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The Cochrane Database of Systematic... Nov 2016Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Health services often manage agitated or violent people, and such behaviour is particularly prevalent in emergency psychiatric services (10%). The drugs used in such situations should ensure that the person becomes calm swiftly and safely.
OBJECTIVES
To examine whether haloperidol plus promethazine is an effective treatment for psychosis-induced aggression.
SEARCH METHODS
On 6 May 2015 we searched the Cochrane Schizophrenia Group's Register of Trials, which is compiled by systematic searches of major resources (including MEDLINE, EMBASE, AMED, BIOSIS, CINAHL, PsycINFO, PubMed, and registries of clinical trials) and their monthly updates, handsearches, grey literature, and conference proceedings.
SELECTION CRITERIA
All randomised clinical trials with useable data focusing on haloperidol plus promethazine for psychosis-induced aggression.
DATA COLLECTION AND ANALYSIS
We independently extracted data. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For continuous data, we estimated the mean difference (MD) between groups and its 95% CI. We employed a fixed-effect model for analyses. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE.
MAIN RESULTS
We found two new randomised controlled trials (RCTs) from the 2015 update searching. The review now includes six studies, randomising 1367 participants and presenting data relevant to six comparisons.When haloperidol plus promethazine was compared with haloperidol alone for psychosis-induced aggression for the outcome not tranquil or asleep at 30 minutes, the combination treatment was clearly more effective (n=316, 1 RCT, RR 0.65, 95% CI 0.49 to 0.87, high-quality evidence). There were 10 occurrences of acute dystonia in the haloperidol alone arm and none in the combination group. The trial was stopped early as haloperidol alone was considered to be too toxic.When haloperidol plus promethazine was compared with olanzapine, high-quality data showed both approaches to be tranquillising. It was suggested that the combination of haloperidol plus promethazine was more effective, but the difference between the two approaches did not reach conventional levels of statistical significance (n=300, 1 RCT, RR 0.60, 95% CI 0.22 to 1.61, high-quality evidence). Lower-quality data suggested that the risk of unwanted excessive sedation was less with the combination approach (n=116, 2 RCTs, RR 0.67, 95% CI 0.12 to 3.84).When haloperidol plus promethazine was compared with ziprasidone all data were of lesser quality. We identified no binary data for the outcome tranquil or asleep. The average sedation score (Ramsay Sedation Scale) was lower for the combination approach but not to conventional levels of statistical significance (n=60, 1 RCT, MD -0.1, 95% CI - 0.58 to 0.38). These data were of low quality and it is unclear what they mean in clinical terms. The haloperidol plus promethazine combination appeared to cause less excessive sedation but again the difference did not reach conventional levels of statistical significance (n=111, 2 RCTs, RR 0.30, 95% CI 0.06 to 1.43).We found few data for the comparison of haloperidol plus promethazine versus haloperidol plus midazolam. Average Ramsay Sedation Scale scores suggest the combination of haloperidol plus midazolam to be the most sedating (n=60, 1 RCT, MD - 0.6, 95% CI -1.13 to -0.07, low-quality evidence). The risk of excessive sedation was considerably less with haloperidol plus promethazine (n=117, 2 RCTs, RR 0.12, 95% CI 0.03 to 0.49, low-quality evidence). Haloperidol plus promethazine seemed to decrease the risk of needing restraints by around 12 hours (n=60, 1 RCT, RR 0.24, 95% CI 0.10 to 0.55, low-quality evidence). It may be that use of midazolam with haloperidol sedates swiftly, but this effect does not last long.When haloperidol plus promethazine was compared with lorazepam, haloperidol plus promethazine seemed to more effectively cause sedation or tranquillisation by 30 minutes (n=200, 1 RCT, RR 0.26, 95% CI 0.10 to 0.68, high-quality evidence). The secondary outcome of needing restraints or seclusion by 12 hours was not clearly different between groups, with about 10% in each group needing this intrusive intervention (moderate-quality evidence). Sedation data were not reported, however, the combination group did have less 'any serious adverse event' in 24-hour follow-up, but there were not clear differences between the groups and we are unsure exactly what the adverse effect was. There were no deaths.When haloperidol plus promethazine was compared with midazolam, there was clear evidence that midazolam is more swiftly tranquillising of an aggressive situation than haloperidol plus promethazine (n=301, 1 RCT, RR 2.90, 95% CI 1.75 to 4.8, high-quality evidence). On its own, midazolam seems to be swift and effective in tranquillising people who are aggressive due to psychosis. There was no difference in risk of serious adverse event overall (n=301, 1 RCT, RR 1.01, 95% CI 0.06 to 15.95, high-quality evidence). However, 1 in 150 participants allocated haloperidol plus promethazine had a swiftly reversed seizure, and 1 in 151 given midazolam had swiftly reversed respiratory arrest.
AUTHORS' CONCLUSIONS
Haloperidol plus promethazine is effective and safe, and its use is based on good evidence. Benzodiazepines work, with midazolam being particularly swift, but both midazolam and lorazepam cause respiratory depression. Olanzapine intramuscular and ziprasidone intramuscular do seem to be viable options and their action is swift, but resumption of aggression with subsequent need to re-inject was more likely than with haloperidol plus promethazine. Haloperidol used on its own without something to offset its frequent and serious adverse effects does seem difficult to justify.
Topics: Aggression; Benzodiazepines; Drug Therapy, Combination; Haloperidol; Humans; Lorazepam; Midazolam; Promethazine; Psychomotor Agitation; Psychotic Disorders; Randomized Controlled Trials as Topic; Restraint, Physical
PubMed: 27885664
DOI: 10.1002/14651858.CD005146.pub3 -
Intensive Care Medicine Sep 2020To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To review and summarize the most frequent medications and dosages used during withholding and withdrawal of life-prolonging measures in critically ill patients in the intensive care unit.
METHODS
We searched PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Virtual Health Library from inception through March 2019. We considered any study evaluating pharmaceutical interventions for pain management during the withholding or withdrawing of life support in adult critically ill patients at the end-of-life. Two independent investigators performed the screening and data extraction. We pooled data on utilization rate of analgesic and sedative drugs and summarized the dosing between the moment prior to withholding or withdrawal of life support and the moment before death.
RESULTS
Thirteen studies met inclusion criteria. Studies were conducted in the United States (38%), Canada (31%), and the Netherlands (31%). Eleven studies were single-cohort and twelve had a Newcastle-Ottawa Scale score of less than 7. The mean age of the patients ranged from 59 to 71 years, 59-100% were mechanically ventilated, and 47-100% of the patients underwent life support withdrawal. The most commonly used opioid and sedative were morphine [utilization rate 60% (95% CI 48-71%)] and midazolam [utilization rate 28% (95% CI 23-32%)], respectively. Doses increased during the end-of-life process (pooled mean increase in the dose of morphine: 2.6 mg/h, 95% CI 1.2-4).
CONCLUSIONS
Pain control is centered on opioids and adjunctive benzodiazepines, with dosages exceeding those recommended by guidelines. Despite consistency among guidelines, there is significant heterogeneity among practices in end-of-life care.
Topics: Adult; Aged; Canada; Critical Illness; Death; Humans; Middle Aged; Netherlands; Pain Management
PubMed: 32833041
DOI: 10.1007/s00134-020-06139-7 -
Dental and Medical Problems 2022Demand for dental implants has increased in recent years and the use of conscious sedation for this type of surgery can be of great benefit. Therefore, the aim of this... (Meta-Analysis)
Meta-Analysis Review
Demand for dental implants has increased in recent years and the use of conscious sedation for this type of surgery can be of great benefit. Therefore, the aim of this systematic review was to evaluate the scientific literature related to the effect of conscious sedation on the reduction of anxiety, and patient and surgeon satisfaction. The Embase, PubMed, ProQuest, Scopus, Ovid, and Cochrane databases were searched without limitations. According to the inclusion and exclusion criteria determined for the study, 10 articles were selected for the final review during several screening stages. These studies were reviewed in their full-text form by the research team and the intended data was extracted. The risk of bias was assessed for each of the selected articles. Five studies were ultimately included. Two of the them compared local anesthesia and conscious sedation, while another 2 compared the consequences of different types of conscious sedation. The anxiety reduction and patient and surgeon satisfaction data was collated. Midazolam was the most frequently used agent. After a thorough review of the final articles extracted based on the study protocol, it was concluded that the use of conscious sedation during implant surgery reduces patient anxiety, and also increases the satisfaction of the patient and surgeon.
Topics: Anxiety; Conscious Sedation; Dental Implants; Humans; Patient Satisfaction; Personal Satisfaction
PubMed: 35403382
DOI: 10.17219/dmp/141868 -
International Journal of Surgery... Mar 2018We performed a systematic review of various anaesthetic medications for endoscopic retrograde cholangiopancreatography (ERCP) and aimed to make a comprehensive... (Meta-Analysis)
Meta-Analysis Review
AIMS
We performed a systematic review of various anaesthetic medications for endoscopic retrograde cholangiopancreatography (ERCP) and aimed to make a comprehensive comparison based on a network meta-analysis.
METHODS
We searched globally recognized electronic databases, including PubMed, Cochrane Central and EMBASE, to retrieve relevant randomized controlled trials (RCTs) of anaesthetic medications for ERCP. Network meta-analysis was conducted by evaluating the procedure time, adverse effects and drug requirements. The cumulative probability P value was utilized to rank the medications under examination.
RESULTS
Seventeen RCTs that examined 1877 patients were included in this research. Under good convergence and efficiency, data analysis was performed using a consistency model. For the comparison of procedure times, we found that a combination of dexmedetomidine and ketamine (P = 0.19) or propofol plus pethidine (P = 0.18) seemed to be the two best medications for reducing procedure time. Additionally, midazolam combined with dexmedetomidine plus pethidine seemed to be the safest application for ERCP (P = 0.36). Propofol plus alfentanil also exhibited a good safety value (P = 0.28). For evaluation of drug requirements, the whole network connection could not be established; thus, comparisons in two subgroups were conducted. The results showed that midazolam combined with dexmedetomidine plus pethidine (P = 0.41) and propofol plus refentanil (P = 0.94) were superior to others in decreasing drug requirements.
CONCLUSIONS
Based on the objective results and our conclusions, we deemed that a combination of midazolam and dexmedetomidine was recommended, and propofol plus opioids also revealed great clinical value. However, we are still expecting more clinical research in the future.
Topics: Alfentanil; Analgesics, Opioid; Anesthetics; Cholangiopancreatography, Endoscopic Retrograde; Dexmedetomidine; Drug Therapy, Combination; Humans; Ketamine; Meperidine; Midazolam; Network Meta-Analysis; Operative Time; Propofol; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29367034
DOI: 10.1016/j.ijsu.2018.01.018 -
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 -
Journal of the Academy of... 2024Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available... (Review)
Review
Effectiveness and Safety of Intravenous Medications for the Management of Acute Disturbance (Agitation and Other Escalating Behaviors): A Systematic Review of Prospective Interventional Studies.
Acute disturbance is a broad term referring to escalating behaviors secondary to a change in mental state, such as agitation, aggression, and violence. Available management options include de-escalation techniques and rapid tranquilization, mostly via parenteral formulations of medication. While the intramuscular route has been extensively studied in a range of clinical settings, the same cannot be said for intravenous (IV); this is despite potential benefits, including rapid absorption and complete bioavailability. This systematic review analyzed existing evidence for effectiveness and safety of IV medication for management of acute disturbances. It followed a preregistered protocol (PROSPERO identification CRD42020216456) and is reported following the guidelines set by Preferred Reporting Items for Systematic Review and Meta-Analysis. APA PsycINFO, MEDLINE, and EMBASE databases were searched for eligible interventional studies up until May 30th, 2023. Data analysis was limited to narrative synthesis since primary outcome measures varied significantly. Results showed mixed but positive results for the effectiveness of IV dexmedetomidine, lorazepam, droperidol, and olanzapine. Evidence was more limited for IV haloperidol, ketamine, midazolam, chlorpromazine, and valproate. There was no eligible data on the use of IV clonazepam, clonidine, diazepam, diphenhydramine, propranolol, ziprasidone, fluphenazine, carbamazepine, or promethazine. Most studies reported favorable adverse event profiles, though they are unlikely to have been sufficiently powered to pick up rare serious events. In most cases, evidence was of low or mixed quality, accentuating the need for further standardized, large-scale, multi-arm randomized controlled trials with homogeneous outcome measures. Overall, this review suggests that IV medications may offer an effective alternative parenteral route of administration in acute disturbance, particularly in general hospital settings.
Topics: Humans; Administration, Intravenous; Psychomotor Agitation; Aggression; Antipsychotic Agents; Prospective Studies
PubMed: 38309683
DOI: 10.1016/j.jaclp.2024.01.004 -
The Cochrane Database of Systematic... Jan 2017Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Proper sedation for neonates undergoing uncomfortable procedures may reduce stress and avoid complications. Midazolam is a short-acting benzodiazepine that is used increasingly in neonatal intensive care units (NICUs). However, its effectiveness as a sedative in neonates has not been systematically evaluated.
OBJECTIVES
Primary objeciveTo assess the effectiveness of intravenous midazolam infusion for sedation, as evaluated by behavioural and/or physiological measurements of sedation levels, in critically ill neonates in the NICU. Secondary objectivesTo assess effects of intravenous midazolam infusion for sedation on complications including the following.1. Incidence of intraventricular haemorrhage (IVH)/periventricular leukomalacia (PVL).2. Mortality.3. Occurrence of adverse effects associated with the use of midazolam (hypotension, neurological abnormalities).4. Days of ventilation.5. Days of supplemental oxygen.6. Incidence of pneumothorax.7. Length of NICU stay (days).8. Long-term neurodevelopmental outcomes.
SELECTION CRITERIA
We selected for review randomised and quasi-randomised controlled trials of intravenous midazolam infusion for sedation in infants aged 28 days or younger.
DATA COLLECTION AND ANALYSIS
We abstracted data regarding the primary outcome of level of sedation. We assessed secondary outcomes such as intraventricular haemorrhage, periventricular leukomalacia, death, length of NICU stay and adverse effects associated with midazolam. When appropriate, we performed meta-analyses using risk ratios (RRs) and risk differences (RDs), and if the RD was statistically significant, we calculated the number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), along with their 95% confidence intervals (95% CIs) for categorical variables, and weighted mean differences (WMDs) for continuous variables. We assessed heterogeneity by performing the I-squared (I2) test.
MAIN RESULTS
We included in the review three trials enrolling 148 neonates. We identified no new trials for this update. Using different sedation scales, each study showed a statistically significantly higher sedation level in the midazolam group compared with the placebo group. However, none of the sedation scales used have been validated in preterm infants; therefore, we could not ascertain the effectiveness of midazolam in this population. Duration of NICU stay was significantly longer in the midazolam group than in the placebo group (WMD 5.4 days, 95% CI 0.40 to 10.5; I2 = 0%; two studies, 89 infants). One study (43 infants) reported significantly lower Premature Infant Pain Profile (PIPP) scores during midazolam infusion than during dextrose (placebo) infusion (MD -3.80, 95% CI -5.93 to -1.67). Another study (46 infants) observed a higher incidence of adverse neurological events at 28 days' postnatal age (death, grade III or IV IVH or PVL) in the midazolam group compared with the morphine group (RR 7.64, 95% CI 1.02 to 57.21; RD 0.28, 95% CI 0.07 to 0.49; NNTH 4, 95% CI 2 to 14) (tests for heterogeneity not applicable). We considered these trials to be of moderate quality according to GRADE assessment based on the following outcomes: mortality during hospital stay, length of NICU stay, adequacy of analgesia according to PIPP scores and poor neurological outcomes by 28 days' postnatal age.
AUTHORS' CONCLUSIONS
Data are insufficient to promote the use of intravenous midazolam infusion as a sedative for neonates undergoing intensive care. This review raises concerns about the safety of midazolam in neonates. Further research on the effectiveness and safety of midazolam in neonates is needed.
Topics: Humans; Hypnotics and Sedatives; Infant, Newborn; Infant, Premature; Infusions, Intravenous; Intensive Care Units, Neonatal; Intensive Care, Neonatal; Length of Stay; Midazolam; Randomized Controlled Trials as Topic
PubMed: 28141899
DOI: 10.1002/14651858.CD002052.pub3 -
Children (Basel, Switzerland) Apr 2022The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing... (Review)
Review
OBJECTIVE
The objective of this study was to evaluate the efficacy and safety of intranasal midazolam as part of a paediatric sedation and analgesic procedure during the suturing of traumatic lacerations in paediatric emergency departments.
METHODOLOGY
A systematic review of clinical trials was completed in July 2021. The databases consulted were PUBMED, SCOPUS, WEB OF SCIENCE, NICE and Virtual Health Library.
ELIGIBILITY CRITERIA
randomised and nonrandomised clinical trials. Two independent, blinded reviewers performed the selection and data extraction. The participants were 746 children, of whom, 377 received intranasal midazolam. All of the children were admitted to an emergency department for traumatic lacerations that required suturing. The quality of the articles was evaluated with the Jadad scale. This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.
RESULTS
Nine studies were included in the review. The intranasal administration of midazolam in healthy children produces anxiolysis and minimal/moderate sedation without serious side effects. Although there are combinations of parenteral drugs that produce deeper sedation, they also have greater adverse effects. No significant differences in the initiation of sedation and the suture procedure were found between the intranasal route and the parenteral route.
CONCLUSIONS
The use of intranasal midazolam in healthy children produces sufficiently intense and long-lasting sedation to allow for the suturing of traumatic lacerations that do not present other complications; therefore, this drug can be used effectively in paediatric emergency departments.
PubMed: 35626821
DOI: 10.3390/children9050644 -
PloS One 2015To assess the efficacy of midazolam for anxiety control in third molar extraction surgery. (Review)
Review
PURPOSE
To assess the efficacy of midazolam for anxiety control in third molar extraction surgery.
METHODS
Electronic retrievals were conducted in Medline (via PubMed, 1950-2013.12), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 3), Embase (via OVID 1974-2013.12), and the System for Information on Grey Literature in Europe (SIGLE). The bibliographies of relevant clinical trials were also checked. Randomized controlled trials satisfying the inclusion criteria were evaluated, with data extraction done independently by two well-trained investigators. Disagreements were resolved by discussion or by consultation with a third member of the review team.
RESULTS
Ten studies were included, but meta-analysis could not be conducted because of the significant differences among articles. All but one article demonstrated that midazolam could relieve anxiety. One article demonstrated that propofol offered superior anxiolysis, with more rapid recovery than with midazolam. Compared with lorazepam and diazepam, midazolam did not distinctly dominate in its sedative effect, but was safer. Two articles used midazolam in multidrug intravenous sedation and proved it to be more effective than midazolam alone.
CONCLUSION
It was found, by comparison and analysis, that midazolam might be effective for use for anxiety control during third molar extraction and can be safely administered by a dedicated staff member. It can also be used with other drugs to obtain better sedative effects, but the patient's respiratory function must be monitored closely, because multidrug sedation is also more risky.
Topics: Anti-Anxiety Agents; Anxiety; Clinical Trials as Topic; Female; Humans; MEDLINE; Male; Midazolam; Molar; Tooth Extraction
PubMed: 25849859
DOI: 10.1371/journal.pone.0121410 -
Medicine Dec 2017Volatile sedation in the intensive care unit (ICU) may reduce the number of adverse events and improve patient outcomes compared with intravenous (IV) sedation. We... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Volatile sedation in the intensive care unit (ICU) may reduce the number of adverse events and improve patient outcomes compared with intravenous (IV) sedation. We performed a systematic review and meta-analysis comparing the effects of volatile and IV sedation in adult ICU patients.
METHODS
We searched the PubMed, Embase, Cochrane Central Register, and Web of Science databases for all randomized trials comparing volatile sedation using an anesthetic-conserving device (ACD) with IV sedation in terms of awakening and extubation times, lengths of ICU and hospital stay, and pharmacologic end-organ effects.
RESULTS
Thirteen trials with a total of 1027 patients were included. Volatile sedation (sevoflurane or isoflurane) administered through an ACD shortened the awakening time [mean difference (MD), -80.0 minutes; 95% confidence intervals (95% CIs), -134.5 to -25.6; P = .004] and extubation time (MD, -196.0 minutes; 95% CIs, -305.2 to -86.8; P < .001) compared with IV sedation (midazolam or propofol). No differences in the lengths of ICU and hospital stay were noted between the 2 groups. In the analysis of cardiac effects of sedation from 5 studies, patients who received volatile sedation showed lower serum troponin levels 6 hours after ICU admission than patients who received IV sedation (P < .05). The effect size of troponin was largest between 12 and 24 hours after ICU admission (MD, -0.27 μg/L; 95% CIs, -0.44 to -0.09; P = .003).
CONCLUSION
Compared with IV sedation, volatile sedation administered through an ACD in the ICU shortened the awakening and extubation times. Considering the difference in serum troponin levels between both arms, volatile anesthetics might have a myocardial protective effect after cardiac surgery even at a subanesthetic dose. Because the included studies used small sample sizes with high heterogeneity, further large, high-quality prospective clinical trials are needed to confirm our findings.
Topics: Airway Extubation; Anesthetics, Inhalation; Humans; Intensive Care Units; Isoflurane; Length of Stay; Methyl Ethers; Randomized Controlled Trials as Topic; Sevoflurane
PubMed: 29245269
DOI: 10.1097/MD.0000000000008976