Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients

Abstract

Objective: We investigated whether preventing hyperglycemia in septic patients affected the plasma concentration of asymmetric-dimethylarginine and if this was associated with clinical benefit. Design: A prospective, multicenter, randomized, controlled, clinical study. Setting: Intensive care units (ICU) in three university hospitals. Patients: A total of 72 patients admitted for severe sepsis or septic shock, who stayed at least 3 days in the ICU. At admission the patients were assigned to receive either tight or conventional glycemic control. Interventions: Determination of circulating levels of asymmetric-dimethylarginine, arginine, interleukin-6, C-reactive-protein and tumor-necrosis-factor-a. Measurements and results: Blood was sampled at admission (no differences between groups), and on the 3rd, 6th, 9th, and 12th (T12) days. Sequential organ failure assessment was scored at each sampling time. All the data were analyzed on an intention-to-treat basis. The control and treatment groups received the same energy intake, glycemia (110.4 ± 17.3 vs. 163.0 ± 28.9 mg/dL, P \ 0.001) and insulin (P = 0.02) supply differed. No differences were found in high plasma levels of asymmetricdimethylarginine (P = 0.812) at any time during the ICU stay. The clinical course, as indicated by markers of inflammation, average and maximum organ failure score, ICU stay and ICU and 90-day mortality, was the same. Conclusions: Intensive insulin treatment, while achieving glucose control, did not reduce asymmetricdimethylarginine in high-risk septic patients fed with no more than 25 kcal/kg per day to limit ventilatory demand and to simplify glucose control. Descriptor: 45 (SIRS/sepsis: clinical studies).

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

“…Overall, 28 articles were excluded ( Figure 1). We included 26 trials [8][9][10][11][12][13]18,[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] in the meta-analysis.…”

“…Research target was ≤ 6.1 mmol/L in 16 trials, [8][9][10][11][12][13]18,25,30,32,33,35,36,[38][39][40] and 9 trials used a more liberal target of ≤ 8.3 mmol/L. [22][23][24][26][27][28]31,34,37 One trial randomly assigned patients to 1 of 3 levels of glycemic control: 4.4-6.1 mmol/L, 6.7-8.3 mmol/L or 10.0-11.1 mmol/L.…”

“…However, 2 trials did not conduct this analysis because they excluded patients after randomization who did not survive at least 3 days. 27,32 For 1 of these trials, 32 we obtained the risk of both mortality and hypoglycemic events from the authors for the 18 patients excluded after randomization, which allowed us to include the intention-to-treat results for that trial.…”

“…[8][9][10][11][12][13]18,22,25,[31][32][33]35,36 The pooled RR was 6.0 (95% CI 4.5-8.0), with some evidence of heterogeneity between studies (Q statistic = 20.7, p = 0.08), with a corresponding I 2 statistic of 37% (95% CI 0%-67%). We were unable to examine the data for effect modification by intensity of insulin therapy because only 1 trial that reported severe hypoglycemia used a target blood glucose level of 8.3 mmol/L or less.…”

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

“…Our analysis included 14,495 patients from 27 studies 128, 330, 331, 332, 337, 338, 339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 356, 357, 358, 359. None of the studies were especially prone to bias.…”