Background

Amikacin efficacy requires a plasma peak concentration (C_max) > 8-10 times the minimal inhibitory concentration (MIC) corresponding to a C_max between 60-80 mg/l. The recommended 30 mg/kg dose was evaluated in critically ill adult leading to underexposure in 20% of patients but was not evaluated in critically ill children.

Objectives

We aimed to assess the incidence and factors associated with a C_max < 60 mg/L in critically ill children treated with a 30 mg/kg dose of amikacine.

Methods

Retrospective observational multicentric study, from November 2017 to June 2018 in two pediatric intensive care unit (PICU) located within two French tertiary academic pediatric hospitals. We included all children admitted in the PICU receiving 30 mg/kg amikacin dose.

Results

We analyzed 24 children. C_max was < 60 mg/L in 16 patients (67%). None had C_max > 80 mg/L. Thirteen (93%) patients from the 14 having a measured MIC achieved a C_max /MIC > 8. Higher level of uremia was significantly associated with a C_max < 60 mg/L. We observed an occurrence or a worsening of acute kidney injury in 12 (50%) of our patients after amikacin injection. Trough concentration was > 2.5 mg/L in 40% of our patients.

Conclusion

Despite the use of a 30 mg/kg amikacin dose, C_max were below pharmacokinetic target in 67% of our population and no C_max was above. However, kidney function was impaired in half of our patients. This reinforces the need to monitor systematically peak and trough concentration in this vulnerable population receiving high doses of aminoglycosides.

Background

Propofol is a useful anesthetic for short invasive procedures with a rapid onset and fast recovery time. Some studies described hypotension in neonates but the mechanisms underlying it are not fully understood.

Objectives

To evaluate the effects of propofol in diluted and undiluted formulation on cardiac function in infants.

Methods

Infants receiving propofol sedation for central line insertion were included. Cases were divided in two groups, those who received undiluted propofol at 1% (P1%) and those who received a diluted formulation (Pd) of equal volumes propofol 1% and 0.9% NaCl. Echocardiograms were collected pre (t₀) and immediately post propofol (t₁) administration and additionally 1 hour post propofol (t₂). For both left ventricle (LV) and right ventricle (RV), myocardial deformation was assessed with tissue Doppler analysis (TDI) and peak longitudinal strain (LS) to evaluate systolic and diastolic function. Systolic and diastolic pressure were collected at t₁.

Results

18 cases were included, of which nine received 1% propofol, and nine received diluted propofol. Adequate procedural sedation was achieved in both groups. In the P1% group, TDI and LS for both RV and LV function were significantly reduced at t₁and t₂. In the Pd Group, only TDI LV was reduced at t₁, but not at t₂. Three infants in the P1% Group and none in the Pd group had clinically significant hypotension at t₁.

Conclusion

Dilution of propofol may minimize myocardial dysfunction whilst maintaining adequate sedation in infants. Further studies are needed to investigate the comparative safety and efficacy of this approach.

Background

Nonpharmacologic approaches are established for the treatment of painful procedures in preterms, but evidence if multiple doses of sucrose might be more effective than a standard dose is lacking.

Objectives

Testing the efficacy of 24%-oral-sucrose in single versus double dose during heel prick in preterms.

Methods

Single centre, double-blind, randomized, controlled trial conducted at III Level Neonatal Intensive Care Unit of Padua University.

We enrolled preterm infants 24-36 gestational weeks needing heel prick procedure to receive a single standard dose of sucrose 2' before or a double dose 2' before and 30" after heel prick in association with non-nutritive sucking and facilitated tucking.

Primary outcome was the efficacy of the two interventions tested by PIPP scale obtained at 30", 60" and 120" after the heel prick. Secondary outcome was the evaluation of the concordance between PIPP scale and others pain scores (NIPS, FLACC and indirect VAS) more feasible in clinical practice.

Results

Seventy-two infants were randomized. No difference in pain perception as measured by PIPP score was found between the two groups: median PIPP values 4.0(IQR 3.0-4.0)vs 3.0(IQR 3.0-4.0) at baseline; 6.0(IQR 5.0-10.0)vs 6.0(IQR 4.0-8.5) at 30”; 6.0(IQR 4.0-7.0)vs 5.0(IQR 4.0-8.5) at 60” and 5.0(IQR 4.0-7.0)vs 5.0(IQR 4.0-7.5) at 120”, in the experimental and standard treatment groups respectively(p=0.9020). There was no correlation between PIPP scores and other pain scales.

Conclusion

Preterms treated with two doses of sucrose 24% did not experience less pain than infants treated with a single standard dose. We do not recommend using other pain scale rather than PIPP.

Background

Endotracheal intubation is a frequently used procedure on neonatal intensive care units and often premedication is used. Little is known about the influence of premedication drugs and of the intubation procedure itself on cerebral tissue oxygen saturation (StO₂) as determined by near infrared spectroscopy (NIRS) and hemodynamic parameters in neonates.

Objectives

To reduce cerebral desaturation, defined as area under baseline, during endotracheal intubation by an accelerated regimen of premedication using the same drugs but a different application sequence and dosage.

Methods

We randomized 24 preterm infants to either up to 3 doses of 2µg/kg Fentanyl followed by 200µg/kg Mivacurium (Protocol A) or 200µg/kg Mivacurium immediately followed by one dose of 2µg/kg Fentanyl (Protocol B). We simultaneously recorded SpO₂, heart rate and cerebral StO₂ as measured by absolute tissue oximetry (FORE-SIGHT, Casmed). Cardiac index was continuously measured by electrical impedance cardiovelocimetry (ICON, Osypka).

Results

Distribution of cerebral StO₂ at baseline, during manipulation and recovery is shown in the figure. Cerebral desaturation, HR and SpO₂ were not significantly different. Significant differences were observed for median cStO2 and cardiac index. Total duration of the procedure was not significantly different.

Distribution (minimum, centiles, median, maximum) of cStO₂ for Protocol A and B during Baseline (1min before 1^st drug), Manipulation, and Recovery (10min after successful intubation)

Conclusion

Neither could we prove a reduction of cerebral desaturation nor an acceleration of the intubation procedure.

Background

Clonidine is in widespread off-label use as a sedative in mechanically ventilated children, despite limited evidence of efficacy. A variety of dosage regimens have been utilised in practice and in previous research studies. A previous observational study included 692 children who received clonidine though did not report opioid sparing effects though improved time at target sedation was reported. One of the reasons attributed to the lack of an opioid-sparing effect is potential underdosing.

Objectives

This study aimed to simulate clonidine pharmacokinetics (PK) to evaluate adequacy of clonidine dosage regimens used in clinical practice and research studies to attain therapeutic plasma levels.

Methods

Using a previously published PK model the projected plasma concentration levels of 692 mechanically ventilated children (demographics taken from a recent study) were generated. Doses from recently published clinical studies were investigated. Adequacy of each regimen to attain therapeutic clonidine plasma concentrations was assessed.

Results

Clonidine intermittent bolus dosage regimens typically of 1-2 µg/kg six to eight hourly did not attain expected therapeutic concentrations of 2 µg/L. Studies using continuous infusions with or without a loading dose attain therapeutic concentrations. Loading doses expedite this.

Conclusion

The variety of dosage regimens used in previous studies of clonidine may have contributed to the lack of efficacy data to support its use. Simulations of clonidine plasma concentrations based on known population pharmacokinetic parameters suggest a loading dose followed by a continuous infusion is required to achieve adequate steady-state concentrations early in treatment. Further pharmacokinetic-pharmacodynamic studies will further aid in the determination of the optimal clonidine dosage regimen.

Background

Already being as a vulnerable population, pediatric patients are more often exposed to off-label drug use (OLDU) compared to that in other age groups. While OLDU incidence tends to raise with decreasing age, those at the extreme, like newborns, need more attention in such drug use.

Objectives

This study aimed to investigate OLDU applications for neonates in Turkey.

Methods

This retrospective study analyzed medical records of OLDU applications that were made to Turkish Medicines and Medical Devices Agency for neonates (≤28 days old). Several demographic characteristics of patients and applying physicians were examined as well as the most common drugs and diagnoses for which OLDU was applied.

Results

Total of 61 OLDU requests (0.7% of all pediatric applications) was made for neonates, and 73.8% applications were approved. Among all applications, 55.7% belonged to girls, and the mean age of patients was 15.8±7.1 days. Most of them were applied by pediatric endocrinology and metabolism specialists (36.1%) and neonatologists (24.6%); and 63.9% was submitted from university hospitals. The drug that was found to be most frequently used off-label was sapropterin (21.3%), followed by sodium glycerophosphate (18.0%) and sirolimus (8.2%). The most common three diagnoses regarding neonatal OLDU applications were detected as “classical phenylketonuria” (21.3%), “feeding problems of newborn (9.8%), and “disorders of glycine metabolism” (8.2%).

Conclusion

In conclusion, phenylketonuria appears to represent the most common reason for OLDU applications in newborns. Furthermore, neonatal OLDU applications seem to be made mostly by non-neonatologists, especially by pediatric endocrinology and metabolism specialists.

Background

Children’s poor compliance during imaging requiring prolonged immobilization, such as MRI, often requires the use of sedative drugs. Dexmedetomidine is a high selective α2-agonist sedative drug, which can be used for this purpose.

Objectives

To evaluate the effectiveness, safety and feasibility of dexmedetomidine for sedation during MRI in non-cooperative children, providing additional data on the most appropriate dosage and time of administration.

Methods

This is a prospective observational study conducted at the paediatric hospital of Padua, Italy, including uncooperative children who had to undergo a brain MRI. Dexmedetomidine iv loading dose of 2 mcg/kg in 10 minutes (up to 3 times) was administered, followed by continuous infusion at 1-2 mcg/kg/h. Level of sedation (Pediatric Sedation State Scale), vital signs (including EtCO2), adverse effects and quality of MRI were recorded.

Results

Twenty-eight children were enrolled. Efficacy was 96.4%. Mean total dose was 3.44±2 mcg/kg. Adequate sedation was achieved within 10 minutes in 71.4%, time to first awakening was 23.8±31.5 minutes and to complete recovery 92.7±57.8 minutes. Adverse effects were haemodinamic and reported in 6 patients: all of them were classified as “minor” according to SIVA score and required no intervention. No respiratory adverse events were recorded. MRI quality was excellent (76.5%) or good (23.5%).

Conclusion

Dexmedetomidine showed a high efficacy and good safety profile for MRI sedation at the dosage regimen used. More data are needed to further validate our preliminary findings.

Background

Phenobarbital is a frequently used anticonvulsive drug in patients undergoing extracorporeal membrane oxygenation (ECMO). The use of ECMO is associated with significant changes in drug pharmacokinetics (PK), which may lead to insufficient or toxic effects.

Objectives

The aim of this study was to characterize PK of phenobarbital in neonates on ECMO.

Methods

Therapeutic data monitoring (TDM) data from 11 (6 female, 5 male) neonates (median (IQR), body weight (BW): 3.16 (2.63-4.02) kg; postnatal age (PNA): 8 (4-17) days, gestational age: 38.6 (38-41) weeks) treated with veno-venous or veno-arterial ECMO were available, 5 phenobarbital concentrations were determined before ECMO, 31 during ECMO and 17 concentrations after decannulation. TDM data from a control group included 50 neonates (BW: 3.3 (2.8 to 3.5) kg, PNA: 2 (1-3) days, GA: 39 (38 to 40) weeks). Population PK analysis was performed using NONMEM® version 7.3. Maturation functions based on BW and PNA for clearance (CL) and based on BW for distribution volume (Vd) were obtained from literature (1).

Results

CL values before start of ECMO were comparable to the reference population. There was a 3.5-fold increase in phenobarbital CL during ECMO compared to the reference population, with a trend towards a time-dependent increase. Furthermore, phenobarbital CL reduced 2-fold after decannulation compared to CL during ECMO. Changes in Vd with ECMO could not be identified.

Conclusion

CL is the only parameter driving steady state concentrations for phenobarbital. ECMO leads to high inter-individual variability in CL of phenobarbital, therefore TDM is essential in these patients.

Background

Ethics of care emphasizes gender difference, it then looks at a distinct way in women's thinking, action, ethical decisions and judgments (Gilligan and Noddings). The central core of this theory is the particularity, partiality and the application of the principle of love and emotion, therefore it is sometimes called maternal ethics or maternal thinking.

Objectives

.“Baier” believes that love-based ethics is a good reflection of the moral vision of femininity, in which love play a basic role, while masculine ethics are generally focus on obligation/duty and not much attention to love and emotion. “Blum” also believes women actually have more capacity to care, this virtue is stronger than men. However it does not create a fundamental moral difference.

Methods

Considering to various theories, should be said in all of moral situations and in encountered with its dilemmas, we cannot appeal to some general moral principles or even just to the principle of justice for solving our issues; Instead, context of ethical decisions and a few kind of considerations effect on ethical decision making.

Results

According to some empirical studies, women are more concerned about their relationships with the world than men and the moral development of the woman brings her from egoism and selfishness to the level of altruism and sacrificing; ultimately, she considers her benefits accompanied with others.

Conclusion

Although it is never possible to exclude ethics from resorting to general principles, but we can benefit from this important issue in the ethics of nursing care especially in the field of ill children.

Background

Background and Aims: Congenital malformations (CM) are defined as abnormal structure of the organism resulting from disrupted embryogenesis. Many factors influence the appearance of CM. Regarding different criteria and authors, the incidence of CM at newborns is between 2 – 7%. The aim of this paper was to determine the incidence of CM at liveborns delivered at SHGO “Mother Teresa” - Cair, Skopje, during the five years period (2000-2004) and five years period (2005-2009). Also, the distribution among organ system had been analyzed.

Objectives

Objectives: Ethylhalogenic Aspects of CM.

Methods

Methods: A retrospective analysis of 19097 liveborns delivered at SHGO Cair, during 2000-2004, has been performed. Database ( Access 2000) from Neonatal Unit has been used. The incidence and percentage of CM among different systems have been determined and a retrospective analysis of 15293 liveborns delivered at SHGO Cair, during 2005-2009, has been performed. Database ( Access 2005) from Neonatal Unit has been used. The incidence and percentage of CM among different systems have been determined.

Conclusion

Conclusions: During the five years period (2000-2004), the incidence of CM is 3,85%. Among years , the incidence varies from 3,2 to 4,3%. During the five years period 2005-2009, the incidence of CM is 3,75%. Congenital malformations still remain an important medical and social problem requesting more serious nationwide engagement, as in medical aspect, socioeconomic, ecological. In cases of Congenital Anomalies comes the expression Ethics. How to act in the preventive and curative aspect and many other ethical dilemmas in CM.