Denise Garvey, M.D.
Hiccups are usually a brief self-limited occasional annoyance of normal daily life associated with little clinical significance. For some unfortunate patients, however, hiccups can be chronic, persistent and resistant to therapy. In the case of the post-operative patient, such intractable hiccups can interfere with nutrition, sleep, and post-operative care, thus prolonging or complicating the patient\'s hospital course.1
A 68-year-old female without significant past medical history fell and fractured her left hip, requiring a total hip replacement. The surgery went well, without any significant complications. On post-op day 1 she developed persistent hiccups. These interfered with oral intake and willingness to participate in physical therapy. On post-op day 2, she was begun on baclofen with subjective improvement of her symptoms. By post-op day 5, she had only episodic occurrences of the hiccups. By post-op day 7, the hiccups had resolved.
A vigorous and well-oriented 90-year-old male had a history of progressive and debilitating lumbar disk disease. His past medical history was notable for hypertension, hypothyroidism, paroxysmal atrial fibrillation, benign prostatic hyperplasia s/p TURP, and a seizure disorder. Previously he was taking furosemide, metoprolol, digoxin, levothyroxine, tolterodine (Detrol), and phenytoin, which were continued. After his prostatectomy three months earlier, he developed hiccups which lasted for hours multiple times per day; these resolved approximately one to two weeks after his surgery.
He was admitted for L3-5 foraminotomy. The surgery went well without complications. His pre-op medications were continued, and he required only routine pain control. The patient was noted to develop bouts of persistent hiccups on post-op day 1. The episodes were frequent and would last hours. They impaired his appetite and kept him from falling asleep or resting during the day. By post-op day 4, the patient was transferred for rehabilitation but hiccups persisted and the patient was beginning to become fatigued from sleep deprivation. He was unable to participate fully in physical therapy. He was noted by nursing to have poor food intake. Baclofen was begun on post-op day 4. By the following day the patient had a subjective improvement of his hiccup symptoms. His nutrition and sleep improved. By post-op day 6, he noted a decreased frequency and duration of the hiccups and was participating fully in therapy. He was discharged without hiccups on post-op day 8.
There is much debate as to the etiology of hiccup. The exact mechanism of hiccup is unknown. Some postulate from experimental animal data that the hiccup reflex center is located within the lower brain stem; this site contains GABA receptors within the reflex arc.2,3 Other researchers further believe it is controlled by an involuntary reflex arc mediated by sensory branches of the phrenic and vagus nerves with some possible sympathetic nerve involvement.4 Some case studies suggest hiccup may be a myoclonus activity rather than a reflex.5
Why some people are more prone to the more severe form of hiccups is unclear. Hiccups can start in the neonatal period.6 Some individuals seem more prone to them than others. There is no epidemiological data noted linking these early \"hiccupers\" to later development of the tendency to have prolonged or intractable hiccuping.
Ultimately, hiccup can be considered to be a discoordination of \"valve function\" between the inspiratory and glottic closure function, to be differentiated from diaphragmatic dysfunction.7 In one small study, hiccup was induced in four of ten normal patients upon rapid phasic distention of the proximal esophagus after deflation; the sudden rapid stretch of receptors may be the important trigger event of the reflex.8
While the etiology of hiccups is unclear, there are many clinical and anecdotal associations.6 These include post-surgical, drugs, endocrine, inflammatory, metabolic, trauma, gastrointestinal, and neurologic. (Table 1).
Numerous studies have noted the effects of various anesthetics on induction of hiccup.9,10 It seems logical that the etiology of hiccup in the post-opera-tive patient is drug related. However the intubation itself may be a contributing factor.11 The literature on
Table 1. Clinical Associations
the epidemiology of post-operative hiccup is limited. One randomized study notes the use of intranasal ethyl chloride to abate acute post-operative hiccup episodes.12 There are no studies which directly assess the post-operative patient with prolonged hiccup in a randomized double-blind controlled manner. There are very few studies which apply this type of rigorous protocol to patients with prolonged hiccup of any etiology. General data has had to be extrapolated to the post-operative patient population.
The management of prolonged hiccups can be problematic. There are many anecdotal reports of a variety of drug treatments (Table 2). Largely, the results have been unsubstantiated. There are two drugs which have stronger evidence. Currently, the only FDA approved drug is chlorpromazine. Yet even the results from this drug have been inconsistent.13 A recent placebo-controlled randomized double-blind study has shown benefit with the GABA agonist baclofen.14,15 Even this drug had mixed results, with the benefit being the patient\'s subjective improvement rather than decreased numbers of hiccups.16 Further studies have evaluated the data with combination therapy including baclofen, omeprazole and cisapride with positive results.17 A recent study by Petroianu et al of patients with idiopathic chronic hiccup found benefit in adding gabapentin to baclofen or combination therapy treatment failures.18
There are no simple answers to the cause or treatment of post-operative or intractable hiccups. Although there are a variety of anecdotal reports, the studies with baclofen seem most promising. It is unclear whether mono versus combination therapy is most beneficial. More studies need to be done.
Table 2. Therapy