Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

Myocarditis and sports in the young: data from a nationwide registry on myocarditis-"MYKKE-Sport".

Background: Myocarditis represents one of the most common causes of Sudden Cardiac Death in children. Myocardial involvement during a viral infection is believed to be higher as a consequence of intensive exertion. Recommendations for return to sports are based on cohort and case studies only. This study aims to investigate the relationship between physical activity and myocarditis in the young. Patient: Every patient in the MYKKE registry fulfilling criteria for suspicion of myocarditis was sent a questionnaire regarding the physical activity before, during and after the onset of myocarditis. Method: This study is a subproject within the MYKKE registry, a multicenter registry for children and adolescents with suspected myocarditis. The observation period for this analysis was 93 months (September 2013-June 2021). Anamnestic, cardiac magnetic resonance images, echocardiography, biopsy and laboratory records from every patient were retrieved from the MYKKE registry database. Results: 58 patients (mean age 14.6 years) were enrolled from 10 centers. Most patients participated in curricular physical activity and 36% in competitive sports before the onset of myocarditis. There was no significant difference of heart function at admission between the physically active and inactive subjects (ejection fraction of 51.8 ± 8.6% for the active group vs. 54.4 ± 7.7% for the inactive group). The recommendations regarding the return to sports varied widely and followed current guidelines in 45%. Most patients did not receive an exercise test before returning to sports. Conclusion: Sports before the onset of myocarditis was not associated with a more severe outcome. There is still a discrepancy between current literature and actual recommendations given by health care providers. The fact that most participants did not receive an exercise test before being cleared for sports represents a serious omission.

Awareness and diagnosis for intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) in neonatal (NICU) and pediatric intensive care units (PICU) - a follow-up multicenter survey.

BACKGROUND: Constantly elevated intra-abdominal pressure (IAH) can lead to abdominal compartment syndrome (ACS), which is associated with organ dysfunction and even multiorgan failure. Our 2010 survey revealed an inconsistent acceptance of definitions and guidelines among pediatric intensivists regarding the diagnosis and treatment of IAH and ACS in Germany. This is the first survey to assess the impact of the updated guidelines on neonatal/pediatric intensive care units (NICU/PICU) in German-speaking countries after WSACS published those in 2013. METHODS: We conducted a follow-up survey and sent 473 questionnaires to all 328 German-speaking pediatric hospitals. We compared our findings regarding awareness, diagnostics and therapy of IAH and ACS with the results of our 2010 survey. RESULTS: The response rate was 48% (n = 156). The majority of respondents was from Germany (86%) and working in PICUs with mostly neonatal patients (53%). The number of participants who stated that IAH and ACS play a role in their clinical practice rose from 44% in 2010 to 56% in 2016. Similar to the 2010 investigations, only a few neonatal/pediatric intensivists knew the correct WSACS definition of an IAH (4% vs 6%). Different from the previous study, the number of participants who correctly defined an ACS increased from 18 to 58% (p < 0,001). The number of respondents measuring intra-abdominal pressure (IAP) increased from 20 to 43% (p < 0,001). Decompressive laparotomies (DLs) were performed more frequently than in 2010 (36% vs. 19%, p < 0,001), and the reported survival rate was higher when a DL was used (85% ± 17% vs. 40 ± 34%). CONCLUSIONS: Our follow-up survey of neonatal/pediatric intensivists showed an improvement in the awareness and knowledge of valid definitions of ACS. Moreover, there has been an increase in the number of physicians measuring IAP in patients. However, a significant number has still never diagnosed IAH/ACS, and more than half of the respondents have never measured IAP. This reinforces the suspicion that IAH and ACS are only slowly coming into the focus of neonatal/pediatric intensivists in German-speaking pediatric hospitals. The goal should be to raise awareness of IAH and ACS through education and training and to establish diagnostic algorithms, especially for pediatric patients. The increased survival rate after conducting a prompt DL consolidates the impression that the probability of survival can be increased by timely surgical decompression in the case of full-blown ACS.

EEG monitoring during anesthesia in children aged 0 to 18 months: amplitude-integrated EEG and age effects.

BACKGROUND: The amplitude-integrated EEG (aEEG) is a widely used monitoring tool in neonatology / pediatric intensive care. It takes into account the amplitudes, but not the frequency composition, of the EEG. Advantages of the aEEG are clear criteria for interpretation and time compression. During the first year of life, the electroencephalogram (EEG) during sedation / anesthesia changes from a low-differentiated to a differentiated EEG; higher-frequency waves develop increasingly. There are few studies on the use of aEEG during pediatric anesthesia. A systematic evaluation of the aEEG in defined EEG stages during anesthesia / sedation is not yet available. Parameters of pediatric EEGs (power, median frequency, spectral edge frequency) recorded during anesthesia and of the corresponding aEEGs (upper and lower value of the aEEG trace) should be examined for age-related changes. Furthermore, it should be examined whether the aEEG can distinguish EEG stages of sedation / anesthesia in differentiated EEGs. METHODS: In a secondary analysis of a prospective observational study EEGs and aEEGs (1-channel recordings, electrode positions on forehead) of 50 children (age: 0-18 months) were evaluated. EEG stages: A (awake), Slow EEG, E2, F0, and F1 in low-differentiated EEGs and A (awake), B0-2, C0-2, D0-2, E0-2, F0-1 in differentiated EEGs. RESULTS: Median and spectral edge frequency increased significantly with age (p < 0.001 each). In low-differentiated EEGs, the power of the Slow EEG increased significantly with age (p < 0.001). In differentiated EEGs, the power increased significantly with age in each of the EEG stages B1 to E1 (p = 0.04, or less), and the upper and lower values of the aEEG trace increased with age (p < 0.001). A discriminant analysis using the upper and lower values of the aEEG showed that EEG epochs from the stages B1 to E1 were assigned to the original EEG stage in only 19.3% of the cases. When age was added as the third variable, the rate of correct reclassifications was 28.5%. CONCLUSIONS: The aEEG was not suitable for distinguishing EEG stages above the burst suppression range. For this purpose, the frequency composition of the EEG should be taken into account.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Activated Clotting Time (ACT) for Monitoring of Low-Dose Heparin: Performance Characteristics in Healthy Adults and Critically Ill Patients.

Dose adjustment of unfractionated heparin (UFH) anticoagulation is an important factor to reduce hemorrhagic events. High doses of heparin can be monitored by Activated Clotting Time (ACT). Because of limited information about the monitoring of low-dose heparin we assessed monitoring by ACT, aPTT and anti-Xa. Blood samples from healthy volunteers (n = 54) were treated ex vivo with increasing UFH doses (0-0.4 IU/ml). Samples from ICU-patients (n = 60), were drawn during continuous UFH infusion. Simultaneous ACT measurements were performed using iSTAT and Hemochron. In UFH treated blood, iSTAT and Hemochron showed a significant change of ACT at ≥0.075 IU/ml and ≥0.1 IU/ml UFH, respectively. In ICU-patients no relationship between ACT and either UFH dose, aPTT and anti-Xa was observed. Hemochron was affected by antithrombin and platelet count. iSTAT was sensitive to CRP and hematocrit. A moderate correlation was identified between UFH dose and aPTT (R2 = 0.196) or anti-Xa (R2 = 0.162). In heparin-spiked blood, ACT is sensitive to heparin at levels of ≥0.1 IU/ml heparin. In ICU-patients, ACT did not correlate with UFH dose or other established methods. Both systems were differently influenced by certain parameters.

Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: Results from the prospective multicenter registry "MYKKE".

Myocarditis represents an important cause for acute heart failure. MYKKE, a prospective multicenter registry of pediatric patients with myocarditis, aims to gain knowledge on courses, diagnostics, and therapy of pediatric myocarditis. The role of mechanical circulatory support (MCS) in children with severe heart failure and myocarditis is unclear. The aim of this study was to determine characteristics and outcome of patients with severe heart failure requiring MCS and/or heart transplantation. The MYKKE cohort between September 2013 and 2016 was analyzed. A total of 195 patients were prospectively enrolled by 17 German hospitals. Twenty-eight patients (14%) received MCS (median 1.5 years), more frequently in the youngest age group (0-2 years) than in the older groups (P < 0.001; 2-12 and 13-18 years). In the MCS group, 50% received a VAD, 36% ECMO, and 14% both, with a survival rate of 79%. The weaning rate was 43% (12/28). Nine (32%) patients were transplanted, one had ongoing support, and six (21%) died. Histology was positive for myocarditis in 63% of the MCS group. Patients within the whole cohort with age <2 years and/or ejection fraction <30% had a significantly worse survival with high risk for MCS, transplantation, and death (P < 0.001). Myocarditis represents a life-threatening disease with an overall mortality of 4.6% in this cohort. The fulminant form more often affected the youngest, leading to significantly higher rate of MCS, transplantation, and mortality. MCS represents an important and life-saving therapeutic option in children with myocarditis with a weaning rate of 43%.

Development and validation of a diagnostic model for early differentiation of sepsis and non-infectious SIRS in critically ill children - a data-driven approach using machine-learning algorithms.

BACKGROUND: Since early antimicrobial therapy is mandatory in septic patients, immediate diagnosis and distinction from non-infectious SIRS is essential but hampered by the similarity of symptoms between both entities. We aimed to develop a diagnostic model for differentiation of sepsis and non-infectious SIRS in critically ill children based on routinely available parameters (baseline characteristics, clinical/laboratory parameters, technical/medical support). METHODS: This is a secondary analysis of a randomized controlled trial conducted at a German tertiary-care pediatric intensive care unit (PICU). Two hundred thirty-eight cases of non-infectious SIRS and 58 cases of sepsis (as defined by IPSCC criteria) were included. We applied a Random Forest approach to identify the best set of predictors out of 44 variables measured at the day of onset of the disease. The developed diagnostic model was validated in a temporal split-sample approach. RESULTS: A model including four clinical (length of PICU stay until onset of non-infectious SIRS/sepsis, central line, core temperature, number of non-infectious SIRS/sepsis episodes prior to diagnosis) and four laboratory parameters (interleukin-6, platelet count, procalcitonin, CRP) was identified in the training dataset. Validation in the test dataset revealed an AUC of 0.78 (95% CI: 0.70-0.87). Our model was superior to previously proposed biomarkers such as CRP, interleukin-6, procalcitonin or a combination of CRP and procalcitonin (maximum AUC = 0.63; 95% CI: 0.52-0.74). When aiming at a complete identification of sepsis cases (100%; 95% CI: 87-100%), 28% (95% CI: 20-38%) of non-infectious SIRS cases were assorted correctly. CONCLUSIONS: Our approach allows early recognition of sepsis with an accuracy superior to previously described biomarkers, and could potentially reduce antibiotic use by 30% in non-infectious SIRS cases. External validation studies are necessary to confirm the generalizability of our approach across populations and treatment practices. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT00209768; registration date: September 21, 2005.

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase. OBJECTIVE: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB. METHODS: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine. RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI: 0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48). CONCLUSION: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

BACKGROUND: Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. OBJECTIVE: The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). METHODS: Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg-1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg-1 ·h-1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 µg·kg-1 ·min-1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. RESULTS: Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg-1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg-1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg-1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 µg·ml-1 , 95% CI: 0.1-0.3 µg·ml-1 , P < 0.001) than older children. CONCLUSION: After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg-1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses.

Systemic inflammatory response syndrome after pediatric congenital heart surgery: Incidence, risk factors, and clinical outcome.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is frequent after cardiac surgery, but data on its incidence and perioperative risk factors are scarce for children with congenital heart disease. METHODS: SIRS incidence within 72 hours following cardiac surgery was evaluated in a secondary analysis of children enrolled to a treatment-free control group of a randomized controlled trial. Intraoperative parameters were investigated for their association with SIRS using multivariable fractional polynomial logistic regression models. Effects of SIRS on various organ functions and length of stay were evaluated using time-varying Cox regression models. RESULTS: In 116 children after cardiac surgery (median age [range]: 7.4 month [1 day-16.2 years]) SIRS occurred in n = 39/102 with and n = 1/14 without cardiopulmonary bypass (CPB). Duration of CPB (hazard ratio [HR]: 2.28 per hour; 95% confidence interval [CI] 1.17; 4.42) and amount of fresh frozen plasma (HR: 1.23 per 10 mL/kg; 95%CI 1.06; 1.42) were identified as predictors for SIRS; neonates seemed to be less susceptible for SIRS development (HR: 0.86; 95%CI 0.79; 0.95). SIRS was associated with organ dysfunction (HR: 2.69; 95%CI 1.41; 5.12) and extended stay in the pediatric intensive care unit (PICU) (median: 168 vs. 96 hours; p = 0.007). CONCLUSIONS: SIRS is a frequent complication after pediatric congenital heart surgery; it affects nearly one third of children and prolongs PICU stay significantly. Duration of CPB and amount of fresh frozen plasma were identified as important risk factors. Neonates seem to be less susceptible to SIRS development.

Feasibility and Accuracy of Cardiac Right-to-Left-Shunt Detection in Children by New Transpulmonary Ultrasound Dilution Method.

Transpulmonary ultrasound dilution (TPUD) method, a novel indicator dilution (ID) technique for cardiac output measurement, detects and quantifies shunts, both in children and adults. However, its accuracy and reproducibility in cardiac right-to-left-shunt (RLS) detection have not been investigated. In a prospective observational study, we assessed the validity of TPUD algorithm for RLS detection in children with congenital heart disease (CHD) and proven RLS in comparison with controls without shunts between February 2010 and October 2011. As TPUD algorithm was unknown, we tested ID curve morphology, appearance time (AT) and central blood volume index (CBVI) as diagnostic criteria. TPUD identified RLS correctly in all 16 RLS subjects [median age (range): 18 months (1 month-15 years 6 months)] and excluded RLS in all 26 controls [74 months (8 months to 17 years 4 months)]. AT was significantly shorter in RLS (P < 0.05). Applying only AT (93.8 % sensitivity, 92.3 % specificity), RLS can be detected by shortening of ≥1.69 s of normally expected AT. RLS ID curves were subdivided into four morphological categories: (I) hump-on-upslope (n = 5); (II) double-hump (n = 3); (III) pseudonormal (n = 3); (IV) abnormal width (n = 5). No correlation was found between specific type of CHD and RLS categories. CBVI measurements were significantly smaller in RLS categories I-III than in controls (P < 0.05). TPUD appears to be a valid method for cardiac RLS detection. Shortened AT and low CBVI are reliable parameters for RLS identification. RLS categories have specific implications for cardiac output, blood volume and RLS fraction measurements. TPUD is valuable to monitor shunt direction and magnitude to optimise haemodynamic and respiratory therapy.

Optimized preoperative fasting times decrease ketone body concentration and stabilize mean arterial blood pressure during induction of anesthesia in children younger than 36 months: a prospective observational cohort study.

BACKGROUND: In pediatric anesthesia, preoperative fasting guidelines are still often exceeded. OBJECTIVE: The objective of this noninterventional clinical observational cohort study was to evaluate the effect of an optimized preoperative fasting management (OPT) on glucose concentration, ketone bodies, acid-base balance, and change in mean arterial blood pressure (MAP) during induction of anesthesia in children. METHODS: Children aged 0-36 months scheduled for elective surgery with OPT (n = 50) were compared with peers studied before optimizing preoperative fasting time (OLD) (n = 50) who were matched for weight, age, and height. RESULTS: In children with OPT (n = 50), mean fasting time (6.0 ± 1.9 h vs 8.5 ± 3.5 h, P < 0.001), deviation from guideline (ΔGL) (1.2 ± 1.4 h vs 3.7 ± 3.1 h, P < 0.001, ΔGL>2 h 8% vs 70%), ketone bodies (0.2 ± 0.2 mmol·l(-1) vs 0.6 ± 0.6 mmol·l(-1) , P < 0.001), and incidence of hypotension (MAP <40 mmHg, 0 vs 5, P = 0.022) were statistically significantly lower and MAP after induction was statistically significantly higher (55.2 ± 9.5 mmHg vs 50.3 ± 9.8 mmHg, P = 0.015) as compared to children in the OLD (n = 50) group. Glucose, lactate, bicarbonate, base excess, and anion gap did not significantly differ. CONCLUSION: Optimized fasting times improve the metabolic and hemodynamic condition during induction of anesthesia in children younger than 36 months of age.

In-line Filtration Decreases Systemic Inflammatory Response Syndrome, Renal and Hematologic Dysfunction in Pediatric Cardiac Intensive Care Patients.

Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS (-11.3 %; 95 % CI -21.8 to -0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI -14.2 to -0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care.

3-Dimensional (3D) laparoscopy improves operating time in small spaces without impact on hemodynamics and psychomental stress parameters of the surgeon.

BACKGROUND AND PURPOSE: Three-dimensional (3D) imaging, a recent technical innovation in laparoscopic surgery, has been postulated to enhance depth perception and facilitate operations. However, it has never been evaluated in conditions where the focus is close to the optical system. Thus, it is unclear whether 3D cameras can improve laparoscopic surgical performance in neonates and infants. We tested 3D versus two-dimensional (2D) vision during laparoscopic surgery in rabbits, mimicking the size of a neonatal patient. MATERIALS AND METHODS: Cadaver New Zealand white rabbits (mean weight 2,755 g) were operated by two surgeons experienced in 2D laparoscopic surgery and two surgical residents (with basic skills in 2D laparoscopy). All surgeons had never performed 3D laparoscopic surgery. Animals underwent six operations: Nissen fundoplication, small bowel anastomosis, and closure of a diaphragmatic defect using either 2D or 3D. Primary endpoint was cumulative operating time and operating time of each operation. Secondary endpoints included the hemodynamic response and psychomental stress level of the surgeons. Finally, subjective data on depth perception were assessed by questionnaires. RESULTS: Cumulative operating time of all three types of operations was significantly shorter with 3D laparoscopy in experts (3D: 23.01 ± 5.65 min vs 2D: 29.51 ± 7.51 min, p < 0.01) and residents (3D: 27.95 ± 3.69 min vs 2D: 33.95 ± 6.21 min, p < 0.05). This effect could be shown for each operation in the expert group and the Nissen fundoplication in the resident group. There were no differences in the hemodynamic response as well as the psychomental stress level between 2D and 3D imaging. 3D provided better depth perception. CONCLUSION: 3D laparoscopy in small spaces is associated with a significant shorter operating time. It induces no additional physical or psychomental stress in surgeons naive to 3D imaging. 3D may therefore facilitate minimal invasive surgery in neonates and infants.

Neonatal aortic arch thrombosis: analysis of thrombophilic risk factors and prognosis.

UNLABELLED: Arterial thrombosis in neonates and children is a rare event and is often associated with external risk factors such as asphyxia or sepsis. We report our experiences with two neonates with spontaneous aortic arch thrombosis mimicking aortic coarctation. Despite single case reports until now, no data exist for the underlying thrombophilic risk factors and prognosis of this rare event. Both patients were carriers of a heterozygous factor V Leiden mutation, which has been reported once before as a risk factor for aortic arch thrombosis. One of our patients was operated upon successfully and is alive. The second patient suffered a large infarction of the right medial cerebral artery and had a thrombotic occlusion of the inferior caval vein. The patient obtained palliative care and died at the age of 6 days. In the literature, we identified 19 patients with neonatal aortic arch thrombosis. Of the 19 patients, 11 (58%) died. Including the two reported patients, the mortality rate of patients with multiple thromboses was 80% (8/10) compared with 18% (2/11) for patients with isolated aortic arch thrombosis; this difference reached statistical significance (p = 0.009). The analysis of thrombophilic disorders revealed that factor V Leiden mutation and protein C deficiency seem to be the most common risk factors for aortic arch thrombosis. CONCLUSION: Neonatal aortic arch thrombosis is a very rare but life-threatening event, with a high rate of mortality, especially if additional thrombotic complications are present. Factor V Leiden mutation seems to be one important risk factor in the pathogenesis of this fatal disease.

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

BACKGROUND: Infused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion. METHODS: In this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005. RESULTS: The incidence rates of respiratory (-5.06%; 95% CI, -9.52 to -0.59%), renal (-3.87%; 95% CI, -7.58 to -0.15%) and hematologic (-3.89%; 95% CI, -7.26 to -0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups. CONCLUSIONS: In-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function. TRIAL REGISTRATION: ClinicalTrials.gov number; NCT00209768.

In-line filtration reduces severe complications and length of stay on pediatric intensive care unit: a prospective, randomized, controlled trial.

PURPOSE: Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients. METHODS: This single-centre, prospective, randomized controlled trial assessed the effects of filtration of intravenous fluids on the reduction of complications in critically ill children admitted to a pediatric intensive care unit (PICU). A total of 807 subjects were randomly assigned to either a control (n = 406) or filter group (n = 401), with the latter receiving in-line filtration. The primary endpoint was reduction in the rate of overall complications, which included the occurrence of systemic inflammatory response syndrome (SIRS), sepsis, organ failure (circulation, lung, liver, kidney) and thrombosis. Secondary objectives were a reduction in the length of stay on the PICU and overall hospital stay. Duration of mechanical ventilation and mortality were also analyzed. FINDINGS: Analysis demonstrated a significant reduction in the overall complication rate (n = 166 [40.9 %] vs. n = 124 [30.9 %]; P = 0.003) for the filter group. In particular, the incidence of SIRS was significantly lower (n = 123 [30.3 %] vs. n = 90 [22.4 %]; P = 0.01). Moreover the length of stay on PICU (3.89 [95 % confidence interval 2.97-4.82] vs. 2.98 [2.33-3.64]; P = 0.025) and duration of mechanical ventilation (14.0 [5.6-22.4] vs. 11.0 [7.1-14.9] h; P = 0.028) were significantly reduced. CONCLUSION: In-line filtration is able to avert severe complications in critically ill patients. The overall complication rate during the PICU stay among the filter group was significantly reduced. In-line filtration was effective in reducing the occurrence of SIRS. We therefore conclude that in-line filtration improves the safety of intensive care therapy and represents a preventive strategy that results in a significant reduction of the length of stay in the PICU and duration of mechanical ventilation (ClinicalTrials.gov number: NCT00209768).

Comparison of transpulmonary thermodilution and ultrasound dilution technique: novel insights into volumetric parameters from an animal model.

Especially in critically ill children with cardiac diseases, fluid management and monitoring of cardiovascular function are essential. Ultrasound dilution technique (UDT) was recently introduced to measure cardiac output (CO) and volumetric parameters, such as intrathoracic and end-diastolic blood volume. We compared UDT with the well-established transpulmonary thermodilution (TPTD) method (PiCCO) for determining CO measurements and derived volumes in a juvenile animal model. Experiments were performed in 18 ventilated, anesthetized piglets during normovolemia and after isovolemic hemodilution. At baseline and 20 min after each step of isovolemic hemodilution, 3 independent measurements of CO and volumetric parameters were conducted with TPTD and UDT, consecutively, under hemodynamically stable conditions. We observed comparable results for CO measurements with both methods (mean 1.98 l/min; range 1.12-2.87) with a percentage error of 17.3% (r = 0.92, mean bias = 0.28 l/min). Global end-diastolic volume (GEDV) and intrathoracic blood volume (ITBV) by TPTD were almost two times greater than analogous volumes [central blood volume (CBV); total end-diastolic volume (TEDV)] quantified by UDT (CBV = 0.58 × ITBV + 27.1 ml; TEDV = 0.48 × GEDV + 23.1 ml). CO measurements by UDT were found to be equivalent and hence interchangeable with TPTD. Discrepancies in volumetric parameters could either be due to the underlying algorithm or different types of indicators (diffusible vs. nondiffusible). Compared with the anatomically defined heart volume, TPTD seems to overestimate end-diastolic volumes. Future studies will be necessary to assign these results to critically ill children and to validate volumetric parameters with reference techniques.