Elsevier

The Lancet

Volume 383, Issue 9931, 24–30 May 2014, Pages 1807-1813
The Lancet

Articles
Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM)

https://doi.org/10.1016/S0140-6736(14)60799-6Get rights and content

Summary

Background

Peritoneal dialysis is the renal replacement therapy of choice for acute kidney injury in neonates, but in some cases is not feasible or effective. Continuous renal replacement therapy (CRRT) machines are used off label in infants smaller than 15 kg and are not designed specifically for small infants. We aimed to design and create a CRRT machine specifically for neonates and small infants.

Methods

We prospectively planned a 5-year project to conceive, design, and create a miniaturised Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM), specifically for neonates and small infants. We created the new device and assessed it with in-vitro laboratory tests, completed its development to meet regulatory requirements, and obtained a licence for human use. Once approved, we used the machine to treat a critically ill neonate

Findings

The main characteristics of CARPEDIEM are the low priming volume of the circuit (less than 30 mL), miniaturised roller pumps, and accurate ultrafiltration control via calibrated scales with a precision of 1 g. In-vitro tests confirmed that both hardware and software met the specifications. We treated a 2·9 kg neonate with haemorrhagic shock, multiple organ dysfunction, and severe fluid overload for more than 400 h with the CARPEDIEM, using continuous venovenous haemofiltration, single-pass albumin dialysis, blood exchange, and plasma exchange. The patient's 65% fluid overload, raised creatinine and bilirubin concentrations, and severe acidosis were all managed safely and effectively. Despite the severity of the illness, organ function was restored and the neonate survived and was discharged from hospital with only mild renal insufficiency that did not require renal replacement therapy.

Interpretation

The CARPEDIEM CRRT machine can be used to provide various treatment modalities and support for multiple organ dysfunction in neonates and small infants. The CARPEDIEM could reduce the range of indications for peritoneal dialysis, widen the range of indications for CRRT, make the use of CRRT less traumatic, and expand its use as supportive therapy even when complete renal replacement therapy is not indicated.

Funding

Associazione Amici del Rene di Vicenza.

Introduction

The increase in incidence of acute kidney injury and its association with poor outcomes in the general population1 have led to a call for action2 to improve early diagnosis, institute new preventive measures, and develop new treatments to improve clinical outcomes.2 Acute kidney injury in adult patients, and to a lesser extent in children, has received a great deal of attention, with the development of standard classification systems,3, 4, 5, 6, 7 assessment of novel biomarkers,8, 9 and recognition of the association between acute kidney injury and the development of chronic kidney disease.10, 11, 12 However, such progress has not been made for infants and neonates.13

Acute kidney injury has been described as a rare disorder in neonates, occurring in 1–2% of the hospital-admitted neonatal population.14 However, more recent single-centre systematic investigation15 into neonatal acute kidney injury using modern definitions showed that it occurs in 16% of newborn infants weighing more than 2 kg who are admitted to neonatal intensive care. Previous underappreciation of the prevalence of the disorder has made neonatal acute kidney injury an orphan-like disease, and has held back the development of technology specifically for renal replacement therapy in infants.

Existing technology for renal replacement therapy is designed for use in adults and has been inadequately adapted for use in neonates and infants, providing challenges to safe and effective treatment. Because of the unique nature of acute kidney injury in infants and its severe complications, a dedicated technology capable of managing blood purification and fluid balance in very small children is sorely needed. Therefore, we undertook a project to develop a continuous renal replacement therapy (CRRT) machine designed specifically for patients of less than 10 kg bodyweight (CARPEDIEM; Cardio-Renal Pediatric Dialysis Emergency Machine), particularly neonates and premature infants. Here we describe the development of the project and report the first use of the CARPEDIEM for the treatment of a newborn baby with clinical indications for CRRT.

Section snippets

Development

We prospectively planned a 5-year project to conceive, design, and create a new miniaturised CRRT machine for neonates and small infants. First, we assessed the limitations and problems with existing CRRT technology and identified the technical and clinical requirements for a new device. The goal was to create a machine with reduced priming volumes and the capacity to accurately handle very low blood and ultrafiltration flows. In small children, total blood volume ranges 200 to 800 mL, and

Results

After 30 months in development, the CARPDIEM was approved for human use. The machine features miniaturised components and fluid control capability suitable for newborn babies and small infants within a weight range of 2·5–10·0 kg (appendix).2, 16 It can operate at a unique range of low flows and pressures, with an accuracy of fluid balance of about 1 g. All of these specifications have been thoroughly validated in several sessions of in-vitro laboratory tests done by four independent operators.

Discussion

CARPEDIEM, a CRRT platform designed specifically for neonates and small infants, was successfully used to manage a critically ill neonate of 2·9 kg bodyweight with multiple organ failure and severe fluid overload (panel). In the past, CRRT machines designed for adults were adapted for paediatric use by simply modifying the operational parameters via software and by using extracorporeal circuits with lower priming volumes. However, these modifications were adequate only for paediatric patients

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