Acute Kidney Injury in Children Operated for Congenital Heart Disease

The purpose of this study was to investigate if repeated inflation of a blood pressure cuff applied around one leg causing mild ischemia ("remote ischemic preconditioning") could protect children operated for congenital heart disease from developing acute kidney injury.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Procedure: Remote ischemic preconditioning (RIPC); Procedure: Control

Detailed Description

Remote ischemic preconditioning (RIPC) refers to an intervention of remote, brief ischemia which confers systemic protection against consequences of reperfusion injury in distant organs. RIPC has been shown to protect various organs during major surgeries. Our hypothesis was that RIPC could protect kidney function in children operated for complex congenital heart disease.

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Children admitted for surgery for congenital heart disease

Exclusion Criteria:

• heart surgeries of low complexity such as closure of septal defects, aortico-pulmonary windows, establishment of glenn shunts, subaortic membrane resection, redirection of anomalous pulmonary veins, valvotomies, repair of pulmonary artery stenosis and surgeries without the use of extracorporeal circulation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control	Procedure: Control; The cuff was applied on the leg without inflation in the control group.
Experimental: Remote ischemic preconditioning (RIPC); See intervention description	Procedure: Remote ischemic preconditioning (RIPC); RIPC was performed by applying a blood pressure cuff around the child's leg. The cuff was inflated to 40 mmHg above the systolic pressure in 4 cycles of 5 minutes. Every cycle of ischemia was followed by 5 minutes of reperfusion. The first RIPC cycle started after anesthesia induction when invasive arterial blood pressure was monitored. Appropriate cuff size was used choosing between four sizes. For reproducibility RIPC was performed on the right leg with only a few exceptions, when the leg was used for invasive catheters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute kidney injury	Categorized according to the RIFLE criteria (22): R= risk= increased p-creatinine * 1.5 and/or urine output < 0.5 ml/kg/hour for 6 hours, I= injury= increased p-creatinine * 2 and/or urine output < 0.5 ml/kg/hour for 12 hours, F= failure= increased p-creatinine * 3 or p-creatinine ≥ 350 µmol/L in the setting of an acute increase of at least 44 µmol/L and/or urine output < 0.3 ml/kg/hour for 24 hours or anuria for 12 hours, L= complete loss of renal function for > 4 weeks (need for dialysis for longer than 4 weeks), E= end-stage renal disease (need for dialysis for longer than 3 months).	Up to 4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay		90 days
Arterial blood pressure	Incidence of postoperative low blood pressure (below the age-reference level)	Up to 3 days
Inotropic Score (IS)	The highest postoperative daily dose (µg/kg//min) was used in the formula: IS = [(dopamine + dobutamine) × 1] + (milrinone × 10) + [(epinephrine + norepinephrine) × 100] to calculate the IS.	Up to 3 days
Reoperation during hospital stay		90 days
Length of stay at the ICU		90 days
Mortality	In-hospital mortality	90 days
Level of cystatin C in plasma		Up to 4 days
Level of Neutrophil Gelatinase-Associated Lipocalin in plasma and urine		Up to 4 days

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Raimond and Dagmar Ringgård-Bohn's Foundation; Snedkermester Sophus Jacobsen and hustru Astrid Jacobsens Foundation; Aase and Ejnar Danielsens Foundation; The Augustinus Foundation, Denmark.; The Dagmar Marshall Foundation; Direktør Kurt Bønnelycke and Hustru fru Grethe Bønnelyckes Foundation; Helen and Ejnar Bjørnows Foundation; Grosserer L.F. Foghts Foundation
• Investigators: Study Director: Kirsten MR Pedersen, MD, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby; Principal Investigator: Vibeke E Hjortdal, MD PhD DMSc, Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby; Study Chair: Hanne B Ravn, MD PhD, Department of Anesthesia and Intensive Care, Aarhus University Hospital, Skejby; Study Chair: Johan V Povlsen, MD, Department of Renal Medicine C, Aarhus University Hospital, Skejby; Study Chair: Michael R Schmidt, MD PhD, Aarhus University Hospital; Study Chair: Erland Erlandsen, MSc, Department of Clinical Biochemistry, Viborg Hospital

Publications and helpful links

General Publications

• Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, Holtby HM, Cox PN, Smallhorn JF, Van Arsdell GS, Redington AN. Randomized controlled trial of the effects of remote ischemic preconditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol. 2006 Jun 6;47(11):2277-82. doi: 10.1016/j.jacc.2006.01.066. Epub 2006 May 15.
• Pedersen KR, Povlsen JV, Christensen S, Pedersen J, Hjortholm K, Larsen SH, Hjortdal VE. Risk factors for acute renal failure requiring dialysis after surgery for congenital heart disease in children. Acta Anaesthesiol Scand. 2007 Nov;51(10):1344-9. doi: 10.1111/j.1399-6576.2007.01379.x.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 10, 2011
• First Submitted That Met QC Criteria: March 14, 2011
• First Posted (Estimate): March 16, 2011

Study Record Updates

• Last Update Posted (Estimate): September 14, 2012
• Last Update Submitted That Met QC Criteria: September 13, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: Child; Infant; Acute kidney injury; Ischemic preconditioning; Congenital heart defects; Cardiac surgical procedures
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Cardiovascular Abnormalities; Heart Diseases; Wounds and Injuries; Acute Kidney Injury; Heart Defects, Congenital
• Other Study ID Numbers: 20080052