Disinvestment in Hydroxyl-ethyl Starches (HES) for Cardiac Surgery

Clinical Impact of Disinvestment in Hydroxyl-ethyl Starches (HES) for Patients Undergoing Cardiac Surgery

The purpose of this study is to determine whether disinvestment in hydroxyl-ethyl starches (HES) for patients undergoing cardiac surgery was safe and effective.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgical Procedures
• Intervention / Treatment: Drug: 6% hydroxyethyl starch

Detailed Description

Fluid replacement therapy is administered to patients requiring volume resuscitation following significant blood loss, or for maintenance fluid requirements. Severe blood loss can lead to anemia, reduced oxygen carrying capacity, and organ failure. Options for fluid replacement include red blood cell transfusion, colloids such as hydroxyethyl starches (HES), albumin, and gelatin as well as crystalloids such as normal saline and Ringer's lactate. Until recently, use of HES at the London hospitals and other major health sciences centers was concentrated in cardiac surgery patients and non-critically ill perioperative patients. In April 2013, the London Health Sciences Centre (LHSC) opted to discontinue the use of HES altogether, based on evidence suggesting that HES may be harmful compared to alternative fluid therapies.

The decision to disinvest in HES became effective on April 2, 2013. The hospitals no longer purchased HES, and clinicians used alternative fluids for volume resuscitation. Alternatives available at the hospitals included Ringer's lactate, normal saline, and albumin. All HES product was removed from patient care areas.

The investigators will perform a before/after analysis of the impact of HES disinvestment using a retrospective observational cohort study design, employing data obtained from administrative and clinical databases. Exposure to HES before disinvestment will be assumed to be 100% of cardiac surgical patients, and, after a washout period surrounding the time of disinvestment, exposure to HES will be assumed to be 0% after disinvestment.

The study population will be defined retrospectively in terms of the intervention received and the time period of the intervention.

• Study Type: Observational
• Enrollment (Actual): 2000

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The proposed study population includes adult patients (age >/= 18) who underwent coronary artery bypass surgery (CABG) with or without valve surgery at the London Health Sciences Centre.

Description

Inclusion Criteria:

• The London Health Sciences Centre disinvested in hydroxyethyl starches on April 2, 2013. The study population will include individuals undergoing cardiac surgery and discharged from hospital in one of two eras:

  • Era 1 (365 days prior to disinvestment in HES): the time period between April 1, 2012 and March 31, 2013, or
  • Era 2 (365 days following disinvestment in HES): the time period between June 1, 2013 and May 31, 2014 (NB: after a 2-month washout period to ensure all HES supplies had been exhausted).

• Specifically, the study population will be comprised of patients who underwent the following cardiac surgical procedures:

  • Coronary artery bypass graft only
  • Coronary artery bypass graft with aortic valve replacement
  • Coronary artery bypass graft with aortic valve repair
  • Coronary artery bypass graft with mitral valve replacement
  • Coronary artery bypass graft with mitral valve repair
  • Coronary artery bypass graft with a valve surgical procedure (replacement and/or repair) involving up two valves

Exclusion Criteria:

• Individuals undergoing heart transplants, aortic dissections, and other cardiac procedures not listed in the inclusion criteria above will be excluded.

• Individuals with any portion of the acute length of stay spanning the washout period (April 1, 2013 to May 31, 2013) will be excluded. Specifically, the following patients will be excluded:

  • Patients admitted prior to April 1, 2013 that remained in hospital on April 1, 2013.
  • Patients admitted during the washout period (April 1, 2013 to May 31, 2013) that remained in hospital on May 31, 2013.
  • Patients admitted and discharged during the washout period.
• We will exclude subsequent cardiac surgical procedures for individuals meeting the inclusion criteria more than once during the study timeframe (i.e. each patient's data will only be used once).
• Individuals enrolled in the randomized controlled clinical trial entitled, "VolulyteTM in Cardiac Surgery" (ClinicalTrials.gov Identifier: NCT01553617) will be excluded from the cohort. The purpose of this study was to assess the efficacy and safety of 6 % Hydroxyethyl Starch 130/0.4 in an Isotonic Electrolyte Solution (VolulyteTM) compared to 5% Human Serum Albumin as volume replacement therapy in elective open-heart surgery in adult patients on cardiopulmonary bypass. Individuals enrolled in the trial were randomized to priming of the cardiopulmonary bypass machine and volume therapy as necessary with either Volulyte or Human Serum Albumin. The study began in October 2012 and was completed in January 2014, with a total enrolment of 133 patients. The approximate number enrolled at LHSC was 30. Because the study period overlaps with that of the pre- and post- disinvestment eras, individuals enrolled in this study will be excluded from the retrospective cohort.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Arm: Exposed: Hydroxyethyl starch; Cardiac surgical patients exposed to 6% hydroxyethyl starch (130/0.4).	Drug: 6% hydroxyethyl starch; Other Names: Voluven (Fresenius Kabi)
Arm: Unexposed: Hydroxyethyl starch; Cardiac surgical patients not exposed to 6% hydroxyethyl starch (130/0.4).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of Stay	Acute hospital length of stay (in days) following cardiac surgery	Following cardiac surgery (on average approximately 10 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of transfusion	The proportion receiving a transfusion of red blood cells or other products.	During or after cardiac surgery, prior to hospital discharge (on average approximately 10 days)
Rates of transfusion	The number of units of red blood cells or other products transfused.	During or after cardiac surgery, prior to hospital discharge (on average approximately 10 days)
Kidney Injury	The proportion experiencing kidney injury as measured by serum creatinine levels.	During or after cardiac surgery, prior to hospital discharge (on average approximately 10 days)
Renal Replacement Therapy	The proportion receiving renal replacement therapy.	During or after cardiac surgery, prior to hospital discharge (on average approximately 10 days)
Cost of care	The total cost of the acute phase of hospitalization based on hospital case cost data.	During the acute phase of the hospital stay (on average approximately 10 days)
In-hospital mortality	The proportion dying during the hospital stay.	Death during the hospital stay (on average approximately 10 days)

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: Western University, Canada

Publications and helpful links

General Publications

• Hong M, Jones PM, Martin J, Kiaii B, Arellano R, Cheng D, John-Baptiste AA. Clinical impact of disinvestment in hydroxyethyl starch for patients undergoing coronary artery bypass surgery: a retrospective observational study. Can J Anaesth. 2019 Jan;66(1):25-35. doi: 10.1007/s12630-018-1245-5. Epub 2018 Nov 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 1, 2015
• Primary Completion (ACTUAL): April 1, 2016
• Study Completion (ACTUAL): April 1, 2018

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (ESTIMATE): December 31, 2014

Study Record Updates

• Last Update Posted (ACTUAL): November 6, 2018
• Last Update Submitted That Met QC Criteria: November 2, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 105755

Drug and device information, study documents

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