Interhospital Transfer of Patients With Acute Pulmonary Embolism
2021; Elsevier BV; Volume: 160; Issue: 5 Linguagem: Inglês
10.1016/j.chest.2021.07.013
ISSN1931-3543
AutoresParth Rali, D. Sacher, Belinda Rivera‐Lebron, Rachel Rosovsky, Jean Elwing, Jonathan Berkowitz, Bushra Mina, Bhavin Dalal, George A. Davis, David M. Dudzinski, Alicia L. Duval, Eugene Ichinose, Christopher Kabrhel, Aniruddh Kapoor, K.U. Lio, R. Lookstein, Michael McDaniel, Roman Melamed, Soophia Naydenov, Shalom Sokolow, Kenneth Rosenfield, Victor F. Tapson, Eduardo Bossone, W. Brent Keeling, Richard N. Channick, Charles B. Ross,
Tópico(s)Acute Myocardial Infarction Research
ResumoAcute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients. Acute pulmonary embolism (PE) is associated with significant morbidity and mortality. The management paradigm for acute PE has evolved in recent years with wider availability of advanced treatment modalities ranging from catheter-directed reperfusion therapies to mechanical circulatory support. This evolution has coincided with the development and implementation of institutional pulmonary embolism response teams (PERT) nationwide and internationally. Because most institutions are not equipped or staffed for advanced PE care, patients often require transfer to centers with more comprehensive resources, including PERT expertise. One of the unmet needs in current PE care is an organized approach to the process of interhospital transfer (IHT) of critically ill PE patients. In this review, we discuss medical optimization and support of patients before and during transfer, transfer checklists, defined roles of emergency medical services, and the roles and responsibilities of referring and receiving centers involved in the IHT of acute PE patients. Venous thromboembolism has long been recognized as a major public health issue.1Beckman M.G. Hooper W.C. Critchley S.E. Ortel T.L. Venous thromboembolism: a public health concern.Am J Prev Med. 2010; 38: S495-S501Abstract Full Text Full Text PDF PubMed Scopus (631) Google Scholar,2Office of the Surgeon General (US); National Heart, Lung, and Blood Institute (US)The Surgeon General's Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Office of the Surgeon General (US), Rockville, MD2008Google Scholar Pulmonary embolism (PE) is the third leading cause of cardiovascular mortality in the United States.3Pulido T. Aranda A. Zevallos M.A. et al.Pulmonary embolism as a cause of death in patients with heart disease: an autopsy study.Chest. 2006; 129: 1282-1287Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar However, unlike acute myocardial infarction, stroke, and trauma, strategies for initial care and support of PE patients have not been standardized. For example, thrombolytic use in rural settings is employed significantly less compared with its use in metropolitan hospitals.4Rush B. Wiskar K. Berger L. Griesdale D.E. The use of thrombolysis for acute pulmonary embolism in the United States: national trends and patient characteristics from 2006 to 2011.J Emerg Med. 2017; 52: 615-621Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database demonstrates mortality disparities in rural vs urban settings, especially in the South.5Centers for Disease Control and PreventionAbout Underlying Cause of Death, 1999-2019.https://wonder.cdc.gov/controller/saved/D76/D70F045Google Scholar, 6Centers for Disease Control and PreventionAbout Underlying Cause of Death, 1999-2019.https://wonder.cdc.gov/controller/saved/D76/D70F043Google Scholar, 7Martin K.A. Molsberry R. Cuttica M.J. Desai K.R. Schimmel D.R. Khan S.S. Time trends in pulmonary embolism mortality rates in the United States, 1999 to 2018.J Am Heart Assoc. 2020; 9e016784Crossref Scopus (20) Google Scholar Survival of the most critically ill PE patients is often dependent on early recognition and diagnosis, expedient decision-making, and appropriate execution of interventions. Management must be expeditious, beginning at triage and continuing through the point of definitive care.8Dalen J.E. Pulmonary embolism: what have we learned since Virchow? Natural history, pathophysiology, and diagnosis.Chest. 2002; 122: 1440-1456Abstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar,9Wood K.E. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism.Chest. 2002; 121: 877-905Abstract Full Text Full Text PDF PubMed Scopus (624) Google Scholar The pulmonary embolism response team (PERT) aims to provide time-sensitive, multidisciplinary individualized care to critically ill patients with acute PE.10Kabrhel C. Rosovsky R. Channick R. et al.A multidisciplinary pulmonary embolism response team: initial 30-month experience with a novel approach to delivery of care to patients with submassive and massive pulmonary embolism.Chest. 2016; 150: 384-393Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar Data from large-scale multisite observational cohorts suggest that patients with acute PE benefit (ie, short-term 30-day mortality) when treated at high-volume centers and by experienced physicians.11Jiménez D. Bikdeli B. Quezada A. et al.Hospital volume and outcomes for acute pulmonary embolism: multinational population based cohort study.BMJ. 2019; 366: l4416Crossref PubMed Scopus (31) Google Scholar, 12Aujesky D. Mor M.K. Geng M. Fine M.J. Renaud B. Ibrahim S.A. Hospital volume and patient outcomes in pulmonary embolism.CMAJ. 2008; 178: 27-33Crossref PubMed Scopus (19) Google Scholar, 13Lin H.C. Lee H.C. Caseload volume-outcome relation for pulmonary embolism treatment: association between physician and hospital caseload volume and 30-day mortality.J Thromb Haemost. 2008; 6: 1707-1712Crossref PubMed Scopus (8) Google Scholar, 14Finkelstein M. Cedillo M.A. Kestenbaum D.C. Shoaib O.S. Fischman A.M. Lookstein R.A. Relationship of hospital volume on outcomes in patients with acute pulmonary embolism: analysis of a 70,000 patient database.Vasc Med. 2020; 26: 38-46Crossref PubMed Scopus (3) Google Scholar The recent European Society of Cardiology (ESC) guidelines for the diagnosis and management of acute PE highlights the value of PERTs for high- and intermediate-risk PEs.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar One of the main challenges in treating these patients is the lack of access to locoregional expert PERT centers. Many patients who present to rural or community hospitals have to be transferred to receive advanced care, often guided by the receiving centers' PERTs.16Zuin M. Barco S. Zuliani G. Roncon L. Management of high-risk pulmonary embolism in an "unstable medical environment": not only a matter of hemodynamic.Thromb Res. 2020; 195: 193-194Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar Literature from other acute medical conditions (ie, ST-elevation myocardial infarction [STEMI] and stroke) suggests that patients requiring interhospital transfer (IHT) have significantly higher morbidity and mortality compared with patients admitted directly to hospitals with expertise and experience.17Kawecki D. Gierlotka M. Morawiec B. et al.Direct admission versus interhospital transfer for primary percutaneous coronary intervention in ST-segment elevation myocardial infarction.JACC Cardiovasc Interv. 2017; 10: 438-447Crossref PubMed Scopus (33) Google Scholar,18Stein L.K. Tuhrim S. Fifi J. Mocco J. Dhamoon M.S. Interhospital transfers for endovascular therapy for acute ischemic stroke.Stroke. 2019; 50: 1789-1796Crossref PubMed Scopus (6) Google Scholar The outcomes of transferred patients are directly affected by many factors, including the care rendered and the duration of time spent at the initial hospital. A timely transfer may be a key element that improves PE outcomes, similar to what is described in other acute medical crises (ie, STEMI, stroke, trauma).19Rolando M.F.C.C. Smith R.S. Committee on Trauma; American College of Surgeons. Resources for optimal care of the injured patient. American College of Surgeons, Chicago, IL2014Google Scholar, 20Powers W.J. Rabinstein A.A. Ackerson T. et al.2018 guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association.Stroke. 2018; 49: e46-e110Crossref PubMed Scopus (3049) Google Scholar, 21O'Gara P.T. Kushner F.G. Ascheim D.D. et al.2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2013; 61: e78-e140Crossref PubMed Scopus (2330) Google Scholar, 22Scholz K.H. Friede T. Meyer T. et al.Prognostic significance of emergency department bypass in stable and unstable patients with ST-segment elevation myocardial infarction.Eur Heart J Acute Cardiovasc Care. 2020; 9: 34-44Crossref PubMed Google Scholar In acute PE, the comparative survival of patients transferred for advanced care vs those directly admitted to hospitals with PERT teams rarely has been studied.23Bloomer T.L. Thomassee E.J. Fong P.P. Acute pulmonary embolism network and multidisciplinary response team approach to treatment.Crit Pathw Cardiol. 2015; 14: 90-96Crossref PubMed Scopus (16) Google Scholar The PERT Consortium consensus practice document discusses the treatment algorithms for acute PE in detail.24Rivera-Lebron B. McDaniel M. Ahrar K. et al.Diagnosis, treatment and follow up of acute pulmonary embolism: consensus practice from the PERT consortium.Clin Appl Thromb Hemost. 2019; 25 (1076029619853037)Crossref PubMed Scopus (86) Google Scholar The focus of this review is to provide step-by-step granularity in assessing critically ill patients with PE and achieving successful IHT. Figure 1 provides a road map for the IHT process of acute PE. A writing group was established by the PERT consortium from members of Clinical Protocols and Education committees in collaboration with the CHEST Pulmonary Vascular Disease network. A conceptual outline was created by P. R., D. S., and C. R. The writing group was divided into topics based on each member's expertise or interest. Each group reviewed and summarized the relevant published literature and incorporated such information into a manuscript. The final draft of the manuscript was circulated among all authors, and revisions were discussed in monthly meetings of protocols, educational, and the CHEST Pulmonary Vascular Disease network committee. Timely, effective therapeutic anticoagulation is the mainstay of treatment in acute PE.25Smith S.B. Geske J.B. Maguire J.M. Zane N.A. Carter R.E. Morgenthaler T.I. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism.Chest. 2010; 137: 1382-1390Abstract Full Text Full Text PDF PubMed Scopus (160) Google Scholar Anticoagulation, barring absolute contraindications, should be started as soon as PE is diagnosed regardless of transfer status.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar,24Rivera-Lebron B. McDaniel M. Ahrar K. et al.Diagnosis, treatment and follow up of acute pulmonary embolism: consensus practice from the PERT consortium.Clin Appl Thromb Hemost. 2019; 25 (1076029619853037)Crossref PubMed Scopus (86) Google Scholar,26Kearon C. Akl E.A. Ornelas J. et al.Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.Chest. 2016; 149: 315-352Abstract Full Text Full Text PDF PubMed Scopus (3149) Google Scholar Many PERTs favor low-molecular-weight heparin (LMWH) as the anticoagulant of choice, based on achieving predictable therapeutic levels within 3 to 4 hours of administration.27Quinlan D.J. McQuillan A. Eikelboom J.W. Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials.Ann Intern Med. 2004; 140: 175-183Crossref PubMed Scopus (339) Google Scholar Additionally, for patients being considered for IHT, LMWH simplifies the anticoagulation plan with a single-dose administration every 12 hours instead of a continuous parenteral drip of unfractionated heparin (UFH) that requires drug monitoring and titration. However, the decision on anticoagulation (UFH vs LMWH) can be individualized after considering the patient's renal function, weight, risk of bleeding, and the anticipated need for interventional procedures. When surgical or interventional procedure or systemic lysis is planned after the transfer, LMWH regimens may be less titratable. In such cases, UFH may offer the most flexibility for interventional procedures. Overall, best practice mandates the establishment of individualized protocols to achieve rapid therapeutic anticoagulation. This includes appropriate bolus and maintenance infusion doses, as well as time metrics and specific goals after anticoagulation. Risk stratification, most commonly following the ESC guidelines, is crucial in guiding the initial approach to patients with acute PE and can be assessed through clinical, right ventricular (RV) imaging by computed tomographic pulmonary angiography (CTPA) or echocardiography, biomarkers (troponin), and the PE severity scores (Pulmonary Embolism Severity Index [PESI] score or simplified PE Severity Index [sPESI] score) for choosing the appropriate therapy.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar The ESC classification risk stratifies patients into low-risk, intermediate-risk (low and high) and high-risk PE. Low-risk PE patients are hemodynamically stable, without any evidence of RV dysfunction and an sPESI score of 0. Intermediate-risk PE patients have an sPESI score ≥ 1 or have higher PESI class (Groups 3, 4, or 5). ESC classification further risk stratifies intermediate PE into intermediate-low-risk and intermediate-high-risk group. In intermediate-low-risk PE, there is evidence for RV dysfunction on imaging (echocardiography/CTPA) or elevated cardiac troponin. These patients have either one but not both criteria. If the patients with intermediate-risk PE have evidence of RV dysfunction on imaging (echocardiography/CTPA) and elevated cardiac troponins, they are then considered intermediate-high-risk PE. High-risk PE is defined as patients who are hemodynamically unstable. The PESI score accounts for patient characteristics (ie, age, male sex, history of heart failure, cancer, chronic lung disease) and clinical parameters (ie, heart rate, systolic BP, respiratory rate, temperature, mental status, oxygen saturation) to risk stratify patients with acute PE. The PESI score risk stratifies the patient into low-risk group (groups 1, 2) and high-risk groups (groups 3, 4, and 5). Mortality increases from 1% in the low-risk group to 24% in high-risk groups.28Rali P.M. Criner G.J. Submassive pulmonary embolism.Am J Respir Crit Care Med. 2018; 198: 588-598Crossref PubMed Scopus (30) Google Scholar,29Donzé J. Le Gal G. Fine M.J. et al.Prospective validation of the Pulmonary Embolism Severity Index: a clinical prognostic model for pulmonary embolism.Thromb Haemost. 2008; 100: 943-948Crossref PubMed Scopus (222) Google Scholar The PESI score is rarely calculated in clinical practice, because it is generally considered cumbersome. In contrast, the simplified PESI (sPESI) is brief, contains a limited number of easily accessible clinical parameters (ie, age, history of cancer, chronic lung disease, heart rate, systolic BP, oxygen saturation) and is therefore much more practical. The sPESI score being very sensitive identifies extremely low-risk patients who are not likely to suffer any adverse outcomes. Assessment of RV size and function by CTPA, echocardiography, or both are essential components of risk stratification of patients with acute PE, with increased RV size and dysfunction associated with poor outcomes.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar Troponin elevation is caused by myocardial ischemia, whereas B-type natriuretic peptide rise is attributable to RV pressure overload in the setting of acute PE. Elevation of biomarkers carries an independent risk of short-term mortality and RV dysfunction.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar,30Klok F.A. Mos I.C. Huisman M.V. Brain-type natriuretic peptide levels in the prediction of adverse outcome in patients with pulmonary embolism: a systematic review and meta-analysis.Am J Respir Crit Care Med. 2008; 178: 425-430Crossref PubMed Scopus (265) Google Scholar New emerging biomarkers, such as increased serum creatinine, lactic acid, or hyponatremia, can further aid in risk stratification.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar Bleeding risk is necessarily assessed in all acute PE patients when considering their candidacy for advanced interventions. BACS score (ie, recent major bleeding, age >75, active cancer, syncope) and PE-CH scores (ie, peripheral arterial disease, age > 65 years, prior stroke with residual effect, history of heart attack) have been recently developed to predict the risk of major bleeding and intracranial hemorrhage in patients considered for systemic thrombolysis.31Jara-Palomares L. Jiménez D. Bikdeli B. et al.Derivation and validation of a clinical prediction rule for thrombolysis-associated major bleeding in patients with acute pulmonary embolism: the BACS score [Published online ahead of print July 23, 2020].Eur Respir J. 2020; : 2002336https://doi.org/10.1183/13993003.02336-2020Crossref PubMed Google Scholar,32Chatterjee S. Weinberg I. Yeh R.W. et al.Risk factors for intracranial haemorrhage in patients with pulmonary embolism treated with thrombolytic therapy: development of the PE-CH Score.Thromb Haemost. 2017; 117: 246-251Crossref PubMed Scopus (37) Google Scholar Anticoagulation is nearly always adequate for patients with low- and intermediate-low-risk PE. Patients with intermediate-high-risk PE (RV dysfunction, sPESI ≥ 1, and elevated troponin or B-type natriuretic peptide) may need escalation of care, and those with high-risk PE (hemodynamic instability) usually do need it.15Konstantinides S.V. Meyer G. Becattini C. et al.2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).Eur Heart J. 2020; 41: 543-603Crossref PubMed Scopus (1145) Google Scholar Comprehensive PERT consensus-based PE-specific management approaches have been described previously.24Rivera-Lebron B. McDaniel M. Ahrar K. et al.Diagnosis, treatment and follow up of acute pulmonary embolism: consensus practice from the PERT consortium.Clin Appl Thromb Hemost. 2019; 25 (1076029619853037)Crossref PubMed Scopus (86) Google Scholar This section focuses on the specific A (airway), B (breathing), and C (circulation) issues that may arise before or during the transfer of critically ill PE patients. Severe hypoxemia may be seen in critically ill PE patients. When supplemental oxygen via nasal cannula is not sufficient to maintain adequate oxygenation, patients can be supported with noninvasive ventilation via high-flow nasal cannula (HFNC) oxygen or bilevel positive-pressure airway pressure, leaving endotracheal intubation as a last resort.33De Jong A. Rolle A. Molinari N. et al.Cardiac arrest and mortality related to intubation procedure in critically ill adult patients: a multicenter cohort study.Crit Care Med. 2018; 46: 532-539Crossref PubMed Scopus (99) Google Scholar Urgent endotracheal intubation in critically ill patients carries a significant risk compared with elective intubation.33De Jong A. Rolle A. Molinari N. et al.Cardiac arrest and mortality related to intubation procedure in critically ill adult patients: a multicenter cohort study.Crit Care Med. 2018; 46: 532-539Crossref PubMed Scopus (99) Google Scholar In critically ill acute PE patients, intubation can potentiate RV failure by causing a reduction in preload and an increase in afterload, which may result in cardiopulmonary arrest. In addition, some induction agents used for endotracheal intubation can reduce systemic vascular resistance and RV preload, which may further precipitate shock. If endotracheal intubation is unavoidable, it is best performed by an experienced provider. One retrospective case series describes awake bronchoscopic-guided intubation while patients receive HFNC oxygen in patients with pulmonary hypertension.34Johannes J. Berlin D.A. Patel P. et al.A technique of awake bronchoscopic endotracheal intubation for respiratory failure in patients with right heart failure and pulmonary hypertension.Crit Care Med. 2017; 45: e980-e984Crossref PubMed Scopus (8) Google Scholar In this series of nine patients, ketamine, fentanyl, and midazolam were the most commonly used induction agents, and all were used at lower doses to avoid hypotension.34Johannes J. Berlin D.A. Patel P. et al.A technique of awake bronchoscopic endotracheal intubation for respiratory failure in patients with right heart failure and pulmonary hypertension.Crit Care Med. 2017; 45: e980-e984Crossref PubMed Scopus (8) Google Scholar In a recently performed, systemic review of 892 critically ill adult patients, ketamine use was associated with a reduction in propofol infusion rate (mean difference in dose, −699 μg/min; 95%CI, −1169 to −230; P = .003). Ketamine was not associated with increased mortality, vasopressor dependence, or hospital length of stay.35Manasco A.T. Stephens R.J. Yaeger L.H. Roberts B.W. Fuller B.M. Ketamine sedation in mechanically ventilated patients: a systematic review and meta-analysis.J Crit Care. 2020; 56: 80-88Crossref PubMed Scopus (12) Google Scholar Using a minimal or reduced dose of propofol is very helpful because propofol along with endotracheal intubation will lead to a decrease in preload, which could result in cardiac arrest in the setting of acute PE. Etomidate, opioids, and benzodiazepines are rapid-acting sedatives commonly used during induction with less profound hemodynamic effects compared with general anesthetics (ie, propofol). However, opioids can act synergistically with other sedatives, such as propofol, and exacerbate hypotension.36Zakaria S. Kwong H.J. Sevransky J.E. Williams M.S. Chandra-Strobos N. Editor's Choice: The cardiovascular implications of sedatives in the cardiac intensive care unit.Eur Heart J Acute Cardiovasc Care. 2018; 7: 671-683Crossref PubMed Scopus (4) Google Scholar In critically ill patients, rapid sequence intubation has been shown to increase the success rate of intubation.37Okubo M. Gibo K. Hagiwara Y. Nakayama Y. Hasegawa K. The effectiveness of rapid sequence intubation (RSI) versus non-RSI in emergency department: an analysis of multicenter prospective observational study.Int J Emerg Med. 2017; 10: 1Crossref PubMed Scopus (32) Google Scholar During the peri-intubation period, avoiding hypoxemia and hypercapnia is important, because the pulmonary vasculature is particularly susceptible to reactive vasoconstriction. Moreover, minimizing time in the supine position has the theoretical advantage of avoiding atelectasis, which can increase pulmonary vascular resistance (PVR) and worsen RV afterload. Once intubated and mechanically ventilated, a reasonable goal in managing the ventilatory strategy of PE patients is to prevent an increase in RV afterload that can ultimately lead to RV failure.38Dalabih M. Rischard F. Mosier J.M. What's new: the management of acute right ventricular decompensation of chronic pulmonary hypertension.Intensive Care Med. 2014; 40: 1930-1933Crossref PubMed Scopus (17) Google Scholar This can be achieved by maintaining a low mean airway pressure, preventing hypoxemia and hypercapnia, and avoiding alveolar de-recruitment and collapse.39Rudolph A.M. Yuan S. Response of the pulmonary vasculature to hypoxia and H+ ion concentration changes.J Clin Invest. 1966; 45: 399-411Crossref PubMed Scopus (371) Google Scholar, 40Harvey R.M. Enson Y. Betti R. Lewis M.L. Rochester D.F. Ferrer M.I. Further observations on the effect of hydrogen ion on the pulmonary circulation.Circulation. 1967; 35: 1019-1027Crossref PubMed Scopus (33) Google Scholar, 41Ventetuolo C.E. 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Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.Crit Care. 2010; 14: R169Crossref PubMed Scopus (226) Google Scholar Excessive positive end-expiratory pressure (PEEP) also can increase lung volumes and transpulmonary pressures, reduce venous return and RV preload, and increase PVR and RV afterload.44Disselkamp M. Adkins D. Pandey S. Coz Yataco A.O. Physiologic approach to mechanical ventilation in right ventricular failure.Ann Am Thorac Soc. 2018; 15: 383-389Crossref PubMed Scopus (11) Google Scholar For these reasons, a lung-protective ventilatory strategy that limits the plateau pressure with a low PEEP and high Fio2 approach can be used whenever possible. Permissive hypercapnia or high Pco2 may be avoided. Administration of supplemental oxygen has been shown to reduce pulmonary artery pressure and PVR and to improve cardiac output in pulmonary arterial hypertension regardless of the inciting cause.43Harjola V.P. Mebazaa A. Celutkiene J. et al.Contemporary management of acute right ventricular failure: a statement from the Heart Failure Association and the Working Group on Pulmonary Circulation and Right Ventricular Function of the European Society of Cardiology.Eur J Heart Fail. 2016; 18: 226-241Crossref PubMed Scopus (286) Google Scholar,45Zamanian R.T. Haddad F. Doyle R.L. Weinacker A.B. Management strategies for patients with pulmonary hypertension in the intensive care unit.Crit Care Med. 2007; 35: 2037-2050Crossref PubMed Scopus (173) Google Scholar In acute PE, hypoxic pulmonary vasoconstriction can contribute to an elevated pulmonary artery pressure and an increased RV afterload. A variety of advanced respiratory support techniques, such as HFNC oxygen and bilevel positive pressure airway pressure, can be used to decrease the work of breathing and reduce air hunger if conventional nasal cannula oxygen fails to maintain adequate oxygenation. Inhaled pulmonary vasodilators, such as nitric oxide or epoprostenol, may counteract the effects of vasoconstrictive cytokines (ie, histamine, serotonin, thromboxane A2) released in acute PE46Smulders Y.M. Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: the pivotal role of pulmonary vasoconstriction.Cardiovasc Res. 2000; 48: 23-33Crossref PubMed Scopus (216) Google Scholar and may improve oxygenation and hemodynamics. However, these agents may not be readily available during transfer, and level 1 evidence is not available supporting their use. Optimal hemodynamic resuscitation before the transfer of critically ill patients is of utmost importance.47Droogh J.M. Smit M. Absalom A.R. 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