Early insulin therapy in very-low-birth-weight infants. Hyperglycemia in extremely- low-birth-weight infants. Early elective insulin therapy can reduce hyperglycemia and increase insulin-like growth factor-I levels in very low birth weight infants. A randomized-controlled trial of prophylactic hydrocortisone supplementation for the prevention of hypotension in extremely low birth weight infants. Perinatal outcomes and the use of oral hypoglycemic agents. Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo-controlled trial. The use of prophylactic intravenous immunoglobulin therapy in very low birthweight infants. Intensive perioperative glucose control does not improve outcomes of patients submitted to open-heart surgery: a randomized controlled trial. A randomized trial comparing peripherally inserted central venous catheters and peripheral intravenous catheters in infants with very low birth weight.
Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates.
                In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm.
                As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04).
                Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)
                2008 Massachusetts Medical Society The cause of hyperglycemia in extremely-low-birth-weight (ELBW) infants is not well understood. We studied infants weighing <1,000 g to investigate the relationship of hyperglycemia to blood levels of insulin-like growth factor (IGF)-I and IGF-II. We also compared two methods of treatment for hyperglycemia: continuous insulin infusion and reduction of glucose intake. Fifty-six ELBW infants were enrolled on day 2 of life. Intravenous glucose intake was increased incrementally to a maximum of 12 mg/kg/min on day 6. Infants who developed hyperglycemia were randomly assigned to receive reduced glucose intake (n = 11) or insulin infusion (n = 12). Infants whose blood sugar remained normal served as controls (n = 33). Blood was drawn on days 3, 8 and 15 in all infants, and again when they developed hyperglycemia. Nutritional intake and laboratory results for the treatment groups were compared with controls. Hyperglycemic infants had lower birth weights than controls. Hyperglycemic infants treated with glucose reduction remained <60 kcal/kg/day longer than control or insulin infusion groups (8.6 +/- 1.3 days vs. 4.1 +/- 0.2 and 5.5 +/- 0.6 days). No infants became hypoglycemic during insulin infusion. There was no difference in baseline blood levels of IGF-I or IGF-II among the groups, and these growth factors did not change in response to hyperglycemia. Hyperglycemic infants had baseline levels of insulin which were similar to normal controls, and endogenous insulin increased in response to hyperglycemia in 15 of the 23 infants who developed hyperglycemia. IGF-I and IGF-II are not related to hyperglycemia. In our population, hyperglycemic infants did not have baseline insulin deficiency and most had a normal insulin response to hyperglycemia. Insulin infusion appears safe in these infants and helped to maintain normal caloric intake, whereas glucose reduction was associated with a prolonged caloric deprivation. To investigate the use of insulin throughout the first week of life in very low birth weight (VLBW) infants (birth weight <1.5 kg) to improve glucose control and increase insulin-like growth factor-I (IGF-I) levels. IGF-I is the dominant hormone involved in fetal growth, and low levels have been implicated in neonatal morbidities, such as retinopathy of prematurity.
                In this pilot randomized controlled study (n = 16), the intervention group received insulin (0.025 U/kg/hr) on days 1 to 7, with 20% dextrose to maintain normoglycemia. Control infants received standard neonatal care. All infants received continuous glucose monitoring.
                The intervention and standard care groups had similar mean gestational age (+/- standard deviation), 26.2 (+/- 2.5) vs 26.9 (+/- 2.7) weeks, and birth weight, 0.79 (+/- 0.26) vs 0.73 (+/- 0.16) kg. The standard care infants were hyperglycemic (sensor glucose >10 mmol/L [180 mg/dL]) for 35.9% of the study period, compared with 7.6% for the insulin-treated infants (P = .035). The duration of time with hypoglycemia (<2.6 mmol/L [47 mg/dL]) did not differ between the 2 groups (P = .746). The insulin-treated group had a 2.4-fold increase in mean IGF-I bioactivity (P = .005).
                Early insulin therapy improves blood glucose control and increases IGF-I bioactivity levels. This could result in less morbidity associated with hyperglycemia and reduced IGF-I levels. Extremely low birth weight (ELBW) infants are at risk for hypotension. Abnormal adrenal function may play a role in the pathogenesis of hypotension, and therefore, the administration of hydrocortisone (HC) may be an effective treatment for hypotension in some infants. However, the efficacy of prophylactic HC to prevent the use of vasopressors for a defined hypotensive state has not been studied. We conducted a randomized-controlled trial to determine the potential role on adrenal insufficiency in early neonatal hypotension and to determine the effectiveness of prophylactic HC in reducing treatment of hypotension in ELBW infants.
                Infants were assigned to receive either HC or placebo within the first 3 hours of life. Therapy was continued for 5 days. The presence of hypotension was based on an operational definition and treatment with vasopressors (VP) was standardized based on an a priori protocol.
                A total of 34 patients were enrolled. Baseline characteristics were similar between groups. Of the HC group 25% received VP at 24 hours of age compared to 44% of the placebo group. On day of life 2, only 7% of the HC group received VP compared to 39% of the placebo group (p<0.05).
                Prophylactic treatment with HC reduces the incidence of hypotension, defined by treatment with VP, among ELBW infants during the first 2 days of life. However, the mounting evidence that prophylactic administration of glucocorticoids in the first days of life is harmful to ELBW infants makes HC prophylaxis unwise until the efficacy of treatment relative to safety can be clearly established. To compare neonatal results from patients with gestational diabetes mellitus (GDM) who were treated with insulin, glyburide and acarbose.
                Seventy patients diagnosed with GDM who needed therapy to complement diet and physical activities were included in the study. One group was assigned to insulin therapy (n = 27), a second group was assigned to glyburide therapy (n = 24) and a third group was assigned to acarbose therapy (n = 19). Maternal characteristics were similar in the three groups. Glucose control was not achieved in five (20.8%) of the patients using glyburide and in eight (42.1%) of patients using acarbose. No statistical difference was observed in fasting and post-prandial glucose levels or in average newborn weight in the three groups. The rate of large for gestational age (LGA) fetuses was 3.7, 25 and 10.5% in the groups treated with insulin, glyburide and acarbose, respectively. Neonatal hypoglycemia was observed in eight newborns, six of which from the glyburide group.
                We believe that glyburide and acarbose can be promising alternative therapies for the treatment of GDM. Glyburide controlled glucose levels in most patients and it was more efficient than acarbose. Glyburide showed a higher rate of macrosomia and neonatal hypoglycemia as compared to other therapies. We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective.
                We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia.
                On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group.
                We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective. Nosocomial infections are a major cause of death in premature infants, especially in very low birthweight (VLBW) infants. The VLBW infants have low serum immunoglobulin G levels, which may have an effect on infections in early infancy. Thus, prophylactic administration of intravenous immunoglobulin (IVIG) is proposed to maintain higher immunoglobulin G and reduce the rate of hospital-acquired infection.
                A study for the effects of prophylactic IVIG therapy in VLBW infants was performed. A total of 61 VLBW infants were enrolled, and divided into the IVIG group (n = 31) and the control group (n = 30). The dose for each infant was 750-1000 mg/kg for those whose birthweight was less than 1000 g, and 500-750 mg/kg for infants whose birthweight was between 1001 and 1500 g. The control group received saline infusion. The infusions were given every 2 weeks until the infant weighed 1800 g, or was discharged.
                The results showed: there were no major differences in the perinatal and neonatal characteristics between the two groups, consistently higher IgG levels were found in the IVIG group, and the age of first documented sepsis was earlier in the control group.
                In this study, the prophylactic IVIG therapy may give substantially higher IgG levels, which may last for 2 months. However, a prophylactic effect for hospital-acquired infections was not observed. The objective of this study was to investigate the relationship between different target levels of glucose and the clinical outcomes of patients undergoing cardiac surgery with cardiopulmonary bypass.
                We designed a prospective study in a university hospital where 109 consecutive patients were enrolled during a six-month period. All patients were scheduled for open-heart surgery requiring cardiopulmonary bypass. Patients were randomly allocated into two groups. One group consisted of 55 patients and had a target glucose level of 80-130 mg/dl, while the other contained 54 patients and had a target glucose level of 160-200 mg/dl. These parameters were controlled during surgery and for 36 hours after surgery in the intensive care unit. Primary outcomes were clinical outcomes, including time of mechanical ventilation, length of stay in the intensive care unit, infection, hypoglycemia, renal or neurological dysfunction, blood transfusion and length of stay in the hospital. The secondary outcome was a combined end-point (mortality at 30 days, infection or length of stay in the intensive care unit of more than 3 days). A p-value of <0.05 was considered significant.
                The anthropometric and clinical characteristics of the patients from each group were similar, except for weight and body mass index. The mean glucose level during the protocol period was 126.69 mg/dl in the treated group and 168.21 mg/dl in the control group (p<0.0016). There were no differences between groups regarding clinical outcomes, including the duration of mechanical ventilation, length of stay in the intensive care unit, blood transfusion, postoperative infection, hypoglycemic event, neurological dysfunction or 30-day mortality (p>0.05).
                In 109 patients undergoing cardiac surgery with cardiopulmonary bypass, both protocols of glycemic control in an intraoperative setting and in the intensive care unit were found to be safe, easily achieved and not to differentially affect clinical outcomes. To determine whether percutaneously inserted central venous catheters (PICC) and peripheral intravenous catheters (PIV) in infants with very low birth weight (VLBW) differ with respect to (1) incidence of sepsis, (2) number of insertion attempts and catheters required for total intravenous therapy, (3) courses of antibiotics, and (4) total duration of intravenous (IV) use.
                A randomized comparative trial was conducted involving 63 VLBW infants (<1,251 g) who required IV therapy. Infants were assigned randomly at 1 week of age to either a PIV or a PICC catheter and followed up prospectively until an IV was no longer required or the infant was transferred out of the neonatal intensive care unit.
                Data were analyzed on an intention-to-treat basis. There was no difference in the incidence of sepsis (P = .64), number of courses of antibiotics (P = .16), or total duration of IV use (P= .34) between the 2 groups. The number of insertion attempts required for total IV therapy was significantly lower in the PICC group than in the PIV group (P = .008). There also was a significantly lower number of total catheters utilized in the PICC group (P = .002). When data were controlled for birth weight strata the results were similar.
                PICC lines reduced the number of painful IV procedures in VLBW infants without additional morbidity.
Evidence from randomized trials in hyperglycemic VLBW neonates is insufficient to determine the effects of treatment on death or major morbidities. It remains uncertain whether the hyperglycemia per se is a cause of adverse clinical outcomes or how the hyperglycemia should be treated. Much larger randomized trials in hyperglycemic VLBW neonates that are powered on clinical outcomes are needed in order to determine whether, and how, the hyperglycemia should be treated.