Felix Neunhoeffer

Evaluation of IL-8-Concentrations in Plasma and Lysed EDTA-Blood in Healthy Neonates and Those with Suspected Early Onset Bacterial Infection

Plasma IL-8 is a diagnostic parameter of early-onset bacterial infection (EOBI) in neonates but has a short half-life. The detergent-lysed whole-blood (DLWB) IL-8 consists of both extracellular and cell-bound IL-8. The objective of this study was to investigate kinetics of plasma and DLWB IL-8 in healthy newborns and those with suspected EOBI and to test the hypothesis that determination of DLWB IL-8 results in higher sensitivity for EOBI detection. Sixty-one neonates with clinical and serologic signs of EOBI composed the study group; 188 neonates with risk factors but without EOBI served as control subjects. IL-8 concentrations were determined in plasma and DLWB. In the control group, DLWB IL-8 concentrations were 280-fold higher (9599 pg/mL; SD 4433) up to 24 h post partum than corresponding plasma levels (34.2 pg/mL; SD 18.1). The sensitivity of DLWB versus plasma IL-8 for EOBI was 0.97 versus 0.71 after 6 h and 0.70 versus 0.32 after 24 h. Corresponding values for specificity were 0.95 versus 0.90 after 6 h and 0.92 versus 0.99 after 24 h. After 24 h, the negative predictive value for DLWB versus plasma IL-8 was 0.80 versus 0.66. DLWB IL-8 showed a higher sensitivity for EOBI within 6 h after first clinical suspicion than plasma IL-8. It also remained elevated longer. Our results suggest that DLWB IL-8 results in a higher sensitivity for EOBI.

Nurse-driven pediatric analgesia and sedation protocol reduces withdrawal symptoms in critically ill medical pediatric patients.

While several analgesia and sedation guidelines and protocols have been developed and implemented for adults, there is still little evidence of clinical use of analgesia and sedation protocols and the impact on withdrawal symptoms in critically ill children.

Serum Concentrations of Interleukin-6, Procalcitonin, and C-Reactive Protein: Discrimination of Septical Complications and Systemic Inflammatory Response Syndrome after Pediatric Surgery.

BACKGROUND Early differentiation between sepsis and systemic inflammatory response syndrome (SIRS) is useful for therapeutic management in neonates and infants after surgery. OBJECTIVE To compare the early (first 2 days) diagnostic value of interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) after surgery in the differentiation of subsequent SIRS and septic complications. METHODS IL-6, PCT, and CRP were measured 0, 24, and 48 hours after surgery in neonates and infants with clinical suspicion of postoperative sepsis. Sensitivity, specificity, and predictive values for SIRS/septic complications were calculated. RESULTS A total of 31 out of 205 neonates and infants showed clinical signs for postoperative sepsis and underwent sepsis work-up. Nine patients developed septic complications, sixteen patients met criteria for SIRS, and six patients showed an uneventful postoperative course during the first five postoperative days. IL-6, PCT, and CRP levels increased in all subgroups after surgery and were significantly higher in the sepsis group (p < 0.05). IL-6 peaked immediately, CRP at 24 to 48 hours, and PCT at 24 hours after surgery. Sensitivity and specificity (area under the curve) for IL-6 (cutoff 673 ng/dL) were 94.4 and 75% (86.2%), for CRP (cutoff 1.48 mg/dL) 76.2 and 75.0% (88.1%), and for PCT (cutoff 16.1 mg/L) 66.7 and 57.1% (65.6%). CONCLUSION IL-6 appears to be an early marker for severe bacterial infections with high sensitivity. IL-6 and CRP were the most reliable markers for the discrimination between SIRS and sepsis within the postoperative period.

Conservative surgery with combined high dose rate brachytherapy for patients suffering from genitourinary and perianal rhabdomyosarcoma

BACKGROUND AND PURPOSE Outcome of patients with genitourinary rhabdomyosarcoma has been improved in the past, but organ preservation rates are too low. Conservative surgery with LDR-brachytherapy has been advocated, but LDR-brachytherapy is often not available. We wanted to establish a novel treatment modality combining HDR-brachytherapy and conservative surgery. MATERIAL AND METHODS We performed an organ preserving tumor resection with intraoperative placement of brachytherapy tubes. Suitable patients were selected following assessment of response to neoadjuvant chemotherapy where organ preserving surgical resection was deemed feasible. In bladder-prostate rhabdomyosarcoma, only tumors located below the bladder neck could be treated by brachytherapy. After surgery, high dose rate brachytherapy was carried out for 30-36Gy total dose. RESULTS A total of 11 patients were treated up to now (embryonal histology n=10, alveolar histology n=1) with a median follow-up of 18months [4-80]. All patients were IRS group III. There were no significant side effects. One patient had local relapse and was successfully treated with re-excision. All other patients are in the first complete remission. One patient developed a neurogenic bladder and required creation of a Mitrofanoff stoma. CONCLUSION Combined conservative surgery and high dose rate brachytherapy is a treatment option for selected rhabdomyosarcoma patients. The paper highlights the essential technical challenges and clearly shows limitations of this treatment approach.

Simultaneous Resection of High-risk Liver Tumors and Pulmonary Metastases in Children

H epatoblastoma (HB) is the most common primary pediatric liver tumor, and hepatocellular carcinoma (HCC) is the second most common malignant liver tumor in children.1 Overall survival of HB patients has increased significantly from 30% to more than 80% in the past, but metastatic disease is still associated with a poor outcome. Lung metastases occur in approximately 20% and respond well to chemotherapy. All international trials recommend surgical treatment for remnant pulmonary metastases after neoadjuvant chemotherapy as well as an aggressive surgical management of pulmonary relapses.2 The timing of resection of pulmonary nodules is still subject of an ongoing discussion. Some surgeons perform the resection of pulmonary metastases after the resection of the primary tumor.3 Other authors prefer the pulmonary metastasectomy before liver resection to avoid the effects of growth stimulation and tumor cell proliferation of metastases triggered by hepatic growth factors secreted after major liver surgery.4 Alternatively, waiting until this growth stimulation has occurred may aid in the detection of previously undetectable micrometastases.4 There is also a controversial debate regarding the optimal surgical approach to pulmonary metastases, especially when bilateral lung involvement is present. Some surgeons prefer metachronous bilateral thoracotomies instead of sternotomy in these cases.3 It has been demonstrated that hepatocyte growth factor (HGF)/scatter factor stimulates growth, invasion, motility, differentiation, and angiogenesis.5 It has also been reported that patients with hepatoblastoma have elevated HGF serum levels, which even increase after surgical resection. Hepatoblastoma cells respond to this factor with migration, invasion, and prolonged survival.5 Thus, simultaneous resection of the primary tumor and lung metastases as singlestage approach might be beneficial regarding tumor biology. Up to now, there is no report on the simultaneous resection of pediatric liver tumors and lung metastases in children. The aim of our study was to evaluate the efficacy of simultaneous resections of pediatric high-risk liver tumors and lung metastases as a single-stage approach. To answer this question, a retrospective review of patient’s records of patients undergoing combined resection of pediatric highrisk liver tumors and pulmonary metastases (n=7) in a 10-year period (May 2003–November 2013) was carried out. All patients received

Acquired von Willebrand syndrome in congenital heart disease surgery: results from an observational case-series

Essentials Bleeding complications during congenital heart disease surgery in neonatal age are very common. We report the perioperative incidence of acquired von Willebrand syndrome (aVWS) in 12 infants. aVWS was detected in 8 out of 12 neonates and infants intraoperatively after cardiopulmonary bypass. Ten patients received von Willebrand factor concentrate intraoperatively and tolerated it well.

Safety and Efficacy of Terlipressin in Pediatric Distributive Shock: A Retrospective Analysis in 20 Children

IntroductionData are still lacking about the use of terlipressin or vasopressin in the treatment of pediatric patients who are in a state of therapy-refractory shock.ObjectiveThe aim of this study was to evaluate the effect of terlipressin on hemodynamics in children with distributive shock and to describe any severe side effects.MethodsConsecutive patients (n = 20) with catecholamine-resistant distributive shock who were treated with terlipressin were retrospectively enrolled in this study. We analyzed response in terms of mean arterial blood pressure, heart rate, vasoactive inotropic score (VIS), urinary output, and serum lactate.ResultsThe hemodynamics of 12 children significantly improved within 6 h of commencing terlipressin (mean blood pressure increase of ≥20 % without VIS increase, or mean blood pressure increase of ≥10 % with VIS decrease of ≥10 %). The hemodynamics of eight patients did not improve, regardless of treatment dosage or duration. More children died in the responders group (n = 7 [58.3 %]) than in the non-responders group (n = 2 [25.0 %]), but this was not statistically significant. Two patients (one in each group) who received high dosages of terlipressin developed rhabdomyolysis. One case of Takotsubo cardiomyopathy was observed, which could be related to terlipressin.ConclusionsAlthough treatment with terlipressin resulted in rapid positive hemodynamic responses in some children, it did not seem to have a positive effect in other pediatric patients. Therefore, the possible benefits of terlipressin should be always weighed against potential severe adverse effects.

Severe Upper Airway Obstruction After Intraoperative Transesophageal Echocardiography in Pediatric Cardiac Surgery: A Retrospective Analysis*

Objectives: The aim of this study was to evaluate if there is a correlation between the use of intraoperative transesophageal echocardiography and an increased rate of extubation failure and to find other risk factors for severe upper airway obstructions after pediatric cardiac surgery. Design: Retrospective analysis. Setting: Cardiac PICU. Patients: Patients 24 months old or younger who underwent surgery for congenital heart disease with cardiopulmonary bypass were retrospectively enrolled and divided into two groups depending on whether they received an intraoperative transesophageal echocardiography or not. We analyzed all cases of early reintubations within 12 hours after extubation due to a documented upper airway obstruction. Intervention: None. Measurements and Main Results: From a total of 424 patients, 12 patients (2.8%) met our criteria of early reintubation due to upper airway obstruction. Ten of 207 children in the transesophageal echocardiography group had to be reintubated, whereas only two of the 217 children in the control group had to be reintubated (4.8% vs 0.9%; p = 0.018). Logistic regression analysis showed a significant correlation between use of intraoperative transesophageal echocardiography and extubation failure (odds ratio, 5.64; 95% CI, 1.18–27.05; p = 0.030). There was no significant relationship among sex (odds ratio, 4.53; 95% CI, 0.93–22.05; p = 0.061), weight (odds ratio, 1.07; 95% CI, 0.82–1.40; p = 0.601), duration of surgery (odds ratio, 1.04; 95% CI, 0.74–1.44; p = 0.834), duration of mechanical ventilation (odds ratio, 1.00; 95% CI, 0.99–1.00; p = 0.998), and occurrence of trisomy 21 (odds ratio, 3.47; 95% CI, 0.83–14.56; p = 0.089). Conclusions: Although the benefits of intraoperative transesophageal echocardiography during pediatric cardiac surgery are undisputed, it may be one factor which could increase the rate of severe upper airway obstruction after extubation with the need for reintubation. We suggest to take precautions before extubating high-risk patients, especially in young male children with genetic abnormalities after cardiac surgery with cardiopulmonary bypass.

Non-invasive assessment of cerebral oxygen metabolism following surgery of congenital heart disease

OBJECTIVES Cerebral protection is a major issue in the treatment of infants with complex congenital heart disease. We tested a new device combining tissue spectrometry and laser Doppler flowmetry for non-invasive determination of cerebral oxygen metabolism following cardiac surgery in infants. METHODS We prospectively measured regional cerebral oxygen saturation cSO 2 and microperfusion (rcFlow) in 43 infants 12-24 h following corrective ( n  = 30) or palliative surgery ( n  = 13) of congenital heart defects. For comparison, cerebral blood flow (CBF) was determined by colour duplex sonography of the extracranial cerebral arteries. Cerebral fractional tissue oxygen extraction, approximated cerebral metabolic rate of oxygen (aCMRO 2 ) and cerebral metabolic rate of oxygen (CMRO 2 ) were calculated. RESULTS cSO 2 was lower [54.6% (35.7-64.0) vs 59.7% (44.5-81.7); P  < 0.01] after neonatal palliation, while rcFlow [69.7 AU (42.5-165.3) vs 77.0 AU (41.2-168.1); P  = 0.06] and cerebral fractional tissue oxygen extraction [0.34 (0.24-0.82) vs 0.38 (0.17-0.55); P  = 0.63] showed a trend towards lower values. We found a positive correlation between aCMRO 2 and CMRO 2 ( r  = 0.27; P  = 0.03). aCMRO 2 was significantly lower after neonatal palliation [4.0 AU (2.1-6.3) vs 4.9 AU (2.2-15.6); P  = 0.02]. CONCLUSIONS According to our experience, combined photospectrometry and laser Doppler flowmetry enable non-invasive assessment of cerebral oxygen metabolism. The method promises new insights into perioperative cerebral perfusion following palliation or corrective surgery in infancy.

Diagnostic value of immature myeloid information in early-onset bacterial infection in term and preterm neonates.

BACKGROUND For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. OBJECTIVE To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. PATIENTS AND METHODS 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. RESULTS Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. CONCLUSION The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.