Patients presenting with acute dyspnea at the emergency department (ED) is a large and heterogeneous patient group with high mortality and readmission rates [[1]x[1]Burki, N.K. and Lee, L.Y. Mechanisms of dyspnea. Chest. 2010; 138: 1196–1201

CrossRef | PubMed | Scopus (41)See all References, [2]x[2]Palla, A., Ribas, C., Rossi, G., Pepe, P., Marconi, L., and Prandoni, P. The clinical course of pulmonary embolism patients anticoagulated for 1 year: results of a prospective, observational, cohort study. J Thromb Haemost. 2010; 8: 68–74

CrossRef | PubMed | Scopus (8)See all References, [3]x[3]Terzano, C., Conti, V., Di Stefano, F., Petroianni, A., Ceccarelli, D., Graziani, E. et al. Comorbidity, hospitalization, and mortality in COPD: results from a longitudinal study. Lung. 2010; 188: 321–329

CrossRef | PubMed | Scopus (69)See all References, [4]x[4]El-Menyar, A., Zubaid, M., Sulaiman, K., AlMahmeed, W., Singh, R., Alsheikh-Ali, A.A. et al. Atypical presentation of acute coronary syndrome: a significant independent predictor of in-hospital mortality. J Cardiol. 2011; 57: 165–171

Abstract | Full Text | Full Text PDF | PubMed | Scopus (12)See all References, [5]x[5]Almagro, P., Calbo, E., Ochoa de Echaguen, A., Barreiro, B., Quintana, S., Heredia, J.L. et al. Mortality after hospitalization for COPD. Chest. 2002; 121: 1441–1448

CrossRef | PubMed | Scopus (373)See all References, [6]x[6]Delerme, S. and Ray, P. Acute respiratory failure in the elderly: diagnosis and prognosis. Age Ageing. 2008; 37: 251–257

CrossRef | PubMed | Scopus (30)See all References, [7]x[7]Hurd, S. The impact of COPD on lung health worldwide: epidemiology and incidence. Chest. 2000; 117: 1S–4S

CrossRef | PubMedSee all References, [8]x[8]Seneff, M.G., Wagner, D.P., Wagner, R.P., Zimmerman, J.E., and Knaus, W.A. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA. 1995; 274: 1852–1857

CrossRef | PubMed | Scopus (435)See all References]. Initial ED management, level of care, and follow-up strategies are important factors for the outcome of acute dyspnea patients [[9]x[9]Eurlings, L.W., Sanders-van Wijk, S., van Kimmenade, R., Osinski, A., van Helmond, L., Vallinga, M. et al. Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score. J Am Coll Cardiol. 2012; 60: 1668–1677

PubMed | Scopus (16)See all References, [10]x[10]Rehman, S.U., Martinez-Rumayor, A., Mueller, T., and Januzzi, J.L. Jr. Independent and incremental prognostic value of multimarker testing in acute dyspnea: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Clin Chim Acta. 2008; 392: 41–45

CrossRef | PubMed | Scopus (35)See all References, [11]x[11]Maisel, A., Mueller, C., Nowak, R., Peacock, W.F., Landsberg, J.W., Ponikowski, P. et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2010; 55: 2062–2076

PubMed | Scopus (221)See all References, [12]x[12]Ray, P., Birolleau, S., Lefort, Y., Becquemin, M.H., Beigelman, C., Isnard, R. et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Crit Care. 2006; 10: R82

CrossRef | PubMed | Scopus (110)See all References]. However, the individual prognosis is difficult to accurately assess. The use of plasma biomarkers for improved determination of prognosis in acute dyspnea has largely focused on patients with congestive heart failure and, to a lesser degree, on patients with chronic obstructive pulmonary disease (COPD). Many biomarker studies include markers of inflammation or cardiac stress [[11]x[11]Maisel, A., Mueller, C., Nowak, R., Peacock, W.F., Landsberg, J.W., Ponikowski, P. et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2010; 55: 2062–2076

PubMed | Scopus (221)See all References, [13]x[13]Ray, P., Delerme, S., Jourdain, P., and Chenevier-Gobeaux, C. Differential diagnosis of acute dyspnea: the value of B natriuretic peptides in the emergency department. QJM. 2008; 101: 831–843

CrossRef | PubMed | Scopus (23)See all References, [14]x[14]Kociol, R.D., McNulty, S.E., Hernandez, A.F., Lee, K.L., Redfield, M.M., Tracy, R.P. et al. Markers of decongestion, dyspnea relief, and clinical outcomes among patients hospitalized with acute heart failure. Circ Heart Fail. 2013; 6: 240–245

CrossRef | PubMed | Scopus (32)See all References, [15]x[15]Latini, R., Masson, S., Anand, I.S., Missov, E., Carlson, M., Vago, T. et al. Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 2007; 116: 1242–1249

CrossRef | PubMed | Scopus (406)See all References, [16]x[16]Januzzi, J.L. Jr., Peacock, W.F., Maisel, A.S., Chae, C.U., Jesse, R.L., Baggish, A.L. et al. Measurement of the interleukin family member ST2 in patients with acute dyspnea: results from the PRIDE (Pro-Brain Natriuretic Peptide Investigation of Dyspnea in the Emergency Department) study. J Am Coll Cardiol. 2007; 50: 607–613

PubMed | Scopus (214)See all References, [17]x[17]Christ, M., Thuerlimann, A., Laule, K., Klima, T., Hochholzer, W., Perruchoud, A.P. et al. Long-term prognostic value of B-type natriuretic peptide in cardiac and non-cardiac causes of acute dyspnoea. Eur J Clin Investig. 2007; 37: 834–841

CrossRef | PubMed | Scopus (21)See all References], whereas the value of blood gas parameters [[18]x[18]Burri, E., Potocki, M., Drexler, B., Schuetz, P., Mebazaa, A., Ahlfeld, U. et al. Value of arterial blood gas analysis in patients with acute dyspnea: an observational study. Crit Care. 2011; 15: R145

CrossRef | PubMed | Scopus (12)See all References, [19]x[19]Lim, B.L. and Kelly, A.M. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department. Eur J Emerg Med. 2010; 17: 246–248

CrossRef | PubMed | Scopus (24)See all References] and the role of biomarkers in unselected patients with acute dyspnea on clinical outcome have been poorly studied.

The underlying causes of dyspnea can be difficult to assess in an early setting. Risk stratification of prognosis is central for clinical decisions on the level of care, treatment intensity, and urgency of reaching a definitive underlying diagnosis. Most plasma biomarkers in acute dyspnea used at the ED have diagnostic purposes (eg, troponin T and C-reactive protein), whereas medical history and scores of vital parameters are used to assess prognosis, level of care, and treatment intensity. In Sweden, the “Medical Emergency Triage and Treatment System Adult” (METTS-A) is a standard tool for risk assessment and triage of ED patients and was used during the time of study enrollment [20x[20]Widgren, B.R. and Jourak, M. Medical Emergency Triage and Treatment System (METTS): a new protocol in primary triage and secondary priority decision in emergency medicine. J Emerg Med. 2011; 40: 623–628

Abstract | Full Text | Full Text PDF | PubMed | Scopus (32)See all References][20].

In patients with COPD and acute dyspnea, a high pressure of carbon dioxide in arterial blood is a well-established predictor of poor prognosis and motivates a high level of care and treatment intensity [[8]x[8]Seneff, M.G., Wagner, D.P., Wagner, R.P., Zimmerman, J.E., and Knaus, W.A. Hospital and 1-year survival of patients admitted to intensive care units with acute exacerbation of chronic obstructive pulmonary disease. JAMA. 1995; 274: 1852–1857

CrossRef | PubMed | Scopus (435)See all References, [21]x[21]Slenter, R.H., Sprooten, R.T., Kotz, D., Wesseling, G., Wouters, E.F., and Rohde, G.G. Predictors of 1-year mortality at hospital admission for acute exacerbations of chronic obstructive pulmonary disease. Respiration. 2013; 85: 15–26

CrossRef | PubMed | Scopus (15)See all References]. However, in the general setting of patients with acute dyspnea at the ED, arterial blood gas analysis is usually not performed. Therefore, it cannot be evaluated or used as a routine biomarker for risk stratification. Increasing evidence points toward that arterial and venous blood gas results can be used interchangeably [[18]x[18]Burri, E., Potocki, M., Drexler, B., Schuetz, P., Mebazaa, A., Ahlfeld, U. et al. Value of arterial blood gas analysis in patients with acute dyspnea: an observational study. Crit Care. 2011; 15: R145

CrossRef | PubMed | Scopus (12)See all References, [19]x[19]Lim, B.L. and Kelly, A.M. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department. Eur J Emerg Med. 2010; 17: 246–248

CrossRef | PubMed | Scopus (24)See all References, [22]x[22]Malatesha, G., Singh, N.K., Bharija, A., Rehani, B., and Goel, A. Comparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessment. Emerg Med J. 2007; 24: 569–571

CrossRef | PubMed | Scopus (47)See all References, [23]x[23]Middleton, P., Kelly, A.M., Brown, J., and Robertson, M. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J. 2006; 23: 622–624

CrossRef | PubMed | Scopus (71)See all References, [24]x[24]Kelly, A.M., McAlpine, R., and Kyle, E. Agreement between bicarbonate measured on arterial and venous blood gases. Emerg Med Australas. 2004; 16: 407–409

CrossRef | PubMedSee all References]. In the ED, venous blood can routinely be drawn and analyzed at a low cost in the same point-of-care equipment as arterial blood with immediate generation of test results [25x[25]ABL800 FLEX analyzer Specifications 2011. (Available from:)http://www.radiometeramerica.com/~/media/Files/RadiometerComCloneset/RAME/Brochure s/Products/ABL800%20specs.pdf.

See all References][25]. To our knowledge, venous carbon dioxide and acid-base balance have never been evaluated as prognostic biomarkers in unselected ED patients admitted because of acute dyspnea.

The aim of the study was to investigate if easily accessible venous blood gas analysis of total carbon dioxide (TCO₂), base excess (BE), potential hydrogen (pH), and partial pressure of carbon dioxide (pCO₂) predicts 1-year risk of readmission or death in patients admitted to the ED due to acute dyspnea.

We studied patients presenting with dyspnea during 2011 at the ED of the University Hospital of Skåne in Malmö, Sweden. In 2011, the department had approximately 83000 visits. The hospital is the only emergency hospital in the municipality of approximately 300000 inhabitants. The study was approved by the regional board of ethics in Lund. All patients of 18 years of age or older presenting with acute dyspnea as the major complaint were eligible for the study. This yielded 5057 visits of patients with acute dyspnea of which 500 were randomly selected for review of patient records. In total, 283 fulfilled study criteria for inclusion in our analyses (Fig. 1Fig. 1). Data collection was performed in 2013 from the medical records of the University Hospital of Skåne. Variables recorded included sex (male/female), age (years), vital signs and symptoms according to METTS-A [20x[20]Widgren, B.R. and Jourak, M. Medical Emergency Triage and Treatment System (METTS): a new protocol in primary triage and secondary priority decision in emergency medicine. J Emerg Med. 2011; 40: 623–628

Abstract | Full Text | Full Text PDF | PubMed | Scopus (32)See all References][20], pulse oximetry (percentages), respiratory rate (RR, rate/min), pH (pH scale), BE (millimoles per liter) [[26]x[26]Morgan, T.J. Invited commentary: putting standard base excess to the test. J Crit Care. 2009; 24: 492–493

Abstract | Full Text | Full Text PDF | PubMed | Scopus (8)See all References, [27]x[27]Kofstad, J. Base excess: a historical review—has the calculation of base excess been more standardised the last 20 years?. Clin Chim Acta. 2001; 307: 193–195

CrossRef | PubMed | Scopus (23)See all References], pCO₂ (kilopascal), TCO₂ (millimoles per liter), medical history, and readmission or death within 1 year. In the METTS-A ED triage system, patients with respiratory complaints are categorized into dyspnea, chest pain, or hyperventilation and ranked into 4 priority levels according to vital signs. Priority 4 comprises patients with normal vital signs; and priority 1, patients with pathologic vital signs needing immediate medical attention [20x[20]Widgren, B.R. and Jourak, M. Medical Emergency Triage and Treatment System (METTS): a new protocol in primary triage and secondary priority decision in emergency medicine. J Emerg Med. 2011; 40: 623–628

Abstract | Full Text | Full Text PDF | PubMed | Scopus (32)See all References][20]. Additional detail on the methods for making the measurements is provided in an online data supplement. The combined end point was either a first hospital readmission regardless of cause or death during the 1-year follow-up period. Date of death was registered from a regional or national population register. Planned revisits were not included.

Venous blood gas parameters were obtained upon arrival to the ED. The blood gas samples were immediately analyzed on a Radiometer ABL800 Flex (Copenhagen, Denmark) [25x[25]ABL800 FLEX analyzer Specifications 2011. (Available from:)http://www.radiometeramerica.com/~/media/Files/RadiometerComCloneset/RAME/Brochure s/Products/ABL800%20specs.pdf.

See all References][25]. Among the parameters analyzed, TCO₂ represents the total dissolved carbon dioxide in the blood and is constituted to approximately 95% of bicarbonate (HCO₃−) and to 5% of carbon dioxide (CO₂), and carbonic acid (H₂CO₃) [28x[28]Centor, R.M. Serum total carbon dioxide. in: H.K. Walker, W.D. Hall, J.W. Hurst (Eds.) Clinical methods: the history, physical, and laboratory examinations. 3rd ed. ; 1990 ([Boston])

See all References][28]. We related the venous blood gas parameters with the risk of readmission or death using Cox proportional hazard models. The following 3 adjustments were used: In model 1, we adjusted for age and sex. In model 2, we included additional adjustment for METTS-A. In model 3, we added saturation, RR, and if statistically significant acid base parameters. Finally, we also adjusted model 3 for a history of COPD. Venous blood gas parameters were divided into quartiles. The 2 central quartiles were merged and defined as the reference group and compared to the top and bottom quartiles, respectively. Statistical analysis was performed in IBM SPSS (Malmö, Sweden) Statistics version 21. P < .05 was considered significant. Schoenfeld's test was performed to assure validity of the proportional hazards. In the subset of the population where both venous and arterial blood gas analyses were performed, we correlated blood gas parameters using Spearman correlation analysis.

A total of 283 patients with acute dyspnea at the ED were evaluated (Fig. 1Fig. 1). The mean age was 66.1 years (66.1 ± 18.5 years), and females (55.8%, 158/283) were more common than males. Most patients admitted for inpatient care was admitted to a general ward (39.9%, 113/283). A large proportion of the patients were directly discharged from the ED (36.7%, 104/283). The remaining were either admitted to an emergency ward (21.2%, 60/283) or an intensive care unit (2.1%, 6/283). During the 1-year follow-up, 74.2% (210/283) of the patients were readmitted or died, of which 67.1% (190/283) had a first readmission and 7.1% (20/283) died with no prior readmission. Detailed patient characteristics are shown in Table 1Table 1.

The bottom quartile of BE ranged from −26 to −1.0 mmol/L; and the top quartile, from 3.0 to 15 mmol/L. The bottom quartile of TCO₂ ranged from 4.0 to 24 mmol/L; and the top quartile, from 30 to 40 mmol/L. The bottom quartile of pH ranged from a value of 7.07 to 7.36; and the top quartile, from 7.44 to 7.59. The bottom quartile of pCO₂ ranged from 2.9 to 5.0 kPa, and the top quartile from 6.5 to 13.5 kPa.

In Cox proportional hazard models adjusted for age and sex, top quartile of BE (hazard ratio [HR], 1.56 [confidence interval {CI}, 1.14-2.15]; P = .006) and bottom quartile of BE (HR, 1.65 [CI, 1.17-2.32]; P = .004) were strongly associated with the end point. In the multivariate models adjusted for age, sex, METTS-A, saturation, and RR, both top quartile (HR, 1.48 [CI, 1.08-2.04]; P = .016) and bottom quartile (HR, 1.54 [CI 1.08-2.18]; P = .017) of BE were associated with increased risk of readmission or death (Table 2Table 2). However, when adjusting for TCO₂, there was no association of top quartile BE with the end point (HR, 1.13 [CI, 0.75-1.71]; P = .570), and the association of bottom quartile BE was no longer significant (HR, 1.63 [CI, 0.99-2.68]; P = .056).

When adjusting for age and sex, patients in the top quartile of TCO₂ had an increased risk of readmission or death (HR, 1.93 [CI, 1.40-2.67]; P = .000). This association was also seen for bottom quartile of TCO₂ (HR, 1.46 [CI, 1.02-2.07]; P = .037). After additional adjustment for age, sex, METTS-A, saturation, and RR, top quartile but not bottom quartile of TCO₂ remained significant (Table 2Table 2). Top quartile of TCO₂ was significant in the multivariate model including BE (HR, 1.59 [CI, 1.03-2.45]; P = .035). Top quartile of TCO₂ also remained significant after adjustment for a history of COPD (HR, 1.61 [CI, 1.15-2.26]; P = .005) with a relative risk increase greater than for prevalent COPD (HR, 1.50 [CI, 1.09-2.06]; P = .012). A Kaplan-Meier plot of TCO₂ in relation to the end point is shown in Fig. 2Fig. 2. In the patient group with top quartile levels of TCO₂, 33.8% (23/68) of the patients were discharged from the ED, 39.7% (27/68) were admitted to a general ward, 22.1% (15/68) were admitted to an emergency ward, and 4.4% (3/68) were admitted to an intensive care unit.

Older age (HR, 1. 01 [CI, 1.01-1.02]; P = .002) and higher priority according to METTS-A (HR, 1.31 [CI, 1.07-1.61]; P = .008) were other factors independently associated with the end point adjusted for BE and TCO₂. Neither pH nor pCO₂ was associated with increased risk of readmission or death (Table 2Table 2). In the subset of patients with both arterial and venous blood gas parameters obtained, there was a good correlation of blood gas parameters. In Spearman correlation analysis, venous pCO₂ and pH were strongly correlated with arterial pCO₂ (n = 43; r^s = 0.763; P = .000) and pH (n = 42; r^s = 0.852; P = .000), respectively.

For patients with acute dyspnea at the ED, TCO₂ ranging from 30 to 40 mmol/L was a predictor of 1-year readmission and mortality. High and low BE was also related to poor outcome. However, this prognostic information was mediated by TCO₂, as BE became nonsignificant in the combined statistical analysis. Total carbon dioxide remained related to the end point with an effect size stronger than for prior COPD.

Surprisingly, little is known about TCO₂ in patients with dyspnea at the ED, its prognostic value, and its impact on patient outcome. The mechanisms causing dyspnea are still incompletely understood [1x[1]Burki, N.K. and Lee, L.Y. Mechanisms of dyspnea. Chest. 2010; 138: 1196–1201

CrossRef | PubMed | Scopus (41)See all References][1], and the knowledge of which factors contribute to the blood concentration of TCO₂ is largely based on experimental animal studies and theoretical conclusions [[29]x[29]Winaver, J., Walker, K.A., and Kunau, R.T. Jr. Effect of acute hypercapnia on renal and proximal tubular total carbon dioxide reabsorption in the acetazolamide-treated rat. J Clin Invest. 1986; 77: 465–473

CrossRef | PubMedSee all References, [30]x[30]Cohen, N.D., Stanley, S.D., Arthur, R.M., and Wang, N. Factors influencing pre-race serum concentration of total carbon dioxide in Thoroughbred horses racing in California. Equine Vet J. 2006; 38: 543–548

CrossRef | PubMed | Scopus (9)See all References, [31]x[31]Astrup, P., Jorgensen, K., Andersen, O.S., and Engel, K. The acid-base metabolism. A new approach. Lancet. 1960; 1: 1035–1039

Abstract | PubMedSee all References, [32]x[32]Atkins, E.L. Assessment of acid-base disorders. A practical approach and review. Can Med Assoc J. 1969; 100: 992–998

PubMedSee all References, [33]x[33]O'Leary, T.D. and Langton, S.R. Calculated bicarbonate or total carbon dioxide?. Clin Chem. 1989; 35: 1697–1700

PubMedSee all References].

In the steady state at the dissociation equilibrium, TCO₂ is used as a surrogate marker of bicarbonate. Both BE and TCO₂ increase as a result of metabolic alkalosis. The underlying causes to these shifts are many. Possible explanations to metabolic alkalosis in the acutely dyspneic patient may be diuretic treatment, hypokalemia, or posthypercapnia [28x[28]Centor, R.M. Serum total carbon dioxide. in: H.K. Walker, W.D. Hall, J.W. Hurst (Eds.) Clinical methods: the history, physical, and laboratory examinations. 3rd ed. ; 1990 ([Boston])

See all References][28]. Total carbon dioxide additionally increases in compensation to respiratory acidosis [28x[28]Centor, R.M. Serum total carbon dioxide. in: H.K. Walker, W.D. Hall, J.W. Hurst (Eds.) Clinical methods: the history, physical, and laboratory examinations. 3rd ed. ; 1990 ([Boston])

See all References][28]. In this study, elevated BE did not associate with the end point when adjusting for TCO₂, although it may have correlated to the end point with a larger study size. This suggests that elevated TCO₂ in the dyspneic patient is not caused by metabolic alkalosis. It also suggests that the raised levels of TCO₂ are not only a consequence of increased bicarbonate levels.

Regardless of the causal mechanism, patients with acute dyspnea and poorer outcome in terms of readmissions and mortality tended to have both elevated TCO₂ and negative BE values. In the multivariate analysis, elevated TCO₂ remained significant, but base deficit became borderline significant. This finding can partly be explained by the presence of hypoventilated and metabolically compensated patients with COPD. As BE is reduced by respiratory acidosis, this can also explain the trend of base deficit with increased rates of readmission and mortality. In comparison to BE that only quantifies metabolic acid base disorders, TCO₂ is a marker of both respiratory and metabolic acid base balance disorders [[34]x[34]Berend, K., de Vries, A.P., and Gans, R.O. Physiological approach to assessment of acid-base disturbances. N Engl J Med. 2014; 371: 1434–1445

CrossRef | PubMed | Scopus (23)See all References, [35]x[35]Berend, K. Acid-base pathophysiology after 130 years: confusing, irrational and controversial. J Nephrol. 2013; 26: 254–265

CrossRef | PubMed | Scopus (8)See all References] that, in this study, correlated to poorer outcome. Therefore, we speculate that TCO₂ in patients with acute dyspnea is an indicator of uncompensated respiratory acidosis. Given this, TCO₂ may be more suitable than BE for assessing acute dyspnea in the chronically ill patients, as it involves both metabolic and respiratory components. Total carbon dioxide may also be more suitable than venous pCO₂ in predicting outcome in the critically ill with history of COPD. It is less transient in nature than the gas parameters and seems to be a better marker for long-term outcome than venous pCO₂ and venous pH that showed no correlation to the end point.

In common conditions causing acute dyspnea such as COPD, pneumonia, ischemic heart disease, congestive heart failure, and pulmonary embolism, deranged TCO₂ levels can represent a transient or permanent systemic impairment. As high TCO₂ predicted poor outcome during as much as 1 year after the acute episode of illness, it can stand for an unmasked underlying cardiopulmonary fragility, which, in the long term, associates with increased readmissions and mortality rates. In the heterogeneous patient group with dyspnea, the diagnostics is challenging, and a correct early management is important for prognosis. There are some biomarkers used for diagnostic and prognostic purposes in dyspnea patients. These have been included in scores often together with vital signs to predict poorer outcome [[9]x[9]Eurlings, L.W., Sanders-van Wijk, S., van Kimmenade, R., Osinski, A., van Helmond, L., Vallinga, M. et al. Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score. J Am Coll Cardiol. 2012; 60: 1668–1677

PubMed | Scopus (16)See all References, [10]x[10]Rehman, S.U., Martinez-Rumayor, A., Mueller, T., and Januzzi, J.L. Jr. Independent and incremental prognostic value of multimarker testing in acute dyspnea: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study. Clin Chim Acta. 2008; 392: 41–45

CrossRef | PubMed | Scopus (35)See all References, [11]x[11]Maisel, A., Mueller, C., Nowak, R., Peacock, W.F., Landsberg, J.W., Ponikowski, P. et al. Mid-region pro-hormone markers for diagnosis and prognosis in acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial. J Am Coll Cardiol. 2010; 55: 2062–2076

PubMed | Scopus (221)See all References], but at present, there is no separate blood biomarker for evaluation of prognosis and risk stratification of dyspnea patients. Traditionally, arterial blood gas analysis has predominantly been used to evaluate blood gas and acid-base disorders. In fact, in this and recent studies, there is a good correlation of venous to arterial blood gas parameters (with the exception of pO₂) [[19]x[19]Lim, B.L. and Kelly, A.M. A meta-analysis on the utility of peripheral venous blood gas analyses in exacerbations of chronic obstructive pulmonary disease in the emergency department. Eur J Emerg Med. 2010; 17: 246–248

CrossRef | PubMed | Scopus (24)See all References, [22]x[22]Malatesha, G., Singh, N.K., Bharija, A., Rehani, B., and Goel, A. Comparison of arterial and venous pH, bicarbonate, PCO2 and PO2 in initial emergency department assessment. Emerg Med J. 2007; 24: 569–571

CrossRef | PubMed | Scopus (47)See all References, [23]x[23]Middleton, P., Kelly, A.M., Brown, J., and Robertson, M. Agreement between arterial and central venous values for pH, bicarbonate, base excess, and lactate. Emerg Med J. 2006; 23: 622–624

CrossRef | PubMed | Scopus (71)See all References, [24]x[24]Kelly, A.M., McAlpine, R., and Kyle, E. Agreement between bicarbonate measured on arterial and venous blood gases. Emerg Med Australas. 2004; 16: 407–409

CrossRef | PubMedSee all References, [36]x[36]Rang, L.C., Murray, H.E., Wells, G.A., and Macgougan, C.K. Can peripheral venous blood gases replace arterial blood gases in emergency department patients?. CJEM. 2002; 4: 7–15

PubMedSee all References]. Easily accessible venous blood gas may thus be used in the ED to add clinically important information in a broad patient group with acute dyspnea without restricting the use of arterial blood gas when indicated.

The causes of dyspnea, death, and readmission were not systematically registered, and the underlying conditions leading to the events remain unclear. However, the intention of the study was to evaluate long-term prognostic factors for all-cause readmission or death in unselected patients with acute dyspnea. The knowledge of the actual underlying conditions seems to be less important for this purpose. The diseases causing dyspnea often coexist and share the same risk factors. A distinction between them is difficult to accurately assess in the clinical setting. Identification of the prognostic factors for specific diagnoses in patients with dyspnea was, therefore, not in the scope of this study. Apart from having dyspnea as the main complaint, we intentionally applied no selection criteria for the study population to maintain the heterogeneity and aiming at making results applicable on a random dyspneic patient seeking medical care. We do acknowledge that many patients were excluded due to missing blood gas parameters. A selection bias would despite this probably have lead to enrichment of even more severely ill patients. Most of the patients excluded were either relatively young patients not hospitalized or terminally ill patients where the ED physician judged that prognostic and diagnostic efforts were unnecessary.

Given the easy accessibility, fast response time, low costs, and negligible risks of a venous blood gas analysis, we find our results encouraging and potentially clinically applicable. Total carbon dioxide may help deciding the level of care upon admission and determining the follow-up strategies for out-of-hospital care in patients with acute dyspnea to prevent readmissions and death. It should, however, be emphasized that the sample size is moderate and replications of our results in similar patient cohorts are essential for clinical implementation.

In conclusion, a high level of TCO₂ in patients with acute dyspnea is a marker for worse outcome. This easily accessible blood gas parameter may prove useful in the ED for risk stratification of dyspnea patients.

Conception and design: NL, AR, KG, OM

Analysis and interpretation: NL, AR, PS, KG, OM

Drafting the manuscript for important intellectual content: NL, AR, PS, SE, TW, KG, OM