Methemoglobinemia : a rare side effect of a healthy diet

Methemoglobinemia: a rare side effect of a healthy diet P Naessens, T Van Der Heggen, A D'Hooghe, K Sauer. AZ Sint-Jan Background An 11-month-old girl, without relevant medical history, presented at the emergency department with central cyanosis and an extremely pale skin, noticed by her parents when she woke up from an afternoon nap. She was alert but irritable, there was no shortness of breath. Her oxygen saturation was 80-85% while breathing ambient air and did not respond to high flow oxygen. Chest X-ray was normal. Venous blood gas analysis showed a normal pO2, but revealed methemoglobin (MetHb) levels of 44%. Before sleeping, the girl had lunch with home grown turnips and broad beans. Methods A literature-search was done in PubMed with MeSH-terms ‘cyanosis’, ‘methemoglobinemia’ and ‘child’. Results Methemoglobinemia is characterized by increased quantities of hemoglobin containing iron in the oxidized ferric form (Fe3+) instead of the usual ferrous (Fe2+) form. It is an uncommon blood disorder, resulting in a ‘functional anemia’ with tissue hypoxia. Patients present with a varying degree of cyanosis, proportional to their MetHb level. Symptoms are usually noticed starting from a 15% fraction (normal MetHb fraction is 1%). Levels higher than 70% can be fatal. The etiology is either congenital or acquired and in most cases due to exposure to oxidizing drugs or toxins, by ingestion or skin contact. In our patient, the presumed causative agent is a high amount of nitrates, a molecule found in well water and some foods, especially in green leafy vegetables and root vegetables. Hereditary methemoglobinemia is rare but should be considered. The diagnosis is confirmed by direct measurement of MetHb, but can be suspected from a normal pO2 concentration on a blood gas, despite cyanosis and a low oxygen saturation. If identified, it is important to remove or discontinue the causative agent. Supplemental oxygen should be administered. Treatment with methylene blue is advised if MetHb level > 20%. In critically ill patients, or if MetHb level > 70%, an exchange transfusion or hemodialysis should be considered immediately. Conclusion Always suspect methemoglobinemia in children with central cyanosis without respiratory distress or cardiac disorder, not responding to oxygen administration. Low oxygen saturation with normal pO2 on blood gas analysis provides the clue to diagnosis. Usually methemoglobinemia is caused by exposure to certain drugs or toxins that can be found even in vegetables. Methylene blue is the treatment of choice

Beta-lactam antibiotics in critically ill children : who is at risk for suboptimal treatment?

Background and aims In critically ill children, severely altered pharmacokinetics often result in subtherapeutic antibiotic concentrations. However, it remains unclear how to recognize those patients most at risk for suboptimal exposure and outcome data are lacking. This study aimed to identify risk factors for target non-attainment and clinical failure in critically ill children treated with beta-lactam antibiotics. Methods This observational cohort study included critically ill children aged 1 month to 15 years, treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam or meropenem. Steady-state trough plasma concentrations were considered therapeutic if ≥ MIC of the (suspected) pathogen. Risk factors were identified by logistic regression analysis. Results 382 trough concentrations were obtained from 157 patients (median age 1.25 years, Q1 0.4; Q3 4.2). Subtherapeutic concentrations were measured in 75.0%, 97.9% and 61.2% of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem, respectively. eGFR (p <0.001) and the absence of vasopressor treatment (p=0.026) were found as independent predictors of target non-attainment, whilst log transformed CRP was significantly related to clinical outcome (p=0.049). An association between antibiotic concentrations and clinical failure (22.9%) was not observed. Conclusions Subtherapeutic β-lactam antibiotic concentrations are common in critically ill children and correlate with renal function. Commonly used eGFR equations are helpful to identify patients who require higher doses. Future studies should focus on dose optimization and evaluation of its effect on clinical outcome

Augmented renal clearance in pediatric intensive care : are we undertreating our sickest patients?

Many critically ill patients display a supraphysiological renal function with enhanced renal perfusion and glomerular hyperfiltration. This phenomenon described as augmented renal clearance (ARC) may result in enhanced drug elimination through renal excretion mechanisms. Augmented renal clearance seems to be triggered by systemic inflammation and therapeutic interventions in intensive care. There is growing evidence that ARC is not restricted to the adult intensive care population, but is also prevalent in critically ill children. Augmented renal clearance is often overlooked due to the lack of reliable methods to assess renal function in critically ill children. Standard equations to calculate glomerular filtration rate (GFR) are developed for patients who have a steady-state creatinine production and a stable renal function. Those formulas are not reliable in critically ill patients with acutely changing GFR and tend to underestimate true GFR in patients with ARC. Tools for real-time, continuous, and non-invasive measurement of fluctuating GFR are most needed to identify changes in kidney function during critical illness and therapeutic interventions. Such devices are currently being validated and hold a strong potential to become the standard of practice. In the meantime, urinary creatinine clearance is considered the most reliable method to detect ARC in critically ill patients. Augmented renal clearance is clearly associated with subtherapeutic antimicrobial concentrations and subsequent therapeutic failure. This warrants the need for adjusted dosing regimens to optimize pharmacokinetic and pharmacodynamic target attainment. This review aims to summarize current knowledge on ARC in critically ill children, to give insight into its possible pathophysiological mechanism, to evaluate screening methods for ARC in the pediatric intensive care population, and to illustrate the effect of ARC on drug exposure, therapeutic efficacy, and clinical outcome

Critically ill children treated with beta-lactam antibiotics : how to identify patients at risk for suboptimal exposure and clinical failure?

Background and aims In critically ill children, severely altered pharmacokinetics often result in subtherapeutic antibiotic concentrations. However, it remains unclear how to recognize those patients most at risk for suboptimal exposure and outcome data are lacking. This study aimed to identify risk factors for target non-attainment and clinical failure in critically ill children treated with beta-lactam antibiotics. Methods This observational cohort study included critically ill children aged 1 month to 15 years, treated intravenously with amoxicillin-clavulanic acid, piperacillin-tazobactam or meropenem. Steady-state trough plasma concentrations were considered therapeutic if ≤ MIC of the (suspected) pathogen. Risk factors for subtherapeutic concentrations and clinical failure were identified by logistic regression analysis. Clinical failure was defined as insufficient lessening of signs and symptoms and the need for alternate antimicrobial therapy. Results 382 trough concentrations were obtained from 157 patients (median age 1.25 years, Q1 0.4; Q3 4.2). Subtherapeutic concentrations were measured in 75.0%, 97.9% and 61.2% of patients treated with amoxicillin-clavulanic acid, piperacillin-tazobactam and meropenem, respectively. eGFR (p <0.001) and the absence of vasopressor treatment (p=0.026) were found as independent predictors of target non-attainment, whilst log transformed CRP was significantly related to clinical outcome (p=0.049). An association between antibiotic concentrations and clinical failure (22.9%) was not observed. Conclusions Subtherapeutic β-lactam antibiotic concentrations are common in critically ill children and correlate with renal function. Commonly used eGFR equations are helpful in daily practice to identify patients who require higher doses. Future studies should focus on dose optimization and evaluation of its effect on clinical outcome