Protein-energy malnutrition

Prepared by - Dr. N. S. Mani. Assistant Professor, Department of Paediatrics, Governemnt Medical College, Mulamkunnathkavu, Valappaya PO 680596, Thrissur.

Marasmus is one of the three forms of serious protein-energy malnutrition (PEM). The other two are kwashiorkor (KW) and marasmic KW. These conditions are associated with a nutritional and energy deficit are frequently associated with infections, mainly gastrointestinal infections. Hospitalized children are at risk for PEM when they have oncologic disease, genetic disease, or neurological disease, Pathophysiology: PEM results from a negative energy balance. This imbalance can result from 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 (1) body composition changes, (2) metabolic changes, (3) anatomic changes. Body composition Body mass: decreased Fat mass: decrease to as low as 5% of the total body weight Total body water: The proportion of water content in the body increases with the increased seriousness of PEM 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 and frequently in 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.
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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 highenergy-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 mid arm circumference 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 vitamins Potassium: 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: 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. deficit in calcium, phosphorus, and magnesium exists. Iron deficiency anemia is observed 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 reduced. 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. Vitamins and micronutrients deficiencient are. ( A to Z ) o Ascorbic acid
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o o o o o o o o o o o o o o o o o o o o o o

B-12 vitamin Calciferol Calcium Copper Essential amino acids Folic acid Iodine Iron Magnesium Manganese Phosphorus Potassium Pyridoxine Retinol Riboflavin Selenium Sodium Sulfur Thiamin Tocopherol Water Zinc

Metabolic changes Energy 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 Muscle mass loss results in a decrease of energy expenditure. Reduced energy metabolism can impair the response of patients with PEM 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 catchup 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.
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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 PEM, 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 PEM 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 PEM. Anatomic changes Digestive 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 PEM. 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
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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 This response is functional in PEM 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 PEM. However, any precipitating factor, such as gastroenteritis or inappropriate renutrition, can disrupt this fragile adaptive mechanism. Furthermore, in serious PEM, 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, highcarbohydrate diets are inappropriate. Growth hormone levels are initially within the reference range,( the only hormone which does not decrease) but they progressively decrease with time, explaining the halt in linear growth observed with PEM. 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 PEM. Thymus atrophy is a characteristic manifestation of PEM, but all T lymphocyteproducing 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 PEM, 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
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malnutrition. Immunological recovery is generally rapid, except if measles is associated. Brain and nervous system Cerebral tissue is usually preserved during PEM. Brain atrophy with impairment of cerebral functions is only present in severe forms of PEM. 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 PEM, but they improve rapidly with recovery. The permanent developmental consequences of PEM 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 is decreased in the same proportion as the weight loss. Bradycardia and hypotension commonly occur in severe forms of malnutrition. Electrolyte imbalances present during PEM 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. Approach to PEM Age: PEM 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).

History: Signs and symptoms of PEM 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 PEM. PEM 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
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the most frequent symptom, and infants generally present with feeding difficulties. Presentation may be accelerated by an acute infection. Physical: A 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 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. Evidence of Moderate Severe (type) Malnutrition Symmetric edema Weight for height No Yes (edema PEM)* SD score -3 SD score <-3 (ie, severe SD score <-2 wastingII) (70-90%) (<70%) SD score -3 SD score <-3 (ie, severe SD score <-2 stunting) (<85%) (85-89%)

Height for age

The most perceptible and frequent clinical feature in PEM 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 PEM. 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 PEM. Apathy is a sign of serious forms of PEM: 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 PEM. 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 PEM. A body temperature of 37.5C can correspond to a fever of 39-40C in a child without PEM, 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,
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neurological, or cardiovascular system, are critical. This set of diagnoses results in optimal planning of the complementary evaluation and therapeutic strategy. Skin changes in PEM are

Checklist of points for conducting the physical examination o Body temperature (measured with a thermometer) - Allowing measurement of low temperatures to detect hypothermia as well as fever o Anemia - Pale mucosa o Edema o Dehydration - Thirst, shrunken eyes o Hypovolemic shock - Weak radial pulse, cold extremities, decreased consciousness o Tachypnea - Pneumonia, heart failure o Abdominal manifestations - Distension, decreased or metallic bowel sounds, large or small liver, blood or mucus in the stools o Ocular manifestations - Corneal lesions associated with vitamin A deficiency o Dermal manifestations - Evidence of infection, purpura o Ear, nose, and throat (ENT) findings - Otitis, rhinitis Lab Studies: o Blood glucose: Hypoglycemia exists if the level is lower than 3 mmol/L. o Examination of blood smears by microscopy or direct detection test: Presence of parasites is indicative of infection. Direct test is suitable but expensive. o Hemoglobin: A level lower than 40 g/L is indicative of severe anemia.
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o Urine examination and culture, Multistix: More than 10 leukocytes per high-power field is indicative of infection. Nitrites and leukocytes are tested on Multistix also. o Stool examination by microscopy: Parasites and blood are indicative of dysentery. o Albumin: Although not useful for diagnosis, it is a guide to prognosis; if albumin is lower than 35 g/L, protein synthesis is massively impaired. o HIV test: HIV test should not be routinely performed; if completed, it should be accompanied by counseling of the child's parents and the result should be confidential. o Electrolytes: Measuring electrolytes is rarely helpful and it may lead to inappropriate therapy. Hyponatremia is a significant finding. Imaging Studies: Radiological examinations are rarely used for the same reasons as the laboratory examinations. Thoracic radiography can show a pulmonary infection despite lack of clinical signs, a primary tuberculosis lesion, cardiomegaly, or signs of rachitism. Other Tests: Skin test results for tuberculosis are often negative in children who are undernourished with tuberculosis or those previously vaccinated with Bacille Calmette-Gurin (BCG) vaccine. Procedures: Lumbar puncture is rarely performed. Urine catheterization or vesical puncture serves to exclude urinary tract infection because direct examination is often not indicative. TREATMENT Nutritional rehabilitation should include appropriate foods for an intake up to 100150 kcal/kg/d. Other therapeutic and preventive actions should include rehydration using the WHO solution in case of associated diarrhea, micronutrient supplementation (eg, iron, vitamin A), context-appropriate screening, and review of immunization status. This management should also incorporate nutritional and sociocultural education adapted to the local conditions. Family-based management is preferred with the child's mother as the key player. Nutritional management of the acute phase of severe PEM (week 1) This period corresponds to maintenance of vital functions and tissue renewal, ie, maintenance needs. During this period, the electrolyte imbalance, infections, hypoglycemia, and hypothermia are treated, and then feeding is started. Oral renutrition of a child with PEM should be started as early as possible, as soon as the child is stable and the hydroelectrolyte imbalances are corrected. Enteral feeds decrease diarrhea and prevent bacteremia from bacterial translocation. modified oral rehydration (ReSoMal) solution The standard solution can be used for watery diarrhea, such as cholera infection. The recommended volume is 5-15 mL/kg/h with a total of 70 mL/kg for the first 12 hours. Because the risk of cardiac failure is increased in children with PEM, compliance with the rehydration regimen is even more critical than in children
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who are well nourished. Therefore, closely monitor the rehydration phase and promptly address signs of cardiac failure, such as tachypnea, tachycardia, edema, or hepatomegaly. In cases of shock, IV rehydration is recommended using a Ringer-lactate solution with 5% dextrose or a mixture of 0.9% sodium chloride with 5% dextrose. Enteral hydration using ReSoMal should be started as early as possible, preferably at the same time as the IV solution. The following rules should be implemented in the initial phase of rehydration: (1) use an NG tube, (2) continue breastfeeding, except in case of shock or coma, and (3) start other food after 3-4 hours of rehydration. Below, comparison of composition of the standard WHO rehydration solution and the solution adapted for severely malnourished children (ie, ReSoMal). Composition Glucose Sodium Potassium Chloride Citrate Magnesium Zinc Copper ReSoMal (mmol/L) 125 45 40 70 7 3 0.3 0.045 WHO (mmol/L) 111 90 20 80 10 -

Osmolarity (mOsm/L) 300 311 The overall goal of nutrition rehabilitation is to overcome the anorexia often associated with PEM 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 PEM. F75 is available as a ready-to-use formula, or it can be prepared using widely available foods listed in Table 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.
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Ingredient Dry milk Sugar Cereal flour Vegetable oil Mineral mix Vitamin mix skimmed

Amount F75 25 g 70 g 35 g 27 g 20 mL 140 mg

in Amount F100 80 g 50 g 60 g 20 mL 140 mg

in

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: To encourage the child to eat as much as possible To restart breastfeeding as soon as possible To stimulate the emotional and physical development To actively prepare the child and mother to return to home and prevent recurrence of malnutrition During the rehabilitation phase, the F100 formula, with a higher protein content (see Table 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 PEM 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 PEM. Only in cases of persistent diarrhea or established lactose intolerance, which is rare, should lactose be excluded. Highfat 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 PEM but rapidly improves with renutrition. Any rehabilitation practices that can minimize long-term developmental consequences should be implemented in children with PEM. Practices available may vary
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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 PEM 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). Infectious complications: Every hospitalized child with PEM should be considered as having a bacterial infection. Treatment of bacterial infections prevents the development of septic shock, improves the response to nutritional rehabilitation, and decreases mortality. If the child has no clinical sign of infection, the WHO recommends 5 days of oral cotrimoxazole therapy. If the child presents with clinical signs of infection, hypoglycemia, or hypothermia (that does not rapidly respond to the kangaroo position), he or she must be considered as seriously infected and treated with parenteral ampicillin and gentamicin. If the child does not improve rapidly, chloramphenicol should be added. Antimalaria treatment is also indicated in endemic areas, either PO, by injection, or intrarectal. Other complications o Severe and symptomatic anemia (<4 g/100 mL) with signs of heart failure should be treated with a blood transfusion of packed red cells to a maximum of 10 mL/kg administered over at least 3 hours. Cardiovascular tolerance should be closely monitored. The benefit of blood transfusion must be balanced with the risks of cardiovascular failure and the risk of infection (eg, hepatitis, HIV) associated with blood transfusion. o Vitamin A deficiency is always present and should be treated in the first few days. Vitamin A replacement facilitates recovery from diarrhea, measles, and respiratory diseases and decreases the risk of blindness. o Lactose intolerance is unusual and often secondary to prolonged diarrhea. If, as dairy products are restarted, diarrhea persists despite antiparasitic treatment and nutritional rehabilitation, a transient lactose intolerance is possible, especially if stools have a low pH and if the child presents with a perianal skin inflammation (diaper rash). In case of lactose intolerance, milk should be withheld and yogurt or a commercially available lactose-free formula can be used. Complications of the rehabilitation phase Poor response to the nutritional rehabilitation: If the above recommendations are applied, children with PEM should improve rapidly, gain weight regularly, and return to age-appropriate developmental status. Usually, poor response to treatment is due to insufficient intake or an underlying infection. However, poor response to therapy requires a complete reassessment of the situation, rather than simply adding a medication or a micronutrient, which is usually ineffective.
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 Psychosocial problems: Often during this period of the rehabilitation, underlying causes of the child's PEM are understood, such as the previously described psychosocial factors. Changes in these underlying factors often are difficult because they are associated with the general socioeconomic conditions. However, changes should be attempted. The underlying factors should be taken into consideration when planning the child's return to home and further follow-up care. Surgical Care: Except in life-threatening emergency situations, such as ileus, surgery should be postponed until children with PEM 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 PEM 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. Diet: See Medical Care. Activity: Children with PEM 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. Drug metabolism during PEM 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 PEM. The hepatic metabolism is altered in PEM; 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. Physical Pathophysiological Profile Pharmacokinetic Parameters Parameter Hypochlorhydria Absorption Mucosal atrophy Enterohepatic circulation Gastrointest Changes in transit time Gut wall and gut bacterial inal tract Impaired pancreatic function metabolism Altered gut microbial flora Changes in protein/fat metabolism Protein binding Imbalance in body water distribution Body Tissue uptake and distribution composition Reduced sodium, potassium, and Retention and elimination magnesium
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Liver Kidney Cardiac system

Metabolism Ultrastructural alterations Hepatic and biliary excretion Decreased protein synthesis Enterohepatic circulation Reduced glomerular Impaired tubular function Decreased cardiac Increased plasma volume filtration Renal clearance flow

output Organ blood Tissue perfusion

Dextrose, Vitamins, and Dosage Minerals Glucose (dextrose) Conscious children: 50 mL 10% glucose or sucrose PO or 5 mL/kg of body weight of 10% glucose IV, followed by 50 mL 10% glucose or sucrose by NG tube 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 5 mg PO on d 1, then 1 mg/d PO thereafter 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, nicotinamic 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) Prophylaxis: 1-2 mg elemental iron/kg/d; not to exceed 15 mg/d Severe iron deficiency anemia: 4-6 mg elemental iron/kg/d divided tid Mild-to-moderate iron deficiency anemia: 3 mg elemental iron/kg/d qd or divided bid Precaution: Gastrointestinal irritation

Vitamin A

Folic acid

Multivitamins

Iron supplements

Albendazole - Orally administered broad-spectrum anthelmintic with specific indications, including ascariasis, hookworm infections, trichuriasis, and strongyloidiasis.
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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: Ascariasis, hookworm infections, and trichuriasis: 400 mg PO in a single dose Strongyloidiasis: 400 mg PO bid for 3 d Contraindications Documented hypersensitivity Interactions Coadministration with carbamazepine may decrease efficacy; dexamethasone, cimetidine, and praziquantel may increase toxicity Preparing for discharge - During rehabilitation, do everything possible to ensure that the child is fully reintegrated into the family and community after discharge. Include the child, the mother, and the health care worker (WHO). Child o Appropriate weight for height (-1 SD) o Eating well and gaining weight o Infections properly treated o Immunization started Mother o Able to look after the child o Able to prepare appropriate food o Able to provide home treatment for diarrhea o Able to recognize the signs that mean she must seek medical assistance Health care worker - Able to ensure the follow-up care of the child Further Outpatient Care: Relapse: Because risk of relapse is greatest soon after discharge, the child should be seen after 1 week, 2 weeks, and 1 month. At each visit, the health worker must be sure that all the points mentioned above are assessed. The child must be measured, weighed, and the results recorded. Immunization should be performed according to national guidelines. Neurodevelopmental assessment: During the first 2 years of life, the nervous system is growing and particularly at risk if nutritional deficiencies are present; therefore, regular assessment of neurodevelopment is important, including head growth measurement, neurodevelopmental item assessment, and IQ evaluation at each visit. Long-term care: Long-term follow-up care should be encouraged, particularly regarding somatic growth and neurodevelopmental performances. Deterrence/Prevention: Inappropriate development, poverty, armed conflict, mishandling of funds, lack of education (particularly women's illiteracy), as well as limited access to medical care represent the primary underlying causes of malnutrition. The best preventive strategies should address these underlying problems.
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 Numerous prevention programs have been implemented, among which the most successful include the following: o Educational programs for girls o Sanitation programs, which improve access to safe water o Nutritional programs, including health education as well as screening of malnourished children o Programs that integrate breastfeeding promotion, diarrhea and infection therapy, and improvement of the nutritional status of mothers and pregnant women Interestingly, programs aimed at improving technical infrastructures, such as electrical networks and information networks, have not demonstrated a positive preventive effect. Integration of preventive action with national policies of education and family planning are necessary conditions for the success of these actions. Integrated action should also include screening, medical care, and follow-up. The frequent failures of preventive programs are often due to unsuitable nutrition interventions, insufficient treatment of diarrheal disease, or operational difficulties. However, ongoing evaluation can decrease the risk of failure. Other key factors in prevention program success are clear strategic objectives, motivated and competent leaders, continuous training at every level, and regular evaluation of the objectives and achievements. Integration with the existing health care system, as well as national and international political support, is critical. Complications: Long-term sequelae, with particular attention to developmental issues, must be mentioned. If growth and development have been extensively impaired and if early massive iron deficiency anemia is present, mental and physical retardation may be permanent. Apparently, the younger the infant at the time of deprivation, the more devastating are the long-term effects. Prognosis: Except for complications mentioned above, prognosis of even severe PEM is good if treatment and follow-up care are correctly applied.

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