Prognostic and Therapeutic Value of Venous to Arterial Carbon Dioxide Difference during Early Resuscitation in Critically Ill Nosocomial Septic Shock Patients
Mohan Kumar Narava, Justin A Gopaldas, KV Venkatesha Gupta
Central venous to arterial carbon dioxide difference, Fluid resuscitation, Nosocomial sepsis, Sepsis, Septic shock, Venoarterial difference in the partial pressure of carbon dioxide gap, 28-day mortality
Citation Information :
Narava MK, Gopaldas JA, Gupta KV. Prognostic and Therapeutic Value of Venous to Arterial Carbon Dioxide Difference during Early Resuscitation in Critically Ill Nosocomial Septic Shock Patients. 2023; 2 (2):46-53.
Introduction: Septic shock is a medical emergency. Various clinical biomarkers have been used to either prognosticate or use them for goal-directed management of the same. The venoarterial difference in the partial pressure of carbon dioxide (Pv-aCO2 gap) has been used as an alternate marker for assessing tissue hypoperfusion and to predicting mortality.
Aim: To determine the therapeutic and prognostic value of central venous to arterial carbon dioxide difference during early resuscitation of critically ill nosocomial septic shock patients.
Objectives: The primary objective was to predict 28-day mortality using the Pv-aCO2 gap. The secondary objectives were to compare the accuracy of lactate clearance, sequential organ failure assessment (SOFA) score against Pv-aCO2 gap as a predictor of 28-day mortality and to determine the association of fluid resuscitation and its effects on the Pv-aCO2 gap.
Materials and methods: A prospective observational cohort study was performed in a tertiary care intensive care unit (ICU). A total of 50 nosocomial septic shock patients were recruited. They are from either ward admissions or those who stayed in ICU beyond 48 hours. A Pv-aCO2 gap was measured serially over 0, 3, and 6 hours. Lactate clearance at 6 hours was measured. SOFA score on days 1 and 2 of admission, fluid resuscitation in the first 6 hours, and cumulative fluid balance over 24 hours and 7 days were calculated. The patients were divided into survivors and nonsurvivors according to the outcome at 28 days. Pv-aCO2 gap was assessed in both groups. The receiver operating characteristic (ROC) curve was plotted to analyze the prognostic value of these variables in predicting 28-day mortality. Data analysis was carried out using the Statistical Package for the Social Sciences (SPSS) version 18.5 package.
Results: The median values of the Pv-aCO2 gap had progressively increased in nonsurvivors (7.17, 7.70, and 8.06 mm Hg) over 0, 3, and 6 hours, respectively, whereas it progressively narrowed (6.84, 6.45, and 6.03 mm Hg) in survivors during the first 6 hours of the resuscitation period. Persistently high Pv-aCO2 gap at the end of 6 hours of resuscitation was observed in nonsurvivors, which were statistically significant (85.3 vs 43.8%, p = 0.004). Survivors and nonsurvivors received a mean crystalloid volume of 1430.8 ± 431.6 mL, irrespective of their Pv-aCO2 gap of < or >6 mm Hg. The discriminatory capacity at predicting 28-day mortality for SOFA score on days 1 and 2, lactate clearance at 6 hours, and Pv-aCO2 gap at 0, 3, and 6 hours were compared. ROC curve analysis showed that SOFA scores on days 1 and 2, lactate clearance at 6 hours, and Pv-aCO2 gap at 3 and 6 hours had predictive value to prognosticate 28-day mortality. The area under the ROC curve (AUROC) for SOFA score on days 1 and 2 was 0.907 [95% confidence interval (CI) was 0.791–0.971, p < 0.001] and 0.943 (95% CI was 0.839–0.989, p < 0.001) respectively. The AUROC for lactate clearance at 6 hours was 0.938 (95% CI was 0.743–0.947, p < 0.001). AUROC for Pv-aCO2 gap values at 3 and 6 hours were 0.814 (95% CI was 0.679–0.910, p < 0.001) and 0.865 (95% CI was 0.738–0.945, p < 0.001), respectively.
Conclusion: Persistent high Pv-aCO2 gap can be used as a prognostic marker for predicting 28-day mortality in nosocomial septic shock patients. Pv-aCO2 gap at 6 hours has almost the same discriminatory capacity as SOFA score on days 1 and 2, and lactate clearance at predicting 28-day mortality. More studies are required to ascertain the value of Pv-aCO2 gap values in estimating the adequacy of fluid resuscitation in nosocomial septic shock patients.
Chatterjee S, Bhattacharya M, Todi SK. Epidemiology of adult-population sepsis in India: a single center 5 year experience. Indian J Crit Care Med 2017;21(9):573–577. DOI: 10.4103/ijccm.IJCCM_240_17
Markwart R, Saito H, Harder T, et al. Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Intensive Care Med 2020;46(8):1536–1551. DOI: 10.1007/s00134-020-06106-2
Paoli CJ, Reynolds MA, Sinha M, et al. Epidemiology and costs of sepsis in the United States-an analysis based on timing of diagnosis and severity level. Crit Care Med 2018;46(12):1889–1897. DOI: 10.1097/CCM.0000000000003342
Tabah A, Buetti N, Staiquly Q, et al. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study. Intensive Care Med 2023;49(2):178–190. DOI: 10.1007/s00134-022-06944-2
Nassar AP Jr, Pires-Neto RC, de Carvalho WB, et al. Characteristics and outcomes of patients with community-acquired and hospital-acquired sepsis: a multicenter cohort study in Brazil. Rev Bras Ter Intensiva 2019;31(2):167–177. DOI: 10.5935/0103-507X.20190013
Rhodes A, Phillips G, Beale R, et al. The surviving sepsis campaign bundles and outcome: results from the international multicentre prevalence study on sepsis (the IMPreSS study). Intensive Care Med 2015;41(9):1620–1628. DOI: 10.1007/s00134-015-3906-y
Liu B, Ding X, Yang J. Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock. Curr Med Res Opin 2016;32(11):1773–1782. DOI: 10.1080/03007995.2016.1206872
Uffen JW, Oosterheert JJ, Schweitzer VA, et al. Interventions for rapid recognition and treatment of sepsis in the emergency department: a narrative review. Clin Microbiol Infect 2021;27(2):192–203. DOI: 10.1016/j.cmi.2020.02.022
Pellegrini JAS, Cordioli RL, Grumann ACB, et al. Point-of-care ultrasonography in Brazilian intensive care units: a national survey. Ann Intensive Care 2018;8(1):50. DOI: 10.1186/s13613-018-0397-3
Hasanin A, Mukhtar A, Nassar H. Perfusion indices revisited. J Intensive Care 2017;5:24. DOI: 10.1186/s40560-017-0220-5
Vallet B, Pinsky MR, Cecconi M. Resuscitation of patients with septic shock: please “mind the gap”! Intensive Care Med 2013;39(9):1653–1655. DOI: 10.1007/s00134-013-2998-5
Mallat J, Pepy F, Lemyze M, et al. Central venous-to-arterial carbon dioxide partial pressure difference in early resuscitation from septic shock: a prospective observational study. Eur J Anaesthesiol 2014;31(7):371–380. DOI: 10.1097/EJA.0000000000000064
Lyu X, Xu Q, Cai G, et al. Efficacies of fluid resuscitation as guided by lactate clearance rate and central venous oxygen saturation in patients with septic shock. Zhonghua Yi Xue Za Zhi 2015;95(7):496–500. PMID: 25916923.
Khwannimit B, Bhurayanontachai R, Vattanavanit V. Comparison of the performance of SOFA, qSOFA and SIRS for predicting mortality and organ failure among sepsis patients admitted to the intensive care unit in a middle-income country. J Crit Care 2018;44:156–160. DOI: 10.1016/j.jcrc.2017.10.023
Ahmed W, Laimoud M. The value of combining carbon dioxide gap and oxygen-derived variables with lactate clearance in predicting mortality after resuscitation of septic shock patients. Crit Care Res Pract 2021;2021:6918940. DOI: 10.1155/2021/6918940
Bitar ZI, Maadarani OS, El-Shably AM, et al. The forgotten hemodynamic (PCO2 Gap) in severe sepsis. Crit Care Res Pract 2020;2020:9281623. DOI: 10.1155/2020/9281623
Ospina-Tascón GA, Bautista-Rincón DF, Umaña M, et al. Persistently high venous-to-arterial carbon dioxide differences during early resuscitation are associated with poor outcomes in septic shock. Crit Care 2013;17(6):R294. DOI: 10.1186/cc13160
Helmy TA, El-Reweny EM, Ghazy FG. Prognostic value of venous to arterial carbon dioxide difference during early resuscitation in critically ill patients with septic shock. Indian J Crit Care Med 2017;21(9):589–593. DOI: 10.4103/ijccm.IJCCM_64_16
Shaban M, Salahuddin N, Kolko MR, et al. The predictive ability of PV-ACO2 gap and PV-ACO2/CA-VO2 ratio in shock: a prospective, cohort study. Shock 2017;47(4):395–401. DOI: 10.1097/SHK.0000000000000765
Marty P, Roquilly A, Vallée F, et al. Lactate clearance for death prediction in severe sepsis or septic shock patients during the first 24 hours in intensive care unit: an observational study. Ann Intensive Care 2013;3(1):3. DOI: 10.1186/2110-5820-3-3
Al Duhailib Z, Hegazy AF, Lalli R, et al. The use of central venous to arterial carbon dioxide tension gap for outcome prediction in critically ill patients: a systematic review and meta-analysis. Crit Care Med 2020;48(12):1855–1861. DOI: 10.1097/CCM.0000000000004578
Marik PE, Byrne L, van Haren F. Fluid resuscitation in sepsis: the great 30 mL per kg hoax. J Thorac Dis 2020;12(Suppl 1):S37–S47. DOI: 10.21037/jtd.2019.12.84
Lat I, Coopersmith CM, De Backer D, et al. The surviving sepsis campaign: fluid resuscitation and vasopressor therapy research priorities in adult patients. Crit Care Med 2021;49(4):623–635. DOI: 10.1097/CCM.0000000000004864
Meng L, Tran NP, Alexander BS, et al. The impact of phenylephrine, ephedrine, and increased preload on third-generation Vigileo-FloTrac and esophageal doppler cardiac output measurements. Anesth Analg 2011;113(4):751–757. DOI: 10.1213/ANE.0b013e31822649fb