Published online November 1, 2006
PEDIATRICS Vol. 118 No. 5 November 2006, pp. 2231-2241 (doi:10.1542/peds.2006-2277)

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POLICY STATEMENT

Prevention and Management of Pain in the Neonate: An Update

American Academy of Pediatrics, Committee on Fetus and Newborn and Section on Surgery, Canadian Paediatric Society and Fetus and Newborn Committee

	ABSTRACT

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
The prevention of pain in neonates should be the goal of all caregivers, because repeated painful exposures have the potential for deleterious consequences. Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU. Although there are major gaps in our knowledge regarding the most effective way to prevent and relieve pain in neonates, proven and safe therapies are currently underused for routine minor yet painful procedures. Every health care facility caring for neonates should implement an effective pain-prevention program, which includes strategies for routinely assessing pain, minimizing the number of painful procedures performed, effectively using pharmacologic and nonpharmacologic therapies for the prevention of pain associated with routine minor procedures, and eliminating pain associated with surgery and other major procedures.

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Key Words: pain • neonates

Abbreviations: IVH—intraventricular hemorrhage • PVL—periventricular leukomalacia • ROP—retinopathy of prematurity

	INTRODUCTION

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Objectives
This updated statement is intended for health care professionals who care for neonates (preterm to 1 month of age). The objectives are to:

1. emphasize that despite increased awareness of the importance of pain prevention, neonates in the NICU continue to be exposed to numerous painful minor procedures daily as part of their routine care;
   
2. present objective means of assessing neonatal pain by health care professionals;
   
3. describe effective strategies to prevent and treat pain associated with routine minor procedures; and
   
4. review appropriate methods to prevent and treat pain associated with surgery and other major procedures.
   

Background
The prevention of pain in neonates is an expectation of parents.¹ However, there are major gaps in our knowledge regarding the most effective way to accomplish this. Although it may not be possible to completely eliminate pain in neonates, much can be done to reduce the amount and intensity of pain. The prevention of pain is important not only because it is an ethical expectation but also because repeated painful exposures can have deleterious consequences.^2–21 These consequences include altered pain sensitivity^{5, 7–9} (which may last into adolescence¹⁵) and permanent neuroanatomic and behavioral abnormalities, as found in animal studies.^{5, 14} It seems that altered pain sensitivity can be ameliorated if effective pain relief is provided.^{7, 17} There is growing concern that the long-term consequences of repeated pain in vulnerable neonates may also include emotional, behavioral, and learning disabilities^{3, 4, 6, 10, 13, 16}; however, there are no definitive data in humans. During the last few years, there has been considerable interest in the diagnosis and treatment of acute pain in the neonate, but there has been little published on the related subjects of stress and chronic pain in this population. In the original statement, stress and chronic pain were briefly discussed in addition to acute pain.² However, neither chronic pain nor stress has been specifically defined for the neonate, and only an intuitive understanding of these concepts is possible. Therefore, this updated statement deals primarily with acute pain prevention.

Neonates at greatest risk of neurodevelopmental impairment as a result of preterm birth (ie, the smallest and sickest neonates) are also those most likely to be exposed to the greatest number of painful stimuli in the NICU,¹⁸ creating a "double-hit" phenomenon. Although effective pain relief is now usually provided for neonates during and after a major surgical procedure,²¹ pain-reducing therapies are often underused for the numerous minor procedures that are a part of routine medical and nursing care for neonates.^{20, 21} Because the most effective and safest ways to prevent pain in the neonate are unknown, striking a proper balance between effective pain relief and avoidance of serious adverse effects from pain medications is a major challenge for caregivers. The subject of pain in the neonate was recently the focus of the Newborn Drug Development Workshop sponsored by the National Institute of Child Health and Human Development and the US Food and Drug Administration. The reader is referred to their publications for a detailed review and their discussions.^22–24

	ASSESSMENT OF PAIN AND STRESS IN THE NEONATE

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Optimal pain management requires competent pain assessment, which can be especially difficult to perform in neonates. The pain-assessment tool used should be multidimensional, including measurements for both physiologic and behavioral indicators of pain, because neonates cannot self-report.^25–29 Physiologic indicators of pain include changes in heart rate, respiratory rate, blood pressure, oxygen saturation, vagal tone, palmar sweating, and plasma cortisol or catecholamine concentrations. Behavioral indicators include changes in facial expressions, body movements, and crying, but these may be absent in some neonates who are neurologically impaired or pharmacologically paralyzed.

When pain is prolonged, striking changes occur in the infant's physiologic and behavioral indicators. During episodes of prolonged pain, neonates enter a state of passivity with few, if any, body movements; an expressionless face; decreased heart rate and respiratory variability; and decreased oxygen consumption, all suggestive of a marked conservation of energy. Prolonged or repeated pain also increases the response elicited by future painful stimuli (hyperalgesia) and even by usually nonpainful stimuli (allodynia). Therefore, pain scales that are used in postoperative neonates should be sensitive to the changes in response that can occur when pain is prolonged.²⁷

The most commonly used assessment tools are listed in Table 1. ^30–45 For each tool, the physiologic and behavioral indicators of pain are described, the population for which they have been validated are delineated, and unique aspects are listed. Whatever assessment tools are used, continual multidisciplinary training of staff in the recognition of neonatal pain and in the use of the chosen pain-assessment tools should be provided.²⁶ Although in recent years, increased interest and research in the assessment of pain and stress in the neonate has occurred, there remains a need to develop a tool to measure pain in pharmacologically paralyzed and severely neurologically impaired infants.⁴⁰

View this table: [in this window] [in a new window]   TABLE 1 Pain-Assessment Tools

 

	REDUCING PAIN FROM BEDSIDE CARE PROCEDURES

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Neonates in the NICU often experience painful procedures during routine care,^{10, 21} such as needle insertions,^46–51 suctioning,^{47, 52, 53} gavage-tube placement,^{51, 52, 54} and tape removal,⁵² as well as stressful disruptions, including diaper changes,⁵⁴ chest physical therapy,⁵⁴ physical examinations,⁵¹ nursing evaluations,⁵² and exposure to environmental stimuli.²⁰ Despite increased awareness by caregivers that neonates in the NICU frequently experience pain, effective pain relief for these routine procedures is often underused.^{20, 21, 55} As discussed more completely later, the continuous infusion of morphine in ventilated preterm neonates may not effectively prevent acute pain from minor painful procedures and may increase adverse events.^{56, 57} However, there are other effective methods of preventing minor procedural pain in neonates, which should be used routinely. As part of a comprehensive pain-prevention program,^{19, 58, 59} each neonatal unit should develop strategies to minimize the number of minor painful or stressful procedures and provide effective nonpharmacologic and/or pharmacologic pain relief for all procedures.

Reduction of Painful Events
Clearly, the most effective way of reducing minor procedural pain in the neonate is to reduce the number of procedures performed.⁵⁸ There currently is a paucity of research regarding effective ways to accomplish this, but strategies for reducing the number of procedures that neonates experience should be developed and their effectiveness should be tested.⁵⁵ Such an approach might include reducing the number of bedside disruptions in care.^{55, 60, 61} Other strategies might include bundling interventions, eliminating unnecessary laboratory or radiographic procedures, using transcutaneous measurements when possible, and minimizing the number of repeat procedures performed after failed attempts.⁵⁸

Nonpharmacologic Pain Prevention for Minor Procedures
A variety of nonpharmacologic pain-prevention and -relief techniques have been shown to effectively reduce pain from minor procedures in neonates. These include use of oral sucrose/glucose,^62–76 breastfeeding,⁷⁷ nonnutritive sucking,^{49, 78} "kangaroo care" (skin-to-skin contact),^{55, 58} facilitated tuck (holding the arms and legs in a flexed position),⁷⁹ swaddling,⁸⁰ and developmental care, which includes limiting environmental stimuli, lateral positioning, the use of supportive bedding, and attention to behavioral clues.⁶¹ These measures have been shown to be useful in preterm and term neonates in reducing pain from a heel stick,^{68, 70–73, 79, 80} venipuncture,^{62, 64, 65, 67, 74, 77, 81} and subcutaneous injections⁸¹ and are generally more effective when used in combination than when used alone.^{63, 65, 68, 69, 80, 82} Concentrated oral sucrose has been widely studied. Oral sucrose eliminates the electroencephalographic changes associated with a painful procedure⁸³ in a neonate, but the mechanism of pain relief by sucking oral sucrose is not known for certain. In one study, endogenous endorphin concentrations did not increase with administration of oral sucrose as originally proposed.⁸⁴ Although the intraoral administration of sucrose to preterm infants without suckling is effective, intragastric administration is not.⁷² Concentrated oral glucose has also been used and diminishes the pain response of venipuncture, but it does not decrease oxygen consumption or energy expenditure, suggesting there may still be a stress response.⁸⁵

A wide range of oral sucrose doses have been used in neonates for pain relief, but an optimal dose has not been established.^{75, 86} The dosage range of sucrose for reducing pain in neonates is 0.012 to 0.12 g (0.05–0.5 mL of 24% solution).^{75, 86} Some authors have suggested that multiple doses for a procedure (2 minutes before and 1–2 minutes after) are more effective than a single dose.^{73, 75} The long-term safety of multiple doses of oral sucrose for painful procedures in neonates has not been established.⁸⁷ Additional research is needed to fully understand the mechanism of action, optimal dose, and safety of repeated doses of oral sucrose in neonates; nevertheless, available data suggest that this is an effective means of alleviating pain for many minor neonatal procedures. Because oral sucrose reduces but does not eliminate pain in neonates, it should be used with other nonpharmacologic measures to enhance its effectiveness.

Topical Anesthetic Pain Prevention for Minor Procedures
Topical anesthetics can effectively reduce pain from some procedures such as a venipuncture,^{62, 88–90} lumbar puncture,⁹¹ and intravenous catheter insertion⁹¹ in term and preterm neonates. These agents must be applied for a sufficient length of time before the procedure (usually 30 minutes for neonates), and they are not effective for a heel-stick blood draw,^{92, 93} because the pain from heel sticks is primarily from squeezing the heel and not from the lancet.⁴⁸ Other nonpharmacologic means of alleviating pain mentioned previously should be used for heel sticks. Topical anesthetics were not effective for peripheral intravenous central catheter placement in one trial.⁹⁴ There is a risk of methemoglobinemia after use of topical lidocaine-prilocaine cream in certain situations.^{95, 96} The risks can be minimized if used no more than once daily, on intact skin only, and not with other drugs known to cause methemoglobinemia.^{97, 98}

Prolonged Mechanical Ventilation
Many preterm neonates receiving intensive care undergo prolonged mechanical ventilation, and its use defines a population of patients experiencing numerous minor painful procedures as described previously. The routine use of continuous pain medication and sedatives for ventilated preterm neonates has been evaluated.²⁴ Two large randomized, controlled trials of the continuous use of intravenous morphine primarily as a potential means of decreasing poor neurologic outcome in preterm neonates receiving mechanical ventilation were published recently.^{56, 57} In both studies, additional open-label morphine was allowed if infants were considered to be in pain. In the first study,⁵⁶ continuous morphine infusion was used for 7 days or less as clinically needed. In this study, morphine had no apparent analgesic effect and did not alter the risk of a poor neurologic outcome (severe intraventricular hemorrhage [IVH], periventricular leukomalacia [PVL], or death). In the second study,⁵⁷ a continuous morphine infusion was used for up to 14 days. In this study, morphine use reduced pain scores slightly but did not alter the risk of severe IVH, cystic PVL, or a composite outcome (severe IVH, cystic PVL, or death within 28 days). In a subsequent analysis, the authors concluded that the use of morphine prolonged the duration of mechanical ventilation.⁹⁹ No large studies on the continuous infusion of fentanyl in ventilated preterm infants have been published, but the literature includes many smaller studies that have recently been reviewed.²⁴ In these studies, fentanyl seemed to result in increased ventilator settings.²⁴ Concern about adverse respiratory effects of continuous opioid infusions in chronically ventilated preterm infants and lack of a demonstrated long-term benefit suggest that their routine use cannot be recommended at this time.

Midazolam has been evaluated as a sedative in mechanically ventilated preterm infants. A Cochrane Database Systematic Review¹⁰⁰ recently concluded that there were insufficient data to promote use of midazolam because of a lack of demonstrated benefit and concern for an increased risk of poor neurologic outcome. This conclusion was supported by another recent review.²⁴ Ketamine hydrochloride was evaluated in a randomized, controlled trial for relief of procedural pain associated with endotracheal suctioning in ventilated preterm neonates.¹⁰¹ However, these authors concluded that ketamine was only modestly effective at reducing pain scores and did not alter physiologic responses in heart rate and systemic blood pressure.

	REDUCING PAIN FROM SURGERY

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Pain is an inevitable consequence of surgery at every age. Pain is of particular importance in the neonate because of the evidence of improved clinical outcomes, including decreased mortality, when adequate pain control is achieved.^{19, 102} Tissue injury, which occurs during all forms of surgery, elicits profound physiologic responses. The more marked these responses to surgery, the greater the morbidities and mortality.¹⁰³ Thus, minimizing the endocrine and metabolic responses to surgery by decreasing pain has been shown to significantly improve outcomes in neonatal surgery. Although it would now be considered unethical to perform surgery without anesthesia, the appropriate levels of anesthesia for various surgical procedures have not been well investigated. Improving pain management and improving outcomes in the neonate require a coordinated strategy of pain reduction, which must be multidimensional, requires a team approach, and should be a first priority in perioperative management. Despite fears that analgesics (opiates in particular) may lead to hypotension or respiratory depression and an increase in postoperative complications, such effects have never been shown in randomized, controlled trials. Indeed, postoperative inotrope requirements were decreased by high-dose opioids in neonates after cardiac surgery,¹⁰⁴ and postoperative respiratory compromise associated with the pain of a thoracotomy can be relieved by adequate analgesia.^{105, 106}

Because of the physiologic and metabolic immaturity of the neonate, doses of medications that are effective for the reduction of pain may be close to the doses that cause toxicity. Therefore, the concept of a "balanced analgesia" has arisen, whereby several approaches to pain reduction can be used simultaneously to decrease the dosage required of each medication and, thereby, reduce toxicity. Early and effective pain treatment is associated with a lower total dose of medications, although therapy should be guided by ongoing pain assessment. The developmental pharmacology of the agents used must also be kept in mind. For example, fentanyl, a drug that is metabolized rapidly in older infants, has a half-life averaging approximately 10 hours in the neonate,¹⁰⁷ and clearance is even lower in preterm infants.¹⁰⁸ The residual effects of intraoperative medications also need to be considered. Muscle relaxants completely prevent behavioral pain responses and may last for several hours postoperatively.

As far as possible, stress and preoperative pain should be relieved before surgical interventions. An infant who is stressed and disturbed, unclothed, hypothermic, overstimulated by noise and light, and already experiencing pain will have elevated basal concentrations of adrenal cortical and medullary hormones and will be susceptible to further stress and complications postoperatively. However, there has been little direct investigation of the effects of preoperative analgesia in neonates. A full discussion of intraoperative strategies to reduce pain in neonates is beyond the scope of this statement. However, anesthesia of sufficient depth to prevent intraoperative pain and stress responses must be provided to decrease postoperative analgesic requirements. For some procedures, regional anesthesia is an effective way of controlling intraoperative pain in neonates, but a detailed discussion about regional anesthesia is also beyond the scope of this statement.

Postoperatively, opioids can be given by continuous infusion or by regular bolus. Randomized trials do not show any substantial benefit of continuous infusion of opioids over intermittent dosing, probably because of the long half-life of many of these agents in the neonate.¹⁰⁹ More recently developed rapidly metabolized agents given by infusion hold promise for nurse-controlled anesthesia using a pump (the nurse providing additional boluses of medication as needed). This technique has not been widely investigated but holds promise for reducing the total dose of and complications from opioids.

Intravenous nonsteroidal antiinflammatory agents such as ketorolac and ketoprofen are well established as a means of reducing postoperative opioid requirements in adults. A small number of randomized, controlled trials in children have also shown effective analgesia, with a reduction in morphine requirements leading to reduced postoperative vomiting compared with an opioid-based analgesic.¹¹⁰ However, bleeding time may be increased,¹¹¹ and some reports¹¹² show an increase in postoperative clinical bleeding, although there are no randomized, controlled trials that have included neonates. A case series of infants younger than 6 months after abdominal surgery suggested a reduction in morphine requirements when ketorolac was used.¹¹³ Lacking any substantial evidence in the neonatal period, nonsteroidal antiinflammatory agents cannot be recommended for use as an adjunct to postoperative anesthesia outside a prospective clinical trial.

Acetaminophen administered orally postoperatively has been shown to reduce morphine requirements after tonsillectomy.¹¹⁴ It is associated with less postoperative vomiting than with an opioid-based analgesic¹¹⁵ and does not affect coagulation. Studies in neonates seem to be limited to use for circumcision, in which it is ineffective for operative and immediate postoperative pain but decreases later postoperative pain scores at 6 hours.¹¹⁶ Acetaminophen should not be used alone for severe pain but can be considered for use during the later postoperative period, after minor procedures, or as an adjunct to other measures. Dosing guidelines based on extensive literature review have been developed,¹¹⁷ and a population kinetic study with a large sample size produced similar guidelines.¹¹⁸ However, rectal acetaminophen should be used cautiously because of erratic absorption.

Although there are few data specific to the neonate, regional analgesia can provide effective postoperative pain relief in some situations.^{119, 120} There has been little systematic study of ancillary comfort measures in the postoperative neonate. Despite the importance of good pharmacologic treatment, the nonpharmacologic means of reducing pain in neonates discussed previously can also be used postoperatively and should be part of a coordinated effort to reduce the pain and stress experienced by infants during the postoperative period.

	REDUCING PAIN FROM OTHER MAJOR PROCEDURES

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Intercostal Drains
Insertion of a chest drain for pneumothorax or pleural fluid drainage is a painful procedure that is sometimes required in an emergency situation. There have been no prospective studies of analgesia for the insertion of chest tubes in the neonate. The recommendations, therefore, are based on general principles.¹⁹ Infiltration of the skin site with a local anesthetic before incision has long-lasting effects on pain responses (see above) and should be used routinely unless there is life-threatening instability. Slow infiltration reduces pain from lidocaine infiltration.¹²¹ Although there are no available data on the use of opioids before or after chest-tube insertion for pain prevention, this seems to be a reasonable approach. Nonpharmacologic means of reducing pain in neonates should be used also.

Chest-Drain Removal
Removal of the chest drain is also known to be very painful.¹²² A prospective study of methohexital for chest-tube removal in the neonate has demonstrated good pain control without significant respiratory compromise.¹²³ In older children, low-dose morphine and topical lidocaine-prilocaine cream were equally effective.¹²²

Intubation
The experience of being intubated is unpleasant^{124, 125} and painful.²¹ Morphine seems not to reduce the occurrence of severe hypoxia with bradycardia during intubation, probably because of the delayed onset of action.¹²⁶ Opioids with a more rapid onset of action, such as fentanyl, are probably preferable.¹²⁷ In a randomized trial, thiopentone was shown to reduce apparent pain in neonates undergoing intubation.¹²⁸ Methohexital in an uncontrolled study was associated with smooth intubating conditions and no apparent distress during intubation.¹²⁹ Studies on medications for use during endotracheal intubation are needed to address the requirements for analgesia, prevention of adverse physiologic responses (particularly bradycardia), and pharmacologic paralysis. This complex issue will be discussed further in a forthcoming statement from the American Academy of Pediatrics and Canadian Paediatric Society on the use of medications for elective intubation of neonates.

Retinal Examination and Surgery for Retinopathy of Prematurity
Retinal examinations for retinopathy of prematurity (ROP) are painful,^{130, 131} and the pain is not completely relieved by use of oral sucrose.^{132, 133} Topical anesthetics are used often, but their effectiveness is limited.¹³⁴ Retinal surgery is also painful and leads to substantial physiologic disturbance that is not adequately treated with topical anesthesia.¹³⁰ There are limited data on the effective prevention of pain from ROP surgery. One small uncontrolled study suggested that continuous intravenous infusion of remifentanil effectively reduced pain from laser therapy for ROP.¹³⁵

Circumcision
Pain relief for circumcision should always be provided. The American Academy of Pediatrics has published a separate statement on this subject.¹³⁶

	RECOMMENDATIONS

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Assessment of Pain and Stress in the Neonate

1. Caregivers should be trained to assess neonates for pain using multidimensional tools.
   
2. Neonates should be assessed for pain routinely and before and after procedures.
   
3. The chosen pain scales should help guide caregivers in the provision of effective pain relief.
   

Reducing Pain From Bedside Care Procedures

1. Care protocols for neonates should incorporate a principle of minimizing the number of painful disruptions in care as much as possible.
   
2. Use of a combination of oral sucrose/glucose and other nonpharmacologic pain-reduction methods (nonnutritive sucking, kangaroo care, facilitated tuck, swaddling, developmental care) should be used for minor routine procedures.
   
3. Topical anesthetics can be used to reduce pain associated with venipuncture, lumbar puncture, and intravenous catheter insertion when time permits but are ineffective for heel-stick blood draws, and repeated use of topical anesthetics should be limited.
   
4. The routine use of continuous infusions of morphine, fentanyl, or midazolam in chronically ventilated preterm neonates is not recommended because of concern about short-term adverse effects and lack of long-term outcome data.
   

Reducing Pain From Surgery

1. Any health care facility providing surgery for neonates should have an established protocol for pain management. Such a protocol requires a coordinated, multidimensional strategy and should be a priority in perioperative management.
   
2. Sufficient anesthesia should be provided to prevent intraoperative pain and stress responses to decrease postoperative analgesic requirements.
   
3. Pain should be routinely assessed by using a scale designed for postoperative or prolonged pain in neonates.
   
4. Opioids should be the basis for postoperative analgesia after major surgery in the absence of regional anesthesia.
   
5. Postoperative analgesia should be used as long as pain-assessment scales document that it is required.
   
6. Acetaminophen can be used after surgery as an adjunct to regional anesthetics or opioids, but there are inadequate data on pharmacokinetics at gestational ages less than 28 weeks to permit calculation of appropriate dosages.
   

Reducing Pain From Other Major Procedures

1. Analgesia for chest-drain insertion comprises all of the following:
   1. general nonpharmacologic measures;
      
   2. slow infiltration of the skin site with a local anesthetic before incision unless there is life-threatening instability (if there was inadequate time to infiltrate before insertion of the chest tube, local skin infiltration after achieving stability may reduce later pain responses and later analgesic requirements); and
      
   3. systemic analgesia with a rapidly acting opiate such as fentanyl.
      
   
   
2. Analgesia for chest-drain removal comprises the following:
   1. general nonpharmacologic measures and
      
   2. short-acting, rapid-onset systemic analgesic.
      
   
   
3. Although there are insufficient data to make a specific recommendation, retinal examinations are painful, and pain-relief measures should be used. A reasonable approach would be to administer local anesthetic eye drops and oral sucrose.
   
4. Retinal surgery should be considered major surgery, and effective opiate-based pain relief should be provided.
   

	COMMITTEE ON FETUS AND NEWBORN, 2005–2006

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Ann R. Stark, MD, Chairperson

David H. Adamkin, MD

^* Daniel G. Batton, MD

Edward F. Bell, MD

Susan E. Denson, MD

William A. Engle, MD

Gilbert I. Martin, MD

	LIAISONS

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^*Keith J. Barrington, MD

Canadian Paediatric Society

Tonse N.K. Raju, MD

National Institutes of Health

Laura Riley, MD

American College of Obstetricians and Gynecologists

Kay M. Tomashek, MD

Centers for Disease Control and Prevention

^*Carol Wallman, MSN, RNC, NNP

National Association of Neonatal Nurses

	STAFF

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Jim Couto, MA

	Section on Surgery, 2005–2006

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Donna A. Caniano, MD, Chairperson

Michael D. Klein, MD

Richard R. Ricketts, MD

Brad W. Warner, MD

Keith P. Lally, MD

Kurt D. Newman, MD

Thomas R. Weber, MD

Richard G. Azizkhan, MD

Mary L. Brandt, MD

A. Alfred Chahine, MD

Frederick J. Rescorla, MD

Michael A. Skinner, MD

George W. Holcomb, III, MD

Frederick C. Ryckman, MD

	Staff

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Chelsea Kirk

	SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE, 2005–2006

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Thomas J. Mancuso, MD, Chairperson

Joseph P. Cravero, MD, Chairperson-Elect

Constance S. Houck, MD

Lynne G. Maxwell, MD

Jeffrey L. Koh, MD

David M. Polaner, MD

Zeev Kain, MD

Patricia J. Davidson, MD, Past Chairperson

	LIAISON

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Randall M. Clark, MD

American Society of Anestheiologists

	CONTRIBUTOR

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
^*G. Allen Finley,MD

	STAFF

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 
Kathleen Kuk Ozmeral

	FOOTNOTES

 
All policy statements from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time.

^* Lead authors

	REFERENCES

TOP ABSTRACT INTRODUCTION ASSESSMENT OF PAIN AND... REDUCING PAIN FROM BEDSIDE... REDUCING PAIN FROM SURGERY REDUCING PAIN FROM OTHER... RECOMMENDATIONS COMMITTEE ON FETUS AND... LIAISONS STAFF Section on Surgery, 2005-2006 Staff SECTION ON ANESTHESIOLOGY AND... LIAISON CONTRIBUTOR STAFF REFERENCES

 

1. Franck LS, Cox S, Allen A, Winter I. Parental concern and distress about infant pain. Arch Dis Child Fetal Neonatal Ed. 2004;89 :F71 –F75[Abstract/Free Full Text]
2. American Academy of Pediatrics, Committee on Fetus and Newborn. Prevention and management of pain and stress in the neonate. Pediatrics. 2000;105 :454 –461[Abstract/Free Full Text]
3. Porter FL, Grunaue RE, Anand KJ. Long-term effects of pain in infants. J Dev Behav Pediatr. 1999;20 :253 –261[Web of Science][Medline]
4. Anand KJ, Scalzo FM. Can adverse neonatal experiences alter brain development and subsequent behavior? Biol Neonate. 2000;77 :69 –82[CrossRef][Web of Science][Medline]
5. Ruda MA, Ling QD, Hohmann AG, Peng YB, Tachibana T. Altered nociceptive neuronal circuits after neonatal peripheral inflammation. Science. 2000;289 :628 –631[Abstract/Free Full Text]
6. Bhutta AT, Anand KJ. Vulnerability of the developing brain: neuronal mechanisms. Clin Perinatol. 2002;29 :357 –372[CrossRef][Web of Science][Medline]
7. Grunau RE, Oberlander TF, Whitfield MF, Fitzgerald C, Lee SK. Demographic and therapeutic determinants of pain reactivity in very low birth weight neonates at 32 weeks' postconceptional age. Pediatrics. 2001;107 :105 –112[Abstract/Free Full Text]
8. Taddio A, Shah V, Gilbert-MacLeod C, Katz J. Conditioning and hyperalgesia in newborns exposed to repeated heel lances. JAMA. 2002;288 :857 –861[Abstract/Free Full Text]
9. Oberlander TF, Grunau RE, Whitfield MF, Fitzgerald C, Pitfield S, Saul JP. Biobehavioral pain responses in former extremely low birth weight infants at four months' corrected age. Pediatrics. 2000;105(1) . Available at: www.pediatrics.org/cgi/content/full/105/1/e6
10. Fitzgerald M, Beggs S. The neurobiology of pain: developmental aspects. Neuroscientist. 2001;7 :246 –257[Abstract/Free Full Text]
11. Kostarczyk E. Recent advances in neonatal pain research. Folia Morphol (Warsz). 1999;58(3 suppl 2) :47 –56
12. Alvares D, Torsney C, Beland B, Reynolds M, Fitzgerald M. Modelling the prolonged effects of neonatal pain. Prog Brain Res. 2000;129 :365 –3173[Medline]
13. Anand KJ. Effects of perinatal pain and stress. Prog Brain Res. 2000;122 :117 –129[Web of Science][Medline]
14. Anand KJ, Coskun V, Thrivikraman KV, Nemeroff CB, Plotsky PM. Long-term behavioral effects of repetitive pain in neonatal rat pups. Physiol Behav. 1999;66 :627 –637[CrossRef][Medline]
15. Buskila D, Neumann L, Zmora E, Feldman M, Bolotin A, Press J. Pain sensitivity in prematurely born adolescents. Arch Pediatr Adolesc Med. 2003;157 :1079 –1082[Abstract/Free Full Text]
16. Maroney DI. Recognizing the potential effect of stress and trauma on premature infants in the NICU: how are outcomes affected? J Perinatol. 2003;23 :679 –683[CrossRef][Medline]
17. Peters JW, Koot HM, De Boer JB, et al. Major surgery within the first 3 months of life and subsequent biobehavioral pain responses to immunization at later age: a case comparison study. Pediatrics. 2003;111 :129 –135[Abstract/Free Full Text]
18. Stevens B, McGrath P, Gibbins S, et al. Procedural pain in newborns at risk for neurologic impairment. Pain. 2003;105 :27 –35[CrossRef][Web of Science][Medline]
19. Anand KJ. Consensus statement for the prevention and management of pain in the newborn. Arch Pediatr Adolesc Med. 2001;155 :173 –180[Abstract/Free Full Text]
20. Simons SH, van Dijk M, Anand KS, Roofthooft D, van Lingen RA, Tibboel D. Do we still hurt newborn babies? A prospective study of procedural pain and analgesia in neonates. Arch Pediatr Adolesc Med. 2003;157 :1058 –1064[Abstract/Free Full Text]
21. Porter FL, Wolf C, Gold J, Lotsoff D, Miller JP. Pain and pain management in newborn infants: a survey of physicians and nurses. Pediatrics. 1997;100 :626 –632[Abstract/Free Full Text]
22. Anand KJ, Johnston CC, Oberlander TF, Taddio A, Lehr VT, Walco GA. Analgesia and local anesthesia during invasive procedures in the neonate. Clin Ther. 2005;27 :844 –876[CrossRef][Web of Science][Medline]
23. Anand KJ, Aranda JV, Berde CB, et al. Analgesia and anesthesia for neonates: study design and ethical issues. Clin Ther. 2005;27 :814 –843[CrossRef][Web of Science][Medline]
24. Aranda JV, Carlo W, Hummel P, Thomas R, Lehr VT, Anand KJ. Analgesia and sedation during mechanical ventilation in neonates. Clin Ther. 2005;27 :877 –899[CrossRef][Web of Science][Medline]
25. International Association for the Study of Pain, Task Force on Taxonomy. Announcement: modification of pain definition. IASP Newsletter. 2001;2 :2
26. Walden M. Pain Assessment and Management: Guideline for Practice. Glenview, IL: National Association of Neonatal Nurses; 2001. Document 1222
27. Craig KD, Whitfield MF, Grunau RVE, Linton J, Hadjistavropoulos HD. Pain in the preterm neonate: behavioral and physiological indices. Pain. 1993;52 :287 –299[CrossRef][Web of Science][Medline]
28. Chiswick ML. Assessment of pain in neonates. Lancet. 2000;355 :6 –8[Web of Science][Medline]
29. Franck LS, Greenberg CS, Stevens B. Pain assessment in infants and children. Pediatr Clin North Am. 2000;47 :487 –512[CrossRef][Web of Science][Medline]
30. Stevens B, Johnston C, Petryshen P, Taddio A. Premature infant pain profile: development and initial validation. Clin J Pain. 1996;12 :13 –22[CrossRef][Web of Science][Medline]
31. Ballantyne M, Stevens B, McAllister M, Dionne K, Jack A. Validation of the premature infant pain profile in the clinical setting. Clin J Pain. 1999;15 :297 –303[CrossRef][Web of Science][Medline]
32. Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score—initial testing of validity and reliability. Paediatr Anaesth. 1995;5 :53 –61[Web of Science][Medline]
33. Lawrence J, Alcock D, McGrath P, Kay J, MacMurray SB, Dulberg C. The development of a tool to assess neonatal pain. Neonatal Netw. 1993;12(6) :59 –66
34. Gallo AM. The fifth vital sign: implementation of the Neonatal Infant Pain Scale. J Obstet Gynecol Neonatal Nurs. 2003;32 :199 –206[CrossRef][Web of Science][Medline]
35. Hummel P, Puchalski M, Weiss M, Creech S. N-PASS: Neonatal Pain Agitation and Sedation Scale—reliability and validity. Poster presented at: the Pediatric Academic Societies annual meeting; May 3–6, 2003; Seattle, WA
36. Grunau RE, Craig KD. Facial activity as a measure of neonatal pain expression. In: Tyler DC, Krane EJ, eds. Advances in Pain Research Therapy. New York, NY: Raven Press; 1990:147–155
37. Grunau RE, Oberlander T, Holsti L, Whitfield MF. Bedside application of the neonatal facial coding system in pain assessment of premature neonates. Pain. 1998;76 :277 –286[CrossRef][Web of Science][Medline]
38. Guinsburg R, de Almeida MF, de Araujo Peres C, Shinzato AR, Kopelman BI. Reliability of two behavioral tools to assess pain in preterm neonates. Sao Paulo Med J. 2003;121 :72 –76[Medline]
39. Peters JW, Koot HM, Grunau RE, et al. Neonatal facial coding system for assessing postoperative pain in infants: item reduction is valid and feasible. Clin J Pain. 2003;19 :353 –363[Web of Science][Medline]
40. Hodgkinson K, Bear M, Thorn J, Van Blaricum S. Measuring pain in neonates: evaluating an instrument and developing a common language. Aust J Adv Nurs. 1994;12 :17 –22[Medline]
41. Blauer T, Gerstmann D. A simultaneous comparison of three neonatal pain scales during common NICU procedures. Clin J Pain. 1998;14 :39 –47[CrossRef][Web of Science][Medline]
42. Debillon T, Zupan V, Ravault N, Magny JF, Dehan M. Development and initial validation of EDIN scale, a new tool for assessing prolonged pain in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2001;85 :F36 –F41[Abstract/Free Full Text]
43. Cignacco E, Mueller R, Hamers JP, Gesler P. Pain assessment in the neonate using the Bernese Pain Scale for Neonates. Early Hum Dev. 2004;78 :125 –131[CrossRef][Web of Science][Medline]
44. Gessler P, Cignacco E. Measures for the assessment of pain in neonates as well as a comparison between the Bernese pain scale for neonates (BPSN) with the premature infant pain profile (PIPP) [in German]. Klin Padiatr. 2004;216 :16 –20[CrossRef][Web of Science][Medline]
45. McIntosh N. Pain in the newborn: a possible new starting point. Eur J Pediatr. 1997;156 :173 –177[CrossRef][Web of Science][Medline]
46. Runefors P, Arnbjornsson E, Elander G, Michelsson K. Newborn infants' cry after heel-prick: analysis with sound spectrogram. Acta Paediatr. 2000;89 :68 –72[CrossRef][Web of Science][Medline]
47. Morison SJ, Grunau RE, Oberlander TF, Whitfield MF. Relations between behavioral and cardiac autonomic reactivity to acute pain in preterm neonates. Clin J Pain. 2001;17 :350 –358[CrossRef][Web of Science][Medline]
48. Lindh V, Wiklund U, Hakansson S. Heel lancing in term new-born infants: an evaluation of pain by frequency domain analysis of heart rate variability. Pain. 1999;80 :143 –148[CrossRef][Web of Science][Medline]
49. Johnston CC, Sherrard A, Stevens B, Franck L, Stremler R, Jack A. Do cry features reflect pain intensity in preterm neonates? A preliminary study. Biol Neonate. 1999;76 :120 –124[CrossRef][Web of Science][Medline]
50. Harrison D, Evans C, Johnston L, Loughnan P. Bedside assessment of heel lance pain in the hospitalized infant. J Obstet Gynecol Neonatal Nurs. 2002;31 :551 –557[CrossRef][Web of Science][Medline]
51. Porter FL, Wolf CM, Miller JP. Procedural pain in newborn infants: the influence of intensity and development. Pediatrics. 1999;104(1) . Available at: www.pediatrics.org/cgi/content/full/104/1/e13
52. Hudson-Barr D, Capper-Michel B, Lambert S, Palermo TM, Morbeto K, Lombardo S. Validation of the Pain Assessment in Neonates (PAIN) scale with the Neonatal Infant Pain Scale (NIPS). Neonatal Netw. 2002;21 :15 –21[Medline]
53. Marceau J. Pilot study of a pain assessment tool in the neonatal intensive care unit. J Paediatr Child Health. 2003;39 :598 –601[CrossRef][Web of Science][Medline]
54. Grunau RE, Holsti L, Whitfield MF, Ling E. Are twitches, startles, and body movements pain indicators in extremely low birth weight infants? Clin J Pain. 2000;16 :37 –45[CrossRef][Web of Science][Medline]
55. Dodds E. Neonatal procedural pain: a survey of nursing staff. Paediatr Nurs. 2003;15 :18 –21[Medline]
56. Simons SH, van Dijk M, van Lingen RA, et al. Routine morphine infusion in preterm newborns who received ventilatory support: a randomized controlled trial. JAMA. 2003;290 :2419 –2427[Abstract/Free Full Text]
57. Anand KJ, Hall RW, Desai N, et al. Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomized trial. Lancet. 2004;363 :1673 –1682[CrossRef][Web of Science][Medline]
58. Gibbins S, Stevens B, Asztalos E. Assessment and management of acute pain in high-risk neonates. Expert Opin Pharmacother. 2003;4 :475 –483[CrossRef][Web of Science][Medline]
59. Halimaa SL. Pain management in nursing procedures on premature babies. J Adv Nurs. 2003;42 :587 –597[CrossRef][Web of Science][Medline]
60. Johnston CC, Stevens B, Pinelli J, et al. Kangaroo care is effective in diminishing pain response in preterm neonates. Arch Pediatr Adolesc Med. 2003;157 :1084 –1088[Abstract/Free Full Text]
61. Sizun J, Ansquer H, Browne J, Tordjman S, Morin JF. Developmental care decreases physiologic and behavioral pain expression in preterm neonates. J Pain. 2002;3 :446 –450[CrossRef][Web of Science][Medline]
62. Abad F, Diaz-Gomez NM, Domenech E, Gonzalez D, Robayna M, Feria M. Oral sucrose compares favourably with lidocaine-prilocaine cream for pain relief during venepuncture in neonates. Acta Paediatr. 2001;90 :160 –165[CrossRef][Web of Science][Medline]
63. Blass EM, Watt LB. Suckling- and sucrose-induced analgesia in human newborns. Pain. 1999;83 :611 –623[CrossRef][Web of Science][Medline]
64. Gradin M, Eriksson M, Holmqvist G, Holstein A, Schollin J. Pain reduction at venipuncture in newborns: oral glucose compared with local anesthetic cream. Pediatrics. 2002;110 :1053 –1057[Abstract/Free Full Text]
65. Carbajal R, Chauvet X, Couderc S, Olivier-Martin M. Randomized trial of analgesic effects of sucrose, glucose, and pacifiers in term neonates. BMJ. 1999;319 :1393 –1397[Abstract/Free Full Text]
66. Storm H, Fremming A. Food intake and oral sucrose in preterms prior to heel prick. Acta Paediatr. 2002;91 :555 –560[CrossRef][Web of Science][Medline]
67. Eriksson M, Gradin M, Schollin J. Oral glucose and venepuncture reduce blood sampling pain in newborns. Early Hum Dev. 1999;55 :211 –218[CrossRef][Web of Science][Medline]
68. Gibbins S, Stevens B, Hodnett E, Pinelli J, Ohlsson A, Darlington G. Efficacy and safety of sucrose for procedural pain relief in preterm and term neonates. Nurs Res. 2002;51 :375 –382[CrossRef][Web of Science][Medline]
69. Stevens B, Johnston C, Franck L, Petryshen P, Jack A, Foster G. The efficacy of developmentally sensitive interventions and sucrose for relieving procedural pain in very low birth weight neonates. Nurs Res. 1999;48 :35 –43[CrossRef][Web of Science][Medline]
70. Ors R, Ozek E, Baysoy G, et al. Comparison of sucrose and human milk on pain response in newborns. Eur J Pediatr. 1999;158 :63 –66[CrossRef][Web of Science][Medline]
71. Overgaard C, Knudsen A. Pain-relieving effect of sucrose in newborns during heel prick. Biol Neonate. 1999;75 :279 –284[CrossRef][Web of Science][Medline]
72. Ramenghi LA, Evans DJ, Levene MI. "Sucrose analgesia": absorptive mechanism or taste perception? Arch Dis Child Fetal Neonatal Ed. 1999;80 :F146 –F147[Abstract/Free Full Text]
73. Johnston CC, Stremler R, Horton L, Friedman A. Effect of repeated doses of sucrose during heel stick procedure in preterm neonates. Biol Neonate. 1999;75 :160 –166[CrossRef][Web of Science][Medline]
74. Deshmukh LS, Udani RH. Analgesic effect of oral glucose in preterm infants during venipuncture: a double-blind, randomized, controlled trial. J Trop Pediatr. 2002;48 :138 –141[Abstract/Free Full Text]
75. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2001;(4) :CD001069
76. Acharya AB, Annamali S, Taub NA, Field D. Oral sucrose analgesia for preterm infant venepuncture. Arch Dis Child Fetal Neonatal Ed. 2004;89 :F17 –F18[Free Full Text]
77. Carbajal R, Veerapen S, Couderc S, Jugie M, Ville Y. Analgesic effect of breastfeeding in term neonates: randomized controlled trial. BMJ. 2003;326 :13[Abstract/Free Full Text]
78. Bo LK, Callaghan P. Soothing pain-elicited distress in Chinese neonates. Pediatrics. 2000;105(4) . Available at: www.pediatrics.org/cgi/content/full/105/4/e49
79. Ward-Larson C, Horn RA, Gosnell F. The efficacy of facilitated tucking for relieving procedural pain of endotracheal suctioning in very low birthweight infants. MCN Am J Matern Child Nurs. 2004;29 :151 –156; quiz 157–158[CrossRef][Medline]
80. Huang CM, Tung WS, Kuo LL, Ying-Ju C. Comparison of pain responses of premature infants to the heelstick between containment and swaddling. J Nurs Res. 2004;12 :31 –40[Medline]
81. Carbajal R, Lenclen R, Gajdos V, Jugie M, Paupe A. Crossover trial of analgesic efficacy of glucose and pacifier in very preterm neonates during subcutaneous injections. Pediatrics. 2002;110 :389 –393[Abstract/Free Full Text]
82. Akman I, Ozek E, Bilgen H, Ozdogan T, Cebeci D. Sweet solutions and pacifiers for pain relief in newborn infants. J Pain. 2002;3 :199 –202[CrossRef][Web of Science][Medline]
83. Fernandez M, Blass EM, Hernandez-Reif M, Field T, Diego M, Sanders C. Sucrose attenuates a negative electroencephalographic response to an aversive stimulus for newborns. J Dev Behav Pediatr. 2003;24 :261 –266[Web of Science][Medline]
84. Taddio A, Shah V, Shah P, Katz J. B-Endorphin concentration after administration of sucrose in preterm infants. Arch Pediatr Adolesc Med. 2003;157 :1071 –1074[Abstract/Free Full Text]
85. Bauer K, Ketteler J, Hellwig M, Laurenz M, Versmold H. Oral glucose before venepuncture relieves neonates of pain, but stress is still evidenced by increase in oxygen consumption, energy expenditure, and heart rate. Pediatr Res. 2004;55 :695 –700[CrossRef][Web of Science][Medline]
86. Stevens B, Yamada J, Ohlsson A. Sucrose for analgesia in newborn infants undergoing painful procedures. Cochrane Database Syst Rev. 2004;(3) :CD001069
87. Johnston CC, Filion F, Snider L, et al. Routine sucrose analgesia during the first week of life in neonates younger than 31 weeks' postconceptional age. Pediatrics. 2002;110 :523 –528[Abstract/Free Full Text]
88. Jain A, Rutter N. Does topical amethocaine gel reduce the pain of venepuncture in newborn infants? A randomized double blind controlled trial. Arch Dis Child Fetal Neonatal Ed. 2000;83 :F207 –F210[Abstract/Free Full Text]
89. Long CP, McCafferty DF, Sittlington NM, Halliday HL, Woolfson AD, Jones DS. Randomized trial of novel tetracaine patch to provide local anaesthesia in neonates undergoing venepuncture. Br J Anaesth. 2003;91 :514 –518[Abstract/Free Full Text]
90. Kaur G, Gupta P, Kumar A. A randomized trial of eutectic mixture of local anesthetics during lumbar puncture in newborns. Arch Pediatr Adolesc Med. 2003;157 :1065 –1070[Abstract/Free Full Text]
91. Moore J. No more tears: a randomized controlled double-blind trial of Amethocaine gel vs. placebo in the management of procedural pain in neonates. J Adv Nurs. 2001;34 :475 –482[CrossRef][Web of Science][Medline]
92. Stevens B, Johnston C, Taddio A, et al. Management of pain from heel lance with lidocaine-prilocaine (EMLA) cream: is it safe and efficacious in preterm infants? J Dev Behav Pediatr. 1999;20 :216 –221[Web of Science][Medline]
93. Jain A, Rutter N, Ratnayaka M. Topical amethocaine gel for pain relief of heel prick blood sampling: a randomized double blind controlled trial. Arch Dis Child Fetal Neonatal Ed. 2001;84 :F56 –F59[Abstract/Free Full Text]
94. Ballantyne M, McNair C, Ung E, Gibbins S, Stevens B. A randomized controlled trial evaluating the efficacy of tetracaine gel for pain relief from peripherally inserted central catheters in infants. Adv Neonatal Care. 2003;3 :297 –307[CrossRef][Medline]
95. Sinisterra S, Miravet E, Alfonso I, Soliz A, Papazian O. Methemoglobinemia in an infant receiving nitric oxide after the use of eutectic mixture of local anesthetic. J Pediatr. 2002;141 :285 –286[CrossRef][Web of Science][Medline]
96. Frey B, Kehrer B. Toxic methemoglobin concentrations in premature infants after application of a prilocaine-containing cream and peridural prilocaine. Eur J Pediatr. 1999;158 :785 –788[CrossRef][Web of Science][Medline]
97. Brisman M, Ljung BM, Otterbom I, Larsson LE, Andreasson SE. Methemoglobin formation after the use of EMLA cream in term neonates. Acta Paediatr. 1998;87 :1191 –1194[CrossRef][Web of Science][Medline]
98. Essink-Tjebbes CM, Hekster YA, Liem KD, van Dongen RT. Topical use of local anesthetics in neonates. Pharm World Sci. 1999;21 :173 –176[CrossRef][Web of Science][Medline]
99. Bhandari V, Bergqvist L, Kronsberg S, Barton BA, Anand KJ; NEOPAIN Trial Investigators Group. Morphine administration and short-term pulmonary outcomes among ventilated preterm infants. Pediatrics. 2005;116 :352 –359[Abstract/Free Full Text]
100. Ng E, Taddio A, Ohlsson A. Intravenous midazolam infusion for sedation of infants in the neonatal intensive care unit. Cochrane Database Syst Rev. 2000;(2) :CD002052
101. Saarenmaa E, Neuvonen PJ, Huttunen P, Fellman V. Ketamine for procedural pain relief in newborn infants. Arch Dis Child Fetal Neonatal Ed. 2001;85 :F53 –F56[Abstract/Free Full Text]
102. Anand KJ, Sippell WG, Aynsley-Green A. Randomised trial of fentanyl anaesthesia in preterm babies undergoing surgery: effects on the stress response [published correction appears in Lancet. 1987;1(8526):234]. Lancet. 1987;1(8524) :62 –66
103. Barker DP, Rutter N. Stress, severity of illness, and outcome in ventilated preterm infants. Arch Dis Child Fetal Neonatal Ed. 1996;75 :F187 –F190[Abstract/Free Full Text]
104. Anand KJ, Hickey PR. Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery. N Engl J Med. 1992;326 :1 –9[Abstract]
105. Soto RG, Fu ES. Acute pain management for patients undergoing thoracotomy. Ann Thorac Surg. 2003;75 :1349 –1357[Abstract/Free Full Text]
106. Cass LJ, Howard RF. Respiratory complications due to inadequate analgesia following thoracotomy in a neonate. Anaesthesia. 1994;49 :879 –880[Web of Science][Medline]
107. Santeiro ML, Christie J, Stromquist C, Torres BA, Markowsky SJ. Pharmacokinetics of continuous infusion fentanyl in newborns. J Perinatol. 1997;17 :135 –139[Medline]
108. Saarenmaa E, Neuvonen PJ, Fellman V. Gestational age and birth weight effects on plasma clearance of fentanyl in newborn infants. J Pediatr. 2000;136 :767 –770[CrossRef][Web of Science][Medline]
109. Bouwmeester NJ, Anand KJ, van Dijk M, Hop WC, Boomsma F, Tibboel D. Hormonal and metabolic stress responses after major surgery in children aged 0–3 years: a double-blind, randomized trial comparing the effects of continuous versus intermittent morphine. Br J Anaesth. 2001;87 :390 –299[Abstract/Free Full Text]
110. Pappas AL, Fluder EM, Creech S, Hotaling A, Park A. Postoperative analgesia in children undergoing myringotomy and placement equalization tubes in ambulatory surgery. Anesth Analg. 2003;96 :1621 –1624[Abstract/Free Full Text]
111. Bean-Lijewski JD, Hunt RD. Effect of ketorolac on bleeding time and postoperative pain in children: a double-blind, placebo-controlled comparison with meperidine. J Clin Anesth. 1996;8 :25 –30[CrossRef][Web of Science][Medline]
112. Rusy LM, Houck CS, Sullivan LJ, et al. A double-blind evaluation of ketorolac tromethamine versus acetaminophen in pediatric tonsillectomy: analgesia and bleeding. Anesth Analg. 1995;80 :226 –229[Abstract]
113. Burd RS, Tobias JD. Ketorolac for pain management after abdominal surgical procedures in infants. South Med J. 2002;95 :331 –333[Web of Science][Medline]
114. Romej M, Voepel-Lewis T, Merkel SI, Reynolds PI, Quinn P. Effect of preemptive acetaminophen on postoperative pain scores and oral fluid intake in pediatric tonsillectomy patients. AANA J. 1996;64 :535 –540[Medline]
115. Padda GS, Cruz OA, Krock JL. Comparison of postoperative emesis, recovery profile, and analgesia in pediatric strabismus repair: rectal acetaminophen versus intravenous fentanyl-droperidol. Ophthalmology. 1997;104 :419 –424[Web of Science][Medline]
116. Howard CR, Howard FM, Weitzman ML. Acetaminophen analgesia in neonatal circumcision: the effect on pain. Pediatrics. 1994;93 :641 –646[Abstract/Free Full Text]
117. Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants. Acta Anaesthesiol Scand. 2001;45 :20 –29[CrossRef][Web of Science][Medline]
118. Anderson BJ, van Lingen RA, Hansen TG, Lin YC, Holford NH. Acetaminophen developmental pharmacokinetics in premature neonates and infants: a pooled population analysis. Anesthesiology. 2002;96 :1336 –1345[CrossRef][Web of Science][Medline]
119. Vas L, Naregal P, Sanzgiri S, Negi A. Some vagaries of neonatal lumbar epidural anaesthesia. Paediatr Anaesth. 1999;9 :217 –223[Web of Science][Medline]
120. Sethna N. Regional anesthesia and analgesia. Semin Perinatol. 1998;22 :380 –389[CrossRef][Web of Science][Medline]
121. Scarfone RR, Jasani M, Gracely EJ. Pain of local anesthetics: rate of administration and buffering. Ann Emerg Med. 1998;31 :36 –40[CrossRef][Web of Science][Medline]
122. Rosen DA, Morris JL, Rosen KR, et al. Analgesia for pediatric thoracostomy tube removal. Anesth Analg. 2000;90 :1025 –1028[Abstract/Free Full Text]
123. Allegaert K, Naulaers G, Debeer A, et al. The use of methohexital during chest tube removal in neonates. Paediatr Anaesth. 2004;14 :308 –312[CrossRef][Medline]
124. Topulos GP, Lansing RW, Banzett RB. The experience of complete neuromuscular blockade in awake humans. J Clin Anesth. 1993;5 :369 –374[CrossRef][Web of Science][Medline]
125. Pokela ML, Koivisto M. Physiological changes, plasma B-endorphin and cortisol responses to tracheal intubation in neonates. Acta Paediatr. 1994;83 :151 –156[Web of Science][Medline]
126. Lemyre B, Doucette J, Kalyn A, Gray S, Marrin ML. Morphine for elective endotracheal intubation in neonates: a randomized trial [ISRCTN43546373]. BMC Pediatr. 2004;4 :20[CrossRef][Medline]
127. Barrington KJ, Byrne PJ. Premedication for neonatal intubation. Am J Perinatol. 1998;15 :213 –216[Web of Science][Medline]
128. Bhutada A, Sahni R, Rastogi S, Wung JT. Randomised controlled trial of thiopental for intubation in neonates. Arch Dis Child Fetal Neonatal Ed. 2000;82 :F34 –F37[Abstract/Free Full Text]
129. Naulaers G, Deloof E, Vanhole C, Kola E, Devlieger H. Use of methohexital for elective intubation in neonates. Arch Dis Child Fetal Neonatal Ed. 1997;77 :F61 –F64[Abstract/Free Full Text]
130. Haigh PM, Chiswick ML, Odonoghue EP. Retinopathy of prematurity: systemic complications associated with different anaesthetic techniques at treatment. Br J Ophthalmol. 1997;81 :283 –287[Abstract/Free Full Text]
131. Belda S, Pallas CR, Ce La Cruz J, Tejada P. Screening for retinopathy of prematurity: is it painful? Biol Neonate. 2004;86 :195 –200[CrossRef][Web of Science][Medline]
132. Grabska J, Walden P, Lerer T, et al. Can oral sucrose reduce the pain and distress associated with screening for retinopathy of prematurity? J Perinatol. 2005;25 :33 –35[CrossRef][Medline]
133. Mitchell A, Stevens B, Mungan N, Johnson W, Lobert S, Boss B. Analgesic effects of oral sucrose and pacifier during eye examinations for retinopathy of prematurity. Pain Manag Nurs. 2004;5 :160 –168[CrossRef][Medline]
134. Marsh V, Young O, Dunaway K, et al. Efficacy of topical anesthetics to reduce pain in premature infants during eye examinations for retinopathy of prematurity. Ann Pharmacother. 2005;39 :829 –833[Abstract/Free Full Text]
135. Sammartino M, Bocci MG, Ferro G, et al. Efficacy and safety of continuous intravenous infusion of remifentanil in preterm infants undergoing laser therapy in retinopathy of prematurity: clinical experience. Paediatr Anaesth. 2003;13 :596 –602[CrossRef][Web of Science][Medline]
136. American Academy of Pediatrics, Task Force on Circumcision. Circumcision policy statement. Pediatrics. 1999;103 :686 –693[Abstract/Free Full Text]

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The following policy statement has been revised:

Prevention and Management of Pain and Stress in the Neonate

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Pediatrics 105: 454-461. [Full Text]

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Additional information

Cindy L Castaldi

Pediatrics Online, 16 Jan 2008 [Full text]

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