Category Archives: Original Research

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

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.

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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

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.

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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

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.

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Effects of Extracorporeal Membrane Oxygenation Initiation on Oxygenation and Pulmonary Opacities

DOI: 10.2478/jccm-2020-0040

Introduction: There is limited data on the impact of extracorporeal membrane oxygenation (ECMO) on pulmonary physiology and imaging in adult patients. The current study sought to evaluate the serial changes in oxygenation and pulmonary opacities after ECMO initiation.
Methods: Records of patients started on veno-venous, or veno-arterial ECMO were reviewed (n=33; mean (SD): age 50(16) years; Male: Female 20:13). Clinical and laboratory variables before and after ECMO, including daily PaO2 to FiO2 ratio (PFR), were recorded. Daily chest radiographs (CXR) were prospectively appraised in a blinded fashion and scored for the extent and severity of opacities using an objective scoring system.
Results: ECMO was associated with impaired oxygenation as reflected by the drop in median PFR from 101 (interquartile range, IQR: 63-151) at the initiation of ECMO to a post-ECMO trough of 74 (IQR: 56-98) on post-ECMO day 5. However, the difference was not statistically significant. The appraisal of daily CXR revealed progressively worsening opacities, as reflected by a significant increase in the opacity score (Wilk’s Lambda statistic 7.59, p=0.001). During the post-ECMO period, a >10% increase in the opacity score was recorded in 93.9% of patients. There was a negative association between PFR and opacity scores, with an average one-unit decrease in the PFR corresponding to a +0.010 increase in the opacity score (95% confidence interval: 0.002 to 0.019, p-value=0.0162). The median opacity score on each day after ECMO initiation remained significantly higher than the pre-ECMO score. The most significant increase in the opacity score (9, IQR: -8 to 16) was noted on radiographs between pre-ECMO and forty-eight hours post-ECMO. The severity of deteriorating oxygenation or pulmonary opacities was not associated with hospital survival.
Conclusions: The use of ECMO is associated with an increase in bilateral opacities and a deterioration in oxygenation that starts early and peaks around 48 hours after ECMO initiation.

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

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.

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

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.

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

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.

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Opioid Use Is Associated with ICU Delirium in Mechanically Ventilated Children

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.

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

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

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

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.

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