Evidence-based clinical guidelines on analgesia and sedation in newborn infants undergoing assisted ventilation and endotracheal intubation.

AIM: This review informed pain control guidelines for clinicians performing mechanical ventilation, nasal continuous positive airway pressure and endotracheal intubation on term and preterm newborn infants. METHODS: We reviewed literature published between 1986 and June 2017 on analgesia and sedation during assisted ventilation and before endotracheal intubation in newborn infants admitted to neonatal intensive care units. The subsequent guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Our review produced five strong standard of care recommendations. One, reduce neonatal stress and use nonpharmacological analgesia during invasive ventilation. Two, favour intermittent boluses of opioids, administered after pain scores and before invasive procedures, during short expected periods of mechanical ventilation, mainly in preterm infants affected by respiratory distress syndrome. Three, do not use morphine infusion in preterm infants under 27 gestational weeks. Four, always use algometric scores to titrate analgesic drugs doses. Five, use premedication before endotracheal intubation for a more rapid, less painful, less traumatic and safer manoeuvre. We also developed 30 conditional recommendations on therapeutic options. CONCLUSION: Our review produced 35 recommendations on standard care and therapeutic options relating to the analgesia and sedation of newborn infants during ventilation and before endotracheal intubation.

Literature review informs clinical guidelines for pain management during screening and laser photocoagulation for retinopathy of prematurity.

AIM: The aim of this study was to carry out a literature review and develop clinical guidelines for pain prevention and control during screening and laser photocoagulation for retinopathy of prematurity (ROP) in neonatal intensive care units (NICUs). METHODS: The Italian Society of Neonatology assessed papers published between 1986 and June 2017 and used the Grading of Recommendations, Assessment, Development and Evaluation approach, to develop new guidelines on pain and ROP. RESULTS: The Society's pain experts assessed the full texts of 47 papers, including randomised or quasi-randomised controlled trials and case-control studies on nonpharmacological and pharmacological measures used in NICUs during the screening and laser photocoagulation of neonates for ROP. The literature suggested methods for reducing the stress and pain associated with ROP screening procedures. The panel concluded that the literature showed that it was feasible to provide laser photocoagulation for ROP in spontaneously breathing patients with adequate analgesia. CONCLUSION: This literature review on managing pain in infants with ROP in NICUs led to the development of national guidelines, which will help physicians and nurses to reduce the stress and pain experienced by premature newborn infants during unavoidable screening and treatment for ROP.

Systematic review of nonpharmacological analgesic interventions for common needle-related procedure in newborn infants and development of evidence-based clinical guidelines.

The aim of this literature review was to develop clinical guidelines for the prevention and control of needle-related pain in newborn infants. The guidelines were developed by the Italian Society of Neonatology, using the Grading of Recommendations, Assessment, Development and Evaluation approach, based on the assessment of 232 papers published between 1986 and 2015. The quality of the evidence was high or moderate for some behavioural and nonpharmacological interventions. CONCLUSION: There was sufficient evidence to strongly support the use of nonpharmacological interventions for common needle-related procedures in newborn infants. Combined interventions seemed to be more effective in relieving procedural pain.

Efficacy and safety of continuous infusion of fentanyl for pain control in preterm newborns on mechanical ventilation.

OBJECTIVE: To evaluate the analgesic superiority and the safety equivalence of continuous fentanyl infusions versus fentanyl boluses in preterm infants on mechanical ventilation. STUDY DESIGN: In this multicenter, double-blind, randomized controlled trial, mechanically ventilated newborns (≤ 32(+6) weeks gestational age) were randomized to fentanyl (continuous infusion of fentanyl plus open-label boluses of fentanyl) or placebo (continuous infusion of placebo plus open-label boluses of fentanyl). The primary endpoint was analgesic efficacy, as evaluated by the Echelle Douleur Inconfort Nouveau-Né (EDIN) and Premature Infant Pain Profile scales. Safety variables were evaluated as well. RESULTS: Sixty-four infants were allocated to the fentanyl group, and 67 were allocated to the placebo group. The need for open-label boluses of fentanyl was similar in the 2 groups (P = .949). EDIN scores were comparable in the 2 groups; 65 of 961 (6.8%) EDIN scores were >6 in the fentanyl group and 91 of 857 (10.6%) in the placebo group (P = .003). The median Premature Infant Pain Profile score was clinically and statistically higher in the placebo group compared with the fentanyl group on days 1, 2, and 3 of treatment (P < .05). Mechanical ventilation at age 1 week was required in 27 of 64 infants in the fentanyl group (42.2%), compared with 17 of 67 infants in the placebo group (25.4%) (P = .042). The first cycle of mechanical ventilation was longer and the first meconium passage occurred later in the fentanyl group (P = .019 and .027, respectively). CONCLUSION: In very preterm infants on mechanical ventilation, continuous fentanyl infusion plus open-label boluses of fentanyl does not reduce prolonged pain, but does reduce acute pain and increase side effects compared with open-label boluses of fentanyl alone.

Procedural pain in neonates: the state of the art in the implementation of national guidelines in Italy.

BACKGROUND: National and international guidelines have been published on pain control and prevention in the newborn, but data on compliance with these guidelines are lacking. AIM: To document current hospital practices for analgesia at neonatal intensive care units (NICUs) 5 years after national guidelines were published in Italy. METHODS: A computer-based questionnaire was sent to all registered Italian level II and level III NICUs to investigate their routine pain control practices. MAIN OUTCOME MEASURES: The analgesia and sedation currently used for invasive procedures as compared with best practices. RESULTS: The questionnaire was returned by 103 of the 118 NICUs (87.3%), most of which (85.4%) knew of the national guidelines on procedural pain control and prevention, and used some analgesic measures during invasive procedures. One or more nonpharmacological interventions were only used routinely by 64.1% of the NICUs for heel pricks and venipuncture, 56.0% for percutaneous insertion of central catheters, 69.7% for nasal CPAP, and 62.4% for eye tests to screen for retinopathy of prematurity. Pain medication was routinely administered at 34.3% NICUs for tracheal intubation, 46.6% for mechanical ventilation (MV), 12.9% for tracheal aspiration, 71.4% for chest tube insertion, 33.0% for lumbar puncture, and 64.0% for postoperative pain. Pain was routinely monitored at only 22.7% of the units during MV, 12.1% for nCPAP, and 21.8% postoperatively. CONCLUSION: This survey showed that most Italian NICUs provide some form of analgesia and sedation for invasive procedures in accordance with national guidelines, but their routine adherence to best practices for pain control and monitoring is still suboptimal.

Guidelines for procedural pain in the newborn.

UNLABELLED: Despite accumulating evidence that procedural pain experienced by newborn infants may have acute and even long-term detrimental effects on their subsequent behaviour and neurological outcome, pain control and prevention remain controversial issues. Our aim was to develop guidelines based on evidence and clinical practice for preventing and controlling neonatal procedural pain in the light of the evidence-based recommendations contained in the SIGN classification. A panel of expert neonatologists used systematic review, data synthesis and open discussion to reach a consensus on the level of evidence supported by the literature or customs in clinical practice and to describe a global analgesic management, considering pharmacological, non-pharmacological, behavioural and environmental measures for each invasive procedure. There is strong evidence to support some analgesic measures, e.g. sucrose or breast milk for minor invasive procedures, and combinations of drugs for tracheal intubation. Many other pain control measures used during chest tube placement and removal, screening and treatment for ROP, or for postoperative pain, are still based not on evidence, but on good practice or expert opinions. CONCLUSION: These guidelines should help improving the health care professional's awareness of the need to adequately manage procedural pain in neonates, based on the strongest evidence currently available.

Follow-up at the corrected age of 24 months of preterm newborns receiving continuous infusion of fentanyl for pain control during mechanical ventilation.

The neurodevelopmental impact of fentanyl given to preterm newborns for pain control is still unknown. The aim of this study was to assess the neurodevelopmental impact of 2 regimens of fentanyl administration by a prospective follow-up evaluation. In our previous multicenter, double-blind, randomized controlled trial, 131 mechanically ventilated newborns (gestational age ≤32 weeks) were randomized to fentanyl (continuous infusion of fentanyl + open label boluses of fentanyl) or placebo (continuous infusion of placebo + open label boluses of fentanyl). Infant development was evaluated using Griffiths Mental Developmental Scales (Griffiths, 1996) until 24 months of corrected age by trained psychologists who were not aware of the group allocation. 106/131 infants survived at discharge; 3 died after discharge, 25 were lost to follow-up (12 in the fentanyl and 13 in the placebo group). Seventy-eight patients were evaluated at 2 years of corrected age. Children in the fentanyl group, compared with those in the placebo group, obtained significantly lower Griffiths general developmental quotient (mean [SD]: 89.95 [13.64] vs 97.18 [12.72], P = 0.024) together with the scores on the eye-hand coordination (mean [SD]: 89.09 [12.13] vs 99.19 [13.19], P = 0.002) and performance skills (mean [SD]: 79.71 [15.80] vs 90.09 [15.28], P = 0.009) scales. After adjustment for clinical confounders (gestational age, CRIB score, and sex) only eye-hand co-ordination was associated with fentanyl infusion. This study demonstrates that continuous infusion of fentanyl in very preterm infants, given at 1 mcg·kg·h during mechanical ventilation, is associated with a significant decrease in eye and hand co-ordination skills. Longer follow-up is needed to evaluate the impact on future motor, cognitive, and behavioral functions.

Pain management during invasive procedures at Italian NICUs: has anything changed in the last 5 years?

OBJECTIVE: To ascertain the extent to which neonatal analgesia for invasive procedures has changed in the last 5 years since the publication of Italian guidelines. METHODS: We compared survey data for the years 2004 and 2010 on analgesia policy and practices for common invasive procedures at Italian Neonatal Intensive Care Units (NICUs); 75 NICUs answered questionnaires for both years and formed the object of this analysis. RESULTS: By 2010, analgesia practices for procedural pain had improved significantly for almost all invasive procedures (p < 0.05), with both non-pharmacological and pharmacological methods being adopted by the majority of NICUs (unlike the situation in 2004). The routine use of medication for major invasive procedures was still limited, however (35% of lumbar punctures, 40% of tracheal intubations, 46% during mechanical ventilation). Postoperative pain treatment was still inadequate, and 41% of facilities caring for patients after surgery did not treat pain routinely. Pain monitoring had definitely improved since 2004 (p < 0.05), but not enough: only 21 and 17% of NICUs routinely assess pain during mechanical ventilation and after surgery, respectively. CONCLUSION: There have been improvements in neonatal analgesia practices in Italy since national guidelines were published, but pain is still undertreated and underscored, especially during major invasive procedures. It is mandatory to address the gap between the recommendations in the guidelines and clinical practice must be addressed through with effective quality improvement initiatives.

Analgesic and sedative drugs in newborns requiring respiratory support.

Infants receiving respiratory assistance may feel pain due to underlying disease or ventilation itself. Pain control during neonatal respiratory care reduces morbidity. This article summarizes the main scientific evidence about the use of drugs during ventilatory assistance, and provides some practical suggestions on pain management in neonates with respiratory support.