You are in: eMedicine Specialties > Pediatrics: General Medicine > Nutrition MarasmusArticle Last Updated: May 22, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 11
  Author: Mario Gehri, MD, Consulting Staff, Department of Pediatrics, Hôpital De L'Enfance, Centre Hospitalier Universitaire Vaudois, Switzerland Coauthor(s): Nicolas Stettler, MD, MSCE, Assistant Professor, Departments of Pediatrics and Epidemiology, University of Pennsylvania School of Medicine; Consulting Staff, Division of Gastroenterology and Nutrition, Children's Hospital of Philadelphia; Ermindo R Di Paolo, PhD, Pharmacist, Department of Pharmacy, Centre Hospitalier Universitaire Vaudois, Vaud, Switzerland Editors: Maria Rebello Mascarenhas, MBBS, Associate Professor of Pediatrics, University of Pennsylvania School of Medicine; Section Chief, Division of Gastroenterology and Nutrition, Director, Nutrition Support Service, Children's Hospital of Philadelphia; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia; Merrily P M Poth, MD, Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences; Jatinder Bhatia, MBBS, Professor of Pediatrics, Chief, Section of Neonatology, Department of Pediatrics, Medical College of Georgia Author and Editor Disclosure Synonyms and related keywords: marasmus, severe malnutrition, protein energy malnutrition, PEM, kwashiorkor, KW, marasmic KW INTRODUCTIONSection 2 of 11
  BackgroundMarasmus is 1 of the 3 forms of serious protein-energy malnutrition (PEM). The other 2 are kwashiorkor (KW) and marasmic KW. These forms of serious PEM represent a group of pathologic conditions associated with a nutritional and energy deficit occurring mainly in young children from developing countries at the time of weaning. They are frequently associated with infections, mainly gastrointestinal infections. The reasons for a progression of nutritional deficit into marasmus rather than KW are unclear and cannot be solely explained by the composition of the deficient diet (ie, a diet deficient in energy for marasmus and a diet deficient in protein for KW). The study of these phenomena is considerably limited by the lack of an appropriate animal model. Marasmus is a serious worldwide problem that involves more than 50 million children younger than 5 years. According to the World Health Organization (WHO), 49% of the 10.4 million deaths occurring in children younger than 5 years in developing countries are associated with PEM. Malnutrition has been a permanent priority of the WHO for decades. Although PEM occurs more frequently in low-income countries, numerous children from higher-income countries are also affected, including children from large urban areas and of low socioeconomic status, children with chronic disease, and children who are institutionalized. Hospitalized children are also at risk for PEM when they experience complex conditions, such as oncologic disease, genetic disease, or neurological disease, requiring prolonged and complicated hospital care. In these conditions, the challenging nutritional management is often overlooked and insufficient, resulting in an impairment of the chances for recovery and the worsening of an already precarious neurodevelopmental situation. PEM results in not only high mortality (even for hospitalized children, without any improvement during the last 2 decades) but also morbidity and suboptimal neurological development. The social and economic implications of PEM and its complications are incalculable. This review is limited to marasmus resulting from an insufficient nutritional intake as observed under impaired socioeconomic conditions, such as those present in developing countries. This condition is most frequently associated with acute conditions (eg, gastroenteritis) or chronic conditions (eg, tuberculosis, HIV infection). PathophysiologyVarious extensive reviews of the pathophysiological processes resulting in marasmus exist. Unlike KW, marasmus can be considered as an adaptation to an insufficient energy intake. Marasmus results from a negative energy balance. This imbalance can result from a decreased energy intake, increased energy expenditure, or both, such as that observed in acute or chronic disease. Children adapt to an energy deficit with a decrease in physical activity, lethargy, a decrease in basal energy metabolism, slowing of growth, and finally weight loss. Pathophysiological changes associated with nutritional and energy deficits can be described as (1) body composition changes, (2) metabolic changes, and (3) anatomic changes. Body compositionBody mass: Body mass is significantly decreased in a heterogeneous way. Fat mass: Fat stores can decrease to as low as 5% of the total body weight and be macroscopically undetectable. The remaining fat is usually stored in the liver, as is often observed in KW but also to a lesser extent in marasmus. Total body water: The proportion of water content in the body increases with the increased seriousness of PEM (marasmus or KW) and is associated with the loss of fat mass, which is poor in water. The proportion of extracellular water also increases, often resulting in edema. Edema is significant in KW but can also be present in marasmus or in the frequently encountered mixed forms of PEM. The increase in extracellular water is proportional to the increase in the total body water. During the first days of therapy, part of the extracellular water shifts to the intracellular compartment and part of it is lost in the urine, resulting in the observed initial weight loss with treatment. Protein mass: Mainly represented by muscle and some organs (eg, heart), protein mass can decrease up to 30% in the most serious forms. The muscle fibers are thin with loss of striation. Muscle cells are atrophic, and muscle tissue is infiltrated with fat and fibrous tissue. Total recovery is long, but it seems possible. Other organ mass: The brain, skeleton, and kidney are preserved, whereas the liver, heart, pancreas, and digestive tract are first affected. Pediatric and adult physiologic change: Finally, physiologic changes are different in infants and children when compared to adults. For example, marasmic infants have an increased tendency to hypothermia and hypoglycemia, requiring the frequent administration of small meals. This can be explained by the body composition imbalance of marasmic children in favor of high–energy-consuming organs, such as brain and kidney, as compared to energy storage organs, such as muscle and fat. Assessment of fat and muscle mass: As described below, assessment of the fat and muscle mass loss can be performed clinically by measuring arm circumference (see Image 1) or skinfold thickness, such as triceps skinfold. The diagram illustrates the validity of this assessment method. Because arm circumference is relatively constant in healthy children aged 1-5 years, it roughly represents a general assessment of nutritional status. Minerals and vitaminsPotassium: Potassium is the electrolyte most studied in marasmus. Total body potassium deficit is associated with decreased muscle mass, poor intake, and digestive losses. This potassium deficit, which can reach 15 mEq/kg, contributes to hypotonia, apathy, and impaired cardiac function. Other electrolytes: Plasma sodium concentration is generally within the reference range, but it can be low, which is then a sign of a poor prognosis. However, intracellular sodium level is elevated in the brain, muscle, and red and white blood cells, explaining the sodium excretion in the first days of recovery. Other minerals: A deficit in calcium, phosphorus, and magnesium stores also exists. Iron deficiency anemia is consistently observed in marasmus. However, in the most serious forms, iron accumulates in the liver, most likely because of the deficit in transport protein. These patients are at higher risk of mortality; therefore, iron is supplemented only after the acute recovery phase is completed. Zinc, selenium, and magnesium are more significantly reduced in KW but are also constantly deficient in marasmus. Several studies have shown improved recovery from malnutrition and decreased mortality with supplementation of these 3 micronutrients. Vitamins: Both fat-soluble vitamins (ie, A, D, E, K) and water-soluble vitamins (eg, B-6, B-12, folic acid) must be systematically administered. Vitamin A is essential to retinal function, has a trophic effect on epithelial tissues, and plays a major role as an antioxidant agent. Vitamin A deficit affects visual function (eg, conjunctivitis, corneal ulcer, night blindness, total blindness) and digestive, respiratory, and urinary functions. Furthermore, vitamin A supplementation programs have resulted in decreased mortality and morbidity, in particular, during diarrheal disease and measles. Vitamin and micronutrient deficiencies can be differentiated in 2 categories listed below. Patients with deficiencies of type 1 nutrients present with late and specific clinical signs. In contrast, patients with deficiencies of type 2 nutrients are difficult to identify because blood levels are unreliable and the clinical signs are nonspecific, such as the growth retardation with mild deficiency and weight loss with significant deficiency. Furthermore, type 2 nutrient deficiencies are often combined. Therefore, these deficiencies are global and require a global nutritional rehabilitation, such as WHO standardized solution. Below are characteristics of type 1 and type 2 deficiencies, according to Golden from a 1991 report.
Below are lists of nutrient classification according to the clinical response to deficiency in type 1, with reduction of tissue concentration, and type 2 with growth deficit.
Metabolic changesEnergy metabolism: With reduced energy intake, a decrease in physical activity occurs along with a slower and, ultimately, lack of growth. Weight loss first occurs by a decrease in fat mass, then a decrease in muscle mass, as clinically measured by changes in arm circumference (see Image 1). Muscle mass loss results in a decrease of energy expenditure. Reduced energy metabolism can impair the response of patients with marasmus to changes in environmental temperature, resulting in an increased risk of hypothermia. Furthermore, during infection, fever is reduced compared to a well-nourished patient. In case of nutrient deficiency, the metabolism is redirected to vital function (requiring 80-100 kcal/kg/d). During recovery, the energy cost of catch-up growth has to be added (up to 100 kcal/kg/d). At this stage, energy needs can be massive. Protein metabolism: Intestinal absorption of amino acids is maintained, despite the atrophy of the intestinal mucosa. Protein turnover is decreased (up to 40% in severe forms), and protein-sparing mechanisms regulated by complex hormonal controls redirect amino acids to vital organs. Amino acids liberated from the loss of muscle mass are recycled in priority by the liver for the synthesis of essential protein. Total plasma proteins, including albumin, are decreased, whereas gamma globulins are often increased by the associated infections. Albumin: An albumin concentration lower than 30 g/L is often considered as the threshold below which edema develops from decreased oncotic pressure. However, in marasmus, albumin concentration can occasionally be below this value without edema. Prealbumin concentration is a sensitive index of protein synthesis. It decreases with decreased protein intake and rapidly increases in a few days with appropriate nutritional rehabilitation. Insulinlike growth factor 1 (IGF-1) is another sensitive marker of nutritional status. Carbohydrate metabolism: This has mainly been studied in order to explain the serious and often fatal hypoglycemia occurring in the initial renutrition phase of marasmic children. Glucose level is often low initially, and the glycogen stores are depleted. Also, a certain degree of glucose intolerance of unclear etiology exists, possibly associated with a peripheral resistance to insulin or with hypokalemia. In the initiation of renutrition or in association with diarrhea or infection, a significant risk of profound and even fatal hypoglycemia occurs. Small and frequent meals are recommended, including during the night, to avoid death in the early morning. Furthermore, the digestion of starch is impaired by the decreased production of amylase by the pancreas. Lactose malabsorption is frequent but is generally without clinical consequences. In most cases, renutrition using milk is possible. Fat metabolism: Dietary fats are often malabsorbed in the initial phase of marasmus renutrition. The mobilization of fat stores for energy metabolism takes place under hormonal control by adrenaline and growth hormone. Blood lipid levels are usually low, and serious dysregulation of lipid metabolism can occur, mainly during KW and rarely during marasmus. Anatomic changesDigestive tract The entire digestive tract from mouth to rectum is affected. The mucosal surface is smooth and thin, and secretory functions are impaired. The decrease in gastric hydrochloric acid (HCl) excretion results in bacterial overgrowth in the duodenum. The peristalsis is slow. Proportionally, the digestive tract is the organ system that loses the largest mass during marasmus. However, these important alterations of the digestive tract interfere only moderately with normal nutrient absorption. Therefore, early enteral renutrition is not contraindicated but is encouraged because some of the nutrients necessary for the recovery of the intestinal mucosa are used directly from the lumen. In addition to the anatomic changes associated with PEM, the frequent intestinal infections by viruses, bacteria, and toxins also contribute to the changes in the digestive tract. Liver volume usually decreases, as do other organ volumes. An enlarged liver suggests the possibility of other diagnoses, such as KW or hepatitis. Liver synthesis function is usually preserved, although protein synthesis is decreased, as reflected by the decreased albumin and prealbumin levels. The neoglycogenesis is decreased, further increasing the risk for hypoglycemia. The detoxifying function of the liver is impaired with structural changes in the liver cells. Therefore, drugs that are metabolized by the liver should be administered with caution, and liver function should be monitored. Endocrine system The main perturbations are observed in the thyroid, insulin, and growth hormone system. As in any stressed state, the adrenergic response is activated (see Image 2). This response is functional in marasmus but less so in KW. Muscle proteins are converted into amino acids, used for the hepatic synthesis of lipoproteins. These lipoproteins contribute to the mobilization of triglycerides from the liver. In contrast, during KW, this function is impaired, resulting in liver steatosis, which is not usually present in marasmus. However, any precipitating factor, such as gastroenteritis or inappropriate renutrition, can disrupt this fragile adaptive mechanism. Furthermore, in serious marasmus, a significant degree of hypothyroidism, with a decrease in the size of the thyroid gland and repercussions on the brain function and psychomotor development exists. In less severe forms, the impaired thyroid function has fewer clinical consequences. Insulin levels are low and contribute to a certain degree of glucose intolerance, especially during KW. Therefore, high-carbohydrate diets are inappropriate. Growth hormone levels are initially within the reference range, but they progressively decrease with time, explaining the halt in linear growth observed with marasmus. After initiation of renutrition, the substantial anabolism results in a rapid linear growth spurt. Hematopoietic system A moderate normochromic or slightly hypochromic anemia is usually present, with normal red blood cell size. Iron and folate deficiencies, intestinal parasites, malaria, and other chronic infections exacerbate the anemia. However, iron stores are present in the liver. Therefore, iron supplementation should not be initially implemented. Oral iron is poorly tolerated by the digestive tract. The other blood cells (eg, thrombocytes, white blood cells) are also affected, but with generally limited clinical consequences. Blood clotting mechanisms are usually preserved, except in the case of serious vitamin K deficiency. Immune system Immune impairment and infections are usually associated with marasmus. Thymus atrophy is a characteristic manifestation of marasmus, but all T lymphocyte–producing tissues are affected. However, B-lymphocyte tissues, such as Peyeri plaques, the spleen, and the tonsils, are relatively preserved. Cellular immunity is most affected, with a characteristic tuberculin anergy. However, antibody production is maintained. In marasmus, a general acquired immunodeficiency occurs, with a decrease in secretory immunoglobulin A (IgA) and an impairment of the nonspecific local defense system, such as mucosal integrity and lymphokine production. Bacteriemia, candidiasis, and Pneumocystis carinii infection are frequently present. Immune impairment is less frequent with moderate malnutrition. Immunological recovery is generally rapid, except if measles is associated. Brain and nervous system Cerebral tissue is usually preserved during marasmus. Brain atrophy with impairment of cerebral functions is only present in severe forms of marasmus. Effects on the brain are more important if malnutrition takes place during the first year of life or during fetal life. Irritability and apathy are characteristic of marasmus, but they improve rapidly with recovery. The permanent developmental consequences of marasmus are difficult to evaluate, but several ongoing studies are evaluating these long-term consequences as well as the benefit of nutritional supplementation with various vitamins and minerals. Cardiovascular system Cardiac muscle fiber is thin, and the contractility of the myofibrils is impaired. Cardiac output, especially systolic function, is decreased in the same proportion as the weight loss. Bradycardia and hypotension commonly occur in severe forms of malnutrition. Electrolyte imbalances present during marasmus modify the ECG findings. With this impaired cardiac function, any increase of intravascular volume during rehydration or blood transfusion can result in a significant cardiac insufficiency. With the rapid metabolic, energy, and electrolyte changes of the initial phase of renutrition, this period is also a period of high risk for arrhythmia or cardiac arrest. Therefore, close clinical monitoring is critical in children with circulatory compromise. FrequencyUnited StatesMarasmus is relatively infrequent in children. In 1995, 228 deaths were attributed to marasmus in the United States. Most of these deaths were in elderly adults, and only 3 occurred in children. However, these data do not include deaths associated with marasmus complicating anorexia nervosa. Incidence of nonfatal marasmus is unclear in the United States because most patients have an underlying condition, and marasmus is not reported as an admission or discharge diagnosis. However, several reports of PEM in hospitalized children exist, suggesting that the diagnosis of marasmus may be underreported in the United States. InternationalNearly 30% of humans currently experience one or more of the multiple forms of malnutrition. Close to 50 million children younger than 5 years have PEM, and half of the children who die younger than 5 years are undernourished (see Image 3). At the same time, a massive global epidemic of obesity, especially in countries in rapid economic transition, is emerging in children and adolescents. Mortality/MorbiditySix million children younger than 5 years die every year of malnutrition. Approximately 70 million present with wasting, and 230 million present with some stunting. Fifty percent of the children in Asia are malnourished, 30% are malnourished in Africa, and 20% are malnourished in Latin America. RaceNo racial predilection exists in the prevalence of malnutrition, but a strong association exists with the geographic distribution of poverty. SexNo sexual predilection exists, although, in some parts of the world, cultural practices place girls at a disadvantage for PEM. AgeMarasmus is more frequent in children younger than 5 years because this period is characterized by increased energy needs and increased susceptibility to viral and bacterial infections. Weaning, which occurs during this period, is often complicated by factors such as geography (eg, drought, poor soil productivity), economy (eg, illiteracy, unemployment), hygiene (eg, access to quality water), public health (eg, number of nurses is more than number of physicians), and culture and dietetics (eg, intrafamily distribution of high-nutrition foods). CLINICALSection 3 of 11
HistorySigns and symptoms of marasmus vary with the importance and duration of the energy deficit, age at onset, associated infections (eg, gastrointestinal infections), and associated nutritional deficiencies (eg, iron deficiency, iodine deficiency). Diets and deficiencies may vary considerably between different geographical regions and even within a country. The AIDS epidemic has also significantly changed the clinical course of classic marasmus. Marasmus is typically observed in infants who are breastfeeding when the amount of milk is markedly reduced or, more frequently, in those who are artificially fed. Failure to thrive is the earliest manifestation, associated with irritability or apathy. Chronic diarrhea is the most frequent symptom, and infants generally present with feeding difficulties. Presentation may be accelerated by an acute infection. The classic clinical course of a child with marasmus is presented in Images 4-5. PhysicalA shrunken wasted appearance is the classic presentation. Anthropometric measurements are critical to rapidly assess the type and severity of the malnutrition. The Wellcome Classification of Malnutrition in Children was generally used, but the WHO has recently revised this classification (see the table below). This simple classification allows a clear presentation of the clinical cases and allows comparisons between countries. Stunted children are usually considered to have a milder chronic form of malnutrition, but their condition can rapidly worsen with the onset of complications such as diarrhea, respiratory infection, or measles. Table 1. WHO Classification of Malnutrition
* Includes KW and KW marasmus (presence of edema always indicates serious PEM) † Standing height should be measured in children taller than 85 cm, and supine length should be measured in children shorter than 85 cm or in children who are too sick to stand. Generally, the supine length is considered to be 0.5 cm longer than the standing height; therefore, 0.5 cm should be deducted from the supine length measured in children taller than 85 cm who are too sick to stand. ‡ Below the median National Center for Health Statistics (NCHS)/WHO reference: The standard deviation (SD) score is defined as the deviation of the value for an individual from the median value of the reference population divided by the standard deviation of the reference population, ie, SD score = (observed value – median reference value) ÷ standard deviation of reference population. § Percentage of the median NCHS/WHO reference II This corresponds to marasmus (without edema) in the Wellcome clinical classification and to grade III malnutrition in the Gomez system. However, to avoid confusion, the term severe wasting is preferred. Construction and use of a wasting diagram simplifies the classification because the exact age of the child is often unknown. The wasting diagram is a large colored board made of vertical columns corresponding to weights from 2-25 kg (or 15 kg, which is often sufficient). The child is weighed and then his or her height is measured on the board in the column corresponding to the measured weight. The diagram is designed so that the height corresponds to the green zone if the child is well nourished, the yellow zone if the child is moderately malnourished, and to the red zone if the child is severely malnourished. Values within the reference range used to design this diagram can be applied to any population regardless of the racial origin. Middle upper arm circumference (MUAC) (see Image 1) is a simple, low-cost, objective method of assessing nutritional status. The MUAC is generally as goodasorbetterthanotheranthropometricmeasuresinpredictingsubsequent mortality incommunity-based studies. It is most useful for large epidemiological surveys. The most perceptible and frequent clinical feature in marasmus is the loss of muscle mass and subcutaneous fat mass. Some muscle groups, such as buttocks and upper limb muscles, are more frequently affected than others. Facial muscles are usually spared longer. Facial fat mass is the last to be lost, resulting, in severe cases, in the characteristic elderly appearance of children with marasmus. Anorexia is frequent and interferes with renutrition. An irritable and whining child who cannot be comforted or separated from the mother demonstrates behaviors often observed with marasmus. Apathy is a sign of serious forms of marasmus: children are increasingly motionless and seem to "let themselves die." In contrast, during rehabilitation, even the slightest smile is a positive sign of recovery. Children's behavior is probably one of the best clinical signs of the severity and evolution of marasmus. Several clinical signs must be assessed in order to detect complications, with special attention to infectious complications (see checklist below). The physical examination must be very thorough because even small abnormalities can be clinically significant. Clinical signs of serious complication can be very subtle in children with marasmus. A body temperature of 37.5°C can correspond to a fever of 39-40°C in a child without marasmus, and a small cough can be the only sign of a serious pneumonia. After history and physical examination, diagnosing the type and severity of the malnutrition, as well as diagnosing associated infections and complications affecting organs or systems, such as the gastrointestinal, neurological, or cardiovascular system, are critical. This set of diagnoses results in optimal planning of the complementary evaluation and therapeutic strategy.
CausesSeveral factors can lead to marasmus. Their relative importance varies between children and between parts of the world. For example, undernutrition associated with war, inappropriate weaning by a young mother, and precipitating infections can influence incidence of marasmus.
DIFFERENTIALSSection 4 of 11
|
| Composition | ReSoMal (mmol/L) | WHO (mmol/L) |
|---|---|---|
| Glucose | 125 | 111 |
| Sodium | 45 | 90 |
| Potassium | 40 | 20 |
| Chloride | 70 | 80 |
| Citrate | 7 | 10 |
| Magnesium | 3 | - |
| Zinc | 0.3 | - |
| Copper | 0.045 | - |
| Osmolarity (mOsm/L) | 300 | 311 |
The overall goal of nutrition rehabilitation is to overcome the anorexia often associated with marasmus as well as to avoid the causes that lead to anorexia. Another goal is to avoid cardiac failure while providing enough energy to avoid catabolism. The goal usually is to provide 80-100 kcal/kg/d in 12 meals per day or continuously by NG tube to avoid hypoglycemia. This amount of calories should be reached progressively in a few days to avoid life-threatening problems such as cardiac failure or hypokalemia.
The WHO recommends use of the F75 solution, which provides 75 kcal/100 mL, mainly as carbohydrates. This solution provides a limited amount of fat, which is often malabsorbed because of the associated pancreatic insufficiency, and a limited amount of proteins, which can precipitate renal failure during initial refeeding of children with marasmus. F75 is available as a ready-to-use formula, or it can be prepared using widely available foods listed in Table 3 below. Recipes and cooking guidelines, including possible alternative foods, are available through the WHO. The ready-to-use formulas, as well as the micronutrient mixtures, are commercially available.
Table 3. Preparation of F75 and F100 diets (WHO)
| Ingredient | Amount in F75 | Amount in F100 |
|---|---|---|
| Dry skimmed milk | 25 g | 80 g |
| Sugar | 70 g | 50 g |
| Cereal flour | 35 g | - |
| Vegetable oil | 27 g | 60 g |
| Mineral mix | 20 mL | 20 mL |
| Vitamin mix | 140 mg | 140 mg |
| Water to mix | 1000 mL | 1000 mL |
Rehabilitation phase (weeks 2-6)
In the rehabilitation phase of treatment, nutritional intake can reach 200 kcal/kg/d. The goal is to reach a continuous catch-up growth in weight and height in order to restore a healthy body weight. Only children who have been weaned from their NG tube can be considered as being in the rehabilitation phase. Therefore, specific goals of this phase are as follows:
During the rehabilitation phase, the F100 formula, with a higher protein content (see Table 3 above) is recommended. With the child's increased appetite during this phase, use of the F75 formula would only lead to a fat increase, without an appropriate gain in fat-free mass. The main risk of this phase of the rehabilitation is that the nutrients provided are not sufficient to sustain the weight gain, which can reach up to 15 g/kg/d. Inexperienced health professionals often underestimate the needs of children with marasmus in this phase of nutritional rehabilitation. The increased iron needs associated with the rapid muscle growth and the hemoglobin increase justify iron supplementation starting in the second week of rehabilitation.
Powdered skim milk is used in the form of F75 or F100 formula. In that form, the lactose concentration is low, about 10 times less than in breast milk, which also is well tolerated by children with marasmus. Only in cases of persistent diarrhea or established lactose intolerance, which is rare, should lactose be excluded. High-fat foods are well tolerated at this point because they slow gastric emptying and may decrease lactose production.
Emotional and physical stimulation is critical during this period. Psychomotor inhibition is evident in children with marasmus but rapidly improves with renutrition. Any rehabilitation practices that can minimize long-term developmental consequences should be implemented in children with marasmus. Practices available may vary depending on the environment. Practices include physiotherapy, sensory stimulation, and massages and should be implemented with or by the mother.
Management of acute complications
Mortality of hospitalized children with marasmus is high, especially during the first few days of rehabilitation. Death is usually caused by infections (ie, diarrhea and dehydration, pneumonia, gram-negative sepsis, malaria, urinary infection) or other causes of death (ie, heart failure associated with anemia, excess of rehydration solution, or excess of proteins in the first days of treatment; hypothermia; hypoglycemia; hypokalemia; hypophosphatemia). Mortality rates can vary from less than 5% to more than 50% of children, depending on the quality of care.
Complications of the rehabilitation phase
Except in life-threatening emergency situations, such as ileus, surgery should be postponed until children with marasmus have completed nutritional rehabilitation. The increased nutritional stress associated with anesthesia, surgery, and the postsurgery period should be carefully evaluated. In order to prepare a child with marasmus for surgery, the child must be in positive energy balance or anabolism, must have mineral deficiencies corrected, and the electrolyte imbalances must be corrected. This goal is usually reached after the initial phase of renutrition, after about a week.
See Medical Care.
Children with marasmus need interaction with other children and their family during rehabilitation (eg, feed in the play area). Activities should be selected to develop both motor and language skills. Physical activities promote the development of motor skills. Duration of activities should be increased progressively as the nutritional status improves.
No practical guidelines exist for the most frequently used medications in marasmus. However, significant changes occur in their pharmacokinetics, resulting in unpredictable responses to drug therapy. Therefore, dosage adaptations are often necessary, and only the best-known medications and the absolutely necessary medications should be used.
Drug metabolism during marasmus
Absorption and bioavailability of oral drugs are decreased by the structural and functional changes of the digestive tract. Drug distribution depends on the fluid distribution, organ perfusion, and albumin level and is therefore significantly modified by marasmus. The hepatic metabolism is altered in marasmus; therefore, drugs metabolized in the liver must be used with caution. Renal elimination of drugs is also impaired with the changes in glomerular filtration and tubular secretion. Consequently, patients generally have a decrease of drug elimination, increase in plasmatic concentration, and increase in risk for toxicity. Drug metabolism perturbations improve rapidly with rehabilitation. Various pathophysiological changes that occur in PEM and their effects on pharmacokinetic parameters are summarized in Table 4.
Table 4. Pathophysiology and its Relation to Pharmacokinetic Parameters in Malnourished Children
| Physical Parameter | Pathophysiological Profile | Pharmacokinetic Parameters |
|---|---|---|
| Gastrointestinal tract | Hypochlorhydria Mucosal atrophy Changes in transit time Impaired pancreatic function Altered gut microbial flora | Absorption Enterohepatic circulation Gut wall and gut bacterial metabolism |
| Body composition | Changes in protein/fat metabolism Imbalance in body water distribution Reduced sodium, potassium, and magnesium | Protein binding Tissue uptake and distribution Retention and elimination |
| Liver | Ultrastructural alterations Decreased protein synthesis | Metabolism Hepatic and biliary excretion Enterohepatic circulation |
| Kidney | Reduced glomerular filtration Impaired tubular function | Renal clearance |
| Cardiac system | Decreased cardiac output Increased plasma volume | Organ blood flow Tissue perfusion |
Table 5. WHO Dosage Guidelines for Glucose (Dextrose if IV), Vitamins, and Minerals
| Dextrose, Vitamins, and Minerals | Dosage |
|---|---|
| Glucose (dextrose) | Conscious children: 50 mL 10% glucose or sucrose PO or 5 mL/kg of body weight of 10% dextrose IV, followed by 50 mL 10% glucose or sucrose by NG tube |
| Vitamin A | Infants <6 months: 50,000 IU/d PO for 2 d, followed by a third dose at least 2 wk later Infants 6-12 months: 100,000 IU/d PO for 2 d, followed by a third dose at least 2 wk later Children >12 months: 200,000 IU/d PO for 2 d, followed by a third dose at least 2 wk later |
| Folic acid | 5 mg PO on day 1, then 1 mg/d PO thereafter |
| Multivitamins | All diets should be fortified with water-soluble and fat-soluble vitamins by adding, for example, the WHO vitamin mix (thiamine 0.7 mg/L, riboflavin 2 mg/L, nicotinic acid 10 mg/L, pyridoxine 0.7 mg/L, cyanocobalamin 1 mcg/L, folic acid 0.35 mg/L, ascorbic acid 100 mg/L, pantothenic acid 3 mg/L, biotin 0.1 mg/L, retinol 1.5 mg/L, calciferol 30 mcg/L, alpha-tocopherol 22 mg/L, vitamin K 40 mcg/L) |
| Iron supplements | Prophylaxis: 1-2 mg elemental iron/kg/d PO; not to exceed 15 mg/d Severe iron deficiency anemia: 4-6 mg elemental iron/kg/d PO divided tid Mild-to-moderate iron deficiency anemia: 3 mg elemental iron/kg/d PO qd or divided bid Precaution: Gastrointestinal irritation |
Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting. Penicillin and aminoglycosides are eliminated by the kidney and have an increased plasma half-life. A decrease by 25% of the usual dosage is recommended with an increased period between doses from 12-24 hours for aminoglycosides and from 6-8 hours for penicillin. Chloramphenicol is still used in low-income countries and recommended in some WHO management protocols. It should be replaced by less toxic drugs (eg, ceftriaxone). Antituberculosis medications, such as isoniazid and rifampicin, are metabolized by the liver. To avoid serious liver failure, their dosage should be decreased by half and liver function should be monitored during treatment. Antimalarial drugs should be administrated according to local guidelines; except for quinine, they are not mentioned in this article.
| Drug Name | Amoxicillin (Amoxil, Biomox, Polymox) |
|---|---|
| Description | Aminopenicillin used for treatment of susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria species, meningococci, and some strains of Haemophilus influenzae, Salmonella species, Shigella species, Escherichia coli, and Enterobacter and Klebsiella species. |
| Adult Dose | 250-500 mg PO q8h; not to exceed 2-3 g/d |
| Pediatric Dose | 15 mg/kg PO q8h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid increases serum levels; allopurinol may increase frequency of amoxicillin rash |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Renal impairment; preexisting seizure disorder; may enhance chance of candidiasis |
| Drug Name | Ampicillin (Marcillin, Omnipen) |
|---|---|
| Description | Aminopenicillin used for the treatment of susceptible bacterial infections caused by streptococci, pneumococci, nonpenicillinase-producing staphylococci, Listeria species, meningococci, and some strains of H influenzae, Salmonella species, Shigella species, E coli, and Enterobacter and Klebsiella species. |
| Adult Dose | 250-500 mg PO q6h 500-3000 mg IV/IM q4-6h; not to exceed 12 g/d |
| Pediatric Dose | 25 mg/kg PO q6h Alternatively, 50 mg/kg IV/IM q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of PO contraceptives |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction |
| Drug Name | Ceftriaxone (Rocephin) |
|---|---|
| Description | Cephalosporin (third generation) used for the treatment of serious infections due to susceptible organisms (eg, H influenzae, Enterobacteriaceae, N meningitidis, S pneumoniae). |
| Adult Dose | 1-2 g IV/IM q12-24h, depending on the type and severity of infection; not to exceed 4 g/d |
| Pediatric Dose | Meningitis: 100 mg/kg/d IV/IM divided q12-24h Other infections: 50-75 mg/kg/d IV/IM divided q12-24h |
| Contraindications | Documented hypersensitivity |
| Interactions | High-dose probenecid may increase serum levels; aminoglycosides may increase risk of nephrotoxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Use with caution in patients with gallbladder, biliary tract, liver, or pancreatic disease or in patients with history of colitis or penicillin hypersensitivity; adjust dose in severe renal insufficiency |
| Drug Name | Gentamicin (Garamycin) |
|---|---|
| Description | Aminoglycoside for gram-negative coverage. First-choice antibiotic associated with ampicillin for severe infection. |
| Adult Dose | Serious infections and normal renal function: 3 mg/kg IV q8h Loading dose: 1-2.5 mg/kg IV q8h Maintenance dose: 1-1.5 mg/kg IV q8h Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion |
| Pediatric Dose | <5 years: 2.5 mg/kg/dose IV q8h >5 years: 1.5-2.5 mg/kg/dose IV q8h or 6-7.5 mg/kg/d divided q8h; not to exceed 300 mg/d; monitor as in adults WHO dose: 7.5 mg/kg IV qd |
| Contraindications | Documented hypersensitivity; impaired audition |
| Interactions | Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur; coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly) |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Narrow therapeutic index (not intended for long-term therapy); caution in renal failure (patient not on dialysis), myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment |
| Drug Name | Nalidixic acid (NegGram) |
|---|---|
| Description | Quinolone antibacterial for PO administration. It is a bactericidal agent, which appears to interfere with DNA polymerization by inhibition of DNA topoisomerase. |
| Adult Dose | 1000 mg PO q6h |
| Pediatric Dose | <3 months: Contraindicated >3 months: 15 mg/kg PO q6h |
| Contraindications | Documented hypersensitivity; convulsive disorders; infants <3 mo |
| Interactions | Potentiates warfarin effects; antacids decrease absorption |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Caution in patients with impaired renal and hepatic function and G-6-PD deficiency; may cause gastrointestinal intolerance, rashes, photosensitivity, and cartilage degeneration (animals) |
| Drug Name | Penicillin G (Pfizerpen) |
|---|---|
| Description | Natural penicillin used for the treatment of sepsis, meningitis, pericarditis, endocarditis, pneumonia, and other infections due to susceptible gram-positive organisms (except Staphylococcus aureus), some gram-negative organisms (Neisseria gonorrhoeae, N meningitidis) and some anaerobes and spirochetes. |
| Adult Dose | 2-24 million IU/d IV/IM divided q4-6h |
| Pediatric Dose | 50,000 IU/kg IV/IM q6h |
| Contraindications | Documented hypersensitivity |
| Interactions | Probenecid can increase effects of penicillin; coadministration of tetracyclines can decrease effects of penicillin |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Renal impairment; preexisting seizure disorder |
| Drug Name | Sulfamethoxazole and trimethoprim (Bactrim, Cotrim, Septra) |
|---|---|
| Description | Synthetic antibacterial combination. Children with no apparent sign of infection should be administered cotrimoxazole as a first-choice antibiotic. |
| Adult Dose | 160 mg trimethoprim (TMP)/800 mg sulfamethoxazole (SMX) PO q12h (ie, 1 double-strength tablet q12h) |
| Pediatric Dose | <2 months: Contraindicated >2 months: 4-5 mg/kg (based on trimethoprim [TMP] component) PO q12h |
| Contraindications | Documented hypersensitivity; megaloblastic anemia due to folate deficiency |
| Interactions | May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly people; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Do not use during last trimester of pregnancy because of potential toxicity to newborn (eg, jaundice, hemolytic anemia, kernicterus); discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBCs frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; caution in folate deficiency (eg, people with chronic alcoholism, elderly people, those receiving anticonvulsant therapy, those with malabsorption syndrome); hemolysis may occur in G-6-PD deficient individuals; AIDS patients may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); administer fluids to prevent crystalluria and stone formation |
| Drug Name | Isoniazid (Laniazid, Nydrazid) |
|---|---|
| Description | Used for specific treatment of tuberculosis either alone for preventive therapy in patients who have a skin test conversion or in combination with other drugs for treatment of all active forms of the disease. |
| Adult Dose | 5-10 mg/kg (up to 300 mg/dose) PO qd; alternatively, 15 mg/kg/dose PO 2 times/wk; not to exceed 900 mg/dose PO twice/wk |
| Pediatric Dose | 5 mg/kg PO qd or 15 mg/kg/dose PO 2 times/wk; not to exceed 300 mg/24h |
| Contraindications | Documented hypersensitivity; previous isoniazid-associated hepatic injury or other severe adverse reactions |
| Interactions | Higher incidence of isoniazid-related hepatitis can occur with alcohol ingestion on daily basis; aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum salts); may increase anticoagulant effects with coadministration; may inhibit metabolic clearance of benzodiazepines; carbamazepine toxicity or isoniazid hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function); coadministration with cycloserine may increase CNS adverse effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram; coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur |
| Drug Name | Rifampin (Rifadin, Rimactane) |
|---|---|
| Description | Also called rifampicin. It is a synthetic derivative of a natural antibiotic rifamycin B. It is used in combination with other antitubercular drugs for the treatment of active tuberculosis. It also has antibacterial activity (eg, S aureus, Streptococcus pyogenes, N gonorrhoeae, H influenzae). |
| Adult Dose | Tuberculosis: 10 mg/kg PO qd; not to exceed 600 mg/d |
| Pediatric Dose | Tuberculosis: 10 mg/kg PO qd; alternatively, 10 mg/kg PO 2 times/wk; not to exceed 600 mg/24h |
| Contraindications | Documented hypersensitivity |
| Interactions | Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur) |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Obtain CBCs and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur |
| Drug Name | Quinine (Formula Q) |
|---|---|
| Description | First antimalarial drug used for the treatment of chloroquine-resistant Plasmodium falciparum malaria. |
| Adult Dose | 540 mg base (650 mg quinine sulfate) PO q8h for 3-7 d |
| Pediatric Dose | 8 mg of base per kg (10 mg/kg quinine sulfate) PO q8h for 7 d |
| Contraindications | Documented hypersensitivity; those with optic neuritis, tinnitus, G-6-PD deficiency, or a history of black water fever |
| Interactions | Aluminum-containing antacids may delay or decrease quinine bioavailability when administered concurrently; cimetidine increases quinine blood levels and creates the potential for toxicity; rifamycins decrease quinine concentrations by increasing hepatic clearance of quinine (effect can persist for several days after discontinuing rifamycins); concurrent administration of acetazolamide or sodium bicarbonate may increase toxicity by increasing quinine blood levels; quinine may enhance action of warfarin and other PO anticoagulants by decreasing synthesis of vitamin K–dependent clotting factors; digoxin serum concentrations may increase when digoxin is administered concurrently with quinine; important to monitor digoxin levels periodically; quinidine may decrease plasma cholinesterase activity, causing a decrease in the metabolism of succinylcholine |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in G-6-PD deficiency and tendency to develop granulocytopenia; prolonged treatment or overdosing with quinine may cause cinchonism; quinine has quinidinelike activity and thus can cause cardiac arrhythmias |
Protozoal infections occur throughout the world and are a major cause of morbidity and mortality in some regions. Immunocompromised patients are especially at risk.
| Drug Name | Albendazole (Albenza) |
|---|---|
| Description | Orally administered broad-spectrum anthelmintic with specific indications, including ascariasis, hookworm infections, trichuriasis, and strongyloidiasis. |
| Adult Dose | Ascariasis, hookworm infections, and trichuriasis: 400 mg PO in a single dose Strongyloidiasis: 400 mg PO bid for 3 d |
| Pediatric Dose | 1-2 years: Ascariasis, hookworm infections, and trichuriasis: 200 mg PO in a single dose Strongyloidiasis: 200 mg PO bid for 3 d >2 years: Administer as in adults |
| Contraindications | Documented hypersensitivity |
| Interactions | Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Discontinue use if LFTs increase significantly (resume when levels decrease to pretest values); abdominal pain, nausea, vomiting, diarrhea, dizziness, vertigo, fever, increased intracranial pressure, and alopecia may occur |
| Drug Name | Metronidazole (Flagyl, Noritate, Protostat) |
|---|---|
| Description | First-line treatment for amoebiasis and giardiasis. |
| Adult Dose | Amebiasis: 750 mg PO q8h for 5-10 d Giardiasis: 250 mg PO q8h for 5 d |
| Pediatric Dose | Amebiasis: 10 mg/kg PO q8h for 5-10 d Giardiasis: 5 mg/kg PO q8h for 5 d |
| Contraindications | Documented hypersensitivity |
| Interactions | May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol; phenobarbital and rifampin may increase metabolism of metronidazole |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Caution in liver impairment, blood dyscrasias, and CNS disease; reduce dose in hepatic disease; monitor for seizures and development of peripheral neuropathy |
| Drug Name | Piperazine (Vermizine) |
|---|---|
| Description | Treatment of ascariasis and trichuriasis. |
| Adult Dose | 3500 mg PO in a single dose |
| Pediatric Dose | <2 years: 50 mg/kg PO in a single dose administered under medical supervision Children 2-12 years: 75 mg/kg PO in a single dose; not to exceed 2.5 g/dose |
| Contraindications | Documented hypersensitivity; convulsive disorders; renal or hepatic dysfunction |
| Interactions | Coadministration with chlorpromazine may increase toxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Most commonly reported reactions include GI and CNS effects; discontinue therapy if effects become significant; prolonged, repeated, and excessive therapy should be avoided because of potential neurotoxicity |
These agents inhibit central synthesis and release of prostaglandins that mediate the effect of endogenous pyrogens in the hypothalamus; thus, they promote the return of the set-point temperature to normal. Acetaminophen (paracetamol) metabolism during malnutrition is well documented. Its half-life is increased with the impaired hepatic metabolism and renal excretion, requiring a dosage decrease.
| Drug Name | Acetaminophen (Acephen, Tylenol, Feverall, Panadol) |
|---|---|
| Description | First-choice antipyretic drug; it is also used for the treatment of mild to moderate pain and fever. Reduces fever by acting directly on hypothalamic heat-regulating centers, which increases dissipation of body-heat via vasodilation and sweating. |
| Adult Dose | 325-650 mg q4-6h or 1000 mg q6-8h; not to exceed 4 g/d |
| Pediatric Dose | <12 years: 10-15 mg/kg/dose PO/PR q4-8h prn; not to exceed 2.6 g/d >12 years: Administer as in adults |
| Contraindications | Documented hypersensitivity; known G-6-P deficiency |
| Interactions | Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity |
| Pregnancy | B - Usually safe but benefits must outweigh the risks. |
| Precautions | Hepatotoxicity possible in people with chronic alcoholism following various dose levels; severe or recurrent pain or high or continued fever may indicate a serious illness; APAP is contained in many OTC products, and combined use with these products may result in cumulative APAP doses exceeding recommended maximum dose |