Oxygen Therapy Lowers Right Ventricular Afterload in Experimental Acute Pulmonary Embolism

Lyhne, Mads Dam; Hansen, James V.; Dragsbæk, Simone Juel; Mortensen, Christian Schmidt; Nielsen‐Kudsk, Jens Erik; Andersen, Asger

doi:10.1097/ccm.0000000000005057

Cited by 9 publications

(11 citation statements)

References 48 publications

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“…The prominent PA pressure response seen with the first of a series of consecutive emboli could possibly be related to an initial strong vasoconstrictor response that are weaker for the following emboli. However, we know that there is a substantial contribution of pulmonary vasoconstriction in acute PE that persists for hours, as we have previously shown prominent effects of pulmonary vasodilatory agents in this model [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 90%

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study

Lyhne,

Schultz,

Mortensen

et al. 2024

BMC Pulm Med

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Background Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. Methods This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. Results Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. Conclusion In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

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Section: Discussionmentioning

confidence: 90%

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study

Lyhne,

Schultz,

Mortensen

et al. 2024

BMC Pulm Med

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“…Throughout the study, an F io 2 of 21% was maintained mimicking atmospheric concentrations. To induce vasodilation with oxygen, F io 2 was increased to 40% for 15 minutes and maintained elevated, as shown previously ( 14 ). Furthermore, sildenafil in a dose of 0.1 mg/kg, dissolved in isotonic saline (0.1 mg/mL) was infused over the course of 6 minutes and measurements 30 minutes after.…”

Section: Methodsmentioning

confidence: 99%

“…In experimental studies, PVR increases abruptly after acute PE and decreases within hours to a stabile plateau (6, 9). Accordingly, attenuation of vasoconstriction seems effective in the first hours after PE (6, 7, 9, 13–16). However, the mean time from onset of acute PE to inclusion in clinical trials is days, at which time PVR may already be decreased by endogenous mechanisms (10–12).…”

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confidence: 99%

Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs

Merit,

Kirk,

Schultz

et al. 2024

Critical Care Explorations

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OBJECTIVES: To investigate the contribution of mechanical obstruction and pulmonary vasoconstriction to pulmonary vascular resistance (PVR) in acute pulmonary embolism (PE) in pigs. DESIGN: Controlled, animal study. SETTING: Tertiary university hospital, animal research laboratory. SUBJECTS: Female Danish slaughter pigs (n = 12, ~60 kg). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: PE was induced by infusion of autologous blood clots in pigs. CT pulmonary angiograms were performed at baseline, after PE (first experimental day [PEd0]) and the following 2 days (second experimental day [PEd1] and third experimental day [PEd2]), and clot burden quantified by a modified Qanadli Obstruction Score. Hemodynamics were evaluated with left and right heart catheterization and systemic invasive pressures each day before, under, and after treatment with the pulmonary vasodilators sildenafil (0.1 mg/kg) and oxygen (Fio 2 40%). PE increased PVR (baseline vs. PEd0: 178 ± 54 vs. 526 ± 160 dynes; p < 0.0001) and obstruction score (baseline vs. PEd0: 0% vs. 45% ± 13%; p < 0.0001). PVR decreased toward baseline at day 1 (baseline vs. PEd1: 178 ± 54 vs. 219 ± 48; p = 0.16) and day 2 (baseline vs. PEd2: 178 ± 54 vs. 201 ± 50; p = 0.51). Obstruction score decreased only slightly at day 1 (PEd0 vs. PEd1: 45% ± 12% vs. 43% ± 14%; p = 0.04) and remained elevated throughout the study (PEd1 vs. PEd2: 43% ± 14% vs. 42% ± 17%; p = 0.74). Sildenafil and oxygen in combination decreased PVR at day 0 (–284 ± 154 dynes; p = 0.0064) but had no effects at day 1 (–8 ± 27 dynes; p = 0.4827) or day 2 (–18 ± 32 dynes; p = 0.0923). CONCLUSIONS: Pulmonary vasoconstriction, and not mechanical obstruction, was the predominant cause of increased PVR in acute PE in pigs. PVR rapidly declined over the first 2 days after onset despite a persistent mechanical obstruction of the pulmonary circulation from emboli. The findings suggest that treatment with pulmonary vasodilators might only be effective in the acute phase of PE thereby limiting the window for such therapy.

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“…If intermediate-low risk PE is perfectly safe to be managed in a conventional unit, we believe that intermediate-high risk patients should ideally benefit for closer surveillance in an intensive care setting considering the risk of hemodynamic decompensation and cardiogenic shock. In all cases, supplemental oxygen should be administered to target an oxygen saturation ≥ 90% [13], and in severely hypoxemic patients oxygen may be delivered via high flow nasal cannulae (HFNC). Noninvasive ventilation may be responsible for worsening RV afterload and do not represent the first choice except in case of associated hypercapnic acidosis.…”

Section: Treatment Of Submassive Pulmonary Embolismmentioning

confidence: 99%

“…In all cases, supplemental oxygen should be administered to target an oxygen saturation ! 90% [13], and in severely hypoxemic patients oxygen may be delivered via high flow nasal cannulae (HFNC). Noninvasive ventilation may be responsible for worsening RV afterload and do not represent the first choice except in case of associated hypercapnic acidosis.…”

Section: Initial Managementmentioning

confidence: 99%

Risk stratification and treatment of pulmonary embolism with intermediate-risk of mortality

Pastré

Sanchis-Borja

Benlounes

2022

Current Opinion in Pulmonary Medicine

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Purpose of reviewIntermediate-risk pulmonary embolisms (PE) represent a heterogeneous group at the high end of hemodynamically stable patients, characterized by a higher mortality rate. This challenging population gathers many unsolved question regarding its therapeutic management. The purpose of this review is to provide an updated overview of the literature regarding further risk stratification and treatment options in this population.Recent findingsIf anticoagulation represents the undisputed first line of treatment, some patients especially in the intermediate-high risk subgroup may necessitate or could benefit from therapeutic escalation with reperfusion therapies. This includes systemic thrombolysis (ST) or catheter-directed therapies (CDT). ST, despite its high efficacy, is not recommended in this population because of prohibitive bleeding complications. Therefore, reduced-dose ST appears to be a promising option and is actually under evaluation. CDT are percutaneous reperfusion techniques developed to acutely decrease pulmonary vascular obstruction with lower-dose or no thrombolytic agents and, thus, potentially improved safety compared to ST.SummaryGreat progress has been made in the recent years providing a wide range of therapeutic options. Optimal selection of patients who could benefit from these treatments is the key and is based on clinical, biological and radiological parameters evaluating right ventricle function and allowing accurate risk stratification. Pulmonary Embolism Response Team represents an efficient modality for therapeutic management especially in the intermediate-high risk subgroup.

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Oxygen Therapy Lowers Right Ventricular Afterload in Experimental Acute Pulmonary Embolism

Cited by 9 publications

References 48 publications

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study

Changes in Pulmonary Vascular Resistance and Obstruction Score Following Acute Pulmonary Embolism in Pigs

Risk stratification and treatment of pulmonary embolism with intermediate-risk of mortality

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