation of hemoglobin with oxygen (2). Hemorrhage causes a reduction in hemoglobin concentration and Q. The measurement of Q is rarely performed in practice, instead arterial blood pressure and heart rate are used as surrogates. Classical physiological responses to hemorrhage are tachycardia and vasoconstriction; however, general anesthesia with volatile agents blunts these responses and intraoperative intravenous fluid therapy (IVFT) can further decrease hemoglobin concentration. Additionally, normal physiological changes in the pregnant bitch (relative anemia, increased heart rate, and a poor reflex response to hypovolemia) further confound the interpretation of hemorrhage during anesthesia (3). The decision to transfuse a patient in response to hemorrhage is based on evaluating these physiological responses alongside quantified blood loss, the presence of acute anemia (hematocrit < 25%), and evidence of tissue hypoxia (e.g., blood hyperlactatemia) (4). The management of a severe case of PPH has not been described in the small animal veterinary literature. This case report describes the anesthetic and critical care support of a dog with PPH that demonstrated evidence of hemorrhagic shock post-procedure; urgent transfusion therapy was required to stabilize the dog. This case has altered the authors’ institutional practice and resulted in a change in management technique for cesarean sections.

Case description

A 4-year-old, 35-kg, Bouvier des Flandres dog was presented to the Centre Hospitalier Universitaire Vétérinaire (CHUV) for dystocia (time of presentation 16:30 h). This was the dog’s third pregnancy, and it had been in labor approximately 18 h before admission. It had vaginally delivered 4 puppies overnight but had progressed no further in parturition. On presentation the dog was anxious but alert, demonstrating a sinus tachycardia [140 beats/min (bpm)] and was panting. Hematocrit and total protein were 37% [reference range (RR): 40% to 56%] and 62 g/L (RR: 53 to 67 g/L). Plasma urea was elevated (23.6 mmol/L; RR: 3.26 to 9.44 mmol/L), which in conjunction with a high normal plasma creatinine concentration (137 μmol/L; RR: 57 to 137 μmol/L) was presumed to be pre-renal in origin, secondary to dehydration (Table 1). Electrolyte abnormalities included elevated serum potassium (5.15 mmol/L; RR: 3.83 to 5.06 mmol/L), decreased sodium (126.6 mmol/L; RR:142.8 to 150.2 mmol/L), and decreased chloride (94.3 mmol/L; RR: 109.0 to 118.6 mmol/L). Abdominal ultrasound revealed that 3 of the remaining 6 fetuses were in distress (heart rate < 150 bpm). As a result, the decision was made to deliver the remaining puppies by cesarean section. Informed consent was obtained from the owners and the dog was prepared for anesthesia and surgery. The dog was immediately started on IVFT with lactated Ringer’s solution (Lactated Ringer’s Solution USP; Baxter, Mississauga, Ontario), 10 mL/kg body weight (BW) per hour and given ampicillin (Ampicillin Sodium Injection USP 1 g; TEVA, Toronto, Ontario), 22 mg/kg BW, IV, through a cannula placed in a cephalic vein. The owners declined a recommendation that a concurrent ovariohysterectomy (OVH) be performed as they wished to breed the dog in the future.

Table 1.

Preoperative hematology/biochemistry, arterial blood gas at the end of anesthesia during a severe intra-uterine hemorrhage, and hematocrit at discharge in a Bouvier des Flandres bitch undergoing cesarean section. Abnormal values are in bold, with reference ranges in parenthesis.

Analyte	Pre-operative	Post-operative/Pre-transfusion	Discharge (24-hour post)
Sample	Venous	Arterial	Venous (Post-transfusion)
Hematocrit (%)(40 to 56)	37a	25	30
Total protein (g/L) (52 to 67)	62	48	42
pH	7.41	7.38	7.45
PaCO2 (mmHg)	20 (37 to 49)	21.8 (35 to 45)	29.8 (37 to 49)
PaO2 (mmHg)	—	600
Na+ (mmol/L) (142.8 to 150.2)	126.6	142	135
K+ (mmol/L) (3.82 to 5.06)	5.15	4.14	4.2
iCa2+ (mmol/L) (1 to 1.42)	1.03	1.2	1.16
Total calcium (mmol/L) (2.33 to 2.69)	2.14	ND	ND
HCO3− (mmol/L)	12.7 (21 to 25)	12.7 (20 to 24)	20.7
Cl− (mmol/L) (109 to 118.6)	94.3	106	106
Glucose (mmol/L) (4.5–8)	7.5	7.0	ND
Lactate (mmol/L) (0 to 2)	1.39	1.6	1.07
Hemoglobin (g/L) (139 to 198)	129	88	ND
White blood cells (109/L) (5.1 to 14.2)	16.76	ND	ND
Segmented neutrophils (109/L) (2.7 to 9.8)	14.08	ND	ND
Band neutrophils (109/L) (0 to 0.3)	0.17	ND	ND
Lymphocytes (109/L) (0.7 to 3.5)	1.17	ND	ND
Monocytes (109/L) (0.1 to 0.9)	1.34	ND	ND
Platelets (109/L) (153 to 400)	449	ND	ND
Urea (mmol/L) (3.26 to 9.44)	23.65	ND	ND
Creatinine (μmol/L) (57 to 137)	137	ND	89
ALT (U/L) (20 to 80)	20	ND	ND
ALP (U/L) (10 to 113)	105	ND	ND

^aHematocrit reported from pre-operative hematology/biochemistry. Post-operative hematocrits determined by centrifugation of microhematocrit tubes.

iCa²⁺ — ionized calcium; ALT — alanine aminotransferase; ALP — alkaline phosphatase; ND — not determined.

The abdomen was clipped and cleaned, and the lumbosacral space was clipped and aseptically prepared to facilitate epidural injection following induction of general anaesthesia. No premedication was administered. Following 5 min of preoxygenation (4 L/min by face mask) general anesthesia was induced, at 17:15 h, with propofol to effect (Propoflo 28 10 mg/mL; Zoetis, Kirkland, Quebec), 5 mg/kg BW, IV. After direct orotracheal intubation (12 mm ID), the patient was connected to a small animal anesthesia machine with a coaxial circle breathing system. General anesthesia was maintained with isoflurane (Isoflurane; Fresenius Kabi, Richmond Hill, Ontario) carried in oxygen. The patient was monitored with a multiparametric anesthesia monitor [(LifeWindow LW9x; Digicare Animal Health, Boynton Beach, Florida, USA); ECG, pulse oximetry, sidestream capnography (P_ETCO₂), invasive blood pressure, and pulse pressure variation]. The dorsal pedal artery was cannulated for invasive blood pressure monitoring as non-invasive measurements (oscillometric technique) were providing erratic values following induction. Fluid therapy was continued with lactated Ringer’s solution at 10 mL/kg BW per hour. The dog ventilated spontaneously during the procedure and exhibited hypocapnea throughout (P_ETCO₂ < 26 mmHg). An epidural injection was performed with morphine (Morphine Sulfate 10 mg/mL, Preservative free; Sandoz, Boucherville, Quebec), 0.1 mg/kg BW, and lidocaine (Lurocaine 2%; Vétoquinol, Lavaltrie, Quebec), 3 mg/kg BW with a total volume of 0.14 mL/kg BW as soon as the dog was intubated (less than 60 s following induction). The epidural injection provided a MAC-sparing effect, with the expired isoflurane maintained between 0.2% and 0.5% during the surgery.

The dog was transferred from the preparation area to the operating theater 15 min after induction of anesthesia. The mean arterial blood pressure (MAP) was 62 mmHg (via arterial cannula measurement) and heart rate was 120 bpm upon arrival in theater. With concerns for hypovolemia, the authors instituted a brief period (approximately 1 min) of controlled (manual) ventilation to a peak pressure of 10 cmH₂O which yielded a pulse pressure variation (PPV) in excess of 20% [RR: 0 to 15% (5); estimated from the arterial blood pressure waveform]. These factors considered in unison were consistent with the presence of hypovolemia. A bolus of lactated Ringer’s solution, 15 mL/kg BW, was administered over the next 25 min. This bolus finished at the time of delivery of the last puppy and IVFT was continued at 10 mL/kg BW per hour. Sixteen and 46 min after the start of surgery and anesthesia, respectively, the last puppy was delivered (actual time 18:01 h). Five puppies were delivered alive, and 1 was delivered dead. There was no improvement in PPV or reduction in heart rate following the fluid bolus. As the surgical team began to close the uterus there was a sudden decrease (over less than 5 min) in MAP to 50 mmHg, accompanied by a reduction in P_ETCO₂ from 24 to 19 mmHg (no concurrent change in respiratory rate). A continuous rate infusion (CRI) of norepinephrine (Norepinephrine Bitartrate Injection USP 1 mg/mL; Sandoz) was started and titrated (0.2 to 0.4 μg/kg BW per minute) to effect (target MAP 65 to 70 mmHg). At this time the dog had received 30 mL/kg BW of isotonic crystalloid fluids (over 45 min since IVFT was instituted) and the expired concentration of isoflurane was 0.2% to 0.3%. For the next 10 min the MAP improved to target levels; however, the heart rate remained elevated at 120 bpm. Another decrease in MAP to 50 mmHg was seen 15 min after beginning the norepinephrine CRI. This hypotension correlated with the closure of the uterus and the surgical team did not report evidence of hemorrhage within the surgical field. At this point hypertonic saline, 2 mL/kg BW, was administered over 10 min, which was associated with a transient (5 min) increase in MAP to 70 mmHg. When the MAP decreased further to 59 mmHg, a CRI of dopamine (DOPamine HCL 1600 μg/mL; Baxter) was started at 8 μg/kg BW per minute (norepinephrine was at 0.4 μg/kg BW per minute at this time). A good response was observed (MAP 70 to 76 mmHg) for the next 10 min. As skin closure was completed the heart rate increased further to 152 bpm and MAP decreased to 61 mmHg, so volatile anesthesia was discontinued (actual time 18:45 h). Arterial blood was sampled for blood gas analysis (Table 1) and coagulation function testing as soon as the drapes were removed at the end of the surgery. Arterial blood gas analysis revealed a metabolic acidosis with respiratory compensation (pH = 7.38, HCO₃⁻ = 12.7 mmol/L, P_aCO₂ = 21.8 mmHg with a simultaneous P_ETCO₂ = 19 mmHg; hematocrit = 25%, total protein = 48 g/L, lactate = 1.6 mmol/L). The in-house prothrombin and activated partial thromboplastin times (SCA 2000; IDEXX, Westbrook, Maine, USA) of citrated whole blood were normal at 12 s (RR: 12 to 17 s) and 102 s (RR: 71 to 102 s), respectively.

Five minutes after discontinuing volatile anesthesia, the patient was transferred to ICU. The cessation of isoflurane provided a marginal increase in MAP to 70 mmHg. During transfer a dark hemorrhagic discharge was noted from the vagina, the presumed origin being the uterus. Heart rate had decreased from approximately 150 to 135 bpm, but MAP had decreased further, to 50 mmHg. Considering the poor response to vasopressors and the hyperkalemia and hyponatremia at presentation, there was a suspicion of hypoadrenocorticism. A 3-mg dose of dexamethasone (Dexamethasone 5, 5 mg/mL; Vétoquinol) was administered IV. Ten minutes later (at 19:00 h), norepinephrine and dopamine CRI’s were increased to 0.6 and 10 μg/kg BW per minute, respectively. A brief (5 min) improvement in MAP (80 mmHg) was seen, then over the following 15 min the MAP gradually decreased to below 70 mmHg again despite increasing norepinephrine to 0.8 μg/kg BW per min. The dog was extubated during this period (19:08 h). However, due to ongoing significant bleeding visible from the vagina, the poor response to crystalloid boluses and vasopressor support the decision was made to transfuse type-specific packed red blood cells (pRBCs) (250 mL, 7.1 mL/kg BW) to the dog over a 1-hour period. A cross match was not performed due to the urgent nature of the situation and because this was the dog’s first transfusion. At the same time, dopamine was discontinued and dobutamine (Dobutamine Injection USP 12.5 mg/mL; Sandoz) instituted starting at 2 μg/kg BW per minute and then increased to 4 μg/kg BW per minute 10 min later. The decision was undertaken due to the elevated heart rate, which had increased to 160 bpm, and concern about the continued administration of dopamine with the concurrent tachycardia. Throughout this time, the patient was obtunded, laterally recumbent, and had continuing hemorrhagic vaginal discharge. The pRBC transfusion was started (at 19:29 h) and following a brief 5-minute test dose (1 mL/kg BW per hour), the remainder of the unit was administered at 10 mL/kg BW per hour and completed within 1 h. Tranexamic acid (TXA) (Tranexamic Acid Injection BP 100 mg/mL; Sterimax, Mississauga, Ontario), 10 mg/kg BW, IV, q8h, was administered for the next 24 h to facilitate hemostasis by minimizing fibrinolysis. Fifteen minutes after starting the transfusion, MAP began to increase from 60 to 69 mmHg. Five minutes later, the patient became more alert and norepinephrine and dobutamine were decreased to 0.4 and 2 μg/kg BW/min, respectively. After the dog had received approximately half the transfusion, norepinephrine and dobutamine were discontinued (at 19:55 h). At this time the MAP was 79 mmHg, the dog regained sternal recumbency, and was quiet but alert. Fluid therapy was decreased to 5 mL/kg BW per hour, and 185 min after the start of anesthesia (at 20:20 h), the dog was returned to a run in the ICU with its puppies.

Overnight the dog was disinterested in nursing the puppies and had a subjectively small quantity of milk. A single dose of oxytocin (Oxytocin 20 IU/mL; Vétoquinol) was administered overnight (1 IU IM, at 20:30 h) for uterine involution. Two additional doses of oxytocin were administered (1 IU SC, at 8:00 h and 10:00 h) in the morning and the dog was prescribed domperidone (TEVA-Domperidone; TEVA, Toronto, Ontario), 2 mg/kg BW, PO, q12h for 7 d at home to support lactation. The next morning, a baseline cortisol (367 nmol/L; RR: 30 to 230 nmol/L) performed on blood sampled at admission was available. At this time, the dog’s hematocrit was stable (increasing from 25% before transfusion to 30% after transfusion) and the dog was discharged later that day with her 9 healthy puppies. No further complications were reported by the owner.

Given the severity of the described case, there was a change in the authors’ institutional practice. Dogs undergoing cesarean section without OVH were recommended to be hospitalized for 24 h and have serial hematocrits performed. Over a 2-year period, 47 dogs were presented to the emergency department for suspected dystocia. Two of these dogs were euthanized; the first because of financial constraints, and the second as it was 1 d post-partum (with no puppies left to deliver) and investigation revealed a gastric dilatation and volvulus. Of the remaining 45 dogs presenting with dystocias, 16 (35.6%) delivered vaginally and 29 (64.4%) required cesarean sections. None of the vaginal deliveries required medical treatment or transfusion for PPH. Of the surgical cases, 13 had a cesarean section without OVH and 16 had a cesarean section with OVH. There were 3 cases (including the current one) of PPH requiring transfusion in dogs that did not undergo OVH at the time of cesarean section. The other 2 dogs requiring transfusions did not require additional medical intervention to maintain arterial blood pressure and the trigger for transfusion was an acute decrease in hematocrit below 20% after surgery (14 and 16 h). Therefore, the overall incidence of PPH requiring medical management or transfusion for dogs presenting for dystocia was 6.7% (3 of 45) at the CHUV over the last 2 y. The incidence of PPH requiring treatment in dogs which were not spayed at the time of cesarean section was 23% (3/13).

Discussion

This report describes the successful medical management of a severe peripartum (intrauterine) hemorrhage in a Bouvier des Flandres bitch undergoing cesarean section without ovariohysterectomy. The exact cause and risk factors associated with the intrauterine hemorrhage are unknown; leaving the uterus in situ may have increased the risk. Potential factors leading to the observed hypotension beyond the hemorrhage include the use of neuraxial blockade, and/or possible concurrent disease. The detection of PPH is not always immediate and may not coincide with surgery. Following the case reported here, a change in the management of cesarian sections was introduced at the authors’ institution, resulting in post-operative blood transfusions in 2 further cases. The management of PPH in the veterinary and human literature will be discussed to provide the reader with practical techniques for managing this complication in practice.

There is only 1 report in the literature pertaining to the treatment of PPH in dogs (6). The report describes the use of medroxyprogesterone acetate (2 mg/kg BW, SC) in 10 dogs with persistent PPH. Though no controls were included, the author described satisfactory cessation of hemorrhage within 24 h. Unfortunately, to date, no standardized approach to the management of PPH has been investigated or described (1).

The incidence of PPH has not been reported in dogs. The reported incidence from the authors’ institution over the last 2 y was 6.7% for all dogs presenting with dystocia. However, all dogs with PPH (n = 3) underwent cesarean section without OVH. All dogs spayed at the time of cesarean surgery or delivering vaginally were unaffected. This may suggest a relationship between PPH and cesarean section without concurrent OVH; however, an appropriately powered prospective study with defined transfusion triggers is required to investigate this association. This retrospective analysis should be interpreted cautiously as the 2 cases of transfusion were precipitated following a change in practice (overnight hospitalization and serial hematocrit measurements) instituted after the case reported here and the small sample size (3 cases) precludes firm conclusions being drawn. Nonetheless, there are commonalities between the authors’ experiences and risk factors reported in the human literature (described below). Together, this supports the necessity for further investigation.

Peripartum hemorrhage is better described in cattle and horses. In large animals the hemorrhage is generally secondary to trauma associated with calving or foaling, with lacerations occurring in the uterus, cervix, or vagina (7). The most common cause of hemorrhage is rupture of the uterine artery within the broad ligament causing a hematoma or potential hemoabdomen. In horses, PPH accounts for 40% of all periparturient deaths in mares (8). The literature in large animals describes conservative (packing body cavities, fluid therapy) and more aggressive (blood transfusion, surgical interventions) techniques for management (7,8). Unfortunately, fundamental differences in etiology and presentation limit direct comparisons among species.

In human medicine, PPH occurs more frequently in high-resource countries (partly due to the increasing proportion of cesarean sections being performed) and is a major cause of postnatal morbidity and mortality (9). The likelihood of major hemorrhage is greater in patients following cesarean section compared to vaginal delivery. A recent review evaluated techniques for the management of PPH in humans (10). The literature supports the correction of antenatal anemias (hemoglobin < 90 g/L, assessed at the beginning of the third trimester) as it will minimize the impact of PPH (11). Antenatal anemia is the only modifiable risk factor in women. Nonmodifiable risk factors for PPH include increasing maternal age, obesity, abnormal placentation, multiple pregnancies, and previous cesarean sections (10). Parturient management of hemorrhage, beyond definitive surgical hemostasis, consists of uterotonic treatments. These can be physical (uterine massage) or pharmaceutical, which include oxytocin, and/or additional uterotonic agents (misoprostol, ergometrine, and carboprost) (10). A recent meta-analysis showed that the prophylactic use of the antifibrinolytic agent TXA before the first incision in combination with oxytocin following delivery reduced the incidence of PPH (12).

Hyperfibrinolysis has been documented in trauma, shock, and invasive surgeries in humans and it increases the risk of hemorrhage. Tranexamic acid (and ɛ-aminocaproic acid) inhibits fibrinolysis by blocking the lysine binding site of plasminogen, thus preventing the formation of plasmin which breaks down fibrin (13). Another factor considered to prevent PPH is early consideration of hysterectomy in patients at risk (10). Based on the risk factors in humans, the patient in the current report was at increased risk due to the cesarean section versus vaginal delivery, being multiparous, not receiving uterotonic agents nor TXA prophylactically, and not having an OVH performed. An investigation into risk factors, as well as prospective studies evaluating the prevalence and prevention of PPH in veterinary species are needed.

The treatment of hypotension in this case required multiple factors to be considered simultaneously. The initial evaluation of the patient before anesthesia suggested presence of mild dehydration, likely due to the dog not eating or drinking normally during the prolonged parturition. One immediate factor which may have been responsible for the hypotension was the use of a lumbosacral epidural anesthetic. Local anaesthetics administered epidurally, alone or combined with an opioid, can cause hypotension by blockade of sympathetic response (14–16). However, epidurals with local anaesthetics limited to the abdominal region cause less hypotension compared to high thoracic epidurals, which also affect sympathetic innervation to the heart leading to decreased heart rate and contractility (16). Interestingly, in the event of PPH in humans, neuraxial analgesia is often recommended (using a rapid acting local anesthetic such as lidocaine) (17). The benefit of local anesthetic boluses through an epidural catheter is the ability to avoid general anesthesia. However, when blood loss is severe (> 1000 mL, approximately > 15 mL/kg BW) neuraxial techniques are to be implemented with caution. The approach to blood loss in the presence of neuraxial analgesia emphasizes preparedness; placement of appropriate cannulas (ideally, 2 large-bore), use of IVFT, vasopressors/inotropes, and considering early implementation of direct arterial blood pressure monitoring (17). In the reported case, despite the administration of several isotonic crystalloid fluid boluses, there was no improvement in the MAP. Given this lack of response, there was the suspicion that this patient was non-fluid responsive, and as a result the authors proceeded to vasopressor and inotropic therapies early on in the anesthetic procedure.

The use of norepinephrine, dopamine, and dobutamine in this case is based on drug availability and preparedness at the authors’ institution. Norepinephrine provides some positive inotropic effect as well as a significant increase in systemic vascular resistance. Dopamine and dobutamine are used for their marked inotropic effect (compared to norepinephrine) (18). As dopamine has a greater chronotropic effect compared to dobutamine, the change to dobutamine was an attempt to remove dopamine as a contributor to the observed tachyarrhythmia in the post-operative period. There are no consensus statements or guidelines regarding the optimal vasopressor or inotrope in hemorrhagic shock in small animals (18). In humans, ephedrine and phenylephrine are commonly used for hypotension secondary to neuraxial techniques during cesarean sections. Of the two, phenylephrine may be a better option as it has been shown to reduce the likelihood of fetal acidosis in elective cesareans (19). A similar benefit of phenylephrine was seen when compared to norepinephrine (20). Dexamethasone was administered in an effort to correct an undiagnosed hypoadrenocorticism or the downregulation of the adrenergic receptors secondary to the presence of sepsis/systemic inflammatory response or prolonged shock. Retrospectively, the presence of a stress leukogram (Table 1), combined with the elevated baseline cortisol measurement ruled out hypoadrenocorticism.

It is possible that the early implementation of vasopressor and inotropic therapies masked the physiological signs of the uterine hemorrhage, complicating the detection of ongoing hemorrhage. Usually, a reduction in heart rate would be expected following correction of hypovolemia and hypotension. In this case, the minimal change in heart rate may have reflected an ongoing physiological response to hemorrhage. Perhaps greater volumes of crystalloid, hypertonic saline, and/or colloid fluids may have mitigated the prolonged pressure support in this case and the need for transfusion, especially considering blood lactate was within reference range, suggesting that oxygen delivery was sufficient to avoid significant generalised hypoxia and anaerobic metabolism. A greater effort to quantify the blood loss (e.g., weighing absorbent pads) may have provide earlier evidence of an acute hemorrhage and supported the decision to transfuse, though the exact volume remaining in the uterus would have remained unknown.

This report describes the successful management of a case of peripartum hemorrhage in a dog. The severity of this case resulted in an institutional change in management (24 h hospitalization and serial hematocrit measurements) for dogs undergoing cesarean section without ovariohysterectomy as uterine hemorrhage is not always immediately apparent. Prospective studies investigating the incidence, predisposing factors, prevention, and treatment of peripartum hemorrhage and other complications associated with dystocias and cesarean sections are required. CVJ