Case of the Month #7

Rathai Anandanadesan

A 74 year old female with a background of hypertension presented to the emergency department with gradually increasing breathlessness and pleuritic chest pain following a recent long haul flight.

She had a CTPA which confirmed a large pulmonary embolus in the pulmonary trunk.  As her vital signs remained stable while receiving 3L/min oxygen therapy via nasal cannula, she was given treatment dose Dalteparin and referred to the medical team for admission.  While waiting to be admitted, she collapsed and had a PEA cardiac arrest.  She was given Alteplase during resuscitation and regained consciousness after 10 minutes of CPR.   By then she was able to maintain her own airway and had a GCS of 14/15.  She was then commenced on an Alteplase infusion to complete systemic thrombolysis treatment.  Bedside echocardiography showed a dilated right ventricle with reduced function. 

An ABG taken post return of spontaneous circulation while receiving oxygen via non-rebreather mask showed:  pH 7.28, paO2 15kPa, paCO2 6.4kPa, HCO3 17mmol/L, BE -4mmol/L, lactate 3mmol/L, Na+ 142mmol/L, K+ 4.2mmol/L, glucose 8mmol/L, and Hb 100g/L. 

However, subsequently after regaining consciousness she required several fluid boluses to which there was a transient improvement in her blood pressure.   

In ICU, her blood pressure continued to drop though transiently responded to fluid resuscitation.  She was commenced on a noradrenaline infusion, but required escalating doses.  She had another PEA cardiac arrest during which she was intubated.   

An ABG taken on 100% O2 showed: pH 6.9, paO2 25kPa, paCO2 8.4kPa, HCO3 10mmol/L, BE -8mmol/L, lactate 8mmol/L, Na+ 138mmol/L, K+3.8mmol/L, glucose 6mmol/L, and Hb of 30g/L.   

The patient was noted to be oozing from line sites and had bruising over her chest. 

The massive haemorrhage protocol was commenced and she was resuscitated with large volume blood transfusion and blood products, given calcium and tranexamic acid.  She had return of spontaneous circulation following 20 minutes of CPR.  Her haemoglobin increased to 110g/L.  Despite ongoing resuscitative measures, her condition continued to deteriorate and she passed away. 

How can acute pulmonary embolism be classified? 

  • Massive PE:  Acute PE with persistent hypotension (systolic BP <90mmHg for at least 15 minutes or requiring vasopressor/inotropic support) that is not due to another cause. 
  • Submassive PE:  Acute PE with signs of right ventricle dysfunction and/or myocardial ischaemia without systemic hypotension. 
  • Low risk PE:  Acute PE with normal cardiac biomarker levels, right ventricular function, and blood pressure. 

Alternatively, the Pulmonary Embolism Severity Index (PESI) can be used to identify low, moderate, and high risk patients.  These categories correlate with low risk, submassive, and massive PE respectively. 

This patient had a massive PE. 

What is the pathophysiology of acute massive PE? 

What investigations may help prognosticate mortality in pulmonary embolism? 

  • Troponins:  This is a sensitive and specific biomarker for irreversible myocardial injury.  Increased levels have been associated with increased short term mortality risk in acute PE.   
  • NT pro-BNP:  BNP shows correlation with right ventricular (RV) dysfunction in acute PE and is also associated with increased short term mortality.   
  • Lactate:  Plasma levels > 2mmol/L can predict PE related complications in high risk patients. 
  • Transthoracic echocardiography (TTE):  Findings of RV overload and dysfunction have been associated with increased short term mortality and PE-related complications.  If accompanied with low cardiac output state, acute RV failure is the leading cause of death in patients with massive PE. 

What are findings suggestive of RV dysfunction on TTE? 

  • Enlarged, dilated RV with RV/LV diameter ratio > 1 in 4-chamber view 
  • Flattened intraventricular septum in the parasternal short axis view 
  • Tricuspid annular plane systolic excursion (TAPSE) <16mm 
  • Dilated inferior vena cava with reduced inspiratory collapsibility in the subcostal view 
  • McConnell sign:  hypokinetic RV free wall with preserved contractility of RV apex 

What are specific treatment options for massive PE? 

  1. Systemic thrombolysis using tissue plasminogen activator (tPA) is most effective if initiated early within 48 hours of onset of symptoms.   

Alteplase is the only tPA approved for systemic thrombolysis in acute PE in the UK and is administered intravenously usually at a dose of 100mg over 2 hours.  

After completion of systemic thrombolysis with a recombinant tPA, a heparin infusion is usually started to maintain anticoagulation. 

In a cardiac arrest it has been suggested to give Alteplase 50mg IV bolus. 

  1. Catheter-directed thrombolysis or thrombus fragmentation, suction thrombectomy, or rheolytic thrombectomy can be used in those where systemic thrombolysis is contraindicated and interventional radiology services are available. 
  1. Surgical embolectomy can be considered in patients with inadequate response or contraindications to thrombolysis or those requiring cardiopulmonary resuscitation.  This procedure can be facilitated with ECMO. 

What is the risk of major haemorrhage following systemic thrombolysis? 

  • Risk of major haemorrhage following thrombolysis: 9%-33%. 
  • Risk of intracranial haemorrhage: 1.5-7% 
  • This patient was high risk of suffering a major haemorrhage as she was elderly, she had already received anticoagulants prior to thrombolysis, and she received CPR during thrombolysis. 

Key take home messages from the case

  • Cardiac biomarkers and echocardiography can be useful in prognosticating risk for mortality in patients with acute PE. 
  • Acute massive PE can lead to RV pressure and volume overload, RV dysfunction, and cardiogenic shock. 
  • Acute RV failure is the leading cause of death in patients with massive PE. 
  • Systemic thrombolysis is currently indicated for massive PE, but is not without significant risk of major haemorrhage. 

Further Reading

Daley MJ, Murthy MS, and Peterson EJ. Bleeding risk with systemic thrombolytic therapy for pulmonary embolism: scope of the problem. Therapeutic Advances in Drug Safety, 2015; 6(2): 57-66.

Jaff MR, McMurtry MS, Archer SL et al. Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association. Circulation, 2011; 123 (16): 1788-1830.

Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Respir J 2019.

Tong CR and Zhang ZH. Evaluation factors of Pulmonary Embolism Severity and Prognosis. Clinical and Applied Thrombosis/Hemostasis, 2015; 21 (3): 273-284.

Yamamoto T. Management of patients with high-risk pulmonary embolism: a narrative review. Journal of Intensive Care, 2018.