[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
Cardiology in the Young 01/2013; · 0.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the results of these patients, new "bridging-strategies" are necessary. Recent reports demonstrate promising results for the concept of "awake ECMO" in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV-ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5-109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was <50%, we conclude that the concept of "awake VV-ECMO" is feasible for the treatment of RF and can be used as a "bridging therapy" to LuTx.
[show abstract][hide abstract] ABSTRACT: Several decades ago, the beneficial effects of goal-directed therapy, which include decompressive laparotomy (DL) and open abdomen procedures in cases of intra-abdominal hypertension (IAH) in children, were proven in the context of closures of abdominal wall defects and large-for-size organ transplantations. Different neonatologic and pediatric disease patterns are also known to be capable of increasing intra-abdominal pressure (IAP). Nevertheless, a considerable knowledge transfer regarding such risk factors has hardly taken place. When left undetected and untreated, IAH threatens to evolve into abdominal compartment syndrome (ACS), which is accompanied by a mortality rate of up to 60% in children. Therefore, the present study looks at the recognition and knowledge of IAH/ACS among German pediatric intensivists.
In June 2010, a questionnaire was mailed to the heads of pediatric intensive care units of 205 German pediatric hospitals.
The response rate was 62%. At least one case of IAH was reported by 36% of respondents; at least one case of ACS, by 25%. Compared with adolescents, younger critically ill children appeared to develop IAH/ACS more often. Routine measurements of IAP were said to be performed by 20% of respondents. Bladder pressure was used most frequently (96%) to assess IAP. Some respondents (17%) only measured IAP in cases of organ dysfunction and failure. In 2009, the year preceding this study, 21% of respondents claimed to have performed a DL. Surgical decompression was indicated if signs of organ dysfunction were present. This was also done in cases of at least grade III IAH (IAP > 15 mmHg) without organ impairment.
Although awareness among pediatricians appears to have been increasing over the last decade, definitions and guidelines regarding the diagnosis and management of IAH/ACS are not applied uniformly. This variability could express an ever present lack of awareness and solid prospective data.
[show abstract][hide abstract] ABSTRACT: Particulate contamination due to infusion therapy carries a potential health risk for intensive care patients.
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.
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.
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).
European Journal of Intensive Care Medicine 04/2012; 38(6):1008-16. · 5.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response.
A total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM).
At study end the cardiac output (10% HES200 143±48 ml/kgBW; 6% HES130 171±47 ml/kgBW; RAc 137±32 ml/kgBW; 4% gelatin 160±42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157±115 U/g creatinine; P<0.05) group compared to hydroxyethylstarch 130 (24±9 U/g creatinine), Ringer's acetate (2±3 U/g creatinine) and SHAM (21±15 U/g creatinine) at the study's end. Creatinine significantly increased by 87±84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845±1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492±604 pg/ml; RAc 874±363 pg/ml; 4% gelatin 1,623±1,242 pg/ml).
Despite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.
Critical care (London, England) 01/2012; 16(1):R16. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: There is evidence to suggest that - dependent on the size and the medical spectrum of a pediatric hospital - intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) gradually become more and more known medical entities. Nevertheless, in everyday clinical life they receive barely consideration and lead a miserable existence. This is noteworthy in so far as at mixed pediatric and neonatologic intensive care units the incidence of IAH and ACS amounts up to 1-15% and mortality rates are as high as 60%. In 2006/ 2007, the World Society of the Abdominal Compartment Syndrome (www.WSACS.org) published definitions and recommendations concerning IAH and ACS primarily in adults, based on the current literature, which seem to be only to a limited extent transferable to physiological and patho-physiological circumstances found in children. Little is known about the recognition and management of the pediatric ACS in Germany.
METHODS: In June 2010, a postal questionnaire was sent to 360 pediatric and neonatologic intensive care units in 205 German hospitals.
RESULTS: From 205 eligible hospitals a total of 125 replies were received (61%). Barely half of the respondents indicated that the ACS plays a role in their clinical practice (40% seldom, 5% consistently and 1% often). In 2009, 36% of all answering hospitals diagnosed IAH´s and about 25% diagnosed at least one ACS. Measurement of intra-abdominal pressure (IAP) is routinely performed by not more than 19%. Intra-abdominal pressure is mostly (96%) assessed via the bladder pressure. 70% of respondents who declare to routinely quantify the IAP only start measurements in patients which show clinical signs of acute or tense abdomen. 17% even start measurements only in cases of beginning organ dysfunction and failure. 69% of respondents comment that they would assess IAP more often if the underlying handling would become more easily and standardized. The younger and smaller babies and newborns are, the more pediatric surgeons are content to decompress their abdomen in cases of exceeded intra abdominal pressure. On the other hand, decompressive laparotomie is performed earlier if first signs of organ dysfunctions become apparent in patients with IAH. In 2009, decompressive laparotomy was performed in 21% of all answering pediatric departments in Germany.
CONCLUSIONS: German pediatric and neonatologic intensivists are familiar with the ACS. However, more than 80% never measure IAP and there is a considerable variance as to which patients are at risk to develop ACS and how often IAP should be measured in these patients. This could indicate a lack of acceptance or simply a persisting need for more data concerning the avoidance and treatment of the ACS in children and adolescents. Each child being at risk to develop an increased IAP should be regularly monitored.
The American surgeon 07/2011; 77(7):S100. · 0.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Zielsetzung: Intraabdominelle Hypertonie (IAH) und Abdominelles Kompartmentsyndrom (AKS) sind in der Pädiatrie seltene (Inzidenz 0,1-15%), aber fatale Entitäten mit einer Mortalität von >60%. Im Erwachsenenalter haben sie sich als unabhängige Prädiktoren für das Entstehen von Multiorganversagen (MOV) und Sepsis erwiesen. Altersabhängig herrscht im Neugeborenen- und Säuglingsalter das primäre AKS vor (Urs.: Gastroschisis, Omphalozele, Nekrotisierende Enterokolitis, Darmperforation/ -ileus, Tumor, Transplantation), im Kindesalter findet sich dagegen eher das sekundäre AKS (Urs.: Verbrennung, Trauma, Sepsis, Schock). Bis heute ist unklar, ob die von der WSACS veröffentlichen Definitionen und Empfehlungen auch für das Kindesalter gelten (www.wsacs.org). Ziel dieser Studie war die Erhebung der in der gängigen Literatur verfügbaren Datenlage zu Inzidenz, Outcome, Messverfahren und -verhalten, pädiatrischen Grenzwerten für den intraabdominellen Druck (IAD), Therapieindikationen und -möglichkeiten samt zugehörigen Literatur-Evidenzgraden im Kindesalter. Methodik: Eine PubMed-Analyse der Suchbegriffe „Abdominal Compartment Syndrome + Children“ ergab 81 Treffer, von denen 67 Artikel auf das AKS bezogen waren (32 Case-Reports, 10 retrospektive Studien, 9 prospektive, nicht-randomisierte Arbeiten sowie Reviews). Anhand der zugehörigen Literaturverzeichnisse wurden zusätzlich 25 relevante Studien und Veröffentlichungen eingeschlossen. Ergebnis: Im klinischen Alltag scheint die Diagnosestellung eher auf klinischer Beobachtung als auf der Anwendung spezifischer, IAD-bezogener Definitionen zu beruhen. Mit abnehmendem Alter und zunehmender Unreife sinkt die Bereitschaft, relativ invasive Druckmessmethoden wie die Blasendruckmessung durchzuführen. Die intragastrale Messung erfolgt nur sehr selten. Peritonealdialysekatheter werden verwendet, sofern sie ohnehin vorhanden sind. Die dekompressive Laparotomie mit temporärem Bauchdeckenverschluss gilt als Goldstandard. Eine zusätzliche Behandlungsoption ist die Punktion und Drainage von Flüssigkeiten. Die von der WSACS definierte druckabhängige Stadieneinteilung der IAH ist nicht auf das Kind übertragbar, denn der Übergang in ein AKS wurde bei Kindern bereits bei einem IAD >10mmHg beobachtet. Schlussfolgerung: Studien sind dringend notwendig, um eine altersadaptierte Einteilung intraabdomineller Druckverhältnisse und daraus ableitbarer Therapieschemata für das Kindesalter zu erhalten. V.a. in Risikogruppen sollte die IAH-Diagnostik durch IAD-Messungen objektiviert werden.
Anasthesiologie und Intensivmedizin 09/2010; 51(Suppl. 6):S741. · 0.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the physical properties and chemical composition of particles captured by in-line microfilters in critically ill children, and to investigate the inflammatory and cytotoxic effects of particles on endothelial cells (HUVEC) and macrophages in vitro.
Prospective, observational study of microfilters following their use in the pediatric intensive care unit. In vitro model utilizing cytokine assays to investigate the effects of particles on human endothelial cells and murine macrophages.
Twenty filter membranes from nine patients and five controls were examined by electron microscopy (EM) and energy dispersion spectroscopy (EDX). The average number of particles found on the surface of the used membranes was 550 cm(2). EDX analysis confirmed silicon as a major particle constituent. Half of the filter membranes showed conglomerates containing an unaccountable number of smaller particles. In vitro, glass particles were used to mimic the high silicon content particles. HUVEC and murine macrophages were exposed to different contents of particles, and cytokine levels were assayed to assess their immune response. Levels of interleukin-1beta, interleukin-6, interleukin-8, and tumor necrosis factor alpha were suppressed.
Particle contamination of infusion solutions exists despite a stringent infusion regiment. The number and composition of particles depends on the complexity of the applied admixtures. Beyond possible physical effects, the suppression of macrophage and endothelial cell cytokine secretion in vitro suggests that microparticle infusion in vivo may have immune-modulating effects. Further clinical trials are necessary to determine whether particle retention by in-line filtration has an influence on the outcome of intensive care patients.
European Journal of Intensive Care Medicine 02/2010; 36(4):707-11. · 5.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels.
In Germany, patients receiving protein C concentrate (Ceprotin, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study.
Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03).
This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.
Critical care (London, England) 01/2010; 14(4):R156. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: Levosimendan is a calcium-sensitizing agent with effective inotropic properties. It has been shown to improve cardiac function, hemodynamic performance, and survival in adults with severe heart failure. However, the effect of Levosimendan in pediatric cardiac surgery has not yet been investigated. Thus, we report on our experience with the intraoperative application of Levosimendan in seven infants (body weight range 2.6-6.3 kg) with severe myocardial dysfunction after complex congenital heart surgery. During the administration of Levosimendan, the heart rate, mean arterial blood pressure, and central venous pressure did not change. The mean arterial lactate level significantly decreased 24 and 48 h after the first infusion compared to baseline. Central venous oxygen saturation increased significantly 24 and 48 h after the onset of Levosimendan infusion. We found intraoperatively administered Levosimendan to be well tolerated in the seven infants with severe myocardial dysfunction after complex congenital heart surgery. Levosimendan is a new rescue drug which has beneficial effects, even in pediatric cardiac surgery.
European Journal of Pediatrics 10/2008; 168(6):735-40. · 1.91 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study describes a modified Seldinger technique for 2- and 3-French peripherally inserted central venous catheters: A device similar to that used in heart catherisation with a standard micro-introducer serving as sheath and an arterial catheter serving as inner dilator was pushed forward over a wire guide that had before been inserted via a peripheral venous catheter. With this method 2-and 3-French catheters could be safely inserted into peripheral veins of 14 paediatric patients. In conclusion successful insertion of a small peripheral venous catheter offers in most cases a possibility for the placement of a central venous line.
European Journal of Pediatrics 02/2008; 167(11):1327-9. · 1.91 Impact Factor