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(Chest. 2006;129:839-840.)
© 2006 American College of Chest Physicians

When Pulmonary Embolism Treatment Isn’t Working

Bruce Davidson, MD, MPH, FCCP and Riyad Karmy-Jones, MD

Seattle, Washington
Dr. Davidson is affiliated with the Pulmonary-Critical Care Medicine Division, University of Washington and Swedish Medical Centers. Dr. Karmy-Jones is affiliated with the Cardiothoracic and Trauma Surgery Divisions, University of Washington and Harborview Medical Centers.

Correspondence to: Bruce Davidson, MD, MPH, FCCP, 801 Broadway, Suite 915, Seattle, WA 98122; email: brucedavidson{at}pobox.com

Objectively proven acute pulmonary embolism (PE) is a satisfying disease to treat—unless the treatment isn’t working. Supplementary oxygen for the ventilation-perfusion component of hypoxia, urgent anticoagulation IV or subcutaneously, and intensive care for patients with more profound abnormalities are relatively easily accomplished. Intensive care may include IV, peripherally administered thrombolysis (absent a serious or absolute contraindication) and IV crystalloid and pressor, with careful attention to right ventricular filling, titrated to support cardiac output.

But some patients, including some without prior known cardiopulmonary impairment, don’t improve. Some worsen. When the evidence-based treatment armory appears to be failing, deep concern ensues. While we’re aware that about 12% of PE patients will die from it,1 that outcome is difficult to accept from a nonmalignant disease so frequently and carefully studied and usually handled so well. Of other treatments to try at this stage, there is only one the average intensivist can employ without calling another specialist to urgently assume control of the patient—repeat thrombolysis.

Repeat thrombolysis is not commonly employed worldwide and there is no consensus about its use. One recent metaanalysis of thrombolysis in PE did not report any repeat thrombolysis,2 nor is it mentioned in either of two reports of large PE registries34. A randomized, partially blinded multi-center trial of PE treatment from German centers5 found it used 8% of the time in deteriorating patients but our impression is that it is uncommonly used in North America. North American physicians are more likely to try other techniques, such as percutaneous embolectomy, catheter fragmentation, angioplasty, and thrombectomy,6 whose rationale is rapid relief of central pulmonary artery obstruction by dispersion of central clots to the periphery. Percutaneous catheter embolectomy has also been reported to have a higher success rate and lower mortality than surgical embolectomy; surgery has a previously reported average mortality of 30%,7 although sporadic and more recent reports show improvement over that figure.78

Concurrent controls are more valid than historical ones. Desperate as we are to save the otherwise salvageable patients dying from PE despite our evidence-based treatment, who among us is using acceptable methodology to study how to do that?

Meneveau and colleagues9 have done so and carefully document a concurrently-controlled series in this issue of CHEST (see page 1043). Although their comparison of surgical thrombectomy on cardiopulmonary bypass vs repeat systemic thrombolysis is neither randomized nor blinded, this one-of-a-kind report of a substantial number of patients failing first thrombolysis provides important clinical guidance. Meneveau et al’s hospital dealt with failed thrombolysis in one of two ways: repeat thrombolysis or open surgical removal of clot with a forceps while the heart was beating. The populations undergoing one treatment or the other were similar, though not identical—for example, there was a higher proportion of patients with shock in the surgical group. Results of other interventions such as mechanical catheter fragmentation, percutaneous suction embolectomy, secondary thrombolytic infusion directly into a central clot, and of other possible techniques are not reported in the paper. That should not be viewed as a weakness of this report—too many centers have no planned fallback management plans whatsoever for such patients. There are other aspects that make the study’s results inconclusive besides heterogeneity of the patient populations: lack of a statistically significant survival benefit, wide confidence intervals around major bleeding rates and outcome, and the multitude of uncertainties that attend results of nonrandomized interventions. But there is an observable trend toward a better in-hospital outcome with rescue surgical thrombectomy.

The surgical management of such patients may not be straightforward either. The objective is to establish hemodynamic stability with sufficient flexibility to deal with the particular circumstances found in the individual patient. Unless impossible, re-imaging after failed thrombolysis should be done to establish that surgically accessible clot remains proximal to the first pulmonary artery branches. Median sternotomy provides the best exposure and cardiopulmonary bypass the best likelihood of stabilizing the circulation. Ascending aortic and dual caval cannulations to minimize blood in the operative field (or faster right atrial cannulation if there is less time) give the surgeon best control—this is precisely the technique reported by Meneveau et al (others have reported femoral-femoral bypass instituted percutaneously for early stabilization10). Although cooling the heart and cardiac arrest might provide better myocardial protection, they take extra time which may confer significant additional risk, and these surgeons didn’t employ them. Clot removal by ring forceps, and, on occasion, cautious gentle balloon extraction of more distal clot (balloon extraction not reported by these authors) can be employed. More distal clot can be removed with circulatory arrest and under direct vision but the bleeding risk is increased (Meneveau et al did not do this). Skin-to-skin time, if things go well, is about 1 h.

Some surgeons might consider embolectomy off-pump11 but must be comfortable with that approach. There is little if anything written about embolectomy after systemic thrombolysis—bleeding has been greatly feared, although there are case reports of safe application of lytics after surgical embolectomy.1213 As a practical matter, with the lytics off by the time the patient reaches the surgical suite, their impact could be minimal. These authors reported operating within 72 h of lytic administration and had no fatal bleeds in the 14 rescue embolectomy patients, indicating that prior lytics is not an absolute contraindication.

This carefully documented report shows the modern feasibility of rescue surgical embolectomy after failed thrombolysis for PE. It includes a comparison to the alternative previously reported strategy of repeat thrombolysis. Importantly, it provides a foundation for physicians caring for PE patients at centers with cardiothoracic surgery to meet and formulate plans for how and when to call for help and what kind of help to call for. These patients often present in extremis after iatrogenic interventions intended to help them (eg, bariatric, joint replacement, or cancer surgery, or chemotherapy). Determining local criteria and detailed plans for rescuing PE patients who fail usual treatment is an important priority for our specialties. Further cooperative clinical studies should ensue. We congratulate Meneveau and colleagues for a carefully documented report of great practical use.

Footnotes

The authors have no conflicts of interest to disclose.

References

  1. Siddique, RM, Siddique, MI, Connors, AF, Jr, et al (1996) Thirty-day case-fatality rates for pulmonary embolism in the elderly. Arch Intern Med 156,2343-2347[Abstract]
  2. Capstick, T, Henry, MT Efficacy of thrombolytic agents in the treatment of pulmonary embolism. Eur Respir J 2005;26,864-874[Abstract/Free Full Text]
  3. Goldhaber, SZ, Visani, L, De Rosa, M Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353,1386-1389[CrossRef][ISI][Medline]
  4. Kasper, W, Konstantinides, S, Geibel, A, et al Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997;30,1165-1171[Abstract]
  5. Konstantinides, S, Geibel, A, Heusel, G, et al Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med 2002;347,1143-1150[Abstract/Free Full Text]
  6. Uflacker, R Interventional therapy for pulmonary embolism. J Vasc Interv Radiol 2001;12,147-164[ISI][Medline]
  7. Yalamanchili, K, Fleisher, AG, Lehrman, SG, et al Open pulmonary embolectomy for treatment of major pulmonary embolism. Ann Thorac Surg 2004;77,819-823[Abstract/Free Full Text]
  8. Gulba, DC, Schmid, C, Borst, H-G, et al Medical compared with surgical treatment for massive pulmonary embolism. Lancet 1994;343,576-577[CrossRef][ISI][Medline]
  9. Meneveau, N, Blonde, M-C, Seronde, M-F, et al Management of unsuccessful thrombolysis in acute massive pulmonary embolism. Chest 2006;129,1043-1050[Abstract/Free Full Text]
  10. Ohteki, H, Norita, H, Sakai, M, et al Emergency pulmonary embolectomy with percutaneous cardiopulmonary bypass. Ann Thorac Surg 1998;66,982-983[Free Full Text]
  11. Ashrafian, H, Kumar, P, Athanasiou, T, et al Minimally invasive off-pump pulmonary embolectomy. Cardiovasc Surg 2003;11,471-473[Medline]
  12. Xu, C, Wang, Z, Zhan, Y, et al Successful thrombolytic therapy following emergent pulmonary embolectomy: a case report. Chin Med J (Engl) 2005;118,1490-1492
  13. Spohr, F, Rehmert, GC, Bottiger, BW, et al Successful thrombolysis after pulmonary embolectomy for persistent postoperative pulmonary embolism. Resuscitation 2004;62,113-118[Medline]



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