anticoagulation must be given without delay unless contraindicated

This Ottawa Pulmonary Embolism Response Team (PERT) was born of a young trauma patient we presented at our Civic ICU M and M rounds with an intermediate high-risk PE (submassive).  We invited all the services involved in the care of the patient to participate in the discussion (trauma, interventional radiology, who ultimately saved the patient with catheter directed thrombectomies, and thrombosis). At the end it was concluded that it took too long to recognize the severity of the impact of the PE and organize definitive treatment.  We agreed that this was not an uncommon occurrence and so the issue of having a pulmonary embolism response team was raised in order to ensure these patients are seen and managed quickly.    

The PERT concept was created in 2012 at Massachusetts General Hospital.  Multidisciplinary teams were assembled consisting of experts in critical care, interventionalists, and thrombosis. The purpose was to ensure rapid assessment and intervention for life-threatening pulmonary emboli.  In addition these expert teams provide a formal mechanism to quickly discuss and exercise a full range of medical and endovascular therapies for these patients.  The process also ensures appropriate follow up, and allows an opportunity to collect, evaluate, and share data regarding the effectiveness of treatment and complications.  

By 2015 there were over 30 institutions across the United States who had formed PE response teams.  That same year, the PERT Consortium was formed https://pertconsortium.org/.   To date there is international membership including the United States, Asia, South America, and Australia.  The PERT database has over 4000 patients registered.  

Centers that have adopted PERTs have been able to demonstrate improved survival compared to pre-PERT cohorts, similar survival rates compared with the non-life threatening PE cohorts, no increased risk of bleeding when low-dose catheter directed thombolysis was used, the use of fewer IVC filters, and a decrease in readmission rates and thus the potential to decrease healthcare costs.  https://doi.org/10.1186/s12931-020-01422-z.   

Most recent opinions on pulmonary embolism response teams from the 2019 European Society of Cardiology and European Respiratory Society Guidelines for pulmonary embolism is that the weight of the evidence and opinions are in favor of the usefulness and efficacy of response teams, and that further research is very likely to have an important impact https://academic.oup.com/eurheartj/article/41/4/543/5556136. 

In terms of potential interventions, we already know from our understanding of physiology that hemoydnamic collapse and death due to RV strain can occur from a life-threatening PE.   We also know from previous literature  that this risk can be mitigated by decreasing the RV clot burden.  A previous trial of  systemic thrombolysis (ST) versus anticoagulation alone demonstrated a significant improvement in hemodynamic parameters and prevention of  hemodynamic collapse.  Unfortunately this was at the expense of an unacceptably high risk of bleeding complicationshttps://www.nejm.org/doi/full/10.1056/nejmoa1302097  A small RCT of 121 patients with PE demonstrated that reduced-dose systemic thrombolysis lowered the risk of pulmonary hypertension at 28 days and was associated with shorter hospital stays when compared to anticoagulation alone.  There were no bleeding complications in either group. https://www.ajconline.org/article/S0002-9149(12)02205-9/fulltext  A trial of reduced dose systemic thrombolysis versus anticoagulation alone is on the horizon (PEITHO-3).  This option will be particularly important in centers without access to other options such as catheter directed therapies  https://www.thieme-connect.com/products/ejournals/pdf/10.1055/a-1653-4699.pdf

Catheter directed therapies including low-dose thombolysis, ultrasound assisted thrombolysis, and thrombectomies have demonstrated a faster decrease in the RV/LV ratio at 24 hours, reduced pulmonary hypertenion, no increase in bleeding risk, and no increased risk of recurrent thrombosis when compared to anticoagulation alone. https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.113.005544.  https://pubmed.ncbi.nlm.nih.gov/26315743/.   https://pubmed.ncbi.nlm.nih.gov/35778309/  https://pubmed.ncbi.nlm.nih.gov/30025734/  In the ultrasound assisted catheter directed thrombolysis RCT, these results were sustained up to one year and patients experienced improvement in functional status and quality of life compared to patients who received anticoagulation alone. https://www.ahajournals.org/doi/full/10.1161/CIRCINTERVENTIONS.120.009012   A recent meta-analysis that included over 9000 patients, comparing CDT versus anticoagulation alone, demonstrated a significant  in-hospital, 30-day, and 90-day mortality benefit to CDT with a tendency towards lower 1-year mortality.   The rates of major and minor bleeding, and blood transfusions were similar in both groups https://www.ajconline.org/article/S0002-9149(22)00632-4/fulltext   A 2022 Randomized Controlled Trial o 85 patients receiving either  CDT and anticoagulation versus anticoagulation  alone demonstrated  improvement in the RV/LV ration at 72 hours and 3 months in the CDT group, and lower risk of death  https://jamanetwork.com/searchresults?q=CDT%20Canary&allSites=1&SearchSourceType=1&exPrm_qqq={DEFAULT_BOOST_FUNCTION}%22CDT%20Canary%22&exPrm_hl.q=CDT%20Canary  A large randomized controlled trial looking at clinical outcomes in catheter directed therapies + anticoagulation versus anticoagulation alone is currently underway with results anticipated in 2024 https://pubmed.ncbi.nlm.nih.gov/35588898/.    

With all of these established and upcoming trials comparing CDT to anticoagulation alone and ST to anticoagulation alone, the logical question is how does CDT compare to ST (be it high or low dose)?   There are obvious clinical scenarios that would necessitate one over the other (urgency, contraindications to systemic thrombolysis, age etc), but for scenarios where either approach could be used, it would be important to know whether one imposes less risk and/or is equally or more effective.  A 2023 meta-analysis of 44 studies, 20,006 patients, comparing outcomes of CDT to ST found that CDT was associated with a decreased risk of death (odd ratio [OR] 0.43, 95% confidence interval [CI] 0.32–0.57), intracerebral hemorrhage (OR 0.44, 95% CI 0.29– 0.64), and blood transfusion (OR 0.46, 95% CI 0.28–0.77).  Additionally, compared with anticoagulation, CDT was also associated with decreased risk of death (OR 0.36, 95% CI 0.25–0.52), with no increased risk of intracerebral hemorrhage (OR 1.33, 95% CI 0.63–2.79).  It should be noted that these findings were mostly based on observational data.  Another important note is that only 3 of the  22 included studies comparing Fibrinolysis to Anticoagulation alone used low dose Fibrinolytics.  To that end, the questions regarding  CDT versus ST remains unanswered.  https://www.cmaj.ca/content/195/24/e833

In the meantime, while we are awaiting clinical trial outcomes,  we want to assess any patient with proximal pulmonary emboli who demonstrate biochemical and radiographic evidence of RV strain with any one of the clinical parameters outlined in our call criteria.  Consequently, the full range of medical and interventional therapies can be discussed by the multidisciplinary pulmonary embolism response team (PERT)  and these patients will be monitored in the Intensive Care Unit.