Category Archives: Review

Balanced crystalloids versus normal saline for initial fluid resuscitation in diabetic ketoacidosis: A systematic review and meta-analysis of randomized controlled trials

Khaled Ahmed Reda Soliman1, Ahmed Osman Hassan Ali2, Farrukh Ameer3, Bashaer Alharbi4, Mohamed Hany Elmasry5, Rawabi Mohammed Alwashmi6, Bandar Saad Alshreef7, Mohammad Saleh H Almabouth8, Kinda Ahmed Hardan9, Aymen Ali Alqurain10

1 Department of Emergency Medicine, Armed Forces Hospital Southern Region, Khamis Mushait, Saudi Arabia
2 Department of Critical Care Medicine, Dr. Soliman Fakeeh Hospital, Riyadh, Saudi Arabia
3 Department of Adult Cardiology, Dr. Soliman Fakeeh Hospital, Fakeeh Care Group, Riyadh, Saudi Arabia
4 Department of Clinical Pharmacy, Ministry of Health, Jeddah, Saudi Arabia
5 Department of ICU and Anesthesia, Care Medical Hospital Almalaz, Riyadh, Saudi Arabia
6 Burydah College, Qassim, Saudi Arabia
7 Healthcare Management, College of Applied Medical Sciences, Shaqra University, Shaqra, Saudi Arabia
8 Department of Internal Medicine, NSH, Medina, Saudi Arabia
9 Senior House Officer of General Medicine, International University of Africa, Riyadh, Saudi Arabia
10 Department of Clinical Practice, Faculty of Pharmacy, Northern Border University, Saudi Arabia

DOI: 10.2478/jccm-2026-0031

Objective: To systematically synthesize evidence from RCTs that evaluate the efficacy and safety of balanced crystalloids compared with normal saline for initial fluid resuscitation of patients with DKA.
Methods: This systematic review and meta-analysis were performed considering PRISMA guidelines and was registered in PROSPERO. A comprehensive search was performed to identify RCTs comparing balanced crystalloids with normal saline in adults and children with DKA. The risk of bias was assessed by using Cochrane RoB 2 tool. A random-effects meta-analysis was performed using R software to calculate pooled Mean Differences for continuous outcomes and Odds Ratios for dichotomous outcomes with 95% Confidence Intervals.
Results: Eleven RCTs were included. In the quantitative synthesis of six RCTs (n = 491) using continuous time-to-event data, balanced crystalloids were not associated with a statistically significant reduction in time to DKA resolution compared with normal saline (Mean Difference [MD] = -1.50 hours; 95% CI: -3.79 to 0.79; p=0.15), with moderate heterogeneity (I2 = 36.2%). The 95% prediction interval ranged from -5.44 to 2.44 hours. However, balanced crystalloids resulted in a significantly greater increase in serum bicarbonate at 12 hours (MD = +2.50 mmol/L; 95% CI: 1.51 to 3.48; p=0.004; I2 = 0.0%). Subgroup analyses by fluid type, DKA severity, and age group showed no significant subgroup differences.
Conclusion: Initial fluid resuscitation with balanced crystalloids was not associated with a shorter time to DKA resolution compared with normal saline, and they were associated with a rapid increase in serum bicarbonate levels; however, this biochemical improvement did not translate into a shorter time to DKA resolution or other clinical benefits. The choice of crystalloids for initial DKA resuscitation remains an area of clinical equipoise because of the substantial heterogeneity and methodological limitations of the available evidence, emphasizing the need for further high-quality research.

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High-fidelity simulation programs in ICU-related ethical non-technical skills training: A narrative review

Alexandra-Maria Boldis, Cristina Petrisor, Darius Turcas, George-Calin Dindelegan

Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.2478/jccm-2026-0021

Objective: Is there a place for non-technical skills training in the ICU? And what teaching strategy should we implement in this process? This narrative review analyzes the benefits of teaching ethics in the ICU environment by applying high-fidelity simulation scenarios to real-life situations, thereby improving communication, moral reasoning, self-reliance, cooperation, and perceptual skills.
Methods: In the literature, there are few publications on the training of ICU residents in non-technical skills and ethical dilemmas using high-fidelity simulations. After searching and scoping the database, we have identified 8 publications relevant to this narrative review.
Results: In the reviewed studies, the main topics discussed and rehearsed using simulations were as follows: communicating an adverse event during anesthesia in one study [5], delivering bad news in two studies [14,18], the ethics of end-of-life care, and the do-not-resuscitate order in three studies [5,18,19], and ethical non-technical skills such as communications, teamwork and confidence in emergent real-life situations in four studies [15,16,17,20].
Conclusions: Developing a more structured approach to teaching ethics-related events is important, particularly in critical care settings. All reviewed studies reached the same conclusion: high-fidelity simulation training is an educational strategy for ICU residents to develop a foundation in ethical considerations and moral reasoning by improving ethical non-technical skills, such as confidence, communication, teamwork, delivering bad news, and end-of-life care.

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Bimodal distribution of trauma-related acute kidney injury (TrAKI): A clinical review

Eleni Sertaridou1, Christina Alexopoulou2, Vasilios Papaioannou2

1 ICU Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece
2 Medical School, Democritus University of Trace; ICU Department, University Hospital of Alexandroupolis, Alexandroupolis, Greece

DOI: 10.2478/jccm-2026-0009

Severe trauma remains the leading cause of mortality and disability among young adults. Trauma-related Acute Kidney Injury (TrAKI) has been associated with worse outcomes, increased healthcare costs, and higher morbidity among survivors. The review aims to evaluate, from a pathophysiological perspective, the risk factors for TrAKI at different time points of trauma treatment, highlighting the need for early diagnosis of the syndrome and the implementation of preventive measures.
TrAKI is triggered at the time the injury occurs and further worsened by factors related to resuscitation process and potential complications. Severe trauma, due to hemorrhagic shock, is considered to act as the first hit. All subsequent necessary lifesaving procedures applied in trauma management, such as fluid resuscitation, massive transfusion and emergency surgery, could act as second hit, triggering “early” TrAKI, within 24-72 hours, due to renal hypoperfusion, hypoxia and reperfusion injury (R/I). The following critical care treatment, seems to act as the final third hit, resulting in “late” TrAKI appeared in 5-7 days or even later, caused by distal complications.
The incidence of TrAKI shows a biphasic pattern, with an “early “peak within 2-3 days after trauma, and a “delayed” occurring a week or later. This distinction could be of clinical importance because of its disparate pathophysiology and outcome. Early recognition of risk factors and diagnosis of TrAKI could improve the application of preventive measures and therapeutic treatment, reducing its prevalence.

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Non-thyroidal illness (euthyroid sick) syndrome: Laboratory aspects and clinical significance in critically ill patients and other diseases – A narrative review

Liong Boy Kurniawan

Department of Clinical Pathology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia

DOI: 10.2478/jccm-2026-0008

Formerly termed euthyroid sick syndrome, non-thyroidal sickness syndrome (NTIS) is a disorder that frequently occurs in acute or chronic illnesses that alter the levels of thyroid hormone and patterns, even in the absence of hypothalamic-pituitary-thyroid axis problems or diseases. The primary findings on the thyroid hormone panel in NTIS are elevated reverse T3 (rT3) and decreased triiodothyronine (T3) levels, which may be followed by other thyroid hormone abnormalities, such as thyroid-stimulating hormone (TSH) and thyroxine (T4). The incidence of NTIS increases among hospitalized patients with critical illness, and there is an associated increase in mortality. NTIS is also associated with worsening outcomes during and after treatment in patients hospitalized with infectious or non-infectious diseases, such as cardiovascular, kidney, lung, diabetes mellitus, autoimmune, and other diseases. In patients with critical illnesses admitted to the Intensive Care Unit (ICU), serial examination of a panel of thyroid function tests, including T3 and rT3, is necessary to estimate the phase of the disease (whether acute, chronic, or recovery) and can be used to predict the risk of mortality during treatment.

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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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