Akash Deep

Effect of Continuous Renal Replacement Therapy on Outcome in Pediatric Acute Liver Failure.

Objectives:To establish the effect of continuous renal replacement therapy on outcome in pediatric acute liver failure. Design:Retrospective cohort study. Setting:Sixteen-bed PICU in a university-affiliated tertiary care hospital and specialist liver centre. Patients:All children (0–18 yr) admitted to PICU with pediatric acute liver failure between January 2003 and December 2013. Interventions:Children with pediatric acute liver failure were managed according to a set protocol. The guidelines for continuous renal replacement therapy in pediatric acute liver failure were changed in 2011 following preliminary results to indicate the earlier use of continuous renal replacement therapy for both renal dysfunction and detoxification. Measurements and Main Results:Of 165 children admitted with pediatric acute liver failure, 136 met the inclusion criteria and 45 of these received continuous renal replacement therapy prior to transplantation or recovery. Of the children managed with continuous renal replacement therapy, 26 (58%) survived: 19 were successfully bridged to liver transplantation and 7 spontaneously recovered. Cox proportional hazards regression model clearly showed reducing hyperammonemia by 48 hours after initiating continuous renal replacement therapy significantly improved survival (HR, 1.04; 95% CI, 1.013–1.073; p = 0.004). On average, for every 10% decrease in ammonia from baseline at 48 hours, the likelihood of survival increased by 50%. Time to initiate continuous renal replacement therapy from PICU admission was lower in survivors compared to nonsurvivors (HR, 0.96; 95% CI, 0.916–1.007; p = 0.095). Change in practice to initiate early and high-dose continuous renal replacement therapy led to increased survival with maximum effect being visible in the first 14 days (HR, 3; 95% CI, 1.0–10.3; p = 0.063). Among children with pediatric acute liver failure who did not receive a liver transplant, use of continuous renal replacement therapy significantly improved survival (HR, 4; 95% CI, 1.5–11.6; p = 0.006). Conclusion:Continuous renal replacement therapy can be used successfully in critically ill children with pediatric acute liver failure to provide stability and bridge to transplantation. Inability to reduce ammonia by 48 hours confers poor prognosis. Continuous renal replacement therapy should be considered at an early stage to help prevent further deterioration and buy time for potential spontaneous recovery or bridge to liver transplantation.

Factors affecting circuit life during continuous renal replacement therapy in children with liver failure.

Despite abnormal clotting, circuits clot during continuous renal replacement therapy (CRRT) in children with acute liver failure (ALF). We report our experience. All children with ALF needing CRRT were studied over 2 years. Patient and circuit factors associated with circuit use were evaluated. Thirty‐one children in liver failure (median age 7.4 years) underwent CRRT, of which 17 (54.8%) died. A total of 98 filtration episodes were used. The smallest access catheter was 6.5 Fr, while the largest was 13.5 Fr. The most common filter used was HFO7 (63%). Mean duration (SD) of circuit use was 33.13(30.83) hours. Of the 98 filtration episodes, circuits blocked in 25, whereas the access catheter blocked in 25. Fifty‐two circuits were changed electively for a variety of reasons. Prostacyclin was the anticoagulant in 62 filtration episodes. The remaining filtration episodes had either no anticoagulation or heparin. The mean (SD) “downtime” was 5.13 (9.15) hours. We found a significant association between fresh frozen plasma (FFP) use with circuit blockade. Neither the duration of CRRT nor the “downtime” influenced mortality. The CRRT circuits blocked in children despite deranged clotting in liver disease. Circuits are changed for a variety of reasons other than clotting. The use of FFP reduces circuit life.

Arterial and end tidal carbon dioxide difference in pediatric intensive care

Background and Aim: Arterial carbon dioxide tension (PaCO2) is considered the gold standard for scrupulous monitoring in pediatric intensive care unit (PICU), but it is invasive, laborious, expensive, and intermittent. The study aims to explore when we can use end-tidal carbon dioxide tension (PETCO2) as a reliable, continuous, and noninvasive monitor of arterial CO2 Materials and Methods: Concurrent PETCO2, fraction of inspired oxygen, PaCO2, and arterial oxygen tension values of clinically stable children on mechanical ventilation were recorded. Children with extra-pulmonary ventriculoatrial shunts were excluded. The PETCO2 and PaCO2 difference and its variability and reproducibility were studied. Results: A total of 624 concurrent readings were obtained from 105 children (mean age [SD] 5.53 [5.43] years) requiring invasive bi-level positive airway pressure ventilation in the PICU. All had continuous PETCO2 monitoring and an arterial line for blood gas measurement. The mean (SD) number of concurrent readings obtained from each child, 4-6 h apart was 6.0 (4.05). The PETCO2 values were higher than PaCO2 in 142 observations (22.7%). The PaCO2–PETCO2 difference was individual admission specific (ANOVA, P < 0.001). The PaCO2–PETCO2 difference correlated positively with the alveolar-arterial oxygen tension [P(A-a)O2] difference (ρ = 0.381 P < 0.0001). There was a fixed bias between the PETCO2 and PaCO2 measuring methods, difference +0.66 KPa (95% confidence interval: +0.57 to +0.76). Conclusions: The PaCO2–PETCO2 difference was individual specific. It was not affected by the primary disorder leading to the ventilation.

Parasternal intercostal electromyography: a novel tool to assess respiratory load in children

Background:Parasternal intercostal muscle electromyography (EMGpara) represents a novel tool to assess respiratory load when volitional techniques are not possible. This study examined the application of EMGpara in healthy, wheezy, and critically ill children.Methods:Surface EMGpara was measured during tidal breathing in 92 healthy children, 20 wheezy preschool children (with measurements repeated following bronchodilator), and 25 mechanically ventilated children during supported ventilation and on continuous positive airways pressure.Results:EMGpara was related to age, height, and weight in the healthy group (r = −0.623, −0.625, −0.641 respectively, all P < 0.0001). An age-based equation for predicted EMGpara was developed and patient data expressed as z-scores. EMGpara was higher in wheezy children prebronchodilator than healthy controls (median interquartile range (IQR) z-score 0.53 (0.07–1.94), P = 0.0073), falling to levels not different to healthy children postbronchodilator (−0.08 (−0.50–1.00)). In the critically ill children, EMGpara was higher (P < 0.0001) than in healthy subjects during both mechanical ventilation (median (IQR) z-score 1.14 (0.33–1.93)) and continuous positive airways pressure (1.88 (0.91–3.03)).Conclusion:EMGpara is feasible in children and infants both healthy and diseased, is raised in those with elevated respiratory load, and is responsive to clinical interventions. EMGpara represents a potential method to assess respiratory status in patients conventionally challenging to assess.

Validity of pediatric index of mortality 2 (PIM2) score in pediatric acute liver failure

No abstract

Treatment of AKI in developing and developed countries: An international survey of pediatric dialysis modalities

Hypothesis Acute kidney injury (AKI) is a common cause of morbidity and mortality worldwide, with a pediatric incidence ranging from 19.3% to 24.1%. Treatment of pediatric AKI is a source of debate in varying geographical regions. Currently CRRT is the treatment for pediatric AKI, but limitations due to cost and accessibility force use of adult equipment and other therapeutic options such as peritoneal dialysis (PD) and hemodialysis (HD). It was hypothesized that more cost-effective measures would likely be used in developing countries due to lesser resource availability. Methods A 26-question internet-based survey was distributed to 650 pediatric Nephrologists. There was a response rate of 34.3% (223 responses). The survey was distributed via pedneph and pcrrt email servers, inquiring about demographics, technology, resources, pediatric-specific supplies, and preference in renal replacement therapy (RRT) in pediatric AKI. The main method of analysis was to compare responses about treatments between nephrologists in developed countries and nephrologists in developing countries using difference-of-proportions tests. Results PD was available in all centers surveyed, while HD was available in 85.1% and 54.1% (p = 0.00), CRRT was available in 60% and 33.3% (p = 0.001), and SLED was available in 20% and 25% (p = 0.45) centers of developed and developing world respectively. In developing countries, 68.5% (p = 0.000) of physicians preferred PD to costlier therapies, while in developed countries it was found that physicians favored HD (72%, p = 0.00) or CRRT (24%, p = 0.041) in infants. Conclusions Lack of availability of resources, trained physicians and funds often preclude standards of care in developing countries, and there is much development needed in terms of meeting higher global standards for treating pediatric AKI patients. PD remains the main modality of choice for treatment of AKI in infants in developing world.

Is size the only determinant of delayed abdominal closure in pediatric liver transplant

The aim was to determine the factors associated with the use of delayed abdominal closure in pediatric liver transplantation (LT) and whether this affected outcome. From a prospectively maintained database, transplants performed in children (≤18 years) were identified (October 2010 to March 2015). Primary abdominal closure was defined as mass closure performed at time of transplant. Delayed abdominal closure was defined as mass closure not initially performed at the same time as transplant; 230 children underwent LT. Of these, 176 (76.5%) had primary closure. Age was similar between the primary and delayed groups (5.0 ± 4.9 versus 3.9 ± 5.0 years; P = 0.13). There was no difference in the graft‐to‐recipient weight ratio (GRWR) in the primary and delayed groups (3.4 ± 2.8 versus 4.1 ± 2.1; P = 0.12). Children with acute liver failure (ALF) were more likely to experience delayed closure then those with chronic liver disease (CLD; P < 0.001). GRWR was similar between the ALF and CLD (3.4 ± 2.4 versus 3.6 ± 2.7; P = 0.68). Primary closure children had a shorter hospital stay (P < 0.001), spent fewer days in pediatric intensive care unit (PICU; P = 0.001), and required a shorter duration of ventilation (P < 0.001). Vascular complications (arterial and venous) were similar (primary 8.2% versus delayed 5.6%; P = 0.52). Graft (P = 0.42) and child survival (P = 0.65) in the primary and delayed groups were similar. Considering timing of mass closure after transplant, patients in the early delayed closure group (<6 weeks) were found to experience a shorter time of ventilation (P = 0.03) and in PICU (P = 0.003). In conclusion, ALF was the main determinant of delayed abdominal closure rather than GRWR. The optimal time for delayed closure is within 6 weeks. The use of delayed abdominal closure does not adversely affect graft/child survival. Liver Transplantation 23 352–360 2017 AASLD.

Hematopoietic stem cell transplantation and acute kidney injury in children: A comprehensive review

AKI in the setting of HSCT is commonly investigated among adult patients. In the same way, malignancies requiring treatment with HSCT are not limited to the adult patient population, AKI following HSCT is frequently encountered within pediatric patient populations. However, inadequate information regarding epidemiology and pathophysiology specific to pediatric patients prevents development of appropriate and successful therapeutic strategies for those afflicted. Addressing AKI in the context of sinusoidal obstruction syndrome, chemotherapy, thrombotic microangiopathy and hypertension post chemotherapy, glomerulonephritis, and graft versus host disease provides greater insight into renal impairment associated with these HSCT‐related ailments. To obtain a better understanding of AKI among pediatric patients receiving HSCT, we investigated the current literature specifically addressing these areas of concern.

Extracorporeal Membrane Oxygenation and Pediatric Liver Transplantation – “A step too far?” Results of a single center experience

Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for refractory hypoxemia. More recently, a potential role has emerged in the context of adult orthotopic liver transplantation (OLT), both as a preoperative or intraoperative emergency rescue technique to facilitate transplantation itself, or to enable recovery from severe acute respiratory failure in the postoperative period. Within the pediatric population, the published evidence of the use of ECMO in liver transplantation is limited to isolated case reports. Here we present a small series of 3 pediatric patients in whom venovenous (VV) ECMO was used to either facilitate emergency liver transplantation (ELT) in the context of preoperative refractory hypoxemia, or assist during postoperative severe respiratory failure unresponsive to conventional therapy. Ethics approval for the reporting of anonymous data was given by the South East London Research Ethics Committee.

Comments on Kreuzer et al.: Dialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome.

Dear Editor, The article by Kreuzer et al. entitled BDialysis-dependent acute kidney injury in children with end-stage liver disease: prevalence, dialysis modalities and outcome^ [1] is aimed at bringing to light the importance of acute kidney injury (AKI) in hepatic failure. However, the article leaves the reader with the feeling that AKI in liver disease is the same for both acute liver failure and acute-on-chronic liver failure (ACLF) while they are in fact completely different entities. Our experience at King’s College Hospital, London, which is a large supraregional centre for liver failure and transplantation, is quite different in that we have found the incidence of AKI in liver failure to be variable depending upon whether it is acute liver failure (where the incidence will depend upon the underlying aetiology, extent of hypovolaemia) or acute decompensation of chronic liver failure (ACLF). The authors have grouped together all hepatic failures, i.e. acute and chronic, and compared the two entities and then reported the prevalence of hepatorenal syndrome (HRS) in the whole cohort of dialysis-dependent AKI patients who were listed for transplant. The figure reported is quite high. The aetiology of AKI in acute liver failure is multi-factorial, the most important being hypovolaemia due to various causes. If hypovolaemia leads to persistent hypotension, it can cause acute tubular necrosis and AKI. There could be aetiologies affecting both the liver and kidney simultaneously, such as drug nephrotoxicity (paracetamol, non-steroidal anti-inflammatory drugs) and HRS, with an important contribution from intra-abdominal hypertension (IAH) and the development of abdominal compartment syndrome. In the recent work by Jalan et al. [2], it is clear that ACLF is distinct from decompensated cirrhosis, with ACLF defined by having more than one extra-hepatic organ system failure; consequently the two entities should be distinguished. Recognit ion of ACLF as a clinical ly and pathophysiologically distinct syndrome with defined diagnostic and prognostic criteria will help to encourage the development of new management pathways and interventions to address the unacceptably high mortality among patients with this syndrome. A new diagnostic score, the Chronic Liver Failure Consortium (CLIF-C) organ failure score, has been developed for the classification and prognostic assessment of patients with ACLF. There is also a new CLIF Consortium Acute Decompensation Score (CLIF-C AD) organ system scoring where age, serum sodium, white cell count, creatinine and international normalized ratio were selected as the best predictors of mortality [2]. The second point of concern is the definition used by Kreuzer et al. [1] to define HRS and AKI in liver disease. Although it is a common practice to use the same AKI criteria as those used in non-liver patients, the criteria are different as both serum creatinine measurements and urine output cannot be relied upon in patients with end-stage liver disease (see AKIN, pRIFLE and KDIGO criteria). The authors make no mention of which criteria were used to diagnose AKI (levels of serum creatinine, etc.) in their patients with liver failure, and I would like to draw the reader’s attention to the International Club of Ascites (ICA) 2012 criteria [3]. In these criteria the urine output component is removed, and the rise in serum creatinine—and not the absolute value is taken, based on the presumption that the rise is within the last 7 days; A reply to this letter can be found at doi: 10.1007/s00467-016-3345-1.