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Anaesthesia Jul 2021Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure-specific efficacy as well as specific...
Tonsillectomy is one of the most frequently performed surgical procedures; however, pain management remains challenging. Procedure-specific efficacy as well as specific risks of treatment options should guide selection of pain management protocols based on evidence and should optimise analgesia without harm. The aims of this systematic review were to evaluate the available literature and develop recommendations for optimal pain management after tonsillectomy. A systematic review utilising preferred reporting items for systematic reviews and meta-analysis guidelines with procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials published in the English language up to November 2019 assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Out of the 719 potentially eligible studies identified, 226 randomised controlled trials met the inclusion criteria, excluding the studies examining surgical techniques. Pre-operative and intra-operative interventions that improved postoperative pain were paracetamol; non-steroidal anti-inflammatory drugs; intravenous dexamethasone; ketamine (only assessed in children); gabapentinoids; dexmedetomidine; honey; and acupuncture. Inconsistent evidence was found for local anaesthetic infiltration; antibiotics; and magnesium sulphate. Limited evidence was found for clonidine. The analgesic regimen for tonsillectomy should include paracetamol; non-steroidal anti-inflammatory drugs; and intravenous dexamethasone, with opioids as rescue analgesics. Analgesic adjuncts such as intra-operative and postoperative acupuncture as well as postoperative honey are also recommended. Ketamine (only for children); dexmedetomidine; or gabapentinoids may be considered when some of the first-line analgesics are contra-indicated. Further randomised controlled trials are required to define risk and combination of drugs most effective for postoperative pain relief after tonsillectomy.
Topics: Acupuncture; Analgesia; Analgesics; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Child; Honey; Humans; Pain Management; Pain, Postoperative; Practice Guidelines as Topic; Tonsillectomy
PubMed: 33201518
DOI: 10.1111/anae.15299 -
Medicina Intensiva Apr 2020Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new...
Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.
Topics: Analgesia; Anesthesia; Benzodiazepines; Conscious Sedation; Critical Care; Critical Illness; Delirium; Evidence-Based Medicine; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Pain Management
PubMed: 31492476
DOI: 10.1016/j.medin.2019.07.013 -
British Journal of Anaesthesia Oct 2022Guidelines have recommended the use of dexmedetomidine or propofol for sedation after cardiac surgery, and propofol monotherapy for other patients. Further outcome data... (Meta-Analysis)
Meta-Analysis Review
Outcomes of dexmedetomidine versus propofol sedation in critically ill adults requiring mechanical ventilation: a systematic review and meta-analysis of randomised controlled trials.
BACKGROUND
Guidelines have recommended the use of dexmedetomidine or propofol for sedation after cardiac surgery, and propofol monotherapy for other patients. Further outcome data are required for these drugs.
METHODS
This systematic review and meta-analysis was prospectively registered on PROSPERO. The primary outcome was ICU length of stay. Secondary outcomes included duration of mechanical ventilation, ICU delirium, all-cause mortality, and haemodynamic effects. Intensive care patients were analysed separately as cardiac surgical, medical/noncardiac surgical, those with sepsis, and patients in neurocritical care. Subgroup analyses based on age and dosage were conducted.
RESULTS
Forty-one trials (N=3948) were included. Dexmedetomidine did not significantly affect ICU length of stay across any ICU patient subtype when compared with propofol, but it reduced the duration of mechanical ventilation (mean difference -0.67 h; 95% confidence interval: -1.31 to -0.03 h; P=0.041; low certainty) and the risk of ICU delirium (risk ratio 0.49; 95% confidence interval: 0.29-0.87; P=0.019; high certainty) across cardiac surgical patients. Dexmedetomidine was also associated with a greater risk of bradycardia across a variety of ICU patients. Subgroup analyses revealed that age might affect the incidence of haemodynamic side-effects and mortality among cardiac surgical and medical/other surgical patients.
CONCLUSION
Dexmedetomidine did not significantly impact ICU length of stay compared with propofol, but it significantly reduced the duration of mechanical ventilation and the risk of delirium in cardiac surgical patients. It also significantly increased the risk of bradycardia across ICU patient subsets.
Topics: Adult; Bradycardia; Critical Illness; Delirium; Dexmedetomidine; Humans; Hypnotics and Sedatives; Intensive Care Units; Propofol; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35961815
DOI: 10.1016/j.bja.2022.06.020 -
British Journal of Anaesthesia Aug 2023Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common... (Meta-Analysis)
Meta-Analysis Review
Effect of perioperative benzodiazepine use on intraoperative awareness and postoperative delirium: a systematic review and meta-analysis of randomised controlled trials and observational studies.
BACKGROUND
Benzodiazepine use is associated with delirium, and guidelines recommend avoiding them in older and critically ill patients. Their perioperative use remains common because of perceived benefits.
METHODS
We searched CENTRAL, MEDLINE, CINAHL, PsycInfo, and Web of Science from inception to June 2021. Pairs of reviewers identified randomised controlled trials and prospective observational studies comparing perioperative use of benzodiazepines with other agents or placebo in patients undergoing surgery. Two reviewers independently abstracted data, which we combined using a random-effects model. Our primary outcomes were delirium, intraoperative awareness, and mortality.
RESULTS
We included 34 randomised controlled trials (n=4354) and nine observational studies (n=3309). Observational studies were considered separately. Perioperative benzodiazepines did not increase the risk of delirium (n=1352; risk ratio [RR] 1.43; 95% confidence interval [CI]: 0.9-2.27; I=72%; P=0.13; very low-quality evidence). Use of benzodiazepines instead of dexmedetomidine did, however, increase the risk of delirium (five studies; n=429; RR 1.83; 95% CI: 1.24-2.72; I=13%; P=0.002). Perioperative benzodiazepine use decreased the risk of intraoperative awareness (n=2245; RR 0.26; 95% CI: 0.12-0.58; I=35%; P=0.001; very low-quality evidence). When considering non-events, perioperative benzodiazepine use increased the probability of not having intraoperative awareness (RR 1.07; 95% CI: 1.01-1.13; I=98%; P=0.03; very low-quality evidence). Mortality was reported by one randomised controlled trial (n=800; RR 0.90; 95% CI: 0.20-3.1; P=0.80; very low quality).
CONCLUSIONS
In this systematic review and meta-analysis, perioperative benzodiazepine use did not increase postoperative delirium and decreased intraoperative awareness. Previously observed relationships of benzodiazepine use with delirium could be explained by comparisons with dexmedetomidine.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42019128144.
Topics: Humans; Aged; Benzodiazepines; Emergence Delirium; Dexmedetomidine; Intraoperative Awareness; Delirium; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36621439
DOI: 10.1016/j.bja.2022.12.001 -
Clinical Interventions in Aging 2019Vulnerable or "frail" patients are susceptible to the development of delirium when exposed to triggers such as surgical procedures. Once delirium occurs, interventions... (Meta-Analysis)
Meta-Analysis
Vulnerable or "frail" patients are susceptible to the development of delirium when exposed to triggers such as surgical procedures. Once delirium occurs, interventions have little effect on severity or duration, emphasizing the importance of primary prevention. This review provides an overview of interventions to prevent postoperative delirium in elderly patients undergoing elective surgery. A literature search was conducted in March 2018. Randomized controlled trials (RCTs) and before-and-after studies on interventions with potential effects on postoperative delirium in elderly surgical patients were included. Acute admission, planned ICU admission, and cardiac patients were excluded. Full texts were reviewed, and quality was assessed by two independent reviewers. Primary outcome was the incidence of delirium. Secondary outcomes were severity and duration of delirium. Pooled risk ratios (RRs) were calculated for incidences of delirium where similar intervention techniques were used. Thirty-one RCTs and four before-and-after studies were included for analysis. In 19 studies, intervention decreased the incidences of postoperative delirium. Severity was reduced in three out of nine studies which reported severity of delirium. Duration was reduced in three out of six studies. Pooled analysis showed a significant reduction in delirium incidence for dexmedetomidine treatment, and bispectral index (BIS)-guided anaesthesia. Based on sensitivity analyses, by leaving out studies with a high risk of bias, multicomponent interventions and antipsychotics can also significantly reduce the incidence of delirium. Multicomponent interventions, the use of antipsychotics, BIS-guidance, and dexmedetomidine treatment can successfully reduce the incidence of postoperative delirium in elderly patients undergoing elective, non-cardiac surgery. However, present studies are heterogeneous, and high-quality studies are scarce. Future studies should add these preventive methods to already existing multimodal and multidisciplinary interventions to tackle as many precipitating factors as possible, starting in the pre-admission period.
Topics: Aged; Antipsychotic Agents; Delirium; Elective Surgical Procedures; Hospitalization; Humans; Incidence; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 31354253
DOI: 10.2147/CIA.S201323 -
British Journal of Anaesthesia Dec 2019Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period.
METHODS
We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function.
RESULTS
Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4 T cells, and the ratios of CD4:CD8 and Th1:Th2 were significantly increased; CD8 T-cells were decreased in the DEX group when compared with the control group.
CONCLUSIONS
DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.
Topics: Adrenergic alpha-2 Receptor Agonists; Dexmedetomidine; Humans; Immunity; Inflammation; Intraoperative Complications; Postoperative Complications; Preoperative Period; Stress, Physiological
PubMed: 31668347
DOI: 10.1016/j.bja.2019.07.027 -
Anaesthesia Mar 2019Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary... (Meta-Analysis)
Meta-Analysis
Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non-systematic reviews were excluded. Twenty-five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26-0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20-0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46-3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48-2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66-1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta-analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.
Topics: Delirium; Dexmedetomidine; Humans; Intensive Care Units; Psychomotor Agitation
PubMed: 30367689
DOI: 10.1111/anae.14472 -
Medicine Jan 2020Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and...
BACKGROUND
Sedoanalgesia secondary iatrogenic withdrawal syndrome (IWS) in paediatric intensive units is frequent and its assessment is complex. Therapies are heterogeneous, and there is currently no gold standard method for diagnosis. In addition, the assessment scales validated in children are scarce. This paper aims to identify and describe both the paediatric diagnostic and assessment tools for the IWS and the treatments for the IWS in critically ill paediatric patients.
METHODS
A systematic review was conducted according to the PRISMA guidelines. This review included descriptive and observational studies published since 2000 that analyzed paediatric scales for the evaluation of the iatrogenic withdrawal syndrome and its treatments. The eligibility criteria included neonates, newborns, infants, pre-schoolers, and adolescents, up to age 18, who were admitted to the paediatric intensive care units with continuous infusion of hypnotics and/or opioid analgesics, and who presented signs or symptoms of deprivation related to withdrawal and prolonged infusion of sedoanalgesia.
RESULTS
Three assessment scales were identified: Withdrawal Assessment Tool-1, Sophia Observation Withdrawal Symptoms, and Opioid and Benzodiazepine Withdrawal Score. Dexmedetomidine, methadone and clonidine were revealed as options for the treatment and prevention of the iatrogenic withdrawal syndrome. Finally, the use of phenobarbital suppressed symptoms of deprivation that are resistant to other drugs.
CONCLUSIONS
The reviewed scales facilitate the assessment of the iatrogenic withdrawal syndrome and have a high diagnostic quality. However, its clinical use is very rare. The treatments identified in this review prevent and effectively treat this syndrome. The use of validated iatrogenic withdrawal syndrome assessment scales in paediatrics clinical practice facilitates assessment, have a high diagnostic quality, and should be encouraged, also ensuring nurses' training in their usage.
Topics: Child; Humans; Iatrogenic Disease; Intensive Care Units, Pediatric; Substance Withdrawal Syndrome
PubMed: 32000360
DOI: 10.1097/MD.0000000000018502 -
The Cochrane Database of Systematic... Sep 2019Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for...
BACKGROUND
Although delirium is typically an acute reversible cognitive impairment, its presence is associated with devastating impact on both short-term and long-term outcomes for critically ill patients. Advances in our understanding of the negative impact of delirium on patient outcomes have prompted trials evaluating multiple pharmacological interventions. However, considerable uncertainty surrounds the relative benefits and safety of available pharmacological interventions for this population.
OBJECTIVES
Primary objective1. To assess the effects of pharmacological interventions for treatment of delirium on duration of delirium in critically ill adults with confirmed or documented high risk of deliriumSecondary objectivesTo assess the following:1. effects of pharmacological interventions on delirium-free and coma-free days; days with coma; delirium relapse; duration of mechanical ventilation; intensive care unit (ICU) and hospital length of stay; mortality; and long-term outcomes (e.g. cognitive; discharge disposition; health-related quality of life); and2. the safety of such treatments for critically ill adult patients.
SEARCH METHODS
We searched the following databases from their inception date to 21 March 2019: Ovid MEDLINE®, Ovid MEDLINE® In-Process & Other Non-Indexed Citations, Embase Classic+Embase, and PsycINFO using the Ovid platform. We also searched the Cochrane Library on Wiley, the International Prospective Register of Systematic Reviews (PROSPERO) (http://www.crd.york.ac.uk/PROSPERO/), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science. We performed a grey literature search of relevant databases and websites using the resources listed in Grey Matters developed by the Canadian Agency for Drugs and Technologies in Health (CADTH). We also searched trial registries and abstracts from annual scientific critical care and delirium society meetings.
SELECTION CRITERIA
We sought randomized controlled trials (RCTs), including quasi-RCTs, of any pharmacological (drug) for treatment of delirium in critically ill adults. The drug intervention was to be compared to another active drug treatment, placebo, or a non-pharmacological intervention (e.g. mobilization). We did not apply any restrictions in terms of drug class, dose, route of administration, or duration of delirium or drug exposure. We defined critically ill patients as those treated in an ICU of any specialty (e.g. burn, cardiac, medical, surgical, trauma) or high-dependency unit.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified studies from the search results; four review authors (in pairs) performed data extraction and assessed risk of bias independently. We performed data synthesis through pairwise meta-analysis and network meta-analysis (NMA). Our hypothetical network structure was designed to be analysed at the drug class level and illustrated a network diagram of 'nodes' (i.e. drug classes) and 'edges' (i.e. comparisons between different drug classes from existing trials), thus describing a treatment network of all possible comparisons between drug classes. We assessed the quality of the body of evidence according to GRADE, as very low, low, moderate, or high.
MAIN RESULTS
We screened 7674 citations, from which 14 trials with 1844 participants met our inclusion criteria. Ten RCTs were placebo-controlled, and four reported comparisons of different drugs. Drugs examined in these trials were the following: antipsychotics (n = 10), alpha agonists (n = 3; all dexmedetomidine), statins (n = 2), opioids (n = 1; morphine), serotonin antagonists (n = 1; ondansetron), and cholinesterase (CHE) inhibitors (n = 1; rivastigmine). Only one of these trials consistently used non-pharmacological interventions that are known to improve patient outcomes in both intervention and control groups.Eleven studies (n = 1153 participants) contributed to analysis of the primary outcome. Results of the NMA showed that the intervention with the smallest ratio of means (RoM) (i.e. most preferred) compared with placebo was the alpha agonist dexmedetomidine (0.58; 95% credible interval (CrI) 0.26 to 1.27; surface under the cumulative ranking curve (SUCRA) 0.895; moderate-quality evidence). In order of descending SUCRA values (best to worst), the next best interventions were atypical antipsychotics (RoM 0.80, 95% CrI 0.50 to 1.11; SUCRA 0.738; moderate-quality evidence), opioids (RoM 0.88, 95% CrI 0.37 to 2.01; SUCRA 0.578; very-low quality evidence), and typical antipsychotics (RoM 0.96, 95% CrI 0.64 to1.36; SUCRA 0.468; high-quality evidence).The NMAs of multiple secondary outcomes revealed that only the alpha agonist dexmedetomidine was associated with a shorter duration of mechanical ventilation (RoM 0.55, 95% CrI 0.34 to 0.89; moderate-quality evidence), and the CHE inhibitor rivastigmine was associated with a longer ICU stay (RoM 2.19, 95% CrI 1.47 to 3.27; moderate-quality evidence). Adverse events often were not reported in these trials or, when reported, were rare; pair-wise analysis of QTc prolongation in seven studies did not show significant differences between antipsychotics, ondansetron, dexmedetomidine, and placebo.
AUTHORS' CONCLUSIONS
We identified trials of varying quality that examined six different drug classes for treatment of delirium in critically ill adults. We found evidence that the alpha agonist dexmedetomidine may shorten delirium duration, although this small effect (compared with placebo) was seen in pairwise analyses based on a single study and was not seen in the NMA results. Alpha agonists also ranked best for duration of mechanical ventilation and length of ICU stay, whereas the CHE inhibitor rivastigmine was associated with longer ICU stay. We found no evidence of a difference between placebo and any drug in terms of delirium-free and coma-free days, days with coma, physical restraint use, length of stay, long-term cognitive outcomes, or mortality. No studies reported delirium relapse, resolution of symptoms, or quality of life. The ten ongoing studies and the six studies awaiting classification that we identified, once published and assessed, may alter the conclusions of the review.
Topics: Antipsychotic Agents; Critical Illness; Delirium; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 31479532
DOI: 10.1002/14651858.CD011749.pub2 -
International Journal of Surgery... Jan 2023Postoperative cognitive dysfunction (POCD) is a common neurological system disorder in surgical patients. The choice of anesthetic can potentially reduce POCD. The... (Meta-Analysis)
Meta-Analysis
Postoperative cognitive dysfunction (POCD) is a common neurological system disorder in surgical patients. The choice of anesthetic can potentially reduce POCD. The authors performed this network meta-analysis to compare different anesthetic drugs in reducing the incidence of POCD for elderly people undergoing noncardiac surgery. We searched MEDLINE, EMBASE, the Cochrane Library, and the Web of Science for randomized controlled trials comparing the different anesthetic drugs for noncardiac surgery in elderly from inception until July, 2022. The protocol was registered on the PROSPERO database (CRD#42020183014). A total of 34 trials involving 4314 patients undergoing noncardiac surgery in elderly were included. The incidence of POCD for each anesthetic drug was placebo (27.7%), dexmedetomidine (12.9%), ketamine (15.2%), propofol (16.8%), fentanyl (23.9%), midazolam (11.3%), sufentanil (6.3%), sevoflurane (24.0%), and desflurane (28.3%). Pairwise and network meta-analysis showed dexmedetomidine was significantly reducing the incidence of POCD when compared with placebo. Network meta-analysis also suggested dexmedetomidine was significantly reducing the incidence of POCD when compared with sevoflurane. Sufentanil and dexmedetomidine ranked the first and second in reducing the incidence of POCD with the surface under the cumulative ranking curve value of 87.4 and 81.5%. Sufentanil and dexmedetomidine had the greatest possibility to reduce the incidence of POCD for elderly people undergoing noncardiac surgery.
Topics: Humans; Aged; Sevoflurane; Anesthetics, Inhalation; Dexmedetomidine; Postoperative Cognitive Complications; Sufentanil; Postoperative Complications
PubMed: 36799783
DOI: 10.1097/JS9.0000000000000001