Significant Published Articles in 2020 for Pharmacy Nutrition Support Practice

Abstract

Purpose: The purpose of this article is to assist the pharmacist engaged in nutrition support therapy in staying current with pertinent literature. Methods: Several clinical pharmacists engaged in nutrition support therapy compiled a list of articles published in 2020 considered important to their clinical practice. The citation list was compiled into a single spreadsheet where the author participants were asked to assess whether the article was considered important to nutrition support pharmacy practice. A culled list of publications was then identified whereby at least 5 out of the 8 author participants considered the paper to be important. Guideline and consensus papers from professional organizations, important to practice but not ranked, were also included. Results: A total of 169 articles were identified; 5 from the primary literature were voted by the group to be of high importance. An additional 17 guidelines, position, recommendation, or consensus papers were also identified. The top-ranked articles from the primary literature were summarized and a narrative regarding its implications to pharmacy nutrition support practice were provided. Conclusion: We recommend that pharmacists engaged in nutrition support therapy be familiar with these articles as it pertains to their practice.

Introduction

Keeping up with the literature is an essential requirement for maintaining an evidence-based clinical practice. However, staying current particularly within a specialized field such as nutrition support (NS), is challenging since many institutions have adopted an integrated practice model whereby the clinical pharmacist provides pharmacotherapy services in addition to specialized services. Clinicians are held accountable for having expertise in numerous therapeutic areas that interface with their clinical practice. Because new knowledge in NS is often integrated within differing clinical practices and numerous journals, it is a daunting task for 1 individual to screen the abundance of journals to seek out those clinical studies, position papers, or clinical guidelines that may enhance or change their current clinical practice. ¹ For the past several years, as clinicians who practice in pharmacy NS, it has been our intent to provide a yearly source of new literature important to pharmacists engaged in NS.^{2 -7} This article identifies and discusses significant articles that were published in 2020.

Methods

To assist pharmacy clinicians engaged in NS in staying current with the most pertinent literature, the corresponding author (R.N.D.) invited 7 clinical pharmacists to participate in this project. All participants are board certified in NS pharmacy. Some authors have multiple board certifications including critical care, pharmacotherapy, and pediatrics. The duration of individual practice experience of the authors ranges from 6 years to more than 30 years post-training. Members of this authorship group have advanced practice roles with direct patient care responsibilities for prescribing parenteral nutrition (PN) and/or enteral nutrition (EN), laboratory analysis, and pharmacotherapy integrated with nutrition therapy (eg, fluid and electrolytes, vitamins, trace elements, prokinetic drugs, insulin, antidiarrheal, and laxative therapy), and some have administrative or supervisory roles with respect to NS therapies. This authorship group has a broad range of practice experiences. Most authors are acute care-based, but some have long-term care (home PN and EN) responsibilities. Current practices of the group range from pediatrics to geriatrics. Some members have a practice with a diverse patient population, whereas others are within a focused patient population (eg, pediatrics, oncology, trauma).

A modified Delphi approach was used to identify articles published from January 2020 to December 2020 that resulted in a change or affirmation of their current clinical practice or considered to be most important for future clinical practice. Some authors collated papers from their personal journal subscriptions, organizational membership newsletters, or institutional-based journal clubs. Others included those articles retrieved from an online search strategy. This methodology for collection of articles has the limitation that the process for identifying significant articles lacked a consistent structured literature search strategy. As a result, it is possible that omission of pertinent articles applicable to pharmacy NS practice that were published in less common journals and not routinely read by the author participants were not identified.

Only those articles available in print format were allowed for potential inclusion. Articles available only in preprint electronic format (with intention of print publication by the journal in 2021 or later) were not evaluated. The citation list was compiled into a spreadsheet whereby the author participants were asked to denote whether the paper was considered most important to pharmacy NS practice. An abstract and complete citation of each paper was provided along with the electronic scoring spreadsheet to assist the author participants with the evaluation process. To ensure an independent voting process without influence from the other participant members, only the corresponding author was aware of others’ rankings. To prevent influence from the other authors on the corresponding author, dichotomous grading of all articles as important or not by the corresponding author was completed prior to review of the results from the other contributors. The votes were tallied. The article was considered most important if at least 5 out of 8 participants voted for a paper to be valuable to pharmacy NS practice. From this scoring system, a culled list of the most important articles was created.

Results

A total of 169 articles were collectively collated for initial evaluation by the authorship group. Seventeen articles comprising guidelines, consensus, recommendation, and position papers were excluded from the ranking process.^{8 -24} An average of 27 articles (range: 15-53) of the 152 from the primary literature were denoted as most important by individual members of the author group. Five papers from the primary literature were collectively identified (receiving 5 or more votes) as most important by the authors.^{25 -29} Results from the sorting process are depicted in Figure 1.

Figure 1.

Flow diagram of identification and sorting of significant articles published in 2020 for nutrition support pharmacy practice.

Of the 22 total primary literature and guidelines/consensus articles, 8 were published in Clinical Nutrition, 4 in Journal of Parenteral and Enteral Nutrition, 2 in Nutrition in Clinical Practice, 2 in Intensive Care Medicine, 2 in American Journal of Gastroenterology, and 4 in assorted medical, pharmacy and pediatric journals. The finalist publications from the primary literature are summarized in the discussion along with a narrative regarding their implications for pharmacy NS practice. A list of guidelines, position, recommendation, and consensus papers are provided in Table 1. The remaining 157 citations from the primary literature not making the finalist papers are provided in an online supplement.

Table 1.

Guidelines, Position, Recommendations, and Consensus Articles (in Alphabetical Order by First Author).

First author	Title
Alhazzani et al 8	Surviving Sepsis Campaign: Guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19)
Arvanitakis et al 9	ESPEN guideline on clinical nutrition in acute and chronic pancreatitis
Bischoff et al 10	ESPEN guideline on home enteral nutrition
Bischoff et al 11	ESPEN practical guideline: Clinical nutrition in liver disease
Bischoff et al 12	ESPEN practical guideline: Clinical nutrition in inflammatory bowel disease
da Silva et al 13	ASPEN consensus recommendations for refeeding syndrome
Gardner et al 14	ACG clinical guideline: Chronic pancreatitis
Hardy et al 15	Parenteral provision of micronutrients to pediatric patients: An international expert consensus paper
Lal et al 16	Considerations for the management of home parenteral nutrition during the SARS-CoV-2 pandemic: A position paper from the Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPEN
Lobo et al 17	Perioperative nutrition: Recommendations from the ESPEN expert group
Martindale et al 18	Summary of proceedings and expert consensus statements from the international summit “Lipids in parenteral nutrition”
Osland et al 19	A framework to support quality of care for patients with chronic intestinal failure requiring home parenteral nutrition
Pimental et al 20	ACG clinical guideline: Small intestinal bacterial overgrowth
Pironi et al 21	ESPEN guideline on home parenteral nutrition
Sheean et al 22	American Society for Parenteral and Enteral Nutrition clinical guidelines: The validity of body composition assessment in clinical populations
Tume et al 23	Nutritional support for children during critical illness: European Society of Pediatric and Neonatal Intensive Care (ESPNIC) Metabolism, Endocrine and Nutrition Section position statement and clinical recommendations
van der Louw et al 24	Optimal clinical management of children receiving ketogenic parenteral nutrition: A clinical practice guide

Discussion

The 5 finalist articles, listed in alphabetical order by the first author, are summarized and critiqued below. Table 2 provides a synopsis and additional details regarding these studies.

Table 2.

Study Objectives, Outcomes, Findings, and Limitations of the Most Important Articles.

Article	Study objectives	Outcomes and findings	Limitations
Al-Lewas 25	Does FO-containing ILE improve clinical outcomes and reduce inflammation for patients with acute pancreatitis compared to soybean oil-containing ILE?	Significant decrease in MODS, SOFA scores. Shorter ICU stay (median, 3 vs 9 d, P = .03) and shorter hospitalization (median 12 vs 18 d, P = .04). CRP was similar at baseline and lower during FO containing ILE over time but not statistically significant at day 7.	Small number of patients per group (n = 23 and 22). CRP is highly variable and difficult to use as a primary marker for reduced inflammation. Providing ILE, as a standalone anti-inflammatory agent without PN, is not consistent with current practice.
Campos-Baeta 26	Evaluate the Y-site compatibility of dexmedetomidine with TNAs containing soybean, MCT, olive, and fish oil ILE.	Dexmedetomidine concentrations were within ±10% of the final expected concentration at 24 h. Mean lipid droplet diameter indicated ILE stability.	Concentration of dexmedetomidine was less than commercially available product. Lacked assessment of volume-weighted PFAT5.
De Koning 27	To ascertain if there is an association between early protein and calorie intakes and 6-month survival in septic (n = 297) and non-septic (n = 126) patients.	Increases in protein and caloric intake during ICU days 4 to 7 for those with sepsis was associated with improved survival. Low calorie and protein intakes during ICU days 4 to 7 for the non-septic patients was associated with worsening mortality.	Retrospective study that can only examine associations and not causalities. Convoluted study design examining empirically grouped energy and protein intakes with timing of nutrient intakes.
Deane 28	Determine whether achieving approximately 100% of goal caloric intake during critical illness using a 1.5 kcal/mL EN formula versus 1 kcal/mL will improve quality of life 6 mo later.	Mortality was similar (29.6% vs 28.1%). Similar EuroQoL five dimensions scores (75% (IQR 60-85) versus 75% (IQR 60-85) at 6 mo was reflective of no or slight problem/pain/anxiety using a visual analog scale in 1222 and 1270 survivors, respectively. Delivery of about 100% compared with 70% of recommended caloric intake does not improve quality of life.	Data used from the TARGET trial. Average duration of EN was 6 d and received 1.1 g/kg/d protein which is lower than recommended targets. Patients were not significantly malnourished.
Fox 29	Evaluated efficacy and safety of insulin glargine when dosed once (n = 35) versus twice (n = 23) daily in older, medical ICU patients with diabetes of which the majority received continuous EN.	Dose of insulin glargine was lower in once daily group than larger group (45 IQR 40, 50) versus 58 (IQR 43, 82) units/d, P = .04) but similar amounts of sliding scale RHI coverage (21 [IQR 13, 31] vs 20 [IQR 13, 35] units/d). Overall glycemic control was comparable between groups; however, episodes of hyperglycemia were greater for the twice daily group (8 vs 6 episodes per patient, P = .02) without statistically significant differences in hypoglycemia.	Retrospective study. Most patients older than 60 y of age. The twice daily group received more insulin and for a longer duration which suggests a difference in acuity between groups.

CRP = C-reactive protein concentration; EN = enteral nutrition; FO = fish oil; ICU = intensive care unit; ILE = lipid injectable emulsion; IQR = interquartile range; EuroQoL = European Quality of Life Score; MODS = multiple organ dysfunction score; PFAT₅ = percent of fat greater than 5 µm; PN = parenteral nutrition; RHI = regular human insulin; SOFA = sequential organ failure assessment; TNA = total nutrient admixture.

Al-Leswas D et al. ²⁵ Intravenous omega-3 fatty acids are associated with better clinical outcome and less inflammation in patients with predicted severe acute pancreatitis: A randomized double blind controlled trial.

In this phase II randomized, double-blind, single-center controlled trial, 44 adult patients admitted for severe acute pancreatitis (SAP) were randomized to receive a fish-oil containing lipid injectable (ILE) emulsion (medium chain triglycerides [MCT], soybean oil [SO], fish oil [FO] ILE group) or an ILE without fish oil (MCT, SO-ILE; control group) within 72 hours of symptom onset. ILE products were isocaloric and infused over 14 hours at a dose of 2 g/kg daily up to 7 days or until discharge, whichever occurred first. The SO, MCT, FO-ILE product contained 50% medium chain triglycerides (MCT), 40% soybean oil and 10% fish oil and the control (MCT, SO-ILE) ILE contained 50% MCT and 50% soybean oil. Patients received standard of care management for severe acute pancreatitis (SAP) per society recommendations with initiation of enteral or PN for insufficient oral intake after 3 days. Baseline characteristics were similar between the 2 groups, including acute physiology and chronic health evaluation II (APACHE II), Glasgow, and Ranson scores and C-reactive protein (CRP) concentration on admission. Eight patients (5 in MCT, SO, FO-ILE, 3 in MCT, SO-ILE control group) received EN initiated between days 3 and 6 of admission and 2 patients (1 in each group) received PN initiated at days 5 and 6 of admission. The primary outcome evaluated CRP as a marker of inflammation and found concentration changed over time (P = .004) and was different between treatment groups (P = .013) on daily CRP assessments. CRP concentration at day 7 was 34% lower in the MCT, SO, FO-ILE group compared to MCT, SO-ILE control; however, this was not significantly different (104.1 ± 23 mg/L vs 157.6 ± 26.8 mg/L, P = .15). Significant reductions in multiple organ dysfunction score (MODS), sequential organ failure assessment (SOFA) score, early warning score, systemic inflammatory response syndrome, total blood leukocyte number, ICU, and overall hospital length of stays were observed in the MCT, SO, FO-ILE group compared to control. One patient in the control group experienced transient hypertriglyceridemia which resolved upon temporary cessation of ILE infusion. The authors concluded that MCT, SO, FO-ILE improves clinical outcomes in patients with predicted SAP that may be linked to reduced inflammation.

This is a novel trial utilizing MCT, SO FO-ILE as an adjunct intervention to down-regulate the inflammatory response in SAP patients. The primary objective of reduction in the inflammatory marker CRP was lower overall despite similar baseline concentrations; however, at the endpoint of the observation (day 7), CRP did not significantly differ between groups. This may be due to the use of a laboratory value that can be highly variable during critical illness. ILE doses were high (average 1900 kcals/day) with 40% to 50% of calories from soybean oil rich in omega-6 fatty acids and ILE was provided as a standalone therapy outside of a balanced nutritional regimen. The high dose and standalone use of ILE are not consistent with standard nutrition practice. Although the high ILE dose regimen was not associated with hypertriglyceridemia, it is unclear whether it altered hepatic function as this was not reported. This potential risk must be taken into consideration for safety. Another important limitation is the small number of patients who received EN or PN despite being classified as SAP. While the lack of NS, specifically EN, may have allowed for better detection of differences in endpoints due to MCT, SO, FO-ILE, it is not consistent with current guidelines recommending early EN within 24 to 48 hours of admission in patients with SAP. ³⁰ The full benefit of MCT, SO, FO-ILE therapy may not have been observed in the setting of early EN as it also down-regulates the inflammatory response. Other study limitations include its small sample size, single-center design, and omission of a control group whereby no ILE was given. Unfortunately, the study is not applicable in the US due to the unavailability of the ILE products used in the study.

This study is hypothesis-generating and suggests larger, multicenter trials are needed to determine if MCT, SO, FO-ILE has a place in the management of SAP patients. However, these data would support the use of fish-oil containing ILE for those patients with SAP who require PN.

Campos-Baeta Y et al. ²⁶ Physicochemical compatibility of dexmedetomidine with PN.

Dexmedetomidine is a highly selective alpha-2 receptor agonist that requires continuous infusion when utilized for sedation in the intensive care unit. Its short serum half-life requires it to be administered as a continuous infusion, which creates challenges with IV compatibilities. This in-vitro physiochemical compatibility study assessed Y-site compatibility of dexmedetomidine with a total nutrient admixture (TNA) containing SO, MCT, olive oil (OO), FO-ILE. This process was conducted in triplicate with identical TNAs infusing at 66 mL/h concurrent with dexmedetomidine (3.7 mcg/mL in 0.9% sodium chloride) infusing at 10 or 36 mL/h. At 30 minutes of co-infusion, samples were collected and tested for chemical stability, physical compatibility, and pH. Utilizing ultraperformance liquid chromatography-high resolution mass spectrometry, all samples were found to be within ±10% of the final expected concentration at 24 hours (94%-110%). Utilizing dynamic light scattering (DLS), the mean droplet diameter (MDD) for all samples were below the recommended threshold of 500 nm (298 ± 10 nm for the 10 mL/h group; 303 ± 5 nm for the 36 mL/h group). The average pH was 6.25 ± 0.01, which is within the 6.06 ± 0.29 and 6.31 ± 0.01 pH for the PN and dexmedetomidine individual solutions, respectively. The authors concluded that dexmedetomidine co-administered via Y-site with the TNA is physicochemically compatible at the infusion rates tested.

There are limitations to this study. As is often the case with physicochemical studies involving PN, analysis is limited to the single PN formulation selected. It is not feasible to assess every possible PN formulation and the reader should consider this when determining final recommendations for Y-site compatibility involving PN. Of note, organic phosphate (sodium glycerophosphate) was used in the TNA which has a different solubility and compatibility profile than inorganic phosphate salts. Secondly, the concentration of dexmedetomidine studied is less than the commercially available ready-to-infuse dexmedetomidine 4 mcg/mL concentration. Physiochemical compatibility is dependent on the concentration of the infusates with concentrations lower than that studied usually considered compatible but higher concentrations classified as not having enough information to ensure compatibility. Finally, USP Chapter <729> requires the use of 2 specific analytical methods to assess the lipid globule size distribution of PN emulsions. ³¹ In addition to the assessment of MDD utilizing DLS as described in this study, it requires assessment of volume-weighted percent of fat greater than 5 µm (PFAT₅). PFAT₅ must be less than 0.05% to ensure acceptable globule-size distribution within the ILE-containing formulation, but this was not analyzed in this study.

Each of these points are critical in assessing the study’s overall application in a clinical setting. Because of the significant omission of evaluating the TNA stability by use of PFAT₅, we advise against co-administration of dexmedetomidine with TNAs.

De Koning, MLY et al. ²⁷ Association of PROtein and CAloric Intake and clinical outcomes in Adult SEPTic and non-septic ICU patients on prolonged mechanical ventilation: The PROCASEPT retrospective study.

The optimal protein and caloric provision and timing of feeding initiation in critically ill patients with and without sepsis are controversial. In this retrospective observational study in a mixed medical-surgical ICU, 423 patients met inclusion criteria (≥18 years of age, mechanical ventilation ≥7 days, and commenced within 48 hours after ICU admission). Patients were categorized by the presence (n = 297) or absence (n = 126) of sepsis. The impact of protein (low: <0.8 g/kg/d, medium: 0.8-1.2 g/kg/d, high: >1.2 g/kg/d) and caloric (low: <80%, medium: 80%-110%, high: >110% of target) intake during ICU days 1 to 3 (early) and 4 to 7 (late) on 6-month mortality was evaluated for patients with and without sepsis. In patients with sepsis, late medium protein and high caloric intakes had lower 6-month mortality. In patients without sepsis, late low protein intake as well as late low energy intake were associated with higher 6-month mortality.

Although this study addresses an important clinical question regarding the impact of protein and caloric intake on long-term outcome in critically ill patients with and without sepsis, study limitations make generalization of the investigators’ findings difficult. Given the retrospective design, it is challenging to confidently determine the association between daily protein and caloric intakes and patient survival. Since daily intakes were retrospectively collected, it is possible that factors not accounted for in the study resulted in certain patients receiving either more or less nutrition. For instance, patients with greater severity of illness may have received a more aggressive approach with higher protein and caloric provision. Conversely, this patient population may have experienced greater EN intolerance resulting in lower intake. It is also unclear whether timely infection source control and appropriate antibiotic therapy was implemented which influences outcome from sepsis. As another consideration, it is surprising that differences in nutrition provision in the first 7 days alone was the most important factor influencing mortality at 6 months. While this study highlights for clinicians that critically ill subpopulations may have different protein and energy requirements for optimal outcomes, the results must be interpreted cautiously.

These data support current practice of restricting caloric intake during the first few days of critical illness followed by increases in protein and energy intake thereafter. Prospective, longitudinal assessment of various clinical outcomes at multiple timepoints with fewer than a 6-month interval would help us better understand the impact of protein and caloric intake in these patients after hospital discharge.

Deane AM et al. ²⁸ Outcomes six months after delivering 100% or 70% of enteral calorie requirements during critical illness (TARGET). A randomized controlled trial.

The impact of energy and protein dosing on clinical and functional outcomes in critically ill patients has been the subject of much debate. Previously, the TARGET trial, a double-blind, multicenter, randomized controlled trial, evaluated an energy-dense EN formulation (1.5 kcal/mL) compared with routine EN (1 kcal/mL) in mechanically ventilated patients. Patients received 103% of target calories with the energy-dense formulation and 69% of target calories with routine EN. Ninety-day survival did not differ between the groups. The current study, a secondary analysis of the TARGET trial, ³² evaluated survivor quality of life at 180 days using the EuroQol 5 dimensions 5-level quality of life questionnaire visual analog scale. Surviving patients were contacted to complete the questionnaires 180 days from randomization and data were available for 2492 patients of the original 3957 TARGET study patients. It was hypothesized that receiving 100% of recommended caloric intake during their ICU stay would improve recovery in critically ill patients compared with those receiving fewer daily calories. No differences were found between the groups in terms of overall quality of life scores, individual quality of life domains (mobility, self-care, usual activity, pain/discomfort, or anxiety/depression), or functional outcomes (workforce participation, disability, and participation in activities).

This study provides additional evidence that the provision of target energy alone may be insufficient to improve long-term clinical or functional outcomes in critically ill patients. The TARGET trial population may have been less likely to see a benefit from aggressive nutritional intervention, as patients were overweight (average body mass index of 29.2 kg/m²), those who were determined to have specific nutrition requirements were excluded, and the average duration of EN was only 6 days. Additionally, patients in the trial received ~1.1 g/kg ideal body weight of protein, which is lower than the recommended targets. ³⁰ Other studies have found that providing adequate protein may positively impact clinical outcomes^33,34; however, prospective randomized controlled trials are lacking.

These data would suggest that quality of life at 6 months is not influenced by whether calorie goals are met or not with short-term EN in those who are not significantly malnourished. Further investigation is warranted to determine if combining an energy and protein-dense EN regimen can positively impact clinical and functional outcomes in critically ill patients.

Fox MA et al. ²⁹ Insulin glargine in critically ill patients: Once/day versus twice/day dosing.

Hyperglycemia is common among critically ill patients receiving NS. Continuous insulin infusions may be the preferred approach to management of severe hyperglycemia; however, intermediate-acting and long-acting insulin regimens as subcutaneous injections have been utilized in stable chronic ICU patients receiving NS. ³⁵ This retrospective study examined the efficacy and safety of a long-acting insulin, insulin glargine, in either a once/day or twice/day dosing regimen for the management of hyperglycemia among older patients in the medical ICU. A total of 58 patients were categorized into a once/day group if receiving insulin glargine 40 units or more or a twice/day group (any dose) for at least 48 hours. The primary form of NS was continuous EN in both groups; however, the daily dose of insulin glargine was lower and median study duration shorter in the once/day group compared to the twice/day group (45 vs 58 units, P = .04 and 3 vs 6 days, P < .001). These factors were likely related to acuity differences between these patient groups due to its retrospective design. Glycemic target, defined as 70 to 180 mg/dL, was achieved in 43% of the once/day group and 52% of the twice/day group. Episodes of hypoglycemia were surprisingly higher (but statistically insignificant) with once/day insulin glargine dosing, primarily while patients were nil per os (nothing by mouth) (NPO). Mortality and acute kidney injury (AKI) (or chronic kidney disease [CKD]) were not reported in this trial and amounts of NS were also not provided.

This study offers some preliminary safety data into the use of subcutaneous insulin glargine, including twice daily dosing in non-surgical ICU patients. The generalizability of the data is limited to the retrospective study design and the inclusion of primarily older adults with underlying diabetes. Although not statistically significant, more of the patients in the once/day treatment arm required vasopressors and started insulin glargine later in their ICU stay, while also having shorter ICU and hospital lengths of stay compared to those given the twice/day regimen. Several unanswered questions remain, including ideal subcutaneous administration sites for insulin glargine for ICU patients, use of insulin glargine in AKI or AKI or CKD, amount of glycemic variability during the observation, influence of stress severity or dosage of vasopressor agents, presence or absence of obesity and any associated weight loss upon insulin sensitivity, ³⁶ and the basal amount of NS required to prevent hypoglycemia with these agents.

These data suggest that patients requiring greater doses of insulin may benefit from twice daily dosing as opposed to once daily in the absence of renal dysfunction. Hypoglycemia occurred in some patients particularly when the patient was NPO or had interruption of EN which suggests EN should not be interrupted when utilizing insulin glargine. More research is required to determine if long-acting insulin regimens are more effective than other less expensive insulin regimens, such as intermediate-acting insulin (namely NPH [neutral protamine Hagedorn insulin]).

Conclusion

With the large volume of publications pertinent to NS therapy from a variety of journals, it is challenging to stay current with the literature. We have identified a select group of papers that we consider important for pharmacy NS clinicians from the primary literature in 2020. Additionally, we have provided a list of pertinent guidelines, consensus, and recommendation articles. Although only those highest ranked articles by a majority consensus were discussed, other publications may be important depending on the patient population and the role of the pharmacist at their respective institution. It is recommended that pharmacists engaged in NS therapy be familiar with those articles that are applicable to their clinical practice. In addition to the articles identified in this manuscript, it is suggested that the supplemental online document should be reviewed to identify those publications that might be pertinent to the reader’s clinical practice.