Review Article TheUseofKetogenicDietinPediatricPatientswithEpilepsy

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International Scholarly Research NetworkISRN PediatricsVolume 2012, Article ID 263139, 10 pagesdoi:10.5402/2012/263139Review ArticleThe Use of Ketogenic Diet in Pediatric Patients with EpilepsyAmanda Misiewicz Runyon and Tsz-Yin SoDepartment of Pharmacy, Moses H. Cone Hospital, Greensboro, NC 27401-1020, USACorrespondence should be addressed to Tsz-Yin So, tszsounc@gmail.comReceived 30 March 2012; Accepted 19 June 2012Academic Editors: M. Adhikari, G. Dimitriou, and Y. ErsahinCopyright 2012 A. Misiewicz Runyon and T.-Y. So. This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work isproperly cited.A ketogenic diet is a nonpharmacologic treatment strategy to control refractory epilepsy in children. Although this diet has beenused successfully to reduce seizures since the 1920s, the anticonvulsant mechanism of ketosis remains unknown. The initiation ofthe diet requires an average four-day hospitalization to achieve ketosis in the patient as well as to provide thorough education ondiet maintenance for both the patient and the caregivers. A ketogenic diet, consisting of low carbohydrate and high fat intake, leaveslittle room for additional carbohydrates supplied by medications. Patients on ketogenic diets who exceed their daily carbohydratelimit have the risk of seizure relapse, necessitating hospital readmission to repeat the diet initiation process. These patients are ata high risk for diversion from the diet. Patients admitted to the hospital setting are often initiated on multiple medications, andmany hospital systems are not equipped with appropriate monitoring systems to prevent clinicians from introducing medicationswith high carbohydrate contents. Pharmacists have the resources and the expertise to help identify and prevent the initiation ofmedications with high carbohydrate content in patients on ketogenic diets.1. Effect of Diet on Epilepsy2. The Use and Effectiveness of Ketogenic DietsA ketogenic diet is a strict diet consisting of minimalcarbohydrate and protein intake and increased fat intake.It is used as a nonpharmacologic mechanism to controlintractable childhood epilepsy [1]. Ketogenic diets mimicthe body’s response to starvation by using fat as theprimary energy source in the absence of an adequate dietarycarbohydrate source. Under normal metabolism, the bodymetabolizes carbohydrates into glucose, the fastest source ofenergy for the body and typically the sole energy source forthe brain. In a fasting state, amino acids cannot provide anadequate energy source for the brain and fatty acids cannotcross the blood brain barrier. The liver uses the fatty acidsto make ketone bodies, which can cross the blood brainbarrier and substitute for glucose as an energy source. Themechanism of how ketosis controls seizures is unknown;however, one theory is that ketones have an anticonvulsanteffect when crossing the blood brain barrier. Regardless ofthe mechanism, the effects of ketosis on seizure control havebeen observed since this diet was introduced in the 1920s[1].The primary indication for a ketogenic diet is intractablechildhood epilepsy. The treatment is typically recommendedwhen traditional antiepileptic drugs (AEDs) have failed orAED therapy causes unacceptable side effects. Approximately30% of children who develop epilepsy will develop refractoryseizures unresponsive to pharmacologic treatment or experience intolerable side effects from antiseizure medications[2]. The International Ketogenic Diet Study Group, a panelof 26 pediatric epilepsy specialists and dieticians, publisheda consensus report agreeing that ketogenic diets shouldbe strongly considered in a child who failed two to threeanticonvulsant therapies, particularly in those patients withsymptomatic generalized epilepsies [3].2.1. Efficacy and Initiation. A 2006 meta-analysis [6] of19 observational studies (1084 patients) found that aftersix months of initiating a ketogenic diet, approximately 60percent of children had a greater than 50 percent seizurereduction and 30 percent had greater than 90 percent seizurereduction [6]. The results of the meta-analysis also suggest

2that children maintained on a ketogenic diet may also be ableto reduce their AED with better seizure control. Children thatbenefited the most from the diet were those with generalizedseizures and those between 1 and 10 years of age [6].Studies investigating the effectiveness of ketogenic dietsare all observational based and focus on the patients thatwere compliant with the diet; however, most of thesestudies have large dropout rates. In the above meta-analysis,about half of the patients dropped out. Families primarilydiscontinued the diet due to the lack of improvement inseizure control [6].More recently, a randomized controlled trial was performed to test the efficacy of a ketogenic diet on drugresistant childhood epilepsy [7]. The study included 145children between 2 and 16 years of age who had at leastdaily seizures and had failed to respond to at least twoantiepileptic drugs. Children were randomly assigned toreceive a ketogenic diet immediately or to a control group,which initiated the diet 3 months after randomization. During the 3 months prior to the initiation of a ketogenic diet,the control group continued their normal diet without anydietary restrictions. The primary endpoint was a reductionin seizures at 3 months, and intention-to-treat analysis wasused. At 3 months, the mean percentage of baseline seizureswas significantly lower in the diet group than in the controlgroup who had experienced an increase in seizures frombaseline (62% versus 137%; P 0.0001) [7]. In addition, 28children in the diet group versus 4 children in the controlgroup experienced a greater than 50% seizure reduction(P 0.0001), and five children in the diet group had greaterthan 90% seizure reduction compared to zero children in thecontrol group (P 0.0582). Of the patients that droppedout from the study, only six patients were reported as beingintolerant to the diet due to increased seizure frequency,extreme drowsiness, constipation, vomiting, or diarrhea [7].One of the six patients who withdrew from the studydeveloped hematuria secondary to renal debris, indicative ofthe risk of kidney stone formation while on a ketogenic diet[7].Initiation of a ketogenic diet most often occurs in aninpatient setting at an epilepsy center in order to safelymonitor glucose levels and urine ketone levels. Traditionally,the diet is initiated after a 24–48-hour fasting period, andit is slowly introduced until the patient successfully achievesthe full ketogenic diet to be discharged home with [3]. Theaverage hospital stay is four days, during which the familyand the patient are educated on the diet. If ketosis is notmaintained, the patient must return to the hospital to restartthe entire diet initiation process; therefore, compliance withthe diet is essential.The compliance of the patients with the diet mainlydepends on the types of diet and the patient population [3].Children who are fed enterally usually demonstrate very highcompliance rates, whereas a diet having a fat : nonfat ratio ofmore than 4.5 : 1 usually leads to poor compliance [3]. Olderchildren and adolescent usually have difficulty adhering tostrict diet ratio. Thus, a lower fat : nonfat ratio is often usedin this population [3].ISRN Pediatrics2.2. Types of Ketogenic Diets. Multiple variations of ketogenicdiets exist, but the most commonly prescribed are the classicketogenic diet, the modified Atkins diet, the low-glycemicindex treatment diet, the medium-chain triglyceride (MCT)diet, and the modified MCT diet (Table 1) [4]. The classicketogenic diet is the oldest of the diets and is one of thestrictest of the diets. A gram scale is required to weigh foodportions because no estimations are permitted. The dietrestricts daily calories calculated by the patient’s dietitianwith a distribution of 85–90% long-chain fatty acid, 6–8% protein, and 2–4% carbohydrates [4]. Table 2 illustratesa sample calculation of daily energy requirements for thisdiet.Unlike the standard Atkins diet, the modified Atkins dietdoes not restrict calories, allowing unlimited protein and fatintake, and is more lenient with the use of estimations ofportion sizes. The modified Atkins dietary requirements arecomprised of 60–70% long-chain fatty acid, 25–30% protein,and 5% carbohydrate [4]. The low-glycemic index (low-GI)treatment diet restricts the patient’s carbohydrate intake tolow-GI carbohydrates, allowing for a larger daily allowanceof carbohydrates. The glycemic index scores individualcarbohydrates based on each food item’s effect on raisingblood glucose within two hours of consumption. The diet’sdietary distribution is 60–70% long-chain fatty acid, 20–30%protein, and 10% carbohydrate [4].Normal dietary fat contains mostly long-chain triglycerides. Medium-chain triglycerides (MCTs), such as decanoicacid and octanoic acid, are absorbed more effectively andare more ketogenic than LCTs because they generate moreketones per unit of energy when metabolized. Patients onthe MCT diet are able to introduce more carbohydratesand proteins in their diet compared to the classic ketogenicdiet [4]. The MCT diet is comprised of 71% medium-chainfatty acid, 10% protein, and 19% carbohydrate. Alternatively,the modified MCT diet combines the use of both longchain and medium-chain fatty acids. The modified MCTdiet distributes the calories as 30% MCT oil, 40–50%conventional or long-chain fatty acids, 10–20% protein,and 5–10% carbohydrates [4]. The classical and modifiedMCT ketogenic diets are equally effective, and differencesin tolerability are not statistically significant. Despite itsflexibility, the MCT diet is disfavored since MCT oil is moreexpensive than other fats and is not covered by insurancecompanies [8].2.3. Monitoring and Tolerability. The duration of the ketogenic diet varies among patients. The expected length oftherapy should be discussed with the patient and/or thefamily prior to starting the diet, but most patients shouldexpect a minimum of a 3-month trial period [3]. In regardsto monitoring the effects of the diet, the anticonvulsantactivity gradually increases over time but usually requiresseveral days to weeks to see a noticeable effect. A six weektreatment period is usually sufficient to determine success orfailure. If seizure control is optimized after a few months,AED therapy may be tapered or discontinued. Monitoringurine ketones is necessary to ensure that the diet is being

ISRN Pediatrics3Table 1: Types of ketogenic diets [4].Macronutrient content (% total daily calories)CommentsFatProteinCarbohydrate(i) 4 : 1 or 3 : 1 (fat : nonfat) ratioClassic ketogenic dietLCT: 85–906–82–4(ii) Unpalatable poor compliance(iii) GI effects: constipation(i) 3 : 1 (fat : nonfat) ratio(ii) Easier to prepareMCT dietMCT: 711019(iii) Greater flexibility with protein andcarbohydrate allowance(iv) GI effects: nausea, vomiting, diarrhea in 50%patientsLCT: 40–50(i) Incorporates LCT and MCTModified MCT diet10–205–10MCT: 30(ii) Fewer GI effects(i) No fasting or hospital stayModified Atkins diet60–7020–305(ii) No calorie restrictions(iii) Less dietitian support(i) Only low-glycemic-index carbohydrates allowedLow-glycemic-index treatment diet 60–7020–3010for 10% daily carbohydrates(ii) Details of how diet is prescribed are not widelyknown [1]LCT: long-chain triglycerides; MCT: medium-chain triglycerides; GI: gastrointestinal.Table 2: Sample calculations of daily energy requirements for the 3 : 1 classic ketogenic diet for a 18 kg patient.Daily caloric requirement(i) Total body weight 68 cal/kg/day(ii) 18 kg 68 cal/kg/day 1224 cal/dayDaily number of dietary units(i) For 3 : 1 (fat : protein/carbohydrate)(a) 3 g fat/unit 9 cal/g fat 27 calories(b) 1 g protein or CHO/unit 4 cal/g protein or carbohydrate (CHO) 4 calories(c) 27 4 31 calories/unit(ii) Daily caloric requirement calories/unit dietary units/day(a) 1224 31 39 units/dayDaily fat content(i) Dietary units/day g fat/unit g fat/day(ii) 39 units/day 3 g fat/unit 117 g fat/dayDaily protein and CHO content (combined)(i) Dietary units/day g protein or CHO/unit g protein or CHO/day(ii) 39 units/day 1 g protein or CHO/unit 39 g protein and CHO/dayDaily protein content 1 g/kg/day(i) 1 g/kg/day 18 kg 18 g/dayDaily carbohydrate content(i) Combined protein and CHO content daily protein content daily carbohydrate content(ii) 39 g protein and CHO/day 18 g protein/day 21 g CHO/dayDivide allotment into 3 meals(i) Fat: 117 3 39 g/meal(ii) Protein: 18 3 6 g/meal(iii) CHO: 21 3 7 g/meal

4ISRN PediatricsTable 3: Carbohydrate content in pediatric antiepileptic medications and daily total carbohydrate estimates for a five-year-old child(weighing 18 kg) on maximum monotherapy of antiepileptic drugs treatment doses (concerns for the patient on a ketogenic diet) [5]a .Medications with high carbohydrate content ( 2 g per dose) are highlighted in bold.Antiepileptic medicationDosage unitGramscarbohydrate perdosage unitCarbamazepine suspension (TEGretol)Carbamazepine chewable tablets(TEGretol)Carbamazepine tablets (TEGretol)ClonazePAM tablets (KlonoPIN)Ethosuximide syrup (Zarontin)Ethosuximide capsules (Zarontin)Felbamate solution (Felbatol)Felbamate tablets (Felbatol)Felbamate tablets (Felbatol)Gabapentin tablets (Neurontin)Gabapentin tablets (Neurontin)Gabapentin tablets (Neurontin)LamoTRIgine tablets (LaMICtal)LamoTRIgine tablets (LaMICtal)LamoTRIgine tablets (LaMICtal)LamoTRIgine tablets (LaMICtal)LamoTRIgine chewable/dispersibletablets (LaMICtal)Levetiracetam oral solution (Keppra)Phenobarbital elixir 0.71 g ethylalcohol/5 mLPhenobarbital tabletsPhenobarbital tabletsPhenobarbital tabletsPhenytoin suspension (Dilantin)Phenytoin infatabs (Dilantin)Phenytoin kapseal (Dilantin)Phenytoin kapseal (Dilantin)Primidone oral suspension (Mysoline)Primidone tablets (Mysoline)Primidone tablets (Mysoline)Sodium divalproex sprinkle capsules(Depakote)Sodium divalproex tablets (Depakote)Sodium divalproex tablets (Depakote)Sodium divalproex tablets (Depakote)Topiramate tablets (Topamax)Topiramate tablets (Topamax)Topiramate tablets (Topamax)Valproic acid syrup (Depakene)Valproic acid capsules (Depakene)100 mg/5 mL2.6535 mg/kg/dayDaily carbohydrate totalfrom maximum dosing ofmedication for a 18 kg5-year-old child (grams)16.7100 mg0.2835 mg/kg/day1.8200 mg2 mg250 mg/5 mL250 mg600 mg/5 mL400 mg600 mg100 mg300 mg400 mg25 mg100 mg150 mg200 160.1435 mg/kg/day0.2 mg/kg/day1.5 g/day1.5 g/day45 mg/kg/day45 mg/kg/day45 mg/kg/day40 mg/kg/day40 mg/kg/day40 mg/kg/day10 mg/kg/day10 mg/kg/day10 mg/kg/day10 15 mg, 25 mg010 mg/kg/day0100 mg/mL0.310 mg/kg/day0.520 mg/5 mL3.45 mg/kg/day15.315 mg30 mg60 mg125 mg/5 mL50 mg30 mg100 mg250 mg/5 mL50 mg250 mg0. mg/kg/day5 mg/kg/day5 mg/kg/day8 mg/kg/day8 mg/kg/day8 mg/kg/day8 mg/kg/day25 mg/kg/day25 mg/kg/day25 mg/kg/day0. mg0.0560 mg/kg/day0.4125 mg250 mg500 mg25 mg100 mg200 mg250 mg/5 mL250 mg0. mg/kg/day60 mg/kg/day60 mg/kg/day9 mg/kg/day9 mg/kg/day9 mg/kg/day60 mg/kg/day60 mg/kg/day0. dailydose for an 18 kg5-year-old childFor a five-year-old child weighing 18 kg, the maximum recommended carbohydrate amount is 21 g per day for the 3 : 1 classic ketogenic diet.

ISRN Pediatrics5Table 4: Carbohydrate content in pediatric analgesics/antipyretics and daily total carbohydrate estimates for a five-year-old child (weighing18 kg) on maximum treatment doses (concerns for the patient on a ketogenic diet) [5]a . Medications with high carbohydrate content ( 2 gper dose) are highlighted in bold.Description (brand name)Acetaminophen extended releasecaplets (Tylenol)Acetaminophen extra strengthcaplets (Tylenol)Acetaminophen extra strengthgel caps (Tylenol)Acetaminophen infant drops(grape and cherry) (Tylenol)Acetaminophen liquidsuspension (cherry) (Tylenol)Acetaminophen regular strengthcaplets (Tylenol)Acetaminophen elixir (Tylenol)Acetaminophen extra strengthliquid (Tylenol)Acetaminophen junior strengthswallowable caplets (Tylenol)Acetaminophen grape flavoredsuspension (Tylenol)Acetaminophen elixir withcodeine (Tylenol withCodeine) 0.35 g ethylalcohol/5 mLAcetaminophen with codeinetablets (Tylenol with Codeine)Acetaminophen chewable tablets(Tylenol)Ibuprofen tablets (Advil)Ibuprofen drops (Motrin)Ibuprofen suspension (Motrin)Ibuprofen chewable tablets(Motrin)Ibuprofen chewable tablets(Motrin)aDosage unitGrams carbohydrateper dosage unit650 mg 0.03500 mg 0.05500 mg 0.050.8 mL 0.71160 mg/5 mL 5325 mg 0.04160 mg/5 mL 1.61000 mg/30 mL 5.7160 mg 0.4160 mg/5 mL 4.8120 mg/5 mL3All strengths0.0580 mg0.25200 mg40 mg/mL100 mg/5 mLMaximum daily dosefor an 18 kg5-year-old child15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose for 5doses/day15 mg/kg/dose ofAPAPb for 5doses/dayDaily carbohydratetotal from maximumdosing of medicationfor a 18 kg 5-year-oldchild (grams) 1 1 1n/a for this patient42.2 113.57.7 140.533.80.23 0.41 0.6315 mg/kg/dose ofAPAP for 5 doses/day15 mg/kg/dose for 5doses/day40 mg/kg/day40 mg/kg/day40 mg/kg/day0.77.44.550 mg 0.2840 mg/kg/day3.9100 mg 0.5440 mg/kg/day3.8 14For a five-year-old child weighing 18 kg, the maximum recommended carbohydrate amount is 21 g per day for the 3 : 1 classic ketogenic diet.N-acetyl-para-aminophenol, or better known as acetaminophen.b APAP:managed correctly, although the amount of urine ketonesdoes not necessarily correlate directly with seizure control[1].Ketogenic diets, like any other treatment, are not withoutrisk and require monitoring of complications. Short-termadverse effects include dehydration, mild metabolic acidosis,and hypoglycemia during fasting [4]. Long-term adverseeffects include nephrolithiasis, constipation, vitamin andmineral deficiencies, increased cholesterol, retarded growthin young children, and decreased bone mineral density [4].Various laboratory values should be monitored initially androutinely (usually every 3 months for the 1st year) whenpatients are started on a ketogenic diet. Such laboratoriesinclude, but are not limited to, serum glucose, albumin,total protein, fasting cholesterol and triglycerides, and serumcreatinine [3].The addition of a ketogenic diet to a patient’s currentantiepileptic drug regimen is generally well tolerated andsafe. There is some evidence demonstrating that the combination of a ketogenic diet with zonisamide is beneficial inreducing seizures [9]. Alternatively, children on phenobarbital have less success in managing seizures when a ketogenic

6ISRN PediatricsTable 5: Carbohydrate content in pediatric antibiotic medications and daily total carbohydrate estimates for a five-year-old child (weighing18 kg) on maximum recommended treatment doses (concerns for the patient on a ketogenic diet) [5]a . Medications with high carbohydratecontent ( 2 g per dose) are highlighted in bold.Daily carbohydratetotal from maximumdosing of medicationfor a 18 kg 5-year-oldchild (grams)Dosage unitGrams carbohydrateper dosage unitMaximum daily dosefor an 18 kg5-year-old child50 mg/mL1.6100 mg/kg/dayn/a for this patient125 mg/5 mL1.7100 mg/kg/day24.5250 mg/5 mL1.85100 mg/kg/day13.3400 mg/5 mL1.88100 mg/kg/day8.46125 mg0.05100 mg/kg/day0.7250 mg0.34100 mg/kg/day2.4250 mg500 mg00100 mg/kg/day100 mg/kg/day00125 mg/5 mL3.3100 mg/kg/day47.5250 mg/5 mL3.3100 mg/kg/day23.8250 mg500 mg0000125 mg/5 mL0.52200 mg/5 mL0.06250 mg/5 mL0.6400 mg/5 mL0.06125 mg0.08250 mg0.34400 mg0.36Amoxicillin/clavulanatepotassium tablets (Augmentin)250 mg0.02Amoxicillin/clavulanatepotassium tablets (Augmentin)500 mg0.02Amoxicillin/clavulanatepotassium tablets (Augmentin)875 mg0.03100 mg/kg/day100 mg/kg/day40 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent100 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent100 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent45 mg/kg/dayamoxicillincomponent100 n pediatric drops(Amoxil)Amoxicillin oral suspension(Amoxil)Amoxicillin oral suspension(Amoxil)Amoxicillin oral suspension(Amoxil)Amoxicillin chewable tablets(Amoxil)Amoxicillin chewable tablets(Amoxil)Amoxicillin capsules (Amoxil)Amoxicillin capsules (Amoxil)Amoxicillin oral suspension(Trimox)Amoxicillin oral suspension(Trimox)Amoxicillin capsules (Trimox)Amoxicillin capsules (Trimox)Amoxicillin/clavulanatepotassium oral ium oral ium oral ium oral ium chewable tablets(Augmentin)Amoxicillin/clavulanatepotassium chewable tablets(Augmentin)Amoxicillin/clavulanatepotassium chewable tablets(Augmentin) 1 1 1

ISRN Pediatrics7Table 5: Continued.AntibioticsAmpicillin oral suspension(Omnipen)Ampicillin oral suspension(Omnipen)Azithromycin oral suspension(Zithromax)Azithromycin tablets(Zithromax)Cefaclor oral suspension(Ceclor)Cefaclor oral suspension(Ceclor)Cefaclor oral suspension(Ceclor)Cefaclor oral suspension(Ceclor)Cefaclor pulvules (Ceclor)Cefaclor pulvules (Ceclor)Cefadroxil oral suspension(Duricef)Cefadroxil oral suspension(Duricef)Cefadroxil capsules (Duricef)Cefadroxil film-coated tablets(Duricef)Cefixime oral suspension(Suprax)Cefixime tablets (Suprax)Cefixime tablets (Suprax)Cefpodoxime proxetil oralsuspension (Vantin)Cefpodoxime proxetil oralsuspension (Vantin)Cefpodoxime proxetil tablets(Vantin)Cefpodoxime proxetil tablets(Vantin)Cefprozil oral suspension(Cefzil)Cefprozil oral suspension(Cefzil)Cefprozil tablets (Cefzil)Cefprozil tablets (Cefzil)Cefuroxime axetil suspension(Ceftin)Cefuroxime axetil tablets (Ceftin)Cefuroxime axetil tablets (Ceftin)Cefuroxime axetil tablets (Ceftin)Cephalexin oral suspension(Keflex)Daily carbohydratetotal from maximumdosing of medicationfor a 18 kg 5-year-oldchild (grams)Dosage unitGrams carbohydrateper dosage unitMaximum daily dosefor an 18 kg5-year-old child125 mg/5 mL4100 mg/kg/day57.6250 mg/5 mL4100 mg/kg/day28.8100 mg/5 mL3.8610 mg/kg/day6.9250 mg0.0610 mg/kg/day 1125 mg/5 mL2.9540 mg/kg/day17187 mg/5 mL2.8340 mg/kg/day10.9250 mg/5 mL2.8340 mg/kg/day8.2375 mg/5 mL2.640 mg/kg/day5250 mg500 mg0.040.0740 mg/kg/day40 mg/kg/day 1 1250 mg/5 mL330 mg/kg/day6.5125 mg/5 mL3.130 mg/kg/day13.4500 mg0.1330 mg/kg/day0.131g0.1330 mg/kg/day 1100 mg/5 mL2.78 mg/kg/day3.9200 mg400 mg0.060.128 mg/kg/day8 mg/kg/dayn/an/a50 mg/5 mL310 mg/kg/day10.8100 mg/5 mL3.0510 mg/kg/day5.5100 mg0.0410 mg/kg/day 1200 mg0.0810 mg/kg/day0.08125 mg/5 mL220 mg/kg/day5.8250 mg/5 mL1.920 mg/kg/day2.7250 mg500 mg0.020.0320 mg/kg/day20 mg/kg/day 0.1 0.1125 mg/5 mL3.2330 mg/kg/day14125 mg250 mg500 mg00030 mg/kg/day30 mg/kg/day30 mg/kg/day000125 mg/5 mL3.13100 mg/kg/day45.1

8ISRN PediatricsTable 5: Continued.AntibioticsCephalexin oral suspension(Keflex)Cephalexin pulvules (Keflex)Cephalexin pulvules (Keflex)Ciprofloxacin tablets (Cipro)Ciprofloxacin tablets (Cipro)Ciprofloxacin tablets (Cipro)Ciprofloxacin oral suspension(Cipro)Ciprofloxacin oral suspension(Cipro)Clarithromycin suspension(Biaxin)Clarithromycin suspension(Biaxin)Clarithromycin tablets (Biaxin)Clarithromycin tablets (Biaxin)Erythromycin base tablets(Ery-Tab)Erythromycin base tablets(Ery-Tab)Erythromycin estolate oralsuspension (Ilosone)Erythromycin estolate oralsuspension (Ilosone)Erythromycin estolate pulvules(Ilosone)Erythromycin estolate tablets(Ilosone)Erythromycin ethylsuccinatedrops (EryPed)Erythromycin ethylsuccinatechewable tablets (EryPed)Erythromycin ethylsuccinatesuspension (E.E.S.)Erythromycin ethylsuccinatesuspension (E.E.S.)Erythromycin ethylsuccinategranules (E.E.S.)Erythromycin ethylsuccinatefilmtabs (E.E.S.)Erythromycin ethyl sulfisoxazole acetyl suspension(Pediazole)Erythromycin ethyl sulfisoxazole acetyl suspension(Pediazole)Nitrofurantoin oral suspension(Furadantin)Penicillin V potassium oralsuspensionDaily carbohydratetotal from maximumdosing of medicationfor a 18 kg 5-year-oldchild (grams)Dosage unitGrams carbohydrateper dosage unitMaximum daily dosefor an 18 kg5-year-old child250 mg/5 mL3.03100 mg/kg/day21.8250 mg500 mg250 mg500 mg750 mg0. mg/kg/day100 mg/kg/day30 mg/kg/day30 mg/kg/day30 mg/kg/day0. mg/5 mL1.430 mg/kg/day3500 mg/5 mL1.340 mg/kg/day1.4125 mg/5 mL315 mg/kg/day6.5250 mg/5 mL2.315 mg/kg/day2.5250 mg500 mg0.07015 mg/kg/day15 mg/kg/day0.070333 mg050 mg/kg/day0500 mg050 mg/kg/day0125 mg/5 mL1.8550 mg/kg/day13.3250 mg/5 mL1.850 mg/kg/day6.5250 mg050 mg/kg/day0500 mg0.1150 mg/kg/day0.210 mg/2.5 mL1.550 mg/kg/dayn/a200 mg1.4450 mg/kg/day6.5200 mg/5 mL3.550 mg/kg/day15.8400 mg/5 mL3.550 mg/kg/day7.9200 mg/5 mL1.550 mg/kg/day6.8400 mg0.250 mg/kg/day0.4200 mg/5 mL1.950 mg/kg/day8.6600 mg/5 mL1.950 mg/kg/day2.925 mg/5 mL0.77 mg/kg/day3.5125 mg/5 mL2.5350 mg/kg/day18.2

ISRN Pediatrics9Table 5: Continued.AntibioticsPenicillin V potassium oralsuspensionPenicillin V potassium tabletsPenicillin V potassium tabletsTrimethoprim (TMP) andsulfamethoxazole (SMX)suspension (Septra)Trimethoprim (TMP) andsulfamethoxazole (SMX) grapesuspension (Septra)Trimethoprim (TMP) andsulfamethoxazole (SMX) tablets(Septra)Trimethoprim (TMP) andsulfamethoxazole (SMX) doublestrength tablets (Septra)aDaily carbohydratetotal from maximumdosing of medicationfor a 18 kg 5-year-oldchild (grams)Dosage unitGrams carbohydrateper dosage unitMaximum daily dosefor an 18 kg5-year-old child250 mg/5 mL3.2850 mg/kg/day11.8250 mg500 mg40 mgTMP/200 mgSMX/5 mL40 mgTMP/200 mgSMX/5 mL80 mgTMP/400 mgSMX/5 mL160 mgTMP/800 mgSMX/5 mL0.09050 mg/kg/day50 mg/kg/day0.302.3520 mg/kg/dayTMP component21.22.3520 mg/kg/dayTMP component21.2020 mg/kg/dayTMP component0020 mg/kg/dayTMP component0For a five-year-old child weighing 18 kg, the maximum recommended carbohydrate amount is 21 g per day for the 3 : 1 classic ketogenic diet.Patient exampleA 4 year old male (18 kg) on a 3 : 1 classic ketogenic diet for refractory seizures has amaximum daily carbohydrate requirement of 21 g/daya (or 6 g/meal) and requirestreatment for acute otitis media. The physician writes a prescription for amoxicillin(400 mg/5 mL) 10 mL orally twice daily for 10 days and recommends acetaminophen(160 mg/5 mL) 8 mL orally every 6 hours as needed for pain or fever.If both medications are given as scheduled doses, the daily carbohydrate content can becalculated as:(i) Amoxicillin: 3.76 g/dose 2 doses 7.5 g carbohydrates/day(ii) Acetaminophen: 8 g CHO/dose 4 doses 32 g carbohydrates/dayThis equates to 39.5 g of carbohydrates per day which is more than the patient’s totaldaily carbohydrate allowance. Essentially, the patient has received more carbohydratesfrom his medicine than he would have received from his daily dietary intake ofcarbohydrates. In this case, the patient would have to restart the inpatient ketosis processin order to maintain ketosis again. If the patient could tolerate swallowing amoxicillintablets (0 g of carbohydrates/day) and acetaminophen junior strength swallowable tablets(3.2 g of carbohydrates/day), the patient would have received a total of 3.2 g ofcarbohydrates from his medicine. If the pharmacist communicates this carbohydrateamount to the nutritionist and/or physician, then the patient’s dietary carbohydrates canbe reduced by 3.2 g in order to maintain the patient’s total daily carbohydrate intake to21 g. In the later scenario, ketosis could have been maintained.Box 1: a A sample calculation of the patient’s daily carbohydrate requirements is provided in Table was added [9]. There are a few drug interactions withketogenic diets that prompt careful monitoring if the interaction cannot be avoided. In particular, monitor bicarbonatelevels in patients on concomitant AED therapy consistingof a carbonic anhydrase inhibitor, such as acetazolamideor methazolamide. The reduction in bicarbonate levels inaddition to the increased acid caused by ketones may causemetabolic acidosis [10].3. Pharmacists’ Involvement to ImproveOutcomes in Patients on Ketogenic DietPharmacists can play an important role in restricting the useof medications with high carbohydrate content. Ultimately,systems should be put in place to protect the patient frommedications with high carbohydrate content in order tomaintain ketosis and, thus, seizure control.

10Table 3 contains a list of pediatric antiepileptic drugs andtheir respective carbohydrate contents [5]. Carbamazpinesuspension, ethosuximide syrup, phenobarbital elixir, andvalproic acid syrup contain the highest amounts of carbohydrate and should be avoided in ketogenic diet patients.Choosing the tablet or capsule formulation for each of thesemedications reduces the daily carbohydrate intake while stillproviding the same dose to the patient. A general rule ofthumb is that carbohydrate content is the highest in suspensions and solutions, lower in chewable and disintegratingtablets, and lowest in tablets and capsules that are meant tobe swallowed whole. Also, labels reading “sugar-free” can bemisleading and often contain carbohydrates, such as sorbitol.The “sugar free” label is used primarily for diabetics and maycontain carbohydrate-containing excipients which will notaffect glycemia but might affect ketosis in the diet [11].Tables 4 and 5 also contain a list of common pediatricantibiotics and antipyretics with their respective carbohydr

ketogenic diet, the modified Atkins diet, the low-glycemic index treatment diet, the medium-chain triglyceride (MCT) diet, and the modified MCT diet (Table 1 )[4]. The classic ketogenic diet is the oldest of the diets and is one of the strictest of the diets. A gram scale is required to weigh food portions because no estimations are permitted .

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