Category Archives: Review

Evidence-based fluid resuscitation of the septic HFpEF patient: A narrative review of the literature

Maxwell Ward, Roshan Acharya, Anthony Loschner

Virginia Polytechnic Institute and State University, Carilion School of Medicine, Roanoke, Virginia, USA

DOI: 10.2478/jccm-2026-0005

Purpose: This narrative review aims to highlight the available evidence on fluid resuscitation in septic patients with heart failure, with a particular focus on heart failure with preserved ejection fraction.
Methods: A PubMed search was conducted using the keywords “sepsis” (or sepsis, or septic shock), “heart failure” (or HF, or HFrEF, or HFpEF or congestive heart failure), and “fluid” (or resuscitation, or fluid resuscitation, or fluid management). The results were summarized in narrative review format.
Results/Conclusions: The presence of HFpEF in septic patients appears to be associated with an increased risk of adverse outcomes. This population may benefit from a more individualized approach to fluid resuscitation. Emerging tools for assessing fluid responsiveness and characterizing septic cardiovascular physiology show promise, but further investigation is needed.

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Interruption of enteral tube feeding during chest physiotherapy in critically ill adults: A scoping review

Ruvistay Gutierrez-Arias1, Francisco Salinas-Barahona2, Pamela Seron3

1 Departamento de Apoyo en Rehabilitación Cardiopulmonar Integral, Instituto Nacional del Tórax, Santiago, Chile; INTRehab Research Group, Instituto Nacional del Tórax, Santiago, Chile; Exercise and Rehabilitation Sciences Institute, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, Santiago, Chile
2 Departamento de Apoyo en Rehabilitación Cardiopulmonar Integral, Instituto Nacional del Tórax, Santiago, Chile; INTRehab Research Group, Instituto Nacional del Tórax, Santiago, Chile; Escuela de Kinesiología, Universidad de Las Américas, Santiago, Chile
3 Departamento de Ciencias de la Rehabilitación, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile; Centro de Excelencia CIGES, Facultad de Medicina, Universidad de La Frontera, Temuco, Chile

DOI: 10.2478/jccm-2026-0002

Introduction: Numerous reports indicate that the nutritional targets of critically ill patients are frequently not met. In daily clinical practice, it is often recommended to temporarily stop enteral tube feeding in patients on mechanical ventilation (MV) who are undergoing chest physiotherapy. This is because adverse events can occur and potentially cause vomiting and increase the risk of aspiration pneumonia.
Aim of the study: To identify, characterise, and analyse the available evidence on the interruption of enteral tube feeding in critically ill adult patients receiving MV before or during chest physiotherapy.
Materials and Methods: We conducted a scoping review following the recommendations of the Joanna Briggs Institute. We conducted a systematic search of MEDLINE (Ovid), Embase (Ovid), CENTRAL (Cochrane Library), CINAHL (EBSCOhost), and other search resources until March 2025. We included studies of any design that addressed the application of chest physiotherapy in adults on MV and receiving enteral tube nutrition. Study selection and data extraction were performed in duplicate, and disagreements were resolved by consensus.
Results: We include four studies that were published between 2018 and 2024. One observational study reported that enteral tube feeding was discontinued due to the application of chest physiotherapy in patients in prone and supine MV. In the other three studies, which contribute to a clinical practice guideline, discontinuation of enteral tube feeding is recommended 30 minutes before using the head-down position as a bronchial drainage manoeuvre. However, no studies report on the safety of chest physiotherapy when enteral tube feeding is either discontinued or continued.
Conclusion: There is no empirical evidence to justify routinely stopping enteral tube feeding during chest physiotherapy in MV patients. Future primary studies should report on the management of enteral tube feeding before or during chest physiotherapy interventions, as well as document any adverse events that may occur during its application.

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Efficacy of inhaled antibiotics in children with ventilator-associated pneumonia: A systematic review and meta-analysis

Sher W. Chee1, Rafdzah A. Zaki2, Shih Y. Hng1, Kah P. Eg1, Qiao Y. Lee1, Jessie A. de Bruyne1, Anna Marie Nathan1

1 Department of Pediatrics, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
2 Department of Social and Preventive Medicine, Centre of Epidemiology and Evidence-Based Practice, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

DOI: 10.2478/jccm-2026-0003

Introduction: The nebulization of antibiotics allows the delivery of high concentration of medication to the lungs without the systemic side-effects.
Aims: We performed a systematic review and meta-analysis to determine the efficacy and safety of inhaled antibiotics in children with ventilator-associated pneumonia (VAP).
Data sources: We searched Web of Science, SCOPUS, MEDLINE Complete, CINAHL and ClinicalTrials.gov trials registry until June 2025. This study was registered (CRD42024504982).
Study selection: We included studies published in the last ten years that recruited children under 18 years old with VAP and treated with inhaled antibiotics. We excluded studies of children with tracheostomy and bronchiectasis.
Data extraction: Type of intervention (inhaled ± intravenous (IV) antibiotics), clinical improvement, duration of mechanical ventilation (MV) and hospitalization, bacterial eradication, and adverse events were recorded.
Results: Seven articles (346 patients) reported the use of inhaled antibiotics in VAP, of which four were randomized controlled trials. These studies included premature infants, neonates and children. The commonest inhaled antibiotic used was colistin (six studies). Meta-analysis revealed that inhaled antibiotics + IV antibiotics versus IV antibiotics +/- inhaled normal saline(placebo) resulted in no significant reduction in duration of MV (MD 0.88 days, 95% CI -2.72, 4.49; p=0.63, I2 = 85%) and ICU stay (MD 0.34[-2.79,3.40]; p=0.83, I2 = 80%). Clinical success (RR 0.68, 95% CI 0.39, 1.21; p=0.19, I2 =24%), microbiological eradication (RR 1.93, 95%CI 0.97,3.78; p=0.06, I2 = 2%) and mortality (RR 0.91, 95% CI 0.67, 1.24; p=0.54, I2 =0%) were also not significantly different. Inhaled antibiotics were not associated with increased nephrotoxicity (RR 0.91, 95% CI 0.18, 4.61; p=0.91, I2 = 30%)
Conclusion: More robust studies are required to confirm the clinical efficacy of inhaled antibiotics in the treatment of VAP. Nonetheless, adjunctive inhaled antibiotics may be safe in children, although close monitoring is still required.

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Impact of protein intervention timings on critically ill patients: A systematic review and meta- analysis

Pranav Kumar Sharma1, Sanjiya Arora2, Tirth Bhavsar3, Mamta Kamboj4, Rahul Kamboj5, Varnika Gupta6, Anitha Sigamani Ramamurthi7, Kumari Uthayakumar8, Ajay Singh9, Sachin Mahendrakumar Chaudhary10, Arghadip Das11, Arianisa Bajrami12, Sumesh Singh13, Devendra Tripathi14

1 Department of Internal Medicine, Lake Cumberland Regional Hospital, Somerset, Kentucky, USA
2 Department of Internal Medicine, Rohilkhand Medical College, Bareilly, Uttar Pradesh, India
3 Department of Internal Medicine, Smt. NHL Municipal Medical College, Ahmedabad, Gujarat, India
4 Department of Internal Medicine, Government Medical College, Patiala, Punjab, India
5 Department of Internal Medicine, King George’s Medical College, Lucknow, Uttar Pradesh, India
6 Department of Internal Medicine, Lala Lajpat Rai Memorial Medical College, Uttar Pradesh, India
7 Department of Internal Medicine, PSG Institute of Medical Sciences and Research, Coimbatore, Tamil Nadu, India
8 Department of Internal medicine, Nanjing Medical University, Nanjing, China
9 Department of Internal Medicine, Sri Ram Murti Smarak Institute of Medical Sciences, Bareilly, Uttar Pradesh, India
10 Department of Internal Medicine, Gujarat Cancer Society Medical College, Hospital and Research Center, Ahmedabad, Gujarat, India
11 Department of Internal Medicine, Nilratan Sircar Medical College and Hospital, Kolkata, West Bengal, India
12 Department of Internal Medicine, University of Tirana, Albania
13 Department of Internal Medicine, Institute of Medicine, Tribhuvan University, Kathmandu, Nepal
14 Department of Internal Medicine, Nazareth Hospital, Philadelphia, PA. USA

DOI: 10.2478/jccm-2025-0047

Background: Critically ill patients experience metabolic alterations that promote muscle atrophy and protein catabolism, increasing morbidity and mortality. While adequate protein provision is essential, the optimal timing remains controversial. Guidelines recommend higher protein targets, but evidence from randomized controlled trials is limited and inconsistent.
Aim: To evaluate the effects of early versus late protein supplementation on mortality, complications, and clinical outcomes in critically ill patients.
Methods: A systematic review and meta-analysis were conducted using PubMed, Embase, Cochrane Library, and Google Scholar (January 2010–December 2022). Studies comparing early and late protein administration in adult ICU patients were included. Primary outcomes were mortality, infectious complications, overall complications, pneumonia, ICU/hospital length of stay, and mechanical ventilation duration.
Results: Thirteen studies (8 RCTs, 3 retrospective, 2 prospective cohorts) involving 10,672 patients were analyzed. Mortality (RR = 0.87, 95% CI: 0.74–1.04, p = 0.11; I² = 36%), overall complications (RR = 0.87, 95% CI: 0.74–1.02, p = 0.08; I² = 26%), infectious complications (RR = 0.86, 95% CI: 0.58–1.27, p = 0.37; I² = 65%), and pneumonia (RR = 0.78, 95% CI: 0.41–1.48, p = 0.34; I² = 0%) showed no significant differences between early protein (EP) and late protein (LP) groups. EP significantly reduced ICU length of stay (MD = –0.28 days, 95% CI: –0.33 to –0.23, p < 0.00001; I² = 99%) and mechanical ventilation duration (MD = –0.66 days, 95% CI: –0.90 to –0.41, p < 0.00001; I² = 85%), but was associated with a longer hospital stay (MD = 0.47 days, 95% CI: 0.31–0.63, p < 0.00001; I² = 98%).
Conclusion: Early protein supplementation does not significantly affect mortality or major complications but may shorten ICU stay and ventilation duration. High heterogeneity for some outcomes warrants cautious interpretation.

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Exploring pharmacological strategies in the management of ARDS: Efficacy, limitations, and future directions

Sultan Almuntashiri

Department of Clinical Pharmacy, College of Pharmacy, University of Ha’il, Ha’il, Saudi Arabia

DOI: 10.2478/jccm-2025-0030

Acute respiratory distress syndrome (ARDS) is a severe inflammatory reaction in the lungs caused by sudden pulmonary and systemic injuries. Clinically, this diverse syndrome is marked by sudden hypoxemic respiratory failure and the presence of bilateral lung infiltrates visible on a chest X-ray. ARDS management remains largely supportive, with a focus on optimizing mechanical ventilation strategies and addressing the underlying causes of lung injury. The current pharmacological approach for ARDS primarily focuses on corticosteroids, neuromuscular blocking agents, and beta-2 agonists, however, none has been definitively proven to be consistently effective in improving clinical outcomes. This review summarizes the latest evidence regarding the effectiveness and limitations of these pharmacological interventions, identifying key areas where further research is needed.

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Non-invasive SpO2/FiO2 ratio (SFR) as surrogate for PaO2/FiO2 ratio (PFR): A scoping review

Madhura Reddy1, Malavika Kulkarni2, Sushma Thimmaiah Kanakalakshmi2, Laxmi Shenoy2, Rama Rani KrishnaBhat2

1 Department of Respiratory Therapy, Manipal College of Health Professions, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India
2 Department of Anesthesiology, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India

DOI: 10.2478/jccm-2025-0024

Patient oxygenation significantly impacts clinical outcomes, and continuous monitoring is essential, especially in critical care settings where hypoxia is the leading cause of mortality. PFR (PaO2/FiO2 ratio or P/F ratio) is an invasive method for measuring oxygenation requiring arterial blood gas (ABG) sampling, however it carries complications making non-invasive methods more desirable. SFR (SpO2/FiO2 ratio or S/F ratio), a non-invasive tool based on pulse oximetry, provides a cost-effective and rapid way to monitor oxygenation status, especially in settings where advanced methods are unavailable. A total of 575 articles were screened from databases including Web of Science, Scopus, PubMed, and CINAHL, with 32 articles meeting the inclusion criteria for this scoping review wherein SFR was used as a surrogate for PFR and a diagnostic tool for acute lung injury and ARDS. A total of 81,637 patient records were analyzed, including ABG values, pulse oximetry readings, mechanical ventilator settings, and patient diagnoses. The study population included adults, pediatric patients, and neonates admitted to critical care units, with common diagnoses including acute hypoxemic respiratory failure, ARDS, and COVID-19. In the context of COVID-19, SFR was used to predict the need for mechanical ventilation, with a cut-off of 300 indicating a threshold for imminent ventilation requirement. The studies demonstrated statistically significant sensitivity and specificity for SFR, highlighting its utility as a non-invasive tool for assessing oxygenation status. SFR has shown potential as a reliable non-invasive surrogate for determining oxygenation status across all populations.

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Characteristics and temporality of the ventilatory techniques in the management of acute respiratory distress syndrome: A scoping review

Théo Battalian1, Raúl Escudero Romero1, Arianne Barzaga Molina2

1 Department of Physiotherapy, School of Medicine, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Spain
2 Department of Kinesiology, Faculty of Medicine, Clínica Alemana Universidad del Desarrollo, Santiago, Chile

DOI: 10.2478/jccm-2025-0019

Introduction: Acute Respiratory Distress Syndrome (ARDS) is a critical condition characterised by acute respiratory failure due to increased alveolar-capillary membrane permeability. This leads to non-cardiogenic pulmonary oedema, hypoxemia, and impaired respiratory compliance, significantly impacting patients’ survival and quality of life. The management of ARDS involves various ventilatory and non-ventilatory therapies. Understanding the optimal timing and application of these therapies is crucial for improving patient outcomes.
Aim of the study: This scoping review aims to identify and synthesise the ventilatory techniques used in managing ARDS, focusing on their temporality and the interplay between different therapies. The study seeks to synthesize the available evidence and summarize current management strategies, highlighting areas for further research and improvement in ARDS care.
Material and Methods: A systematic search of PubMed, EBSCO, and ScienceDirect databases was conducted, following the Joanna Briggs Institute guidelines (2015), for articles published between 2013 and 2023. Studies involving adult patients (18 years or older) diagnosed with ARDS and receiving ventilatory support in the ICU were included. Exclusion criteria included other acute respiratory pathologies, clinically extreme obese patients, and patients with tracheostomy.
Results: 437 articles were identified through the database search, of which 23 met the inclusion criteria and were included in the final review. Most articles were published between 2015-2019 (43.5%), originated from the USA (34.78%), and employed observational study designs (73.91%). The included studies reported on patients aged between 23 and 79 years, with intrapulmonary causes being the most common aetiology for ARDS. Various ventilatory strategies were identified, including conventional oxygen therapy, high-flow nasal cannula (HFNC), non-invasive ventilation (NIV), invasive ventilation (IMV), and combined approaches. Temporality was reported in 35% of the articles, but none of them as their primary focus.
Conclusions: The review highlights the diversity of ventilatory techniques employed in ARDS management and the importance of individualizing treatment strategies based on patient response and disease severity. The temporality of these interventions remains a crucial aspect, requiring further investigation to establish clearer guidelines for optimizing the timing and sequence of ventilatory support in ARDS. The findings underscore the need for future research to focus on patient-centred outcomes and the long-term implications of ARDS management, including quality of life and functional status.

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Management strategies and outcomes predictors of interstitial lung disease exacerbation admitted to an intensive care setting: A narrative review

Ans Alamami

Department of Critical Care Medicine, Hamad General Hospital, Doha, Qatar

DOI: 10.2478/jccm-2025-0013

Background: Interstitial lung disease (ILD) is a cluster of diseases that affect the lungs, characterized by different degrees of inflammation and fibrosis within the parenchyma. In the intensive care unit (ICU), ILD poses substantial challenges because of its complicated nature and high morbidity and mortality rates in severe cases. ILD pathophysiology frequently entails persistent inflammation that results in fibrosis, disrupting the typical structure and function of the lung. Patients with ILD frequently experience dyspnea, non-productive cough, and tiredness. In the ICU setting, these symptoms may worsen and lead to signs of acute respiratory failure with significantly impaired gas physiology.
Methodology: A systematic search was conducted in reputable databases, including PubMed, Google Scholar, and Embase. To ensure a comprehensive search, a combination of keywords such as “interstitial lung disease,” “intensive care,” and “outcomes” was used. Studies published within the last ten years reporting on the outcomes of ILD patients admitted to intensive care included. 
Result: Effective management of ILD in an ICU setting is challenging and requires a comprehensive approach to address the triggering factor and providing respiratory support, Hypoxemia severity is a critical predictor of mortality, with lower PaO2/FiO2 ratios during the first three days of ICU admission associated with increased mortality rates. The need for mechanical ventilation, particularly invasive mechanical ventilation (IMV), is a significant predictor of poor outcomes in ILD patients. Additionally, higher positive end-expiratory pressure (PEEP) settings, and severity of illness scores, such as the Acute Physiology and Chronic Health Evaluation (APACHE) score, are also linked to increased mortality. Other poor prognostic factors include the presence of shock and pulmonary fibrosis on computed tomography (CT) images. Among the various types of ILDs, idiopathic pulmonary fibrosis (IPF) is associated with the highest mortality rate. Furthermore, a high ventilatory ratio (VR) within 24 hours after intubation independently predicts ICU mortality.
Conclusion: This literature review points out outcome predictors of interstitial lung disease in intensive care units, which are mainly hypoxemia, the severity of the illness, invasive ventilation, the presence of shock, and the extent of fibrosis on CT Images.

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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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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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