In recent years, paramedics have started using a class of medications called antiemetics to alleviate nausea and vomiting in the prehospital setting. Anecdotally, their use in the field has had good results, but there has been very little research on the topic, with only one study on their use in this setting.
MECHANISMS AND ETIOLOGIES OF VOMITING
Nausea or vomiting can occur by three mechanisms. First, vomiting can occur by the brain stem activating the brain's chemoreceptor trigger zone. This region contains serotonin (5-HT3), muscarinic cholinergic (M1), dopamine type 2 (D2), neurokinin type 1 (NK1), histamine (H1) and mu-opioid receptors. Stimulation of any receptor can result in activation of the zone, causing the patient to become nauseous and vomit. Second, stimulation of the chemoreceptor trigger zone can occur from irritation of the ear labyrinth, producing the same effect. Finally, stimulation of the gastrointestinal vagus nerve can activate the D2, NK1 or 5-HT3 receptors.1
Some of the most common underlying causes of nausea or vomiting include gastroenteritis, bowel obstruction, pancreatitis, gallstones, head trauma and some medications. These medications are found in Table 1.
Table 1: Medications That Can Cause Nausea/Vomiting
- Opiates: morphine, hydromorphone, fentanyl
- NSAIDs: ibuprofen, naproxen, ketorolac
- Chemotherapeutic agents: cyclophosphamide, methotrexate, mercaptopurine
- Bisphosphonates: alendronate (Fosamax), ibandronate (Boniva), risedronate (Actonel)
- Anesthetic agents: nitrous oxide, sevoflurane, ketamine
Prehospital treatment of nausea and vomiting often involves phenothiazines, the largest of the five main classes of neuroleptic antipsychotic drugs. The two phenothiazines commonly used by paramedics are promethazine (Phenergan) and prochlorperazine (Compazine). Phenothiazines exert their antiemetic effect by blocking D2 receptors in the chemoreceptor trigger zone. Additionally, they antagonize histamine and muscarinic receptors, augmenting their antiemetic effect.
The onset of action for prochlorperazine is immediate when given intravenously (with a peak response in 2-4 hours), 60 minutes when given rectally and 30-40 minutes when given orally. The half-life is 7-9 hours. The onset of action for promethazine is approximately 3-5 minutes when given IV, 20 minutes when given intramuscularly and 60 minutes when given orally.
The side effects associated with phenothiazines are hypotension, sedation and extrapyramidal symptoms (EPS). EPS can manifest as involuntary lip smacking, akathisia and involuntary limb movements. Standard treatment of EPS, secondary to administration of phenothiazines, is diphenhydramine 25-50 mg IV. Concurrent administration of diphenhydramine with a phenothiazine is effective in preventing EPS. Both promethazine and prochlorperazine are compatible when mixed in the same syringe with diphenhydramine. Less common but more serious side effects associated with phenothiazines are QT interval prolongation, neuroleptic malignant syndrome, torsades de pointes and respiratory depression.1
Neuroleptic malignant syndrome has been reported after just a single dose of a phenothiazine. It is characterized by muscle rigidity, hyperthermia, mental status changes and autonomic instability. Patients at risk for developing this syndrome are those concurrently using antipsychotics, lithium anticholinergic drugs and those with a history of a similar event. Respiratory depression is especially prevalent in children under 2. The FDA issued a black box warning concerning the administration of phenothiazines for nausea due to the risk of apnea in these patients. Patients with glaucoma should not receive either prochlorperazine or promethazine secondary to the anticholinergic side effects. Similarly, patients with bone marrow suppression should not receive this class of medications.