NICE Sugar

Screen Shot 2018-08-07 at 10.46.16.png

Intensive insulin therapy in the MICU/SICU

  • Included 6104 medical/surgical patients with an anticipated ICU length of stay > 3 days
  • Randomized patients to intensive control (BG 81-108 mg/dL) vs. conventional control (<180 mg/dL)
  • Primary outcome (90-day mortality) was more common with intensive control (27.5% vs. 24.9%, p=0.02, NNH 38) and was primarily driven by cardiovascular causes
  • Subgroup analysis of primary endpoint showed possible benefit with intensive control with trauma (OR 0.77, 95% CI 0.5-1.18, p=0.07) and with corticosteroids at baseline (OR, 0.88, 95% CI 0.66-1.19, p=0.06)
  • No difference in 28-day mortality (22.3% vs. 20.8%, p=0.17)
  • Mean morning BG values were 118 mg/dL (intensive) vs. 145 mg/dL (conventional)
  • More patients in the intensive group received corticosteroids (34.6% vs. 31.7%, p=0.02). The significance of this finding is very controversial
  • Severe hypoglycemia (BG < 40 mg/dL) occurred more with intensive control (6.8% vs. 0.5%, p<0.001, NNH 16)
  • There were no differences in morbidity outcomes, such as length of stay, duration of mechanical ventilation
  • There were no differences in morbidity outcomes, such as length of stay, duration of mechanical ventilation, need for renal replacement therapy, or infections
  • Two major differences in comparison to the Leuven trials (van den Berghe
    et al) are that NICE-SUGAR was multi-center and used less parenteral nutrition — both of which increase external validity


Among critically ill patients, intensive glucose control increased 90-day mortality and the incidence of severe hypoglycemia compared to conventional therapy.

See the paper here



Screen Shot 2018-08-07 at 10.54.19.png

Alteplase within 3 hours for acute ischemic stroke

  • Included 624 patients presenting within 3 hours of ischemic stroke not meeting a long list of exclusion criteria, many related to risk of bleeding. There was no exclusion on the basis of severity of stroke or maximum age.
  • Primary outcomes were split between two phases of the study. In phase I (n=291), the primary outcome was NIHSS improvement at 24 hours. In phase II (n=333), the primary outcome was a global assessment of four clinical outcome scales at 3 months
  • Baseline NIHSS score was median of 14-15
  • At 24 hours (phase I), there was no difference in NIHSS improvement
  • At 3 months (phase II), the odds ratio of a “favorable outcome” (global test) was 1.7 (95% CI 1.2-2.6), favoring TPA
  • The NIHSS subgroup of the global test was improved compared to placebo (31% vs. 20%, p=0.0033, NNT=9)
  • Symptomatic ICH occurred more frequently with TPA (6.4% vs. 0.60/0, p<0.001, NNH=17)
  • ICH was more common in patients with more severe stroke (NIHSS 20 vs. 14) or CT evidence of cerebral edema (9% vs. 4%)
  • Minor bleeding was more common with TPA (23% vs. 3%, NNH 5)
  • There was no difference in mortality


In patients presenting within 3 hours of ischemic: stroke, alteplase improved 3-
month neurological function (NNT=9) but did not impact 24-hour symptoms or mortality. In patients receiving alteplase, approximately one-quarter had minor bleeding, and 6.4% had symptomatic ICH (NNH=17).

See the paper here


Screen Shot 2018-08-07 at 11.45.43.png

Monitoring gastric residuals in mechanically ventilated patients

  • Included 449 intubated patients who were expected to required more than 48 hours of mechanical ventilation and who received enteral nutrition within 36 hours of intubation
  • Excluded recent abdominal surgery; those with any history of upper GI surgeries; and those with any history, of GI bleeding
  • Randomized patients to intervention (no gastric residual monitoring; intolerance determined based on vomiting) or control (residuals monitored Q6hr; intolerance defined as residual > 250 mL or vomiting)
  • Ventilator-associated pneumonia (VAP) suspicion required a positive chest x-ray and at least two of the following criteria: WBC > 10 or < 4; temp > 38.5 or < 35.5; Purulent tracheal aspirates.
  • VAP was confirmed in those with suspicion of VAP who had a confirmatory culture from BAL, protected brush, or tracheobronchial aspirate.
  • VAP diagnosis was adjudicated by a blinded committee.
  • Primary endpoint (patients with at least one VAP episode) was non-inferior between intervention and control (16.7% vs. 15.8%, 90% CI-4.8% to 6.7%). The study did rule-out a pre-specified 10% non- inferiority margin.
  • Other outcome measures related to VAP were also non-inferior (eg, cumulative VAP incidence, total number of VAP episodes)
  • Vomiting was more common in the intervention group (39.6% vs. 27%, OR 1.86 [90% CI 1.32-2.61], p=0.003)
  • Intervention patients had a lower mean caloric deficit within the first seven dayS (319 vs. 509 calories), although this difference is unlikely to be clinically relevant
  • Feeding intolerance (defined differently between the two groups) was more common with the control group (39.6% vs. 63.5%)
  • Vomiting is a concerning endpoint in that it may have led to adverse events that were not captured by the Primary endpoint. As an example, non-bacterial pneumonitis from aspiration would not have met the; primary endpoint criteria.
  • Although there were no difference in ICU length of stay, duration of mechanical ventilation, or mortality, it is not clear whether the study was powered to detect these endpoints specifically.
  • 90-95% of patients in the study were medical (non-surgical). It is not clear whether these results are applicable to surgical patients who are more likely to experience feeding intolerances.
  • Guidelines differ on the appropriate volume to hold enteral nutrition.
  • Other guidelines recommend a holding parameter of 500 mL, which would have altered this study’s incidence of “feeding intolerance” in the control group.
  • The authors fairly argue that the standard practice of gastric residual monitoring is not evidence-based.
  • There are no data supporting the practice of checking gastric residuals. supporting specific cut-offs that should prompt intervention to improve feeding intolerance, or that checking gastric residuals decreases VAP incidence rates.


Among non-surgical mechanically ventilated patients, NOT monitoring gastric residuals was non-inferior to monitoring residuals for the incidence of ventilator-associated pneumonia but resulted in a greater risk of vomiting.

See the paper here


Powered by WordPress.com.

Up ↑