Bringing Enhanced Recovery After Surgery to the NICU: An Implementation Trial.

INTRODUCTION: Enhanced Recovery After Surgery (ERAS) guidelines are bundled evidence-informed recommendations implemented to improve quality and safety of perioperative care. This study aims to determine feasibility of NICU implementation of an ERAS Guideline for Intestinal Resection, describing clinical outcomes and adherence to recommendations following light-touch implementation. METHODS: Infants <28 days undergoing laparotomy for intestinal resection in a closed-NICU were prospectively enrolled. Exclusion criteria included prematurity (<32wks), instability, or major comorbidity. Clinical data reflecting 13 ERAS recommendations were collected through chart review. Descriptive statistics are presented as median [interquartile range]. Thirty-day post-discharge outcomes include NICU and hospital length of stay (LOS), ventilator days, surgical site infection (SSI), re-intubation, readmission, reoperation, and mortality. Adherence was calculated as the percentage of patients eligible for each recommendation whose care was adherent. RESULTS: Ten infant-parent dyads were enrolled (five females; GA 37 weeks [35, 38.8]; birthweight 2.97 kg [2.02, 3.69]). Surgical diagnoses included intestinal atresia/web (n = 6), anorectal malformation (n = 3), and segmental volvulus (n = 1). NICU LOS was 16 days [11, 21], hospital LOS 20 days [18, 30], and 2.5 ventilator days/patient [2, 3]. There was reduced opioid use, no SSIs, one re-intubation, three readmissions, three reoperations, and no mortalities. Adherence to ERAS recommendations ranged 0-100 % with a pooled adherence rate of 73 %. CONCLUSION: It is feasible to introduce ERAS to the NICU with acceptable overall adherence. Assessing adherence was challenging for some measures. There were promising early clinical findings including a reduction in opioid use. This implementation trial will inform development of an ERAS protocol for surgical NICUs. LEVEL OF EVIDENCE: IV (Cohort Study).

Parental perceptions and experiences of care in the surgical neonatal intensive care unit.

BACKGROUND: Parents endure significant stress when their newborns require surgery while in the neonatal intensive care unit (NICU). Our study aims to explore the surgical NICU experience from the parents' perspective and identify areas that may improve this experience. A secondary objective was to integrate their feedback to refine the implementation strategy of the neonatal enhanced recovery after surgery (ERAS®) guideline. METHODS: In December 2019, five surgical NICU parents participated in a focus group. Conversation surrounded parents' perspectives and experiences of the surgical NICU. Inductive analysis was performed to identify data, themes, and concepts that emerged from the discussion. RESULTS: Participants identified four major interrelated themes that impacted the surgical parents' NICU experience. These themes include (1) parental state, both physical and emotional, (2) the altered parental caregiver role which necessitates identifying alternative meaningful parental experiences, (3) the care team dynamic, incorporating consistency and effective communication, and (4) the discharge process which may be significantly eased through graduated, hands-on training. CONCLUSION: Key elements of the neonatal ERAS® guideline address major themes and stressors identified by parents. The parental perspective may help clinicians appreciate the parent surgical NICU experience and assist in improving family-centered care to surgical infants and their families.

Comparing Three Methods of Therapeutic Hypothermia Among Transported Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable. Most centers initiate passive TH at referral hospitals, while active cooling is typically initiated during transport. The objective of this study was to evaluate the effectiveness of three methods of cooling during transport of neonates with HIE in southern Alberta. In this prospective cohort study, 186 neonates with HIE were transported between January 2013 and December 2021. Among the 186 neonates, 47 were passively cooled, 36 actively cooled with gel packs, and 103 cooled with a servo-controlled cooling device. The clinical characteristics were comparable for the three groups, with no difference in adverse events. Fifteen neonates (8%) died and 54 neonates (29%) suffered radiologically determined brain injury. Servo-controlled cooling was found to be superior to other methods in maintaining a target temperature without significant fluctuation during transport and with temperature in the target range on arrival at tertiary care facilities. The rate of overcooling was also lower in the servo-controlled group compared with other groups. There were no statistically significant differences between the groups in relation to mortality and brain MRI changes associated with HIE. Adjusting for GA, 10-minute Apgar score, base excess, HIE stage, and need for intubation during transport, passive cooling increased the odds of temperature fluctuation outside the range by 12-fold and gel pack cooling by 13-fold compared with servo-controlled cooling. The use of servo-controlled TH devices should be the preferred practice wherever feasible. (REB17-1334_REN3).

Advanced neonatal procedural skills: a simulation-based workshop: impact and skill decay.

BACKGROUND: Trainees aiming to specialize in Neonatal Perinatal Medicine (NPM), must be competent in a wide range of procedural skills as per the Royal College of Canada. While common neonatal procedures are frequent in daily clinical practice with opportunity to acquire competence, there are substantial gaps in the acquisition of advanced neonatal procedural skills. With the advent of competency by design into NPM training, simulation offers a unique opportunity to acquire, practice and teach potentially life-saving procedural skills. Little is known on the effect of simulation training on different areas of competence, and on skill decay. METHODS: We designed a unique simulation-based 4-h workshop covering 6 advanced procedures chosen because of their rarity yet life-saving effect: chest tube insertion, defibrillation, exchange transfusion, intra-osseus (IO) access, ultrasound-guided paracentesis and pericardiocentesis. Direct observation of procedural skills (DOPS), self-perceived competence, comfort level and cognitive knowledge were measured before (1), directly after (2), for the same participants after 9-12 months (skill decay, 3), and directly after a second workshop (4) in a group of NPM and senior general pediatric volunteers. RESULTS: The DOPS for all six procedures combined for 23 participants increased from 3.83 to 4.59. Steepest DOPS increase pre versus post first workshop were seen for Defibrillation and chest tube insertion. Skill decay was evident for all procedures with largest decrease for Exchange Transfusion, followed by Pericardiocentesis, Defibrillation and Chest Tube. Self-perceived competence, comfort and cognitive knowledge increased for all six procedures over the four time points. Exchange Transfusion stood out without DOPS increase, largest skill decay and minimal impact on self-assessed competence and comfort. All skills were judged as better by the preceptor, compared to self-assessments. CONCLUSIONS: The simulation-based intervention advanced procedural skills day increased preceptor-assessed directly observed procedural skills for all skills examined, except exchange transfusion. Skill decay affected these skills after 9-12 months. Chest tube insertions and Defibrillations may benefit from reminder sessions, Pericardiocentesis may suffice by teaching once. Trainees' observed skills were better than their own assessment. The effect of a booster session was less than the first intervention, but the final scores were higher than pre-intervention. TRIAL REGISTRATION: Not applicable, not a health care intervention.

Impact of multiple intubation attempts on adverse tracheal intubation associated events in neonates: a report from the NEAR4NEOS.

OBJECTIVE: To determine the relationship between number of attempts and adverse events during neonatal intubation. STUDY DESIGN: A retrospective study of prospectively collected data of intubations in the delivery room and NICU from the National Emergency Airway Registry for Neonates (NEAR4NEOS) in 17 academic centers from 1/2016 to 12/2019. We examined the association between tracheal intubation attempts [1, 2, and ≥3 (multiple attempts)] and clinical adverse outcomes (any tracheal intubation associated events (TIAE), severe TIAE, and severe oxygen desaturation). RESULTS: Of 7708 intubations, 1474 (22%) required ≥3 attempts. Patient, provider, and practice factors were associated with higher TI attempts. Increasing intubation attempts was independently associated with a higher risk for TIAE. The adjusted odds ratio for TIAE and severe oxygen desaturation were significantly higher in TIs with 2 and ≥3 attempts than with one attempt. CONCLUSION: The risk of adverse safety events during intubation increases with the number of intubation attempts.

An assessment of the impact of dexmedetomidine on opioid use in a neonatal intensive care unit.

OBJECTIVE: To evaluate the impact of dexmedetomidine on opioid use in neonates. METHODS: A retrospective chart review of neonates that received dexmedetomidine compared to matched historical controls in a surgical tertiary NICU. The primary endpoint was overall opioid exposure. Secondary endpoints included the duration of regular opioid use, duration of opioid wean, duration of mechanical ventilation, and time to achieve full enteral feeds. RESULTS: There were no statistically significant differences in opioid exposure (60.3 vs 42.6 mcg ME/kg, p = .25), duration (583 vs 340 h, p = .07), or wean duration (261 vs 147 h, p = .12) between the two cohorts. In fact, these parameters showed clinically, if not statistically, significant increases in the dexmedetomidine cohort. Opioid exposure per day, length of NICU stay, duration of mechanical ventilation, and days to full enteral feeds did not differ between cohorts. CONCLUSION: This retrospective cohort study did not show reduced opioid exposure in surgical neonates receiving dexmedetomidine, which is in contrast to other literature. It highlights the limitations of using a medication without appropriate guidance and assessment tools to support its use.

Intubation Competence During Neonatal Fellowship Training.

OBJECTIVES: To characterize neonatal-perinatal medicine fellows' progression toward neonatal intubation procedural competence during fellowship training. METHODS: Multi-center cohort study of neonatal intubation encounters performed by neonatal-perinatal medicine fellows between 2014 through 2018 at North American academic centers in the National Emergency Airway Registry for Neonates. Cumulative sum analysis was used to characterize progression of individual fellows' intubation competence, defined by an 80% overall success rate within 2 intubation attempts. We employed multivariable analysis to assess the independent impact of advancing quarter of fellowship training on intubation success. RESULTS: There were 2297 intubation encounters performed by 92 fellows in 8 hospitals. Of these, 1766 (77%) were successful within 2 attempts. Of the 40 fellows assessed from the start of training, 18 (45%) achieved procedural competence, and 12 (30%) exceeded the deficiency threshold. Among fellows who achieved competence, the number of intubations to meet this threshold was variable, with an absolute range of 8 to 46 procedures. After adjusting for patient and practice characteristics, advancing quarter of training was independently associated with an increased odds of successful intubation (adjusted odds ratio: 1.10; 95% confidence interval 1.07-1.14). CONCLUSIONS: The number of neonatal intubations required to achieve procedural competence is variable, and overall intubation competence rates are modest. Although repetition leads to skill acquisition for many trainees, some learners may require adjunctive educational strategies. An individualized approach to assess trainees' progression toward intubation competence is warranted.

Impact of Physician Training Level on Neonatal Tracheal Intubation Success Rates and Adverse Events: A Report from National Emergency Airway Registry for Neonates (NEAR4NEOS).

INTRODUCTION: Neonatal tracheal intubation (TI) outcomes have been assessed by role, but training level may impact TI success and safety. Effect of physician training level (PTL) on the first-attempt success, adverse TI-associated events (TIAEs), and oxygen desaturation was assessed. METHODS: Prospective cohort study in 11 international NEAR4NEOS sites between October 2014 and December 2017. Primary TIs performed by pediatric/neonatal physicians were included. Univariable analysis evaluated association between PTL, patient/practice characteristics, and outcomes. Multivariable analysis with generalized estimating equation assessed for independent association between PTL and outcomes (first-attempt success, TIAEs, and oxygen desaturation ≥20%; attending as reference). RESULTS: Of 2,608 primary TIs, 1,298 were first attempted by pediatric/neonatal physicians. PTL was associated with patient age, weight, comorbidities, TI indication, difficult airway history, premedication, and device. First-attempt success rate differed across PTL (resident 23%, fellow 53%, and attending 60%; p < 0.001). There was no statistically significant difference in TIAEs (resident 22%, fellow 20%, and attending 25%; p = 0.34). Desaturation occurred more frequently with residents (60%), compared to fellows and attendings (46 and 53%; p < 0.001). In multivariable analysis, adjusted odds ratio of the first-attempt success was 0.18 (95% CI: 0.11-0.30) for residents and 0.80 (95% CI: 0.51-1.24) for fellows. PTL was not independently associated with adjusted odds of TIAEs or severe oxygen desaturation. CONCLUSION: Higher PTL was associated with increased first-attempt success but not TIAE/oxygen desaturation. Identifying strategies to decrease adverse events during neonatal TI remains critical.

Developing implementation strategies to adopt Enhanced Recovery After Surgery (ERAS®) guidelines.

BACKGROUND: Strong implementation strategies are critical to the success of Enhanced Recovery after Surgery (ERAS®) guidelines, though little documentation exists on effective strategies, especially in complex clinical situations and unfamiliar contexts. This study outlines the process taken to adopt a novel neonatal ERAS® guideline. METHODS: The implementation strategy was approached in a multi-pronged, concurrent but asynchronous fashion. Between September 2019 and January 2020, healthcare providers from various disciplines and different specialties as well as parents participated in the strategy. Multidisciplinary teams were created to consider existing literature and local contexts including potential facilitators and/or barriers. Task forces worked collaboratively to develop new care pathways. An audit system was developed to record outcomes and elicit feedback for revision. RESULTS: 32 healthcare providers representing 9 disciplines and 5 specialties as well as 8 parents participated. Care pathways and resources were created. Elements recommended for a successful implementation strategy included identification of champions, multidisciplinary stakeholder involvement, consideration of local contexts and insights, patient/family engagement, education, and creation of an audit system. CONCLUSION: A multidisciplinary and structured process following principles of implementation science was used to develop an effective implementation strategy for initiating ERAS® guidelines.

Reducing discomfort of eye drops prior to retinal examination in the neonatal intensive care unit.

OBJECTIVE: To evaluate the effectiveness in reducing pain by giving oral sucrose and non-pharmacological comfort measures prior to topical administration of mydriatic eye drops on premature infants undergoing retinopathy of prematurity (ROP) screening eye exams in a neonatal intensive care unit (NICU). STUDY DESIGN: A prospective quality improvement study was conducted in the NICU where infants were given oral sucrose prior to administration of mydriatic eye drops while a second person performed facilitated tucking and containment. Premature Infant Pain Profile (PIPP) scores were recorded during eye drop administration and compared to a group that did not receive any comfort measures. RESULT: Sixty-eight infants were enrolled. Mean PIPP scores increased an average of 1.5 (SD = 1.5) during administration of mydriatic drops without comfort measures compared to 0.6 (SD = 0.8) when comfort measures were used. This difference was statistically significant (p < 0.001). CONCLUSIONS: Oral sucrose and simple comfort measures can be effective in reducing pain associated with mydriatic eye drops.

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations.

BACKGROUND: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. METHODS: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. RESULTS: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. DISCUSSION: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties.

Inositol in preterm infants at risk for or having respiratory distress syndrome.

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. A drop in inositol levels in infants with respiratory distress syndrome (RDS) can be a sign that their illness will be severe. OBJECTIVES: To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes including: death (neonatal and infant deaths), bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), necrotizing enterocolitis (NEC) and sepsis. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 11), MEDLINE via PubMed (1966 to 5 November 2018), Embase (1980 to 5 November 2018), and CINAHL (1982 to 5 November 2018). We searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCT) and quasi-randomised trials. SELECTION CRITERIA: We included all randomised controlled trials of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention. Outcomes included neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis. DATA COLLECTION AND ANALYSIS: The three review authors independently abstracted data on neonatal outcomes and resolved any disagreements through discussion and consensus. Outcomes were reported as typical risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or number needed to treat for an additional harmful outcome (NNTH). We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: Six published randomised controlled trials were identified, with a total of 1177 infants. Study quality varied for the comparison 'Inositol supplementation to preterm infants (repeat doses in any amount and any duration of treatment) versus control' and interim analyses had occurred in several trials for the outcomes of interest. In this comparison, neonatal death was found to be significantly reduced (typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.16 to -0.01; NNTB 11, 95% CI 6 to 100; 3 trials, 355 neonates). Infant deaths were not reduced (typical RR 0.89, 95% CI 0.71 to 1.13; typical RD -0.02, 95% CI -0.07 to 0.02; 5 trials, 1115 infants) (low-quality evidence). ROP stage 2 or higher or stage 3 or higher was not significantly reduced (typical RR 0.89, 95% CI 0.75 to 1.06; typical RD -0.04, 95% CI -0.10 to 0.02; 3 trials, 810 infants) (moderate-quality evidence). There were no significant findings for ROP (any stage), NEC (suspected or proven), sepsis, IVH grade greater than II (moderate-quality evidence). For the comparison 'Inositol supplementation IV initially followed by enteral administration (repeat doses of 80 mg/kg/day) in preterm infants born at less than 30 weeks' postmenstrual age (PMA) compared to placebo for preterm infants at risk for or having respiratory distress syndrome' the results from two studies of high quality were included (N = 760 neonates). Recruitment to the larger study (N = 638) was terminated because of a higher rate of deaths in the inositol group. We did not downgrade the quality of the study. The meta-analyses of the outcomes of 'Type 1 ROP or death before determination of ROP outcome using the adjudicated ROP outcome', 'Type 1 ROP including adjudicated ROP outcome', 'All-cause mortality (outcome collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)' and 'Severe IVH (grade 3 or 4)' did not show significant findings (moderate-quality evidence). There were no significant findings for the outcomes 'BPD or death by it prior to 37 weeks' postmenstrual age (outcomes collected through first event: death, hospital discharge, hospital transfer, or 120 days after birth)', 'Late onset sepsis (> 72 hours of age)', and 'Suspected or proven NEC' (high-quality evidence). AUTHORS' CONCLUSIONS: Based on the evidence from randomised controlled trials to date, inositol supplementation does not result in important reductions in the rates of infant deaths, ROP stage 3 or higher, type 1 ROP, IVH grades 3 or 4, BPD, NEC, or sepsis. These conclusions are based mainly on two recent randomised controlled trials in neonates less than 30 weeks' postmenstrual age (N = 760), the most vulnerable population. Currently inositol supplementation should not be routinely instituted as part of the nutritional management of preterm infants with or without RDS. It is important that infants who have been enrolled in the trials included in this review are followed to assess any effects of inositol supplementation on long-term outcomes in childhood. We do not recommend any additional trials in neonates.

Implementation of Neonatal Neurocritical Care Program Improved Short-Term Outcomes in Neonates With Moderate-to-Severe Hypoxic Ischemic Encephalopathy.

BACKGROUND: Despite the introduction of therapeutic hypothermia, infants with moderate-to-severe hypoxic-ischemic encephalopathy remain at risk of mortality and morbidity. A dedicated service with standardized management protocols and improved communication may help improve care. We aimed to evaluate the impact of a dedicated neonatal neurocritical care service on short-term outcomes in infants with hypoxic-ischemic encephalopathy. METHODS: We performed a retrospective cohort study (July 2008 to December 2017) on term and near-term infants admitted to two tertiary neonatal intensive care units with moderate-to-severe hypoxic-ischemic encephalopathy, before and after neonatal neurocritical care service implementation. The primary outcome was brain magnetic resonance imaging findings consistent with those of hypoxic-ischemic encephalopathy. Secondary outcomes included the cooling initiation rate, hospital stay duration, antiseizure medication use, and inotrope use. Regression analysis and interrupted time series analysis were performed after adjusting for confounding factors. RESULTS: In total, 216 infants with moderate-to-severe hypoxic-ischemic encephalopathy were analyzed-109 before and 107 after neonatal neurocritical care implementation. After adjusting for confounding factors, there was a significant reduction in primary outcomes (adjusted odds ratio: 0.3, confidence interval: 0.15 to 0.57, P < 0.001) after neonatal neurocritical care implementation. Average hospital stay duration reduced by 5.2 days per infant (P = 0.03), identification of eligible infants for cooling improved (P < 0.001), antiseizure medication use reduced (P = 0.001), and early inotropes use reduced (P = 0.04). CONCLUSION: Implementation of a neonatal neurocritical care service associated with decreased brain injury shortened the hospital stay duration and improved the care of infants with moderate-to-severe hypoxic-ischemic encephalopathy.

Introduction of Continuous Video EEG Monitoring into 2 Different NICU Models by Training Neonatal Nurses.

BACKGROUND: Continuous video electroencephalographic (EEG) (cvEEG) monitoring is emerging as the standard of care for diagnosis and management of neonatal seizures. However, cvEEG is labor-intensive and the need to initiate and interpret studies on a 24-hour basis is a major limitation. PURPOSE: This study aims at establishing consistency in monitoring of newborns admitted to 2 different neonatal intensive care units (NICUs) managed by the same neurocritical care team. METHODS: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues, and identify amplitude-integrated EEG abnormalities. Guidelines, checklists, and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. A cohort of 100 infants with moderate to severe hypoxic-ischemic encephalopathy before and after the training program was compared. RESULTS: During the study period, 192 cvEEGs were obtained. The time to initiate brain monitoring decreased by 31.5 hours posttraining; this, in turn, led to an increase in electrographic seizure detection (20% before vs 34% after), decrease in seizure clinical misdiagnosis (65% before and 36% after), and reduction in antiseizure medication burden. IMPLICATIONS FOR PRACTICE: Training experienced NICU nurses to set up, start, and monitor cvEEGs can decrease the time to initiate cvEEGs, which may lead to better seizure diagnosis and management. IMPLICATIONS FOR RESEARCH: Further understanding of practice bundles for best supporting infants at risk and being treated for seizures needs to be evaluated for integration into practice.Video Abstract Available at https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx.

Inositol in preterm infants at risk for or having respiratory distress syndrome.

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. OBJECTIVES: To assess the effectiveness and safety of supplementary inositol in preterm infants with or without respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov and Controlled-trials.com were searched in September 2014. The reference lists of identified randomised controlled trials (RCTs), personal files and Web of Science were searched. SELECTION CRITERIA: All RCTs of inositol supplementation of preterm infants compared with a control group that received a placebo or no intervention were included. Outcomes of interest were neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular haemorrhage (IVH), necrotizing enterocolitis (NEC) and sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted independently by the three review authors and any discrepancy was resolved through consensus. Outcomes were reported as relative risk (RR), risk difference (RD) and number needed to treat to benefit (NNTB) or to harm (NNTH). MAIN RESULTS: Four published RCTs and one ongoing RCT were identified. Study quality varied and interim analyses had occurred in all trials of repeat doses of inositol that provided data for the outcomes of interest in this review. In these trials neonatal death was found to be significantly reduced (3 trials, 355 neonates; typical RR 0.53, 95% CI 0.31 to 0.91; typical RD -0.09, 95% CI -0.17 to -0.03; NNTB 11, 95% CI 6 to 33). Infant deaths were reduced (3 trials, 355 infants; typical RR 0.55, 95% CI 0.40 to 0.77; typical RD -0.18, 95% CI -0.27 to -0.08; NNTB 6, 95% CI 4 to 13). ROP stage ≥ 3 was significantly reduced (2 trials, 262 infants; typical RR 0.09, 95% CI 0.01 to 0.67; typical RD -0.08, 95% CI -0.13 to -0.03; NNTB 13, 95% CI 8 to 33) and IVH grade > II was significantly decreased (3 trials, 355 infants; typical RR 0.53, 95% CI 0.31 to 0.90; typical RD -0.09, 95% CI -0.16 to -0.02; NNTB 11, 95% CI 6 to 50). Neither sepsis nor NEC differed significantly between groups. One study (74 infants) that administered a single dose of inositol (60 or 120 mg/kg) found no significant differences in adverse outcomes using RR, but an increased RD for BPD at 36 weeks postmenstrual age (RD 0.23, 95% CI 0.03 to 0.43; NNTH 4, 95% CI 2 to 33). This result should be interpreted with caution as only one dose of inositol was given and only the RD, but not the RR, was significant. One ongoing large study of repeat doses of inositol in preterm infants was identified. AUTHORS' CONCLUSIONS: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A large size multi-centre randomised controlled trial is currently ongoing and the trial will likely confirm or refute the findings from this systematic review.

The mystery of persistent pulmonary hypertension: an idiopathic infantile arterial calcification.

BACKGROUND: Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disorder, characterized by wide spread calcifications in arterial walls, leading to vaso-occlusive ischaemia of multiple organs. Mortality is high, and there is no definitive treatment. CASE PRESENTATION: A male neonate, 36+5 weeks gestation, 2.81 kg, was admitted to NICU for respiratory distress. At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary oedema. An echocardiogram (ECHO) indicated moderate persistent pulmonary hypertension (PPHN) of unclear etiology. A diagnosis of Idiopathic infantile arterial calcification was made and a trial of Editronate therapy was given without success. CONCLUSION: IIAC is a rare disorder, it should be considered whenever a neonate presents with unexplainable cardiac failure, PPHN, echogenic vessels on X-ray/ultrasound and, or concentric hypertrophic ventricles on ECHO. Serial antenatal ultrasound findings of echogenic cardiac foci should raise the suspicion of IIAC. Further studies to determine the long term effects of Editronate on vascular calcifications, disease outcome, and other treatment options are needed.

Inositol for respiratory distress syndrome in preterm infants.

BACKGROUND: Inositol is an essential nutrient required by human cells in culture for growth and survival. Inositol promotes maturation of several components of surfactant and may play a critical role in fetal and early neonatal life. OBJECTIVES: To assess the effectiveness/safety of supplementary inositol in preterm infants with respiratory distress syndrome (RDS) in reducing adverse neonatal outcomes. SEARCH METHODS: The Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, CINAHL, Clinicaltrials.gov and Controlled-trials.com were searched in May, 2011. The reference lists of identified randomized controlled trials (RCTs), personal files and Web of Science were searched. SELECTION CRITERIA: All RCTs of inositol supplementation to preterm infants with a control group that received a placebo or no intervention were included. Outcomes of interest were neonatal death, infant death, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), and sepsis. DATA COLLECTION AND ANALYSIS: Data on neonatal outcomes were abstracted independently by the three review authors and any discrepancy was resolved through consensus. Outcomes were reported as relative risk (RR), risk difference (RD) and number needed to treat to benefit (NNT). MAIN RESULTS: Four published and one ongoing randomized controlled trials were identified. Study quality varied and interim analyses had occurred in all trial that provided data for the outcomes. Neonatal death was found to be significantly reduced [three trials, 355 neonates, typical RR 0.53 (95% CI 0.31 to 0.91); RD -0.09 (95% CI -0.17 to -0.03); NNT 11 (95% CI 6 to 33). Infant deaths were reduced [three trials, 355 infants, typical RR 0.55 (95% CI 0.40 to 0.77); RD -0.18 (95% CI -0.27 to -0.08); NNT 6 (95% CI 4 to 13). ROP, stage ≥ 3 was significantly reduced [two trials, 262 infants, typical RR 0.09 (95% CI 0.01 to 0.67); typical RD -0.08 (95% CI -0.13 to -0.03); NNT 13 (95% CI 8 to 33)]. IVH grade > II was significantly decreased [three trials, 355 infants typical RR 0.53 (95% CI 0.31 to 0.90; typical RD -0.09 (95% CI -0.16 to -0.02); NNT 11 (95% CI 6 to 50). Neither sepsis nor NEC differed significantly between groups. One ongoing pharmacokinetics study of inositol in preterm infants was identified. AUTHORS' CONCLUSIONS: Inositol supplementation results in statistically significant and clinically important reductions in important short-term adverse neonatal outcomes. A multicenter randomized controlled trial of appropriate size is justified to confirm these findings.

The influence of context on pain practices in the NICU: perceptions of health care professionals.

In this qualitative descriptive study, we explored health care professionals' perceptions of the influence of context (i.e., organizational culture, structure, resources, capabilities/competencies, and politics) on evidence-based pain practices. A total of 16 focus groups with 147 health care professionals were conducted in three neonatal intensive care units (NICUs) in central and eastern Canada. Three overarching themes emerged from the data, which captured influences on optimal pain practices in the NICU, including (a) a culture of collaboration and support for evidence-based practice, (b) threats to autonomous decision making, and (c) complexities in care delivery. These results were consistent with theoretical conceptualizations of how context influences practice, as well as recent empirical research findings. This study supports the importance of context in shaping evidence-based practices by health care professionals in the management of pain in the NICU.