Maram Sakkijha

Intensive versus conventional insulin therapy: A randomized controlled trial in medical and surgical critically ill patients

Objective:The role of intensive insulin therapy in medical surgical intensive care patients remains unclear. The objective of this study was to examine the effect of intensive insulin therapy on mortality in medical surgical intensive care unit patients. Design:Randomized controlled trial. Settings:Tertiary care intensive care unit. Patients:Medical surgical intensive care unit patients with admission blood glucose of >6.1 mmol/L or 110 mg/dL. Intervention:A total of 523 patients were randomly assigned to receive intensive insulin therapy (target blood glucose 4.4–6.1 mmol/L or 80–110 mg/dL) or conventional insulin therapy (target blood glucose 10–11.1 mmol/L or 180–200 mg/dL). Measurements and Main Outcomes:The primary end point was intensive care unit mortality. Secondary end points included hospital mortality, intensive care unit and hospital length of stay, mechanical ventilation duration, the need for renal replacement therapy and packed red blood cells transfusion, and the rates of intensive care unit acquired infections as well as the rate of hypoglycemia (defined as blood glucose ≤2.2 mmol/L or 40 mg/dL). There was no significant difference in intensive care unit mortality between the intensive insulin therapy and conventional insulin therapy groups (13.5% vs. 17.1%, p = 0.30). After adjustment for baseline characteristics, intensive insulin therapy was not associated with mortality difference (adjusted hazard ratio 1.09, 95% confidence interval 0.70–1.72). Hypoglycemia occurred more frequently with intensive insulin therapy (28.6% vs. 3.1% of patients; p < 0.0001 or 6.8/100 treatment days vs. 0.4/100 treatment days; p < 0.0001). There was no difference between the intensive insulin therapy and conventional insulin therapy in any of the other secondary end points. Conclusions:Intensive insulin therapy was not associated with improved survival among medical surgical intensive care unit patients and was associated with increased occurrence of hypoglycemia. Based on these results, we do not advocate universal application of intensive insulin therapy in intensive care unit patients. Trial Registration:Current Controlled Trials registry (ISRCTN07413772) http://www.controlled-trials.com/ISRCTN07413772/07413772; 2005.

Permissive underfeeding and intensive insulin therapy in critically ill patients: a randomized controlled trial

BACKGROUND Nutritional support has been recognized as an essential part of intensive care unit management. However, the appropriate caloric intake for critically ill patients remains ill defined. OBJECTIVE We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy (IIT) compared with that of conventional insulin therapy (CIT) on the outcomes of critically ill patients. DESIGN This study had a 2 × 2 factorial, randomized, controlled design. Eligible patients were randomly assigned to permissive underfeeding or target feeding groups (caloric goal: 60-70% compared with 90-100% of calculated requirement, respectively) with either IIT or CIT (target blood glucose: 4.4-6.1 compared with 10-11.1 mmol/L, respectively). RESULTS Twenty-eight-day all-cause mortality was 18.3% in the permissive underfeeding group compared with 23.3% in the target feeding group (relative risk: 0.79; 95% CI: 0.48, 1.29; P = 0.34). Hospital mortality was lower in the permissive underfeeding group than in the target group (30.0% compared with 42.5%; relative risk: 0.71; 95% CI: 0.50, 0.99; P = 0.04). No significant differences in outcomes were observed between the IIT and CIT groups. CONCLUSION In critically ill patients, permissive underfeeding may be associated with lower mortality rates than target feeding. This trial was registered at controlled-trials.com as ISRCTN96294863.

Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults

BACKGROUND The appropriate caloric goal for critically ill adults is unclear. We evaluated the effect of restriction of nonprotein calories (permissive underfeeding), as compared with standard enteral feeding, on 90-day mortality among critically ill adults, with maintenance of the full recommended amount of protein in both groups. METHODS At seven centers, we randomly assigned 894 critically ill adults with a medical, surgical, or trauma admission category to permissive underfeeding (40 to 60% of calculated caloric requirements) or standard enteral feeding (70 to 100%) for up to 14 days while maintaining a similar protein intake in the two groups. The primary outcome was 90-day mortality. RESULTS Baseline characteristics were similar in the two groups; 96.8% of the patients were receiving mechanical ventilation. During the intervention period, the permissive-underfeeding group received fewer mean (±SD) calories than did the standard-feeding group (835±297 kcal per day vs. 1299±467 kcal per day, P<0.001; 46±14% vs. 71±22% of caloric requirements, P<0.001). Protein intake was similar in the two groups (57±24 g per day and 59±25 g per day, respectively; P=0.29). The 90-day mortality was similar: 121 of 445 patients (27.2%) in the permissive-underfeeding group and 127 of 440 patients (28.9%) in the standard-feeding group died (relative risk with permissive underfeeding, 0.94; 95% confidence interval [CI], 0.76 to 1.16; P=0.58). No serious adverse events were reported; there were no significant between-group differences with respect to feeding intolerance, diarrhea, infections acquired in the intensive care unit (ICU), or ICU or hospital length of stay. CONCLUSIONS Enteral feeding to deliver a moderate amount of nonprotein calories to critically ill adults was not associated with lower mortality than that associated with planned delivery of a full amount of nonprotein calories. (Funded by the King Abdullah International Medical Research Center; PermiT Current Controlled Trials number, ISRCTN68144998.).

Near-Target Caloric Intake in Critically Ill Medical-Surgical Patients Is Associated With Adverse Outcomes

BACKGROUND The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients. METHODS The study was conducted as a nested cohort study within a randomized controlled trial in a tertiary care intensive care unit (ICU). The main exposure in the study was average caloric intake/target for the first 7 ICU days. The primary outcomes were ICU and hospital mortality. Secondary outcomes included ICU-acquired infections, ventilator-associated pneumonia (VAP), duration of mechanical ventilation days, and ICU and hospital length of stay (LOS). The authors divided patients (n = 523) into 3 tertiles according to the percentage of caloric intake/target: tertile I <33.4%, tertile II 33.4%-64.6%, and tertile III >64.6%. To adjust for potentially confounding variables, the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes (tertile I was used as reference) and multiple linear regression for continuous outcomes. RESULTS Tertile III was associated with higher adjusted hospital mortality, higher risk of ICU-acquired infections, and a trend toward higher VAP rate. Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation, ICU LOS, and hospital LOS. CONCLUSIONS The data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality, ICU-acquired infections, mechanical ventilation duration, and ICU and hospital LOS. Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients.

The Impact of Implementing an Enteral Tube Feeding Protocol on Caloric and Protein Delivery in Intensive Care Unit Patients

BACKGROUND The purpose of this study was to determine the effect of an enteral tube feeding protocol on caloric and protein delivery to intensive care unit (ICU) patients. METHODS This prospective study consisted of 2 phases: before and after the implementation on an enteral-feeding protocol. The following data were collected: demographics, Acute Physiology and Chronic Health Evaluation II score and Simplified Acute Physiology Score II, caloric and protein requirements, the location of the feeding tube tip, and prokinetic agents use. The primary endpoint was caloric and protein intake as a percentage of the requirement. Secondary endpoints were gastric residuals >150 mL, vomiting episodes, ICU and hospital lengths of stay, mechanical ventilation duration, and ICU and hospital mortality. RESULTS There were no significant differences between the control (n = 100) and protocol groups (n = 103) in baseline characteristics. The protocol was associated with significant improvement in the 7-day average of caloric intake/requirement (53.9 +/- 2.3% vs 64.5 +/- 2.2%, p = .001) and protein intake/requirement (56.7 +/- 2.6% vs 67.4% +/- 2.7%, p = .005). Caloric and protein intake improved whether the patient was receiving prokinetic agent or not. There was a trend toward lower gastric residual volumes and vomiting episodes in the protocol group. Patients receiving gastric feeding showed significant improvement in caloric intake to levels comparable to patients with postpyloric feeding. CONCLUSIONS Enteral tube feeding protocol is effective in improving feeding delivery in ICU patients independent of prokinetic agent use. Protocol for enteral tube feeding should be considered in the management of ICU patients, given the positive impact of this nonpharmacologic, non-interventional tool.

Permissive Underfeeding or Standard Enteral Feeding in High– and Low–Nutritional-Risk Critically Ill Adults. Post Hoc Analysis of the PermiT Trial

Rationale: The optimal nutritional strategy for critically ill adults at high nutritional risk is unclear. Objectives: To examine the effect of permissive underfeeding with full protein intake compared with standard feeding on 90‐day mortality in patients with different baseline nutritional risk. Methods: This is a post hoc analysis of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients) trial. Measurements and Main Results: Nutritional risk was categorized by the modified Nutrition Risk in Critically Ill score, with high nutritional risk defined as a score of 5‐9 and low nutritional risk as a score of 0‐4. Additional analyses were performed by categorizing patients by body mass index, prealbumin, transferrin, phosphate, urinary urea nitrogen, and nitrogen balance. Based on the Nutrition Risk in Critically Ill score, 378 of 894 (42.3%) patients were categorized as high nutritional risk and 516 of 894 (57.7%) as low nutritional risk. There was no association between feeding strategy and mortality in the two categories; adjusted odds ratio (aOR) of 0.84 (95% confidence interval [CI], 0.56‐1.27) for high nutritional risk and 1.01 (95% CI, 0.64‐1.61) for low nutritional risk (interaction P = 0.53). Findings were similar in analyses using other definitions, with the exception of prealbumin. The association of permissive underfeeding versus standard feeding and 90‐day mortality differed when patients were categorized by baseline prealbumin level (≤0.10 g/L: aOR, 0.57 [95% CI, 0.31‐1.05]; >0.10 and ≤0.15 g/L: aOR, 0.79 [95% CI, 0.42‐1.48]; >0.15 g/L: aOR, 1.55 [95% CI, 0.80, 3.01]; interaction P = 0.009). Conclusions: Among patients with high and low nutritional risk, permissive underfeeding with full protein intake was associated with similar outcomes as standard feeding.