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The International Journal on Drug Policy Oct 2021Drug-related deaths globally are increasing year on year, with the largest proportion of these being opioid-related. The opioid antagonist naloxone distributed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Drug-related deaths globally are increasing year on year, with the largest proportion of these being opioid-related. The opioid antagonist naloxone distributed for take-home use ('Take-Home Naloxone (THN)') has been championed as one method of tackling this public health crisis, however to be effective it must be available at an opioid overdose. Ownership and carriage are therefore fundamental to THN success. This study aimed to assess the prevalence of ownership and carriage of THN internationally among people who use drugs (PWUD).
METHODS
NHS Scotland Journals, AMED, EMBASE, HMIC, MEDLINE, PsycINFO, CINAHL Complete, PubMed, Cochrane Library, PROSPERO and grey literature were searched for articles which measured prevalence of THN ownership or carriage between 1996 and 2020. Ownership was defined as report of a personal supply of THN. Carriage was defined as the participant carrying THN on their person at time of data collection or reporting a frequency of how often they carry THN. Risk of bias was evaluated using the Joanna Briggs Checklist for Prevalence Studies.
RESULTS
Systematic search yielded 6363 papers, with ten eligible papers identified. Eight articles were included in ownership prevalence and five articles included for carriage prevalence, with an overlap of three studies between both measures. Pooled prevalence indicated moderate ownership levels (57%, CI 47-67%) but lower carriage levels (20%, CI 12-31%). Analysis was complicated by the limited number of available studies and lack of standardised terminology and measurement.
CONCLUSION
Understanding naloxone ownership and carriage globally is hampered by limited evidence and heterogeneity across studies. From the available data, prevalence of THN carriage overall appears low, despite moderate ownership. Given the variation across studies, future research should seek to utilise more standardised terminology and methods of measurement. Furthermore, services distributing THN must ensure the importance of regular carriage of naloxone is consistently emphasised.
Topics: Drug Overdose; Humans; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Ownership; Prevalence
PubMed: 34078563
DOI: 10.1016/j.drugpo.2021.103298 -
The Cochrane Database of Systematic... Apr 2014The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The scientific literature examining effective treatments for opioid dependent adults clearly indicates that pharmacotherapy is a necessary and acceptable component of effective treatments for opioid dependence. Nevertheless, no studies have been published that systematically assess the effectiveness of the pharmacological detoxification among adolescents.
OBJECTIVES
To assess the effectiveness of any detoxification treatment alone or in combination with psychosocial intervention compared with no intervention, other pharmacological intervention or psychosocial interventions on completion of treatment, reducing the use of substances and improving health and social status.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (2014, Issue 1), PubMed (January 1966 to January 2014), EMBASE (January 1980 to January 2014), CINHAL (January 1982 to January 2014), Web of Science (1991-January 2014) and reference lists of articles.
SELECTION CRITERIA
Randomised controlled clinical trials comparing any pharmacological interventions alone or associated with psychosocial intervention aimed at detoxification with no intervention, placebo, other pharmacological intervention or psychosocial intervention in adolescents (13 to 18 years).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures recommended by The Cochrane Collaboration
MAIN RESULTS
Two trials involving 190 participants were included. One trial compared buprenorphine with clonidine for detoxification. No difference was found for drop out: risk ratio (RR) 0.45 (95% confidence interval (CI): 0.20 to 1.04) and acceptability of treatment: withdrawal score mean difference (MD): 3.97 (95% CI -1.38 to 9.32). More participants in the buprenorphine group initiated naltrexone treatment: RR 11.00 (95% CI 1.58 to 76.55), quality of evidence moderate.The other trial compared maintenance treatment versus detoxification treatment: buprenorphine-naloxone maintenance versus buprenorphine detoxification. For drop out the results were in favour of maintenance treatment: RR 2.67 (95% CI 1.85, 3.86), as well as for results at follow-up RR 1.36 [95% CI 1.05to 1.76); no differences for use of opiate, quality of evidence low.
AUTHORS' CONCLUSIONS
It is difficult to draw conclusions on the basis of two trials with few participants. Furthermore, the two studies included did not consider the efficacy of methadone that is still the most frequent drug utilised for the treatment of opioid withdrawal. One possible reason for the lack of evidence could be the difficulty in conducting trials with young people due to practical and ethical reasons.
Topics: Adolescent; Buprenorphine; Clonidine; Humans; Maintenance Chemotherapy; Naloxone; Naltrexone; Narcotic Antagonists; Opiate Substitution Treatment; Opioid-Related Disorders; Patient Dropouts; Randomized Controlled Trials as Topic
PubMed: 24777492
DOI: 10.1002/14651858.CD006749.pub3 -
The Cochrane Database of Systematic... Apr 2023Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature.
OBJECTIVES
To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration.
SEARCH METHODS
Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry.
SELECTION CRITERIA
We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration.
DATA COLLECTION AND ANALYSIS
According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies.
MAIN RESULTS
In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.
Topics: Child; Child, Preschool; Humans; Infant; Infant, Newborn; Analgesia; Analgesics, Opioid; Clinical Protocols; Morphine; Pain, Postoperative
PubMed: 37018131
DOI: 10.1002/14651858.CD015016.pub3 -
European Journal of Clinical... Jun 2015The aim of the study was to determine the extent of inter-individual variation in clearance of intravenous morphine in children and to establish which factors are... (Review)
Review
OBJECTIVES
The aim of the study was to determine the extent of inter-individual variation in clearance of intravenous morphine in children and to establish which factors are responsible for this variation.
METHODS
A systematic literature review was performed to identify papers describing the clearance of morphine in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL, and Cochrane library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.
RESULTS
Twenty-eight studies were identified. After quality assessment, 20 studies were included. Only 10 studies gave clearance values for individual patients. The majority of the studies were in critically ill patients. Inter-individual variability of morphine clearance was observed in all age groups, but greatest in critically ill neonates (both preterm and term) and infants. In critically ill patients, the CV was 16-97% in preterm neonates, 24-87% in term neonates, 35 and 134% in infants, 39 and 55% in children, and 74% in adolescents. The CV was 37 and 44% respectively in non-critically ill neonates and infants. The mean clearance was higher in children (32 and 52 ml min(-1) kg(-1)) than in neonates (2 to 16 ml min(-1) kg(-1)).
CONCLUSIONS
Large inter-individual variation was seen in morphine clearance values in critically ill neonates and infants.
Topics: Child; Critical Illness; Humans; Individuality; Morphine
PubMed: 25845657
DOI: 10.1007/s00228-015-1843-x -
Current Opinion in Supportive and... Sep 2014Inhaled nebulized and intranasal opioid administration is available with a proven short onset of action for the relief of pain. As breathlessness episodes are short,... (Review)
Review
PURPOSE OF REVIEW
Inhaled nebulized and intranasal opioid administration is available with a proven short onset of action for the relief of pain. As breathlessness episodes are short, these routes of administration seem to be attractive for breathlessness management. This review describes the recent studies evaluating the effectiveness of inhaled nebulized and intranasal application of opioids for patients suffering from refractory breathlessness.
RECENT FINDINGS
Since 2012, one systematic review and three primary studies have been identified. The systematic review summarized five studies including seventy patients testing nebulized fentanyl and two studies including five patients evaluating intranasal application. Two randomized controlled trials tested inhaled fentanyl or morphine and one retrospective chart review described the application of intranasal fentanyl in newborn babies. Inhaled fentanyl did not improve the intensity or unpleasantness of perceived dyspnea, but the rate of increase in dyspnea intensity and unpleasantness ratings between isotime and peak exercise was less after treatment with fentanyl. Inhaled morphine improved breathlessness in chronic obstructive pulmonary disease patients.
SUMMARY
There is currently not enough evidence to support the use of inhaled application of opioids for the relief of breathlessness. There are no controlled trials assessing the efficacy and effectiveness of intranasal opioid application, but a pilot trial is underway to provide preliminary data.
Topics: Administration, Inhalation; Administration, Intranasal; Analgesics, Opioid; Dyspnea; Fentanyl; Humans; Morphine
PubMed: 25004175
DOI: 10.1097/SPC.0000000000000071 -
European Journal of Anaesthesiology Sep 2023Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively. (Meta-Analysis)
Meta-Analysis
The postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve and field blocks: A systematic review and meta-analysis, with trial sequential analysis.
BACKGROUND
Liposomal bupivacaine is claimed by the manufacturer to provide analgesia for up to 72 h postoperatively.
OBJECTIVES
To compare the postoperative analgesic efficacy of liposomal bupivacaine versus long-acting local anaesthetics for peripheral nerve or field blocks.
DESIGN
A systematic review and meta-analysis with trial sequential analysis.
DATA SOURCES
MEDLINE, Embase and Web of Science, among others, up to June 2022.
ELIGIBILITY CRITERIA
We retrieved randomised controlled trials comparing liposomal bupivacaine versus bupivacaine, levobupivacaine or ropivacaine for peripheral nerve and field blocks after all types of surgery. Our primary endpoint was rest pain score (analogue scale 0 to 10) at 24 h. Secondary endpoints included rest pain score at 48 and 72 h, and morphine consumption at 24, 48 and 72 h.
RESULTS
Twenty-seven trials including 2122 patients were identified. Rest pain scores at 24 h were significantly reduced by liposomal bupivacaine with a mean difference (95% CI) of -0.9 (-1.4 to -0.4), I2 = 87%, P < 0.001. This reduction in pain scores persisted at 48 h and 72 h with mean differences (95% CI) of -0.7 (-1.1 to -0.3), I2 = 82%, P = 0.001 and -0.7 (-1.1 to -0.3), I2 = 80%, P < 0.001, respectively. There were no differences in interval morphine consumption at 24 h ( P = 0.15), 48 h ( P = 0.15) and 72 h ( P = 0.07). The quality of evidence was moderate.
CONCLUSIONS
There is moderate level evidence that liposomal bupivacaine reduces rest pain scores by 0.9 out of 10 units, when compared with long-acting local anaesthetics at 24 hours after surgery, and by 0.7 up to 72 hours after surgery.
Topics: Humans; Anesthetics, Local; Pain, Postoperative; Bupivacaine; Analgesics; Morphine; Peripheral Nerves; Analgesics, Opioid
PubMed: 37038770
DOI: 10.1097/EJA.0000000000001833 -
Pediatric Surgery International Jan 2022This systematic review examines the feasibility and safety of implementing Enhanced recovery after Surgery (ERAS) protocols in children. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review examines the feasibility and safety of implementing Enhanced recovery after Surgery (ERAS) protocols in children.
STUDY DESIGN
A systematic search of Medline, PubMed, and the Cochrane library for papers describing ERAS implementation in children between January 2000 and January 2021. The systematic review was performed according to the PRISMA statement. The meta-analysis was done using R Software (Ver 4.0.2). p value of < 0.05 was considered statistically significant.
RESULTS
Sixteen studies, describing a total of 1723 patients, were included in the meta-analysis. An average of 15 (range 11-16) relevant components were implemented with an overall compliance close to 84%. The time to initiate feeds and reach full enteral nutrition was reduced in ERAS group with mean difference (MD) of - 21.20 h (95% CI - 22.80, - 19.59, p < 0.01), and - 2.20 days (95% CI - 2.72, - 1.71, p < 0.01), respectively. The use of opioids for postoperative analgesia was reduced with MD of -0.86 morphine equivalents mg/kg (95% CI - 1.40, - 0.32, p < 0.01). The length of hospital stay showed a significant reduction with MD of -2.54 days (95% CI - 2.94, - 2.13, p < 0.01). There was no difference in the complication and readmission rates between the groups.
CONCLUSION
ERP implementation in pediatric perioperative care is a viable option in a variety of surgical settings. There is clear evidence of a decrease in hospital stay duration with no increase in complication or readmission rates. The length of hospital stay reduced in inverse proportion to the number of ERAS elements implemented. Parental satisfaction is increased by initiating enteral feeding early, minimizing catheter and drain use, and reducing opioid use.
Topics: Analgesics, Opioid; Child; Clinical Protocols; Enhanced Recovery After Surgery; Humans; Length of Stay; Morphine; Perioperative Care; Postoperative Complications
PubMed: 34524519
DOI: 10.1007/s00383-021-05008-8 -
The Cochrane Database of Systematic... Nov 2012This is an update of the original review published in Issue 1, 2003. Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an... (Review)
Review
BACKGROUND
This is an update of the original review published in Issue 1, 2003. Ketamine is a commonly used anaesthetic agent, and in subanaesthetic doses is also given as an adjuvant to opioids for the treatment of cancer pain, particularly when opioids alone prove to be ineffective. Ketamine is known to have psychotomimetic (including hallucinogenic), urological and hepatic adverse effects.
OBJECTIVES
To determine the effectiveness and adverse effects of ketamine as an adjuvant to opioids in the treatment of cancer pain.
SEARCH METHODS
Studies were originally identified from MEDLINE (1966 to 2002), EMBASE (1980 to 2002), CancerLit (1966 to 2002), The Cochrane Library (Issue 1, 2001); by handsearching reference lists from review articles, trials, and chapters from standard textbooks on pain and palliative care. The manufacturer of ketamine (Pfizer Parke-Davis) provided search results from their in-house database, PARDLARS.An improved and updated search of the following was performed in May 2012: CENTRAL, MEDLINE & OVID MEDLINE R, EMBASE.
SELECTION CRITERIA
Randomized controlled trials (RCTs) of adult patients with cancer and pain being treated with an opioid, and receiving either ketamine (any dose and any route of administration) or placebo or an active control. Studies having a group size of at least 10 participants who completed the trial.
DATA COLLECTION AND ANALYSIS
Two independent review authors identified four RCTs for possible inclusion in the review, and 32 case studies/case series reports. Quality and validity assessment was performed by three independent review authors, and two RCTs were excluded because of inappropriate study design. Patient-reported pain intensity and pain relief was assessed using visual analogue scales (VAS), verbal rating scales or other validated scales, and adverse effects data were collated. For the update three RCTs were identified for possible inclusion in the review.
MAIN RESULTS
Three new studies were identified by the updated search. All three were excluded from the review. Two studies were eligible for inclusion in the original review and both concluded that ketamine improves the effectiveness of morphine in the treatment of cancer pain. However, pooling of the data was not appropriate because of the small total number of participants (30), and the presence of clinical heterogeneity. Some patients experienced hallucinations on both ketamine plus morphine and morphine alone and were treated successfully with diazepam. No other serious adverse effects were reported.
AUTHORS' CONCLUSIONS
Since the last version of this review three new studies were identified but excluded from the review. Current evidence is insufficient to assess the benefits and harms of ketamine as an adjuvant to opioids for the relief of cancer pain. More RCTs are needed.
Topics: Adult; Analgesics; Chemotherapy, Adjuvant; Drug Therapy, Combination; Hallucinations; Humans; Ketamine; Morphine; Neoplasms; Pain; Palliative Care; Randomized Controlled Trials as Topic
PubMed: 23152217
DOI: 10.1002/14651858.CD003351.pub2 -
The Cochrane Database of Systematic... Jun 2013The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The reinforcing properties of nicotine may be mediated through release of various neurotransmitters both centrally and systemically. People who smoke report positive effects such as pleasure, arousal, and relaxation as well as relief of negative affect, tension, and anxiety. Opioid (narcotic) antagonists are of particular interest to investigators as potential agents to attenuate the rewarding effects of cigarette smoking.
OBJECTIVES
To evaluate the efficacy of opioid antagonists in promoting long-term smoking cessation. The drugs include naloxone and the longer-acting opioid antagonist naltrexone.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register for trials of naloxone, naltrexone and other opioid antagonists and conducted an additional search of MEDLINE using 'Narcotic antagonists' and smoking terms in April 2013. We also contacted investigators, when possible, for information on unpublished studies.
SELECTION CRITERIA
We considered randomised controlled trials comparing opioid antagonists to placebo or an alternative therapeutic control for smoking cessation. We included in the meta-analysis only those trials which reported data on abstinence for a minimum of six months. We also reviewed, for descriptive purposes, results from short-term laboratory-based studies of opioid antagonists designed to evaluate psycho-biological mediating variables associated with nicotine dependence.
DATA COLLECTION AND ANALYSIS
We extracted data in duplicate on the study population, the nature of the drug therapy, the outcome measures, method of randomisation, and completeness of follow-up. The main outcome measure was abstinence from smoking after at least six months follow-up in patients smoking at baseline. Abstinence at end of treatment was a secondary outcome. We extracted cotinine- or carbon monoxide-verified abstinence where available. Where appropriate, we performed meta-analysis, pooling risk ratios using a Mantel-Haenszel fixed-effect model.
MAIN RESULTS
Eight trials of naltrexone met inclusion criteria for meta-analysis of long-term cessation. One trial used a factorial design so five trials compared naltrexone versus placebo and four trials compared naltrexone plus nicotine replacement therapy (NRT) versus placebo plus NRT. Results from 250 participants in one long-term trial remain unpublished. No significant difference was detected between naltrexone and placebo (risk ratio (RR) 1.00; 95% confidence interval (CI) 0.66 to 1.51, 445 participants), or between naltrexone and placebo as an adjunct to NRT (RR 0.95; 95% CI 0.70 to 1.30, 768 participants). The estimate was similar when all eight trials were pooled (RR 0.97; 95% CI 0.76 to 1.24, 1213 participants). In a secondary analysis of abstinence at end of treatment, there was also no evidence of any early treatment effect, (RR 1.03; 95% CI 0.88 to 1.22, 1213 participants). No trials of naloxone or buprenorphine reported abstinence outcomes.
AUTHORS' CONCLUSIONS
Based on data from eight trials and over 1200 individuals, there was no evidence of an effect of naltrexone alone or as an adjunct to NRT on long-term smoking abstinence, with a point estimate strongly suggesting no effect and confidence intervals that make a clinically important effect of treatment unlikely. Although further trials might narrow the confidence intervals they are unlikely to be a good use of resources.
Topics: Buprenorphine; Humans; Naloxone; Naltrexone; Narcotic Antagonists; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Tobacco Use Cessation Devices
PubMed: 23744347
DOI: 10.1002/14651858.CD003086.pub3 -
The Cochrane Database of Systematic... Apr 2023Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management... (Review)
Review
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). No studies reported any harms. 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). 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. No studies reported if any harms occurred. The evidence is very uncertain about the effect of opioids on episodes of bradycardia or hypotension. 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.
Topics: Humans; Infant; Infant, Newborn; Analgesics; Analgesics, Opioid; Apnea; Bradycardia; Fentanyl; Hypotension; Morphine; Pain; Pain, Procedural
PubMed: 37019853
DOI: 10.1002/14651858.CD015056.pub2