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Three Part Question

In [adults with acute pulmonary embolism] is [elevated plasma lactate] a [prognostic indicator of morbidity and mortality]

Clinical Scenario

A 62 year old male emergency department patient presents with an acute pulmonary embolism. Patient is tachycardic and requiring supplemental oxygen. You debate over where to place the patient (ICU, progressive, general floor). You consider whether elevated plasma lactate (greater than or equal to 2 mmol/L) might be a good prognostic indicator of death or clinical deterioration.

Search Strategy

Medline 1946-08/14 using OVID interface, Cochrane Library (2014), PubMed clinical queries
[(Exp pulmonary embolism) AND (exp lactates/blood)]. Limit to English language

Search Outcome

4 papers were identified; two were relevant to the clinical question

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Vanni S, Viviani G, Baioni M, et al. March 2013 United States	270 patients with mean age 73 (55.9% women) with symptomatic, objectively confirmed pulmonary embolism presenting to a single Level III emergency department.	Prospective observational study	Primary endpoint was all-cause death at any point within 30 days after presentation. Secondary endpoints were the composite of all-cause death and clinical deterioration because of pulmonary embolism and pulmonary embolism–related death.	Results show patients who died had a significantly higher mean plasma lactate level (4.7 mmol/L; 95% CI 2.7 to 6.8 mmol/L) than survivors (1.6 mmol/L; 95% CI 1.5 to 1.7 mmol/L). When considering only patients who died because of pulmonary embolism, the difference remained highly significant (5.5 mmol/L versus 1.6 mmol/L; 95% CI 2.8 to 8.2 versus 1.6 to 1.8 mmol/L). Overall, Mortality appeared to progressively increase with higher plasma lactate levels.	The study was conducted in a single hospital. The ED in this study is the referral center for major emergencies and patients are usually a high-risk sample of the general population. Next, Echocardiography may not be available at all centers. Each patient's plasma lactate level was measured only once. Treating physicians were not blinded to the lactate levels, which may have introduced bias.
Vanni S, Socci F, Pepe G, et al. August 2011 Italy	Adult patients who were admitted for symptomatic PE and had lactate drawn within 6 hours of presentation.	Retrospective cohort study	Primary outcome was in-hospital death due to any cause; secondary outcome was mortality related to PE.	Patients who died had significantly higher mean plasma lactate level (5.8 mmol/L, 95% CI = 3.2 to 8.4) than did survivors (1.3 mmol/L, 95% CI = 1.5 to 1.8; p < 0.001). Similar results were obtained when death related to PE was considered (OR = 4.94, 95% CI = 1.38 to 17.63).	This was a retrospective study. Small sample size with large number of individuals excluded due to missing plasma lactate levels. Included patients tended to be less compromised, which may alter results.

Comment(s)

Acute pulmonary embolism (PE) represents a spectrum of disease ranging from asymptomatic to sudden death. Apart from cardiogenic shock, few clinical predictors have been identified that can accurately predict the short-term prognosis of these patients. Identification of apparently stable PE patients who are at high short-term risk for clinical deterioration is critical to optimize disposition and treatment decisions in the ED. To that end, a variety of potential prognostic indicators such as troponin, BNP, and echocardiogram have been examined, however their utility has been limited by poor positive predictive value. We reviewed the use of plasma lactate levels as a predictor of morbidity and mortality in patients presenting with pulmonary embolism. Of four studies identified using our search terms, two (one retrospective and one prospective cohort study) addressed the clinical question. Both studies were conducted by the same research group at a single emergency department in Italy and demonstrated higher mortality risk among patients with a plasma lactate level greater than 2mmol/L. In the retrospective study, plasma lactate ≥ 2 mmol/L was associated with in-hospital mortality, independent of hypotension, malignancy, tachycardia, or right ventricular dysfunction (OR = 4.60, 95% CI = 1.57 to 13.53). Elevated lactic acid was also associated with development of shock, need for mechanical ventilation, and need for vasopressors. In the prospective study, patients with lactate level ≥ 2 mmol/L showed higher mortality than patients with a lower level (17.3% vs. 1.6%; HR 11.67, 95% CI 3.32 to 41.03). Furthermore, plasma lactate as a stand-alone test performed similarly to a validated clinical prediction rule for PE prognosis (the simplified Pulmonary Embolism Score Index). The current evidence suggests that patients with PE and lactic acid levels greater than 2mmol/L are at elevated risk of clinical deterioration and death. If these findings are corroborated by larger studies in other populations, lactic acid levels may be useful, independently or in the context of a clinical prediction rule, in identifying PE patients at risk for deterioration.

Clinical Bottom Line

Patients with pulmonary embolism and plasma lactate greater than 2mmol/L appear to be at increased risk of clinical deterioration and death.

References

1. Vanni S, Viviani G, Baioni M, Pepe G, Nazerian P, Socci F, Bartolucci M, Bartolini M, Grifoni S. Prognostic Value of Plasma Lactate Levels Among Patients With Acute Pulmonary Embolism: The Thrombo-Embolism Lactate Outcome Study Annals of Emergency Medicine 2013;61(3):330-338
2. Vanni S, Socci F, Pepe G, Nazerian P, Viviani G, Baioni M, Conti A, Grifoni S. High Plasma Lactate Levels Are Associated With Increased Risk of In-hospital Mortality in Patients With Pulmonary Embolism Academic Emergency Medicine 2011 Aug;18(8):830-5