Neonatal Pain Associated with Caregiving Procedures

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Acute Pain in Children

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Neonatal Pain Associated with Caregiving Procedures

Richard E. Marshall, MD* /

The question of whether newborn infants feel pain is a topic of general interest that has been discussed in the lay press and has focused on circumcision and surgery. Articles about circumcision have asked whether it should be a routine procedure and whether local anesthesia should be administered as part of the procedure. Premature infants who undergo operations for repairing the patent ductus arteriosus traditionally receive muscle paralysis and the mild anesthetic, nitrous oxide. Parents have expressed deep concern about whether a more powerful analgesia should routinely be used for such surgery.21, 37, 67, 73 The question of whether newborn infants feel pain is a problem for health care providers as well as parents. A national survey, to which 64 nurses from 142 neonatal intensive care units (NICUs) responded, revealed that 59 per cent believe that newborn infants do not feel pain in a manner similar to an adult. Yet 77 per cent responded that pain medication was underutilized. Ninety-five per cent reported that agitation was a problem in the NICU, but 40 per cent noted that no medication was given to agitated infants with chronic lung disease. 26 It is clear that there is still considerable uncertainty about whether infants feel pain and whether analgesia and anesthesia are warranted for aversive newborn caregiving interventions. This review examines the literature on infant pain associated with clinical care and suggests guidelines for future studies in this new area. A major problem in determining whether newborns experience pain after aversive procedures is that infants are preverbal and do not have direct methods of saying that "something you are doing hurts me." However, there is another component of the response to pain that is associated with direct damage to tissues. 56 There is ample clinical, morphologic, and biochemical evidence to suggest that infants have the capacity to *Professor of Pediatrics/Human Development, Michigan State University, East Lansing, Michigan

Pediatric Clinics of North America-Vol. 36, No.4, August 1989

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respond to tissue damage associated with aversive stimuli that are considered painful by adults. 4 Therefore, it is possible to examine the responses of newborn infants to stimuli that have been found unequivocally to be painful to adults. Such aversive stimuli in the newborn have been associated with necessary diagnostic and therapeutic interventions such as blood drawing and circumcision. We can classify the responses to these stimuli as analogous to painful adult responses and categorize these acute responses as physiologic, biochemical, and behavioral. 46. 52. 55 Such responses are summarized in Table 1. We will examine this information in more detail and use it as a guideline, using blood drawing from the heel lance, circumcision, surgery, and treatment for pain in the NICU as examples.

BLOOD DRAWING FROM THE HEEL LANCE PROCEDURE

The procedure of drawing blood from the heels of infants has been described in detail. 23 The heel is warmed by wrapping it in a wet cloth for about 5 min. After being cleansed with alcohol, the heel is grasped firmly and punctured with a lance. Ideally, enough blood should flow so that squeezing the heel is not required in order to obtain the sample of blood required to fill the capillary tubes. A dry piece of cotton or gauze is used to secure hemostasis. The procedure itself is worthy of comment. There is considerable variation in technique. The blood drawers use different amounts of pressure to apply the lancet to the heel. Clinical observation also shows that variable pressure is applied in squeezing the heel, when required to obtain adequate blood flow. Therefore, although it is possible to describe a series of responses to heelsticks, there will be some unknown variability in the procedure itself that may account for the range of responses that are elicited. Whenever the data are available, precise technical details about the heelstick procedure will be presented.

PHYSIOLOGICAL MEASURES

Heart Rate (Term Infants) Owens and Todt57 studied the responses of 20 healthy term newborns (10 male and 10 female) to a heelstick on the second day of life. They used a three lead EKG to calculate the heart rate at 15 sec intervals during the entire procedure which consisted of warming the heel (15 to 30 min), cleansing with alcohol (1.5 min), heel lance, and massage. An unknown number of subjects required repeated heelsticks to obtain an adequate blood flow. Massage of the heel was routinely applied to improve blood flow. The average rate in increase in heart rate was 49.0 bpm (SD ± 27.5 bpm) over the preceding rate during the heel warming baseline with

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Table 1. Changes in Neonatal Patients Undergoing Caregiving Procedures AGE OF INFANT MEASUREMENT

Physiological Heart rate Transcutaneous p02

Respiratory rate Systolic blood pressure Vagal tone Behavioral Facial expression

Emotional sweating Palmar water loss Crying

RESPONSE

Heel lance Circumcision Circumcision

Increased heart rate Increased heart rate Decrease in TCp02

Term Term Term

57 64,77

Heel lance

Term Preterm

11 9,53

Circumcision Heel lance Heel lance

Increase in TCp02 No significant change in TCp02 Increase Increase Increase

Term Term Term

64

Circumcision

Decrease

Term

62

Heel lance

Term

31

Heel lance

1. 2. 3. 4. 1.

Term

35

Heel lance

1.

Term

57

Circumcision

1.

Term

77

Term

61

Term

27

Term

50

2.

Photogrammetryquantitative video analysis

Modified Brazelton Newborn Assessment Scale Mother/infant interaction Biochemical Serum cortisol

TERM OR PRETERM

STIMULUS

Brow bulge Eye squeeze Nasolabial fold Open lips Increase in palmar water loss Increase in percentage of time crying Increase in percentage of time crying Nature and perception of cry changed Immediate withdrawal of both legs Facial grimacing Crying Changes in behavior category

REFERENCE

64

11 11

Heel lance

1.

Circumcision

2. 3. 1.

Circumcision

1. Minor changes

Term

49

Circumcision

Increase in cortisol level

Term

32,74,76

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measured as the infant awoke, cried, and calmed down. Results demonstrated that infants of more than 37 weeks' gestational age had 200 to 300 per cent increases in palmar water loss within a minute of the heelstick. The increase in palmar water loss became more pronounced as the infants became older, and there was a nearly 500 per cent increase by 2 weeks after birth. The increases in palmar water loss were of brief duration, and the infants returned to the preheelstick baseline by 4 min.35

PSYCHOLOGICAL MEASURES

Crying Owens and Todt measured crying in 20 healthy term infants after a heel lance. A microphone was placed within 20 to 30 cm of the infant's mouth and a cassette recorder was used to record the infant's cries. Crying was defined as "audible distress vocalization" and interobserver reliability was 96.2 per cent. The duration of the crying following heel lance was 207 sec and was significant compared to the pretreatment phase by analysis of variance with P<0.01. 57 Facial Expressions Grunau and Craig examined 140 term babies on the second day of life to determine if there were any distinctive facial expressions associated with a heel lance. Thirty-six continuous segments were recorded by videotape including 2 segments before the heel lance and 10 segments after the procedure. Nine distinct facial behaviors were adopted from adult studies and modified for infants. 14, 18, 54 The nine distinct behaviors they scored were: (1) brow bulge, (2) eye squeeze, (3) nasolabial fold, (4) open lips, (5) stretch mouth-vertical position, (6) stretch mouth-horizontal position, (7) lip purse, (8) taut tongue, and (9) chin quiver. Interobserver reliability for facial coding was 88 per cent. After the heel lance, four distinct facial characteristics appeared within 3 seconds in over 95 per cent of the subjects: brow bulge, eye squeeze, nasolabial fold, and open lips. It was thought that during the last 24 to 36 sec of the observations, differences in pressure during the squeezing of the heel had a "variable impact on the facial expression subsequent to the heel lance. "31

BEHAVIORAL MEASURES

Photogramming-Quantitative Video Analysis Franck studied 10 healthy term newborns who received heelsticks at 4 hours of age. She used a video screen that was calibrated to the actual distance of the subject from the camera lens. She recorded time on the video screen in 0.01 sec by taking measurements of the distances and movements of the legs and ankle joints across the grid. It was possible to determine quantitative parameters of movement in time. Representative data revealed that the unaffected leg moved in 0.3 sec and the leg with the

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heels tick moved in 0.4 sec. Additional quantitative data about facial grimacing and crying were obtained on repeated heelsticks with this new, promising technique. 27

AMELIORATING PAIN

Changing the Lance Harpin assessed the infants' reactions to two methods of blood sampling by heel lances by measuring water loss with an evaporimeter. Blood was drawn from a heel by either a conventional sterile metal stylet or a springloaded syringe (autolet). Eighteen subjects were in each group. The time required to obtain the blood samples was not significantly different for each group-about 3 min. However, as summarized in Table 2, the groups required different amounts of time to return to baseline-3 min for the autolet compared to 6 min for the stylet. There was also approximately 25 per cent more total water loss in the stylet group. Both these differences were significant at P
Gomco Technique The penis is cleansed with an antiseptic and draped. The dorsal aspects of the prepuce are grasped with mosquito hemostats approximately 2 and 4 cm apart. A blunt probe is used to separate the inner epithelium of the prepuce from the glans penis. It is important not to dissect along the posterior portion of the glans because there are many small, fragile, bleeding vessels in that area. After the dissection is complete, a crush injury is made along the anterior surface of the prepuce. The lower blade of the straight hemostat is placed between the prepuce and the glans, being sure to avoid the urethra. The hemostat is closed for 2 to 3 sec to crush the foreskin in the midline. Then a cut is made along the crush injury with scissors. The clamp and prepuce with the slit are placed over the bell portion of the clamp and the edges of the dorsal slit are approximated with the

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baseplate of the clamp. Caution requires that just enough of the prepuce is pulled through the clamp. A 5-min wait is required for hemostasis. The prepuce is then removed with a scalpel blade held parallel to the upper surface of the baseplate. The bolt on the baseplate is then loosened and the clamp removed. The wound is dressed with Vaseline impregnated sterile gauze. 48 I

PHYSIOLOGICAL

Heart Rate Williamson and Williamson 77 recorded the heart rate of 10 healthy term infants throughout the entire 26-min procedure of circumcision. During the 3-min interval required for dissection between the prepuce and glans penis there was a 54.1 ± 17.8 increase in bpm over the baseline heart rate. This difference was significant at P
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respiratory sinus arrhythmia was extracted from the heart period data according to the method of Porges. 59 A representative analysis of the data evaluated the responses of 32 circumcised infants over 5 periods: preoperative baseline, preoperative restraint, surgery (collapsing the intervals from cleansing the penis to the removal of the Gomco clamp), postoperative restraint, and postoperative baseline. Vagal tone was significantly lower (v = 2.36) during surgery than during the preoperative (v = 2.98) and postoperative (v = 3.51) periods by the post hoc Newman-Keuls tests. 62

BEHAVIOR

Modified Brazelton Scale Twenty infants were randomly assigned to an early (2 day) and delayed (3 week) circumcision group. Each group was examined three times using the Brazelton Behavioral Assessment Scale, during which the examiner was blind to the circumcision status of the subject. A reduction scale was derived from the Brazelton examination so that infants were assigned to the behavioral categories of average, subdued, or hyperactive. Nearly 90 per cent of the early circumcision group changed behavior categories for at least 4 hours after circumcision compared to 16 per cent in the delayed group (P
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and infant during feeding sessions. Our data suggest that circumcision has a brief and transitory effect on mother-infant interactions. 49 Crying Williamson and Williamson,77 in the study previously described, found that 10 infants during the 3-min dissection period cried 93.7 per cent more than during the baseline period. This was significant at P
METABOLIC

Corticosteroids It is well known that painful events lead to an increase in serum corticosteroids. 34 Serum corticosteroids have been examined after circumcision. Tennes and Carter75 examined serum cortisol and found no significantly different levels in 23 boys (mean 15.8 f.Lg per cent) and 17 girls (mean 14.1 f.Lg per cent). Ten of the boys had been circumcised within 24 hours of the cortisol sampling and 10 boys after 24 hours. There were no significant differences between the means of the two groups (19.56 f.Lg per cent SD±12.9 compared to 12.89 f.Lg per cent SD±9.00). However, three other groups of investigators have found that steroids increased significantly after circumcisions. Talbert et aF4 measured serum cortisol and cortisone after circumcision during the first 6 hours of life. Three measurement values were obtained from heelsticks: a baseline value and samples 20 and 40 min postcircumci-

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sion. Postcircumcision baseline cortisol (n = 5) increased from a baseline mean of 5.8 (SO ±3.9) to a 20-min level of mean 14.7 (SO ± 2. 7) (P<0.0025) and a 40-min level of mean 15.5 (SO ± 5.0) (P<0.005). Baseline cortisone (n=5) increased from a mean of 7.3 (SO± 1.38) to a 20-min mean of 8.5 (SO±0.99) (P<0.050). The 40-min level was not significantly elevated. Gunnar et aP3 measured serum cortisol in samples obtained from venipuncture after birth in eight healthy term infants who were circumcised between 57 and 80 hours. Baseline cortisol measurements were obtained before the infant was strapped to the circumcision board and 30 min later. After the circumcision was performed, mean baseline values of approximately 8 f.Lg per ml increased to mean levels of approximately 24 f.Lg per ml, which was statistically significant using the paired t test at P
AMELIORATION OF PAIN

Local Anesthesia The studies that have attempted to ameliorate the pain associated with circumcision are summarized in Table 2. Kirya and Werthmann 43 described a technique of penile dorsal nerve block that was designed to produce what they called a "painless procedure." Their technique required injections of 0.2 to 0.4 ml of lidocaine at 10 and 12 o'clock at the base of the penis with a 27 gauge needle angled at about 25 degrees to a depth of no more than 0.25 to 0.50 cm. They then waited about 2 to 3 min for the anesthetic to take effect and began the circumcision. They injected 52 subjects. Success was judged by a subjective estimate of the absence of crying at any time except during the time of injection. Crying during circumcision was only found in two subjects. The success rate of the procedure was 96.2 per cent. The swelling from the lidocaine injection was said to have disappeared by 24 hours. Williamson and Williamson 77 used the Kirya and Werthmann technique to study the effects of dorsal penile nerve block on crying time, heart rate, and TCp02. Twenty experimental patients received lidocaine injections and were compared to a control group of 10 subjects who received no injections. Each infant was studied for a total of 26 min. Significantly different results were obtained from the two groups during the 3-min interval when the most invasive surgery was done. The TCp02 fell 4.7 mm per Hg± 10.6 (P
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Table 2. Results of Measurements in Neonatal Patients Undergoing Caregiving Procedures PROCEDURE

Heel lance

INTERVENTION

Improved heel lance Pacifier

Circumcision

Lidocaine penile dorsal nerve block

MEASUREMENT

Palmar water loss (emotional sweating) Behavior

Crying

1. Crying 2. Heart rate 3. Transcutaneous oxygen

1. Clinical assessment of anesthesia efficacy 2. Heart rate 3. Crying Serum cortisol

Serum cortisol Crying

1. Heart rate 2. Oxygen saturation 3. Blood pressure

Pacifier

1. Serum cortisol 2. Crying

RESULT

REFERENCE

Less palmar water loss with improved lance

36

1. Less crying 2. More alert 3. Behavior Decreased crying

19

1. Decreased crying time 2. Decreased heart rate, rate decreased with anesthesia 3. Decreased in TCp02 1. Anesthesia clinically effective 2. Decreased heart rate rise with anesthesia 3. Decreased crying with anesthesia No difference between serum cortisol levels in lidocaine and cortisol subjects 1. Decreased serum cortisol in lidocaine group 2. Decreased crying in lidocaine group 1. Lower heart rate with increased lidocaine 2. Lower fall in oxygen saturation with lidocaine 3. No effect on blood pressure 1. No effect on cortisol 2. Decreased crying

43

77

40

76

72

51

33

Outcome measures were clinical observations (agitation and distress), heart rate, and crying. Fourteen of the fifteen infants had minimal signs of distress, interpreted as a good response to anesthesia, compared to one of the saline sham controls and none of the controls. There was Significantly less crying and heart rate increase (P
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controls who were circumcised without any anesthesia. A 1 ml sample of blood was drawn for a cortisol level before the circumcision and 30 min after the clamp was applied. The anesthetic was 2 mg per kg of lidocaine, and all the circumcisions were done by the same operator. The group cortisol mean before surgery was approximately 10 f.lg per dl and rose to 22.9 f.lg per dl after surgery. There were no statistical differences in serum cortisol levels of the two groups. Stang et aF2 divided 60 healthy term infants at random into three equal groups of 20. One group received 0.8 ml (8 mg) of lidocaine prior to their circumcision, the second group received 0.8 ml of normal saline as a sham control, and the final group received no injections prior to circumcision. Plasma cortisol samples were obtained by heels tick after the infants were placed on the circumstraint board and 90 min later .. Infants were soothed continuously by an attendant who offered pacifiers. The circumcisions were performed by 17 different pediatricians with no pediatrician doing more than 3 circumcisions. The plasma cortisol levels were averaged over 30 and 90 min and were significantly lower for the lidocaine-injected infants than for both the sham controls and controls (P<0.05). The percentage of crying time for the lidocaine subjects was also significantly less than that for the sham and no injection group (P
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half served as controls without pacifiers. The pacifier group cried about 35 per cent less than the control group (P
Perhaps no issue in neonatology has become more controversial recently than pain relief for surgery in newborn infants. The problems associated with analgesia and surgery were highlighted by the well-known case of Baby Lawson. Jeffery Lawson was operated on for ligation of a patent ductus arteriosus with Pavulon for paralysis without analgesia or anesthesia. He died 6 weeks after surgery. His mother was concerned that no pain relief was provided during the surgery, and the issues that she raised as a parent have focused medical attention on the problems of analgesia for newborn surgery. 10, 13, 22, 67 Two major questions have emerged from the current discussion about analgesia and surgery: (1) Are there safe analgesic agents available for pain relief during surgery for critically ill newborns? (2) Do surgical patients give any indication that they feel pain during surgery and might this experience of pain have an impact upon the response to surgery? To address the question of analgesia safety, we can focus on the analgesic that has received the most attention, fentanyl, a potent synthetic opioid analgeSic. There have been numerous studies in the anesthesiology literature which have demonstrated that fentanyl can be administered safely to neonates undergoing surgery. 12, 28, 38, 65, 81 The question of whether newborn infants undergoing surgery can experience pain has been carefully studied by Anand and his colleagues. 6 They focused their attention on the issue of whether newborns can react to the stress of surgery by releasing specific hormones and metabolites that have been associated with the stress of surgery in older patients. In their initial studies, they found that newborns had a profound rise in blood sugar during and after surgery. This hyperglycemia was associated with an initial rise in catecholamines and a subsequent rise in glucagon. They suggested that the initial rise in glucose was initiated by the catecholamines and sustained later by glucagon. Once it was established that newborns could mount a stress response to surgery, it was possible to use this as a basis for two important clinical trials to determine whether analgesia and anesthesia could modify the stress response to surgery. 2 In their first study, preterm babies about to undergo ligation for a patent ductus arteriosus were given nitrous oxide and curare with or without fentanyl (10 /-Lg per ml). At the start of the study, there were no clinical or hormonal differences between the two groups, whose subjects weighed 1 kg and were operated on at 2 weeks of age. However, at the end of the study, there were differences in hormonal, metabolic, and clinical responses between the two groups. Plasma adrenaline rose significantly during surgery in the nonfentanyl control group, and this rise persisted for 24 hours postoperatively. Blood glucose rose 300 per cent in the control group during surgery, and this elevation persisted for up to 6

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hours. Other substrates that were significantly higher in the control infants included lactate and pyruvate as well as total gluconeogenic substrates (lactate, pyruvate, alanine, and glycerol). From the clinical perspective, the patients in the control group required more ventilatory support and had more circulatory and metabolic complications. 6 This study demonstrates that the fentanyl-treated patients had a dampened response to the stress of surgery. It cannot be proved that this response was due to pain relief, but it implies that the conventional anesthetic regimen did not ameliorate stress as effectively as the fentanyl did. It is clear that there are some important clinical implications to this study: (1) The prevention of hyperglycemia may be helpful in preventing complications from hyperosmolality, including intracranial hemorrhage. 7 (2) Although it is difficult to interpret results from such a small sample (n = 8 in each group), it may be possible to achieve fewer postoperative complications with fentanyl. Anand's second study used a similar approach. He studied 45 neonates undergoing cardiac surgery who required cardiopulmonary bypass and deep hypothermic circulatory arrest. Infants were randomized to receive conventional anesthesia with or without sufentanil during surgery and postoperatively. Sufentanil is an opioid analgesic that is said to be about 10 times more potent than fentanyl with half its duration of action. 30 Results indicated that blood glucose, lactate, pyruvate, and alanine as well as plasma betaendorphin levels were lower in the sufentanil-treated group. The data again suggest that opiates can alter the severe stress reaction associated with neonatal surgery. 5

NEONATAL INTENSIVE CARE UNIT There is little literature that deals directly with the issue of pain in NICU patients. There are reports that demonstrate a fall in transcutaneous p02 associated with handling and routine care. 15, 47, 71 There are also studies showing that chest physiotherapy, particularly suctioning, can lead to a fall in TCp02 ranging between 20 and 30 mm per Hg.25, 63, 69 However, it is not clear whether these changes in oxygen are associated directly with pain or with other mechanisms such as mechanical obstruction of the airway associated with suctioning. There are also reports in the literature that have examined intubation to determine whether intervention with drugs could alter physiologic changes that accompany intubation. Kelly and Finer42 studied the effects of atropine and pancuronium on physiologic changes associated with nasal intubation. They found a Significant decrease in TCp02 (27.2 mm per Hg) combined with significant increases in mean arterial blood pressure (57 per cent) and intracranial pressure (18.9 cm per H 20) during intubation. The control infants and those who received atropine had Significant decreases in heart rate during intubation. Those patients who received pancuronium and atropine had significantly smaller changes in intracranial pressure and heart rate without any major effect on TCp02 or blood pressure. The authors suggest that the changes associated with intubation may represent

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cardiovascular re~onses as well as mechanical factors.4z Friesen et aP9 measured antertOr fontanel pressure in 12 patients who required surgery. Half of the patients received atropine and intubation was performed while the patients were awake. The anterior fontanel pressure increased from 7.7 cm per HzO to 23.3 cm per H 20 (P<0.05). In those patients who received atropine, pancuronium, and one of four anesthetics (isoHurane, halothane, fentanyl, or ketamine), there was no significant rise in anterior fontanel pressure. The mechanism by which intubation increased anterior fontanel pressure was not examined during this study, but the authors suggest that it might be related to coughing and forced expiration. 29 The studies cited are representative of what has been accomplished. There is an awareness that routine care of the newborn is accompanied by physiologic changes that might be adverse, but no controlled clinical studies have examined directly the impact of painful, invasive procedures on NICU patients. It is clear from personal experience and discussions with neonatologists that local anesthesia is widely used for the insertion of intravenous cutdowns. Porter et al 60 have preliminary data on a controlled study that examines directly the question of pain in the NICU patient. Twenty-eight infants who were about to undergo lumbar punctures were randomly divided into groups which did or did not receive lidocaine local anesthesia prior to their lumbar punctures. Heart rate, respiratory rate, transcutaneous pOz and pC02were continuously monitored for 20 min before, during, and after the lumbar puncture. Aseptic cleansing preparations resulted in significant increases in heart rate (P = 0.0001) and mean TCpCOz (P = 0.04), and decreases in minimum TCpOz(P=O.OOI). Lumbar punctures in the control group resulted in further decreases in minimum TCpOz (P=0.05) and respiratory rate (P=O.OI), and further increases in TCpC0 2 (P=0.02). No statistical changes in any measurement were observed in the lidocaine group after the lidocaine injection except for a significant decrease in heart rate (P = 0.02) that returned to baseline before the end of the procedure. Lidocaine produced no adverse effects. These preliminary data suggest that lidocaine increases physiologic stability and may ameliorate the adverse effects of the invasive procedures required for the care of sick neonates. 60

CONCLUSIONS AND SUGGESTIONS FOR FUTURE RESEARCH The data presented in this review and summarized in Table 1 clearly demonstrate that both circumcision and heels ticks have diVerse effects on newborn behavior, metabolism, and physiology. These effects are associated with what would be considered painful experiences in older children and adults. Data summarized in Table 2 suggest what may be done to alleviate the discomfort associated with circumcision and heelsticks. At the present time, the amelioration of pain associated with circumcision may be of greater importance, because there is new evidence to suggest that routine circumcision may be advisable. Wiswell et aF9, 80 have recently demonstrated that circumcised boys are 10 to 20 times less likely to have urinary tract infections in early infancy. There is also recent evidence to suggest that

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uncircumcised males are more likely to get the acquired immunodeficiency syndrome. 20. 70 For these and other reasons, WiswelFB now advises that circumcision be routine as a protective health measure. It would be helpful if there were more reports on the use of lidocaine for penile dorsal nerve block to determine whether the procedure might be used more frequently without adverse complications. There are certain general guidelines that future studies on pain in the newborn should follow. These studies must protect the rights of the infants being studied. As this review frequently demonstrates, opportunities exist for studying neonatal pain by utilizing diagnostic and therapeutic procedures that are part of newborn care. Such studies should be controlled and randomly designed. The results should permit rigorous statistical analyses. I would like to conclude by suggesting some areas for future study that I think might be important in enhancing our understanding of newborn pain: 1. Postoperative analgesia. Many health care providers are concerned that

postoperative analgesia is an unexplored area. Nurses and neonatologists often are more willing to use opiates than their surgical colleagues who have had unfortunate experiences with respiratory depression when using these compounds. It should be possible to examine the use of postoperative analgesia in a critical manner. More information about the dosage and metabolism of opiates in newborns is becoming available. 45• 82 There is also a new clinical scoring system for observing postoperative pain. 8 2. The development of an effective, safe, topical, local anesthetic for use in term and preterm infants. One of the objections to the use of lidocaine to alleviate discomfort associated with circumcisions and lumbar punctures is the pain associated with the local injection of lidocaine. Some argue that the pain of the local injection may be more trouble than the relief that the lidocaine brings. If there were a safe, topical, local anesthetic, such an objection could be overcome. The topical anesthetic might be useful in alleviating the pain associated with many neonatal procedures, including heels ticks and possibly even starting intravenous lines. 3. Are there long-term consequences of neonatal pain? From the physical perspective, it is well known to neonatologists that heel cord nodules are frequently found in NICU graduates as a result of heelsticks. 58• 68 But we know virtually nothing about whether there is memory of infant pain and if such memory has any behavioral consequences. Parents have anecdotally told me their children who have been patients in the NICU have an increased tolerance to pain in later life. They have used such expressions as "she could walk through a plate glass window and not complain." 4. What would be the impact of the use of more analgesia in the NICU on the parents and the caregivers? One of the most difficult problems that parents face in the NICU is loss of control over the destiny of their infants. Parents want to feel that all that could be done to alleviate suffering is done. If more attention were paid to pain and analgesia, parents would be more satisfied with the care their infants receive.

I also believe that it is difficult for nurses and physicians who work in the NICU to watch infants undergo procedures for which analgesia might be helpful. If we paid more attention to neonatal pain, perhaps we would decrease caregiver burnout.

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ACKNOWLEDGMENTS I thank Sandra Marsik, Rosann Prudhoe, and Frances Shelley for secretarial assistance and Judy Marshall for editorial help.

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