Acute neurological deficit with submassive pulmonary emboli
- Adam Calthrop ,
- Asad Shabbir ,
- Michael Raffles and
- Kieran Hogarth
- Royal Berkshire NHS Foundation Trust, Reading, UK
- Correspondence to Adam Calthrop; adam.calthrop@nhs.net
Abstract
Pulmonary embolism (PE) is frequently encountered in the emergency department. Syncope, often as a consequence of impending haemodynamic collapse, is associated with increased mortality. While loss of consciousness owing to cerebral hypoperfusion and reduced left ventricular preload is a common cause of collapse with large volume PE, other syndromes can also cause neurological deficit in thromboembolic disease. Here, we describe a case of a woman in her 60s, presenting to the emergency department with features of high-risk PE. During clinical examination, the patient collapsed and became unresponsive with a Glasgow Coma Scale of 4/15 despite normal haemodynamics. Neurological signs were noted and CT revealed evidence of a large territory cerebral infarction. Further cardiovascular investigations identified a grade 4 patent foramen ovale. We describe a challenging case of established venous thromboembolism complicated by paradoxical embolism, highlighting the importance of thorough clinical examination and investigation and discuss the current evidence base of treatments.
Background
Pulmonary embolism (PE) is a common cause of morbidity and mortality.1–5 Symptoms of PE such as dyspnoea are frequently encountered in emergency departments and urgent care services.6 7 Patent foramen ovale (PFO) is a common foetal remnant present in up to 25% of the population.8 There is some evidence that the presence of PFO is associated with increased risk of adverse outcomes in patients with PE, particularly ischaemic stroke.9 Certainly, the pathophysiology of paradoxical embolism through PFO as a cause of cryptogenic stroke has been explored thoroughly in the literature.9–13 This recent evidence has led to a consensus on the management of PFO through percutaneous closure alongside antiplatelet therapy in specific patients suspicious of being at high risk of future paradoxical embolism.14 However, the optimum strategy to manage patients with simultaneous PE and ischaemic stroke in the setting of PFO remains unclear.
Case presentation
A woman in her 60s, with a background of essential hypertension and obesity presented to the emergency department, with a 2-week history of dyspnoea, especially on exertion. This rapidly worsened in the days preceding presentation, with exercise tolerance falling to just four steps. She denied chest pain, cough, fever, orthopnoea or paroxysmal nocturnal dyspnoea. The symptoms started 2 days after receiving her first dose of the AstraZeneca COVID-19 vaccine. The patient took ramipril 10 mg once daily for hypertension. She reported no drug allergies. A sibling had recently suffered a stroke at 60 years of age. The patient was independent of all activities of daily living.
She was reviewed in the resus area of the emergency department due to severe hypoxia. The patient was profoundly tachypnoeic with a respiratory rate of 26–30. She was hypoxic with fluctuating oxygen saturations of 92%–94% despite receiving 15 L/min oxygen via a non-rebreathe mask. Her respiratory examination revealed equal air entry to both lung bases with no additional sounds. Blood pressure was 158/86 mm Hg and the patient’s pulse rate was 87 bpm. Her heart sounds were normal. She was alert and orientated with a Glasgow Coma Scale score of 15/15. The patient’s abdomen was soft with no tenderness on palpation. The right calf was noted to be larger than the left, but with no pain on palpation or difference in colour. Her temperature was 36.1°C with no clear skin changes or rashes. She did not report any weakness, speech disturbance, facial droop or balance issues.
Investigations
An arterial blood gas analysis was carried out to assess oxygenation status (table 1) which revealed a severe type 1 respiratory failure, with respiratory alkalosis due to hypocapnia. Blood tests were sent including full blood count, urea and electrolytes, C-reactive protein, liver function tests, D-dimer, high-sensitivity troponin-T, prothrombin time and Activated partial thromboplastin time (table 2). A rapid COVID-19 PCR test was negative.
Arterial blood gas (ABG) on 15 L oxygen/min via a non-rebreathe mask
| Values | Reference range | |
| pH | 7.480 | 7.350–7.450 |
| pCO2 (kPa) | 4.58 | 4.70–6.40 |
| PO2 (kPa) | 8.67* | 11.1–14.4 |
| Na+ (mmol/L) | 144 | 133–146 |
| K+ (mmol/L) | 3.4 | 3.4–4.6 |
| Cl- (mmol/L) | 107 | 98–107 |
| Ca2+ (mmol/L) | 1.17 | 1.15–1.29 |
| Urea (mmol/L) | 9.0* | 2.5–7.8 |
| Creatinine (µmol/L) | 76 | 45–90 |
| Glucose (mmol/L) | 6.5 | 4.0–11.1 |
| Lactate (mmol/L) | 1.7* | 0.5–1.6 |
| Haemoglobin (g/L) | 115 | 115–165 |
| sO2 (%) | 92.0* | 95.0–99.0 |
| F02Hb (%) | 90.8* | 94.0–98.0 |
| FC0Hb (%) | 0.8 | 0.5–1.6 |
| FMetHb (%) | 0.6 | 0.0–1.6 |
| FHHb (%) | 7.9* | 0.0–6.0 |
| Base excess (mmol/L) | 0.9 | −2.0–3.0 |
| HCO3 - (mmol/L) | 25.1 | 21.0–28.0 |
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*Abnormal values.
Clinical haematology and biochemistry
| Value | Reference range | |
| Haemoglobin (g/L) | 112* | 120–170 |
| White cell count (109 /L) | 12.5* | 4–10 |
| Platelet count (109 /L) | 285 | 150–410 |
| Mean cell volume (fL) | 77.2* | 83–101 |
| Mean cell haemoglobin concentration (g/L) | 293* | 315–345 |
| Neutrophil count (109 /L) | 10.3* | 2–7 |
| Lymphocyte count (109 /L) | 1.6 | 1–3 |
| Prothrombin time (s) | 17.3* | 9.4–12.2 |
| Activated partial thromboplastin time (s) | 29.1 | 21–31 |
| D-dimer (ng/mL) | 18,587* | <500 |
| Sodium (mmol/L) | 142 | 133–146 |
| Potassium (mmol/L) | 3.5 | 3.5–5.3 |
| Urea (mmol/L) | 11.5* | 2.5–7.8 |
| Creatinine (umol/L) | 81 | 59–104 |
| eGFR (mL/min/1.73 m2) | 67* | >93 |
| Albumin (g/L) | 47 | 35–50 |
| Bilirubin (µmol/L) | 6 | 1–17 |
| Alkaline phosphatase (U/L) | 136 | 60–350 |
| Alanine aminotransferase (U/L) | 14 | 1–50 |
| C-reactive protein (mg/L) | 14* | <3 |
| High sensitivity troponin-T (ng/L) | 154* | 0–14 |
| SARS-CoV-2 PCR | Negative | +/- |
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*Abnormal values.
An ECG showed features of right ventricular strain (figure 1), with T-wave inversion in leads V1–V6 and prominent S-waves. A chest radiograph was unremarkable. Point of care echocardiography was attempted, but non-diagnostic images were acquired owing to poor acoustic windows.
12-Lead ECG taken on presentation at the emergency department. *T-wave inversion with deep S-waves suggestive of right ventricular strain.
On the basis of the history, examination findings and point of care investigations, the pretest probability of a large PE was high. Therefore, anticoagulation with low-molecular-weight heparin (LMWH) was prescribed and a CT pulmonary angiogram (CTPA) was scheduled to confirm the diagnosis. We elected to administer anticoagulation prior to the CTPA. However, before administration of LMWH, the patient stated that she felt unwell, before collapsing and losing all muscle tone. Although the patient had a palpable pulse, she was unresponsive with a threatened airway and a crash call was put out. The team, led by an emergency medicine consultant, proceeded to assess the patient. The airway was stabilised with a jaw thrust. A nasopharyngeal airway was placed due to trismus preventing placement of an oropharyngeal airway. The patient had become more tachypnoeic with a respiratory rate of 32. Her oxygen saturations dropped to 86% on 15 L oxygen/min using a Water’s circuit. There was a quiet bilateral wheeze on auscultation. The patient’s blood pressure was 156/88 mm Hg with a pulse rate of 110bpm. Rhythm monitoring confirmed sinus rhythm. Heart sounds remained normal. The patient exhibited intermittent decerebrate posturing and did not respond to stimuli. Her GCS was 4/15 (E1V1M2).
Following discussion with the intensive care team, a differential diagnosis of embolisation of large PE through a communication between the venous and arterial circulation was considered, alongside alternative explanations such as haemorrhagic stroke and brainstem stroke. In order to facilitate the safe transfer of the patient to the CT department and improve oxygenation, the patient was intubated. The CTPA showed filling defects within the left main pulmonary artery and its lobar branches, as well as the lobar branches of the right main pulmonary artery (figure 2) confirming bilateral PE. A visible contrast blush from the right atrium into the left atrium was noted (figure 3).
CT pulmonary angiogram. *Filling defects within the left main pulmonary artery and its lobar branches, and lobar branches of the right main pulmonary artery.
CT pulmonary angiogram. *Contrast blush through intra-atrial septum from right atrium to left atrium suggestive of patent foramen ovale.
Another concerning finding was a completely thrombosed left common carotid artery (figure 4), from its origin and extending beyond the superior window of the scan. A brain CT was performed which excluded intracranial haemorrhage, however it revealed an area of low density within the left temporal lobe involving middle and inferior gyri, in keeping with infarction (figure 5). Hyperdensities within the left terminal carotid extending into the anterior cerebral artery, middle cerebral artery, basilar tip and proximal posterior cerebral artery were noted, in keeping with intravascular thrombus (figure 6). Multifocal mature cerebellar infarcts were also identified.
CT pulmonary angiogram. *Thrombosed left common carotid artery.
CT head scan on stroke windows shows area of established infarction within left middle temporal gyrus (red arrow).
Hyperdense vessel (A1ACA and M1MCA) in keeping with intravascular thrombus.
The cardiology team recommended an enhanced transthoracic echocardiogram with agitated saline to exclude septal defects. This showed a grade 4 PFO, with preserved left ventricular systolic function and severe septal hypertrophy (video 1).
Differential diagnosis
Prior to obtaining the echocardiogram, the haematology team was consulted due to a suspicion of vaccine-induced immune thrombocytopaenia and thrombosis (VITT). Testing for PF4 antibodies was recommended in conjunction to treatment with immunoglobulin and plasma exchange. The patient tested negative for PF4 antibodies and had persistently normal platelet levels, so a diagnosis of VITT was unlikely and immunoglobulin treatment with plasma exchange was stopped.
An alternative consideration during the acute event was of arrhythmia, however the patient was placed on cardiac telemetry after she collapsed, and this demonstrated no bradyarrhythmia or tachyarrhythmia. With the aid of a bubble-echocardiogram, the diagnosis of paradoxical embolism through a PFO was made.
Treatment
The patient was taken directly from the CT scanner to the intensive care unit (ICU) 1 hour after the episode of collapse. An emergency consult from a stroke physician was sought regarding thrombolysis. It was felt that the established left MCA infarct demonstrated on CT was of uncertain age and possibly older than 6 hours, therefore thrombolysis for stroke would not be indicated. Mechanical thrombectomy for the basilar tip thrombus was discussed and felt to have a very low benefit of restoring neurological function, with a high risk of complication, and therefore further intracranial imaging to characterise the cerebral vasculature was not performed. The indication for thrombolysis for her PE and the risk–benefit balance was discussed between the ICU and neurology teams, but the risk of causing bleeding into recently infarcted brain was thought to outweigh any possible short-term mortality benefit or long-term reduction of pulmonary hypertension. Although the risk of anticoagulation causing haemorrhagic transformation was considered, it was felt that the risk of not adequately treating the submassive pulmonary emboli was greater. As a result, the patient was anticoagulated with LMWH at a dose of 175 units/kg once daily and given aspirin 300 mg once daily via a nasogastric tube.
Outcome and follow-up
Despite intensive supportive care, the patient’s condition did not improve. Three days after presentation, the patient’s cardiorespiratory function deteriorated. Fixed and dilated pupils were noted. These clinical signs were felt to represent a non-survivable neurological event. The patient passed away shortly afterwards.
Discussion
This case report describes a patient who presented with PE and RV strain, followed by paradoxical embolism leading to ischaemic stroke and subsequent brain death. Large clinical studies of patients with proximal PE are lacking owing to the disease frequently presenting with collapse and cardiac arrest.15 Most evidence for acute treatment of PE are derived from small clinical trials and observational data. The European Society of Cardiology (ESC) guidelines on diagnosis and management of PE place emphasis on identifying patients at risk of early death, advocating early echocardiography and measurement of troponin to identify features of RV strain. However, the precise upper limits of biochemical and clinical markers to identify those at risk of early death from PE remain unclear.3
In the pulmonary embolism thrombolysis (PEITHO) trial, 1005 normotensive patients with confirmed PE and features of RV strain were randomised to receive either thrombolysis with anticoagulation, or placebo with anticoagulation. This double-blind trial found no statistically significant difference in 30-day all-cause mortality. Although death secondary to PE-induced respiratory failure and cardiovascular collapse was reduced in the thrombolysis group, this was at the expense of a significantly increased risk of haemorrhage and haemorrhagic stroke.16 No difference in long-term mortality or incidence of chronic thromboembolic pulmonary hypertension were identified in long term follow-up.17
PFO can be diagnosed by contrast-enhanced transcranial Doppler (TCD), transthoracic echocardiography (TTE) with agitated saline, or transoesophageal echocardiography (TOE) with agitated saline. The sensitivity of TTE to diagnose PFO is approximately 60%.18 19 When combined with the valsalva manoeuvre this can be improved to >90%.18 While TOE is the gold-standard to diagnose PFO, the procedure requires sedation and is invasive, making it high-risk in acutely unwell patients with PE. However, contemporary evidence including several observational studies and a large meta-analysis suggests that TTE is non-inferior to TOE, and should be considered as the first line imaging modality to confirm PFO.20–23 TCD is another non-invasive imaging modality used to screen for PFO, with a sensitivity of 70% at baseline, and 92% when combined with the valsalva manoeuvre.18 However, TCD may produce more false-positives as it is not specific to intracardiac right-to-left shunt.18 There is limited evidence concerning patients with PE and confirmed PFO. However, it has been identified that patients with confirmed PFO are approximately nine times more likely to have an ischaemic stroke, and more likely to have a recurrent PE.9 This suggests that patients with PE might benefit from PFO screening, as this may have an impact on secondary prevention of future PE, and closure should be considered.
While incidence of concomitant PE and acute ischaemic stroke is rare, the available evidence suggests that these patients have a poor prognosis, with 1 review of 29 cases reporting a mortality rate of 31%.24 However, in this small series, patients receiving systemic thrombolysis and thrombectomy did have more favourable outcomes compared with anticoagulation alone, although this difference in mortality did not reach statistical significance (p=0.102). Of note, 90% of these patients had a PFO on TOE.24 One prospective cohort study of 361 patients with symptomatic PE used cerebral MRI to determine frequency of recent ischaemic stroke in this group. Patients underwent cerebral MRI 7 days after enrolment, as well as contrast TTE. They found that silent and symptomatic ischaemic stroke was more frequent in patients with a PFO, although their relative risk CIs were large.25 Neurologists and Emergency Physicians, who regularly see undifferentiated patients presenting with acute neurological deficit, should be vigilant for features of concomitant embolic disease, with a low threshold to screen for PFO.
In our case, the CTPA images did raise the suspicion of PFO (figure 3), but there is currently limited evidence on the use of CT to diagnose PFO, with one retrospective study of 268 adults with PE suggesting that CTPA was superior to non-contrast TTE at detecting PFO. However, the CT images were interpreted by experienced cardiothoracic radiologists and the TTE studies were interpreted by cardiologists with advanced imaging experience.26 In summary, guidelines on the management of PE and concomitant PFO are limited by a lack of evidence. Future study should focus on short-term and long-term patient-focused outcomes in the setting of confirmed PE, to best establish priority of potential interventions and aid in clinical decision making. Furthermore, research should establish whether treatment of those with PE and concomitant PFO with systemic thrombolysis is warranted, given the high incidence of PFO in the general population. As in our case, systemic thrombolytic therapy should be considered on an individualised patient basis, based on risks of bleeding and complications from PE.
Learning points
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Features consistent with high-risk pulmonary embolism (PE) include right ventricular strain on ECG, elevated troponin and syncope.
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In normotensive patients who collapse in the setting of PE, secondary thromboembolic phenomena such as acute stroke should be considered.
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In the setting of concomitant venous and arterial thromboembolism, an enhanced transthoracic echocardiogram with agitated saline should be performed to exclude cardiac septal defects as a cause of paradoxical embolism.
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Systemic thrombolytic therapy, percutaneous thrombectomy and surgical thrombectomy should be considered in cases of paradoxical embolism on an individualised patient basis taking into account comorbidities, bleeding risks and availability of thrombectomy services.
Ethics statements
Patient consent for publication
Footnotes
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Twitter @TheEMboardround
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Contributors AC was involved in the management of the patient, planned and conceptualised the case report and wrote the initial manuscript. AS was involved in the management of the patient, interpretation of the echocardiogram and assisted in preparation of the manuscript. MR was involved in the management of the patient and assisted in preparation of the manuscript. KH was involved in the management of the patient, interpretation of the computed tomography imaging and assisted in preparation of the manuscript. All authors contributed both to the care of this patient and the writing process of the manuscript.
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Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
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Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.
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Competing interests None declared.
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Provenance and peer review Not commissioned; externally peer reviewed.
- © BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.
References
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