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Patients treated with ECMO are at great risk of nosocomial infections, and around 10% of isolates are gram-positive pathogens. Linezolid (LZD) is effective in the treatment of these infections but appropriate dosing is challenging. The aim was to evaluate the occurrence of thrombocytopenia during ECMO when treated with LZD. An LZD trough concentration of 8 mg/L was set as the cutoff value for thrombocytopenia occurrence among critically ill patients who received parenteral LZD therapy at a dose of 600 mg every 8 h during ECMO. Eleven patients were included in this prospective observational study. Median LZD trough concentrations were 7.85 (interquartile range (IQR), 1.95-11) mg/L. Thrombocytopenia was found in 81.8% of patients. Based on the median LZD trough concentrations cutoff value, patients were divided into two groups, 1.95 (IQR, 0.91-3.6) and 10.3 (IQR, 9.7-11.7) mg/L, respectively. Median platelet values differed significantly between groups on admission, ECMO day 0, ECMO day 1, and LZD sampling day [194 and 152.5, (p < 0.05)], [113 and 214, (p < 0.05)], [76 and 147.5, (p < 0.01)], and [26 and 96.5, (p < 0.01)], respectively. Duration of LZD therapy was similar between the groups. Significant platelet reduction was observed in both groups, emphasizing the need for closer monitoring to prevent LZD-associated thrombocytopenia.

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Drowning remains a significant global health concern, claiming over 300,000 lives annually, with a disproportionate impact on young individuals in low-and middle-income countries. Conventional mechanical ventilation, while common, falls short in addressing the hypoxemia and hypercapnia often observed in severe near-drowning cases. Veno-venous extracorporeal membrane oxygenation (vvECMO) emerges as a critical intervention for cardiopulmonary failure post-drowning. This case report delves into the pivotal role of ischemia-reperfusion injury (IRI) in a near-drowning-related pathology. Following the initial insult, reoxygenation exacerbates the inflammatory cascade, resulting in a surge of pro-inflammatory mediators. In this context, CytoSorb®, a hemoadsorption cartridge, demonstrates promise by effectively removing these mediators from circulation. This report outlines its application in a critically ill adolescent patient who experienced near-drowning, presenting a compelling case for CytoSorb as an adjunctive therapy in managing IRI-induced hyperinflammation.

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OBJECTIVE: This retrospective (matched paired) clinical trial aimed to compare the efficacy of dexamethasone vs. methylprednisolone at equipotent (high) doses in patients with coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS). METHODS: A total of 347 patients with moderate and severe COVID-19-associated ARDS were administered either a high (equipotent) dose of dexamethasone (32 mg) or methylprednisolone (180 mg) for a duration of up to 10 days. All participants received the standard of care for critically ill COVID-19 patients. RESULTS: The primary outcomes included length of stay in the ICU, ICU mortality, and discharge from the hospital. Based on the obtained results, a tendency towards more favorable clinical outcomes concerning the length of stay in the ICU (in the group of patients treated with non-invasive mechanical ventilation (NIV), p<0.05), ICU mortality, and discharge from the hospital (in the group of patients who were intubated, p<0.05) in patients receiving the high dose of dexamethasone compared to those receiving methylprednisolone was observed. CONCLUSION: It appears that severe cases of COVID-19, especially intubated ones, treated with high doses of dexamethasone have a more favorable clinical outcome than the use of equipotent doses of methylprednisolone. However, larger multicenter studies are needed to validate our observations.

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During veno-venous extracorporeal membrane oxygenation (vv ECMO) therapy, antimicrobial drugs are frequently used, and appropriate dosing is challenging due to there being limited data to support the dosage. Linezolid is effective against multidrug-resistant Gram-positive pathogens frequently isolated in ECMO patients. In total, 53 steady-state linezolid levels were obtained following 600 mg intravenous (IV) injections every 8 h, and these were used to develop a population pharmacokinetic (PopPK) model in patients with COVID-19-associated acute respiratory distress syndrome (CARDS) on vv ECMO. The data were analyzed using a nonlinear mixed-effects modelling approach. Monte Carlo simulation generated 5000 patients' individual PK parameters and corresponding concentration-time profiles using the PopPK model, following the administration of 600 mg/8 h (a higher-than-standard dosing) and 600 mg/12 h (standard). The probabilities of pharmacokinetic/pharmacodynamic (PK/PD) target attainment (PTA) and the cumulative fraction of responses (CFR) for three pathogens were calculated and compared between the two dosing scenarios. Linezolid 600 mg/8 h was predicted to achieve greater than or equal to 85%Tf>MIC in at least 90% of the patients with CARDS on vv ECMO compared to only approximately two thirds of the patients after dosing every 12 h at a minimal inhibitory concentration (MIC) of 2 mg/L. In addition, for the same MIC, fAUC24/MIC ≥ 80 was achieved in almost three times the number of patients following an 8-h versus a 12-h interval. PopPK simulation predicted that a significantly higher proportion of the patients with CARDS on vv ECMO would achieve the PK/PD targets following the 8-h dosing interval compared to standard linezolid dosing. Nevertheless, the safety concern, in particular, for thrombocytopenia, with higher-than-standard linezolid dosage is reasonable, and consequently, monitoring is essential.

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Acute respiratory distress syndrome (ARDS) is a severe clinical condition characterized by acute respiratory failure and a high mortality risk despite conventional mechanical ventilatory support. Veno-venous extracorporeal membrane oxygenation (vvECMO) has emerged as an effective life-support technology for patients with ARDS. However, complications may arise following the decannulation of vvECMO, with a relatively frequent development of systemic hyperinflammation (SHI). Among the various treatment strategies for SHI, the use of hemoadsorption with CytoSorb® has shown promising results in removing excessive levels of cytokines and attenuating the hyperinflammatory response. In this case series, we present three critically ill patients with ARDS secondary to pneumonia who underwent vvECMO and subsequently received prophylactic hemoadsorption with CytoSorb® following decannulation as a part of our clinical practice. This case series aims to describe the potential positive effects of hemoadsorption in preventing the development of SHI after vvECMO decannulation in ARDS patients.

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BACKGROUND: Critical care medicine is a young branch of medicine, of which the development was much faster in High Income Countries (HICs) than in Low Resources Settings (LRS). Slovenia, as one of the successor states of former Yugoslavia, passed the process of transition and joined the European Union successfully. On the contrary, Bosnia and Herzegovina (B&H) went through the extremely difficult process of transition (four years of civil war), which left a deep scar to the healthcare system, including critical care medicine. OBJECTIVE: To examine the impact of HICs on the development of critical care in LRS. METHOD: This review examined the process of growing up the first modern Medical Intensive Care Unit (MICU) in the Republic of Srpska. RESULTS: The five-year process of transferring critical care knowledge from Slovenia to the health care system of Republic of Srpska has contributed to the existence of modern and state of the art MICU with tremendous social effects. CONCLUSION: The model of using the impact of HICs for improving critical care in LRS can be extrapolated to other similar settings.

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Background: Response to the outbreak of poliomyelitis in mid-1950 led to recognition and consequent development of critical care. Seventy years later the humankind was struck by COVID-19, another major challenge for critical care medicine which was especially big in Low-Resources-Settings where more than two thirds of the world population live, including the population of the Republic of Srpska (RS). Design and methods: The main aim was to show an overview of all interventions in order to boost hospitals' capacities to the level which is sufficient to manage high amount of critically ill COVID-19 patients in the RS. A before-after cohort study design was conducted to evaluate the effects of interventions for increase in preparedness and capacity of ICUs for admission and treatment of COVID-19 critically ill patients in nine hospitals in the RS. Results: Following interventions, the biggest and university affiliated hospital in the RS has increased ICU capacities: total number of ICU beds increased by 38% and number of ventilators by 114%. Availability of machines for veno-venous extracorporeal membrane oxygenation (vvECMO) increased by 100%. Number of doctors who were involved in treatment of critically ill patients increased by 47% and nurse/patient's ratio reached 1:2.5. Similarly, all other hospitals experienced boosting of ICU beds by 189% and ventilators by 373% while number of doctors increased by 108% and nurse/patient's ratio reached 1:4. Conclusion: All interventions implemented during COVID-19 pandemic outbreak in the RS resulted in increasing capacity for treatment of critically ill patients, but the education of health care professionals was identified as the most important conducted intervention.

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INTRODUCTION: This study was created to analyze dynamic alterations in coagulation, hematological and biochemical parameters and their association with mortality of COVID-19 patients. To identify the most sensitive biomarkers as predictors of mortality more research is required. METHODS: The present study was a prospective, one-year-long observational study conducted on all critically ill, COVID-19 patients with respiratory failure. The following data were collected: demographic and clinical characteristics of the study population, comorbidities, coagulation, biochemical and hematological parameters. The primary outcome was the proportion of patients who died. RESULTS: 91 patients with median age 60 (50-67), 76.9% male, met the acute respiratory distress syndrome criteria. It was tested whether dynamic change (delta-Δ) of parameters that were found to be predictors of mortality is independently associated with poor outcome. Adjusted (multivariate) analysis was used, where tested parameters were corrected for basic and clinical patients characteristics. The only inflammatory parameter which dynamic change had statistically significant odds ratio was ΔCRP (p < 0.005), while among coagulation parameters statistically significant OR was found for Δ fibrinogen (p < 0.005) in predicting mortality. CONCLUSION: Monitoring of coagulation, hematological and biochemical parameters abnormalities and their dynamical changes can potentially improve management and predict mortality in critically ill COVID -19 patients.

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Background and Objectives: Coronavirus disease 2019 (COVID-19) is a novel infectious disease that has spread worldwide. As of 5 March 2020, the COVID-19 pandemic has resulted in approximately 111,767 cases and 6338 deaths in the Republic of Srpska and 375,554 cases and 15,718 deaths in Bosnia and Herzegovina. Our objective in the present study was to determine the characteristics and outcomes of critically ill pregnant/postpartum women with COVID-19 in the Republic of Srpska. Materials and Methods: The retrospective observational study of prospectively collected data included all critically ill pregnant/postpartum women with COVID-19 in a university-affiliated hospital between 1 April 2020 and 1 April 2022. Infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) from nasopharyngeal swab specimens and respiratory secretions. Patients' demographics, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analysed. Results: Out of the 153 registered pregnant women with COVID-19 treated at the gynaecology department of the University Clinical Centre of the Republic of Srpska, 19 (12.41%) critically ill pregnant/postpartum women (median age of 36 (IQR, 29-38) years) were admitted to the medical intensive care unit (MICU). The mortality rate was 21.05% (four patients) during the study period. Of all patients (19), 14 gave birth (73.68%), and 4 (21.05%) were treated with veno-venous extracorporeal membrane oxygenation (vvECMO). Conclusions: Fourteen infants were born prematurely and none of them died during hospitalisation. A high mortality rate was detected among the critically ill pregnant/postpartum patients treated with mechanical ventilation and vvECMO in the MICU. The preterm birth rate was high in patients who required a higher level of life support (vvECMO and ventilatory support).

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End-stage renal disease and its treatment with continuous ambulatory peritoneal dialysis (CAPD) can affect almost all organs and organ systems including vascular endothelium. Consequently, disturbance in the production of vasoactive substances endothelin-1 (ET-1) and nitric oxide (NO) occurs in these patients. There are only a small number of studies that investigated the impact of long-term CAPD on imbalance in production of vasoactive substances ET-1 and NO among these patients. Therefore, our study aimed to investigate the impact of duration of CAPD on potential overproduction of ET-1 and NO in uremic patients. This study included 23 uremic patients [10 males, mean age: 56.3 (±16.2) years] treated with CAPD. All studied patients were further divided into subgroups, groups A and B. Group A included patients on treatment with CAPD <5 years, and group B included those on treatment longer than five years. Our results showed that serum levels of these vasoactive substances are significantly higher among patients treated with CAPD longer than five years (ET-1: 51.24 ± 32.11 vs. 139.53 ± 42.42; NO: 15.50 ± 2.57 vs. 26.57 ± 5.96, respectively). We concluded that imbalance in production of vasoactive substances is present in long-term CAPD treatment and this imbalance can lead to disturbance in the local blood flow control.

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BACKGROUND: We are facing the outburst of coronavirus disease 2019 (COVID-19) defined as a serious, multisystem, disorder, including various neurological manifestations in its presentation. So far, autonomic dysfunction (AD) has not been reported in patients with COVID-19 infection. AIM: Assessment of AD in the early phase of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus). PATIENTS AND METHODS: We analyzed 116 PCR positive COVID-19 patients. After the exclusion of 41 patients with associate diseases (CADG), partitioned to patients with diabetes mellitus, hypertension, and syncope, the remaining patients were included into a severe group (45 patients with confirmed interstitial pneumonia) and mild group (30 patients). Basic cardiovascular autonomic reflex tests (CART) were performed, followed by beat-to-beat heart rate variability (HRV) and systolic and diastolic blood pressure variability (BPV) analysis, along with baroreceptor sensitivity (BRS). Non-linear analysis of HRV was provided by Poincare Plot. Results were compared to 77 sex and age-matched controls. RESULTS: AD (sympathetic, parasympathetic, or both) in our study has been revealed in 51.5% of severe, 78.0% of mild COVID-19 patients, and the difference compared to healthy controls was significant (p = 0.018). Orthostatic hypotension has been established in 33.0% COVID-19 patients compared to 2.6% controls (p = 0.001). Most of the spectral parameters of HRV and BPV confirmed AD, most prominent in the severe COVID-19 group. BRS was significantly lower in all patients (severe, mild, CADG), indicating significant sudden cardiac death risk. CONCLUSION: Cardiovascular autonomic neuropathy should be taken into account in COVID-19 patients' assessment. It can be an explanation for a variety of registered manifestations, enabling a comprehensive diagnostic approach and further treatment.

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INTRODUCTION: Hydrogen ion concentration which is expressed as pH value is in human blood maintained in narrow physiological range (7.36-7.44 in arterial blood). This range is crucial for normal functioning of most biochemical reactions. Extreme acidosis with pH < 6.8 is incompatible with life, unless pathophysiologic process is rapidly reversed. Timely, standardized, and structured approach to assessment and management of extreme critical illness is essential to maximize the chances of patient's survival. CASES: We present a series of 3 critically ill patients admitted to Medical intensive care unit (MICU) diagnosed with extreme metabolic acidosis (pH ⩽ 6.8). Each patient was treated using Checklist for Early Recognition and Treatment of Acute Illness and INjury (CERTAIN) which is a standard decision support tool in our MICU. Causes of extreme metabolic acidosis included hemorrhagic shock, sepsis, and acute renal failure and diabetic ketoacidosis. Rapid assessment, prompt resuscitation (IV fluids, vasopressors, mechanical ventilation, and renal replacement), and application of specific causal treatment led to positive outcomes in all 3 patients. DISCUSSION: Medical physiology textbooks set the lower limit of pH value at which life is possible to 6.8. However, examples from clinical practice show that if adequate resuscitation measures are taken early in the acute phase of the disease, the biochemical cascade of reactions that are considered irreversible (at pH ⩽ 6.8) may be reversed after all. CONCLUSION: Critical care approach to extreme metabolic acidosis is a prime example of applied clinical physiology where basic science and clinical practice connect. With these case series we show that timely and structured approach to critical illness shifts the boundaries of reversibility for some of the most severe physiologic derangements.

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Introduction: Treatment of sepsis and septic shock can be a challenge even for intensive care units (ICUs) in high income countries, but it is especially difficult for ICUs with limited resources. Aim: To evaluate the impact of CERTAIN on treatment of critically ill septic patients in low-resource medical ICU. Materials and Methods: In a before-and-after study design, we compared clinical outcomes, processes, and complications (hospital acquired infections) 1 year before and 2 years after (2016 and 2017) introduction of CERTAIN. Results: A total of 125 patients with sepsis were prospectively identified for a 3-year period. Mean patient age, gender distribution, number of patients on mechanical ventilation (33 [76.7%] vs. 42 [84%] vs. 24 [75%]) and vasopressor use (23 [53.5%] vs. 34 [68%] vs. 24 [75%]) were similar before (2015) and 2 years after (2016 and 2017) the implementation of CERTAIN. Severity of illness (Simplified Acute Physiology Score II [SAPS II score]) was higher after the implementation. The checklist was incorporated in the daily practice with 100% adherence to its use. The duration of mechanical ventilation (5.3 ± 5.3 vs. 4.2 ± 3.6 vs. 3.7 ± 5.5), antibiotic treatment (8.2 ± 5.4 vs. 6.9 ± 4.1 vs. 5.8 ± 5.6), central venous catheter use (6.2 ± 5.7 vs. 5.7 ± 4.6 vs. 4.2 ± 6.1), ICU stay (8.4 ± 5.4 vs. 7.1 ± 4.1 vs. 5.8 ± 5.6), and the incidence of nosocomial infection (33.3% vs. 30% vs. 12.5%) decreased in the period after the onset of the intervention, but the results did not reach statistical significance. When adjusted for baseline characteristics, CERTAIN was not associated with hospital mortality (odds ratio 0.88, 0.38-2.04). Conclusion: CERTAIN was readily adopted in the ICU workflow and was associated with improvement in treatment of critically ill patients with sepsis.

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INTRODUCTION: This study was carried out to investigate the impact of duration of different renal replacement therapies such as hemodialysis and continuous ambulatory peritoneal dialysis on potential overproduction of endothelin-1 (ET-1) and pulmonary function tests in these patients. MATERIALS AND METHODS: The study included 26 patients (14 males, mean age 54.9±16.2 years) with end stage renal diseases (ESRD) receiving regular hemodialysis (HD) and 23 patients (10 males, mean age 55.8±15.8 years) with ESRD treated with continuous ambulatory peritoneal dialysis (CAPD). The spirometry values were recorded before the onset of HD and prior to emptying the peritoneal cavity in CAPD patients and ET-1 was measured using the enzyme immunoassay (EIA) methodology. Two groups of patients (groups 1 and 2) were further divided into subgroups (group A and group B). Groups A (1-A and 2-A) included patients treated with any type of renal replacement therapy (RRT) (HD or CAPD) less than 5 years, and groups B (1-B and 2-B) included patients treated with any type of RRT (HD or CAPD) longer than 5 years. RESULTS: Patients treated with HD or CAPD for more than five years were found to have significantly higher serum levels of ET-1 (HD = 41.49±21.28 vs. 185.13±73.67, p<0.01; PD = 51.24±32.11 vs. 139.53±42.42, p<0.01, respectively). Values of most pulmonary function parameters differed significantly between groups treated longer or shorter than 5 years: FVC (HD = 108.4±13.34 vs. 80.82±11.26, p<0.01; CAPD = 97.20±18.99 vs. 73.25±10.73, p<0.01, respectively), FEV1 (HD = 108.33±15.8 vs. 76.73±4.9, p<0.01; CAPD = 100.67±18.31 vs. 66.75±6.25, p<0.01, respectively). CONCLUSIONS: Prolonged duration of any type of renal replacement therapy is associated with higher serum levels of ET-1 and with lower pulmonary function tests in ESRD patients.

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In many areas of the world, critical care providers caring for COVID-19 patients lacked specific knowledge and were exposed to the abundance of new and unfiltered information. With support from the World Health Organization, we created a multimodal tele-education intervention to rapidly share critical care knowledge related to COVID-19 targeting providers in a region of Southeastern Europe. We delivered 60-minute weekly interactive tele-education sessions over YouTubeTM between March 2020 and May 2020, supplemented by a dedicated webpage. The intervention was reinforced using a secure social media platform (ViberTM), providing continuous rapid knowledge exchange among faculty and learners. A high level of engagement was observed, with over 2000 clinicians participating and actively interacting over a 6-week period. Surveyed participants were highly satisfied with the intervention. Tele-education interventions using social media platforms are feasible, low-cost, and effective methods to share knowledge during the COVID-19 pandemic.

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BACKGROUND: This study aimed to demonstrate that having clinical pharmacist as a member of oncology team in low and middle income countries might lead to significant reduction in the number of erlotinib interactions in the treatment of non-small cell lung cancer patients. METHODS: A group of 44 patients was labeled as intervention group and they were analyzed prospectively in the period from 1 January 2017 to 1 May 2018 during clinical pharmacist's participation in regular weekly multidisciplinary oncology team meetings. The control group consisted of 44 out of 110 patients treated with erlotinib before the involvement of a clinical pharmacist in oncology team, match paired with 44 patients in intervention group. RESULTS: Clinically significant interactions were identified in two-thirds of studied patients (57 out of 88). Most drug interactions, 38%, potentially result in decrease of serum concentration of erlotinib. Clinical pharmacist provided therapy modification suggestions for 32 out of 44 (72.72%) patients in the intervention group, most of which were accepted by doctors. In the intervention group, there were significantly less clinically significant interactions compared to the control group (10 versus 24, p = 0.002). Progression-free survival was significantly longer in the pharmacist's intervention group (p = 0.001). CONCLUSIONS: Clinical pharmacist's intervention led to significant decrease in erlotinib interactions which may result in treatment optimization of lung cancer patients.

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Background: This study looked at the characteristics and outcomes of critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the Western Balkans in the post-pandemic period. Materials and Methods: This retrospective observational study of medical records and associated data collected during the post-pandemic period included all mechanically ventilated adult patients of two university-affiliated hospitals of the Western Balkans between 1 January and 31 March 2019 who had influenza A (H1N1) pdm09 infection confirmed by real-time reverse transcriptase-polymerase chain reaction from nasopharyngeal swab specimens and respiratory secretions. Results: The study included 89 patients, 49 males (55.1%), aged 56.09 ± 12.64 years. The median time from shift from hospital time to intensive care unit was 1 day (range: 1-2). In the post-pandemic period, cases observed in this study were found to have the following comorbidities: cardiovascular diseases in 44 (49.4%) patients and diabetes in 21 (23.6%) patients. Thirty-one patients (34.8%) in this study were obese. All 89 patients (100%) experienced some degree of acute respiratory distress syndrome, and 39 (44%) had multiorgan failure. Eighty-three patients (93%) were intubated and mechanically ventilated, 6 (7%) received non-invasive mechanical ventilation, 12 (13%) were treated with vvECMO and 36 (40%) received renal replacement therapy. Vasoactive support was needed by 56 (63%) patients. The median duration of mechanical ventilation was 9 (6-15.5) days. The hospital mortality rate was 44%. Conclusion: Critically ill patients with confirmed influenza A (H1N1) pdm09 infection in the post-pandemic season were older, required vasoactive drugs more often, and there was a trend of higher survival compared to H1N1 infection patients in the previous pandemic seasons.

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Roles of nitric oxide (NO) and endothelin-1 (ET-1) in the local regulation of blood flow under physiological conditions are important and well known, while data on their effects and interactions in conditions of hyperbaric hyperoxia is still insufficient. This was a prospective observational study which included patients who underwent hyperbaric oxygen therapy (HBOT) in accordance with existing therapeutic protocol for peripherial arterial disease (PAD) during time period of six months, between january and july of 2016. Clinical stage of PAD according to Fontain was taken into account, as well as risk factors, demographic, anthropometric and clinical characteristics of studied patients. The study included 64 patients with a mean age (±Sd) 60.2±12.7 years, of whom 28 were female. Patients' NO serum levels in all observed categories before and after HBOT were not signifficantly different, except for stage II PAD (NObefore HBOT 21.9±9.6 vs. NOafter HBOT 26.2±12.1 (p = 0.04)). On the contrary, in all studied patients ET-1 level increased signifficantly after HBOT (ET-1before HBOT 4.2±11.6 vs. ET-1after 18.3±21.0 (p < 0.001)). Treatment of PAD using HBOT leads to the predominance of vasoconstrictor effects probably caused by elevation of serum ET-1 concentrations, while other factors such as exposure time to hyperbaric conditions, activation of antioxidant molecules, and the influx of other interfering substances must be considered in interpreting the effects of NO molecules.

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