High-sensitive troponinT, interleukin-8, and interleukin-6 link with post-surgery risk in infant heart surgery.

BACKGROUND: This study focuses on biomarkers in infants after open heart surgery, and examines the association of high-sensitive troponin T (hs-cTnT), interleukin-6 (IL-6), and interleukin-8 (IL-8) with postoperative acute kidney injury (AKI), ventilatory support time and need of vasoactive drugs. METHODS: Secondary exploratory study from a double-blinded clinical randomized trial (Mile-1) on 70 infants undergoing open heart surgery with cardiopulmonary bypass (CPB). In this sub-study, the entire study population was examined without considering the study drugs. The biomarkers' peak concentration (highest concentration at 2 or 6 h post-CPB) were used for statistical analyses. RESULTS: Peak IL-8, hs-cTnT, and IL-6 occurred at 2 h post-CPB for 96%, 79%, and 63% of the patients, respectively. The odds ratio of developing AKI2-3 for IL-6 > 293 pg/mL was 23.4 (95% CI 5.3;104.0), for IL-8 > 100 pg/mL it was 11.5 (3.0;44.2), and for hs-cTnT >5597 pg/mL it was 6.1 (1.5; 24.5). In more than two third of the patients with the highest peak concentrations of IL-8, IL-6, and hs-cTnT, there was a need for ventilatory support for >24 h and use of vasoactive drugs at 24 h post-CPB, while in less than one third of the patients with the lowest peak concentrations of IL-8 and hs-cTnT such requirements were observed. CONCLUSIONS: The peak biomarker concentrations and CPB-time strongly predicted AKI2-3, with IL-6 and IL-8 emerging as strongest predictors. Furthermore, our findings suggest that measuring hs-cTnT and IL-8 just 2 h post-CPB-weaning may assist in identifying infants suitable for early extubation and highlight those at risk of prolonged ventilation.

A retrospective analysis of the duration of mechanical ventilation in Scandinavian paediatric heart centres.

AIM: Early extubation after cardiac surgery shortens paediatric intensive care unit (PICU) length of stay (LOS) and decreases complications from mechanical ventilation (MV). We explored the duration of MV in Scandinavian paediatric heart centres. METHODS: We retrospectively reviewed the MV duration and PICU LOS of 696 children operated for atrial septal defect (ASD), ventricular septal defect (VSD), tetralogy of Fallot (TOF) or total cavopulmonary connection (TCPC) in four Scandinavian centres in 2015-2016. Neonates (n = 90) were included regardless of heart surgery type. RESULTS: Patients with ASD were extubated at a median of 3.25 h (interquartile range [IQR] 2.00-4.83), followed by patients with TCPC (median 5.00 h, IQR 2.60-16.83), VSD (median 7.00 h, IQR 3.69-22.25) and TOF (median 18.08 h, IQR 6.00-41.38). Neonates were not extubated early (median 94.42 h, IQR 45.03-138.14). Although MV durations were reflected in PICU LOS, this was not as apparent among those extubated within 12 h. The Swedish centres had shortest MV durations and PICU LOS. Extubation failed in 24/696 (3.4%) of patients. CONCLUSION: Scandinavian paediatric heart centres differed in the duration of postoperative MV. Deferring extubation up to 12 h postoperatively did not markedly prolong PICU LOS.

Renal function and inflammatory response in neonates undergoing cardiac surgery with or without antegrade cerebral perfusion-a post hoc analysis.

Background: Cardiopulmonary bypass (CPB) may lead to tissue hypoxia, inflammatory response, and risk for acute kidney injury (AKI). We evaluated the prevalence of AKI and inflammatory response in neonates undergoing heart surgery requiring CPB with or without antegrade cerebral perfusion (ACP). Methods: Forty neonates were enrolled. The patients were divided into two groups depending on the use of ACP. AKI was classified based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Inflammatory response was measured using plasma concentrations of interleukins 6 (IL-6) and 10 (IL-10), white blood cell count (WBC), and C-reactive protein (CRP). Results: Eight patients (20%) experienced AKI: five (29%) in the ACP group and three (13%) in the non-ACP group (P = 0.25). Postoperative peak plasma creatinine and urine neutrophil gelatinase-associated lipocalin were significantly higher in the ACP group than in the non-ACP group [46.0 (35.0-60.5) vs 37.5 (33.0-42.5), P = 0.044 and 118.0 (55.4-223.7) vs 29.8 (8.1-109.2), P = 0.02, respectively]. Four patients in the ACP group and one in the non-ACP group required peritoneal dialysis (P = 0.003). Postoperative plasma IL-6, IL-10, and CRP increased significantly in both groups. There were no significant differences between the ACP and non-ACP groups in any of the inflammatory parameters measured. Conclusions: No significant difference in the AKI occurrence or inflammatory response related to CPB modality could be found. In our study population, inflammation was not the key factor leading to AKI. Due to the limited number of patients, these findings should be interpreted with caution.

Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data.

OBJECTIVES: We compared the effect of two inodilators, levosimendan and milrinone, on the plasma levels of myocardial injury biomarkers, that is, high-sensitivity troponin T and heart-type fatty acid binding protein, and on N-terminal prohormone of brain natriuretic peptide as a biomarker of ventricular function. We hypothesized that levosimendan could attenuate the degree of myocardial injury when compared with milrinone. DESIGN: A post hoc, nonprespecified exploratory secondary analysis of the Milrinone versus Levosimendan-1 trial (ClinicalTrials.gov Identifier: NCT02232399). SETTING: Two pediatric tertiary university hospitals. PATIENTS: Infants 1-12 months old, diagnosed with ventricular septal defect, complete atrioventricular septal defect, or Tetralogy of Fallot undergoing corrective surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy patients received a loading dose of either levosimendan or milrinone at the start of cardiopulmonary bypass followed by an infusion of the respective drug, which continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: Plasma levels of the three cardiac biomarkers were measured prior to the initiation of cardiopulmonary bypass and 2, 6, and 24 hours after weaning from cardiopulmonary bypass. In both groups, the levels of high-sensitivity troponin T and heart-type fatty acid binding protein were highest at 2 hours post cardiopulmonary bypass, whereas the highest level of N-terminal prohormone of brain natriuretic peptide occurred at 24 hours post cardiopulmonary bypass. There was no significant difference in the biomarkers' plasma levels between the study groups over time. Neither was there a significant difference in the postoperative peak plasma levels of the cardiac biomarkers. CONCLUSIONS: In this post hoc analysis of the MiLe-1 trial, there was no demonstrable difference in the postoperative cardiac biomarker profile of myocardial injury and ventricular function when comparing infants managed in the perioperative period with levosimendan versus milrinone.

Lung Injury After Neonatal Congenital Cardiac Surgery Is Mild and Modifiable by Corticosteroids.

OBJECTIVES: The present study was performed to determine whether lung injury manifests as lung edema in neonates after congenital cardiac surgery and whether a stress-dose corticosteroid (SDC) regimen attenuates postoperative lung injury in neonates after congenital cardiac surgery. DESIGN: A supplementary report of a randomized, double-blinded, placebo-controlled clinical trial. SETTING: A pediatric tertiary university hospital. PARTICIPANTS: Forty neonates (age ≤28 days) undergoing congenital cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: After anesthesia induction, patients were assigned randomly to receive intravenously either 2 mg/kg methylprednisolone or placebo b, which was followed by hydrocortisone or placebo bolus six hours after weaning from CPB for five days as follows: 0.2 mg/kg/h for 48 hours, 0.1 mg/kg/h for the next 48 hours, and 0.05 mg/kg/h for the following 24 hours. MEASUREMENTS AND MAIN RESULTS: The chest radiography lung edema score was lower in the SDC than in the placebo group on the first postoperative day (POD one) (p = 0.03) and on PODs two and three (p = 0.03). Furthermore, a modest increase in the edema score of 0.9 was noted in the placebo group, whereas the edema score remained at the preoperative level in the SDC group. Postoperative dynamic respiratory system compliance was higher in the SDC group until POD three (p < 0.01). However, postoperative oxygenation; length of mechanical ventilation; and tracheal aspirate biomarkers of inflammation and oxidative stress, namely interleukin-6, interleukin-8, resistin, and 8-isoprostane, showed no differences between the groups. CONCLUSIONS: The SDC regimen reduced the development of mild and likely clinically insignificant radiographic lung edema and improved postoperative dynamic respiratory system compliance without adverse events, but it failed to improve postoperative oxygenation and length of mechanical ventilation.

Levosimendan Versus Milrinone for Inotropic Support in Pediatric Cardiac Surgery: Results From a Randomized Trial.

OBJECTIVE: The present study aimed to determine the differential effects of intraoperative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was used for myocardial function evaluation using biventricular longitudinal strain with 2-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. DESIGN: A secondary analysis of a randomized, prospective, double-blinded clinical drug trial. SETTING: Two pediatric tertiary university hospitals. PARTICIPANTS: Infants between 1 and 12 months old diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. INTERVENTIONS: The patients were randomly assigned to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. MEASUREMENTS AND MAIN RESULTS: Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning, and before hospital discharge. The association between perioperative parameters and postoperative myocardial function also was investigated. Images were analyzed for left ventricular (n = 67) and right ventricular (n = 44) function. The day after surgery, left ventricular longitudinal strain deteriorated in both the milrinone and levosimendan groups (33% and 39%, respectively). The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (nonsignificant difference). For both groups, biventricular longitudinal strain approached preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day 1 (p = 0.014). CONCLUSIONS: Levosimendan was comparable with milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.

Reduction of Inflammation by High-Dose Methylprednisolone Does not Attenuate Oxidative Stress in Children Undergoing Bidirectional Glenn Procedure With or Without Aortic Arch or Pulmonary Arterial Repair.

OBJECTIVE: Corticosteroids attenuate an inflammatory reaction in pediatric heart surgery. Inflammation is a source of free oxygen radicals. Children with a cyanotic heart defect are prone to increased radical stress during heart surgery. The authors hypothesized that high-dose methylprednisolone reduces inflammatory reaction and thereby also oxidative stress in infants with a univentricular heart defect undergoing the bidirectional Glenn procedure. DESIGN: A double-blind, placebo-controlled, randomized clinical trial. SETTING: Operating room and pediatric intensive care unit of a university hospital. PARTICIPANTS: The study comprised 29 infants undergoing the bidirectional Glenn procedure with or without aortic arch or pulmonary arterial repair. INTERVENTIONS: After anesthesia induction, the patients received intravenously either 30 mg/kg of methylprednisolone (n = 15) or the same volume of saline as placebo (n = 14). MEASUREMENTS AND MAIN RESULTS: Plasma interleukin-6, interleukin-8, interleukin-10 (biomarkers of inflammation), and 8-hydroxydeoxyguanosine concentrations (a biomarker of oxidative stress) were measured at the following 4 time points: preoperatively, during cardiopulmonary bypass, after protamine administration, and 6 hours postoperatively. The study parameters did not differ between the study groups preoperatively. Methylprednisolone reduced the proinflammatory cytokines interleukin-6 and interleukin-8 and increased the anti-inflammatory cytokine interleukin-10 postoperatively. Despite reduced inflammation, there were no differences in 8-hydroxydeoxyguanosine between the methylprednisolone and placebo groups. CONCLUSIONS: The proinflammatory reaction and increase in free radical stress were not interrelated during congenital heart surgery in cyanotic infants with a univentricular heart defect undergoing the bidirectional Glenn procedure. High-dose methylprednisolone was ineffective in attenuating free radical stress.

The Effect of Levosimendan Versus Milrinone on the Occurrence Rate of Acute Kidney Injury Following Congenital Heart Surgery in Infants: A Randomized Clinical Trial.

OBJECTIVES: It has been shown that, in contrast to other inotropic agents, levosimendan improves glomerular filtration rate after adult cardiac surgery. The aim of this study was to investigate the efficacy of levosimendan, compared with milrinone, in preventing acute kidney dysfunction in infants after open-heart surgery with cardiopulmonary bypass. DESIGN: Two-center, double-blinded, prospective, randomized clinical trial. SETTING: The study was performed in two tertiary pediatric centers, one in Sweden (Gothenburg) and one in Finland (Helsinki). PATIENTS: Infants between 1 and 12 months old, diagnosed with Tetralogy of Fallot, complete atrioventricular septal defect or nonrestrictive ventricular septal defect, undergoing total corrective cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two infants were randomized to receive a perioperative infusion of levosimendan (0.1 µg/kg/min) or milrinone (0.4 µg/kg/min). The infusion was initiated at the start of cardiopulmonary bypass and continued for 26 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1. Secondary outcomes included the following: 1) acute kidney injury according to the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes; 2) acute kidney injury with serum creatinine corrected for fluid balance; 3) plasma neutrophil gelatinase-associated lipocalin; 4) cystatin C; 5) urea; 6) lactate; 7) hemodynamic variables; 8) use of diuretics in the PICU; 9) need of dialysis; 10) length of ventilator therapy; and 11) length of PICU stays. There was no significant difference in postoperative serum creatinine between the treatment groups over time (p = 0.65). The occurrence rate of acute kidney injury within 48 hours was 46.9% in the levosimendan group and 39.5% in the milrinone group (p = 0.70). There were no significant differences in other secondary outcome variables between the groups. CONCLUSIONS: Levosimendan compared with milrinone did not reduce the occurrence rate of acute kidney injury in infants after total corrective heart surgery for atrioventricular septal defect, ventricular septal defect, or Tetralogy of Fallot.

Heart-Type Fatty Acid Binding Protein and High-Dose Methylprednisolone in Pediatric Cardiac Surgery.

OBJECTIVES: Corticosteroids possess cardioprotection in experimental cardiac ischemia/reperfusion. The authors hypothesized that if cardioprotection of corticosteroids occured during pediatric cardiac surgery, then methylprednisolone used in cardiopulmonary bypass prime would reduce postoperative concentrations of heart-type fatty-acid-binding protein, a cardiac biomarker. DESIGN: A double-blind, placebo-controlled, randomized clinical trial. SETTING: Operating room and pediatric intensive care unit of a university hospital. PARTICIPANTS: Forty-five infants and young children undergoing ventricular or atrioventricular septal defect correction. INTERVENTIONS: The patients received one of the following: 30 mg/kg of methylprednisolone intravenously after anesthesia induction (n = 15), 30 mg/kg of methylprednisolone in cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma heart-type fatty-acid-binding protein (hFABP) was measured. Preoperatively, hFABP did not differ among the study groups. Methylprednisolone administered preoperatively and in the cardiopulmonary bypass prime solution reduced hFABP by 44% (p = 0.010) and 38% (p = 0.033) 6 hours postoperatively. hFABP significantly correlated with concomitant troponin T after protamine administration (R = 0.811, p < 0.001) and 6 hours postoperatively (R = 0.806, p < 0.001). CONCLUSIONS: Methylprednisolone in cardiopulmonary bypass prime solution administered only a few minutes before cardiac ischemia confered cardioprotection of the same magnitude as preoperative methylprednisolone as indicated by hFABP concentrations. Rapid cardioprotective actions of corticosteroids in pediatric heart surgery observed previously experimentally may have occurred.

Stress-Dose Corticosteroid Versus Placebo in Neonatal Cardiac Operations: A Randomized Controlled Trial.

BACKGROUND: Corticosteroids can improve the hemodynamic status of neonates with postoperative low cardiac output syndrome after cardiac operations. This study compared a prophylactically administered stress-dose corticosteroid (SDC) regimen against placebo on inflammation, adrenocortical function, and hemodynamic outcome. METHODS: Forty neonates undergoing elective open heart operations were randomized into two groups. The SDC group received perioperatively 2 mg/kg methylprednisolone, and 6 hours after the operation, a hydrocortisone infusion (0.2 mg/kg/h) was started with tapering doses for 5 days. Placebo was administered in a similar fashion. An adrenocorticotropic hormone stimulation test was performed after the therapy. The primary endpoint of the study was plasma concentration of interleukin (IL-6). Secondary clinical outcomes included plasma cortisol, IL-10, C-reactive protein, echocardiographic systemic ventricle contractility evaluated by the Velocity Vector Imaging program, the inotropic score, and time of delayed sternal closure. RESULTS: The IL-6 values of the SDC group were significantly lower postoperatively than in the placebo group. Significantly lower inotropic scores (p < 0.05), earlier sternal closure (p = 0.03), and less deterioration in the systemic ventricle mean delta strain values between the preoperative and the first postoperative assessment (p = 0.01) were detected for the SDC group. The SDC therapy did not suppress the hypothalamic-pituitary-adrenal axis more than placebo. The mean plasma cortisol level did not decline in the placebo group after the operation. CONCLUSIONS: The SDC regimen for 5 days postoperatively in neonates was safe and did not cause suppression of the hypothalamic-pituitary-adrenal axis. Furthermore, the open heart operation per se did not lead to adrenal insufficiency in neonates.

High-Dose Methylprednisolone Has No Benefit Over Moderate Dose for the Correction of Tetralogy of Fallot.

BACKGROUND: The optimal dose of methylprednisolone during pediatric open heart surgical procedures is unknown. This study compared the antiinflammatory and cardioprotective effects of high and lower doses of methylprednisolone in children undergoing cardiac operations. METHODS: Thirty children, between 1 and 18 months old and undergoing total correction of tetralogy of Fallot, were randomized in double-blind fashion to receive either 5 or 30 mg/kg of intravenous methylprednisolone after anesthesia induction. Plasma concentrations of methylprednisolone, interleukin-6 (IL-6), IL-8, and IL-10, troponin T, and glucose were measured at anesthesia induction before administration of the study drug, at 30 minutes on cardiopulmonary bypass (CPB), just after weaning from CPB, and at 6 hours after CPB. Troponin T and blood glucose were also measured on the first postoperative morning. RESULTS: Significantly higher methylprednisolone concentrations were measured in patients receiving 30 mg/kg of methylprednisolone at 30 minutes on CBP, after weaning from CPB and at 6 hours after CPB (p < 0.001). No differences were detected in IL-6, IL-8, IL-10, or troponin concentrations at any time point. Blood glucose levels were significantly higher in patients receiving 30 mg/kg of methylprednisolone at 6 hours after CPB (p = 0.04) and on the first postoperative morning (p = 0.02). CONCLUSIONS: Based on the measured concentrations of interleukins or troponin T, a 30 mg/kg dose of methylprednisolone during pediatric open heart operations does not offer any additional antiinflammatory or cardioprotective benefit over a 5 mg/kg dose. Higher dose of methylprednisolone exposes patients more frequently to hyperglycemia.

The Effect of Methylprednisolone on Plasma Concentrations of Neutrophil Gelatinase-Associated Lipocalin in Pediatric Heart Surgery.

OBJECTIVES: Plasma neutrophil gelatinase-associated lipocalin is a kidney injury marker used in pediatric heart surgery. Neutrophil gelatinase-associated lipocalin is also a constituent of specific granules of neutrophils. Corticosteroids are widely used in pediatric heart surgery. Methylprednisolone inhibits degranulation of neutrophil-specific granules. Use of corticosteroids has not been taken into account in studies of neutrophil gelatinase-associated lipocalin in pediatric heart surgery. We studied the influence of systemically administered methylprednisolone on plasma neutrophil gelatinase-associated lipocalin concentrations in pediatric heart surgery. DESIGN: Two separate double-blinded randomized trials. SETTING: PICU at a university-affiliated hospital. PATIENTS: Forty neonates undergoing open-heart surgery and 45 children undergoing ventricular and atrioventricular septal defect correction. INTERVENTIONS: First trial (neonate trial), 40 neonates undergoing open-heart surgery received either 30 mg/kg IV methylprednisolone (n = 20) or placebo (n = 20). Second trial (ventricular septal defect trial), 45 children undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone IV after anesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15), or placebo (n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma neutrophil gelatinase-associated lipocalin and creatinine were measured in both series. Lactoferrin levels were measured as a marker of neutrophil-specific granules in the ventricular septal defect trial only. No differences in creatinine levels occurred between the groups of either trial. Preoperative, neutrophil gelatinase-associated lipocalin did not differ between the study groups of either trial. Preoperatively administered methylprednisolone in the neonate trial reduced neutrophil gelatinase-associated lipocalin by 41% at 6 hours postoperatively (p = 0.002). Preoperatively administered methylprednisolone in the ventricular septal defect trial reduced neutrophil gelatinase-associated lipocalin by 47% (p = 0.010) and lactoferrin by 52% (p = 0.013) 6 hours postoperatively. Lactoferrin levels in the ventricular septal defect trial correlated with neutrophil gelatinase-associated lipocalin (R = 0.492; p = 0.001) preoperatively and after weaning from cardiopulmonary bypass (R = 0.471; p = 0.001). CONCLUSIONS: Preoperatively administered methylprednisolone profoundly decreases plasma neutrophil gelatinase-associated lipocalin levels. Neutrophil gelatinase-associated lipocalin seems to originate to a significant extent from activated neutrophils. Preoperative methylprednisolone is a confounding factor when interpreting plasma neutrophil gelatinase-associated lipocalin levels as a kidney injury marker in pediatric heart surgery.

Effect of timing and route of methylprednisolone administration during pediatric cardiac surgical procedures.

BACKGROUND: We compared the antiinflammatory and cardioprotective effects of the two most common regimens of corticosteroid administration in pediatric cardiac surgical procedures: a single dose delivered either at anesthesia induction or by cardiopulmonary bypass (CPB) prime. METHODS: Forty-five children, aged between 1 and 18 months and undergoing ventricular septal or atrioventricular septal defect correction, were randomized in double-blind fashion into three groups. The anesthesia induction group received 30 mg/kg methylprednisolone intravenously after anesthesia induction, and the CPB-prime group received 30 mg/kg methylprednisolone by CPB circuit. The placebo group received saline solution. Plasma concentrations of methylprednisolone, interleukin (IL)-6, IL-8 and IL-10, and troponin were measured at anesthesia induction before the study drug, 30 minutes on CPB, after patients were weaned from CPB, and 6 hours after cessation of CPB. RESULTS: Equally high methylprednisolone concentrations were detected in both methylprednisolone groups, but the measured peak concentration occurred earlier in the induction group. Significantly lower IL-8 concentrations were observed just after patients were weaned from and 6 hours after CPB in the anesthesia induction group compared with the placebo (p = 0.002, p = 0.001) and prime groups (p = 0.003, p = 0.006). Significant reductions of troponin were detected in both methylprednisolone groups compared with placebo (induction, p = 0.001; prime, p = 0.002) 6 hours after patients were weaned from CPB. CONCLUSIONS: Methylprednisolone administration at anesthesia induction was superior in terms of antiinflammatory action. Methylprednisolone administration in CPB-prime only a few minutes before aortic cross-clamping and cardioplegia resulted in mean troponin reductions similar to those of administration at anesthesia induction. Corticosteroids may have direct cardioprotective properties, as reported in experimental studies.

Methylprednisolone in neonatal cardiac surgery: reduced inflammation without improved clinical outcome.

BACKGROUND: Corticosteroids are widely used in pediatric open-heart surgery to reduce systemic inflammatory response and to mediate possible cardioprotective effects. However, the optimal dosing of corticosteroids is unknown and their administration varies considerably between different institutions. METHODS: Forty neonates undergoing open-heart surgery were randomized in a double-blind fashion equally into 2 groups. After the induction of anesthesia, 1 group received 30 mg/kg intravenous methylprednisolone and the other a placebo. Concentrations in plasma of interleukin 6 (IL-6), IL-8, IL-10, free methylprednisolone and total methylprednisolone were obtained for the following: (1) at anesthesia induction before the study drug was administered; (2) 30 minutes on cardiopulmonary bypass; (3) 5 minutes after protamine administration; and (4) 6 hours after weaning from cardiopulmonary bypass. Troponin T was measured at time points T1, T3, T4, and also at 6:00 on the first postoperative morning. Physiological and clinical outcome parameters were also recorded. RESULTS: Intravenous methylprednisolone resulted in high plasma drug concentrations that peaked at T2. Methylprednisolone significantly lowered concentrations of proinflammatory cytokines IL-6 and IL-8 and raised levels of anti-inflammatory IL-10. No significant differences in troponin T levels were detected. Blood glucose levels were significantly higher in the methylprednisolone group, and patients in this group received more often insulin therapy than controls. No significant differences were observed in other clinical or physiological outcome measurements. CONCLUSIONS: Intravenous 30 mg/kg methylprednisolone administered before cardiopulmonary bypass resulted in high effective plasma drug concentrations and a decreased inflammatory response. However, no cardioprotective effect or better clinical outcome was noticed.

Eight-year follow-up of photorefractive keratectomy for myopia.

PURPOSE: We evaluated 8-year results of excimer laser photorefractive keratectomy (PRK) for myopia in terms of stability and late complications. METHODS: Ninety-two myopic eyes of 55 patients were treated with a single-step method using an Aesculap-Meditec MEL 60 excimer laser with a 5.0-mm ablation zone. Treated eyes were divided into three groups according to preoperative refraction: low myopes (< or = -6.00 D), medium myopes (-6.10 to -10.00 D), and high myopes (>-10.00 D). RESULTS: Change in myopic regression stabilized in all myopia groups within 12 months, although a small myopic shift occurred up to 8 years after PRK. Mean change in refraction between 2 and 8 years was -0.42 +/- 0.48 D for low myopes, -0.37 +/- 0.34 D for medium myopes, and -0.41 +/- 0.50 D for high myopes. The percentage of eyes within +/- 1.00 D of emmetropia 8 years after PRK was 78.3% in the low myopia group, 68.8% in the medium myopia group, and 57.1% in the high myopia group. One eye lost 2 lines of best spectacle-corrected visual acuity due to irregular astigmatism. In 13.0% of eyes, a residual trace corneal haze was observed, which had no effect on visual acuity. Apart from the loss of 2 lines of BSCVA in one eye, there were no other late complications during the study period. CONCLUSIONS: The mean change in refraction between 2 and 8 years was less than -0.50 D, regardless of preoperative refraction, and may be attributed to natural age-related refractive change. The appearance of residual corneal haze after 8 years correlated with the amount of myopic correction. PRK was a safe and stable surgical procedure in this group of patients.