Complications of Bariatric Surgery: Dumping Syndrome and Drug Disposition

As more insurance plans cover bariatric surgery, pharmacists need to understand its potential complications and some unique concerns about medications after the surgery.

Weight loss has become a national pastime and a $20 billion industry. On any given day, 100 million Americans are dieting. Television viewers are inundated with commercial announcements for weight loss products and programs, usually promoted by a celebrity. ABC News recently called the weight loss industry “The Big Fat Trap,” and reported that celebrities who are paid to lose weight in the public eye earn, on average, $33,000 per pound lost. They also report that bariatric surgery, the intervention most likely to result in predictable and sustained weight loss, costs patients between $11,500 and $26,000.¹ Each year, nearly 144,000 obese Americans^2,3 choose bariatric surgery when diets fail, despite the fact that this surgery often involves postsurgical complications. As more insurance plans cover bariatric surgery, pharmacists need to understand it, its potential complications, and some unique concerns about medication following the surgery.

Bariatric surgery comprises a number of different surgeries. The surgeries may be restrictive (by decreasing stomach size) and/or malabsorptive (by affecting the ileum). Vertical banded gastroplasty (called stomach stapling by the lay population) creates a small stomach pouch with an outlet along the lesser curvature of the stomach, and is restrictive only. Vertical banded gastroplasty has largely been replaced by laparoscopic banded gastroplasty, which does not reduce stomach size, but restricts the stomach opening. Gastric sleeve surgery severely reduces stomach size. Roux-en-Y gastric bypass (RYGB) partitions the stomach into a functional restrictive 20-mL stomach pouch with an outlet to an anastomosed loop of small intestine. Its malabsorptive feature—the bypassed section of small intestine—causes weight loss by circumventing the area of the gut that absorbs many calories. Biliopancreatic diversion augments gastric restriction with intestinal bypass with additional anatomic rearrangement to limit nutrient exposure in the distal ileum, effectively creating malabsorption.^4,5

Dumping Syndrome

Dumping syndrome is a side effect of malabsorptive bariatric procedures such as RYGB and biliopancreatic diversion. Its procholinergic symptoms (Table 1^5-8) follow the rapid passage of undigested carbohydrates from the stomach into the jejunum. Symptoms are also emotionally distressing, causing anxiety and apprehension. Approximately 40% of people who undergo bariatric surgery develop dumping syndrome, and most studies report that it does not increase or decrease weight loss.⁶

Many patients who develop dumping syndrome are nonadherent to recommended postsurgical diets. Clinicians often explain dumping syndrome’s symptoms to motivate patients to avoid unacceptable foods, but the specter of bad symptoms usually has minimal influence on patients’ food choices.^6,7 The symptoms are self-limited and usually subside 1 to 2 hours after the consumption of sweet foods or foods high in simple carbohydrates. Dumping syndrome often resolves over time, but for 12% of patients, it continues for more than 2 years after surgery.⁹

Dumping syndrome can also occur in patients who have not had bariatric surgery. People with diabetes, vagotomy, pancreatic exocrine insufficiency, duodenal ulcer, Zollinger-Ellison syndrome or extensive upper gastrointestinal repair sometimes develop dumping syndrome. ^5,10,11

Dumping syndrome occurs as 2 distinct types, and patients can have 1 or both:

Early dumping begins during or immediately following a meal. Patients report nausea, vomiting, bloating, cramping, diarrhea, dizziness, and fatigue. Its etiology is osmotically driven fluid shifts from the blood to the lumen. Early dumping is characterized by hemoconcentration that causes cardiovascular effects.^10,12

Late dumping occurs 1 to 3 hours after a meal. Patients experience hypoglycemia, weakness, sweating, and dizziness. Late dumping’s etiology is rebound hypoglycemia after surging insulin overcompensates for the glucose load delivered to the portal circulation, and the blood glucose level falls preciptiously.^10,12

Both types of dumping syndrome alter levels of peptides and vasoactive substances, including neurotensin, vasoactive intestinal peptide, catecholamines, serotonin, and substance P.13 Early dumping syndrome is more common than late dumping syndrome.¹¹

Bariatric surgeons diagnose dumping syndrome based on the patient’s report of symptoms and observation of the patient after a carbohydrate-rich meal. Additionally, surgeons record postprandial serial pulse rate and hematocrit to screen for cardiovascular effects, and perform prolonged postprandial glucose testing to confirm reactive hypoglycemia. Scintigraphic (radioactive tracing) gastric emptying tests are also helpful, especially if the condition is related to a nonsurgical problem (eg, diabetes mellitus). ¹⁰

Finding Relief

Clinicians treat dumping syndrome through dietary alterations by encouraging patients to reduce simple carbohydrate intake. Patients must avoid forbidden foods and change their eating behaviors (patients should cut food into small pieces, chew thoroughly, eat slowly, and wait 1 hour after a meal before drinking beverages).^7,8

Patients whose symptoms persist often respond to octreotide 25 to 100 mcg subcutaneously 30 minutes before meals or long-acting depot injections of octreotide 10 to 20 mg/month. This somatostatin analogue slows gastric emptying, delays small bowel transit, and inhibits vasoactive peptide release.^13,14

For late dumping syndrome, administering acarbose 25 mg before breakfast, lunch, and dinner often alleviates rebound hypoglycemia. Acarbose inhibits carbohydrate absorption in the small intestine, prevents postprandial hyperinsulinemia, and reduces insulin concentrations. Acarbose alleviates postprandial hypotension and tachycardia by slowing the gastric empting rate and subsequently delivering high-osmolality nutrients to the duodenum in a more measured way.^14,15

Drug Disposition

Currently, there is some uncertainty about bariatric surgery’s influence on specific drug pharmacokinetics.¹⁶ Malabsorptive surgery affects nutrient absorption and orally administered medications (Online Table 2^17-21). Oral bioavailability depends on a combination of drug parameters (eg, solubility, permeability, gastrointestinal metabolism). The surgical procedure employed also influences bioavailability, especially if the stomach is bypassed.

Table 2: Considerations for Oral Dosing after Bariatric Surgery

· Procedures that truncate the stomach reduce gastric mixing, which is important in the disintegration process of oral forms of medication.

· RYGB increases the stomach’s pH and may decrease solubility of weakly acidic drugs.

· RYGB surgery reduces drug (and food)/biliopancreatic secretion mixing; therefore, drugs that depend on bile salts to enhance their solubility (eg, cyclosporine, phenytoin, levothyroxine, tacrolimus) may be compromised after RYGB.

· RYGB bypasses the duodenum and the proximal jejunum and may shorten passage time through the intestine. Drugs with poor water solubility and extended-release formulations may have inadequate transit time for dissolution and absorption.

· Studies have documented decreased bioavailability for several drugs after RYGB surgery (eg, amoxicillin, azithromycin, cyclosporine A, levothyroxine, nitrofurantoin, mycophenolic acid, phenytoin, phenobarbital sirolimus, tacrolimus, tamoxifen).

· Procedures that reduce the stomach size may increase mucosal toxicity of nonsteroidal anti-inflammatory drugs, salicylates, oral bisphosphonates, and oral iron tablet formulations.

· Any procedure that causes dumping increases gut transit time and may decease drug absorption.

RYGB = Roux-en-Y gastric bypass.

Adapted from references 17- 21.

Endnote

Patients may report seeing oral medications in their stool. If problems with drug absorption arise, switching to a liquid formulation sometimes helps. Intranasal, transdermal, rectal, and subcutaneous dosage forms are other alternatives. As patients lose weight, changes in lean body mass may result in a need for lower drug doses. After patients have bariatric surgery, pharmacists should monitor their drug therapy carefully.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy.

References:

• 100 million dieters, $20 billion: the weight-loss industry by the numbers. ABC News website. http://abcnews.go.com/Health/100-million-dieters-20-billion-weight-loss-industry/story?id=16297197. Accessed May 17, 2014.
• Bariatric surgery statistics. American Society for Bariatric Surgery website. www.bariatric-surgery.info/statistics.htm. Accessed May 18, 2014.
• Livingston EH. The incidence of bariatric surgery has plateaued in the US. Am J Surg. 2010;200:378-385.
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• Mine S, Sano T, Tsutsumi K, et al. Large-scale investigation into dumping syndrome after gastrectomy for gastric cancer. J Am Coll Surg. 2010;211:628-636.
• Papamargaritis D, Koukoulis G, Sioka E, et al. Dumping symptoms and incidence of hypoglycaemia after provocation test at 6 and 12 months after laparoscopic sleeve gastrectomy. Obes Surg. 2012;22:1600-1606.
• Geer RJ, Richards WO, O’Dorisio TM, et al. Efficacy of octreotide in the treatment of severe postgastrectomy dumping syndrome. Ann Surg. 1990;212:678-687.
• Sato D, Morino K, Ohashi N, et al. Octreotide improves early dumping syndrome potentially through incretins: a case report. Endocr J. 2013;60:847-853.
• Buscemi S, Mattina A, Genova G, Genova P, Nardi E, Costanzo M. Seven-day subcutaneous continuous glucose monitoring demonstrates that treatment with acarbose attenuates late dumping syndrome in a woman with gastrectomy for gastric cancer. Diabetes Res Clin Pract. 2013;99:e1-e2.
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