Capnography as a tool for triaging and diagnosis of diabetic ketoacidosis in the emergency department: A prospective observational study

Abstract

OBJECTIVES: The cornerstone of management of acidosis in a patient with diabetic ketoacidosis (DKA) has traditionally been carried out by blood gas analysis, which is expensive and associated with significant risk. It is against this background that the correlation between end tidal carbon dioxide (EtCO₂ ), blood pH, and EtCO₂ bicarbonate levels was analyzed. The predictive value of EtCO₂ was also analyzed in the diagnosis of DKA. Finally, we aimed to determine the value of EtCO₂ as a screening test for the exclusion of DKA.

MATERIALS AND METHODS: This was a prospective cohort study carried out in the emergency department of a tertiary care teaching hospital from September 2020 to September 2021. Patients with suspected DKA underwent simultaneous blood gas collection and EtCO₂ analysis.

RESULTS: A total of 123 patients with blood sugar levels >250 mg/dl and moderate to large (≥2+) urine ketones were studied. A cut off value of EtCO₂ ≤24 was determined to rule in DKA with a sensitivity of 93.02% and specificity of 91.9%. EtCO₂ >26 could effectively rule out the diagnosis of DKA with sensitivity of 98.8% and specificity of 75.7%. A significant linear correlation between pH and EtCO₂ (P < 0.0001, r = 0.82) and HCO3 and EtCO₂ (r = 0.896, P < 0.0001) was found.

CONCLUSIONS: EtCO₂ values ≤24 can accurately identify patients with DKA in the presence of elevated blood sugar and urinary ketones and must be considered a valuable addition to the diagnostic criteria. EtCO₂ values >26 can be an effective triaging tool for ruling our DKA. A significant linear correlation between pH and EtCO₂ and pH and HCO3 was observed. EtCO₂ can be considered a surrogate marker for the degree of response to the treatment in DKA.

Introduction

Diabetic ketoacidosis (DKA) is one of the most significant and life threatening complications of diabetes mellitus. The impact of diabetes on mankind has seen a steady increase over the past 25 years, with India being a major contributor. Known as the world’s capital of diabetes, India is close to touching the alarming mark of 69.9 million by 2025 and 80 million by 2030.[1] There is a global variation in mortality associated with DKA and diabetes. In developed countries, the overall mortality rate among children and adolescents is between 0.15% and 0.35% while in certain developing countries, rates range from 3.4% to 13.4%.[2] The average cost per hospitalization in 2003 for DKA was $10, 876 ± 11,024 with around 20%–30% of the charges being attributed to laboratory investigations.[2] With such a high burden of disease, it becomes prudent for countries to develop easier and more inexpensive ways to diagnose the disease.

In a hospital’s emergency department (ED), DKA is traditionally diagnosed based on the laboratory values of blood sugar, urinary or blood ketones, and arterial or venous blood gases (ABG or VBG). While the first two can be determined by rapid, painless, and inexpensive laboratory tests, ABGs are painful, complex, expensive, and associated with significant risk to the patient.[3] For obvious reasons, closely monitoring the degree of acidosis and response to therapy by performing serial blood gases is simply not sustainable. Blood samples are also prone to preanalytical errors due to improper collection, handling, or transportation. About 70% of all the errors occur in the pre analytical phase, i.e., while collecting the blood sample and transporting it to the laboratory.[4] In this situation, capnography is an alternative, noninvasive, and inexpensive method of assessing the metabolic acidosis of DKA by studying the ventilatory response to the latter.[5,6] The reason for measuring end tidal carbon dioxide (EtCO₂ ) in metabolic acidosis is that as the pH decreases, a compensatory increase in respiratory rate leads to alkalosis and a fall in EtCO₂ . The greater the severity of acidosis, the lower the HCO3; which in turn results in lower EtCO₂ . When a patient is found to have a high blood glucose value, they are often triaged to the high acuity area for further management. This process often leads to overcrowding in the critical area and is distressing to the medical team.

For this subset of patients, we had aimed to investigate the utility of EtCO₂ as a diagnostic criterion and a screening tool for DKA.

The availability of a rapid, noninvasive, sensitive screening tool that has the ability to rule out DKA in those with severe hyperglycemia will avoid unnecessary and expensive treatments.

A highly specific test may expedite the diagnosis and, by extension, the monitoring of the degree of acidosis in DKA.

Material and Methods

Diabetic ketoacidosis (DKA) is one of the most significant and life threatening complications of diabetes mellitus. The impact of diabetes on mankind has seen a steady increase over the past 25 years, with India being a major contributor. Known as the world’s capital of diabetes, India is close to touching the alarming mark of 69.9 million by 2025 and 80 million by 2030.[1] There is a global variation in mortality associated with DKA and diabetes. In developed countries, the overall mortality rate among children and adolescents is between 0.15% and 0.35% while in certain developing countries, rates range from 3.4% to 13.4%.[2] The average cost per hospitalization in 2003 for DKA was $10, 876 ± 11,024 with around 20%–30% of the charges being attributed to laboratory investigations.[2] With such a high burden of disease, it becomes prudent for countries to develop easier and more inexpensive ways to diagnose the disease.

In a hospital’s emergency department (ED), DKA is traditionally diagnosed based on the laboratory values of blood sugar, urinary or blood ketones, and arterial or venous blood gases (ABG or VBG). While the first two can be determined by rapid, painless, and inexpensive laboratory tests, ABGs are painful, complex, expensive, and associated with significant risk to the patient.[3] For obvious reasons, closely monitoring the degree of acidosis and response to therapy by performing serial blood gases is simply not sustainable. Blood samples are also prone to preanalytical errors due to improper collection, handling, or transportation. About 70% of all the errors occur in the pre analytical phase, i.e., while collecting the blood sample and transporting it to the laboratory.[4] In this situation, capnography is an alternative, noninvasive, and inexpensive method of assessing the metabolic acidosis of DKA by studying the ventilatory response to the latter.[5,6] The reason for measuring end tidal carbon dioxide (EtCO₂ ) in metabolic acidosis is that as the pH decreases, a compensatory increase in respiratory rate leads to alkalosis and a fall in EtCO₂ . The greater the severity of acidosis, the lower the HCO3; which in turn results in lower EtCO₂ . When a patient is found to have a high blood glucose value, they are often triaged to the high acuity area for further management. This process often leads to overcrowding in the critical area and is distressing to the medical team.

For this subset of patients, we had aimed to investigate the utility of EtCO₂ as a diagnostic criterion and a screening tool for DKA.

The availability of a rapid, noninvasive, sensitive screening tool that has the ability to rule out DKA in those with severe hyperglycemia will avoid unnecessary and expensive treatments.

A highly specific test may expedite the diagnosis and, by extension, the monitoring of the degree of acidosis in DKA.

Results

A total of 138 patients with BSLs >250 mg/dl and moderate to large (2+) ketones on urine dipstick testing were considered for enrolment. 15 patients were excluded from analysis due to the lack of consent or unavailable EtCO₂ values. The final sample consisted of 123 patients. A flow diagram of our study is presented in Figure 1.

Figure 1. Flow diagram of study design

Overall 86 patients (69.9%) were diagnosed with DKA and the remaining 37 were diagnosed as having diabetic ketosis without acidosis.

Out of the total 123 patients, 104 were previously diagnosed diabetics. Males constituted 66.7% (n = 81) of the study population. The mean age of the participants was 42.30 ± 17.03 years. Table 1 shows a statistically significant difference between the two groups (DKA and non DKA) regarding age, EtCO₂ , pH, bicarbonate, PaCO2, and urinary ketones. A spearman’s rank correlation coefficient test revealed a significant linear correlation between pH and EtCO₂ (P < 0.0001, r = 0.82, 95% CI [0.75–0.87]) [Figure 2] and HCO3 and EtCO₂ (r = 0.896, P < 0.0001, 95% CI[0.85–0.93]) [Figure 3].

Table 1. Demographic and biochemical data of patients with diabetic ketoacidosis and nondiabetic ketoacidosis

Figure 2. Scatter diagram, illustrating a correlation between HCO3‑ and EtCO2 levels in DKA (solid square) and non‑DKA (circle). DKA: Diabetic ketoacidosis, EtCO2 : End‑tidal carbon dioxide

Figure 3. Scatter diagram showing correlation between pH and EtCO2 levels in DKA (solid square), non‑DKA (circle). DKA: Diabetic ketoacidosis, EtCO2 : End‑tidal carbon dioxide

End tidal carbon dioxide as a diagnostic test for diabetic ketoacidosis

EtCO₂ was analyzed as diagnostic criteria for DKA in patients with high blood sugar and urinary ketones. The plotted receiver operating characteristic curve seen in Figure 4 shows area under the curve of 0.967.

Figure 4. ROC curve of EtCO2 for diagnosis of DKA. ROC: Receiver operating characteristics, EtCO2 :End‑tidal carbon dioxide, DKA: Diabetic ketoacidosis

This curve was also used to determine a cut off value of 24 with sensitivity of 93.02, specificity of 91.89, and Youden’s index of 0.8492 showing that a EtCO₂ ≤24 can be used to rule in DKA in patients with blood sugars >250 mg/dl and positive urinary ketones while EtCO₂ >24 can be used to rule out DKA.

A value of EtCO₂ ≤12 was 100% specific for the diagnosis of DKA and an EtCO₂ >28 was a 100% sensitive in ruling out DKA.

The positive predictive value of EtCO2 ≤24 as a diagnostic test for DKA was 0.96, 95% CI (89.9–98.8) and the negative predictive value was 0.85, 95% CI(72.3–92.5) with an accuracy of 92.68%, 95% CI (86.6–96.6).

The posterior probability (odds) for a positive test (i.e., EtCO2 ≤24) diagnosing DKA was calculated as 96%(25.6), 95% CI(90–99) and the posterior probability(odds) for a negative test was 16%(0.2), 95% CI (7–28).

In short, the results of this study show that approximately 1 in 1 patient with a positive test (EtCO₂ ≤24) are diagnosed as DKA and 1 in 1.2 patients with a negative test (EtCO₂ >24) are diagnosed as non DKA. Table 2 shows sensitivities and specificities of various values of EtCO₂ for diagnosis of DKA.

Table 2. Sensitivities and specificities of various values of end‑tidal carbon dioxide for diagnosis of diabetic ketoacidosis

End tidal carbon dioxide as a screening test for ruling out diabetic ketoacidosis (>26)

A value EtCO₂ >26 was analyzed as a screening test to rule out the diagnosis of DKA. The sensitivity and specificity of the test were found to be 98.84%, 95% CI (93.6–99.9) and 75.68%, 95% CI (58.8–88.2), respectively [Table 3].

Table 3. Data table of EtCO2 >26 as a screening test to rule out DKA

The percentage of misclassification with this test is only 8.13%.

The positive predictive value of EtCO₂ >26 as a test for ruling out DKA was 0.90, 95% CI (84.3–94.3) and the negative predictive value was 0.96, 95% CI (79.8–99.5) with an accuracy of 91.87%, 95% CI (85.6–96).

The posterior probability (odds) for a positive test (i.e., EtCO₂ >26) ruling out DKA was calculated as 90%(9.4), 95% CI(2.30–7.18) and the posterior probability (odds) for a negative test was 4%, 95% CI (0–0.11).

Hence, EtCO₂ >26 can be used as a screening test for ruling out DKA.

Discussion

DKA is one of the life threatening complications of diabetes mellitus. It occurs both in type I and type II diabetes. The acidosis of DKA was traditionally diagnosed and monitored through blood gas analysis, which is both time consuming and expensive and comes with a risk of serious complications.

The need for repeated arterial punctures has reduced following the acceptance of venous blood gas monitoring. We suggest going further down this road and opting for less invasive procedures like EtCO₂ monitoring instead of VBG analysis. While numerous studies have explored the association of metabolic acidosis with capnography, most have targeted the pediatric population or had small sample sizes.[8 11] The present study, in contrast, recruited all its participants from the adult population and had a comparatively large sample size. The study assessed three possible roles of EtCO₂ : (a) its role as a triage tool for excluding DKA; (b) as an additional diagnostic criterion for DKA; and (c) its role in monitoring the treatment (degree of acidosis).

To the best of our knowledge, this is the first study carried out in an ED in India to analyze the relationship between EtCO₂ and DKA.

When the EtCO₂ values were measured and compared between the two groups, the average EtCO₂ was significantly lower among those with acidosis than among those without (14.51 ± 6.45 vs. 29.89 ± 5.69, P < 0.0001). As expected, significant differences in values for bicarbonate and pH were noted between the two groups. There was a significant linear correlation between EtCO₂ and bicarbonate (r = 0.896, P < 0.0001) and EtCO₂ and pH (r = 0.825, P < 0.0001). These results are in accordance with similar studies conducted in pediatric and adult patients.[5,12]

This preliminary evidence shows that EtCO₂ monitoring during the course of treatment is a modality for monitoring the degree of acidosis in patients with DKA. Noninvasive EtCO₂ monitoring would act as a surrogate marker for variations in pH or bicarbonate. This would improve patient comfort by removing the need for repeated blood gas analysis and also decrease the potential complications of repeated venipuncture. The inclusion of EtCO₂ as a criterion for monitoring patients’ response to treatment might have the additional benefit of reducing health care costs.

The close relationship of EtCO₂ with pH and bicarbonate further prompted the analysis of EtCO₂ as a diagnostic criterion for DKA. The cut off determined for the diagnosis of DKA was EtCO₂ ≤24, with a sensitivity and specificity of 93.02% and 91.89%, respectively. The positive and negative predictive values were 96.4% and 85.0% with an accuracy of 92.7%. The compelling predictive value of capnography in detecting diabetic ketoacidosis (DKA), as observed not only in this study but also in prior studies[5-10], strongly suggests the inclusion of end-tidal carbon dioxide (EtCO2) measurements in the diagnostic criteria for DKA.

Similar studies have shown a significant difference between DKA and non DKA groups with regard to EtCO₂ values. They have concluded that capnography values of more than 24.5 mmHg could rule out the diagnosis of DKA with a sensitivity and specificity of 0.90.[5,6]

This study also assessed the utility of EtCO₂ as a screening tool for ruling out DKA in the ED. EtCO₂ >26 was found to be 98.84% sensitive in ruling out DKA. This highlights the potential of EtCO₂ as an additional tool in the armament of an ED physician to discriminate between those who would require floor admission and those that would require higher care. A similar study carried out on 58 pediatric patients (1–18 years old) with type 1 diabetes stated that EtCO₂ >30 could rule out DKA with 100% sensitivity.[5]

The authors of this study are of the opinion that EtCO₂ monitoring in a patient with DKA should become routine practice as there are several potential benefits with almost no chances of harm. There is enough precursory data to also indicate that EtCO₂ levels should be analyzed for inclusion in the diagnostic algorithm for DKA. Monitoring EtCO₂ during the course of the treatment seems to accurately reflect the changes in acidosis (pH and bicarbonate). The authors of this study firmly believe that monitoring EtCO₂ would only improve the quality of treatment and patient comfort.

Unfortunately, there is a large amount of heterogeneity in the available literature using capnography in the assessment of DKA. Further studies looking at confounding factors in EtCO₂ would help determine more definitive recommendations in the future.

Limitations

The main limitation of this study is that it is a single center study with a relatively smaller sample size. A more precise estimate of these cut off points could be obtained with a larger sample size. Furthermore, the patient group consisted of a high male to female ratio.

Furthermore, although mainstream capnometry was used for this study, the possibility of variation in results with sidestream capnometry also exists and must be evaluated. Finally, potential confounders of EtCO₂ were also not assessed.

Conclusion

EtCO₂ values can accurately identify patients with DKA in the presence of elevated blood sugar and urinary ketones. Capnography values ≤24 must be considered a valuable addition to the diagnostic criteria of DKA. EtCO₂ should be used as a tool to measure the degree of response to treatment (changes in acidosis) in a patient with DKA as a surrogate to blood gas analysis. EtCO₂ >26 can be used as a screening test for ruling out DKA. EtCO₂ is highly sensitive in ruling out DKA and should be considered a formidable additional tool to help in triaging patients. Supplemental studies are needed to find more data in support of these recommendations.

How to cite this article: Bhattaram S, Shinde VS, Khumujam PP, Anilkumar AP, Reddy DK. Capnography as a tool for triaging and diagnosis of diabetic ketoacidosis in the emergency department: A prospective observational study. Turk J Emerg Med 2023;23:169-75.

Ethical approval has been obtained from the university ethics committee:
• Name Institutional Ethics Committee of Dr. D. Y. Patil Medical College and Hospital
• City Pimpri, Pune
• Country – India
• Approval No IESC/PGS/2019/177
• Approval Date – November 8, 2019.

Informed consent was taken. Informed consent for publication has been granted by the patient and/or next of kin in both the cases.

Authorship provides credit for a researcher’s contributions to a study and carries accountability. Authors are expected to fulfill the criteria below:
• SB ‑ Writing ‑ original draft (lead), formal analysis (lead), final draft (lead)
• VS ‑ Conceptualization (lead), supervision (lead), methodology (lead)
• PK ‑ Writing ‑ original draft (supporting), Writing ‑ original draft preparation (supporting)
• DR ‑ Data curation (supporting)
• AP ‑ Data curation (lead).

None Declared.

None.

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