Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.

BACKGROUND: Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life. OBJECTIVES: To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge. SEARCH METHODS: We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions.  Primary outcomes were analgesia and sedation, and all-cause mortality to discharge. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data.  MAIN RESULTS: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine. AUTHORS' CONCLUSIONS: We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.

When all I wanted was to hold my baby-The experiences of parents of infants who received therapeutic hypothermia.

AIM: The knowledge is limited about how parents experience the time when their infant is receiving therapeutic hypothermia (TH) after severe perinatal asphyxia. The aim of this study was to explore parents' experience of closeness and involvement in their infant's care while in the neonatal intensive care unit (NICU) with their newborn undergoing TH. METHODS: Face-to-face, semi-structured interviews were conducted with parents (n = 11) whose infants (n = 8, aged 3-5 years at the time of the study) underwent TH at a level III Swedish NICU during 2013-2016. The interviews were analysed using qualitative content analysis. RESULTS: All the parents shared the trauma of being both physically and psychologically separated from their infant. They all described a need for information and emotional support, and reported that the NICU staff had influenced the extent to which they as parents had been able to be near and actively participate in the care. Parents described the wish to be closer to their infant and to be more actively involved in their infant's care. CONCLUSION: Strategies to enable parent-infant closeness and active guidance from staff might help alleviate the emotional stress of parents and promote their participation during TH.

Neonatal resuscitation after birth: Swedish midwives' experiences of and perceptions about separation of mothers and their newborn babies.

INTRODUCTION: This study aimed to investigate midwives' experiences of and perceptions about mother-baby separation during resuscitation of the baby following birth. METHODS: A qualitative study was conducted using an author-designed questionnaire. Fifty-four midwives from two Swedish birth units with different working methods regarding neonatal resuscitation - at the mother's bedside in the birth room or in a designated resuscitation room outside the birth room - completed the questionnaire. Data were analyzed using qualitative content analysis. RESULTS: Most midwives had experience of removing a newborn baby in need of critical care from the birth room, thus separating the mother and baby. The midwives identified the difficulties and challenges involved in carrying out emergency care in the birth room after birth and had divergent opinions about what they considered possible in these birth situations. They agreed on the benefits, for both mother and baby, in performing emergency care in the birth room and avoiding a separation altogether, if possible. CONCLUSIONS: There are good opportunities to reduce separation of mother and baby after birth; training, knowledge, education and the right environmental conditions are important factors in successfully implementing new ways of working. It is possible to work towards reducing separation and this work should continue and strive to eliminate separation as far as possible.

Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy: A Systematic Review.

BACKGROUND: Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess benefits and harms of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing TH for hypoxic-ischemic encephalopathy. METHODS: We included randomized and observational studies reporting any intervention (either drugs or non-pharmacological interventions) to manage pain and sedation in newborn infants (> 33 weeks' gestational age) undergoing TH. We included any dose, duration and route of administration. We also included any type and duration of non-pharmacological interventions. Our prespecified primary outcomes were analgesia and sedation assessed using validated pain scales in the neonatal population; circulatory instability; mortality to discharge; and neurodevelopmental disability. A systematic literature search was conducted in the PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and Web of Science databases, with no language restrictions. Included studies underwent risk-of-bias assessment (Cochrane risk-of-bias tool and ROBINS-I) and data extraction performed by two authors independently. The plan had been to use effect measures such as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, however the included studies are presented in a narrative synthesis due to their paucity and heterogeneity. RESULTS: Ten studies involving 3551 infants were included-one trial and nine observational studies. Most studies examined the use of phenobarbital or other antiepileptic drugs with primary outcomes related to seizure activity. The single trial that was included compared pentoxifylline with placebo. Among the primary outcomes, six studies reported circulatory instability and five reported mortality to discharge without relevant differences; two studies reported on neurodevelopmental disability and one study reported on pain scale. Three studies were ongoing. CONCLUSIONS: We found limited evidence to establish the benefits and harms of the interventions for the management of pain and sedation in newborn infants undergoing TH. Long-term outcomes were not reported. Given the very low certainty of evidence-due to imprecision of the estimates, inconsistency and limitations in study design (all nine observational studies with overall serious risk of bias)-for all outcomes, clinical trials are required to determine the most effective interventions in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020205755.

Interventions for the management of Pain and Sedation in Newborns undergoing Therapeutic hypothermia for hypoxic-ischemic encephalopathy (IPSNUT): protocol of a systematic review.

BACKGROUND: Clinical research has shown that therapeutic hypothermia after neonatal hypoxic-ischemic injury improves survival without disability. There is no consensus regarding pain relief or sedation during therapeutic hypothermia in newborns; however, therapeutic hypothermia seems to be associated with pain and stress, and adequate analgesia and sedation are central to maximize the effect of therapeutic hypothermia. Pain needs to be adequately managed in all patients, especially the newborn infant due to the potential short- and long-term negative effects of inadequately treated pain in this population. METHODS: We will perform a systematic review of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. We will include randomized, quasi-randomized controlled trials and observational studies. The use of pharmacological or non-pharmacological interventions will be compared to other pharmacological and or non-pharmacological interventions or no intervention/placebo. The primary outcomes for this review will be analgesia and sedation assessed with validated pain scales, circulatory instability, mortality to discharge, and moderate-to-severe neurodevelopmental disability. We will search the following databases: CINAHL, ClinicalTrials.gov , Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Two independent researchers will screen the records for inclusion, extract data using a data extraction form, and assess the risk of bias in the included trials. DISCUSSION: The result of this review will summarize the knowledge regarding the management of pain and sedation in infants treated with therapeutic hypothermia and potentially provide clinicians with guidance on the effective and safe methods. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020205755.