Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis.

OBJECTIVES: To study the clinical profile and risk factors of cerebral edema and acute kidney injury in children with diabetic ketoacidosis. DESIGN: Retrospective review of medical records. PATIENTS: Fifty consecutive patients (age <18 years) admitted to our pediatric intensive care unit with a diagnosis of diabetic ketoacidosis over 5 years. MATERIALS AND METHODS: Retrospective analysis of medical records was done, and data including patients' age, sex, presenting features, biochemical profile including blood glucose, osmolality, urea, creatinine, and venous blood gas, electrolytes were recorded at admission, at 12 and 24 hours. Treatment details including fluid administration, rate of fall of glucose, time to resolution of diabetic ketoacidosis were noted. Complications such as cerebral edema and acute kidney injury were recorded. Patients with and without cerebral edema and acute kidney injury were compared. Variables that were significant on univariate analysis were entered in a multiple logistic regression analysis to determine the independent predictors for cerebral edema and acute kidney injury. Odds ratio and 95% confidence interval were calculated using SPSS version 22. MEASUREMENTS AND MAIN RESULTS: Between November 2015 and 2020, 48 patients were admitted for a total of 50 episodes of diabetic ketoacidosis. Two patients had recurrent diabetic ketoacidosis. Median age was 9.5 years (range 1-17). Thirty-one patients (62%) had new-onset type I diabetes mellitus. Twenty-two patients (44%) presented with severe diabetic ketoacidosis. Cerebral edema and acute kidney injury were seen in 11 (22%) and 15 (30%) patients, respectively. On multiple logistic regression analysis, higher blood urea level, lower serum bicarbonate level, and higher corrected sodium levels at admission were identified to be variables independently associated with risk of cerebral edema. CONCLUSIONS: Higher corrected sodium, higher urea level, and lower serum bicarbonate levels at admission are predictive of cerebral edema in patients presenting with diabetic ketoacidosis. The severity of dehydration and acidosis in DKA appears to be a common factor responsible for the development of dysfunction of both brain and kidney. HOW TO CITE THIS ARTICLE: Raghunathan V, Jevalikar G, Dhaliwal M, Singh D, Sethi SK, Kaur P, et al. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med 2021;25(12):1446-1451.

Pediatric liver transplantation in severe hepatopulmonary syndrome and use of inhaled nitric oxide for post-transplant hypoxemia-a single center experience.

Data on pediatric patients with HPS undergoing LT are limited. Our aim was to study the spectrum and outcomes of pediatric patients with HPS undergoing LDLT. The role ofiNO for post-LDLT refractory hypoxemia was also assessed. Patients (aged < 18 years) undergoing LT were retrospectively studied. HPS was diagnosed based on European Respiratory Society Taskforce 2004 criteria. HPS was graded based on oxygenation criteria and contrast-enhanced echocardiogram. Post-operative course was studied. Refractory post-operative hypoxemia was treated with iNO by institutionally developed protocol. 23/150 pediatric patients undergoing LDLT had HPS. BA was the most common underlying cause (52.2%). By oxygenation criteria, 6 (26.1%) had VS-HPS. VS-HPS was associated with longer LOS (p = .031) and prolonged oxygen requirement (p = .001) compared with other HPS patients. 4/6 patients with VS-HPS had pO2 < 45 mm Hg. Among these, 2 developed ICH post-operatively and 1 died. 3 developed refractory post-operative hypoxemia, successfully treated with iNO. Mean duration of iNO was 26.3 days. In the group of patients with HPS, the incidence of HAT and portal vein thrombosis was 17.3% and 4.3%, respectively. One year post-LDLT survival of patients with HPS was similar to non-HPS patients (86.9% vs 94.4%; p = .88). We concluded that, pediatric patients with VS-HPS, especially those with pre-operative pO2 < 45 mm Hg, have long and difficult post-LT course. Refractory postoperative hypoxemia can be successfully overcome with strategic use of iNO. Vigilant monitoring and good intensive care support are essential.

Pediatric ABO-incompatible kidney transplantation: Evolving with the advancing apheresis technology: A single-center experience.

Recent literature has endorsed favorable outcomes following ABOi kidney transplantation in pediatric population. Nevertheless, reluctance to pursue an ABOi still remains pervasive. This could be ascribed to various legitimate reasons, namely less extensive pediatric ABOi data, technical difficulties encountered during PP, cost restraints, and concerns regarding higher rates of antibody-mediated rejection, infectious complications, and post-transplant lymphoproliferative disorder as compared to adults. However, given the similar excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians should consider this option sooner if a compatible donor or swap is not available. Here, we describe the outcomes of three pediatric ABOi performed at our institute in India (from 2014 till now), wherein distinct apheresis modalities had been employed in each desensitization protocol, and our techniques evolved with advancing science in apheresis. This case series includes India's first published pediatric ABO-incompatible transplant (Case 2) and the youngest child to undergo ABO-incompatible renal transplant in SAARC nations (Case 3).

Safety and Outcomes of Midline and Peripherally Inserted Central Catheters in a Pediatric Intensive Care Unit.

OBJECTIVES: We describe our experience with use of midline catheters in PICU and compare the performance of midline catheters to peripherally inserted central catheters (PICC). METHODS: A review of hospital records was done to including all pediatric patients admitted in the pediatric intensive care unit of a tertiary care centre who underwent placement of midline catheters or PICC, over a period of 18 months (July, 2019 to January, 2021). Patient details, indication, type of catheter and number of attempts at insertion, type and number of infusions administered, dwell time and complications were retrieved from the records. Comparison was made between the midline and PICC groups. RESULTS: The median (IQR) age of children was 7 (3-12) years (75.5% males). 161 midline catheters and 104 PICC were inserted with first attempt success rates of 87.6% and 78.8%, respectively. Median cubital vein was used for majority of the insertions (52.8%). Common complications with midline catheters were pain (n=9, 5.6%), blockage (n=8, 5%) and thrombophlebitis (n=6, 3.7%). Median (interquartile range) dwell time in midline group was 7 (5-10) days. The duration of backflow and dwell time were higher in the PICC group compared to midline group (5.5 vs 3 days; P<0.001 and 9 vs 7 days; P<0.001, respectively). CONCLUSION: Retrospective data showed that midline catheters had good utility in PICU, especially in moderately sick children (PRISM score up to 12), and provide a secure intravenous access, which can last for a week.

Switching from continuous veno-venous hemodiafiltration to intermittent sustained low-efficiency daily hemodiafiltration (SLED-f) in pediatric acute kidney injury: A prospective cohort study.

INTRODUCTION: Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step-down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low-efficiency daily dialysis with pre-filter replacement (SLED-f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED-f as a transition step-down therapy after CKRT in critically ill pediatric patients with acute kidney injury. METHODS: A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi-organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED-f. RESULTS: Eleven patients underwent 105 SLED-f sessions (mean of 9.55 +/- 4.90 sessions per patient), as a part of step-down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED-f, urea reduction ratio was 64.1 +/- 5.3%, Kt/V was 1.13 +/- 0.1, and beta-2 microglobulin reduction was 42.5 +/-4%. Incidence of hypotension and requirement of escalation of inotropes during SLED-f was 18.18%. Filter clotting occurred twice in one patient. CONCLUSION: SLED-f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU.

Scrub Typhus Associated with Guillain-Barré Syndrome (GBS).

Scrub typhus is a vector-borne disease caused by Orientia tsutsugamushi. Clinical manifestations generally occur due to vasculitis and inflammation and can have variable degrees of systemic involvement. Meningoencephalitis and cerebellitis are well-known neurological manifestations of scrub typhus, but the occurrence of Guillain-Barré syndrome is extremely rare. The authors report a 7-y-old boy who developed fever followed by rapidly progressive ascending quadriparesis with areflexia and whose etiological workup revealed positive IgM scrub typhus antibody, as well as, a high OXK titer (1:80). Nerve-conduction studies in all four limbs were suggestive of demyelinating neuropathy. He showed complete recovery after treatment with intravenous immunoglobulin (2 g/kg) and azithromycin.

Severity and Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) occurs secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A retrospective study, involving 6 tertiary-care centers in Haryana, was conducted to evaluate the clinical features, severity, laboratory findings, and outcomes of patients with MIS-C. Disease severity was graded (mild/moderate/severe) and presence of cardiac abnormalities noted. Patients with and without cardiac abnormalities and with and without severe disease were compared. Forty-eight children with MIS-C were included (median age - 9.5 y). Fever (100%), gastrointestinal (83.3%) and mucocutaneous (50%) symptoms were common. Only 16.7% patients had previous history of documented SARS-CoV-2 infection/contact. Severe disease and cardiac abnormalities were seen in 47.9% and 54.2% patients, respectively. NT-proBNP > 1286.5 pg/mL and thrombocytopenia (≤ 119500/µL) were significant risk factors for severe MIS-C. Forty-five patients (93.8%) recovered and 3 died. Median hospitalization duration was 7 d (5-9.5). MIS-C must be considered as a possibility in any febrile child, even if a positive epidemiological history is absent. High NT-proBNP and thrombocytopenia are significant risk factors for severe MIS-C. (Trial Registration: The study was registered with the Clinical Trials Registry, India (CTRI/2021/09/036491)).

Wilms tumor with Mulibrey Nanism: A case report and review of literature.

BACKGROUND: Mulibrey-Nanism (Muscle-liver-brain-eye Nanism = dwarfism; MUL) is a rare genetic syndrome. The underlying TRIM37 mutation predisposes these children to develop tumors frequently. In the largest published series of MUL, 8% patients were reported to develop Wilms tumor (WT). The published literature lacks data regarding the best treatment protocol and outcome of this cohort of children with WT and MUL. We report here a 2-year-old boy with WT and MUL and present a review of literature on WT in MUL. CASE: Our patient had associated cardiac problems of atrial septal defect, atrial flutter and an episode of sudden cardiac arrest. We managed him successfully with chemotherapy, surgery and multi-speciality care. He is alive and in remission at follow-up of 6 months. CONCLUSION: A total of 14 cases (including present case) of WT have been reported in MUL and treatment details were available for six cases. They were managed primarily with surgery, chemotherapy with/without radiotherapy, and all achieved remission. The outcome data is available only for two cases, one has been followed up till 15 years post treatment for WT and other is our patient.

Corrigendum: PCRRT Expert Committee ICONIC position paper on prescribing kidney replacement therapy in critically sick children with acute liver failure.

[This corrects the article DOI: 10.3389/fped.2021.833205.].

Soluble Interleukin-2 Receptor Level as a Marker of Hemophagocytic Lymphohistiocytosis in Children With Severe Dengue.

Dengue induced-hemophagocytic lymphohistiocytosis (HLH) is increasingly recognized as an important cause of secondary HLH. Early identification of dengue HLH and directed therapy for HLH may help to alter the outcomes in critically ill patients. Soluble interleukin-2 receptor (IL2R) is a useful inflammatory marker and is seen to correlate with HLH disease activity. There is scarcity of data on IL2R in pediatric dengue patients with HLH. All patients (age < 18 years) with severe dengue confirmed by positive dengue IgM ELISA admitted to PICU were retrospectively enrolled. Patientswere screened for presence of HLH according to HLH 2004 criteria. Hemogram, ferritin, fibrinogen, liver, and renal function tests were noted. Patients who met four or more HLH criteria were treated with steroids and IL2R levels were sent to confirm the diagnosis of HLH. Out of 15 patients, nine patients met the criteria of HLH. IL2R levels were high in all HLH patients (mean 51,711, range 18,000-98,715 pg/mL). Mean ferritin levels were high in the HLH group as compared to non-HLH group (mean ferritin 34,593 vs. 3,206 ng/mL; p-value 0.004). Liver dysfunction was notably higher in the HLH group compared to non-HLH group (mean alanine aminotransferase 6,621 U/L vs. 165.6 U/L; p-value 0.04, mean aspartate aminotransferase 2,145 U/L vs. 104.2 U/L; 0.04, bilirubin level 4.2 mg/dL vs. 0.7 mg/dL; p-value 0.03). Four patients in the HLH group had acute kidney injury (AKI) and two required renal replacement therapy in the form of sustained low efficiency dialysis (SLED). Requirement for invasive ventilation was exclusively seen in HLH group and three patients developed ARDS. Two patients each in HLH and non-HLH group had shock requiring vasoactive therapy in addition to fluids. Mean days of ICU and hospital stay were higher in HLH group vs. non-HLH group but not statistically significant (6.4 vs. 4.4; p-value 0.32 and 8.44 vs. 5.6; p-value 0.18 days, respectively). All children in HLH group received steroids as per HLH protocol. In the HLH group, seven survived while two died. In the non-HLH group, all five patients survived. We concluded that IL2R levels are high in dengue HLH and useful for definitive diagnosis. Early recognition of this condition in severe dengue and prompt steroid therapy improves chances of better outcome.

Pediatric ABO-incompatible Living Related Donor Liver Transplantation: Experience from Indian Subcontinent.

We present our experience with pediatric ABO-incompatible liver transplantation in India. Data of patients <18 years of age undergoing ABO-incompatible liver transplantation our hospital between January, 2011 and November, 2018 were analyzed. Plasmapheresis was done pre-transplant till antibody titer was <16 units. Rituximab/Intravenous immunoglobulin was used for immunosuppression, in addition to standard drugs (mycophenolate mofetil, steroids, and tacrolimus). Out of 203 patients that underwent liver transplant during this period, 8 underwent ABO-incompatible liver transplantation; 4 (3 boys) had blood group O+ve. Median (range) age was 28 (7-91) mo, PELD score was 24.5 (14-42), and pre-transplant antibody titer range was 1:32-1024. Number of plasmapheresis sessions required ranged from 1-6. Post-operatively two patients had rise in antibody titer >64 requiring plasmapheresis. All 8 patients survived without rejection/biliary issues. Mean (range) of post-transplant hospital stay was 19.1 (13-22) d and follow-up period was 38.1 (7.1-84.4) mo. Pediatric ABO-incompatible liver transplantation can be successfully performed using plasmapheresis with optimal immune-suppression and vigilant post-op monitoring.

PCRRT Expert Committee ICONIC Position Paper on Prescribing Kidney Replacement Therapy in Critically Sick Children With Acute Liver Failure.

Management of acute liver failure (ALF) and acute on chronic liver failure (ACLF) in the pediatric population can be challenging. Kidney manifestations of liver failure, such as hepatorenal syndrome (HRS) and acute kidney injury (AKI), are increasingly prevalent and may portend a poor prognosis. The overall incidence of AKI in children with ALF has not been well-established, partially due to the difficulty of precisely estimating kidney function in these patients. The true incidence of AKI in pediatric patients may still be underestimated due to decreased creatinine production in patients with advanced liver dysfunction and those with critical conditions including shock and cardiovascular compromise with poor kidney perfusion. Current treatment for kidney dysfunction secondary to liver failure include conservative management, intravenous fluids, and kidney replacement therapy (KRT). Despite the paucity of evidence-based recommendations concerning the application of KRT in children with kidney dysfunction in the setting of ALF, expert clinical opinions have been evaluated regarding the optimal modalities and timing of KRT, dialysis/replacement solutions, blood and dialysate flow rates and dialysis dose, and anticoagulation methods.

A cautionary tale of multiple-dose drug products: Fluticasone and salmeterol combination inhaler waste.

RATIONALE: Some drugs can only be dispensed in multiple-dose containers. Multiple-dose packaging may pose a problem for hospitals in terms of drug wastage and cost. Oral inhalers, such as fluticasone propionate and salmeterol combination inhalers, are only available as multiple-dose formats in Canada. OBJECTIVES: The objectives of this study are to quantify the amount of fluticasone propionate and salmeterol combination inhaler waste and to assess possible factors that could be contributing to waste. METHODS: A retrospective chart review of 189 patients was conducted. Patients were included if they had received an order for fluticasone propionate and salmeterol combination inhaler at one of the 12 acute hospital sites of Fraser Health Authority. The primary outcome was the proportion of patients who were dispensed one or more inhalers unnecessarily. The number of inhalers dispensed was compared with the number of inhalers needed to complete a patient's order duration. The chart was also reviewed for possible factors that could have contributed to extra inhalers being dispensed unnecessarily. RESULTS: Thirty-seven patients (19.6%) had at least one inhaler dispensed unnecessarily and thus wasted. About 17.4% of the total amount of inhalers dispensed were dispensed unnecessarily, and 76.3% of doses dispensed were wasted. The cost of inhalers wasted for our sample was $5151.12 (CAD). The most common factors that contributed to inhaler waste appeared to be loss of medication during patient transfers and storage of inhalers as wardstock. CONCLUSIONS: The use of drugs that are only available in multiple-dose formats results in significant drug wastage and unnecessary health care expenditure. To minimize wastage of drug product, procedures could be implemented to ensure that drugs are properly transferred with the patient when a patient transfers locations in the hospital. As well, a review of wardstock inventory may minimize waste. Further assessment of multiple-dose drug product waste and evaluations of methods to mitigate waste are encouraged.