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OVERVIEW
Guidelines for the safe administration of drugs through an enteral feeding tube are available, but research shows that often nurses don't adhere to them. This can lead to medication error and tube obstruction, reduced drug effectiveness, and an increased risk of toxicity. This article describes the factors to consider before administering a drug through a feeding tube, examines the gap between recommended and common practice, and discusses what the most recent guidelines recommend and why.
It's common knowledge among nurses that before adding drugs to a patient's IV bag or syringe, the nurse must first check the drugs' stability and compatibility. Yet a surprising number of nurses fail to follow similar precautions when preparing drugs for administration through an enteral feeding tube. This can lead to tube obstruction, reduced drug effectiveness, and an increased risk of toxicity. In fact, medication errors overall remain quite common,1 despite a decade-long movement to reduce them, prompted largely by the Institute of Medicine's 2000 report To Err Is Human: Building A Safer Health System.2
 | Figure. No caption available. |
Practice recommendations for administering medication through an enteral feeding tube have been available for many years.3-7 Most recently, the American Society for Parenteral and Enteral Nutrition (ASPEN) developed evidence-based guidelines for safe medication administration (I served on the task force); these are outlined in Table 1.8 Despite all of these resources, surveys of nurses working in various settings reveal that the use of inappropriate technique is widespread.9-15 According to survey responses, one reason for the use of inappropriate technique could be that many nurses rely chiefly on their own experience and that of coworkers for information, rather than on institutional protocols or pharmacists.9, 14 Limited science content in the curricula of some nursing schools may also play a role.
 | TABLE 1. Guidelines for Administering Medication Through an Enteral Feeding Tube |
THE LINK BETWEEN DRUG ADMINISTRATION AND EFFECTS
In pharmaceutics—the science of drug preparation and administration—the physical and chemical properties of drug molecules are considered in the design of appropriate dosage forms. A drug's release from an oral form and its subsequent absorption are controlled by these properties and by the conditions within the patient's gastrointestinal (GI) tract. (Editor's note: The terms formulation, form, and formula aren't synonymous. Drug formulation refers to the development and engineering of drug products. Dosage form refers to the type of completed preparation; forms mentioned in this article include solid immediate- and sustained-release tablets and capsules, as well as liquid solutions, suspensions, and emulsions. Formula refers to enteral nutrition formula. Also, because drug formulations can vary greatly among manufacturers, even when the dosage form is the same, brand names aren't given unless a specific product is meant or was named by researchers.)
Drug absorption through the GI tract depends largely on two factors: the degree to which a drug is soluble and the degree to which it can permeate the intestinal mucosa. A drug's solubility depends on its ability to dissolve—to change "from a solid to a dispersed form by immersion" in a solvent, according to Stedman's Online Medical Dictionary. Limited dissolution is one of the most common reasons for ineffective drug absorption.16 Dissolution depends on many factors, including the surface area of the drug particles and their diffusivity and solubility in a solvent.16 Moreover, a drug's solubility in water doesn't necessarily indicate its solubility in GI contents, which is affected by, among other things, the pH of those contents and the drug's solubility in fat.16, 17
Many drugs are formulated for oral administration. Administering an oral drug by any route other than the mouth might alter its bioavailability (the availability of active drug at the intended site) and thus its therapeutic effect, perhaps even causing toxicity. The U.S. Food and Drug Administration approves a drug specifically for both its formulation and its intended route of administration. Giving an oral drug through a feeding tube goes beyond those limits, and it's unclear what the manufacturer's liability would be if adverse effects occurred. Further complicating matters is the fact that the design of oral dosage forms and drug delivery systems is becoming increasingly sophisticated.18-21 For example, although still in development, so-called emulsions within emulsions may allow "incompatible substances" to be delivered together.21
Before administering a drug through a feeding tube, a clinician must consider the possible effect of the feeding formula on drug absorption, according to the ASPEN guidelines,8 as well as the length of the patient's functional bowel, the internal diameter and length of the tube, the composition of the tube, the routine flushing regimen, the location of the distal end of the feeding tube relative to the site of drug absorption, the size of the distal opening(s), the need to keep a drug separate from a tube feeding formula, and the size of the oral syringe for both accurate drug dosing and safe intraluminal pressures.
All of these factors must be taken into account to minimize the likelihood of complications. As the ASPEN guidelines note, tube obstruction "is both time- and resource-intensive to address, and therefore is best prevented."8 Unexpected responses to drug therapy can prove injurious or even fatal to patients and increase the burden of care on clinicians and caregivers. Moreover, complications that result from inappropriate drug administration through an enteral feeding tube aren't typically captured in adverse drug event rates.8 It's possible that such complications are both underrecognized and underreported. A review of medication error research concluded that observation was the most accurate method for detecting such errors.22
WHAT SURVEYS OF PRACTICE TELL US
Several surveys have shown that some common practices in enteral drug administration can interfere with drug delivery.9-14 Overall, there is a lack of consistency in practice among and even within facilities. A 1988 survey of pediatric nurses at hospitals in eight states revealed that enteral drug administration techniques varied significantly—yet 97% of the respondents were confident that their techniques were appropriate and effective.11 The authors attributed the variability to a lack of standardized protocols. In a more recent nationwide survey of critical care nurses, Belknap and colleagues found that a majority of respondents used one to three inappropriate techniques for administering medication through an enteral feeding tube.9 Indeed, within my hospital, a survey conducted before implementation of a drug administration protocol revealed that our practices for drug administration through feeding tubes weren't uniform.10
Several common inappropriate techniques have been identified. Belknap and colleagues found that when multiple drugs were to be given at the same time, 68% of respondents administered them together instead of separately.9 And dosage forms were altered: 25% and 15% of respondents reported routinely crushing enteric-coated and sustained-release tablets, respectively, before administering them through a feeding tube. Also, 57% didn't routinely flush the tube before administering a drug, and 19% didn't consult the pharmacist about the availability of liquid dosage forms. When a liquid dosage form was given through a tube, only 60% diluted it first. In another survey of acute care nurses at 11 Rhode Island hospitals, 53% indicated that even when a liquid dosage form was available, they didn't order it.13 And a survey of nurses at a midwestern medical center found that just 38% flushed the tube between drugs when more than one was given.12
These practices aren't unique to acute care. A nationwide survey by Seifert and Johnston of long-term care nurses found that 49% of respondents said that when multiple drugs were to be given at the same time, they mixed the drugs together; 15% and 13% reported routinely crushing enteric-coated and sustained-release tablets, respectively.14 Although 92% routinely consulted the pharmacist about liquid dosage forms, when such forms were available the nurses used them only 61% of the time. When the nurses did use these forms, 36% didn't routinely dilute them first. Respondents who reported using one inappropriate technique usually used others.
When critical care nurses were asked about their sources of information on this topic, they cited clinical experience (57%), coworkers (22%), and nursing school (13%).9 About a third of the nurses were aware of printed guidelines at their institutions, but only 5% ranked this as their primary source. Similarly, long-term care nurses said their top-three main sources of information were clinical experience (55%), nursing school (19%), and coworkers (17%).14 From 67% (rural nurses) to 75% (urban nurses) were aware of printed guidelines, but just 17% cited these as a main information source. Pharmacists were viewed as key sources by only 6% and 12% of the critical care and long-term care nurses, respectively.
Fortunately, awareness of how these issues affect patient safety is growing, fostering greater collaboration across disciplines.23, 24
WHAT THE ASPEN GUIDELINES RECOMMEND AND WHY
The following are the major recommendations in the current guidelines, with rationales and examples.
Do not add medication directly to an enteral feeding formula. When a patient receives both medication and nutrition through a feeding tube, it can be harmful to mix them before delivery, despite the convenience of doing so. Mixing disrupts the sterility of prepackaged enteral formula, as well as that of the delivery system used in feeding. Mixing also creates the potential for drug–formula interactions leading to tube obstruction, altered drug or nutrient bioavailability, altered GI function, or a combination of these. Avoiding such interactions requires knowing whether the drug and the formula are compatible and likely to remain stable after mixing.
With patients on parenteral nutrition, drugs are not added to the formula unless compatibility and stability data support doing so; the situation for patients on enteral nutrition is analogous.8 (A substance is stable when it's resistant to chemical or physical changes; two or more substances are compatible when they can be combined without undergoing chemical or physical changes that alter bioavailability.) Any such information cannot be extrapolated to different formulations of the same drug, to other drugs in the same class, or to other feeding formulas. For example, in one study, the addition of liquid morphine at a low concentration (2 mg/mL) to enteral formula resulted in decreased pH and noticeable precipitate; the addition of the same drug at a higher concentration (20 mg/mL) did not.25 An evaluation of compatibility and stability must go beyond visual examination and identify any physical or chemical changes that occur upon mixing.
There is limited information on the compatibility and stability of a few common drug products and commercially available enteral formulas.25-30 Compatibility can be affected by formula-related factors, including type and concentration of protein and its fiber and mineral content, as well as by the drug product's pH, alcohol and mineral content, viscosity, and osmolality (a property that encompasses the concentration of and pressure exerted by particles in solution).26, 28 Two studies found that the concentrations of some drugs in various formulas fell significantly during the 12-hour and 24-hour study periods.29, 30 Another study found that of 24 incompatible drug–formula mixtures, 23 (96%) resulted in tube obstruction; of those, fewer than a third could be cleared by flushing with water.26 Even when compatibility and stability data support adding a drug product to a formula, the clinician must evaluate the therapeutic benefit. For example, will an adequate amount of the drug be available at the intended site?
Administer each medication separately through an appropriate access site. This requires consideration of the access site, the drug formulation, and its preparation for administration.
Is the access site appropriate? Before administration, ask whether the drug requires gastric acid, bile, pancreatic secretions, or a combination of these for adequate dissolution, as well as where in the GI tract most of the drug is absorbed. Many drugs must be administered into the stomach or duodenum to ensure proper dissolution and absorption, although as the guidelines point out, "there are distinct and occasionally unknown sites of absorption of specific drugs."8 Administering a drug below the duodenum risks bypassing the sites where these processes best occur, and that, in turn, will affect both drug bioavailability and effectiveness. For example, warfarin appears to be absorbed high in the proximal small bowel,31, 32 and iron given orally dissolves in the stomach and is predominantly absorbed in the duodenum7; administration of either through a jejunostomy tube risks poor bioavailability.
Is the drug formulation appropriate? Drugs intended for oral administration are designed for a healthy GI tract. To deliver an oral drug through a feeding tube is to destroy its carefully designed delivery mechanism—and quite possibly to alter how it will perform in the GI tract.
Drug classification systems have been developed to help clinicians predict a drug's performance in the body, based on measures such as solubility and permeability.33, 34 It's possible that such a system may also help clinicians predict whether administration via an enteral feeding tube is appropriate. The formulation of drugs with high solubility and high permeability (such as metronidazole) is usually uncomplicated; these drugs are probably of least concern for administration through a feeding tube. But the formulation of drugs with low solubility or low permeability or both (such as the protease inhibitors) can be quite complex; such drugs should probably not be altered for administration through a feeding tube. Indeed, according to Takagi and colleagues, of the 200 top-selling immediate-release oral dosage forms, about 40% are considered "practically insoluble" in water.35 Yet these forms can deliver the intended dose of active drug to the intended site, an indication of just how sophisticated drug formulation has become.
Formulation issues can be drug product—or dosage form—specific. The presence of excipients—nontherapeutic ingredients such as fillers, binders, buffers, and preservatives—must also be considered. For example, quinapril (Accupril) tablets contain magnesium carbonate. If a tablet were to be crushed and dissolved in water, the carbonate would raise the pH of the solution, causing the active drug to degrade rapidly to a poorly absorbed metabolite.36 Different formulations of a drug may demonstrate significant differences in stability or bioavailability. For example, in one animal study, the equivalent of 10 mg/kg of itraconazole was given as either a solid-dispersion coating or as a semisolid emulsion.37 The latter formulation provided about twice the bioavailability.
Enteric-coated and sustained-release dosage forms should not be crushed for administration through feeding tubes.3 Tablets with enteric coatings don't crush readily, and the resulting powder tends to clump in water, increasing the likelihood of tube obstruction. Crushing sustained-release dosage forms destroys the protective coating, resulting in erratic blood levels and potential toxicity. The results can be disastrous, as in a case described by Schier and colleagues38 of a 38-year-old woman hospitalized with pneumonia. Upon stabilization, her medications were changed to oral forms of hydralazine, labetalol, and extended-release nifedipine, which were crushed and given through a nasogastric tube. She developed bradycardia with hypotension, had an asystolic cardiac arrest, and was resuscitated. The next day the same drugs were given the same way, and she died. The crushed nifedipine was deemed a contributing factor.
Liquid-filled gelatin capsules can also cause problems; once the capsule is breached it's difficult to ensure that the full dose has been extracted. Although the guidelines recommend giving liquid dosage forms (rather than solid ones) when possible, many commercially available liquid dosage forms aren't appropriate for administration via a feeding tube.39 Some common excipients can increase osmolality and cause diarrhea. And injectable dosage forms aren't designed for administration into the GI tract at all. (For more on this, see the discussion of dilution below.)
Determine the best way to prepare a drug for administration through a feeding tube. Most solid immediate-release tablets should be crushed to a very fine powder before being dissolved in sterile water. (An immediate-release gelatin capsule containing solid drug should first be opened and its contents then treated the same way.) Crushing results in a small particle size, which usually improves dissolution and decreases the likelihood of tube obstruction; however, the resultant increase in particle surface area can "accelerate changes in molecular structure" and make interaction with other substances more likely.8
Any solid dosage form contains both active drug and excipients, and these may behave differently upon mixing in a solvent. (The physical and chemical properties of the solvent—usually but not always water—also play a role; dilution is discussed in the next section.) For example, consider how table sugar and sand mix with warm water: the table sugar dissolves, but the sand does not, falling to the bottom. Most drugs will behave somewhere along the sugar–sand continuum. How well a given drug mixes into solution must be taken into account, or incomplete dosing might result. For example, sedimentation may be evident. To ensure that the patient receives the intended dosage, the mortar and pestle, medicine cup, or oral syringe (or any combination of these) used in preparing the dose should be rinsed and the rinse solution administered. Because a mortar and pestle require thorough cleaning between uses to avoid cross-contamination, the use of a medicine cup for crushing is preferable. (If the drug being administered might be allergenic, cytotoxic, carcinogenic, or teratogenic, it shouldn't be crushed in a patient care area at all, but rather by the pharmacist under highly controlled conditions, and only when necessary.)
Some immediate-release tablets, including those designed to disintegrate in the mouth, might dissolve readily in water without prior crushing. But some orally disintegrating tablets (such as lansoprazole [Prevacid SoluTabs]) must not be crushed, because they contain enteric-coated microgranules. And some capsules (such as doxycycline [Oracea]) contain both immediate- and delayed-release granules.
Dilute the solid or liquid medication as appropriate and administer using a clean oral syringe. After a solid dosage form is pulverized, the powder must be diluted before administration through an enteral feeding tube. Liquid dosage forms usually require dilution as well.
Sterile water or saline are the preferred diluents for most drug products.8 Ideally, the same mixture of solvents used by the manufacturer is used to avoid drug degradation, but in practice that is rarely possible. Sterile water meets United States Pharmacopeia standards. Tap water should not be used; it can and often does contain contaminants, including pathogenic microorganisms, pesticides, pharmaceuticals, and heavy metals8, 40 that might interact with a drug and reduce its bioavailability. Only syringes manufactured and intended for oral or enteral use should be used to measure and administer a medication through a feeding tube.41 (To prevent inappropriate administration, the syringe tip should be too large to fit Luer ports or other nonenteral access devices.)
Many oral liquid drug products are formulated for children; when giving an adult such a product, a larger volume may be necessary even before dilution to achieve correct dosing. Liquid dosage forms usually contain excipients (such as thickeners, stabilizers, suspension agents, and sweeteners) that increase the liquid's viscosity and osmolality. The volume of diluent required (and thus the amount of diluent to be used) will be determined by the viscosity and osmolality of the liquid dosage form, the length of the feeding tube, its internal diameter, and the location of the distal tip. The higher a drug product's viscosity or osmolality, the more diluted it should be before administration through a tube. For a patient on restricted fluid intake (such as one with heart failure or kidney disease), the smallest possible amount of diluent should be used.
Suspensions tend to have much higher viscosity than solutions. Some suspensions may contain granules, including sustained-release granules. Highly viscous or granular suspensions tend to resist flowing through a tube; dilution helps to overcome this but may not be sufficient, especially if the tube is narrow. It's difficult to know what volume of diluent is needed in such cases. But studies have shown that dilution of a liquid drug product before administration is associated with improved delivery of the drug dose to the distal end of the tube.42, 43
The higher the osmolality of a drug product, especially when administered directly into the small intestine, the more likely are GI intolerance and diarrhea.6 Some liquid drug products have high osmolality (above 600 mOsm/kg can be considered high); for example, that of one commonly used acetaminophen elixir exceeds 5,000 mOsm/kg and that of diphenoxylate liquid exceeds 8,000 mOsm/kg.6 A single dose of such products will require significant dilution (150 to 250 mL of diluent) before administration. Products containing electrolytes, such as liquid potassium chloride, also tend to have high osmolality. (One handbook reports that, depending on the brand, the pH of potassium chloride varies from 2.4 to 6.2; pH is another factor that must be taken into account be cause the formula's pH can affect a drug's stability.44)
Avoid mixing medications intended for administration through an enteral feeding tube. Most clinicians know they shouldn't mix different drugs in the same IV bag or syringe without first ensuring the drugs' stability and compatibility; the same rule applies here for both solid and liquid dosage forms. It's hard enough to predict stability for any one drug product altered for administration through a feeding tube; when more than one drug is administered at the same time, predicting stability and compatibility becomes even more difficult. Thus, when more than one drug is scheduled for administration, they must be given separately.
The potential for drug–drug interactions (as well as for those involving excipients) increases when two or more dosage forms are crushed together. Crushing involves applying significant force to a drug product, and it increases the amount of particulate surface area available for interaction. Either can accelerate changes to molecular structure and result in altered physical and chemical properties; such risks increase exponentially when more than one drug, with its excipients, is crushed.
When a drug product is altered, its stability can be compromised. Indeed, one study found that when two nonsteroidal antiinflammatory drugs with similar molecular structures were similarly prepared as solid dispersions, they exhibited very different solubility.45 Mixing two or more dosage forms creates a new entity; it's unknown how each drug would be released.
The same kinds of concerns pertain to mixing two or more liquid dosage forms. Their stability after mixing and their compatibility with each other and with any solvents used would have to be considered, as would their likely miscibility (the ability to mix in any ratio and remain mixed). Because such data aren't readily available, every new mixture must be studied before predictions can be made. Mixing one liquid drug product with another may also alter viscosity and affect how the mixture flows through a tube. It's also often unknown how a particular mixture of liquid dosage forms might behave in the body.
Stop the feeding and flush the tube with at least 15 mL sterile water before and after administering each medication. Flushing the tube has been shown to decrease the incidence of tube obstruction.46 As with dilution, only sterile water or saline should be used.
It's impossible to know what quantities of enteral formula, active drug, excipients, and other products are left in the residue inside the feeding tube. For example, when researchers crushed losartan tablets (Cozaar) and diluted the resulting powder in water, they knew that some drug would precipitate; they also found "unknown degradation products," which decayed more rapidly when exposed to light and oxygen.47
Flush the tube one final time with at least 15 mL sterile water to ensure delivery of the total dose and reduce residue within the lumen.
Restart the feeding in a timely manner to avoid compromising nutritional status. For most medications, stopping enteral feeding and flushing the tube before and after drug administration is sufficient to separate feeding from drug administration; feeding can resume after the final flush. But for a few drugs—including the fluoroquinolones, penicillin, carbamazepine, phenytoin, voriconazole, and warfarin—a longer nutrient-free interval may be necessary. There are reports of significantly reduced drug efficacy when such drugs are given too close in time to an enteral feeding.6 The ASPEN guidelines recommend a separation time of at least 30 minutes,8 but some drugs may require longer periods. Delaying a feeding is less disruptive for patients on an intermittent feeding regimen than for those on a continuous regimen. Even when the evidence on a drug isn't conclusive—as in one systematic review of more than 30 years of research into the possible interaction between phenytoin and enteral formula48—it's recommended that the patient care plan consider the scheduling of drug administration and feeding and that patients be closely monitored.
COLLABORATION BETWEEN NURSES AND PHARMACISTS
Nurses don't have to navigate these guidelines alone. Pharmacists are responsible for giving others on the care team pharmacologic information, including the physical and chemical properties of specific drugs and their various formulations and dosage forms, as well as an interpretation of the published stability and compatibility data. In one Dutch study, a multidisciplinary program reduced the number of tube obstructions and medication errors by promoting practice guidelines, holding training sessions for nurses, establishing a database of oral dosage forms, and having pharmacists offer patient-specific recommendations.49
The pharmacist can also address whether it's appropriate to administer a particular drug through a feeding tube, its likely bioavailability when given by that route, and what the potential complications might be, including drug–nutrient interactions. The pharmacist will be able to recommend ways to simplify a patient's drug regimen. These might include temporarily discontinuing any drugs that aren't immediately essential; adjusting the dosing schedule to minimize the number of drugs given at the same time; using liquid or immediate-release dosage forms when available; and, if a drug isn't well suited to administration through a feeding tube, using another route of administration or switching to a similar product that can be given via a tube. Institutional protocol may even allow the pharmacist to prepare the prescribed drug for administration through a feeding tube before dispensing it, when appropriate. Specific preparations intended for tube administration that have been studied may be found in pharmacy reference manuals and in the literature.44, 50 Study data should indicate that a particular preparation will be stable over time and that the full intended dosage will be delivered to the distal end of the tube.
For 24 additional continuing nursing education articles related to the topic of drug therapy, go to www.nursingcenter.com/ce .
 | FIGURE 1. An enteral feeding tube can terminate in the stomach, duodenum, or jejunum. When administering oral medication through an enteral feeding tube, it's important to consider whether the drug requires gastric acid, bile, pancreatic secretions, or a combination of these, for adequate dissolution, as well as where in the GI tract most of the drug is absorbed. |
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