Virtual Reality for the Management of Pain and Anxiety for IR Procedures: A Prospective, Randomized, Pilot Study on Digital Sedation.

PURPOSE: To assess the analgesic and anxiolytic effects of virtual reality (VR) augmentation in patients undergoing peripherally inserted central catheter (PICC) placement or fine-needle aspiration thyroid biopsy. MATERIALS AND METHODS: This is a prospective, single-center randomized controlled trial with 107 patients enrolled. Patients were randomly assigned to receive standard of care (SOC) or SOC+VR during PICC or thyroid biopsy procedures. Pain and anxiety were individually measured using the visual analog scale (VAS) before and after the procedure. Vital signs including heart rate and systolic and diastolic blood pressure were recorded. One-way analysis of variance test and Games-Howell post hoc analysis were used to assess effect size and statistical significance between SOC and SOC+VR measures. RESULTS: The PICC cohort consisted of 59 patients (33 in SOC+VR and 26 in SOC), with a median age of 53.1 years (interquartile range [IQR], 38.3-62.7 years). The thyroid biopsy cohort consisted of 48 patients (26 in SOC+VR and 22 in SOC), with a median age of 60.1 years (IQR, 49.0-67.2 years). One-way analysis of individuals undergoing thyroid biopsies with adjunctive VR revealed an effect size of -1.74 points (SE ± 0.71; P = .018) on VAS pain scale when compared with SOC. Analysis of individuals undergoing PICC placements revealed an effect size of -1.60 points (SE ± 0.81; P = .053) on VAS anxiety when compared with SOC. CONCLUSIONS: VR as a nonpharmacologic adjunct reduced some procedure-related pain and anxiety without increasing the procedural duration.

Reducing Procedural Pain and Avoiding Peripheral Intravenous Catheters by Implementing a Feeding Protocol for Late Preterm Infants: A Quality Improvement Project.

BACKGROUND: Late preterm births account for a large portion of preterm births, yet the optimal method of nutrition and enteral feeding in this population remains unclear and often involves intravenous (IV) fluids. PURPOSE: To develop and implement a late preterm feeding protocol in order to decrease the necessity of IV access, decrease the use of starter parenteral nutrition (PN), and reduce the pain endured by an infant in the neonatal intensive care unit. METHODS: The Plan-Do-Study-Act quality improvement model was utilized as a framework for the implementation of this quality improvement project. A literature review was conducted and subsequently, a feeding protocol was developed and included the more judicious use of starter PN. This protocol was implemented, evaluated, and adopted. A second Plan-Do-Study-Act cycle was completed with the addition of an auto-text reminder incorporated into admission notes in the electronic medical record. RESULTS: The implementation of the protocol significantly reduced placement of IV access and the use of starter (PN) in late preterm infants without considerable differences in balancing measures. The percentage of infants who received peripheral IV access declined considerably from 70% to 42% ( P = .0017) subsequently, less pain endured by the infants. There was a decrease in the initiation of starter PN from 55% to 7% ( P < .00001). IMPLICATIONS FOR PRACTICE: Administering enteral feedings on admission to stable, late preterm infants reduced the need for peripheral IV access and thus decreased pain from this procedure.

The effect of virtual reality glasses applied during intrauterine device insertion on pain, anxiety and satisfaction: Randomized controlled study.

BACKGROUND AND AIM: This study was carried out to determine the effect of the use of "virtual reality glasses," on anxiety, pain, and satisfaction level in order to reduce anxiety and pain during intrauterine device (IUD) insertion, which is a painful and stressful procedure for women and to divert attention to increase satisfaction. METHODS: This randomized controlled study in the gynecology clinic of a state hospital with 80 women who were accepted to participate in the study. Data were collected using structured patient information form, numerical pain rating scale, state-trait anxiety inventory, patient satisfaction evaluation form, and virtual reality glasses. RESULTS: Post-procedural pain scores in the control group after IUD application were higher than post-procedural pain in the virtual reality group. Measurements of post-procedure anxiety in the control group were higher than measurements of post-procedural in the virtual reality group. Satisfaction levels of women with virtual reality glasses during IUD insertion were also found to be high. CONCLUSIONS: It was determined that the use of virtual reality glasses, one of the methods of distraction during IUD insertion, was effective in reducing pain and anxiety and increasing patient satisfaction.

Efficacy of Lidocaine Spray for Pain Reduction during Colposcopy-Directed Cervical Biopsies: A Randomized Controlled Trial.

Objectives: The objective of this study was to evaluate the efficacy of lidocaine spray in reducing the pain during colposcopy-directed cervical biopsy (CDB). Methods: From December 2017 to February 2019, 312 women undergoing CDBs were enrolled. The participants were randomized to three groups: group 1 (lidocaine spray), in which lidocaine spray was applied thoroughly to the cervix; group 2 (placebo), in which normal saline was applied thoroughly to the cervix; and group 3 (control), in which no anesthetic agent was applied to the cervix. Each woman completed a 10 cm visual analog scale to classify the subjective pain experience at three time points: baseline, immediately after biopsy, and 10 min after the procedure. The primary outcome of this study was the biopsy pain score. Results: The 312 enrolled women were randomly assigned to the three groups, amounting to 104 women per group. The clinical and pathological characteristics of the participants in all groups were comparable. The baseline, the biopsy, and the post-procedure pain scores were comparable among the three groups. There was a significant increase in the pain score from baseline to biopsy and from baseline to post-procedure in each group. The pain-score changes from baseline to biopsy in the lidocaine spray group significantly decreased when compared with the normal saline group (<0.001), and tended to decrease, though not significantly (p = 0.06), when compared with the control group. No complication with the intervention was observed. Conclusions: The application of lidocaine spray to the cervix has the benefit of reducing the pain associated with CDBs by a small amount. However, the intervention is safe and may be considered in nulliparous and/or overly anxious women undergoing the procedure.

Analgesic and Anxiolytic Effects of Virtual Reality During Minor Procedures in an Emergency Department: A Randomized Controlled Study.

STUDY OBJECTIVE: We aimed to assess the analgesic and anxiolytic efficacy of distraction, a nonpharmacologic intervention provided by 3-dimensional (3D) virtual reality (VR) compared with that provided by 2-dimensional (2D) VR during minor emergency department (ED) procedures. METHODS: This randomized controlled study conducted in the ED of a teaching hospital included patients aged more than or equal to 18 years undergoing minor procedures. The patients watched the same computer-generated VR world either in 3D in a head-mounted display (intervention) or in 2D on a laptop screen (control). Our main outcomes were pain and anxiety during the procedure, assessed on a 100-mm visual analog scale. Secondary outcomes included the impression of telepresence in the computer-generated world assessed using the Igroup Presence Questionnaire, and the prevalence and intensity of cybersickness measured on a 100-mm visual analog scale. RESULTS: The final analysis included 117 patients. The differences in median procedural pain and anxiety levels between the 2D and 3D VR groups were not significant: -3 mm (95% confidence interval [CI] -14 to 8) and -4 mm (95% CI -15 to 3), respectively; the difference in telepresence was 2.0 point (95% CI 0 to 2.0), and the proportion difference of cybersickness was -4% (95% CI -22 to 14), with an intensity difference of -5 mm (95% CI -9 to 3). CONCLUSION: During minor procedures in adult patients in the ED, distraction by viewing a 3D virtual world in a head-mounted VR display did not result in lower average levels of procedural pain and anxiety than that by 2D viewing on a screen despite a higher sense of telepresence. There were no significant differences in the prevalence and intensity of cybersickness between the 2 groups.

Virtual reality hypnosis for needle-related procedural pain and fear management in children: a non-inferiority randomized trial.

Needle-related procedures can cause pain and fear in children and may lead to avoidance of future medical care. The aim of this study is to investigate whether virtual reality hypnosis (VRH) is non-inferior to medical hypnosis (MH) by a trained healthcare provider in reducing pain in children. This non-inferiority randomized trial was conducted at a teaching hospital in the Netherlands. Children aged 6 to 18 years were randomized to treatment with VRH or MH. The primary outcome was self-reported pain, using the Wong-Baker FACES Scale (WBFS) with the non-inferiority margin defined as a difference of 1.5 points. Secondary outcomes included observer-reported pain (Numeric Rating Scale), fear (scored by children and observers with the Children's Fear Scale), blood pressure, heart rate, treatment satisfaction, and adverse effects. We randomized 138 children to VRH or MH treatment and included 114 children in the analyses (VRH n = 60, MH n = 54). We found non-inferiority for VRH compared to MH on patient-reported pain (mean difference = - 0.17, 95%CI - 1.01;0.66). Secondary outcomes were comparable between VRH and MH groups. Both treatments scored high on patient satisfaction (VRH median = 9.0, MH median = 10.0, p = 0.512). CONCLUSION: VRH may be an effective and safe treatment option besides MH for reducing patient-reported pain in children during a needle-related procedure. VRH was non-inferior to MH in patient-reported fear and both treatments were comparable in terms of patient-reported fear, observer-reported pain and fear, physical distress, and patient satisfaction. TRIAL REGISTRATION: ICTRP https://trialsearch.who.int/ , trial ID NL9385; date registered: 03/04/2021. WHAT IS KNOWN: • Medical hypnosis is effective in reducing procedural distress in children during needle-related procedures. • Virtual reality (VR) is an audiovisual electronic device that guides users into an immersive three-dimensional environment. WHAT IS NEW: • This study shows that VR hypnosis is non-inferior to medical hypnosis in reducing pain and fear in children undergoing a needle-related procedure. • Both VR hypnosis and medical hypnosis were appreciated highly by children to distract them during needle-related procedures.

Active production of music as distraction for venipuncture in children and adolescents: a randomized clinical trial.

More than 50% of children report considerable pain during venipuncture or intravenous cannulation. Despite the tools and techniques may be employed to reduce pain and distress in everyday clinical practice, the care offered is frequently insufficient. Music's potential effect in healthcare settings has received increasing attention. This study aimed to verify if the active production of music with a Leap Motion Controller could help decreasing pain and distress during venipuncture in children and adolescents. We conducted an open-label randomized controlled clinical trial with parallel arms. Children aged 8 to 17 were enrolled at the blood-drawing center of the Institute for Maternal and Child Health IRCCS Burlo Garofolo of Trieste, Italy. We hypothesized that in order to demonstrate an adequate improvement in the pain score in the intervention group, at least 200 children, 100 in each group, were needed, with alpha 5% and 1-beta 80%. Differences between the groups were evaluated with the nonparametric Mann-Whitney U-test. The subjects were randomly assigned either to the active production of music group or to the standard of care group. The primary outcome was the median self-reported procedural pain score between experimental and standard of care group. Secondary outcomes were: the median pain and distress scores according to parental judgment and operators' judgment between the experimental and control group. Three hundred subjects entered the study and were randomized, 150 in the active production of music group and 150 in the standard of care group. Median self-reported pain scores were 1 (0-2) in the active production of music group and 2 (1-2) in the standard of care group and this difference was statistically significant (p = 0.0016). Median procedural distress was 1 (0-3) in the active production of music group and 3 (1-6) in the standard of care group, according to parental judgment, and this difference was statistically significant (p = 0.0000016). CONCLUSION: This research showed that the active production of music is a valuable distraction technique to decrease venipuncture related pain and distress in children and adolescents. TRIAL REGISTRATION: The study protocol was registered with ClinicalTrial.gov (June 28[th] 2022, NCT05441241) before the start of the subjects' enrolment. WHAT IS KNOWN: • The benefits of music on pain and anxiety are well known and have been tested during different painful procedures. • The effect of active production of music has never been tested in children during venipuncture. WHAT IS NEW: • In our study median self-reported pain scores and median procedural distress, according to parental judgment, were lower in the active production of music group than in the standard of care group and these differences were statistically significant.

Breastfeeding or breast milk for procedural pain in neonates.

BACKGROUND: Pain in the neonate is associated with acute behavioural and physiological changes. Cumulative pain is associated with morbidities, including adverse neurodevelopmental outcomes. Studies have shown a reduction in changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in neonates experiencing pain or stress. Non-pharmacological measures (such as holding, swaddling and breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for analgesia. This is an update of a review first published in 2006 and updated in 2012. OBJECTIVES: The primary objective was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, gestational age and the amount of supplemental breast milk given. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries (ICTRP, ISRCTN and clinicaltrials.gov) in August 2022; searches were limited from 2011 forwards. We checked the reference lists of included studies and relevant systematic reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates. We included both term (≥ 37 completed weeks postmenstrual age) and preterm infants (< 37 completed weeks' postmenstrual age) up to a maximum of 44 weeks' postmenstrual age. The study must have reported on either physiological markers of pain or validated pain scores. DATA COLLECTION AND ANALYSIS: We assessed the methodological quality of the trials using the information provided in the studies and by personal communication with the authors. We extracted data on relevant outcomes, estimated the effect size and reported this as a mean difference (MD). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Of the 66 included studies, 36 evaluated breastfeeding, 29 evaluated supplemental breast milk and one study compared them against each other. The procedures conducted in the studies were: heel lance (39), venipuncture (11), intramuscular vaccination (nine), eye examination for retinopathy of prematurity (four), suctioning (four) and adhesive tape removal as procedure (one). We noted marked heterogeneity in the control interventions and pain assessment measures amongst the studies. Since many studies included multiple arms with breastfeeding/supplemental breast milk as the main comparator, we were not able to synthesise all interventions together. Individual interventions are compared to breastfeeding/supplemental breast milk and reported. The numbers of studies/participants presented with the findings are not taken from pooled analyses (as is usual in Cochrane Reviews), but are the overall totals in each comparison. Overall, the included studies were at low risk of bias except for masking of intervention and outcome assessment, where nearly one-third of studies were at high risk of bias. Breastfeeding versus control Breastfeeding may reduce the increase in heart rate compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration of sucrose/glucose (20% to 33%) with skin-to-skin contact (low-certainty evidence, 8 studies, 784 participants). Breastfeeding likely reduces the duration of crying compared to no intervention, lying on table, rocking, heel warming, holding by mother, skin-to-skin contact, bottle feeding mother's milk and moderate concentration of glucose (moderate-certainty evidence, 16 studies, 1866 participants). Breastfeeding may reduce percentage time crying compared to holding by mother, skin-to-skin contact, bottle feeding mother's milk, moderate concentration sucrose and moderate concentration of sucrose with skin-to-skin contact (low-certainty evidence, 4 studies, 359 participants). Breastfeeding likely reduces the Neonatal Infant Pain Scale (NIPS) score compared to no intervention, holding by mother, heel warming, music, EMLA cream, moderate glucose concentration, swaddling, swaddling and holding (moderate-certainty evidence, 12 studies, 1432 participants). Breastfeeding may reduce the Neonatal Facial Coding System (NFCS) score compared to no intervention, holding, pacifier and moderate concentration of glucose (low-certainty evidence, 2 studies, 235 participants). Breastfeeding may reduce the Douleur Aigue Nouveau-né (DAN) score compared to positioning, holding or placebo (low-certainty evidence, 4 studies, 709 participants). In the majority of the other comparisons there was little or no difference between the breastfeeding and control group in any of the outcome measures. Supplemental breast milk versus control Supplemental breast milk may reduce the increase in heart rate compared to water or no intervention (low-certainty evidence, 5 studies, 336 participants). Supplemental breast milk likely reduces the duration of crying compared to positioning, massage or placebo (moderate-certainty evidence, 11 studies, 1283 participants). Supplemental breast milk results in little or no difference in percentage time crying compared to placebo or glycine (low-certainty evidence, 1 study, 70 participants). Supplemental breast milk results in little or no difference in NIPS score compared to no intervention, pacifier, moderate concentration of sucrose, eye drops, gentle touch and verbal comfort, and breast milk odour and verbal comfort (low-certainty evidence, 3 studies, 291 participants). Supplemental breast milk may reduce NFCS score compared to glycine (overall low-certainty evidence, 1 study, 40 participants). DAN scores were lower when compared to massage and water; no different when compared to no intervention, EMLA and moderate concentration of sucrose; and higher when compared to rocking or pacifier (low-certainty evidence, 2 studies, 224 participants). Due to the high number of comparator interventions, other measures of pain were assessed in a very small number of studies in both comparisons, rendering the evidence of low certainty. The majority of studies did not report on adverse events, considering the benign nature of the intervention. Those that reported on adverse events identified none in any participants. Subgroup analyses were not conducted due to the small number of studies. AUTHORS' CONCLUSIONS: Moderate-/low-certainty evidence suggests that breastfeeding or supplemental breast milk may reduce pain in neonates undergoing painful procedures compared to no intervention/positioning/holding or placebo or non-pharmacological interventions. Low-certainty evidence suggests that moderate concentration (20% to 33%) glucose/sucrose may lead to little or no difference in reducing pain compared to breastfeeding. The effectiveness of breast milk for painful procedures should be studied in the preterm population, as there are currently a limited number of studies that have assessed its effectiveness in this population.

Opioids for procedural pain in neonates.

BACKGROUND: Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported. OBJECTIVES: To evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was December 2021. SELECTION CRITERIA: We included randomized controlled trials conducted in preterm and term infants of a postmenstrual age (PMA) up to 46 weeks and 0 days exposed to procedural pain where opioids were compared to 1) placebo or no drug; 2) non-pharmacological intervention; 3) other analgesics or sedatives; 4) other opioids; or 5) the same opioid administered by a different route. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods and any harms. We used a fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, and their confidence intervals (CI). We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 13 independent studies (enrolling 823 newborn infants): seven studies compared opioids to no treatment or placebo (the main comparison in this review), two studies to oral sweet solution or non-pharmacological intervention, and five studies (of which two were part of the same study) to other analgesics and sedatives. All studies were performed in a hospital setting. Opioids compared to placebo or no drug Compared to placebo, opioids probably reduce pain score assessed with the Premature Infant Pain Profile (PIPP)/PIPP-Revised (PIPP-R) scale during the procedure (MD -2.58, 95% CI -3.12 to -2.03; 199 participants, 3 studies; moderate-certainty evidence); may reduce Neonatal Infant Pain Scale (NIPS) during the procedure (MD -1.97, 95% CI -2.46 to -1.48; 102 participants, 2 studies; low-certainty evidence); and may result in little to no difference in pain score assessed with the Douleur Aiguë du Nouveau-né (DAN) scale one to two hours after the procedure (MD -0.20, 95% CI -2.21 to 1.81; 42 participants, 1 study; low-certainty evidence). The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R scale up to 30 minutes after the procedure (MD 0.14, 95% CI -0.17 to 0.45; 123 participants, 2 studies; very low-certainty evidence) or one to two hours after the procedure (MD -0.83, 95% CI -2.42 to 0.75; 54 participants, 2 studies; very low-certainty evidence). The evidence is very uncertain about the effect of opioids on episodes of bradycardia (RR 3.19, 95% CI 0.14 to 72.69; 172 participants, 3 studies; very low-certainty evidence). Opioids may result in an increase in episodes of apnea compared to placebo (RR 3.15, 95% CI 1.08 to 9.16; 199 participants, 3 studies; low-certainty evidence): with one study reporting a concerning increase in severe apnea (RR 7.44, 95% CI 0.42 to 132.95; 31 participants, 1 study; very low-certainty). The evidence is very uncertain about the effect of opioids on episodes of hypotension (RR not estimable, risk difference 0.00, 95% CI -0.06 to 0.06; 88 participants, 2 studies; very low-certainty evidence). No studies reported parent satisfaction with care provided in the neonatal intensive care unit (NICU). Opioids compared to non-pharmacological intervention The evidence is very uncertain about the effect of opioids on pain score assessed with the Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale during the procedure when compared to facilitated tucking (MD -4.62, 95% CI -6.38 to -2.86; 100 participants, 1 study; very low-certainty evidence) or sensorial stimulation (MD 0.32, 95% CI -1.13 to 1.77; 100 participants, 1 study; very low-certainty evidence). The other main outcomes were not reported. Opioids compared to other analgesics or sedatives The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R during the procedure (MD -0.29, 95% CI -1.58 to 1.01; 124 participants, 2 studies; very low-certainty evidence); up to 30 minutes after the procedure (MD -1.10, 95% CI -2.82 to 0.62; 12 participants, 1 study; very low-certainty evidence); and one to two hours after the procedure (MD -0.17, 95% CI -2.22 to 1.88; 12 participants, 1 study; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of apnea during (RR 3.27, 95% CI 0.85 to 12.58; 124 participants, 2 studies; very low-certainty evidence) and after the procedure (RR 2.71, 95% CI 0.11 to 64.96; 124 participants, 2 studies; very low-certainty evidence) and on hypotension (RR 1.34, 95% CI 0.32 to 5.59; 204 participants, 3 studies; very low-certainty evidence). The other main outcomes were not reported. We identified no studies comparing different opioids (e.g. morphine versus fentanyl) or different routes for administration of the same opioid (e.g. morphine enterally versus morphine intravenously). AUTHORS' CONCLUSIONS: Compared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. The evidence is very uncertain about the effect of opioids on episodes of bradycardia, hypotension or severe apnea. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.

Non-opioid analgesics for procedural pain in neonates.

BACKGROUND: Neonates are an extremely vulnerable patient population, with 6% to 9% admitted to the neonatal intensive care unit (NICU) following birth. Neonates admitted to the NICU will undergo multiple painful procedures per day throughout their stay. There is increasing evidence that frequent and repetitive exposure to painful stimuli is associated with poorer outcomes later in life. To date, a wide variety of pain control mechanisms have been developed and implemented to address procedural pain in neonates. This review focused on non-opioid analgesics, specifically non-steroidal anti-inflammatory drugs (NSAIDs) and N-methyl-D-aspartate (NMDA) receptor antagonists, which alleviate pain through inhibiting cellular pathways to achieve analgesia.  The analgesics considered in this review show potential for pain relief in clinical practice; however, an evidence summation compiling the individual drugs they comprise and outlining the benefits and harms of their administration is lacking. We therefore sought to summarize the evidence on the level of pain experienced by neonates both during and following procedures; relevant drug-related adverse events, namely episodes of apnea, desaturation, bradycardia, and hypotension; and the effects of combinations of drugs.  As the field of neonatal procedural pain management is constantly evolving, this review aimed to ascertain the scope of non-opioid analgesics for neonatal procedural pain to provide an overview of the options available to better inform evidence-based clinical practice.  OBJECTIVES: To determine the effects of non-opioid analgesics in neonates (term or preterm) exposed to procedural pain compared to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration. SEARCH METHODS: We searched the Cochrane Library (CENTRAL), PubMed, Embase, and two trial registries in June 2022. We screened the reference lists of included studies for studies not identified by the database searches. SELECTION CRITERIA: We included all randomized controlled trials (RCTs), quasi-RCTs, and cluster-RCTs in neonates (term or preterm) undergoing painful procedures comparing NSAIDs and NMDA receptor antagonists to placebo or no drug, non-pharmacological intervention, other analgesics, or different routes of administration.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our main outcomes were pain assessed during the procedure and up to 10 minutes after the procedure with a validated scale; episodes of bradycardia; episodes of apnea; and hypotension requiring medical therapy. MAIN RESULTS: We included two RCTs involving a total of 269 neonates conducted in Nigeria and India.  NMDA receptor antagonists versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention One RCT evaluated using oral ketamine (10 mg/kg body weight) versus sugar syrup (66.7% w/w at 1 mL/kg body weight) for neonatal circumcision.  The evidence is very uncertain about the effect of ketamine on pain score during the procedure, assessed with the Neonatal Infant Pain Scale (NIPS), compared with placebo (mean difference (MD) -0.95, 95% confidence interval (CI) -1.32 to -0.58; 1 RCT; 145 participants; very low-certainty evidence). No other outcomes of interest were reported on. Head-to-head comparison of different analgesics One RCT evaluated using intravenous fentanyl versus intravenous ketamine during laser photocoagulation for retinopathy of prematurity. Neonates receiving ketamine followed an initial regimen (0.5 mg/kg bolus 1 minute before procedure) or a revised regimen (additional intermittent bolus doses of 0.5 mg/kg every 10 minutes up to a maximum of 2 mg/kg), while those receiving fentanyl followed either an initial regimen (2 µg/kg over 5 minutes, 15 minutes before the procedure, followed by 1 µg/kg/hour as a continuous infusion) or a revised regimen (titration of 0.5 µg/kg/hour every 15 minutes to a maximum of 3 µg/kg/hour). The evidence is very uncertain about the effect of ketamine compared with fentanyl on pain score assessed with the Premature Infant Pain Profile-Revised (PIPP-R) scores during the procedure (MD 0.98, 95% CI 0.75 to 1.20; 1 RCT; 124 participants; very low-certainty evidence); on episodes of apnea occurring during the procedure (risk ratio (RR) 0.31, 95% CI 0.08 to 1.18; risk difference (RD) -0.09, 95% CI -0.19 to 0.00; 1 study; 124 infants; very low-certainty evidence); and on hypotension requiring medical therapy occurring during the procedure (RR 5.53, 95% CI 0.27 to 112.30; RD 0.03, 95% CI -0.03 to 0.10; 1 study; 124 infants; very low-certainty evidence). The included study did not report pain score assessed up to 10 minutes after the procedure or episodes of bradycardia occurring during the procedure. We did not identify any studies comparing NSAIDs versus no treatment, placebo, oral sweet solution, or non-pharmacological intervention or different routes of administration of the same analgesics. We identified three studies awaiting classification.  AUTHORS' CONCLUSIONS: The two small included studies comparing ketamine versus either placebo or fentanyl, with very low-certainty evidence, rendered us unable to draw meaningful conclusions. The evidence is very uncertain about the effect of ketamine on pain score during the procedure compared with placebo or fentanyl. We found no evidence on NSAIDs or studies comparing different routes of administration. Future research should prioritize large studies evaluating non-opioid analgesics in this population. As the studies included in this review suggest potential positive effects of ketamine administration, studies evaluating ketamine are of interest. Furthermore, as we identified no studies on NSAIDs, which are widely used in older infants, or comparing different routes of administration, such studies should be a priority going forward.

Virtual reality and noise canceling headphone distraction during pediatric dermatologic procedures.

Pain and anxiety related to medical procedures have long been recognized as a significant healthcare concern. If a patient's procedural pain and anxiety are not addressed, long-term physical and psychological sequelae including increased perceived pain, anxiety, disruptive behavior, trauma reactions, or refusal of future procedures can occur. The objective of our study was to assess the utility of a virtual reality (VR) headset or noise-canceling headphones (HP) compared to treatment as usual (TAU) in reducing pain and anxiety during pediatric dermatology procedures. Results indicated a significant difference between pre- versus post-procedure anxiety in the VR and HP groups but not the TAU group suggesting non-pharmacologic technology-based interventions such as VR and headphones may reduce patients' anxiety during pediatric dermatology procedures.

Assessment of salivary cortisol concentrations for procedural pain monitoring in newborns.

OBJECTIVES: The study aimed to evaluate the usefulness of salivary cortisol (SC) for the assessment of procedural pain intensity in preterm and term newborns. METHODS: Three groups of neonates (term, 370-416 weeks; moderate to late preterm, 320-366; and very preterm, <320) hospitalized in neonatal intensive care unit were assessed for the study. Response to nappy change, lung ultrasound (LUS), and blood sampling was analyzed. The intensity of pain was evaluated using continuous heart rate and blood oxygen saturation (SpO2) monitoring, Neonatal Infant Pain Scale (NIPS), and SC concentrations. Saliva samples were collected before and 20 min after the procedure's end. RESULTS: Seventy-one infants were examined: 30 term, 21 moderate to late preterm, and 20 very preterm. SC has increased significantly in response to nappy change only in very preterm newborns (2.13 ng/mL [1.55-3.68] vs. 2.84 ng/mL [1.93-9.06], p = 0.01). LUS did not affect concentrations of SC in any group. Significant increase in SC was observed after blood sampling in term and very preterm infants (2.2 ng/mL [1.45-2.92] vs. 4.29 ng/mL [3.88-5.73], p = 0.002, and 1.88 ng/mL [1.47-4.13] vs. 5.3 ng/mL [3.42-8.02], p = 0.002, respectively). A significant correlation between values of SC increase and NIPS scores was found (Spearman's rank correlation coefficient [rs] = 0.31, p = 0.001). CONCLUSIONS: We observed the increase in SC concentrations in response to painful stimulus. The presence of a correlation between NIPS scores and SC increase suggests that SC can be used as an objective parameter to assess pain in neonates.

Effects of Kangaroo Mother Care on Repeated Procedural Pain and Cerebral Oxygenation in Preterm Infants.

OBJECTIVE: The study aimed to investigate the effects of kangaroo mother care (KMC) on repeated procedural pain and cerebral oxygenation in preterm infants. STUDY DESIGN: Preterm infants of 31 to 33 weeks of gestational age were randomly divided into an intervention group (n = 36) and a control group (n = 37). Premature infant pain profile (PIPP) scores, heart rate, oxygen saturation, regional cerebral tissue oxygenation saturation (rcSO2), and cerebral fractional tissue oxygen extraction (cFTOE) were evaluated during repeated heel stick procedures. Each heel stick procedure included three phases: baseline, blood collection, and recovery. KMC was given to the intervention group 30 minutes before baseline until the end of the recovery phase. RESULTS: Compared with the control group, the intervention group showed lower PIPP scores and heart rates, higher oxygen saturation, and rcSO2 from the blood collection to recovery phases during repeated heel sticks. Moreover, there were significant changes in cFTOE for the control group, but not the intervention group associated with repeated heel stick procedures. CONCLUSION: The analgesic effect of KMC is sustained over repeated painful procedures in preterm infants, and it is conducive to stabilizing cerebral oxygenation, which may protect the development of brain function. KEY POINTS: · KMC stabilizes cerebral oxygenation during repeated heel sticks in preterm infants.. · The analgesic effect of KMC is sustained over repeated painful procedures in preterm infants.. · KMC may protect the development of brain function..

Improving Consistency in the Use of Sucrose With Comfort Measures During Minor Painful Procedures.

BACKGROUND: Inconsistent pain management practices can have negative physiologic and neurodevelopmental consequences in the neonate. Low rates of oral sucrose use with comfort measures for pain management during minor painful procedures were identified at a level III neonatal intensive care unit. Underutilization of pain management resources occurs despite the availability of evidence-based pain management interventions. PURPOSE: To improve consistency in the use of oral sucrose solution with comfort measures during peripheral intravenous catheter insertion attempts in the neonatal intensive care unit in patients greater than or equal to 32 0/7th weeks postmenstrual age. METHODS: Quality improvement methods were used to implement an evidence-based procedural pain algorithm for minor painful procedures and optimize pain management processes over a 15-week period in a 26-bed, level III neonatal intensive care unit. RESULTS: There was an increase in the average percentage of documented use of sucrose with comfort measures during peripheral intravenous catheter insertion attempts from 20% to 27%. There was a 41% increase in the average presence of a sucrose order indicated for procedural pain. There were improvements in staff knowledge of sucrose dosing and perceived behavior of staff after completing the education. IMPLICATIONS FOR PRACTICE AND RESEARCH: Procedural pain management should be used as a quality indicator and guidelines should be established with the support of key stakeholders in neonatal intensive care settings. Future projects should address barriers related to workflow and accessibility of sucrose, include other common needlestick procedures, and expand the role of parent participation in pain management practices.Video Abstract available at:https://journals.lww.com/advancesinneonatalcare/pages/video.aspx?v=60 .

A Systematic Review of Multisensory Stimulation on Procedural Pain Among Preterm Neonates.

PURPOSE: This systematic review aims to evaluate the quality of studies and synthesize the literature on multisensory stimulation (MSS) on procedural pain among hospitalized preterm neonates. SUMMARY OF KEY POINTS: Search strategies were applied to PubMed/Medline, CINAHL, SCOPUS, and PEDro. A total of 414 studies were identified, 104 were screened, and 4 were included. Two independent reviewers extracted data from identified studies that were synthesized qualitatively and quantitatively. CONCLUSION AND RECOMMENDATIONS FOR CLINICAL PRACTICE: There is strong evidence of MSS in decreasing procedural pain, but additional research is needed to identify the beneficial effects of MSS with a standardized protocol to promote good clinical practice in neonatal intensive care settings. WHAT THIS ADDS TO THE EVIDENCE: High-quality evidence supports beneficial effects of MSS, but standardization of the MSS protocol and its administration needs to be established.

Different effects of intravenous and local anesthesia in patients undergoing ultrasound-guided radiofrequency ablation of thyroid nodules: a prospective cohort study.

PURPOSE: To compare the efficacy and safety of intravenous anesthesia (IV) with local anesthesia (LA) in patients undergoing ultrasound (US)-guided radiofrequency ablation (RFA) of thyroid nodules. METHODS: 50 patients with American Society of Anesthesiologists classification grades I-II undergoing US-guided thyroid RFA were enrolled and randomly (1:1) divided into IV (conscious sedation with Ramsay Sedation Scale [RSS] scores of 2-3 with an anesthesiologist) and LA (subcutaneous anesthesia with lidocaine without an anesthesiologist) groups. Pre-, intra- and post-procedural blood pressure (BP) (SBP0/DBP0, SBP1/DBP1, and SBP2/DBP2), intra- and post-procedural pain (NRS1 and NRS2), ablated area volume, treatment time and adverse events were analyzed and compared. RESULTS: Age, sex, weight, number, nature, volume of nodules, and SBP0/DBP0 showed no difference between both groups. 11 and 0 patients' SBP1/DBP1 were elevated in the LA and IV groups. NRS1 differed between both groups. 6 patients in the LA group had moderate or severe pain, but none in the IV group. No between-group difference in SBP2/DBP2, NRS2, ablation completion rate and ablated volume was noted. The median procedure duration differed from 1109 (176) s in IV group and 723 (227) s in LA groups. There was no increased incidence of adverse events in IV group. CONCLUSIONS: IV with RSS scores of 2-3 maintained intra-procedural BP and relieved intra-procedural pain better, without affecting the ablation efficacy and increasing complications. Despite increased treatment time, IV is a potential option for patients undergoing US-guided RFA of thyroid nodules.

Clown therapy for procedural pain in children: a systematic review and meta-analysis.

Among the distraction techniques used for the non-pharmacological management of acute pediatric pain, one of the most performed is clown therapy. Despite the presence in the literature of some systematic reviews that evaluate its effectiveness, none of them examines its outcomes on procedural pain which has therefore been investigated in this study. The literature search for randomized controlled trials (RCTs) was performed on the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and Scopus over a time frame ranging from each database setup date to 31 July 2021. The primary outcome was the procedural pain of children. We used the Cochrane Risk of Bias tool to assess the risk of bias of the included studies. Six RCTs were selected for this review, which included a total of 517 pediatric subjects. Children undergoing clown therapy during the venipuncture or peripheral vein cannulation procedure reported less pain than those exposed to the standard of care (SMD = -0.55; 95% CI: -1.23, 0.13) but the result was not found to be statistically significant. School-aged children and adolescent reported significantly less pain (SMD = -0.51; 95% CI: -0.92, -0.09). Compared to the standard of care, children's anxiety was significantly lower with clown therapy (SMD = -0.97; 95% CI: -1.38, -0.56). CONCLUSION: Clown therapy seems effective in reducing procedural pain in children, particularly for older age groups, but due to poor methodological quality and the high risk of bias of the studies included, the results obtained should be considered with caution. WHAT IS KNOWN: • Clown therapy is one of the most used techniques in the non-pharmacological management of acute pediatric pain. • Laughter physiologically stimulates the production of beta-endorphins, substances with an effect similar to opiates. WHAT IS NEW: • Clown therapy seems effective in reducing procedural pain and anxiety in children. • The intervention in school-age children or adolescents produces a statistically significant decrease in the symptom.

Adolescents' pain and distress during peripheral intravenous cannulation in a paediatric emergency setting.

The objective of the study is to investigate pain and distress experienced by a group of adolescents and children during peripheral intravenous cannulation in a paediatric emergency department. This cross-sectional study was performed between November 2019 and June 2020 at the paediatric emergency department of the Institute for Maternal and Child Health of Trieste, Italy. Eligible subjects were patients between 4 and 17 years old undergoing intravenous cannulation, split into three groups based on their age: adolescents (13-17 years), older children (8-12 years), and younger children (4-7 years). Procedural distress and pain scores were recorded through validated scales. Data on the use of topical anaesthesia, distraction techniques, and physical or verbal comfort during procedures were also collected. We recruited 136 patients: 63 adolescents, 48 older children, and 25 younger children. There was no statistically significant difference in the median self-reported procedural pain found in adolescents (4; IQR = 2-6) versus older and younger children (5; IQR = 2-8 and 6; IQR = 2-8, respectively). Furthermore, no significant difference was observed in the rate of distress between adolescents (79.4%), older (89.6%), and younger (92.0%) children. Adolescents received significantly fewer pain relief techniques.Conclusion: This study shows that adolescents experience similar pain and pre-procedural distress as younger children during peripheral intravenous cannulation. What is Known: • Topical and local anaesthesia, physical and verbal comfort, and distraction are useful interventions for pain and anxiety management during intravenous cannulation in paediatric settings. • No data is available on pain and distress experienced by adolescents in the specific setting of the emergency department. What is New: • Adolescents experienced high levels of pre-procedural distress in most cases and similar levels of pain and distress when compared to younger patients • The number of pain relief techniques employed during procedures was inversely proportional to patient's age, topical or local anaesthesia were rarely used.

A randomized controlled trial on virtual reality distraction during venous cannulation in young children.

BACKGROUND AND OBJECTIVES: Pain management in children is often inadequate, and the single most common painful procedure in children who are hospitalized is needle procedures. Virtual reality (VR) has been shown to decrease anxiety and pain in children undergoing painful procedures primarily in children from the age of 7 years. Our aim for this study is to investigate patient satisfaction and pain reduction by using a three-dimensional VR interactive game as a distraction in 4-7 years old children during venous cannulation. METHODS: In this randomized clinical trial, we enrolled 106 children aged 4-7 years who were scheduled for venous cannulation. Patients assigned to the control group were adherent to standard of care, including topical numbing cream, positioning, and distraction in this group by games of choice on a tablet/smartphone. In the study group, children were adherent to standard of care and were distracted by an interactive VR game. Primary outcomes were patient satisfaction and the procedural pain assessed by using Wong-Baker Faces Pain Rating Scale; secondary outcomes were the procedural time and any adverse events. RESULTS: We found an overall high level of patient satisfaction with our regime of topical numbing cream, positioning, and distraction. The primary outcome of pain during the procedure was median 20 mm (IQR 0-40) and 20 mm (IQR 0-55) (Wong-Baker 0-100 mm) in the VR group and the control group, respectively (difference: 0 mm, 95%CI: 0-20, p = .19). No significant difference was found in procedural times. The number of adverse effects was low, with no significant difference between the two groups. CONCLUSIONS: VR distraction is an acceptable form of distraction for children 4-7 years old when combined with topical numbing cream and positioning during preoperative venous cannulation. No difference was found between VR- and smartphone/tablet distraction.

Tablet personal computer distraction during intravenous placement for young children in the pediatric emergency department: A pilot study.

BACKGROUND: Intravenous (IV) placement is a common procedure experienced by children visiting the pediatric emergency department (PED). However, uncontrolled anxiety and pain cause children to interfere with the procedure. In this pilot study, we sought to evaluate the effectiveness of tablet personal computers as a distraction method during IV placement. METHODS: This is a single-center pilot study conducted at a tertiary teaching hospital. Children visiting the PED were eligible if they were aged 3-5 years and required IV placement during the PED visit. After written consent was obtained from the guardian, the child was randomly assigned to a control group or an intervention group. For the intervention group, an animated video was played via tablet PC during IV placement. For both groups, children's anxiety, heart rate, and pain scale scores (the Face, Legs, Activity, Cry, Consolability and Evaluation Enfant Douleur) and guardian satisfaction were recorded. RESULTS: 22 children were eligible for the final analysis. There was no significant difference in the pain scale scores between the two groups, with the exception of the degree of pain relief after the procedure measured using Evaluation Enfant Douleur (intervention group: 6.0, interquartile range (IQR): 4.2-6.8, and control group; 3.0, IQR: 2.0-3.8, P = 0.011) and Face, Legs, Activity, Cry, Consolability (intervention group: 4.0, IQR: 4.0-4.2 and control group; 3.0, IQR: 1.5-3.5, P = 0.043). CONCLUSION: In this pilot study, distraction using tablet personal computers may have reduced children's distress during the recovery phase after venipuncture. Further study with a larger sample size and different methods of distraction is essential.