Targeted Blood-pressure Management and Acute Kidney Injury After Coronary Artery Bypass Surgery

Impact of Targeted Blood-pressure Management on Incidence of Acute Kidney Injury After Off-pump Coronary Artery Bypass Surgery: A Randomized Controlled Trial

Acute renal injury (AKI) is a common complication after cardiac surgery and is associated with worse outcomes. It is now realized that intraoperative hypotension is an important risk factor for the development of AKI. In a recent randomized controlled trial of patients undergoing major noncardiac surgery, intraoperative individualized blood-pressure management reduced the incidence of postoperative organ dysfunction. The investigators hypothesize that, for patients undergoing off-pump CABG, targeted blood-pressure management during surgery may also reduce the incidence of postoperative AKI.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Preventive Medicine; Intraoperative Hypotension; Coronary Artery Bypass, Off-Pump; Intraoperative Care
• Intervention / Treatment: Drug: Targeted blood-pressure management; Drug: Routine blood-pressure management

Detailed Description

Acute renal injury (AKI) is a common complication after cardiac surgery. In patients undergoing noncardiac surgery, intraoperative hypotension may lead to hypoperfusion of important organs and result in organ injuries such as AKI, myocardial injury, and stroke. The development of organ injuries is associated with wose outcomes including higher 30-day or even 1-year mortality. In a recent randomized controlled trial, patients undergoing major noncardiac surgery received either individualized (systolic blood pressure [SBP] maintained within 10% of the reference level) or standard (SBP maintained above 80 mmHg or within 40% of the reference level) blood-pressure management strategy during surgery. The results showed that individualized blood-pressure management reduced the incidence of postoperative organ dysfunction. Intraoperative hypotension is very common during off-pump coronary artery bypass grafting (CABG) surgery. The investigators hypothesize that, for patients undergoing off-pump CABG, good blood-pressure management with norepinephrine may also reduce the incidence of postoperative AKI. The purpose of this study is to investigate the effect of targeted blood-pressure management during off-pump CABG surgery on the incidence of postoperative AKI.

• Study Type: Interventional
• Enrollment (Estimated): 612
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dong-Xin Wang, MD, PHD; Phone Number: 8610-83572784; Email: wangdongxin@hotmail.com
• Study Contact Backup: Name: Li Huang, MD, PhD; Phone Number: 8610-83572460; Email: huanglibd@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Recruiting
      • Beijing University First Hospital
      • Contact: Dong-Xin Wang, MD, PHD; Phone Number: 8610-83572784; Email: wangdongxin@hotmail.com
      • Contact: Li Huang, MD, PhD; Phone Number: 8610-83572460; Email: huanglibd@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 50 years;
• Scheduled to undergo off-pump CABG surgery.

Exclusion Criteria:

• Refuse to participate;
• Untreated or uncontrolled severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg);
• Chronic kidney disease with a glomerular filtration rate < 30 ml/min/1.73 m2 or end-stage renal disease requiring renal-replacement therapy;
• Inability to communicate during the preoperative period because of coma, profound dementia, language barrier, or end-stage disease;
• Requirement of vasopressors/inotropics to maintain blood pressure before surgery;
• Second or emergency surgery;
• Expected survival of less than 24 hours.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeted blood-pressure management; Prophylactic norepinephrine infusion is started at the beginning of anesthetic induction and maintained throughout surgery. The target is to maintain systolic blood pressure at 110 mmHg or higher during surgery.	Drug: Targeted blood-pressure management; Prophylactic norepinephrine infusion is started before anesthetic induction and maintained throughout surgery. The target is to maintain systolic blood pressure at 110 mmHg or higher.; Other Names: Norepinephrine
Active Comparator: Routine blood-pressure management; Phenylephrine (25-50 ug) is injected or vasopressors is infused only when necessary. The target is to maintain systolic blood pressure at 90 mmHg or higher during surgery.	Drug: Routine blood-pressure management; Phenylephrine (25-50 ug) is injected or vasopressors is infused only when necessary. The target is to maintain systolic blood pressure at 90 mmHg or higher during surgery.; Other Names: Phenylephrine and other vasopressors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute kidney injury (AKI) within 7 days after surgery	Development of AKI within 7 days after surgery is diagnosed according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria	Up to 7 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in hospital after surgery	Length of stay in hospital after surgery	Up to 30 days after surgery
Duration of mechanical ventilation after surgery	Duration of mechanical ventilation after surgery	Up to 30 days after surgery
Cognitive function in 1- and 2-year survivors	Cognitive function in 1- and 2-year survivors is assessed with the modified Telephone Interview for Cognitive Status (TICS-m, score ranges from 0 to 40, with higher score indicating better function).	At the end of the 1st and 2nd years after surgery
All-cause 30-day mortality	All-cause 30-day mortality	At 30 days after surgery
Classification of AKI within 7 days after surgery	Development of AKI within 7 days after surgery is diagnosed according to the KDIGO criteria	Up to 7 days after surgery
Length of stay in intensive care unit (ICU) after surgery	Length of stay in intensive care unit (ICU) after surgery	Up to 30 days after surgery
Incidence of non-MACE complications within 30 days after surgery	Non-MACE complications within 30 days after surgery indicate new-onset medical conditions other than MACEs that produce harmful effects on patients' recovery and required therapeutic intervention.	Up to 30 days after surgery
Incidence of delirium within 7 days after surgery	Development of delirium within 7 days after surgery is assessed with the Confusion Assessment Method (3D-CAM for patients without mechanical ventilation and CAM-ICU for patients with mechanical ventilation).	Up to 7 days after surgery
Incidence of major adverse cardiovascular events (MACEs) within 30 days after surgery	MACEs within 30 days after surgery include cardiovascular death, non-fatal cardiac arrest, acute myocardial infarction, revascularization, and stroke.	Up to 30 days after surgery
2-year overall survival after surgery	2-year overall survival after surgery	Up to 2 years after surgery
2-year major adverse cardiovascular event (MACE)-free survival after surgery	MACEs within 2 years after surgery include cardiovascular death, non-fatal cardiac arrest, acute myocardial infarction, revascularization, and stroke.	Up to 2 years after surgery
Quality of life in 1- and 2- year survivors: SF-36	Quality of life in 1- and 2-year survivors is assessed with the 36-Item Short Form Health Survey (SF-36). The SF-36 evaluates 8 different domains of quality of life, i.e., physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The score of each domain ranges from 0 to 100, with high score indicating better function.	At the end of the 1st and 2nd years after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain severity within 3 days after surgery: NRS	Pain severity is assessed with the Numeric Rating Scale (NRS, an 11-point scale where 0=no pain and 10=the worst pain) twice daily (8:00-10:00 am, 18:00-20:00 pm) after surgery.	Up to 3 days after surgery
Daily prevalence of delirium during postoperative days 1-7	Daily prevalence of delirium during postoperative days 1-7	During the first 7 days after surgery
Duration of intraoperative cerebral desaturation (sub-study)	Duration of cerebral desaturation is monitored by near-infrared spectroscopy. Cerebral desaturation is defined as a decrease of more than 10% from baseline. Performed in part of enrolled patients.	During surgery

Collaborators and Investigators

• Sponsor: Peking University First Hospital
• Investigators: Principal Investigator: Dong-Xin Wang, MD, PhD, Peking University First Hospital

Publications and helpful links

General Publications

• Walsh M, Devereaux PJ, Garg AX, Kurz A, Turan A, Rodseth RN, Cywinski J, Thabane L, Sessler DI. Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension. Anesthesiology. 2013 Sep;119(3):507-15. doi: 10.1097/ALN.0b013e3182a10e26.
• Bijker JB, van Klei WA, Vergouwe Y, Eleveld DJ, van Wolfswinkel L, Moons KG, Kalkman CJ. Intraoperative hypotension and 1-year mortality after noncardiac surgery. Anesthesiology. 2009 Dec;111(6):1217-26. doi: 10.1097/ALN.0b013e3181c14930.
• Futier E, Lefrant JY, Guinot PG, Godet T, Lorne E, Cuvillon P, Bertran S, Leone M, Pastene B, Piriou V, Molliex S, Albanese J, Julia JM, Tavernier B, Imhoff E, Bazin JE, Constantin JM, Pereira B, Jaber S; INPRESS Study Group. Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1346-1357. doi: 10.1001/jama.2017.14172.
• Kheterpal S, Tremper KK, Heung M, Rosenberg AL, Englesbe M, Shanks AM, Campbell DA Jr. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009 Mar;110(3):505-15. doi: 10.1097/ALN.0b013e3181979440.
• Katayama H, Kurokawa Y, Nakamura K, Ito H, Kanemitsu Y, Masuda N, Tsubosa Y, Satoh T, Yokomizo A, Fukuda H, Sasako M. Extended Clavien-Dindo classification of surgical complications: Japan Clinical Oncology Group postoperative complications criteria. Surg Today. 2016 Jun;46(6):668-85. doi: 10.1007/s00595-015-1236-x. Epub 2015 Aug 20.
• Bennett-Guerrero E, Welsby I, Dunn TJ, Young LR, Wahl TA, Diers TL, Phillips-Bute BG, Newman MF, Mythen MG. The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery. Anesth Analg. 1999 Aug;89(2):514-9. doi: 10.1097/00000539-199908000-00050.
• Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol. 2006 Jan;1(1):19-32. doi: 10.2215/CJN.00240605. Epub 2005 Oct 19.
• Schopka S, Diez C, Camboni D, Floerchinger B, Schmid C, Hilker M. Impact of cardiopulmonary bypass on acute kidney injury following coronary artery bypass grafting: a matched pair analysis. J Cardiothorac Surg. 2014 Jan 18;9:20. doi: 10.1186/1749-8090-9-20.
• Monk TG, Saini V, Weldon BC, Sigl JC. Anesthetic management and one-year mortality after noncardiac surgery. Anesth Analg. 2005 Jan;100(1):4-10. doi: 10.1213/01.ANE.0000147519.82841.5E.
• Abelha FJ, Botelho M, Fernandes V, Barros H. Determinants of postoperative acute kidney injury. Crit Care. 2009;13(3):R79. doi: 10.1186/cc7894. Epub 2009 May 22.
• Coca SG, Peixoto AJ, Garg AX, Krumholz HM, Parikh CR. The prognostic importance of a small acute decrement in kidney function in hospitalized patients: a systematic review and meta-analysis. Am J Kidney Dis. 2007 Nov;50(5):712-20. doi: 10.1053/j.ajkd.2007.07.018.
• Bijker JB, Persoon S, Peelen LM, Moons KG, Kalkman CJ, Kappelle LJ, van Klei WA. Intraoperative hypotension and perioperative ischemic stroke after general surgery: a nested case-control study. Anesthesiology. 2012 Mar;116(3):658-64. doi: 10.1097/ALN.0b013e3182472320.
• Rettig TCD, Peelen LM, Geuzebroek GSC, van Klei WA, Boer C, van der Veer JW, Hofland J, van de Garde EMW, Noordzij PG. Impact of Intraoperative Hypotension During Cardiopulmonary Bypass on Acute Kidney Injury After Coronary Artery Bypass Grafting. J Cardiothorac Vasc Anesth. 2017 Apr;31(2):522-528. doi: 10.1053/j.jvca.2016.07.040. Epub 2016 Jul 30.
• Hiltebrand LB, Koepfli E, Kimberger O, Sigurdsson GH, Brandt S. Hypotension during fluid-restricted abdominal surgery: effects of norepinephrine treatment on regional and microcirculatory blood flow in the intestinal tract. Anesthesiology. 2011 Mar;114(3):557-64. doi: 10.1097/ALN.0b013e31820bfc81.
• Boettger S, Nunez DG, Meyer R, Richter A, Fernandez SF, Rudiger A, Schubert M, Jenewein J. Delirium in the intensive care setting and the Richmond Agitation and Sedation Scale (RASS): Drowsiness increases the risk and is subthreshold for delirium. J Psychosom Res. 2017 Dec;103:133-139. doi: 10.1016/j.jpsychores.2017.09.011. Epub 2017 Oct 4.
• Chanques G, Garnier O, Carr J, Conseil M, de Jong A, Rowan CM, Ely EW, Jaber S. The CAM-ICU has now a French "official" version. The translation process of the 2014 updated Complete Training Manual of the Confusion Assessment Method for the Intensive Care Unit in French (CAM-ICU.fr). Anaesth Crit Care Pain Med. 2017 Oct;36(5):297-300. doi: 10.1016/j.accpm.2017.02.003. Epub 2017 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2018
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: August 9, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 31, 2023
• Last Update Submitted That Met QC Criteria: May 28, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Acute Kidney Injury; Intraoperative Hypotension; Preventive Medicine; Intraoperative Care; Coronary Artery Bypass, Off-Pump
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury; Hypotension; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Protective Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Cardiotonic Agents; Respiratory System Agents; Sympathomimetics; Vasoconstrictor Agents; Mydriatics; Nasal Decongestants; Adrenergic alpha-1 Receptor Agonists; Norepinephrine; Phenylephrine
• Other Study ID Numbers: 2018-118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No