Does daily kangaroo care provide sustained pain and stress relief in preterm infants?

OBJECTIVES: 1. Determine whether stress in preterm infants, measured with salivary cortisol, decreases after five days of Kangaroo Care (KC) compared to five days of Standard Care (SC). 2. To determine whether kangaroo care provides sustainable pain relief beyond the period of skin-to-skin holding. STUDY DESIGN: Preterm infants (n = 38) born at 27-30 weeks gestational age were randomized to either the KC or the SC group and received the allocated intervention starting on day of life (DOL) five and continuing for five days. Salivary cortisol was collected on DOL five and again on DOL ten. Differences were analyzed using repeated measures ANOVA and t tests. Pain during nasal suctioning over five days was assessed using the Premature Infant Pain Profile (PIPP). RESULT: 1. Adequate saliva samples for salivary cortisol were collected for 13 KC infants and 11 SC infants. There was no main effect of group (p = 0.49), but there was a significant main effect of age (DOL five versus DOL ten), with salivary cortisol levels decreasing in both groups (p = 0.02). 2. Pain scores for both groups (n = 38) indicted mild to moderate pain during suctioning, with no significant difference in pain scores between groups. CONCLUSION: 1. KC did not affect salivary cortisol levels in preterm neonates, but levels in both the KC and SC groups decreased over time from DOL five to ten. Salivary cortisol may vary with age of infant. 2. Infants experience pain during routine suctioning and may require pain management.

Anesthesia and analgesia in the NICU.

Painful procedures in the neonatal intensive care unit are common, undertreated, and lead to adverse consequences. A stepwise approach to treatment should include pain recognition, assessment, and treatment, starting with nonpharmacologic and progressing to pharmacologic methods for increasing pain. The most common nonpharmacologic techniques include nonnutritive sucking with and without sucrose, kangaroo care, swaddling, and massage therapy. Drugs used to treat neonatal pain include the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen, and local and topical anesthetics. The indications, advantages, and disadvantages of the commonly used analgesic drugs are discussed. Guidance and references for drugs and dosing for specific neonatal procedures are provided.

A pilot study of preemptive morphine analgesia in preterm neonates: effects on head circumference, social behavior, and response latencies in early childhood.

Use of preemptive analgesia in Neonatal Intensive Care Units is recommended for severe and/or invasive procedures. However, the potential long-term consequences of such analgesia, which may be prolonged, are only beginning to be studied. In this pilot study, a subset of subjects previously enrolled in the Neurological Outcomes and Preemptive Analgesia in Neonates (NEOPAIN) trial was assessed at early childhood. These ex-preterm infants (born at 23-32 weeks of gestational age) required intubation within 72 h postpartum and were randomized to receive either preemptive morphine analgesia (maximum of 14 days) or placebo within 8h post-intubation. At 5-7 years of age, neuropsychological outcomes, morphometrics, adaptive behavior, parent-rated behavior, motivation, and short-term memory were measured. Although overall IQ and academic achievement did not differ between the morphine treated (n=14) and placebo (n=5) groups, preemptive morphine analgesia was associated with distinct differences in other outcome variables. Head circumference of morphine treated children was approximately 7% smaller (Cohen'sd: 2.83, effect size large) and body weight was approximately 4% less (Cohen'sd: 0.81, effect size large); however, height did not differ. In the short-term memory task (delayed matching to sample), morphine treated children exhibited significantly longer choice response latencies than placebo children (3.86±0.33 and 2.71±0.24 s, respectively) (p<0.03) and completed approximately 27% less of the task than placebo children (Cohen'sd: 0.96, effect size large). Parents described morphine treated children as having more social problems, an effect specific to creating and maintaining friendships (Cohen'sd: -0.83, effect size large). Despite the small sample size and the preliminary nature of this study, these results are strongly suggestive of long-lasting effects of preemptive morphine analgesia. A larger investigation with more comprehensive assessments of some of these key features will enable a more complete understanding of the relationship between preemptive morphine treatment and long-term neurocognitive, behavioral, and adaptive outcomes.

Drug testing for newborn exposure to illicit substances in pregnancy: pitfalls and pearls.

Estimates of the prevalence of drug usage during pregnancy vary by region and survey tool used. Clinicians providing care to newborns should be equipped to recognize a newborn who has been exposed to illicit drugs during pregnancy by the effects the exposure might cause at the time of delivery and/or by drug testing of the newborn. The purpose of this paper is to provide an overview of the literature and assess the clinical role of drug testing in the newborn. Accurate recognition of a newborn whose mother has used illicit drugs in pregnancy cannot only impact decisions for healthcare in the nursery around the time of delivery, but can also provide a key opportunity to assess the mother for needed services. While drug use in pregnancy is not an independent predictor of the mother's ability to provide a safe and nurturing environment for her newborn, other issues that often cooccur in the life of a mother with a substance abuse disorder raise concerns for the safety of the discharge environment and should be assessed. Healthcare providers in these roles should advocate for unbiased and effective treatment services for affected families.

Neonatal regionalization through telemedicine using a community-based research and education core facility.

INTRODUCTION: Although regionalization of neonatal intensive care is associated with improved outcomes, implementation has been difficult because of increased deliveries of sicker neonates in smaller nurseries. Telemedicine has been used successfully for medical care and education but it has never been utilized to modify patterns of delivery in an established state network. METHODS: The Community Based Research and Education Core Facility of the Center for Translational Neuroscience established a network of 15 telemedicine units with real-time teleconferencing and diagnostic quality imaging, called Telenursery, placed in neonatal intensive care units, using T1 lines to link these units with a large academic neonatal practice. Weekly educational conferences were conducted to establish guidelines for obstetrical, neonatal and pediatric care in a program called PedsPLACE (Physician Learning and Collaborative Education). Patterns of delivery were assessed through a linked Medicaid database before and after the Telenursery initiative to determine if the most at-risk neonates were transferred to the academic perinatal center for delivery. Clinician satisfaction with the PedsPLACE educational conference was high as assessed through written survey instruments. RESULTS: Medicaid deliveries at the regional perinatal centers increased from 23.8% before the intervention to 33% in neonates between 500 and 999 grams (P < .05) and was unchanged in neonates between 2001-2500 grams. CONCLUSION: Telemedicine is an effective way to translate evidence-based medicine into clinical care when combined with a general educational conference. Patterns of deliveries appear to be changing so that those newborns at highest risk are being referred to the regional perinatal centers.

Drugs of choice for sedation and analgesia in the neonatal ICU.

Painful procedures in the neonatal ICU are common, undertreated, and lead to adverse consequences. The drugs most commonly used to treat neonatal pain include the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen, and local and topical anesthetics. This article discusses the indications for and advantages and disadvantages of the commonly used analgesic drugs. Guidance and references for drugs and dosing for specific neonatal procedures are provided.

Peds PLACE: quality continuing medical education in Arkansas.

The University of Arkansas for Medical Sciences (UAMS) and Arkansas Children's Hospital (ACH) sponsor Peds PLACE (Pediatric Physician Learning and Collaborative Education), a telemedicine continuing education program. This study assessed to what extent participants were satisfied with Peds PLACE and how to improve it. It was found that 95% of the participants agreed that the presentations related to their professional needs and 98% that it increased their knowledge. In addition, 81% evaluated the presentations as some of the best they have attended and 93% agreed that the information would translate into professional practice and enhance patient care. Comments were positive and correlated with the survey data. Participants recommended several ways to improve Peds PLACE.

Achieving success connecting academic and practicing clinicians through telemedicine.

OBJECTIVE: Practicing clinicians, especially in rural areas, are often isolated from learning opportunities and interactions with subspecialty providers. Pediatric Physician Learning and Collaborative Education, an interactive, educational, telemedicine program, was developed to address this need. We evaluated the success of this program through surveys with practicing and academic physicians. METHODS: Pediatric Physician Learning and Collaborative Education was assessed by using 2 evaluation forms collected from October 2007 to May 2008. One of the forms was completed by 197 attendees from the University of Arkansas for Medical Sciences and 172 attendees from remote sites. Another form was completed by 131 participants from Arkansas Children's Hospital, an academic, freestanding, children's hospital. Both evaluation forms asked participants to use a 5-point Likert scale to rank a number of criteria and included a section for participants to write comments and recommendations. Additional data were collected through an open-response e-mail survey of participants. RESULTS: Ninety-five percent of the participants agreed that the presentations related to their professional needs, 98% agreed that the presentations increased their subject-matter knowledge, 81% evaluated the presentations as some of the best they had attended, and 93% agreed that the information would translate into professional practice, enhancing patient care. Health care personnel from the University of Arkansas for Medical Sciences evaluated the presentations significantly higher than did remote participants. Nursing staff members evaluated the presentations significantly higher than did medical staff members. Comments were generally positive and correlated with the Likert-scale data. CONCLUSION: Participants reported being highly satisfied with Pediatric Physician Learning and Collaborative Education and considered it an effective way to address the continuing education needs of practitioners throughout Arkansas, especially in rural and underserved areas.

Drugs of choice for sedation and analgesia in the neonatal ICU.

Painful procedures in the neonatal ICU are common, undertreated, and lead to adverse consequences. The drugs most commonly used to treat neonatal pain include the opiates, benzodiazepines, barbiturates, ketamine, propofol, acetaminophen, and local and topical anesthetics. This article discusses the indications for and advantages and disadvantages of the commonly used analgesic drugs. Guidance and references for drugs and dosing for specific neonatal procedures are provided.

Long-term deficits of preterm birth: evidence for arousal and attentional disturbances.

OBJECTIVE: Quantitative measures of pre-attentional, attentional and frontal lobe processes were compared to evaluate quantitative measures of these deficits in Ex-Preterm vs. Ex-Term adolescents. METHODS: We compared 43 Ex-Preterm with 26 Ex-Term adolescents using the P50 auditory potential, the Psychomotor Vigilance Task (PVT), a reaction time (RT) test, and Near Infrared Spectroscopy (NIRS). RESULTS: The mean amplitude (+/-SE) of the P50 amplitude was similar in the Ex-Preterm (1.8+/-1.4 microV) vs. Ex-Term adolescents (1.8+/-0.6 microV, df = 68, F = 0.05, p = 0.8), but the Ex-Preterm group showed a trimodal distribution in amplitude (High, 3.3+/-0.4 microV, df=42.25, F=19.2, p < 0.01; Medium, 1.7+/-0.1 microV, df = 39, F = 0.41, p = 0.53; Low, 0.7+/-0.1 microV, df = 40, F = 49.5, p < 0.01) suggested by statistically significant variance between populations (Kolmogorov-Kuiper test, df = 42.25, F = 5.4, p < 0.01). Mean RT was longer in Ex-Preterm (250+/-8 ms) vs. Ex-Term subjects (200+/-5 ms, df = 68, F = 18.8, p < 0.001). PVT lapses were increased in Ex-Preterm subjects, and varied inversely with P50 amplitude (Overall Mean 17+/-5 lapses, df = 67, F = 5.34, p < 0.05; Low P50 amplitude, 25+/-10, df = 40, F = 8.8, p < 0.01; Medium, 21+/-11, df = 38, F = 5.37, p < 0.05; High, 6+/-2, df = 39, F = 6.78, p < 0.01) vs. Ex-Term subjects (2+/-0.4 lapses, p < 0.01). NIRS levels did not differ statistically, but tended to correlate with P50 amplitude in the Ex-Preterm group. CONCLUSIONS: These findings suggest differential pre-attentional, attentional and frontal lobe dysfunction in Ex-Preterm adolescents. SIGNIFICANCE: These measures could provide a means to objectively assess differential dysregulation of arousal and attention in Ex-Preterm adolescents, allowing optimization of therapeutic designs.

Neurodevelopmental changes of fetal pain.

Pain in the developing fetus is controversial because of the difficulty in measuring and interpreting pain during gestation. It has received increased attention lately because of recently introduced legislation that would require consideration of fetal pain during intentional termination of pregnancy. During development, sensory fibers are abundant by 20 weeks; a functional spinal reflex is present by 19 weeks; connections to the thalamus are present by 20 weeks; and connections to subplate neurons are present by 17 weeks with intensive differentiation by 25 weeks. These cells are important developmentally, but decline as a result of natural apoptosis. Mature thalamocortical projections are not present until 29 to 30 weeks, which has led many to believe the fetus does not experience emotional "pain" until then. Pain requires both nociception and emotional reaction or interpretation. Nociception causes physiologic stress, which in turn causes increases in catecholamines, cortisol, and other stress hormones. Physiological stress is different from the emotional pain felt by the more mature fetus or infant, and this stress is mitigated by pain medication such as opiates. The plasticity of the developing brain makes it vulnerable to the stressors that cause long-term developmental changes, ultimately leading to adverse neurological outcomes. Whereas evidence for conscious pain perception is indirect, evidence for the subconscious incorporation of pain into neurological development and plasticity is incontrovertible. Scientific data, not religious or political conviction, should guide the desperately needed research in this field. In the meantime, it seems prudent to avoid pain during gestation.

Do ventilated neonates require pain management?

Mechanical ventilation is a stressful experience in neonates resulting in changes in neuroendocrine parameters, pain scores, and physiologic responses. Assisted ventilation in neonates is presumed to be associated with chronic repetitive pain, which in turn is associated with adverse long-term sequelae. Reasons to routinely sedate ventilated neonates include improved ventilator synchrony, improved pulmonary function, and decreased neuroendocrine responses, including cortisol, beta-endorphine, and catecholamines. Reasons not to treat include the well-known adverse side effects of pain medication, especially the opiates, including hypotension from morphine, chest wall rigidity from fentanyl, and tolerance, dependence, and withdrawal from both opiates and benzodiazepines. Additionally, adverse effects such as death and IVH are not improved with preemptive treatment. Chronic pain assessment is poorly validated and difficult to assess in this population, and most studies have evaluated only acute pain scores. If patients are treated, opiates are the most common class of drugs, with morphine the most well studied. Fentanyl may be advantageous in hypotensive, younger neonates because it has fewer cardiovascular effects. The benzodiazepines, midazolam and lorazepam, have been used in ventilated neonates, but midazolam has been associated with adverse effects in one small study so concern remains regarding its use. Significant gaps in our knowledge exist, especially in regard to long-term effects of treatment, or lack thereof, and in the assessment of the chronic pain associated with assisted ventilation.

Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial.

BACKGROUND: Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates. METHODS: Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat. FINDINGS: Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024). INTERPRETATION: Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

Use of DNA fingerprinting in decision making for considering closure of neonatal intensive care units because of Pseudomonas aeruginosa bloodstream infections.

BACKGROUND: Bloodstream infections with Pseudomonas aeruginosa have been well-described in neonatal intensive care units (NICU) and have resulted in the temporary closure of some nurseries to new admissions. Nosocomial transmission of these infections has been verified by fingerprint analysis of the isolates. We utilized molecular fingerprinting to identify the source of bloodstream infections in an NICU and used this information to apply infection control measures that allowed the nursery to stay open and continue to accept referrals. METHODS: In June 1998 three premature infants transferred to our hospital (Hospital A) from Hospitals B and C had bloodstream infections with P. aeruginosa. Subsequently one additional neonate transferred from Hospital B was colonized with P. aeruginosa. Random amplification of polymorphic deoxyribonucleic acid (RAPD) was performed on the four isolates. All transfers from Hospital B were cultured, and surveillance programs were instituted in Hospitals A and B. Targeted infection control measures for all transfers were implemented. RESULTS: The four isolates were the same clone by RAPD. Investigation of the environment in Hospital A did not identify any source of the organism. Surveillance cultures on 49 neonates at Hospital A revealed only one patient colonized at an endotracheal tube. This patient was also a transfer from Hospital B. Results from Hospital B identified 4 of 40 (10%) neonates colonized. All isolates were clones identical with the bloodstream isolates from the neonates with bloodstream infections. Infection control measures for all babies transferred from Hospital B resulted in no new cases of P. aeruginosa bacteremia during the next 5 years. CONCLUSIONS: The use of molecular fingerprinting of isolates of P. aeruginosa allowed for a prompt and directed infection control plan to be implemented in Hospitals A and B. It also allowed the NICU in Hospital A to continue to accept referrals from other hospitals and to implement a targeted infection control plan for patients transferred from Hospital B.