Serotonin Syndrome vs. Seizures in obese patients

This clinical review feature article is presented in conjunction with the Department of Emergency Medicine Education at the University of Texas Southwestern Medical Center, Dallas.

Learning Objectives

• Identify obesity-related health problems and discuss their impact on the health and well-being of obese individuals.
• Identify the two clinical approaches to weight loss.
• Identify actions, precautions and side effects of adrenergic, serotonergic and alternative weight loss medications.
• Identify and differentiate three classifications of bariatric surgery and the common complications of each.
• Describe and explain various components of a bariatric response plan.

Key Terms
Adrenergic: Pertaining to the fibers of the sympathetic nervous system that use epinephrine (adrenalin) as a neurotransmitter.

Anastomosis: Surgical joining of two vessels, ducts or bowel segments.

Benzodiazepines: A class of psychotropic drugs used for sedation, anxiety, seizures, muscle spasm and amnesia, and which includes Valium.

Cardiac sphincter: The muscular fibers at the junction of the lower esophagus and stomach that prevent backward movement of food from the stomach into the esophagus.

Deep vein thrombosis: A thrombus (blood clot) in one of the deep veins of the body.

Ephedrine: A stimulant drug used to suppress appetite and enhance weight loss and concentration.

Fentanyl (sublimaze): A synthetic narcotic used to control moderate to severe pain.

Gastroesophageal reflux: A condition in which food travels backward from the stomach to the esophagus, causing irritation of the esophagus.

Innervated: A state in which a body part has been supplied with nerves or nervous stimuli.

Laparoscopic surgery: A minimally invasive surgical procedure performed with only small incisions.

Leptin: A protein hormone that regulates energy intake and usage, including appetite and metabolism.

Methamphetamine: A drug class that stimulates the central nervous system.

Obesogenic: An environment and its components that contribute to obesity.

Phentermine: A stimulant medication used for weight loss that mimics the actions of the sympathetic nervous system.

Pulmonary hypertension: Abnormally high pressure in pulmonary circulation.

Roux-en-Y gastric bypass (RYGB): An invasive procedure used for morbid obesity that decreases stomach size through creation of a pouch. This procedure also separates the small intestine into two arms, rerouting the jejunum to the stomach and the duodenum to the distal ileum.

Stomal stenosis: An abnormal constriction or narrowing of an opening or passageway (stoma).

Thermogenesis: Production of heat, especially at the cellular level.

Ventricular gallop: In adults, an extra heart sound (S3) that indicates the presence of myocardial failure.

The dispatch report was for a "woman passed out." Everyone on the rescue squad knew the address. It was Dorothy, a 38-year-old bariatric patient who weighed about 300 pounds and had a history of deep vein thrombosis.

On scene, Dorothy’s roommate explained that Dorothy was post-op from a Roux-en-Y gastric bypass (RYGB). When asked what happened, the roommate said Dorothy was having a small bowl of chocolate ice cream to celebrate coming home. After Dorothy started to have severe abdominal cramping and suddenly passed out, her roommate called 9-1-1.

As the crew proceeded into the bedroom, they could hear the arrival of the engine company, whose help would be needed if the crew were to safely care for the patient. After ensuring the patient’s airway and breathing were adequate, the EMT obtained a blood sugar reading, which was low. Although Dorothy was awake and able to maintain her airway independently, the paramedic knew that oral glucose might not be the best choice and elected to immediately administer IV glucose. With assistance, Dorothy was able to walk to the stretcher in the living room, and she agreed to be taken to the hospital. Talking to the emergency department attending later, the EMT and paramedic found out that Dorothy was sent to a dietician for education about how to live with her gastric bypass.

Obesity & Complications
It has been estimated that one-third of Americans are obese, and some of those people are morbidly obese, or greater than 100 pounds over their healthy body weight. Although such people are at increased risk for complications related to obesity, many don’t see themselves as being at risk for obesity-related health conditions. In one survey by Shape Up America, a nonprofit organization founded by former Surgeon General C. Everett Koop, MD, seven out of 10 overweight Americans didn’t consider themselves unhealthy or think their weight posed a risk to their health. Further, Malcolm K. Robinson, MD, of Harvard Medical School, suggests that not only will obesity impact the health and well-being of the patient but the patient may also expect to lose up to 20 years of life expectancy.

Although health problems associated with obesity are numerous (see Table 1, p. 44), some people take action to reduce their weight and address these conditions using a variety of methods. If successful, some patients can look forward to a reversal of many of these illnesses and a return to good health. But these weight-loss interventions aren’t without risk, too.

Adrenergic Agents & Side Effects
At its core, obesity is an imbalance between food intake and energy expenditure. Weight loss measures must be taken to correct this. The clinical approaches to weight loss fall into two categories: medical or surgical. It’s important for EMS providers to understand these bariatric therapies and the problems they can cause.

The earliest medical approaches focused on increasing energy expenditure. Adipose tissue, or fat, is a form of energy storage for the body. Lipids within fat are released for energy when needed, in part by the sympathetic nervous system.

Adipose tissue is highly innervated with sympathetic nerves for adrenergic stimulation. Epinephrine (aka, adrenaline) attaches to beta 3 sympathetic receptors in fat and activates lipolysis, the division of fat into fatty acids, fatty acids being used for energy.

Stimulation of beta 3 adrenergic receptors is usually responsible for thermogenesis, an example of which would be heat production from shivering. Bariatric medications seek to stimulate these beta 3 adrenergic receptors to raise the resting metabolic rate and thereby adjust the ratio of intake versus expenditure to create a caloric deficit and ultimately weight loss.

Used since the 1930s, amphetamines are the earliest examples of these stimulants or adrenergic medications for weight loss, but they were frequently abused. Newer agents, such as phentermine, first approved by the FDA as a diet suppression medication in 1959, have less abuse potential and cause less severe central nervous stimulation.

However, this class of drugs is not without risks. As an adrenergic stimulant, these "diet pills" can lead to hypertension, palpitations and tachydysrhythmias. The effect is even more pronounced if the patient is concurrently being treated for depression and has been prescribed a monoamine oxidase inhibitor (MAOI) class antidepressant. Most medical authorities recommend a two-week "wash-out" period between the end of MAOI use and the start of the adrenergic agent. Without that wash-out period, the combination of MAOIs and adrenergic stimulants can lead to potentially life-threatening hypertensive crises and strokes. Similarly, using such illicit drugs as cocaine or methamphetamine in tandem with these adrenergic stimulants can lead to hypertensive crisis.

Because diet pills have potential for abuse, the FDA has classified these medications as controlled substances under the Controlled Substances Act. Table 2 (p. 46) lists some of the drugs in the adrenergic classification by generic name, trade name and schedule.

Another major side effect attributed to this class of bariatric medications is primary pulmonary hypertension. Pulmonary hypertension’s effect on the bariatric patient is twofold. First, pulmonary hypertension decreases the heart’s ability to increase cardiac output, especially during times of exertion, leading to shortness of breath and fatigue. Second, pulmonary hypertension will eventually cause the right ventricle to fail, a condition called cor pulmonale . Coupled with left-sided heart failure secondary to increased systemic vascular resistance caused by obesity, the patient will go into complete heart failure.

Compounding these complications is the fact that many bariatric patients are also diabetic. Adrenergic stimulants may decrease the patient’s insulin need. Without an adjustment of their insulin dose, a patient may inadvertently overdose on insulin, leading to hypoglycemia.

For a variety of reasons, increasing numbers of patients are turning to alternative or complementary medicine for weight loss. Such weight loss supplements include chromium picolinate, ma huang and white willow bark. These substances are thought to be adrenergic—similar to ephedrine or caffeine. When combined with drugs from the adrenergic class of bariatric medications, these substances pose a great risk for hypertension-related medical emergencies.

Selective Serotonin Reuptake Inhibitors
The other class of bariatric medications seeing greater use is serotonergic agents. Like the adrenergic agent epinephrine, serotonin is a central nervous system (CNS) neurotransmitter that impacts mood and appetite. Originally used as antidepressants, serotonin agents are also prescribed as an appetite suppressant, impacting the intake side of the energy imbalance. They work by either increasing the amount of serotonin available or by inhibiting the reuptake and destruction of serotonin in the distal neuron.

This latter action forms the basis for the effect of selective serotonin reuptake inhibitors (SSRI). SSRI medications allow serotonin to remain in the synapse longer, thereby continuing to stimulate the nerves. Examples include fluoxetine (Prozac) and sibutramine (Merida).

Both Prozac and Merida can cause dizziness, nausea, insomnia and significant increases in blood pressure. The latter is cause for concern. Most physicians won’t prescribe these medications if the patient has a history of coronary artery disease (CAD) or congestive heart failure (CHF). Unfortunately, in many cases, one of the long-term outcomes of obesity is CHF and many of the signs of CHF (such as ventricular gallop, peripheral edema, rales or crackles in the base of the lungs, are obscured in the obese patient).

Serotonin syndrome is a potentially life-threatening side effect of SSRI; it occurs when excessive amounts of serotonin build up in the CNS. This stimulation of the CNS also leads to increased adrenergic activity and is causes the signs associated with serotonin syndrome, which include fever (without infection), clonus (shivering without cold), agitation, tremors and sweating. Serotonin syndrome may result from normal therapeutic levels of SSRI and interactions with MAOIs, tricyclic antidepressants, fentanyl, phentermine, methamphetamine and cocaine. These medications combine synergistically with SSRI to cause serotonin syndrome.

Untreated serotonin syndrome can lead to seizures, hypotension and dysrhythmia. Prehospital care is largely supportive. Benzodiazepines are used to control tremors and clonus.

Bariatric Surgery
Bariatric surgery has become an increasingly popular method of permanent weight reduction, especially with the advent of laparoscopic surgery. It’s estimated that more than 140,000 patients had bariatric surgery in 2004 and that greater than 50% of those surgeries were laparoscopic.

Although the mortality associated with this type of surgery is low (0.1% to 2% depending on the procedure), the complications usually necessitate EMS.

There are three classifications of bariatric surgery: restrictive, malabsorptive and combination. All three bariatric surgeries are intended to block the patient’s intake of excess calories, impacting the energy formula on the intake side.

Restrictive bariatric surgery procedures include gastric banding and gastroplasty. The FDA approved gastric banding, also known as lap banding, in 2001. Lap banding is a minimally invasive laparoscopic procedure that places an inflatable ring at the neck of the stomach near the fundus and proximal to the cardiac sphincter. This inflatable ring creates a small pouch and limits the amount of food the patient can eat.

The alternative to gastric banding is vertical banded gastroplasty (VBG), aka, stomach stapling. Like lap banding, gastric banding creates a small pouch but the procedure also includes a double row of staples that isolates the majority of the stomach from the pouch.

Gastric bypass is an example of a malabsorptive procedure. These procedures involve bypassing the stomach entirely and even removing as much as two-thirds of the stomach. Because of a number of nutritional complications, this procedure is discouraged in favor the RYGB combination procedure.

RYGB may be the most common bariatric surgery in the U.S., but it’s quickly being eclipsed by gastric banding (laparoscopic RYGB trials are being conducted). In such a procedure, the bariatric surgeon creates a one-ounce pouch at the stomach’s inlet and then detaches the small intestine at the jejunum and attaches it to the stomach at the pouch. The remaining arm of the duodenum is also attached to the distal ileum, creating a Y-shaped circuit.

RYGB has a proven record of sustained weight loss but is not without complications. Obvious complications include those common to all abdominal surgeries, including dehiscence (a spontaneous opening at the wound with or without evisceration) and hernia.

Other adverse effects include surgical complications at the site of the connections, or anastomosis. Some 20% of RYGB patients experience leakage of stomach contents into the abdominal cavity as a result of force from overeating at the staple line. These spilled stomach contents can lead to peritonitis. The symptom pattern associated with peritonitis includes dyspnea, tachycardia, abdominal pain and general restlessness.

Approximately 20% of patients who undergo RYGB may experience stomal stenosis, a narrowing of the stomach inlet that results in post-prandial epigastric pain, not dissimilar to the pain felt with gastroesophageal reflux after eating. A key sign of stomal stenosis is regurgitation of undigested food.

Dumping Syndrome
Gastric dumping syndrome is a form of rapid gastric emptying that occurs when a concentrated carbohydrate, such as sugar, enters the digestive tract. The higher osmolarity of the carbohydrates in the small intestines causes fluid shifts in the intestine. These fluid shifts are often accompanied by pain and nausea, and patients experiencing them often complain of feeling bloated or experience diarrhea.

The sugar spike also results in hyperglycemia and a subsequent rise in circulating insulin. As the fluid rapidly passes through the digestive system, the patient becomes hypoglycemic. The symptom pattern associated with hypoglycemia includes lightheadedness, weakness and even syncope. The EMS provider must be alert to the possibility of hypoglycemia induced by dumping syndrome even if the patient has just finished eating.

Treatment, Transport & Sensitivity
There’s a stigma surrounding obesity. In studies, even overweight people reported feeling obesity was unattractive. This "weight bias" can translate into subtle and sometimes not so subtle behaviors that patients can detect.

A greater sensitivity toward obesity comes from understanding that it has a complex etiology. Some believe that obesity is biological, a problem created by protein receptors in the lateral hypothalamus. Others believe that the cause of obesity may be genetic and point to research on the leptin gene. Still others believe that Americans live in an "obesogenic society where increased portions, sedentary lifestyles and unhealthy food lead to obesity.

Regardless of the etiology of obesity, the problem isn’t going to be solved in the field. Perhaps more importantly, if the patient has a negative experience with an EMS provider, they may be less inclined to seek help from other health-care providers. The EMS provider would be well served by maintaining a professional demeanor and acknowledging the difficulty of the patient’s situation.

In EMS terms, a patient is obese when they exceed the load-carrying capacity of the equipment or crew. In those cases, special resources should be brought to the scene.

Special response to bariatric patients should be thought of as a risk-control strategy. By utilizing specialized protocols and procedures, the responding department or agency can decrease their worker’s compensation claims and retain workers longer.

Some crews use specialized lift teams, which combine special tools, such as pneumatic lift devices, and training to move large patients with a minimum of effort. Some agencies have outfitted specialized bariatric ambulances. These agencies may stock large-body stretchers that can carry patients who weigh up to 700 pounds and have extra handholds that permit multiple EMS providers a grip point to help with lifting. These ambulances may also come equipped with ramps and winches to pull the patient into the ambulance.

Conclusion
EMS providers are duty-bound to act when called to the scene of a bariatric patient and may have other duties to that patient that dictated by the Americans with Disabilities Act. Therefore, every EMS system should have a bariatric response plan in place.

But more importantly, EMS providers should see bariatric patients not as a burden, but as another special population of patients deserving of our care and compassion. JEMS

Richard Beebe, MS, RN, NREMT-P, is the paramedic program director for Bassett Healthcare’s Center for Rural Emergency Medical Services Education, clinical assistant professor at the State University of New York at Cobleskill and a practicing paramedic in the town of Guilderland, N.Y. He has been an EMT since 1974 and an EMS educator since 1987. Mr. Beebe is the also the co-author of Fundamentals of Basic Emergency Care (third edition) and the Professional Paramedic Series.

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