Signa Vitae

Journal for Intensive Care and Emergency Medicine

Biomarkers of sepsis in neonates and children


Sepsis, and related complications, is still a common cause of death in hospitalized patients worldwide, especially in critically ill neonates and children. Sepsis is also responsible for significant morbidity, and financial burden. It is very important to recognize sepsis early, since delayed diagnosis is associated with worse outcome. The early detection of sepsis remains a great challenge for clinicians because the use of blood cultures, the gold standard for diagnosis of bacteremia, is fraught with difficulties. The role of different immune and metabolic biomarkers is to improve the diagnosis, treatment and prognosis of sepsis. White blood cell count, C-reactive protein and procalcitonin are currently the most widely used biomarkers, but they have limited abilities to distinguish sepsis from other inflammatory conditions or to predict outcome. In this review, these biomarkers will be discussed along with novel diagnostic, prognostic and treatment response biomarkers, including interleukins -6, -8, -18, tumor necrosis factor – alpha, CD11b, CD64 and CD15s. The future of sepsis biomarkers lies in extensive validation studies of all novel biomarkers and their combinations as early predictors of sepsis. Also, research to identify novel sepsis biomarkers and develop specific therapeutic strategies based on biomarker information has to be continued.

Key words: infant, child, biomarkers, CD15s antigen, C-reactive protein, procalcitonin

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Anesthesia for carotid endarterectomy: where do we stand at present?


Carotid endarterectomy (CEA) is a surgical procedure performed to reduce the incidence of embolic and thrombotic stroke. Although only a preventive procedure, CEA carries the risk of perioperative complications. There is constant searching for an optimal anesthetic technique. There are pros and cons for both anesthetic techniques used: regional (RA) and general anesthesia (GA). A large number of studies have compared RA and GA techniques in CEA surgery patients. The primary outcome was the proportion of patients with stroke, myocardial infarction, or death. However, neither the GALA trial nor the pooled analysis was adequately powered to reliably detect an effect of type of anesthesia on mortality. It may therefore be appropriate to consider other additional parameters (stress response, incidence of postoperative delirium and cognitive impairment, functional recovery, total surgery time, intensive care unit requirement, hospital stay, hospital costs and patients satisfaction) when comparing the outcomes of the two techniques.

Although, the debate continues as to whether regional anesthesia or general anesthesia is safer, the choice of anesthetic technique is a complex decision and surgical teams should be able to offer both RA and GA. The individual approach is the ideal choice and should be determined at the discretion of the surgeon, anesthetist and patient depending on the clinical situation and own preferences.

Key words: surgery, carotid endarterectomy, anesthesia, general, regional, outcome

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Acute intoxication and poisoning in children: the experience of a tertiary-care hospital from 2001-2012


The frequency and distribution of acute intoxications and poisoning from non-pharmacological substances in children was evaluated in this observational-descriptive study. This was done by analyzing all admissions to the Emergency Room of our University in Rome during the period 1st January 2001 to 31st December 2012. We found 249 patients aged 0-14 years: 147 males and 102 females. The highest incidence occurred in the first 4 years of life: 44.2% in the 1-2 year age-group. Cases were mostly related to solvents (44.6%), natural products (17.7%), agricultural products (12.9%), corrosive acids and alkaline caustics (14.8%). Most admissions occurred during the time slot 18:00 to 21:00 (23.7%). No clinical symptoms were observed in 116 children (46.6% of the total), and physical examination was unrevealing. The remaining 133 displayed nausea/vomiting (22%) and pharyngeal hyperemia (18.8%). Laboratory tests and imaging studies were only performed in selected cases. In terms of consulting requests, the Poisons Center was contacted 156 times (62.6% of cases), the Pediatric Intensive Care Unit 38 times (15.2%), and the surgeon-endoscopist 18 times (7.2%). A short period of observation and monitoring in the Emergency Room was warranted in 106 children (42.5%). Gastroprotective drugs were used in 75 cases (30.1%) and activated charcoal in 18 (7.2%). Nintey-five children (38.2%) were admitted to the pediatric department , but no complications occurred. Targeted information programs in schools and during pediatric check-ups should decrease the risk of ingestion of non-pharmacological substances in children, and the costs of its management.

Key words: intoxication, poisoning, child

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Immature granulocyte count on the new Sysmex XN-9000: performance and diagnosis of sepsis in the intensive care unit


Introduction. The amount of immature leukocytes reflects marrow response to bacterial infection, and this may be quantified as the band or immature granulocyte (IG) count. The aim of this study was to analyze the IG count performance of the Sysmex XN-9000 hematology analyzer in intensive care unit (ICU) patients.

Methods. 480 peripheral blood samples from adult patients admitted to the ICU (301 control, 119 sepsis and 60 septic shock) were analyzed with Sysmex XN-9000. Serum C reactive protein (CRP) was measured on Siemens ADVIA 2400. IG count in peripheral blood was determined either by XN-9000 or optical microscopy (OM). Agreement between the two methods was assessed with Pearson’s correlation, Passing-Bablok regression and Bland Altman bias. Diagnostic accuracy was estimated through ROC curves analysis. Sysmex XN-9000 imprecision and within-run precision were also evaluated.

Results. Pearson’s correlation (r) relative to IG count, as absolute and percentage values, was 0.89 (p <0.0001) and 0.74 (p <0.0001), respectively, with a Bias of 0.22 and 1.69 respectively. The Area Under the curve (AUC) for the IG count for diagnosing sepsis was greater on XN-9000 than OM and equal to the serum CRP. The diagnostic accuracy of IG counts improves when taking into account the conventional criteria for diagnosing sepsis.

Conclusion. IG count appears suitable and reliable when performed using XN-9000. Even if a modest overestimation was found, the diagnostic accuracy showed by IG analysis on XN-9000 may represent a valid alternative to OM count for diagnosing sepsis in ICU patients.

Key words: immature granulocyte, Sysmex XN, sepsis, automated cell count

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Methicillin-Resistant Staphylococcus Species in a cardiac surgical intensive care unit


Objective. Multi-drug resistant bacterial infections, in particular when Methicillin-Resistant Staphylococcus Aureus (MRSA) is involved, have become a relevant problem in both general and specialized intensive care units. The aim of this study was to identify the epidemiology of MRSA infections in a Cardiac Surgical Intensive Care Unit, to assess their impact on mortality and to identify predictors of MRSA infection and mortality in this population.

Design and settings. A 7-year observational study in a cardiac surgery teaching center.

Participants. Eight thousand, one hundred and sixty-two microbiological samples were obtained from 7,313 patients who underwent cardiac surgery in the study period.

Interventions. None.

Variables of interest and main results. Twenty-eight patients (0.38%) had MRSA infection. The most frequent site of MRSA isolation was from bronchoalveolar samples. Hospital mortality was 50% in patients with MRSA infection and 2% in patients without MRSA infection (p<0.001).

Few preoperative independent predictors of MRSA infection and hospital mortality were found at multivariate analysis. Outcomes were found to be most influenced by perioperative variables. MRSA infection was the strongest predictor of mortality, with an odds ratio of 20.5 (95% CI 4.143-101.626).

Conclusions. Methicillin-resistant Staphylococcus aureus infections following cardiac surgery still have a strong impact on the patients’ outcome. More efforts should be directed toward the development of new risk analysis models that might implement health care practices and might become precious instruments for infection prevention and control.

Key words: Methicillin-Resistant Staphylococcus Aureus, infections, cardiac surgery, mortality, intensive care, cardiac anaesthesia

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Testing of potential biomarkers of cerebral ischemia and vasospasm in patients with cerebral aneurysm surgery


Biomarkers for the prediction of vasospasm and delayed cerebral ischemia in patients with a ruptured cerebral aneurysm could be helpful.

In this prospective clinical study, endothelin-1, lactate, pCO2, and pO2 were measured in arterial and internal jugular vein blood before, during and after surgical treatment of a cerebral aneurysm, and were tested as potential predictors of neurologic outcome in patients.

Forty-one patients were enrolled in the study, 23 of them were operated on after aneurismal rupture with development of subarachnoid hemorrhage (SAH) and 18 patients were operated on for a nonruptured aneurysm.

All of the involved patients survived. There was no difference in neurologic outcome between those operated on with a ruptured or nonruptured aneurysm.

Endothelin-1 and lactate concentrations as well as pO2 and pCO2 from arterial and venous blood samples and their venoarterial difference did not differ between groups with and without an aneurismal rupture. Venoarterial difference of endothelin-1 concentrations on the day after surgery significantly differed between the groups with favorable and nonfavorable neurologic outcome. Other variables did not show a statistically significant difference.

Significant correlation was found between endothelin-1 and lactate concentrations, suggesting involvement of the same pathophysiological process.

Another interesting finding was lower arterial and venous pCO2 in patients with lower initial Glasgow Coma Scale (GCS) score and higher Hunt Hess score in the phase after extubation.

We can conclude that the measured biochemical parameters did not show sufficient predictive power to be useful for prediction of cerebral vasospasm and neurologic outcome in everyday clinical practice. However, some correlations that do exist between them suggest involvement of the same pathophysiological process.

Key words: cerebral aneurysm, neurosurgery, endothelin-1, biomarkers, delayed cerebral ischemia

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Effects of therapeutic hypothermia and kinetics of serum protein S100B after cardiopulmonary resuscitation


Introduction. Post-resuscitation care is regulated by international guidelines. A milestone of these is the application of therapeutic hypothermia (TH). The aims of our study were: to determine the 30-day-mortality for our patients, to monitor the efficacy and effects of TH, and to investigate serum protein S100B – as an early prognostic marker.

Materials and Methods. In our study, 57 patients, treated after cardiopulmonary resuscitation (CPR) on a multidisciplinary intensive care unit, were included. Patients were divided into groups who received and who didn’t receive TH. 30-day-mortality was determined as an end-point. Effects of TH were monitored using statistical analysis according to clinical parameters and laboratory tests. Serum protein S100B levels were measured with ELISA technique on 20 randomised patients at admission and the 1st, 3rd and 5th day after CPR.

Results. Total 30-day-mortality was 74%. TH did not reduced the 30-day-mortality (73% vs. 74%, p>0.05). We found a significant correlation between TH and serum lactate concentration after admission (0h, p=0.006) and at 12 (p=0.045) and 36 (p=0.049) hours after CPR. On the 3rd (p=0.005) and 4th (p=0.043) day after CPR, as a result of TH, platelet count was significantly higher compared to normothermic samples. There was no significant difference in protein S100B levels between the normothermic and TH group and protein S100B levels did not correlate with 30-day-mortality.

Conclusion. Despite recommendations of international guidelines, we cannot prove the beneficial effect of TH, or a correlation of protein S100B levels with a positive outcome.

Key words: cardiac arrest, cardiopulmonary resuscitation, post-resuscitation care, therapeutic hypothermia, protein S100B

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Effects of enteral nutrition on clinical outcomes among mechanically ventilated and sedated patients in the pediatric intensive care unit


Objective. To analyze the effects of enteral nutrition on outcomes and complications of critically ill children in the pediatric intensive care unit (PICU).

Design. Retrospective cohort study.

Setting. PICU in a tertiary care academic medical center.

Patients. Patients up to age 17 years who were admitted to the PICU between January 1, 2011, and December 31, 2013.

Interventions. Intubation for more than 48 hours and requiring any sedative medications. Patients with surgical contraindications to feeding were excluded.

Measures and Main Results. A total of 165 patients met inclusion criteria. Both manual review of the electronic health record and automated data capture (whenever technically feasible) were conducted. Data were collected in REDCap software and analyzed using a statistical discovery program. The mean (SD) calorie intake within the first 10 days of PICU admission was 40% (31.9%) of the prescribed calories. Only 67% of the patients had feeding initiated within 48 hours of admission. No significant difference in hospital or PICU length of stay or ventilator-free days was observed in patients who met one-third of their nutritional goals (50.3%) compared with patients who did not (49.7%). Mortality was nonsignificantly higher among patients who did not meet nutritional goals (P=.07). No association was found between higher doses of opioids or benzodiazepines and nutrition tolerance or gastrointestinal complications.

Conclusions. Early adequate enteral nutrition had no statistically significant impact on the short-term clinical outcomes of PICU patients.

Key words: critical illness, deep sedation, energy intake, pediatric intensive care unit, pediatrics, respiration, artificial

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Continuous cardiopulmonary resuscitation training compared to single training by laypersons


Background. Compression-Only Cardiopulmonary Resuscitation (COCPR) has been broadly studied during the last few years and specially introduced into lay rescuers’ training. The aim of the study was to compare the quality of COCPR performed by laypersons (Group A) who attended a single cardiopulmonary resuscitation (CPR) training course, and those (Group B) who underwent regular CPR training every 6 months.

Methods. Both groups completed the “Heartsaver CPR AED” course of the American Heart Association. After 30 minutes they were required to perform COCPR on a manikin with a skills reporter system.

Results. Comparing the 76 once only trained laypersons to the 74 continuously trained lay rescuers, we found that average age (20 versus 40 years old), male gender (54% versus 93%), body mass index (BMI) (24.9 versus 27.3 kg/m2) and regular physical exercise (55% versus 36%) proved significant predictors, p<0.01, p<0.01, p<0.01 and p=0.04 respectively. Regarding COCPR-quality, the percentage of efficient chest compressions (43% versus 58%), average depth of compression (45 versus 50 mm) and percentage of error-free compressions (36% versus 50%) indicated a significant statistical difference, with p=0.01, p=0.01 and p<0.01 respectively. However, the average frequency of compressions per minute (121 versus 124), the percentage of correct hand positioning during chest compressions (87% versus 90%) and the average duty cycle (47% versus 45%) did not display a significant difference.

Conclusion. The continuous CPR training group obtained better results regarding quality of chest compressions when compared with single CPR training.

Key words: cardiac massage, cardiopulmonary resuscitation, out-of-hospital cardiac arrest, emergency medicine, resuscitation

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Comparison of the Eosinophil Count to C – reactive protein, Leukocyte Count, and Neutrophil Count for the detection of bacterial infection in ill-appearing children with fever admitted to the Emergency Department


Introduction. From late 19th century to the present day, several authors have investigated the value of low eosinophil count as a biomarker of bacterial infection. In this study, we examined the value of eosinopenia for diagnosing bacterial infection in ill-appearing children admitted to the pediatric emergency department.

Methods. Retrospective review of the medical records of children age 1 month to 14 years who appeared ill on admission to the emergency department (ED). Data collected included; C-reactive protein (CRP) level leukocyte, neutrophil, eosinophil counts, results of microbiological tests, radiologic evaluation, and treatment given in the ED. Final outcome data were also collected.

Results. In total, 878 met our case definition and inclusion criteria. 521 patients had confirmed or presumed bacterial infection and 355 patients had presumed or confirmed viral infection. Nineteen patients died; all had bacterial infections. Neutrophil, eosinophil counts and CRP level were independent risk factors for bacterial infection in the multivariate analysis (p<0.05). The receiver operating characteristics (ROC) curves analysis for discriminating bacterial and viral infection showed that the eosinophil count (≤50 cells/μL) (area under the ROC curve [AUROC] 0.671; 95% Confidence Interval [CI]: 0.639-0.702) was similar to the neutrophil count (AUROC 0.655; 95% CI: 0,622-0.686), and CRP level (AUROC 0.710; 0.678-0.740) (p>0.05). The sensitivities of the leukocyte, neutrophil, and eosinophil counts and CRP level were 57.5%, 62.9%, 61%, and 57.1%, respectively. The specificities of them were 59.1%, 63.3%, 67%, and 77.4%, respectively.

Conclusion. In our study population, although the accuracies of eosinophil, neutrophil counts, and CRP level were not enough, they had similar in distinguishing viral from bacterial infection in ill appearing febrile children. By comparison the leukocyte count had limited predictive value.

Key words: eosinopenia, CRP, acute phase reactants, childhood

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Volaemic resuscitation in critical patients with severe haemorrhagic shock. Complications due to impaired microvascular system and ischaemia/reperfusion syndrome: A Case Report


Severe trauma is one of the most common causes of death all around the world. Complications of haemorrhagic shock, such as coagulopathy, hypothermia and metabolic acidosis, form the lethal triad in trauma.

In this case report we present a male patient admitted with severe haemorrhagic shock – haemoglobin (Hb) 5.6 mg/dL, arterial pressure (AP) 60/53 mmHg, heart beat (HB) 140 bpm, hypothermia (35 0C), lactic acidosis pH 7.21, lactates (Lac) 3.9 mmol/L, excess bases BE(E) – 12.8 mmol/L.

Volume resuscitation was started in the emergency department (ED), and continued in the operating room (OR). Fluid resuscitation was guided taking into account a number of factors, such as maintaining fluid and electrolyte balance, protecting the microcirculation, avoidance of ischaemia / reperfusion syndrome, minimization and inhibition of free radical synthesis, responsible for oxidative stress, by administration of high doses of antioxidants.

During Intensive Care Unit (ICU) admission, the patient developed severe left lower limb ischaemia. After clinical and laboratory investigations, it was decided to perform a femoral-popliteal by-pass. Failure of the by-pass resulted in amputation of the left lower limb. The patient was discharged from ICU after 27 days of intensive therapy and nursing.

In conclusion, we can affirm that the adjustment of fluid management, as well as administration of substances with antioxidant properties, improved the clinical status of the patient and chance of survival.

Key words: haemorrhagic shock, volaemic resuscitation, ischaemia, reperfusion, oxidative stress

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Prehospital preterm difficult breech delivery – two case reports


We report on two cases of prehospital initiated precipitated preterm deliveries with breech presentation, which were completed at the hospital. Case 1 involved a precipitated breech delivery in a multipara, and case 2 an unrecognizeddizygotic (diamniotic, dichorionic) twin pregnancy, with precipitated preterm breech delivery of the first twin, in a multipara.

Key words: breech delivery, emergency

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Bilateral Pneumothorax and Subcutaneous Emphysema following Endoscopic Retrograde Cholangiopancreatography with Sphincterectomy


Endoscopic retrograde cholangiopancreatography (ERCP) is a valuable diagnostic and therapeutic procedure in the management of pancreatic and extrahepatic biliary tract diseases. Although rare, it is related to several complications including retroperitoneal duodenal perforation. The perforation results in air accumulation in the retroperitoneal, pleural or subcutaneous space. We present a case of 63-year-old female with massive bilateral pneumothorax and subcutaneous emphysema following therapeutic ERCP.

Key words: endoscopic retrograde cholangiopancreatography, pneumothorax, subcutaneous emphysema, complications of endoscopic retrograde cholangiopancreatography

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Neonatal early onset sepsis due to Moraxella osloensis: Case-report and revision of the literature


We report the first case of early-onset systemic neonatal infection associated with Moraxella osloensis bacteriemia in a full term baby. The genus Moraxella is constituted by a group of pleomorphic bacteria obligate aerobes, Gram-negative, oxidase positive and indole negative infrequently isolated from clinical specimens. The organism is rarely reported in the literature as the causative agent of infection in humans, mostly in immunocompromised patients. Only 12 cases of M. osloensis-related infections during childhood have been reported in the literature so far. This unique report of M. osloensis infection, during the neonatal period, concerns the isolation of the bacteria in purulent secretions from the eyes of a 3-week-old baby with opthalmia. In our patient, the precocity of the onset of symptoms allows us to hypothesize a vertical transmission of the bacteria.

Key words: Moraxella, newborn, sepsis

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Carbamazepine overdose presenting as a diabetes insipidus – like condition in a child


Carbamazepine is a commonly used antiepileptic medication. In overdoses it can produce various side effects involving neurological, cardiac, hematological and endocrinal systems. Inappropriate secretion of Anti Diuretic Hormone (ADH) is a well-known complication of carbamazepine toxicity. We are reporting an unusual complication in an adolescent girl with intentional carbamazepine overdose. A sixteen year old female with carbamazepine ingestion presented to our hospital with altered sensorium. On admission she was found to have a very high serum carbamazepine level and metabolic acidosis. In contrast to the possible inappropriate secretion of ADH, as an adverse effect of carbamazepine, her hospital course was complicated with a diabetes insipidus – like condition following treatment with multiple doses of activated charcoal and sodium bicarbonate therapy.

Key words: Carbamazepine, Diabetes Insipidus, activated charcoal, child

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Reversible peripartum cardiomyopathy in a triplet pregnancy


Peripartum cardiomyopathy (PPCM) is a rare form of dilated cardiomyopathy that occurs in previously healthy women in the last month of pregnancy and up to several months after delivery. The incidence of PPCM is low, but its morbidity and mortality rate are high, with a substantial risk of poor outcome of the pregnancy. Patients who have recovered from PPCM run a high risk of reoccurrence in subsequent pregnancies. In this case report we present a 32-year old female patient who developed acute heart failure (HF) associated with significantly reduced systolic function due to PPCM soon after a delivery of triplets. Treatment was immediately initiated in the intensive coronary unit with oxygen-therapy, loop diuretics, aldosterone blockers, beta blockers, angiotensin-converting enzyme (ACE) inhibitors and bromocriptine. During the follow up period, a year and a half after delivery, a complete recovery of systolic function was observed with no residual symptoms.

Key words: dilated cardiomyopathy, triplet pregnancy, peripartum period

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An unusual infection in a patient with peripherally inserted central catheter


A peripherally inserted central catheter (PICC) is widely used in transfusion therapy and for monitoring many kinds of diseases, especially in critically ill patients. Compared with other catheters, it has a lower risk of catheter-related bloodstream infections. Aeromonas Hydrophila (AH) is a kind of opportunistic pathogen, vibrionaceae aeromonas, and gram-negative brevibacterium, widely distributed in nature, in all kinds of body fluid. It usually causes gastrointestinal infections, and rarely causes Aeromonas septicemia. To date, there has been no report of a PICC-related AH infection. We report the case of a 40-year-old female with breast cancer, who suffered post-op. severe sepsis and double lower limb cellulitis with multiple organ failure. All of this was due to AH invading the blood through the PICC.

Key words: Aeromonas Hydrophila, peripherally inserted central catheter, sepsis, multiple organ failure

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Ingestion of foreign bodies in children: the experience of a third-level single center from 2001 to 2012

Foreign body (FB) ingestion in pediatrics is a worldwide problem of significant relevance especially for children aged 6 months-3 years. (1,2) We have performed a retrospective collaborative study to evaluate features and outcomes of FB ingestions in all 0-to-18-year-old patients from January 2001 to December 2012 in our polyclinic. Our evaluation was performed using the GIPSE database, recording and tabulating patient’s age and sex, hours and month of admission to the emergency department, type of FB ingested, symptoms, examinations performed, advice required, type of therapy, and data about eventual hospitalization, in a specific database.

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Comparison of intubation performance between four different laryngoscope blades used by novice medical students during child resuscitation

Asphyxia is a major cause of cardiac arrest in children, (1-3) therefore restoring the airway and ensuring adequate oxygenation of the patient are essential life-saving procedures. (3,4) According to the 2010 guidelines of the European Resuscitation Council (ERC), the gold standard for airway management during resuscitation for both adults and children is endotracheal intubation (ETI). (1)

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