Hiccups, known medically as singultus, are involuntary spasms of the diaphragm muscle, which is the sheet of muscle separating the chest cavity from the abdomen. This spasm is followed by the sudden closure of the vocal cords, producing the characteristic “hic” sound. While often considered a minor annoyance, when this symptom occurs during cancer treatment, it can become persistent, causing significant discomfort and interfering with quality of life. The link between certain cancer therapies and the onset of singultus is a recognized side effect in oncology. Understanding this connection involves examining how these treatments disrupt the body’s involuntary reflex pathways.
Understanding the Physiological Mechanism
The hiccup is a reflex arc, a pathway of nerves that begins with sensory input and ends with a motor response. This reflex involves three main components: an afferent limb, a central processing unit, and an efferent limb. The afferent, or sensory, pathway is primarily mediated by the vagus nerve and the phrenic nerves, which transmit signals from the chest and abdomen up to the brainstem.
Chemotherapy and related supportive medications can irritate or stimulate these nerves along their path, lowering the threshold for the reflex to fire. For example, certain treatments can cause gastrointestinal distress, such as reflux or bloating, which irritates the vagus nerve in the esophagus and stomach region. This irritation sends an abnormal signal to the central hiccup center, which is thought to be located in the brainstem.
The central unit then sends a motor signal down the efferent pathway, which is conducted by the phrenic nerve to the diaphragm. This nerve stimulation causes the muscle to contract suddenly and erratically. Chemotherapy agents can also directly affect the central nervous system, disrupting neurotransmitter levels in the brainstem and triggering the reflex from the top down. The result is the sudden, involuntary contraction of the diaphragm, followed immediately by the glottis closing to produce the characteristic sound.
High-Risk Therapeutic Agents
Two main classes of therapeutic agents are frequently associated with triggering singultus. Corticosteroids, particularly Dexamethasone, are widely used to prevent nausea and vomiting associated with chemotherapy and are considered a major culprit. Studies indicate that Dexamethasone may cause hiccups in a significant percentage of patients, even more frequently than the chemotherapy drug itself.
The mechanism behind Dexamethasone-induced hiccups is thought to involve the steroid lowering the threshold for synaptic transmission in the midbrain, thereby sensitizing the hiccup reflex arc. Certain cytotoxic drugs, specifically platinum-based agents such as Cisplatin and Oxaliplatin, are also strongly implicated. When Cisplatin is combined with Dexamethasone, the risk of hiccups increases substantially.
It is speculated that these platinum agents may also irritate peripheral nerves, which could contribute to triggering the diaphragm spasms. The overall incidence of singultus varies greatly depending on the specific drug combination and patient characteristics.
Strategies for Relief
Managing singultus begins with non-pharmacological interventions aimed at interrupting the reflex arc. Simple physical maneuvers can be attempted, such as holding the breath to increase carbon dioxide levels, which may suppress the reflex center. Stimulating the vagus nerve by gargling with water, sipping ice-cold water, or even swallowing a teaspoon of granulated sugar can also be effective. Patients may also find relief by making dietary adjustments, including avoiding carbonated beverages, extremely hot or cold foods, and large meals that can distend the stomach and irritate the vagus nerve.
If these physical methods fail to provide sustained relief, the oncology team may consider pharmacological interventions. The only medication specifically approved by the US Food and Drug Administration for treating hiccups is the antipsychotic drug Chlorpromazine, which acts as a dopamine antagonist. Other prescription medications commonly used off-label include Gabapentin, an anticonvulsant, Metoclopramide, which enhances gastric motility, and Baclofen, a muscle relaxant. It is important to contact the medical team if hiccups interfere with eating, sleeping, or last longer than 48 hours.