Category Archives: Original Research

Total Intravenous Versus Inhalation Anesthesia in Patients Undergoing Laparoscopic Cholecystectomies. Effects on Two Proinflammatory Cytokines Serum Levels: Il-32 and TNF-Alfa.

Adina Hadade1*, Daniela Ionescu1, Teodora Mocan2, Alexandru Necula3, Victor Cristea4

1 Department of Anesthesia and Intensive Care, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
2 Department of Physiology, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
3 Department of Surgery, Regional Institute for Gastroenterology and Hepatology “Prof dr Octavian Fodor”, Cluj-Napoca, Romania
4 Department of Clinical Immunology, “IuliuHatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

DOI: 10.1515/jccm-2016-0008

Introduction: It has been reported that as compared with total intravenous anesthesia (TIVA), inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.
The aim of the study is to investigate if there is an in-vivo relationship between proinflammatory cytokines, Interleukin-32 (IL-32) and Tumour necrosis factor – α (TNF- α), in patients undergoing laparoscopic cholecystectomies with two different anesthetic techniques, TIVA or inhalation anesthesia.
Material and Methods: Twenty two consecutive patients undergoing laparoscopic cholecystectomies were prospectively randomized into two groups: Group 1: TIVA with target-controlled infusion (TIVA-TCI) (n=11) and Group 2: isoflurane anesthesia (ISO) (n=11). IL-32 and TNF-α were determined before the induction of anesthesia (T1), before incision (T2) and at 2h (T3) and 24h (T4) postoperatively. Our primary outcome was to compare plasma levels of IL-32 and TNF- α concentrations (expressed as area-under-the-curve) over 24 hours between study groups. Our secondary outcome was to establish whether there is a correlation between plasma levels of IL-32 and of TNF-α at each time point between the two groups.
Results: Area-under-the-curve (AUC) of IL-32 plasma concentration was 7.53 in Group 1 (TIVA) versus 3.80 in Group 2 (ISO), p= 1. For TNF-α, AUC of plasma concentration was 733.9 in Group 1 (TIVA) and 668.7 in Group 2 (ISO), p= 0.066. There were no significant differences in plasma concentrations of both IL-32 and TNF- α between the groups.
Conclusions: IL-32 expression in response to minor surgery is very low. There were no significant difference between plasma levels ofTNF- α and IL-32 after TIVA versus inhalation anesthesia during the first 24 hours postoperatively. Further studies are needed on larger groups to investigate whether there can be a correlation between these interleukins after 2 different anesthetic techniques and the impact of this correlation on postoperative outcome.

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Factors Favouring the Development of Clostridium Difficile Infection in Critically Ill Patients

Bianca-Liana Grigorescu1, Raluca Ştefania Fodor1*, Adrian Dan Cioc2, Mihaly Veres2, Monica Orlandea2, Bogdan Lăzescu2, Emoke Almasy2

1 University of Medicine and Pharmacy of Tîrgu Mureş, 38 Gheorghe Marinescu street Tîrgu Mureş, 540139, Romania
2 County Clinical Emergency Hospital Tîrgu Mureş, Romania, 50 Gheorghe Marinescu street Tîrgu Mureş, 540139, Romania

DOI: 10.1515/jccm-2016-0006

Clostridium difficile, an anaerobic, spore-forming, toxin-forming, gram-positive bacillus present in the bacterial flora of the colon is the principal cause of nosocomial diarrhoea in adults.
Aim: Assessment of favouring factors of Clostridium difficile infections as well as the interactions between them, in critically ill hospitalized patients undergoing complex medical and surgical treatments.
Material and Methods: A retrospective case-control study involving eighty patients admitted in the Intensive Care Unit (ICU) of the County Clinical Emergency Hospital Tîrgu-Mureş was conducted between January and October 2014. Patients aged eighteen years and over, who had undergone complex medical and surgical treatment, were divided into two subgroups. Group 1 included patients who developed diarrhoea but were not diagnosed as having a Clostridium difficile infection (CDI). Group 2 included patients who developed diarrhoea due to CDI as indicated by a positive culture and the expression of exotoxin. The assessed parameters were age, length of stay (LOS), antibiotic spectrum, association with proton pump inhibitors (PPI) or H2-receptor antagonists, immunological status, the presence or lack of gastrointestinal tract surgery.
Results: The mean age was 64.6 years with an average LOS of 10 days. Fifty-six percent of patients came to the ICU from internal medicine wards and forty-three percent from surgical wards. 20.5% of them were immunosuppressed. Co-association of ceftriaxone and pantoprazole significantly increased the risk of CDI compared to co-administration of any other antibiotic or pantoprazole (p=0.01). The odds ratio for Pantoprazole together with any antibiotic versus antibiotic therapy alone was significantly higher (p=0.018) with a sevenfold increase in the risk of positive exotoxin increase.
Conclusions: Antibiotic use is associated with “no risk to develop CDI” in the first five days of administration. PPIs associated therapy increased the risk of CDI in first seventy-two hours regardless of the antibiotic type, and contributes to an active expression of CD exotoxin.

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Recent Advances Of Mucosal Capnometry And The Perspectives Of Gastrointestinal Monitoring In The Critically Ill. A Pilot Study

Péter Palágyi1*, Sándor Barna2, Péter Csábi3, Péter Lorencz1, Ildikó László1, Zsolt Molnár1

1 Department of Anaesthesiology and Intensive Therapy, University of Szeged, Hungary
2 Department of Anaesthesiology and Intensive Therapy, Bács-Kiskun County Hospital, Teaching Hospital of the University of Szeged, Hungary
3 Department of Anaesthesia and Intensive Care, Wexham Park Hospital, United Kingdom

DOI: 10.1515/jccm-2016-0002

Mucosal capnometry involves the monitoring of partial pressure of carbon dioxide (PCO2) in mucous membranes. Different techniques have been developed and applied for this purpose, including sublingual or buccal sensors, or special gastrointestinal tonometric devices. The primary use of these procedures is to detect compensated shock in critically ill patients or patients undergoing major surgery. Compensatory mechanisms, in the early phases of shock, lead to the redistribution of blood flow towards the vital organs, within ostensibly typical macro-haemodynamic parameters. Unfortunately, this may result in microcirculatory disturbances, which can play a pivotal role in the development of organ failure. In such circumstances mucosal capnometry monitoring, at different gastrointestinal sites, can provide a sensitive method for the early diagnosis of shock. The special PCO2 monitoring methods assess the severity of ischaemia and help to define the necessary therapeutic interventions and testing of these monitors have justified their prognostic value. Gastrointestinal mucosal capnometry monitoring also helps in determining the severity of ischaemia and is a useful adjunctive in the diagnosis of occlusive splanchnic arterial diseases. The supplementary functional information increases the diagnostic accuracy of radiological techniques, assists in creating individualized treatment plans, and helps in follow-up the results of interventions. The results of a pilot study focusing on the interrelation of splanchnic perfusion and gastrointestinal function are given and discussed concerning recent advances in mucosal capnometry.

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Predictors Of Mortality In Patients With ST-Segment Elevation Acute Myocardial Infarction And Resuscitated Out-Of-Hospital Cardiac Arrest

Andreea Bărcan, Monica Chițu*, Edvin Benedek, Nora Rat, Szilamer Korodi, Mirabela Morariu, Istvan Kovacs

University of Medicine and Pharmacy of Tirgu Mureș, Romania, Department of Internal Medicine, Clinic of Cardiology

DOI: 10.1515/jccm-2016-0001

Introduction: In patients with out-of-hospital cardiac arrest (OHCA) complicating an ST-segment elevation myocardial infarction (STEMI), the survival depends largely on the restoration of coronary flow in the infarct related artery. The aim of this study was to determine clinical and angiographic predictors of in-hospital mortality in patients with OHCA and STEMI, successfully resuscitated and undergoing primary percutaneous intervention (PCI).
Methods: From January 2013 to July 2015, 78 patients with STEMI presenting OHCA, successfully resuscitated, transferred immediately to the catheterization unit and treated with primary PCI, were analyzed. Clinical, laboratory and angiographic data were compared in 28 non-survivors and 50 survivors.
Results: The clinical baseline characteristics of the study population showed no significant differences between the survivors and non-survivors in respect to age (p=0.06), gender (p=0.8), the presence of hypertension (p=0.4), dyslipidemia (p=0.09) obesity (p=1), smoking status (p=0.2), presence of diabetes (p=0.2), a clinical history of acute myocardial infarction (p=0.7) or stroke (p=0.17). Compared to survivors, the non-survivor group exhibited a significantly higher incidence of cardiogenic shock (50% vs 24%, p=0.02), renal failure (64.3% vs 30.0%, p=0.004) and anaemia (35.7% vs 12.0%, p=0.02). Three-vessel disease was significantly higher in the non-survivor group (42.8% vs. 20.0%, p=0.03), while there was a significantly higher percentage of TIMI 3 flow postPCI in the infarct-related artery in the survivor group (80.% vs. 57.1%, p=0.03). The time from the onset of symptoms to revascularization was significantly higher in patients who died compared to those who survived (387.5 +/- 211.3 minutes vs 300.8 +/- 166.1 minutes, p=0.04), as was the time from the onset of cardiac arrest to revascularization (103.0 +/- 56.34 minutes vs 67.0 +/- 44.4 minutes, p=0.002). Multivariate analysis identified the presence of cardiogenic shock (odds ratio [OR]: 3.17, p=0.02), multivessel disease (OR: 3.0, p=0.03), renal failure (OR: 4.2, p=0.004), anaemia (OR: 4.07, p=0.02), need for mechanical ventilation >48 hours (OR: 8.07, p=0.0002) and a duration of stay in the ICU longer than 5 days (OR: 9.96, p=0.0002) as the most significant independent predictors for mortality in patients with OHCA and STEMI.
Conclusion: In patients surviving an OHCA in the early phase of a myocardial infarction, the presence of cardiogenic shock, renal failure, anaemia or multivessel disease, as well as a longer time from the onset of symptoms or of cardiac arrest to revascularization, are independent predictors of mortality. However, the most powerful predictor of death is the duration of stay in the ICU and the requirement of mechanical ventilation for more than forty-eight hours.

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Plasma Neutrophil Gelatinase Associated Lipocalin (NGAL) – Early Biomarker for Acute Kidney Injury in Critically Ill Patients

Raluca Fodor1, Bianca Grigorescu2*, Mihaly Veres2, Monica Orlandea2, Judita Badea2, Katalin Hlavathy2, Adrian Cioc2

1 Department of Anaesthesiology and Intensive Care, University of Medicine and Pharmacy, Tirgu Mures, Romania
2 Department of Anaesthesiology and Intensive Care, Emergency County Hospital, Tirgu Mures, Romania

DOI: 10.1515/jccm-2015-0023

Introduction: NGAL (Neutrophil Gelatinase Associated Lipocalin) is a biomarker recently introduced into clinical practice for the early diagnosis of acute kidney injury (AKI). The aim of this study was to correlate the plasmatic NGAL value determined at admission with clinical progression and severity of AKI in critically ill patients.
Material and method: Thirty two consecutive critically ill adult patients at risk of developing AKI (trauma, sepsis), admitted in Intensive Care Unit of the Clinical County Emergency Hospital Mures, between January to March 2015 were enrolled in the study. For each patient included in the study plasma NGAL levels were determined on admission, and these were correlated with the degree of AKI development (according to AKIN criteria) at 48 hours and 5 days post admission. The discriminatory power of NGAL, creatinine, creatinine clearance and corrected creatinine (depending on water balance) were determined using the ROC (receiver-operating characteristic) and likelihood ratios.
Results: ROC curve analysis showed a better discriminatory capacity in terms of early diagnosis of AKI for NGAL (AUC=0.81 for NGAL, AUC=0.59 for creatinine, AUC=0.62 for corrected creatinine, AUC=0.29 for creatinine clearance). The value of likelihood ratio was also significantly higher for NGAL (3.01±2.73 for NGAL, 1.27±1.14 for creatinine, 1.78±1.81 for corrected creatinine, and 0.48±0.33 for creatinine clearance).
Conclusions: NGAL biomarker has a better discrimination capacity for early prediction of acute kidney injury compared to previously used markers.

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An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis

Janos Szederjesi1*, Emoke Almasy1, Alexandra Lazar1, Adina Huțanu2, Iudita Badea1, Anca Georgescu3

1 Department of Anesthesiology and Intensive Care, University of Medicine and Pharmacy Tirgu Mures, Romania
2 County Clinical Emergency Hospital Tirgu Mures, Romania
3 Department of Infectious Diseases, University of Medicine and Pharmacy Tirgu Mures, Romania

DOI: 10.1515/jccm-2015-0022

Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR), urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT) is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP) is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body.
The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.
Material and method: Sixty patients, diagnosed as being “septic”, were admitted to the intensive care unit (ICU). Based on laboratory results and clinical findings a diagnosis of “severe sepsis“ was made, and correlated with PCT and CRP values. The APACHE II, SAPS II and SOFA severity scores were calculated, analyzed and correlated with PCT and CRP.
Results: Fifty two patients (86.67%) presented with criteria for severe sepsis. Multivariate correlation analysis indicated a significant positive association between procalcitonin and all severity scores (APACHEII p<0.0001, SOFA p<0.0001, SAPS II p<0.0001). CRP proved to be significantly correlated only with the SAPS II score (p=0.0145). Mortality rate was high, with 48 patients (80%) dying. There was no significant correlation between the levels of the PCT and CRP biomarkers and severe sepsis (p=0.2059 for PCT, p=0.6059 for CRP).
Conclusions: The procalcitonin levels are highly correlated with the severity scores (APACHE II, SAPS II, SOFA) regularly used in ICUs and therefore can be used for determining the severity of the septic process. Quantitive procalcitonin and C-reactive protein analysis was not shown to be useful in diagnosing severe sepsis. However, PCT and CRP can be used to predict the fatal progression of the septic patient.

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Health Care Professional’s Attitude Towards the Effective Management of Pain in the Critically Ill Neonate

Laura Mihaela Suciu1, Manuela Cucerea1, Marta Simon1, Andreea Avasiloaiei2, Olimpia Petrescu3, Suciu Bogdan Andrei4

1 Department of Pediatrics, University of Medicine and Pharmacy Tîrgu Mures, Romania
2 Department of Pediatrics, University of Medicine and Pharmacy Iasi, Romania
3 Department of Neonatology, County Hospital Brasov, Romania
4 Anatomy and Embryology Department, University of Medicine and Pharmacy Tîrgu Mures, Romania

DOI: 10.1515/jccm-2015-0018

Introduction: Over the past 25 years, caregiver’s knowledge of pain in newborn infants has advanced from the beliefs that newborn infants do not feel pain, to the knowledge that preterm infants experience more pain compare to older children and adults. However, caregivers know that pain exists in this population and research has supported that pain continues to be untreated up to 65% of the time.
Aim of the study: The purpose of this study was to investigate the attitude and knowledge of health care professionals from the area of Neonatology in Romania regarding procedural pain management in newborn infants.
Material and methods: The sample consisted of 85 physicians and nurses (110 invited) working in five Neonatal Care Centres. Data were collected using a self-completion, 17 items questionnaire designed for this study.
Results: With a response rate of 77.27% which was similar in nurses and physicians, respondents in our study were aware about the pain experience during procedural interventions, recognized the items of pain scales assessment, and are not comfortable with the parental presence during painful procedures. Twenty-five percent of nurses versus 9% of physicians reported rushed care as an important barrier of adequate non-pharmacological pain management (95% IC, 0.319-0.003)
Conclusions: The use of pain protocols for an effective management of pain during neonatal period is required.

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The Effect of the Antioxidant Drug “U-74389G” on Haemoglobin Levels Following a Hypoxemia/ Re-oxygenation Protocol in Rats

Constantinos Τsompos1, Constantinos Panoulis2, Konstantinos Τοutouzas3, George Ζografos3, Apostolos Papalois4

1 Department of Obstetrics & Gynecology, Mesologi County Hospital, Etoloakarnania, Greece
2 Department of Obstetrics & Gynecology, Aretaieion Hospital, Athens University, Attiki, Greece
3 Department of Surgery, Ippokrateion General Hospital, Athens University, Attiki, Greece
4 Experimental Research Center ELPEN Pharmaceuticals, S.A. Inc., Co.

DOI: 10.1515/jccm-2015-0017

Critically ill patients usually present with circulatory hypoxemia and this is associated with a poorer prognosis. The aim of this experimental study was to examine the effect of U-74389G with specific regard to a hypoxemia/re-oxygenation protocol, on mean blood haemoglobin (Hgb) levels in rats.
Materials and methods: Forty rats (mean weight 231.9 g) were used in the study. Hgb levels were measured at sixty minutes (groups A and C) and at 120 minutes (groups B and D) of re-oxygenation. U-74389G was administered only in groups C and D.
Results: U-74389G administration non-significantly increased the Hgb levels by 3.95+2.10% (p=0.0604). Re-oxygenation time non-significantly increased the Hgb levels by 3.39+2.12% (p=0.1285). U-74389G administration and re-oxygenation time together, significantly increased the Hgb levels by 2.55%+1.25% (p=0.0423).
Conclusions: Results of this study indicate that U-74389G administration, re-oxygenation time, but mainly their interaction significantly increase the Hgb levels within the studied time limits.

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The Use of Novel Adopters for Acute Rib Fixation in Critical Chest Trauma, Undertaken by Orthopaedic Surgeons: an Observational Cohort Study

Paul J. Jermin, James Perry, Sanjay Kalra, Elizabeth Flockton, Henry K. Rourke

Department of Orthopaedics, Royal Liverpool and Broadgreen University Hospitals, Liverpool, United Kingdom

DOI: 10.1515/jccm-2015-0016

Background: Surgical stabilisation of acute rib fractures has recently undergone rapid change in the UK with respect to what type of injury is surgically stabilised and who undertakes the operation. This paper presents a review of the literature on surgical fixation and presents our early clinical experience using a recently introduced stabilising system.
Methods: Data was prospectively collected from the first 10 patients undergoing surgical stabilisation of acute rib fractures using the Synthes Matrix RIB plating system. The data included demographics, Injury Severity Score, length of stay in Intensive Care, length of time on a ventilator, analgesic requirements, pneumonia rates and mortality. Patients were followed up until they were discharged from hospital.
Results: Patients had an average Injury Severity Score of 26 (16-57), the average number of ribs fractured was 8.2 (4-14), nine patients had flail chest and one had multiple fractures, mean time from injury to fixation was 2.8 days. In the reported cohort, there were no deaths, two pneumonias (one had pneumonia on presentation). The average length of stay on a ventilator was three days and the average length of stay in Intensive Care was ten days.
Conclusion: The early results of this procedure are encouraging. We feel that the modern implants will provide superior results to the highly variable implants that have previously been used. Our results support the literature, showing that with this system, there is a decrease in mortality and morbidity and a decrease in the length of time on a ventilator and stay in Intensive Care.

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New Targets for End-Stage Chronic Kidney Disease Therapy

Niki Prakoura, Panos Kavvadas, Christos Chatziantoniou

Inserm UMR S 1155 and University Pierre et Marie Curie, Paris,  France

DOI: 10.1515/jccm-2015-0015

Severe forms of chronic kidney disease can lead to a critical, end-stage condition, requiring renal replacement therapy, which may involve a form of dialysis or renal transplantation. Identification and characterization of novel markers and/or targets of therapy that could be applied in these critically ill patients remains the focus of the current research in the field of critical care medicine and has been the objective of our studies for some years past. To this end, we used models of renal vascular disease, Ang II, L-NAME or mice overexpressing renin, treated with AT1 antagonists at different stages of progression, to create cohorts of animals during progression, reversal or escape from therapy. Transcriptomic analysis and comparisons were performed and genes were selected according to the following criteria: a) not previously described in the kidney, b) highly upregulated during progression and returning to the normal levels during reversal, and c) producing proteins that are either circulating or membrane receptors.
The involvement of the selected genes in the mechanisms of renal disease was confirmed in additional models of renal disease, initiated in other compartments of the kidney such as glomeruli (administration of nephrotoxic serum) or the tubular interstitium (unilateral ureteral obstruction). The potential of the therapy was tested using mice lacking the expression of these genes and by in vivo administration of antisense oligonucleotides which blocked the transcription of the targeted genes. This strategy allowed the identification of periostin, an extracellular matrix protein normally involved in bone and tooth development, in addition to the discoidin domain receptor1 (DDR1) as potential targets of therapy against renal inflammation and fibrosis.

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