14: Pain in the Neonate

Before the 1980s, it was a common belief that preterm infants lacked the neurodevelopmental capacity to feel pain. This resulted in severe undertreatment of pain in the neonate during their hospitalization. Although neonatology has made strides in the past 20 years to understand pain, it remains challenged to effectively assess and treat the various types of pain experienced in the neonatal intensive care unit (NICU).

1. Definition. Pain has been defined by the International Association for the Study of Pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in such terms of such damage.” When an infant responds to pain, it involves a collection of biochemical, physiologic, and behavioral reactions. There are many different layers of an infant's response that can be understood by gestational age and development. Noxious stimuli lead to tissue damage, causing the release of sensitizing substances such as prostaglandins, bradykinin, serotonin, substance P, and histamine. These chemicals produce an impulse that is then transmitted to the nociceptive pathways. Nociception refers to the reflex movement occurring with exposure to noxious stimuli that does not require cortical involvement or the ability to perceive pain.

2. Development. Development of sensory nerve endings begins very early in the process of nociception and follows as:

   1. 7.5–15 weeks' gestation. Peripheral cutaneous sensory receptors develop in the perioral, facial, palmar, and abdominal areas and proximal extremities.

   2. 8–19 weeks' gestation. Spinal reflexes are able to respond to noxious stimuli, and neurons populate the dorsal root ganglion.

   3. 20 weeks' gestation. Mucous membranes and remaining cutaneous areas are populated with sensory nerve endings.

   4. 20–24 weeks' gestation. Thalamic afferents involved in conscious perception of pain reach the subplate zone and the cortical plate.

   5. 23–27 weeks' gestation. Thalamic afferents reach the visual cortex.

   6. 26–28 weeks' gestation. Thalamic afferents reach the auditory cortical plate.

3. Repeated exposure to noxious stimuli. This can cause physiologic and behavioral disorganization, leading to changes in the neurodevelopmental system of the infant. This may cause the infant to develop an inability to respond to pain or an exaggerated physiologic response to painful stimuli in the future.

1. Birth trauma. Neonatal pain associated with birth trauma is typically a result of vacuum-assisted births. Some babies may show signs of bruising on the face or head simply as a result of the trauma of passing through the birth canal. Forceps deliveries can leave temporary marks or bruises on the baby's face and head. Cephalohematomas are more common with forceps delivery or vacuum extraction. Tylenol may be used for the treatment of associated pain. Collarbone fractures are the most common birth-related fracture. If the fracture is painful, limiting movement of the arm and shoulder may be helpful.

2. Acute procedural pain. The frequency of painful procedures in the NICU can range from 5–15 per day. The most optimal method of pain control is to minimize the amount of painful procedures. Painful procedures performed in the NICU include endotracheal tube (ETT) suctioning, intubation, mechanical ventilation, chest tube insertion, retinopathy of prematurity (ROP) examinations, central line placement, intravenous (IV) placement, heelsticks, lumbar puncture, circumcision, patent ductus arteriosus (PDA) ligation, and peritoneal drain placement.

3. Acute postoperative pain. Postsurgical pain remains an issue in the NICU. The largest risk with postsurgical pain is undertreating. Postoperative pain protocols help standardize practice between health care professionals. Routine pain assessment should be performed using scales specific to postoperative or prolonged pain. It is important to alternate pain medications for maximum pain control with minimal toxicity. Opioids are the medications of choice and can be given by continuous infusion or bolus.

4. Chronic pain. Chronic pain remains to be well-defined within neonatology. Some view chronic pain as the extension of uncontrolled acute pain. Pain assessment tools should include validated measurement for chronic pain. Research needs to continue to develop in this critical area of pain.

One of the most challenging aspects of neonatal pain is recognition of the symptoms. Careful assessment is critical when evaluating preterm infants for signs of pain. Assessment must include physiologic as well as behavioral symptoms.

1. Common symptoms of pain in the neonate. Commonly assessed symptoms of pain include increased heart rate, changes in respiratory rate, and fluctuations in blood pressure, as well as changes in facial expression such as brow bulge, eyes squeezed shut, nasolabial furrow, crying, and increased movement.

2. Continued pain symptoms. Infants experiencing prolonged pain may exhibit decreased heart rate, decreased respiratory rate, decreased oxygen consumption, lethargy, decreased perfusion, and cool extremities.

3. Pain versus discomfort. Differentiating between infant pain and discomfort can be challenging for health care professionals. Premature infants can exhibit minimal response to pain, especially if they are septic or physiologically stressed. Older infants who have experienced multiple incidents or prolonged pain may over or under react to pain. Lack of pain response can also be observed in infants with neurologic impairment or those who have been chemically paralyzed.

4. Pain assessment scales. Listed below are the four most commonly used pain scales and are compared in Table 14–1.

   1. Premature Infant Pain Profile (PIPP). This scale addresses procedural and postoperative pain. It contains 2 physiologic indicators: heart rate and oxygen saturation. It includes 3 facial indicators (brow bulge, eye squeeze, and nasolabial furrow). Total scores of 7–12 indicate mild to moderate pain requiring nonpharmacologic pain measures. Scores >12 indicate moderate to severe pain and require pharmacologic pain intervention in addition to comfort measures.

   2. CRIES Neonatal Pain Assessment Tool (Crying; Requires O₂ for SaO₂ <95%; Increased vital signs; Expression; Sleepless). This scale addresses postoperative pain in 32–37 weeks' gestation infants as well as procedural pain in preterm and term neonates. It measures 5 parameters, including crying, increase in oxygen requirement, increase in vital signs, expression, and sleeplessness. Total scores range from 0–10. Scores <4 indicate mild pain requiring nonpharmacologic intervention. Scores ≥5 indicate moderate to severe pain requiring pharmacologic intervention as well as comfort measures.

   3. Neonatal Infant Pain Scale (NIPS). This scale addresses procedural pain in preterm and newborn infants as well as postoperative pain. Total scores range from 0 to 7. No parameters for level of pain are included for this tool. Midlevel scoring indicates moderate to severe pain requiring pharmacologic management. It includes the assessment of 5 behaviors and 1 physiologic parameter: facial expression, crying, relaxation or tension in the arms and legs, state of arousal, and breathing pattern.

   4. Neonatal Pain, Agitation, and Sedation Scale (N-PASS). This scale considers pain/agitation and sedation. It is used for both preterm and term neonates with the following types of pain: prolonged, postoperative, and mechanical ventilation. It contains 4 behavioral symptoms and 4 physiologic indicators: crying, irritability, behavioral state, extremities tone, heart rate, respiratory rate, blood pressure, and oxygen saturation. Points are added based on gestational age for a total score. Scores >3 indicate the need for nonpharmacologic or pharmacologic measures. Sedation scores between 5 and 10 are considered deep sedation.

1. Nonpharmacologic. Preferable for mild procedural pain due to the short-term efficacy and absence of side effects. Most effective when combined with a reduction in lighting and sound. Not to be used in place of pharmacologic therapy with severe and chronic pain.

   1. Nonnutritive suck. The type of suck associated with a pacifier without breast milk or formula. When used in combination with oral sucrose (24%), it is effective in reducing the pain associated with heelsticks, peripheral IV catheter (PIV) placement, and ROP examinations.

   2. Positioning. A prone position can cause an improvement in breathing effort and decrease the infant's oxygen requirement.

   3. Swaddling. Wrapping an infant securely in a blanket can cause a decrease in heart rate, an increase in oxygen saturation, and an increase in ability to organize behaviors. Good to use with PIV starts, ROP examinations, and ETT suctioning.

   4. Facilitated tuck. Holding the infant's arms and legs gently in a flexed position. Effective with PIV starts, ROP examinations, and ETT suctioning in decreasing heart rate and recovery time.

   5. Music. Effective in infants >31 weeks' gestation. It assists with the regulation and reduction of heart rate as well as increase in oxygen saturation.

   6. Kangaroo care. Research supports its use to decrease the pain response. It is effective for use in decreasing pain with heelsticks.

   7. Sucrose. When combined with nonnutritive suck, shown to be very efficacious with heelsticks. Facilities should adopt a specific protocol to standardize the use of oral sucrose, which is most effective when combined with nonnutritive suck. Dosage range is 0.012–0.12 g or 0.05–0.5 mL of a 24% solution. Optimal pain relief is noted if given ∽2 minutes before the heelstick followed by 1–2 minutes after completion. Sucrose is effective in infants >27 weeks' gestation; however, it is not approved by the US Food and Drug Administration. Safety regarding repeated dosages of sucrose has been investigated and has been shown to demonstrate ongoing effectiveness. Nonetheless, caution should be taken in administering multiple doses, and administration should be limited to the management of acute procedural pain.

2. Pharmacologic. Most often light pain and moderate pain of short duration are best dealt with by nonpharmacologic pain measures. Pain assessment scores >12 indicate moderate to severe pain and strongly suggest pharmacologic pain intervention along with comfort measures. Procedures that require the use of pharmacologic pain intervention include intubation, mechanical ventilation, chest tube insertion, central line placement, lumbar puncture, circumcision, PDA ligation, and placement of peritoneal drains. Commonly used pain relief drugs in neonates are (see Chapter 148 for specific drug dosing information) as follows: topical: EMLA (eutectic mixture of lidocaine and prilocaine) cream; infiltration: 0.5–1% lidocaine; systemic: morphine, fentanyl, diazepam, midazolam.

As identified by the Neonatal Intensive Care Quality Improvement Collaborative include the following:

1. Reduce the frequency of avoidable painful procedures such as ETT suctioning and heelsticks.

2. Develop protocol for standardization of sucrose administration.

3. Perform frequent pain assessment.

4. Implement strategies to manage pain during the following: heelsticks, peripheral vascular procedures, circumcision, nonemergent intubation, mechanical ventilation.

5. Implement strategies to manage pain during the postoperative period.

6. Implement strategies to wean neonates effectively and safely from opiates.

Pain continues to be an emerging field of study within the discipline of neonatology. Much research is needed regarding the ongoing assessment and treatment of neonatal pain. Heath care professionals need to diligently document pain assessment and follow-up scores postintervention to insure proper pain management. Clinical practice guidelines need to be developed for the neonatal community at large for standardization of practice. Research continues to evolve to support accurate assessment of pain in the neonate. Monitoring skin conduction scores during painful procedures is an area of current investigation. Research is also focused on measuring the impact of pain on the infant's brain. Measurements would include values during the experience of noxious stimuli and the long-term impact on the neurodevelopment of the infant. It is through continuous research and commitment to reducing the experience of pain for the neonate that we will fully understand and effectively treat the neonate while supporting their viability.