Tight glycemic control in critically ill pediatric patients: a systematic review and meta-analysis.

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Insulin 1 endocrinologydiseasesdrugs
hyperglycemia 4 endocrinologydiseases
hypoglycemia 31 endocrinologydiseases

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Select Drug Character Offset Drug Term Instance
Insulin 4016 mortality benefit [[13], [14]]. Furthermore, a recent trial, the Heart and Lung Failure—Pediatric Insulin Titration (HALF-PINT) trial, was stopped early because the data indicated a low likelihood of benefit
Select Disease Character Offset Disease Term Instance
hyperglycemia 1915 and severe hypoglycemia (OR, 4.11; 95% CI, 2.67–6.32).ConclusionsAmong critically ill children with hyperglycemia , TGC does not result in a decrease in hospital mortality, but appears to reduce a new need for dialysis.
hyperglycemia 2650 greater than 150 mg/dl, and more than 30% a concentration exceeding 200 mg/dl [[1]–[4]]. The extent of hyperglycemia is associated with adverse outcomes, including organ failure, length of stay in the PICU, and death
hyperglycemia 9921 limit of glucose goal 110–140 mg/dl).Because of the concern that the pathophysiological effect of hyperglycemia may differ between patients with and without cardiac surgery, we stratified trials by PICU setting into
hyperglycemia 26552 insulin therapy protocols. These diversities may have influenced the pathophysiology and implications of hyperglycemia . We present the findings stratified by some widely debated variables—glucose goal in the tight control
hypoglycemia 1151 effects and quality of evidence. The primary outcome was hospital mortality. The secondary outcomes were hypoglycemia (any, severe), sepsis, new need for dialysis, and seizures.ResultsA total of 4030 patients were included
hypoglycemia 1768 dialysis (OR, 0.63; 95% CI, 0.45–0.86). However, TGC was associated with a significant increase in any hypoglycemia (OR, 4.39; 95% CI, 2.39–8.06) and severe hypoglycemia (OR, 4.11; 95% CI, 2.67–6.32).ConclusionsAmong
hypoglycemia 1824 associated with a significant increase in any hypoglycemia (OR, 4.39; 95% CI, 2.39–8.06) and severe hypoglycemia (OR, 4.11; 95% CI, 2.67–6.32).ConclusionsAmong critically ill children with hyperglycemia, TGC does
hypoglycemia 2086 but appears to reduce a new need for dialysis. However, TGC is associated with higher incidence of hypoglycemia .Systematic review registrationPROSPERO registration number CRD42017074039.Electronic supplementary materialThe
hypoglycemia 3064 ambitious goals in clinical practice, however, there are significant challenges in increased risk of hypoglycemia , additional personnel training, efficient utilization of medical resources, and radical revamping of
hypoglycemia 3822 and reduced the infection rate and length of stay, but also presented extremely high rates of severe hypoglycemia . However, subsequent multicenter large RCTs of TGC have failed to replicate this mortality benefit [[13],
hypoglycemia 5998 goal could vary between trials); and the primary or secondary outcomes included hospital mortality, hypoglycemia (any, severe), new need for dialysis, sepsis, or seizures.Exclusion criteriaTrials were excluded if
hypoglycemia 8674 in-hospital and 30-day outcomes were reported, the former was used for analysis.The secondary outcomes were hypoglycemia (any, severe), sepsis, new need for dialysis, and seizures. We defined severe hypoglycemia as a blood
hypoglycemia 8765 outcomes were hypoglycemia (any, severe), sepsis, new need for dialysis, and seizures. We defined severe hypoglycemia as a blood glucose level below 40 mg/dl and any hypoglycemia as a blood glucose level below 60 mg/dl.
hypoglycemia 8826 dialysis, and seizures. We defined severe hypoglycemia as a blood glucose level below 40 mg/dl and any hypoglycemia as a blood glucose level below 60 mg/dl. We defined sepsis to encompass the terms septicemia, bacteremia,
hypoglycemia 10491 in children and adults, and may assist in the safer provision of tight glycemic control, with less hypoglycemia [[24]]. Thus, we stratified trials by whether they used continuous glucose monitoring to control blood
hypoglycemia 15184 studies)0.95 (0.62–1.45)3 fewer per 1000 (from 20 fewer to 23 more)⊕ ⊕ ⊕⊝ moderatebCriticalSevere hypoglycemia (glucose < 40 ml/dl)3835 (5 studies)4.11 (2.67–6.32)42 more per 1000 (from 23 more to 69 more)b⊕
hypoglycemia 15326 studies)4.11 (2.67–6.32)42 more per 1000 (from 23 more to 69 more)b⊕ ⊕ ⊕ ⊕ highCriticalAny hypoglycemia (glucose < 60 mg/dl)3747 (4 studies)4.57 (2.24–9.33)157 more per 1000 (from 61 more to 299 more)⊕
hypoglycemia 17177 0.84–1.52).Fig. 3Association of tight glucose control vs usual glucose control with hospital mortality, any hypoglycemia and severe hypoglycemia. CI confidence interval, Agus 2010 [[14]], Agus 2017 [[15]], Alsweiler 2012
hypoglycemia 17201 tight glucose control vs usual glucose control with hospital mortality, any hypoglycemia and severe hypoglycemia . CI confidence interval, Agus 2010 [[14]], Agus 2017 [[15]], Alsweiler 2012 [[17]], Jeschke 2010 [[27]],
hypoglycemia 17561 after removing one study at a time showed similar results for hospital mortality.Secondary outcomes: hypoglycemia , sepsis, new need for dialysis, seizuresHypoglycemia was reported in five published trials. TGC was
hypoglycemia 17718 seizuresHypoglycemia was reported in five published trials. TGC was associated with an increased risk of severe hypoglycemia (OR, 4.11; 95% CI, 2.67–6.32; I2 = 0%; 42 more per 1000 patients; high quality) and any hypoglycemia
hypoglycemia 17821 hypoglycemia (OR, 4.11; 95% CI, 2.67–6.32; I2 = 0%; 42 more per 1000 patients; high quality) and any hypoglycemia (OR, 4.39; 95% CI, 2.39–8.06; I2 = 83%; 157 more per 1000 patients; high quality) (Table 2 and Fig. 3).New
hypoglycemia 19247 (6.2)94/1651 (5.7)1.10 (0.81–1.49)0 Overall6110/1974 (2.9)113/2047 (5.5)0.95 (0.62–1.45)40Any hypoglycemia (< 60 mg/dl) Very tight control2112/392 (28.6)17/396 (4.3)9.35 (1.49–58.83)88 Moderately tight
hypoglycemia 19486 (16.9)99/1514 (6.5)3.00 (2.07–4.34)54 Overall5371/1925 (19.3)116/1910 (6.1)4.39 (2.39–8.06)83Severe hypoglycemia (< 40 mg/dl) Very tight control224/392 (6.1)5/396 (8.7)5.23 (1.95–14.00)0 Moderately tight control385/1533
hypoglycemia 20921 (3.5)64/1516 (4.2)0.79 (0.50–1.26)26 Overall6110/1974 (5.6)113/2047 (5.0)0.95 (0.62–1.45)40Any hypoglycemia (< 60 mg/dl) Noncardiac surgery2104/342 (30.4)45/394 (11.4)2.97 (2.01–4.41)0 Cardiac surgery3267/1533
hypoglycemia 21151 (17.4)71/1516 (4.7)5.72 (1.95–16.73)91 Overall5371/1925 (19.3)116/1910 (6.1)4.39 (2.39–8.06)83Severe hypoglycemia (< 40 mg/dl) Noncardiac surgery225/392 (6.4)9/394 (2.3)2.95 (1.35–6.42)0 Cardiac surgery384/1533
hypoglycemia 22441 (3.5)27/533 (4.2)0.70 (0.18–2.69)49 Overall6110/1974 (5.6)113/2047 (5.0)0.95 (0.62–1.45)40Any hypoglycemia (< 60 mg/dl) Using CGM3259/1533 (30.4)99/1514 (11.4)3.00 (2.07–4.36)54 Not using CGM224/392 (6.1)5/396
hypoglycemia 22657 CGM224/392 (6.1)5/396 (4.7)5.23 (1.95–4.00)0 Overall5371/1925 (19.3)116/1910 (6.1)4.39 (2.39–8.06)83Severe hypoglycemia (< 40 mg/dl) Using CGM285/1533 (30.4)22/1514 (11.4)3.88 (2.41–6.26)0 Not using CGM3112/392 (28.6)17/396
hypoglycemia 23786 significant reduction in dialysis. On the other hand, we found clear evidence for the main harm of TGC: hypoglycemia increased roughly 4-fold. However, the rate of hypoglycemia varied greatly across RCTs. We performed
hypoglycemia 23846 clear evidence for the main harm of TGC: hypoglycemia increased roughly 4-fold. However, the rate of hypoglycemia varied greatly across RCTs. We performed three prespecified subgroup analyses, stratified by cardiac
hypoglycemia 24297 benefits of TGC reported in the initial trial by Vlasselaers et al. [[12]], yet it suggests a high risk of hypoglycemia .Compared with other studiesA previous meta-analysis of four RCTs examined the benefits and risks of
hypoglycemia 24563 findings, the meta-analysis found no significant differences in mortality but an increased risk of hypoglycemia between TGC and usual care in critically ill children. They reported, however, that TGC appeared to
hypoglycemia 26343 variability, including nutritional supplementation, target of tight glycemic control, definition of hypoglycemia , blood glucose monitoring, quality of glucose control, and duration and route used for the insulin therapy
hypoglycemia 27988 a reduction in new need for dialysis. However, TGC was associated with a markedly increased risk of hypoglycemia . These findings were consistent with recent guidelines [[22], [23]]. Thus, adoption of TGC in critically
hypoglycemia 28459 new need for dialysis in critically ill children.Tight glycemic control greatly increases the risk of hypoglycemia in critically ill children.Additional fileAdditional file 1:is Supplemental Digital Content: Table S1.

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