How Dangerous is Pulmonary Embolism?

The diagnosis and management of pulmonary embolism(PE), like most things in emergency medicine; it’s about risk stratification. In chest pain, the low risk patient is approached very differently to the high risk, ST elevation chest pain patient. It is exactly the same in PE. There is that group of patients who are sick; they are short of breath and hypoxic and don’t pass the end of the bed test. We know that these patients are sick and need treatment.

Then there is that ambulant well looking group that we apply PERC rules and Wells Scores and D-dimers to. The risk of mortality can’t be the same in these two groups. Sometimes however we may be over-investigating the well group and it may just possible that we are doing more harm than good.

Let’s look at the risk and assessment them appropriately.

Where is the evidence?

The ‘landmark’ PE study, whose figures are most often quoted, appeared in the Lancet in 1960(1). It included 35 patients that were very sick, ie., patients confined to a hospital bed for some 10 days. The death rate from PE in this group was 17%.

This certainly doesn’t describe the majority of patients I see in the ED.

In 1990 in JAMA(2), a study of 931 patients was published, which looked at the value of V/Q scans in acute pulmonary embolism. 30% of the patients in this study were ED patients. The rate of mortality was 5%.

In 1997, Nielsen(3) took 87 patients with a deep venous thrombosis and a known PE. The PE in this group was silent. Patients were randomised to either receive anticoagulation or no anticoagulation. No deaths were recorded.

Kline in 2008(4), whilst developing the PERC rule, enrolled 8138 patients in a prospective study. 47 PE’s were missed, with 1 death, giving a mortality of 0.2%.

In 2010 Pollack(5) looked at 1880 patients in the ED, who had a PE confirmed on CTPA. There was a mix of patient severity here. Mortality occurred in 20 cases of which 3 had anticoagulant given and 3 had fibrinolytic therapy. Total mortality was 1%.

We start to see exactly what we would expect, that unstable patients with PE, don’t do as well as physiologically normal patients in an ambulatory setting, whose risk may be < 1%.

What if we treat with anticoagulation: Is it dangerous?

Can treatment be more dangerous than the disease?

Dahri(6) in a meta-analysis demonstrated a 6 month bleeding risk of 2.8%. Overall, the risk of fatal haemorrhage was 0.5%.

Carrier in 2010(7) conducted a systematic review, looking at bleeding events in those treated for venous thromboembolism. 69 studies were reviewed and included patients with deep venous thrombosis and PE. Patients received anticoagulation for 3 months. They concluded that the rate of fatal bleeding in the first 3 months was 0.2%.

Pollack(5) in 2010 had also found a mortality rate from haemorrhage of 0.2%.

Can the Investigations for PE, be more harmful than the disease?

Contrast induced nephropathy(CIN) is a potential complication of CTPA. Mitchell(8) looked at 633 patients who had CTPA’s in an outpatient setting ie., well patients. CIN developed in 11% of patients, 6 developed renal failure and 4 of those 6 died from it. From this study, mortality from CTPA was 0.7% and renal failure 1%. The risk of acute kidney injury is low if the GFR>45ml/min.

Thus, putting this into context, if we perform 5 CTPA’s per week, over a year, we are causing 2 deaths per year. We don’t see them, as they occur downstream.

Surely this can’t be right! These figures are so high.

What about radiation exposure?

The median dose of exposure form a CTPA is 9,6mSv(9). This is equivalent to approximately 130 chest rays. Newman extrapolated from these figures and calculated that 1 case in 2000 CTPA’s is fatal.

Conclusion

If we risk stratify our patients, we know that the mortality changes. The real mortality of well patients is perhaps < 1% and approaches the lower figure of 0.2%, in physiologically normal, ambulant patients.The CT Pulmonary Angiogram, may have a renal failure risk of 0.7% and radiation risk that may lead to a  mortality of up to 1 patient per 2000 CTPA’s.

If the diagnosis is made in the well group of patients and they are treated, the risk of fatal bleeding at 3 months approaches 0.2%.

If we took 2000 patients, who were ambulant, with normal physiological parameters, the mortality rate of 1% gives 20 deaths.

The mortality from investigating these patients would be, 1 death from malignancy and 14 from renal failure. The mortality from anticoagulant induced bleeding is 4 patients.

Therefore:

  • Mortality when we do nothing = 20 patients
  • Mortality from investigation and management = 19 patients.

Perhaps this is one of those cases where less is more. However, this only applies to low risk patients.

Thus, more work is needed here and a discussion of the treatment of well patients with essentially subsegmental PE’s. In EMCORE 2017, we will be discussing the whole topic of contrast induced nephropathy and if its real or not.

Watch this space, more to come.

References

1 Barritt DW et al. Anticoagulant drugs in the treatment of pulmonary embolism: A controlled trial. The Lancet vol, 275;7138;18 June 1960.pp.1309-1312.

2 Pioped investigators.  Value of the ventilation/perfusion scan in acute pulmonary embolism. Results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990 May 23-30;263(20):2753-9.

3 Nielsen Hk et al. Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation. J Intern Med. 1994 May;235(5):457-61.

4 Kline JA et al. Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008 May;6(5):772-80

5 Pollack CV et al.  Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol. 2011 Feb 8;57(6):700-6

6 Dahri K et al. The risk of bleeding with warfarin: a systematic review and performance analysis of clinical prediction rules. Thromb Haemost. 2007 Nov;98(5):980-7.

7 Carrier M et al.  Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010 May 4;152(9):578-89

8 Mitchell AM et al. Incidence of contrast-induced nephropathy after contrast-enhanced computed tomography in the outpatient setting. Clin J Am Soc Nephrol. 2010 Jan;5(1):4-9.

9 Smith-Bindman R et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009 Dec 14;169(22):2078-86.

10 Newman D et al Rethinking Testing for Pulmonary Embolism: Less Is More. June 2011Volume 57, Issue 6, Pages 622–627