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Journal of Gastrointestinal Surgery :... Nov 2022Routine rectal administration of 100 mg of diclofenac or indomethacin was demonstrated to be an effective prevention method to prevent post-endoscopic retrograde... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Routine rectal administration of 100 mg of diclofenac or indomethacin was demonstrated to be an effective prevention method to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. The systematic review and meta-analysis aimed to estimate the incidence and severity of post-ERCP pancreatitis (PEP) and explore the discrepancies of PEP incidences among different subgroups.
METHODS
The PubMed, Web of Science, and Ovid EMBASE databases were searched for studies published until December 2020. Only randomized controlled trials (RCTs) reported rectal administration of 100 mg or higher doses of diclofenac or indomethacin, with PEP as the primary outcomes were eligible for inclusion. The overall and severity of PEP were estimated. Subgroup analysis was performed based on geographic regions, risk level, study beginning time, type of NSAIDs, administration time, and sample size.
RESULTS
There were 26 randomized controlled trials (RCTs) with 7954 patients in 31 NSAIDs arms. The pooled incidences were 7.2% for overall PEP (95% confidence interval (CI) 5.9-8.5%), 5.0% for mild PEP (95% CI, 4.0-6.0%), and 1.5% for moderate and severe PEP (0.8-2.3%). PEP rate were higher in patients receiving rectal indomethacin than that of patients receiving rectal diclofenac (7.8% (95% CI, 6.4-9.3%) vs 3.8% (95% CI, 2.2-5.3%), p = 0.009). The PEP rates of high-risk patients and average-risk patients were 8.9% (95% CI, 5.6-12.2%) and 6.4% (95% CI, 5.1-7.6%), respectively (p = 0.160).
CONCLUSIONS
The incidence of PEP was higher in patients receiving 100 mg rectal indomethacin than patients receiving 100 mg diclofenac. The effect of 100 mg diclofenac versus indomethacin on preventing PEP requires further study.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Incidence; Pancreatitis; Indomethacin; Hyperplasia
PubMed: 35941494
DOI: 10.1007/s11605-022-05399-6 -
Hip International : the Journal of... Mar 2022Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can...
BACKGROUND
Heterotopic ossification (HO) is defined as the formation of lamellar bone in extraskeletal soft tissues. HO can be a severe complication after hip arthroplasty but can possibly be prevented by postoperative treatment with non-steroidal anti-inflammatory drugs (NSAIDs) or radiotherapy. Diclofenac is 1 of the most used drugs in HO prophylaxis because it is effective and long established. However, there is still no uniform therapy regimen in terms of duration, dose and side effect profile regarding the application of diclofenac in HO prevention. We have, therefore, conducted the first systematic review investigating diclofenac for HO prophylaxis after hip arthroplasty. The aim of this study is to assess the efficacy, dose and duration of diclofenac therapy in preventing HO after total hip arthroplasty (THA).
METHODS
According to the PRISMA Guidelines we performed a systematic literature search in EMBASE via Ovid, in MEDLINE via PubMed and in the Cochrane Library addressing all studies in English and German regarding the prophylaxis of HO with diclofenac after THA. We identified 731 potential studies and included 6 randomised controlled trials with 957 patients.
RESULTS
The studies were heterogeneous with regard to duration of therapy, dose, comparative group and follow-up period. The therapy duration ranged from 9 to 42 days, the applied diclofenac doses ranged from 75 mg to 150 mg daily. Patients treated with diclofenac showed a significant reduction in the total incidence of HO regarding to the Brooker Classification compared to placebo and no clinically relevant ossifications occured (Brooker III and IV).
CONCLUSIONS
Diclofenac is efficacious in the prevention of HO and can be used routinely after THA. The existing data indicates that a minimum dose of 75 mg diclofenac per day started on the first postoperative day for a minimum of 9 days is needed to prevent HO with an acceptable incidence of side effects, such as gastrointestinal symptoms.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Hip; Diclofenac; Humans; Incidence; Ossification, Heterotopic
PubMed: 33272062
DOI: 10.1177/1120700020978194 -
Antibiotics (Basel, Switzerland) Jan 2022To investigate the efficacy and safety of interventions for early stage pericoronitis. (Review)
Review
BACKGROUND
To investigate the efficacy and safety of interventions for early stage pericoronitis.
METHODS
We searched for randomized controlled trials (RCTs) in databases from inception to July 2020, without language restriction. RCTs assessing adolescents and adults were included.
RESULTS
Seven RCT with clinical diversity were included, so, it was not possible to conduct meta-analyses. Individual study data showed an improvement in oral health quality of life in favor of topical benzydamine versus diclofenac capsule (Mean difference (MD) -1.10, 95% Confidence interval (CI) -1.85 to -0.35), and no difference between topical benzydamine and flurbiprofen capsule (MD -0.55 95% CI -1.18 to 0.0). There was no difference between diclofenac and flurbiprofen capsules (MD 0.55, 95% CI -0.29 to 1.39). An imprecise estimate of effects was found for all outcomes, considering (i) oral versus topic pharmacological treatment, (ii) different oral pharmacological treatments, (iii) pharmacological treatment associated with laser versus placebo laser, (iv) pharmacological treatment associated with different mouthwashes, and (v) conventional treatment associated to antimicrobial photodynamic therapy versus conventional treatment, with low to very low certainty of evidence.
CONCLUSIONS
Until future well-designed studies can be conducted, the clinical decision for early stage pericoronitis should be guided by individual characteristics, settings and financial aspects.
PubMed: 35052948
DOI: 10.3390/antibiotics11010071 -
Cureus Jul 2023Mandibular third-molar extraction is a frequently executed minor oral surgical procedure, with a subsequent recovery period lasting several days. Typically, preemptive... (Review)
Review
Mandibular third-molar extraction is a frequently executed minor oral surgical procedure, with a subsequent recovery period lasting several days. Typically, preemptive administration of non-steroid anti-inflammatory drugs (NSAIDs) and steroids has been employed, resulting in a notable decrease in postoperative complications like pain, facial swelling, trismus, and alveolar osteitis. This systematic review's primary goal was to investigate the efficacy of preemptive analgesia with dexamethasone and diclofenac in minimizing the post-surgical complications following the surgical extraction of the mandibular third molars. The systematic search was carried out to identify relevant literature in digital databases including PubMed®, Cochrane Library, Web of Science, and Scopus, from January 1990 to January 2022. The search used specific keywords. The randomized clinical trials assessing the efficacy of dexamethasone and diclofenac or dexamethasone alone compared to diclofenac or placebo as preemptive analgesics were considered inclusion criteria for this systematic review. Case reports, literature reviews, letters to the editor, and non-English publications were not included. Two authors screened the titles and abstracts, and articles fulfilling the study criteria were included. After reading the full text and data collection, analysis was performed. The included article's bias was evaluated by the Risk of Bias 2 (RoB 2) tool. A digital database search yielded a total of 207 articles. After excluding duplicates and articles written in languages other than English, 90 were removed. Based on the title and abstract, out of 177, 95 studies were excluded. After full-text reading of 22 articles, 17 were eliminated because they did not meet the inclusion and exclusion criteria. The remaining five studies were found eligible and included in the systematic review. Four studies were of low risk, while one study had some concerns. Two studies evaluated the combination of dexamethasone with diclofenac, while three evaluated dexamethasone alone. Total samples included samples of 436 third-molar surgeries in 420 patients. There was a substantial decrease in the mean pain score and swelling measurement when diclofenac alone was compared with coadministration of diclofenac and dexamethasone. Preemptive administration of dexamethasone and diclofenac has been shown to effectively reduce pain and facial swelling, with the exception of trismus, in third-molar surgeries when compared to diclofenac alone. As a result, it is recommended to administer these drugs prior to the commencement of third-molar extraction. However, further research is mandatory, specifically good quality randomized controlled trials involving large cohorts, in order to assess any significant variations and validate these findings.
PubMed: 37654946
DOI: 10.7759/cureus.42709 -
Korean Journal of Anesthesiology Dec 2023Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery.
METHODS
CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis.
RESULTS
We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs.
CONCLUSIONS
Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.
Topics: Humans; Pregnancy; Female; Diclofenac; Ketorolac; Celecoxib; Cesarean Section; Network Meta-Analysis; Anti-Inflammatory Agents, Non-Steroidal; Indomethacin; Pain
PubMed: 37066603
DOI: 10.4097/kja.23014 -
Annals of Medicine Dec 2024Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults.
METHODS
We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554.
RESULTS
We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity between the studies was low.
CONCLUSIONS
Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).
Topics: Humans; Tension-Type Headache; Analgesics; Adult; Network Meta-Analysis; Ibuprofen; Acetaminophen; Bayes Theorem; Treatment Outcome; Diclofenac; Randomized Controlled Trials as Topic; Naproxen; Ketoprofen; Anti-Inflammatory Agents, Non-Steroidal; Female; Male
PubMed: 38813682
DOI: 10.1080/07853890.2024.2357235 -
The Lancet. Gastroenterology &... Sep 2021Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs)... (Meta-Analysis)
Meta-Analysis
Non-steroidal anti-inflammatory drugs, intravenous fluids, pancreatic stents, or their combinations for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a systematic review and network meta-analysis.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs), intravenous fluid, pancreatic stents, or combinations of these have been evaluated in randomised controlled trials (RCTs) for the prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis, but the comparative efficacy of these treatments remains unclear. Our aim was to do an exploratory network meta-analysis of previous RCTs to systematically compare the direct and indirect evidence and rank NSAIDs, intravenous fluids, pancreatic stents, or combinations of these to determine the most efficacious method of prophylaxis for post-ERCP pancreatitis.
METHODS
We searched PubMed, Embase, and the Cochrane Central Register from inception to Nov 15, 2020, for full-text RCTs that evaluated the efficacy of NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for post-ERCP pancreatitis prevention in adult (aged ≥18 years) patients undergoing ERCP. Summary data from intention-to-treat analyses were extracted from published reports. We analysed incidence of post-ERCP pancreatitis across studies using network meta-analysis under the frequentist framework, obtaining pairwise odds ratios (ORs) and 95% CIs. We used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system for the confidence rating. This study is registered with PROSPERO, CRD42020172606.
FINDINGS
We identified 1503 studies, of which 55 RCTs evaluating 20 interventions in 17 062 patients were included in the network meta-analysis. The mean incidence of post-ERCP pancreatitis in the placebo or active control group was 12·2% (95% CI 11·4-13·0). Normal saline plus rectal indometacin (OR 0·02, 95% CI 0·00-0·40), intramuscular diclofenac 75 mg (0·24, 0·09-0·69), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·30, 0·16-0·55), intravenous high-volume Ringer's lactate (0·31, 0·12-0·78), 5-7 Fr pancreatic stents (0·35, 0·26-0·48), rectal diclofenac 100 mg (0·36, 0·25-0·52), 3 Fr pancreatic stents (0·47, 0·26-0·87), and rectal indometacin 100 mg (0·60, 0·50-0·73) were all more efficacious than placebo for preventing post-ERCP pancreatitis in pairwise comparisons. 5-7 Fr pancreatic stents (0·59, 0·41-0·84), intravenous high-volume Ringer's lactate plus rectal diclofenac 100 mg (0·49, 0·26-0·94), intravenous standard-volume normal saline plus rectal indometacin 100 mg (0·04, 0·00-0·66), and rectal diclofenac 100 mg (0·59, 0·40-0·89) were more efficacious than rectal indometacin 100 mg. The GRADE confidence rating was low to moderate for 98·3% of the pairwise comparisons.
INTERPRETATION
This systematic review and network meta-analysis summarises the available literature on NSAIDs, pancreatic stents, intravenous fluids, or combinations of these for prophylaxis of post-ERCP pancreatitis. Rectal diclofenac 100 mg is the best performing rectal NSAID in this network meta-analysis. Combinations of prophylaxis might be more effective, but there is little evidence. These findings help to establish prophylaxis of post-ERCP pancreatitis for future research and practice, and could reduce costs and increase adoption of prophylaxis.
FUNDING
None.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cholangiopancreatography, Endoscopic Retrograde; Fluid Therapy; Global Health; Humans; Incidence; Pancreatitis; Postoperative Complications; Stents
PubMed: 34214449
DOI: 10.1016/S2468-1253(21)00170-9 -
The Cochrane Database of Systematic... Dec 2022Cataract surgery is the most common ambulatory incisional surgery performed in the USA. Cystoid macular edema (CME), the accumulation of fluid in the central retina due... (Review)
Review
BACKGROUND
Cataract surgery is the most common ambulatory incisional surgery performed in the USA. Cystoid macular edema (CME), the accumulation of fluid in the central retina due to leakage from dilated capillaries, is the most common cause of vision impairment following cataract surgery. Acute CME, defined as CME of less than four months' duration, often resolves spontaneously. CME that persists for four months or longer is termed chronic CME. Non-steroidal anti-inflammatory drugs (NSAIDs) have been used to treat CME. This update adds new evidence and analyses to the previously published review.
OBJECTIVES
To examine the effectiveness of NSAIDs in the treatment of CME following cataract surgery.
SEARCH METHODS
We searched the CENTRAL (2022, Issue 3); Ovid MEDLINE; Embase; PubMed; LILACS; mRCT (discontinued in 2014, last searched August 2011), ClinicalTrials.gov, and WHO ICTRP databases. We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 20 March 2022. SELECTION CRITERIA: We included randomized controlled trials evaluating the effects of NSAIDs for CME following cataract surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened all titles and abstracts, reviewed full-text publications against eligibility criteria, independently extracted data from newly included trials and assessed risk of bias for each included trial. We contacted trial authors for clarification or to request missing information. We provided a narrative synthesis of all included trials and their results. For continuous and dichotomous outcomes, we separately performed pooled analysis and reported mean difference (MD) and risk ratio (RR) as well as the associated 95% confidence interval (CI) whenever feasible. Two review authors independently graded the overall certainty of the evidence for each outcome using the GRADE approach.
MAIN RESULTS
We included nine trials with a total of 390 participants (393 eyes). Study participants' mean age was 72.2 years (interquartile range [IQR] 68.8 to 73.6) and 72% were women (IQR 69% to 74%). Three trials included participants with acute CME, and four included participants with chronic CME; the remaining two trials enrolled both participants with acute and chronic CME or participants with unknown CME duration. We assessed trials as having unclear (33%) or high risk of bias (67%). Visual improvement of two or more lines at the end of treatment Data from one trial in participants with acute CME show no treatment effect of topical ketorolac compared to placebo (RR 2.00, 95% CI 0.46 to 8.76; 22 participants). Data from a three-arm trial in participants with acute CME demonstrate that, when compared with topical prednisolone, topical ketorolac (RR 1.33, 95% CI 0.58 to 3.07; 17 participants) or topical ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) may have little or no effect on visual improvement. Results of subgroup analysis from two studies in participants with chronic CME suggest that, after treatment for 90 days or longer, NSAIDs may increase participants' likelihood of visual improvement by 1.87 fold (RR 2.87, 95% CI 1.58 to 5.22; I = 33%; 2 trials, 121 participants) relative to placebo. However, there was no evidence of treatment effects in the subgroup with two months of treatment or less (RR 0.72, 95% CI 0.30 to 1.73; P = 0.19, I = 41%; 2 trials, 34 participants). Overall, this evidence is very low certainty. A single-study estimate in patients with mixed CME indicates that topical diclofenac may increase the likelihood of visual improvement by 40% when compared to topical ketorolac (RR 1.40, 95% CI 1.02 to 1.94; 68 participants). However, the same trial reported no difference between the groups in mean final visual acuity in Snellen lines (MD 0.40, 95% CI -0.93 to 1.73). A three-arm trial in patients with mixed CME reporting visual changes in ETDRS letters in comparisons between ketorolac and diclofenac (34 participants) or bromfenac (34 participants) suggests no evidence of effects. Overall, NSAIDs may slightly improve visual acuity in participants with mixed CME but the evidence is very uncertain. Persistence of improvement of vision one month after discontinuation of treatment One trial of participants with chronic CME tested oral indomethacin (RR 0.40, 95% CI 0.10 to 1.60; 20 participants) and the other compared topical ketorolac to placebo (RR 4.00, 95% CI 0.51 to 31.1; 26 participants). While there is no evidence of treatment effects, evidence suggests substantial between-group heterogeneity (P = 0.07, I = 69.9%; very low-certainty evidence). None of the trials in patients with acute or mixed CME reported this outcome. Proportion of participants with improvement in leakage on fundus fluorescein angiography One three-arm trial in participants with acute CME shows that, when compared with topical prednisolone, there is no treatment benefit of topical ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or topical ketorolac and topical prednisolone combination therapy (RR 1.56, 95% CI 0.72 to 3.38; 17 participants). This evidence is very low certainty. The combined estimate from two trials in participants with chronic CME indicates NSAIDs have little to no effect over placebo on improving leakage (RR 1.93, 95% CI 0.62 to 6.02; 40 participants; very low-certainty evidence). Neither of the trials in patients with mixed CME reported this outcome. Proportion of participants with improved contrast sensitivity Very low-certainty evidence from one trial in participants with acute CME shows no treatment benefit of ketorolac (RR 1.11, 95% CI 0.45 to 2.75; 17 participants) or ketorolac and prednisolone combination therapy (RR 1.78, 95% CI 0.86 to 3.69; 17 participants) compared with topical prednisolone. None of the trials in patients with chronic or mixed CME reported this outcome. Proportion of participants with improved central macular thickness on optical coherence tomography; measures of quality of life No included trial reported these outcomes. Adverse effects Most trials observed no differences in ocular adverse events, such as corneal toxicity or elevated intraocular pressure, between comparison groups.
AUTHORS' CONCLUSIONS
Evidence on effects of NSAIDs in patients with CME is very uncertain and further investigation is warranted. Our findings are limited by small sample sizes, and heterogeneity in interventions, assessments, and reporting of clinically important outcomes.
Topics: Humans; Female; Aged; Male; Macular Edema; Anti-Inflammatory Agents, Non-Steroidal; Ketorolac; Diclofenac; Quality of Life; Cataract; Prednisolone
PubMed: 36520144
DOI: 10.1002/14651858.CD004239.pub4 -
Critical Reviews in Food Science and... 2022Autoimmune and inflammatory diseases affect innumerous people and are considered a significant cause of morbidity and mortality worldwide and sp can work as important...
Autoimmune and inflammatory diseases affect innumerous people and are considered a significant cause of morbidity and mortality worldwide and sp can work as important therapies in the approach of these diseases. For this reason the aim of this review is to evaluate the effects of or curcumin in five autoimmune and/or inflammatory diseases for instance, Inflammatory Bowel Disease, Osteoarthritis, Systemic Lupus Erythematous, Psoriasis, and Sclerosis. MEDLINE, EMBASE, and Cochrane Library were searched and PRISMA guidelines were used to build this systematic review. sp or curcumin have been gaining ground in the treatment of autoimmune and inflammatory diseases due to the wide range of bioactive compounds capable of exerting substantial anti-inflammatory and antioxidant actions. The effects can be associated with improvement of symptoms and induction of remission in Inflammatory Bowel Disease patients; reduction of erythema and induration of lesions in psoriasis; and slow down the disease progression in patients with sclerosis. Furthermore, curcumin shows effects equivalent to ibuprofen and diclofenac, without the adverse effects generally reported by patients. or its derivatives can be used safely and efficiently as adjuvants or as a main therapy for these diseases that increase year by year in the world population.
Topics: Adjuvants, Immunologic; Anti-Inflammatory Agents; Antioxidants; Curcuma; Curcumin; Humans; Inflammatory Bowel Diseases
PubMed: 33938775
DOI: 10.1080/10408398.2020.1850417 -
BMC Pediatrics Aug 2023Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Children in acute pain often receive inadequate pain relief, partly from difficulties administering injectable analgesics. A rapid-acting, intranasal (IN) analgesic may be an alternative to other parenteral routes of administration. Our review compares the efficacy, safety, and acceptability of intranasal analgesia to intravenous (IV) and intramuscular (IM) administration; and to compare different intranasal agents.
METHODS
We searched Cochrane Library, MEDLINE/PubMed, Embase, Web of Knowledge, Clinicaltrials.gov, Controlled-trials.com/mrcr, Clinicaltrialsregister.eu, Apps.who.int/trialsearch. We also screened reference lists of included trials and relevant systematic reviews. Studies in English from any year were included. Two authors independently assessed all studies. We included randomised trials (RCTs) of children 0-16, with moderate to severe pain; comparing intranasal analgesia to intravenous or intramuscular analgesia, or to other intranasal agents. We excluded studies of procedural sedation or analgesia. We extracted study characteristics and outcome data and assessed risk of bias with the ROB 2.0-tool. We conducted meta-analysis and narrative review, evaluating the certainty of evidence using GRADE. Outcomes included pain reduction, adverse events, acceptability, rescue medication, ease of and time to administration.
RESULTS
We included 12 RCTs with a total of 1163 children aged 3 to 20, most below 10 years old, with a variety of conditions. Our review shows that: - There may be little or no difference in pain relief (single dose IN vs IV fentanyl MD 4 mm, 95% CI -8 to 16 at 30 min by 100 mm VAS; multiple doses IN vs IV fentanyl MD 0, 95%CI -0.35 to 0.35 at 15 min by Hannallah score; single dose IN vs IV ketorolac MD 0.8, 95% CI -0.4 to 1.9 by Faces Pain Scale-Revised), adverse events (single dose IN vs IV fentanyl RR 3.09, 95% CI 0.34 to 28.28; multiple doses IN vs IV fentanyl RR 1.50, 95%CI 0.29 to 7.81); single dose IN vs IV ketorolac RR 0.716, 95% CI 0.23 to 2.26), or acceptability (single dose IN vs IV ketorolac RR 0.83, 95% CI 0.66 to 1.04) between intranasal and intravenous analgesia (low certainty evidence). - Intranasal diamorphine or fentanyl probably give similar pain relief to intramuscular morphine (narrative review), and are probably more acceptable (RR 1.60, 95% CI 1.42 to 1.81) and tolerated better (RR 0.061, 95% CI 0.03 to 0.13 for uncooperative/negative reaction) (moderate certainty); adverse events may be similar (narrative review) (low certainty). - Intranasal ketamine gives similar pain relief to intranasal fentanyl (SMD 0.05, 95% CI -0.20 to 0.29 at 30 min), while having a higher risk of light sedation (RR 1.74, 95% CI 1.30 to 2.35) and mild side effects (RR 2.16, 95% CI 1.72 to 2.71) (high certainty). Need for rescue analgesia is probably similar (RR 0.85, 95% CI 0.62 to 1.17) (moderate certainty), and acceptability may be similar (RR 1.15, 95% CI 0.89 to 1.48) (low certainty).
CONCLUSIONS
Our review suggests that intranasal analgesics are probably a good alternative to intramuscular analgesics in children with acute moderate to severe pain; and may be an alternative to intravenous administration. Intranasal ketamine gives similar pain relief to fentanyl, but causes more sedation, which should inform the choice of intranasal agent.
Topics: Child; Humans; Ketorolac; Ketamine; Pain; Analgesia; Fentanyl
PubMed: 37596559
DOI: 10.1186/s12887-023-04203-x