Introduction

Both cardiopulmonary collapse and sudden cardiorespiratory arrest are unusual during delivery. They are even more life-threatening in low-resource settings [1, 2]. Proper management of the critically ill patient in cardiopulmonary collapse requires rapid identification of its etiology. Etiologies include obstetric and non-obstetric events [3, 4]. In the obstetric field, cardiopulmonary collapse may be caused by pulmonary embolism (PE) or amniotic fluid embolism (AFE) during labor. Some risk factors include abdominal surgery, obesity, hypertension, severe preeclampsia, chronic medical diseases, and prolonged immobilization [5]. Hypercoagulability in pregnancy has been estimated to increase the risk of venous thromboembolism by about fivefold. However, it is infrequent among healthy women [6, 7]. The incidence of venous thromboembolism (VTE) was 0.4 per 1000 pregnancies, of which 83.3% were deep vein thrombosis and 16.7% were pulmonary embolism in Chinese pregnant women [8]. According to the report of Morikawa and others, the incidence of VTE after cesarean delivery (0.0074%) was significantly higher than that after vaginal delivery (0.0012%) [9, 10]. Due to its rarity, awareness of this pathology is low among reproductive-age and pregnant women, particularly, in low-middle-income countries (LMICs) [11]. APE is often rapidly fatal [12, 13]. A delayed recognition could lead to maternal death, but a misdiagnosis results in overtreatment and neglect of other pathologies [14]. According to a report of Elgendy, the rates of in-hospital mortality were almost 200-fold higher among those who had APE (29.3 vs 0.13, per 1000 pregnancy-related, P < 0.001) and the rates of in-hospital mortality have not improved (2.6% in 2007 vs 2.5% in 2015, Ptrends = 0.74) [15]. If APE occurs before delivery, both maternal–fetal outcomes are dramatically poor [16]. Clinically, the prognosis of PE is better than AFE. PE can be treated with timely intervention but requires early recognition. PE contributes highly to peripartum maternal death [17, 18]. The suspicion of PE can be confirmed by imaging modalities, Wells score, D-dimer, and histopathological endpoints [19, 20].

PE can occur before delivery, during delivery, and in the postpartum period [16, 21]. However, the rarest is PE during cesarean section (C-section). Optimal management requires timely recognition, and treatment requires a multidisciplinary team which involves the coordinated action of the cardiologist, obstetrician, anesthesiologist, and surgeon. An implemented treatment includes thrombolysis and anticoagulation [22]. Early surgical embolectomy and bridged with extracorporeal membrane oxygenation may be required in some severe cases [23,24,25]. Cesarean hysterectomy is often undertaken due to the massive active bleeding after failed conservative treatment, coagulation disturbances, and a high risk of postpartum hemorrhage (PPH) that treatment of PE requires [26]. Nevertheless, hysterectomy is not optimal for a young woman who desires to preserve fertility. Meanwhile, the paucity of strong evidence in the medical literature makes it difficult to assess the safety of conservative treatment in this emergency.

Hereby, we present an uncommon case of acute embolism pulmonary during cesarean section in an otherwise healthy woman and thereby contribute to the literature on the possibility of uterine preservation where applicable.

Case presentation

A 36-year-old woman, Gravida 3 Para 1, spontaneous abortion 2, was admitted to Tu Du Hospital due to spontaneous labor with vaginal bleeding sign. The patient’s medical history was otherwise unremarkable. Her obstetric history recorded a previous cesarean section for breech presentation and two miscarriages. At hospitalization, the patient had normal vital signs. She was at term after an uncomplicated gestation except for placenta previa Grade I. She had a known abnormal placentation site at 28 weeks of gestational age.

Therefore, an emergency C-section was scheduled. Before surgery, the patient was normotensive with a pulse of 82 beats per minute (bpm) and respiratory rate of 20 times per min. Her pre-pregnancy body mass index (BMI) was 21.6 kg/m2. In this pregnancy, her BMI was 25.6 kg/m2 (maternal weight: 54 kg, maternal height: 145 cm). Her legs were noted without gross varicose veins. Complete blood count was normal; coagulation parameters included prothrombin time (PT) of 98%, international normalized ration (INR) of 1.01, temps de quick (TQ) of 13.4 s, activated partial thromboplastin time (APTT) of 28.8 s, and plasma fibrinogen of 480 mg/dL. Electrocardiogram (ECG) showed sinus tachycardia of 116 bpm. The chest radiograph was normal. Obstetric examination revealed infrequent episodes of mild uterine contraction, a closed cervix, and intact membranes. Ultrasound showed normal fetal development in transverse lie, with an estimated weight of 3100 g with normal Doppler blood flow. The cardiotocography (CTG) proceeded as Group I by the American College of Obstetricians and Gynecologists criteria (ACOG 2009). The airway was Mallampati grade II.

At the beginning of the cesarean delivery, her blood pressure was at 130/80 mmHg, pulse rate was 100 bpm, and peripheral transcutaneous oxygen saturation (SpO2) was 100%. The patient underwent general anesthesia with tracheal intubation. After 10 min of surgery, a healthy male newborn weighing 3100 g was delivered with reported Apgar scores of 7 and 8 at 1 and 5 min, respectively, and a normal placenta was gently extracted. Transparent amniotic fluid was approximately 500 ml. However, the patient’s cardiopulmonary system collapsed immediately after placental extraction. At this time, her vital signs deteriorated with blood pressure (BP) at 90/60 mmHg, tachycardia at 125 beats/min, and SpO2 suddenly dropping to 86%. Shock index (SI) of 1.4 (0.5–0.7). Therefore, the initial differential diagnosis was amniotic embolism versus acute pulmonary embolism (Table 1). A “Red Code” was called by anesthesia while the obstetricians continued to manage the surgery. A multidisciplinary team managed the resuscitation. She responded to a total of 30 mg doses of ephedrine.

Table 1 Wells criteria for clinical probability assessment of pulmonary embolism
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During surgery, the obstetrician focused on hemostasis carefully. Bilateral artery ligation, placental bed sutures, and B-Lynch compression sutures were all performed due to the high risk of PPH. Uterotonic drugs including oxytocin, methyl ergonovine, carboprost, and tranexamic acid were administered. The uterus was contracted, so the team decided to preserve the uterus. The uterus and abdomen were quickly and carefully closed to minimize the surgical time. An abdominal drain was placed. Total estimated blood loss was measured at 500 ml and surgical time duration was 100 min. Urine output was measured at 100 ml during surgery.

Meanwhile, urgent transthoracic echocardiography showed a sizable thrombus in the pulmonary vasculature, in the subclavian vein, in the right jugular vein, and in the right ventricular cavity (Fig. 1 and Supplementary videos 1, 2, 3, and 4, respectively). Thus, a diagnosis of pulmonary embolism was established. Ultrasonic assessment demonstrated no abnormalities in the lower limb veins.

Fig. 1
figure 1

Ultrasonic findings showed a sizable thrombus (white arrow) in the pulmonary vascular (A), in the subclavian vein (B), in the right jugular vein (C), and in the right ventricular (D), respectively

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After surgery, the patient was transferred immediately to the intensive care unit (ICU) where she was cared for by a multidisciplinary team consisting of obstetrician, anesthetist, cardiologist, hematologist, and sonographer. Ventilation was maintained by a positive pressure-supported respirator. She was sedated, paralyzed, and maintained with a narcotic, an anticonvulsant drug, and a muscle relaxant drug (Fentanyl 100 mg 02 ampules combined with Midazolam 5 mg 05 ampules intravenous infusion at 6 ml/h, with Rocuronium 10 mg/ml × 5 ampules in 45 ml sodium chloride 0.9% for 50 ml infused via an intravenous electric pump at 10 ml/h). Additional analgesia included subcutaneous morphine sulfate 10 mg and diclofenac 100-mg rectal suppository.

D-dimer levels were markedly increased to 46,700 ng/ml. The coagulation profile showed a weak to moderate blood clot contraction with PT = 62%, INR = 1.29, TQ = 13.8 s, TCK = 34 s, and fibrinogen = 136 mg/dl. Hemoglobin level fell to 7.6 g/dl. The patient was transfused with 2 units of AB-positive packed red blood cells (350 ml/unit) and was given 4 packs of fresh frozen plasma (200 ml/unit), as well as all 10 packs of cryoprecipitate (50 ml/unit). The patient received a therapeutic dose of one ampule of low-molecular-weight heparin (25,000 IU/5 ml/ampule). The abdomen drained 200 ml of abdominal cavity fluid without active bleeding. An intravenous broad-spectrum antibiotic (tarzocin 4.5 g/ampule every 6 h) was given to prevent the secondary infection.

After counseling with an interdisciplinary team, the patient was transferred to Cho Ray Hospital, a tertiary general hospital for further management after 16 h of obstetric and hemodynamic stabilization. At the tertiary center, chest X-ray was normal, and cardiac ultrasound revealed mild right ventricular dilation and normal left systolic function. Unfortunately, the computed tomographic pulmonary angiography (CTPA) confirmed nearly total occlusion of segmental arterial branches from the upper lobes of both lungs, the left and the right lower lobar branches. The descending branch of the left pulmonary artery was partially occluded; the lateral basal and the posterior basal arterial branches of the left lower lobe were completely occluded. Both lungs had small pleural effusions and passive atelectasis of inferior areas. Abdominal ultrasound showed free air, infiltration, and a small amount of fluid in the lower right abdomen. The hepatic and renal function tests as well as the electrolyte profile were within normal limits. However, high sensitivity Troponin 1 and NT-proBNP were elevated at 637.5 pg/mL and 96.75 pmol/L, respectively. The complete blood count test showed moderate anemia with Hb of 79 g/L (7.9 g/dL), an increased white blood cell count (WBC) of 17.69 G/L, and a low platelet count of 119 G/L.

At the tertiary hospital, the patient received 2 additional units of blood and was intensively treated with anti-coagulant therapy. Specifically, heparin 10,000 IU was first administered with 50 ml sodium chloride 0.9% solution, giving a bolus of 15 ml (3000 IU) and maintenance of 4–6 ml per hour (18 IU/kg) monitored by activated clotting time (ACT) levels (147–172 s). On the second day, the patient was extubated; oxygenation was supported with a nasal cannula. Heparin was stopped. Lovenox 60 mg/0.6 ml was subcutaneously injected twice a day at 12-h intervals. Additionally, she received pantoprazole for gastroesophageal reflux disease (GERD) during her admission to the intensive care unit. She was discharged after 2 weeks in good health, with normal consciousness and without neurological injuries. The patient and her family felt grateful to the team for saving her life.

Discussion

Cardiopulmonary complications of C-sections are a leading cause of maternal morbidity and mortality, particularly in low-middle-income countries or in low-resource settings [2]. Almost all cases of thromboembolism (TE) are diagnosed during the postpartum period. An APE that occurs immediately during C-section seems rarely to be reported. This pathology is mainly documented through a case by case in the literature [7, 27, 28]. According to the retrospective study of Lai et al., out of 1377 pregnant women who underwent C-section, only 7 cases developed venous TE and 86% of cases were within 7 days of postpartum. This study revealed that hypertension and the presence of varicose veins were associated with TE following C-section [29]. In our case, several risk factors contributed to this woman’s cardiorespiratory collapse. First, an advanced maternal age > 35 years old, previous cesarean delivery, and C-section due to placenta previa in this pregnancy (Table 2). After the coronavirus disease 2019 (COVID-19) pandemic, the incidence of VTE seems likely to increase [30,31,32]. Particularly, the PE cases associated with the placental implantation site have been recorded recently at our center. Placenta previa resulting in a massive PPH may be a high risk for VTE [33, 34]. However, none of the similar reports has been documented in the literature. Therefore, the underlying mechanism of this occurrence due to hidden blood clots from the deep veins before surgery or from placenta previa after placental delivery remains controversial.

Table 2 Summary of peripartum pulmonary embolism over the past last 10 years in the literature
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A timely diagnosis of APE remains totally difficult since it is overlapped with other complications and is camouflaged by the physiological changes in pregnancy [16]. In the case of a parturient with signs of sudden cardiopulmonary arrest during C-section, the initial differential diagnosis includes anaphylaxis, pulmonary embolism (PE), and acute coagulopathy and even cerebral hemorrhage due to amniotic fluid embolism, or cerebral hemorrhage due to severe preeclampsia. However, this patient did not suffer hypertension during pregnancy. The patient showed no immediate signs of allergic reaction to the general anesthesia and the collapse did not occur immediately.

Clinically, the catastrophic manifestation of PE and AFE is similar. In the current case, since the patient was under general anesthesia, the initial clinical symptoms such as dyspnea, shortness of breath, and chest pain were absent. Diagnosis criteria in AFE have been studied [47]. According to the Society of Maternal Fetal Medicine (SMFM) and the Amniotic Fluid Embolism Foundation, the four proposed diagnostic criteria for AFE include (1) sudden cardiac arrest or both respiratory and hemodynamic collapse, (2) disseminated intravascular coagulopathy (DIC), (3) absence of fever, and (4) clinical onset during labor or within 30 min of delivery [12, 48]. Well’s diagnostic criteria for PE were met in our patient [20]. An increased D-dimer is a valuable predictive marker for PE (Table 1). The D-dimer cut-off value of 800 ng/mL ensures high sensitivity and increases specificity compared to the conventional threshold of 500 ng/mL. Considering this higher threshold can reduce the number of unnecessary CT scans and subsequently unnecessary radiation exposure in women after Cesarean delivery [49, 50]. Nevertheless, the value of D-dimer is still limited since the concentration depends on the gestational age [14]. Recently, the value of the Fibrin monomer test has also been a concern since its concentration is nearly unchanged during pregnancy [51]. However, our patient was assessed with a low risk of VTE during the antenatal period following The Royal College of Obstetricians and Gynaecologists (RCOG Green-top Guideline, no. 37a. Reducing the risk of thrombosis and embolism during pregnancy and the puerperium. London: RCOG, 2015); thus, the screening modalities were not indicated [34]. According to local guidelines, no routine thromboprophylaxis was given during the antenatal care. Moreover, the patient was in emergent condition with hemorrhage originating from placenta previa. Thus, the surgery was a priority.

But more than 90% of pregnant women with suspected PE do not have PE [14]. The gold standard for diagnosis of PE is found at autopsy. Fortunately, the patient lived, so the only evidence for PE was the ultrasonic findings of the blood clot in the heart and pulmonary artery. Ultrasound can be performed at the bedside more rapidly than a CT scan and so is a more useful diagnostic tool in a critical situation [19]. CT angiopathy can be indicated to confirm the diagnosis of APE when the patient is in stable condition [7, 24, 52].

Ultrasound can also help differentiate between PE and AFE. Histopathologically, AFE material can include amniotic fluid, as well as fetal cells, hair, or other debris entering the mother’s bloodstream through the placental bed. It is usually rapidly progressive and has a very high mortality [53]. These materials are sonographically different in appearance from a clot. In our patient, no strange structure was on ultrasound. Thus, cardiopulmonary collapse due to PE was the most likely diagnosis in this pregnant woman.

The neonatal outcome should be mentioned. In this case, PE occurred after fetal extraction. The infant was unaffected. However, when PE occurs prior to cord clamping, the wellbeing of both mother and child is at risk. Emergency C-section may be necessary to save the newborn life. Additionally prompt delivery improves maternal outcome by reducing maternal vena cava compression due to the gravida uterus, thus increasing maternal cardiac output, and may improve the hypercoagulability of pregnancy [21, 46, 53].

The modern management of PE includes anti-coagulation, thrombolysis, and surgical pulmonary embolectomy. The choice of management should be based on the patient’s status and the size of the thrombus clot [26, 38]. However, no practical guidelines have been established for this difficult entity [46]. Thrombolytic therapy could be used if the PE occurs before labor [18]. Remarkably, thrombolysis and administration of tissue plasminogen activator may be contraindicated at the onset of massive hemorrhage during surgery [23, 24]. Postpartum thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) needs to be strictly monitored because the treatment may lead to massive bleeding [25, 54]. In the present case, anticoagulant treatment using intravenous heparin and low molecular weight heparin subcutaneous injection were indicated during obstetric stabilization without excessive vaginal bleeding.

In general, it is a risk to conserve the uterus in a pregnant woman with PE because of the high risk of PPH and the associated coagulopathies. Previously, almost all reports have recommended emergent cesarean hysterectomy in the management of pulmonary embolism during cesarean delivery. Intra-uterine tamponade using a Bakri® postpartum balloon may be performed for temporary hemostasis [23]. In this case, the patient was administered 1 g of tranexamic acid as a routine drug in the PPH during C-section. The team did not assess the pulmonary embolism at the initial moment. However, the risks and benefits of this drug administration are still controversial due to the risk of thrombosis [55,56,57]. Karakosta et al. have recently reported a case of uterine conservation after acute life-threatening PE during C-Section which required postpartum rescue hysterectomy due to massive bleeding [26]. Initial uterine conservation carries the risk of subsequent emergency hysterectomy. Immediate resuscitation and coagulopathy monitoring is essential. Life-saving treatment must always be a priority over future fertility. However, when there is a multidisciplinary team immediately available and when immediate surgery could be undertaken if necessary, uterine conservation with preservation of future fertility can be considered. In addition, aside from uterotonic drugs, the time duration between a cesarean hysterectomy and all hemostatic procedures in uterine conservative surgery is also a main concern since it relates directly to maternal outcomes. In our case, the total surgical time duration from the onset of APE to abdominal closure was 110 min. Due to a lack of evidence, the team could not compare this surgical time to any documents in the literature. Further studies are required to clarify this entity. Nevertheless, regarding the surgical methods, the hemostatic procedures relating to this surgery were mentioned in a recent article. In this article, the total time duration of the uterine conservative surgery was shorter than that of a cesarean hysterectomy [58].

Particularly, postpartum care needs to be strictly monitored in APE cases due to the high risk of PPH and infectious post-surgery. Song et al. have reported a case of obstructive uropathy caused by a 20-cm-sized hematoma anterior to the bladder in Retzius space following postpartum pulmonary embolism [59]. Recently, elevated plasma lipocalin-2 levels have been a promising biomarker in predicting long-term major adverse events among normotensive patients with APE for risk stratification in the intermediate-risk group [60]. Most importantly, multidisciplinary management with interhospital transfer and advanced armamentarium is necessarily required to control the coagulopathy profile, prevent multi-organ dysfunction, and reduce significant mortality [23, 61]. Maintenance therapy using LMWH or warfarin should be continued for at least 6 weeks postnatal and for a minimum of 3 months in total as these have proven safe in breastfeeding women. The subsequent pregnancy needs to be treated with VTE prophylaxis [62].

Conclusions

The diagnosis of APE remains a challenge due to its rarity, sudden onset, and non-specific symptoms. A high index of suspicion for acute pulmonary embolism during cesarean delivery is potentially necessary, even in any parturient woman. Immediate interdisciplinary resuscitation can minimize maternal death. Although cesarian hysterectomy has been the standard treatment, when the right resources are present, uterine conservation may be considered. Further data is required to determine under which conditions cesarean hysterectomy or uterine conservative management is better.