Hiccup during weaning from mechanical ventilation: the use of nefopam
Le Kremlin-Bicetre, France
* E-mail: thgeeraerts{at}hotmail.com
Editor—We report the use of nefopam in two cases with severe hiccup occurring during mechanical ventilation weaning in neurosurgical patients. The first patient was a 46-yr-old male admitted to intensive care after a subarachnoid haemorrhage with early generalized seizures requiring sedation and mechanical ventilation. Neurosurgical clipping was performed 24 h after arrival, and an intracranial pressure (ICP) device and an external ventricular shunt were implanted. I.V. sedation with midazolam and sufentanil and enteral anti-convulsive treatment (phenytoin 100 mg/8 h) and nimodipine (60 mg/4 h) by nasogastric tube were started. When sedation was stopped 3 days after surgery, the patient developed severe hiccup at a frequency of 20 min–1, leading to inefficient mechanical ventilation, including in pressure support mode. Continuous aspiration in the naso-gastric tube was unsuccessful. I.V. treatment with droperidol 0.5 mg and ondansetron 4 mg, used twice, were ineffective. A slow i.v. infusion of nefopam (40 mg in 10 min) decreased hiccup frequency and stopped it in nearly 10 min. Pressure support ventilation (14 mbar) was then possible and efficient. During nefopam treatment, ICP remained stable around 10–15 mm Hg without any seizure whereas heart rate increased from 79 to 90 beats min–1. Continuous infusion (100 mg per day) of nefopam was given after the first bolus. Hiccup started again approximately 3 h after the first injection and i.v. administration of 40 mg nefopam was again effective. During the following 2 days, similar episodes were also treated by repeated nefopam 40 mg infusion. Weaning of mechanical ventilation was then possible without complication.
The second case was a 45-yr-old male with a severe traumatic brain injury 12 yr earlier resulting in left hemiplegia and chronic hydrocephalus with ventriculo-peritoneal shunt, who was admitted with septic shock secondary to severe pneumonia and peritonitis. The peritonitis was related to small bowel necrosis and surgery for intestinal resection and removal of the peritoneal part of the ventricular shunt was required. An ICP device was placed on the first postoperative day. During the ventilation weaning period, 7 days after surgery, severe hiccup occurred when the pressure support mode was used. Continuous aspiration in the naso-gastric tube and increase in pressure support (up to 20 mbar) were unsuccessful. A slow i.v. infusion of nefopam (40 mg in 10 min) stopped the hiccup in about 10 min. During nefopam treatment, the ICP remained unchanged at 15 mm Hg without any seizure, and heart rate increased from 87 to 101 beats min–1. Hiccup started again approximately 8 h after the first injection, requiring another i.v. administration of nefopam, 40 mg, once again rapidly effective. The next day, a similar episode was also treated by another nefopam 40 mg infusion. Weaning of mechanical ventilation was delayed after a ventriculo-atrial shunt was placed surgically.
Hiccup has been reported as a frequent problem in stroke patients or those with ventriculo-peritoneal shunt.1 2 The incidence of hiccup in patients undergoing mechanical ventilation is unknown; however, hiccup during mechanical ventilation could lead to patient-ventilator asynchrony. In our patients, the hiccup became an issue for mechanical ventilation weaning.
In addition to its analgesic effect, nefopam has been shown to inhibit hiccup in ‘medical’ patients or in the two first postoperative days among ‘surgical’ patients.3 4 The originality of our case reports is its use during mechanical ventilation weaning. A dose–response effect is likely, as 40 mg bolus worked consistently, whereas continuous infusion did not. We hypothesize that nefopam's effect was related to its action on serotoninergic receptors and its anticholinergic effects.5 Moreover, as hiccup can be linked with heartbeat,6 the nefopam-induced increase in heart rate (around 10 beats min–1 in both cases) could have decreased the hiccup frequency and even stopped it. The use of the nefopam in patients at risk of seizure remains controversial. We did not see seizures or any change in ICP in our two neurosurgical patients.
References
1 Karian JM, Buchheit WA. Intractable hiccup as a complication of ventriculoperitoneal shunt: case report. Neurosurgery (1980) 7:283–4.[Web of Science][Medline]
2 Kumar A, Dromerick AW. Intractable hiccups during stroke rehabilitation. Arch Phys Med Rehabil (1998) 79:697–9.[CrossRef][Web of Science][Medline]
3 Bilotta F, Rosa G. Nefopam for severe hiccups. N Engl J Med (2000) 343:1973–4.
4 Bilotta F, Pietropaoli P, Rosa G. Nefopam for refractory postoperative hiccups. Anesth Analg (2001) 93:1358–60.
5 Girard P, Coppe MC, Verniers D, Pansart Y, Gillardin JM. Role of catecholamines and serotonin receptor subtypes in nefopam-induced antinociception. Pharmacol Res (2006) 54:195–202.[CrossRef][Web of Science][Medline]
6 Chen BY, Vasilakos K, Boisteanu D, Garma L, Derenne JP, Whitelaw WA. Linkage of hiccup with heartbeat. J Appl Physiol (2000) 88:2159–65.
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