Premedication practices for neonatal tracheal intubation: Results from the EPIPPAIN 2 prospective cohort study and comparison with EPIPPAIN 1.

To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty-one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49-20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12-11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46-8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.

Premedication practices for tracheal intubation in neonates transported by French medical transport teams: a prospective observational study.

OBJECTIVES: Premedication practices for neonatal tracheal intubations have not yet been described for neonatal transport teams. Our objective is to describe the use of sedation/analgesia (SA) for tracheal intubations and to assess its tolerance in neonates transported by medical transport teams in France. SETTING: This prospective observational study was part of the EPIPPAIN 2 project and collected around-the-clock data on SA practices in neonates intubated by all five paediatric medical transport teams of the Paris region during a 2-month period. Intubations were classified as emergent, semiemergent and non-emergent. Sedation level and conditions of intubation were assessed with the Tonus, Reactivity, Awareness and Conditions of intubation to Help in Endotracheal intubation Assessment (TRACHEA score). The scores range from 0 to 10 representing an increasing ladder from adequate to inadequate sedation, and from excellent to very poor conditions of intubation. PARTICIPANTS: 40 neonates intubated in 28 different centres. RESULTS: The mean (SD) age was 34.9 (3.9) weeks, and 62.5% were intubated in the delivery room. 30/40 (75%) of intubations were performed with the use of SA. In 18/30 (60.0%) intubations performed with SA, the drug regimen was the association of sufentanil and midazolam. Atropine was given in 19/40 intubations. From the 16, 21 and 3 intubations classified as emergent, semiemergent and non-emergent, respectively, 8 (50%), 19 (90.5%) and 3 (100%) were performed with SA premedication. 79.3% of intubations performed with SA had TRACHEA scores of 3 or less. 22/40 (55%) infants had at least one of the following adverse events: muscle rigidity, bradycardia below 100/min, desaturation below 80% and nose or pharynx-larynx bleeding. 7/24 (29.2%) of those who had only one attempt presented at least one of these adverse events compared with 15/16 (93.8%) of those who needed two or more attempts (p<0.001). CONCLUSION: SA premedication is largely feasible for tracheal intubations performed in neonates transported by medical transport teams including intubations judged as emergent or semiemergent. TRIAL REGISTRATION NUMBER: NCT01346813; Results.

A simple tool to measure procedural restraint intensity in children: validation of the PRIC (Procedural Restraint Intensity in Children) scale.

PURPOSE: Restraint is often used when administering procedures to children. However, no metrologically scale to measure the restraint intensity had yet been validated. This study validated the metrological criteria of a scale measuring the restraint intensity, Procedural Restraint Intensity in Children (PRIC), used during procedures in children. DESIGN AND METHODS: The PRIC scale performance was measured by a group of 7 health professionals working in a children's hospital, by watching 20 videos of health care procedures. This group included 2 physicians, 1 pediatric resident, and 4 nurses. The intra-class correlation coefficients were calculated to evaluate the inter-rater and test-retest reliability and the construct validity with the correlation between PRIC scale and a numerical rating scale. RESULTS: One hundred and forty measurements were made. Inter-rater and test-retest correlation coefficients were 0.98 and 0.98, respectively. The 2 scales were positively correlated with a Spearman coefficient of 0.93. CONCLUSIONS: This study validated the Procedural Restraint Intensity in Children (PRIC) scale in metrological terms with some limitation. However, there is not gold standard scale to precisely validate the reliability of this tool and this study has been conducted in "experimental" conditions. Nevertheless, this is the first scale measuring the intensity of physical restraint with a metrological validation. The next step will be to validate it in real clinical situations.

Epidemiology and neonatal pain management of heelsticks in intensive care units: EPIPPAIN 2, a prospective observational study.

BACKGROUND: Heelstick is the most frequently performed skin-breaking procedure in the neonatal intensive care units (NICUs). There are no large multicenter studies describing the frequency and analgesic approaches used for heelsticks performed in NICUs. OBJECTIVES: To describe the frequency of heelsticks and their analgesic management in newborns in the NICU. To determine the factors associated with the lack of specific preprocedural analgesia for this procedure. DESIGN: EPIPPAIN 2 (Epidemiology of Procedural PAin In Neonates) is a descriptive prospective epidemiologic study. SETTING: All 16 NICUs in the Paris region in France. PARTICIPANTS: All newborns in the NICU with a maximum corrected age of 44 weeks +6 days of gestation on admission who had at least one heelstick during the study period were eligible for the study. The study included 562 newborns. METHODS: Data on all heelsticks and their corresponding analgesic therapies were prospectively collected. The inclusion period lasted six weeks, from June 2, 2011 to July 12, 2011. Newborns were followed from their admission to the 14th day of their NICU stay or discharge, whichever occurred first. RESULTS: The mean (SD) gestational age was 33.3 (4.4) weeks and duration of participation was 7.5 (4.4) days. The mean (SD; range) of heelsticks per neonate was 16.0 (14.4; 1-86) during the study period. Of the 8995 heelsticks studied, 2379 (26.4%) were performed with continuous analgesia, 5236 (58.2%) with specific preprocedural analgesia. Overall, 6764 (75.2%) heelsticks were performed with analgesia (continuous and/or specific). In a multivariate model, the increased lack of preprocedural analgesia was associated with female sex, term birth, high illness severity, tracheal or noninvasive ventilation, parental absence and use of continuous sedation/analgesia. CONCLUSIONS: Heelstick was very frequently performed in NICUs. Although, most heelsticks were performed with analgesia, this was not systematic. The high frequency of this procedure and the known adverse effects of repetitive pain in neonates should encourage the search of safe and effective strategies to reduce their number.

The burden of venipuncture pain in neonatal intensive care units: EPIPPAIN 2, a prospective observational study.

BACKGROUND: Newborns in intensive care units (ICUs) undergo numerous painful procedures including venipunctures. Skin-breaking procedures have been associated with adverse neurodevelopment long-term effects in very preterm neonates. The venipuncture frequency and its real bedside pain management treatment are not well known in this setting. OBJECTIVES: To describe venipuncture frequency, its pain intensity, and the analgesic approach in ICU newborns; to determine the factors associated with the lack of preprocedural analgesia and with a high pain score during venipuncture. DESIGN: Further analysis of EPIPPAIN 2 (Epidemiology of Procedural Pain In Neonates), which is a descriptive prospective epidemiologic study. SETTING: All 16 neonatal and pediatric ICUs in the Paris region in France. PARTICIPANTS: All newborns in the ICU with a maximum corrected age under 45 weeks of gestation on admission who had at least one venipuncture during the study period. METHODS: Data on all venipunctures, their pain score assessed with the DAN scale and their corresponding analgesic therapies were prospectively collected. The inclusion period lasted six weeks, from June 2, 2011, to July 12, 2011. Newborns were followed from their admission to the 14th day of their ICU stay or discharge, whichever occurred first. RESULTS: 495 newborns who underwent venipunctures were included. The mean (SD) gestational age was 33.0 (4.4) weeks and duration of participation was 8.0 (4.5) days. A total of 257 (51.9%) neonates were very preterm (<33 weeks). The mean (SD; range) number of venipunctures per neonate during the study period was 3.8 (2.8; 1-19) for all neonates and 4.1 (2.9; 1-17) for neonates <33 weeks. Of the 1887 venipunctures, 1164 (61.7%) were performed successfully in one attempt, 437 (23.2%) with continuous analgesia, 1434 (76.0%) with specific preprocedural analgesia. In multivariate models, lack of preprocedural analgesia was associated with higher disease-severity score, intrauterine growth retardation, invasive or noninvasive ventilation, venipuncture performed on the first day of hospitalization or at nighttime, and the use of continuous sedation/analgesia. High pain scores were significantly associated with absence of parents during procedures, surgery during the study period, and higher number of attempts. CONCLUSIONS: Venipuncture is very frequent in preterm and term neonates in the ICUs. 76% were performed with preprocedural analgesia. Strategies to reduce the number of attempts and to promote parental presence seem necessary.

Early Diagnosis of Migraine Necessary in Children: 10-Year Follow-Up.

BACKGROUND: The prevalence of migraine in individuals younger than 20 years old is 8%, with a mean age at onset of younger than 8 years. However, the long-term prognosis of migraine attacks has not been clearly established. OBJECTIVE: Our main objective was to evaluate disease course 10 years after migraine diagnosis in a cohort of children and adolescents. METHODS: Migraine was diagnosed in 1999 in a pediatric headache reference center using International Headache Society criteria. In 2009, all patients were interviewed by telephone on the persistence and characteristics of any headaches. The main end point was prevalence of persistent migraine attacks in 2009. Variables associated with persistent attacks were analyzed. RESULTS: Overall, 142 children were diagnosed with migraine in 1999. Of these, 84 were interviewed by telephone in 2009. In 1999, the mean age was 11.6 ± 3.1 years, 54% were male, and 50% had migraine without aura. Migraine attacks were common (1-3 attacks/week in 38%). Mean age at onset was 7 years and 4 months (±3 years). In 2009, migraine prevalence was 39/84 (46% [95% confidence interval 36-56]), 12 patients (14%) were headache-free, and 62 patients (74%) had tension-type headaches that were isolated headaches in 33 (39%) patients. The rate of patients with at least one migraine attack per week fell from 37% to 8% (P = 0.001) over the 10-year period. Age at the first visit to the center was significantly higher in 2009 migraine sufferers than nonsufferers (12.5 ± 3.0 versus 10.9 ± 3.1 years (P = 0.02)). In multivariate analysis, age ≥12 years at the time of first presentation was the only significant factor associated with long-term chronic migraine (odds ratio = 3.0 [1.1-8.0]). CONCLUSIONS: Ten years after first presentation, 46% of patients had migraine but the frequency of attacks had diminished. The only factor associated with chronic migraine was age ≥12 years at first presentation.

Does neonatal pain management in intensive care units differ between night and day? An observational study.

OBJECTIVE: To determine whether analgesic use for painful procedures performed in neonates in the neonatal intensive care unit (NICU) differs during nights and days and during each of the 6 h period of the day. DESIGN: Conducted as part of the prospective observational Epidemiology of Painful Procedures in Neonates study which was designed to collect in real time and around-the-clock bedside data on all painful or stressful procedures. SETTING: 13 NICUs and paediatric intensive care units in the Paris Region, France. PARTICIPANTS: All 430 neonates admitted to the participating units during a 6-week period between September 2005 and January 2006. DATA COLLECTION: During the first 14 days of admission, data were collected on all painful procedures and analgesic therapy. The five most frequent procedures representing 38 012 of all 42 413 (90%) painful procedures were analysed. INTERVENTION: Observational study. MAIN OUTCOME ASSESSMENT: We compared the use of specific analgesic for procedures performed during each of the 6 h period of a day: morning (7:00 to 12:59), afternoon, early night and late night and during daytime (morning+afternoon) and night-time (early night+late night). RESULTS: 7724 of 38 012 (20.3%) painful procedures were carried out with a specific analgesic treatment. For morning, afternoon, early night and late night, respectively, the use of analgesic was 25.8%, 18.9%, 18.3% and 18%. The relative reduction of analgesia was 18.3%, p<0.01, between daytime and night-time and 28.8%, p<0.001, between morning and the rest of the day. Parental presence, nurses on 8 h shifts and written protocols for analgesia were associated with a decrease in this difference. CONCLUSIONS: The substantial differences in the use of analgesics around-the-clock may be questioned on quality of care grounds.

EVENDOL, a new behavioral pain scale for children ages 0 to 7 years in the emergency department: design and validation.

Numerous behavioral pain measures have been validated for young children, but none is appropriate to assess pain in emergency departments (EDs), where caregivers need a simple, easily completed scale. Our objective was to elaborate and validate a tool, relevant in any painful situation, with agitation or prostration, and for any age under 7 years. Five items (scored 0 to 3) were developed by pediatric pain and emergency caregivers. The new scale, called EVENDOL, was tested at children's arrival and after analgesics, at rest, and during mobilization. The validation study included 291 children from birth to 7 years old in 4 French EDs, and independent observations by the ED nurse and a researcher. The Cronbach coefficient was excellent (0.83 to 0.92). Construct validity was demonstrated by a decrease in scores after nalbuphine: 8.14 to 3.62 of 15 at rest (P<.0001), 11.87 to 6.65 at mobilization (P = .0011); by good correlations between EVENDOL and nurse or researcher numerical scores: 0.79 to 0.92 (P<.0001); by good correlations between children's self-assessment scores and EVENDOL in children ages 4 to 7 (0.64 to 0.93). Discriminant validity with tiredness, anxiety, and hunger was good. Interrater reliability was excellent between nurses and researcher (weighted kappa 0.7 to 0.9), and in a group of 6 nurses (simultaneous assessment of 122 videos). The treatment threshold was determined at 4 of 15. EVENDOL has excellent validity and can be used for all children under age 7 in EDs, for any age and any pain, acute as well as more prolonged.

Analgesic effects of EMLA cream and oral sucrose during venipuncture in preterm infants.

OBJECTIVE: The goal of this study was to compare the analgesic effect of sucrose with that of the combination of sucrose and the local anesthetic cream EMLA during venipuncture in preterm neonates. METHODS: This randomized, double-blind prospective study included infants younger than 37 weeks' gestational age during 1 routine venipuncture for blood sampling. Each child randomly received either sucrose plus application of a placebo cream (S group) or sucrose plus EMLA cream (S+E group) before venipuncture. Venipuncture-induced pain was assessed through videotapes of the procedures by using the Douleur Aiguë Nouveau-né (DAN) behavioral scale. Pain was assessed at 2 phases: during venipuncture (from needle introduction to its removal) and during the recovery period (30 seconds after needle removal). Pain scores over time and between treatments were compared by using repeated-measures analysis of variance. RESULTS: The study included 76 children (37 in the S group, 39 in the S+E group). Mean (SD) DAN pain scores for the S group and the S+E group were 7.7 (2.1) and 6.4 (2.5), respectively, during venipuncture and 7.1 (2.8) and 5.7 (3.3) during the postinjection period. A significant time and treatment effect in favor of the S+E group was observed. CONCLUSION: The combination of sucrose and EMLA cream revealed a higher analgesic effect than sucrose alone during venipuncture in these preterm infants.

Epidemiology and treatment of painful procedures in neonates in intensive care units.

CONTEXT: Effective strategies to improve pain management in neonates require a clear understanding of the epidemiology and management of procedural pain. OBJECTIVE: To report epidemiological data on neonatal pain collected from a geographically defined region, based on direct bedside observation of neonates. DESIGN, SETTING, AND PATIENTS: Between September 2005 and January 2006, data on all painful and stressful procedures and corresponding analgesic therapy from the first 14 days of admission were prospectively collected within a 6-week period from 430 neonates admitted to tertiary care centers in the Paris region of France (11.3 millions inhabitants) for the Epidemiology of Procedural Pain in Neonates (EPIPPAIN) study. MAIN OUTCOME MEASURE: Number of procedures considered painful or stressful by health personnel and corresponding analgesic therapy. RESULTS: The mean (SD) gestational age and intensive care unit stay were 33.0 (4.6) weeks and 8.4 (4.6) calendar days, respectively. Neonates experienced 60,969 first-attempt procedures, with 42,413 (69.6%) painful and 18,556 (30.4%) stressful procedures; 11,546 supplemental attempts were performed during procedures including 10,366 (89.8%) for painful and 1180 (10.2%) for stressful procedures. Each neonate experienced a median of 115 (range, 4-613) procedures during the study period and 16 (range, 0-62) procedures per day of hospitalization. Of these, each neonate experienced a median of 75 (range, 3-364) painful procedures during the study period and 10 (range, 0-51) painful procedures per day of hospitalization. Of the 42,413 painful procedures, 2.1% were performed with pharmacological-only therapy; 18.2% with nonpharmacological-only interventions, 20.8% with pharmacological, nonpharmacological, or both types of therapy; and 79.2% without specific analgesia, and 34.2% were performed while the neonate was receiving concurrent analgesic or anesthetic infusions for other reasons. Prematurity, category of procedure, parental presence, surgery, daytime, and day of procedure after the first day of admission were associated with greater use of specific preprocedural analgesia, whereas mechanical ventilation, noninvasive ventilation and administration of nonspecific concurrent analgesia were associated with lower use of specific preprocedural analgesia. CONCLUSION: During neonatal intensive care in the Paris region, large numbers of painful and stressful procedures were performed, the majority of which were not accompanied by analgesia.

EMLA cream and nitrous oxide to alleviate pain induced by palivizumab (Synagis) intramuscular injections in infants and young children.

OBJECTIVE: Palivizumab (Synagis [Abbot Laboratories, Kent, United Kingdom]) is recommended for the prevention of severe lower respiratory tract infections caused by respiratory syncytial virus in infants at high risk. These injections are very painful, and currently the use of analgesics is not systematic. The objective of this study was to compare the efficacy of EMLA with premixed 50% nitrous oxide/oxygen, used alone or combined with EMLA, for pain alleviation during palivizumab injections. METHODS: This randomized, double-blind, multicenter study included children who were younger than 24 months. Each child randomly received during the first 3 monthly injections 3 different analgesic interventions: (1) EMLA: application of EMLA plus air inhalation; (2) nitrous oxide/oxygen: inhalation of 50/50 nitrous oxide/oxygen plus application of a placebo cream; and (3) nitrous oxide/oxygen plus EMLA: inhalation of 50/50 nitrous oxide/oxygen plus application of EMLA. Each child was his or her own control. Procedural pain was assessed through videotapes with the Modified Behavioral Pain Scale. The procedure itself was subdivided in 2 periods: (1) injection and (2) recovery (first 30 seconds after the removal of the needle). Modified Behavioral Pain Scale scores over time (injection and recovery periods) and among treatments were compared by repeated-measures analysis of variance. RESULTS: Fifty-five children were included. Mean +/- SD Modified Behavioral Pain Scale pain scores for EMLA, nitrous oxide/oxygen, and nitrous oxide/oxygen plus EMLA were, respectively, 9.3 +/- 1.0, 8.8 +/- 1.2, and 8.2 +/- 1.8 during the injection and 7.8 +/- 1.7, 7.4 +/- 1.9, and 6.9 +/- 2.4 during the recovery period. A significant time and treatment effect in favor of the combined nitrous oxide/oxygen plus EMLA was observed. CONCLUSIONS: The administration of 50/50 nitrous oxide/oxygen to infants and young children is effective in decreasing the pain associated with palivizumab intramuscular injections. The combined nitrous oxide/oxygen plus EMLA cream was more effective than either EMLA cream or nitrous oxide/oxygen alone.

Combined treatment with arsenic trioxide and all-trans-retinoic acid in patients with relapsed acute promyelocytic leukemia.

PURPOSE: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. PATIENTS AND METHODS: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. RESULTS: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. CONCLUSION: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.