Observational Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 6, 2023; 11(16): 3765-3779
Published online Jun 6, 2023. doi: 10.12998/wjcc.v11.i16.3765
Hypoperfusion context as a predictor of 28-d all-cause mortality in septic shock patients: A comparative observational study
Sahil Kataria, Omender Singh, Deven Juneja, Amit Goel, Madhura Bhide, Devraj Yadav
Sahil Kataria, Omender Singh, Deven Juneja, Amit Goel, Madhura Bhide, Devraj Yadav, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, New Delhi 110017, India
Author contributions: Kataria S, Singh O, and Juneja D designed the study; Kataria S, Bhide M, and Yadav D collected the data and analyzed the results; Kataria S and Juneja D performed the majority of the writing and prepared the tables; Singh O, Goel A, Devraj Y, and Bhide M provided input in writing the paper and reviewed the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Max Super Specialty Hospital, Saket, Institutional Review Board (Approval No. TS/MSSH/MHIL/SKT-1/MHEC/CC/20-14).
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Deven Juneja, DNB, Director, Institute of Critical Care Medicine, Max Super Speciality Hospital, Saket, 1, Press Enclave Road, New Delhi 110017, India. devenjuneja@gmail.com
Received: November 30, 2022
Peer-review started: November 30, 2022
First decision: January 17, 2023
Revised: January 17, 2023
Accepted: April 18, 2023
Article in press: April 18, 2023
Published online: June 6, 2023

As per the latest Surviving Sepsis Campaign guidelines, fluid resuscitation should be guided by repeated measurements of blood lactate levels until normalization. Nevertheless, raised lactate levels should be interpreted in the clinical context, as there may be other causes of elevated lactate levels. Thus, it may not be the best tool for real-time assessment of the effect of hemodynamic resuscitation, and exploring alternative resuscitation targets should be an essential research priority in sepsis.


To compare the 28-d mortality in two clinical patterns of septic shock: hyperlactatemic patients with hypoperfusion context and hyperlactatemic patients without hypoperfusion context.


This prospective comparative observational study carried out on 135 adult patients with septic shock that met Sepsis-3 definitions compared patients with hyperlactatemia in a hypoperfusion context (Group 1, n = 95) and patients with hyperlactatemia in a non-hypoperfusion context (Group 2, n = 40). Hypoperfusion context was defined by a central venous saturation less than 70%, central venous-arterial PCO2 gradient [P(cv-a)CO2] ≥ 6 mmHg, and capillary refilling time (CRT) ≥ 4 s. The patients were observed for various macro and micro hemodynamic parameters at regular intervals of 0 h, 3 h, and 6 h. All-cause 28-d mortality and all other secondary objective parameters were observed at specified intervals. Nominal categorical data were compared using the χ2 or Fisher’s exact test. Non-normally distributed continuous variables were compared using the Mann-Whitney U test. Receiver operating characteristic curve analysis with the Youden index determined the cutoff values of lactate, CRT, and metabolic perfusion parameters to predict the 28-d all-cause mortality. A P value of < 0.05 was considered significant.


Patient demographics, comorbidities, baseline laboratory, vital parameters, source of infection, baseline lactate levels, and lactate clearance at 3 h and 6 h, Sequential Organ Failure scores, need for invasive mechanical ventilation, days on mechanical ventilation, and renal replacement therapy-free days within 28 d, duration of intensive care unit stay, and hospital stay were comparable between the two groups. The stratification of patients into hypoperfusion and non-hypoperfusion context did not result in a significantly different 28-d mortality (24% vs 15%, respectively; P = 0.234). However, the patients within the hypoperfusion context with high P(cv-a)CO2 and CRT (P = 0.022) at baseline had significantly higher mortality than Group 2. The norepinephrine dose was higher in Group 1 but did not achieve statistical significance with a P > 0.05 at all measured intervals. Group 1 had a higher proportion of patients requiring vasopressin and the mean vasopressor-free days out of the total 28 d were lower in patients with hypoperfusion (18.88 ± 9.04 vs 21.08 ± 8.76; P = 0.011). The mean lactate levels and lactate clearance at 3 h and 6 h, CRT, P(cv-a)CO2 at 0 h, 3 h, and 6 h were found to be associated with 28-d mortality in patients with septic shock, with lactate levels at 6 h having the best predictive value (area under the curve lactate at 6 h: 0.845).


Septic shock patients fulfilling the hypoperfusion and non-hypoperfusion context exhibited similar 28-d all-cause hospital mortality, although patients with hypoperfusion displayed a more severe circulatory dysfunction. Lactate levels at 6 h had a better predictive value in predicting 28-d mortality than other parameters. Persistently high P(cv-a)CO2 (> 6 mmHg) or increased CRT (> 4 s) at 3 h and 6 h during early resuscitation can be a valuable additional aid for prognostication of septic shock patients.

Keywords: Capillary refill time, Central venous saturation, Hypoperfusion, Lactate, Mortality, PCO2 gap, Septic shock

Core Tip: Two different clinical patterns among hyperlactatemic septic shock patients can be effectively differentiated when utilizing three easily employable perfusion parameters. Lactate levels are still the best available tool, but persistence of high central venous-arterial PCO2 gradient (> 6 mmHg) or raised capillary refill time (> 4 s) at 3 h and 6 h along with lactate metrics during early resuscitation can be valuable for guiding resuscitation of septic shock patients.