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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Anti-platelet Therapy Resistance – Concept, Mechanisms and Platelet Function Tests in Intensive Care Facilities
It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or non-responders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.
Challenges of Critical Cardiac Imaging in Cardiogenic Shock
To the editor of JCCM
I am writing in reference to the article published by Theodora Benedek and Dan Dobreanu in the first issue of JCCM, entitled “Current Concepts and New Trends in the Treatment of Cardiogenic Shock Complicating
Acute Myocardial Infarction”.
Cardiogenic shock (CS) represents a critical and life-threatening condition. Survival of patients with CS depends largely, not only on the appropriateness of the therapeutic measures, but also on the correct identification of the underlying disease [1].
Treatment of this underlying condition represents a key element for the correction of the patho-phyisiological pathways responsible for the development of a CS.
In many cases, CS occurs in association with an acute myocardial infarction, usually large infarcts, located on the anterior ventricular wall [2]. Prompt revascularisation is crucial in these cases, as the re-establishment of coronary flow would immediately improve the haemodynamic status of these critically ill patients. However, in routine clinical practice, the diagnosis of an acute coronary syndrome remains challenging, especially when the physician is faced with a patient who arrives in the emergency room (ER) intubated, after surviving a cardiac arrest of unknown aetiology. [More]
Neutrophil Viability as a Clinical Outcome Marker in Mechanically Ventilated Critically Ill Trauma Patients: A Case Series
Background: Trauma in its early stages leads to an acute inflammatory condition affecting all cellular lines. Neutrophil granulocytes make up the largest population of human white blood cells and are fundamental to the innate immune system. The objective of our pilot study was to evaluate neutrophil death and viability alterations in critically ill trauma patients in correlation with their clinical outcome.
Material and method: Critical ill trauma patients were enrolled in the study. In order to assess alterations in cellular death, blood samples were drawn using EDTA containing tubes and analyzed in the first twenty four hours after admission, then after forty eight and seventy two hours. Annexin V was used as a marker for apoptotic cells and propidium iodide for necrotic cells.
Results: The first two cases exhibited an increase in cellular viability by the second day as shown by a small increase in neutrophil apoptosis and a decrease in neutrophil necrosis. These patients progressed to a positive clinical outcome. The second two cases showed slight modifications in either physiological or pathological cellular death, and increasing levels of cellular necrosis. These patients progressed to a negative clinical outcome.
Conclusions: These cases suggest that neutrophil cell viability and death were associated with the patient’s clinical outcome.
Health Care Professional’s Attitude Towards the Effective Management of Pain in the Critically Ill Neonate
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.
The Effect of the Antioxidant Drug “U-74389G” on Haemoglobin Levels Following a Hypoxemia/ Re-oxygenation Protocol in Rats
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.
The Use of Novel Adopters for Acute Rib Fixation in Critical Chest Trauma, Undertaken by Orthopaedic Surgeons: an Observational Cohort Study
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.
New Targets for End-Stage Chronic Kidney Disease Therapy
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.
Oxidative Stress and Antioxidant Therapy in Critically Ill Polytrauma Patients with Severe Head Injury
Traumatic Brain Injury (TBI) is one of the leading causes of death among critically ill patients from the Intensive Care Units (ICU). After primary traumatic injuries, secondary complications occur, which are responsible for the progressive degradation of the clinical status in this type of patients. These include severe inflammation, biochemical and physiological imbalances and disruption of the cellular functionality. The redox cellular potential is determined by the oxidant/antioxidant ratio. Redox potential is disturbed in case of TBI leading to oxidative stress (OS). A series of agression factors that accumulate after primary traumatic injuries lead to secondary lesions represented by brain ischemia and hypoxia, inflammatory and metabolic factors, coagulopathy, microvascular damage, neurotransmitter accumulation, blood-brain barrier disruption, excitotoxic damage, blood-spinal cord barrier damage, and mitochondrial dysfunctions. A cascade of pathophysiological events lead to accelerated production of free radicals (FR) that further sustain the OS. To minimize the OS and restore normal oxidant/antioxidant ratio, a series of antioxidant substances is recommended to be administrated (vitamin C, vitamin E, resveratrol, N-acetylcysteine). In this paper we present the biochemical and pathophysiological mechanism of action of FR in patients with TBI and the antioxidant therapy available.
Oxidative Stress in the Critically Ill Polytrauma Patient
The critically ill patient with primary multiple traumas and having secondary complications, presents a complex challenge to the trauma team. The most commonly encountered primary injuries are traumatic brain, spinal cord, pulmonary and abdominal injuries or trauma to the pelvis and the extremities. Moreover, severe inflammations, infections, hyper-metabolism, as well as biochemical and physiological imbalances, lead to a significant increase in morbidity and mortality.
Most recently, the role of free radicals has been a largely debated and reported topic. Once produced in excess, free radicals are responsible for inducing oxidative stress. The redox species known to have a destructive effect on cells include the superoxide anion, the hydroxyl radical, hydrogen peroxide, nitric oxide, peroxynitrite, lipid peroxyl and alkoxy lipid. Under normal conditions, free radicals are produced in the human body in small amounts, their activity being minimized by the body’s physiologically anti-oxidant systems which include superoxide dismutase, catalase, glutathione, glutathione peroxidase, peroxiredoxins, and glutaredoxins.
In the critically ill patient, severe physiological and biochemical imbalances significantly reduce the body’s anti-oxidant capacity, disrupting the redox balance [1]. A series of biomarkers are in use, designed to quantify oxidative stress. These comprise interleukin 1 beta, interleukin 6, interleukin 10, tumor necrosis alpha, components of the complement, plasmatic levels of antioxidant enzymes and the microRNA species [2]. [More]