Safety and role of ketogenic parenteral nutrition for intractable childhood epilepsy

doi:10.1016/j.braindev.2011.11.008

Brain and Development

Volume 34, Issue 8, September 2012, Pages 620-624

https://doi.org/10.1016/j.braindev.2011.11.008 Get rights and content

Abstract

To retrospectively evaluate the safety and role of ketogenic parenteral nutrition in patients with intractable childhood epilepsy. The ketogenic parenteral nutrition was given to 10 patients who were unable to absorb nutrients through the intestinal tract because of various gastrointestinal disorders and required complete bowel rest. This nutrition consisted of conventional intravenous fat emulsion (20% Lipision) plus dextrose and amino acid (6% Trophamine) hyperalimentation in a 4:1 (or 3:1) lipid to non-lipid ratio, infused during the bowel rest. If the ketogenic parenteral nutrition allowed normal daily functioning or resolved the underlying problems, we soon changed it to the enteral ketogenic diet (KD). The mean (±SD) duration of the ketogenic parenteral nutrition was 4.1 (±1.5) days. Although a brief span of several days, all patients could maintain ketosis and the efficacy of the previous enteral KD during the ketogenic parenteral nutrition. Complications included elevated aspartate aminotransferase and/or alanine aminotransferase in one patient. Amylase and lipase increased in one patient. Serum triglyceride level increased to the level of 1885 mg/dl in one patient, but normalized in one week after discontinuation of the ketogenic parenteral nutrition and resuming of the enteral KD. Nine patients (90%) remained on the enteral KD after the ketogenic parenteral nutrition (the mean follow-up period was 9 months), including 2 patients who successfully completed the diet with seizure free state. Only one patient discontinued the ketogenic parenteral nutrition because of persistent increase of the amylase and lipase levels. The ketogenic parenteral nutrition proved to be a relatively safe short-term method of continuing KD to maintain ketosis for seizure control, while patients were unable to absorb nutrients through their intestinal tract.

Introduction

Since the resurgence of the ketogenic diet (KD) in the mid 1990s, it has been used worldwide for the treatment of refractory pediatric epilepsy [1]. The KD is an established, effective nonpharmacologic treatment for intractable childhood epilepsy.

Like anticonvulsant therapy, there may be many ways in which to provide the KD and each of them may be valid. Generally, the KD is given to drug-resistant children with epilepsy by enteral formula or diet. Even though the effectiveness of the KD, there are many patients who often have coexisting medical problems that may impair the intake of oral foods, and therefore parenteral nutrition support might be needed. During acute illness, efforts should be made to preserve ketosis by providing parenterally administered nutrients, using intravenous lipids, protein, and limited glucose to maintain ketosis. When enteral feeding is contraindicated, previous experience showing some beneficial effects of the ketogenic parenteral nutrition has been reported only in one case [2]. At this time, however, there is insufficient evidence to recommend the use of the ketogenic parenteral nutrition for these conditions.

The purpose of this study was to provide practical recommendations and guidelines for the management of the ketogenic parenteral nutrition. Herein, we report on the successful maintenance of ketosis using the ketogenic parenteral nutrition in 10 patients with intractable childhood epilepsy who required bowel rest.

Section snippets

Methods

A retrospective analysis evaluated the safety outcomes in 10 patients with intractable epilepsy who were treated with the ketogenic parenteral nutrition. Subjects were recruited between November 2008 and March 2010. All patients had multiple seizures per day, despite the appropriate use of at least two antiepileptic drugs, and had previously showed the efficacy of enteral KD. The ketogenic parenteral nutrition was given to patients who were unable to absorb nutrients through the intestinal

Patient characteristics & the reasons for the ketogenic parenteral nutrition

Of the 10 patients (7 male, 3 female), four patients were diagnosed with Lennox-Gastaut syndrome, three with infantile spasms, and Dravet syndrome, generalized epilepsy and focal epilepsy, respectively, in each of the three remaining patients. Patients experienced their first seizure at a mean age of 3 years (range, 7 months to 6.5 years). The mean (±SD) age of the patients at initiation of the ketogenic parenteral nutrition was 64.7 (±45.5) months.

The ketogenic parenteral nutrition was given to

Discussion

Despite effectiveness of the KD in controlling seizures, children with intractable epilepsy often have other co-morbid conditions, including gastrointestinal and respiratory problems, which require parenteral nutrition. In what other situations could a ketogenic parenteral nutrition be beneficial? In general, a ketogenic parenteral nutrition can be started when enteral KD is contraindicated and prolonged bowel rest is required. One of the most commonly reported complications of the KD was

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Use of parenteral medium-chain triglyceride emulsion for maintaining seizure control in a 5-year-old girl with intractable diarrhea
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Early- and late-onset complications of the ketogenic diet for intractable epilepsy
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Acute pancreatitis causing death in a child on the ketogenic diet
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Cited by (27)

Core outcome set development for childhood epilepsy treated with ketogenic diet therapy: Results of a scoping review and parent interviews
2022, Seizure
Clinical trials on childhood epilepsy treated with ketogenic diet (KD) use a wide range of outcomes, however, patients and decision-makers often do not perceive the outcomes used as the most important. We sought parental opinion on outcomes of importance and compared these to outcomes reported in published research.
Ethical approval (London-Surrey-REC19/LO/1680). A scoping review identified outcomes reported in previous studies of childhood epilepsy and KD. Parents were recruited from nine KD centres (UK), charities and social media (international), then interviewed (Jan-April 2020) to explore priority outcomes. Content analysis identified all outcomes in transcripts. Parent identified outcomes were compared with those in the scoping review. Outcomes were collated and grouped into domains according to the COMET Taxonomy.
Of 2663 articles;147 met inclusion criteria. 921 verbatim outcomes were sorted into 90 discrete outcomes, reduced to 70 in consultation with the study advisory group, then classified into 21 domains. Parents (n = 21) identified 39 outcomes as important from the scoping review and seven new outcomes. They prioritised both physiological and functional outcomes in contrast to past studies, which prioritised physiological outcomes.
Little consistency exists in the outcomes used in childhood epilepsy and KD research. Those traditionally used do not adequately reflect parents’ important outcomes for their child. Clinical trials should consider the broader priorities of parents when choosing outcomes, in particular, functional outcomes. Identified outcomes will inform an international two-round Delphi-study with parent, professional and researcher participants to develop a core outcome set for this clinical area (COMET registration #1116).
Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus
2022, Seizure
Super-refractory status epilepticus (SRSE) is extremely difficult to control and associated with poor outcomes. Ketogenic diet (KD) has been increasingly used for SRSE treatment. Enteral ketosis induction in SRSE is sometimes unfeasible, leading to the use of parenteral KD which has limited data among children.
To assess the effectiveness of KD and compare parenteral and enteral ketosis induction as treatment options in pediatric SRSE patients.
This study is a retrospective medical record review of children < 15 years old diagnosed with SRSE who received KD as one of the treatment modalities during 2007–2021 at King Chulalongkorn Memorial Hospital, Thailand.
KD was used in 14 (77.8%) of the 18 pediatric SRSE cases whose age ranged from 2 months to 13.5 years. The leading etiologies of SRSE were immune-mediated encephalitis, infectious encephalitis, and epilepsy. Ketosis was induced via enteral route (kEN) in 8/14 and parenteral route (kPN) in 6/14 cases. The median time from the onset of SRSE to KD initiation was 6 days (IQR 4.8–9.3) with no demonstrable difference between groups. The median time to achieve significant ketosis was significantly shorter in the kPN (2 days; IQR 1.8–4) compared to the kEN group (5 days (3.3–7.8)). Nonetheless, the median time after ketosis induction to SRSE termination when anesthetic infusion was stopped was not statistically difference between the kPN (14 days; IQR 8.5–18) and the kEN group (10.5 days (5.5–15.3)). Hypertriglyceridemia was found more in the kPN (6/6, 100%) compared to the kEN group (3/8, 37.5%). All survivors (12/14) were seizure free at discharge.
Parenteral ketosis induction achieved the target ketosis quicker than enteral induction but showed no difference in efficacy and duration for SRSE termination in our study. The adverse effects were minimal and controllable. Both parenteral and enteral KD could be considered early during SRSE treatment.
Updates on the ketogenic diet therapy for pediatric epilepsy
2022, Biomedical Journal
The ketogenic diet (KD) is a high-fat, low-carbohydrate diet, in which fat, instead of glucose, acts as a major energy source through the production of ketone bodies. The KD was formally introduced in 1921 to mimic the biochemical changes associated with fasting and gained recognition as a potent treatment for pediatric epilepsy in the mid-1990s. Recent clinical and scientific knowledge supports the use of the KD in drug-resistant epilepsy patients for its anti-seizure efficacy, safety, and tolerability. The KD is also receiving growing attention as a potential treatment option for other neurological disorders. This article will review on the recent updates on the KD, focusing on its mechanisms of action, its alternatives, expansion on its use in terms of age groups and different regions in the world, and future issues.
REVIEW: Practical strategies to maintain anabolism by intravenous nutritional management in children with inborn metabolic diseases
2021, Molecular Genetics and Metabolism
Citation Excerpt :
Finally, the total fluid volume is made up with normal saline. An intravenous ketogenic diet can sustain ketosis as well as an enteral ketogenic diet without causing more hyperlipidemia [87–92], even when initiated in the neonatal period [90]. Similar to rarely reported observations in the literature, at our institution two cases of pancreatitis have been observed on intravenous ketogenic diet, thus its application has been reserved only for those metabolic cases where continued administration of a ketogenic diet is essential [87].
One of the most vital elements of management for patients with inborn errors of intermediary metabolism is the promotion of anabolism, the state in which the body builds new components, and avoidance of catabolism, the state in which the body breaks down its own stores for energy. Anabolism is maintained through the provision of a sufficient supply of substrates for energy, as well as critical building blocks of essential amino acids, essential fatty acids, and vitamins for synthetic function and growth. Patients with metabolic diseases are at risk for decompensation during prolonged fasting, which often occurs during illnesses in which enteral intake is compromised. During these times, intravenous nutrition must be supplied to fully meet the specific nutritional needs of the patient. We detail our approach to intravenous management for metabolic patients and its underlying rationale. This generally entails a combination of intravenous glucose and lipid as well as early introduction of protein and essential vitamins. We exemplify the utility of our approach in case studies, as well as scenarios and specific disorders which require a more careful administration of nutritional substrates or a modification of macronutrient ratios.
Application of ketogenic diets for pediatric neurocritical care
2020, Biomedical Journal
Citation Excerpt :
When enteral feeding is contraindicated, some beneficial effects of an intravenous ketogenic diet have been reported [14,15]. The first large series by Jung et al., in 2012 reported 10 children with intractable epilepsy who received an intravenous ketogenic diet in the chronic stage [15]. The first case report of an adult, a 21-year-old female, with super-refractory status epilepticus who received a parenteral ketogenic diet after 2 weeks of acute therapy was reported by Strzelczyk et al., in 2013 [14].
In this review, we summarize the general mechanisms of the ketogenic diet, and the application of a ketogenic diet in pediatric intensive care units for the neurological disorders of children and young infants. A ketogenic diet is a high-fat, low-carbohydrate, adequate-protein diet. It can alter the primary cerebral energy metabolism from glucose to ketone bodies, which involves multiple mechanisms of antiepileptic action, antiepileptogenic properties, neuro-protection, antioxidant and anti-inflammatory effects, and it is potentially a disease-modifying intervention. Although a ketogenic diet is typically used for the chronic stage of pharmacoresistant of epilepsy, recent studies have shown its efficacy in patients with the acute stage of refractory/super-refractory status epilepticus. The application of a ketogenic diet in pediatric intensive care units is a challenge because of the critical status of the patients, who are often in a coma or have a nothing by mouth order. Moreover, a ketogenic diet needs to be started early and sometimes through parenteral administration in patients with critical conditions such as refractory status epilepticus or febrile infection-related epilepsy syndrome. Animal models and some case reports have shown that the neuro-protective effects of a ketogenic diet can be extended to other emergent neurological diseases, such as traumatic brain injury and ischemic stroke.
The ketogenic diet for super-refractory status epilepticus patients in intensive care units
2019, Brain and Development
Super-refractory status epilepticus (SRSE) is one of the most challenging issues in intensive care units (ICUs) in that it is associated with high morbidity and mortality. Although the ketogenic diet (KD) has been reported to be effective in treating of SRSE, the use of the diet as therapy can be complicated by concomitant medical problems specific to critically ill patients. In this study, we aimed to describe our experience of the KD for SRSE patients in ICUs.
We retrospectively reviewed the medical records of 16 patients (10 males, 6 females) with SRSE who were treated with the KD in the ICUs at Samsung Medical Center from July 2005 to July 2017.
The median age of seizure onset was 8 years (interquartile range 5–13.5). Prior to diet initiation, the patients were in convulsive or non-convulsive SRSE for a median of 23 days (range, 3–420). The median time to achieve ketosis was 3 days (range, 2–6). The KD was continued for a median of 2.1 months (range, 0.1–15.8). Of the 16 patients, nine (56.3%) achieved seizure freedom, six (37.5%) reported >50% seizure reduction, and one (6.2%) had <50% seizure improvement after the KD. There was no significant change in the number of antiepileptic drugs. The most commonly encountered complication during the KD was gastrointestinal disturbance.
Our experience indicates that the KD is an effective alternative therapeutic strategy for SRSE patients in ICUs with adequate efficacy and safety in reducing seizure frequency and weaning from prolonged mechanical ventilation, although functional outcome was not favorable for most patients. Close monitoring and preventive management of potential adverse effects are critical elements for success with the KD in patients with SRSE.

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¹: These authors contributed equally to this work and are co-first authors.

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Original articleSafety and role of ketogenic parenteral nutrition for intractable childhood epilepsy

Abstract

Introduction

Section snippets

Methods

Patient characteristics & the reasons for the ketogenic parenteral nutrition

Discussion

The KD: From molecular mechanisms to clinical effects

Epilepsy Res

Use of parenteral medium-chain triglyceride emulsion for maintaining seizure control in a 5-year-old girl with intractable diarrhea

JPEN J Parenter Enteral Nutr

Early- and late-onset complications of the ketogenic diet for intractable epilepsy

Epilepsia

Improving tolerability of the ketogenic diet in patients with abnormal endoscopic findings

Brain Dev

Acute pancreatitis causing death in a child on the ketogenic diet

J Child Neurol

Original article
Safety and role of ketogenic parenteral nutrition for intractable childhood epilepsy