Do certain subpopulations of adults with drug-resistant epilepsy respond better to modified ketogenic diet treatments? Evaluation based on prior resective surgery, type of epilepsy, imaging abnormalities, and vagal nerve stimulation.

OBJECTIVE: Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. METHODS: Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. RESULTS: Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. CONCLUSIONS: Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.

Modified ketogenic diets in adults with refractory epilepsy: Efficacious improvements in seizure frequency, seizure severity, and quality of life.

OBJECTIVE: This study evaluates the efficacy of a modified ketogenic diet (MKD) on seizure frequency, severity, and quality of life (QOL), as well as potential complications of MKD therapy among adults with drug-resistant epilepsy (DRE). METHODS: Changes in seizure frequency, severity, QOL, and side effects were retrospectively examined among adults, ≥17 years of age, with DRE (≥2 antiepileptic drugs [AEDs]), after 3 months of MKD therapy. Attention was paid to medication or vagus nerve stimulator (VNS) changes as well to evaluate potential confounders. RESULTS: A total of 60% (n = 33) of the 55 individuals reported ≥50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in QOL. More patients following a modified ketogenic diet - 15 g net carbohydrate daily (MKD-15) (95%) compared with a MKD-50 (69%) reported improvement in QOL (p = 0.02). Weight among the entire sample declined from 77.5 (20) kg to 73.9 (19.0) kg (p < 0.0001), and total cholesterol (TC), low density lipoprotein (LDL), and total cholesterol:high density lipoprotein (TC:HDL) increased significantly (p = 0.03, p = 0.04, and p = 0.02, respectively). Free carnitine values were available for a select number of patients, 26 (47%) at baseline, and 7 (13%) at follow-up, of which 8 (31%) at baseline, and 2 (29%) at follow-up had carnitine deficiency (<25 nmol/mL). Constipation was noted in 5 patients (9%), and no kidney stones were reported during the study period. There were no statistical differences in number or dose changes for AED or VNS during the study period. SIGNIFICANCE: Modified ketogenic diet therapies reduce seizure frequency and severity and improve QOL among adults with DRE with few side effects outside of weight loss, a desired outcome among many adults with DRE. More restrictive MKDs may offer improved seizure severity and QOL. Modified ketogenic diet therapy increases LDL cholesterol, which may be cardioprotective if related to an increase in LDL particle size with high saturated fat intake; however, more research is needed examining LDL particle size changes among those receiving MKD therapy.

Ventilatory equivalent for oxygen as an extubation outcome predictor: A pilot study.

INTRODUCTION: Weaning predictors can help liberate patients in a timely manner from mechanical ventilation. Ventilatory equivalent for oxygen (VEqO2), a surrogate for work of breathing and a measure of the efficiency of breathing, may be an important noninvasive alternative to other weaning predictors. Our study's purpose was to observe any differences in VEqO2 between extubation outcome groups. METHODS: Employing a metabolic cart, oxygen consumption (V˙ O2), minute volume (VE), tidal volume (VT), and breathing frequency were recorded during a spontaneous breathing trial (SBT) to calculate VEqO2 and the rapid shallow breathing index (RSBI) in 34 adult participants in the intensive care unit. Five-breath means of VEqO2 and the RSBI collected throughout the SBT were examined between SBT pass and fail groups and extubation pass and fail groups using the Mann-Whitney U test with p < 0.05. RESULTS: Data from 31 participants were analyzed between SBT outcome groups. Data from 20 participants were examined for extubation outcome after a successful SBT. Median (interquartile range) VEqO2 was not different between extubation groups. Participants who passed the SBT had a higher median VEqO2 than those who did not at the midpoint (25.3 L/L V˙ O2 [22-33 L/L V˙ O2] vs. 23.7 L/L V˙ O2 [18-24 L/L V˙ O2], p = 0.035) and at the end (25.5 L/L V˙ O2 [23-34 L/L V˙ O2] vs. 21.3 L/L V˙ O2 [20-24 L/L V˙ O2], p = 0.017) of the SBT. DISCUSSION: VEqO2 may show differences in SBT outcomes, but not differences between extubation outcomes. VEqO2 may be able to detect differences in work during an SBT, but may not be able to predict change in workload in the respiratory system after extubation. The small sample size may also have prevented any differences in extubation outcomes to be shown. CONCLUSION: VEqO2 was higher in patients that passed their SBT. VEqO2 was not useful in identifying extubation success or failure in adult mechanically ventilated patients.

Erratum: Ventilatory equivalent for oxygen as an extubation outcome predictor: A pilot study.

[This corrects the article on p. 65 in vol. 55, PMID: 31489359.].

Nutrition in the Neurocritical Care Unit: a New Frontier.

PURPOSE OF REVIEW: This review presents the most current recommendations for providing nutrition to the neurocritical care population. This includes updates on initiation of feeding, immunonutrition, and metabolic substrates including ketogenic diet, cerebral microdialysis (CMD) monitoring, and the microbiome. RECENT FINDINGS: Little evidence exists to support differences in feeding practices among the neurocritical care population. New areas of interest with limited data include use of immunonutrition, pre/probiotics for microbiome manipulation, ketogenic diet, and use of CMD catheters for substrate utilization monitoring. SUMMARY: Acute neurologic injury incites a cascade of adrenergic and neuroendocrine events resulting in a pro-inflammatory and hypercatabolic state, which is associated with an increase in morbidity and mortality. Nutritional support provides substrates to mitigate the damaging effects of hypermetabolism. Despite this practice, studies on feeding delivery outcomes remain inconsistent. Guidelines suggest use of early enteral nutrition using standard polymeric formulas. Population heterogeneity, variability in interventions, complexities of the metabolic and inflammatory responses, and paucity of nutrition research in patients requiring neurocritical care have led to controversies in the field. It is imperative that more pragmatic and reproducible research be conducted to better understand underlying pathophysiology and develop interventions that may improve outcomes.

International Recommendations for the Management of Adults Treated With Ketogenic Diet Therapies.

OBJECTIVE: To evaluate current clinical practices and evidence-based literature to establish preliminary recommendations for the management of adults using ketogenic diet therapies (KDTs). METHODS: A 12-topic survey was distributed to international experts on KDTs in adults consisting of neurologists and dietitians at medical institutions providing KDTs to adults with epilepsy and other neurologic disorders. Panel survey responses were tabulated by the authors to determine the common and disparate practices between institutions and to compare these practices in adults with KDT recommendations in children and the medical literature. Recommendations are based on a combination of clinical evidence and expert opinion regarding management of KDTs. RESULTS: Surveys were obtained from 20 medical institutions with >2,000 adult patients treated with KDTs for epilepsy or other neurologic disorders. Common side effects reported are similar to those observed in children, and recommendations for management are comparable with important distinctions, which are emphasized. Institutions differ with regard to recommended biochemical assessment, screening, monitoring, and concern for long-term side effects, and further investigation is warranted to determine the optimal clinical management. Differences also exist between screening and monitoring practices among adult and pediatric providers. CONCLUSIONS: KDTs may be safe and effective in treating adults with drug-resistant epilepsy, and there is emerging evidence supporting the use in other adult neurologic disorders and general medical conditions as well. Therefore, expert recommendations to guide optimal care are critical as well as further evidence-based investigation.

Higher Caloric Exposure in Critically Ill Patients Transiently Accelerates Thyroid Hormone Activation.

INTRODUCTION: The inflammatory response of critical illness is accompanied by nonthyroidal illness syndrome (NTIS). Feeding has been shown to attenuate this process, but this has not been explored prospectively over time in critically ill patients. OBJECTIVE: To explore the impact of calorie exposure on NTIS over time in critically ill patients. METHODS: Mechanically ventilated patients with systemic inflammatory response syndrome (SIRS) were randomized to receive either 100% or 40% of their estimated caloric needs (ECN). Thyroid hormones were measured daily for 7 days or until intensive care unit discharge or death. Mixed level regression modeling was used to explore the effect of randomization group on plasma triiodothyronine (T3), reverse triiodothyronine (rT3), thyroxine (T4), and thyroid stimulating hormone (TSH), as well as the T3/rT3 ratio. RESULTS: Thirty-five participants (n=19 in 100% ECN; n=16 in 40% ECN) were recruited. Adjusting for group differences in baseline T3/rT3 ratio, the parameters defining the fitted curves (intercept, linear effect of study day, and quadratic effect of study day) differed by randomization group (P = 0.001, P = 0.01, and P = 0.02 respectively). Plots of the fitted curves revealed that participants in the 100% ECN group had a 54% higher T3/rT3 ratio on postintervention day 1 compared with the 40% ECN group, a difference which attenuated over time. This was driven by a 23% higher plasma T3 and 10% lower plasma rT3 levels on postintervention 1. CONCLUSIONS: Higher caloric exposure in NTIS patients transiently attenuates the drop of the plasma T3/rT3 ratio, an effect that is minimized and finally lost over the following 3 days of continued higher caloric exposure.

Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy.

Ketogenic diet (KD) therapy is an established form of treatment for both pediatric and adult patients with intractable epilepsy. Ketogenic diet is a term that refers to any diet therapy in which dietary composition would be expected to result in a ketogenic state of human metabolism. While historically considered a last-resort therapy, classic KDs and their modified counterparts, including the modified Atkins diet and low glycemic index treatment, are gaining ground for use across the spectrum of seizure disorders. Registered dietitian nutritionists are often the first line and the most influential team members when it comes to treating those on KD therapy. This paper offers registered dietitian nutritionists insight into the history of KD therapy, an overview of the various diets, and a brief review of the literature with regard to efficacy; provides basic guidelines for practical implementation and coordination of care across multiple health care and community settings; and describes the role of registered dietitian nutritionists in achieving successful KD therapy.

Enteral nutrition formula selection: current evidence and implications for practice.

Many new enteral nutrition (EN) formulas have been created over the past several decades with a variety of intended uses. Although each is intended to promote improved outcomes, research is often unclear and, in many cases, conflicting. It is important to note that EN products are considered medical foods by the U.S. Food and Drug Administration and therefore do not have to complete premarket review or approval and are not regulated to the same extent as pharmaceuticals. While standard EN formulas are designed to meet the basic macro- and micronutrient requirements of individuals who cannot meet nutrition needs orally, specialty EN products have been developed to exhibit pharmacologic properties, such as immune-enhancing formulas containing arginine, glutamine, nucleotides, and ω-3 fatty acids. With the vast number of products available, rising costs of healthcare, and the drive toward evidence-based practice, it is imperative that clinicians carefully consider research regarding use of specialty formulas, paying close attention to the quality, patient population, clinical end points, and cost to patient and/or facility.

Use of 3 tools to assess nutrition risk in the intensive care unit.

BACKGROUND: Identifying patients at nutrition risk proves difficult in the intensive care unit (ICU) due to the nature of critical illness. No consensus exists on the most appropriate method to identify these patients. Traditional screens and assessments are often limited due to their subjective nature. The purpose of the quality improvement project was to compare proportions of ICU patients deemed at nutrition risk using 3 different tools. MATERIAL AND METHODS: A convenience sample of 294 patients admitted to the ICU was used. Patients were assessed using the institution's routine nutrition screening method, the Subjective Global Assessment (SGA), and the NUTrition Risk in Critically ill (NUTRIC) score. Information was collected on demographics, severity of illness, hospital and ICU length of stay (LOS), and disposition. Descriptive statistics were used to examine counts/proportions of risk categories; means ± SD were used to summarize demographic and clinical variables. RESULTS: A total of 139 patients (47%) were deemed at nutrition risk or malnourished by at least 1 tool. Patients identified were older and had a lower body mass index, more weight loss, more fat and muscle wasting, more fluid accumulation, and lower average handgrips than those not at nutrition risk; they also had longer hospital and ICU LOS, higher rates of requiring further rehabilitation upon discharge, and higher mortality during hospitalization. CONCLUSION: Traditional screening and assessment tools did not uniformly identify patients as malnourished or at nutrition risk in the ICU and therefore may be inappropriate for use in this population. Inclusion of physical assessment, functional status, and severity of illness may be useful in predicting nutrition risk in the ICU.

Ketogenic diet for adults in super-refractory status epilepticus.

OBJECTIVE: To describe a case series of adult patients in the intensive care unit in super-refractory status epilepticus (SRSE; refractory status lasting 24 hours or more despite appropriate anesthetic treatment) who received treatment with the ketogenic diet (KD). METHODS: We performed a retrospective case review at 4 medical centers of adult patients with SRSE treated with the KD. Data collected included demographic features, clinical presentation, diagnosis, EEG data, anticonvulsant treatment, and timing and duration of the KD. Primary outcome measures were resolution of status epilepticus (SE) after initiation of KD and ability to wean from anesthetic agents. RESULTS: Ten adult patients at 4 medical centers were started on the KD for SRSE. The median age was 33 years (interquartile range [IQR] 21), 4 patients (40%) were male, and 7 (70%) had encephalitis. The median duration of SE before initiation of KD was 21.5 days (IQR 28) and the median number of antiepileptic medications used before initiation of KD was 7 (IQR 7). Ninety percent of patients achieved ketosis, and SE ceased in all patients achieving ketosis in a median of 3 days (IQR 8). Three patients had minor complications of the KD including transient acidosis and hypertriglyceridemia and 2 patients ultimately died of causes unrelated to the KD. CONCLUSION: We describe treatment of critically ill adult patients with SRSE with the KD, with 90% of patients achieving resolution of SE. Prospective trials are warranted to examine the efficacy of the KD in adults with refractory SE. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for intensive care unit patients with refractory SE, a KD leads to resolution of the SE.

Predictors of insulin requirements among hospitalized adults receiving parenteral nutrition.

OBJECTIVE: The objective of this quality improvement project was to determine factors predictive of parenteral nutrition (PN) insulin therapy. METHODS: Patients receiving PN at a tertiary care academic medical center between January 1, 2009, and December 1, 2012, 18 years or older were included. Variables collected included demographics, medical information, and PN-specific data. χ(2) and Student t tests were used to determine differences between patients who did and did not require PN insulin. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to determine associations between characteristics. Stepwise forward logistic regression was used determine the best predictors of PN insulin. RESULTS: A total of 1388 patients were started on PN. After adjusting for potential confounders, strong associations existed between PN insulin requirements and diabetes mellitus (DM) diagnosis (OR, 8.90; 95% CI, 4.98-15.90, P < .001), overweight/obese status (body mass index ≥25.0 kg/m(2)) (OR, 2.12; 95% CI, 1.04-4.30, P = .04), intensive care unit (ICU) admission (OR, 1.79; 95% CI, 1.03-3.11, P = .04), blood glucose (BG) on day of PN start >120 mg/dL (OR, 2.32; 95% CI, 1.32-4.05, P = .003), mean BG >180 mg/dL while receiving PN (OR, 6.10; 95% CI, 2.18-17.04, P = .001), and hemoglobin A1c (A1c) ≥5.7% (OR, 3.18; 95% CI, 1.84-5.50, P < .001). Among variables available at PN initiation, DM diagnosis (P < .001), A1c ≥5.7% (P < .001), BG >120 mg/dL on PN start day (P < .001), and ICU admission (P < .001) predicted the need for PN insulin.