A pragmatic, open-label, randomized controlled trial of Plasma-Lyte-148 versus standard intravenous fluids in children receiving kidney transplants (PLUTO).

Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplant. This is partly because doctors give very large volumes of artificial fluids to keep the new kidney working. When severe, fluid imbalance can lead to seizures, cerebral edema and death. In this pragmatic, open-label, randomized controlled trial, we randomly assigned (1:1) pediatric kidney transplant recipients to Plasma-Lyte-148 or standard of care perioperative intravenous fluids (predominantly 0.45% sodium chloride and 0.9% sodium chloride solutions). We then compared clinically significant electrolyte and acid-base abnormalities in the first 72 hours post-transplant. The primary outcome, acute hyponatremia, was experienced by 53% of 68 participants in the Plasma-Lyte-148 group and 58% of 69 participants in the standard fluids group (odds ratio 0·77 (0·34 - 1·75)). Five of 16 secondary outcomes differed with Plasma-Lyte-148: hypernatremia was significantly more frequent (odds ratio 3·5 (1·1 - 10·8)), significantly fewer changes to fluid prescriptions were made (rate ratio 0·52 (0·40-0·67)), and significantly fewer participants experienced hyperchloremia (odds ratio 0·17 (0·07 - 0·40)), acidosis (odds ratio 0·09 (0·04 - 0·22)) and hypomagnesemia (odds ratio 0·21 (0·08 - 0·50)). No other secondary outcomes differed between groups. Serious adverse events were reported in 9% of participants randomized to Plasma-Lyte-148 and 7% of participants randomized to standard fluids. Thus, perioperative Plasma-Lyte-148 did not change the proportion of children who experienced acute hyponatremia compared to standard fluids. However fewer fluid prescription changes were made with Plasma-Lyte-148, while hyperchloremia and acidosis were less common.

Multicentre randomised controlled trial: protocol for Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO).

INTRODUCTION: Acute electrolyte and acid-base imbalance is experienced by many children following kidney transplantation. When severe, this can lead to complications including seizures, cerebral oedema and death. Relatively large volumes of intravenous fluid are administered to children perioperatively in order to establish perfusion to the donor kidney, the majority of which are from living and deceased adult donors. Hypotonic intravenous fluid is commonly used in the post-transplant period due to clinicians' concerns about the sodium, chloride and potassium content of isotonic alternatives when administered in large volumes.Plasma-Lyte 148 is an isotonic, balanced intravenous fluid that contains sodium, chloride, potassium and magnesium with concentrations equivalent to those of plasma. There is a physiological basis to expect that Plasma-Lyte 148 will reduce the incidence of clinically significant electrolyte and acid-base abnormalities in children following kidney transplantation compared with current practice.The aim of the Plasma-Lyte Usage and Assessment of Kidney Transplant Outcomes in Children (PLUTO) trial was to determine whether the incidence of clinically significantly abnormal plasma electrolyte levels in paediatric kidney transplant recipients will be different with the use of Plasma-Lyte 148 compared with intravenous fluid currently administered. METHODS AND ANALYSIS: PLUTO is a pragmatic, open-label, randomised controlled trial comparing Plasma-Lyte 148 to current care in paediatric kidney transplant recipients, conducted in nine UK paediatric kidney transplant centres.A total of 144 children receiving kidney transplants will be randomised to receive either Plasma-Lyte 148 (the intervention) intraoperatively and postoperatively, or current fluid. Apart from intravenous fluid composition, all participants will receive standard clinical transplant care.The primary outcome measure is acute hyponatraemia in the first 72 hours post-transplant, defined as laboratory plasma sodium concentration of <135 mmol/L. Secondary outcomes include symptoms of acute hyponatraemia, other electrolyte and acid-base imbalances and transplant kidney function.The primary outcome will be analysed using a logistic regression model adjusting for donor type (living vs deceased donor), patient weight (<20 kg vs ≥20 kg pretransplant) and transplant centre as a random effect. ETHICS AND DISSEMINATION: The trial received Health Research Authority approval on 20 January 2020. Findings will be presented to academic groups via national and international conferences and peer-reviewed journals. The patient and public involvement group will play an important part in disseminating the study findings to the public domain. TRIAL REGISTRATION NUMBERS: 2019-003025-22 and 16586164.

A case series of perioperative variables in relation to short-term outcomes in pediatric renal transplant recipients.

Multiple perioperative variables have been shown in existing literature to influence long-term outcomes of pediatric RTx, such as allograft survival. Their impact on short-term outcomes is not as well-documented. This case series aims to investigate the effects of nine perioperative variables on two short-term outcomes in pRTR: 1-week post-operative eGFR and post-operative LOS. A total of 73 pRTR transplanted over 3 years from 2012 to 2014 at a single center were studied retrospectively and statistical analyses were performed. There was higher 1-week post-operative eGFR in pRTR who received living donor transplants compared to those who received deceased donor transplants (P=.01), with mean eGFR of 135 mL/min/1.73 m2 and 82 mL/min/1.73 m2 , respectively. Aorta-IVC anastomosis was associated with longer LOS compared to iliac vessel anastomosis (P=.03), with median LOS of 19 and 13 days, respectively. There were no significant effects on 1-week eGFR or LOS of the seven other variables: pRTR age and gender, donor age, preoperative donor SBP, intraoperative mean CVP before graft perfusion, intraoperative median SBP z score after graft perfusion, and intraoperative fluid volume. Living donor transplants were associated with higher 1-week post-operative eGFR compared to deceased donor transplants. Aorta-IVC anastomosis was significantly associated with longer LOS compared to iliac vessel anastomosis.

Insights in Transplanting Complex Pediatric Renal Recipients With Vascular Anomalies.

BACKGROUND: Children with end-stage kidney disease may have coexisting iatrogenic or congenital vascular anomalies making transplantation difficult. We describe our approach in 5 recipients with vascular anomalies and significant comorbidities, including one case of blood group incompatibility. METHODS: Five children aged 3 to 17 years (median, 7 years), weighing 14 to 34 kg (median, 18 kg) kg of whom 4 had occluded inferior vena cava or iliac veins and 2 had previous complex vascular reconstructions before transplantation for midaortic syndrome and multiple aortic aneurysms, respectively underwent renal transplantation. To establish implant feasibility surgery was commenced in 2 recipients before the donor surgery. RESULTS: There was 4 (80%) of 5 patient survival after 1 death from sepsis (with a functioning graft) and 2 cases of delayed graft function. At the latest median follow-up of 19 months, there was 100% (death-censored) renal allograft survival with estimated glomerular filtration rates (mL/min per 1.73 m) of 43 to 72 (median, 55). CONCLUSIONS: We conclude that major vascular anomalies do not necessarily preclude transplantation in complex pediatric patients and that surgical exploration of the recipient before commencing the donor surgery is valuable where feasibility and safety are uncertain. In addition, we have developed a novel classification system of congenital vascular abnormalities and propose its use in complex pediatric transplantation.

Cardiac Dysrhythmias in Children Undergoing Extracorporeal Shock Wave Lithotripsy Under General Anesthesia or Propofol Sedation: A Prospective, Observational Cohort Study.

OBJECTIVE: To assess the frequency and severity of cardiac dysrhythmias and identify any intraoperative or postoperative complications in children undergoing extracorporeal shock wave lithotripsy (ESWL). METHODS: All children coming to our institution for ESWL from June 2014 to January 2015 were prospectively enrolled in an observational cohort study. Intraoperative cardiac dysrhythmias and perioperative and postoperative complications were recorded. RESULTS: In total, 21 children aged 1-18 years were enrolled receiving a total of 26 treatments. Intravenous sedation was used in 19 cases and general anesthesia with an inhalational agent in 7 cases. Cardiac dysrhythmias occurred in 58% of children. No hemodynamic instability was noted. No therapies were terminated because of dysrhythmias, and there were no postoperative cardiac dysrhythmias. CONCLUSION: ESWL remains a safe therapy for children with urinary stone disease. Although we experienced more dysrhythmias than currently published literature, there were no long-term adverse outcomes and children were able to go home the same day.

The effect of age on the dose of remifentanil for tracheal intubation in infants and children.

INTRODUCTION: This study aimed to determine the age-specific bolus dose of remifentanil (ED(50)) to facilitate tracheal intubation without the use of neuromuscular blocking agents. METHODS: ASA 1-2 subjects were recruited into three groups of 0-3 months (group I), 4-12 months (group II), and 1-3 years (group III) of age. A sequential up-and-down design determined the remifentanil bolus dose, which was initially started at 3 mcg x kg(-1) and adjusted in 1 mcg x kg(-1) increments (range 1-6 mcg x kg(-1)). Following pretreatment with glycopyrrolate 10 microg x kg(-1) and an induction dose of propofol 5 mg x kg(-1), remifentanil was administered with a blinded study investigator commencing tracheal intubation after 60 s. After tracheal intubation, the time to return of spontaneous ventilation was measured. Logistic regression was used to predict the ED(50) and ED(95) of remifentanil. RESULTS: Sixty-four subjects were recruited. Tracheal intubation was successful at first attempt in over 90% of subjects in each age group. Satisfactory intubating conditions were achieved in 85%, 63%, and 75% of subjects in groups I, II, and III, respectively. The logistic regression results for ED(50) (95% CI) were 3.1 (2.5-3.8), 3.7 (2.0-5.4), and 3.0 (2.1-3.9) mcg x kg(-1), and ED(95) (95% CI) were 5.0 (3.0-7.0), 9.4 (1.5-17.4), and 5.6 (2.9-8.4) mcg x kg(-1) in groups I, II, and III, respectively. Infants aged 4-12 months (group II) showed a marked variability in dose response; however, the mean ED(50) and ED(95) were not different to groups I and III. Older children had a longer duration of apnea than infants, 331 vs 180 s (P < 0.05). DISCUSSION: The ED(50) of remifentanil for tracheal intubation was higher in all age groups than previously reported. Ideal intubating conditions were achieved in 50% of subjects with remifentanil doses of 3.1-3.7 mcg x kg(-1). Higher doses will be required for higher success rates and with anticholinergic pretreatment, doses of up to 6 mcg x kg(-1) were tolerated, without adverse effects, in two patients. Further investigation of the variability in dose response in infants and assessment of the safety this technique is warranted.

The effect of propofol concentration on dispersion of myocardial repolarization in children.

BACKGROUND: QT interval prolongation on the electrocardiogram (ECG) may be drug-induced and is traditionally associated with torsades des pointes. A better predictor of torsades des pointes is the time interval between the peak and the end of the T-wave (Tp-e). Older studies of propofol's effect on the corrected interval (QTc) are conflicting and confounded by polypharmacy. It was recently shown that target-controlled infusion of propofol at 3 microg/mL has no effect on QTc or Tp-e. This plasma concentration of propofol is at the extreme lower end of the range for surgical anesthesia. In this randomized, double-blind, clinical study, we investigated the dose-response relationship between propofol, QTc, and Tp-e in a range of doses clinically relevant for surgical anesthesia. METHODS: Sixty healthy unpremedicated children, aged 3-10 yr, were recruited. Subjects were randomized to receive target-controlled infusions of propofol, to achieve 1 of 3 plasma concentrations: 3, 4.5, and 6 microg/mL. A preoperative 12 lead ECG was performed and repeated 5 min after induction. Two investigators, blinded to group allocation and to the timing of the ECG traces, independently measured QTc and Tp-e within and between each group. Paired t-tests were used to compare QTc and Tp-e within groups. One-way analysis of variance was used for intergroup analysis. The primary outcome measure was a change of >25 ms in Tp-e both within and between groups. RESULTS: ECG recordings were obtained in 51 children. There were no demographic or ECG differences at baseline, at which time QTc and Tp-e values were within normal limits. There were no differences in QTc or Tp-e after induction within or between the three different groups. DISCUSSION: Propofol has no effect on myocardial repolarization in healthy children at clinically relevant doses. This suggests that propofol would be a rational choice for children with a preexisting repolarization abnormality.