Anticholinergic Drugs Could Be Safely Used for ‘Death Rattle’ Breathing in MG, Case Report Suggests

The anticholinergic agent glycopyrrolate — known to decrease stomach acid and saliva production — could be safely used to control “death rattle” breathing in people with myasthenia gravis (MG), a recent case report suggests.

The report, titled “Glycopyrrolate and the Management of “Death Rattle” in Patients with Myasthenia Gravis,” was published in the Journal of Palliative Medicine.

“Death rattle” is the term used for noisy breathing that can result from the buildup of secretions in the airway, typically as a result of a dying person losing consciousness. While some have argued that the phenomenon itself is natural and probably doesn’t require treatment, these noises can be distressing for the people around the dying person.

As such, pharmacological interventions to reduce the secretions that build up — and, in so doing, the noises — are sometimes administered to patients exhibiting “death rattle” breathing. Usually, treatment involves medicines that block the action of the signaling molecule acetylcholine, which are called anticholinergic drugs. Examples include atropine (brand names Sal-Tropine, AtroPen, Atreza), hyoscine butylbromide (brand name Buscopan), and glycopyrrolate (brand name Cuvposa).

One of the main causes of myasthenia gravis is the immune system attacking acetylcholine receptors on muscle cells. Because of this, anticholinergic drugs are typically avoided in people with MG out of a fear that they could further reduce acetylcholine’s ability to send signals, which could worsen symptoms or trigger crises.

Now, however, a new case report suggests the treatment may be used safely.

The report describes an 83-year-old man with generalized myasthenia gravis, which was controlled with medication. The patient developed cancer, and was admitted to the hospital for related pain and confusion.

“During admission, it became apparent that he was dying from his metastatic cancer,” the researchers said.

The patient was given opioids and steroids to manage the pain. When he was unable to continue taking oral MG medications due to difficulty swallowing, an intravenous therapy — neostigmine — was given instead.

A few days later, the man developed a “death rattle” due to the buildup of secretions in the airway. Notably, this was due to MG-related complications, not loss of consciousness, as is more common.

Ultimately, the decision was made to administer glycopyrrolate, even with the risk of exacerbating his MG symptoms. An initial dose of 200 ug was administered by subcutaneous (under-the-skin) injection. It was well-tolerated and effective. Therefore, over the course of the next day, a larger dose — 600 ug — was given.

“The patient’s death rattle remained controlled for the remainder of the admission, and he died peacefully 48 hours later,” the investigators said.

The reason for the relative safety of glycopyrrolate may be its selectivity. There are two major types of acetylcholine receptors: nicotinic and muscarinic. While there are several differences between these receptor types, the one of greatest import here is that nicotinic receptors are found on muscles and are targeted in MG. Muscarinic receptors are found in secretory glands and are the ones targeted to control a death rattle.

Glycopyrrolate is much more selective for muscarinic receptors, which may contribute to the safety and efficacy seen in this case.

The researchers note that, of course, this single observation in one person is not enough evidence from which to draw a confident conclusion. Higher doses of glycopyrrolate might still exacerbate MG, despite the medicine’s relative selectivity, they said

In addition, glycopyrrolate wasn’t the only medication being given. The patient also was given neostigmine, which works by “boosting” the signaling power of acetylcholine — in a sense, working in direct opposition to glycopyrrolate, so possibly lessening its potency or interacting in other ways.

Whether the anticholinergic drug would be safe and/or effective on its own will need to be studied in the future, the researchers said. And, further studies in larger sample sizes could help to validate these observations.

“This article describes the successful use of a subcutaneous anticholinergic agent for the management of death rattle in a patient with myasthenia gravis. The use of such agents in this demographic has not previously been described,” the researchers concluded.