• Zainab Al Duhailib, Ahmed F Hegazy, Raj Lalli, Kyle Fiorini, Fran Priestap, Alla Iansavichene, and Marat Slessarev.
• Division of Critical Care, Department of Medicine, Western University, London Health Sciences Centre, London, ON, Canada.
• Crit. Care Med. 2020 Dec 1; 48 (12): 1855-1861.

ObjectivesIn this systematic review and meta-analysis, we assessed whether a high CO2 gap predicts mortality in adult critically ill patients with circulatory shock.Data SourcesA systematic search of MEDLINE and EMBASE electronic databases from inception to October 2019.Study SelectionStudies from adult (age ≥ 18 yr) ICU patients with shock reporting CO2 gap and outcomes of interest. Case reports and conference abstracts were excluded.Data ExtractionData extraction and study quality assessment were performed independently in duplicate.Data SynthesisWe used the Newcastle-Ottawa Scale to assess methodological study quality. Effect sizes were pooled using a random-effects model. The primary outcome was mortality (28 d and hospital). Secondary outcomes were ICU length of stay, hospital length of stay, duration of mechanical ventilation, use of renal replacement therapy, use of vasopressors and inotropes, and association with cardiac index, lactate, and central venous oxygen saturation.ConclusionsWe included 21 studies (n = 2,155 patients) from medical (n = 925), cardiovascular (n = 685), surgical (n = 483), and mixed (n = 62) ICUs. A high CO2 gap was associated with increased mortality (odds ratio, 2.22; 95% CI, 1.30-3.82; p = 0.004) in patients with shock, but only those from medical and surgical ICUs. A high CO2 gap was associated with higher lactate levels (mean difference 0.44 mmol/L; 95% CI, 0.20-0.68 mmol/L; p = 0.0004), lower cardiac index (mean difference, -0.76 L/min/m; 95% CI, -1.04 to -0.49 L/min/m; p = 0.00001), and central venous oxygen saturation (mean difference, -5.07; 95% CI, -7.78 to -2.37; p = 0.0002). A high CO2 gap was not associated with longer ICU or hospital length of stays, requirement for renal replacement therapy, longer duration of mechanical ventilation, or higher vasopressors and inotropes use. Future studies should evaluate whether resuscitation aimed at closing the CO2 gap improves mortality in shock.

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