Acute mortality in critically ill patients undergoing echocardiography with or without an ultrasound contrast agent

JACC Cardiovasc Imaging. 2014 Jan;7(1):40-8. doi: 10.1016/j.jcmg.2013.08.012. Epub 2013 Nov 27.


Objectives: The objective of this observational study was to compare 48-h all-cause mortality (as well as hospital stay mortality) among critically ill patients who underwent echocardiography either with or without an ultrasound contrast agent (UCA).

Background: The safety of perflutren-based UCAs has been questioned by the U.S. Food and Drug Administration (particularly when administered to critically ill patients) following rare reports of deaths or life-threatening adverse reactions that occurred in close temporal relationship to UCA administration.

Methods: This was a retrospective observational outcome study conducted in critically ill patients to compare all-cause 48-h and hospital stay mortality subsequent to echocardiography procedures performed either with or without a UCA. The study utilized discharge data from a database maintained by Premier, Inc. (Charlotte, North Carolina). Premier's database is the largest U.S. hospital-based, service-level comparative database for quality and outcomes research, and provides detailed resource utilization data along with patients' primary and secondary diagnoses and procedure billing codes. A propensity score-matching algorithm between UCA-enhanced echocardiography patients and non-contrast-enhanced echocardiography patients was utilized to reduce the potential for imbalance in covariates of selected patients in the comparison of mortality between groups.

Results: Patients undergoing echocardiography with a UCA had lower mortality at 48 h compared with patients undergoing non-contrast-enhanced echocardiography (1.70% vs. 2.50%), with an odds ratio = 0.66 (95% confidence interval [CI]: 0.54 to 0.80). Patients undergoing echocardiography with a UCA had lower hospital stay mortality compared with patients undergoing noncontrast echocardiography (14.85% vs. 15.66%), with an odds ratio = 0.89 (95% CI: 0.84 to 0.96).

Conclusions: In critically ill, propensity-matched hospitalized patients undergoing echocardiography, use of a UCA is associated with a 28% lower mortality at 48 h in comparison with patients undergoing non-contrast-enhanced echocardiography. These results are reassuring, given previous reports suggesting an association between UCAs and increased mortality in critically ill patients.

Keywords: APR-DRG; All Patient Refined Diagnosis Related Group; CI; FDA; Food and Drug Administration; ICU; TTE; UCA; cTTE; confidence interval; contrast echocardiography; contrast enhanced ultrasound; contrast-enhanced transthoracic echocardiography; intensive care unit; nTTE; non–contrast-enhanced transthoracic echocardiography; transthoracic echocardiography; ultrasound contrast agent; ultrasound contrast agents.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cause of Death / trends
  • Contrast Media*
  • Critical Illness / mortality*
  • Echocardiography / methods*
  • Female
  • Follow-Up Studies
  • Hospital Mortality / trends
  • Humans
  • Length of Stay / trends
  • Male
  • Middle Aged
  • Odds Ratio
  • Prognosis
  • Propensity Score
  • Retrospective Studies
  • Risk Factors
  • Survival Rate / trends
  • United States / epidemiology
  • Young Adult


  • Contrast Media