a. Tachycardia

b. Tachypnea

c. Elevated blood pressure (with secondary increase in

intracranial pressure)

d. Decreased arterial oxygen saturation

e. Hyperglycemia secondary to hormonal and metabolic stress responses

3. Behavioral indications consistent with perception of

pain (8,18–20)

a. Simple motor responses (i.e., withdrawal of an

extremity from a noxious stimulus)

40 Section I ■ Preparation and Support

b. Facial expressions (i.e., grimace)

c. Altered cry (primary method of communicating

painful stimuli in infancy)

d. Agitation

D. Specific Indications

1. Analgesia

In general, the potency of analgesic treatment selected

should be related directly to the anticipated or assessed

level of pain (1,7).

a. Mild pain

(1) Nonpharmacologic approaches (see H)

(2) Local and/or topical anesthesia

(3) Nonopioid analgesics (e.g., acetaminophen)

b. Moderate and severe pain

(1) IV opioid analgesics (see E)

(2) Local and/or topical anesthesia

(3) Benzodiazepines (see E)

2. Sedation

Sedatives may be co-administered with analgesics to

enhance the anticipated benefits. Because of the escalated risks associated with deep sedation, conscious

sedation should be the usual clinical endpoint.

a. Benzodiazepines (see E)

b. Chloral hydrate (see E)

c. Nonpharmacologic approaches (see H)

E. Precautions

1. Be aware, when assessing patients, that

a. The clinical assessment of pain in the newborn is

imprecise. The Neonatal Pain Agitation and

Sedation Scale (N-PASS) was recently developed to

assess ongoing pain, agitation and sedation levels in

term and premature neonates (19). Neonatal pain

scales vary in content, utility, reliability, and ease of

use and include physiologic, behavioral, and contextural parameters (18–20,25) (see Appendix A.1).

b. Physiologic and behavioral indicators of pain are

nonspecific and may be related to many other factors.

Ideally, a neonatal pain scale would be fast and

easy to use; have reliability and validity for term, preterm, ventilated, and sedated neonates; be able to

discriminate between other states (e.g., hunger);

and account for confounding factors (e.g., medications, sepsis, cardiac disease) that may reduce the

specificity of behavioral and physiologic responses.

In reality, however, these scales show varying degrees

of sensitivity and specificity (which markedly effects

interpretation), a wide interrater variability of pain

scores that can reduce the sensitivity, and behavioral

responses of the preterm or neurologically impaired

neonate (which can reduce the specificity of the

pain assessment) (20).

c. Intubated neonates receiving muscle relaxants may

have altered physiologic indicators and completely

ablated behavioral indicators.

d. A high index of suspicion is required to identify

newborn infants in pain (1,8,18).

2. Be aware, when medicating patients, that:

a. There are numerous potential complications associated with analgesic and sedative agents (Appendix

A.2) (26–28). Commonly used sedatives and

analgesics for the pediatric patient are listed in

Appendix A.2.

b. Large inter- and intraindividual variations in

response have been documented (26–30). In addition, data have been steadily accumulating on the

PK/PD of sedatives and analgesics in the newborn

(31–34). Neonates, especially premature neonates,

have immature hepatic microsomal enzyme systems

which mature over 3 to 6 months (15). Many drugs,

including morphine, are metabolized by these systems; therefore, these neonates will have significant

increases in half-life (>50%) compared with adults

and older children for these agents (29,30). The glomerular filtration rate (GFR) is decreased during

the first week of life, affecting the elimination of

active metabolites of opioids (e.g., morphine)

(29,30). Preterm infants will primarily produce the

M3G metabolite of morphine, which has antianalgesic properties and a longer half-life compared

with morphine (30). Neonates have a large percentage of body mass as water and a decreased plasma

concentration of albumin and alpha-glycoprotein

(12,15). These variables influence the PK/PD of

sedatives, analgesics and concomitant medications,

which may interact with these agents (34).

c. Medications must always be titrated slowly (1,6–

8,26).

d. Co-administration of opioids, benzodiazepines, and

other sedatives may result in greatly exaggerated

respiratory depressant effects, including apnea (26).

This combination requires a decrease in dosage of

each medication.

3. Resuscitation equipment and medications should be

immediately available. Be prepared to support ventilation and perform tracheal intubation if needed; respiratory depression is a common side effect of a number of

analgesic and sedative agents (21).

4. Be aware that

a. Newborn infants who have developed tolerance to a

sedative or analgesic agent, by either direct or in

utero exposure, may exhibit symptoms of the neonatal abstinence syndrome upon abrupt cessation of

the drug or administration of the appropriate reversal agent (e.g., naloxone or flumazenil) (24,35). For

example, naloxone administered to opioiddependent neonates may precipitate acute, severe

withdrawal symptoms (24).

Chapter 6 ■ Analgesia and Sedation in the Newborn 41

b. Chronic analgesic therapy with agents known to

induce tolerance, such as opioids, should be weaned

gradually, with close monitoring for evidence of

withdrawal symptoms. Administration of semisynthetic opioids, such as fentanyl, produces tolerance

more rapidly in infants and young children compared with the natural opioids (35). Tolerance may

be produced within 3 to 5 days with fentanyl, compared with 1 to 2 weeks for morphine (21,35).

Fentanyl is frequently used in neonates undergoing

very painful procedures because of its rapid onset of

analgesia, hemodynamic stability, and ability to prevent pain-induced increase in pulmonary vascular

resistance (21,35).

5. When using analgesics for a painful procedure

a. Consider both the duration and the intensity of

anticipated pain when selecting medications and

methods. For example, short procedures with mild

to moderate discomfort, such as lumbar puncture,

may be best managed with topical and local anesthetics (1,5–8).

b. Minimize the number of painful episodes. Multiple

procedures performed at the same time may avoid

the need for repeated administration of analgesics.

c. Ensure that oxygen, suction, airway, resuscitation

equipment, and reversal agents are readily available.

d. Follow nothing-by-mouth guidelines for surgery.

e. Have a nurse or other professional not involved in

the procedure constantly monitor respirations, pulse

oximetry, heart rate, and level of consciousness.

6. Chloral hydrate, is no longer regarded as a first-line,

safe sedative for infants or young children (36–38). This

agent should be used with caution in neonates (particularly premature neonates) secondary to the risk of

hyperbilirubinemia and accumulation of toxic metabolites. For these reasons, a single dose only is recommended if other agents are not appropriate or available.

F. Advantages and Disadvantages of

Commonly Used Agents in the

Pediatric Patient

See Appendix A.2

G. Complications

See Appendix A.2

H. Nonpharmacologic Approaches

1. Swaddling and skin-to-skin contact during heel-stick

procedures has been shown to reduce behavioral pain

responses (1,6).

2. Nonnutritive sucking has been demonstrated to significantly reduce crying in response to painful stimuli (1,6).

3. Sucrose (1,6,8,39)

a. Infants who drank 2 mL of a 12% sucrose solution

prior to blood collection via heel stick cried 50% less

than control infants during the same procedure.

b. Infants who received sucrose on a pacifier prior to

and during circumcision cried significantly less than

control infants.

c. 2 mL of 12% to 50% sucrose administered orally

2 minutes prior to the procedure is an effective neonatal analgesic with few adverse effects. However, there