Leuven I trial - Intensive Blood Glucose control in a Cardiovascular and Surgical ICU is associated with a decrease in mortality and improved secondary outcomes.

Author: Peter Tofts, MD; Edited: Martin Cearras, MD

Find the original article here!

Intensive Insulin Therapy in Critically Ill Patients | New England Journal of Medicine

Summary:

In this single center study, a conventional approach to blood glucose (BG) control with a goal of 180-200 was compared to an intensive insulin use starting with glucose > 110 to achieve a goal of 80-110mg/dl. The authors studied a surgical ICU population, and the intensive approach shows a difference in mortality, blood stream infections, acute renal injury and critical illness polyneuropathy.

PICOTT:

Population: N= 1548 Inclusion: adult patients admitted to a Surgical ICU on mechanical ventilation. Exclusion: deferred consent or moribund

Intervention: Treatment: Rx insulin infusion when BG >110 mg/dL to maintain BG 80 to 110 mg/dL

Comparison: Rx insulin infusion when BG >215 mg/dL to maintain BG 180 to 200 mg/dL

Outcomes:

• Primary: death from any cause during ICU stay

• Secondary: In-hospital death, ICU LOS, prolonged stay >14 days, readmission, need for ventilatory support, renal replacement therapy, or inotropic or vasopressor support, Critical illness polyneuropathy, markers of infection, transfusion requirement and hyperbilirubinemia.

Type of Question: Therapy

Type of Study: RCT

Interpretation of the Study:

The intensive blood glucose control group showed statistically significant improvements in mortality and secondary outcomes, including reduced bloodstream infections, sepsis, acute kidney injury requiring renal replacement therapy, and critical illness polyneuropathy. However, the incidence of hypoglycemia was higher in the intensive control group, though it was not associated with the feared increased mortality.

Primary outcome:

• All-cause mortality in the ICU: Intensive Insulin Rx 35/765 (4.6%) vs Conventional Rx 63/783 (8%); P <0.04. Relative Risk (RR) 57%, relative risk reduction (RRR): 43%. Risk difference (RD) 3.4%. Number Needed to Treat (NNT) = 30 patients need intensive glucose control to save one extra life.

Secondary Outcomes:

• Mortality during hospitalization: Intensive Rx 55/765 (7.2%) vs Conventional Rx 85/783 (10.9%); P 0.01. RR 66% RRR 34% RD 3.7% NNT 27

• Blood stream infections: Intensive Rx 86/765 (11.2%) vs Conventional Rx 134/783 (17.1%). RR: 65% RRR: 35% RD 5.9% NNT 17

• Acute renal failure needing RRT: Intensive Rx 37/765 (4.8%) vs Conventional Rx 64/783 (8.2%). RR 58% RRR 41% RD 3.4% NNT 30

• Critical illness Polyneuropathy: Intensive Rx 45/157 (28.7%) vs Conventional Rx 107/206 (51.9%). RR 55% RRR 45% RD 23% NNT 5

Overall Risk of bias: Low 

The authors met most validity criteria. They compensated for the lack of blinding by using a separate team for glucose control. The early trial termination could overestimate results due to fewer outcomes, leading to larger confidence intervals. Despite the low absolute mortality, they used a lower p < 0.01 to address this.

Context: 

At the time of publication, there was some data on better outcomes with tighter glucose control in acute coronary syndrome, but no RCTs had shown which strategy was superior.

Teaching points:

Stopping trials early

Verdict:

Somewhat settled - Might change with more data