In 2010 a paper published in the Lancet called into question the use of sucrose as an analgesic for heelsticks. (I will use the US term as I think most people understand that it refers to lancing the heel of the infant in order to obtain blood for lab testing.)
That paper used multiple component analysis of the EEG to analyze brain wave responses to the procedure, and showed that the use of sucrose, in a randomized trial with about 30 newborn babies per group (44 total with interpretable results), did not change the EEG response to the heelstick.
I thought this was interesting information, but I was appalled by the suggestion of the authors that ‘ sucrose should not be used routinely for procedural pain in infants without further investigation’. Sucrose had already been proven to reduce behavioural responses to pain, in several thousand babies in randomized controlled trials. The fact that it did not change EEG responses was interesting, and called into question the site and mechanism of action, but not its efficacy. Giving sucrose before a heelstick reduces crying (can completely prevent it) inhibits other behavioural changes like the facial grimaces that babies make when they hurt, and reduces physiologic deterioration which occurs with pain.
We have an ethical obligation to reduce the pain of our patients, even if we can’t prove that the EEG responses are inhibited, a baby who cries less, grimaces less, has less desaturation and less tachycardia is a good thing.
Why write about this now? Well the original paper came out before I started blogging, and a new commentary has been published by the pain study group of the Italian Society of Neonatology, (Lago P, Garetti E, Pirelli A, et al for The Pain Study Group of the Italian Society of Neonatology: Sucrose for procedural pain control in infants: Should we change our practice? Acta Paediatrica 2013) The commentary focuses on the implications of the work by Slater, and comes to similar conclusion to my own, routine sucrose use of skin breaking procedures reduces pain responses, in a literature which now includes controlled trials in over 5000 babies, and systematic reviews which consistently show a reduction in pain responses.
One place I disagree with the Italian commentators is their repetition of the misinformation about the number of doses of sucrose and ‘outcomes’, suggesting that there is a maximum number of doses that should be given. This is based on a misleading interpretation by the original authors of their own controlled study published in 2002 (Johnston CC et al). That was a controlled trial of 107 very immature babies who routinely got sucrose for painful procedures over a 7 day period, starting in the first 48 hours of life, or received sterile water instead. It was a very well performed study that showed that the sucrose reduced pain responses, and continued to reduce pain responses over the entire week despite multiple doses being given, but did not affect the NAPI assessment of the babies (which is a neurobehavioural assessment performed in very early life) nor the NNBRS (the nursery neurobiologic risk scores) at 2 weeks of age or at discharge. What they did show on secondary analysis was that the infants who got more doses of sucrose had higher NNBRS. This has been interpreted by many, including the Italian commentary authors, that they had worse long-term outcomes. That is not the case. There was no long term outcome data collected in that study.
To know what that might mean you need to look at the NNBRS, which was constructed by Brazy et al in 1991. It is a composite score to predict risk for neurologic outcomes, and includes items for worst pH, Seizures, IVH, PVL, infection and hypoglycemia. So at discharge the babies who had more doses of sucrose had higher scores on those items. Also in the controls, the babies who had more invasive procedures had higher scores on those items.
In other words sicker babies, who had more invasive procedures, and in the sucrose group also had more sucrose, ended up with higher NNBRS.
That does not mean that multiple doses of sucrose worsened long term outcomes! This misinterpretation is widespread, and has led to unnecessary limitations of the total number of doses of sucrose to be given in a 24 hour period. A 2012 review for example gave the same limit (based on Celeste Johnston’s own re-analysis that the NNBRS was increased in those who got more than 10 doses per day). There is a statistical association between getting more than 10 doses of sucrose a day and having a higher NNBRS, that doesn’t mean that sucrose becomes toxic above 10 doses a day! It seems very unlikely that sucrose increased acidosis, IVH, PVL, seizures, infections or hypoglycemia, and none of these effects have ever been ascribed to sucrose.
What it does mean though is that if you are performing more than 10 painful skin breaking procedures per day you should try not to! Pain hurts.
What this also means is that trials comparing placebo to sucrose are unethical.
What this also means is that parents should have a word in this debate! Parents out there, demand optimal analgesia for your babies.
Thanks for that thought Annie, I think many parents new to the NICU don’t know how to ask for analgesia. Most of us did not even know the term before we came to the unit.
We need information, unbiased so we can learn to advocate and make sure our babies are experiencing as little pain as possible in their situation. Babies need relief in a way that is least “medicated”.
Maybe we should develop some materials to be given to parents on admission to the NICU, to try and empower them to ask for pain relief.
Dr Barrington: Do you worry about hyperosmolarity of sucrose and its linkage to NEC?
Interesting question: although there are some medications that have been associated with NEC that were hyperosmolar, (such as aqueous vitamin E) and some feeds that led to a very high rate of NEC that were hyperosmolar (such as the old formulation of nutramigen) sucrose has never been associated with NEC in the trials. This might well be because we give such small volumes, 0.1 to 0.3 mL is sufficient for the size of baby that is at risk for NEC, and we give it in the mouth, so it is diluted by saliva even before it enters the stomach to be diluted by gastric secretions.
Pain and pain relief in the NICU is simply something that was never discussed with us. There were several procedures that I know were done without any type of pain relief. The removal of umbilical lines sticks out as something particularly traumatizing.
Pain, light sensitivity, and noise sensitivity were all sort of grouped together in my mind. I assume because they were all treated about the same in the NICU… a concerted effort to reduce exposure to each but in the end there was far too much exposure and little effort to treat exposure. I now know better and wish I demanded better at the time.
Heelsticks became so commonplace and seemingly minor in relation to everything else that I simply did not consider how painful they were at the time. Now I look at the pixelated pattern of scars on my daughter’s outer heel and am reminded on the hundred or so painful “procedures” that should have been at treated in some way.
Is sucrose also used for tape changing, catheter placement, NG/OG placement etc?
The answer to the question is ‘sometimes’. But I think not often. Tape changes are certainly painful, I don’t know for sure if sucrose has ever been investigated for that, but it may not have been, some forms of pain respond better to one treatment compared to another, for example morphine infusions are not very good at preventing pain from heelsticks. I think that for IV catheter placement, the pain is very similar to a heelstick, and we certainly give sucrose here, but with the number of failed attempts it is often difficult to get good analgesia. If you meant for urine catheter placement I would say often nothing is given, For NG/OG placement I think there is a lack of understanding how unpleasant they are, and a dose of sucrose would be a good idea.
I actually published a paper about this in 2011, with Celeste Johnston, (Johnston C, Barrington KJ, Taddio A, Carbajal R, Filion F: Pain in canadian nicus: Have we improved over the past 12 years? Clin J Pain 2011, 27(3):225-232). I can send you a pdf file if you want one and cant otherwise get access, but we measured the proportion of times when pain management was used for several different procedures, it wasn’t a very impressive result.
I give sucrose prior to NG tube placement and tape removal. I’ve passed plenty of NG tubes on adults in the past, they don’t like it and are able to say so, and I see no reason to believe that babies don’t find it just as unpleasant without having the means to tell me.
What dose of sucrose do other people give? I work on the assumption that you only need to give enough per dose to cover the front of the tongue – just two or three drops if you use one of the little pipettes. That’s a tiny amount of sucrose that you don’t have to worry about giving slightly more often.
Dr. Barrington, thank you for your comments on the work of Slater and, later, Asmerom. I don’t have the science to evaluate either for myself with much confidence, and I’m a passionate believer in sucrose.