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CHAPTER 12 Pain and Pain Relief

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299

BOX

12.5

• Is the infant being adequately assessed at appropriate intervals?

• Are analgesics ordered for prevention and relief of pain?

• Is the analgesic strong enough for the pain expected or the pain

• Is the timing of the drug administration appropriate for the pain

• Is the route of administration appropriate (preferably oral or intrave-

• Is the infant adequately monitored for side effects?

• Are side effects appropriately managed?

• Has the analgesic regimen provided adequate comfort and satisfac-

CRITICAL QUESTIONS TO ASK ABOUT PAIN MANAGEMENT IN NEONATES

being experienced?

expected or being experienced?

nous) for the infant?

tion from the family’s perspective?

Questions to Consider About Nonpharmacologic Strategies

• Is the strategy appropriate for the infant’s developmental level, condition, and type of pain?

• Is the timing of the strategy sufﬁcient to optimize its effects?

• Is the strategy adequately effective in preventing or alleviating the infant’s pain?

• Is the family satisﬁed with the strategy for prevention or relief of pain?

From Agency for Health Care Policy and Research, Public Health Service. Acute Pain Management Guideline Panel. Acute Pain Management: Operative or Medical Procedures and Trauma—Clinical Practice Guideline. AHCPR Pub No 92-0032. Rockville, MD: U.S. Department of Health and Human Services; 1992.

Laboratory Data

Hormonal and metabolic changes are listed in

Box 12.1. Serum glucose levels and reagent test

strips monitor for hyperglycemia, which may result in increased serum osmolality and increase the risk for IVH. Glucosuria, ketonuria, and proteinuria result in elevated specific gravity. Metabolic acidosis may result from increased serum levels of lactate, pyruvate, ketones, and nonesterified fatty acids. These data also may be indicative of other serious neonatal problems (e.g., sepsis, acute tubular necrosis).

In the search of more objective measures of pain assessment, use of heart rate variability (HRV), skin conductance (SC) measurements, and brain-oriented techniques such as NIRS, EEG, and magnetic resonance imaging (MRI) are being investigated. Although HRV is a reliable measure of the neonate’s response to acute and prolonged pain,

135,155

lack of

availability of monitoring devices may preclude its use clinically.98 SC, which measures stress-induced sweating in the palms and soles of the feet, has shown conflicting results in research, especially in preterm infants.

206,292,381,402

This requires further investigation in the preterm infant before it will be ready for clinical use.

403

After heel lance, there is an increase of skin blood flow as measured by laser Doppler imaging that correlates to NIPS scores. In a randomized placebo-controlled trial, use of sucrose before

heel lance resulted in decreased NIPS scores that correlated with lower skin blood flow. The

researchers concluded that laser Doppler imaging is potentially a useful method for assessing neonatal procedural pain.

398

Current and future research is focused on brain-oriented approaches (e.g., NIRS, EEG, and MRI) instead of pain-assessment tools. Painful stimuli cause hemodynamic changes in the brains of preterm and term infants.

45,366,367

As early as 25 weeks of gestation, preterm infants have increased oxygenated hemoglobin in response to a heel

367

stick.

Cerebral changes are dependent on GA and sleep-wake state; less robust changes are seen in the younger GA infant and while asleep compared with the awake infant.

367

The first study to assess the correlation between cortical hemodynamic activity (by NIRS) during a heel stick in 25- to 43-week PMA neonates and the PIPP score found significant correlation between the NIRS and the pain score.

366

Use of the NIRS remains clinically challenging because multiple factors (i.e., movement, external stimuli, birth weight, medications, ventilator settings, infection, PDA) alter results.

199

EEG changes in the frontal lobes of the brain during noxious and painful stimuli have been researched in preterm and full-term infants. Developmental maturation in response to touch and pain has been found in the neonate: (1) before 35 weeks of gestation, nonspecific neuronal bursts to both touch and pain were the dominant response, and (2) after 35 to 37 weeks of gestation, specific responses to touch versus pain were present.

133

Using EEG, a template of neonatal brain activity during a nociceptive procedure (heel stick) has been developed, provides an objective assessment of neonatal pain, and is sensitive to the administration of analgesia for pain relief.

192

Another study of EEG changes in infants greater than 37 weeks and less than 42 weeks of gestation who were presented

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with light touch, cold, and a heel stick found significant differences in the cortical peak responses to each stimuli.

267

The researchers also found that only 65% of these newborns cried with heel stick, but all of them had EEG changes with the painful stimuli.

267

MRI has documented procedural, pain-related stress to alterations in brain maturation in preterm infants in an NICU.61 Research into the

use of EEG and MRI for pain assessment, especially technical challenges such as movement artifact, is in its infancy.

96,199

Future assessment of neonatal pain may

combine validated and reliable tools as well as laboratory data collected at the point-of-care.

One such study used a multimodal approach to measure pain: (1) electromyography (EMG), EEG, and NIRS; (2) video-recording of behavioral responses; and (3) EEG to monitor autonomic responses (i.e., heart and respiratory rates, oxygen saturation with pulse oximetry, and cardiovascular activity).

421

In more than 100 test occasions, this multimodal system is precise, accurate, and 100% sensitive and specific in detecting touch versus a heel stick.

421

Simultaneous use of NIRS and EEG on 30 newborn infants who were exposed to innocuous tactile stimuli and noxious (heel lance) stimuli showed that both technologies recorded quantifiable and distinct activity to each of the stimuli in group analysis, with individual variation among newborns within the group.

407

The heel lance resulted in a peak hemodynamic change on the NIRS that was 10-fold larger than the cortical response to touch. However, this study also found that hemodynamic and electrophysiologic responses do not always occur together in an individual newborn, but when they do occur together (in 64% of heel lances), the responses are significantly correlated in their magnitude.

407

TREATMENT

The neonate relies on the skilled observations, assessment, and interventions of care providers for prompt, safe, and effective relief of pain. Pain management is an interactive, relationship-based process that comprises (1) the environment of pain management, (2) preparation of the newborn for a procedure, (3) pain relief during a procedure, and (4) restoring safety

and security to the infant after a procedure.47

Barriers in providing adequate analgesia in these patients include an unfamiliarity with medication doses and with regional techniques and concern over increased drug sensitivity in neonates. Because routine care can be irritating to newborns, differentiating between agitation, which may respond well to comfort measures, and pain, which will not, is mandatory. Opioids are the mainstay of pharma-

cologic treatment; however, other useful medications and techniques may be used for pain relief.13 Guidelines for managing pain in the neonate are listed in Box 12.6. Tables 12.9 and

12.10 present evidence-based pain management

strategies for commonly performed painful procedures and surgical interventions.

Pharmacologic Measures

Absorption, metabolism, distribution, and clearance

of drugs in the neonate differ from those in the older child and adult (see Chapter 10). These differences are summarized in Table 12.11.

OPIOIDS AND BENZODIAZEPINES

Opioids have their primary effect on the μ-receptor in the brain and spinal cord. High-affinity μ-receptors are associated with analgesia, and low-affinity μ-receptors are associated with respiratory depression. There may be fewer high-af-

finity μ-receptors in the newborn that are less sensitive to the analgesic effects of opioids. Higher initial doses of opioids may therefore be necessary for effect, which may in turn increase the risk for respiratory depression. A

randomized, double-blind study of postoperative (e.g., thoracic or abdominal surgery) pain relief in full-term newborns receiving either continuous or intermittent morphine found an age-related difference in morphine requirements and metabo-

57,58

lism. needed less morphine postoperatively (e.g., loading dose [50 mcg/kg], continuous dose [5 to 10 mcg/ kg/hr], and need for additional “breakthrough” doses) than neonates older than 7 days (e.g., loading dose [100 mcg/kg] and continuous dose [10 mcg/kg/hr]). This study also found that neonates being mechanically ventilated had slower morphine metabolism and clearance.57 A retrospective analysis of the postoperative use of morphine in 82

Younger infants (e.g., 7 days or younger)

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301

BOX

12.6

• Use strategies to prevent pain (e.g., avoid recurrent painful stimuli).

• Use developmental care and environmental interventions to reduce

• Use comfort measures (e.g., breast milk/sucrose/glucose, nonnutri-

• Sucrose administration recommendations:

• Preterm infants: 0.1–0.4 mL; dipping a paciﬁer into sucrose

• Term infants: 2 mL

• Administer 2 minutes before a painful procedure*

• Analgesic effect lasts about 5 minutes

• Use pharmacologic therapy for preemptive analgesia (see Table

• Use pharmacologic therapy for ongoing pain.

• Use of a combination of pain interventions (e.g., sucking, con-

*Recent research found that waiting 2 minutes before starting a procedure after sucrose administration is not necessary. Modiﬁed from Anand KJ and the International Evidence-Based Group for Neonatal Pain: Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med. 2001;155:173; Prince W, Horns K, Latta T, et al. Treatment of neonatal pain without a gold standard: the case for caregiving interventions and sucrose administration. Neonatal Netw. 2004;23:33.

GUIDELINES FOR PAIN MANAGEMENT IN THE NEONATE

noxious stimuli and stress in the NICU

tive sucking, containment with swaddling or facilitated tucking).

results in 0.1-mL intake

12.13).

tainment, medication) may have an additive or synergistic clinical

255

effect.

279

287

(see Chapter 13).

full-term neonates after thoracic and/or abdominal surgery

129

found that both dosage and duration of infusion prolonged mechanical ventilation. After extubation, no apnea or hypotension was associated with morphine use.

Decreased protein binding, drug metabolism, and drug clearance may contribute to higher plasma and CNS concentrations and prolonged drug effect. Effective drug doses and metabolism by the individual neonate depend on weight, GA, postnatal age, genetic variation, and the corresponding pharmacokinetics and pharmacodynamics, which may change in the first days of life.

384,397

All doses must be titrated to the individual neonate’s needs and current clinical circumstances.

397

All of the opioids have similar mechanisms

of action; however, there are a few important differences in side effects (see Table 12.13). Morphine is the most commonly used opioid and may cause hypotension in dehydrated patients or when used in high doses; it provides

more sedation than fentanyl. Recent research on

the blood pressure effects of morphine administration showed (1) no hypotensive effects on ventilated newborns

344

or on preterm infants

405

given analgesic doses20 and (2) occurrence of hypotensive effects with loading and higher dosages.

28,405

However,

morphine should be used with caution in preterm infants of 23 to 26 weeks of gestation and those with preexisting hypotension.

185

For acute procedural pain (e.g., heel stick), a loading dose of morphine followed by continuous IV infusion does not provide adequate analgesia for invasive procedures in ventilated preterm infants.

Fentanyl is the preferred drug in many NICUs because of its cardiovascular stability and its ability to decrease pulmonary vascular resistance. It can, however, cause chest wall

rigidity and decreased lung compliance if administered too quickly. Neuromuscular blocking agents or slow administration of the drug will prevent this problem. Fentanyl is also commonly used in patients on extracorporeal membrane oxygenation (ECMO) to provide sedation and analgesia and to prevent increases in pulmonary vascular resistance and pressure.

254

Fentanyl is also used for artificial ventilation, persistent pulmonary hypertension of the newborn (PPHN), diaphragmatic hernia, and postoperative pain. short duration, fentanyl relieves procedural pain.

397

Because of its rapid onset and

397

Sufentanil is 10 times more potent than fentanyl

and significantly more expensive. It is shorter acting and can have even greater effects on lung and chest wall compliance. Hydromorphone and methadone have also been used, particularly in the postoperative period and for infants on long term-opioids.

Administering drugs on a PRN schedule results in peaks and valleys of pain relief and increases in side effects. Because an analgesic is most effective if given before the peak of pain (wind-up), continuous infusions or regular administration can help prevent undue neonatal suffering.

13,384

Benzodiazepines are commonly used in the NICU for sedation. Midazolam (Versed)

has been increasingly used to provide sedation in mechanically ventilated neonates. A meta-anal-

ysis of the research on midazolam concluded that there are significant adverse effects and no clinical benefit to the use of midazolam; there is insufficient evidence to justify the use of midazolam for ventilated neonates in the

TABLE

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12.9

NURSE-DIRECTED/PERFORMED PROCEDURES AND EVIDENCE-BASED NEONATAL PAIN RELIEF

TACTILE: SWADDLING/

NURSING CARE STRATEGIES

SKIN-TO-SKIN/ KANGAROO CARE

BREASTFEEDING MASSAGE

ORAL: NONNUTRITIVE SUCKING OR SUCROSE/ GLUCOSE

CONTAINMENT/ FACILITATED TUCKING/ HOLDING OR ROCKING

MEDICATIONS: TOPICAL EMLA

REGIONAL INFILTRATION WITH LIDOCAINE OPIOIDS

Heel lance X X X X Venipuncture X X X X X X X Arterial stick X X X X Gavage tube

X X X X

insertion IM injection ETT or nasal

X X

X* X X

X X X

suction Catheterization

†

X X Nonopioid

of bladder Dressing

X* X* X X Nonopioid changes/tape removal/suture removal

NONOPIOID ANALGESIA OR GENERAL ANESTHESIA

†

analgesia

†

analgesia

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Using a combination of nonpharmacologic comfort strategies potentiate their pain-relieving effects as does combining comfort measures and pharmacologic measures.

*If already kangaroo caring.

†

Postprocedure. ETT, Endotracheal tube; IM, intramuscular injection. Modiﬁed from Gardner SL. Clinical practice tool: nurse-directed/performed procedures and nurse assisted procedures: evidence-based neonatal pain relief; 2008. Used with permission.

TABLE

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12.10

NURSE-ASSISTED PROCEDURES AND EVIDENCE-BASED NEONATAL PAIN RELIEF*

NURSING CARE STRATEGIES

SKIN-TOSKIN/ KANGAROO CARE

BREASTFEEDING

ORAL: NONNUTRITIVE SUCKING OR SUCROSE/GLUCOSE PACIFIER

TACTILE: SWADDLING/ CONTAINMENT/ FACILITATED TUCKING/HOLDING AND ROCKING

MEDICATIONS: TOPICAL: EMLA CREAM, AMETHOCAINE GEL

REGIONAL INFILTRATION WITH LIDOCAINE OPIOIDS

NONOPIOID ANALGESIA OR GENERAL ANESTHESIA

PICC line insertion/removal X X X X Taps: lumbar, suprapubic,

X X X X ventricular, paracentesis, bone marrow

Line placement/removal: (CVP; Broviac); ECMO; arterial/venous cutdowns

Chest tube insertion/

X X X X X Consider general

anesthesia Nonopioid analgesia

X X X X

†

Nonopioid analgesia

removal ETT intubation, NCPAP,

‡

X X Nonopioid analgesia

ventilation Circumcision X X X Nonopioid analgesia Scopes:

X (pre-procedure) X X Nonopioid analgesia endoscopybronchoscopy

Eye examination for ROP X Any surgical procedure: PDA

†

X X X Nonopioid analgesia

†

Nonopioid analgesia ligation; TEF/gastroschisis repair/omphalocele/ CDH/inguinal hernia; CHD repair/shunt placement

Diagnostic procedures

X X X such as echocardiography, ultrasonography, x-ray examination

Manipulative procedures

X X

such as casting for clubfeet

†

CHAPTER 12 Pain and Pain Relief

*Using a combination of nonpharmacologic, comfort strategies potentiates their pain relieving effects as does combining comfort measures and pharmacologic measures.

†

Postprocedure.

‡

With NCPAP/ventilation.

CDH, Congenital diaphragmatic hernia; CHD, congenital heart disease; CVP, central venous pressure; ECMO, extracorporeal membrane oxygenation; ETT, endotracheal tube; PDA, patent ductus arteriosus; PICC, peripherally inserted central catheter; ROP, retinopathy of prematurity; TEF, tracheoesophageal ﬁstula.

Modiﬁed from: Gardner SL: Clinical practice tool: nurse assisted procedures: evidence-based neonatal pain relief, 2008. Used with permission.

303

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TABLE

12.11

DIFFERENCES CAUSE EFFECTS

Altered gastric activity Presence of alkaline amniotic ﬂuids at birth

Decreased gastric emptying time Increased absorption of some drugs Decreased protein binding Lower levels of albumin, α-acid glycoprotein

Increased volume of distribution Larger volume of body water in the newborn Larger initial dose may be needed for effect (e.g.,

Decreased drug metabolism Immature liver enzyme systems Prolonged effect of some medications (e.g.,

Decreased drug clearance Immature renal system and decreased glomerular

From Rovee-Collier C, Hayne H. Reactivation of infant memory: implications for cognitive development. Adv Child Dev. 1987;10:185.

PHARMACOLOGIC DIFFERENCES BETWEEN NEWBORNS AND ADULTS

Variable drug absorption Immature gastric mucosa Consumption of alkaline milk

Increased levels of free drug (opioids, local Increased competition for binding sites by endogenous substances (bilirubin)

ﬁltration rate

anesthetics)

neuromuscular blocking agents, local anesthetics)

morphine, fentanyl, neuromuscular blockers)

Prolonged effect of some medications (morphine)

NICU (see Table 12.13). potentiate the effects of opiates.

295

Benzodiazepines

373

Therefore, when they are used in combination (e.g., fentanyl and midazolam), lower doses of each medication may be used to gain the same effect as would be attained if either one was used separately. There is increasing concern regarding the neurotoxicity of midazolam note that although benzodiazepines provide sedation, they have no analgesic effect.

258

(see Table 12.13). It is important to

373

The long-term effects of analgesic use on the developing brain are poorly understood because of a paucity of data on neurodevelopmental outcomes. Several researchers have found a protective effect of analgesic use on neurodevelopmental outcomes, perhaps because of decreased fluctuation in blood pressure, cerebral blood flow, oxygenation, respiratory synchrony with ventilation, and stress hormones.

19,27,32,240,266

More recent studies on the long-term neurologic effects of morphine analgesia in ventilated preterm infants caution against the lack of protective effects and have documented (1) an increase in severe IVH,28 (2) a decrease in the incidence of IVH that did not influence poor neurologic outcomes,

364

and (3) subtle neurobehavioral differences in preterm infants exposed to morphine analgesia.

335

LOCAL ANESTHETICS

Local anesthetics have a variety of uses and provide analgesia by preventing the transmission of noxious stimuli at either the peripheral receptor site or the spinal cord. Bupivacaine, ropivacaine, and lidocaine are the most commonly used local anesthetics (see Table 12.12). A recent study showed that bupivacaine confers better analgesia for neonatal circumcision than that achieved with lidocaine.

380

Bupivacaine is longer acting but more cardiotoxic than lidocaine. Both are more toxic in neonates than in adults because of increased organ sensitivity and free fraction of drug. The cardiovascular toxicity may be enhanced if epinephrine-containing local anesthetics are used. The long-acting local anesthetics levobupivacaine (available in Europe) and ropivacaine are as effective as bupivacaine but less cardiotoxic.

419

Procainamide is used as a continuous infusion in many centers because of its rapid ester metabolism and decreased toxicity.

Regional Technique. Regional techniques provide

adequate analgesia, thus reducing the need for higher doses of opioids (Table 12.13).

Advantages include the following

120

• Stress responses are significantly decreased.

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305

TABLE

12.12

BLOCK POTENTIAL USES COMPLICATIONS

Spinal In place of general

Caudal/ epidural

Dorsal penile nerve/ring block

Intercostal nerve block

TYPES OF REGIONAL BLOCKADE

Potential Uses

Inability to access anesthesia for surgery below the umbilicus; decreased incidence of postoperative apnea

Intraoperative and postoperative analgesia for thoracic, abdominal, perineal, and lower extremity surgery

Circumcision, analgesia for any penile surgery

Rib fracture, thoracic surgery

space; incomplete

block or inadequate

duration of anesthesia

Inadequate block;

local or opioid-related

toxicity; nerve

damage, paralysis

Hematoma formation;

end-organ damage if

epinephrine-contain-

ing solutions are used

Pneumothorax; local

anesthetic toxicity

(highest rate of

absorption)

• Normal respiratory patterns return more quickly.

• The need for postoperative ventilation may be avoided or shortened.

• Intestinal motility recovers more quickly.

• Morbidity decreases, particularly with the use of epidural blocks.

Dorsal Penile Nerve/Ring Block.

231

The dorsal penile

nerve block is extremely easy to perform with a high degree of success that can provide surgical anesthesia for circumcision.

231

The block is performed by injecting 1% lidocaine 3 to 5 mm below the skin at the 2 o’clock and 10 o’clock positions on the dorsum of the penis (Fig. 12.7). In a full-term neonate, 0.5 mL/side is used, and 0.2 mL/kg/side is used in premature infants. An alternative technique less likely to cause hematoma is to inject a subcutaneous ring of 0.5% or 1% lidocaine around the base of the penis. All solutions should be without epi-

nephrine, and a “wait time” of 5 to 8 minutes is necessary to achieve adequate anesthesia.

252

Several studies of pain responses to circum-

cision with a combination of pharmacologic

and nonpharmacologic interventions for neonatal pain have been published. Use of a dorsal penile nerve block/ring block and oral sucrose solution found that infants receiving the combination of a block and oral sucrose had lower pain scores than those who received a ring block or sucrose alone.

341

A more recent study of

ring block, oral sucrose, and eutectic mixture of lidocaine and prilocaine (EMLA) cream found better pain relief with use of all of these methods together.

358

Dorsal penile block, sucrose, and EMLA cream were not as effective as the ring block, oral sucrose, and EMLA. When only EMLA and sucrose were used, there was a significant increase in heart rate and duration of crying time.

358

Liposomal lidocaine was compared with EMLA and dorsal penile block in a study of 54 full-term infants being circumcised; liposomal lidocaine was found to be a safe and effective topical anes-

252

thetic.

A video study found that the dorsal penile nerve block was significantly more effective for pain relief during circumcision than use of topical EMLA cream.

152

A recent meta-analysis of 14 studies of infant circumcision found that pain was dramatically decreased with the combined use of dorsal penile block, acetaminophen, oral sucrose, and topical analgesic cream.48 However, the addition of liposomal lidocaine to sucrose did not further decrease the pain of venipuncture in healthy term newborns.

Epidural Block. The epidural space is an area sur-

394

rounding the dura of the spinal cord. This space can be accessed from the caudal, lumbar, or thoracic region. An epidural block is performed by a skilled pediatric anesthesiologist, often with the patient under general anesthesia.

275

A small catheter can be left in the space, or a one-time dose of medication can be given. Local anesthetics act by anesthetizing either the local nerve roots or the spinal tracts at the level of the spinal cord where they are placed. The most commonly used medications in neonates are the local anesthetics procainamide, ropivacaine, or bupi- vacaine. They are often used in combination with low doses of opioids and/or clonidine, which have both local and systemic action. The major advan-

tages of these techniques include their ability to provide continuous pain relief and the potential to minimize respiratory depression, facilitate extubation, and hasten recovery.

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TABLE

12.13

ANALGESICS, SEDATIVES, AND REVERSAL AGENTS FOR THE NEONATE

DRUG DOSAGE COMMENTS

OPIOIDS

Morphine 0.05–0.1 mg/kg/dose q 4–6 hr PRN IV, IM,

or sub-Q Continuous IV infusion: 10–15 mcg/kg/hr (up to 30–40 mcg/kg for ventilator therapy and major surgery) Mean onset of action: 5 min Peak effect: 15 min Duration: 4–5 hr

CNS and respiratory depressant; bronchospasms; peripheral vasodilation with hypovolemic infants; hypotension, decreased gastric/intestinal motility; intestinal obstruction; risk for NEC; increased intracranial pressure; seizures; urinary retention. Easily reversed with naloxone; slower onset but longer duration than for fentanyl; withdrawal symptoms may occur. Ceiling effect (after reaching a therapeutic level, higher doses result in more adverse rather than analgesic effects) reached by using doses up to

0.5 mg/kg. Sleep-wake cycling, measured by EEG, resumed soon after surgery in neonates ≥32 weeks of gestation who received high doses of morphine and midazolam. Does not alter the physiologic response to ETT suctioning. As premedication for ETT intubation: use only if other opioids not available; must wait at least 5 minutes for onset of action.

Fentanyl (Sublimaze)

0.3–2 mcg/kg/dose q 1–2 hr PRN IV or sub-Q Continuous IV infusion: 0.3–5 mcg/kg/hr Onset of action: 2–3 min Peak effect: 3–4 min Duration: 30–60 min

Same as for morphine. Eighty to 100 times more potent than morphine. Rapid onset of action; decreases motor activity; does not increase intracranial pressure in the absence of respiratory depression. Easily reversed with naloxone; short duration of action; may cause bradycardia, hypotension, apnea, seizures, or rigidity if given too rapidly; hypothermia. Less hypotension, urinary retention, GI motility effects than with morphine. days). Drug of choice for premedication for ETT intubation insertion in nonintubated infants.

Sufentanil citrate (Sufenta)

0.5–1 mcg/kg/dose q 30 min to 1 hr Peak effect: 5–6 min Duration: 30 min

Ten times more potent than fentanyl; has a quicker onset and shorter duration of action than fentanyl. Use with caution in neonates with intraventricular hemorrhage, hepatic or renal impairment, or pulmonary disease. Same side effects as for fentanyl. Bolus and continuous infusion affects EEG results in VLBW/ELBW infants; use of sufentanil must be considered in EEG interpretation.

Remifentanil 1–3 mcg/kg/dose IV

Repeat in 2–3 min PRN Onset of action: within 1 min of administration Duration: 3–10 min

Meperidine (Demerol)

Same as for fentanyl. Easily reversed with naloxone. Short duration of action. Limited experience in neonates.

Premedication for ETT intubation, PICC line insertion, and laser surgery for ROP: acceptable analgesic.

Not recommended in preterm or term infants. The active metabolite normeperidine accumulates in tissues and causes CNS stimulation (e.g., tremors, muscle twitching, hyperactive reﬂexes, dilated pupils) and also lowers the seizure threshold level.

306

345

Withdrawal symptoms occur with prolonged use (>5

237

227

297

237

8,39

; safe for PICC line

237

TABLE

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12.13

Acetaminophen/ paracetamol (Tylenol)

ANALGESICS, SEDATIVES, AND REVERSAL AGENTS FOR THE NEONATE—CONT’D

Oral loading dose term infants and q 8 hr in preterm infants <32 weeks of gestation IV loading dose

310

: 20 mg/kg PO; then 10 mg/kg PO q 6 hr in

310

: 20 mg/kg; then 10 mg/kg IV q 6 hr for term infants and q 8 hr for preterm infants <32 weeks of gestation Rectal loading dose

310

: 30–40 mg/kg; then 1–18 mg/kg q 6 hr for term infants and q 8 hr for preterm infants <32 weeks of gestation

Ibuprofen (Advil,

4–10 mg/kg/dose q 6–8 hr PO Gastric irritant—administer with or after feeding; use with

Motrin)

Lidocaine 0.5%–1% solution (to avoid

systemic toxicity, volume should be less than 0.5 mL/kg of 1% lidocaine solution—5 mg/kg)

Bupivacaine Levobupivacaine Ropivacaine

2.5 mg/kg one-time epidural dose Continuous IV infusion: 0.2 mg/kg/hr (maximum dose)

EMLA (lidocaine and prilocaine)

2.5–5 g to site for at least 60 min Peak effect: 2–3 hr Duration: 1–2 hr after removal

Amethocaine gel* (4%) liposome-encapsulated

1.5 g to site for 30 min to 1 hr

tetracaine (Ametrope)

Liposomal lidocaine

Onset of action: 20–30 min Available in the United States without a prescription. Does not cause methemoglobin-

(4%) cream

CHAPTER 12 Pain and Pain Relief

307

NONOPIOIDS

Used for mild to moderately severe pain8: given alone does not relieve surgical pain, heel lance pain, or pain of eye examination

305

Potentiates the effects and signiﬁcantly reduces the need for opioids after major surgery.

189,305

Do not use in patients with G6PD deﬁciency. May cause hepatotoxicity in overdose .

caution in neonates with necrotizing enterocolitis, impaired renal function, hypertension, compromised cardiac function, or pulmonary hypertension.

LOCAL ANESTHETICS

Local inﬁltration anesthesia for invasive procedures; use solution without epinephrine to avoid vasoconstriction. Use topical creams (EMLA/amethocaine) before needle insertion; warm solution to body temperature; inject slowly to reduce the pain of injection.

253

One case report of a term newborn developing methemoglobinemia after circumcision with lidocaine and topical EMLA cream.

235

Monitor for CNS (e.g., seizures, irritability) and cardiotoxic (e.g., ventricular dysrhythmias) side effects. Monitor catheter integrity. Epidural infusion is titrated to effect but must not exceed maximum dose. Levobupivacaine and ropivacaine are less cardiotoxic than bupivacaine.

Vasoconstriction at the site. Site must be covered with water-impermeable dressing (e.g., Tegaderm). Single doses have not been shown to cause methemoglobinemia in preterm or term neonates.

389

Does not relieve pain of heel lance.13 The possibility of toxicity is increased when EMLA is applied to (1) open skin and (2) a larger area than recommended by the manufacturer.

312

Cannot be used on abraded skin or mucous membranes.

Site must be covered with water-impermeable dressing (e.g., Tegaderm). Vasodilation at the site—mild transient (~20 min) erythema or blanching.

213,253,301,388

Case report of ELBW preterm infant developing a clinically signiﬁcant cardiac arrhythmia after topical use for PICC insertion.

271

emia; can be applied without an occlusive dressing and has fewer vasoactive effects. Effective in relieving immunization pain in infants.

391

Barbiturates Do not provide pain relief; help reduce agitation precipitated by painful events.

SEDATIVE-HYPNOTICS

Frequently produce hyperalgesia and increased reaction to painful stimuli; contraindicated for neonates who have pain and also require sedation.

Continued

UNIT TWO Support of the Neonate308

https://t.me/medicina_free

TABLE

12.13

Phenobarbital Loading: 10–20 mg/kg IV to maximum

Dexmedetomidine HCl (Precedex)

Chloral hydrate 25–75 mg/kg/dose q 6 hr PRN, PO, or PR

Benzodiazepines Do not provide pain relief. Produce sedation, muscle

Diazepam (Valium) 0.02–0.3 mg/kg IV, IM, or PO q 6–8 hr Do not dilute injection; venous sclerosing; may displace

Lorazepam (Ativan) 0.05–0.1 mg/kg/dose (give over ≥3 min) q 4–8 hr Respiratory depressant, partial airway obstruction, drows-

ANALGESICS, SEDATIVES, AND REVERSAL AGENTS FOR THE NEONATE—CONT’D

SEDATIVE-HYPNOTICS

Prolonged sedation possible once therapeutic levels achieved (20–25 mg/mL); 40 mg/kg Maintenance: 5–7 mg/kg in two divided doses beginning 12 hr after last loading dose

Bolus for procedural sedation: 1–3 mcg/kg Slow IV infusion: Loading dose: 0.5 mcg/kg over 10 minutes Continuous IV infusion: Maintenance dose: 0.25–0.6 mcg/ kg/hr Distribution half-life: 6 min Elimination half-life: 2 hr

Onset: 10–15 min Duration: 2–4 hr

depresses CNS—motor and respiratory; slow onset of action; little or no pain

relief; not easily reversed; withdrawal symptoms may occur; incompatible with