Prognostic Value of Different Dead Space Indices in Mechanically Ventilated Patients With Acute Lung Injury and ARDS

doi:10.1378/chest.07-0935

Chest

Volume 133, Issue 1, January 2008, Pages 62-71

https://doi.org/10.1378/chest.07-0935 Get rights and content

Study objective

The aim of this prospective observational study was to evaluate the utility of derived dead space indexes to predict survival in mechanically ventilated patients with acute lung injury (ALI) and ARDS.

Study population

Thirty-six patients with ALI (Murray score, ≥1; Pao₂/fraction of inspired oxygen [Fio₂] ratio, < 300) in critical care departments at two separate hospitals entered the study.

Measurements

At ICU admission, 24 h, and 48 h, we measured the following: simplified acute physiologic score II; Pao₂/Fio₂ ratio; respiratory system compliance; and capnographic indexes (Bohr dead space) and physiologic dead space (Enghoff dead space [Vdphys/Vt]), expired normalized CO₂ slope, carbon dioxide output, and the alveolar ejection volume (Vae)/tidal volume fraction (Vt) ratio.

Results

The best predictor was the Vae/Vt ratio at ICU admission (Vae/Vt-adm) and after 48 h (Vae/Vt-48 h) [p = 0.013], with a sensitivity of 82% and a specificity of 64%. The difference between Vae/Vt-48 h and Vae/Vt-adm show a sensitivity of 73% and a specificity of 93% with a likelihood ratio (LR) of 10.2 and an area under the receiver operating characteristic (ROC) curve of 0.83. The interaction between the Pao₂/Fio₂ ratio and Vae/Vt-adm predict survival (p = 0.003) with an area under the ROC curve of 0.84, an LR of 2.3, a sensitivity of 100%, and a specificity of 57%. The Vdphys/Vt after 48 h predicted survival (p = 0.02) with an area under the ROC curve of 0.75, an LR of 8.8, a sensitivity of 63%, and a specificity of 93%. Indexes recorded 24 h after ICU admission were not useful in explaining outcome.

Conclusions

Noninvasive measures of Vae/Vt at ICU admission and after 48 h of mechanical ventilation, associated with Pao₂/Fio₂ ratio provided useful information on outcome in critically ill patients with ALI.

Section snippets

Materials and Methods

We prospectively studied 36 mechanically ventilated patients with ALI who had been admitted to the ICU of the Hospital of Sabadell (Sabadell, Spain) [22 patients] and the Hospital of Cattinara, Trieste (Trieste, Italy) [14 patients]. The protocol was approved by the ethics committees at both institutions, and informed consent was waived because of the observational nature of the study. ALI was defined as a Murray lung injury score of ≥1¹³ and a Pao₂/fraction of inspired oxygen (Fio₂) ratio of <

Results

We included 36 patients, 12 female and 24 male, with a mean age of 66 ± 15.2 years. No patients died within the first 48 h. Patients coming from the two ICUs differed in mean age (Sabadell Hospital, 61.3 ± 16.5 years; Trieste Hospital, 73.4 ± 9.4 years; p < 0.05). The clinical variables studied (Tables 1, 2) and the mortality rate were similar in the Sabadell and Trieste Hospitals (41% and 36%, respectively; difference was not significant). Consequently, the data were analyzed as if from a

Discussion

In ARDS patients, pioneering studies¹⁸ have shown that physiologic dead space and its evolution in the first days of the disease were associated with death. Only in the last decade have Vdphys/Vt measurements regained the attention of researchers. Nuckton et al² published the most successful study suggesting that high Vdphys/Vt is independently associated with increased risk of death in ARDS patients. The disadvantage of this method is the need for ventilator adjustments to obtain dead space

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Cited by (74)

Letter to the editor: “Increased respiratory dead space could associate with coagulation activation and poor outcomes in COVID-19 ARDS”
2023, Journal of Critical Care
Correlation between increased D-dimer in blood with dead space in patients with COVID-19 and acute respiratory distress syndrome
2022, Acta Colombiana de Cuidado Intensivo
Desde diciembre de 2019, un número de casos de neumonía por síndrome respiratorio agudo severo (SARS) CoV2/COVID-19 en Wuhan, China, se identificaron como causa de insuficiencia respiratoria aguda, y se propagaron por el mundo a gran velocidad. Debido al gran número de casos y a la necesidad de entender más esta condición, surge la necesidad de identificar herramientas que gradúen la intensidad y el pronóstico vital de los pacientes. El objetivo de este estudio es determinar la relación entre el espacio muerto medido por capnografía volumétrica o por ventilatory ratio y el aumento de los niveles de dímero D en los pacientes con diagnóstico de neumonía por COVID-19 y que cumplan los criterios de Berlín para síndrome de dificultad respiratoria aguda (SDRA).
Se realizó un estudio observacional de una cohorte prospectiva, monocéntrico, sobre el uso de dímero D y la correlación con el espacio muerto. Se incluyeron adultos mayores de 18 años con diagnóstico de neumonía por COVID-19 y SDRA hospitalizados en las unidades de cuidados intensivos del Hospital Santa Clara en Bogotá, Colombia, desde agosto de 2020 hasta julio de 2021.
El estudio incluyó 67 pacientes, con diagnóstico de SARS-CoV-2 confirmado en todos ellos, no se encontró asociación entre dímero D y espacio muerto en el día 1 y 3 de la hospitalización en la UCI.
El dímero D no se correlaciona con el aumento del espacio muerto en nuestro estudio y tampoco se asoció con los desenlaces clínicos relevantes en los pacientes con SDRA.
Since December 2019, a number of cases of CoV2/COVID-19 severe acute respiratory syndrome (SARS) pneumonia in Wuhan China have been identified as a cause of acute respiratory failure and have spread around the world at high speed. Due to the large number of cases and the need to better understand this condition, tools are required to grade the intensity and vital prognosis of patients. The objective of this study is to determine the relationship between the dead space measured by volumetric capnography or ventilatory ratio and the increase in D-dimer levels in patients diagnosed with COVID-19 pneumonia and who meet the Berlin criteria for Acute Respiratory Distress Syndrome (ARDS).
A single-centre observational study of a prospective cohort on the use of D-dimer and the correlation with dead space. Adults older than 18 years with a diagnosis of pneumonia due to COVID-19 and ARDS hospitalized in the intensive care units of Hospital Santa Clara in Bogotá, Colombia, from August 2020 to July 2021 were included.
The study included 67 patients, all with a confirmed SARS-CoV-2 diagnosis, no association was found between D-dimer and dead space on day 1 and 3 of hospitalization in the ICU.
D-dimer was not correlated with increased dead space in our study and was not associated with relevant outcomes in patients with ARDS.
Opportunities for improved clinical trial designs in acute respiratory distress syndrome
2022, The Lancet Respiratory Medicine
Citation Excerpt :
ARDS characterised by diffuse consolidations on CT differs from ARDS with focal consolidations on CT in terms of baseline respiratory mechanics and response to positive end-expiratory pressure (PEEP),13,14 as well as biological markers of pulmonary epithelial injury such as RAGE (receptor for advanced glycation end-products), which is expressed with higher levels in the plasma in patients with diffuse radiographic opacities.15 Other sources of heterogeneity in ARDS that are reflected in clinical outcomes and, in some cases, in biomarker profiles include physiological derangements such as the degree of hypoxaemia, shunt fraction, and dead space;16,17 timing of onset;18–20 and trajectory of resolution.21 Two distinct biological phenotypes of ARDS, termed hyperinflammatory and hypoinflammatory, have been consistently identified through latent class analysis22 across five randomised clinical trials (RCTs), two observational cohorts, and in a paediatric RCT (figure 1).23–28
The acute respiratory distress syndrome (ARDS) is a common critical illness syndrome with high morbidity and mortality. There are no proven pharmacological therapies for ARDS. The current definition of ARDS is based on shared clinical characteristics but does not capture the heterogeneity in clinical risk factors, imaging characteristics, physiology, timing of onset and trajectory, and biology of the syndrome. There is increasing interest within the ARDS clinical trialist community to design clinical trials that reduce heterogeneity in the trial population. This effort must be balanced with ongoing work to craft an inclusive, global definition of ARDS, with important implications for trial design. Ultimately, the two aims—to design trials that are applicable to the diverse global ARDS population while also advancing opportunities to identify targetable traits—should coexist. In this Personal View, we recommend two primary strategies to improve future ARDS trials: the development of new methods to target treatable traits in clinical trial populations, and improvements in the representativeness of ARDS trials, with the inclusion of global populations. We emphasise that these two strategies are complementary. We also discuss how a proposed expansion of the definition of ARDS could affect the future of clinical trials.
Standardizing PaO2 for PaCO2 in P/F ratio predicts in-hospital mortality in acute respiratory failure due to Covid-19: A pilot prospective study
2021, European Journal of Internal Medicine
Up to fifteen percent of patients with novel pandemic coronavirus disease (Covid-19) have acute respiratory failure (ARF). Ratio between arterial partial pressure of oxygen (PaO2) and fraction of inspired oxygen (FiO2), P/F, is currently used as a marker of ARF severity in Covid-19. P/F does not reflect the respiratory efforts made by patients to maintain arterial blood oxygenation, such as tachypnea and hyperpnea, leading to hypocapnia. Standard PaO2, the value of PaO2 adjusted for arterial partial pressure of carbon dioxide (PaCO2) of the subject, better reflects the pathophysiology of hypoxemic ARF. We hypothesized that the ratio between standard PaO2 over FiO2 (STP/F) better predicts Covid-19 ARF severity compared to P/F.
Aim of this pilot prospectic observational study was to observe differences between STP/F and P/F in predicting outcome failure, defined as need of invasive mechanical ventilation and/or deaths in Covid-19 ARF. Accuracy was calculated using Receiver Operating Characteristics (ROC) analysis and areas under the ROC curve (AUROC) were compared.
349 consecutive subjects admitted to our respiratory wards due to Covid-19 ARF were enrolled. STP/F was accurate to predict mortality and superior to P/F with, respectively, AUROC 0.710 versus 0.688, p = 0.012.Both STP/F and PF were accurate to predict outcome failure (AUROC respectively of 0.747 and 0.742, p = 0.590).
This is the first study assessing the role of STP/F in describing severity of ARF in Covid-19. According to results, STP/F is accurate and superior to P/F in predicting in-hospital mortality.
Phosgene inhalation toxicity: Update on mechanisms and mechanism-based treatment strategies
2021, Toxicology
Phosgene (carbonyl dichloride) gas is an indispensable high-production-volume chemical intermediate used worldwide in numerous industrial processes. Published evidence of human exposures due to accidents and warfare (World War I) has been reported; however, these reports often lack specificity because of the uncharacterized exposure intensities of phosgene and/or related irritants. These may include liquid or solid congeners of phosgene, including di- and triphosgene and/or the respiratory tract irritant chlorine which are often collectively reported under the umbrella of phosgene exposure without any appreciation of their differences in causing acute lung injury (ALI). Among these irritants, phosgene gas is somewhat unique because of its poor water solubility. This prevents any appreciable retention of the gas in the upper airways and related trigeminal sensations of irritation. By contrast, in the pulmonary compartment, amphiphilic surfactant might scavenge this lipophilic gas. The interaction of phosgene and the surfactant may affect basic physiological functions controlled by Starling’s and Laplace’s laws, which can be followed by cardiogenic pulmonary edema. The phenotypic manifestations are dependent on the concentration × exposure duration (C × t); the higher the C × t is, the less time that is required for edema to appear. It is hypothesized that this type of edema is caused by cardiovascular and colloid osmotic imbalances to initial neurogenic events but not because of the injury itself. Thus, hemodynamic etiologies appear to cause imbalances in extravasated fluids and solute accumulation in the pulmonary interstitium, which is not drained away by the lymphatic channels of the lung. The most salient associated findings are hemoconcentration and hypoproteinemia. The involved intertwined pathophysiological processes coordinating pulmonary ventilation and cardiopulmonary perfusion under such conditions are complex. Pulmonary arterial catheter measurements on phosgene-exposed dogs provided evidence of ‘cor pulmonale’, a form of acute right heart failure produced by a sudden increase in resistance to blood flow in the pulmonary circulation about 20 h postexposure. The objective of this review is to critically analyze evidence from experimental inhalation studies in rats and dogs, and evidence from accidental human exposures to better understand the primary and secondary events causing cardiopulmonary dysfunction and an ensuing life-threatening lung edema. Mechanism-based diagnostic and therapeutic approaches are also considered for this form of cardiogenic edema.
Comparison of the pulmonary dead-space fraction derived from ventilator volumetric capnography and a validated equation in the survival prediction of patients with acute respiratory distress syndrome
2016, Chinese Journal of Traumatology - English Edition
Citation Excerpt :
The prediction equation constructed by Frankenfield DC et al7 for dead space fraction has been proved to be capable of avoiding the abovementioned disturbances. In fact, most pioneering studies have found that the dead space fraction can reliably predict the threshold values for prognosis (i.e. >60%).2–4,6,12–14 However, we found that the mean Vd/Vt among survivors was volatile and consistently <0.50.
This prospective observational study aims to evaluate the accuracy of dead-space fraction derived from the ventilator volumetric capnography (volumetric CO₂) or a prediction equation to predict the survival of mechanically ventilated patients with acute respiratory distress syndrome (ARDS).
Consecutive VD/VT measurements were obtained based upon a prediction equation validated by Frankenfield et al for dead-space ventilation fraction: VD/VT = 0.320 + 0.0106 (PaCO₂-ETCO₂) + 0.003 (RR) + 0.0015 (age) in adult patients who had infection-related severe pneumonia and were confirmed as having ARDS. Here PaCO₂ is the arterial partial pressure of carbon dioxide in mmHg; ETCO₂, the end-tidal carbon dioxide measurement in mmHg; RR, respiratory rate per minute; and age in years. Once the patient had intubation, positive end expiratory pressure was adjusted and after P_high reached a steady state, VD/VT was measured and recorded as the data for the first day. VD/VT measurement was repeated on days 2, 3, 4, 5 and 6. Meanwhile we collected dead-space fraction directly from the ventilator volumetric CO₂ and recorded it as Vd/Vt. We analyzed the changes in VD/VT and Vd/Vt over the 6-day period to determine their accuracy in predicting the survival of ARDS patients.
Overall, 46 patients with ARDS met the inclusion criteria and 24 of them died. During the first 6 days of intubation, VD/VT was significantly higher in nonsurvivors on day 4 (0.70 ± 0.01 vs 0.57 ± 0.01), day 5 (0.73 ± 0.01 vs. 0.54 ± 0.01), and day 6 (0.73 ± 0.02 vs. 0.54 ± 0.01) (all p = 0.000). Vd/Vt showed no significant difference on days 1–4 but it was much higher in nonsurvivors on day 5 (0.45 ± 0.04 vs. 0.41 ± 0.06) and day 6 (0.47 ± 0.05 vs. 0.40 ± 0.03) (both p = 0.008). VD/VT on the fourth day was more accurate to predict survival than Vd/Vt. The area under the receiver-operating characteristic curve for VD/VT and Vd/Vt in evaluating ARDS patients survival was day 4 (0.974 ± 0.093 vs. 0.701 ± 0.023, p = 0.0024) with the 95% confidence interval being 0.857–0.999 vs. 0.525–0.841.
Compared with Vd/Vt derived from ventilator volumetric CO₂, VD/VT on day 4 calculated by Frankenfield et al's equation can more accurately predict the survival of ARDS patients.

View all citing articles on Scopus

This study was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica and Instituto de Salud Carlos III Red GIRA (G03/063), Red Respira (ISCiii RTIC 03/11), and Institut Universitari Fundació Parc Taulí.

The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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Chest

Original ResearchCRITICAL CARE MEDICINEPrognostic Value of Different Dead Space Indices in Mechanically Ventilated Patients With Acute Lung Injury and ARDS

Study objective

Study population

Measurements

Results

Conclusions

Section snippets

Materials and Methods

Results

Discussion

Br J Anesth

Chest

Br J Anaesth

Chest

Respir Physiol

End-tidal CO2-arterial CO2differences: a useful intraoperative mortality marker in trauma surgery

J Trauma

Pulmonary dead-space fraction as a risk factor for death in the acute respiratory distress syndrome

N Engl J Med

Dead space

Intensive Care Med

Prognostic value of the pulmonary dead-space fraction during the first 6 days of acute respiratory distress syndrome

Respir Care

Lung function studies II: the respiratory dead-space

Am J Physiol

Physiologically based indices of volumetric capnography in patients receiving mechanical ventilation

Eur Respir J

Evaluation of a noninvasive method for cardiac output measurement in critical care patients

Intensive Care Med

The expiratory capnogram: a measure of ventilation-perfusion inequalities

Thorax

Volumetric capnography as a bedside monitoring of thrombolysis in major pulmonary embolism

Intensive Care Med

Original Research
CRITICAL CARE MEDICINE
Prognostic Value of Different Dead Space Indices in Mechanically Ventilated Patients With Acute Lung Injury and ARDS

End-tidal CO₂-arterial CO₂differences: a useful intraoperative mortality marker in trauma surgery