CO2 gap changes compared with cardiac output changes in response to intravenous volume expansion and/or vasopressor therapy in septic shock
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Abstract
Background. The difference in partial pressure of carbon dioxide (PCO2) between mixed or central venous blood and arterial blood, known as the ∆PCO2 or CO2 gap, has demonstrated a strong relationship with cardiac index during septic shock resuscitation. Early monitoring of the ∆PCO2 can help assess the cardiac output (CO) adequacy for tissue perfusion.
Objectives. To investigate the value of ∆PCO2 changes in early septic shock management compared with CO.
Methods. This observational prospective study included 76 patients diagnosed with septic shock admitted to Cairo University Hospital’s Critical Care Department between December 2020 and March 2022. Patients were categorised by initial resuscitation response, initial ∆PCO2 and 28-day mortality. The primary outcome was the relationship between the ∆PCO2 and CO changes before and after initial resuscitation, with secondary outcomes including ICU length of stay (LOS) and 28-day mortality.
Results. Peri-resuscitation ∆PCO2 changes predicted a ≥15% change in the cardiac index (CI) (area under the curve (AUC) 0.727; 95% CI 0.614 - 0.840) with 66.7% sensitivity and 62.8% specificity. The optimal ∆PCO2 change cut-off value was <−1.85, corresponding to a <−22% threshold for a 15% cardiac index increase. The PCO2 gap ratio (gap/gap ratio of T1- PCO2 gap to T0-PCO2 gap) also predicted a ≥15% change in cardiac index (AUC 745; 95% CI 0.634 - 0.855) with 63.6% sensitivity and 79.1% specificity. The optimal CO2 gap/gap ratio cut-off value was <0.71. A significant difference in 28-day mortality was noted based on the gap/gap ratio.
Conclusion. Peri-resuscitation ∆PCO2 and the gap/gap ratio are useful non-invasive bedside markers for predicting changes in CO and preload responsiveness.
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References
Cecconi M, De Backer D, Antonelli M, et al. Consensus on circulatory shock and hemodynamic monitoring. The task force of the European Society of Intensive Care Medicine. Intensive Care Med 2014;40(12):1795-1815. https://doi.org/10.1007/s00134-014-3525-z
Diaztagle Fernández JJ, Rodríguez Murcia JC, Sprockel Díaz JJ. Venous-to-arterial carbon dioxide difference in the resuscitation of patients with severe sepsis and septic shock: A systematic review. Med Intensiva 2017;41(7):401-410. https://doi.org/10.1016/j.medin.2017.03.008
Cuschieri J, Rivers EP, Donnino MW, et al. Central venous-arterial carbon dioxide difference as an indicator of cardiac index. Intensive Care Med 2005;31(6):818-822. https://doi.org/10.1007/ s00134-005-2602-8
Vincent, JL, De Backer D. Oxygen transport—the oxygen delivery controversy. Intensive Care Med 2004;30:1990-1996. https://doi.org/10.1007/s00134-004-2384-4
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. https://doi.org/10.1097/EJA.0000000000000064
Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315(8):801-810. https://doi.org/10.1001/ jama.2016.0287
Vincent JL, Moreno R, Takala J, et al. Working group on sepsis-related problems of the European Society of Intensive Care Medicine. The SOFA (sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med 1996;22(7):707-710.
Ospina-Tascon GA, Bautista-Rincon DF, Umana 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. https://doi.org/10.1186/cc13160
Bakker J, Vincent JL, Gris P, et al. Veno-arterial carbon dioxide gradient in human septic shock. Chest 1992;101:509-515.
Peake SL, Delaney A, Bailey M, et al. ARISE Investigators; ANZICS Clinical Trials Group, Goal- directed resuscitation for patients with early septic shock. N Engl J Med 2014 Oct 16;371(16):1496- 506. https://doi.org/10.1056/NEJMoa1404380
Levy MM, Evans LE, Rhodes A. The surviving sepsis campaign bundle. Crit Care Med 2018;46(6):997-1000. https://doi.org/10.1097/CCM.0000000000003119
Mallat J, Lemyze M, Tronchon L, et al. Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock. World J Crit Care Med 2016;5(1):47-56. https://doi. org/10.5492/wjccm. v5. i1.47
Vallée F, Vallet B, Mathe O, et al. Central venous-to-arterial carbon dioxide difference: an additional target for goal-directed therapy in septic shock? Intensive Care Med 2008;34(12):2218- 2225. https://doi.org/10.1007/s00134-008-1199-0
Van Beest PA, Lont MC, Holman ND, et al. Central venous-arterial PCO2 difference as a tool in the resuscitation of septic patients. Intensive Care Med 2013;39(6):1034-1039. https://doi. org/10.1007/s00134-013-2888-x
Nassar B, Badr M, Van Grunderbeeck N, et al. Central venous-to-arterial PCO2 difference as a marker to identify fluid responsiveness in septic shock. Sci Rep 2021;11(1):17256. https://doi. org/10.1038/s41598-021-96806-6
Pierrakos C, De Bels D, Nguyen T, et al. Changes in central venous-to-arterial carbon dioxide tension induced by fluid bolus in critically ill patients. PLoS One 2021;16(9):e0257314. https:// doi.org/10.1371/journal.pone.0257314
Mecher CE, Rackow EC, Astiz ME, et al. Venous hypercarbia is associated with severe sepsis and systemic hypoperfusion. Crit Care Med 1990;18(6):585-589. https://doi.org/10.1097/00003246- 199006000-00001
Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for the management of sepsis and septic shock 2016. Intensive Care Med 2017;43:304-77.
Jalil BA, Cavallazzi R. Predicting fluid responsiveness: A review of the literature and a guide for the clinician. Am J Emerg Med 2018 Nov;36(11):2093-2102. https://doi.org/10.1016/j.ajem.2018.08.037 20. Wiedemann HP, Wheeler AP, Bernard GR, et al. Comparison of two fluid-management strategies
in acute lung injury. N Engl J Med 2006;354:2564-2575.
Boyd JH, Forbes J, Nakada TA, et al., Fluid resuscitation in septic shock: A positive fluid balance
and elevated central venous pressure are associated with increased mortality. Crit Care Med
;39:259-265.
Ronflé R, Lefebvre L, Duclos G, et al. Venous-to-arterial carbon dioxide partial pressure difference:
Predictor of septic patient prognosis depending on central venous oxygen saturation. Shock 2020;53(6):710-716. https://doi.org/10.1097/SHK.0000000000001442