I usually don’t post about studies of painful procedures where there was no analgesic prophylaxis in some of the the subjects, except to criticize them, and if they are recent, to call for their retraction. So when I first saw this study, which recorded pain responses to arterial punctures in newborns, I was going to file it in the recycle bin. However, after reading the methods, I found that they did have a protocol to use 25% glucose and facilitated tucking during the arterial punctures. The article doesn’t say that the protocol was actually followed, which is a problem in many NICUs; despite good intentions, pain is often not adequately prevented. So let’s assume for this article that the protocol was followed, not a bad protocol, but not optimal. Sucrose is probably preferable to glucose as it tastes sweeter, and the initial analgesic effect is probably due to the intensity of the taste, with a sort of distraction effect, later effects, by about 2 minutes are probably related to endorphin release. Also sucrose is more effective if combined with a soother/pacifier/dummy or whatever the local term is. (Alberice RMC, et al. Assessment of newborn pain during arterial puncture: an observational analytical study. Rev Bras Ter Intensiva. 2021).

The article, as I read it, is a translation of an article in Portuguese, I love the translation of what I suppose is cleaning the skin with antiseptic as “degermation”.

No surprise; aterial punctures hurt!

If we give the authors the benefit of the doubt, and assume that all the babies received the glucose/swaddling intervention, pain was between minimal and severe, with nearly 50% reaching a PIPP score of 12 or more, despite a reasonable analgesic approach.

The NICU that this was from seems to do an awful lot of arterial punctures, they were actually performed by their lab techs! The messages of the article are: don’t do blood work unless you need to; if you need to then capillary sampling can be performed with much lower PIPP scores than the scores reported here when using a combination of sucrose, soother, and swaddling, or skin to skin care. If you do need to do an arterial puncture then consider EMLA or liposomal lidocaine in addition.

In a previous study of infants who had previously had multiple blood sampling (infants of diabetic mothers) it was shown that they start to have adverse responses when someone comes the next day to prepare them for another heel prick, Taddio A, et al. Conditioning and Hyperalgesia in Newborns Exposed to Repeated Heel Lances. JAMA. 2002;288(7):857-61, during the degermation phase the infants were able to anticipate that something bad was about to happen.

In this newer study, (Mehler K, et al. Pain response to vaccination in newborn infants of diabetic mothers. Early Hum Dev. 2020;149:105139) in infants of diabetic mothers who were about to have their 2 month vaccination, all the babies received 20% glucose with a soother prior to the 2 IM injections that the German standards required. Control infants were from a previous study that the authors published, which is one weakness of this study. The controls had a median of 1 heel stick as neonates (maximum 3) while the infants of diabetic mothers had suffered between 4 and 19, median 5.

The IDM babies had a greater increase in their heart rate, and took longer to recover than the controls.

They also had greater increases in their salivary cortisol after the vaccine.

Although there is some overlap in the results, the authors also examined a more direct measure of pain sensistivity, using the Frey filaments, where you poke the baby with progressively stiffer filaments to see at what threshold they have a withdrawal response. This suggested that the IDM babies had hyperalgesia, responding at a lower threshold than the previous control group.

Of course, the difference in responses my not be because of a “memory” of the painful experiences as a neonate, and may be due to other factors, such as epigenetic changes associated with maternal diabetes. But one possible explanation is that repeated painful experiences as a newborn may have long term consequences in pain reactions at 2 months of age.

Yet another reason, as if we needed more, that pre-emptive analgesia, prior to planned painful procedures, is important.

Indeed, it is a moral imperative.