A child presenting with acute renal failure secondary to a high dose of indomethacin: a case report

<p>Abstract</p> <p>Introduction</p> <p>Acute renal failure caused by nonsteroidal anti-inflammatory drugs administered at therapeutic doses is generally mild, non-anuric and transitory. There are no publications on indomethacin toxicity secondary to high doses in children. The aim of this article is to describe acute renal failure secondary to a high dose of indomethacin in a child and to review an error in a supervised drug prescription and administration system.</p> <p>Case presentation</p> <p>Due to a medication error, a 20-day-old infant in the postoperative period of surgery for Fallot's tetralogy received a dose of 10 mg/kg of indomethacin, 50 to 100 times higher than the therapeutic dose. The child presented with acute, oligo-anuric renal failure requiring treatment with continuous venovenous renal replacement therapy, achieving complete recovery of renal function with no sequelae.</p> <p>Conclusion</p> <p>In order to reduce medication errors in critically ill children, it is necessary to develop a supervised drug prescription and administration system, with controls at various levels.</p

Predicting non-invasive ventilation failure in children from the SpO₂/FiO₂ (SF) ratio

PURPOSE: Our objective was to assess whether SpO₂/FiO₂ (SF) ratio could be a useful NIV outcome predictor in children with acute respiratory failure (ARF) and tried to develop a predictive model of NIV failure. METHODS: Prospective, observational, multicenter study. Episodes of ARF-fulfilling inclusion criteria from 15 January 2010 to 14 January 2011 were treated with NIV according to a pre-established protocol. Clinical variables were collected at baseline and at 1, 2, 6, 12 and 24 h. Failure criterion was the need for endotracheal intubation. Failures were considered as "early" if occurring ≤6 h after NIV initiation, "intermediate" if occurring between 6 and 24 h, and "late" if occurring after 24 h. Variables with a p < 0.1 in univariate analysis corrected by age were included in multivariate analysis. Models were calculated based on multivariate analysis. RESULTS: During the study period, 390 episodes were included. NIV success rate was 81.3 %. Among ARF causes, failure occurred most frequently in ARDS episodes. The failure predictive model for the whole sample included SF ratio at 1 h, age and PRISM III-24 (area under the curve AUC of 0.755). For early NIV failures, SF ratio at 1 h was the only variable within model (AUC 0.748). The analysis of intermediate NIV failures identified 3 variables independently linked to NIV outcome: PRISM III-24, RR decrease at 6 h, and SF ratio at 6 h (AUC 0.895). No model was identified for late NIV failure. CONCLUSIONS: SF ratio is a reliable predictor of early NIV failure in children

Outcome of paediatric intensive care survivors

The development of paediatric intensive care has contributed to the improved survival of critically ill children. Physical and psychological sequelae and consequences for quality of life (QoL) in survivors might be significant, as has been determined in adult intensive care unit (ICU) survivors. Awareness of sequelae due to the original illness and its treatment may result in changes in treatment and support during and after the acute phase. To determine the current knowledge on physical and psychological sequelae and the quality of life in survivors of paediatric intensive care, we undertook a computerised comprehensive search of online databases for studies reporting sequelae in survivors of paediatric intensive care. Studies reporting sequelae in paediatric survivors of cardiothoracic surgery and trauma were excluded, as were studies reporting only mortality. All other studies reporting aspects of physical and psychological sequelae were analysed. Twenty-seven studies consisting of 3,444 survivors met the selection criteria. Distinct physical and psychological sequelae in patients have been determined and seemed to interfere with quality of life. Psychological sequelae in parents seem to be common. Small numbers, methodological limitations and quantitative and qualitative heterogeneity hamper the interpretation of data. We conclude that paediatric intensive care survivors and their parents have physical and psychological sequelae affecting quality of life. Further well-designed prospective studies evaluating sequelae of the original illness and its treatment are warranted

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012

OBJECTIVE: To provide an update to the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," last published in 2008. DESIGN: A consensus committee of 68 international experts representing 30 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict of interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independent of any industry funding. A stand-alone meeting was held for all subgroup heads, co- and vice-chairs, and selected individuals. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. METHODS: The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations as strong (1) or weak (2). The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. Recommendations were classified into three groups: (1) those directly targeting severe sepsis; (2) those targeting general care of the critically ill patient and considered high priority in severe sepsis; and (3) pediatric considerations. RESULTS: Key recommendations and suggestions, listed by category, include: early quantitative resuscitation of the septic patient during the first 6 h after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm a potential source of infection (UG); administration of broad-spectrum antimicrobials therapy within 1 h of the recognition of septic shock (1B) and severe sepsis without septic shock (1C) as the goal of therapy; reassessment of antimicrobial therapy daily for de-escalation, when appropriate (1B); infection source control with attention to the balance of risks and benefits of the chosen method within 12 h of diagnosis (1C); initial fluid resuscitation with crystalloid (1B) and consideration of the addition of albumin in patients who continue to require substantial amounts of crystalloid to maintain adequate mean arterial pressure (2C) and the avoidance of hetastarch formulations (1B); initial fluid challenge in patients with sepsis-induced tissue hypoperfusion and suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids (more rapid administration and greater amounts of fluid may be needed in some patients (1C); fluid challenge technique continued as long as hemodynamic improvement is based on either dynamic or static variables (UG); norepinephrine as the first-choice vasopressor to maintain mean arterial pressure ≥65 mmHg (1B); epinephrine when an additional agent is needed to maintain adequate blood pressure (2B); vasopressin (0.03 U/min) can be added to norepinephrine to either raise mean arterial pressure to target or to decrease norepinephrine dose but should not be used as the initial vasopressor (UG); dopamine is not recommended except in highly selected circumstances (2C); dobutamine infusion administered or added to vasopressor in the presence of (a) myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output, or (b) ongoing signs of hypoperfusion despite achieving adequate intravascular volume and adequate mean arterial pressure (1C); avoiding use of intravenous hydrocortisone in adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability (2C); hemoglobin target of 7-9 g/dL in the absence of tissue hypoperfusion, ischemic coronary artery disease, or acute hemorrhage (1B); low tidal volume (1A) and limitation of inspiratory plateau pressure (1B) for acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure (PEEP) in ARDS (1B); higher rather than lower level of PEEP for patients with sepsis-induced moderate or severe ARDS (2C); recruitment maneuvers in sepsis patients with severe refractory hypoxemia due to ARDS (2C); prone positioning in sepsis-induced ARDS patients with a PaO (2)/FiO (2) ratio of ≤100 mm Hg in facilities that have experience with such practices (2C); head-of-bed elevation in mechanically ventilated patients unless contraindicated (1B); a conservative fluid strategy for patients with established ARDS who do not have evidence of tissue hypoperfusion (1C); protocols for weaning and sedation (1A); minimizing use of either intermittent bolus sedation or continuous infusion sedation targeting specific titration endpoints (1B); avoidance of neuromuscular blockers if possible in the septic patient without ARDS (1C); a short course of neuromuscular blocker (no longer than 48 h) for patients with early ARDS and a PaO (2)/FI O (2) 180 mg/dL, targeting an upper blood glucose ≤180 mg/dL (1A); equivalency of continuous veno-venous hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1B); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding in patients with bleeding risk factors (1B); oral or enteral (if necessary) feedings, as tolerated, rather than either complete fasting or provision of only intravenous glucose within the first 48 h after a diagnosis of severe sepsis/septic shock (2C); and addressing goals of care, including treatment plans and end-of-life planning (as appropriate) (1B), as early as feasible, but within 72 h of intensive care unit admission (2C). Recommendations specific to pediatric severe sepsis include: therapy with face mask oxygen, high flow nasal cannula oxygen, or nasopharyngeal continuous PEEP in the presence of respiratory distress and hypoxemia (2C), use of physical examination therapeutic endpoints such as capillary refill (2C); for septic shock associated with hypovolemia, the use of crystalloids or albumin to deliver a bolus of 20 mL/kg of crystalloids (or albumin equivalent) over 5-10 min (2C); more common use of inotropes and vasodilators for low cardiac output septic shock associated with elevated systemic vascular resistance (2C); and use of hydrocortisone only in children with suspected or proven "absolute"' adrenal insufficiency (2C). CONCLUSIONS: Strong agreement existed among a large cohort of international experts regarding many level 1 recommendations for the best care of patients with severe sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for this important group of critically ill patients

Hepatic PEcoma: an unusual tumor in an infrequent location

Los tumores de células neoplásicas perivasculares epitelioides (PEComas) son una familia de tumoraciones caracterizada apenas un par de décadas antes. Componen un grupo inusual de neoplasias, que puede aparecer en distintas localizaciones del organismo. Por lo general, los PEComas se consideran tumores benignos, pero hay ciertas características histológicas que hacen de algunos subgrupos lesiones sospechosas de una malformación maligna. El tratamiento de estos tumores consiste en la resección quirúrgica, pero no existe tratamiento oncológico por completo eficaz. Se presenta el caso clínico de una mujer sometida a la resección de una lesión hepática con diagnóstico posterior de PEComa con rasgos de proceso malignoPerivascular epithelioid cell neoplasms (PEComas) are a tumor family defined as such just a couple of decades ago. They make an unusual group of neoplasms, which can appear in different locations of the organism. PEComas are usually considered to be benign tumors, but there are some histological features that make some subgroups suspicious of malignancy. The treatment of these tumors consist in their surgical resection, with no current effective complementary oncological treatment known. We present the clinical case of a woman that underwent surgery for a resection of a hepatic lesion labeled afterwards as a PEComa with malignant features

PEComa hepático: un tumor inusual en una localización infrecuente.

Perivascular epithelioid cell neoplasms (PEComas) are a tumor family defined as such just a couple of decades ago. They make an unusual group of neoplasms, which can appear in different locations of the organism. PEComas are usually considered to be benign tumors, but there are some histological features that make some subgroups suspicious of malignancy. The treatment of these tumors consist in their surgical resection, with no current effective complementary oncological treatment known. We present the clinical case of a woman that underwent surgery for a resection of a hepatic lesion labeled afterwards as a PEComa with malignant features

Tools for the Individualized Therapy of Teicoplanin for Neonates and Children

ABSTRACT The aim of this study was to develop a population pharmacokinetic (PK) model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the software constructed for individualized therapy. We developed a nonparametric population model fitted to PK data from neonates, infants, and older children. We then implemented this model in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility. It was used to predict the dosages required to achieve optimal teicoplanin predose targets (15 mg/liter) from day 3 of therapy. We performed individual simulations for an infant and a child from the original population, who provided early first dosing interval concentration-time data. An allometric model that used weight as a measure of size and that also incorporated renal function using the estimated glomerular filtration rate (eGFR), or the ratio of postnatal age (PNA) to serum creatinine concentration (SCr) for infants &lt;3 months old, best described the data. The median population PK parameters were as follows: elimination rate constant (Ke) = 0.03 · (wt/70) −0.25 · Renal (h −1 ); V = 19.5 · (wt/70) (liters); Renal = eGFR 0.07 (ml/min/1.73 m 2 ), or Renal = PNA/SCr (μmol/liter). Increased teicoplanin dosages and alternative administration techniques (extended infusions and fractionated multiple dosing) were required in order to achieve the targets safely by day 3 in simulated cases. The software was able to predict individual measured concentrations and the dosages and administration techniques required to achieve the desired target concentrations early in therapy. Prospective evaluation is now needed in order to ensure that this individualized teicoplanin therapy approach is applicable in the clinical setting. (This study has been registered in the European Union Clinical Trials Register under EudraCT no. 2012-005738-12.) </jats:p