Intravenous Lidocaine in the Treatment of Hiccup.

ABSTRACT: The word "hiccup" refers to an involuntary, spasmodic contraction of the diaphragm that is followed by the abrupt closure of the glottis to produce the characteristic sound. Among the many documented causes of this occurrence are those due to neurogenic dysfunction. In the past few decades, lidocaine has been shown to be effective in treating a variety of disorders thought to involve neuropathic mechanisms, including seizures, chronic pain, and arrhythmias. We describe a postsurgical patient in whom two successive intravenous infusions of lidocaine, 1.5 mg/kg followed the next day by 0.75 mg/kg, terminated his hiccup twice, whereas multiple other treatments failed to alleviate the problem. Various causes of this phenomenon are discussed, as well as a possible mechanism for the successful treatment.

HICCUP, the medical term for which is singultus, is a pervasive disorder that transcends all ages and cultures. (1,2) Despite its prevalence, the pathophysiology behind this phenomenon remains an enigma. In most cases, hiccup is merely an annoyance, but in severe cases, the consequences of postoperative hiccup can be dramatic, leading to increased postsurgical pain, exhaustion, arrhythmias, and 'wound dehiscence. (2,3) Literally hundreds of invasive, pharmacologic, and nonpharmacologic "alternative" treatments have been described for hiccup, with two of the most frequently used medical ones being phenothiazines and butyrophenones. (1,2) We report a case of severe, recurrent hiccup exacerbated by recent abdominal surgery and' successfully treated with boluses of intravenous lidocaine.

CASE REPORT

A 47-year-old, 68 kg man with a history of irritable bowel syndrome, seronegative arthritis, and nephrolithiasis came to the Massachusetts General Hospital (MGH) with a small bowel obstruction from diverticulitis. The patient had a history of recurrent bouts of hiccup treated not with medications, but rather with an unconventional technique that the patient derived himself from experience. This consisted of quickly drinking a glass of water while "upside down"; that is, in extreme flexion at the lumbar spine while standing up. According to the patient, this maneuver almost always abolished his hiccups immediately.

After treatment for a ureteral stone with extracorporeal shock wave lithotripsy, the patient was admitted to MGH because of a diverticular abscess of the sigmoid colon and was brought to the operating room for exploratory laparotomy. A lumbar epidural catheter was placed, and after a smooth intravenous induction with sodium thiopental, a combined general endotracheal-epidural anesthetic was instituted. During the surgery, anesthesia was maintained with 0.5% to 1.2% isoflurane, and an epidural infusion of 0.1% bupivacaine/hydromorphone (0.02 mg/mL) running at 12 mL/hr. Since the patient was paralyzed with cisatracurium throughout the procedure, no hiccups were noted intraoperatively. A low anterior resection was done, and the intraoperative course and emergence from anesthesia were unremarkable.

In the postanesthesia care unit, the patient began to have hiccups resembling his usual bouts, approximately once every 10 seconds. The nasogastric tube was checked and found to be functioning properly. Over the next 24 hours, he was treated with multiple medications, including metoclopramide, prochlorperazine, chlorpromazine, and haloperidol. The relief obtained with each of these ranged from none at all to less than 2 hours of partial relief. After the last of these injections, the patient had a dystonic reaction necessitating treatment with diphenhydramine and discontinuance of all phenothiazine and butyrophenone therapies. At this time, the patient's medications included an epidural infusion of 0.1% bupivacaine at a rate ranging between 5 and 10 mL/hr, morphine via a patient-controlled analgesia device for breakthrough pain, and antibiotics.

On postoperative day 1, the pain service was consulted.

The patient described his pain as minimal at rest but excruciating with hiccup, the episodes of which were still occurring several times per minute. A 100 mg infusion, (1.5 mg/kg) of intravenous lidocaine was administered over 5 minutes, with no sedation or untoward effects. Within, a few minutes, the hiccup completely resolved, and the patient remained hiccup-free for 8 hours, after which it returned gradually, albeit with diminished frequency and intensity. However, when we saw the patient next on postoperative day 2, he was in significant distress because the hiccup had returned. We first administered 2 mL of normal saline intravenously and then 2 mg of intravenous verapamil, both of which had no effect. After a 20-minute interval, we gave him half the original dose of lidocaine (50 mg) which once again resulted in immediate eradication of hiccup. The patient remained free of hiccup for the remainder of his hospital stay and was discharged home without complications.

DISCUSSION

Hiccup may accompany a wide range of disorders, some of which include central nervous system dysfunction, toxic-metabolic abnormalities, diaphragmatic irritation, medications and recreational drugs, infections, and psychogenic causes. (1,4) One of the most common contexts in which it is encountered is in the perioperative period, where it may be due to medications such as opioids and short-acting barbiturates, manipulation of the diaphragm or other organs during surgery, inadequate ventilation, and gastric distention. (1,3,5) In this setting, hiccup can not only cause discomfort, but also may lead to increased postoperative pain, physical and psychologic exhaustion, and wound dehiscence. (2,3)

Despite references to hiccup dating back to the ancient Greeks, the pathophysiology of this ubiquitous disorder remains incompletely understood. In an animal study, Oshima et al (6) found that mechanical stimulation of the dorsal epipharynx of anesthetized cats elicited a hiccup-like response, whereas chemical stimulation with gastric juice or mechanical stimulation of other parts of the upper airway failed to elicit the reflex. This response was dependent on the phase of the respiratory cycle, being suppressed during expiration and inhibited by [CO.sub.2] and chlorpromazine. In a certain subset of people, the hiccup reflex may in part be due to neuronal dysfunction. These abnormalities may be either at the level of nerve roots, cranial, peripheral, and autonomic nerves, or the reflex arc between the inspiratory and glottic closure complexes. (7,8)

One of the primary uses of lidocaine in medicine is as a local anesthetic where its ability to block sodium channels enables it to completely abolish nerve conduction. However, even in subanesthetic doses, lidocaine possesses membrane-stabilizing properties that diminish neuronal excitability and reduce ectopic discharges. It seems logical therefore that lidocaine might also prove beneficial in the treatment of certain patients with hiccup, particularly those in whom a neurogenic etiology is postulated.

Previously, two reports have shown intravenous lidocaine to be effective in the treatment of hiccup, though in slightly different contexts. The first of these revealed a decreased incidence in methohexital-induced hiccups during general anesthesia when patients were pretreated with intravenous lidocaine. (9) The other was a report of a patient whose hiccup resolved after a lidocaine bolus followed by a continuous infusion. (10) Interestingly, in this second paper the use of the oral sodium channel blocker mexiletine was not found to be effective. One possible explanation for this is that it is the peak, rather than the steady state blood level of the sodium channel blocker that is responsible for the cessation of hiccup. Another is that these two medications may work on different subtypes of sodium channels.

In our patient, the systemic absorption of epidural bupivacaine may have contributed to the membrane-stabilizing effect of lidocaine, and thus played a role in the cessation of hiccup. An alternative explanation is that the patient exhibited a positive placebo response despite his negative response to the intravenous administration of normal saline. In conclusion, this report and previous ones indicate that the use of sodium channel blockers may be an effective treatment for chronic, intractable hiccup.

References

(1.) Launois S, Bizec JL, Whitelaw WA, et al: Hiccup in adults: an overview. Eur Respir J 1993; 6:563-575

(2.) Lewis JH: Hiccups: causes and cures. J Clin Gastroenterol 1985; 7:539-552

(3.) Hansen BJ, Rosenberg J: Persistent postoperative hiccups: a review. Acta Anaesthesiol Scand 1993; 37:643-646

(4.) Rousseau P: Hiccups. South Med J 1995; 88:175-181

(5.) Lauterbach EC: Hiccup and apparent myoclonus after hydrocodone: review of the opiate-related hiccup and myoclonus literature. Clin Neuropharmacol 1999; 22:87-92

(6.) Oshima T, Sakamoto M, Arita H: Hiccuplike response elicited by mechanical stimulation of the dorsal epipharynx in cats. J Appl Physiol 1994; 76:1888-1895

(7.) Davis JN: An experimental study of hiccup. Brain 1970; 93:851-872

(8.) Askenasy JJM: About the mechanism of hiccup. Eur Neural 1992; 32:159-163

(9.) Weksler N, Stav A, Ovadia L, et al: Lidocaine pretreatment effectively decreases the incidence of hiccups during methohexitone administration for dilatation and curettage. Acta Anaesthesiol Scand 1992; 36:772-774

(10.) Dunst, MN, Margolin K, Horak D: Lidocaine for severe hiccups (Letter). N Engl J Med 1993; 329:890-891

KEY POINTS

* In the postoperative period, the occurrence of hiccup can result in a variety of adverse consequences including increased pain, exhaustion, and wound dehiscence.

* Despite the large number of described therapies for hiccup, its treatment in the perioperative setting when patients are often unable to take pills can be difficult.

* Intravenous lidocaine administered via bolus doses may provide significant relief from hiccup.

* The beneficial effects of lidocaine for hiccup maybe due to its membrane-stabilizing properties.