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Cancer Treatment Reviews Apr 2024Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cancer-related pain often requires opioid treatment with opioid-induced constipation (OIC) as its most frequent gastrointestinal side-effect. Both for prevention and treatment of OIC osmotic (e.g. polyethylene glycol) and stimulant (e.g. bisacodyl) laxatives are widely used. Newer drugs such as the peripherally acting µ-opioid receptor antagonists (PAMORAs) and naloxone in a fixed combination with oxycodone have become available for the management of OIC. This systematic review and meta-analysis aims to give an overview of the scientific evidence on pharmacological strategies for the prevention and treatment of OIC in cancer patients.
METHODS
A systematic search in PubMed, Embase, Web of Science and the Cochrane Library was completed from inception up to 22 October 2022. Randomized and non-randomized studies were systematically selected. Bowel function and adverse drug events were assessed.
RESULTS
Twenty trials (prevention: five RCTs and three cohort studies; treatment: ten RCTs and two comparative cohort studies) were included in the review. Regarding the prevention of OIC, three RCTs compared laxatives with other laxatives, finding no clear differences in effectivity of the laxatives used. One cohort study showed a significant benefit of magnesium oxide compared with no laxative. One RCT found a significant benefit for the PAMORA naldemedine compared with magnesium oxide. Preventive use of oxycodone/naloxone did not show a significant difference in two out of three other studies compared to oxycodone or fentanyl. A meta-analysis was not possible. Regarding the treatment of OIC, two RCTs compared laxatives, of which one RCT found that polyethylene glycol was significantly more effective than sennosides. Seven studies compared an opioid antagonist (naloxone, methylnaltrexone or naldemedine) with placebo and three studies compared different dosages of opioid antagonists. These studies with opioid antagonists were used for the meta-analysis. Oxycodone/naloxone showed a significant improvement in Bowel Function Index compared to oxycodone with laxatives (MD -13.68; 95 % CI -18.38 to -8.98; I = 58 %). Adverse drug event rates were similar amongst both groups, except for nausea in favour of oxycodone/naloxone (RR 0.51; 95 % CI 0.31-0.83; I = 0 %). Naldemedine (NAL) and methylnaltrexone (MNTX) demonstrated significantly higher response rates compared to placebo (NAL: RR 2.07, 95 % CI 1.64-2.61, I = 0 %; MNTX: RR 3.83, 95 % CI 2.81-5.22, I = 0 %). With regard to adverse events, abdominal pain was more present in treatment with methylnaltrexone and diarrhea was significantly more present in treatment with naldemedine. Different dosages of methylnaltrexone were not significantly different with regard to both efficacy and adverse drug event rates.
CONCLUSIONS
Magnesium oxide and naldemedine are most likely effective for prevention of OIC in cancer patients. Naloxone in a fixed combination with oxycodone, naldemedine and methylnaltrexone effectively treat OIC in cancer patients with acceptable adverse events. However, their effect has not been compared to standard (osmotic and stimulant) laxatives. More studies comparing standard laxatives with each other and with opioid antagonists are necessary before recommendations for clinical practice can be made.
Topics: Humans; Laxatives; Analgesics, Opioid; Narcotic Antagonists; Constipation; Oxycodone; Opioid-Induced Constipation; Magnesium Oxide; Cohort Studies; Naloxone; Polyethylene Glycols; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Quaternary Ammonium Compounds; Naltrexone
PubMed: 38452708
DOI: 10.1016/j.ctrv.2024.102704 -
Japanese Journal of Clinical Oncology Mar 2023the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the efficacy and safety of benzodiazepines alone or in combination with opioids for dyspnea in patients with cancer.
METHODS
Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Ichushi-Web were searched for articles published from database inception to 23 September 2019. Studies of benzodiazepines alone or in combination with opioids for dyspnea were included. The primary outcome measure was the relief of dyspnea. The secondary outcome measures were anxiety, somnolence and severe adverse events.
RESULTS
of 505 publications initially identified, two trials and one trial were included in the meta-analysis of midazolam alone and in combination with morphine, respectively. With regard to the relief of dyspnea, midazolam alone showed no significant difference compared with morphine alone, with a relative risk of 0.95 (95% confidence interval: 0.47-1.89). Meanwhile, midazolam plus morphine was significantly more effective than morphine alone, with a relative risk of 1.33 (95% confidence interval: 1.02-1.75). For anxiety relief, a meta-analysis could not be performed because of insufficient data. The incidence of somnolence and severe adverse events was not significantly different between the experimental and control groups for either midazolam alone or in combination with morphine.
CONCLUSIONS
benzodiazepines alone do not significantly improve dyspnea compared with opioids alone, but a combination of benzodiazepines and opioids may be more effective. Evidence from randomized controlled trials focusing on patients with cancer has not been generated in recent years. Further appropriately designed randomized controlled trials are required.
Topics: Humans; Benzodiazepines; Midazolam; Sleepiness; Dyspnea; Neoplasms; Morphine; Analgesics, Opioid
PubMed: 36636762
DOI: 10.1093/jjco/hyac206 -
Harm Reduction Journal Apr 2023Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV)... (Review)
Review
BACKGROUND
Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV.
METHODS
We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies.
RESULTS
After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV.
DISCUSSION
Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication.
Topics: Humans; Adult; Hydromorphone; HIV Infections; Substance Abuse, Intravenous; Delayed-Action Preparations; Retrospective Studies; Case-Control Studies; Hepatitis C; Hepacivirus; Endocarditis; Endocarditis, Bacterial
PubMed: 37118805
DOI: 10.1186/s12954-023-00788-9 -
Value in Health : the Journal of the... Feb 2021The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare...
OBJECTIVES
The rapid increase in opioid overdose and opioid use disorder (OUD) over the past 20 years is a complex problem associated with significant economic costs for healthcare systems and society. Simulation models have been developed to capture and identify ways to manage this complexity and to evaluate the potential costs of different strategies to reduce overdoses and OUD. A review of simulation-based economic evaluations is warranted to fully characterize this set of literature.
METHODS
A systematic review of simulation-based economic evaluation (SBEE) studies in opioid research was initiated by searches in PubMed, EMBASE, and EbscoHOST. Extraction of a predefined set of items and a quality assessment were performed for each study.
RESULTS
The screening process resulted in 23 SBEE studies ranging by year of publication from 1999 to 2019. Methodological quality of the cost analyses was moderately high. The most frequently evaluated strategies were methadone and buprenorphine maintenance treatments; the only harm reduction strategy explored was naloxone distribution. These strategies were consistently found to be cost-effective, especially naloxone distribution and methadone maintenance. Prevention strategies were limited to abuse-deterrent opioid formulations. Less than half (39%) of analyses adopted a societal perspective in their estimation of costs and effects from an opioid-related intervention. Prevention strategies and studies' accounting for patient and physician preference, changing costs, or result stratification were largely ignored in these SBEEs.
CONCLUSION
The review shows consistently favorable cost analysis findings for naloxone distribution strategies and opioid agonist treatments and identifies major gaps for future research.
Topics: Analgesics, Opioid; Costs and Cost Analysis; Humans; Methadone; Models, Economic; Naloxone; Narcotic Antagonists; Opiate Overdose; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 33518022
DOI: 10.1016/j.jval.2020.07.013 -
The Cochrane Database of Systematic... Jan 2021This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.
OBJECTIVES
Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.
SEARCH METHODS
For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.
SELECTION CRITERIA
Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.
MAIN RESULTS
This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12,724 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.
AUTHORS' CONCLUSIONS
In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.
Topics: Adult; Anti-Obesity Agents; Appetite Depressants; Bias; Blood Pressure; Body Weight; Bupropion; Diet, Reducing; Drug Combinations; Female; Fructose; Humans; Hypertension; Lactones; Male; Middle Aged; Naltrexone; Orlistat; Phentermine; Piperidines; Pyrazoles; Randomized Controlled Trials as Topic; Safety-Based Drug Withdrawals; Time; Topiramate
PubMed: 33454957
DOI: 10.1002/14651858.CD007654.pub5 -
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 -
Integrative Medicine Research Sep 2023An increasing amount of clinical evidence of acupuncture's effect on protracted opioid abstinence syndrome (POAS) has emerged in recent years. The aim of this study was... (Review)
Review
BACKGROUND
An increasing amount of clinical evidence of acupuncture's effect on protracted opioid abstinence syndrome (POAS) has emerged in recent years. The aim of this study was to evaluating the evidence of efficacy of acupuncture for POAS. clinical and scientific research work.
METHODS
Four English-language databases (PubMed, Medline, Embase, Cochrane Libraries) and three Chinese-language databases (CNKI, WanFang and VIP Libraries) were searched, with coverage from database inception to March 31, 2022. Randomized clinical trials (RCTs) evaluating the effects of acupuncture and acupuncture-related therapies for prophylaxis or treatment of POAS were included. Data were screened and extracted independently according to pre-set tabular formats. RCT quality was assessed using risk of bias tool in the Cochrane Collaboration. The primary outcome was opiate withdrawal scale. The secondary outcomes are depression, anxiety for assessing protracted symptoms. The scores on the above scales are proportional to the severity of the symptoms.
RESULTS
Twenty-eight trials met the inclusion criteria and provided data for the meta-analysis. A total of only 3 studies (11%) were judged to be low-risk overall due to various biases in them. Acupuncture-related therapy showed statistical differences in improving protracted withdrawal symptom scores compared with sham acupuncture (5 studies, Standard mean difference (SMD), -1.85, 95% CI [-3.21, -0.50], = 0.007), western medicine(7 studies, SMD, -0.72, 95% CI [-1.22, -0.21], = 0.005)and no treatment(3 studies, SMD,-2.26, 95% CI [-3.82, -0.69], = 0.005)with high heterogeneity.
CONCLUSIONS
Acupuncture maybe safe and effective in relieving POAS individuals' protracted withdrawal symptoms. However, the results of our review should be interpreted with caution because of the high risk of bias of the included trials.
STUDY REGISTRATION
The protocol of this review has been registered at PROSPERO (CRD42022335505).
PubMed: 37637184
DOI: 10.1016/j.imr.2023.100976 -
The International Journal on Drug Policy Oct 2022Continuing professional development (CPD) for opioid agonist therapy (OAT) has been identified as a key health policy strategy to improve care for people living with... (Review)
Review
BACKGROUND
Continuing professional development (CPD) for opioid agonist therapy (OAT) has been identified as a key health policy strategy to improve care for people living with opioid use disorder (OUD) and to address rising opioid-related harms. To design and deliver effective CPD programs, there is a need to clarify how they work within complex health system and policy contexts. This review synthesizes the literature on OAT CPD programs and educational theory to clarify which interventions work, for whom, and in what contexts.
METHODS
A systematic review and realist synthesis of evaluations of CPD programs focused on OAT was conducted. This included record identification and screening, theory familiarization, data collection, analysis, expert consultation, and iterative context-intervention-mechanism-outcome (CIMO) configuration development.
RESULTS
Twenty-four reports comprising 21 evaluation studies from 5 countries for 3373 providers were reviewed. Through iterative testing of included studies with relevant theory, five CIMO configurations were developed. The programs were categorized by who drove the learning outcomes (i.e., system/policy, instructor, learner) and their spheres of influence (i.e., micro, meso, macro). There was a predominance of instructor-driven programs driving change at the micro level, with few policy-driven macro-influential programs, inconsistent with the promotion of CPD as a clear opioid crisis policy-level intervention.
CONCLUSION
OAT CPD is challenged by mismatches in program justifications, objectives, activities, and outcomes. Depending on how these program factors interact, OAT CPD can operate as a barrier or facilitator to OUD care. With more deliberate planning and consideration of program theory, programs more directly addressing diverse learner and system needs may be developed and delivered. OAT CPD as drug policy does not operate in isolation; programs may feed into each other and intercalate with other policy initiatives to have micro, meso, and macro impacts on educational and population health outcomes.
Topics: Analgesics, Opioid; Health Policy; Humans; Opiate Substitution Treatment; Opioid Epidemic; Opioid-Related Disorders
PubMed: 35930903
DOI: 10.1016/j.drugpo.2022.103807 -
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 -
Pediatric Critical Care Medicine : a... May 2023Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Pediatric delirium (PD) is a neuropsychiatric syndrome caused by a complex interplay between predisposing factors (e.g., age, cognitive impairment), acute illness, and environmental triggers. PD is associated with substantial morbidity and mortality. The objective of this study is to systematically review and evaluate factors associated with PD in hospitalized pediatric patients.
DATA SOURCES
A systematic search of PubMed, Embase, Ovid Medline, Web- of-Science, Cochrane, CIHNAL, and Google Scholar databases was conducted for relevant studies (1990-2022).
STUDY SELECTION
We included studies that compared pediatric patients with and without delirium. Reviews, editorials, congress abstracts, or studies that did not report factors for PD were excluded. No restrictions were imposed on language.
DATA EXTRACTION
Title and abstract were independently screened by two reviewers. Individual characteristics, study design, and outcomes were independently extracted.
DATA SYNTHESIS
Categorical dichotomous data were summarized across groups using Mantel-Haenszel odds ratios (ORs) with 95% 95% CIs. Either fixed-effect or random effects models were used as indicated by the results of a heterogeneity test. Of 1,846 abstracts, 24 studies were included. We identified 54 factors studied in univariate analyses, and 27 of these were associated with PD in multivariable analyses. In pooled analyses, greater odds of PD were associated with developmental delay (OR 3.98; 95% CI 1.54-10.26), need for mechanical ventilation (OR 6.02; 95% CI 4.43-8.19), use of physical restraints (OR 4.67; 95% CI 1.82-11.96), and receipt of either benzodiazepines (OR 4.10; 95% CI 2.48-6.80), opiates (OR 2.88; 95% CI 1.89-4.37), steroids (OR 2.02; 95% CI 1.47-2.77), or vasoactive medication (OR 3.68; 95% CI 1.17-11.60).
CONCLUSIONS
In this meta-analysis, we identified seven factors associated with greater odds of developing delirium during pediatric critical illness.
Topics: Humans; Child; Benzodiazepines; Cognitive Dysfunction; Critical Illness; Delirium
PubMed: 36790201
DOI: 10.1097/PCC.0000000000003196