Background
Pulmonary Embolism (PE) and diabetic ketoacidosis (DKA) are common in South Africa. Both conditions require protocol-based treatment at a higher level of care. This report discusses the successful management of a patient with massive bilateral PE and DKA using systemic thrombolytics in a resource-limited regional public hospital's emergency department.
Case Presentation
An 80-year-old female was triaged to the emergency department from a local clinic with a preliminary diagnosis of DKA. (Table 11.1)
Triage vitals
| Category | Result |
|---|---|
| BP | 110/60 |
| HR | 130 |
| RR | 18 |
| Room Air SpO2 | 67% |
| HGT | 28 |
| Urine analysis | Ketones 2+ Glucose 3+ |
| South African Triage Score | Red |
The patient reported the following symptoms: a 2-week history of a unilateral swollen and painful right lower limb, mild ongoing chest pain, as well as moderate dyspnoea. She was previously well, with no history of chronic diseases, and could perform her daily activities. The patient had moderate respiratory distress on clinical examination, cold peripheries, appropriate mentation, and intact peripheral pulses. She had a right unilateral lower limb swelling, suggestive of deep vein thrombosis (DVT). ECG revealed sinus tachycardia without any overt features of right ventricular strain. (Figure 11.1)
A limited compression ultrasound of the right leg confirmed a large thrombus of the common femoral vein of the right lower limb. A primary point-of-care echocardiogram did not reveal typical acute right ventricular strain, but the right ventricle was mildly hypertrophied. Venous blood gas analysis indicated that the patient had respiratory compensated high anion gap metabolic acidosis with hyperglycaemia. The patient had normal renal function, a raised D-Dimer of 4.40mg/l (0.0-0.25), and a normal C-reactive protein level. The chest x-ray was normal. A computed tomography (CT) pulmonary arteriogram confirmed a large occlusive thrombus in the right and left main pulmonary arteries, extending into lobar and segmental branches of the right lobe and the left upper lobe, a dilated pulmonary trunk of 31.3mm and a dilated right ventricle. The patient was diagnosed with bilateral pulmonary embolism complicated by diabetic ketoacidosis.
Management
The patient was administered fluids and initiated on an infusion of ultrashort-acting insulin. During the evening, the patient became hypotensive (mean arterial pressure of less than 65mmHg), had worsening hyperlactatemia (1.9mmol/L -> 4.6mmol/L), and deteriorating metabolic acidosis complicated by respiratory acidosis. The bilateral pulmonary embolism prompted consideration for systemic thrombolysis, the only contra-indication being advanced age. Consent for systemic thrombolysis was obtained. After initiation of inotropic infusion of adrenaline to maintain a mean arterial pressure of 65mmHg, Actilyse 100mg was infused over 2 hours. No adverse effects or abnormal bleeding occurred. The patient's haemodynamic status improved significantly after systemic thrombolysis with a resolution of the clinical shock state. The patient continued to receive treatment as per the local DKA protocol. The patient's DKA resolved, and she was successfully transitioned to a subcutaneous insulin.
Discussion
This case describes successful systemic thrombolysis of a geriatric patient who presented with a massive pulmonary embolism complicated by diabetic ketoacidosis at a regional hospital emergency department. Diabetes Mellitus (DM), DKA, and advanced age are all considered risk factors for developing venous thromboembolism. Aging increases the risk of thrombophilia due to a disproportionate increase in fibrinogen, factors VIII, IX, and other coagulation proteins. Enhanced platelet activity and increased inflammatory cytokines contribute to the pro-thrombotic aging state.(1) Diabetes Mellitus is also recognized as a hypercoagulable state. Several factors contribute to the increased thrombotic risk in patients with DM. Firstly, endothelial abnormalities lead to increased platelet activation. Additionally, there is an increase in the levels of factor VII, factor VIII, factor XI, and Kallikrein and von Willebrand Factor. Conversely, the level of protein C, a key anticoagulant, is decreased. Clot structures in DM are also more resistant to degradation due to increased levels of tissue plasminogen activator. Furthermore, platelet function is also deranged in DM related to an increased aggregation sensitivity to adenosine diphosphate and an increase in thromboxane B2, B-thromboglobulin, platelet factor 4, and fibronectin.(2)
Diabetic Ketoacidosis is a medical emergency commonly associated with Type 1 DM but can also be found in Type 2 DM. Importantly, it also heightens the risk of thromboembolism during acute presentations. Decreases in protein C and S levels are more pronounced during acute presentations of DKA and remain reduced for twenty-four, up to 120 hours after resolution of the DKA. Levels of von Willebrand factor, a potent platelet activator, are also increased and remain increased after resolution of the DKA. Homocysteine, which further reduces protein C activation, also increases during acute DKA presentations.(2) Independent risk factors such as severe dehydration with increased whole blood viscosity, a hyperosmolar state, recurrent hospitalisations with prolonged bed rest, and the need for invasive venous catheters also increase the risk of thromboembolism in patients who present with DKA. Most thromboembolic events in patients with DM and DKA are due to arterial cardiovascular or cerebrovascular thrombotic events. The pathophysiological effects of DKA on the coagulation system suggest an increased risk of venous thromboembolism (VTE) as well; however, this association is less clear. Many reports describing the co-existence of both DKA and VTE also report that other conditions increase the risk of coagulation, such as protein C deficiency or hyperhomocystinaemia. Scordi-Bello et al., however, reported seven cases of DKA who presented with fatal pulmonary VTE. None of the patients in this case series had other vital VTE risk factors.(3) A systematic review and meta-analysis suggested an increased risk of VTE associated with DM (HR 1.35; CI, 1-17 – 1.55), although heterogeneity between studies was relatively high.(4) A bidirectional two-sample Mendelian Randomization study found no causality between DM and VTE.(5)
The emergency management of this patient posed a unique resuscitative challenge. One of the hallmarks of DKA is the presence of a high anion gap metabolic acidosis. To maintain an acid-base balance, the respiratory system (respiratory compensation) is utilized to assist with buffering the acid load. Central stimulation increases both respiratory rate and tidal volume. This increases the patient's minute volume, and CO2 exhaled over time to compensate for the metabolic acidosis. Any disruption in the patient's respiratory function would limit their ability to compensate for the presence of metabolic acidosis. By obstructing the pulmonary vessels, pulmonary embolism results in a V/Q mismatch, impacting the patient's ability to utilize the respiratory system to compensate for the underlying metabolic acidosis. In addition, massive pulmonary embolism causing obstructive shock leads to systemic hypotension, diminished tissue perfusion, and hyperlactatemia. This worsens metabolic acidosis, increasing the need for respiratory compensation, which is already disrupted. Thus, managing significant cardiovascular compromise secondary to PE in DKA is essential. In our case, systemic thrombolysis was the only option available. Thrombolysis carries a high bleeding risk in the elderly. The PEITHO trial, which studied the efficacy and safety of thrombolysis in intermediate-risk pulmonary embolism, found that patients over the age of sixty-five have three times the risk of bleeding compared to younger patients.(6) It is, therefore, crucial to counsel patients and family members appropriately regarding the risks associated with their condition and implement shared decision-making when choosing a treatment pathway.
Conclusion
This case report describes the successful thrombolysis of a geriatric patient who presented with bilateral pulmonary embolism complicated by diabetic ketoacidosis. Aging, DM, and DKA are all associated with increased thrombotic risks. Although DM is mainly related to arterial thrombosis, there is also a significant risk of venous thromboembolism. Patients who present with both DKA and pulmonary embolism pose a unique resuscitation challenge. Treating clinicians need to consider the effect of the embolism on the patient's ability to compensate for the underlying metabolic acidosis. The resuscitation goals should be clearly defined, and shared decision-making with patients and family members is critical before administering a systemic thrombolytic.