Ten-year experience of whole lung lavage in pediatric Pulmonary Alveolar Proteinosis.

BACKGROUND: Pulmonary Alveolar Proteinosis (PAP) is extremely rare and can be caused by hereditary dysfunction of the granulocyte macrophage colony-stimulating factor receptor (GM-CSF) receptor, autoantibodies against GM-CSF, or other diseases leading to alveolar macrophage (AM) dysfunction. This leads to protein accumulation in the lung and severe dyspnea and hypoxemia. Whole lung lavage (WLL) is the first line treatment strategy. METHODS: Here, we present data from more than ten years of WLL practice in pediatric PAP. WLL performed by the use of a single lumen or double lumen tube (SLT vs. DLT) were compared for technical features, procedure time, and adverse events. RESULTS: A total of n=57 procedures in six PAP patients between 3.5 and 14.3 years of age were performed. SLT based WLL in smaller children was associated with comparable rates of adverse events but with longer intervention times and postprocedural intensive care treatment when compared to DLT based procedures. DISCUSSION: Our data shows that WLL is feasible even in small children. DLT based WLL seems to be more effective, and our data supports the notion that it should be considered as early as possible in pediatric PAP. CONCLUSION: WLL lavage is possible in small PAP patients but should performed in close interdisciplinary cooperation and with age appropriate protocols.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Intra-Abdominal Hypertension and Compartment Syndrome after Pediatric Liver Transplantation: Incidence, Risk Factors and Outcome.

In pediatric liver transplantation (pLT), the risk for the manifestation and relevance of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) is high. This observational study aimed to evaluate the incidence, relevance and risk factors for IAH and ACS by monitoring the intra-abdominal pressure (IAP), macro- and microcirculation (near-infrared spectroscopy (NIRS)), clinical and laboratory status and outcomes of 27 patients (16 female) after pLT (median age at pLT 35 months). Of the patients, 85% developed an elevated IAP, most of them mild. However, 17% achieved IAH° 3, 13% achieved IAH° 4 and 63% developed ACS. A multiple linear regression analysis identified aortal hepatic artery anastomosis and cold ischemia time (CIT) as risk factors for increased IAP and longer CIT and staged abdominal wall closure for ACS. ACS patients had significantly longer mechanical ventilation (p = 0.004) and LOS-PICU (p = 0.003). No significant correlation between NIRS or biliary complications and IAH or ACS could be shown. IAH and ACS after pLT were frequent. NIRS or grade of IAH alone should not be used for monitoring. A longer CIT is an important risk factor for higher IAP and ACS. Therefore, approaches such as the ex vivo machine perfusion of donor organs, reducing CIT effects on them, have great potential. Our study provides important basics for studying such approaches.

[Case Series Report: Management of Anesthesia in Children Undergoing Complex Surgery of Tracheoesophageal Fistula after Ingestion of Button Batteries]. / Fallberichte: Kinder mit tracheoösophagealer Fistel nach Knopfbatterieningestion.

Button battery ingestions in children increased in recent years and may lead to life-threatening complications, especially if the battery is impacted in the esophagus. The pH close to the negative pole of the battery can rise in a very alkalotic range (pH > 10) leading to severe tissue damage. Therefore, in this case series report, the clinical courses of four children with button battery ingestion leading to tracheoesophageal fistulas are presented. The diagnosis and removal of the button battery was delayed in all cases. The surgical reconstruction of the trachea was performed in intravenous anesthesia and with extended monitoring. The intraoperative oxygenation was maintained using a combination of extracorporeal membrane oxygenation (ECMO) and mechanical ventilation via an endobronchial tube. To prevent these life-threatening complications, the awareness of the parents and child care providers should be raised, and the manufacturers should redesign their products to secure the battery compartment. In children with suspected battery ingestions, the immediate localization and removal of the battery (< 2 h) is of highest importance. Local administration of honey or sucralfate can be considered in ingestions < 12 h but should not delay an endoscopic removal.

Interventional Bronchus Occlusion Using Amplatzer Devices - A Promising Treatment Option for Children with Persistent Air Leak.

BACKGROUND: Persistent air leak (PAL) is a severe complication of secondary spontaneous pneumothorax (SSP). Surgical interventions are usually successful when medical treatment fails, but can be associated with significant complications and loss of potentially recoverable lung parenchyma. METHODS: Retrospective analysis of efficacy and safety of interventional bronchus occlusions (IBO) using Amplatzer devices (ADs) in children with PAL secondary to SSP. RESULTS: Six patients (four males, 4-15 years of age) underwent IBO using ADs as treatment for PAL. Necrotizing pneumonia (NP) was the most common cause (n=4) of PAL. Three patients were previously healthy and three suffered from chronic lung disease. All patients required at least two chest tubes prior to the intervention for a duration of 15-43 days and all required oxygen or higher level of ventilatory support. In three cases, previous surgical interventions had been performed without success. All children improved after endobronchial intervention and we observed no associated complications. All chest tubes were removed within 5-25 days post IBO. In patients with PAL related to NP (n=4), occluders were removed bronchoscopically without re-occurrence of pneumothorax after a mean of 70 days (IQR: 46.5-94). CONCLUSION: IBO using ADs is a safe and valuable treatment option in children with PAL independent of disease severity and underlying cause. A major advantage of this procedure is its less invasiveness compared to surgery and the parenchyma- preserving approach.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Pediatric urgent heart transplantation with age or weight mismatched donors: Reducing waiting time by enlarging donor criteria.

BACKGROUND: Despite considerable progress in heart transplantation, pediatric waiting list mortality is still high, and often patients do not have enough time to wait. We hypothesized that extending the donor criteria regarding age and weight mismatch does not significantly affect the early follow-up. METHODS: We retrospectively analyzed our pediatric heart transplantation patients operated on from 2014 to 2020 for high (>3.0) or low (<0.6) donor-recipient weight ratio (DRWR) or chronological age mismatches (donor organ >5 years older than recipient age). This patient cohort constituted "mismatched heart transplantations" (mHTX). We compared mHTX preoperative status, postoperative course, 1-year survival, and early clinical follow-up to standard pediatric heart transplantations (sHTX). RESULTS: We performed 20 pediatric heart transplantations-10 mHTX and 10 sHTX. The minimum DRWR was 0.44, the maximum was 5.60, and the maximum age mismatch was 42.6 years. Median days in the intensive care unit (p = .436) and time-to-first-rejection episode (p = .925) were comparable. Nine patients in each group were alive after 1 year, two patients were operated within 1 year of follow-up. One mHTX patient developed cardiac allograft vasculopathy after 15 months and died 648 days after transplantation (p = .237). All other patients were alive at the end of follow-up and in good clinical conditions (median follow-up for mHTX was 732.5 days, 1149.5 days for sHTX). CONCLUSION: Postoperative course and early follow-up after mHTX were comparable to sHTX. In urgent clinical situations, extended donor criteria may be considered an additional option for pediatric heart transplantation.

Multicenter Experience With Mechanical Circulatory Support Using a New Diagonal Pump in 233 Children.

Technological innovations in pediatric extracorporeal life support circuits can reduce system-related complications and may improve patients' outcome. The Deltastream DP3 (Medos Medizintechnik AG, Stolberg, Germany) is a novel rotational pump with a diagonally streamed impeller that can be used over a broad range of flows. We collected patient data from seven pediatric centers to conduct a retrospective cohort study. We examined 233 patients whose median age was 1.9 (0-201) months. The DP3 system was used for cardiopulmonary support as veno-arterial extracorporeal membrane oxygenation (ECMO) in 162 patients. Respiratory support via veno-venous ECMO was provided in 63 patients. The pump was used as a ventricular assist device in eight patients. Median supporting time was 5.5 (0.2-69) days and the weaning rate was 72.5%. The discharge home rate was 62% in the pulmonary group versus 55% in the cardiac group. Extracorporeal cardiopulmonary resuscitation was carried out in 24 patients (10%) with a survival to discharge of rate of 37.5%. About 106 (47%) children experienced no complications, while 33% suffered bleeding requiring blood transfusion or surgical intervention. Three patients suffered a fatal cerebral event. Renal replacement therapy was performed in 28% and pump or oxygenator exchange in 26%. Multivariable analysis identified system exchange (OR 1.94), kidney failure (OR 3.43), and complications on support (OR 2.56) as risk factors for dismal outcome. This novel diagonal pump has demonstrated its efficacy in all kinds of mechanical circulatory and respiratory support, revealing good survival rates.

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.

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.

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.

Monitoring of adenovirus infection in pediatric transplant recipients by quantitative PCR: report of six cases and review of the literature.

Adenoviral (AdV) infections after transplantation remain a challenge in pediatric patients. Qualitative and quantitative PCR offer new approaches to early diagnosis and monitoring. However, their role in the management of AdV infections in pediatric transplant recipients remains to be determined. We report six children with positive qualitative serum-PCR for AdV on routine follow-up after transplantation (liver n = 4, hematopoetic stem cells (HSCT) n = 1, combined liver and HSCT n = 1). None of these children were symptomatic at the time of first detection of AdV. Two patients remained asymptomatic, one developed hemorrhagic cystitis and enteritis. Three children with positive PCR developed high viral load on quantitative PCR, all developed clinical AdV sepsis with further rising virus load. Despite antiviral therapy with cidofovir, these three patients died of septic multiorgan failure. Positive qualitative AdV-PCR from blood after pediatric transplantation is not necessarily followed by clinical disease. In case of positive AdV-PCR, monitoring by serial quantitative PCR is useful regarding treatment decision and prevention of fatal disease.