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Journal of Critical Care Aug 2021Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Compare outcomes of adult patients admitted to ICU- length of ICU stay, length of mechanical ventilation (MV), and time until extubation- according to the use of propofol versus midazolam.
METHODS
We searched MEDLINE, EMBASE, LILACS, and Cochrane databases to retrieve RCTs that compared propofol and midazolam used as sedatives in adult ICU patients. We applied a random-effects, meta-analytic model in all calculations. We applied the Cochrane collaboration tool and GRADE. We separated patients into two groups: acute surgical patients (hospitalization up to 24 h) and critically-ill patients (hospitalization over 24 h and whose articles mostly mix surgical, medical and trauma patients).
RESULTS
Globally, propofol was associated with a reduced MV time of 4.46 h (MD: -4.46 [95% CI -7.51 to -1.42] p = 0.004, I2 = 63%, 6 studies) and extubation time of 7.95 h (MD: -7.95 [95% CI -9.86 to -6.03] p < 0.00001, I2 = 98%, 16 studies). Acute surgical patients sedation with propofol compared to midazolam was associated with a reduced ICU stay of 5.07 h (MD: -5.07 [95% CI -8.68 to -1.45] p = 0.006, I2 = 41%, 5 studies), MV time of 4.28 h (MD: -4.28; [95% CI -4.62 to -3.94] p < 0.0001, I2 = 0%, 3 studies), extubation time of 1.92 h (MD: -1.92; [95% CI -2.71 to -1.13] p = 0.00001, I2 = 89%, 9 studies). In critically-ill patients sedation with propofol compared to midazolam was associated with a reduced extubation time of 32.68 h (MD: -32.68 [95% CI -48.37 to -16.98] p = 0.0001, I2 = 97%, 9 studies). GRADE was very low for all outcomes.
CONCLUSIONS
Sedation with propofol compared to midazolam is associated with improved clinical outcomes in ICU, with reduced ICU stay MV time and extubation time in acute surgical patients and reduced extubation time in critically-ill patients.
Topics: Adult; Critical Care; Humans; Hypnotics and Sedatives; Intensive Care Units; Midazolam; Propofol; Respiration, Artificial
PubMed: 33838522
DOI: 10.1016/j.jcrc.2021.04.001 -
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 -
Minerva Anestesiologica Dec 2022The aim of this systemic review and meta-analysis was to evaluate the efficacy and safety of remimazolam compared with propofol when used for procedural sedation and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this systemic review and meta-analysis was to evaluate the efficacy and safety of remimazolam compared with propofol when used for procedural sedation and general anesthesia.
EVIDENCE ACQUISITION
Data sources were PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicaTrials.gov, searched up to March 21, 2022. RCTs comparing remimazolam and propofol in patients undergoing procedural sedation or general anesthesia were searched. Pooled risk ratios (RRs) or standardized mean difference, 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. The trial sequential analysis was used for sensitivity analysis.
EVIDENCE SYNTHESIS
Ten studies with 1813 patients were included. Compared with propofol, remimazolam had lower success rate of sedation/general anesthesia (RR, 1.02; 95% CI: 1.01 to 1.03; P=0.004; N.=1402). However, remimazolam had lower incidence of hypoxia, hypotension, and injection pain than propofol. No difference in incidence of nausea and vomiting, time to awake and to discharge was found. Subgroup studies showed that remimazolam had lower success rate than propofol when used for procedural sedation, not general anesthesia. The trial sequential analysis adjusted confidence interval was 1.01 to 1.04 for success rate.
CONCLUSIONS
Remimazolam could be alternatively used in procedural sedation and general anesthesia. Additional research is needed to develop higher quality evidence on the use of remimazolam, especially in general anesthesia.
Topics: Humans; Anesthesia, General; Benzodiazepines; Hypnotics and Sedatives; Hypotension; Propofol
PubMed: 36326772
DOI: 10.23736/S0375-9393.22.16817-3 -
Current Clinical Pharmacology 2019Opioid analgesics are commonly used along with propofol during general anesthesia. Due to the dearth of data on the quality of anesthesia achieved with this combination,... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of Fentanyl, Remifentanil, Sufentanil and Alfentanil in Combination with Propofol for General Anesthesia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
BACKGROUND
Opioid analgesics are commonly used along with propofol during general anesthesia. Due to the dearth of data on the quality of anesthesia achieved with this combination, the present meta-analysis was carried out.
METHODS
Electronic databases were searched for appropriate studies using a suitable search strategy. Randomized clinical trials comparing the combination of remifentanil/sufentanil/alfentanil with propofol with fentanyl and propofol, were included. The outcome measures were as follows: total propofol dose to achieve the desired general anesthesia; time of onset and duration of general anesthesia; depth of general anesthesia; and recovery time (time for eye-opening and time taken for extubation). Risk of bias was assessed and Forest plots were generated for eligible outcomes. The weighted mean difference [95% confidence intervals] was used as the effect estimate.
RESULTS
Fourteen studies were included in the systematic review and 13 were included in the metaanalysis. Statistically significant differences were observed for remifentanil in comparison to fentanyl when combined with propofol: Propofol dose (in mg) -76.18 [-94.72, -57.64]; time of onset of anesthesia (min) -0.44 [-0.74, -0.15]; time taken for eye-opening (min) -3.95 [-4.8, -3.1]; and time for extubation (min) -3.53 [-4.37, -2.7]. No significant differences were observed for either sufentanil or alfentanil about the dose of propofol required and due to scanty data, pooling of the data could not be attempted for other outcome measures for either sufentanil or alfentanil.
CONCLUSION
To conclude, we found that remifentanil has a statistically significant anesthetic profile than fentanyl when combined with propofol. Scanty evidence for both alfentanil and sufentanil precludes any such confirmation.
Topics: Alfentanil; Anesthesia, General; Anesthesia, Intravenous; Anesthetics, Intravenous; Fentanyl; Humans; Propofol; Randomized Controlled Trials as Topic; Remifentanil; Sufentanil
PubMed: 30868958
DOI: 10.2174/1567201816666190313160438 -
Frontiers in Pharmacology 2023The primary objective of this study was to compare the risk of hypotension, as well as the induction and recovery characteristics between remimazolam and propofol in...
The primary objective of this study was to compare the risk of hypotension, as well as the induction and recovery characteristics between remimazolam and propofol in patients receiving surgery under general anesthesia. The Embase, Medline, Google scholar, and the Cochrane Library databases were searched from inception to March 2022 for randomized controlled trials The primary outcome was the risk of post-induction hypotension between the two agents, while the secondary outcomes included anesthetic depth, induction efficacy, time to loss of consciousness (LOC), hemodynamic profiles, time to eye opening, extubation time as well as the incidence of injection pain and postoperative nausea/vomiting (PONV). Meta-analysis of eight studies published from 2020 to 2022 involving 738 patients revealed a significantly lower risk of post-induction hypotension with the use of remimazolam compared to that with propofol [risk ratio (RR) = 0.57, 95% confidence interval (CI): 0.43 to 0.75, < 0.0001, I = 12%, five studies, 564 patients]. After anesthetic induction, the anesthetic depth measured by bispectral index (BIS) was lighter in the remimazolam group than that in the propofol group (MD = 9.26, 95% confidence interval: 3.06 to 15.47, = 0.003, I = 94%, five studies, 490 patients). The time to loss of consciousness was also longer in the former compared to the latter (MD = 15.49 s, 95%CI: 6.53 to 24.46, = 0.0007, I = 61%, three studies, 331 patients). However, the use of remimazolam correlated with a lower risk of injection pain (RR = 0.03, 95%CI: 0.01 to 0.16, < 0.0001, I = 0%, three studies, 407 patients) despite comparable efficacy of anesthetic induction (RR = 0.98, 95%CI: 0.9 to 1.06, = 0.57, I = 76%, two studies, 319 patients). Our results demonstrated no difference in time to eye opening, extubation time, and risk of PONV between the two groups. Remimazolam was associated with a lower risk of post-induction hypotension after anesthetic induction compared with propofol with similar recovery characteristics. Further studies are required to support our findings. https://www.crd.york.ac.uk/prospero/; Identifier: CRD42022320658.
PubMed: 36814492
DOI: 10.3389/fphar.2023.1101728 -
Intensive Care Medicine Jul 2022Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU).... (Meta-Analysis)
Meta-Analysis
Conventional gabaminergic sedatives such as benzodiazepines and propofol are commonly used in mechanically ventilated patients in the intensive care unit (ICU). Dexmedetomidine is an alternative sedative that may achieve lighter sedation, reduce delirium, and provide analgesia. Our objective was to perform a comprehensive systematic review summarizing the large body of evidence, determining if dexmedetomidine reduces delirium compared to conventional sedatives. We searched MEDLINE, EMBASE, CENTRAL, ClinicalTrials.gov and the WHO ICTRP from inception to October 2021. Independent pairs of reviewers identified randomized clinical trials comparing dexmedetomidine to other sedatives for mechanically ventilated adults in the ICU. We conducted meta-analyses using random-effects models. The results were reported as relative risks (RRs) for binary outcomes and mean differences (MDs) for continuous outcomes, with corresponding 95% confidence intervals (CIs). In total, 77 randomized trials (n = 11,997) were included. Compared to other sedatives, dexmedetomidine reduced the risk of delirium (RR 0.67, 95% CI 0.55 to 0.81; moderate certainty), the duration of mechanical ventilation (MD - 1.8 h, 95% CI - 2.89 to - 0.71; low certainty), and ICU length of stay (MD - 0.32 days, 95% CI - 0.42 to - 0.22; low certainty). Dexmedetomidine use increased the risk of bradycardia (RR 2.39, 95% CI 1.82 to 3.13; moderate certainty) and hypotension (RR 1.32, 95% CI 1.07 to 1.63; low certainty). In mechanically ventilated adults, the use of dexmedetomidine compared to other sedatives, resulted in a lower risk of delirium, and a modest reduction in duration of mechanical ventilation and ICU stay, but increased the risks of bradycardia and hypotension.
Topics: Adult; Bradycardia; Critical Illness; Delirium; Dexmedetomidine; Humans; Hypnotics and Sedatives; Hypotension; Intensive Care Units; Randomized Controlled Trials as Topic; Respiration, Artificial
PubMed: 35648198
DOI: 10.1007/s00134-022-06712-2 -
The Cochrane Database of Systematic... Oct 2020Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is a common adverse effect of anaesthesia and surgery. Up to 80% of patients may be affected. These outcomes are a major cause of patient dissatisfaction and may lead to prolonged hospital stay and higher costs of care along with more severe complications. Many antiemetic drugs are available for prophylaxis. They have various mechanisms of action and side effects, but there is still uncertainty about which drugs are most effective with the fewest side effects.
OBJECTIVES
• To compare the efficacy and safety of different prophylactic pharmacologic interventions (antiemetic drugs) against no treatment, against placebo, or against each other (as monotherapy or combination prophylaxis) for prevention of postoperative nausea and vomiting in adults undergoing any type of surgery under general anaesthesia • To generate a clinically useful ranking of antiemetic drugs (monotherapy and combination prophylaxis) based on efficacy and safety • To identify the best dose or dose range of antiemetic drugs in terms of efficacy and safety SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and reference lists of relevant systematic reviews. The first search was performed in November 2017 and was updated in April 2020. In the update of the search, 39 eligible studies were found that were not included in the analysis (listed as awaiting classification).
SELECTION CRITERIA
Randomized controlled trials (RCTs) comparing effectiveness or side effects of single antiemetic drugs in any dose or combination against each other or against an inactive control in adults undergoing any type of surgery under general anaesthesia. All antiemetic drugs belonged to one of the following substance classes: 5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, corticosteroids, antihistamines, and anticholinergics. No language restrictions were applied. Abstract publications were excluded.
DATA COLLECTION AND ANALYSIS
A review team of 11 authors independently assessed trials for inclusion and risk of bias and subsequently extracted data. We performed pair-wise meta-analyses for drugs of direct interest (amisulpride, aprepitant, casopitant, dexamethasone, dimenhydrinate, dolasetron, droperidol, fosaprepitant, granisetron, haloperidol, meclizine, methylprednisolone, metoclopramide, ondansetron, palonosetron, perphenazine, promethazine, ramosetron, rolapitant, scopolamine, and tropisetron) compared to placebo (inactive control). We performed network meta-analyses (NMAs) to estimate the relative effects and ranking (with placebo as reference) of all available single drugs and combinations. Primary outcomes were vomiting within 24 hours postoperatively, serious adverse events (SAEs), and any adverse event (AE). Secondary outcomes were drug class-specific side effects (e.g. headache), mortality, early and late vomiting, nausea, and complete response. We performed subgroup network meta-analysis with dose of drugs as a moderator variable using dose ranges based on previous consensus recommendations. We assessed certainty of evidence of NMA treatment effects for all primary outcomes and drug class-specific side effects according to GRADE (CINeMA, Confidence in Network Meta-Analysis). We restricted GRADE assessment to single drugs of direct interest compared to placebo.
MAIN RESULTS
We included 585 studies (97,516 randomized participants). Most of these studies were small (median sample size of 100); they were published between 1965 and 2017 and were primarily conducted in Asia (51%), Europe (25%), and North America (16%). Mean age of the overall population was 42 years. Most participants were women (83%), had American Society of Anesthesiologists (ASA) physical status I and II (70%), received perioperative opioids (88%), and underwent gynaecologic (32%) or gastrointestinal surgery (19%) under general anaesthesia using volatile anaesthetics (88%). In this review, 44 single drugs and 51 drug combinations were compared. Most studies investigated only single drugs (72%) and included an inactive control arm (66%). The three most investigated single drugs in this review were ondansetron (246 studies), dexamethasone (120 studies), and droperidol (97 studies). Almost all studies (89%) reported at least one efficacy outcome relevant for this review. However, only 56% reported at least one relevant safety outcome. Altogether, 157 studies (27%) were assessed as having overall low risk of bias, 101 studies (17%) overall high risk of bias, and 327 studies (56%) overall unclear risk of bias. Vomiting within 24 hours postoperatively Relative effects from NMA for vomiting within 24 hours (282 RCTs, 50,812 participants, 28 single drugs, and 36 drug combinations) suggest that 29 out of 36 drug combinations and 10 out of 28 single drugs showed a clinically important benefit (defined as the upper end of the 95% confidence interval (CI) below a risk ratio (RR) of 0.8) compared to placebo. Combinations of drugs were generally more effective than single drugs in preventing vomiting. However, single NK₁ receptor antagonists showed treatment effects similar to most of the drug combinations. High-certainty evidence suggests that the following single drugs reduce vomiting (ordered by decreasing efficacy): aprepitant (RR 0.26, 95% CI 0.18 to 0.38, high certainty, rank 3/28 of single drugs); ramosetron (RR 0.44, 95% CI 0.32 to 0.59, high certainty, rank 5/28); granisetron (RR 0.45, 95% CI 0.38 to 0.54, high certainty, rank 6/28); dexamethasone (RR 0.51, 95% CI 0.44 to 0.57, high certainty, rank 8/28); and ondansetron (RR 0.55, 95% CI 0.51 to 0.60, high certainty, rank 13/28). Moderate-certainty evidence suggests that the following single drugs probably reduce vomiting: fosaprepitant (RR 0.06, 95% CI 0.02 to 0.21, moderate certainty, rank 1/28) and droperidol (RR 0.61, 95% CI 0.54 to 0.69, moderate certainty, rank 20/28). Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol showed clinically important benefit, but low doses showed no clinically important benefit. Aprepitant was used mainly at high doses, ramosetron at recommended doses, and fosaprepitant at doses of 150 mg (with no dose recommendation available). Frequency of SAEs Twenty-eight RCTs were included in the NMA for SAEs (10,766 participants, 13 single drugs, and eight drug combinations). The certainty of evidence for SAEs when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to low. Droperidol (RR 0.88, 95% CI 0.08 to 9.71, low certainty, rank 6/13) may reduce SAEs. We are uncertain about the effects of aprepitant (RR 1.39, 95% CI 0.26 to 7.36, very low certainty, rank 11/13), ramosetron (RR 0.89, 95% CI 0.05 to 15.74, very low certainty, rank 7/13), granisetron (RR 1.21, 95% CI 0.11 to 13.15, very low certainty, rank 10/13), dexamethasone (RR 1.16, 95% CI 0.28 to 4.85, very low certainty, rank 9/13), and ondansetron (RR 1.62, 95% CI 0.32 to 8.10, very low certainty, rank 12/13). No studies reporting SAEs were available for fosaprepitant. Frequency of any AE Sixty-one RCTs were included in the NMA for any AE (19,423 participants, 15 single drugs, and 11 drug combinations). The certainty of evidence for any AE when using one of the best and most reliable anti-vomiting drugs (aprepitant, ramosetron, granisetron, dexamethasone, ondansetron, and droperidol compared to placebo) ranged from very low to moderate. Granisetron (RR 0.92, 95% CI 0.80 to 1.05, moderate certainty, rank 7/15) probably has no or little effect on any AE. Dexamethasone (RR 0.77, 95% CI 0.55 to 1.08, low certainty, rank 2/15) and droperidol (RR 0.89, 95% CI 0.81 to 0.98, low certainty, rank 6/15) may reduce any AE. Ondansetron (RR 0.95, 95% CI 0.88 to 1.01, low certainty, rank 9/15) may have little or no effect on any AE. We are uncertain about the effects of aprepitant (RR 0.87, 95% CI 0.78 to 0.97, very low certainty, rank 3/15) and ramosetron (RR 1.00, 95% CI 0.65 to 1.54, very low certainty, rank 11/15) on any AE. No studies reporting any AE were available for fosaprepitant. Class-specific side effects For class-specific side effects (headache, constipation, wound infection, extrapyramidal symptoms, sedation, arrhythmia, and QT prolongation) of relevant substances, the certainty of evidence for the best and most reliable anti-vomiting drugs mostly ranged from very low to low. Exceptions were that ondansetron probably increases headache (RR 1.16, 95% CI 1.06 to 1.28, moderate certainty, rank 18/23) and probably reduces sedation (RR 0.87, 95% CI 0.79 to 0.96, moderate certainty, rank 5/24) compared to placebo. The latter effect is limited to recommended and high doses of ondansetron. Droperidol probably reduces headache (RR 0.76, 95% CI 0.67 to 0.86, moderate certainty, rank 5/23) compared to placebo. We have high-certainty evidence that dexamethasone (RR 1.00, 95% CI 0.91 to 1.09, high certainty, rank 16/24) has no effect on sedation compared to placebo. No studies assessed substance class-specific side effects for fosaprepitant. Direction and magnitude of network effect estimates together with level of evidence certainty are graphically summarized for all pre-defined GRADE-relevant outcomes and all drugs of direct interest compared to placebo in http://doi.org/10.5281/zenodo.4066353.
AUTHORS' CONCLUSIONS
We found high-certainty evidence that five single drugs (aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron) reduce vomiting, and moderate-certainty evidence that two other single drugs (fosaprepitant and droperidol) probably reduce vomiting, compared to placebo. Four of the six substance classes (5-HT₃ receptor antagonists, D₂ receptor antagonists, NK₁ receptor antagonists, and corticosteroids) were thus represented by at least one drug with important benefit for prevention of vomiting. Combinations of drugs were generally more effective than the corresponding single drugs in preventing vomiting. NK₁ receptor antagonists were the most effective drug class and had comparable efficacy to most of the drug combinations. 5-HT₃ receptor antagonists were the best studied substance class. For most of the single drugs of direct interest, we found only very low to low certainty evidence for safety outcomes such as occurrence of SAEs, any AE, and substance class-specific side effects. Recommended and high doses of granisetron, dexamethasone, ondansetron, and droperidol were more effective than low doses for prevention of vomiting. Dose dependency of side effects was rarely found due to the limited number of studies, except for the less sedating effect of recommended and high doses of ondansetron. The results of the review are transferable mainly to patients at higher risk of nausea and vomiting (i.e. healthy women undergoing inhalational anaesthesia and receiving perioperative opioids). Overall study quality was limited, but certainty assessments of effect estimates consider this limitation. No further efficacy studies are needed as there is evidence of moderate to high certainty for seven single drugs with relevant benefit for prevention of vomiting. However, additional studies are needed to investigate potential side effects of these drugs and to examine higher-risk patient populations (e.g. individuals with diabetes and heart disease).
Topics: Adult; Anesthesia, General; Antiemetics; Drug Therapy, Combination; Female; Humans; Male; Network Meta-Analysis; Placebos; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33075160
DOI: 10.1002/14651858.CD012859.pub2 -
Clinical Toxicology (Philadelphia, Pa.) Feb 2018Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate...
CONTEXT
Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate that lamotrigine overdose is usually benign. However, there are reported cases of cardiac arrest and mortality following lamotrigine overdose. We undertook a systematic review of the literature on lamotrigine overdoses to better understand the clinical severity, the relevance of serum concentrations, and therapeutic interventions for overdose.
OBJECTIVES
To characterize manifestations of acute lamotrigine overdose, determine if serum concentrations predict poisoning severity, and evaluate the effectiveness of overdose management interventions.
METHODS
We performed a literature search across eight databases, including Medline, EMBASE, and the Cochrane Library, from database inception to April 2014. Major bibliographic databases were updated on 31 May 2017. Articles were eligible if they described acute or acute on chronic lamotrigine overdose. At least one serum lamotrigine concentration had to be reported for inclusion. Reports on chronic poisoning, studies describing adverse effects of therapeutic use, and animal studies were excluded.
RESULTS
We retrieved 6238 records; 48 (51 cases) met the inclusion criteria. Cases primarily involved adults (70.6%). Potentially life-threatening symptoms of overdose included seizures (55%), Glasgow Coma Scale ≤8 (20%), hypotension (12%), and wide complex tachycardia (WCT) and cardiac arrest (6%). Among the 25 cases exposed to lamotrigine alone (13 adult; 12 pediatric), 2 adult fatalities occurred (4 g and 7.5 g ingested) and 8 pediatric cases experienced seizures (all children ≤3.5-years-old, 75% without an underlying seizure disorder, ≥ 525 mg ingested). The lowest seizure-associated serum concentration was 3.8 mg/L and 25.6 mg/L for pediatric and adult patients, respectively, suggesting children may be more susceptible to CNS toxicity. Cardiovascular toxicities occurred primarily in adult patients (threshold >25 mg/L). Overdose interventions included benzodiazepines (53%), propofol or barbiturates (14%), NaHCO (20%), lipid therapy (12%), and extracorporeal elimination (10%). NaHCO yielded no response in four of nine cases with conduction delays; however, two of the four cases subsequently responded with lipid therapy.
CONCLUSIONS
Most cases reporting lamotrigine exposures observed mild or no toxicity; however, large exposures were associated with severe CNS depression, seizures, cardiac conduction delays, wide complex tachycardia, and death. In adults with a serum concentration >25 mg/L, severe toxicity may occur. In patients ≤3.5 years of age, ingestions of ≥525 mg may produce severe CNS depression and seizures.
Topics: Adult; Anticonvulsants; Child; Drug Overdose; Humans; Lamotrigine; Renal Dialysis
PubMed: 28862044
DOI: 10.1080/15563650.2017.1370096 -
Journal of Pain and Symptom Management Apr 2021Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed,... (Review)
Review
CONTEXT
Near the end of life when patients experience refractory symptoms, palliative sedation may be considered as a last treatment. Clinical guidelines have been developed, but they are mainly based on expert opinion or retrospective chart reviews. Therefore, evidence for the clinical aspects of palliative sedation is needed.
OBJECTIVES
To explore clinical aspects of palliative sedation in recent prospective studies.
METHODS
Systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered at PROSPERO. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014-December 2019), combining sedation, palliative care, and prospective. Article quality was assessed.
RESULTS
Ten prospective articles were included, involving predominantly patients with cancer. Most frequently reported refractory symptoms were delirium (41%-83%), pain (25%-65%), and dyspnea (16%-59%). In some articles, psychological and existential distress were mentioned (16%-59%). Only a few articles specified the tools used to assess symptoms. Level of sedation assessment tools were the Richmond Agitation Sedation Scale, Ramsay Sedation Scale, Glasgow Coma Scale, and Bispectral Index monitoring. The palliative sedation practice shows an underlying need for proportionality in relation to symptom intensity. Midazolam was the main sedative used. Other reported medications were phenobarbital, promethazine, and anesthetic medication-propofol. The only study that reported level of patient's discomfort as a palliative sedation outcome showed a decrease in patient discomfort.
CONCLUSION
Assessment of refractory symptoms should include physical evaluation with standardized tools applied and interviews for psychological and existential evaluation by expert clinicians working in teams. Future research needs to evaluate the effectiveness of palliative sedation for refractory symptom relief.
Topics: Hospice and Palliative Care Nursing; Humans; Hypnotics and Sedatives; Palliative Care; Prospective Studies; Retrospective Studies; Terminal Care
PubMed: 32961218
DOI: 10.1016/j.jpainsymman.2020.09.022 -
Anaesthesiology Intensive Therapy 2021One ampoule of propofol is often divided into several syringes or is sometimes combined with other drugs that may lead to incompatibility and instability. A systematic... (Review)
Review
One ampoule of propofol is often divided into several syringes or is sometimes combined with other drugs that may lead to incompatibility and instability. A systematic review of literature (PubMed, Science Direct, and Google Scholar) identified 37 pieces of research which suggest that the data on propofol stability are limited. Results of all of the identified studies indicated that the stability of propofol is less than 24 hours. Additionally, the evidence shows that glass packaging as well as storing in cold and dark conditions promote stability. What is more, propofol was proved to be incompatible with 23 of the 36 drugs tested. In conclusion, there is a relatively small body of literature that measures the physical stability of propofol. The findings of this review recommend keeping propofol in glass and storing it no longer than 24 hours. Compatibility data must be considered in co-administrations with propofol.
Topics: Humans; Pharmaceutical Preparations; Propofol; Syringes
PubMed: 33586420
DOI: 10.5114/ait.2021.103542