Neonatal Pain Assessment
Historically a lack of knowledge and understanding on neonatal pain has hindered the development of comprehensive pain management strategies in the clinical area (Rouzan, 2001). There was a misconception that neonates were incapable of experiencing pain. This was a view accepted by many clinicians in the medical community (Alexander and Todres, 1998). These views were based on underlying theories that neonates had an underdeveloped central nervous system and a lack of pain receptors. There was also an assumption that new fibres require myelination to function in pain perception and that neonates were unable to remember painful experiences (Frank and Gregory, 1993, Stevens et al, 1995). Pain responses in preterm neonates were thought to be largely sub cortical, with functional maturation of higher brain centres being required to produce a pain experience. However recent studies dispel this theory by highlighting that acute pain activates the sensory cortex in even the extreme preterm neonate (Bartocci et al, 2005, Fitzgerald, 2005). Developmental neurobiologists also now support the view that neonates can experience pain and demonstrate specific pain behaviours. Fitzgerald and Howard (2003) reflect that early periods of development are particularly vulnerable to the effects of acute or repetitive pain exposures.
Research by Brummelte et al (2012) & Ranger et al (2014) has shown a positive association between the number of painful procedures and increased risk of poor neurodevelopmental outcomes in preterm infants.
Pain Management
Strategies have been developed in many units to manage post operative pain and major procedural pain. However the implementation of strategies to management or prevent pain during minor procedures such as venepuncture and heel lance remain poorly developed (Anand, 2001).
The Administration of Sucrose as a Method of Pain Management
In recent years the administration of oral sucrose with or without non-nutritive sucking has been extensively studied for the relief of procedural pain. Sucrose has been reviewed for its effect in crying babies (Smith, 1992), and its pain relieving effects for procedures (Stevens 1997).
How Does Sucrose Work
The physiological effects of oral sucrose and non-nutritive sucking are thought to be mediated by both endogenous opioid and non-opioid systems (Blass 1999). However the underlying mechanisms are believed to differ. The mechanisms involved are likely to be dependent on the normal functioning of central mechanisms, and may be synergistic or additive.
Evidence of Outcome
Cochrane review 2016: There was high-quality evidence for the beneficial effect of sucrose (24%) with non-nutritive sucking (pacifier dipped in sucrose) or 0.5 mL of sucrose orally in preterm and term infants: There was high-quality evidence to support the use of 2 mL 24% sucrose prior to venepuncture: and intramuscular injections:
Ramenghi et al (1999) reported that the administration of sucrose to the stomach by nasogastric tube was not an effective analgesia. The onset of action is reportedly 10 seconds, and is therefore so rapid that there is not enough time for absorption to occur (Blass and Shah, 1995). The duration of action is 5 to 10 minutes with the peak action being around 2 minutes. Sucrose cannot therefore be related to clearance from the circulation of any measurable agent (Blass and Shah, 1995).
Clinical Application
Neonates routinely experience pain and discomfort from both invasive and non-invasive procedures in the neonatal unit. The benefits of sucrose administration during heel lance and venepuncture has been well documented (Carbajal, 2003, Abad et al, 1996, Johnston, 1998). There is now extensive evidence in support of the administration of sucrose for procedural pain, frequently in conjunction with both pharmacological and non-pharmacological interventions (Anand, 2001).
Further clinical indications for the administration of sucrose include eye examinations, oral suctioning, subcutaneous or intramuscular injection, nasogastric or orogastric tube insertion (Anand, 2001). The use of sucrose in addition to pharmacological measures has been recommended in more invasive procedures such as central catheter placement, lumbar puncture and chest tube insertion (Anand, 2001).
Dosing and Gestational Age Parameters
There is insufficient evidence to recommend optimum dosing and age parameters for sucrose administration (Stevens et al, 2004). A Cochrane systematic review conducted in 2004 reported that sucrose volumes ranging from 0.05ml to 2ml had been identified (Stevens, 2004). However it is not the volume but the sweet substance that produces the analgesic effect, therefore studies report 0.05ml to 0.5ml of 24% to 25% sucrose as an adequate volume (Stevens et al, 2004, Stevens et al 2010).
Carbajal (2002) and Gibbons et al (2002) reported that sucrose can be effective in neonates as young as 25 weeks gestation. However there have been concerns surrounding developmental outcomes in infants less than 32 weeks corrected gestational age (Stevens 2004). Barr et al (1999) in an early study reviewed sucrose administration during immunisation. The authors reported that sucrose was less effective in infants older than 3 months. Lefrak et al (2007) in a review of sucrose analgesia highlighted that it should be emphasised to clinicians that it was the sweet taste that produced the analgesic effect and not the volume of sucrose administered. The authors reflected that this would reduce potential administration errors caused by giving large volumes and giving the solution via a nasogastric tube. Emphasis should also be placed on the 2- minute peak effectiveness and the fact that the duration of sucrose action is temporary and the analgesic not sedative for the irritable infant (Lefrak et al 2007).
There is evidence that some sucrose analgesic effects persist up to 12 months of age although numbers of studies including children over 3 months old are limited. Sucrose solutions of 24% or stronger reduce the cry duration after immunisation (Barr 1995, Levindon 1998 & Thyr 2007). Studies conducted to date on children older than 12 months have failed to provide consistent evidence of pain reduction. It seems reasonable to offer sucrose to infants up to 12 months old, whilst being aware the effects are not as profound or reliable as following its administration in neonates.
Recommendations for Administration
Studies have reviewed the optimum method of administration. This can range from sucrose administered via a syringe on to the tongue, sucrose directly on to a pacifier (dummy) or sucrose administered on the tongue followed by giving the baby a pacifier. It has been reported that the optimum effect is achieved from either administering sucrose on to the tongue followed by a pacifier (Gibbons et al 2002) or by giving a pacifier dipped in the sucrose solution (Stevens et al 1999). It is also recommended that the effect of sucrose could be further enhanced by utilising other comfort measures such as facilitated tuck, swaddling kangaroo care.
Adverse Effects of Sucrose
Few studies have reported on adverse effects as a result of sucrose administration. However in a randomised controlled trial, Johnston (2000) reported lower scores on certain components of the “Neurobehavioural Assessment of the Preterm Infant” in babies who received higher numbers of doses of sucrose than those who received fewer. The babies who received more doses also had Neurobiological Risk Scores at 2 weeks postnatal age but not at discharge. As a result of the possible long term effects which have been implicated by these findings it has been advised that sucrose be used with caution and limited numbers of doses given in infants less than 32 weeks post conceptual age. However Stevens et al (2005), in a study reviewing management of repeated procedural pain with sucrose, concluded that the ongoing use of sucrose in infants with prolonged hospitalisations requiring repeated doses of sucrose over time resulted in no long term adverse effects.
Short-term side effects of oral sucrose were reported by two studies. Carbajal (2002) reported slight transient oxygen desaturation in 7 of 54 of their sample of neonates who received 0.3 ml of 30% sucrose. Gibbons et al (2002) reported adverse effects as those which occurred immediately after administration such as choking coughing, vomiting. Adverse effects were noted in most often in the immature infant (4 of 23). The adverse effects were not clinically significant and none of the infants who received sucrose with non-nutritive sucking had any adverse effects. Further concerns in relation to possible adverse effects have been alterations in glucose homeostasis and necrotising enterocolitis. Sucrose however has not been proven to cause these adverse effects (Lefrak et al 2007).
Further Research:
There has been abundant evidence showing statistically significant reduction of behavioural pain outcomes after sweet taste analgesia. There have been many studies in the last decade to understand the mechanism of pain better in the non verbal population in order to determine the treatment strategies. In future, neonatal pain studies using oral sucrose should select more ethically acceptable topics rather than continue to conduct “placebo” or “no treatment” controlled trials in infants. Further research should focus on dosing and any effect on long term neurodevelopment.