Prevention of Procedural Pain in Neonates

Abstract

Neonates admitted to neonatal intensive care units are exposed to a high number of painful procedures for their survival. Faced with a pain that is predictable, it is imperative to implement analgesia before carrying out the procedure, to reduce the impact of the painful experience, maximize the infant’s capacity for recovery, and activate their internal inhibitory control system. In addition, other sources of stress are present in an intensive care environment, which contribute to increase sensitivity of the neonates to future episodes of pain. To minimize the consequences of this harmful environment, especially in the most vulnerable babies, premature and/or those with a serious clinical situation, there are validated recommendations for special care to wherever possible prevent pain, family’s empowerment for comfort care, and support. Pain management is not just about administering a medication or another treatment, but rather integrated approaches that reduce or block the nociceptive activity of the trauma associated with invasive procedures. To minimize the adverse effects, pain management in neonatal care units requires the use of effective pharmacological and non-pharmacological interventions. The selection of analgesic interventions by healthcare professionals will depend on the type of the procedure, as well as the clinical condition of the newborn.

1. Introduction

Neonates in need of special care are exposed to high levels of stress and pain. The International Association for the Study of Pain considers pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or as described in terms of such harm [1]. In neonatal care units, pain from medical procedures for diagnosis or treatment purposes falls under this definition.

Around 24 weeks of gestation, pain pathways are already present, with the ability to detect and transmit sensory information about pain events. Although babies do not verbalize their pain, it is not impossible for them to feel and experience it [2].

Several studies demonstrate the impact of unrelieved pain in early childhood, on the clinical stability of neonates and on the potential to change the physiology of their developing nervous system, on their sensitivity to behavioral abnormalities later in life. To minimize hyperalgesia and allodynia, especially in the most vulnerable infants with severe sickness, the reduction of adverse environment is recommended [3, 4].

For good practices and the safety of neonates in healthcare environments, professionals must consider that if a medical procedure is painful for adults, it will be also painful for infants. This chapter will focus on painful procedures performed on neonates, except pain following surgery, chronic pain, or other painful stimulus persistent in time (e.g., mechanical ventilation).

Some neonates are at high risk of suffering undertreatment of pain, efforts should be focused on those procedures most frequently and on more vulnerable neonates. The key to minimize expected pain in the context of neonate care is the anticipation of the analgesia. There are effective pharmacological and non-pharmacological interventions for pain management. Despite the existence of guidelines for the prevention and minimization of pain associated with invasive procedures, the incorporation of evidence into clinical practice tends to be slow or incomplete. According to studies there is a higher frequency of painful procedures performed in very preterm babies and on those which have a high severity of the disease. For every day of hospitalization, researchers have observed 5 to 17 painful procedures in neonates. Preprocedural analgesia according to guidelines is an actual and a current concern, there is a high variability of practices between clinicians and units of care [5, 6].

2. Pain in neonates

Painful stimulus performed in neonates activates their sympathetic nervous system, which is observable by physiologic changes such as the increase of the heart rate, intracranial pressure, and blood pressure, as by the decrease of the oxygen saturation. Additional observable effects could be included, such as respiratory patterns, sweating, and skin color changes. During painful stimulation, there are also observed behaviourally changes in neonate facial expression, bodily movement, changes in sleeping, activity level, restlessness, and crying. The facial expression of an infant in pain is characterized by an open mouth, bulging brow, eyes squeezed tight shut, taut cupped tongue, and a deepening of the furrow between the nose and corner of the mouth.

When infants are not provided with pain relief, they become stressed, and their cortisol levels increase. Electroencephalography or electromyography methods have been used to identify pain in infants which are useful for the research of the efficacy of several measures for pain management.

Assessing pain is fundamental for making good clinical decisions, must be undertaken, and documented in the individual process of care of the neonate. In this context, pain assessment should be done before, during, and after each potentially painful intervention to evaluate the efficacy of the pre-emptive analgesia, as on the recovery of the neonate to physiological and behavioral changes.

The tools most widely used and recommended for acute pain and clinical practice are summarized in Table 1 [6, 7].

Assessment tool	Population	Physiologic indicators	Behavioral indicators	Context	Score
NFCS; Neonatal Facial Coding Scale [8]	Preterm and term neonates, infants at 4 months of age	None	Facial muscle group movement		0–10
PIPP; Premature; Infant Pain Profile revised [9]	Preterm and term newborn; <28 weeks	Heart rate; Oxygen saturation	Facial expression	Gestational age; Alert status	Full-term newborn 0–18; Preterm newborn 0–21
NIPS; Neonatal Infant Pain Scale [10]	Preterm and term newborn; 28–41 weeks	Breathing pattern	Facial expression; Crying; Movements of the upper and lower limbs	Alert status	0–7
BPSN; Bernese Pain Scale for Neonates [11]	Preterm and term newborn; 27–41 weeks	Breathing pattern; Heart rate; Oxygen saturation; Skin color	Duration of crying; Time to calm down.; Facial expression; Posture	Alert status	0–27
NIAPAS; Neonatal Infant Acute Pain Assessment Scale [12]	Preterm and term newborn; 23–42 weeks	Heart rate; Oxygen saturation; Breathing pattern	Facial expression; Crying; Muscle tone; Reaction to manipulation	Gestational age; Alert status	0–18
N-PASS; Neonatal Pain, Agitation, and Sedation Scale [13]	Preterm and term newborn; 23–40 weeks	Vital signs	Crying; Facial expression; Muscle tone	Gestational age; Alert status	Pain; 0 a 10; Sedation; −10 a 0
EDIN; Echelle Douleur Inconfort Nouveau-né [14]	Preterm newborn; 25–36 weeks	None	Facial expression; Body Movements; Quality of interaction; Comfort	Sleep quality	0 a 15

Table 1.

Acute pain assessment tools on neonates.

3. Predictability of pain on neonatal interventions

Painful events performed in neonatal care units are associated with actual or potential tissue damage of the skin or mucosae of the neonates. According to the degree of the invasiveness of the procedure, it should be categorized as mild to severe pain predictability (Table 2) [7, 8, 9, 10, 11, 12, 13, 14, 15].

Pain scoresa	Mild (0–3)	Moderate (4–6)	Severe (7–10)
Painful procedures	Feeding tube placement; Nasal, Oral suctioning; Umbilical catheterization; Urinary catheter insertion; Gastric tube insertion; Adhesive removal	Heelstickb; Intramuscular injectionb; Subcutaneous injectionb; Venipunctureb; Intravenous cannulationb; Drain removal; Peripheral insertion of central catheterb; Tracheal aspiration; Wound treatment	Tracheal intubation; Chest-drain insertionb; Lumbar punctureb; Eye treatment for retinopathy of prematurity

Table 2.

Categorization of painful procedures performed in neonates.

^a

According to Neonatal Facial Coding Scale.

^b

Needle procedure.

4. Procedural pain management

All neonates have the right to receive optimal comfort to minimize stress and pain, supported by healthcare professionals and their parents. As expected that care providers prevent or treat any infant experiencing pain, avoiding unnecessary pain and discomfort, using appropriate non-pharmacological and pharmacological interventions.

In a neonatal context it is preconized to minimize the impact of the painful experience, with a focus on the maximization of the ability of neonates to recover from it. In this sense, it is not just administering a drug or another treatment, but performing an integrated approach that reduces or blocks the nociceptive activity of the trauma associated with the painful procedure and modifies the situational factors that aggravate it.

The key to manage the pain of invasive procedures is its anticipation. A variety of non-pharmacologic strategies can be implemented in conjunction with pharmacological interventions. Parents or caregivers should be involved to help with comfort measures of pain relief.

Taking care of the environment should be added to the pre-emptive analgesia for painful procedures (Table 3). Minimization of acoustic, visual, tactile, or vestibular stimuli, safeguarding sleep, protecting skin, and optimizing nutrition, reduces stress, and increases the comfort and stability of the neonates [15, 16].

Environmental measures; Promoting silence; minimize the sound of the monitoring devices in the unit. Promoting sleep and rest. Promoting day-night cycle. Protection from bright light, either using dimmable spotlights or using covers in the incubators. Behavioral measures; Minimal manipulation of the neonate. Reduction in the number of procedures (e.g., grouping laboratory tests), and selection of the less painful method (e.g., venepuncture versus heel lance for blood collection). Performed painful procedures only when justified (e.g., aspiration of secretions) Protect skin, use the minimum number of adhesives, and remove it carefully. Preparatory information and parental involvement regarding pain management strategies (e.g., physical contact). Containment of the newborn. Optimal analgesia prior to invasive procedures; Non-pharmacological interventions Pharmacological interventions

Table 3.

Beneficial measures to protect neonates.

4.1 Non-pharmacologic interventions

The quality of procedural pain management in neonates should include neuroprotective core measures, and follow the family-centred care (e.g., partnering with families, and positioning) [7, 8, 9, 10, 11, 12, 13, 14, 15].

4.1.1 Positioning, containment, and swaddling

These interventions consist of restricting the movement of the limbs, and limiting the proprioceptive activity of the tactile system of the newborn. In the neonatal context, containment promotes self-regulation and is not exclusive to the performance of painful procedures but is also considered a protective developmental care measure. As a non-pharmacological intervention, it is recommended to start 3 minutes before, and remain during and after the procedure until recovery of the neonate. Studies have shown that swaddling a preterm reduces the pulse rate in response to procedural pain.

For all procedures consider these strategies, but with considering the association of others non-pharmacological or pharmacological interventions depending on the degree of the pain of the procedure.

4.1.2 Sweet solutions and breastfeeding

Sweet solutions are recommended by numerous professional organizations; however, inconsistencies are raised regarding their classification, especially in relation to sucrose, categorized as a non-pharmacological, or pharmacological intervention. In this chapter, sweet solutions are considered and included in the non-pharmacological group.

Administration of sucrose (24%), glucose (20 to 30%), or breast milk, alone or in combination with other interventions, has been widely studied for the relief of acute pain in preterm and full-term neonates.

Many protocols recommend giving a sweet solution 2 minutes prior to the painful procedure with an estimated volume of 0.5 to 2.0 ml, administered in the anterior portion of the tongue. The recommended dose for a full-term neonate is approximately 2 ml, for premature infants the dose will be smaller (4–10 ml is the total volume of sucrose that can be administered in a 24-hour period).

Breastfeeding, when available, should be the first choice to relieve pain when undergoing painful procedures, such as venepuncture or during heel lance for blood collection. It consists of placing the newborn on the breast, before, during, and after the procedure, and should not be discontinued.

Breastfeeding significantly decreases the variability of the physiological responses of the newborn compared with other interventions (e.g., containment, non-nutritive sucking, and/or administration of sucrose). There is a smaller increase in heart rate, a decrease in the duration of total crying time, and pain intensity. Breastfeeding is a natural alternative and has a similar efficacy to other sweet solutions. In the unavailability of breastfeeding for reasons associated with the mother or the newborn clinical conditions, only breast milk can be used; however, the associated multisensory experience is lost, and analgesic efficacy is lower.

4.1.3 Pacifier and non-nutritive sucking

Non-nutritive sucking refers to the use of a pacifier to promote infant sucking.

The sucking behavior begins to be present between the 24th and 27th week of gestation; however, it’s from the 34th week that becomes rhythmic and strong. Pacifier provides a pain-relieving effect by decreasing the baby’s vitality level and crying time. Studies have suggested that sucking triggers the secretion of serotonin, which directly or indirectly affects the transmission of painful stimuli.

It is recommended to associate non-nutritive sucking with containment, kangaroo care, and/or administration of sweet solutions, including breast milk. Some issues associated with this intervention require special attention in the Baby Friendly Hospital Program where the use of pacifiers is only allowed for newborns in the context of procedural pain management.

4.1.4 Kangaroo care

Kangaroo care has become an accepted practice in many neonatal care units and has been found to be effective in minimizing preterm infants’ pain response to heel sticks. The combination of being with body skin-to-skin contact and hearing a familiar voice helps neonates to regulate themselves. The Kangaroo care method is a natural measure, economic, increasing the release of endorphins in painful stimuli in newborn babies, and is effective in maintaining parents-baby attachment to reduce pain during invasive procedures. Skin-to-skin contact requires time of preparation, and it’s necessary to implement 15 minutes early of the painful procedure.

Low birth weight, neonates weighing <2000 g who are clinically stable should be provided Kangaroo Care early in the first week of life.

4.2 Pharmacological interventions

Pharmacological methods are often needed to control severe acute pain. Although there is significant advances in this area, the balance between pain relief and the risk-benefit of drug effects for neonates remains a challenge for healthcare teams.

Pharmacological options have been investigated in clinical trials with infants, widely tested, and implemented for analgesia on procedural pain.

The most used for moderate-to-severe pain are acetaminophen and the nonsteroidal anti-inflammatory drug, in combination with opioids (e.g., morphine, fentanyl), or adjuvant analgesics namely sedatives, antidepressants, or anticonvulsants.

Nowadays there are other options, such as local anesthetic cream (effective only after 30 to 60 minutes of application, depending on the specific medication), or appropriate analgesia administered by a non-painful route, such as intranasal fentanyl.

The following table briefly presents analgesia recommendations for the most frequent procedures performed in neonatal units of care (Table 4) [7, 8, 9, 10, 11, 12, 13, 14, 15].

Procedure	Analgesia	Recommendations
Gastric tube insertion	Non-pharmacological measures.	Perform rapidly, and avoid injury.; Use lubricant.
Umbilical catheterization	Non-pharmacological measures.	Avoid sutures on skin around the umbilical stump
Tracheal aspiration in ventilated newborn	Non-pharmacological measures.; Consider opioid infusion.	Consider this procedure only when secretions are present and not routinely.; Perform the technique rapidly, preferably in a closed circuit, with 4 hands.; Limit aspiration to the beginning of the endotracheal tube.
Venipuncture Intravenous cannulation	Non-pharmacological measures.; Consider topical anesthetic.
Heelstick	Non-pharmacological measures.; Consider skin-to-skin contact.	Venipuncture should be considered.; Gentle manipulation of the heel.; Use mechanical devices instead of the manual lance.; Note: Topical anesthetic, acetaminophen, and warming heel are ineffective.
Peripheral insertion of central catheter	Non-pharmacological measures.; Consider topical anesthetic.; Consider opioid infusion.
Subcutaneous and intramuscular injections	Non-pharmacological measures.; Consider topical anesthetic.	Avoid the intramuscular route, preferring, whenever possible, the intravenous route.
Suprapubic puncture	Non-pharmacological measures; Topical anesthetic; Consider acetaminophen, opioid infusion, or subcutaneous infiltration—nerve block
Tracheal intubation	Consider opioid infusion, a small dose of intravenous ketamine.; Intubation with a muscle relaxant (if an experienced clinician is present) is strongly recommended.	Intubation without analgesia only in delivery room resuscitation situations and/or emergency situations. Ideal sequence: Oxygen Neuromuscular blocking agents Analgesic and/or hypnotic Muscle relaxant
Wound dressing	Non-pharmacological measures.; Consider acetaminophen, and opioid infusion.	Consider acetaminophen, opioid infusion, deep sedation, or general anesthesia for extensive or deep wounds.
Ophthalmological screening	Non-pharmacological measures.; Consider topical anesthetic (eye drops).; Consider opioid infusion with opioid bolus or ketamine.	Avoid or use blepharostat instruments.; Monitor the procedure with the appropriate pain scale.
Chest tube removal	Non-pharmacological measures.; Consider topical anesthetic.
Chest tube placement	Non-pharmacological measures.; Topical anesthetic.; Consider opioid infusion.	Opioid bolus in ventilated neonates. In non-ventilated patients, consider ketamine bolus, always anticipating the need for ventilatory support.; Monitor procedure with appropriate pain tools and adjust analgesia (bolus or opioid perfusion) according to the score of pain.
Lumbar puncture	Non-pharmacological measures.; Consider topical anesthetic if not urgent or subcutaneous infiltration with lidocaine.; Consider opioid infusion or midazolam.	Avoid extreme flexion of the neck, regardless of the selected position (risk of trauma and hypoxemia).

Table 4.

Pain management for the most common neonatal procedures.

The selection of the interventions above described should not be generalized to all neonates but should recognize and follow an individual pain management approach [16]. In all the situations, combining two or more non-pharmacological interventions has an additive and/or synergistic effect on minimizing pain. With pharmacological measures, this association has benefits to reduce the dose, frequency, and possible side effects of the drugs.

Advances in technologies are becoming an opportunity for pain management by healthcare teams, new alert items, pain assessment tools in informatic devices, and new fields for non-pharmacological intervention documentation [17].

5. Recognizing neonates at high risk of pain

The identification of the main factors associated with neonatal procedural pain, allows a better care for pain prevention and protection of premature and/or sick babies in neonatal intensive care units.

Several observational studies identified factors related to a higher incidence of painful procedures in premature infants and in the first 3 days of the neonate in the unit stay [5, 6]. The most frequent acute pain results from skin-breaking procedures. Preterm infants with very low birth weight, and/or neonates receiving nasal oxygen, continuous positive airway pressure, or ventilation support, are exposed to a high number of procedures.

Prematurity is associated with a greater use of specific pre-procedural analgesia, and ventilated preterm neonates, with the lowest gestational age, which has the lowest amount of pharmacological pain relief during procedures. Neonates at the highest risk for neurological impairment have the lowest number of opioids administered during the first day of life.

Sweet-taste solutions are less likely to be used in infants in the first week of life and vary significantly during tissue damaging procedures. Less pre-procedural analgesia is used during the first day of admission as well as during the night shift. Considering the type of painful procedures, pharmacological analgesia is significantly higher for needle sticks.

Regarding organizational context as a predictor for pain management, the existence of pain protocols was not a predictor for analgesia use. Parental presence during procedures was predictive for a greater use of specific pre-procedural analgesia.

Optimal pain management according to clinical guidelines needs to be incremented, especially for procedures with an expected moderate to high score of severe pain, in the first week of a neonate’s hospitalization [6].

6. Best practices on procedural pain management

Good practice recommendations are considered essential for clarifying and contextualizing measures to reduce pain associated with painful procedures in neonate care units.

6.1 Preventing neonate pain and relief

• It must be mandatory to anticipate pain before carrying out the procedures.

• Consistent pain management is important to reduce adverse effects, promote comfort, attachment, and self-regulation.

• Consider a multimodal analgesic approach to procedural pain management in neonates.

• Implement effective pain management strategies.

• Family is encouraged, empowered, and supported to provide comfort to their infant.

• The selection of the most appropriate medication-based treatment approach for a preterm or term infant involves a careful analysis of risks and benefits.

• Use the most efficacious and least invasive way to administer analgesic drugs.

• Efforts should be aggregated for the implementation of strategies on modifiable predictive factors for neonates’ pain in their first days of life.

• Developing best-approach protocols for acute pain in neonates to develop uniformity in pain management and reduce the wide variability of practices.

• Protocols must be updated and multidisciplinary as a clinical tool to support informed decisions about effective pain relief.

• Using standardized pain assessment tools.

• Pain assessment requires training and education.

6.2 Creating a neonate-centred care

• Develop a neonate plan for pain management. Identifying neonates at high risk for painful procedures is essential for optimizing pain care (e.g., critically ill infants, and premature babies).

• Taking a history of the pain, including the history of painful procedures, from the first day of hospitalization of the neonate in the unit. Frequency, location, and intensity, what interventions have been undertaken, and the impact of the pain.

• Observing how the neonate’s pain presents, physically, emotionally, and behaviourally. The best way of judging whether a baby is in pain is to observe carefully, and know his patterns.

• Pain assessment should be ongoing and incorporated into the plan of care for all neonates.

• Infant response to analgesic interventions should be documented and guide future management strategies.

• Empowering the parents, providing individualized support and family collaboration.

• Providing information to families on the importance of pain management and their involvement in the process.

• Parents were invited to participate in their baby’s comfort care.

• Both clinicians and families can work towards the direction of more personalized pain management strategies. For neonates include breastfeeding, non-nutritive sucking, swaddling, skin-to-skin touch, positioning, and containment.

• Parents were permitted to be present at all procedures and to participate in making decisions.

6.3 Decreasing procedural pain

• Routine procedures should be avoided.

• Carry out diagnostic and therapeutic procedures more safely, with materials suitable and with experienced professionals or skills training.

• In relation to more invasive and severe painful procedures, it is suggested to carry out pain management education and multidisciplinary simulation training.

• Institutionalizing Pain Management. Appropriate pain management becomes part of the culture of care.

• Creating an interdisciplinary work group with administrative authority to guide changes.

• Development of explicit policies and protocols.

• Create a culture of comfort and reduce pain for all children in the institutional system.

• An ongoing education. Educational initiatives at the site of care in small groups and be repeated frequently.

• Audits with feedback

• Applies to children’s rights, ‘right to receive relief from pain and suffering to the maximum extent possible’.

• Inadequate pain relief is considered malpractice.

7. Conclusion

Pain is commonly from medical procedures for diagnosis or treatment purposes, performed in newborn infants, term, or preterm, which require special care. To reduce the impact of pain in neonatal units, it is mandatory to associate painful procedures, with effective measures for the prevention of pain. Healthcare professionals and parents recognize the vantages of the implementation of an individualized developmental care approach to reduce and avoid pain and discomfort experienced during neonate stay in the hospital.

Pain is regarded as a human rights issue, and education and skills training are mandatory to perform procedures more safely, with appropriate materials, and optimal pain relief measures. Protocols should be up to date, with a multidisciplinary focus, avoiding unnecessary pain and discomfort in neonates.

Acknowledgments

The author thanks to the Pain in Child Health, a research training initiative of the Canadian Institutes of Health Research, for sharing knowledge and promoting the development of the study of pain in neonates and children. This work is funded by national funds through the Foundation for Science and Technology, under the project UIDP/04923/2020.

Conflict of interest

The authors declare no conflict of interest.