A randomized, double-blind, placebo-controlled pilot trial of triiodothyronine in neonatal heart surgery. Triiodothyronine repletion in infants during cardiopulmonary bypass for congenital heart disease. Pulmonary effects of triiodothyronine (T3) and hydrocortisone (HC) supplementation in preterm infants less than 30 weeks gestation: results of the THORN trial--thyroid hormone replacement in neonates. Postnatal triiodothyronine replacement and respiratory distress syndrome of the preterm infant. A randomized, masked study of triiodothyronine plus thyroxine administration in preterm infants less than 28 weeks of gestational age: hormonal and clinical effects. The effect of preoperative dexamethasone on the immediate and delayed postoperative morbidity in children undergoing adenotonsillectomy. Oculocardiac reflex and postoperative vomiting in paediatric strabismus surgery. A randomised controlled trial comparing four anaesthetic techniques. Prophylactic ondansetron in prevention of postoperative nausea and vomiting following pediatric strabismus surgery: a dose-response study. The effect of supplementation of docosahexaenoic acid and arachidonic acid on visual acuity and neurodevelopment in larger preterm infants.
This study was undertaken to evaluate the effect of triiodothyronine replacement on the early postoperative course of neonates undergoing aortic arch reconstruction.
                We performed a randomized, double-blind, placebo-controlled trial of triiodothyronine supplementation in neonates undergoing either a Norwood procedure or two-ventricle repair of interrupted aortic arch and ventricular septal defect. Patients were assigned to receive a continuous infusion of triiodothyronine (0.05 micro/kg/h) or placebo for 72 hours after cardiopulmonary bypass. Primary end points were a composite clinical outcome score and cardiac index at 48 postoperative hours.
                We enrolled 42 patients (triiodothyronine n = 22, placebo n = 20). Baseline characteristics were similar in the treatment groups. Study drug was discontinued prematurely because of hypertension (n = 1) and ectopic atrial tachycardia (n = 1), both cases in the triiodothyronine group. Free and total triiodothyronine levels were higher in the triiodothyronine group than in the placebo group at 24, 48, and 72 postoperative hours (P < .001). The median clinical outcome scores were 2.0 (range 0-4) with triiodothyronine and 2.0 (range 0-7) with placebo (P = .046). Compared with those in the placebo group, neonates assigned to triiodothyronine had shorter median time to negative fluid balance (2.0 vs 2.5 days, P = .027). Cardiac index values were 2.11 +/- 0.64 L/min x m2 with triiodothyronine and 2.05 +/- 0.72 L/min x m2 with placebo (P = .81). Heart rate and diastolic blood pressure were not influenced by triiodothyronine supplementation, but systolic blood pressure was higher in the triiodothyronine group (P < .001). No serious adverse events were attributed to triiodothyronine administration.
                Triiodothyronine supplementation was safe and resulted in more rapid achievement of negative fluid balance after aortic arch reconstruction. Cardiac index at 48 hours was not significantly improved. Cardiopulmonary bypass suppresses circulating thyroid hormone levels. Although acute triiodothyronine repletion has been evaluated in adult patients after cardiopulmonary bypass, triiodothyronine pharmacokinetics and effects have not previously been studied in infants undergoing operations for congenital heart disease. We hypothesized that triiodothyronine deficiency in the developing heart after bypass may adversely affect cardiac function reserve postoperatively.
                Infants less than 1 year old undergoing ventricular septal defect or tetralogy of Fallot repair were randomized into 2 groups. Group T (n = 7) received triiodothyronine (0.4 microg/kg) immediately before the start of cardiopulmonary bypass and again with myocardial reperfusion. Control (NT, n = 7) patients received saline solution placebo or no treatment.
                These groups underwent similar ischemic and bypass times and received similar quantities of inotropic agents after the operation. The NT group demonstrated significant depression in circulating levels, compared with prebypass levels, for free triiodothyronine and total triiodothyronine at 1, 24, and 72 hours after bypass. Group T demonstrated similar low thyroxine values, but free and total triiodothyronine levels were maintained at prebypass levels for 24 hours and remained elevated over those of group NT (P <.05) at 72 hours. Heart rate was transiently elevated in group T compared with group NT (P <.05), and peak systolic pressure-rate product increased after 6 hours.
                These data imply that (1) triiodothyronine in the prescribed dose prevents circulating triiodothyronine deficiencies and (2) triiodothyronine repletion promotes elevation in heart rate without concomitant decrease in systemic blood pressure. Elevation of peak systolic pressure-rate product implies that triiodothyronine repletion improves myocardial oxygen consumption and may enhance cardiac function reserve after cardiopulmonary bypass in infants. The THORN trial was a multicenter, randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that administration of triiodothyronine (T(3)) and hydrocortisone would decrease mortality and respiratory morbidity in preterm infants of less than 30 wk gestation. Two hundred fifty-three infants were randomized to receive either 6 micro g.kg(-1).d(-1) of T(3) with 1 mg.kg(-1).d(-1) of hydrocortisone or 5% dextrose (placebo) as a continuous i.v. infusion for 7 d. The dose was halved on d 5. Our first primary outcome was death or ventilator dependence at 1 wk, and the second was death or oxygen dependence at 2 wk. The overall mortality rate for both groups was 11.4%. Relative risk of death or ventilator dependence at 1 wk, treated versus placebo, was 0.87, p = 0.2, and death or oxygen dependence at 2 wk, 1.00, p = 0.9. We examined the relationship between free T(3) (FT(3)) and free thyroxine (FT(4)) levels in the first 7 d and the primary outcome death or ventilator dependence at 1 wk in all 253 babies. We found significant positive correlations of p = 0.05 for FT(3) and p = 0.002 for FT(4). Thus the higher the FT(3) and FT(4) levels, the better the outcome. No beneficial effects of T(3) and hydrocortisone were shown. In this study, although FT(3) levels were doubled by the treatment infusion, FT(4) levels were significantly suppressed. The lack of any beneficial effect of T(3) in our study may be explained by suppression of FT(4) in the treatment group. Improvements in the management of respiratory distress syndrome (RDS) include pre- and postnatal stimulation of pulmonary maturity, and triiodothyronine (T3) is believed to influence directly surfactant production. Its circulating levels are low in premature infants with RDS probably due to a low thyroxine T4-T3 hepatic conversion mechanism. While a state of hypotriiodothyroninemia exists at birth, we studied the influence of postnatal intravenous T3 administration on the course of RDS in preterm infants of less than 32 weeks' gestation. Fifty preterm infants with RDS were studied (mean gestational age 30.4 +/- 1.2 weeks and birth weight 1,180 +/- 220 g). They were at random assigned to treatment with 50 micrograms L-T3 (Thyrotardin) or to the control group. Mortality rate, peak oxygen concentrations, duration of artificial ventilation and development of major complications of RDS were the criteria to estimate the influence of T3 treatment on RDS. We failed to detect a statistically significant difference between the two groups in all of the mentioned criteria except for FiO2 concentrations required to maintain PaO2 between 50 and 60 mm Hg (p less than 0.05). These observations suggest a relative beneficial effect of T3 replacement on the course of RDS in preterm infants of less than 32 weeks of gestation. A randomized, placebo-controlled, masked study was conducted of the responses of thyroid parameters, cortisol, and the cardiovascular system to a single dose of triiodothyronine (T(3)) 24 h after birth, followed by a daily dose of thyroxine (T(4)) during 6 wk to infants <28 wk gestational age. Thirty-one infants were assigned to three groups: 1) group A: T(3) 24 h after birth plus daily T(4) during 6 wk; 2) group B: placebo T(3) and T(4) during 6 wk; and 3) group C: placebo T(3) and placebo T(4). T(4), free T(4), T(3), free T(3), reverse T(3), thyroid-stimulating hormone, and cortisol were measured in cord blood and on days 1, 3, 7, 14, 21, 42, and 56. Data on pulse rate, blood pressure, and cumulative dose of inotropic agents were collected. T(3) (0.5 microg/kg) resulted in a plasma increase until day 3. Thereafter, plasma T(3) levels were comparable between the groups. T(4), free T(4), and reverse T(3) were increased in groups A and B during the period of T(4) administration. Thyroid-stimulating hormone suppression was of shorter duration in group A. T(3) and T(4) administration did not have any effect on cortisol levels. We did not find any effects of T(3) or of T(4) administration on the cardiovascular system. A single injection of T(3) (0.5 microg/kg) given 22-26 h after birth only leads to a 2-d increase of T(3) levels and does not have effects on the cardiovascular system. This study does not support the use of T(3) according to our regimen in preterm infants. In this prospective, randomized, double-blind, placebo-controlled study, we examined the effect of preoperative dexamethasone on postoperative nausea and vomiting (PONV) and 24-h recovery in children undergoing tonsillectomy. One hundred thirty children, 2-12 yr of age, ASA physical status I or II, completed the study. All children received oral midazolam 0.5-0.6 mg/kg preoperatively. Anesthesia was induced with halothane and nitrous oxide in 60% oxygen and maintained with nitrous oxide and isoflurane. Intubation was facilitated by mivacurium 0.2 mg/kg. Each child received fentanyl 1 microgram/kg i.v. before initiation of surgery, as well as dexamethasone 1 mg/kg (maximal dose 25 mg) (steroid group) or an equal volume of saline (control group). Intraoperative fluids were standardized to 25-30 mL/kg lactated Ringer's solution. All tonsillectomies were performed under the supervision of one attending surgeon using an electrodissection technique. Postoperatively, fentanyl and acetaminophen with codeine elixir were administered as needed for pain. Rescue antiemetics were administered when a child experienced two episodes of retching and/or vomiting. Before home discharge, the incidence of PONV, need for rescue antiemetics, quality or oral intake, and analgesic requirements did not differ between groups. However, during the 24 h after discharge, more patients in the control group experienced PONV (62% vs 24% in the steroid group) and complained of poor oral intake. Additionally, more children in the control group (8% vs 0% in the steroid group) returned to the hospital for the management of PONV and/or poor oral intake. The preoperative administration of dexamethasone significantly decreased the incidence of PONV over the 24 h after home discharge in these children. Implications: In this double blind, placebo-controlled study, we examined the efficacy of a single large dose (1 mg/kg; maximal dose 25 mg) of preoperative dexamethasone on posttonsillectomy postoperative nausea and vomiting (PONV) in children 2-12 yr of age undergoing tonsillectomy. Compared with placebo, dexamethasone significantly decreased the incidence of PONV in the 24 h after discharge, improved oral intake, decreased the frequency of parental phone calls, and resulted in no hospital returns for the management of PONV and/or poor oral intake. Oculocardiac reflex (OCR) and postoperative vomiting are major complications of paediatric strabismus surgery.
                Children (3-16 yr) undergoing elective strabismus surgery as inpatients were randomly allocated to four anaesthetic techniques: (A) thiopentone induction and isoflurane maintenance; (B) as (A) plus ondansetron 5 mg x m(-2) i.v.; (C) propofol induction and maintenance; (D) as (C) plus lignocaine 2 mg x kg(-1) i.v. All children received prophylactic atropine 0.02 mg x kg(-1) and alfentanil. Nitrous oxide was omitted.
                Data on 157 children were analysed. The cumulative incidence of vomiting within 6 and 24 h after surgery with thiopentone-isoflurane was 26% and 46%, respectively. Adding ondansetron decreased the incidence to 8% and 33%, respectively. This improvement was significant within 6 h only; the number-needed-to-treat was 5.5 (95% CI 2.9-46). Propofol was not different from thiopentone-isoflurane. The addition of lignocaine to propofol was of no benefit. The risk of an OCR was significantly increased with propofol (incidence 40%) compared with isoflurane (14%); the number-needed-to-harm was 3.9 (95% CI 2.6-8).
                Thiopental-isoflurane-air/O2-alfentanil resulted in a moderate risk of vomiting. Adding ondansetron significantly decreased this risk, but 6 children have to be treated for one to benefit in the early postoperative period. Propofol and propofol-lignocaine showed no benefit on vomiting but significantly increased the risk of an OCR despite high-dose prophylactic atropine. This study evaluated the antiemetic effectiveness, dose-response, and clinical usefulness of prophylactic ondansetron in the prevention of postoperative nausea and vomiting (PONV) in children undergoing strabismus repair.
                The authors observed 180 children, American Society of Anesthesiologists physical status I or II, 2-12 yr of age, who were undergoing strabismus repair. After induction of anesthesia with halothane and nitrous oxide in oxygen or intravenous thiopental, children received either placebo (saline) or intravenous ondansetron in doses of 25, 50, 75, 100, and 150 /microg/kg (n = 30). The trachea was intubated and ventilation was controlled. Perioperative analgesic and fluid requirements were standardized. Episodes of nausea and vomiting were recorded for the first 24 h postoperatively. Data such as nonsurrogate (parental satisfaction scores and duration of postanesthesia care unit stay) and therapeutic (numbers needed to prevent and harm) outcome measures were collected.
                The incidences of PONV in the placebo and 25-, 50-, 75-, 100-, and 150-,microg/kg ondansetron groups were 83, 77, 47, 30, 30, and 27%, respectively. The incidence was less in the 75(P = 0.002), 100- (P = 0.002), and 150-microg/kg (P < 0.001) ondansetron groups compared with placebo. Duration of stay in the postanesthesia care unit was shorter in the 75-, 100-, and 150-microg/kg ondansetron groups (P < 0.002) compared with the placebo group. Parental assessment scores for the child's perioperative experience and the positive number needed to prevent PONV were also better and favorable in the 75-, 100-, and 150-microg/kg ondansetron groups compared with the placebo group. The incidence (P > 0.99) and severity (P = 0.63) of PONV were similar in the 75- and 150-microg/kg ondansetron groups. Surrogate, nonsurrogate, and therapeutic outcome measures revealed that 75 microg/kg ondansetron provided the same benefits as did 100 and 150 microg/kg.
                The routine prophylactic use of ondansetron at a dose of 75 microg/kg is as effective as 150 microg/kg in preventing PONV and improving the "true" outcome measures after strabismus repair in children. Preterm infants may be born with deficits of both docosahexaenoic acid (DHA) and arachidonic acid (AA), but studies on supplementation of DHA and AA for preterm infants are limited.
                Preterm infants with a gestational age between 30 and 37 weeks who met all the inclusion criteria were enrolled in this double blind, randomized, comparative study. Infants over 2000 g body weight, over 32 weeks of gestation and in full feeding status would enter into the active intervention period of 6 months. Sixteen infants received Neoangelac Plus with AA and DHA supplementation. Eleven infants received Neoangelac without AA and DHA supplementation. The babies had scheduled physical examinations and their cognitive development, visual acuity, and vital signs to be checked. Adverse events were also recorded.
                The mean Mental Development Index (MDI) scores for the supplementation and non-supplementation groups were 96.1 +/- 8.6 and 91.7 +/- 10.4 respectively at 6 months and 98.7 +/- 8.0 and 90.5 +/- 6.9 respectively at 1 year. The mean Physical Development Index (PDI) scores of these two groups were 102.2 +/- 10.5 and 95.4 +/- 13.2 respectively at 6 months and 98.0 +/- 5.8 and 86.7 +/- 11.1 respectively at 1 year. By repeated measures ANOVA, significant differences existed between groups for MDI and PDI (p = 0.020 and 0.008). However, there were no differences in visual acuity, physical examination variables or vital signs between these two groups. No obvious adverse effects were observed during the study period.
                These results showed possible benefits in the neurodevelopment of larger preterm infants given formula supplemented with DHA and AA.
At present, there is a lack of evidence concerning the effects of triiodothyronine supplementation in infants undergoing cardiac surgery. Further randomised controlled trials which include sufficiently large subject numbers in a variety of different age strata (neonates, infants and older children) need to be undertaken.