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NUTRITION REQUIREMENTS IN PATIETNTS WITH ACUTE BRAIN INJURY UNDERGOING PENTOBARBITAL
INFUSION
By
Wenxi Liu
Honors Thesis
Advisor: Denise Rhoney, PharmD, FCCP, FCCM, FNCS
UNC Eshelman School of Pharmacy
University of North Carolina
April 2016
Abstract
Pentobarbital infusion can be a treatment intervention to manage acute brain injury patients
with refractory increases in intracranial pressure (ICP). In fact, acute brain injury patients often
experience metabolic changes, which result in different nutritional requirements. These considerations
are critical since inappropriate nutrition can result in complications such as refeeding syndrome or
underfeeding. The purpose of this study was to assess calories received through nutrition feeding for
patients with acute brain injury who underwent pentobarbital infusion, compared against predicted
nutrition requirements, and evaluate the need for more accurate methods to optimize nutrition
regimens.
This is a retrospective cohort study of acute brain injury adult patients admitted to University of
North Carolina (UNC) hospital neuroscience Intensive Care Unit (ICU) from May 1, 2010 to August 31,
2013 who underwent pentobarbital infusion for longer than 48 hours and at least 16 years old. Data
were collected 48 hours before, during, and 48 hours after pentobarbital infusion.
Eighteen patients were included in the study. The median age was 57 years (Interquartile range,
IQR 54 – 63). Patients spent an average of 6.4 days in the pentobarbital phase. Mean total nutrition
calories from tube feed for pre-pentobarbital was 1385.4 kcal ± 542.4; during pentobarbital phase was
510.3 kcal ± 317.1; and post-pentobarbital phase was 1021 kcal ± 509. In addition, both Harris-Benedict
equation and 25 kcal/kg predicted higher total nutritional calories required for these patients with
acute brain injury receiving pentobarbital infusion.
Introduction
Acute brain injury is the leading cause of death and disability in the United States with 53,000
traumatic brain injury (TBI)-related injuries account for approximately 53,000 per year, one third of all
injury-related deaths. Following TBI, neurologic sequelae such as cerebral edema, elevated intracranial
pressure (ICP), and seizures are common. In addition, metabolic changes involving elevated catabolic
rate and extensive nitrogen loss. Brain is often the regulator for metabolic activity, and injuries from
TBI can cause irregular cellular metabolism and dynamic cerebral and systemic inflammatory response.
Treatment goal for acute brain injury is to minimize secondary injury to brain tissues. Quite often,
elevated ICP serves as a marker for secondary injury and is maintained at ICP < 20 mm Hg.
Furthermore, appropriate sedation medications can be used to lower metabolic demand and decrease
ICP. Also, sedation can also blunt sympathetic responses such as hypertension and tachycardia;
however, it’s important to cautious of hypotension and cerebral vasodilation. Moreover, barbiturate
can also be used to induce coma in order to facilitate with ICP management and post-traumatic
seizures.
Pentobarbital is commonly used as the barbiturate to reduce brain metabolism and cerebral
blood flow along with management of ICP. For pentobarbital, loading dose of 5 – 20 mg/kg given as
bolus, followed by 1 – 4 mg/kg/hr; continuous EEG monitoring is necessary to maintain burst
suppression pattern. Physiologically, pentobarbital results in a reduction in systemic and cerebral
metabolic demands along with a reduction of gastrointestinal motility.
One of the commonly used equations to measure energy requirement is Harris-Benedict
equation, which takes into account weight, height, age, and gender, not addressing metabolic changes
of brain injury patients receiving pentobarbital infusion. Additionally, 25 kcal/kg/day is another method
of estimating energy requirement. Current guideline addressing nutrition complications of TBI patients
doesn’t discuss anything concerning patient receiving pentobarbital infusion. However, there’s no
single method of estimating energy requirements in this patient population, and the importance to
provide adequate nutritional energy has becoming an issue. Various complications can arise from both
overfeeding and underfeeding acute brain injury patients. Complications from overfeeding include
metabolic acidosis, hypertonic dehydration, electrolyte imbalance, hyperglycemia, and
hypertriglyceridemia. Furthermore, complications from underfeeding include decreased respiratory
muscle strength, impaired organ functions, poor wound healing, increased risk of infection, and
wasting syndrome including weight loss and muscle atrophy.
Acute brain injury patients often experience hyper-metabolic state, which can lead to irregular
cellular catabolism, hyperglycemia, protein wasting, and increased nutrition energy demand and
consequently increase body’s basal metabolic rate. In fact, various studies claim that energy
expenditure recorded by indirect calorimetry was considerably lower than that calculated from both
Harris-Benedict equation and 25 kca/kg/day. Indeed, current, established equations used to predict
energy requirements cannot accurately predict energy needed for acute brain injury patients.
Ultimately, the use of pentobarbital infusion in brain injury patients for either elevated intracranial
pressure or status epileptics has provided additional challenge due to its intrinsic properties to lower
cerebral metabolic demand. The objective of the study is to assess total calories received via enteral
feeding for acute brain injury patients receiving pentobarbital infusion and to compare calories
received against predicted caloric requirements using standardized equations.
Methods
This is a retrospective, single-centered cohort study that included patients who are admitted to
UNC Neurosurgical ICU in Chapel Hill, NC between 2010 – 2013 and are greater than or older than 16
years old, suffer from acute brain injury, and received pentobarbital infusion for greater than 48 hours.
Primary study endpoints include difference between caloric needs predicted using standard equations
(Harris-Benedict and 25 kcal/kg/day) and total calories received during pentobarbital. In addition,
clinical study endpoints include adverse effects of nutrition regimen, ICU and hospital length of stay,
clinical disposition, and in-hospital mortality.
Data Collection and Statistical Analysis
Data were collected from electronic medical records in the UNC Hospital WebCis system from
May 1, 2010 to August 31, 2013. Patient’s records were reviewed to extract data including past medical
history; reason for pentobarbital infusion; length of hospital/ICU stay; and discharge disposition.
Furthermore, tube-feeding data (48 hours before, during, and 48 hours after pentobarbital infusion)
were collected such as volume of tube feed received and adverse events. Additionally, nutrition
requirements for patients were calculated using standard equations (Harris-Benedict and 25
kcal/kg/day) and compared against the nutritional calories the patients actually received during
pentobarbital infusion, along with clinical outcomes of patients. Data collected was analyzed using
descriptive statistics with Stata version 13.1. Data extracted were expressed as either median and
interquartile range (IQR) or frequency and percent.
Results
A total of 18 patients were included in the final analysis with median age of 57 years
(Interquartile range, IQR, 54 – 63), admission Glasgow Coma Scale of 5 (IQR 3-7), male gender (68.8 %)
as shown in Table 1. In terms of reasons to receive pentobarbital infusion, 11 patients (61.1 %)
received pentobarbital for refractory epilepticus and 7 patients (38.9 %) received pentobarbital for
refractory ICP. Finally, patients spent an average of 6.4 days (Standard deviation, SD, 2.7) in the
pentobarbital phase.
Table 1 – Patient Characteristics
Median total nutritional calories from tube feed for pre-pentobarbital phase was 1385.4 kcal ±
542.4; during pentobarbital phase of 510.3 kcal ± 317.1; and post-pentobarbital of 1021 kcal ± 509. In
addition, median residual volume for pre-pentobarbital phase was 71.82 mL, during pentobarbital
phase was 118.82 mL, and post-pentobarbital phase had least residual volume was 11.83 mL.
Moreover, median max tube feeding rate achieved was 55 mL/hr for pre-pentobarbital phase, 10
mL/hr during pentobarbital phase, and 20 mL/hr for post-pentobarbital phase (Table 2). In contrast,
both Harris-Benedict equation (1961 kcal ± 438) and 25 kcal/kg (2063.3 kcal ± 628.5) predicted higher
total nutritional calories required for these patients with acute brain injury receiving pentobarbital
infusion.
In terms of adverse events that occurred during tube feeding, 2 out of 18 patients (11.1 %) had
diarrhea and 3 out of 18 patients (16.7 %) experienced abdominal distention. Otherwise, no other
significant adverse events were observed. Median hospital length of stay was 25 (IQR 12 – 36), and
median length of ICU stay was 18 (IQR 10 – 29). Finally, 11 patients (61.11 %) experienced death, 1
patient (5.56 %) was discharged home, 3 patients (16.67%) were discharged to rehab facility, and 3
patients (16.67 %) were discharged to nursing facility.
Table 2 – Nutrition Energy Received during Pentobarbital Infusion
Conclusion
Established equations predicted nearly twice as many total calories required when compared to
calories actually received in this cohort of acute brain injury patients receiving pentobarbital.
Additionally, the reduction in calories received by these patients is due to a practice of using “trick
feeds” during pentobarbital infusion to prevent aspiration due to GI motility reduction. Diarrhea and
abdominal distention were the most commonly observed adverse events during nutrition feeding.
Therefore, a more accurate alternative method should be implemented for better estimation of
nutrition requirements for acute brain injury patients treated with pentobarbital infusion. Nonetheless,
the study does possess numerous limitations such as its retrospective cohort study design and
relatively small sample size, all of which have limited generalization of results to similar acute brain
injury patients undergoing pentobarbital infusion in other parts of the country.
Since established equations consistently predicted higher nutrition requirements than the
amount administered to acute brain injury patients receiving pentobarbital infusion. For future
direction, further studies are needed to examine other methods such as indirect calorimetry in
determining energy requirements in acute brain injury patients undergoing pentobarbital infusion.
Certainly, indirect calorimetry is a more accurate measure of energy requirements since it assesses
energy requirements by evaluating patient’s own oxygen requirement and carbon dioxide production,
which consequently would be a better predictor of patient’s energy needs. However, indirect
calorimetry is hard to operate and labor intensive in addition to high expense of the calorimetry
machine.
References
1. Urbano, L.A. Oddo, M. Therapeutic Hypothermia for Traumatic Brain Injury. Curr Neurol
Neurosci Rep. July 2012; 12: 580-591.
2. Cook, A. Peppard, A. Magnuson, B. Nutrition in Clinical Practice. Nutrition Considerations in
Traumatic Brain Injury, Nutrition in Clinical Practice. December 2008; 23(6): 608-617.
3. Morbitzer, K. (2013). Nutrition Requirements in Induced Moderate Prolonged Hypothermia for
Traumatic Brain Injury. Accessed October 17, 2014.
4. Urbano LA, Oddo M. Therapeutic hypothermia for traumatic brain injury. Current neurology
and neuroscience reports 2012;12:580-91.
5. brain injury. Nutrition in clinical practice : official publication of the American Society for
Parenteral and Enteral Nutrition 2008;23:608-20.
6. Frattalone AR, Ling GS. Moderate and severe traumatic brain injury: pathophysiology and
management. Neurosurgery clinics of North America 2013;24:309-19.