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Three Part Question

In [a patient presenting to A&E with a massive PE and cardiogenic shock] is [thrombolysis indicated] in [reducing mortality]

Clinical Scenario

A 54 year old woman presents to the emergency department with evidence of a massive PE. On presentation she is in cardiogenic shock. You wonder whether thrombolysis would reduce this patient's chance of mortality

Search Strategy

Medline (In-Process, Other Non-Indexed Citations and Medline) 1966-04/04 using OVID interface.
[(pulmonary AND emblo$ AND (thrombolysis OR streptokinase).mp.(mp=ti, ad, ot, rw, sh)]
LIMIT to human AND english

Search Outcome

Altogether 585 papers were found of which 3 were relevant to original question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Jerjes-Sanchez C etal 1995 Mexico	8 consecutive patients presenting with massive PE and cardiogenic shock. All had high index of clinical suspicion and suggestive echo. 4/8 had V/Q scan prior to deterioration and transfer to A&E (from another hospital). Randomized to either streptokinase plus heparin or heparin alone	Prospective randomized controlled trial	Reversal of cardiogenic shock	Reversal of cardiogenic shock in streptokinase and heparin group. Deterioration and death in group receiving only heparin	Small sample size (trial terminated due to ethical reasons - the overwhelming response in streptokinase and heparin group). Non Computerised randomization. Despite randomization, there were different baseline characteristics in respect of the total time of onset of symptoms to treatment, as 4 patients transferred from other hospitals. However both groups had similar baseline characteristics of time of onset of cardiogenic shock to treatment
			Mortality	0% (streptokinase group) vs 100%(heparin only group)
			Pulmonary arterial hypertension at 2 year follow up	Nil evident inthose followed up (4/4)
			Recurrent PE at 2 year follow up	Nil evident in those followed up (4/4)
Le Conte P et al 2003 USA	21 patients presenting with massive PE and cardiogenic shock (2 patients resuscitated from cardiac arrest before inclusion). Massive PE diagnosed on basis of clinical probability and either VQ scan, spiral CT or transthoracic US. Shock defined as systolic blood pressure <90mmHg or drop of >40mmHg. Patients received 0.6mg/kg Alteplase over 15min, not exceeding 50mg	Retrospective	Improvement of vital signs 2hrs after start of thrombolysis	Statistically significant improvement in Systolic BP, diastolic BP + sO2 (p<0.01). No statistically significant change in HR or RR	Retrospective (patients identified by pharmacy) and a small sample size, creating possible selection bias. No patient follow up after discharge. Small sample size and therefore can't make conclusions with regards to serious adverse effects, particularly cerebral haemorrhage.
			Mortality	4 patients died within 4hrs of admission (including the 2 patients who had experienced cardiac arrest before inclusion) and 1 patient from underlying metastatic disease whilst an inpatient. Overall mortality=23.8%
			Incidence of haemorrhagic events	5 minor haemorrhagic complications. No major haemorrhagic complications
Caldicott D et al 2002 Australia	1 patient presenting to the emergency department with massive PE and cardiogenic shock. Treated with tenecteplase and heparin	Case reoprt	Symptomatic relief	Relief of symptoms within 30 minutes of treatment	Low quality evidence. No patient follow up
			Reversal of cardiogenic shock	Rapid reversal
			Mortality	Patient survived to discharge

Comment(s)

There have been no further randomised controlled trials in this area since the development of newer thrombolytics, which are known to be associated with fewer side effects. Since the incidence of massive PE associated with cardiogenic shock is very low, it is unlikely that a randomised controlled trial, with evidence of a reduction in mortality in those thrombolysed, will be carried out. Despite this the current BTS guidelines recommend that 50mg alteplase IV "may be given on clinical grounds alone if cardiac arrest is imminent"

Clinical Bottom Line

In adults with massive PE and cardiogenic shock where cardiac arrest is deemed imminent, the BTS guidelines recommend that 50mg alteplase IV should be given. Therefore thrombolysis should be considered as a treatment option in this select group of patients.

References

1. Jerjes-Sanchez C, Ramirez-Rivera A, de Lourdes Garcia M, Arriaga-Nava R, Valencia S, Rosado-Buzzo A, Pierzo J.A, Rosas E Streptokinase and heparin versus heparin alone in massive pulmonary embolism: a randomised controlled trial. Journal of Thrombosis and Thrombolysis 1995;2:227-229
2. Le Conte P, Hutchet L, Trewick D, Longo C, Vial I, Batard E, Yatim D, Youze M.D, Baron D Efficacy of alteplase thrombolysis for ED treatment of pulmonary embolism with shock American Journal of Emergency Medicine 2003;21(5):438-440
3. Caldicott D, Parasivam S, Harding J, Edwards N, Bochner F Tenecteplase for massive pulmonary embolus Resuscitation 2002;55(2):211-213