Dataset Information

In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.

ABSTRACT: Objectives:Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 acute respiratory distress syndrome and to evaluate the resulting implications for ventilatory management. Design:We adapted a high-fidelity computational simulator, previously validated in several studies of acute respiratory distress syndrome, to: 1) develop quantitative insights into the key pathophysiologic differences between the coronavirus disease 2019 acute respiratory distress syndrome and the conventional acute respiratory distress syndrome and 2) assess the impact of different positive end-expiratory pressure, Fio2, and tidal volume settings. Setting:Interdisciplinary Collaboration in Systems Medicine Research Network. Subjects:The simulator was calibrated to represent coronavirus disease 2019 acute respiratory distress syndrome patients with both normal and elevated body mass indices undergoing invasive mechanical ventilation. Interventions:None. Measurements and Main Results:An acute respiratory distress syndrome model implementing disruption of hypoxic pulmonary vasoconstriction and vasodilation leading to hyperperfusion of collapsed lung regions failed to replicate clinical data on type 1 coronavirus disease 2019 acute respiratory distress syndrome patients. Adding mechanisms to reflect disruption of alveolar gas-exchange due to the effects of pneumonitis and heightened vascular resistance due to the emergence of microthrombi produced levels of ventilation perfusion mismatch and hypoxemia consistent with data from type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, while preserving close-to-normal lung compliance and gas volumes. Atypical responses to positive end-expiratory pressure increments between 5 and 15 cm H2O were observed for this type 1 coronavirus disease 2019 acute respiratory distress syndrome model across a range of measures: increasing positive end-expiratory pressure resulted in reduced lung compliance and no improvement in oxygenation, whereas mechanical power, driving pressure, and plateau pressure all increased. Fio2 settings based on acute respiratory distress syndrome network protocols at different positive end-expiratory pressure levels were insufficient to achieve adequate oxygenation. Incrementing tidal volumes from 5 to 10 mL/kg produced similar increases in multiple indicators of ventilator-induced lung injury in the type 1 coronavirus disease 2019 acute respiratory distress syndrome model to those seen in a conventional acute respiratory distress syndrome model. Conclusions:Our model suggests that use of standard positive end-expiratory pressure/Fio2 tables, higher positive end-expiratory pressure strategies, and higher tidal volumes may all be potentially deleterious in type 1 coronavirus disease 2019 acute respiratory distress syndrome patients, and that a highly personalized approach to treatment is advisable.

SUBMITTER: Das A

PROVIDER: S-EPMC7505291 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.

Das Anup A Saffaran Sina S Chikhani Marc M Scott Timothy E TE Laviola Marianna M Yehya Nadir N Laffey John G JG Hardman Jonathan G JG Bates Declan G DG

Critical care explorations 20200918 9

<h4>Objectives</h4>Patients with coronavirus disease 2019 acute respiratory distress syndrome appear to present with at least two distinct phenotypes: severe hypoxemia with relatively well-preserved lung compliance and lung gas volumes (type 1) and a more conventional acute respiratory distress syndrome phenotype, displaying the typical characteristics of the "baby lung" (type 2). We aimed to test plausible hypotheses regarding the pathophysiologic mechanisms underlying coronavirus disease 2019 ...[more]

PMID: 32984832

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Project description:ObjectivesTo characterize the incidence and characteristics of propofol-associated hypertriglyceridemia in coronavirus disease 2019 versus noncoronavirus disease 2019 acute respiratory distress syndrome.DesignSingle-center prospective, observational cohort study.SettingMedical ICU and regional infectious containment unit.PatientsPatients with acute respiratory distress syndrome admitted from April 7, 2020, to May 15, 2020, requiring continuous propofol administration.InterventionsNone.Measurements and main resultsOf 50 patients enrolled, 54% had coronavirus disease 2019 acute respiratory distress syndrome. Median Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were 35.5 (interquartile range, 30.2-41) and 8 (interquartile range, 6-9). Pao2/Fio2 ratio was 130.5 (interquartile range, 94.5-193.8). Patients with coronavirus disease 2019-associated acute respiratory distress syndrome experienced a higher rate of hypertriglyceridemia (triglyceride ≥ 500 mg/dL) than noncoronavirus disease 2019-associated acute respiratory distress syndrome (9 [33.3%] vs 1 [4.3%]; p = 0.014). Those with coronavirus disease 2019, compared with those without, received more propofol prior to becoming hypertriglyceridemic (median, 5,436.0 mg [interquartile range, 3,405.5-6,845.5 mg] vs 4,229.0 mg [interquartile range, 2,083.4-4,972.1 mg]; p = 0.027). After adjustment for propofol dose with logistic regression (odds ratio, 5.97; 95% CI, 1.16-59.57; p = 0.031) and propensity score matching (odds ratio, 8.64; 95% CI, 1.27-149.12; p = 0.025), there remained a significant difference in the development of hypertriglyceridemia between coronavirus disease 2019-associated acute respiratory distress syndrome and noncoronavirus disease 2019-associated acute respiratory distress syndrome. There was no difference between groups in time to hypertriglyceridemia (p = 0.063). Serum lipase was not different between those who did or did not develop hypertriglyceridemia (p = 0.545). No patients experienced signs or symptoms of pancreatitis.ConclusionsPatients with coronavirus disease 2019 acute respiratory distress syndrome experienced a higher rate of propofol-associated hypertriglyceridemia than noncoronavirus disease 2019 acute respiratory distress syndrome patients, even after accounting for differences in propofol administration.

Project description:ObjectivesDue to the rapid rate of severe acute respiratory syndrome coronavirus 2 transmission and the heterogeneity of symptoms of coronavirus disease 2019, expeditious and effective triage is critical for early treatment and effective allocation of hospital resources.DesignA post hoc analysis of respiratory data from non-invasive venous waveform analysis among patients enrolled in an observational study was performed.SettingVanderbilt University Medical Center.PatientsPeripheral venous waveforms were recorded from admission to discharge in enrolled coronavirus disease 2019-positive patients and healthy age-matched controls.InterventionsData were analyzed in LabChart 8 to transform venous waveforms to the frequency domain using fast Fourier transforms. The peak respiratory frequency was normalized to the peak cardiac frequency to generate a respiratory non-invasive venous waveform analysis respiratory index. Paired Fisher exact tests were used to compare each patient's respiratory non-invasive venous waveform analysis respiratory index at admission and discharge. A nonparametric one-way analysis of variance was used for multiple comparisons between patients with coronavirus disease 2019 and healthy controls for respiratory non-invasive venous waveform analysis respiratory index.Measurements and main resultsFifty coronavirus disease 2019-positive patients were enrolled between April 2020, and September 2020, and 45 were analyzed; 34 required supplemental oxygen and 11 did not. The respiratory non-invasive venous waveform analysis respiratory index was significantly higher for the 34 patients with coronavirus disease 2019 who received supplemental oxygen (median, 0.27; interquartile range, 0.11-1.28) compared with the 34 healthy controls (median, 0.06; interquartile range, 0.03-0.14) (p < 0.01). For patients with coronavirus disease 2019 who received supplemental oxygen, respiratory non-invasive venous waveform analysis respiratory index was significantly lower at hospital discharge (p = 0.02; 95% CI, 0.10-1.9) compared with hospital admission (median = 0.12; interquartile range, 0.05-0.56). For patients with coronavirus disease 2019, a respiratory non-invasive venous waveform analysis respiratory index of 0.64 demonstrated sensitivity of 92%, specificity of 47%, and positive predictive value of 93% for predicting requirement of supplemental oxygen during the hospitalization.ConclusionsRespiratory non-invasive venous waveform analysis respiratory index represents a novel physiologic respiratory measurement with a promising ability to triage early care and predict the need for oxygen support therapy in coronavirus disease 2019 patients.

Project description:ObjectivesMicrovascular thrombosis contributes to acute respiratory distress syndrome pathophysiology and has been demonstrated in coronavirus disease 2019-associated acute respiratory distress syndrome. Clinical laboratory measurements of coagulation and disseminated intravascular coagulation, such as coagulation factor function, platelet count, and fibrinogen, may not fully reflect the extent of microvascular thrombosis present in these patients. We investigated thromboelastography in patients with coronavirus disease 2019-associated acute respiratory distress syndrome with the objective of characterizing suspected coagulopathy and impaired fibrinolysis.DesignRetrospective observational cohort study.SettingSingle-center academic medical center.PatientsTen patients with polymerase chain reaction-confirmed coronavirus disease 2019 disease complicated by acute respiratory distress syndrome.InterventionsMeasurement of thromboelastography (n = 10) and thrombolysis with alteplase (n = 4).Measurements and main resultsHypercoagulability and decreased or absent fibrinolysis were demonstrated by thromboelastography. Thrombocytopenia and hypofibrinogenemia were not observed, while seven of 10 patients had elevated d-dimer values. For patients who received thrombolytic therapy, repeat thromboelastography demonstrated improvements in coagulation index and lysis at 30 minutes reflecting reduced hypercoagulability and increased fibrinolysis. One major bleeding complication was detected following thrombolysis. Eight of 10 patients survived and were successfully extubated, and six of 10 have since been discharged.ConclusionsIn coronavirus disease 2019 patients with acute respiratory distress syndrome in whom thromboelastography was performed, hypercoagulability and impaired fibrinolysis were observed. In the context of autopsy studies demonstrating pulmonary microvascular thromboses in coronavirus disease 2019 patients, noninvasive detection of hypercoagulability and deficient fibrinolysis in coronavirus disease 2019 acute respiratory distress syndrome using thromboelastography could improve understanding and management of coronavirus disease 2019.

Dataset Information

In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.

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In Silico Modeling of Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Pathophysiologic Insights and Potential Management Implications.

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