JAMA: Surgical Physiology Topic Collection

Neurocognitive Development of Children 4 Years After Critical Illness and Treatment With Tight Glucose Control A Randomized Controlled Trial Neurocognitive Development and Tight Glucose Control

Mesotten D, Gielen M, Sterken C, et al. — Wed, 24 Oct 2012 00:00:00 GMT

Context

A large randomized controlled trial revealed that tight glucose control (TGC) to age-adjusted normoglycemia (50-80 mg/dL at age <1 year and 70-100 mg/dL at age 1-16 years) reduced intensive care morbidity and mortality compared with usual care (UC), but increased hypoglycemia (≤40 mg/dL) (25% vs 1%).

Objective

As both hyperglycemia and hypoglycemia may adversely affect the developing brain, long-term follow-up was required to exclude harm and validate short-term benefits of TGC.

Design, Setting, and Patients

A prospective, randomized controlled trial of 700 patients aged 16 years or younger who were admitted to the pediatric intensive care unit (ICU) of the University Hospitals in Leuven, Belgium, between October 2004 and December 2007. Follow-up was scheduled after 3 years with infants assessed at 4 years old between August 2008 and January 2012. Assessment was performed blinded for treatment allocation, in-hospital (83%) or at home/school (17%). For comparison, 216 healthy siblings and unrelated children were tested.

Main Outcome Measures

Intelligence (full-scale intelligence quotient [IQ]), as assessed with age-adjusted tests (Wechsler IQ scales). Further neurodevelopmental testing encompassed tests for visual-motor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration); attention, motor coordination, and executive functions (Amsterdam Neuropsychological Tasks); memory (Children's Memory Scale); and behavior (Child Behavior Checklist).

Results

Sixteen percent of patients declined participation or could not be reached (n = 113), resulting in 569 patients being alive and testable at follow-up. At a median (interquartile range [IQR]) of 3.9 (3.8-4.1) years after randomization, TGC in the ICU did not affect full-scale IQ score (median [IQR], 88.0 [74.0-100.0] vs 88.5 [74.3-99.0] for UC; P = .73) and had not increased incidence of poor outcomes (death or severe disability precluding neurocognitive testing: 19% [68/349] vs 18% [63/351] with UC; risk-adjusted odds ratio, 0.93; 95% CI, 0.60-1.46; P = .72). Other scores for intelligence, visual-motor integration, and memory also did not differ between groups. Tight glucose control improved motor coordination (9% [95% CI, 0%-18%] to 20% [95% CI, 5%-35%] better, all P ≤ .03) and cognitive flexibility (19% [95% CI, 5%-33%] better, P = .02). Brief hypoglycemia evoked by TGC was not associated with worse neurocognitive outcome.

Conclusion

At follow-up, children who had been treated with TGC during an ICU admission did not have a worse measure of intelligence than those who had received UC.

Trial Registration

clinicaltrials.gov Identifier NCT00214916.

Fish Oil and Postoperative Atrial Fibrillation The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) Randomized Trial Fish Oil to Prevent Postoperative Atrial Fibrillation

Mozaffarian D, Marchioli R, Macchia A, et al. — Wed, 21 Nov 2012 00:00:00 GMT

Context

Postoperative atrial fibrillation or flutter (AF) is one of the most common complications of cardiac surgery and significantly increases morbidity and health care utilization. A few small trials have evaluated whether long-chain n-3-polyunsaturated fatty acids (PUFAs) reduce postoperative AF, with mixed results.

Objective

To determine whether perioperative n-3-PUFA supplementation reduces postoperative AF.

Design, Setting, and Patients

The Omega-3 Fatty Acids for Prevention of Post-operative Atrial Fibrillation (OPERA) double-blind, placebo-controlled, randomized clinical trial. A total of 1516 patients scheduled for cardiac surgery in 28 centers in the United States, Italy, and Argentina were enrolled between August 2010 and June 2012. Inclusion criteria were broad; the main exclusions were regular use of fish oil or absence of sinus rhythm at enrollment.

Intervention

Patients were randomized to receive fish oil (1-g capsules containing ≥840 mg n-3-PUFAs as ethyl esters) or placebo, with preoperative loading of 10 g over 3 to 5 days (or 8 g over 2 days) followed postoperatively by 2 g/d until hospital discharge or postoperative day 10, whichever came first.

Main Outcome Measure

Occurrence of postoperative AF lasting longer than 30 seconds. Secondary end points were postoperative AF lasting longer than 1 hour, resulting in symptoms, or treated with cardioversion; postoperative AF excluding atrial flutter; time to first postoperative AF; number of AF episodes per patient; hospital utilization; and major adverse cardiovascular events, 30-day mortality, bleeding, and other adverse events.

Results

At enrollment, mean age was 64 (SD, 13) years; 72.2% of patients were men, and 51.8% had planned valvular surgery. The primary end point occurred in 233 (30.7%) patients assigned to placebo and 227 (30.0%) assigned to n-3-PUFAs (odds ratio, 0.96 [95% CI, 0.77-1.20]; P = .74). None of the secondary end points were significantly different between the placebo and fish oil groups, including postoperative AF that was sustained, symptomatic, or treated (231 [30.5%] vs 224 [29.6%], P = .70) or number of postoperative AF episodes per patient (1 episode: 156 [20.6%] vs 157 [20.7%]; 2 episodes: 59 [7.8%] vs 49 [6.5%]; ≥3 episodes: 18 [2.4%] vs 21 [2.8%]) (P = .73). Supplementation with n-3-PUFAs was generally well tolerated, with no evidence for increased risk of bleeding or serious adverse events.

Conclusion

In this large multinational trial among patients undergoing cardiac surgery, perioperative supplementation with n-3-PUFAs, compared with placebo, did not reduce the risk of postoperative AF.

Trial Registration

clinicaltrials.gov Identifier: NCT00970489