Providing adequate pain management for procedure-related pain remains complex for infants in the Neonatal Intensive Care Unit (NICU). Although research has been conducted to find ways to manage pain, effective treatments that are free from adverse effects are elusive. Indeed, in a joint statement by the American Academy of Pediatrics and the Canadian Paediatric Society, the committees reported that major gaps remain in our knowledge regarding the most effective ways to prevent and relieve pain in neonates.1
Currently, for preterm infants, severe pain, such as postoperative pain, is controlled with pharmacologic agents.2,3
However, sweet solutions, primarily sucrose, have been recommended extensively for minor procedural pain relief in term and preterm infants.4
A host of individual studies and a recent Cochrane review revealed that single doses of sucrose administered orally reduce crying, facial grimacing, motor activity, and, in some cases, heart rate in term, preterm, and older infants during minor painful procedures.5–9
Those in many NICUs consider the use of sucrose the clinical standard for managing acute procedure-related pain. In fact, across Canada, 64% of the nurseries have protocols for administering sucrose for procedural pain management; nevertheless, extensive variability in specific dosing guidelines between units is evident.10
Another group conducted an extensive chart review of critically ill infants hospitalized for >28 days and found that, over the course of their NICU stay, sucrose was administered 40% of the time, and an additional 17% of the time sucrose was used in combination with morphine.11
Of concern here is the use of sucrose in combination with opioids when empirical evidence for efficacy and/or safety is absent.
It is important to note that preterm or critically ill term-born infants undergo repeated skin-breaking events. The average number of painful procedures can be as high as 15 per day in the first few weeks of life.12,13
If sucrose were administered for each procedure, the tiniest and sickest infants could be exposed to relatively high volumes of sugar during a period of rapid brain development.14
To give this level of exposure some perspective, if an infant who weighs 1000 g has even 10 painful procedures per day, and for each procedure 0.5 to 1.0 mL of 24% sucrose is given, we would be administering the same quantity as if we were giving a 10-kg1-year-old a half can of Coke Classic per day, the concentration of sugar in a Coke Classic being ~11% (42 g/355 mL). Although we recognize that our example is of a liquid that has additional constituents that may add to its negative effects (eg, caffeine), our intent is to provide an example understood by a wide audience and one to which adults themselves could easily relate.
To date, 4 studies have examined the effects of repeated doses of sucrose over specific time periods. In the first study, infants born at <31 weeks’ gestation were given either sterile water or 0.1 mL of 24% sucrose during the first week of life.15
Infant development was assessed at 32, 36, and 40 weeks of age. At ages 36 and 40 weeks, greater exposure to sucrose (>10 doses in 24 hours) was associated with poorer motor and attentional developmental outcomes. In another study, infants born between 27 and 30 weeks’ gestational age were given 0.1 mL of 24% sucrose before all painful procedures until 28 days of life or discharge.16
The average cumulative number of procedures over the 28 days in which sucrose was administered was 248, with 71 of these procedures occurring in the first week of life. Early clinical outcomes and safety were evaluated. A very low incidence of adverse events was reported, and the incidence of hyperglycemia, oral infections, necrotizing enterocolitis, intraventricular hemorrhage (grades III or IV), or death did not differ between treatment and control groups. However, developmental outcomes were not assessed. Next, either sterile water or lower volumes (0.5 mL/kg) of 25% sucrose were given to infants born at 25 to 33 weeks’ gestational age for each procedure over 3 days.17
No immediate adverse effects were found, and pain responsiveness remained constant; however, once again, developmental effects were not assessed. Finally, in the most recent study, sucrose did not prevent the development of hyperalgesia in term-born infants of diabetic mothers given sucrose for all needle procedures in the first 24 hours.18
In summary, although it seems that in the short-term sucrose is safe,9
only 1 study has evaluated later neurodevelopment.15
Of critical importance is the fact that the existing studies addressed effects of sucrose administered in preterm infants over a brief period of only 3 days,17
the first week of life,15
or the first 28 days16
and in term infants in the first day.18
However, for infants born very preterm, sucrose is used over longer periods, and the relatively high cumulative amount of sucrose during the entire NICU stay has yet to be evaluated.
In the following section we highlight research that has examined mechanisms of action, including studies of neurochemical alterations after chronic sugar exposure found in animal models.