Hiccups: Still Better Than Miley Cyrus

There are a few things that make a great spouse or friend. One of those things is not twerking like Miley Cyrus at the VMA's. The other in my opinion is lifting you up when you’re down but also keeping you grounded when you get a bit too annoying confident. Amanda unknowingly is an expert at the latter (yes, you’re also good at encouraging me as well). Over the past year she has asked me many basic medical questions, typically at the dinner table, all of which I seemingly can never answer appropriately. Thus, was the inception of this series – “So My Wife Asked Me…”. These particular blogs will be a bit more basic in nature but hopefully informative nonetheless. Because let’s face it, one of the worst feelings as a doctor is being unable to answer a simple question. So Amanda’s question was…

““Where do Hiccups come from and what should I do to stop them?””

I retort back with “good question” aka my 2-second time filler when I don’t have a satisfactory answer.  My typical answer to this question is that it’s diaphragmatic irritation/spasm, most commonly idiopathic. The most common known etiologies being central nervous system processes like CVAs. Finally, what to do about them? I got nothing for ya because really everyone has their own superstitious way about eliminating hiccups but they are all too zany to make actual sense.  Chronic, pathological hiccups are another story with many people suggesting chlorpromazine but the only medication I’ve actually used was Baclofen for a patient with a posterior CVA.

Let’s start with where they come from. The mechanism of the actual hiccup on a macro level is easier to explain than the mechanism on the micro level. Most sources agree that the hiccup is indeed sudden contraction of the diaphragm in conjunction with the closure of the glottis. It’s also proposed that there is a reflex arc involved with the afferent portion being the vagus and phrenic nerves along with the sympathetic chain. The efferent pathway is thought to be the recurrent laryngeal nerve that induces the glottis closure. That is pretty much the general consensus because those are the nerves that innervate those specific structures.

Regarding the etiology? Well the list of potential causes is literally over 100 items long, at least according to Dynamed as well as looking at other sources. You know what that means? Your grandma, your dumb friend who insists he/she is always right, and the guy making awkward conversation with you on the bus are probably all correct. Everything has potentially been linked to hiccups. The few epidemiologic studies there are about hiccups are pretty laughable and only look at intractable (> 48 hr) hiccups. There’s one from 1968 that looked at 220 cases [1] and there’s one that looked at 20 cases of chronic hiccups in 1992. [2] The ancient 1968 study (per UpToDate since I can’t access the article) found the majority of patients were older males (~80%), many of which had vascular (20%) and CNS comorbidities (17%). The newer study from 1992 found reflux esophagitis to be the most frequent cause of intractable hiccups (10 of the 20 cases).

So now we know anything is possible when it comes to hiccups etiologies. But how do we treat this scourge? I like to break the treatment down into 3 categories 1) Things you hear second hand that people insist work but inevitably fail 2) Interventions I might give consideration 3) Hail Mary Group - interventions that I’d only consider in the most refractory of cases.

Starting with the non-pharmacologic, less plausible interventions, I found there are exactly 0 studies regarding the use of these in acute hiccups. There really is no evidence so I’ll go ahead and list these on order of least ridiculous to most ridiculous.

• Holding breath
• Breathing into a paper bag
• Causing fright
• Biting a freaking lemon
• Inducing sneezing with black pepper
• Applying pressure to the bridge of nose, upper lip, or eyebrow area (a friend’s favorite)
• Swallowing difficult to swallow items such as granulated sugar, peanut butter, or molasses
• Drinking water from the opposite side of the cup
• Lifting the uvula with a spoon…
• Finally, sexual intercourse! – Was actually found to stop intractable hiccups in a single case report [3]

Then there are a few they recommend that clinicians can try such as:

• Induction of vomiting with emetic
• Breathing 5% carbon dioxide
• Stimulating vagus nerve by supraorbital pressure

Those all sound equally if not more ridiculous. I can’t help but think of someone gouging a person’s eyes when it comes to supraorbital pressure. I was considering posting a picture for humor’s sake but found all the google images to be very disturbing. So I didn't. You're welcome.

Moving to things I’d actually consider treating a patient with or doing myself. In this category I’d either want a physical maneuver that was somewhat plausible for stopping the reflex arc or medication with a proven track record but also without a heavy-duty side effect profile. Here were my choices for this:

• Drinking Ice Water [4]
• Performing Valsalva Maneuver
• Compressing diaphragm by pulling knees to chest or leaning forward
• Ok, I’d actually consider the supraorbital pressure here as well - still thinking of eye gouging though.
• Acupuncture
• Baclofen
• Reglan
• Gabapentin

The first four I chose to add to my repertoire because they are more known to cause a vagal response. It’s more plausible to see these overriding the reflex arc than let’s say… biting a lemon. The last four have decent evidence to moderate evidence but without too harsh of a side effect profile. Acupuncture and Baclofen actually have the best evidence. There have actually have been a number of randomized trials showing acupuncture to be superior to Reglan and placebo. An analysis of 3 randomized trials of 162 patients found a risk ratio of 1.87 (95% CI 1.26-2.78) [5]. However, a Cochrane review found that the type of acupuncture was significant as 4 needle and 1 hour acupuncture duration was superior (p < 0.05) to 3 needle and 30 minute acupuncture. [6]

Out of all the prescription medications, Baclofen has the best evidence, especially for decreasing severity of hiccups. This is mainly based on a case series of 37 patient with intractable hiccups which found Baclofen 5mg TID (titrated up to 75 mg/day) completely resolved 53% and considerably improved another 29% of patients seen in follow up. [7] There was also a tiny (n=4?!) randomized trial that somehow found significant improvement in severity but no frequency of hiccups. [8] Reglan and Gabapentin have also had individual case series show complete resolution in 100% (and within 30 minutes to boot) and 81% of patients. The Reglan option is particularly appealing since it’s a commonly used medication and apparently has had shown good effect in the past.

View fullsize

Last but not least, the Hail Mary group. Basically the only candidate in this group is Chlorpromazine (Thorazine) which is actually the only FDA approved drug for intractable hiccups. It has decent evidence showing complete resolution of intractable hiccups in 41 of 50 patients in a case series while reducing symptoms in another five. [9] But really, EPS symptoms scare me. And although Chlorpromazine is much less likely to cause EPS symptoms than other traditional antipsychotics like Haldol, I’m sure patients would like to ideally control their own bodily movements. 

There are other less savory interventions like phrenic nerve blocks, Haldol, and various surgeries and procedures that you could also try if you want to scrape the bottom of the barrel. But if you passed the gauntlet and are still refractory at this point you are probably pretty ill (Chemotherapy, CVA) and might be willing to try these interventions.

---

Wrapping up, I learned that it is indeed OK to say “we don’t know” when it comes to hiccups and that your annoying friend/family member is probably correct when they think global warming, signals from the TV, or Miley Cyrus' twerking can cause hiccups. I was also able to refine my algorithm a bit for hiccups (Maneuvers > likely Reglan > Baclofen > Gabapentin >> Thorazine). So here’s to another question of Amanda’s I can now confidently answer. At least until next time she ruins my self-esteem keeps me grounded.

TL;DR - Feel free to try whatever maneuvers you want, no real evidence for any of them. Baclofen/Accupuncture > Reglan/Gabapentin > Chlorpromazine in my book.