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 DOI: 10.1177/0884533609357434

2010 25: 10Nutr Clin PractLingtak-Neander Chan

A ''Gutsy Move'': Tackling Enteral Feeding Intolerance in Critically Ill Patients  

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10

Nutrition in Clinical PracticeVolume 25 Number 1February 2010 10-12

© 2010 American Society for Parenteral and Enteral Nutrition

10.1177/0884533609357434http://ncp.sagepub.com

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There exists little dispute that in critically ill patients, enteral feeding is associated with improving clinical outcomes, minimizing infection-related complica-

tions, preserving gut epithelial cell mass and the function of gut-associated lymphoid tissue, and offering cost-saving benefits over parenteral feeding alone.1-3 Therefore, unless it is contraindicated, enteral nutrition (EN) is preferred over parenteral nutrition (PN) in critically ill patients. Nevertheless, it is rare that the implementation process for EN in these patients goes smoothly and uneventfully with caloric goals being met without setbacks or obstacles. Numerous prospective and retrospective clinical studies have shown that most intensive care unit (ICU) patients receiving EN never actually received target calories.4-7 Although interventional procedures and medication admin-istration may interrupt the infusion of EN, the most com-mon cause of EN infusion interruption is gastrointestinal (GI) intolerance. Up to 60% of ICU patients experience GI intolerance or motility disturbances, necessitating the tran-sient cessation of EN infusion.8 The common symptoms of EN intolerance include elevated gastric residual volume (GRV), bloating, nausea, vomiting, abdominal distention, and diarrhea.

The causes of EN intolerance are multifactorial, and the primary etiology varies among patients. Inflammatory responses associated with critical illness, traumatic injuries, drugs used in the ICU setting for sedation or hemodynamic support, fluid and electrolyte disturbances, hyperglycemia, dysregulation of gut hormones and neurotransmitters in the enteric nervous system, and dysfunction of the pacemaker cells of the GI smooth muscles can all alter GI motility, lead-ing to EN intolerance. An improved understanding in the regulation of GI motility would help us more logically

From the School of Pharmacy and Graduate Program in Nutritional Sciences, University of Washington, Seattle.

Address correspondence to: Lingtak-Neander Chan, PharmD, BCNSP, School of Pharmacy, University of Washington, Box 357630, 1959 NE Pacific Street, HSC, H-375E, Seattle, WA 98195-7630; e-mail: neander@u.washington.edu.

approach patients with EN intolerance to tailor patient-specific diagnostic approaches, monitoring parameters, and therapeutic strategies. In this volume of Nutrition in Clinical Practice, 3 outstanding articles are aimed to provide an in-depth and critical evaluation on the current knowledge contributing to enteral feeding intolerance in critically ill patients, as well as explore strategies to maximize the bene-fits of EN while minimizing the complications associated with enteral feeding in patients with end-organ dysfunction.

In the first article, Dr Ukleja has provided a state-of- the-art review on the current knowledge of the regulation of GI motility.9 Different aspects, including neuronal innervations and pacing, hormonal regulation, postoperative ileus, and acute colonic pseudoobstruction, are described. More importantly, how critical illness may affect these aspects is discussed. The second half of the article includes a brief overview of the established methods to assess GI motility and upper GI transit time. Unfortunately only some of the diagnostic approaches have been validated in critically ill patients. In addition, the ICU setting limits the feasibility of many of the diagnostic methods described. The exception is the acetaminophen (also known as paracetamol in Europe and Asia) absorption test. The feasibility of using the aceta-minophen absorption test in the ICU setting has been reported in several studies.10-14 There are a few limitations, however, that clinicians should keep in mind when the acetaminophen absorption test is performed to assess upper GI transit time. First, to accurately apply the pharmacoki-netic principles, acetaminophen should be administered as an oral liquid instead of as a crushed oral tablet. Second, because acetaminophen is absorbed mostly in the small bowel, its absorption kinetics reflect gastric emptying rate and upper GI transit time but not small bowel motility. Therefore the result is most meaningful and interpretable when it is obtained from a patient with a nasogastric or gas-tric feeding tube instead of small bowel feeding tube. Third, long-term use of drugs or compounds that induce CYP2E1 (eg, ethanol) or CYP3A4 (eg, rifampin, carbamazepine, phenytoin) can affect the absorption kinetics of acetami-nophen by increasing its first-pass metabolism. Finally, unless baseline data (ie, acetaminophen absorption kinetics

A “Gutsy Move”: Tackling Enteral Feeding Intolerance in Critically Ill Patients

Lingtak-Neander Chan, PharmD, BCNSP

Invited Commentary

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A “Gutsy Move” / Chan 11

in the same patient before dysmotility is suspected) are avail-able, the absorption kinetic data cannot be interpreted accu-rately in patients with upper GI surgery, such as Roux-en-Y gastric bypass, Bilroth procedures, or sleeve or total gastrec-tomy, because these procedures alter the rate of acetami-nophen absorption. It is also important to remember that aspiration of gastric content (eg, measuring GRV) shortly after acetaminophen administration (eg, within the first 2 hours of drug administration) can alter the absorption kinet-ics, leading to inaccurate results.

In ICU patients with EN intolerance due to docu-mented GI hypomotility, reversing the cause(s) of hypo-motility should be the primary management approach. Optimizing existing interventions—such as correcting fluid and electrolyte disorders; decreasing or discontinu-ing drugs that are known to slow GI transit (eg, opioid analgesics), if possible; and adequately controlling and stabilizing blood glucose by the use of continuous insulin infusion can often lead to improved EN tolerance in patients with mild symptoms and without underlying motility disorders. Data from both healthy people and patients with diabetic gastroparesis have shown that blood glucose concentration is a positive predictor of delayed gastric emptying rate.15-17 Reducing fasting blood glucose from 190 mg/dL to about 155 mg/dL, or post-prandial blood glucose from 280 mg/dL to 170 mg/dL can increase the gastric emptying rate by almost 20%, with a measurable increase in the number of gastric contrac-tions.18 Whether a similar magnitude of improvement can be achieved in ICU patients is not clear. But the message reinforces the importance and benefits of optimal glyc-emic management in critically ill patients.

In addition to the above-mentioned strategies, the addi-tion of pharmacotherapy may prove useful in some patients. Dr Fraser, whose research team has conducted clinical investigations and published extensively about prokinetic use in ICU patients, has elegantly summarized the mecha-nism of action, comparative efficacy, and place of therapy for the available prokinetic agents.19 It must be emphasized that neither erythromycin nor metoclopramide has been approved by the US Food and Drug Administration for use in the ICU to reverse EN intolerance. This off-label use is extrapolated from their established efficacy in treating diabetic gas-troparesis. The use of these 2 drugs is not without poten-tially serious side effects: metoclopramide can cause dystonic reaction (especially at higher doses or in older patients), whereas erythromycin can disrupt cardiac electrical con-ductance and may lead to prolonged QT intervals and ven-tricular arrhythmia.20-22 The cardiac risk is accentuated by the presence of electrolyte disorders (especially magnesium and potassium). Erythromycin can also dramatically increase the clinical effect of many drugs (eg, cyclosporine, tac-rolimus, methadone, fentanyl) by inhibiting intestinal and hepatic metabolic enzymes (CYP1A2 and CYP3A4) as well as P-glycoprotein, a transport protein present in the kidneys,

intestinal epithelial cells, and blood-brain barrier. In addi-tion, intravenous (IV) erythromycin must be diluted before administration (note: there has been a shortage of IV eryth-romycin in the United States). The amount of dilutional fluid required is proportional to the dose. Therefore, in fluid-restricted patients, IV erythromycin should be used with caution. With the latest research suggesting that the efficacy of erythromycin is inversely proportional to plasma erythro-mycin concentration23 and that most of the side effects and toxicities are dose related, it is probable that the commonly adopted regimen, which is derived from its antimicrobial efficacy, is excessive for EN tolerance. Future research with lower doses of erythromycin will be necessary.

Interventions intended to manage acute illnesses, such as agitation, pain, shock, and infections, may have unin-tended effects toward GI tract functions. Dr Btaiche and his colleagues have addressed this issue very extensively in the third article of this review series.24 The discussion echoes the review in physiology provided in the Ukleja article.9 The detailed information helps clinicians appreciate the com-plexity of the causes of EN intolerance and GI motility dis-orders in most ICU patients. Therefore, the treatment strategy should always be individualized, according to the most likely causes in each patient at the given time and clinical condition. More importantly, EN intolerance is not limited to GI hypomotility. Diarrhea and constipation are common reasons leading to cessation of enteral feeding. Careful evaluation of potential causes such as infections (eg, by Clostridium difficile), dosage form–related complications (eg, nonabsorbable sugar such as sorbitol in liquid medica-tions), food allergy, postoperative hypersecretion, or a bezoar is needed to determine a patient-specific treatment plan.

In addition to having an individualized management plan to reverse EN intolerance, implementation of an EN protocol has been shown to increase the adequacy of EN as well as reduce the time to reach the target infusion rate. Unfortunately, many studies that evaluated EN proto-cols either did not address or found no improvements in clinical outcomes such as hospital length of stay, duration of mechanical ventilation, or survival, despite an increased utilization of EN.25,26 Although institution-specific barriers for guideline implementation and adherence could certainly limit the success of the EN protocol, one must also chal-lenge the feasibility and safety of using a universal protocol in a relatively heterogeneous group of patients. For example, would a protocol that works for cardiac surgery patients be tolerated by patients undergoing abdominal surgery? Likewise, would the titration and monitoring parameters in a protocol used in a trauma unit be safe in a medical ICU with mostly elderly patients with multiple comorbidities, such as diabetes, neuromuscular diseases, or even delirium? Similar to assessing the causes of EN intolerance, the devel-opment and refinement of an EN protocol should be based on the type of patients encountered. Patient safety also should be assessed on a regular basis. The safety and success

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12 Nutrition in Clinical Practice / Vol. 25, No. 1, February 2010

of an EN protocol require the understanding and collabora-tion of clinicians involved in all disciplines. For instance, the inclusion of prokinetic agents in an EN protocol should also address dosing and formulation issues, especially in special patient populations (eg, patients receiving renal replace-ment therapy, with Roux-en-Y gastric bypass, or with underlying cardiac abnormalities) to minimize adverse events. Interdisciplinary communication and education should be encouraged during the development and refine-ment process, and each discipline would learn from others to achieve the common goal.

The critical care setting is not a homogeneous environ-ment. The diversity and complexity of patients continue to evolve, even within the same ICU. The inter-ICU and inter-institutional variances are likely to become more significant because of the differences in patient demographics, availa-ble resources and manpower, and the specialty experience within different institutions. The research in tight glycemic control in ICU patients in the past 8 years is a clear reminder of these important yet complex issues. Therefore, as we con-tinue to optimize the use of EN in ICU patients, future research should also evaluate different strategies to maxi-mize and individualize the benefits of nutrition support in general. This may include the judicial use of PN in conjunc-tion with EN or electively underfeeding specific patients during certain critical periods. Ultimately, improving clinical outcomes of ICU patients must be one of the goals of maxi-mizing enteral feeding.

References

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