A Clinical Practice Guideline Promoting Opioid Awareness in a Level IV NICU

Neonates may be exposed to significant amounts of opioids in the NICU. The objective of this project was to investigate opioid exposure of neonates in a level IV NICU, enhance provider knowledge of this problem through education, and develop a clinical practice guideline to promote increased opioid awareness and more effective monitoring of therapy in neonates. Methods. This project explored neonatal opioid exposure in a level IV NICU via a retrospective chart review. Neonates classified as high users of opioids were included in the chart review. A systematic review of literature guided the construction of an evidence-based clinical practice guideline (CPG) to reduce opioid exposure in neonates. A pre- and post-survey was conducted to assess the participants learning after the presentation of the guideline. Input from NICU stakeholders was elicited on a working draft of the CPG. A final draft of the CPG was submitted for institutional approval. Results. The amount of opioids received from admission to discharge in IV morphine milligram equivalents (MME) revealed a median of 19.7 MME. The median number of days that neonates received opioids was 20 days. Post-test results following presentation of the CPG and chart review data demonstrated significant change in 2 of 6 pre-survey questions: (1) participants believed there is an increased use of opioids in the NICU (P=0.004) and (2) participants considered the effects of opioids when prescribing or administering them (P=0.006). Conclusions. Most neonates were found to have significant opioid exposure in the charts reviewed. Following presentations of the data and CPG, learning was observed among participants. A CPG that enhances providers' opioid awareness, prescribing and management, and surveillance of therapy has the potential to reduce opioid exposure in this population. Further study will need to be conducted following approval and implementation of the CPG.

Running head: PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU A Clinical Practice Guideline Promoting Opioid Awareness in a Level IV NICU Allison Kendall The University of Utah College of Nursing 1 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 2 Abstract Problem. Neonates may be exposed to significant amounts of opioids in the NICU. The objective of this project was to investigate opioid exposure of neonates in a level IV NICU, enhance provider knowledge of this problem through education, and develop a clinical practice guideline to promote increased opioid awareness and more effective monitoring of therapy in neonates. Methods. This project explored neonatal opioid exposure in a level IV NICU via a retrospective chart review. Neonates classified as high users of opioids were included in the chart review. A systematic review of literature guided the construction of an evidence-based clinical practice guideline (CPG) to reduce opioid exposure in neonates. A pre- and post-survey was conducted to assess the participants learning after the presentation of the guideline. Input from NICU stakeholders was elicited on a working draft of the CPG. A final draft of the CPG was submitted for institutional approval. Results. The amount of opioids received from admission to discharge in IV morphine milligram equivalents (MME) revealed a median of 19.7 MME. The median number of days that neonates received opioids was 20 days. Post-test results following presentation of the CPG and chart review data demonstrated significant change in 2 of 6 pre-survey questions: (1) participants believed there is an increased use of opioids in the NICU (P=0.004) and (2) participants considered the effects of opioids when prescribing or administering them (P=0.006). Conclusions. Most neonates were found to have significant opioid exposure in the charts reviewed. Following presentations of the data and CPG, learning was observed among participants. A CPG that enhances providers' opioid awareness, prescribing and management, PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 3 and surveillance of therapy has the potential to reduce opioid exposure in this population. Further study will need to be conducted following approval and implementation of the CPG. Introduction Throughout the years, the scientific understanding of neonatal pain has shifted. Initially, a lack of research and perceived misconceptions regarding a neonate's ability to feel pain resulted in inadequate pain treatment. When it became apparent through research that neonates indeed feel pain, caregivers recognized the detrimental effects of inadequate pain control on preterm and term infants in the newborn intensive care unit (NICU), which resulted in the increased use of opioids in the NICU. Liberal use of opioid and sedative drugs in the neonatal population has recently been called into question by experts in neonatology who have studied the sequelae of long-term opioid use (Cramton & Gruchala, 2013). Problem Description Today, neonates are commonly prescribed opioids for pain management in the NICU. The most common pharmacologic agents used for pain in newborns are opioids, with fentanyl and morphine being the most common, especially for persistent pain (Keels, Sethna, COFAN, & SOAAP, 2016). In 2009, approximately 7.2 million outpatient opioid prescriptions were prescribed to children in the United States, doubling in the past decade (Galinkin & Koh, 2014). There is a fine balance between treating pain and avoiding the adverse events associated with excessive opioid exposure, as opioids are the most commonly used agent in the pharmacologic management of pain in the neonatal population (Lewis, Erte, Ezell, & Gauda, 2015; Rana et al., 2017). Available Knowledge PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 4 Evidence suggests that there is long-term harm associated with excessive and prolonged opioid exposure in the neonatal period (Attarian et al., 2014). As duration of opioid therapy for pain management lengthens, increased drug tolerance, prolonged drug withdrawal symptoms, and longer hospital stays have been observed (Anand et al., 2010). Children who are prescribed opioids for as little as 7 days can develop opioid dependence and exhibit drug-specific withdrawal symptoms (Galinkin & Koh, 2014). Long-term use of both opioids and benzodiazepines in neonates can lead to prolonged mechanical ventilation, delay in passage of meconium and carries inherent risk for tolerance and withdrawal, necessitating prolonged dose taper regimens (Rana et al., 2017). There is also evidence from animal studies that pain control with morphine worsens long-term negative consequences such as hyperalgesia (Lewis et al., 2015). Evidence is accumulating that poor long-term neurodevelopmental outcomes have been associated with neonatal morphine administration (Attarian et al., 2014). Analgesics and sedatives are known to be potent modulators of several receptor signaling pathways in the developing brain that are implicated in the critical regulation of neural tissue proliferation (Keels et al., 2016). A smaller average head circumference has been documented in infants exposed to morphine as well (Attarian et al., 2014). Extremely low birthweight (ELBW) infants exposed to opioids had worse cognitive index scores at 20 months of age (Kocek, Wilcox, Crank, & Patra, 2016). For every 1 milligram per kilogram increase in cumulative morphine use, the cognitive index score was shown to decrease by an average 0.238 points (Kocek et al., 2016). Furthermore, exposure to morphine increases apoptosis in human microglial cells and neuronal-like cells in neonatal rats (Attarian et al., 2014). PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 5 Although the true long-term impact of morphine may be difficult to quantify, standardized guidelines regarding the use and monitoring of opioids are necessary to attenuate potential adverse effects on neonatal development (Attarian et al., 2014). Treatment of opioid withdrawal and tolerance, as well as overall management of therapy, have become increasingly difficult as the use of opioids in the NICU has expanded. Studies of appropriate dosing and long-term effects of these analgesics given during the neonatal period are lacking and/or conflicting (Keels at al., 2016). Thus, opioid awareness, as well as closer monitoring and periodic evaluation of ongoing opioid use, are needed in this population in order to ensure optimal clinical outcomes. Rationale The Precaution Adoption Process Model (PAPM) explains how an individual comes to decisions to act, and how he or she translates that decision into action (Weinstein, Sandman, & Blalock, 2008). The PAPM guides individual behavior from a lack of knowledge to a more comprehensive understanding of the identified problem, and a process for taking action to correct the problem through a series of stages. The PAPM stages prior to actions are defined in terms of mental states, rather than in terms of factors external to the person, such as current or past behavior (Weinstein et al., 2008). This project focused on a presumed increase of opioid use in the neonatal population. There is a clear need for a better understanding regarding the detrimental effects of opioid exposure on infants in order to optimize opioid awareness in the NICU. Upon completion of a retrospective chart review and opioid awareness clinical practice guideline, this information presented to stakeholders codified the tenets regarding judicious opioid use in the NICU, and encouraged maintenance of change over time. The educational intervention modeled after the PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 6 PAPM is aimed at informing clinicians of ways in which they can reduce opioid exposure and improve clinical outcomes for these patients. It is ultimately their decision to act upon the evidence provided to them about neonatal opioid use. Specific Aims The purpose of this project was to explore opioid exposure of neonates in a level IV NICU, and to enhance provider knowledge through education and developing a clinical practice guideline (Appendix A) that promotes opioid awareness through monitoring and evaluating the continuation of opioid therapy in neonates. Methods Context The project was implemented in the NICU at a large pediatric medical center located in Salt Lake City, Utah. The facility is a regional medical catchment facility for high-risk neonates from the surrounding states of Wyoming, Nevada, Montana, Idaho, and Utah, an area commonly referred to as the Intermountain West. Infants treated at this medical center often present with severe, life-threatening conditions. These infants are subsequently transported to the facility from outlying hospitals for severe medical and surgical interventions. Conditions for which newborns are transported include serious congenital birth defects, sepsis, pulmonary hypertension, and prematurity with the attendant complications. A related and complementary quality improvement project was implemented concurrently at the time of this project. This quality improvement project focused on the development and implementation of a standardized post-operative pain management guideline for opioid-naïve NICU infants. The guideline was intended to increase consistency in pain PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 7 assessment and to reduce opiate exposure through standardization of prescribing practices to improve pain management and clinical outcomes (Birkeland, 2018). Interventions This quality improvement project explored total opioid exposure in a level IV NICU to inform the creation of a guideline that improved opioid awareness based on current evidence (Appendix A). The first objective of this project was to conduct a thorough review of the literature and published guidelines to guide creation of an institutional guideline for opiate management and surveillance. The second objective was accomplished by conducting a retrospective chart review of neonates who were categorized as high risk for prolonged opioid exposure based on a diagnosis of one of the following diseases: bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), persistent pulmonary hypertension of the newborn (PPHN), and extracorporeal membrane oxygenation (ECMO) from admission to discharge in the level IV NICU, to determine current trends in opioid prescribing for pain management. Children with the selected diagnoses are known to be high users of opioids due to the complexity and severity of their illnesses. Variables of interest were examined that characterized current prescribing practices and opioid exposure in the NICU. Fifty-one charts were included in this review of patients in the level IV NICU from November 2017-November 2018. The variables in the retrospective chart review included the medical record number (MRN), sex, weight on admission, race/ethnicity, diagnosis, gestational age at birth, referring institution, gestational age when admitted to the level IV NICU, amount of opioids received from admission to discharge, average opioid exposure per day at the level IV NICU, number of days exposed to opioids, and total number of days in the level IV NICU. PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 8 Additional questions were also included. These asked if the patient was prescribed opioids at discharge, and if the patient died before discharge, total opioid exposure at the time of death (if applicable), and weight at discharge or death. For consistency, all opioid exposure was converted into IV morphine milligram (mg) equivalents (Table 1). The final three objectives pertain to the creation, revision and process of institutional adoption of the guideline. Information gathered from the retrospective chart review, along with the findings gleaned from the literature review provided the foundation for accomplishing the third objective, which was the creation of a clinical practice guideline (CPG) that endorses best practices of opioid therapy management including prescribing, surveillance, and weaning from opioids (Appendix A). The fourth objective was achieved by eliciting input from NICU stakeholders following a presentation of findings from the chart review and discussion of the proposed CPG. A pre- and post-survey was conducted to assess the participants learning after the presentation of the guideline (Appendix B). The final objective was accomplished by submission of the final draft of the proposed CPG to the appropriate institutional committee to initiate the process for institutional adoption. Study of the Interventions The impact of this quality improvement project was evaluated by conducting a retrospective chart review and assessment of knowledge using a pre-and post-survey. To assess the impact of the interventions, the chart review was conducted based on current evidence by Lewis et al. (2015) that found a cumulative opioid increase per infant of 134 milligrams per time epoch in the tertiary NICU being studied. This demonstrated an increase in medical opiate exposure over time in ICU infants, similar to the hypothesized outcome of the chart review for this quality improvement project. The pre-and post-survey evaluated the knowledge of NICU PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 9 stakeholders regarding the topic of opioid use, detrimental effects of exposure in neonates, as well the evaluation of their opioid prescribing practices (Appendix B). Measures A retrospective chart review was essential to conduct, analyze and gather the variables of interest in order to quantitatively determine the significance of opioid exposure in the neonatal population. A chart review provided a quality assessment that highlights evidence-based practice regarding opioid administration in the NICU, which was then introduced in the guideline. Scatterplot and bar-graph diagrams were used to illustrate distribution of the data gleaned from the chart review. This created an organized visual representation of average opioid exposure, as well as neonates who were outliers in opioid exposure. Participant's knowledge regarding opioid use and effects of opioids on neonates was measured by questionnaire before the results were presented to stakeholders. The same questionnaire was given to participants following the presentation. Scores were compared from pre- and post-presentation to compare and assess participants learning. Analysis The neonatal demographics from the retrospective chart review were computed into descriptive statistics, using frequency tables. A scatterplot of cases conveyed a visual distribution of morphine exposure among the neonates included in the chart review. Data gathered in the chart review helped set a foundation for the opioid awareness guideline. Scores from the preand post-surveys were compared using a paired t-test to evaluate changes respondents' knowledge about opioid use and the effects of opioids on the neonatal population. Ethical Considerations PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 10 The University of Utah Institutional Review Board determined this study to be nonhuman subject research, as it was acknowledged to be a quality improvement project. There were no potential conflicts of interest. Results A retrospective chart review of 51 patients was completed for analysis using designated inclusion criteria and diagnoses of BPD, CDH, PPHN, or ECMO from November 2017 to November 2018. Neonatal demographics were populated into descriptive statistics using frequency tables. BPD was the most prevalent diagnosis (n=17) followed by PPHN (n=12), CDH (n=13), and ECMO (n=2) (Table 2). Five of the 51 neonates died before discharge (Table 3). The amount of opioids received from admission to discharge in IV morphine milligram equivalents (MME) revealed a median of 19.7 MME (± 174 MME) (Table 4). Data analysis excluded a patient who received a total of 3750 MME. Inclusion of this outlier in the analysis would have significantly skewed the results (Figure 1). The median number of days that neonates received opioids was 20 days (± 27 days) (Table 5). The analysis excluded data of five patients who were outliers (Figure 2), as these would have significantly skewed the results (Figure 2). Three presentations were given to assess the participants' knowledge about opioid use and the effects of opioids on the neonatal population using a pre- and posttest survey. Of the total 30 participants, 8 (27%) were pharmacists, 9 (30%) were neonatal nurse practitioners, 2 (6%) were neonatologists, and 11 (37%) were registered NICU nurses. Participants answered the pre- and posttest questions using a 5-point Likert-scale ranging from "strongly disagree" to "strongly agree." For analysis, the responses were numbered 1 through 5, with 1= "strongly disagree," 2= "disagree," 3= "neither agree nor disagree," 4= "agree," and 5= "strongly agree." PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 11 The pre-test scores showed that participants were neutral whether they believed opioid use had increased in the NICU (3.3 ± 1.09). Participants agreed that there are long-term developmental outcomes related to opioid exposure (4.5 ± 0.5). The pre-test results also showed that stakeholders considered the adverse effects when prescribing/administering opioids (4 ± 0.52). Participants also agreed that finding alternatives to opioids would minimize adverse outcomes (4.1 ± 0.57). Nineteen of the 30 participants who had prescriptive privileges agreed that they consider alternatives to opioids when prescribing pain medication in the NICU (4.18 ± 0.66). When asked if they felt confident when prescribing/administering opioids, participants' responses were neutral (3.7 ± 0.69). Overall, comparison of the pre-and posttest scores only showed significant improvement in 2 of the 6 survey questions. Post-test results after the presentation demonstrated that participants believed there is an increased use of opioids in the NICU (P=0.004). Additionally, participants considered the effects of opioids when prescribing/administering them (P=0.006). Participants' belief that long-term opioid use can adversely affect developmental outcomes and participants' consideration of prescribing or administering alternatives to opioids did not change after the presentation of data from the chart review. There was also no significant change in post-test scores on whether finding alternatives to opioids would minimize the long-term adverse outcomes in infants, or whether stakeholders felt confident in what was being treated when prescribing/administering opioids (P=0.134). The posttest included an open-ended question response asking the stakeholder to include any additional information that he or she thought would be helpful to include in a CPG on neonatal opioid awareness. The most frequent participant response pertained to use of alternative drug options to reduce opioid use. Others recommended a decrease in the patient-to- PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 12 nurse care ratio for infants who were withdrawing from opioids. Some participants suggested use of additional medications to assist neonates during the process of weaning off opioids. Finally, some participants suggested delaying an opioid wean in patients for certain clinical symptoms such as gastrointestinal disturbances. Discussion Summary Results from the chart review demonstrated a significant iatrogenic opioid exposure among neonates in the level IV NICU. Pre- and post-test scores indicated an increase in stakeholders' belief that there is an increase in opioid use in the NICU. Additionally, the surveys found an increase in participants saying they considered the effects of opioids when prescribing/administering them. The other survey questions did not indicate a significant change in knowledge based on education, which may have resulted from the low number of participants completing the survey. Interpretation Few articles that relate to iatrogenic exposure of opioids in the NICU population were found during the review of literature. Only three studies were conducted that examined hospitalacquired opioid exposure over three time epochs in a NICU setting that showed a significant increase in opioid exposure and withdrawal symptoms over time (Lewis et al., 2015). Articles that examined detrimental effects of opioid exposure in the neonates were also sparse. Many studies identified the long-term developmental outcomes associated with prolonged opioid exposure. The lack of relevant studies indicates the need for more research on the effects of opioids on the NICU population. PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 13 The CPG was designed by integrating data from both pediatric and neonatal studies to create a guideline promoting opioid awareness. Study findings that served as the underpinning for the CPG showed that structured guidelines improve clinical outcomes through the optimization of pain assessments, as well as structured prescribing doses and weaning specifications. The intent of the final CPG draft is to reduce neonatal opioid exposure in the NICU. Implementation will be necessary to validate the claim regarding the effectiveness of the CPG. The full impact of this project remains unclear until the CPG is finally adopted and implemented. Limitations Limitations to this study included the time constraints for implementation of the project. The effect of the CPG on opioid awareness and prescribing/monitoring practices was not evaluated in this project. The low rate of stakeholder participation in the data and CPG presentations was also a significant factor. A greater number of respondents may have shown very different findings regarding learning of participants. Moreover, the project's focus on examining opioid use in neonates with limited diagnoses may have led to an over- or underrepresentation of opioid use in the entirety of NICU patients. Further education and implementation regarding the CPG are necessary to realistically reach a goal of sustainability regarding opioid awareness. Conclusions Findings from this project indicated a lack of research regarding iatrogenic opioid exposure and the effects of opioids on the NICU population. Short- and long-term effects on the clinical and developmental outcomes of neonates experiencing long-term opioid exposure requires further study, as evidenced by the paucity of information that was uncovered in the PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 14 review of literature for this project. Further study of clinical outcomes following implementation of the guideline will need to be conducted to assess its efficacy in reducing opioid exposure in neonates and whether opioid prescribing and management practices change as a result. PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 15 References Anand, K. J. S., Wilson, D. F., Berger, J., Harrison, R., Meert, K. L., Zimmerman, J., … Nicholson, C. (2010). Tolerance and withdrawal from prolonged opioid use in critically ill children. Pediatrics, 125(5), e1208-e1225. Retrieved from http://doi.org.ezproxy.lib.utah.edu/10.1542/peds.2009-0489 Attarian, S., Tran, L. C., Moore, A., Stanton, G., Meyer, E., & Moore, R. P. (2014). The neurodevelopmental impact of neonatal morphine administration. Brain Sciences, 4(2), 321-334. http://doi.org/10.3390/brainsci4020321 Birkeland, A. (2018). Standardizing post-operative pain management in the NICU (Unpublished Doctorate of Nursing manuscript). University of Utah: Salt Lake City, UT. Cramton, R. E., & Gruchala, N. E. (2013). Babies breaking bad: Neonatal and iatrogenic withdrawal syndromes. Current Opinion in Pediatrics, 25(4), 532-542. doi: 10.1097/MOP.0b013e328362cd0d Galinkin, J., & Koh, J. L. (2014). Recognition and management of iatrogenically induced opioid dependence and withdrawal in children. American Academy of Pediatrics, 133(1), 152-155. doi: 10.1542/peds.2013-3398 Joe, P., & Dudell, G. (2015). Treatment of iatrogenic opiate withdrawal in the NICU. East Bay Newborn Specialists Guideline. Retrieved from https://www.eastbaynewborn.com/docs/Treatment%20of%20Iatrogenic%20Opiate%20W ithdrawal%20in%20the%20NICU%20(2).pdf Keels, E., Sethna, N., Committee on Fetus and Newborn, & Section on Anesthesiology and Pain Medicine (2016). Prevention and Management of Procedural Pain in the Neonate: An Update. Pediatrics, 137(2), e20154271. https://doi.org/10.1542/peds.2015-4271 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 16 Kocek, M., Wilcox, R., Crank, C., & Patra, K. (2016). Evaluation of the relationship between opioid exposure in extremely low birth weight infants in the neonatal intensive care unit and neurodevelopmental outcome at 2 years. Early Human Development, 92, 29-32. Retrieved from https://doi-org.ezproxy.lib.utah.edu/10.1016/j.earlhumdev.2015.11.001 Lago, P., Garetti, E., Pirelli, A., Merazzi, D., Bellieni, C. V., Levet, P. S., … Ancora, G. (2014). Non-pharmacological intervention for neonatal pain control. Italian Journal of Pediatrics, 40(Suppl 2), A52. https://doi.org/10.1186/1824-7288-40-S2-A52 Lewis, T., Erte L. B., Ezell, T., & Gauda, E. (2015). Pharmacoepidemiology of opiate use in the neonatal ICU: Increasing cumulative doses and iatrogenic opiate withdrawal. Journal of Opioid Management, 11(4), 305-312. doi: 10.5055/jom.2015.0279 Rana, D., Bellflower, B., Sahni, J., Kaplan, A. J., Owens, N. T., Arrindell, E. L., & ... Dhanireddy, R. (2017). Reduced narcotic and sedative utilization in a NICU after implementation of pain management guidelines. Journal of Perinatology, 37(9), 10381042. doi:10.1038/jp.2017.88 Steinhorn, R., McPherson, C., Anderson, P. J., Neil, J., Doyle, L. W., & Inder, T. (2015). Neonatal Morphine Exposure in Very Preterm Infants - Cerebral Development and Outcomes. The Journal of Pediatrics, 166(5), 1200-1207. doi: 10.1016/j.jpeds.2015.02.012 Weinstein, N. D., Sandman, P. M., & Blalock, S. J. (2008). The precaution adoption process model. Retrieved from https://www.psandman.com/articles/PAPM.pdf PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 17 Table 1 Milligram morphine equivalent conversion chart Drug Morphine Fentanyl Hydromorphone Methadone Morphine: Opiate Equivalence Ratio 1:1 20:1 5:1 10:1 IV: Oral Conversion Ratio 3:1 Always IV IV/PO 1:1 Oxycodone 30:20 PO (Lewis at al., 2015). Table 2 Patient diagnoses included in chart review Diagnoses Frequency Bronchopulmonary Dysplasia (BPD) Persistent Pulmonary Hypertension of the Newborn (PPHN) Congenital Diaphragmatic Hernia (CDH) Extracorporeal Membrane Oxygenation (ECMO) Combined Diagnoses Total Table 3 Infant mortality Patient Outcomes Frequency Cumulative Percent Yes 5 9.8 No 46 90.2 Total 51 100.0 17 12 13 2 7 51 Cumulative Percent 33.3 23.5 25.5 3.9 13.7 100.0 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 18 Table 4 Total MME during hospitalization Amount of opioids received from admission to discharge (converted to IV morphine mg equivalents) Mean 89 Median 19.7 Standard Deviation 174 Minimum 0 Table 5 Duration of opioid exposure Number of days exposed to opioids Mean Median Standard Deviation Range Minimum Maximum 24 20 27 161 0 161 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU Figure 1. MME patient distribution 19 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU Figure 2. Distribution of total days of opioid exposure 20 PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 21 Appendix A Clinical Practice Guideline: Opioid Awareness Guideline in a Level IV NICU Background: Neonates are commonly exposed to opiates and benzodiazepines leading to increased tolerance and prolonged withdrawal symptoms (Lewis, Erte, Ezell, & Guada, 2015). Children prescribed opioids for as little as 7 days can develop opioid dependence and exhibit withdrawal symptoms (Galinkin & Koh, 2014). Drug withdrawal when the opiate is discontinued is significantly correlated with both the dose, and duration of exposure (Joe & Dudell, 2015). Iatrogenic withdrawal is one unintended consequence of increased use of opioids in neonates. Research is suggesting long-term harm from opioid use, including neuronal cell death, early alterations in cerebral structure, short-term neurobehavioral problems, prolonged mechanical ventilation, and delay in passage of meconium (Steinhorn et al., 2015; Attarian et al., 2014; Rana et al., 2017). Introduction: The presumed increase of opioids in the newborn intensive care unit (NICU) demonstrates a need for an opioid awareness guideline to minimize adverse clinical outcomes in neonates treated for pain. There is a fine balance between treating pain and avoiding the adverse events associated with opiate exposure (Lewis et al., 2015). Current trends in treatment of neonatal pain lead to an increase in opioid use for longer periods of time. The use of pain and sedation guidelines have been shown to improve pain assessment and clinical outcomes (Rana et al., 2017). Aim: Create a heightened awareness and balance of opioid exposure of neonates in a level IV NICU, through consistent monitoring and evaluation of opioid therapy in neonates. Inclusion Criteria: This guideline is intended for neonates who continue to receive opioids > 7 days postoperatively, and/or greater than 10 days for other circumstantial reasons deeming them a hospital-acquired chronic opioid user. Exclusion Criteria: - For neonatal abstinence syndrome see: PO (Oral) NAS Morphine Weaning Schedule For immediate post-operative pain in naïve opioid users see: Post-op pain management guideline for non-ventilated/ventilated patients. - Goals for opioid management in the NICU: - Optimize non-pharmacologic pain management first. - Standardize opioid use in hospital-acquired opioid dependent neonates. - Recognize opioid withdrawal in the neonatal population. (Lago et al., 2014) PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 22 Recommended management of pharmacologic opioid use for a neonate currently receiving opioids: Incorporate non-pharmacologic comfort measures prior to pharmacologic therapy. Swaddling, cue-based care, cluster care, kangaroo care, undisrupted sleep, and control/reduce light and noise. 1. Continue non-pharmacologic measures, while continuing comfort measures. 2. Assess neonate for pain/agitation using the Neonatal Pain Agitation Sedation Score (NPASS) every 3-4 hours with cares. 3. Determine which category neonate falls under: Neonatal Abstinence Syndrome Immediate post-op pain management Refer to: PO (oral) NAS Weaning Protocol Refer to: NICU Comfort Protocol for Post-Op NonVentilated /Ventilated Patients (NAS) Hospital-acquired chronic opioid recipient >10 days or post-operative neonate receiving opioids greater than 7 days See Below Instructions: • This guideline is intended for the neonatal population. • Calculate the dose/kg the neonate receives per dose, convert to morphine milligram equivalents using the chart below. Drug Morphine: Opiate Equivalence Ratio IV: Oral Conversion Ratio Morphine 1:1 *2:1 Fentanyl 20:1 Always IV Hydromorphone 5:1 IV/PO Methadone 10:1 1:1 Oxycodone 30:20 *PCH NICU PO MORPHINE CONVERSION: 2:1 • • • • • • PO (Lewis et al., 2015) Start at the stage of the dose/kg the neonate is currently receiving. Wean/increase opioid dose per guideline. At all levels: Utilize the NPASS, and score neonate with cares (Q3-4 hours). Every 48 hours if Neonatal Withdrawal Inventory (NWI) scores have remained below 7, advance to the next level. When weaning, PRN Morphine rescue dosing should be administered for NWI Scores > 8 or WAT scores >3. If there is a need to go up to 3 PRN doses in 24 hours, then hold at current stage. If need to give more than 4 PRN doses, decrease by one stage. PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU Level Medication Total Dose Stage 1 Morphine mg. equivalents 0.3 mg/kg Stage 2 Morphine mg. equivalents 0.27 mg/kg Stage 3 Morphine mg. equivalents 0.24 mg/kg Stage 4 Morphine mg. equivalents 0.21 mg/kg Stage 5 Morphine mg. equivalents 0.18 mg/kg Stage 6 Morphine mg. equivalents 0.15 mg/kg Stage 7 Morphine mg. equivalents 0.12 mg/kg Stage 8 Morphine mg. equivalents 0.09 mg/kg Stage 9 Morphine mg. equivalents 0.06 mg/kg Stage 10 Morphine mg. equivalents 0.03 mg/kg • Measurable lowest total IV dose: 0.1 mg • Measureable lowest total PO dose: 0.04 mg Route IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO IV/ PO 23 Frequency Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours Q4 hours-DC after 48 hours Recognition of opioid withdrawal: Once the neonate has weaned off of opioids, assess for these signs/symptoms of withdrawal: Gastrointestinal Neurologic Excitability Autonomic Signs Dysfunction Tremors Poor feeding Increased sweating Irritability Uncoordinated and constant sucking Nasal stuffiness Increased wakefulness Vomiting Fever High-pitched crying Diarrhea Mottling Dehydration Temperature Instability Increased muscle tone (hypertonia) Hyperactive deep tendon reflexes Poor weight gain Exaggerated Moro reflex Seizures Frequent yawning & Sneezing • Once opioids have been completely ceased, the patient needs to be observed for signs of withdrawal for the next 72 hours. PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 24 Appendix B Pre-Presentation Survey on Opioid Awareness Job Title: __________ Years of Experience in current field (including fellowship if applicable): _____ Strongly Disagree 1. I believe that there is an increase in opioid use in the NICU. 2. I believe that long-term opioid use can affect developmental outcomes. 3. I consider the effects of opioid exposure when prescribing/administering opioids. 4. As a clinician, I consider prescribing alternatives to opioids on my patients (if applicable). 5. I feel that finding alternatives to opioids would minimize harmful long-term outcomes. 6. I feel confident in what I am treating when prescribing/administering opioids. 7. What additional information do you think would be helpful to include in a clinical practice guideline on neonatal opioid awareness? Disagree Neither Agree nor Disagree Agree Strongly Agree PROMOTING OPIOID AWARENESS IN A LEVEL IV NICU 25 Post-Presentation Survey on Opioid Awareness Strongly Disagree 1. I believe that there is an increase in opioid use in the NICU. 2. I believe that long-term opioid use can affect developmental outcomes. 3. I consider the effects of opioid exposure when prescribing/administering opioids. 4. As a clinician, I consider prescribing alternatives to opioids on my patients (if applicable). 5. I feel that finding alternatives to opioids would minimize harmful long-term outcomes. 6. I feel confident in what I am treating when prescribing/administering opioids. 7. What additional information do you think would be helpful to include in a clinical practice guideline on neonatal opioid awareness? Disagree Neither Agree nor Disagree Agree *Survey Format Adapted from Krista Schulte, DNP, NNP-BC Strongly Agree