Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient

PRELIMINARY REMARKS (INTENT OF GUIDELINES) A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint “harmonization process” with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies. Literature searches were then performed using key words (critically ill, critical care, intensive care, nutrition, enteral, parenteral, tube feeding, and those related to assigned topics such as pancreatitis, sepsis, etc.) to evaluate the quality of evidence supporting a response to those questions, which were then used to derive a subsequent treatment recommendation. The literature search included MEDLINE, PubMed, Cochrane Database of Systemic Reviews, the National Guidelines Clearing House and an Internet search using the Google search engine for scholarly articles through an end date of December 31, 2013 (including ePub publications). While preference was given to RCTs, other forms of resource material were used to support the response, including nonrandomized cohort trials, prospective observational studies, and retrospective case series. Use of publications was limited to full-text articles available in English on adult humans. For all included RCTs, two readers completed data abstraction forms (DAFs) examining the data and assessing the quality of the research methodology to produce a shared evaluation achieved by consensus for each study (example of DAF provided in the supplemental data, Supplemental Digital Content 1, https://links.lww.com/CCM/B571). DAFs were constructed only for RCTs. When the strongest available evidence was a published meta-analysis, the studies from the meta-analysis were used to determine the quality of the evidence and assessed by two evidence assessors. The data from included trials were entered into Review Manager 5.2 software to create forest plots aggregating the effect size for each intervention and outcome (3). The key forest plots supporting the recommendation are included throughout the text and in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). No new forest plots were created when a meta-analysis was evaluated. Since release of the 2009 A.S.P.E.N. and SCCM Clinical Guidelines, the concepts of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group have been adopted (4–7). A full description of the methodology has been previously published (4). The data from the Review Manager analysis was uploaded to GRADEPro software (8), where the body of evidence for a given intervention and outcome was evaluated for overall quality. One analyst created each GRADE table that was then independently confirmed by a second analyst. The GRADE tables are provided in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). Due to the inordinately large number of RCTs evaluated, observational studies were critically reviewed, but not utilized to construct the GRADE tables. However, in the few cases where observational studies were the only available evidence in a population, their quality of evidence was reviewed, using GRADE (Table 1). When no RCT or observational study was available to answer a question directly, consensus of the author group on the best clinical practice approach was used, and the recommendation was designated “based on expert consensus.”TABLE 1: Type of EvidenceA recommendation for clinical practice was based on both the best available evidence and the risks and benefits to patients. While small author teams developed each recommendation and provided the supporting rationale, a full discussion by the entire author group followed, and every committee member was polled anonymously for their agreement with the recommendation. Achievement of consensus was arbitrarily set at 70% agreement of authors with a particular recommendation. Only one recommendation (H3a) did not meet this level of agreement, with a final consensus of 64%. All other consensus-based recommendations reached a level of agreement of 80% or higher. As with all A.S.P.E.N. and SCCM clinical guidelines, this manuscript was subjected to rigorous peer review by clinical content experts from all the practice disciplines that would use the guidelines, both internal and external to the organizations. A summary of the guidelines is presented in the supplement data (Supplemental Digital Content 1, https://links.lww.com/CCM/B571). A nutrition bundle based on the top guidelines (as voted on by the committee) for the bedside practitioner is presented in Table 2.TABLE 2: Bundle StatementsCONFLICT OF INTEREST All authors completed both an A.S.P.E.N. and SCCM conflict of interest form for copyright assignment and financial disclosure. There was no input or funding from industry, nor were any industry representatives present at any of the committee meetings. DEFINITIONS Nutrition Therapy refers specifically to the provision of either enteral nutrition (EN) by enteral access device and/or parenteral nutrition (PN) by central venous access. Standard therapy (STD) refers to provision of IV fluids, no EN or PN, and advancement to oral diet as tolerated. INTRODUCTION The significance of nutrition in the hospital setting (and especially the ICU) cannot be overstated. Critical illness is typically associated with a catabolic stress state in which patients demonstrate a systemic inflammatory response coupled with complications of increased infectious morbidity, multiple organ dysfunction, prolonged hospitalization, and disproportionate mortality. Over the past three decades, exponential advances have been made in the understanding of the molecular and biological effects of nutrients in maintaining homeostasis in the critically ill population. Traditionally, nutrition support in the critically ill population was regarded as adjunctive care designed to provide exogenous fuels to preserve lean body mass and support the patient throughout the stress response. Recently this strategy has evolved to represent nutrition therapy, in which the feeding is thought to help attenuate the metabolic response to stress, prevent oxidative cellular injury, and favorably modulate immune responses. Improvement in the clinical course of critical illness may be achieved by early EN, appropriate macro- and micronutrient delivery, and meticulous glycemic control. Delivering early nutrition support therapy, primarily by the enteral route, is seen as a proactive therapeutic strategy that may reduce disease severity, diminish complications, decrease LOS in the ICU, and favorably impact patient outcomes. A. NUTRITION ASSESSMENT Question: Does the use of a nutrition risk indicator identify patients who will most likely benefit from nutrition therapy? A1. Based on expert consensus, we suggest a determination of nutrition risk (for example, Nutritional Risk Score [NRS-2002], NUTRIC score) be performed on all patients admitted to the ICU for whom volitional intake is anticipated to be insufficient. High nutrition risk identifies those patients most likely to benefit from early EN therapy. Rationale: Poor outcomes have been associated with inflammation generated by critical illness that leads to deterioration of nutrition status and malnutrition (9). However, malnutrition in the critically ill has always been difficult to define. An international consensus group modified definitions to recognize the impact of inflammation. Objective measures of baseline nutrition status have been described by A.S.P.E.N. and the Academy of Nutrition and Dietetics (10, 11). On the other hand, nutrition risk is easily defined and more readily determined by evaluation of baseline nutrition status and assessment of disease severity. All hospitalized patients are required to undergo an initial nutrition screen within 48 hours of admission. However, patients at higher nutrition risk in an ICU setting require a full nutrition assessment. Many screening and assessment tools are used to evaluate nutrition status, such as the Mini Nutritional Assessment (MNA), the Malnutrition Universal Screening Tool (MUST), the Short Nutritional Assessment Questionnaire (SNAQ), the Malnutrition Screening Tool (MST), and the Subjective Global Assessment (SGA) (12). However, only the NRS-2002 and the NUTRIC score determine both nutrition status and disease severity. Although both scoring systems were based on retrospective analysis, they have been used to define nutrition risk in RCTs in critically ill patients (13–16). Patients at “risk” are defined by an NRS-2002 > 3 and those at “high risk” with a score ≥ 5; or a NUTRIC score ≥ 5 (if interleukin-6 is not included, otherwise ≥ 6) (13, 18). Interleukin-6 is rarely available as a component for the NUTRIC score; therefore, Heyland et al has shown a NUTRIC score ≥ 5 still indicates high nutrition risk (19). Two prospective nonrandomized studies show that patients at high nutrition risk are more likely to benefit from early EN with improved outcome (reduced nosocomial infection, total complications, and mortality) than patients at low nutrition risk (13, 18). While widespread use and supportive evidence is somewhat lacking to date, improvement in these scoring systems may increase their applicability in the future by providing guidance as to the role of EN and PN in the ICU. Question: What additional tools, components or surrogate markers provide useful information when performing nutrition assessments in critically ill adult patients? A2. Based on expert consensus, we suggest that nutritional assessment include an evaluation of comorbid conditions, function of the gastrointestinal (GI) tract, and risk of aspiration. We suggest not using traditional nutrition indicators or surrogate markers, as they are not validated in critical care. Rationale: In the critical care setting, the traditional serum protein markers (albumin, prealbumin, transferrin, retinol-binding protein) are a reflection of the acute phase response (increases in vascular permeability and reprioritization of hepatic protein synthesis) and do not accurately represent nutrition status in the ICU setting (20). Anthropometrics are not reliable in assessment of nutrition status or adequacy of nutrition therapy (21). Individual levels of calcitonin, C-reactive protein (CRP), IL-1, tumor necrosis factor (TNF), IL-6, and citrulline are still investigational and should not be used as surrogate markers. Ultrasound is emerging as a tool to expediently measure muscle mass and determine changes in muscle tissue at bedside in the ICU, given its ease of use and availability (22, 23). A CT scan provides a precise quantification of skeletal muscle and adipose tissue depots; however it is quite costly unless a scan taken for other purposes is used to determine body composition (24, 25). Both may be valuable future tools to incorporate into nutrition assessment; however, validation and reliability studies in ICU patients are still pending. Assessment of muscle function is still in its infancy. Its measurement, reproducibility, and applicability are still being validated for use in critically ill patients, and may be of value in the future. Question: What is the best method for determining energy needs in the critically ill adult patient? A3a. We suggest that indirect calorimetry (IC) be used to determine energy requirements, when available and in the absence of variables that affect the accuracy of measurement. [Quality of Evidence: Very Low] A3b. Based on expert consensus, in the absence of IC, we suggest that a published predictive equation or a simplistic weight-based equation (25–30 kcal/kg/day) be used to determine energy requirements. (See section Q for obesity recommendations.) Rationale: Clinicians should determine energy requirements in order to establish the goals of nutrition therapy. Energy requirements may be calculated either through simplistic formulas (25–30 kcal/kg/day), published predictive equations, or IC. The applicability of IC may be limited at most institutions by availability and cost. Variables in the ICU that affect the timing and accuracy of IC measurements include the presence of air leaks or chest tubes, supplemental oxygen (e.g., nasal cannula, bilevel positive airway pressure), ventilator settings (fractional inspiratory oxygen and positive end-expiratory pressure), continuous renal replacement therapy (CRRT), anesthesia, physical therapy, and excessive movement (26). More than 200 predictive equations have been published in the literature, with accuracy rates ranging from 40–75% when compared to IC, and no single equation emerges as being more accurate in an ICU (27–32). Predictive equations are less accurate in obese and underweight patients (33–36). Equations derived from testing hospital patients (Penn State, Ireton-Jones, Swinamer) are no more accurate than equations derived from testing normal volunteers (Harris-Benedict, Mifflin St. Jeor) (37). The poor accuracy of predictive equations is related to many non-static variables affecting energy expenditure in the critically ill patient, such as weight, medications, treatments, and body temperature. The only advantage of using weight-based equations over other predictive equations is simplicity. However, in critically ill patients following aggressive volume resuscitation or in the presence of edema or anasarca, clinicians should use dry or usual body weight in these equations. Additional energy provided by dextrose-containing fluids and lipid-based medications such as propofol should be accounted for when deriving nutrition therapy regimens to meet target energy goals. Achieving energy balance as guided by IC measurements compared to predictive equations may lead to more appropriate nutrition intake. While two RCTs (38, 39) that met our inclusion criteria (with data from 161 patients) showed that higher mean intake of energy and protein were provided in IC-directed study patients compared to controls whose nutrition therapy was directed by predictive equations, issues with study design prevent a stronger recommendation for use of IC. In a study of burn patients, use of IC-directed nutrition therapy helped provide the minimal effective intake, avoiding the excesses of overfeeding seen in controls whose therapy was directed by the Curreri formula. Complications between groups (diarrhea and hyperglycemia) were no different, but traditional outcome parameters were not evaluated (38). A second study in general ICU patients used both EN and PN to meet target energy goals determined by IC measurement or a weight-based predictive equation (25 kcal/kg/day) (39). While the IC-directed energy goal was no different than the value obtained by predictive equation (1976 ± 468 vs 1838 ± 468 kcal/day, respectively, p = 0.60), only study patients were monitored vigilantly by an ICU dietitian, while controls were managed by standard of care (less frequent ICU dietitian monitoring), which led to significantly more energy and protein per day in the study patients. The trend toward reduced mortality in study patients compared to controls (RR = 0.63; 95% CI, 0.39–1.02; p = 0.06) is difficult to reconcile in light of their increased morbidity with regard to ICU LOS (17.2 + 14.6 vs 11.7 + 8.4 days, p = 0.04) and duration of mechanical ventilation (16.1 + 14.7 vs 10.5 + 8.3 days, p = 0.03) (38, 39). Whether measured by IC or estimated by predictive equations, energy expenditure should be reevaluated more than once per week, and strategies to optimize energy and protein intake should be used (39, 40). Question: Should protein provision be monitored independently from energy provision in critically ill adult patients? A4. Based on expert consensus, we suggest an ongoing evaluation of adequacy of protein provision be perforMed Rationale: In the critical care setting, protein appears to be the most important macronutrient for healing wounds, supporting immune function, and maintaining lean body mass. For most critically ill patients, protein requirements are proportionately higher than energy requirements and thus are not easily met by provision of routine enteral formulations (which have a high nonprotein calorie-to-nitrogen ratio [NPC:N]). Patients with suboptimal EN due to frequent interruptions may benefit from protein supplementation. The decision to add protein modules should be based on an ongoing assessment of adequacy of protein intake. Weight-based equations (e.g., 1.2–2.0 g/kg/day) may be used to monitor adequacy of protein provision by comparing the amount of protein delivered to that prescribed, especially when nitrogen balance studies are not available to assess needs (see section C4) (41, 42). Serum protein markers (albumin, prealbumin, transferrin, CRP) are not validated for determining adequacy of protein provision and should not be used in the critical care setting in this manner (20, 43). B. INITIATE EN Question: What is the benefit of early EN in critically ill adult patients compared to withholding or delaying this therapy? B1. We recommend that nutrition support therapy in the form of early EN be initiated within 24–48 hours in the critically ill patient who is unable to maintain volitional intake. [Quality of Evidence: Very Low] Rationale: EN supports the functional integrity of the gut by maintaining tight junctions between the intraepithelial cells, stimulating blood flow, and inducing the release of trophic endogenous agents (such as cholecystokinin, gastrin, bombesin, and bile salts). EN maintains structural integrity by maintaining villous height and supporting the mass of secretory IgA-producing immunocytes (B cells and plasma cells) that comprise the gut-associated lymphoid tissue (GALT), and in turn contribute to mucosal-associated lymphoid tissue (MALT) at distant sites such as the lungs, liver, and kidneys (44–46). Adverse change in gut permeability from loss of functional integrity is a dynamic phenomenon that is time dependent (channels opening within hours of the major insult or injury). The consequences of the permeability changes include increased bacterial challenge (engagement of GALT with enteric organisms), risk for systemic infection, and greater likelihood of multiple organ dysfunction syndrome (MODS) (45, 46). As disease severity worsens, increases in gut permeability are amplified and the enteral route of feeding is more likely to favorably impact outcome parameters of infection, organ failure, and hospital LOS (47). The specific reasons for providing EN are to maintain gut integrity, modulate stress and the systemic immune response, and attenuate disease severity (44, 47, 48). Additional endpoints of EN therapy may include use of the gut as a conduit for the delivery of immune-modulating agents and use of enteral formulations as an effective means for stress ulcer prophylaxis. Three previous meta-analyses aggregated data from RCTs comparing early versus delayed EN. One meta-analysis of eight trials by Heyland showed a trend toward reduced mortality (RR = 0.52; 95% CI, 0.25–1.08; p = 0.08) (49), when EN was started within 48 hours compared to delayed initiation of EN started after that point. A second meta-analysis of 12 trials by Marik showed significant reductions in infectious morbidity (RR = 0.45; 95% CI, 0.30–0.66; p = 0.00006) and hospital LOS (mean 2.2 days; 95% CI, 0.81–3.63 days; p = 0.001) when early EN was started on average within 36 hours of ICU admission (50). A third meta-analysis of six trials by Doig showed a significant reduction in pneumonia (OR = 0.31; 95% CI, 0.12–0.78; p = 0.01) and mortality (OR = 0.34; 95% CI, 0.14–0.85; p = 0.02), but no difference in multiple organ failure (MOF) when early EN was started within 24 hours of admission to the ICU, compared to EN started after that point (51). Of an updated meta-analysis of 21 RCTs that met our inclusion criteria comparing the provision of early EN versus delayed EN, all reported on mortality (Figure 1), with 13 reporting on infection (Figure 2). Provision of early EN was associated with a significant reduction in mortality (RR = 0.70; 95% CI, 0.49–1.00; p = 0.05) and infectious morbidity (RR = 0.74; 95% CI, 0.58–0.93, p = 0.01), compared to withholding early EN (delayed EN or STD).Figure 1: Early enteral nutrition (EN) vs delayed EN, mortality.Figure 2: Early enteral nutrition (EN) vs delayed EN, infectious complications.Question: Is there a difference in outcome between the use of EN or PN for adult critically ill patients? B2. We suggest the use of EN over PN in critically ill patients who require nutrition support therapy. [Quality of Evidence: Low to Very Low] Rationale: In the majority of critically ill patients it is practical and safe to use EN instead of PN. The beneficial effects of EN compared to PN are well documented in numerous RCTs involving a variety of patient populations in critical illness, including trauma, burns, head injury, major surgery, and acute pancreatitis (47, 49, 52–54). While few studies have shown a differential effect on mortality, the most consistent outcome effect from EN is a reduction in infectious morbidity (generally, pneumonia and central line infections in most patient populations, and specifically, abdominal abscess in trauma patients) and ICU LOS. Six previous meta-analyses comparing EN to PN showed significant reductions in infectious morbidity with use of EN (49, 55–59). Non-infective complications (risk difference = 4.9; 95% CI, 0.3–9.5; p = 0.04) and reduced hospital LOS (weighted mean difference [WMD] = 1.20 days; 95% CI, 0.38–2.03; p = 0.004) were seen with use of EN compared to PN in one of the meta-analyses by Peter (57). Five of the meta-analyses showed no difference in mortality between the two routes of nutrition support therapy (49, 55–59). One meta-analysis by Simpson showed a significantly lower mortality (RR = 0.51; 95% CI, 0.27–0.97; p = 0.04) despite a significantly higher incidence of infectious complications (RR = 1.66; 95% CI, 1.09–2.51; p = 0.02) with use of PN compared to EN (59). In 12 studies (53, 58, 60–69) representing 618 patients that met our inclusion criteria, 9 reported on infection (Figure 3), which was shown to be significantly less with EN than PN (RR = 0.56; 95% CI, 0.39–0.79; p < .00001). ICU LOS also was shorter with EN compared to PN by nearly one full day (MD = –0.82; 95% CI, –1.29 to –0.34, p = 0.0007). Hospital LOS and mortality were not significantly different. These differences in outcome from the separate routes of feeding largely reflect findings from older studies and may diminish in the future with improvements in glycemic control, protocolized medical management and new lipid emulsions.Figure 3: Enteral nutrition (EN) vs parenteral nutrition (PN), infectious complications.Question: Is the clinical evidence of contractility (bowel sounds, flatus) required prior to initiating EN in critically ill adult patients? B3. Based on expert consensus, we suggest that, in the majority of MICU and SICU patient populations, while GI contractility factors should be evaluated when initiating EN, overt signs of contractility should not be required prior to initiation of EN. Rationale: The literature supports the concept that bowel sounds and evidence of bowel function, i.e., passing flatus or stool, are not required for initiation of EN. GI dysfunction in the ICU setting occurs in 30–70% of patients, depending on the diagnosis, premorbid condition, ventilation mode, medications, and metabolic state (70). Proposed mechanisms of ICU and postoperative GI dysfunction are related to mucosal barrier disruption, altered motility, atrophy of the mucosa, and reduced mass of GALT. GI intolerance has been variably defined (e.g., absence or abnormal bowel sounds, vomiting, bowel dilatation, diarrhea, GI bleeding, high gastric residual volumes [GRVs], etc.) and appears to occur in up to 50% of patients on mechanical ventilation. Bowel sounds are indicative only of contractility and do not necessarily relate to mucosal integrity, barrier function, or absorptive capacity. The argument for initiating EN regardless of the extent of audible bowel sounds is based on studies (most of which involve critically ill surgical patients) reporting the feasibility and safety of EN within the initial 36–48 hours of admission to the ICU. Nonetheless, reduced or absent bowel sounds may reflect greater disease severity and worsened prognosis. Patients with normal bowel sounds have been shown to have lower ICU mortality than those with hypoactive or absent bowel sounds (11.3% vs 22.6% vs 36.0%, respectively) (71). ICU LOS has been shown to increase with greater number of symptoms of GI intolerance (2.9 days when asymptomatic versus up to 16.8 days with four symptoms of intolerance) (72). Not surprisingly, success of EN delivery is reduced with a greater number of symptoms of GI intolerance. A greater number of signs of intolerance may warrant increased vigilance as EN is started, and may necessitate further clinical evaluation. Question: What is the preferred level of infusion of EN within the GI tract for critically ill patients? How does the level of infusion of EN affect patient outcomes? B4a. We recommend that the level of infusion be diverted lower in the GI tract in those critically ill patients at high risk for aspiration (see section D4) or those who have shown intolerance to gastric EN. [Quality of Evidence: Moderate to High] B4b. Based on expert consensus we suggest that, in most critically ill patients, it is acceptable to initiate EN in the stomach. Rationale: Initiating EN therapy in the stomach is technically easier and may decrease the time to initiation of EN. The choice of level of infusion (i.e., whether the tip of the feeding tube is in the stomach, different segments of the duodenum [D1, D2, D3 or D4], or the jejunum) within the GI tract may be determined by patient selection within ICU practitioners’ institutional framework (ease and feasibility of placing small bowel enteral access devices, institutional policies, and