A Higher Amount of Nutritional Intake as a Possible Cause of Hyperglycemia in Extremely Premature Infants in Parenteral and Enteral Nutrition at the Tertiary Neonatal Intensive Care Unit.

BACKGROUND: This study aimed to find an association between infants who had hyperglycemia and those who did not, those treated with insulin or not and several prenatal and postnatal variables or the suboptimal prescription of parenteral nutrition. METHODS: We conducted a retrospective study, which included extremely premature infants (<28 weeks of gestation) admitted to the tertiary NICU, University Medical Centre Ljubljana, between 1 January 2021 and 31 December 2021. Blood glucose measurements, insulin treatment, general characteristics, nutritional data and complications of prematurity were obtained retrospectively from hospital data. RESULTS: There were 21 infants included in the study who did not receive insulin and 17 who were treated with insulin. Infants receiving insulin were younger and lighter compared to the non-insulin treatment group (mean gestational age 178 vs. 188 days; median birth weight 680 g vs. 990 g). The younger insulin group of infants received the same daily number of total macronutrients per kg per day compared to the older non-insulin group, i.e., glucose, lipids and amino acids, as recommended for the gestational age and birth weight. After adjusting for gestational age, no significant association with complications of prematurity was found. CONCLUSIONS: The postulated explanation (with the prescription of a higher amount of macronutrients during the first seven days) for hyperglycemia and treatment with insulin in the less mature and lighter infants cannot be supported by the data given.

Special Issue: Intensive Care for Critically Ill Neonates: Clinical Diagnosis and Treatment.

Many physicians and researchers in the recent past have recognized the need to provide care and to study term and preterm infants when sufficient knowledge had not yet been attained, and to research how to approach and care for the most vulnerable children, i [...].

External validation of population pharmacokinetic models of gentamicin in paediatric population from preterm newborns to adolescents.

The aim of this study was to externally validate the predictive performance of published population pharmacokinetic models of gentamicin in all paediatric age groups, from preterm newborns to adolescents. We first selected published population pharmacokinetic models of gentamicin developed in the paediatric population with a wide age range. The parameters of the literature models were then re-estimated using the PRIOR subroutine in NONMEM®. The predictive ability of the literature and the tweaked models was evaluated. Retrospectively collected data from a routine clinical practice (512 concentrations from 308 patients) were used for validation. The models with covariates characterising developmental changes in clearance and volume of distribution had better predictive performance, which improved further after re-estimation. The tweaked model by Wang 2019 performed best, with suitable accuracy and precision across the complete paediatric population. For patients treated in the intensive care unit, a lower proportion of patients would be expected to reach the target trough concentration at standard dosing. The selected model could be used for model-informed precision dosing in clinical settings where the entire paediatric population is treated. However, for use in clinical practice, the next step should include additional analysis of the impact of intensive care treatment on gentamicin pharmacokinetics, followed by prospective validation.

Association between colonization of the respiratory tract with Ureaplasma species and bronchopulmonary dysplasia in newborns with extremely low gestational age: a retrospective study.

AIM: To ascertain the incidence of respiratory tract colonization in extremely low gestational age newborns (ELGANs) with Ureaplasma parvum and Ureaplasma urealyticum and determine if there is a difference in the severity of bronchopulmonary dysplasia (BPD) between ELGANs with and without Ureaplasma species (spp) colonization. METHODS: We reviewed the medical records of ELGANs 23 0/7-27 6/7 weeks of gestation, tested for U. parvum and U. urealyticum in our Center from January 1, 2009 to December 31, 2019. Ureaplasma spp were identified with the Mycofast Screening Revolution assay based on liquid broth cultures or with polymerase chain reaction. RESULTS: This study enrolled 196 preterm newborns. Fifty (25.5%) newborns had Ureaplasma spp respiratory tract colonization, with U. parvum being the predominant species. The incidence rate of respiratory tract colonization with Ureaplasma spp slightly increased in the studied period. The incidence rate for 2019 was 16.2 per 100 infants. BPD severity significantly correlated with Ureaplasma spp colonization (P = 0.041). After controlling for other risk factors for BPD in a regression model, preterm infants colonized with Ureaplasma spp had 4.32 times (95% confidence interval, CI 1.20-15.49) higher odds for developing moderate-to-severe BPD. CONCLUSIONS: U. parvum and U. urealyticum could be associated with the development of BPD in ELGANs.

Molecular Typing of Mastadenoviruses in Simultaneously Collected Nasopharyngeal Swabs and Stool Samples from Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures.

This study determines and compares the frequency of human mastadenovirus (HAdV) presence in children with acute bronchiolitis (AB), acute gastroenteritis (AGE), and febrile seizures (FS), ascertains types of HAdVs associated with each individual syndrome and contrasts the findings with a control group of children. The presence of HAdVs was ascertained in simultaneously collected nasopharyngeal (NP) swabs and stool samples amplifying the hexon gene by RT-PCR; these were sequenced to determine the types of HAdVs. HAdVs were grouped into eight different genotypes. Of these, three (F40, F41, and A31) were found solely in stool samples, whereas the others (B3, C1, C2, C5, and C6) were found in both stool samples and NP swabs. The most common genotypes in NP swabs were C2 (found in children with AGE and FS) and C1 (only in children with FS), whereas in stool samples genotypes F41 (in children with AGE) and C2 (in children with AGE and FS) prevailed, and C2 was simultaneously present in both samples. HAdVs were more often detected in stool samples than in NP swabs in patients (with the highest estimated viral load in stool samples in children with AB and AGE) and healthy controls and were more common in NP swabs in children with AGE than in children with AB. In most patients, the characterized genotypes in NP swabs and stool samples were in concordance.

Comparison of Neonatal Morbidity and Mortality Following Spontaneous and Medically Indicated Preterm Births: A Retrospective Population-Based Study Using Data from the Slovenian National Perinatal Information System 2013-2018.

BACKGROUND This retrospective population-based study analyzed data from the Slovenian National Perinatal Information System (NPIS) between 2013 and 2018 to compare neonatal morbidity and mortality following spontaneous and medically indicated preterm births. MATERIAL AND METHODS Retrospective population-based cohort. Entries to the NPIS database were searched by gestational age (GA) <37 weeks in Slovenia between 2013 and 2018. Of 9200 (6252 following spontaneous birth, 2948 following medically indicated) neonates included, 1358 were born at extremely to very preterm GA (998 following spontaneous birth, 360 following medically indicated). Logistic regression analysis was used to examine the association between neonatal mortality and composite severe neonatal morbidity and preterm birth type (spontaneous vs medically indicated) controlling for potential confounding variables. Analysis was first performed for all preterm births (GA 22 0/7 to 36 6/7) and later only for extremely to very preterm births (GA 22 0/7 to 31 6/7). RESULTS Neonatal mortality was significantly lower following spontaneous preterm birth at extremely to very preterm GA (odds ratio [OR] 0.34; 95% confidence interval [CI] [0.14, 0.81]), while there was no association in all preterm births group (OR 0.56; 95% CI [0.26, 1.20]). No significant correlation between preterm birth type and neonatal morbidity was found (OR 0.76; 95% CI [0.54, 1.09] for all preterm births and OR 0.71; 95% CI [0.47, 1.07] for extremely to very preterm births). CONCLUSIONS In this population study from Slovenia between 2013 and 2018, medically indicated preterm births at <32 weeks of GA were associated with significantly increased neonatal mortality but not neonatal morbidity.

Postnatal CMV Infection and Antiviral Treatment in Extremely Premature Infants: A 12-Year Retrospective Analysis.

BACKGROUND: The impact and outcomes of postnatal cytomegalovirus (CMV) infection are not entirely clear. We aimed to determine the associations between treatment outcomes of postnatal CMV infection and its antiviral treatment. METHODS: Retrospective study in a tertiary center. Infants of < 29 weeks gestational age who were tested for postnatal CMV infection were included. CMV-infected infants were compared to uninfected infants (control group). CMV-infected infants were either treated with ganciclovir and/or valganciclovir (CMVPT group) or not (CMVPNT group). Demographic, clinical, laboratory, treatment, and outcome data were collected. Primary outcomes were the length of stay, death before discharge and hearing impairment, cognitive and motor development as assessed by the Denver Developmental Screening Test II, and neurologic impairment at the corrected age of 1.5-2 years. RESULTS: We included 103 extremely premature infants. The Median (interquartile range [IQR]) length of stay was 94 (69-112) days in control, 85 (70-102) days in CMVPNT, and 100 (88-137) days in the CMVPT group. Mortality before discharge was 6% in control, 3.8% in CMVPNT, and 3.7% in the CMVPT group. Normal hearing at follow-up was found in 30/37 infants in control (81.1%), 13/13 infants in CMVPNT (100%), and 17/20 infants in the CMVPT group (85%). Denver Developmental Screening Test II results did not differ among the three groups. Neurologic impairment was found in 21/37 infants (56.8%) in control, 9/13 infants in CMVPNT (69.2%), and 14/20 infants in CMVPT group (70%). CONCLUSIONS: The associations between antiviral treatment of postnatal CMV infection and better treatment outcomes were nonsignificant.

What Constitutes a "Good Death"?-A Representative Cross-Sectional Survey Among the General Public in Croatia.

Understanding the attitudes of a particular society on a "good death" is important when it comes to end-of-life decision-making and palliative care. In the Republic of Croatia no systematic research has been done on the attitudes of the general population about the concept of a "good death". This cross sectional survey was conducted on a three-stage random sample, stratified by regions, counties and locations within those counties (N = 1203) during November and December, 2019. ANOVA, to determine differences, factor analysis and multiple regression analysis were used. The most important characteristics of a good death outlined by the respondents were: the absence of pain, the presence and unencumberedness of family and loved ones, the importance of a sense of fulfilment and meaning in life in this regard, reconciliation with God, the presence of awareness and sobriety, and the possibility of treatment.

Experiences and attitudes of medical professionals on treatment of end-of-life patients in intensive care units in the Republic of Croatia: a cross-sectional study.

BACKGROUND: Decisions about limitations of life sustaining treatments (LST) are made for end-of-life patients in intensive care units (ICUs). The aim of this research was to explore the professional and ethical attitudes and experiences of medical professionals on treatment of end-of-life patients in ICUs in the Republic of Croatia. METHODS: A cross-sectional study was conducted among physicians and nurses working in surgical, medical, neurological, and multidisciplinary ICUs in the total of 9 hospitals throughout Croatia using a questionnaire with closed and open type questions. Exploratory factor analysis was conducted to reduce data to a smaller set of summary variables. Mann-Whitney U test was used to analyse the differences between two groups and Kruskal-Wallis tests were used to analyse the differences between more than two groups. RESULTS: Less than third of participants (29.2%) stated they were included in the decision-making process, and physicians are much more included than nurses (p < 0.001). Sixty two percent of participants stated that the decision-making process took place between physicians. Eighteen percent of participants stated that 'do-not-attempt cardiopulmonary resuscitations' orders were frequently made in their ICUs. A decision to withdraw inotropes and antibiotics was frequently made as stated by 22.4% and 19.9% of participants, respectively. Withholding/withdrawing of LST were ethically acceptable to 64.2% of participants. Thirty seven percent of participants thought there was a significant difference between withholding and withdrawing LST from an ethical standpoint. Seventy-nine percent of participants stated that a verbal or written decision made by a capable patient should be respected. Physicians were more inclined to respect patient's wishes then nurses with high school education (p = 0.038). Nurses were more included in the decision-making process in neurological than in surgical, medical, or multidisciplinary ICUs (p < 0.001, p = 0.005, p = 0.023 respectively). Male participants in comparison to female (p = 0.002), and physicians in comparison to nurses with high school and college education (p < 0.001) displayed more liberal attitudes about LST limitation. CONCLUSIONS: DNACPR orders are not commonly made in Croatian ICUs, even though limitations of LST were found ethically acceptable by most of the participants. Attitudes of paternalistic and conservative nature were expected considering Croatia's geographical location in Southern Europe.

No increase in GFAP and S-100B in very preterm infants with mild periventricular leukomalacia or intraventricular hemorrhage: a pilot study.

AIM: To determine the serum levels of glial fibrillary acidic protein (GFAP) and S-100B in very preterm infants with and without periventricular leukomalacia (PVL) and/or intraventricular hemorrhage (IVH). METHODS: The study enrolled preterm infants born between 23 and 32 weeks of gestation admitted to the Neonatal Intensive Care Unit, University Medical Center Ljubljana. PVL and IVH were determined with cranial ultrasound. Peripheral blood was collected in the first 24 hours after delivery and once between days 4 to 7. GFAP and S-100B concentrations were measured in serum samples. Infants with PVL or IVH were compared with infants without PVL or IVH. RESULTS: Of 40 patients (mean gestational age 29.4 weeks), 7 had IVH and/or PVL. S-100B was detectable in peripheral blood in all patients at every measurement. In the group with IVH or PVL, the median S-100B at the first sampling was 0.43 (IQR 0.29-0.60) ng/mL, and 0.40 (IQR 0.33-1.01) ng/mL at the second sampling. In the group without PVL or IVH, it was 0.40 (IQR 0.29-0.6) ng/mL at the first sampling and 0.43 (IQR 0.34-0.62) ng/mL at the second sampling. The median GFAP was 0 regardless of the group and sampling time. The groups did not significantly differ in serum GFAP or S-100B levels. CONCLUSION: Peripheral blood levels of GFAP and S-100B were not significantly increased in very preterm infants that developed PVL or IVH. The predictive value of GFAP and S-100B as biomarkers of neonatal brain injury should be further explored in a larger cohort of neonates with more extensive IVH or PVL.

The relationship between the nurses' work environment and the quality and safe nursing care: Slovenian study using the RN4CAST questionnaire.

INTRODUCTION: The safety and quality of patient care are basic guidelines in finding new and improved solutions in nursing. Important and influential factors shape the nurses' work environment in hospitals. PURPOSE: With the study, we intended to investigate whether the perception of nurses' work environment is related to the safety culture and the quality of patient care and whether it differs according to nurses' level of education. METHODS OF WORK: The study with a quantitative research method was conducted at the six clinical departments of the University Medical Centre, Ljubljana in 2019. We used a survey questionnaire from the European survey Nurse forecasting in Europe (RN4CAST). RESULTS: 270 nurses were included in the study. The response rate was 54%. The study confirmed that there is a correlation between the assessment of the nurses' work environment and the general assessment of patient safety (r = 0.36; p <0.001), the general assessment of the quality of nursing care (r = 0.32; p <0.001), the confidence in patient self-care at discharge (r = 0.29; p <0.001) and the quality of patient care in the previous year (r = 0.27; p = 0.001). The results showed frequent verbal abuse of nurses, in 44.9% by patients and their relatives and in 35.4% by staff. Graduate nurses rated the work environment more negatively than healthcare technicians (p = 0.003). DISCUSSION AND CONCLUSION: We confirmed the correlation between the assessment of nurses' work environment and patient safety and the quality of health care, and that employees' education influences the assessment and perception of the work environment.

Noninvasive ventilation for respiratory distress syndrome is a potential risk factor for retinopathy of prematurity : Single Slovenian tertiary center study.

Retinopathy of prematurity (nROP) among extremely low gestational age newborns (ELGAN) in Slovenia has increased in recent years. At the same time mortality has further decreased and less invasive approaches for treatment of respiratory distress syndrome have been established. With the aim to study the possible association between the incidence of ROP and the duration of noninvasive ventilation, this retrospective study comprised ELGANs born during the first period (2010/2011), when invasive respiratory support was the prevalent method and in the second period (2015/2016), when noninvasive respiratory support was adopted. The results showed that the duration of noninvasive ventilation is a potential risk factor for ROP. Controlling for known risk factors for ROP and then adjusting for gestational age, number of transfusions and fraction of inspired oxygen (FiO2), the odds of ROP were 1.22 times greater (95% confidence interval, CI 1.01-1.48) with every additional week of noninvasive ventilation (p = 0.03).

How health care professionals confront and solve ethical dilemmas - a tale of two countries: Slovenia and Croatia.

AIM: To assess the differences in the way how Slovenian and Croatian health care professionals (HCPs) confront ethical dilemmas and perceive the role of hospital ethics committees (HECs). METHODS: This cross-sectional, survey-based study involved HCPs from three Slovenian and five Croatian university medical centers (UMC). The final sample sizes were 308 (244 or 79.2% women) for Slovenia and 485 (398 or 82.1% women) for Croatia. RESULTS: Compared with Croatian physicians, Slovenian physicians reported a higher share of ethical dilemmas regarding waiting periods for diagnostics or treatment, suboptimal working conditions due to interpersonal relationships in the ward, and end-of-life treatment withdrawal, and a lower share regarding access to palliative care and patient information protection. Compared with Croatian nurses, Slovenian nurses reported a lower share of ethical dilemmas regarding the distribution of limited resources, recognizing the patient's best interests, and access to palliative care. Compared with Croatian other HCPs, Slovenian other HCPs reported a lower burden of ethical dilemmas regarding waiting periods for diagnostics or treatment, distribution of limited resources, and access to palliative care. When encountering an ethical dilemma, all HCPs in both countries would first consult their colleagues. Slovenian and Croatian HCPs recognized the importance of the HECs to a similar extent, but viewed their role differently. CONCLUSION: Croatian and Slovenian HCPs are confronted with different ethical dilemmas and perceive the role of HECs differently.

Serum hepcidin and ferritin as markers of iron deficiency in premature infants born at less than 32 weeks of gestation: prospective observational study.

BACKGROUND: Preterm infants born at less than 32 weeks of gestation are at higher risk of low total iron stores (iron deficiency). Serum ferritin is used as a valid total iron stores and iron deficiency biomarker, usually as a combination of ferritin and red blood cell counts. METHODS: Serum hepcidin and ferritin values and red blood cell counts were obtained from 37 of 40 included premature infants born at less than 32 weeks of gestation at risk of iron deficiency. The first sample was obtained in the first week of life, and the second at transfer from the Neonatal intensive care unit to the maternity ward, when serum ferritin level below 25 µg/L has been defined as very low total iron stores (iron deficiency). RESULTS: Ferritin median levels decreased from a median value of 152 µg/L at the first measurement to 54 µg/L at the second measurement. Hepcidin median levels also decreased from 30.1 µg/L to 2.1 µg/L. We found a positive and statistically significant correlation between levels of ferritin and hepcidin at both measurements (r = 0.57; p < 0.001 and r = 0.72; p < 0.001, respectively). Compared to serum hepcidin, ferritin at the first measurement has not statistically significant higher power in predicting children with iron deficiency before discharge from the hospital. CONCLUSIONS: We found a correlation between ferritin and hepcidin levels. Nevertheless, hepcidin does not have a worse power in predicting children with iron deficiency compared to ferritin.

Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001-2018.

BACKGROUND: Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. METHODS: GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. RESULTS: Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. CONCLUSIONS: A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

The first nationwide study on facing and solving ethical dilemmas among healthcare professionals in Slovenia.

BACKGROUND: Healthcare professionals (HCPs), patients and families are often faced with ethical dilemmas. The role of healthcare ethics committees (HECs) is to offer support in these situations. AIM: The primary objective was to study how often HCPs encounter ethical dilemmas. The secondary objective was to identify the main types of ethical dilemmas encountered and how HCPs solve them. SUBJECTS AND METHODS: We conducted a cross-sectional, survey-based study among HCPs in 14 Slovenian hospitals. A questionnaire was designed and validated by HCPs who were selected by proportional stratified sampling. Data collection took place between April 2015 and April 2016. RESULTS: The final sample size was n = 485 (385 or 79.4%, female). The response rates for HCPs working in secondary and tertiary level institutions were 45% and 51%, respectively. Three hundred and forty (70.4%) of 485 HCPs (very) frequently encountered ethical dilemmas. Frequent ethical dilemmas were waiting periods for diagnostics or treatment, suboptimal working conditions due to poor interpersonal relations on the ward, preserving patients' dignity, and relations between HCPs and patients. Physicians and nurses working in secondary level institutions, compared to their colleagues working in tertiary level institutions, more frequently encountered ethical dilemmas with respect to preserving patients' dignity, protecting patients' information, and relations between HCPs and patients. In terms of solutions, all HCPs most frequently discussed ethical dilemmas with co-workers (colleagues), and with the head of the department. According to HCPs, the most important role of HECs is staff education, followed by improving communication, and reviewing difficult ethical cases. CONCLUSIONS: Waiting periods for diagnostics and treatment and suboptimal working conditions due to poor interpersonal relations are considered to be among the most important ethical issues by HCPs in Slovenian hospitals. The most important role of HECs is staff education, improving communication, and reviewing difficult ethical cases.

An In Vitro Evaluation of the Red Cell Damage and Hemocompatibility of Different Central Venous Catheters.

BACKGROUND: The aim of our study was to evaluate the damaging impact of characteristics of the central venous catheters (CVCs) on red blood cells. METHODS: CVCs from three different manufacturers were analyzed, including the presence of coating, tunnel geometry, length, lumen diameter, and number of lumens with two respective flow rates (33 mL/min and 500 mL/min). Blood cell damage was defined by analyzing microparticle (MP) and hematologic analysis. MPs were isolated by ultracentrifugation of erythrocyte concentrate and analyzed on a flow cytometer. RESULTS: Characteristics of catheters were not associated with blood cell damage at a low flow rate but showed an effect with a high flow rate. CVCs with a polyhexanide methacrylate coating have caused statistically less blood cell damage than noncoated CVCs. The length of lumens, diameter, and geometry of the tunnel showed no differences in blood cell damage. Meanwhile, the number of lumens was predicted to have a greater effect on the erythrocyte damage, which was revealed with the formation of MPs and hematological parameters. CVCs with five lumens caused significantly less damage to the blood cells than CVCs with a single lumen. Moreover, a high flow rate of 500 mL/min caused less damage to the blood cells than a low rate of 33 mL/min. CONCLUSION: Properties of CVCs are an important factor for quality patient care, especially when transfusing blood with high flow rates, as we want to provide a patient with high-quality blood with as few damaged cells as possible.

Maturation of midazolam clearance in critically ill children with severe bronchiolitis: A population pharmacokinetic analysis.

PURPOSE: The aim of the present study was to develop a population pharmacokinetic model of midazolam, and to evaluate the influence of maturation process and other variability factors in critically ill children with severe acute bronchiolitis, who received a long-term intravenous infusion of midazolam. METHODS: In the study were included 49 critically ill children of both genders (from 0 to 130 weeks of age) with severe acute bronchiolitis hospitalised in intensive care units. Nonlinear mixed effects modelling approach was applied for data analyses and simulations. RESULTS: The final model is a two-compartment model that includes the effects of body weight using allometric scaling with fixed exponents and maturation of clearance. For a typical subject, scaled to the adult body weight of 70 kg, population pharmacokinetic values were estimated at 8.52 L/h for clearance (when maturation function was 1), 25.5 L/h for intercompartmental clearance, and 5.71 L and 39.8 L for the volume of the central and peripheral compartment, respectively. Based on the final model, maturation reaches 50% of the adult clearance in 45.9 weeks of postmenstrual age. The influence of gender, ABCB1 genotype and biochemical parameters on midazolam clearance was not detected. Results of simulations indicate the need for reduced dosing in certain groups of patients in order to maintain plasma concentrations of midazolam within recommended values. CONCLUSIONS: The developed population pharmacokinetic model can contribute to the dosing optimisation of midazolam, especially in critically ill children as it includes the influence of size and maturation of clearance, which are important parameters for achieving the desired plasma concentrations of midazolam.

Prolonged hospitalization is a risk factor for delirium onset: one-day prevalence study in Slovenian INTENSIVE CARE UNITS.

Delirium is a clinical syndrome often underestimated in the intensive care units (ICU). The aim of this study was to determine the prevalence and factors that influence the onset of delirium. A questionnaire was sent to intensivists in Slovenian ICUs, who estimated the prevalence of delirious patients. The questionnaire consisted of demographic data, type of ICU, diagnosis, reason for admission to the ICU, type of anesthesia and surgery, clinical condition, type of supportive therapy, presence of delirium, data on discharge, transfers between departments or patient outcome on day 30. Patient consciousness was assessed by the Richmond Agitation-Sedation Scale (RASS) and the presence of delirium by the validated delirium-screening Confusion Assessment Method for the ICU (CAM-ICU). Replies received from intensivists included data on 103 patients. According to RASS ≥-3, the prevalence of delirium was 9.5% (7 out of 74 patients). There was no difference in the prevalence of delirium between surgical and medical ICU patients (p=0.388). Delirious patients had longer hospital stay (p=0.002) and ICU stay (p=0.032) compared to patients without delirium. All delirious patients survived until day 30, whereas 19 patients without delirium died (p=0.092). Logistic regression analysis dismissed any association of delirium with patient mortality (p=0.998). Age, gender, anesthesia, mechanical ventilation, and type of surgical procedure could not be evaluated as risk factors for delirium. In Slovenian ICUs, a lower proportion of delirium was observed, as reported from similar studies. Risk factors such as gender, age, mechanical ventilation, sedation, anesthesia, or department could not predict delirium. However, prolonged hospitalization of ICU patients could predict the onset of delirium, but the presence of delirium did not increase patient mortality.

Severe Hyperkalemia Immediately After Birth.

BACKGROUND Hyperkalemia is an important cause of arrhythmias and a medical emergency that requires urgent treatment. The etiology is usually multifactorial. It is most frequently caused by impaired potassium secretion, followed by transcellular potassium shifts and an increased potassium load. CASE REPORT A male newborn developed monomorphic ventricular tachycardia 2 hours after birth. He was born in the 35th week of gestation by urgent C-section following placental abruption. Laboratory results showed hemolytic anemia (Hb 99 g/L, Hct 0.31) with increased bilirubin levels and reticulocytosis, thrombocytopenia (39×109/L), hypoglycemia (0.8 mmol/L), and severe hyperkalemia (9.8 mmol/L). Umbilical artery blood gas analysis showed hypoxemia with acidosis (pO2 3.8 kPa, pH 7.21, pCO2 7.84 kPa, HCO3 23.3 mmol/L, BE -5 mmol/L). Creatinine (102 µmol/L) and urea (9.8 mmol/L) were mildly elevated. Inflammatory markers were also increased (CRP 26 mg/L, blood leukocyte count 24×109/L). Early-onset sepsis, caused by Candida albicans, was confirmed approximately 24 hours after birth. Non-invasive ventilation with 35-40% O2 was necessary due to transient tachypnea. The neonate received a transfusion of packed red blood cells, a 10% glucose infusion, and empirical antibiotic therapy. Hyperkalemia accompanied by arrhythmias was treated with calcium gluconate, insulin, Sorbisterit enema, and, finally, by exchange transfusion. CONCLUSIONS We report a case of severe hyperkalemia in a newborn immediately after birth. Making a decision as early as possible regarding exchange transfusion is essential in patients with hyperkalemia with electrocardiogram changes and hemodynamic instability.