A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair.

STUDY OBJECTIVE: To compare the efficacy and complication profile of oral midazolam therapy and continuous-flow 50% nitrous oxide in alleviating anxiety during laceration repair in children 2 to 6 years old. METHODS: We conducted a prospective, randomized clinical trial using 4 study groups who required laceration repair: (1) children who received standard care alone, which included comforting and topical anesthesia augmented with injected lidocaine if needed; (2) children who received standard care and oral midazolam; (3) children who received standard care and nitrous oxide; and (4) children who received standard care, oral midazolam, and nitrous oxide. Videotapes were blindly scored using the Observational Scale of Behavioral Distress-Revised (OSBD-R) to assess distress during baseline, wound cleaning, lidocaine injecting, suturing, and recovery. Adverse effects were noted during suturing and by parent questionnaires completed 24 hours after suturing and at suture removal. OSBD-R data were analyzed using repeated-measures analysis of variance. Adverse effect data were analyzed using categorical models. RESULTS: Two hundred four subjects were enrolled (midazolam plus nitrous oxide 52, midazolam 51, nitrous oxide 51, standard care 50; mean patient age was 4.1 years; 66% were boys). Mean OSBD-R scores were lower for groups that received nitrous oxide during wound cleaning by 2.2 points (95% confidence interval [CI] 1.1 to 3.2), lidocaine injecting by 2.5 points (95% CI 1.4 to 3.5), and suturing by 2.9 (95% CI 1.8 to 3.9). Adverse effects occurred more frequently, and recovery times were longer for groups that received midazolam. CONCLUSION: For facial suturing in 2- to 6-year-old children, regimens including continuous-flow nitrous oxide were more effective in reducing distress, and had fewer adverse effects and shorter recovery times than midazolam.

Long-term effects of pain in infants.

Pain and stress have been shown to induce significant physiological and behavioral reactions in newborn infants, even in those born prematurely. Infants who are born prematurely or seriously ill are commonly exposed to multiple painful and stressful events as part of their prolonged hospitalizations and required medical procedures. There is now evidence that these early events not only induce acute changes, but that permanent structural and functional changes may also result. This article reviews the growing body of evidence of likely long-term effects of early pain and stress on the human infant. It is hoped that a better understanding of this literature will promote more responsive and sensitive management of infants and young children during their encounters with the medical community and will ultimately facilitate the healthy growth and development of all children.

Procedural pain in newborn infants: the influence of intensity and development.

OBJECTIVE: Previous reports have shown that pain is managed inadequately in newborn infants. Ironically, clinicians believe that infants can experience pain much like adults, that infants are exposed daily to painful procedures, and that pain protection should be provided. In adults, a close relationship has been shown in how adults behave in response to pain, how painful they sense the stimulus to be, and physical measurements of the intensity of the stimulus. Whether similar parallels exist in newborn infants has not been examined. If these parallels do not exist in infants, it may help explain why clinicians fail to manage procedural pain in infants more effectively. The objective of this study was to determine whether the magnitude of infants' responses to nursing/medical procedures: 1) differs as a function of the invasiveness or intensity of the procedure; 2) differs as a function of intrauterine (gestational age at birth) and/or extrauterine (conceptional age) development; and 3) parallels the subjective pain ratings of clinicians for those procedures. METHODS: A broad developmental and clinical range of newborn infants was studied shortly before (baseline and preparatory periods), throughout, and shortly after (recovery period) required nursing/medical procedures during hospitalization. Heart rate, oxygen saturation, mean arterial pressure, and behavioral state (percentage of time spent in sleep or in agitation) were measured, and the magnitude of change in each in response to procedures was calculated. Procedures were categorized as mildly, moderately, and highly invasive to examine differences in response magnitude as a function of procedural invasiveness. Responses were compared as a function of prematurity and postnatal age. Clinicians' procedural pain ratings were compared with the magnitude of infants' responses. RESULTS: Of the original 152 infants, 135 were studied at least two times (range 2-27). Significant changes occurred in physiologic and behavioral measures in response to procedures indicative of pain responses. The magnitude of response generally increased with increased procedural invasiveness although there was considerable overlap of magnitude with invasiveness. Both premature and full-term infants differentiated procedural invasiveness. Very premature infants (<28 weeks' gestational age) exhibited increased increments in response magnitude with increasing postnatal age. Clinician's ratings of procedural painfulness were correlated with and predicted the magnitude of heart rate response to individual procedures. CONCLUSIONS: Similar to what has been shown in adults, newborn and developing infants show increased magnitude physiologic and behavioral responses to increasingly invasive procedures, demonstrating that even very prematurely born infants respond to pain and differentiate stimulus intensity. However, the considerable overlap of magnitude with invasiveness suggests that there is not a physiologic or behavioral threshold that clearly marks the presence of pain. Inconsistencies in physiologic and behavioral responses make reliance on a pain index difficult. The best approach may be one of universal precaution to provide pain management systematically to reduce the acute and long-term impact of early procedural pain. development, stimulus intensity, pain response.

Absence of diurnal variability of airway reactivity and hypoxic ventilatory drive in adolescents with stable asthma.

BACKGROUND: Symptoms from asthma are often prominent at night. In adults significant circadian variation has been shown with reduced peak expiratory flow rates and increased bronchial reactivity to methacholine in the early morning hours. Because adolescence is the age group with the greatest increase in asthma-related deaths in the 1980s, we hypothesized that adolescents might be susceptible to circadian variation of airway reactivity. OBJECTIVE: We sought to measure circadian variation of reactivity to methacholine (PC20) and hypoxic ventilatory drive (HVD), both of which would accentuate asthma that occurs at night and may predispose to death. METHODS: Sixteen children with asthma of various severity, aged 9 to 18 years, were studied at 4 PM and again at 4 AM to define circadian variation in FEV1, PC20, and HVD. Eleven children were studied on a second day 4 to 10 weeks after the first study. RESULTS: There was no systematic variation between 4 PM and 4 AM for FEV1 (P =.69), PC20 (P =.94), or HVD (P =.47). Six of the 16 children had PC20 values that were greater than 2-fold different between 4 PM and 4 AM; 3 of these were more reactive (requiring less methacholine) at 4 PM, and 3 were more reactive at 4 AM. At the second study, results were similar, with no systematic variation. Diurnal variability for PC20 was not consistent over the 2 study days, and at the second study all children with diurnal variability were more reactive at 4 PM. CONCLUSION: These data on airway reactivity, HVD, and other measures modulated by cholinergic neural mechanisms do not identify any systematic diurnal variation that would place an adolescent at risk for nighttime problems with asthma.

The effect of handling and immobilization on the response to acute pain in newborn infants.

BACKGROUND: Previous reports have suggested that healthy, full-term newborn infants who are in more aroused behavioral states tend to respond more robustly to painful events. Others have shown that acutely ill premature and full-term infants who undergo significant handling and immobilization as part of required nursery procedures respond less robustly to concurrent painful events. PURPOSE: To investigate, using an experimental manipulation, the effect of arousal associated with handling and immobilization on response to acute pain in generally healthy, premature and full-term newborn infants. METHODS: Infants were randomly assigned to a group that underwent a series of handling and immobilization procedures before a heelstick or to a group that underwent the heelstick without previous handling and immobilization. Heart rate, behavioral state, and facial activity were compared between the handled (n = 21) and nonhandled (n = 27) infants during an undisturbed baseline, a preparatory, and a standard heelstick procedure. RESULTS: In the handled group, heart rate increased over baseline levels in response to the handling but promptly returned to prehandling levels. There were no significant differences between handled and nonhandled groups in mean heart rate, behavioral state, or facial activity during the baseline or preparatory periods before the heelstick. However, in response to the heelstick, handled infants had a higher mean heart rate, greater behavioral arousal, and displayed more facial activity as compared with nonhandled infants. CONCLUSIONS: Healthy premature and full-term newborn infants who undergo common nursery experiences such as handling and immobilization as part of their routine care can exhibit greater physiologic and behavioral reactivity to subsequent painful procedures. The effects of the previous handling may be undetectable, using conventional indices of reactivity, until the painful event. These findings emphasize the importance of identifying reliable markers of previous stress, particularly for newborn infants who may become clinically compromised as a result of the physiologic instability associated with response to pain.

Comparison of fentanyl/midazolam with ketamine/midazolam for pediatric orthopedic emergencies.

OBJECTIVE: Emergency management of pediatric fractures and dislocations requires effective analgesia, yet children's pain is often undertreated. We compared the safety and efficacy of fentanyl- versus ketamine- based protocols. METHODOLOGY: Patients 5 to 15 years of age needing emergency fracture or joint reduction (FR) were randomized to receive intravenous midazolam plus either fentanyl (F/M) or ketamine (K/M). Measures of efficacy were observational distress scores and self- and parental-report. Measures of safety were frequency of abnormalities in and need for support of cardiopulmonary function and other adverse effects. RESULTS: During FR, K/M subjects (n = 130) had lower distress scores and parental ratings of pain and anxiety than did F/M subjects (n = 130). Although both regimens equally facilitated reductions, deep sedation, and procedural amnesia, orthopedists favored K/M. Recovery was 14 minutes longer for K/M. Fewer K/M subjects had hypoxia (6% vs 25%), needed breathing cues (1% vs 12%), or required oxygen (10% vs 20%) than did F/M subjects. Two K/M subjects required assisted ventilation briefly. More K/M subjects vomited. Adverse emergence reactions were rare but equivalent between regimens. CONCLUSIONS: During emergency pediatric orthopedic procedures, K/M is more effective than F/M for pain and anxiety relief. Respiratory complications occurred less frequently with K/M, but respiratory support may be needed with either regimen. Both regimens facilitate reduction, produce amnesia, and rarely cause emergence delirium. Vomiting is more frequent and recovery more prolonged with K/M.

Pain and pain management in newborn infants: a survey of physicians and nurses.

BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted.

Dementia and response to pain in the elderly.

To investigate the effect of dementia on response to pain, 51 community-dwelling, generally healthy, cognitively intact individuals > or = 65 years old and 44 community- or nursing home-dwelling persons > or = 65 years old with varying severity of dementia were studied. Cognitive status was assessed by standardized clinical evaluation and psychometric test performance. The following responses were measured before, during and after a standard venipuncture procedure: heart rate, the amplitude of respiratory sinus arrhythmia (RSA), self-reported anxiety and pain, and videotaped facial expressions. Although RSA did not differentiate procedural phases, in both samples, mean heart rate increased in the preparatory phase and decreased in the venipuncture phase. Independent of age, increasing severity of dementia was associated with blunting of physiologic response as measured by diminished heart rate increase in the preparatory phase and heart rate increase with venipuncture. Dementia significantly interfered with the subjects' ability to respond to direct questions about anxiety and pain. Those who were able to respond were relatively accurate self-assessors: higher anxiety was associated with greater magnitude heart rate responses. Facial expression was increased in demented individuals but it could not be classified by specific emotions. We conclude that dementia influences both the experience and reporting of pain in elderly individuals.

Neonatal stress reactivity: predictions to later emotional temperament.

To investigate the relations among popular measures of neonatal stress and their link to subsequent temperament, 50 full-term newborns from a normal care nursery were examined responding to a heelstick blood draw. Baseline and heelstick measures of behavioral state, heart period, vagal tone, and salivary cortisol were obtained. Recovery measures of behavioral and cardiac activity were also analyzed. Mothers completed Rothbart's Infant Behavior Questionnaire when their infants reached 6 months of age. Baseline vagal tone predicted cortisol in response to the heelstick, suggesting that baseline vagal tone reflects the infants' ability to react to stressors. Greater reactivity to the heelstick (more crying, shorter heart periods, lower vagal tone, and higher cortisol) was associated with lower scores on "Distress-to-Limitations" temperament at 6 months. This finding was consistent with the expectation that the capacity to react strongly to an aversive stimulus would reflect better neurobehavioral organization in the newborn. Recovery measures of cardiac activity approximated and were correlated with baseline measures indicating the strong self-righting properties of the healthy newborn. Finally, vagal tone and salivary cortisol measures were not significantly related, suggesting the importance of assessing both systems in studies of the ontogeny of stress-temperament relations.

A controlled clinical trial of local anesthesia for lumbar punctures in newborns.

To evaluate the efficacy of subcutaneous administration of lidocaine for reducing physiologic instability in acutely ill newborns during clinically required procedures, 81 neonates who required lumbar punctures within the first month of life were stratified by birth weight and respiratory support and randomly assigned to an experimental or a control group. The experimental group received an injection of 0.1 mL/kg of 1% lidocaine prior to the lumbar puncture. The control group received a nonanesthetized lumbar puncture without placebo. Changes in heart rate, respiratory rate, transcutaneous oxygen and carbon dioxide tensions, and heart rate variability from baseline, preparatory (positioning/handling), lumbar puncture, and recovery periods were measured. The administration of lidocaine did not minimize physiologic instability in response to the lumbar puncture nor was it associated with any detectable adverse effects other than prolonging the duration of the lumbar puncture. Although significant physiologic changes were observed in response to preparatory procedures, few additional changes beyond those occurred in response to lumbar punctures in either the experimental or control group. It is concluded that local anesthesia failed to influence manifestations of physiologic instability during neonatal lumbar punctures and that preparatory procedures were more destabilizing than either the administration of lidocaine or the lumbar puncture itself. The results suggest that the management of newborns requires emphasis on minimizing the destabilizing effects of required and frequent handling procedures.

Newborn pain cries and vagal tone: parallel changes in response to circumcision.

Clinical studies have demonstrated that the cries of chronically stressed, medically compromised infants are characteristically higher and more variable in pitch than those of healthy infants. Other studies have indicated that the vagal tone of chronically stressed infants is significantly reduced in comparison to that of normal infants. A neural model of cry production has been proposed which suggests that decreased vagal tone among infants at risk may, in fact, be related to these increases in cry pitch. Using routine, unanesthetized circumcision as a model of stress, we were able to examine the relation between cry acoustics and vagal tone in normal, healthy newborns undergoing an acutely stressful event. Vocalizations, heart, and respiratory waveforms were continuously recorded from 49 (32 experimental; 17 control) 1-2-day-old, full-term infants during preoperative, surgical, and postoperative periods. Vagal tone, as measured by the amplitude of respiratory sinus arrhythmia extracted from heart period data, was significantly reduced during the severe stress of circumcision, and these reductions were paralleled by significant increases in the pitch of the infants' cries. In addition, individual differences in vagal tone measured prior to circumcision surgery were predictive of physiological and acoustic reactivity to subsequent stress. These results emphasize the potential role of vagal control of the autonomic nervous system during stress.

Neonatal pain cries: effect of circumcision on acoustic features and perceived urgency.

The relation between neonatal cry features elicited by painful circumcision procedures and the perceived urgency of those cries was investigated. Vocalizations were recorded during circumcision of 30 normal newborn males, analyzed by spectrographic methods and validated with computer techniques. The most invasive procedures elicited significantly longer crying bouts; shorter quiet intervals; shorter, more frequent vocalizations; higher peak fundamental frequencies; fewer harmonics; and greater variability of the fundamental. Cries elicited by the most intrusive procedures were judged by adult listeners to be the most urgent, and cries from similarly invasive procedures were judged to be of the same degree of urgency. Cries appeared to be judged along 3 dimensions described by harmonic, temporal, and pitch characteristics. Subjective judgments and objective quantitative data converge to demonstrate that infants' cries are perceived as varying and, objectively, do systematically vary with respect to the intensity of painful stimuli.

Effect of phenobarbital on motor activity and intraventricular hemorrhage in preterm infants with respiratory disease weighing less than 1500 grams.

The use of prophylactic phenobarbital to reduce motor activity and intraventricular hemorrhage was investigated in a controlled exploratory trial with 19 low birthweight premature infants with respiratory disease. Although phenobarbital significantly suppressed movement, it was associated with an increased incidence of intraventricular hemorrhage (IVH). Phenobarbital-treated infants were over eight times more likely to experience IVH than were untreated infants. These data indicate that inhibition of motor activity by phenobarbital may not alleviate the key pathogenetic factors in IVH.

Circumcision: II. Effects upon mother-infant interaction.

The effects of circumcision upon mother-infant interaction were examined in an observational study of 59 mother-infant pairs during hospital feedings on days 2 and 3 of life. Each pair was observed during 4 hospital feedings using a specifically designed mother-infant interaction observation system that examined 43 discreet behaviours relating to feeding, gaze, facial expression, vocalizations and touch. The experimental group was circumcised after the second feeding and the control group after the fourth feeding. Analysis revealed no major behavioral differences between the experimental and control groups. Yet, different trends between the two groups were observed regarding two variables shortly after surgery. These differences disappeared by 24 h post-operatively. Differences related to the frequency of feeding intervals and infant availability scores. The study also revealed a surprisingly limited repertoire of behavior exhibited by both the mother and infant during feeding sessions. Our data suggest that circumcision has brief and transitory effects on mother-infant interactions observed during hospital feeding sessions, the only time mothers who are not rooming-in have an opportunity to be with their infants.