Epidurally administered local anesthetics are commonly used in both acute and chronic pain management. We present a case of recurrent persistent hiccups after epidural steroid and bupivacaine injection for chronic pain and subsequent epidural analgesia with bupivacaine for acute postoperative pain relief.
Case Report
A 65-yr-old man presented to the anesthesia pain clinic for evaluation and treatment of lumbar spinal stenosis. He was treated with an epidural steroid injection of 11 mL total volume of a mixture of 0.08% bupivacaine and 80 mg of triamcinolone at the L2-3 level. After his first 2 epidural injections, he developed leg weakness that resolved after approximately 4 h. After his third epidural injection, he developed mild urinary retention that resolved without consequence 6 h later. All 3 epidural injections were associated with the onset of hiccups approximately 1 h later that persisted for 5–7 days after the procedure. The patient complained of the leg weakness and urinary retention but did not report the hiccups until before the third injection. In an effort to minimize the side effects of leg weakness and urinary retention, the fourth epidural injection was performed with a 10 mL mixture of triamcinolone and normal saline alone. The 4 injections were performed approximately 8 wk apart. The patient did not develop urinary retention or leg weakness and, for the first time, he did not experience persistent hiccups after the epidural injection. Two months later, he received one other epidural steroid injection with the same 10 mL mixture of triamcinolone 80 mg and normal saline and again did not develop hiccups.
Approximately 1 yr later, the patient was scheduled for revision of a total knee replacement. During preoperative anesthetic discussions a lumbar epidural catheter was chosen for management of postoperative pain. The patient did not inform the acute pain management team of his previous experience with epidural injections or the development of hiccups. The epidural catheter was placed preoperatively at the L2-3 level and a test dose of 3 mL of 1.5% lidocaine with epinephrine 1:200,000 was given with no significant vital sign changes or leg weakness. Ten mL of 0.25% bupivacaine was injected through the epidural catheter in 2 equally divided doses near completion of the surgical procedure. Fentanyl 100 μg was also given via the epidural catheter near the conclusion of the surgical procedure. Postoperatively, an infusion of 0.0625% bupivacaine and 10 μg fentanyl was started at a rate of 3.5 mL/h. Approximately 5 h after the start of the infusion, the patient developed persistent hiccups, which were not initially reported to the acute pain service. On postoperative day 3, the patient informed the acute pain service that he was experiencing hiccups and that he had previously experienced persistent hiccups after epidural injections. The patient’s neurologic examination was stable throughout his postoperative course with sensory blockades to the T10 dermatome, pain scores on the visual analog scale ranging from 1–3, and minimal motor blockade allowing the routine rehabilitation regimen. On postoperative day 3, the epidural catheter was subsequently removed and the patient was prepared for discharge from the hospital. The patient declined any attempts at treatment for the hiccups and they resolved 9 days later.
Discussion
Hiccups (hiccoughs, singultus) combine a sudden inspiration immediately followed by an active closure of the glottis and are a common phenomenon (1). Hiccups are experienced at one time or another by almost everyone, yet their origin is not well understood (2).
Hiccups lasting longer than 48 hours are referred to as persistent hiccups, and those lasting more than 2 months are considered intractable (3). Persistent or intractable hiccups may lead to fatigue, sleep disturbances, dehydration, and even wound dehiscence in the perioperative period (4).
The exact mechanism of hiccups is not completely understood. Hiccups result from a stimulation of the central or peripheral components of a hiccup reflex arc (5). Although the central connection between the afferent and the efferent limbs of the hiccup reflex arc cannot be ascribed to a specific anatomic location, it probably involves interactions among brainstem and midbrain areas, including the respiratory center, phrenic nerve nuclei, medullary reticular formation, hypothalamus, and nonspecific anatomic locations in the spinal cord between C3-5 (5). The afferent portion of the hiccup reflex arc comprises the phrenic and vagal nerves and the sympathetic chain arising from T6-12 (6).
Multiple causes have been attributed to the etiology of hiccups. The most common are of gastrointestinal origin, such as gastric distention or gastroesophageal reflux disease (4). Metabolic derangements and drugs are also frequently implicated as causes for hiccups (1,4,7). Over 100 known organic causes of hiccups have been identified (6,8).
Epidural bupivacaine has never been implicated as a cause for hiccups prior to this case. A thoracic epidural steroid injection was described as the cause of hiccups by Slipman et al. (9). Their patient received 2 separate thoracic epidural steroid injections containing betamethasone and 1% lidocaine. The patient developed persistent hiccups 15 and 18 hours after the first and second thoracic epidural steroid injections, respectively. The authors attributed the hiccups to the steroid in the mixture owing to previous reports of steroid, by multiple routes of administration, being implicated as the cause of hiccups (9).
Local anesthetics given by the epidural route have never been implicated as the cause of hiccups. To the contrary, lidocaine via the IV or nebulized route of administration has been advocated as a therapy for persistent or intractable hiccups (10,11).
Our patient had the distinct advantage of having epidural injections containing many combinations of drugs as described, thus serving as his own control. When triamcinolone and dilute bupivacaine were given by lumbar epidural injections, hiccups occurred several times. Clearly, when the bupivacaine was removed from the mixture, the hiccups did not occur. Later, when bupivacaine was again given epidurally for postoperative pain management, the hiccups recurred. It seems clear in this case that bupivacaine given epidurally, or its physiologic effects, can be implicated as the source of the hiccups. Given the multiple combinations of medicines he received in the epidural space, the one common factor that was always present when hiccups occurred was bupivacaine in dilute concentration.
It is unclear, however, if the hiccups were a direct result of the bupivacaine or a result of the physiologic effect of local anesthetic in the epidural space. Epidural local anesthetics have physiologic effects on many organ systems (12). Lower thoracic and upper lumbar epidural local anesthetics cause sympathetic blockade that results in a small contracted gut owing to parasympathetic dominance (12). This physiologic effect seems to be in contrast to the gastric distension that is frequently implicated as a cause of hiccups (4).
Epidural blockade can also affect diaphragmatic function. Thoracic epidural anesthesia with lidocaine increases electrical diaphragmatic activity after upper abdominal or thoracic surgery (13,14). The most likely explanation for the thoracic epidural anesthesia-related increase in diaphragmatic activity seems to be the interruption of an inhibitory reflex of phrenic nerve motor drive, related either to direct deafferentation of visceral sensory pathways or to a diaphragmatic load reduction as a result of increased abdominal compliance (12). The effect of lumbar epidural anesthesia on diaphragmatic electrical activity has not been reported.
Clearly, epidural block can cause physiologic changes that may contribute to the development of hiccups. Because of the complexity and incomplete understanding of the physiologic mechanism of hiccups, it is unclear in this case whether it was the bupivacaine or its physiologic effects on the gastrointestinal system, the diaphragm, the abdominal wall musculature, or some other undetermined effect that actually resulted in the development of hiccups. The prolonged nature of the hiccup episodes seem to suggest that the mechanism is more complex, as bupivacaine’s duration of action is approximately 200–400 minutes (15).
Although our patient declined treatment, there are many therapies which have been successful in treating hiccups. Pharmacologic therapies are many, but the most common treatments include metoclopramide, chlorpromazine, and, more recently, baclofen (1). Procedural interventions are also numerous and include phrenic nerve block and pharyngeal stimulation (16–18).
In summary, we present what we believe to be a rare case of recurrent persistent hiccups after lumbar epidural injection of dilute bupivacaine. It may be useful to query patients specifically about the development of hiccups after epidural block to determine if this effect may be more common than suspected. It is important to recognize this possible side effect so that patients who experience hiccups after epidural block can be reassured and effectively treated should the side effect persist. Should further epidural injections be necessary in this patient, it may be interesting to evaluate the response of an alternative epidural local anesthetic.
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