Lack of Antibiotic Benefit in Acute Uncomplicated Severe Malnutrition

Another terrific summary of an NEJM article on the use of amoxicillin for acute uncomplicated severe malnutrition in Niger.  Link:  86 second Quick Take on Antibiotics for Malnutrition

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Missing Bacteria in Refractory Malnutrition

A recent article in the NY Times reports on a Nature study (Link: Bacteria and Malnutrition) which showed that certain bacteria were essential in resolving malnutrition.  Here is an excerpt:

When children are starving, the bacteria that live in their intestines may determine whether they can be saved, scientists working in Bangladesh are reporting. And they say it may become imperative to find a way to give children bacteria as well as food.

The study, done by researchers from Washington University School of Medicine in St. Louis and the International Center for Diarrheal Disease Research in Dhaka, the Bangladeshi capital, was published by Nature last week…stool samples showed that severely malnourished children often lack the needed species and do not acquire them even when they are fed nutrition-dense therapeutic foods like the peanut-based Plumpy’Nut or lentil-based porridges for weeks. As a result, they may remain stunted and mentally handicapped although they are getting enough calories to live.

Another “chilling” story from NY Times describes E.P.R. (Link: “Emergency Preservation and Resuscitation“) which involves rapidly chilling catastrophic trauma victims by draining their blood and replacing with cold salt water.  This has the potential to dramatically improve survival and has been effective in animal models.

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Malnutrition Redefined

Defining malnutrition accurately is the focus of a new report (JPEN 2013; DOI: 10.1177/0148507113479972). Thanks to Kipp Ellsworth for this article.

The Pediatric Malnutrition Definitions Workgroup was formed in April 2010 and makes numerous relevant contributions to precisely defining malnutrition.  The reasons for this workgroup and report are to promote the following:

  • early identification of those at risk for malnutrition
  • allow better comparison of malnutrition prevalence & collect meaningful data
  • develop uniform screening tools
  • develop thresholds for intervention
  • improve assessment of outcomes

“Pediatric malnutrition (undernutrition) is defined as an imbalance between nutrient requirement and intake, resulting in cumulative deficits of energy, protein, or micronutrients that may negatively affect growth, development, or other relevant outcomes.”

First, malnutrition is subdivided into two categories: illness-related malnutrition and non-illness-related malnutrition.  Illness-related malnutrition refers to malnutrition caused by chronic conditions, burns, and surgery.  It is the predominant cause in developed countries.  Non-illness-related malnutrition refers to malnutrition caused by environmental or behavioral factors (including food aversions or anorexia).

Illness-related malnutrition occurs due to nutrient loss, increased energy expenditure, decreased nutrient intake, or altered nutrient utilization.

In brief, patients need to be assessed in five domains: anthropometrics, growth charts, chronicity, etiology/pathogenesis, and functional status.

Summary of recommendations:

  1. Record anthropometric variables on admission and serially.  These measurements include weight, height, BMI, mid-upper arm circumference (MUAC) and consider triceps skin fold (TSF) and mid-arm muscle circumference.  Obtain head circumference if younger than 2 years.
  2. In infants/children <2 years, measure length with recumbent board. In older patients unable to stand, consider alternative measurement like tibia length or knee height for a height proxy.
  3. Use the 2006 World Health Organization growth charts in patients younger than 2 years and the CBC 2000 growth charts for children 2-20 years. In addition, use corrected age (number of weeks/months premature + chronological age) for preterm infants until they are 3 years old.
  4. Use a decline in z score for individual anthropometric measurements as the indication of faltering growth.
  5. Use 3 months as a cutoff to classify as acute or chronic.
  6. Include description of predominant mechanism of malnutrition: decreased intake, increased requirements, excessive losses, or failure to assimilate/malabsorption.
  7. Recognize the role of inflammation on nutrition status.
  8. Assess impact of malnutrition: consider developmental assessment, lean body mass measurements, and measures of muscle strength.

By having a better established uniform definition of malnutrition, impact on outcomes will be easier to assess. In addition to the potential outcomes noted above (#8), others that will need to be examined in relation to malnutrition include length of hospital stay, wound healing, frequency of infections, behavioral problems, and disease-specific resource utilization.

This article also reviews previous definitions and potential problems with their usage.  For example, Waterlow criteria rely on percentiles and standard deviations and are used widely.  In hospitalized children, accurate serial weights and heights can be challenging due to fluid retention and poor mobility.

The authors note that malnutrition is likely underdiagnosed and inadequately treated.  Some recent estimates indicate that malnutrition is present “in 40% of patients with neurologic conditions, 34.5% in those with infectious diseases, 33.3% of those with cystic fibrosis, 28.6% in those with cardiovascular disease, 27.3% in oncology patients, and 23.6% in those with GI diseases. Patients with multiple diagnoses are most likely to be malnourished (43.8%).”

Bottomline: A lot of patients are malnourished.  Recognition of malnutrition (defining what is malnutrition) should improve outcomes.

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Microbiome and the risk of Kwashiokor

On the way home from work, NPR highlighted a study that suggests that altered microbiome may increase the risk of Kwashiokor (Gut Microbes May Play Deadly Role In Malnutrition : Shots  – NPR).

Interestingly, a separate article indicates that antibiotics lowers the mortality in severe acute malnutrition (NEJM 2013; 368: 425-35).  In this study, 2767 children from 18 feeding clinics in Malawi (2009-2011) were enrolled in a randomized, double-blind, placebo-controlled trial.  Children were 6 to 59 months of age with severe acute malnutrition.  Those who received amoxicillin, cefdinir, and placebo recovered in 88.7%, 90.9%, and 85.1% respectively.  The relative risk of death in the placebo group was 1.55 compared to amoxicillin and 1.80 compared to cefdinir.  The children in the antibiotic group also had improved growth.

The authors suggest that the reason for improvement is likely to be due to fewer invasive bacterial infections.  These infections are frequent and thought to be related to translocation across compromised mucosal surfaces.  However, perhaps the antibiotics act by producing a more favorable microbiome which in turn promotes improvement.  As such, microbes have a role in contributing to obesity (Microbial transfer for metabolic syndrome? | gutsandgrowth) and to starvation.

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Reasons for refeeding syndrome

Refeeding syndrome (RFS) is defined as the potentially fatal shifts in fluid and electrolytes that may occur in malnourished patients who are abruptly refed either enterally or parenterally.  The biochemical hallmark is hypophosphatemia.  Other changes can include hypokalemia, hypomagnesemia, and thiamin deficiency.  RFS can worsen the prognosis of children with celiac crisis as well (JPGN 2012; 54: 522-5).

A chart review from Lucknow, India from Jan-Dec 2010, identified 5 cases of RFS among 35 celiac patients.  All were severely malnourished.  All had anemia, hypoalbuminemia, hypophosphatemia, hypokalemia, and hypomagnesemia.  All improved with initial caloric restriction followed by gradual escalation of caloric intake along with electrolyte supplementation.

This article shows that a variety of causes of malnutrition can lead to refeeding syndrome. Considering refeeding syndrome in any severely malnourished child may help improve the prognosis by altering the nutritional management.

Additional references:

  • Nutr Clin Pract 2012; 27: 34-40. Reviewed refeeding syndrome publications since 2000.  Hypophosphatemia occurred in 96% of cases (26 of 27).
  • Crit Care Med 2010; 14: R172-R178.  Refeeding syndrome with anorexia.
  • Nutrition 2010; 26: 156-67. Review of refeeding syndrome treatment.
  • Nutr Clin Pract 2008; 23: 166-71.  Death due to refeeding syndrome.
  • JPEN 1990: 14.1; 90-97. Refeeding syndrome review.
  • Crit Care Med 1990; 18: 1030-1033. Review.

Minimizing malnutrition in Biliary Atresia

A retrospective study in Liver Transplantation reviews a single center experience with the use of parenteral nutrition (PN) in patients with end-stage liver disease due to biliary atresia (Liver Transpl 2012; 18: 121-129).  In this study which spanned the past twenty years, 25 PN BA patients were compared to 22 non-PN BA patients –all patients were younger than 36 months.  PN was started when maximal enteral nutrition failed to improve markers of malnutrition (triceps skinfold thickness, & mid-arm circumference).  Among the PN BA patients, there was a higher gastrointestinal bleeding rate and ascites; however, there was no difference in the rates of bacteremia, length of intensive care unit stay after liver transplantation, or patient/graft survival.  The authors speculate that the outcome for the PN BA patients would have been much worse without the PN as malnourished BA patients are at increased risk for graft failure and post-transplant complications.  It is noteworthy that PN patients did have progression of their liver disease that seemed to accelerate with the administration of PN, perhaps due to PN-associated cholestasis.  Specific changes included higher bilirubin levels, lower platelet counts, worsened coagulopathy, and higher calculated PELD scores.

Additional References:

  • Hepatology 2007; 46: 1632-38.  Growth failure and outcomes in infants with BA.
  • J Pediatr 2005; 147: 180-85.  Outcomes of 755 BA patients listed for liver transplantation.