Incidence of venous thromboembolic events not related to vascular catheters in a prospective cohort of critically ill children.

The risk for venous thromboembolism (VTE) is considered to be low in the general paediatric intensive care unit (PICU) population, and pharmacological thromboprophylaxis is not routinely used. PICU patients considered at high-risk of VTE could possibly benefit from pharmacological thromboprophylaxis, but the incidence of VTE in this group of patients is unclear. This was an observational, prospective study at a tertiary multi-disciplinary paediatric hospital. We used comprehensive ultrasonography screening for VTE in critically ill children with multiple risk factors for VTE. Patients admitted to PICU ≥ 72 h and with ≥ two risk factors for VTE were included. Patients receiving pharmacological thromboprophylaxis during their entire PICU stay were excluded. The primary outcome of the study was VTEs not related to the use of a CVC. Ultrasonography screening of the great veins was performed at PICU discharge. Seventy patients with median (interquartile range) 3 (2-4) risk factors for VTE were evaluated. Median age was 0.3 years (0.03-4.3) and median PICU length of stay 9 days (5-17). Regarding the primary outcome, no symptomatic VTEs occurred and no asymptomatic VTEs were found on ultrasonography screening, resulting in an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). CONCLUSION: Our results indicate that VTEs not related to a vascular catheter are a rare event even in a selected group of severely ill small children considered to be at high risk of VTE. WHAT IS KNOWN: • Children in the PICU often have several risk factors for venous thromboembolism (VTE). • The incidence of VTE in PICU patients is highly uncertain, and there are no evidence-based guidelines regarding VTE prophylaxis. WHAT IS NEW: • This study found an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). • This indicates that such VTE events are rare even in PICU patients with multiple risk factors for VTE.

Complications of Pediatric Midline Catheters: A Prospective Observational Pilot Study.

BACKGROUND: Midline catheters are peripheral intravenous (IV) catheters in which the tip of the catheter does not reach the central circulation. In children, the use of midline catheters could lead to decreased complications from central venous catheters. To validate the safety of midline catheter use in children, we aimed to describe the complications and dwell time of pediatric midline catheters. The primary outcome was the incidence of catheter-related venous thromboembolism (VTE). METHODS: We conducted an observational, prospective study including consecutive patients at a tertiary multidisciplinary pediatric hospital. One hundred pediatric midline catheters were followed for thrombotic, infectious, and mechanical complications. After catheter removal, Doppler ultrasonography was performed to detect asymptomatic VTE. RESULTS: The mean age was 6.0 years (standard deviation [SD], 4.7), and median catheter dwell time was 6 (4-8) days. Most midline catheters were inserted in arm veins, most commonly in the basilic vein (56%). Catheter-related VTE was diagnosed in 30 (30%; 95% confidence interval [CI], 21%-40%) cases, corresponding to an incidence rate of 39 (95% CI, 26-55) cases per 1000 catheter days. Eight of 14 saphenous vein catheters were complicated by VTE compared to 22 of 86 arm vein catheters, suggesting an imbalance in favor of arm vein insertion site. Two patients needed anticoagulation therapy due to catheter-related VTE. Thirty (30%) catheters were removed unintentionally or due to complications, 22 of these needed additional IV access to complete the intended therapy. No catheter-related bloodstream infection (95% CI, 0%-4%) occurred. Mechanical complications occurred in 33 (33%; 95% CI, 24%-43%) midline catheters. CONCLUSIONS: In children, thrombotic and mechanical complications of midline catheters are common, but only few VTEs are severe enough to warrant anticoagulation therapy. Systemic infectious complications are rare. Seventy-eight percent of patients did not need additional venous access to complete short-term IV therapy. Considering the rate of clinically relevant complications and the catheter dwell time, pediatric midline catheters could be an alternative to central venous access for short-term (5-10 days) IV therapy.

Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis.

BACKGROUND: Reduced kidney volume (KV) following prematurity is a proxy for reduced nephron number and is associated with the development of hypertension and end-stage renal disease in adults. We investigated whether extreme prematurity affects KV, function, and blood pressure in school-aged children and if nephrocalcinosis (NC) developed during the neonatal period had additional effects. METHODS: We investigated 60 children at a mean age of 7.7 years: 20 born extremely preterm (EPT < 28 weeks gestational age with NC (NC+)), 20 born EPT without NC (NC-), and 19 born as full-term infants (control). We measured KV by ultrasound, collected blood and urine samples to evaluate renal function, and measured office and 24-h ambulatory blood pressure (ABPM). RESULTS: Children born EPT had significantly smaller kidneys (EPT (NC+ NC-) vs control (estimated difference, 11.8 (CI - 21.51 to - 2.09 ml), p = 0.018) and lower but normal cystatin C-based glomerular filtration rate compared with control (estimated difference, - 10.11 (CI - 0.69 to - 19.5), p = 0.035). KV and function were not different between NC+ and NC- groups. Change in KV in relation to BSA (KV/BSA) from the neonatal period to school age showed significantly more EPT children with neonatal NC having a negative evolution of KV (p = 0.01). Blood pressure was normal and not different between the 3 groups. Fifty percent of EPT had a less than 10% day-to-night decline in ABPM. CONCLUSIONS: Kidney growth and volume is affected by EPT birth with NC being a potential aggravating factor. Circadian blood pressure regulation seems abnormal in EPT-born children.

Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters.

BACKGROUND: Venous thrombosis (VT) in children is often associated with a central venous catheter (CVC). We aimed to determine the incidence of VT associated with percutaneous non-tunnelled CVCs in a general paediatric population, and to identify risk factors for VT in this cohort. METHODS: Observational, prospective study enrolling consecutive patients at a tertiary multi-disciplinary paediatric hospital. A total of 211 percutaneous, non-tunnelled CVCs were analysed. Data regarding potential risk factors for CVC-related VT were collected. Compression ultrasonography with colour Doppler was used to diagnose VT. RESULTS: Overall, 30.3% of children developed CVC-related VT, with an incidence rate of 29.6 (confidence interval, 22.5-36.9) cases/1000 CVC days. Upper body CVC location, multiple lumen CVCs, and male gender were independent risk factors for VT in multivariate analysis. All upper body VTs were in the internal jugular vein (IJV). The occurrence of CVC-related VT did not affect length of paediatric ICU or hospital stay. In patients with VT, femoral CVCs, young age, paediatric ICU admission, and a ratio of CVC/vein diameter >0.33 were associated with VT being symptomatic, occlusive, or both. IJV VT was often asymptomatic and non-occlusive. CONCLUSIONS: Paediatric non-tunnelled CVCs are frequently complicated by VT. Avoiding IJV CVCs and multiple lumen catheters could potentially reduce the overall risk of VT. However, IJV VT was more likely to be smaller and asymptomatic compared with femoral vein VT. More data are needed on the risk of complications from smaller, asymptomatic VT compared with the group of VT with symptoms or vein occlusion. Femoral vein CVCs and CVC/vein diameter >0.33 could be modifiable risk factors for VT with larger thrombotic mass. CLINICAL TRIAL REGISTRATION: ACTRN12615000442505.

Complex Fluid Collection on Abdominal Ultrasound Indicates Need for Surgery in Neonates with Necrotizing Enterocolitis.

Aim The aim of this study was to determine whether a correlation exists between the sonographic findings and the clinical outcomes, defined as surgery or death, in neonates with radiographically and/or histopathologically confirmed necrotizing enterocolitis (NEC). Material and Methods In this retrospective study, the case notes of 58 patients admitted to Karolinska University Hospital, Stockholm, Sweden, with radiographically confirmed NEC from September 2010 to August 2013, were reviewed. We included all newborns who underwent both plain abdominal radiographs and an abdominal ultrasound on the same day. The images were reviewed retrospectively. Patients' characteristics, clinical data, and histopathological data were recorded from the case notes. We excluded newborns who developed free gas before surgery. Abdominal ultrasound images were reviewed for free intraperitoneal gas, peritoneal fluid, pneumatosis intestinalis, portal gas, bowel vascularity, bowel wall thickness, and peristalsis. We correlated the sonographic features with the clinical outcomes; defined as the need for surgery or death. Results Overall, 25 neonates were included. Out of these, 11 patients underwent surgery and 5 patients died. The sonographic finding of complex fluid collection was statistically significant, predicting severe NEC that needed surgery. No other sonographic features were related to the need for surgery or death. Conclusion Complex fluid collection shown with abdominal ultrasound appears to be strongly correlated to the need for surgery in newborn infants with severe NEC.

Recurrence of acute appendicitis after non-operative treatment of appendiceal abscess in children: a single-centre experience.

BACKGROUND/PURPOSE: The aim of this study was to evaluate the incidence of recurrence of acute appendicitis after initial successful non-operative treatment of appendiceal abscess in children. METHODS: This study was an observational cohort study of children treated non-operatively for appendiceal abscess at a large tertiary referral centre from 2006 to 2010. The primary outcome was recurrence of acute appendicitis. Secondary outcome variables were re-admission and interval appendectomy. RESULTS: Eighty-nine patients were discharged after successful non-operative treatment of appendiceal abscess. The median age was 10.1 (1.3-16.3) years. Nine patients underwent surgery during the follow-up period. Five patients were re-admitted with ongoing symptoms leading to an appendectomy. They all returned shortly after discharge and are considered failures of initial treatment. Two of 82 patients returned with a new episode of acute appendicitis during the trial period. Hence, the recurrence rate was 2.4 % during 5.1 years of follow-up. CONCLUSION: Our data support the strategy of not performing an interval appendectomy after successful non-operative treatment with antibiotics of an appendiceal abscess in children.

Novel mutations in the MNX1 gene in two families with Currarino syndrome and variable phenotype.

The Currarino syndrome (CS) consists of a sacral defect, an anorectal malformation and a pre-sacral mass. It manifests as an autosomal dominant congenital malformation in familial settings, with varying penetrance. The disease-causing gene, Motor neuron and pancreas homeobox-1 (MNX1), is known to be mutated in almost all familial cases, but due to the lack of genotype-phenotype correlation, there is a need for better clinical and molecular genetic characterization of the CS. Here, we report two novel mutations in the MNX1 gene in two cases. Each case was found to be familial upon further investigation of the other members of each family. The first affected case (a one year old boy) exhibited a missense mutation, p.Phe289Ser, in exon 3 in the highly conserved third helix of the homeodomain, which is considered to affect the DNA binding property and transcription regulation of the protein. The mutation seemed to display full penetrance of the disease in this family, but with different time of on-set. The second affected case (a 5 months old boy) displayed a 13 basepair insertion in exon 1, creating a complex frameshift mutation which results in a premature truncation of the protein that lacks the third helix homeodomain. Other members of the boy's family, who harbored the same mutation, were found to be completely asymptomatic. In conclusion, we detected two novel mutations in the MNX1 gene in cases with CS, which supports mutational analysis in the diagnosis of CS, even though the variability in the genotype and phenotype correlation maintains.

Does enteral contrast increase the accuracy of appendicitis diagnosis?

BACKGROUND: Several approaches traditionally have helped opacify the bowel when computed tomography (CT) is used to diagnose appendicitis. With the development of multidetector row CT (MDCT), the need for enteral contrast agents is less obvious. Purpose The objective of this study was to evaluate retrospectively the accuracy of MDCT demonstration of appendicitis using enteral contrast agents. METHODS: We reviewed radiologic reports of all 246 adult patients with suspected appendicitis who underwent 16-slice MDCT during 2005-2006 at our department. The use of enteral contrast agents and the route of administration were documented by one investigator. A radiologist evaluated whether the responses in the reports were consistent with diagnosis of appendicitis. The accuracy of the radiologic reports was assessed using the results of surgery, histopathology and 3 to 21 months of follow-up. RESULTS: Of patients studied, 14.6% received no enteral contrast agent, 8.5% received both oral contrast and rectal contrast (enema), 46.7% received oral contrast and 30.1% received rectal contrast enemas. The accuracies for the CT diagnosis of appendicitis with different combinations of agents ranged from 95% to 100%, with no significant difference among groups. CONCLUSION: Our study shows that the accuracy for diagnosis of appendicitis by abdominal 16-slice MDCT is high regardless of enteral contrast use. Therefore, further use of enteral contrast agents for CT diagnosis of appendicitis in adults cannot be recommended.

"Wandering liver" in a neonate: case report and review of the literature.

Wandering liver describes the phenomenon where the liver moves freely from the right side of the abdomen to the left. It is believed to be associated with a persistent ventral mesentery, and most reported cases were diagnosed during investigations of intestinal obstruction. The operative findings describe lax or absent suspensory ligaments of the liver and a long colonic mesentery. There are only a few presentations of asymptomatic wandering liver, and there is no clear course of treatment of those cases. We present a case of wandering liver in a prematurely born neonate and a review of the literature.

Pharmacokinetics and safety of gadobutrol-enhanced magnetic resonance imaging in pediatric patients.

OBJECTIVES: This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years. MATERIALS AND METHODS: In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated. RESULTS: A total of 130 patients (2-6 years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 micromol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients. CONCLUSIONS: Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.

Oophoropexy, hyperbaric oxygen therapy, and contrast-enhanced ultrasound after asynchronous bilateral ovarian torsion.

A girl with asynchronous, bilateral ovarian torsion with previous oophorectomy presented with her second torsion. A laparoscopic untwisting of the torsed ovary was performed, treatment with hyperbaric oxygen therapy was given, and the outcome was followed with contrast-enhanced ultrasound. After 1 month, a laparoscopic oophoropexy was performed. The detorsed ovary regained its circulation and decreased in size. It looked normal at the time for oophopexy and at follow-up. This case supports the evidence of an ovarian-sparing approach to ovarian torsion in children and supports oophoropexy after torsion of a detorsed, otherwise normal ovary in the premenarcheal girl.

Impact of radiologic imaging on the surgical decision-making process in suspected appendicitis in children.

RATIONALE AND OBJECTIVES: To evaluate how the surgeons' decision-making process in appendicitis in children is affected by radiologic imaging. MATERIALS AND METHODS: Prospective study including 593 children with suspected appendicitis was conducted. The surgeon's initial clinical disposition was recorded, designating the patient for operation, observation, or discharge. Thereafter, the patients were randomized to undergo either ultrasound only or ultrasound and abdominal computed tomography. The studies were evaluated by radiologists, who indicated if appendicitis was present or not. After radiology was completed, the surgeon re-examined the patient and made the final disposition. The change of disposition pathway was recorded. Final diagnoses were established by means of surgical, histopathologic, and/or clinical follow-up findings. RESULTS: Two hundred forty-four patients had appendicitis. The initial clinical disposition called for 88 operations, 338 observations, and 167 discharges. In total, 347 patients had their treatment plan changed from the initial disposition, resulting in 252 operations, 65 observations, and 276 discharges. In 11 patients, an unnecessary operation was possibly avoided. In 28 patients who turned out to have appendicitis, a possible inappropriate discharge was avoided. Eighteen patients had a false-negative radiologic diagnosis. Of these, 17 underwent surgery because of convincing clinical findings. The difference between the impact on surgeons' decision-making between the two randomized groups was not substantially different. The negative appendectomy rate was 3.7%. CONCLUSION: Radiologic imaging with ultrasound and/or computed tomography provides valuable guidance whether a patient should be discharged, observed, or given surgical treatment, leading to beneficial changes in management plan. Still, false-negative results may occur and a close clinical re-examination is of utmost importance for the appropriate final decision.

Suspected appendicitis in children: diagnosis with contrast-enhanced versus nonenhanced Helical CT.

PURPOSE: To compare the diagnostic accuracy of limited-area (lower abdominal) nonenhanced helical computed tomography (CT), intravenous contrast material-enhanced helical CT of the entire abdomen, and the combination of both. MATERIALS AND METHODS: Three hundred six children suspected of having appendicitis, who were previously included in a prospective study, underwent limited-area nonenhanced helical CT of the lower abdomen and contrast-enhanced CT of the entire abdomen. No oral or rectal contrast material was administered. The CT scans were retrospectively reviewed by three independent readers both separately and together. The readers were blinded to all clinical information and to the results of previous ultrasonographic and CT examinations. Final diagnoses were established on the basis of surgical, histopathologic, or clinical follow-up findings. The Pearson chi(2) test was performed to compare values between groups. The Student two-sample t test was performed to determine statistically significant differences in age and sex. RESULTS: One hundred twenty-nine patients (42%) had appendicitis. Readers diagnosed appendicitis with 66% pooled sensitivity and 96% pooled specificity with limited-area nonenhanced CT. With contrast-enhanced CT of the entire abdomen, appendicitis was diagnosed with 90% pooled sensitivity and 94% pooled specificity. With both sequences together, readers diagnosed appendicitis with 90% pooled sensitivity and 94% pooled specificity. The difference between the sensitivity of limited-area nonenhanced CT and that of contrast-enhanced CT was statistically significant (P <.001). CONCLUSION: Sensitivity of helical CT for suspected appendicitis in children improved significantly with abdominal contrast-enhanced CT compared with limited-area nonenhanced CT. No further improvement in sensitivity was achieved with the combination of both sequences in comparison to that with contrast-enhanced CT alone.

Suspected appendicitis in children: US and CT--a prospective randomized study.

PURPOSE: To evaluate the accuracy of ultrasonography (US) and of abdominal computed tomography (CT) performed in addition to US in the diagnosis of childhood appendicitis. MATERIALS AND METHODS: Six hundred children with suspected appendicitis were included in a prospective randomized study. After clinical examination, the patients were randomly assigned to undergo US only (283 patients) or US with abdominal CT (317 patients). Radiologic findings were correlated with surgical, histopathologic, and clinical follow-up findings. RESULTS: Two hundred forty-four (40.7%) of all patients had appendicitis. In the US only group, US had a sensitivity of 86%, specificity of 95%, positive predictive value of 91%, negative predictive value of 92%, and diagnostic accuracy of 92%. The combination of US and CT performed in the other group yielded a sensitivity of 99%, specificity of 89%, positive predictive value of 87%, negative predictive value of 99%, and diagnostic accuracy of 93%. Analysis of data on US performed in all 600 patients and on CT performed in 317 patients revealed, respectively, sensitivities of 80% and 97%, specificities of 94% and 93%, positive predictive values of 91% and 92%, negative predictive values of 88% and 98%, and diagnostic accuracies of 89% and 95%. The overall negative appendectomy rate was 3.7%; and the perforation rate, 21%. CONCLUSION: US is valuable in the diagnosis of appendicitis in children. In inconclusive cases, performing additional abdominal CT can improve diagnostic accuracy and thereby decrease the negative appendectomy rate without an increase in the perforation rate.