Steady-State End-Tidal Alveolar Dead Space Fraction and D-Dimer: Bedside Tests To Exclude Pulmonary Embolism

doi:10.1378/chest.120.1.115

Chest

Volume 120, Issue 1, July 2001, Pages 115-119

https://doi.org/10.1378/chest.120.1.115 Get rights and content

Study objective

Less than 35% of patients suspectedof having pulmonary embolism (PE) actually have PE. Safe bedsidemethods to exclude PE could save health-care resources and improveaccess to diagnostic testing for suspected PE. In patients withsuspected PE, we sought to determine the sensitivity, specificity, andnegative predictive value of (1) a steady-state end-tidal alveolar deadspace fraction (AVDSf) of < 0.15, (2) a negative D-dimer result, and(3) the combination of a steady-state end-tidal AVDSf of < 0.15 and anegative D-dimer result.

Study design

Prospectivecohort study.

Setting

Tertiary-care center in Ottawa, Ontario, Canada.

Patients

Consecutiveinpatients, outpatients, and emergency department patients withsuspected PE referred to the Departments of Nuclear Medicine or Radiology for investigation of suspected PE.

Interventionsand measurements

All study patients had D-Dimer and alveolardead space measurements prior to determining outcome (PE or no PE) withventilation/perfusion scans and/or noninvasive leg vein imaging and/orpulmonary angiography.

Results

Two hundred forty-sixeligible and consenting patients underwent diagnostic imaging thatexcluded PE in 163 patients, diagnosed PE in 49 patients, and wasindeterminant in 34 patients. A negative D-dimer result excluded PEwith a sensitivity of 83.0% (95% confidence interval [CI], 69.2 to92.4%), a negative predictive value of 91.2% (95% CI, 83.4 to96.1%), and a specificity of 57.6%. A steady-state end-tidal AVDSf of< 0.15 excluded PE with a sensitivity of 79.5% (95% CI, 63.5 to90.7%), a negative predictive value of 90.7% (95% CI, 82.5 to95.9%), and a specificity of 70.3%. The combination of a negative D-dimer result and a steady-state end-tidal AVDSf of < 0.15 excluded PE with a sensitivity of 97.8% (95% CI, 88.5 to 99.9%), a negativepredictive value of 98.0% (95% CI, 89.4 to 99.9%), and a specificityof 38.0%.

Conclusion

This simple combination ofbedside tests may safely rule out PE without further diagnostic testingin large numbers of patients with suspected PE.

Section snippets

Patients

All inpatients and outpatients at the Ottawa Hospital - General Campus suspected of having PE and referred for a ventilation/perfusion ( $\dot{V}$ / $\dot{Q}$ ) scan or pulmonary angiogram from January 1996 to August 1998 were approached for consent to participate in the study. Patients were excluded from the study if they (1) were < 18 years of age, (2) were unable to give informed consent, (3) had a contraindication to pulmonary angiography, (4) were receiving mechanical ventilation, or (5) were

Results

We approached 293 patients, of whom 282 were eligible for participation in the study. Of these 282 patients, 246 consented. Of the 246 consenting patients, 49 patients (19.9%) had PE, 163 patients (66.3%) did not have PE, and 34 patients (13.8%) could not be classified with “gold standard” outcome measures (Table 1). Female patients were less likely to have PE. Patients with PE were significantly older (mean age, 58.9 years) than patients without PE (mean age, 50.6 years). More than 94% of our

Discussion

In this study, we have demonstrated that a negative D-dimer result and a steady-state end-tidal AVDSf of < 0.15 is a potentially safe method for excluding PE in patients with suspected PE. These bedside methods are simple, noninvasive, and inexpensive. Since both the D-dimer measurement and the steady-state end-tidal alveolar dead space measurement require minimal expertise and inexpensive equipment, these tests could be made available in all hospitals. The negative predictive value of this

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Cited by (61)

Dyspnea Postpulmonary Embolism From Physiological Dead Space Proportion and Stroke Volume Defects During Exercise
2020, Chest
Many patients with pulmonary embolism (PE) report dyspnea on exertion following long-term treatment. Increased physiological dead space proportion (V_D/V_T) and decreased cardiac stroke volume reserve may distinguish persistent effects of PE itself from symptoms reflecting comorbid conditions or deconditioning.
This retrospective study analyzed a consecutive series of incremental symptom-limited cardiopulmonary exercise tests that had been ordered to evaluate persistent dyspnea on exertion following long-term treatment for acute PE. Physiological V_D/V_T was determined at anaerobic threshold from exhaled CO₂ and transcutaneous Pco₂ (validated against Paco₂ measurements). Cardiac stroke volume reserve was estimated at rest and at anaerobic threshold by using oxygen consumption/pulse and previously validated estimates of the arteriovenous oxygen content difference.
Cardiopulmonary exercise tests were performed on 40 patients with post-PE dyspnea. In 65.0% (95% CI, 50.2-79.8), V_D/V_T at anaerobic threshold was abnormally elevated, stroke volume reserve was decreased, or both defects occurred. V_D/V_T at anaerobic threshold was abnormally elevated (≥ 0.27) in 35.0% (95% CI, 20.2-49.8). V_D/V_T at anaerobic threshold significantly correlated with the extent of unmatched perfusion defects on subsequent ventilation-perfusion scans (P = .0085). In 55.0% (95% CI, 39.6-70.4), stroke volume reserve at anaerobic threshold was abnormally decreased (≤ 128% of the resting value). Both defects were present in 25.0% (95% CI, 11.6-38.4).
Increased V_D/V_T at anaerobic threshold and decreased stroke volume reserve during exercise are common among patients with dyspnea on exertion after long-term treatment of PE. The defects can be disclosed noninvasively by using cardiopulmonary exercise testing.
Short-term effects of non-invasive ventilation on cerebral blood flow and cognitive function in COPD
2018, Respiratory Physiology and Neurobiology
Investigate the acute effects of non-invasive ventilation (NIV) on cerebral blood flow (CBF) and on cognitive functions in COPD.
Nine non-hypercapnic stable COPD and twelve healthy controls were enrolled. CBF (transcranial Doppler), cognitive tests and cardiorespiratory response were performed at baseline, during one hour of NIV and after 30 min.
Both groups had an increase in tidal volume and reduction in respiratory rate during NIV, but only controls showed PaCO₂ reductions (41.2 ± 4.6 to 36.5 ± 7.3 in controls vs. 40.9 ± 4.5 to 42.9 ± 5.9 in COPD). During NIV CBF was significantly reduced in healthy controls and COPD, although this effect was less pronounced in the latter. At the same time, healthy controls demonstrated an improvement in cognitive executive function compared to COPD in the Trail Making Test part B (90.5 vs. 180s; respectively).
NIV application for one hour reversibly reduced CBF in healthy controls and non-hypercapnic stable COPD patients, despite no significant reductions of the PaCO₂ in the latter group. It was associated with minor cognitive improvements in the executive function in healthy volunteers, but not in COPD.
Capnography during critical illness
2016, Chest
Capnography has made steady inroads in the ICU and is increasingly used for all patients who are mechanically ventilated. There is growing recognition that capnography is rich in information about lung and circulatory physiology and provides insight into many diseases and treatments. These include conditions of impaired matching of ventilation and perfusion, such as pulmonary embolism and obstructive lung diseases; circulatory questions, such as the adequacy of chest compressions during cardiac arrest or fluid responsiveness in patients in shock; and the safety of procedural sedation. In this review, we emphasize analysis of the entire capnographic waveform as a way to glean additional useful information. We also discuss important limitations of capnography, especially when it is considered to be a surrogate for Paco₂.
Pulmonary embolism in Bradford, UK: Role of end-tidal CO<inf>2</inf> as a screening tool
2014, Clinical Medicine, Journal of the Royal College of Physicians of London
End-tidal CO₂ (ETCO₂) can represent dead space ventilation. The authors aimed to define the optimum ETCO₂ to conclusively exclude a pulmonary embolic event. One hundred consecutive patients with suspected pulmonary embolisms (PEs) were enrolled over 6 months in 2012. Symptoms, demographic date, Wells’ score, D-dimer levels and the gold standard computed tomography pulmonary angiogram (CTPA) results were collated for analysis. ETCO₂ was measured within 24 hours of presentation in all 100 patients. Patient ages ranged from 18 years to 93 years. PE was diagnosed in 38% of cases. The average ETCO₂ in patients with a positive CTPA was 3.35 kPa (range 2.4–4.2 kPa, SD 0.50). The average ETCO₂ in patients without a PE was 4.41 kPa (range 1.3–6.6 kPa, SD 1.10). All patients positive for a PE obtained an ETCO₂ <4.3 kPa (32.3 mmHg). This point (4.3 kPa) had a sensitivity and specificity (100% and 68% respectively), with a negative predictive value of 100% and positive predictive value of 66%. ETCO₂ may reliably be used to screen and exclude patients with suspected PEs. If used in combination with D-dimer with clinical probability as a screening tool, CTPA will be required in only a minority of patients.
Capnography as a diagnostic tool for pulmonary embolism: A meta-analysis
2013, Annals of Emergency Medicine
Citation Excerpt :
The median age of included patients ranged from 38 to 70 years, and there was variation in patient selection (inpatients and outpatients) and consecutiveness. The prevalence of pulmonary embolism ranged from 5% to 69%, and D-dimer assay sensitivities ranged from 83%27 to 100%17; specificities, from 22%30 to 57%.27 Expired CO2 was measured with different types of meters (even self-modified devices) using mainstream or sidestream flow.
Multiple studies have evaluated capnography for the diagnosis of pulmonary embolism; accordingly, we conduct a meta-analysis of these trials.
We performed a systematic search from 1990 to 2011, using MEDLINE, EMBASE, and the Cochrane Library, including studies evaluating capnography as a diagnostic tool alone or in conjunction with other tests. After study quality evaluation, we calculated the pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios.
We included 14 trials with 2,291 total subjects, with a 20% overall prevalence of pulmonary embolism. The pooled diagnostic accuracy for capnography was sensitivity 0.80 (95% confidence interval [CI] 0.76 to 0.83), specificity 0.49 (95% CI 0.47 to 0.51), negative likelihood ratio 0.32 (95% CI 0.23 to 0.45), positive likelihood ratio 2.43 (95% CI 1.70 to 3.46), and diagnostic odds ratio 10.4 (95% CI 6.33 to 17.1). The area under the summary receiver operating characteristic curve was 0.84. To reach pulmonary embolism posttest probabilities less than 1%, 2%, or 5%, pulmonary embolism prevalence or pretest probability had to be less than 3%, 5%, or 10% respectively. Because of interstudy differences in dead space measurements methodologies, the best cutoff in alveolar dead space or end tidal CO2 conferring the best negative likelihood ratio could not be evaluated.
Pooled data suggest a potential diagnostic role for capnography when the pulmonary embolism pretest probability is 10% or less, perhaps after a positive D-dimer test result.
Cardiopulmonary exercise test in patients with subacute pulmonary emboli
2012, Heart and Lung: Journal of Acute and Critical Care
Citation Excerpt :
A possible explanation for the increased incidence of men in the PE group was a higher prevalence of heart failure in men (50.9% vs 25.5%; P = .006), which is a known risk factor for PE. Respiratory dead space estimation has been suggested to diagnose PE and can be calculated using several equations.6,8,20 The ventilatory equivalent for CO2 (VE/VCO2) is a noninvasive method for estimating increased dead space.
Patients presenting with suspected pulmonary embolism (PE) may present a challenge, particularly if diagnostic testing is not immediately available or clinically not indicated (iodine allergy, pregnancy, renal dysfunction). These patients have abnormal regional gas exchange that can be recognized by a cardiopulmonary exercise test (CPET), which may become helpful in their evaluation.
A retrospective analysis was performed of outpatients evaluated for subacute exertional dyspnea of 2 to 12 weeks duration with a test for PE and CPET. A total of 108 patients met inclusion criteria. Thirty patients (27.8%) had confirmed PE.
The patients with PE had increased nadir ventilatory equivalent ratio for carbon dioxide (VE/VCO₂), decreased peak oxygen uptake/predicted, and decreased end exercise saturation (P < .005 for all). All patients but 1 had normal breathing reserve (>15%). A normal nadir VE/VCO₂ excluded PE with 100% sensitivity. By using a “flow chart strategy,” the exercise test had 92.8% sensitivity and 92.1% specificity for PE. Eight patients with PE died during follow-up (3.8 ± 4.6 years), 6 of PE-related causes. Peak VO₂/kg was the best predictor of all-cause mortality and nadir VE/VCO₂ for PE-related mortality. There were no serious complications from any of the exercise tests.
PE may be excluded by a normal nadir VE/VCO₂ in patients presenting with subacute dyspnea. A combination of decreased peak VO₂/kg, increased nadir VE/VCO₂, normal breathing reserve, and exercise-induced desaturation may be sensitive and specific for PE. CPET may assist in identifying subacute PE in patients with contraindications to use of computed tomography angiography or ventilation perfusion scans.

View all citing articles on Scopus

This study was conducted at the Ottawa Hospital - General Campus.

Financial support was provided by the Ottawa General Hospital

Research Fund and the Clinical Trials and Research Unit of the Division of Hematology, Ottawa Hospital- General Campus.

Dr. Rodger was the recipient of the Thrombosis Interest Group of Canada Research Fellowship. Dr. Wells was the recipient of a Research Scholarship from the Heart and Stroke Foundation of Canada.

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Chest

Clinical InvestigationsPulmonary EmbolismSteady-State End-Tidal Alveolar Dead Space Fraction and D-Dimer: Bedside Tests To Exclude Pulmonary Embolism

Study objective

Study design

Setting

Patients

Interventionsand measurements

Results

Conclusion

Section snippets

Patients

Results

Discussion

A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism

Arch Intern Med

The clinical course of pulmonary embolism

N Engl J Med

Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis study (PIOPED)

JAMA

Use of the alveolar dead space fraction (Vd/Vt) and plasma D-dimers to exclude acute pulmonary embolism in ambulatory patients

Acad Emerg Med

Clinical Investigations
Pulmonary Embolism
Steady-State End-Tidal Alveolar Dead Space Fraction and D-Dimer: Bedside Tests To Exclude Pulmonary Embolism