Tag Archives: sepsis

Midodrine initiation criteria, dose titration, and adverse effects when administered to treat shock: A systematic review and semi-quantitative analysis

Madeleine M. Puissant, Kaitlin J Armstrong, Richard R Riker, Samir Haydar, Tania D Strout, Kathryn E Smith, David B Seder, David J Gagnon

Maine Medical Center, Portland, USA

DOI: 10.2478/jccm-2025-0007

Objective: Systematically examine the literature describing midodrine to treat shock and to summarize current administration and dosing strategies.
Data sources: Structured literature search conducted in MEDLINE (PubMed) from inception through May 10, 2023.
Study Selection and Data Extraction: Abstracts and full texts were assessed for inclusion by two blinded, independent reviewers. English-language publications describing use of midodrine in adult patients with shock were included. Data were extracted by two blinded, independent abstractors using a standardized extraction tool. Quality assessments were completed by paired reviewers using JBI methodology.
Data Synthesis: Fifteen of 698 (2%) screened manuscripts were included with 1,714 patients with a variety of shock types. Seven studies (47%) were retrospective, two (13%) prospective observational, and six (40%) randomized controlled studies. Midodrine was initiated to facilitate intravenous vasopressor (IVP) weaning in most (11, 73%) studies; only two (13%) reported IVP weaning protocol use. Starting doses were 10 mg every 8 hours (4, 27%) or three times a day (3, 20%), 20 mg every 8 hours (2, 13%); six studies (40%) did not report initial midodrine dosing. A midodrine titration protocol was reported in 6 (40%) studies. Thirteen (87%) studies evaluated for bradycardia, identified in 6 (46%) studies among 204 patients; only one (0.5%) patient required midodrine discontinuation. Three (20%) studies reported on hypertension with an incidence of 7-11%. Four (27%) studies assessed for ischemia; 5/1128 (0.4%) patients experienced mesenteric ischemia requiring midodrine discontinuation.
Relevance to Patient care and Clinical Practice: This review explores the pragmatic details involved in initiating, titrating, and weaning midodrine for the bedside clinician and identifies rates of adverse events and complications.
Conclusions: Published literature describing midodrine use for shock is heterogeneous and comprised primarily of low or very low quality data. Future controlled trials addressing the shortcomings identified in this systematic review are warranted.

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Association between hospital case volume and mortality in pediatric sepsis: A retrospective observational study using a Japanese nationwide inpatient database

Shingo Ohki1,2, Makoto Otani3, Shinichi Tomioka1,4, Kosaku Komiya5, Hideki Kawamura6, Taka-aki Nakada7, Satoshi Nakagawa8, Shinya Matsuda3, Nobuaki Shime1

1 Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
2 Shonan Kamakura General Hospital, Kamakura, Japan
3 University of Occupational and Environmental Health, Kitakyushu, Japan
4 Kotonoha Collaboration Clinic, Kitakyushu, Japan
5 Faculty of Medicine, Oita University, Oita, Japan
6 Kagoshima University Hospital, Kagoshima, Japan
7 Graduate School of Medicine, Chiba University, Chiba, Japan
8 National Center for Child Health and Development, Tokyo, Japan

DOI: 10.2478/jccm-2025-0006

Introduction: The survival benefits of treatment at high-volume hospitals (HVHs) are well-documented for several critical pediatric conditions. However, their impact on pediatric sepsis, a leading cause of mortality among children, remains understudied.
Aim of the study: To investigate the association between hospital case volume and mortality rates in pediatric sepsis.
Material and Methods: We conducted a retrospective cohort study using data from the Diagnosis Procedure Combination database. The study included patients who met the following criteria: 1) aged 28 days to 17 years; 2) discharged from the hospital between April 2014 and March 2018; 3) had a sepsis diagnosis coded under the International Classification of Diseases, 10th revision; 4) underwent blood cultures on hospital admission day (day 0) or day 1; 5) received antimicrobial agents on day 0 or 1; and 6) required at least one organ support measure (e.g., mechanical ventilation or vasopressors) on day 0 or 1. Hospitals were categorized by case volume during the study period, with HVHs defined as those in the highest quartile and low-volume hospitals (LVHs) as those in the remaining quartiles. In-hospital mortality rates between HVH and LVH groups were compared using mixed-effects logistic regression analysis with propensity score (PS) matching.
Results: A total of 934 pediatric patients were included in the study, with an overall in-hospital mortality rate of 16.1%. Of them, 234 were treated at 5 HVHs (≥26 patients in 4 years), and 700 at 234 LVHs (<26 patients in 4 years). Upon PS matching, patients treated at HVHs demonstrated significantly lower odds of in-hospital mortality compared with those treated at LVHs (odds ratio, 0.42; 95% confidence interval, 0.22–0.80; P = 0.008).
Conclusions: In pediatric patients with sepsis, treatment at HVHs was associated with lower odds of in-hospital mortality.

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Insights into sepsis-induced apoptosis: Interplay between programmed cell death and interleukin-7

Anca Meda Văsiesiu, Oana Coman, Raluca Stefania Fodor, Anca Bacârea, Bianca‐Liana Grigorescu

George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania

DOI: 10.2478/jccm-2025-0003

The pathophysiology of sepsis is orchestrated by a delicate and dynamic interaction between pro-inflammatory and anti-inflammatory responses. Essential factors influencing this process include interleukin-7 (IL-7), the programmed cell death protein 1/programmed death ligand 1 (PD-1/PD-L1) axis, and cellular apoptosis. These elements shape the immune response in sepsis, influencing its progression and outcomes. IL-7 is an important cytokine maintaining lymphocyte function and survival. At the same time, the PD-1/PD-L1 axis acts as a modulatory checkpoint suppressing immune activation to prevent overreaction but can exacerbate immunosuppression during sepsis. Cellular apoptosis impairs the host’s ability to mount an effective defence, especially against secondary infections.
Despite extensive research, the precise mechanisms through which sepsis results in organ dysfunction and immune dysregulation remain incompletely understood. The global burden of sepsis emphasizes the urgent need for innovative approaches, paving the way for personalized, immune-based therapies.
This review aims to delve into and synthesize the current knowledge regarding cellular apoptosis, the regulatory role of the PD-1/PD-L1 axis, and the critical functions of IL-7 in sepsis, with a focus on their underlying mechanisms, clinical relevance, and potential as targets for future immunomodulatory treatments.

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Characteristics of the Cerebrospinal Fluid in Septic Patients with Critical Illness Polyneuropathy – A Retrospective Cohort Study

Yanyang Zhang1, Jinfu Ma2, Qing Zhao1, Hui Liu1

1 1st Medical Center of Chinese PLA General Hospital, Beijing, China
2 The 305th Hospital of Chinese PLA, Beijing, China

DOI: 10.2478/jccm-2024-0018

Background: Critical illness polyneuropathy (CIP) is a complex disease commonly occurring in septic patients which indicates a worse prognosis. Herein, we investigated the characteristics of cerebrospinal fluid (CSF) in septic patients with CIP.
Methods: This retrospective study was conducted between Match 1, 2018, and July 1, 2022. Patients with sepsis who underwent a CSF examination and nerve electrophysiology were included. The levels of protein, glucose, lipopolysaccharide, white blood cell (WBC), interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF) α in CSF were measured. The fungi and bacteria in CSF were also assessed.
Results: Among the 175 septic patients, 116 (66.3%) patients were diagnosed with CIP. 28-day Mortality in CIP patients was higher than that in non-CIP patients (25.0% vs. 10.2%, P = 0.02) which was confirmed by survival analysis. The results of propensity score matching analysis (PSMA) indicated a significant difference in the level of protein, WBC, IL-1, IL-6, IL-8, and TNFα present in the CSF between CIP patients and non-CIP patients. The results of the receiver operating characteristic (ROC) analysis showed that IL-1, WBC, TNFα, and their combined indicator had a good diagnostic value with an AUC > 0.8.
Conclusion: The increase in the levels of WBC, IL-1, and TNFα in CSF might be an indicator of CIP in septic patients.

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Extracorporeal Membrane Oxygenation as Circulatory Support in Adult Patients with Septic Shock: A Systematic Review

Muhammad Faisal Khan1, Mohsin Nazir1, Muhammad Khuzzaim Khan2, Raj Kumar Rajendram3, Faisal Shamim1*

1 Department of Anesthesiology, Aga Khan University Hospital, Karachi, Pakistan
2 Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan
3 College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

DOI: 10.2478/jccm-2024-0017

Introduction: The utilization of extracorporeal membrane oxygenation (ECMO) in adult patients experiencing septic shock is a subject of ongoing debate within the medical community. This study aims to comprehensively address this issue through a systematic review conducted in accordance with the PRISMA guidelines.
Aim of Study: The primary objective of this study is to assess the outcomes of ECMO utilization in adult patients diagnosed with septic shock, thereby providing insights into the potential benefits and uncertainties associated with this treatment modality.
Materials and Methods: Our research encompassed a thorough search across electronic databases for relevant English-language articles published up until April 2023. The inclusion criteria were based on studies reporting on ECMO usage in adult patients with septic shock. Among the eligible studies meeting these criteria, a total of eleven were included in our analysis, involving a cohort of 512 patients. The mean age of the participants was 53.4 years, with 67.38% being male.
Results: In the pooled analysis, the mean survival rate following ECMO treatment was found to vary significantly across different ECMO modalities. Patients receiving venovenous-ECMO (VV-ECMO) and veno-venous-arterial ECMO (VVA-ECMO) demonstrated higher survival rates (44.5% and 44.4%, respectively) compared to those receiving venoarterial-ECMO (VA-ECMO) at 25% (p<0.05). A chi-square test of independence indicated that the type of ECMO was a significant predictor of survival (χ²(2) = 6.63, p=0.036). Additionally, patients with septic shock stemming from respiratory failure demonstrated survival rates ranging from 39% to 70%. Predictors of mortality were identified as older age and the necessity for cardiopulmonary resuscitation (CPR).
Conclusions: In septic shock patients, ECMO outcomes align with established indications like respiratory and cardiogenic shock. VV-ECMO and VVA-ECMO suggest better prognoses, though the optimal mode remains uncertain. Patient selection should weigh age and CPR need. Further research is vital to determine ECMO’s best approach for this population.

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The Utility of Serial Lipid Measurements as a Potential Predictor of Sepsis Outcome: A Prospective Observational Study in a Tertiary Care Hospital

Afrah Abdul Malick1, Jeyakumar Manavalan2, Viveka Murugiah1, Manikandan Bose1, Hariharan Alexander1, Suganthy Kanakasekaran1

1 Velammal Medical College Hospitals and Research Institute, Madurai, Tamil Nadu, India
2 Sri Manakula Vinayagar medical college and Hospital, Puducherry, India

DOI: 10.2478/jccm-2024-0015

Background and aim: Sepsis is the major cause of morbidity and mortality for patients admitted to an intensive care unit worldwide. Currently, Procalcitonin (PCT) is a widely used prognostic marker for sepsis. The high cost of estimating Procalcitonin limits its utility in all health facilities. Lipid Profile, being a frequently done routine investigation, is studied in sepsis patients to predict the prognosis of sepsis. This study was aimed to assess the association between lipid profile parameters, procalcitonin and clinical outcomes in patients with sepsis.
Materials and methods: It is a prospective observational study conducted in a tertiary care hospital in the Department of Biochemistry in collaboration with the Intensive Care Unit (ICU). We included 80 sepsis patients from medical and surgical ICUs. Among them, 59 (74%) survived and 21 (26%) expired. Serum lipid profile, procalcitonin and variables required for APACHE II score are measured at two intervals, one during admission and on day 5. All the parameters were compared between the survivors and the non-survivors.
Results: Serum PCT levels were reduced on Day 5 [3.32 (1.27-11.86)] compared to Day 0 [13.42 (5.77-33.18)] in survivors. In survivors, Total Cholesterol, LDL-C and Non-HDL-C were significantly elevated on Day 5 compared to Day 0. In non-survivors, HDL-C significantly decreased on Day 5. Between survivors and non-survivors, HDL-C significantly decreased on Day 5 (23.88 ± 10.19 vs 16.67 ± 8.27 mg/dl). A Negative correlation was observed between HDL-C & PCT.
Conclusion: Serum Lipid profile levels, namely Total cholesterol, HDL-C and LDL-C, have possible associations with the severity of sepsis. HDL-C have a negative association with the clinical scoring system in sepsis patients. Overall, the findings from our study suggest that lipid profile parameters have possible implications in predicting the outcome of patients with sepsis.

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Is Carboxyhaemoglobin an Effective Bedside Prognostic Tool for Sepsis and Septic Shock Patients?

Bianca‐Liana Grigorescu1, Oana Coman2, Anca Meda Văsieșiu3, Anca Bacârea4, Marius Petrișor2, Irina Săplăcan5, Raluca Ștefania Fodor1

1 Department of Anesthesia and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2 Department of Simulation Applied in Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3 Department of Infectious Diseases, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4 Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
5 County Emergency Clinical Hospital, Targu Mures, Romania

DOI: 10.2478/jccm-2023-0031

Introduction: Proper management of sepsis poses a challenge even today, with early diagnosis and targeted treatment being the most important steps. Easy, cost-effective bedside tools are needed in order to pinpoint towards the outcome of sepsis or septic shock.
Aim of study: This study aims to find a correlation between Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II) and Simplified Acute Physiology Score II (SAPS II) severity scores, the Neutrophil-Lymphocytes Ratio (NLR) and carboxyhaemoglobin (COHb) levels in septic or septic shock patients with the scope of establishing a bed side cost-effective prognostic tool.
Materials and methods: A pilot, prospective, observational, and ongoing study was conducted on 61 patients admitted with sepsis or septic shock according to the SEPSIS 3 Consensus definition. We followed clinical and paraclinical parameters on day 1 (D1) and day 5 (D5) after meeting the inclusion criteria.
Results: On D1 we found a statistically significant positive correlation between each severity score (p <0.0001), r = 0.7287 for SOFA vs. APACHE II with CI: 0.5841-0.8285, r = 0.6862 for SOFA vs. SAPS II with CI: 0.5251-0.7998 and r = 0.8534 for APACHE II vs. SAPS II with CI: 0.7663 to 0.9097. On D5 we observed similar results: a significant positive correlation between each severity score (p <0.0001), with r = 0.7877 for SOFA vs. APACHE II with CI: 0.6283 to 0.8836, r = 0.8210 for SOFA vs. SAPS II with CI: 0.6822 to 0.9027 and r = 0.8880 for APACHE II vs. SAPS II., CI: 0.7952 to 0.9401. Nil correlation was found between the severity scores, NLR and COHb on D1 and D5.
Conclusion: Cost-effective bedside tools to pinpoint towards the outcome of sepsis are yet to be found, however the positive correlation between the severity scores point out to a combination of such tools for prognosis prediction of septic or septic shock patients.

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Fluids and early vasopressors in the management of septic shock: Do we have the right answers yet?

Carlos Sanchez E.1, Michael R. Pinsky2, Sharmili Sinha3, Rajesh Chandra Mishra4, Ahsina Jahan Lopa5, Ranajit Chatterjee6

1 Department of Critical Care Medicine, King Salman Hospital, Riyadh, Saudi Arabia
2 Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
3 Department of Critical Care Medicine, Apollo Hospitals, Bhubaneswar, India
4 Department of Critical Care Medicine, Ahmedabad Khyati Multi-speciality Hospitals, Ahmedabad, India. Department of Critical Care Medicine, Ahmedabad Shaibya Comprehensive Care Clinic, Ahmedabad, India
5 ICU and Emergency Department, Shahabuddin Medical College Hospital, Dhaka, Bangladesh
6 Department of Critical Care Medicine, accident and emergency, Swami Dayanand Hospital Delhi, India

DOI: 10.2478/jccm-2023-0022

Septic shock is a common condition associated with hypotension and organ dysfunction. It is associated with high mortality rates of up to 60% despite the best recommended resuscitation strategies in international guidelines. Patients with septic shock generally have a Mean Arterial Pressure below 65 mmHg and hypotension is the most important determinant of mortality among this group of patients. The extent and duration of hypotension are important. The two initial options that we have are 1) administration of intravenous (IV) fluids and 2) vasopressors, The current recommendation of the Surviving Sepsis Campaign guidelines to administer 30 ml/kg fluid cannot be applied to all patients. Complications of fluid over-resuscitation further delay organ recovery, prolong ICU and hospital length of stay, and increase mortality. The only reason for administering intravenous fluids in a patient with circulatory shock is to increase the mean systemic filling pressure in a patient who is volume-responsive, such that cardiac output also increases. The use of vasopressors seems to be a more appropriate strategy, the very early administration of vasopressors, preferably during the first hour after diagnosis of septic shock, may have a multimodal action and potential advantages, leading to lower morbidity and mortality in the management of septic patients. Vasopressor therapy should be initiated as soon as possible in patients with septic shock.

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Early Lactate Clearance as a Determinant of Survival in Patients with Sepsis: Findings from a Low-resource Country

Fazal Rehman1, Saad Bin Zafar1, Adil Aziz1, Abdul Aziz1, Pirbhat Shams Memon1, Taymmia Ejaz1, Summaira Aziz2

1 Department of Medicine, The Aga Khan University Hospital, Karachi, Pakistan
2 Department of Community Health Sciences, The Aga Khan University Hospital, Karachi, Pakistan

DOI: 10.2478/jccm-2023-0005

Background: Single lactate measurements have been reported to have prognostic significance, however, there is a lack of data in local literature from Pakistan. This study was done to determine prognostic role of lactate clearance in sepsis patients being managed in our lower-middle income country.
Methods: This prospective cohort study was conducted from September 2019-February 2020 at the Aga Khan University Hospital, Karachi. Patients were enrolled using consecutive sampling and categorized based on their lactate clearance status. Lactate clearance was defined as decrease by 10% or greater in repeat lactate from the initial measurement (or both initial and repeat levels <=2.0 mmol/L).
Results: A total 198 patients were included in the study, 51% (101) were male. Multi-organ dysfunction was reported in 18.6% (37), 47.7% (94) had single organ dysfunction, and 33.8% (67) had no organ dysfunction. Around 83% (165) were discharged and 17% (33) died. There were missing data for 25.8% (51) of the patients for the lactate clearance, whereas 55% (108) patients had early lactate clearance and 19.7% (39) had delayed lactate clearance.On univariate analysis, mortality rate was higher in patients with delayed lactate clearance (38.4% vs 16.6%) and patients were 3.12 times (OR = 3.12; [95% CI: 1.37-7.09]) more likely to die as compared with early lactate clearance. Patients with delayed lactate clearance had higher organ dysfunction (79.4% vs 60.1%) and were 2.56 (OR = 2.56; [95% CI: 1.07-6.13]) times likely to have organ dysfunction. On multivariate analysis, after adjusting for age and co-morbids, patients with delayed lactate clearance were 8 times more likely to die than patients with early lactate clearance [aOR = 7.67; 95% CI:1.11-53.26], however, there was no statistically significant association between delayed lactate clearance [aOR = 2.18; 95% CI: 0.87-5.49)] and organ dysfunction.
Conclusion: Lactate clearance is a better determinant of sepsis and septic shock effective management. Early lactate clearance is related to better outcomes in septic patients.

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Successful Extracorporeal Blood Purification Therapy Using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report

Stefano Ferraro1, Stefania Bianzina2, Sonila Mocka3, Francesca Cappadona4, Giovanni Battista Traverso4, Fabio Massarino4, Pasquale Esposito4,5

1 Unità di Nefrologia, San Paolo Hospital, Savona, Italy
2 Neonatal and Pediatric Intensive Care Unit, Emergency Department, IRCCS Istituto Giannina Gaslini, Genova, Italy
3 Unità di Nefrologia, Sant’Andrea Hospital, La Spezia, Italy
4 Clinica Nefrologica, Dialisi, Trapianto, IRCCS Ospedale Policlinico San Martino, Genova, Italy
5 Department of Internal Medicine, University of Genova, Italy

DOI: 10.2478/jccm-2022-0028

Introduction: In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI.
Case presentation: We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient’s haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris® haemodiafilter set, in series with an adsorber device (CytoSorb®). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient’s conditions still improved and renal function recovered.
Conclusions: Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock.

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