This study focused on hiccups in patients with cancer and found that most had short-term, limited symptomatology. However, over one-third of patients developed symptoms that lasted a week or longer, and a small subset had ongoing, frequent symptoms that continued for several weeks or longer. Furthermore, a third of patients develop hiccup-induced symptoms, such as insomnia and pain. Interestingly, to our knowledge, few earlier studies have reported on the extent to which patients access medical care for hiccup palliation, but here we observed that approximately one in 10 patients sought help in an emergency department or hospital for hiccup palliation. In contrast to earlier reports that tended heavily to emphasize the complications of hiccups, this study observed that hiccups are seemingly inconsequential in the majority but clearly troubling in a small subset [4, 10]. This hiccup-related morbidity – when coupled with the many other known challenges faced by patients with cancer – show that hiccups are highly problematic for a subgroup of patients with cancer.
Although hiccups appear to be trivialized because of their commonplace nature and self-limited course, the National Institute of Health (NIH) and the National Organization for Rare Disorders (NORD) have categorized intractable hiccups as a rare disease [18, 19]. The latter is a designation for illnesses or disease entities that affect fewer than 200,000 people at a snapshot in time. Although the current study was not designed to comment on the percentage of all cancer patients who develop hiccups, it does provide perspectives on hiccup-related morbidity, underscoring how this entity can lead to morbidity and an increased need to access medical care in a small but notable group of patients with cancer. Based on such morbidity, this study suggests that the NIH’s and NORD’s designation of labeling hiccups as a rare disease is merited and that hiccups in patients with cancer should not be summarily downplayed.
Interestingly, this study underscores the challenges of demonstrating the therapeutic efficacy of hiccup interventions. To date, only a small number of published randomized, controlled trials, each with fewer than 40 patients, have suggested that agents such as baclofen and metoclopramide might palliative hiccups; this paucity of research suggests that more such research should be conducted [13, 20,21,22]. Admittedly, in most patients, the hiccups eventually resolve on their own with no or little intervention; this study confirms the same. However, in other patients, as seen in this study, a variety of therapeutic agents have been employed, leaving open the possibility that the last intervention to be tried presumably prior to spontaneous resolution of hiccups might be falsely declared as effective. This aspect of spontaneous resolution, the rarity of persistent/chronic hiccups, and that fact that only one drug provides precedent for how to acquire FDA approval of a drug for hiccups highlight the challenges of studying hiccup palliation in a rigorous and definitive manner. Yet, the data presented here -- including the complications of sleep disturbance, emergency department visits and hospitalizations, musculoskeletal pain, and others – suggest the need to develop novel study designs for hiccup palliation and to thereby enable healthcare providers to have access to a broader and more effective armamentarium of interventions for managing hiccups.
Finally, this study has limitations, the most notable of which is its retrospective design, which carries inherent challenges, including reporting bias. Although we had sought to provide a greater degree of balance in the literature on hiccups, reporting bias is likely at work in the current study, too. Those patients with more problematic hiccups were perhaps more likely to voice their concerns to their healthcare providers, and healthcare providers were more likely to include such information in the medical record if the hiccups were more severe or problematic. It should be noted, however, that hiccups are likely trivialized not only among healthcare providers but also among patients. Thus, in effect, any study of hiccups is likely to show some degree of bias toward more severe symptomatology, if for no other reason, then because patients themselves forget to mention minor, transient symptoms. In this context, despite this potential bias, the current study succeeded in its goal of illustrating a full spectrum of hiccups symptoms in patients with cancer – from mild and transient to relatively severe and persistent. The current study also showed that this symptomatology can be burdensome and that patients’ needs are sometimes unmet.
