Parenteral Nutrition Orders Research Articles

Provider Support of Parenteral Nutrition Order Writing by Registered Dietitians

Provider Support of Parenteral Nutrition Order Writing by Registered Dietitians

Nutritional Support in Pancreatic Diseases.

This review summarizes the main pancreatic diseases from a nutritional approach. Nutrition is a cornerstone of pancreatic disease and is sometimes undervalued. An early identification of malnutrition is the first step in maintaining an adequate nutritional status in acute pancreatitis, chronic pancreatitis and pancreatic cancer. Following a proper diet is a pillar in the treatment of pancreatic diseases and, often, nutritional counseling becomes essential. In addition, some patients will require oral nutritional supplements and fat-soluble vitamins to combat certain deficiencies. Other patients will require enteral nutrition by nasoenteric tube or total parenteral nutrition in order to maintain the requirements, depending on the pathology and its consequences. Pancreatic exocrine insufficiency, defined as a significant decrease in pancreatic enzymes or bicarbonate until the digestive function is impaired, is common in pancreatic diseases and is the main cause of malnutrition. Pancreatic enzymes therapy allows for the management of these patients. Nutrition can improve the nutritional status and quality of life of these patients and may even improve life expectancy in patients with pancreatic cancer. For this reason, nutrition must maintain the importance it deserves.

Offering Guidance and Learning to Prescribers to Initiate Parenteral Nutrition using a Validated Electronic Decision TREE (OLIVE TREE).

Parenteral nutrition (PN) is recommended in patients nutritionally at risk and unable to receive oral or enteral nutrition. A standardized electronic PN order format could enhance appropriate PN prescribing. We developed the OLIVE TREE (Offering guidance and Learning to prescribers to Initiate PN using a Validated Electronic decision TREE), embedded in our electronic health record. We aimed to evaluate its validity and impact on physicians' prescribing behavior. A non-randomized before-after study was carried out in a tertiary care center. The OLIVE TREE comprises 120 individual items. A process validation was performed to determine interrater agreement between a pharmacist and the treating physician. To estimate the proportion of patients for whom the OLIVE TREE had an effective and potential impact on physicians' prescribing behavior, a proof of concept study was conducted. The proportion of patients for whom PN was averted and the proportion of decisions not in line with the recommendation were also calculated. The process validation in 20 patients resulted in an interrater agreement of 95.0%. The proof of concept in 73 patients resulted in an effective and potential impact on prescribing behavior in 50.7% and 79.5% of these patients, respectively. Initiation of PN was not averted and recommendations of the OLIVE TREE were overruled in 42.5% of the patients. Our newly developed OLIVE TREE has a good process validity. A substantial impact on prescribing behavior was observed, although initiation of PN was not avoided. In the next phase, the decision tree will be implemented hospital-wide.

Impact of computerized physician order entry system on parenteral nutrition medication errors in a teaching neonatal intensive care unit

Parenteral nutrition (PN) offers a quality therapeutic option when enteral feeding is non-tolerated or impossible. However, it can be associated with an increased risk of medical errors, especially in sensitive populations such as newborns. This study aimed at determining the impact of the implementation of a computerized physician order entry (CPOE) system on PN medication errors in the neonatology department in the largest teaching hospital in Tunisia. The frequency of medication errors in PN, in a teaching neonatal intensive care unit, was prospectively reviewed by a pharmacist between December 2018 and March 2019 in a two-phase interventional study (pre and post locally developed CPOE System implementation). Implementation of CPOE system decreased PN order errors from 379 to 147 representing a 61.1% reduction. The decreases on PN order errors per stage, i.e. prescribing and preparation, were form 207 to 22 (89.4%), and from 117 to 66 (43.6%), respectively. Mean nutrients intakes were in conformity to the recommended daily intakes during the CPOE phase of the study. CPOE is a protective tool against prescription and preparation errors. It significantly impacted all items of the ordering process. In addition to the rigorous application of the recommendations, the CPOE system allows to reduce the risk of PN medication errors. This improves the safety and quality of medicines in newborns.

Centralized insourcing of sterile compounding: One multihospital health system's journey.

The process and challenges associated with an initiative to pivot from insourcing the batch compounding of high-volume sterile preparations to insourcing patient-specific compounding of parenteral nutrition (PN) at a health-system central fill pharmacy (CFP) serving 8 hospitals in central Florida are described. The insourcing initiative was prompted by a need for greater oversight of sterile compounding to ensure patient safety and the potential for cost savings. In 2014 the health system opened a CFP to provide replenishment of automated dispensing machines and insourcing of 19 compounded sterile preparations (CSPs) as the hub of a hub-and-spoke distribution system for 8 local hospitals. The need to comply with a 2016 proposed Food and Drug Administration requirement limiting the distribution by 503A pharmacies of non-patient-specific CSPs beyond 1 mile and the state of Florida's scope of practice definition related to sterile compounding prompted the CFP to switch from CSP insourcing to PN insourcing. The business case was based on substantial projected cost savings of more than $900,000 annually from PN insourcing versus outsourcing. A hybrid model for insourcing PN preparation was developed by using the PN compounding device, solutions, and additives from different vendors. Standardization of PN formulations and order templates streamlined the ordering process and reduced the unnecessary use of additives and associated costs. With careful planning, the CFP successfully pivoted from insourcing CSPs to insourcing PN. A collaborative approach with early and frequent communication among key health-system and vendor stakeholders was vital to the success of the initiative.

Changes in Parenteral Nutrition Requirements and BMI in Patients with Parenteral Nutrition-Dependent Short Bowel Syndrome after Stopping Teduglutide-9 Years of Follow-Up.

Teduglutide (TED) is widely used in patients with short-bowel-syndrome-associated intestinal failure (SBS-IF) to enhance intestinal adaptation and reduce the need for parenteral support (PS). There are limited data on the effects of discontinuing TED. In this study, we describe the changes in parenteral nutrition (PN) requirements and body mass index (BMI) in a 9-year follow-up of patients receiving home parenteral nutrition after discontinuation of the TED treatment. We performed a retrospective analysis of changes in weekly PN orders and BMI in all patients with PN-dependent SBS from two Polish home parenteral nutrition (HPN) centers who received teduglutide between 2009 and 2013 and still required HPN 9 years after discontinuation of the TED treatment. Data included in the analysis were collected prospectively at mandatory visits to the HPN centers at 12, 24, 60, 84, and 108 months after drug discontinuation and compared with values before and after TED treatment. Weekly PN volume values varied significantly between all of the above time points from baseline to 9 years after TED discontinuation (χ2 = 34.860, p < 0.001). After an initial increase within the first year after treatment discontinuation (not statistically significant), the PN volume requirements remained stable for 4 years and increased 5–9 years after treatment discontinuation. The rate of patients requiring an increase in PN volume was 84.62% at 60 and 84 months and 92.30% at 108 months. At 9 years after cessation of the TED treatment, 53.85% of the study group required a 21.21% increase in PN volume compared with values before treatment. The need for PN volume in patients with PN-dependent SBS who discontinued the TED treatment increased within the first year and 4–5 years after treatment cessation, and in some cases might even exceed pretreatment values after 9 years.

Parenteral nutrition compatibility and stability: A comprehensive review.

Several guidance documents support best practices across the stages of the parenteral nutrition (PN) use process to optimize patient safety. The critical step of PN order verification and review by the pharmacist requires a contextual assessment of the compatibility and stability implications of the ordered PN prescription. This article will provide working definitions, describe PN component characteristics, and present a wide-ranging representation of compatibility and stability concerns that need to be considered prior to preparing a PN admixture. This paper has been approved by the American Society for Parenteral and Enteral Nutrition (ASPEN) Board of Directors.

What is the ideal clinical pharmacy practice model? A satisfaction comparative study

AbstractIntroductionCurrent pharmacy practice models vary. Unit‐based pharmacists are in charge of patients in specific locations, placing emphasis on timely order verification. In contrast, service‐based pharmacists are assigned to multidisciplinary teams who provide consultations without order verification duties. Hybrid‐based pharmacists provide clinical activities in addition to half‐day order verification. There are conflicting opinions regarding the ideal model in providing care. Currently, there are limited studies comparing these approaches in a specialized health care system.ObjectivesThe primary objective of this study is to compare staff satisfaction; nurses, physicians, pharmacist peers, patients, and self‐satisfaction, with respect to the three models.MethodsThis is a prospective study conducted in a tertiary care facility comparing different pharmacy practice models by assessing the satisfaction of different members of the health care team through satisfaction surveys. Assuming 15% difference, 116 observations were required for each arm. Secondary end points compared the number of medication errors reported, clinical interventions documented, order verification, adverse drug reactions reported, protocol/guideline reviews, and total parenteral nutrition orders entered as well as nonformulary reviews within each model. The study was approved by Research Advisory Council.ResultsA total of 377 surveys were collected. In the total general average of overall satisfaction, unit‐based model achieved a rate of 70.61%, service‐based 69.84%, and the hybrid model 59.9%. Both unit and service‐based models had a higher overall satisfaction when compared to hybrid model; unit‐based (70.61% vs 59.97%, P = .005), service‐based (69.84% vs 59.97%, P = .009). Nurses and patients favored unit‐based pharmacists with a satisfaction rate of 72% and 89%, respectively. The unit‐based pharmacists were the most satisfied, 76%, compared to their peers in other models.ConclusionBased on this study, the majority of the surveyed cohort, including nurses, patients, and self‐surveyed pharmacists, favored the unit‐based model.

Parenteral Nutrition Prescribing and Order Review Safety Study: The Need for Pharmacist Intervention.

Errors have been reported in the literature to occur at each step of the parenteral nutrition (PN) use process, necessitating standardized processes, clinician competence, and open communication for those involved. This study was performed at Central Admixture Pharmacy Services (CAPS®) in collaboration with the American Society for Parenteral and Enteral Nutrition (ASPEN) with the purpose to study the need for and success of PN pharmacist interventions. A survey was developed and sent to all CAPS customers for study enrollment and to identify their demographic and practice characteristics. For those enrolled, CAPS pharmacists reviewed every PN order in a 1-month period using an error/intervention tool to capture data on prescription elements requiring intervention, along with acceptance of that intervention. Two hundred thirty-two unique CAPS customers (23% response rate) participated in the study, representing 37,634 unique PN prescriptions. Two hundred forty-eight PN prescriptions (0.66%) from 59 customers required ≥1 intervention. The top 3 intervention types were electrolyte dose clarification, calcium/phosphorus incompatibility, and amino acid dose clarification. A greater number and percentage of interventions were required for neonatal prescriptions, as compared with adult and pediatric prescriptions. No significant difference was found in many of the other customer characteristics. This study supports the need for institutions to develop systems to comply with published PN safety recommendations, including knowledgeable and skilled pharmacists to complete the order review and verification steps for this high-alert medication.

Nutrition Support Team Oversight and Appropriateness of Parenteral Nutrition in Hospitalized Adults: A Systematic Review.

Inappropriate parenteral nutrition (PN) administration often occurs in hospitalized patients, increasing the risk of complications. Nutrition support teams (NSTs) regulate and approve PN use in some hospitals. This systematic review examined whether appropriateness of PN use in hospitalized adult patients increased under NST oversight. Ten databases were searched systematically to select studies from 2004 to 2020 that analyzed appropriateness of PN use in adult hospitalized patients under NST oversight. Studies were included if appropriateness of PN was examined and NSTs were involved in PN orders or recommendations. Studies were evaluated using the Quality Criteria Checklist from the Academy of Nutrition and Dietetics Evidence Analysis Library. Nine studies were included in the final analysis. One received a positive rating on the quality checklist, whereas 8 received a neutral rating. Inappropriate PN use varied from 4.3% to 18%. Two studies compared PN use between multiple hospitals, both with and without NSTs. Two compared appropriateness before and after NST implementation, whereas another 2 studies compared it before and after NST restructuring. Three studies examined appropriateness of PN with NST oversight at a single facility with no control group. Overall, NSTs were associated with decreased incidence of inappropriate PN use. No studies were randomized, and several did not describe demographics between groups. Although NSTs appear to decrease inappropriate PN use, the results are limited because of study design or reporting. Future studies should monitor and evaluate clinical outcomes, such as mortality, and utilize more rigorous methodologies.

Trace Elements' Contamination of Pediatric Parenteral Nutrition Solutions in Canada: A Cause for Concern.

Trace elements' (TEs) contamination of parenteral nutrition (PN) solutions is an ongoing concern. The aims of this study were 1) to measure actual TE concentrations in PN admixtures compared with ordered concentrations and 2) compare TE intake with current recommendations. PN admixtures from discarded bags were collected from patients receiving home PN and on inpatient wards. Samples were collected from 72 patients (39 inpatients, 33 receiving home PN). Age, percentage energy intake from PN, and PN orders were collected from patients' charts. PN samples were analyzed for TEs, including chromium (Cr) and manganese (Mn), and concentration measurements compared with ordered concentrations and current recommendations. Measured Cr and Mn concentrations were higher than ordered concentrations: 5.3 ± 1.7 vs 2.8 ± 1.5 µg/L; P < 0.0001 and 11.9 ± 5.9 vs 0.00 µg/L; P < 0.0001, respectively. Chromium contamination alone accounted for over 100% of current recommendations for patients 0-12 months and between 63% and 92% for children >1 year. Contamination of Mn provided all the measured Mn in PN admixtures, since Mn is excluded from PN orders at our institution. Between 70% and 120% of current Mn recommendations were met from contamination. Cr should be excluded from PN admixtures for children 0-12 months and only one-fourth the current recommendation should be added for pediatric patients >1 year. Manganese should also be excluded from PN admixture for pediatric patients but plasms monitoring 2-3 times per year is recommended for those on long-term PN.

Enteral and Parenteral Order Writing Survey—A Collaborative Evaluation Between the Academy of Nutrition and Dietetics’ Dietitians in Nutrition Support Dietetics Practice Group and the American Society for Parenteral and Enteral Nutrition (ASPEN) Dietetics Practice Section

IntroductionIn 2014 and 2017, the Centers for Medicare and Medicaid Services authorized nutrition-related ordering privileges for registered dietitian nutritionists (RDNs) in hospital and long-term care settings, respectively. Despite this practice advancement, information describing current parenteral nutrition (PN) and enteral nutrition (EN) ordering practices is lacking. Dietitians in Nutrition Support, a dietetic practice group of the Academy of Nutrition and Dietetics and the Dietetics Practice Section of the American Society of Parenteral and Enteral Nutrition (ASPEN) utilized a survey to describe PN and EN ordering practices among RDNs in the United States. MethodsA cross-sectional study design was utilized to describe RDN PN and EN ordering privileges. Respondents were asked to describe PN and EN ordering privileges, primary practice setting, primary patient population served, nutrition specialty certification, highest degree earned, career length, and, if applicable, the nature of prior denials for ordering privileges or reasons for not applying for ordering privileges. ResultsSeven hundred two RDNs completed the survey (12% response rate), with 664 RDNs providing complete data. The majority of respondents (n=558) cared for adult/geriatric patients. Among this subset, 47% had no PN ordering privileges; 14% could order and sign PN; 28% could order PN with provider cosignature; and 10% could order partial PN with provider cosignature. Nineteen percent of RDNs had no EN ordering privileges; 37% could order and sign EN; and 44% could order EN with provider cosignature. RDNs with ordering privileges were more likely to have a nutrition specialty certification and work in an academic or community hospital setting. ConclusionPN and EN ordering privileges are varied because of institution and state requirements. Future research describing the outcomes associated with RDN ordering privileges is needed. This article has been approved by the Academy’s Research, International, and Scientific Affairs team and Council on Research and the ASPEN Board of Directors. This article has been co-published with permission in Nutrition in Clinical Practice. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.

Use of Integrated Clinical Decision Support Tools to Manage Parenteral Nutrition Ordering: Experience From an Academic Medical Center

Parenteral nutrition (PN) is a complex therapy with numerous opportunities for error during the prescribing, preparation, and administration processes. Advances in technology, such as computerized provider order entry (CPOE), electronic health records (EHRs), and clinical decision support (CDS) have helped decrease the risks associated with PN therapy. These technologies can be utilized to guide prescribing, provide automated safety checks, and increase overall safety and accuracy in PN ordering, compounding, and administration. In recent years, increased awareness of the risks associated with PN therapy, in particular issues with ordering and transcription, have magnified the need for improved support of PN ordering within currently available systems. Additionally, drug shortages continue to impact key components of PN admixtures, further increasing the risks associated with this complex therapy. These concerns and risks present an opportunity for the development of new functionality, as well as improvements in and innovative utilization of available technology within systems supporting the PN use process. This discussion will highlight the risks associated with PN, examine the role of drug shortages on the safety of this therapy, describe the application of available technology to manage shortages, and report the experience of using commercially available CDS tools at one academic medical center. It will also include a discussion of the transition from paper orders to CPOE/EHR-based orders for PN and the transition from one commercially available electronic system to another at this particular institution.

Quality control of parenteral nutrition compounding: gravimetric and component verification control

Introduction: parenteral nutrition (PN) compounding is a process with a high probability of errors. Objective: to analyze PN compounding errors detected using a gravimetric control (GC) and a component verification control (CVC). Methods: a prospective analysis was carried out during a three-year period (January 2016 to December 2018). The MedicalOne Parenteral® software program was used to calculate the theoretical weight of each PN based on density and volume. Each elaborated PN was weighed to obtain the real weight. Gravimetric error (%) ((real weight - theoretical weight) x 100 / theoretical weight) was considered correct if within the ± 5 % interval. The CVC consisted of checking that the correct ingredients and volumes were added according to the PN order. Results: during the study period a total number of 28,761 PNs were checked out; 20,612 adult PNs (APN) were weighed and 124 were considered incorrect (0.60 %). Of the 1,203 non-neonatal pediatric PNs (NPPN), 15 (1.25 %) were incorrect, and of the 6,946 neonatal PNs (NPN), 164 (2.96 %) were incorrect. Regarding the CVC, 71 errors were detected in the APN (0.70 %), 6 (1.34 %) in the NPPN, and 5 (0.21 %) in the NPN group. The total number of errors included: adding more volume of one component [38 (46.34 %)], adding a wrong component [27 (32.93 %)], and absent volume of one component [17 (20.73 %)]. Conclusions: the quality control carried out allowed to detect errors during the preparation of PNs and prevented them from reaching the patient. More incorrect NPNs were detected through GC. The main error detected with CVC was adding more volume of a component.

Sodium glycerophosphate and prescribed calcium concentrations in pediatric parenteral nutrition: a retrospective observational study and economic evaluation

Abstract Background The risk of precipitation limits calcium and phosphate concentrations that can be administered parenterally to pediatric patients. As an alternative to dipotassium phosphate, sodium glycerophosphate (NaGlyP) is claimed to reduce the risk of precipitation in solutions for parenteral administration. Objectives To determine the calcium concentrations, NaGlyP, and dipotassium phosphate prescribed in pediatric parenteral nutrition orders and the cost–benefit of the organic phosphate. Methods We retrospectively collected cross-sectional data for parenteral nutrition orders from September 2014 to August 2015 for pediatric patients including neonates and children aged &lt;18 years who were admitted to King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Calcium concentration, calcium concentration adjustments, and costs of phosphate used per bag were analyzed. Results Of 2,192 parenteral nutrition orders, NaGlyP was used in 2,128 (97.1%) with calcium concentrations in the range of 0.84–139.91 mmol/L, which were significantly higher than calcium concentrations used with dipotassium phosphate (0.00–12.21 mmol/L, P &lt; 0.001). There was no report of visible precipitation. Median costs of NaGlyP and dipotassium phosphate used per unit bag were not significantly different (35.88 and 41.25 Thai baht [THB] or 1.04 and 1.20 USD per bag, respectively, P&gt;0.99; (1 USD equivalent to 34.241 THB U.S. Federal Reserve Bank G5.A annual average rate 2015). Conclusions Higher calcium concentrations could be achieved without increasing the direct cost per unit bag significantly as a result of using NaGlyP, an alternative to dipotassium phosphate as a source of phosphate for patients who require high amounts of calcium in parenteral nutrition.

RDN Parenteral Nutrition Order Writing: Improving Electrolyte and Glucose Management

RDN Parenteral Nutrition Order Writing: Improving Electrolyte and Glucose Management

Changes in Neonatal Mineral Administration and Contaminant Exposure due to Sodium Phosphate Shortage.

Background National pharmaceutical shortages continue to affect clinical patient care, including neonatal patients. Early postnatal nutrition influences health and growth of infants; quantitative reports describing specific effects of drug shortages on neonatal care are not common. Methods Parenteral nutrition (PN) orders created during the study period were modified to adjust for sodium phosphate unavailability. Original PN orders were collected retrospectively and compared with the modified orders for daily mineral doses, calcium:phosphorus ratio, and potential aluminum exposure. The corrected phosphorus dose was determined to compensate for algorithm-driven changes in phosphorus administration. Results The PN corrected phosphorus dose decreased from 58.9 ± 19.7 mg/kg/day to 42.7 ± 21.7 mg/kg/day (mean ± standard deviation [SD], n = 226 from 22 patients, range, 0–63.4 mg/kg/day, p &lt; 0.05) below the minimal recommended daily dose. There was a coincident doubling of the calcium:phosphorus ratio to &gt; 2.5:1, which was above the desired ratio of 1.8:1. Using potassium phosphate as the only intravenous phosphate source increased the potential aluminum exposure to 60% (9.6 ± 5.0) above the recommended Food And Drug Administration (FDA) limit. Discussion Neonatal PN phosphate administration decreased during the sodium phosphate shortage, raised calcium:phosphate ratios, and increased the potential aluminum exposure. Drug shortages continue to affect preterm infants. Coordinated efforts of health professionals with administrative resources are needed to provide effective short-term solutions and develop long-term strategies. Clinical Relevance Providing optimal PN to neonates is essential for postnatal health and growth. This report describes the effect of a national drug shortage of injectable sodium phosphate on PN composition and infant mineral administration.

Evaluation of the safety of iron dextran with parenteral nutrition in the paediatric inpatient setting

Practitioners often avoid administering iron dextran in parenteral nutrition (PN) for hospitalised children because of the concern for anaphylaxis. The primary aim of the present study was to determine the risk of anaphylaxis associated with exposure to PN containing iron dextran in the inpatient setting. Charts were reviewed for all children admitted to The Children's Hospital of Philadelphia from January 1, 2011 to December 30, 2013 who received PN containing low molecular weight (LMW) iron dextran. Subject characteristics, primary diagnoses and PN orders were evaluated. The pharmacy adverse events database was queried for adverse drug reactions. Over three years, 89 subjects received PN containing a maintenance dose of LMW iron dextran with a total of 2774 days of exposure. Subjects ranged from two months to 21 years of age and received between 1 and 196 days of PN containing iron dextran. The mean dose of iron dextran in children decreased as the weight category increased from <5 kg (0.21 ± 0.05 mg/kg/day) to ≥40 kg (1.9 ± 0.5 mg/day; P-value for trend <0.005). No anaphylactic reactions occurred in any subjects. PN containing a maintenance dose of LMW iron dextran can be safely administered to hospitalised children, and further studies are need to evaluate the potential to prevent iron deficiency anaemia and the need for additional IV iron infusions.

Incidence and Severity of Prescribing Errors in Parenteral Nutrition for Pediatric Inpatients at a Neonatal and Pediatric Intensive Care Unit.

Pediatric inpatients are particularly vulnerable to medication errors (MEs), especially in highly individualized preparations like parenteral nutrition (PN). Aside from prescribing via a computerized physician order entry system (CPOE), we evaluated the effect of cross-checking by a clinical pharmacist to prevent harm from PN order errors in a neonatal and pediatric intensive care unit (NICU/PICU). The incidence of prescribing errors in PN in a tertiary level NICU/PICU was surveyed prospectively between March 2012 and July 2013 (n = 3,012 orders). A pharmacist cross-checked all PN orders prior to preparation. Errors were assigned to seven different error-type categories. Three independent experts from different academic tertiary level NICUs judged the severity of each error according to the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) Index (categories A-I). The error rate was 3.9% for all 3,012 orders (118 prescribing errors in 111 orders). 77 (6.0%, 1,277 orders) errors occurred in the category concentration range, all concerning a relative overdose of calcium gluconate for peripheral infusion. The majority of all events (60%) were assigned to categories C and D (without major harmful consequences) while 28% could not be assigned due to missing majority decision. Potential harmful consequences requiring interventions (category E) could have occurred in 12% of assessments. Next to systematic application of clinical guidelines and prescribing via CPOE, order review by a clinical pharmacist is still required to effectively reduce MEs and thus to prevent minor and major adverse drug events with the aim to enhance medication safety.

Impact of Nutrition on Non-Relapse Mortality and Acute Graft Versus Host Disease during Allogeneic Hematopoietic Cell Transplantation for Hematologic Malignancies

The process of allogeneic hematopoietic cell transplantation (HCT) is often associated with poor oral intake and as a result, nutritional status declines. Although it might seem obvious that optimal nutrition is likely to improve outcomes of transplantation, there are no clinical data that directly support this assumption. It is also unclear whether artificial nutrition support (ANS) should be provided as enteral tube feeding (ETF) or parenteral nutrition (PN).In this study we analysed day 100 non-relapse mortality (NRM) and incidence and severity of acute graft versus host disease (GvHD) according to both the route and adequacy of nutritional intake together with other known prognostic factors. A total of 484 patients who underwent HCT for hematological malignancy at a single institution between 2000 and 2014 were included. Myeloablative conditioning was used in 285 (59%) patients, 272 of whom received a TBI based regimen. Reduced intensity conditioning was given to 199 (41%) patients. For the 236 (49%) unrelated donor cell recipients in vivo T-cell depletion with alemtuzumab was used. Myeloablative HCT recipients were advised to have an enteral feeding tube inserted prophylactically at day 1 post HCT. ANS was initiated in 228 (47%) patients who met pre-defined feeding criteria that include actual or anticipated oral intake below 1/3 of estimated requirement for 5 or more days or significant weight loss or low body mass index. Total of 245 (51%) patients had adequate enteral nutrition (EN) either orally (N=198) or with use of ETF (N=47). Patients in whom ETF could not be established received PN (N=148, 31%) in order to provide adequate nutrition. The remaining 91 (19%) patients had inadequate nutrition due to either curtailed ANS (N=33) or a failure to start ANS because of a lack of feeding access via any route (N=58).The effects of patient, disease and transplant factors were studied in univariate analyses on NRM, acute GvHD and engraftment, following which multivariate analyses showed significant associations of NRM with age > 50 years (hazard ratio (HR) 2.3; 95% confidence interval (CI) 1.4 - 3.7; P=0.001); previous autograft (HR 2.4; 95% CI 1.3 - 4.5; P=0.007) and positive recipient CMV serology (HR 1.9; 95% CI 1.1 - 3.2; P=0.019). In addition, HRs were significantly increased in the PN and inadequate nutrition groups compared to those with adequate enteral intake: adequate PN: HR 3.2; 95% CI 1.7 - 6.0, inadequate nutrition: HR 4.4; 95% CI 2.4 - 8.0; all P<0.001 (Figure). There were increased incidences of gastrointestinal GvHD of any stage and acute GvHD > grade 1 in patients who received PN (HR 2.0; 95% CI 1.2 - 3.3; P=0.006, and HR 1.8; 95% CI 1.1 - 3.0; P=0.018, respectively), but not in those with inadequate nutrition compared to adequate EN. Other significant covariates in the model for both increased overall and gut GvHD were the use of myeloablative versus reduced intensity conditioning P=0.001 and P<0.001 and female donor to male recipient versus other combinations P=0.047 and P=0.025 respectively.In conclusion the data show that adequate nutrition during allogeneic HCT is associated with improved non-relapsed mortality at 100 days. Adequate EN is associated with significantly better results for this outcome than adequate PN. Furthermore adequate EN, predominantly via oral intake may be associated with lower incidence of overall and gut GvHD when compared to PN, perhaps because of its ability to maintain gut mucosal integrity and for support of the gastrointestinal tract environment, including gut microflora. Although the retrospective nature of this study can only indicate association, the significant hazard ratios reported warrant further research into optimising enteral nutrition in recipients of HCT. [Display omitted] DisclosuresMilojkovic:Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Ariad: Honoraria. Apperley:Incyte: Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Ariad: Honoraria, Speakers Bureau.