**The Skinny on Gastric Bypass What Pharmacists Need to Know **

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Vol. No: 30:02 Posted: 2/22/05

The Skinny on Gastric Bypass

What Pharmacists Need to Know

A. Fussy, PharmD Candidate,

BS Pharm Sci, minor Nutrition Sci,

North Dakota State University

Status: post Lap Roux-En-Y 6/03/03

US Pharm. 2005;2:HS-3-HS-12.

The ever-increasing obesity ep idemic in the United States has been

well established in current medical literature. Some statistics

report that as many as two thirds1 of U.S. citizens are overweight,

and as many as half of those individuals, roughly 50 million,2 are

classified as being obese (having a body mass index [bMI] of 30 or

more).1 Unfortunately, those who are considered morbidly obese are

the largest growing subgroup of obese individuals—encompassing

nearly 12 million people.1,2 Morbid obesity is defined as having a

BMI of greater than or equal to 40 and being at least 100 pounds

above ideal body weight standards.3 It has been well documented that

morbid obesity is associated with numerous health-related

comorbidities,1-8 as listed in TABLE 1.

The evolution of laparoscopic (minimally invasive) surgical

techniques that have improved surgical outcomes, coupled with an

increasing willingness among third-party payers to cover bariatric

procedures (in hopes of counteracting the enormous costs of obesity-

related comorbidities), has led to a dramatic increase in the number

of patients seeking surgical intervention.9,10 In fact, Medicare

announced in July 2004 that it is shunning fad diets and instead

focusing on considering paying for obesity surgery in order to

provide a permanent and effective means of weight loss.10

THE ROLE OF PHARMACISTS

According to the American Society for Bariatric Surgery, over

110,000 patients were projected to undergo bariatric (weight loss)

surgery in 2004.9 That number was up from the 25,000 surgeries

performed in 1998.10 The increasing popularity of gastric bypass

surgery leads to a new gamut of health care concerns that are

relevant to the practice of pharmacy, both in the inpatient and

outpatient settings.

Pharmacists will need to acquire an acceptable knowledge base on the

malabsorptive and nutritional deficiency characteristics associated

with these particular patients in order to provide appropriate

pharmaceutical care, adequate patient monitoring, medically sound

supplementation recommendations, and patient counseling. In doing

so, there are several parameters for pharmacists to consider,

including the different types of weight loss surgeries performed,

how they work to induce weight loss, the health complications and

risks that result, and patient monitoring parameters that are

important to ensure a patient's health. Pharmacists will play an

important role in the postsurgical management of electrolytes, pain

management, parenteral nutrition, prophylactic use of anticoagulants

and antibiotics to prevent clot formation, and life-long medication

and nutritional supplementation monitoring for appropriateness of

therapy in bariatric patients.11,12

TYPES OF BARIATRIC SURGERIES

The term " gastric bypass " is often misused as a sort of blanket

term, meant to encompass all forms of bariatric surgery. However,

the surgeries differ extensively in the nature of their anatomical

restrictive and malabsorptive capacities. These differences incurred

from bariatric surgery lead to varying changes in digestion and

absorption, which are important parameters affecting the extent of

weight loss, the potential for nutritional deficiencies, and the

possibility of pharmacokinetic and bioavailability variations in

drug absorption.2-8

Purely Restrictive Procedures

The most common bariatric procedures performed in the U.S. today can

be divided into two basic categories: purely restrictive procedures

and combination procedures that are malabsorptive and restrictive in

nature.1,4,12 Purely restrictive surgeries include vertical banded

gastroplasty (VBG) and adjustable gastric banding (AGB), often

called the Lap-Band surgery. They involve the formation of a small

pouch at the top of the stomach that restricts the volume of food a

patient is able to consume. Food is then allowed to pass normally

(albeit more slowly) through the rest of the digestive system.12

Weight loss is not nearly as drastic with these restrictive

surgeries, and they are less commonly performed in general. As these

surgeries do not involve intestinal bypass, nutrient deficiencies

are far less common in these procedures and

malabsorption/bioavailability concerns do not exist (see FIGURES 1

AND 2).2-8

Combination Procedures

The combination procedures include the Roux-En-Y (pronounced roo-en-

y) gastric bypass (RYGB) and biliopancreatic diversion (BPD) with or

without a duodenal switch (DS) (see FIGURES 3, 4, and 5).1,12 BPD

involves extensive resectioning of the small bowel and removal of

two thirds of the lower portion of the stomach. In this procedure

absorption is limited to a brief portion of the end (ileum) of the

small intestine, which results in extensive malabsorption of

nutrients. Although weight loss is extensive with this surgery,

significant complications, malnutrition, and inconvenient frequent

foul-smelling stools can occur. For this reason, BPD is largely

reserved for the superobese (BMI of 50 or higher).2,4,7,12

The other combination procedure, RYBG, is considered the gold

standard in bariatric procedures. It is the most commonly performed,

longest and most extensively studied bariatric procedure to date,

and is the most effective procedure (endorsed by the National

Institutes of Health) in terms of producing long-lasting, successful

weight loss.2-8 For this reason, the remainder of this article will

focus on the nutritional and malabsorptive concerns associated with

just this procedure (although still applicable to BPD/DS), as it is

the most common procedure that pharmacists are likely to encounter.

The RYGB surgery involves formation of a small 1-ounce pouch at the

junction of the esophagus and the very top of the stomach (the

cardia). This portion of the stomach is resistant to stretching,

which helps keep the pouch small over time and greatly limits the

amount of food that the patient can consume. The pouch is created by

stapling off a small thumb-sized portion from the rest of the

stomach, which may or may not then be permanently separated. The

small pouch merely functions as a reservoir for food and does not

produce stomach acid. The remaining separated stomach continues to

produce stomach acid and gastric juices but will never again receive

food. The small intestine is then cut about 18 inches downstream

from the lower stomach base. The free piece of bowel (called the

Roux limb) is then reattached upwards to the small pouch at a stomal

(outlet) site. This connection is purposefully shaped into a narrow

outlet roughly the size of a pencil eraser, in order to restrict the

rate that food passes out of the pouch. This keeps the patient

fuller for a longer period of time and is the restrictive portion of

the procedure. 2,4-8,12,13

The 18-inch small bowel portion " hanging " off the end of the lower

separated stomach is then attached to the Roux limb at a certain

distance (50­150 cm) from the stomal connection, in a Y-shaped

formation. This allows for a small amount of gastric juice still

produced in the bottom stomach to be introduced to passing food to

aid in digestion. This is the portion of the surgery that creates

malabsorption of calories, by bypassing the duodenum and early

jejunum (as well as the entire lower stomach) where the majority of

absorption occurs.2,4-8,12,13

POST ROUX-EN-Y GASTRIC BYPASS

Immediately post-op the patient is required to adhere to a liquid

diet for roughly a month, followed by a progressively more solid

diet until a normal diet is resumed about six to eight weeks post-op

(depending on the surgeon's requirements). At any given sitting,

patients are able to consume only one quarter to three quarters of a

cup of food, depending upon its consistency, resulting in a large

reduction in caloric intake.12-14 This reduction in intake, coupled

with the malabsorption, results in dramatic weight loss. It is

estimated that 95% of patients will lose an average of 70­75% of

their excess weight within two years of surgery, and at five years

post-op, up to 85% of patients will maintain a minimum of 50% of

their excess weight loss.9 (It is important to note that due to this

massive weight loss in such a short period, patients may be at an

increased risk of gallstone formation. Some surgeons will opt to

circumvent this risk by removing the gallbladder at the time of

surgery, or they may also opt for a more conservative approach of

prescribing a gallstone dissolution agent such as ursodiol for the

first three to six months post-op, when the most rapid weight loss

occurs.)11

In addition to massive weight loss, nearly all comorbidities

associated with the obesity are completely reversed or substantially

improved following the surgery.1,4,15 In fact, almost 80% of

patients experience complete resolution of their type 2 diabetes

within days of surgery,12 and other comorbidities such as GERD,

hypertension, and sleep apnea also disappear along with the

weight.1,4,12,15 However, the surgery is not without risks, and the

features that allow for the tremendous weight loss are the same

culprits that induce malabsorption of certain drugs and vital

nutrients, and an adverse reaction called dumping syndrome.

DUMPING SYNDROME

Dumping syndrome is caused by intake of highly concentrated

substances that fill the lower small intestines too quickly before

they are digested. This occurs when RYGB patients eat meals high in

refined sugars or fat, even in small quantities. The concentrated

highly osmolar substances travel the shortened distance to the lower

intestine quickly, resulting in a fluid shift into the small

intestine. This can result in cramping, tachycardia, diaphoresis,

vomiting, or diarrhea in the early dumping phase. A later dumping

phase can occur as a result of the efficiency of the small bowel in

absorbing simple sugars. A small amount of simple sugars may cause a

rapid glucose spike in the blood, triggering insulin release. The

small amount of sugar ingested is not large enough in comparison to

the amount of insulin that is released, and hypoglycemia may ensue.

This causes the patient to feel extremely fatigued and sleepy.

Unfortunately, the hypoglycemia may also stimulate hunger, causing a

vicious cycle of overeating and potentially surgery failure. For

this reason, most bariatricians recommend limiting the sugar content

in foods to less than 16 g per serving (also known as " sweet 16 " ).

Pharmacists can also instruct patients to consume a high-protein

diet consisting of frequent small, dry meals (no fluids 30 minutes

before or 1­2 hours after ingestion), with mi nimal refined

carbohydrates or fats, in order to avoid dumping.7,8,12-16

NUTRIENT DEFICIENCIES

Some of the most common nutrient deficiencies that occur in RYGB

patients are calcium, folate, vitamin B12, and iron deficiencies,

and protein malnourishment.16 Additional surgical complications are

outlined in TABLES 2 AND 3.2,3,5-8,11,12,14 The nutrient

deficiencies that occur are due to the fact that a large portion of

the small intestine is bypassed following the surgery, in order to

create malabsorption of calories for enhanced weight loss

(consequently, vital nutrients are malabsorbed as well). The type

and extent of nutritional deficiencies vary greatly, depending upon

the length of small intestines bypassed, which is different for

every patient. Individuals therefore will have varying

supplementation needs, but all patients will require one to two

daily multivitamins for the rest of their lives after surgery.2-

8,12,14,16 See TABLE 4 for supplementation needs for RYGB patients.

Calcium Deficiency

Calcium is predominantly absorbed into the body by the duodenum,

which is bypassed in RYBG surgery. As a result, calcium deficiency

can be a common occurrence in patients if appropriate life-long

supplementation is not initiated. Additionally, the solubility and

amount of elemental calcium provided vary greatly among the various

calcium salts and thus should be considered when a product is

recommended. This is particularly important in bypass patients who

do not have stomach acid present in the new stomach pouch to aid in

absorption. As a result, the absorption of less soluble calcium

salts (calcium carbonate) that require stomach acid for absorption

is lower, and the absorption of more soluble calcium salts (calcium

citrate) that do not require stomach acid for absorption is higher.

RYGB patients are also more susceptible to lactose intolerance, as

the lactase enzyme that breaks down milk sugars is secreted at the

distal bypassed portion of the stomach. This may result in decreased

intake of dairy products, further worsening deficiency.7,12,16-30

Of particular concern regarding calcium supplementation is the

number of providers who still recommend calcium carbonate­containing

products to RYGB patients, even in the face of the achlorhydric

environment that the new stomach pouch creates. Calcium carbonate

products are often recommended despite their relatively insoluble

nature due to the larger degree of elemental calcium they provide in

comparison to other salt forms (carbonate provides 40% elemental

calcium, vs. citrate which provides 21%). To overcome the solubility

issue, many providers advise that patients take their carbonate

products with food to enhance absorption. It has been proposed that

after food intake, the acid-producing parietal cells (located in the

body of the stomach) become stimulated to produce more acid, thus

improving absorption. This mechanism does not apply to RYGB

patients, however, as the bottom portion of the stomach is entirely

bypassed after surgery and the acid-secreting parietal cells will

never again be stimulated by food intake. Absorption of carbonate-

containing products will therefore not be enhanced by this means.

This is the perfect reason for pharmacists to come into play and to

recommend more soluble salt forms such as citrate or

microcrystalline hydroxyapatite concentrate (MCHC), which are the

most absorbable forms for RYGB patients.7,12,16-30

Vitamin B12 Deficiency

Vitamin B12 deficiency can also occur after RYGB. Hydrochloric acid

and pepsin released in the lower stomach are required to separate

B12 from protein sources in food. After separation occurs, the B12

attaches to binder proteins present in saliva and gastric juice.

Pancreatic enzymes from the upper small intestine are then secreted,

which release the B12 from the binder proteins. The B12 then binds

to intrinsic factor (produced in the lower portion of the stomach)

in the duodenum and is transported to the distal ileum of the small

intestine, where it is absorbed in the presence of

calcium.5,7,12,14,16,31-34

Following RYGB where the lower portion of the stomach is removed or

partitioned off, cells are lost that secrete both hydrochloric acid

and intrinsic factor. Additionally, the pancreatic enzymes that

release the B12 from binder proteins are lost as the upper portion

of the small intestine is bypassed, and absorption that occurs in

the distal ileum is also impaired, as this portion of the small

intestine may be bypassed. To worsen matters, B12 absorption in the

distal ileum is dependent upon the presence of calcium, which is

another common deficiency after RYGB, and folic acid deficiency

(which can also occur after RYGB) may impair B12 absorption as well.

Pharmacists serve the important role of ensuring proper B12

prophylactic supplementation with sublingual or intranasal

preparations that will be released directly into the bloodstream for

absorption, thus avoiding the problematic loss of digestive juices

and intrinsic factor. Parenteral monthly injections are also an

option for patients, although usually reserved for diagnosed

deficiency.5,7,12,14,16,31-34

Protein Malnourishment

Protein malnourishment can be a common risk in the first 12 months

following RYGB as well, as the amount of calories patients are able

to consume is extremely diminished given the small pouch size. In

addition, animal proteins may be more difficult for bypass patients

to digest and absorb, as the bulk of digestion (following breakdown

in the stomach) occurs in the small intestine. This occurs when

pancreatic enzymes are released into the small intestines, which

break the protein down into absorbable peptides and amino acids.

Following the surgery, the 1-ounce pouch may have difficulty

churning/digesting animal proteins adequately, given its small size,

and when a portion of the small intestine is bypassed, the digestive

process is also consequently reduced. Thus, it is important to

ensure adequate protein intake from easily absorbable and complete

(high quality) protein sources, such as whey or egg albumen/egg

whites.5,7,12-15,35

Supplements such as whey are complete protein sources that provide

all the essential amino acids needed in the diet and are easier for

bypass patients to efficiently break down in the months immediately

after surgery when their protein intake is the most impaired. The

highest quality whey proteins on the market are whey protein

isolate, ion exchange whey protein, whey hydrolysate, or whey

peptides. These contain very high levels of branched chain amino

acids (leucine, valine, isoleucine), which can prevent muscle

catabolism or wasting that can occur with protein malnourishment.

These supplements also have a high Net Protein Utilization (NPU), a

high Protein Efficiency Ratio (PER), and a high Biological Value

(BV), which indicate that they are utilized very efficiently by the

body. The maximum amount of protein that can be absorbed by the

average person per meal is 30 g, which most of these provide in one

to two 4-ounce servings. All of these characteristics can be found

by examining the supplement's product label.5,7,12-15,35

It is important to note that many RYGB patients may need protein

supplementation for life to ensure proper intake, but after one year

postsurgery some may be able to take in adequate amounts of protein

through their diets (approximately 0.8­1 g of protein per kg body

weight, or a minimum of 60 g daily), after their pouches are fully

healed, and these liquid supplements will no longer be necessary. It

is also important to remember to check the supplement label for

sugar content, to ensure it contains less than 16 g of sugar per

serving, in order to prevent dumping syndrome.5,7,12-15,35

Iron Deficiency

The major site of absorption for iron is in the first part of the

small intestine, the duodenum. This portion of the intestine is

bypassed following RYGB, and thus iron deficiency (and possibly

anemia) is a possible result. As a consequence of the surgery, food

has a lack of contact time with gastric acid, which results in a

reduced conversion of dietary iron from the insoluble ferric form to

the more soluble ferrous form. The different iron salt formulations

available for supplementation provide varying amounts of elemental

iron, varying extents of absorption, and variable side effects.

Ferrous sulfate is less effectively absorbed in RYGB patients as a

result of the lack of stomach acid present that is required for

absorption, and it has a higher degree of GI complaints than other

salt forms. Polysaccharide iron, carbonyl iron, ferrous fumarate,

and ferrous gluconate are more absorbable forms of iron for RYGB

patients, and some studies suggest that taking vitamin C with the

iron supplement will enhance absorption after

surgery.5,7,12,13,16,32,33,36

PREVENTING MEDICATION MISADVENTURES

Another important role that pharmacists have in providing care to

bariatric patients is to monitor medication profiles for

appropriateness of therapy. For example, metformin should be avoided

in patients who have B12 deficiency, due to the drug's ability to

cause the deficiency itself, and many bariatric surgeons recommend

that NSAIDs be avoided permanently following bypass surgery,7,13,25

due to the enhanced risk of GI bleeding, given the small surface

area of the new pouch. Enteric-coated preparations are also a

concern as they may have altered absorption, given the extent of

intestinal bypass. The solubility of all drugs in general must be

considered, given the achlorhydric nature of the RYGB patient's new

anatomy.25 There are also special considerations when administering

total parenteral nutrition (TPN) to bariatric patients. Pharmacists

should be on alert for refeeding syndrome in bariatric patients.

Refeeding syndrome is a nutritional complication that can occur in

obese patients experiencing massive weight loss during the post-

operative period when they are severely malnourished. The syndrome

is primarily associated with hypophosphatemia, as well as drops in

serum potassium, magnesium, calcium, and less commonly, cardiac

dysfunction and fluid retention as well. The mechanism of these

electrolyte abnormalities is thought to be related to the acute

administration of macronutrients (primarily dextrose) that promote

anabolism (muscle building) in a state of overall depleted

electrolyte body stores (due to post-operative malnourishment).

Cardiac dysfunction is thought to be related to an acute volume

expansion that increases cardiac demand. Lipid and dextrose

concentratons for post-op bariatric patients should be dosed lower

than the amount needed to maintain their current weight, while

protein, on the other hand, should be dosed at 1­2 g per kg adjusted

body weight in order to avoid muscle catabolism.12

Additionally, as pregnancy is not recommended in the first 18 months

following the surgery, pharmacists have a role in ensuring that

bypass patients are utilizing appropriate contraceptive methods.

This is particularly important, as fertility may improve in obese

patients who lose weight, and there have been case reports of

malabsorption of oral contraceptives. This may require some patients

to convert to other means of contraception (barrier methods,

transdermal patches).6-8,13,37

Considering all of the above concerns and the growing number of

bariatric surgeries being performed, the role of pharmacists as part

of a multidisciplinary team to provide bariatric patients with

appropriate medical care is vital and will continue to grow in the

future.

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Vol. No: 30:02 Posted: 2/22/05