It is time for a (potentially unpopular) rant. Over the last few months, the topic of using sucrose for pain control in neonates has come up a number of times. It has been called the standard of care. It has been stated that it is unethical to run any more trials with a non-treatment arm, because we know that sucrose works.

I have a problem with that.

The idea of using sucrose to control pain has always sort of bothered me. We would never offer sucrose to an adult in pain, but in infants it is apparently a wonder drug. That seems weird. It requires us to believe that infants are fundamentally different; to really believe that children are not just small adults.

It is a minor issue, but one that has been stuck in my mind since medical school. If you were bringing a new analgesic to market, you would have to test its efficacy in a placebo controlled trial. In other words, you would test it against sugar. Sugar pills are synonymous with the placebo effect. However, as long as you are young enough to be incapable of speaking up, placebo somehow becomes treatment.

I have been unable to find a single study indicating that sucrose decreases pain in adults. I don’t know any adults whose response to pain is to grab some sugar. In patients who can communicate, sucrose does not control pain. That should probably tell us something.

If sucrose doesn’t control pain, why are there so many studies in infants that seem to conclude the opposite? (Harrison 2017; Gray 2015; Stevens 2013) I think the problem is the ‘gold standard’ being used in those studies. Neonates cannot report pain levels, so we have to rely on surrogate markers. We assess the appearance of their face or their behaviour. We ask their parents if they thought the analgesic worked. However, none of those surrogate markers tells us anything about the neonate’s actual pain.

I can always make a patient look pain free. A large dose of rocuronium will give anyone the appearance of being pain free. However, if that was my go to strategy for pain management in the emergency department, someone would rightfully have contacted the authorities. Propofol is also incredibly effective any making patients appear pain free, but we all agree that an additional analgesic is essential as part of our sedation packages.

So infants may look more comfortable after sucrose, but are they really experiencing less pain?. In two RCTs of sucrose versus placebo, Slater used electroencephalogram (EEG) to monitor brain and spinal cord nociceptive pathway activity after a painful procedure. Although the standard pain scores (based on the infant’s’ outward appearance) were decreased by sucrose, there was no difference in the neuronal activity in the nociceptive pathways. (Slater 2010; Slater 2010) The premature infant pain profile (PIPP) is one of the common pain scales used in these studies and it has been directly compared to infrared spectroscopy of the brain. Although the overall correlation isn’t bad, a significant minority of infants (10 of 33) had cortical responses to pain without a change in the PIPP. (Slater 2008) Although these are small, imperfect studies, (and all come from the same researcher), they illustrate that an infant’s outward appearance may not correlate well with pain responses in the brain.

Now EEG is clearly a disease oriented, surrogate outcome. If a patient told me she was in pain, but the EEG didn’t reveal any pain, I would trust the patient. I would much rather see a patient describe a decrease in pain than see a changing pattern on an EEG. Unfortunately, in neonates we only have surrogate outcomes. They cannot tell us about their pain. We use facial patterns and crying to make inferences about pain. In that context, I am not sure that EEG data can be so easily discounted.

Neonates can’t tell us about their pain, but young children can. The Cochrane review of sucrose in children aged 1 to 16 years found 8 trials with 808 participants. Sucrose did not reduce pain scores in toddlers or school aged children. (Harrison 2015) It strikes me as odd that sucrose stops working as soon as children are old enough to tell us that it isn’t working.

Pain is a subjective experience, and trying to assess it objectively is fraught with difficulties. In emergency medicine, we have come to a pretty wide agreement that clinicians cannot accurately judge pain in adult patients. (Mäntyselkä 2001; Guru 2000; Miner 2006; Ruben 2015; Schäfer 2016) Vital signs and patient appearance do not reflect the patient’s reported pain levels. (Marco 2006; Lord 2011) We know these techniques don’t work in adults, but we use them in infants because they are all we have.

I will admit, this is not a simple topic. There is an important distinction to be made between pain and distress. Pain is much less important that the distress it causes for the patient. Patient satisfaction has little to do with specific decreases in pain scores. (Ducharme 1995; Ward 1996; Kelly 2000) I have seen many patients who describe 6/10 pain who decline analgesics in the emergency department. They are not distressed, and I don’t argue with them. I have also seen patients with 3/10 pain asking for help. They are distressed and I do my best to help them.

Unfortunately, this distinction doesn’t help us manage the neonate. The neonate can neither report pain nor distress. We can’t ask the neonate, “would you like some more pain medication?” The neonate is at our mercy, and I think that places an increased ethical imperative on us as health care professionals.

The fact that infants cannot communicate makes them an especially vulnerable population. They can’t ask for analgesia for themselves, so we have to be much more diligent about their pain. We need to take pain control seriously. The desire to treat an infant’s pain is exactly why so many providers use sucrose. I think we should be doing the opposite. Our youngest patients cannot confront us. They cannot tell us “stop, that hurts”. Therefore, I think we have a responsibility to ensure the analgesics we use actually decrease pain. Placebo is not adequate.

So I will agree with the comment that prompted me to finally write this piece: I think it is unethical to run any more trials of sucrose for pain. I think it is unethical to treat children with placebo.

Could sucrose be an analgesic? It is possible. The science here is too weak to be sure either way. However, considering infants’ vulnerable position, I think it is essential to prove that sucrose has analgesic properties in verbal populations before exposing those who can’t communicate. Show me an RCT of sucrose reducing pain in an adult, and I will happily use in infants.

I don’t want to be misunderstood here: I am not arguing for less analgesia in infants. I think it is extremely important to treat pain. What I am arguing against is using a substance that doesn’t provide pain relief for anyone who is actually capable of reporting a pain scale.

We have better options that should be used. We have topical anesthetics, intranasal fentanyl, and all the real analgesics we use in adults. I have seen far too many infants put through an LP without lidocaine or any analgesic, because the focus was shoving a sucrose covered pacifier in their mouth to stop the crying. We wouldn’t do that with an adult; I am not sure why we allow it in infants.

I think it is fair to use sucrose in any condition that you would be willing to treat with placebo in an adult. If after controlling an adult’s pain, you offered him a candy, I am sure he would be happy. However, if you are going to do a lumbar puncture on me, please use lidocaine; don’t just shove a pacifier in my mouth and pretend like that the sugar is controlling my pain.

References

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Cite this article as: Justin Morgenstern, "Sucrose: Analgesic or placebo?", First10EM blog, December 4, 2017. Available at: https://first10em.com/sucrose-placebo/