Motivation: Last Sunday evening, I was crouching before a window in a dim room watching the dying sun and tracing uneasy thoughts about end of summer break and impending residency. My solemn reverie was suddenly interrupted by high pitched sounds. My brother had been struck by a bout of hiccups - incessant hiccups. I called out for him to stop or restrain himself. He shot back that since I was now a doctor, I could at least tell him how to stop hiccups. I did not know. I lost the argument. Well, how do you treat hiccups?
As background, a hiccup - or the medical term singultus - is a sudden inspiration ending with sudden glottic closure. There is no known physiological reason for hiccup! The most common cause of hiccups is gastric distension. The hiccup reflex arc has afferent nerve pathways of phrenic and vagus nerves, central mediator in the brainstem, and efferent pathways involving the phrenic nerve. Thus, irritation at any point in the pathway from thoraco-abdominal pathology to CNS neoplasms can give rise to hiccups. Hiccups lasting more than 48 hours are termed persistent while hiccups lasting longer than a month are called intractable. Traditional pharmacotherapy of hiccups involves the antipsychotic chlorpromazine though the literature is thin on evidence. But, given the side effects of chlorpromazine, alternative therapy is needed. Recently, gabapentin was tried.
Paper: Porzio, G. et. al. Gabapentin in the Treatment of Hiccups in Patients With Advanced Cancer: A 5-Year Experience. Clinical Neuropharmacology (2010) 33: 179-180. http://www.ncbi.nlm.nih.gov/pubmed/20414106
Methods: This study was conducted in Italy on patients with advanced cancer in two settings: (1) a palliative in-patient care unit and (2) home comfort care service. Patients were assessed for presence of persistent (>48 hours) hiccups that were rated at least 7 out of 10 in the patient's subjective assessment of severity of hiccups (10 means worst hiccups of life). These patients were treated with gabapentin (300 mg thrice daily) with titration according to response.
Results:
Patients: In the palliative in-hospital service, 37 of 944 patients (3.9%) had severe hiccups. In the home care setting, 6 of 134 patients (4.5%) had severe hiccups. Most patients (31/43) had advanced abdominal cancers. The rest had advanced cancers from other locations.
Gabapentin result: After gabapentin administration, of the 37 inpatients, 31 experienced complete resolution while 4 had improvements. Two end-stage patients on midazolam therapy experienced worsening of hiccups. Among the 6 home care patients, 4 had complete resolution while the other 2 had improvement. The maximum used dose of gabapentin was 1200 mg/day. The most common side-effect was transient drowsiness.
Discussion: The paper in its design and power has many limitations, but it does demonstrate some remarkable results. Among the 37 in-patients with severe hiccups, 35 (>90%) had improvements in hiccups, and the majority experienced complete resolution! Another benefit of gabapentin over current therapy with chlorpromazine is that the only major side effect of gabapentin (in this trial) is transient drowsiness. The paper, of course, has many limitations. There was no placebo arm to the intervention, and the trial was unblinded. So, the observed effect could be entirely a placebo response or an observer bias.
Despite the fact that about 4% of patients with advanced cancers are afflicted with severe hiccups decreasing quality of life, there have not been large randomized trials conducted for treatment of hiccups. The future for hiccups trials does not appear too bright either. This prospective design may be the level of the quality of data that is going to be available for some time. So, if I had to treat hiccups, I would probably try gabapentin first given the tolerable side-effect profile of the drug.
As background, a hiccup - or the medical term singultus - is a sudden inspiration ending with sudden glottic closure. There is no known physiological reason for hiccup! The most common cause of hiccups is gastric distension. The hiccup reflex arc has afferent nerve pathways of phrenic and vagus nerves, central mediator in the brainstem, and efferent pathways involving the phrenic nerve. Thus, irritation at any point in the pathway from thoraco-abdominal pathology to CNS neoplasms can give rise to hiccups. Hiccups lasting more than 48 hours are termed persistent while hiccups lasting longer than a month are called intractable. Traditional pharmacotherapy of hiccups involves the antipsychotic chlorpromazine though the literature is thin on evidence. But, given the side effects of chlorpromazine, alternative therapy is needed. Recently, gabapentin was tried.
Paper: Porzio, G. et. al. Gabapentin in the Treatment of Hiccups in Patients With Advanced Cancer: A 5-Year Experience. Clinical Neuropharmacology (2010) 33: 179-180. http://www.ncbi.nlm.nih.gov/pubmed/20414106
Methods: This study was conducted in Italy on patients with advanced cancer in two settings: (1) a palliative in-patient care unit and (2) home comfort care service. Patients were assessed for presence of persistent (>48 hours) hiccups that were rated at least 7 out of 10 in the patient's subjective assessment of severity of hiccups (10 means worst hiccups of life). These patients were treated with gabapentin (300 mg thrice daily) with titration according to response.
Results:
Patients: In the palliative in-hospital service, 37 of 944 patients (3.9%) had severe hiccups. In the home care setting, 6 of 134 patients (4.5%) had severe hiccups. Most patients (31/43) had advanced abdominal cancers. The rest had advanced cancers from other locations.
Gabapentin result: After gabapentin administration, of the 37 inpatients, 31 experienced complete resolution while 4 had improvements. Two end-stage patients on midazolam therapy experienced worsening of hiccups. Among the 6 home care patients, 4 had complete resolution while the other 2 had improvement. The maximum used dose of gabapentin was 1200 mg/day. The most common side-effect was transient drowsiness.
Discussion: The paper in its design and power has many limitations, but it does demonstrate some remarkable results. Among the 37 in-patients with severe hiccups, 35 (>90%) had improvements in hiccups, and the majority experienced complete resolution! Another benefit of gabapentin over current therapy with chlorpromazine is that the only major side effect of gabapentin (in this trial) is transient drowsiness. The paper, of course, has many limitations. There was no placebo arm to the intervention, and the trial was unblinded. So, the observed effect could be entirely a placebo response or an observer bias.
Despite the fact that about 4% of patients with advanced cancers are afflicted with severe hiccups decreasing quality of life, there have not been large randomized trials conducted for treatment of hiccups. The future for hiccups trials does not appear too bright either. This prospective design may be the level of the quality of data that is going to be available for some time. So, if I had to treat hiccups, I would probably try gabapentin first given the tolerable side-effect profile of the drug.
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