Periviable birth: A review of ethical considerations.

BACKGROUND: Advances in perinatology and medical technology have pushed the limits of viability to unprecedented extremes, leading to a growing population of NICU "graduates" with a wide range of health issues. Although survival rates from 22 weeks of gestation onwards have improved over the last 30 years, the incidence of disabilities remains the same. Providing intensive care to a high-risk population with significant mortality and morbidity raises the fundamental conflict between sanctity and quality of life. Potential severe handicap and need for frequent tertiary care inevitably impact the whole family unit and may outweigh the benefit of survival. The aim of this study is to explore and summarize the ethical considerations in neonatal care concerning perivable birth. METHODS: Eligible studies published on PubMed were included after a systematic search using the PICO methodology. RESULTS: Forty-eight studies were systematically reviewed regarding guidelines, withholding or withdrawing treatment, parental involvement, and principles applied in marginal viability. As periviable birth raises an array of complex ethical and legal concerns, strict guidelines are challenging to implement. CONCLUSIONS: Active life-sustaining interventions in neonatology should be balanced against the risk of putting infants through painful and futile procedures and survival with severe sequelae. More evidence is needed on better prediction of long-term outcomes in situations of imminent preterm delivery, while good collaboration between the therapeutic team and the parents for life-and-death decision-making is of utmost importance. HIPPOKRATIA 2021, 25 (1):1-7.

Intravenous lipid emulsion as an antidote in clinical toxicology: a systematic review.

OBJECTIVE: Intravenous lipid emulsions (ILE) were developed many decades ago to supply nutritional requirements to patients unable to obtain adequate enteral nutrition. The utility of ILE was extended to therapeutics, facilitating the delivery of drugs. More recently, the potential for ILE to act as an antidote for inversion of drug toxicity has been recognized. This review aims to summarize the literature on ILE therapy as an antidote. Suggested mechanisms of action, safety profile, and recommendations on the administration of ILE in cases of drug intoxication are highlighted. MATERIALS AND METHODS: A complete literature survey was performed using the PubMed database search to collect available information regarding mechanisms of ILE action as an antidote, ILE administration for drug toxicity, and presentation of adverse events. RESULTS: A total of 102 studies met the selection criteria for inclusion in the review. Mainly used for local anesthetics toxicity, ILE therapy has been expanded in clinical toxicology involving overdose treatment of drugs other than local anesthetics. Partitioning in a lipid phase of fat droplets is a mechanism named the lipid sink phenomenon that has primarily been described to explain this action of ILE and remains the most widely accepted. At the same time, recent research has also revealed several molecular mechanisms that may contribute to ILE efficacy. CONCLUSIONS: ILE therapy comprises a recognized approach in clinical toxicology. Due to the lack of randomized clinical trials, recommendations on administration are based on animal studies and published cases. Thus, the constantly increased knowledge about ILE therapy supports the need for a detailed appraisal.

Views of cancer patients regarding cardiopulmonary resuscitation in Greece.

Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.

The effect of antioxidant supplementation on bacterial translocation after intestinal ischemia and reperfusion.

The intestine is highly sensitive to ischemia/reperfusion (I/R) injury. Intestinal I/R may cause local tissue injury and disruption of the intestinal mucosal barrier, allowing the passage of viable bacteria and endotoxins from the gastrointestinal lumen to distant organs. This phenomenon, known as bacterial translocation (BT), may lead to systemic disorders with high morbidity and mortality. Oxidative stress mediators such as reactive oxygen species, polymorphonuclear neutrophils and nitric oxide are believed to contribute to the intestinal I/R injury. Many antioxidants have shown protective effects against I/R injury of various organs. The present article provides an overview of studies investigating the effect of antioxidant supplementation on BT after intestinal I/R.

Reoxygenation of asphyxiated newborn piglets: administration of 100% oxygen causes significantly higher apoptosis in cortical neurons, as compared to 21%.

OBJECTIVE: Evaluation of neuronal changes in an animal experimental model of normocapnic hypoxia- reoxygenation. MATERIALS AND METHODS: Fifty male piglets were the study subjects; normocapnic hypoxia was induced in 40 piglets and ten were sham-operated (controls). When bradycardia and/or severe hypotension occurred, reoxygenation was initiated. Animals were allocated in 4 groups according to the oxygen concentration, they were resuscitated with 18%, 21%, 40%, and 100% O2. Persisting asystole despite 10 minutes of cardiopulmonary resuscitation and return of spontaneous circulation were the endpoints of the experiment. Surviving animals were euthanized and brain cortex samples were collected, hematoxylin and eosin-stained, and examined for apoptotic bodies observing 10 consecutive high power fields. RESULTS: Histological examination of the control group did not show any pathological change. On the contrary, apoptosis of neurons was found in 87.5% of treated animals. When specimens were examined according to the oxygen concentration used for resuscitation, we found marked intergroup variability; a higher percentage of apoptotic neurons was observed in piglets of group 4 (100% oxygen) compared to the others (P=0.001). CONCLUSIONS: This preliminary data shows that normocapnic hypoxia and reoxygenation in Landrace/Large White piglets resulted in significant histological changes in the brain cortex. The degree of pathological changes in cortical neurons was significantly associated with the oxygen concentration used for reoxygenation, with a higher percentage of apoptotic neurons being observed in piglets reoxygenated with 100% compared to 18% O2 and to 21% O2.

Metabolomics network characterization of resuscitation after normocapnic hypoxia in a newborn piglet model supports the hypothesis that room air is better.

Perinatal asphyxia is attributed to hypoxia and/or ischemia around the time of birth and may lead to multiorgan dysfunction. Aim of this research article is to investigate whether different metabolomic profiles occurred according to oxygen concentration administered at resuscitation. In order to perform the experiment, forty newborn piglets were subjected to normocapnic hypoxia and reoxygenation and were randomly allocated in 4 groups resuscitated with different oxygen concentrations, 18%, 21%, 40%, and 100%, respectively. Urine metabolic profiles at baseline and at hypoxia were analysed by (1)H-NMR spectroscopy and metabolites were also identified by multivariate statistical analysis. Metabolic pathways associations were also built up by ingenuity pathway analysis (IPA). Bioinformatics analysis of metabolites characterized the effect of metabolism in the 4 groups; it showed that the 21% of oxygen is the most "physiological" and appropriate concentration to be used for resuscitation. Our data indicate that resuscitation with 21% of oxygen seems to be optimal in terms of survival, rapidity of resuscitation, and metabolic profile in the present animal model. These findings need to be confirmed with metabolomics in human and, if so, the knowledge of the perinatal asphyxia condition may significantly improve.

Antihypertensive therapy in children: differences in medical approach between the United States and Europe.

Similarly to a series of chronic diseases, essential arterial hypertension (HTN) may be manifested during childhood as a blood pressure (BP) reading which repeatedly rises above the 95(th) percentile of population-specific standards. Since BP tends to track along the same percentiles throughout life, children with higher BPs are more likely to become hypertensive adults. When healthy measures aimed at reducing BP (i.e. body weight reduction, aerobic physical exercise, low sodium intake) have failed, pharmacological treatment is usually required. This paper aims to undertake a review of antihypertensive pharmacological therapy in children, examining the drugs used in chronic treatment as well as those administered to treat hypertensive crisis (i.e. a BP major than 99(th) percentile of paediatric normograms). Moreover, several important differences registered in the therapeutic approach to paediatric HTN between US and European Guidelines will be underlined.

Effects of early amiodarone administration during and immediately after cardiopulmonary resuscitation in a swine model.

BACKGROUND: Aim of this experimental study was to compare haemodynamic effects and outcome with early administration of amiodarone and adrenaline vs. adrenaline alone in pigs with prolonged ventricular fibrillation (VF). METHODS: After 8 min of untreated VF arrest, bolus doses were administered of adrenaline (0.02 mg/kg) and either amiodarone (5 mg/kg) or saline (n = 8 per group) after randomisation. Cardiopulmonary resuscitation (CPR) was commenced immediately after drug administration, and defibrillation was attempted 2 min later. CPR was resumed for another 2 min after each defibrillation attempt, and the same dose of adrenaline was given every 4th minute during CPR. Haemodynamic monitoring and mechanical ventilation continued for 6 h after return of spontaneous circulation (ROSC), and the pigs were euthanised at 48 h. Researchers were blinded for drug groups throughout the study. RESULTS: There was no difference in rates of ROSC and 48-h survival with amiodarone vs. saline (5/8 vs. 7/8 and 0/8 vs. 3/8, respectively). Diastolic aortic pressure and coronary perfusion pressure were significantly lower with amiodarone during CPR and 1 min after ROSC (P < 0.05). The number of electric shocks required for terminating VF, time to ROSC and adrenaline dose were significantly higher with amiodarone (P < 0.01). The incidence of post-resuscitation tachyarrhythmias tended to be higher in the saline group (P = 0.081). CONCLUSION: Early administration of amiodarone did not improve ROSC or 48-h survival rates, and was associated with worse haemodynamics in this swine model of cardiac arrest.

Influence of LMA cuff pressure on the incidence of pharyngolaryngeal adverse effects and evaluation of the use of manometry during different ventilation modes: a randomized clinical trial.

BACKGROUND: Pharyngolaryngeal discomfort is a significant complication following the use of laryngeal mask airway (LMA). The present study aimed to investigate the relation of LMA cuff pressure and the occurrence of pharyngolaryngeal discomfort during spontaneous ventilation (SV), pressure support (PSV) and pressure control ventilation (PCV). METHODS: A hundred and twenty patients, ASA I-III, were included in this study. Originally the patients were divided into three groups: the 1st group was left to breath spontaneously, the 2nd group was placed under PSV while PCV was used in the 3rd group. Each group was divided into two subgroups: A) intervention group (maintaining cuff pressure at 60 cmH2O, measurement in 10 min intervals) and B) observation group (no intervention in cuff pressure, measurement in 10 min intervals). Anesthesia was induced with propofol and fentanyl and maintained with sevoflurane in air/oxygen. Patients were assessed 2 and 24 hours post-surgery, for sore throat, dysphonia or dysphagia. RESULTS: A and B subgroup comparison at 24 hours revealed a statistically significant difference in the presence of pharyngolaryngeal discomfort in the PSV group (10% versus 55% respectively, P=0.006). Furthermore, when assessing the effect of maintaining a constant cuff pressure regardless of mode of ventilation, significantly fewer adverse effects were observed (8.3% vs. 35%, P=0.001) when compared to the non-intervention subgroup. CONCLUSION: Maintaining LMA cuff pressure in values which do not exceed 60 cmH2O probably contributes in decreasing pharyngolaryngeal discomfort independently of ventilation mode. The ventilation mode which leads to the highest incidence of pharyngolaryngeal morbidity when cuff pressures are not closely monitored is PSV.

First experience of the use of the C-MAC PM videolaryngoscope in a clinical setting by anesthetic nurses: a comparison with anesthetists.

BACKGROUND: The Storz C-MAC videolaryngoscope has been found to facilitate endotracheal intubation and to be easy to use by novice users. However, it has never been studied in those who will probably use it most, anesthetists and anesthetic nurses. The aim of the present study was to identify the number of attempts needed before the participants were able to intubate 2 consecutive patients within 30 seconds. METHODS: Following a didactic session, 22 anesthetists and 21 anesthetic nurses were included in the study and attempted to intubate 184 patients with predicted easy laryngoscopy scheduled to undergo elective surgery. The number of attempts before achieving 2 consecutive successful intubations and time to intubation were recorded for both groups of participants. Perception of ease of use for the device was also recorded. RESULTS: Overall, anesthetic nurses required more attempts before achieving 2 consecutive successful intubations (5.9 +/- 3.24 vs 2.73+/- 1.67, p < 0.0005). They also had significantly more failures until 2 consecutive successful intubations were achieved, compared to anesthetists (4.1 +/- 2.8 vs 1.32 +/- 1.25, p < 0.0005). A significantly higher percentage of anesthetic nurses required more than 3 attempts before achieving 2 consecutive intubations (75% vs 36%, p = 0.016). Regarding the intubation time, no significant differences were recorded between specialties. Anesthetic nurses assessed the C-MAC as easier to use than anesthetists did. CONCLUSIONS: This is the first clinical study assessing the use of the C-MAC videolaryngoscope by inexperienced anesthetists and anesthetic nurses indicating that it is easy to learn and to use in their hands.

The role of immunohistochemistry in the study of the newborn kidney.

The identification of the different cell types involved in human nephrogenesis, when solely based on morphology, may lead to errors in its interpretation, given the complexity of the histological picture of the fetal and of the newborn kidney. In this study, the most recent works utilizing immunohistochemistry for the identification of the multiple cell types involved in human nephrogenesis are reviewed. The role of WT1, MUC1, Thymosin beta 10, Thymosin beta 4, CD10 and CD44 in the different phases of glomerulogenesis and of tubulogenesis is here described, with particular emphasis on their expression in the early phases of nephrogenesis. On the basis of our data, immunohistochemistry appears to be a useful tool in the study of human nephrogenesis, giving new data on the different steps of the differentiation of metanephric mesenchyme towards the multiple cell types characterizing the mature human kidney. Moreover, allowing a better knowledge of the protein products involved in the generation of new nephrons, immunohistochemistry could open new perspectives in the field of renal regenerating medicine, evidencing the factors able to prolong nephrogenesis after birth, helping us to reach our goal: allowing newborn kidneys to restore their nephron endowment, escaping susceptibility to hypertension and renal disease in adulthood.

Drugs in newborn resuscitation: the more we learn the least we use.

Temperature control, airway management and support of circulation remain the gold-standards for the majority of neonates requiring resuscitation at birth. For the minority of neonates in which the basic steps of resuscitation fail to reverse an adverse situation, drug administration is justifiable. The 2010 International Liaison Committee on Resuscitation (ILCOR) guidelines for newborn resuscitation state: "Drugs are rarely indicated in resuscitation of the newly born infant. Bradycardia in the newborn infant is usually caused by inadequate lung inflation or profound hypoxia, and establishing adequate ventilation is the most important step to correct it. However, if the HR remains less than 60 min-1 despite adequate ventilation and chest compressions, it is reasonable to consider the use of drugs. These are best given via an umbilical venous catheter". Even though drugs have been used in neonatal resuscitation for long, their doses, order and route of administration have been issues of debate among neonatologists, mainly due to the lack of data in human studies. This review will examine existing evidence behind the medications currently used in neonatal resuscitation.

CD10 in the developing human kidney: immunoreactivity and possible role in renal embryogenesis.

CD10 was first identified in tumor cells of acute lymphoblastic leukemia. Most studies on CD10 expression have dealt with tumor pathology. Since no data are available for specific role in the fetal kidney, this study aimed at investigating CD10 expression during the different phases of renal embryogenesis. To this end, the expression of CD10 was evaluated in the kidney of two human fetus and in three newborns. In both fetuses, immunostaining for CD10 was compartmentalized and mainly concentrated in the mid-deep cortex. Reactivity for CD10 was stronger in the glomerular epithelium, in proximal tubules and in metanephric mesenchymal cells. At 25 weeks of gestation, CD10 was also detected in the subcapsular regions, including some pretubular aggregates of cap mesenchymal cells and renal vesicles. At 34 weeks of gestation, we observed an increased immunoreactivity for CD10 in visceral and parietal glomerular epithelium. At 39 weeks of gestation, CD10 was also expressed in the collecting tubules and in the Henle loops. Our data show a strong expression of CD10 in all stage of human kidney development, characterized by dynamic changes and support the hypothesis that CD10 plays a relevant role in renal embryogenesis.

MUC1 marks collecting tubules, renal vesicles, comma- and S-shaped bodies in human developing kidney tubules, renal vesicles, comma- and s-shaped bodies in human kidney.

MUC1 is a transmembrane glycoprotein, apically expressed in most epithelial cells, used in the differential diagnosis of carcinomas and for discrimination of tumors of non-epithelial origin showing epithelioid features. Little attention has been paid so far though, on its possible significance in embryonic tissues. A preliminary study from our group revealed MUC1 expression in the cap mesenchymal cells during human nephrogenesis, suggesting a role for MUC1 in the process of mesenchymal-to-epithelial transition. This study aimed at investigating the expression pattern of MUC1 in various developing structures of human fetal kidney. Expression of MUC1 was examined in kidneys of 5 human fetuses. MUC1 immunoreactivity was detected in ureteric bud tips, in collecting tubules, in cap mesenchymal cells undergoing the initial phases of mesenchymal-to-epithelial transition, in renal vesicles, comma-bodies, and S-shaped bodies. Our previous preliminary report suggested a role for MUC1 in the initial phases of the process of mesenchymal-to-epithelial transition. The present data suggest that MUC1 expression characterizes multiple structures during human nephrogenesis, from the ureteric bud, to the initial phases of mesenchymal-to-epithelial transition and that MUC1 should be added to the genes activated during the process of mesenchymal-to-epithelial transition in the cap mesenchyme of human kidney.

Quality of life and pre-operative anxiety level in patients scheduled to undergo thoracic surgery.

PURPOSE: Increased preoperative anxiety levels may lead to adverse outcomes. We aimed at assessing the relationship between quality of life (QoL) and preoperative anxiety level during the 4-week preoperative period in patients scheduled to undergo thoracic surgery and we tried to identify patients who could benefit from preoperative supportive measures. METHODS: One hundred patients comprised the study population (52 men and 48 women) out of the initial 136, who were scheduled to undergo thoracic surgery. Mean age was 56±15 years (±SD). After obtaining informed consent, participants were asked to answer a questionnaire, through a personal interview, 12 to 15 h prior to their scheduled thoracic operation. The questionnaire included questions on demographics and incorporated the State Anxiety Inventory (STAI) and SF-36 scales. RESULTS: Female patients (p=0.023), unemployed patients (p=0.01) and patients that were scheduled for a mediastinoscopy (p=0.001) experienced increased anxiety level. Lower scores in several parameters related to the QoL were found to be associated with increased anxiety level. Limitations in patients' ability to work or to perform other everyday activities as a result of mental health problems (p=0.006), low vitality (p<0.001), bad general mood (p<0.001), deteriorated general health (p<0.001) and general mental health (p<0.001) were associated with preoperative anxiety. No differences were found in anxiety level among lung cancer and non-lung cancer patients. CONCLUSION: This study showed an inverse proportional correlation between preoperative QoL and anxiety during the 4-week period prior to thoracic surgery. Appropriate pharmaceutical and psychological support may improve patients' anxiety level.

Acute otitis media in neonatal life: a review.

Acute otitis media is frequently encountered by general practitioners and pediatricians. In the neonatal period acute otitis media may present as an isolated local infection or as part of septicemia. Diagnosis of the condition by otoscopy is difficult. Considering the wide spectrum of middle ear disorders (acute otitis media, otitis media with effusion, chronic suppurative otitis media) one can appreciate why opinions on the management of the condition are diverse. This is a review of the literature on clinical presentation, etiology, risk factors, treatment and prevention of acute otitis media in neonatal life.

Macintosh and Glidescope® performance by Advanced Cardiac Life Support providers: a manikin study.

BACKGROUND: The aim of the present study was to assess whether the use of the Glidescope® would improve the success rates and the duration of intubation attempts during airway management when compared to direct laryngoscopy in Advanced Cardiac Life Support (ACLS) providers with no prior experience in videolaryngoscopy. METHODS: This cross-over randomized study involved 44 ACLS providers. The educational session for the participants included a brief presentation of the equipment and a demonstration of the Glidescope®. All intubations were performed using a 7.5-mm endotracheal tube on an adult manikin. A size 3 Macintosh blade and a standard Glidescope® adult blade were used. Glidescope® videolaryngoscope was used. The primary endpoints were: duration of each endotracheal intubation attempt and success rate for each device. A secondary endpoint was the perception of ease of use with each device. Each participant was asked to assess the ease of use of each device using a visual analogue scale (0=extremely difficult and 10=extremely easy). RESULTS: No statistically significant difference was observed in the time required to successful intubation of the trachea with the Macintosh laryngoscope and the Glidescope®. However, significantly fewer intubation attempts were required with the Glidescope® compared to the Macintosh laryngoscope. In addition, most candidates found that using the videolaryngoscope was easy. CONCLUSION: This study demonstrated that the Glidescope® videolaryngoscopy performed at least as well as conventional laryngoscopy in ACLS providers. Although simpler ventilation techniques should be applied first during critical airway management, this study suggests that, when intubation is needed, videolaryngoscopy cna be helpful.

Congenital cytomegalovirus infection.

Congenital cytomegalovirus (CMV) infection is a serious health problem. The obstacles for limiting this infection are the lack of public awareness on this issue, especially owing to the asymptomatic nature of CMV infections, the inefficacy of therapy, and the unsuccessful vaccine trials to date. It is therefore important to organize the current data to estimate the results and to report that the development of a vaccine against CMV must be of the highest priority.

Effect of low-dose oral erythromycin on gastric aspirates in ventilated neonates less than 32 weeks of gestation. Preliminary results.

In this prospective study, the 24-hour gastric aspirate volume was carefully recorded before, 24 and 48 h after administering 1.7 mg/kg/8-hourly of oral erythromycin to 16 ventilated neonates less than 32 weeks of gestation. Their median gestational age was 28.5 weeks (range 23-31 weeks), their median birthweight was 1,045 g (range 690-1,560 g) and the median day of life at which erythromycin was commenced was 9.5 days (range 4-16 days). Prior to administering erythromycin median 24-hour gastric aspirate volume, expressed as a percentage of the milk volume given over the same period, was 38.5% (range 20.0-100%). It was significantly lower 24 h (median 12%, range 0-41%, p = 0.0004) and 48 h (median 5%, range 0-21%, p = 0.0004) after commencing erythromycin. There was also significant reduction of gastric aspirate volume between 24 and 48 h after commencing erythromycin (p = 0.0024). Milk volume increment over the same period was not significant (p = 0.1022). These preliminary results warrant further evaluation through a randomised controlled trial.