Newborns are often exposed to minor invasive
procedures such as venepuncture. Current evidence suggests that neonates
are able to perceive pain. Studies have documented that babies born at
less than 32 weeks of gestation are exposed to 10-15 painful procedures
each day during the first few weeks of life, and in almost 80%, no
treatment for pain relief is offered [1]. Pain in neonates is known to
cause adverse short and long-term effects. Prolonged or repeated pain
also increases the response elicited by future painful stimuli (hyperalgesia)
and even by usually non-painful stimuli (allodynia). The consequences
include altered pain sensitivity (which may last into adolescence) and
permanent neuro-anatomical, behavioral, emotional and learning
disabilities [2].
Healthcare providers are constantly on the lookout
for a safe and effective pharmacological or non-pharmacological method
to alleviate pain in neonates. Orally administered sweet solutions such
as glucose and sucrose have been shown to be effective in reducing
procedural pain in neonates. One Cochrane review examined 44 randomized
trials enrolling 3496 infants for efficacy, effect of dose and safety of
sucrose for relieving procedural pain in neonates [3]. Despite
significant clinical heterogenicity in the dose of sucrose and tools
used to measure effect of pain, there was significant reduction in total
cry time and composite pain scores during heel lancing. Expressed breast
milk (EBM) which contains 7% lactose is a good physiological alternative
[4]. Studies have reported the analgesic effect of breastfeeding before,
during and after venepuncture [5].
Despite convincing evidence, routine measurement of
indicators of pain and use of pain-relieving measures is limited.
Non-availability of sucrose in India and aversion of many neonatologists
to administering anything other than breast milk to neonates may be
contributing factors. In this issue, Sahoo, et al. [6] report
reduced cry duration and pain score on using EBM or 25% dextrose before
venepuncture. Their study shows 25% dextrose was more effective; EBM
also significantly reduced the cry duration and pain score. Although,
this is a well-conducted randomized controlled trial, exclusion of
eligible subjects after obtaining consent and allocation of study group
is undesirable. Probability of selection bias in such a scenario defeats
the purpose of randomization. Administration of high concentration of
dextrose can potentially cause hyperglycemia, rebound hypoglycemia and
difficulty in subsequent breastfeeding. It is not clear whether
investigators looked for these side effects.
There are inherent difficulties in conducting studies
on neonatal pain. Standardization of dose of exposure (amount of pain)
is difficult. Amount of pain inflicted is dependent on who conducted
venepuncture, with what type/brand of needle and how the prick was
given. Another concern with studies evaluating measures to reduce pain
in neonates is about choice of a valid measure to detect and quantify
pain. A recent study has suggested that although sucrose decreases
clinical observation scores, there is no reduction in nociceptive brain
activity and magnitude or latency of the spinal nociceptive reflex
withdrawal response [7]. Whether the ability of sucrose to reduce the
pain score or the duration of cry can be interpreted as reduced pain is
not clear. Further studies are needed to evaluate the effect of sucrose,
breast milk or other non-pharmacological measures in high-risk groups
like extreme premature neonates exposed to repeated painful stimuli.
Future studies should aim to report effect of these measures on
long-term cognitive and behavioral outcomes.
1. Stevens B, McGrath P, Gibbins S, Beyene J, Breau
L, Camfield C. Procedural pain in newborns at risk for neurology
impairment. Pain. 2003;105:27-35.
2. American Academy of Pediatrics, Committee on Fetus
and Newborn, Section on Surgery and Section on Anesthesiology and Pain
Medicine. Prevention and management of pain in the neonate: an update.
Pediatrics. 2006;118;2231-41.
3. Stevens B, Yamada J, Ohlsson A. Sucrose for
analgesia in newborn infants undergoing painful procedures. Cochrane
Database Syst Rev. 2010; 1. CD001069; CD001069.pub 3.
4. Upadhyay A, Aggarwal R, Narayan S, Joshi M, Paul
VK, Deorari AK. Analgesic effect of expressed breast milk in procedural
pain in term neonates: a randomized, placebo-controlled, double-blind
trial. Acta Paediatr. 2004; 93:1-5.
5. Shah PS, Aliwalas LL, Shah VS. Breastfeeding or
breast milk for procedural pain in neonates. Cochrane Database Syst Rev.
2006; 3:CD004950.
6. Sahoo JP, Rao S, Nesargi S, Ranjit T, Ashok C,
Bhat S. Expressed breast milk vs 25% dextrose in procedural pain
in neonates, a double blinded randomized controlled trial. Indian
Pediatr. 2013;50:203-7.
7. Slater R, Cornelissen L, Fabrizi L, Patten D,
Yoxen J, Worley A, et al. Oral sucrose as an analgesic drug for
procedural pain in newborn infants: a randomized controlled trial.
Lancet. 2010; 376:1225-32.