CE Article: Nausea and Vomiting

      You are called for a 15-year-old boy who suddenly developed nausea and vomiting (N&V) after school. He feels better after vomiting, has normal vital signs, and his parents tell you they think it's just the stomach flu like his sister had a few weeks ago. Your partner tells you that you have another 9-1-1 call pending, so you suggest the parents have him checked if he is not better in a day and tell the engine crew to get the "AMA" form signed. Your next shift, you learn the child had surgery to remove a testicle after it infarcted.

   There are myriad causes for nausea and vomiting, some of which are benign and some deadly. EMS providers and patients often think of it as the "flu." While this is a possibility, it is our job to sort out the benign from the deadly and make sound management choices. This article will review recognition and management of illnesses with vomiting as a common chief complaint.

PATHOPHYSIOLOGY

   Few things in medicine elicit a visceral response as powerful as vomiting. The normal genesis for vomiting is complex (see Figure 1). Outside the brain, signals arise from afferent receptors (vagus and sympathetic nerves) in the gastrointestinal (GI) tract. These can be from direct irritation (infectious agents or choking) or distention (GI obstruction). Signals can also arise from non-GI sources. This is why patients with heart attacks, kidney stones and testicular torsion can vomit. Inside the brain is a chemoreceptor zone within the fourth ventricle. This region senses chemical imbalances such as hypoxia, nausea-inducing medications, toxins (e.g., ipecac, opiates and chemotherapy agents) and acidotic states. Finally, other areas of the brain, such as the cerebellum, via the vestibular system or the cortex itself, as in a stroke, may trigger nausea and vomiting.

   The vomiting center within the medulla acts as the incident commander for vomiting.¹ This area processes incoming stimuli from vomiting triggers outside and inside the brain. It is also thought to be the area where nausea is controlled. It then sends out signals to the vagus nerve (to the esophagus, stomach and duodenum), the phrenic nerve (to the diaphragm) and spinal nerves (to the intercostals and abdominal rectus).² These signals begin a series of coordinated events that lead to the coordinated and complex act of vomiting. See Figure 1.

MEDICATION CAUSES

   You are dispatched for a 78-year-old female whose chief complaint is N&V. She has crampy, diffuse abdominal pain and thinks it's the casino food she ate last night. She denies chest pain, dyspnea, fever or headache. She was recently started on Bactrim for a bladder infection. Her other medications include Cardizem, digoxin, simvastatin, calcium and Synthroid. The ED staff informs you later her digoxin level was elevated from an interaction with the Bactrim, and that's what triggered her vomiting.

   Numerous medications cause nausea and vomiting. The classic offenders are antibiotics, opiate analgesics (morphine, oxycodone, hydrocodone and codeine) and chemotherapy agents (see Table I). Other medications that can cause vomiting include oral contraceptives, antiretroviral/antiseizure prophylaxis, digoxin, metformin and lithium. It is important to review the patient's medications, especially any new ones or changes in dosing.

ABDOMINAL CAUSES

   A 42-year-old female calls 911 because of vomiting. It started yesterday, and now she has a fever and chills. As you elicit a "PQRST," she admits to having some colicky right upper quadrant pain, and had a similar episode last year that she was not evaluated for. She has orthostatic dizziness without syncope. She denies any past medical problems, alcohol use, chest pain, dyspnea or diarrhea. Her heart rate is 104, blood pressure 116/78, respiratory rate 28 and temperature 101°F. You start an IV, administer 50 micrograms of fentanyl and 4 milligrams of ondansetron (Zofran) and give her a liter of normal saline.

   The emergency department physician thanks you for your care and drawing blood, and invites you to watch as she performs a bedside ultrasound, which shows gallbladder distention and wall thickening with stones. This is typical for acute cholecystitis. It is removed laparoscopically the next day.

   The gastrointestinal system is a very common source of nausea and vomiting. Gallbladder disease is a classic example. Pancreatitis, most often from alcohol, gallstones or, rarely, certain drugs, is another entity that can cause N&V. Patients will often complain of a constant epigastric pain that radiates to the back. Do not be fooled by the patient's numerical rating of the pain, as their perceived severity does not correlate with severity of the disease. These patients are sicker than they look, and mortality rates can be as high as 5%-10%. Death is caused by hypovolemic shock from bleeding and third-spacing, and from renal and pulmonary complications.³

   "Classic" appendicitis presents with periumbilical abdominal pain that migrates to the right lower quadrant, anorexia (lack of hunger), fever and N&V. Appendicitis is difficult to detect in the early stages, but never assume someone with vague abdominal pain, N&V and abdominal tenderness (especially in the right lower quadrant) is just suffering from the "stomach flu." Patients with prior abdominal surgeries can develop adhesions that predispose them to obstructions. Small bowel obstruction presents with intermittent, colicky abdominal pain, N&V, lack of bowel movements, and typically a history of prior abdominal surgeries. While some consider it an unglamorous nursing home call, patients may die from incarceration and subsequent strangulation of the bowel, causing ischemia and perforation.

INFECTIONS AND ENDOCRINE CAUSES

   A 32-year-old female's chief complaint is N&V. She reports mild, diffuse abdominal pain only with emesis. She also has a productive cough, dyspnea and fever. She denies headache, diarrhea or difficulty urinating. The past medical history includes insulin-dependent diabetes, kidney stones and fibromyalgia. On exam, she looks ill: Her vital signs are heart rate 124, blood pressure 116/78, respiratory rate 36, temperature 101.5°F and pulse oximetry of 88% on room air. She has crackles in her right lung base. Her belly is soft, but mildly tender in all quadrants.

   Your partner asks what you think is going on. You suggest that, given her fever, cough and dyspnea, she may well have pneumonia, but, more important, infections are a common trigger for diabetic ketoacidosis (DKA). You reassure him it's not just the "flu." Her blood sugar reads high, and you draw blood tubes, administer Zofran and a liter saline bolus.

   Infectious and endocrine emergencies are another common source of N&V. Pneumonia classically presents with fever, cough and dyspnea with or without N&V. Pyelonephritis (kidney infection) presents with constant flank pain, fevers and N&V. Meningitis is caused by a variety of pathogens and presents with varying amounts of headache, neck pain, altered mental status, fever, rash and N&V. EMS providers are most likely to see outbreaks among people living in close quarters, such as military personnel, college students and some immigrant populations.

   Abdominal infections are another source of N&V. There are a host of viral, bacterial and parasitic infections that can cause N&V. Patients will also typically have some degree of fever, crampy abdominal pain and diarrhea. There is often a history of other close contacts with the same illness. Patients like to believe it was the last food they ate; however, incubation times for various pathogens vary.

   DKA is commonly triggered by infectious diseases such as pneumonia, kidney infections, intra-abdominal infections and meningitis. These same infections in and of themselves can present with N&V. Diabetics may also have acute coronary syndromes or a lack of insulin as triggers for DKA. Alcoholic ketoacidosis is a similar problem with heavy drinkers, except here there is not an excess of glucose but there is a metabolic acidosis. Lastly, one should always remember that pregnancy-related hormones can induce N&V.

CENTRAL NERVOUS SYSTEM CAUSES

   A 78-year-old male says he started vomiting about 2 hours ago and complains of everything spinning (vertigo). On further questioning, he complains of an occipital headache and has trouble walking. His blood pressure is elevated, but the rest of his vitals are normal. Past medical history includes hypertension, smoking and high cholesterol. You tell your partner that the patient probably has an inner ear problem and ask him to draw up the Phenergan while you start a line. He tells you that he's seen this before and thinks it is a cerebellar infarct. You give silent thanks for an experienced partner, and together you quickly load the patient and notify the ED of your suspicions.

   The CNS is responsible for many causes of N&V. Cerebellar infarcts are rare, but half of them include N&V.⁴ You are actually more likely to see N&V with hemorrhagic stroke than with the most common form of ischemic stroke. Patients who suffer from migraine headaches frequently have N&V, although the exact number who call 9-1-1 is likely low. The head trauma patient may have N&V, although this is usually not the chief complaint and can be gleaned from the circumstances surrounding the call, e.g., a patient in a rollover motor vehicle crash. Alcoholics are a high-risk group in which you should consider the possibility of occult trauma (for example, subdural hematomas) if they present with headache and N&V. The combination of clotting problems and repetitive falls and concussions predisposes them to subdural bleeding with or without N&V.

ENVIRONMENTAL AND TOXICOLOGICAL CAUSES

   A husband and wife both began vomiting about 2 hours after preparing dinner with mushrooms they had gathered in the woods. You begin to wonder if it is simple food poisoning, until your learned partner tells you about Amanita poisoning. Amanita is found in the United States and is responsible for 90% of deaths from mushroom poisoning via liver toxins and liver failure. You later learn the mushrooms you brought in were identified as Chlorophyllum molybdites, the most commonly ingested toxic mushroom in the U.S.⁵ Luckily, these are not the hepatotoxic variety of Amanita your partner was worried about. Other common toxicological and environmental etiologies of N&V include acetaminophen (Tylenol), alcohol, salicylates (aspirin), isoniazid (INH), carbon monoxide poisoning, acute mountain sickness, theophylline, organophosphates/pesticides and toxic mushrooms.⁶

   Alcohol-related problems are such a common EMS call that they deserve special mention. Its abuse can predispose to CNS hemorrhage, as discussed above. Acute intoxication itself produces N&V. If N&V is coupled with epigastric abdominal pain, think of pancreatitis, which can lead to irritation of the gastric lining, producing N&V and serious gastrointestinal bleeding. The most feared complication is portal hypertension with accompanying esophageal varices.

   Lastly, no review of N&V would be complete without reiterating a common cause: ischemia. Acute coronary syndrome (ACS) is often accompanied by N&V; however, a recent large international review of 1,763 patients with proven myocardial infarction without chest pain found 24% presented with N&V.⁷ Unexplained N&V in patients at risk for acute coronary syndrome is cause for worry about ACS. Mesenteric ischemia, another underappreciated cause of N&V, involves reduced blood flow to the gut. These are typically older patients with longstanding hypertension, atrial fibrillation, diabetes and/or smoking, who present with diffuse, colicky, abdominal N&V, diarrhea and pain "out of proportion" to the exam. This is exactly the kind of patient you do not want to assume has "flu." Next-day follow-up with their doctor or taking a wait-and-see approach is inappropriate and dangerous.

MANAGEMENT

   Nowadays, fast symptomatic relief of N&V is relatively quick and simple. It not only makes the patient more comfortable, but makes the assessment and further treatment of the patient who was retching in your ambulance much easier. Patients also do not have to wait in a busy ED to be evaluated before they receive relief from their N&V. There is no disease process that will be missed because the ED providers did not actually witness an episode of vomiting.

   EMS providers will have varied options for treating N&V, depending on local protocols and approved medications in the local scope of practice. There are a variety of antiemetic medications commonly used in hospitals across the U.S. (see Table I). We will focus on four antiemetics that are commonly available and used by many EMS systems. A recent article in EMS Magazine provides an in-depth discussion.⁸ Having a good working knowledge of the medications in your formulary is important, as antiemetics do not all work the same and have different adverse reaction profiles (Table II).

   Acute extrapyramidal symptoms (EPS) are possible with most antiemetic medications, especially the phenothiazines (promethazine and prochlorperazine). The two most common acute examples of EPS are the dystonic reaction and akathisia. Dystonia manifests as involuntary, sustained muscle contractions, often in the head or neck region. Torticollosis is one example.

   Akathisia is underappreciated by most emergency medicine providers. Patients report having "restlessness and inner tension or discomfort, an urge to constantly move their legs, and difficulty in maintaining a posture for several minutes, such as sitting still in a chair or standing in one place. They display semi-purposeful or purposeless limb movements and tend to repeatedly shift their bodily position while sitting, and shift weight from foot to foot or pace while standing. In its milder presentation, the disorder may resemble anxiety."⁹ It is easily mistaken for anxiety or agitation. EMS systems that treat N&V should have protocols in place to treat EPS. Paramedics must familiarize themselves with the various symptoms of EPS and be ready to administer diphenhydramine or benzodiazepines.

OXYGEN

   Our first medication takes us back to the basics. There is research suggesting that supplemental oxygen reduces the incidence of nausea and/or vomiting during ambulance transport of patients with minor trauma.¹⁰ As we all know, nausea, motion sickness and vomiting increase the discomfort of patients with traumatic injuries and cause further distress and anxiety. The act of vomiting may subsequently result in dehydration, aspiration of emesis and increased intracranial pressure, and its impact on vagal stimulation causes adverse changes in heart rate and blood pressure. A good example is the spine board-immobilized patient who is being transported for a possible cervical spine injury. If the patient becomes nauseated and begins to vomit, he risks aspiration and exacerbation of the spinal injury. Management of this patient generally requires additional personnel, thus taxing the resources of smaller EMS systems.

   Oxygen is an inexpensive and widely available intervention that has been successful in the treatment of perioperative and postoperative N&V. Oxygen may be a simple method of reducing uncomfortable and potentially dangerous vomiting in EMS patients during transport.¹¹

ONDANSETRON (ZOFRAN)

   Ondansetron is a selective serotonin 5-HT3 receptor antagonist that works by blocking serotonin in the intestinal tract and CTZ (chemoreceptor trigger zone). It is available in solution for both IV and IM injection, as well as a rapid ODT (orally disintegrating tablet) and an oral solution. The standard dose for adults is 4 mg for IV or IM administration and 8 mg for the ODT. For pediatric patients (under 40 kilograms), the standard dose is 0.1 mg/kg up to 4 mg.

   Ondansetron has very low incidence of adverse reactions, and the only contraindication is hypersensitivity. Zofran was originally developed to prevent nausea in chemotherapy patients, but its use has become more widespread in the emergency medicine setting since it became available as a generic. Most of the reported adverse effects have been attributed to chemotherapeutic agents taken by the patients.

   Ondansetron was recently studied in the prehospital setting (Multnomah County, Oregon) for undifferentiated N&V in 952 EMS patients.¹² It was shown to be "moderately" effective in decreasing N&V in a wide variety of patients with undifferentiated symptoms. The study also showed it to be safe for both adult and pediatric patients in the prehospital setting with no reported adverse effects.

PROMETHAZINE (PHENERGAN)

   Promethazine is a phenothiazine that works as an H1 antagonist. Although it was originally designed as an anti-psychotic, it is primarily used as an anti-emetic.

   For EMS use, promethazine is supplied in 25 mg/ml Carpuject syringes, as well as 25 mg/ml and 50 mg/ml vials for injection. The standard adult dose of promethazine is 12.5–25 mg and can be administered IV, IM and rectally.

   There are several adverse drug effects associated with promethazine that include the extrapyramidal reactions: akathisia, dystonia, tremors and slurred speech. An important concern when administering promethazine intravenously is the potential for local tissue necrosis in the event of IV extravasation or accidental intra-arterial injection. The drug should be diluted, given slowly into a large vein through a distal port and stopped immediately if the patient complains of pain. If there is any doubt in the patency of the IV or no suitable veins are available, promethazine should be given IM or not at all.

   Promethazine may cause sedation or respiratory depression and should be avoided in patients who have a decreased level of consciousness or have taken narcotics, alcohol, sedatives, barbiturates and other phenothiazines. Promethazine is also contraindicated in patients who take MAOI medications, as there is a possibility that adverse hypertensive effects will occur.

METOCLOPRAMIDE (REGLAN)

   Metoclopramide is a dopamine antagonist that works by minimizing the effects of dopamine at the D2 receptor in the chemoreceptor zone. Metaclopramide also promotes increased gastric motility and emptying, which reduces gastric distention.

   The preferred routes of administration for the prehospital setting are IV or IM; the typical adult dosage is 5–10 mg. Metoclopramide is supplied in a 5 mg/ml concentration and comes in 2, 10 and 30 ml vials.

   Metoclopramide is contraindicated in patients who are taking MAOI medications or those who may have an intestinal obstruction or GI bleeding. Caution should be used when administering metoclopramide to patients with renal insufficiency, hypertension, liver cirrhosis, heart failure and seizure disorders.

   The known adverse effects associated with metoclopramide include muscle restlessness or rigidity, confusion, tachycardia, hallucinations, EPS and possible neuroleptic malignant syndrome. Most of the extrapyramidal reactions associated with metoclopramide occurred in adolescent patients who received high IV doses.

SUMMARY

   The causes of N&V can be medications; abdominal, infectious, endocrine and CNS illnesses; environmental and toxicological conditions and ischemia. There are several interventions that EMS providers can use to minimize patient's N&V, including oxygen and medications such as promethazine (Phenergan), ondansetron (Zofran) and metoclopramide (Reglan). Most important, remember that there are many other potentially deadly causes of N&V apart from the flu.

References

   1. Malagelada JR, Malagelada C. Nausea and vomiting. In: Sleisenger & Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management, 8th ed. Saunders Elsevier: Philadelphia, PA, 2006.

   2. Zun LS, Singh A. Nausea and vomiting. In: Rosen's Emergency Medicine: Concepts and Clinical Practice, 6th ed. Saunders Elsevier: Philadelphia, PA, 2006.

   3. Megener K, Baillic J. Fortnightly review: Acute pancreatitis. BMJ 316:44, 1998.

   4. Edlow JA, Newman-Toker DE, Savitz SI. Diagnosis and initial management of cerebellar infarction. Lancet Neurology 10:951, 2008.

   5. Schneider SM, Donnelly MW. Toxic mushroom ingestions. In PA Auerbach (ed), Wilderness Medicine. Mosby Elsevier, Philadelphia, PA, 2007.

   6. Tintinally JE, Kelen, GD, Stapczynski JS. Emergency Medicine: A Comprehensive Study Guide, 6th edition. McGraw-Hill Inc., 2004.

   7. Budaj A, White K, Montalescot G, et al. Acute coronary syndromes without chest pain, an underdiagnosed and undertreated high-risk group: Insights form the global registry of acute coronary events. Chest 126:461, 2004.

   8. Jaslow D, Klimke A. Prehospital pharmacology: Anti-emetics. Emerg Med Serv 36(11): 56–61, 2007.

   9. Drotts DL, Vinson DR. Prochlorperazine induces akathisia in emergency patients. Ann Emerg Med 34:469–475, 1999.

   10. A randomized controlled trial of oxygen for reducing nausea and vomiting during emergency transport of patients older than 60 years with minor trauma. Mayo Clin Proc 77(1):35–38, 2002.

   11. Smith, E. Oxygen for reducing nausea and vomiting during emergency ambulance transportation: A systematic review of randomized controlled trials. J Emerg Primary Health Care 1(2), 2001.

   12. Warden CR, Moreno R, Daya M. Prospective evaluation of ondansetron for undifferentiated nausea and vomiting in the prehospital setting. Prehosp Emerg Care 12(1):87–91, Jan-Mar 2008.

   Fritz Fuller, BS, PA-C, REMT-P, a 23-year EMS veteran with private, fire, government and international stints, is now with the Department of Emergency Medicine at Valley Medical Center in Renton, WA, and the Acoma-Canoncito-Laguna Indian Health Service Hospital in San Fidel, NM. Contact him at mtwiens@yahoo.com.

   Geoff North, BS, REMT-P, a 20-year EMS veteran, is a firefighter and paramedic with the Gig Harbor, WA, Fire Department, and is on the faculty of Central Washington University's Paramedic Program. Contact him at gnorth@piercefire.org.

Table I: Common Antiemetic Medications

   Antihistamines

   Dimenhydrinate (Dramamine)

   Diphenhydramine (Benadryl)

   Meclizine (Antivert)

   Anticholinergics

   Scopolamine (Transderm-Scp)

   Dopamine antagonists

   Metoclopramide (Reglan)

   Droperidol (Inapsine)

   Promethazine (Phenergan)

   Prochlorperazine (Compazine)

   Serotonin antagonists

   Dolasetron (Anzemet)

   Ondansetron (Zofran)