Acute and Critical Care

Original Article

Infection
Trajectories of mean arterial pressure/norepinephrine equivalent dose index in patients with septic shock receiving low-dose hydrocortisone: a retrospective cohort study in Thailand: Auttawut Chalermwutanon, Sawangjit Saejaow, Veerapong Vattanavanit; Acute Crit Care. 2026;41(1):107-116. Published online February 9, 2026; DOI: https://doi.org/10.4266/acc.000125

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Abstract PDF Supplementary Material: Background
We aimed to analyze the trajectories of the mean arterial pressure/norepinephrine equivalent dose (MAP/NEQ) index in patients with septic shock treated with low-dose hydrocortisone and to determine the association of these trajectories with mortality. Methods: A retrospective cohort of 203 patients with septic shock receiving low-dose hydrocortisone was examined. MAP and NEQ data were collected from electronic health records, and groupbased trajectory modeling was employed to identify distinct patterns in the MAP/NEQ index over the initial 72 hours of treatment. Univariable and multivariable logistic regression analyses were conducted to assess the associations of MAP/NEQ index trajectories with clinical variables and in-hospital mortality. Results: The overall in-hospital mortality rate was 56.2%. Three MAP/NEQ index trajectory patterns were identified: unchanged (76.8%), gradually increased (14.3%), and rapidly increased (8.9%). The shock reversal rates were 50% for the unchanged group, 89.7% for the gradually increased group, and 100% for the rapidly increased group. Compared with the unchanged group, both gradually and rapidly increased groups were associated with significantly lower mortality, with adjusted odds ratios of 0.15 (95% CI, 0.05–0.40; P<0.001) and 0.29 (95% CI, 0.09–0.92; P=0.035), respectively. Conclusions: In patients with septic shock treated with low-dose hydrocortisone, gradually and rapidly increased MAP/NEQ index trajectories were associated with significantly lower mortality risks and higher rates of shock reversal compared to those with unchanged trajectories. These findings highlight the importance of monitoring the MAP/NEQ index to guide treatment and improve septic shock outcomes.

Review Article

Basic science and research
Critical illness-related corticosteroid insufficiency: latest pathophysiology and management guidelines: Fremita Chelsea Fredrick, Anish Kumar Reddy Meda, Bhupinder Singh, Rohit Jain; Acute Crit Care. 2024;39(3):331-340. Published online August 30, 2024; DOI: https://doi.org/10.4266/acc.2024.00647

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Intensive care unit (ICU) admissions in the United States exceed 5.7 million annually, often leading to complications such as post-intensive care syndrome and high mortality rates. Among these challenges, critical illness-related corticosteroid insufficiency (CIRCI) requires emphasis due to its complex, multiple-cause pathophysiology and varied presentations. CIRCI, characterized by adrenal insufficiency during critical illness, presents in up to 30% of ICU patients and may manifest as an exaggerated inflammatory response. Factors such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, tissue corticosteroid resistance, and drug-induced suppression contribute to CIRCI. Diagnosis is a complex process, relying on a comprehensive assessment including clinical presentation, laboratory findings, and dynamic stimulatory testing. Treatment involves intensive medical care and exacting glucocorticoid therapy. Recent guidelines advocate for individualized approaches tailored to patient presentation and etiology. Understanding the pathophysiology and treatment of CIRCI is vital for clinicians managing critically ill patients and striving to improve outcomes. This research paper aims to explore the latest developments in the pathophysiology and management of CIRCI.

Citations

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Higher Serum Cortisol is Associated with Delayed Shock Resolution in Septic Shock Patients
Sophon Dumrongsukit, Suranut Charoensri, Kamonwan Mulalin, Anupol Panitchote
Journal of Intensive Care Medicine.2026;[Epub] CrossRef
Trajectories of mean arterial pressure/norepinephrine equivalent dose index in patients with septic shock receiving low-dose hydrocortisone: a retrospective cohort study in Thailand
Auttawut Chalermwutanon, Sawangjit Saejaow, Veerapong Vattanavanit
Acute and Critical Care.2026; 41(1): 107. CrossRef
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Ja Hye Kim
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Diagnostics.2025; 15(20): 2588. CrossRef

Original Articles

Immunology
Patterns of inflammatory immune responses in patients with septic shock receiving vitamin C, hydrocortisone, and thiamine: clustering analysis in Korea: Seung-Hun You, Oh Joo Kweon, Sun-Young Jung, Moon Seong Baek, Won-Young Kim; Acute Crit Care. 2023;38(3):286-297. Published online August 21, 2023; DOI: https://doi.org/10.4266/acc.2023.00507

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Abstract PDF Supplementary Material

Background
Sepsis is characterized by heterogeneous immune responses that may evolve during the course of illness. This study identified inflammatory immune responses in septic patients receiving vitamin C, hydrocortisone, and thiamine.
Methods
This was a single-center, post-hoc analysis of 95 patients with septic shock who received the vitamin C protocol. Blood samples were drawn on days 1–2, 3–4, and 6–8 after shock onset. Group-based multi-trajectory modeling was used to identify immune trajectory groups.
Results
The median age was 78 years (interquartile range, 70–84 years), and 56% were male. Clustering analysis identified group 1 (n=41), which was characterized by lower interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-10 levels, and these levels remained stationary or mildly increased until day 7. Conversely, group 2 (n=54) expressed initially higher IL-6, TNF-α, and IL-10 levels that decreased rapidly by day 4. There was a nonsignificant increase in lymphocyte count and a decrease in C-reactive protein level until day 7 in group 2. The intensive care unit mortality rate was significantly lower in group 2 (39.0% vs. 18.5%, P=0.03). Group 2 also had a significantly higher decrease in the mean (standard deviation) vasopressor dose (norepinephrine equivalent: –0.09±0.16 μg/kg/min vs. –0.23±0.31 μg/kg/min, P<0.001) and Sequential Organ Failure Assessment score (0±5 vs. –4±3, P=0.002) between days 1 and 4.
Conclusions
There may be different subphenotypes in septic patients receiving the vitamin C protocol.

Citations

Citations to this article as recorded by

Systematic review, meta-analysis, and meta-regression of the association of serial leukocyte counts in critically ill patients and mortality
Nishkantha Arulkumaran, Fiona Dewar, Gareth Ambler, Maria Del Pilar Arias Lopez, Claudia Dos Santos, Jan J. De Waele, Jeffrey Lipman, José-Artur Paiva, Jean-Francois Timsit
Annals of Intensive Care.2026; 16: 100054. CrossRef
Vitamin C for sepsis: from mechanisms to individualized therapy
Yang Xiao, Fang Gong, Lina Zhang, Chunmei Gui
Frontiers in Medicine.2025;[Epub] CrossRef
Micronutrients as therapy in critical illness
Christian Stoppe, Ellen Dresen, Angelique de Man
Current Opinion in Critical Care.2024; 30(2): 178. CrossRef
Novel cortisol trajectory sub-phenotypes in sepsis
Fei Leng, Zhunyong Gu, Simeng Pan, Shilong Lin, Xu Wang, Ming Zhong, Jieqiong Song
Critical Care.2024;[Epub] CrossRef

Basic science and research
Comparison of salivary and serum cortisol levels in mechanically ventilated patients and non-critically ill patients: Jung Hee Kim, Yoon Ji Kim, Sang-Min Lee, Jinwoo Lee; Acute Crit Care. 2020;35(3):149-155. Published online August 31, 2020; DOI: https://doi.org/10.4266/acc.2020.00297

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Abstract PDF

Background
Although the measuring free cortisol is ideal for assessment of hypothalamicpituitary-adrenal function, it is not routinely measured. Salivary cortisol correlates well with the biologically active free cortisol. Therefore, this study measured the morning basal as well as adrenocorticotropic hormone-stimulated salivary cortisol levels in mechanically ventilated patients and compared the results with non-critically ill patients.
Methods
We prospectively enrolled 49 mechanically ventilated patients and 120 patients from the outpatient clinic. Serum and saliva samples were collected between 8 AM and 10 AM. Salivary cortisol levels were measured using an enzyme immunoassay kit. The salivary samples were insufficient in 15 mechanically ventilated patients (30.6%), and these patients were excluded from the final analysis.
Results
Mechanically ventilated patients (n=34) were significantly older and had lower body mass index and serum albumin levels and higher serum creatinine levels than non-critically ill patients (n=120). After adjustment for these parameters, both basal and stimulated salivary and serum cortisol levels were higher in mechanically ventilated patients. The increase in cortisol was not significantly different between the two groups. Serum cortisol levels showed a positive correlation with salivary cortisol levels. Among mechanically ventilated patients, both basal serum and salivary cortisol levels were lower in survivors than in non-survivors.
Conclusions
Both basal total serum and salivary cortisol levels were elevated in mechanically ventilated patients and in non-survivors.

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