Low-dose tenecteplase during cardiopulmonary resuscitation in massive pulmonary embolism

We report the case of an 18-year-old male who presented to the Emergency Department with sudden onset dyspnea. The patient was intubated on arrival, but suffered a cardiac arrest soon after. Point-of-care echocardiography during cardiopulmonary resuscitation revealed a grossly dilated right atrium and right ventricle, which alerted the Emergency physician to the possibility of massive pulmonary embolism leading to cardiac arrest. Due to no discernible history or risk factors in favour of pulmonary embolism, a decision was taken for thrombolysis with half dose Tenecteplase. Return of spontaneous circulation was achieved 14 min after thrombolysis, with massive pulmonary embolism subsequently being confirmed on CT Pulmonary Angiography.


Introduction
Detection of Pulmonary Embolism (PE) in the Emergency department is a competence-based diagnosis, requiring a high index of suspicion, strong clinical acumen, and rapid focussed assessment.PE is relatively less common as compared to Acute Coronary Syndrome (ACS), so there is an inherent tendency to undermine the potential for this diagnosis in a patient presenting with chest pain or dyspnea.Additionally, PE presentations can often be vague and varied, which adds to the conundrum in diagnosis and treatment.
Unprovoked pulmonary embolism leading to cardiac arrest remains the nemesis of the Emergency Physician.Mortality in massive PE with cardiac arrest is as high as Patient was combative, agitated, with a GCS of 11 (E4V2M5), pupils were bilateral 3 mm, briskly reactive.Random blood sugar was 165 mg/dl.Unable to record the Blood pressure on arrival due to the combative nature of the patient, however subsequently the Systolic blood pressure was found to be 60 mm Hg.Patient was profusely diaphoretic with cold, clammy extremities, and acrocyanosis was noted over the lips.
A decision was taken to intubate the patient in view of respiratory failure with impending arrest.A rapid sequence induction was done, and patient was intubated and mechanically ventilated.Shortly after intubation, there was loss of central pulses, and CPR was initiated as per ACLS protocol.Initial rhythm was Pulseless Electrical Activity (PEA), which remained persistent through the CPR.
A point-of-care ultrasonography (POCUS) performed during CPR (in the intervals for pulse checks) showed a plethoric inferior vena cava (IVC) and massively dilated right atrium and right ventricle on the apical view, while a short axis view showed the right ventricle indenting the left ventricle (D-cup sign).A presumptive diagnosis of massive pulmonary embolism was made during CPR, and a decision was taken for thrombolysis of the patient after taking the family into confidence.
Owing to no discernible history or risk factors suggestive of pulmonary embolism, it was decided to use only 20 mg of Tenecteplase.Intravenous Tenecteplase was administered with ongoing CPR (about 8 min into CPR).Return of spontaneous circulation (ROSC) was achieved 14 min after thrombolysis, with a total duration of 22 min of CPR.Targeted temperature control was initiated and patient was shifted to ICU, with the CT Pulmonary Angiography deferred until stabilization of the patient.
Subsequently a CT Pulmonary Angiography (CT-PA) was done, which showed a large filling defect in the left main pulmonary artery and bilateral descending pulmonary arteries, thereby confirming the diagnosis of massive pulmonary embolism leading to cardiac arrest.Mechanical thrombo-suction was further done for the patient after which he had an insidious improvement.

Differential diagnosis
Drug overdose / Toxidrome Septic Shock with nidus as Lower respiratory tract infection Adult Respiratory Distress Syndrome

Treatment and outcome
The patient had a protracted ICU stay with multi-organ involvement (including acute renal injury requiring dialysis, an ischaemic stroke, intra-abdominal bleed, hemothorax, and a difficult weaning requiring tracheostomy).It is worth noting that the bleeding complications were delayed, and arose much later in the course of hospital stay, and therefore could also be attributed to the concurrent use of anticoagulants.However, with a dedicated team and excellent inter-disciplinary approach, he went on to make a full recovery (barring a mild residual left upper arm paresis in the non-dominant arm secondary to the ischaemic stroke).
Blood work up for a pro-thrombotic state was negative, bilateral lower limb venous doppler was negative for deep vein thrombosis, and there were no precipitating or predisposing factors for pulmonary embolism (example recent travel history or immobilization) in this case.It was therefore labelled as a case of unprovoked, massive pulmonary embolism leading to cardiac arrest.

Discussion
Confirming a clinical suspicion of pulmonary embolism in a critically ill patient in the Emergency Department (ED) poses a unique challenge as these patients are often too unstable to be mobilized for a CT pulmonary angiography (CT-PA), which is the gold standard for diagnosis.In such cases, a rapid, focused, bed-side point-of-care ultrasonography (POCUS) can greatly aid in the diagnosis and decision-making process [3].
Cardiac arrest following pulmonary embolism carries a mortality of 70% in the first hour itself, while the overall mortality may reach 95% [1].Confirmed or suspected pulmonary embolism as the cause of cardiac arrest is an indication to administer thrombolytic therapy during cardiopulmonary resuscitation (CPR) as per the American Heart Association (AHA) recommendations for Advanced Cardiac Life Support (ACLS).There is increasing evidence to support the use of Alteplase and Tenecteplase for thrombolysis in massive pulmonary embolism, especially when leading to cardiac arrest [2,4].
A systematic literature review showed only one other case of Thrombolysis with Low dose (20 mg) Tenecteplase during CPR [5] (a 29-year-old male who suffered a massive PE requiring CPR while undergoing a complex tibial plateau fracture repair).In this case, 20 mg Tenecteplase was administered after 70 min of CPR, and ROSC was achieved after 2 min of CPR.
However, there have been other case reports citing full dose Tenecteplase, as well as Alteplase for thrombolysis during CPR in case of massive PE causing cardiac arrest, and subsequently leading to favourable outcomes [6][7][8][9].Of these, bleeding as a major complication was reported in only one case of a 34-year-old woman undergoing an emergency Caesarean section, who suffered from massive uterine bleeding after thrombolysis with Tenecteplase for massive PE during CPR [9].
Use of Low-dose Tenecteplase had a favourable outcome in our patient despite the protracted hospital stay.Considering the extremely poor survival in massive PE with cardiac arrest, thrombolysis during CPR may give the best chance at survival in the acute phase of resuscitation, as well as discharge.
It is also worth noting that in our case, a favourable end-outcome was achieved with half dose Tenecteplase.This may therefore be considered in patients with haematological disorders or other contraindications to full dose Tenecteplase.However, it is essential to note that there may be delayed bleeding complications due to concurrent use of anticoagulants.More research in this area is warranted.
There were 3 things that added to the novelty of this case: • ROSC achieved with Low dose Tenecteplase.• Late bleeding complications observed despite Low dose Tenecteplase.• Unprovoked, massive PE leading to cardiac arrest, which made the diagnosis a challenge, and the decision for thrombolysis up for debate.

Conclusion
Although pulmonary embolism as the cause of cardiac arrest is seen in a small number of in-hospital-cardiac arrests (IHCA), thrombolysis during CPR should be strongly considered when massive pulmonary embolism is known or strongly suspected as the cause of cardiac arrest.There is growing evidence to suggest that administration of thrombolytic therapy during CPR can significantly improve the rate of ROSC and survival to discharge rates for such patients [2,10].