Dyspepsia means that there is upper abdominal discomfort. In lots of folks with dyspepsia it gets worse after eating, or only happens after eating. In adults dyspepsia has been studied carefully. Endoscopy may show an inflammatory or acid-related disease that can be treated with drugs. However, most dyspepsia is functional, meaning that the symptoms are real but there is no easily discovered disease.
Functional dyspepsia occurs through one or more of three mechanisms:
- visceral hyperalgesia
- defective receptive relaxation with consequent increases in intragastric pressure
- abnormal motility.
Visceral hyperalgesia occurs when sensory nerves in the stomach become over sensitive. Then the pain nerves send messages to the brain that there is pain, even after events that should not cause pain, like normal stomach contractions. Newborn infants, especially ill preemies, may be more susceptible to visceral hyperalgesia for several reasons, including: 1) non-functioning descending pain-inhibitory nerve pathways, 2) no coping mechanisms, 3) repeated pain experiences.
Infants are unable to say when they have dyspepsia. However, infants do not eat if it hurts to eat. Therefore, if an infant refuses to eat, clinicians should always consider why it hurts to eat, or why the infant is afraid it will hurt to eat. Functional dyspepsia is not an accepted diagnosis for children unable to provide an accurate pain history. However, it seems like postprandial dyspepsia may be a common cause for infants and toddlers to refuse to eat. A fundoplication may further complicate dyspepsia by creating more dyspepsia by reducing stomach receptive relaxation and stimulating more pain nerves in the stomach area.
If a child refuses to eat and there is no anatomic reason to explain the symptom, dyspepsia is high on the list of diagnostic possibilities. If a child refused to eat and has a normal endoscopy, it is reasonable to treat for functional dyspepsia at any age. In everyone except those with seizures or cardiac conduction defects I recommend a tricyclic antidepressant. Tricyclics are used for chronic pain everywhere in the body, and work well to treat visceral hyperalgesia. If the child is irritable and/or has trouble sleeping through the night or diarrhea, amitriptyline is the drug of choice, beginning at 0.2 to 0.3 mg/kg an hour or two before bedtime, and increasing by the same amount once a week until there is a response or stop at 1 mg/kg, whichever comes first. Side effects of amitriptyline are relaxation, sedation and constipation. Sometimes the side effects are desirable. Imipramine is midway in side effects between amitriptyline and nortriptyline. Cyproheptidine may be used as well, for its serotonin 1 receptor antagonism probably resulting in improving stomach receptive relaxation. For children with seizures or cardiac conduction defects, I start with gabapentin.
I avoid all unnecessary procedures on children with visceral hyperalgesia, because procedures may cause further hyperalgesia secondary to discomfort and arousal. Therefore I advocate a trial of pain medicine before manometry in most cases. (Sometimes parents or referring docs request manometry before treating, because who wants to use drugs when you are not sure what you are treating? Manometry always shows what works and what does not work.) More than half the time treating pain results in a happy baby and an overjoyed family. If there is no response, and no overt central nervous system reason for food refusal, it is reasonable to find out what works and what does not work in upper GI tract motility. We can do esophageal and gastrointestinal manometry at an age, any size.
Dr. Paul Hyman
Professor of Pediatrics and Pediatric Gastrointestinal Motility Specialist,
Louisiana Children’s Hospital, New Orleans
Hi Krisi–I am following a 31 week preemie/now 38 weeks, currently in the NICU, who had a very complicated medical course involving meningitis. She was intubated for over a week, and had significant emisis on a daily basis for 3+ weeks. Not suprisingly, she has opted not eat, despite having ruled out flow issues, etc.
I suspect her esophagus and or gut are uncomfortable, despite the fact that the only time she really fusses is with eating. She takes her pacifier (although not eagerly) , but would throw the bottle at us if she could.
PPI intervention is now frowened upon in our NICU, and I do not believe she has an intolerance to her formula.
I showed our Neo the info you provided from Dr. Hyman, and while he found it interesting, says it is just an opinion at this point. Do you have any research to support Dr. Hyman’s use of tricyclic meds in the NICU? And do you have any info that could be used from a research perspective around PPI tx? In the past we have had some excellent results with this treatment, but now our Docs feel we need to reconsider its use given recent findings.
Your article is great, definetly timely, and your Newsletter always on the cusp of where we are at in the NICU–I love it! Thanks for your efforts, and any thoughts on the above info would be greatly appreciated!
–Kelly
From Dr. Hyman:
I have not used amitriptyline in infants less than 4 months old. Never used it in the NICU. I do not begin any chronic pain treatment until the disease acuity is minimal, and the patient is stable. NICU infants are mostly unstable, and so are not candidates for chronic pain treatment.
Once in a while there might be an 8 month old 7 Kg ex-premee on a vent who has been stable for several months but BPD requires continued hospitalization. If that child had a trach and the feeding therapists desired some medication to reduce sensory sensitivity, I might start gabapentin or amitriptyline. Chronic pain treatment might be appropriate for such a child.
I’ve used gabapentin after heart surgery in infants as young as 2 months in a mostly successful attempt to avoid fundoplication and gastrostomy. We presented that data in abstract form ( Hyman P, Firestone-Baum C, Chepolis D, Monagas JJ. Gabapentin for early satiety in medically fragile infants. Gastroenterol. 2011; 140: S-743) , and the manuscript has been submitted.
Hope this answers the question.
Paul
Thank you Dr.Hyman for clarifying further the use of pain medicines.
Kelly, it is true that most NICU’s will not use PPI’s with preterm infants for several reasons. One reason is that PPI’s have been linked to possible increased risk of NEC (necrotizing enterocolitis) though there are also reports of Vitamin E and PPIs potentially having a protective effect.
Another reason is the possible increased risk of bone fractures though there is conflicting data concerning this. Dietary calcium exposed to gastric acid improves bioavailability and so it is postulated that reducing stomach acid may decrease the amount of calcium absorbed. However, there are contradictory reports of the effect of PPIs on bone density and risk of fractures.
Since our options are limited on interventions to increase gut comfort, you might consider trying the following:
– you could try continuous feeds or slow bolus to ensure comfort during tube feeding.
– you could try an elemental formula or partially hydrolyzed formula that might have a faster gastric emptying time and therefore improve
comfort.
– establish a good stooling pattern which might also improve comfort.
– Since the baby has a good non-nutritive suck, you trial the Bionix bottle on 0 and work up slowly to increase tolerance.
Hope that gives you a few ideas, thank you for the comment! (answered with assistance from Dr. Katherine Freeman, MD FAAP, pediatric gastroenterologist and Nanette Martin RN, MSN, CPNP)
Hi Dr. Hyman,
Wondering if you have ever treated any children with Cornelia De Lange syndrome (CDLS)? My daughter, Izabelle is almost 8 years old. Kiddos with CDLS can have a multitude of GI issues. Most commonly, reflux. Many are also tube fed. My daughter is non-verbal and cannot tell me where it hurts, but her behaviors tell me that she is hurting. We recently had an EGD which came clean, aside from some gastritis. There were no eosinophils (which there was in the past). In speaking with her GI doc today, we are going to start her on some gabapentin. I am reluctant to start amitryptline because of the cardiac side effects and also because she does have a VSD. She is also on .025 mg of clonidine as well which she can have up to 3 times a day. Does this treatment sound appropriate? She does eat orally and sometimes refuses to eat (she has to poo or her tummy hurts) and when she belches, it sounds like it is coming from waaaay down deep! I am not looking for a diagnosis or anything like that, I am just hoping for some supportive information regarding the use of gabapentin to treat stomach pain. I am an RN and frequently give this medication to patients with neuropathy, especially in diabetics. I have never seen this given for gi purposes. Any insight or information would be greatly appreciated. Thank y
ou very much for your time
There are several issues in your email that deserve comment.
First, when non-verbal children are in distress, it is so difficult to determine if they are in physical or emotional pain, or both. You are frustrated, but so is Izabelle, because of the communication gap.
Gabapentin is drug for chronic, neuropathic pain. Overall, it is helpful in only a minority of patients, but it is so safe it is always worth a try. Do not be afraid to push the drug to high doses: as high as 15 mg/kg/dose TID, before you give up on it. I use it most often for improving feeding volumes in infants recovering from early life cardiac surgery. Often we are able to avoid feeding tubes for cardiac babies, and get them home earlier than we did without gabapentin. I use it as a second line pain med for bellyachers, especially if they are suicidal so I cannot use amitriptyline. You can swallow a whole bottle of gabapentin and nothing bad happens.
A VSD does not automatically exclude using amitriptyline. The doses of amitriptyline that we use for chronic neuropathic pain are very small compared to the doses that cause arrhythmias. Check with Izabelle’s cardiologist. If Izabelle has a safe QT interval, the risk of amitriptyline is minimal, even with a VSD. If her VSD is associated with prolonged Q-T, your cardiologist will advise against amitriptyline. It’s worth asking, because amitriptyline is more likely than gabapentin to help.
See my review of psychotropic meds for functional GI complains in JPGN September 2014.
Paul Hyman