Combination of Remote Pre- and Postconditioning Fails to Help Cardiac Surgery Patients

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Remote ischemic preconditioning combined with remote postconditioning fails to improve clinical outcomes in patients undergoing cardiac surgery, according to a randomized study published online September 7, 2013, ahead of print in the European Heart Journal.

Yunseok Jeon, MD, PhD, of Seoul National University Hospital (Seoul, South Korea), and colleagues looked at 1,280 patients who underwent elective cardiac surgery from June 2009 to November 2010, randomizing them to remote ischemic pre- and postconditioning (n = 644) or a control group (n = 636) on the morning of surgery.

In the combined conditioning group, a blood pressure cuff was placed around the upper arm and inflated to 200 mm Hg for 5 minutes and deflated for 5 minutes. This inflation-deflation cycle was repeated 4 times. The protocol was applied twice immediately after induction of anesthesia prior to cardiopulmonary bypass or coronary anastomoses for remote preconditioning, and immediately after the completion of bypass or anastomoses for postconditioning. Patients in the control arm had the same blood pressure cuff around the upper arm, but pressure was not applied.

There was no difference in the primary composite outcome (in-hospital death, MI, arrhythmia requiring treatment, stroke, coma, renal failure or dysfunction, respiratory failure, cardiogenic shock, GI complication, and multiorgan failure) between the combined conditioning group and the control group or in other postoperative outcomes (table 1).

Table 1. Postoperative Outcomes

 

Combined Remote Conditioning
(n = 644)

Controls
(n = 636)

P Value

Primary Composite

38.0%

38.1%

0.998

In-Hospital Mortality

1.6%

2.2%

0.392

MI

0.8%

0.9%

0.746

Cardiogenic Shock

13.5%

13.1%

0.809

Atrial Fibrillation

21.4%

20.9%

0.821

Stroke

1.6%

1.6%

0.978


On multivariate logistic regression analysis, combined remote ischemic pre- and postconditioning did not decrease the composite outcome (adjusted OR 1.00; 95% CI 0.79-1.26; P = 0.971). In addition, there was no difference in the length of ICU (2.0 days) and hospital stay (9.0 days) between the 2 groups. Postoperative characteristics such as need for inotropic support, mechanical ventilation time, and the use of a mechanical assist device were also similar between groups.

On subgroup analysis, in patients who received off-pump CABG, multivariable regression revealed that combined pre- and postconditioning was associated with an increase in the composite outcome (adjusted OR 1.54; 95% CI 1.02-2.30; P = 0.038).

The authors note that remote ischemic preconditioning is thought to have systemic protective effects on distal organs including the heart, lungs, and kidneys. However, they add, “[t]hese results suggest that [the treatment] does not improve the clinical outcome of cardiac surgery patients.”

Propofol May Interfere with Preconditioning Benefits

“This is a large trial which shows no benefit in clinical outcome in patients undergoing CABG with a combination of remote pre- and postconditioning, and it thus contrasts with our recent trial that did show reduced all-cause mortality with remote preconditioning in CABG patients,” commented Gerd Heusch, MD, PhD, of the University of Essen Medical School (Essen, Germany), in an e-mail communication with TCTMD. “The common denominator of all negative trials in the field is the use of propofol, which interferes with remote preconditioning whereas inhalation anesthetics do not.”

Propofol (0.04-0.07 mg/kg/min) was used in the trial for anesthesia maintenance.

“Unfortunately,” Dr. Heusch said, “the present trial therefore does not argue against cardioprotection by remote conditioning but simply shows that one can also spoil this benefit.”

The study authors note that propofol, a scavenger of oxygen-free radicals, has abrogated the cardioprotective effects of preconditioning in previous studies. However, they add, the current dose of propofol was lower than in prior trials.

Study Details

Cardiac surgery was elective and included cardiac valve surgery, CABG, combined valve and CABG surgery, ascending aorta or aortic arch surgery, and congenital heart defect repair.

 


Source:
Hong DM, Lee E-H, Kim HJ, et al. Does remote ischaemic preconditioning with postconditioning improve clinical outcomes of patients undergoing cardiac surgery? Remote Ischaemic Preconditioning with Postconditioning Outcome Trial. Eur Heart J. 2013;Epub ahead of print.

 

 

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Disclosures
  • Drs. Jeon and Heusch report no relevant conflicts of interest.

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