Category Archives: Original Research

Prognostic Value of Bone Formation and Resorption Proteins in Heterotopic Ossification in Critically-Ill Patients. A Single-Centre Study

Alice Georgia Vassiliou¹, Edison Jahaj¹, Zafeiria Mastora¹, Ioannis Karnezis², Ioanna Dimopoulou¹, Stylianos E. Orfanos¹, Anastasia Kotanidou¹

1 First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece
2 Department of Orthopedics, Evangelismos Hospital, Athens, Greece

DOI: 10.2478/jccm-2020-0046

Introduction: A potential complication in critically ill patients is the formation of bone in soft tissues, termed heterotopic ossification. The exact pathogenetic mechanisms are still undetermined. Bone morphogenetic proteins induce bone formation, while signalling through the receptor activator of nuclear factor kappa-Β (RANK) and its ligand (RANKL), regulates osteoclast formation, activation, and survival in normal bone modelling and remodelling. Osteoprotegerin protects bone from excessive bone loss by blocking RANKL from binding to RANK.
Aim: The study aimed to investigate these molecules as potential prognostic biomarkers of heterotopic ossification development in critically ill patients.
Materials and Methods: In this prospective observational study, BMP-2, RANKL, and osteoprotegerin were measured by ELISA in twenty-eight critically-ill, initially non-septic patients, on admission to an ICU, seven days post-admission, and thirty days after ICU discharge.
Results: In the critically-ill cohort, nine of the twenty-eight patients developed heterotopic ossification up to the 30-day follow-up time-point. The patients who developed heterotopic ossification exhibited significantly reduced BMP-2 and RANKL levels on ICU admission, compared to patients who did not; Osteoprotegerin readings were similar in both groups.
Conclusions: Critically-ill patients who will subsequently develop heterotopic ossification, have significantly lower BMP-2 and RANKL levels at the time of ICU admission, suggesting that these proteins may be useful as prognostic markers for this debilitating condition.

Keywords: osteoprotegerin, critically-ill, heterotropic ossification, receptor activator of nuclear factor kappa-Β ligand, bone morphogenetic proteins

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Mortality Rate and Predictors among Patients with COVID-19 Related Acute Respiratory Failure Requiring Mechanical Ventilation: A Retrospective Single Centre Study

Christophe de Terwangne¹, Antonio Sorgente², Redente Tortora³, Diana Cheung³, Frederic Duprez³, Sammy Place¹, Jerome R. Lechien⁴, Lucio Capulzini², Michael De Cubber², Sven Saussez⁴, Fabio Silvio Taccone⁵, Shahram Mashayekhi³

1 Department of Internal Medicine, Centre Hospitalier EpiCURA Hornu, Hornu, Belgium
2 Department of Cardiology, Centre Hospitalier EpiCURA, Hornu, Belgium
3 Department of Intensive Care, Centre Hospitalier EpiCURA, Hornu, Belgium
4 Department of Human Anatomy and Experimental Oncology, University of Mons, Mons, Belgium
5 Department of Intensive Care, Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium

DOI: 10.2478/jccm-2020-0043

Aim: The objective of the study was to assess mortality rates in COVID-19 patients suffering from acute respiratory distress syndrome (ARDS) who also requiring mechanical ventilation. The predictors of mortality in this cohort were analysed, and the clinical characteristics recorded.
Material and method: A single centre retrospective study was conducted on all COVID-19 patients admitted to the intensive care unit of the Epicura Hospital Center, Province of Hainaut, Belgium, between March 1st and April 30th 2020.
Results: Forty-nine patients were included in the study of which thirty-four were male, and fifteen were female. The mean (SD) age was 68.8 (10.6) and 69.5 (12.6) for males and females, respectively. The median time to death after the onset of symptoms was eighteen days. The median time to death, after hospital admission was nine days. By the end of the thirty days follow-up, twenty-seven patients (55%) had died, and twenty–two (45%) had survived. Non-survivors, as compared to those who survived, were similar in gender, prescribed medications, COVID-19 symptoms, with similar laboratory test results. They were significantly older (p = 0.007), with a higher co-morbidity burden (p = 0.026) and underwent significantly less tracheostomy (p < 0.001). In multivariable logistic regression analysis, no parameter significantly predicted mortality.
Conclusions: This study reported a mortality rate of 55% in critically ill COVID-19 patients with ARDS who also required mechanical ventilation. The results corroborate previous findings that older and more comorbid patients represent the population at most risk of a poor outcome in this setting.

Keywords: mortality, critically ill, mechanical ventilation, Coronavirus, SARS-CoV-2

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The Susceptibility of MDR-K. Pneumoniae to Polymyxin B Plus its Nebulised Form Versus Polymyxin B Alone in Critically Ill South Asian Patients

Md. Jahidul Hasan¹, Raihan Rabbani², Ahmad Mursel Anam³, Ario Santini⁴, Shihan Mahmud Redwanul Huq²

1 Clinical Pharmacy Services, Square Hospitals Ltd., Dhaka, Bangladesh
2 ICU and Internal Medicine, Square Hospitals Ltd., Dhaka, Bangladesh
3 High Dependency Unit (HDU), Square Hospitals Ltd., Dhaka, Bangladesh
4 University of Medicine, Pharmacy, Science and Technology of Targu Mures, Romania

DOI: 10.2478/jccm-2020-0044

Introduction: Critically ill patients in intensive care units are at high risk of dying not only from the severity of their illness but also from secondary causes such as hospital-acquired infections. USA national medical record-data show that approximately 10% of patients on mechanical ventilation in an intensive care unit developed ventilator-associated pneumonia. Polymyxin B has been used intravenously in the treatment of multi-drug resistant gram-negative infections, either as a monotherapy or with other potentially effective antibiotics, and the recent international guidelines have emphasised the use of nebulised polymyxin B together with intravenous polymyxin B to gain the optimum clinical outcome in ventilator-associated pneumonia cases caused by multi-drug resistant gram-negative infections.
Methods: One hundred and seventy-eight patients with ventilator-associated pneumonia due to multi-drug resistant K. pneumoniae were identified during the study period. Following the inclusion and exclusion criteria, 121 patients were enrolled in the study and randomly allocated to two study groups. Group 1 patients were treated with intravenous Polymyxin B plus nebulised polymyxin B (n=64) and Group 2 patients with intravenous Polymyxin B alone (n=57). The study aimed to compare the use of Polymyxin B plus its nebulised form to polymyxin B alone, in the treatment of MDR-K. pneumoniae associated ventilator-associated pneumonia in critically ill patients.
Results: In Group 1, a complete clearance of K. pneumoniae was found in fifty-nine patients (92.1%; n=64) compared to forty patients (70.1%, n=57) in the Group 2 (P<0.003). The average time till extubation was significantly higher in Group 2 compared to Group 1 (P<0.05). The total length-of-stay in the ICU was significantly higher in Group 2 compared to Group 1. (P<0.05). These results support the view that the Polymyxin B dual-route regime may be considered as an appropriate antibiotic therapy, in critically ill South Asian patients with ventilator-associated pneumonia.

Keywords: ventilator-associated pneumonia, multi-drug resistant K. pneumoniae, Polymyxin B

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Post-Traumatic Stress Disorder and Burnout in Healthcare Professionals During the SARS-CoV-2 Pandemic: A Cross-Sectional Study

Ioannis Ilias¹, Vassiliki Mantziou², Efstratios Vamvakas², Efstathia Kampisiouli², Maria Theodorakopoulou², Chariklia Vrettou², Evangelia Douka², Alice G. Vassiliou², Stylianos Orfanos², Anastasia Kotanidou², Ioanna Dimopoulou²

1 Elena Venizelou Hospital, Athens, Greece
2 National and Kapodistrian University of Athens

DOI: 10.2478/jccm-2020-0042

Introduction: Healthcare professionals who are directly involved in the diagnosis, treatment, and general care of patients with SARS-CoV-2 are at risk of developing adverse psychological reactions. A cross-sectional study of healthcare professionals aimed to determine the impact of the SARS-CoV-2 pandemic on the mental health of healthcare professionals in two of the largest referral hospitals in Athens, Greece.
Methods: The study was conducted in the two largest SARS-CoV-2 referral hospitals in Athens, Greece. An assessment and the interrelationship of post-traumatic stress disorder, using the Impact of Event Scale-Revised [IES-R]) and burnout, using the Maslach Burnout Inventory [MBI]) was carried out.
Results: A total of 162 subjects were enrolled in the study. Fifty-six (35%) had an IES-R score > 33, suggesting post-traumatic stress disorder. Forty-nine (30%) had an MBI score > 27. Seventy-five (46%) had a personal accomplishment score of < 33 and 46 (28%) had a depersonalization score >10. Stepwise backward logistic regression revealed that the only independent variable that was retained regarding the presence of post-traumatic stress disorder was the emotional exhaustion score of the MBI (at a cut-off of 24 in this scale, the 95% CI of the odds ratio for the presence of post-traumatic stress disorder was 1.077-1.173).
Conclusions: In this sample of first-line Greek healthcare professionals against SARS-CoV-2, most of them were proven to be quite resilient to this challenge. One-third of them had post-traumatic stress disorder, which depended on their degree of emotional exhaustion. Healthcare professionals, as represented by this study, performed their duties without feeling helpless and developing adverse psychological reactions.

Keywords: extracorporeal membrane oxygenation, COVID-19, SARS-CoV-2, acute respiratory distress syndrome (ARDS), myocarditis, cardiac injury, cardiogenic shock

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Feasibility and Safety of Peripheral Intravenous Administration of Vasopressor Agents in Resource-limited Settings

Ajay Padmanaban¹, Ramesh Venkataraman¹, Senthilkumar Rajagopal¹, Dedeepiya Devaprasad², Nagarajan Ramakrishnan¹

1 Apollo Hospitals Chennai, Chennai, India
2 Apollo Cancer Hospitals, Chennai, India

DOI: 10.2478/jccm-2020-0030

Background: Vasopressors are conventionally administered through a central venous catheter (CVC) and not through a peripheral venous catheter (PVC) since the latter is believed to be associated with increased risk of extravasation. Placement of a CVC requires suitably trained personnel to be on hand, and in resource-limited settings, this requirement may delay placement. Because of this and in cases where suitably trained personnel are not immediately available, some clinicians may be prompted to utilise a PVC for infusing vasopressors. The objective of this study is to assess the feasibility and safety of vasopressors administered through a PVC.
Materials and methods: Patients who received vasopressors through a PVC for more than one hour were included in a single centre, consecutive patient observational study. Patients with a CVC at the time of initiation of vasopressors were excluded. Data regarding the size, location of PVCs, dose, duration and number of vasopressors infused were recorded. The decision to place CVC was left to the discretion of the treating physician. Extravasation incidents, severity and management of such events were recorded.
Results: One hundred twenty-two patients age 55(4) years [mean (SD)] were included in the study. The commonest PVC was of 18G calibre (57%), and the most common site of placement was the external jugular vein (36.5%). Noradrenaline was the most common vasopressor used at a dose of 10.6 (7) mcg/min [mean (SD)] and the median duration of nine hours (IQR: 6-14). CVC was placed most commonly due to an increasing dose of vasopressors after 4.5(4) hours [mean (SD)]. Grade 2 Extravasation injury occurred in one patient after prolonged infusion of fifty-two hours, through a small calibre (20G) PVC, which was managed conservatively without any sequelae.
Conclusion: Vasopressors infused through a PVC of 18G or larger calibre into the external jugular, or a forearm vein is feasible and safe. Clinicians need to balance the safety of peripheral vasopressor infusion with the additional costs and complications associated with CVC in resource-limited settings.

Keywords: central venous catheter, vasopressors, peripheral venous catheter, hemodynamic emergencies

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A Comparison of Nosocomial Infection Density in Intensive Care Units on Relocating to a New Hospital

Zeynep Ture¹, Tugba Ustuner², Ario Santini³, Serhat Aydogan², İlhami Celik²

1 Erciyes University Faculty of Medicine Kayseri, Turkey
2 City Hospital of Kayseri, Turkey
3 George Emil Palade University of Medicine, Pharmacy Science, and Technology of Targu Mures, Romania

DOI: 10.2478/jccm-2020-0028

Background: The study aimed to investigate the changes in nosocomial infection density after patients were transferred to the intensive care unit (ICU) of a new-build hospital.
Methods: The types and rates of nosocomial infections were obtained for a one-year period retrospectively before leaving the old hospital premises and for a one-year periods after moving into the new hospital. The intensive care unit in the “old” premises was comprised of a 17-bedded hall, and thirty-three nurses shifted to work forty-eight hours a week, with each nurse assigned to provide care for two patients. The intensive care unit in the “new” premises consisted of single rooms, each with twenty-eight beds.
Results: The median nosocomial infection density decreased from 23 to 15 per 1000 in-patient days. The catheter-related urinary tract infection rate decreased from 7.5 to 2.6 per100 catheter days.
Conclusions: Treatment of patients in the new hospital resulted in a decrease in nosocomial infection density.

Keywords: nosocomial infection density, infection control measures, causative microorganisms, antimicrobial susceptibility

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Opioid Use Is Associated with ICU Delirium in Mechanically Ventilated Children

Neha Gupta¹, Allison Woolley², Saurabh Talathi¹, Ganisher Davlyatov³, Candice Colston³, Leslie Hayes³

1 University of Oklahoma Health Sciences Center, Oklahoma City, USA
2 Children’s of Alabama, Birmingham, USA
3 University of Alabama at Birmingham, Birmingham, USA

DOI: 10.2478/jccm-2020-0026

Introduction: Pediatric delirium is a significant problem when encounterd in an intensive care unit (ICU). The pathophysiology of pediatric delirium is complex and the etiology is typically multifactorial. Even though various risk factors associated with pediatric delirium in a pediatric ICU have been identified, there is still a paucity of literature associated with the condition, especially in extremely critically ill children, sedated and mechanically ventilated. Aim of the study: To identify factors associated with delirium in mechanically ventilated children in an ICU.
Material and Methods: This is a single-center study conducted at a tertiary care pediatric ICU. Patients admitted to the pediatric ICU requiring sedation and mechanical ventilation for >48 hours were included. Cornell Assessment of Pediatric Delirium scale was used to screen patients with delirium. Baseline demographic and clinical factors as well as daily and cumulative doses of medications were compared between patients with and without delirium. Firth’s penalized maximum likelihood logistic regression was used on a priori set of variables to examine the association of potential factors with delirium. Two regression models were created to assess the effect of daily medication doses (Model 1) as well as cumulative medication doses (Model 2) of opioids and benzodiazepines.
Results: 95 patient visits met the inclusion criteria. 19 patients (20%) were diagnosed with delirium. Older patients (>12 years) had higher odds of developing delirium. Every 1mg/kg/day increase in daily doses of opioids was associated with an increased risk of delirium (OR=1.977, p=0.017). Likewise, 1 mg/kg increase in the cumulative opioid dose was associated with a higher odds of developing delirium (OR=1.035, p=0.022). Duration of mechanical ventilation was associated with the development of delirium in Model 1 (p=0.007).
Conclusions: Age, daily and cumulative opioid dosage and the duration of mechanical ventilation are associated with the development of delirium in mechanically ventilated children.

Keywords: intensive care unit, pediatric delirium, mechanically ventilated children

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Monitoring Anticoagulation with Unfractionated Heparin on Renal Replacement Therapy. Which Is the Best aPTT Sampling Site?

Florin Ioan Anton¹, Paul Adrian Rus², Natalia Hagau³

1 Regina Maria Hospital, Cluj-Napoca, Romania
2 Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Emergency Clinical County Hospital, Cluj-Napoca, Romania
3 Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Regina Maria Hospital, Cluj-Napoca, Romania

DOI: 10.2478/jccm-2020-0024

Background: Controlled anticoagulation is key to maintaining continuous blood filtration therapies. Objective: The study aimed to compare different blood sampling sites for activated partial thromboplastin time (aPTT) to evaluate anticoagulation with unfractionated heparin (UFH) in continuous renal replacement therapy (CRRT) and identify the most appropriate sampling site for safe patient anticoagulation and increased filter life span.
Method: The study was a prospective observational single-centre investigation targeting intensive care unit (ICU) patients on CRRT using an anticoagulation protocol based on patient characteristics and a weight-based modified nomogram. Eighty-four patients were included in the study. Four sampling sites were assessed: heparin free central venous nondialysis catheter (CVC), an arterial line with heparinised flush (Artery), a circuit access line (Access), and a circuit return line (Postfilter). Blood was sampled from each of four different sites on every patient, four hours after the first heparin bolus. aPTT was determined using a rapid clot detector, point of care device.
Results: A high positive correlation was obtained for aPTT values between CVC and Access sampling sites (r (84) =0.72; p <0 .05) and a low positive correlation between CVC and Arterial sampling site (r (84) =0.46, p < 0.05). When correlated by artery age, the young Artery (1-3 day old) correlates with CVC, Access and Postfilter (r (45) = 0.74, p >0.05). The aPTT values were significantly higher at Postfilter and Arterial sampling site, older than three days, compared to the CVC sampling site (p<0.05).
Conclusion: Considering patient bleeding risks and filter life span, the optimal sampling sites for safe assessment of unfractionated heparin anticoagulation on CRRT during CVVHDF were the central venous catheter using heparin free lavage saline solution, a heparinised flushed arterial catheter not older than three days, and a circuit access line

Keywords: heparin, aPTT sampling sites, continuous renal replacement therapy

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Takotsubo Syndrome: Is This a Common Occurrence in Elderly Females after Hip Fracture?

Carlo Rostagno¹, Gianluca Polidori², Alice Ceccofiglio², Alessandro Cartei², Alberto Boccaccini², Adriano Peris², Gaia Rubbieri², Roberto Civinini¹, Massimo Innocenti¹

1 Universita degli Studi di Firenze, Firenze, Italy
2 Azienda Ospedaliero Universitaria Careggi, Firenze, Italy

DOI: 10.2478/jccm-2020-0022

Background: The prevalence of Takotsubo syndrome in hip fracture is not known.
Methods: Hip fracture patients were evaluated in a multidisciplinary unit. Patients with ECG abnormalities and increased troponin I values at the time of hospital admission were included in the study Follow-up was clinical at 30 days and by telephonic interview at one year.
Results: Between October 1st 2011 to September 30th 2016, 51of 1506 patients had preoperative evidence of myocardial damage. Eight, all females, fulfilled the Mayo criteria for Takotsubo syndrome, six had no coronary lesions. Hip surgery was uneventful, and all eight were alive at thirty days, and seven of these were still alive after one year. Forty-three patients had myocardial infarction: mortality at thirty days and one year were 11% and 44% (p<0.0001, Student’s t-test;log-rank test).
Conclusion: At least 15% of patients with hip fracture and preoperative myocardial damage had Takotsubo syndrome. They were all elderly females. Contrary to myocardial infarction, Takotsubo syndrome has a favourable long term prognosis.

Keywords: Takotsubo syndrome, hip-fracture, ischemic heart disease

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The Diagnostic and Prognostic Role of Vascular Endothelial Growth Factor C in Sepsis and Septic Shock

Emoke Almasy¹, Janos Szederjesi¹, Bianca Liana Grigorescu², Iudita Badea¹,
Marius Petrisor³, Cristina Manasturean⁴, Valentina Negrea⁴, Agota-Evelyn Timar¹,
Oana Coman¹, Leonard Azamfirei¹, Ario Santini⁵, Sanda Maria Copotoiu¹

1 Anesthesiology and Intensive Care Clinic, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
2 Discipline of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
3 Department of Simulation Applied to Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Romania
4 Infectious Diseases Clinic, University Hospital Targu Mures, Romania
5 The University of Edinburgh, UK

DOI: 10.2478/jccm-2020-0020

Introduction: Variations in the expression of vascular endothelial growth factor (VEGF) could be used as a biomarker in critically ill patients with sepsis and septic shock. Inflammation potently upregulates VEGF-C expression via macrophages with an unpredictable response. This study aimed to assess one of the newer biomarkers (VEGF-C) in patients with sepsis or septic shock and its clinical value as a diagnostic and prognostic tool.
Material and methods: The study involved 142 persons divided into three groups. Group A consisted of fifty-eight patients with sepsis; Group B consisted of forty-nine patients diagnosed as having septic shock according to the Sepsis -3 criteria. A control group of thirty-five healthy volunteers comprised Group C. Severity scores, prognostic score and organ dysfunction score, were recorded at the time of enrolment in the study. The analysis included specificity and sensitivity of plasma VEGF-C for diagnosis of septic shock. Circulating plasma VEGF-C levels were correlated with the APACHE II, MODS and severity scores and mortality.
Results: The mean (SD) plasma VEGF-C levels in septic shock patients (1374(789) pg./m), on vasopressors at the time of admission to the ICU, were significantly higher 1374(789)pg./mL, compared the mean (SD) plasma VEGF-C levels in sepsis patients (934(468) pg./mL); (p = 0.0005, Student’s t-test.) Plasma VEGF-C levels in groups A and B were shown to be significantly correlated with the APACHE II (r = 0.21, p = 0.02; r = 0.45, p = 0.0009) and MODS score (r = 0.29, p = 0.03; r = 0.4, p = 0.003). There was no association between plasma VEGF-C levels and mortality [p = 0.1]. The cut-off value for septic shock was 1010 pg./ml.
Conclusions: VEGF-C may be used as a prognostic marker in sepsis and septic shock due to its correlation with APACHE II values and as an early marker to determine the likelihood of developing MODS. It could be used as an early biomarker for diagnosing patients with septic shock.

Keywords: sepsis, septic shock, lymphangiogenesis, vascular endothelial growth factor C

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