The authors reply.

e962 www.ccmjournal. org September 2018 • Volume 46 • Number 9 REFERENCES 1. Turktan M, Ozcengiz D, Esquinas AM: Acidosis and Survival Among Septic Patients. A New Therapeutic Shield. Crit Care Med 2018; 46:e961 2. Roberts BW, Mohr NM, Ablordeppey E, et al: Association between partial pressure of arterial carbon dioxide and survival to hospital discharge among patients diagnosed with sepsis in the emergency department. Crit Care Med 2018; 46:e213–e220 3. Fuller BM, Mohr NM, Drewry AM, et al: Partial pressure of arterial carbon dioxide and survival to hospital discharge among patients requiring acute mechanical ventilation: A cohort study. J Crit Care 2017; 41:29–35 The authors reply: We would like to thank Turktan et al (1) for their interest in our recent article (2), published in Critical Care Medicine. In their letter to the editor (1), several important points regarding our results are raised. First, the median (interquartile range [IQR]) Paco 2 among survivors and nonsurvivors was 44 mm Hg (35–57 mm Hg) versus 39 mm Hg (31–45 mm Hg) respectively, and they note that both these medians are within the clinically normal Paco 2 range (i.e., 35–45 mm Hg). Given the right skew of our data, it seemed more appropriate to report median values as a measure of central tendency as opposed to means. That being said, the mean Paco 2 among survivors versus nonsurvivors was 49 versus 41 mm Hg respectively, and almost twice as many survivors had a Paco 2 greater than 45 mm Hg as compared to nonsurvivors, (44% [190/429] vs 23% [40/171], respectively [chi-square test, p < 0.001]). Turktan et al (1) also appropriately note the potential for confounding. Statistically significant differences in several variables did exist between survivors and nonsurvivors. However, it is unlikely that these differences were clinically meaningful for several variables. For example, the difference in mean age between survivors and nonsurvivors was 5 years (60 vs 65, respectively), and the difference in median Acute Physiology and Chronic Health Evaluation (APACHE) II scores was 1 point (17 vs 18 respectively). This is in contrast to the statistically and clinically significant survival difference of 15% between patients with hypercapnia compared with normocapnia (83% vs 68%, respectively). In addition, rigorous statistical methods were used to adjust for confounders including multivariable logistic regression and propensity score matching, and higher Paco 2 remained an independent predictor of survival to hospital discharge. Finally, the hypercapnic group had a “higher” APACHE II score compared with the nonhypercapnic group (median [IQR], 19 [14–24] vs 16 [12–21], respectively, p < 0.001). Thus, confounding by severity of illness would be expected to be in the opposite direction (i.e., confounding would result in the hypercapnia group appearing to have a lower survival rate). Based on our current analysis, along with other work in this domain (3), hypercapnia seems well tolerated in this patient population and may even be a potential therapeutic target. However, we agree with Turktan et al (1) that the observational design of our study (2) does not allow for causal inference, and further research is required. We believe our results provide scientific rationale for future clinical trials testing early manipulation of Paco 2 in patients with sepsis. The authors have disclosed that they do not have any potential conflicts of interest.