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World Neurosurgery May 2024Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Ischemic stroke significantly contributes to high mortality and disability rates. Cerebral edema is a common consequence of ischemic stroke and can lead to aggravation or even death. Current treatment strategies are limited to decompressive craniectomy and the intravascular administration of hypertonic drugs, which have significant side effects. Acetazolamide (ACZ) plays a therapeutic role in cerebral edema by inhibiting aquaporin-4 (AQP-4) and improving collateral circulation. This study aimed to perform a meta-analysis and systematic review of ACZ therapy for ischemic stroke and evaluate its efficacy in animal models.
METHODS
We searched Embase, Cochrane Library, PubMed, Web of Science, Chinese National Knowledge Infrastructure, Wanfang Database, and Chinese Biomedical Literature Database until April 2023 for studies on ACZ in ischemic animal models. The quality of the animal trials was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Stroke.
RESULTS
After screening 376 articles, only 5 studies were included. We found that ACZ reduced brain edema in cerebral ischemia 24 hours after onset (standard mean difference, -2.00; 95% confidence interval, -3.57 to -0.43, P = 0.01). ACZ also inhibited AQP-4 expression 24 hours after onset (standard mean difference-1.46; 95% confidence interval, -2.01 to -0.91, P < 0.001). Brain edema and AQP-4 expression also showed a declining trend on the third day after onset, although there were not enough data to support this. The effect of ACZ on brain ischemia in animals' neurological function is uncertain because of the limited research data.
CONCLUSIONS
ACZ inhibited AQP-4 and alleviated brain edema after ischemic stroke in the early stages but seemingly could not improve the neurological function.
Topics: Acetazolamide; Ischemic Stroke; Animals; Brain Edema; Humans; Treatment Outcome; Aquaporin 4; Carbonic Anhydrase Inhibitors; Disease Models, Animal
PubMed: 38423457
DOI: 10.1016/j.wneu.2024.02.123 -
BMJ Open Respiratory Research Apr 2020Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acetazolamide (AZM) is used for various conditions (eg, altitude sickness, sleep apnoea, glaucoma), but therapy is often limited by its side effect profile. Our objective was to estimate the risk of commonly reported side effects based on meta-analyses. We hypothesised that these risks are dose-dependent.
METHODS
We queried MEDLINE/EMBASE (Medical Literature Analysis and Retrieval System Online/Excerpta Medica dataBASE) up until 04/10/2019, including any randomised placebo-controlled trial in which adults received oral AZM versus placebo reporting side effects. Eligibility assessment was performed by two independent reviewers. Data were abstracted by one reviewer who verified key entries at a second time point. For side effects reported by 3 studies a pooled effect estimate was calculated, and heterogeneity assessed via I; for outcomes reported by 5 studies effect modification by total daily dose (EMbyTDD; <400 mg/d, 400-600 mg/d, >600 mg/d) was assessed via meta-regression. For pre-specified, primary outcomes (paraesthesias, taste disturbances, polyuria and fatigue) additional subgroup analyses were performed using demographics, intervention details, laboratory changes and risk of bias.
RESULTS
We included 42 studies in the meta-analyses (N=1274/1211 in AZM/placebo groups). AZM increased the risk of all primary outcomes (p<0.01, I ≤16% and low-to-moderate quality of evidence for all)-the numbers needed to harm (95% CI; n) for each were: paraesthesias 2.3 (95% CI 2 to 2.7; n=39), dysgeusia 18 (95% CI 10 to 38, n=22), polyuria 17 (95% CI 9 to 49; n=22), fatigue 11 (95% CI 6 to 24; n=14). The risk for paraesthesias (beta=1.8 (95% CI 1.1 to 2.9); P=0.01) and dysgeusia (beta=3.1 (95% CI 1.2 to 8.2); P=0.02) increased with higher AZM doses; the risk of fatigue also increased with higher dose but non-significantly (beta=2.6 (95% CI 0.7 to 9.4); P=0.14).
DISCUSSION
This comprehensive meta-analysis of low-to-moderate quality evidence defines risk of common AZM side effects and corroborates dose dependence of some side effects. These results may inform clinical decision making and support efforts to establish the lowest effective dose of AZM for various conditions.
Topics: Acetazolamide; Adult; Dose-Response Relationship, Drug; Dysgeusia; Fatigue; Humans; Paresthesia; Randomized Controlled Trials as Topic
PubMed: 32332024
DOI: 10.1136/bmjresp-2020-000557 -
The Cochrane Database of Systematic... Feb 2023The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea... (Review)
Review
BACKGROUND
The term central sleep apnoea (CSA) encompasses diverse clinical situations where a dysfunctional drive to breathe leads to recurrent respiratory events, namely apnoea (complete absence of ventilation) and hypopnoea sleep (insufficient ventilation) during sleep. Studies have demonstrated that CSA responds to some extent to pharmacological agents with distinct mechanisms, such as sleep stabilisation and respiratory stimulation. Some therapies for CSA are associated with improved quality of life, although the evidence on this association is uncertain. Moreover, treatment of CSA with non-invasive positive pressure ventilation is not always effective or safe and may result in a residual apnoea-hypopnoea index.
OBJECTIVES
To evaluate the benefits and harms of pharmacological treatment compared with active or inactive controls for central sleep apnoea in adults.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 30 August 2022.
SELECTION CRITERIA
We included parallel and cross-over randomised controlled trials (RCTs) that evaluated any type of pharmacological agent compared with active controls (e.g. other medications) or passive controls (e.g. placebo, no treatment or usual care) in adults with CSA as defined by the International Classification of Sleep Disorders 3rd Edition. We did not exclude studies based on the duration of intervention or follow-up. We excluded studies focusing on CSA due to periodic breathing at high altitudes.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were central apnoea-hypopnoea index (cAHI), cardiovascular mortality and serious adverse events. Our secondary outcomes were quality of sleep, quality of life, daytime sleepiness, AHI, all-cause mortality, time to life-saving cardiovascular intervention, and non-serious adverse events. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included four cross-over RCTs and one parallel RCT, involving a total of 68 participants. Mean age ranged from 66 to 71.3 years and most participants were men. Four trials recruited people with CSA associated with heart failure, and one study included people with primary CSA. Types of pharmacological agents were acetazolamide (carbonic anhydrase inhibitor), buspirone (anxiolytic), theophylline (methylxanthine derivative) and triazolam (hypnotic), which were given for between three days and one week. Only the study on buspirone reported a formal evaluation of adverse events. These events were rare and mild. No studies reported serious adverse events, quality of sleep, quality of life, all-cause mortality, or time to life-saving cardiovascular intervention. Carbonic anhydrase inhibitors versus inactive control Results were from two studies of acetazolamide versus placebo (n = 12) and acetazolamide versus no acetazolamide (n = 18) for CSA associated with heart failure. One study reported short-term outcomes and the other reported intermediate-term outcomes. We are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce cAHI in the short term (mean difference (MD) -26.00 events per hour, 95% CI -43.84 to -8.16; 1 study, 12 participants; very low certainty). Similarly, we are uncertain whether carbonic anhydrase inhibitors compared to inactive control reduce AHI in the short term (MD -23.00 events per hour, 95% CI -37.70 to 8.30; 1 study, 12 participants; very low certainty) or in the intermediate term (MD -6.98 events per hour, 95% CI -10.66 to -3.30; 1 study, 18 participants; very low certainty). The effect of carbonic anhydrase inhibitors on cardiovascular mortality in the intermediate term was also uncertain (odds ratio (OR) 0.21, 95% CI 0.02 to 2.48; 1 study, 18 participants; very low certainty). Anxiolytics versus inactive control Results were based on one study of buspirone versus placebo for CSA associated with heart failure (n = 16). The median difference between groups for cAHI was -5.00 events per hour (IQR -8.00 to -0.50), the median difference for AHI was -6.00 events per hour (IQR -8.80 to -1.80), and the median difference on the Epworth Sleepiness Scale for daytime sleepiness was 0 points (IQR -1.0 to 0.00). Methylxanthine derivatives versus inactive control Results were based on one study of theophylline versus placebo for CSA associated with heart failure (n = 15). We are uncertain whether methylxanthine derivatives compared to inactive control reduce cAHI (MD -20.00 events per hour, 95% CI -32.15 to -7.85; 15 participants; very low certainty) or AHI (MD -19.00 events per hour, 95% CI -30.27 to -7.73; 15 participants; very low certainty). Hypnotics versus inactive control Results were based on one trial of triazolam versus placebo for primary CSA (n = 5). Due to very serious methodological limitations and insufficient reporting of outcome measures, we were unable to draw any conclusions regarding the effects of this intervention.
AUTHORS' CONCLUSIONS
There is insufficient evidence to support the use of pharmacological therapy in the treatment of CSA. Although small studies have reported positive effects of certain agents for CSA associated with heart failure in reducing the number of respiratory events during sleep, we were unable to assess whether this reduction may impact the quality of life of people with CSA, owing to scarce reporting of important clinical outcomes such as sleep quality or subjective impression of daytime sleepiness. Furthermore, the trials mostly had short-term follow-up. There is a need for high-quality trials that evaluate longer-term effects of pharmacological interventions.
Topics: Male; Adult; Humans; Aged; Female; Sleep Apnea, Central; Carbonic Anhydrase Inhibitors; Buspirone; Apnea; Triazolam; Theophylline; Acetazolamide; Heart Failure; Hypnotics and Sedatives; Disorders of Excessive Somnolence
PubMed: 36861808
DOI: 10.1002/14651858.CD012922.pub2 -
Indian Journal of Endocrinology and... 2023The data on the characteristics of patients with idiopathic intracranial hypertension (IIH) following levothyroxine (LT4) replacement are limited. Here, we report a case... (Review)
Review
The data on the characteristics of patients with idiopathic intracranial hypertension (IIH) following levothyroxine (LT4) replacement are limited. Here, we report a case and systematically review published cases of idiopathic intracranial hypertension (IIH) following levothyroxine (LT4) replacement. The systematic review was performed as per the PRISMA guidelines. Our patient is a 46-year-old lady with hypothyroidism (thyrotropin: 319 mIU/L, free thyroxine: 0.04 ng/dl), treated with 100 μg.d of LT4 and presented a month later with headache, visual diminution, bilateral lateral rectus palsies, and papilledema. Cerebrospinal fluid (CSF) pressure was 32 cmH2O. Drainage of CSF, oral acetazolamide, and modification of LT4 dose resulted in prompt symptomatic improvement and complete reversal of IIH. In the systematic review (n = 21), the median age of patients (7 males) was 13 (IQR: 8.8- 26.5) years. The median duration of hypothyroid symptoms was 4 (n = 10, IQR: 0.44-6.25) years whereas that from initiation of LT4 replacement to the diagnosis of IIH was 2 (n = 20, IQR: 1.17-4) months. Initial median serum thyrotropin and thyroxine were 100 (n = 14, IQR: 72.5-421.6) mIU/L, and 1.13 (n = 12, IQR: 1.0-2.45) μg/dl which changed to 2.2 (n = 7; IQR: 0.23-3.40) mIU/L and 8.90 μg/dl (n = 8, IQR: 6.43-14.85 μg/dl), respectively at diagnosis of IIH after LT4 treatment with median daily LT4 doses of 0.89 (n = 8, IQR: 0.60 - 1.17) times the maximum recommended dose for age. To conclude, we report an adult woman with IIH following LT4 replacement for primary hypothyroidism, a rare entity. Pediatric age, prolonged symptom duration, and use of higher LT4 replacement dose may be associated with IIH following LT4 replacement.
PubMed: 37215264
DOI: 10.4103/ijem.ijem_439_22 -
Thorax Oct 2023Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic... (Meta-Analysis)
Meta-Analysis
Acetazolamide for metabolic alkalosis complicating respiratory failure with chronic obstructive pulmonary disease or obesity hypoventilation syndrome: a systematic review.
BACKGROUND
Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression.
METHODS
We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide to placebo in patients with chronic obstructive pulmonary disease, obesity hypoventilation syndrome or obstructive sleep apnoea, hospitalised with acute respiratory deterioration complicated by metabolic alkalosis. The primary outcome was mortality and we pooled data using random-effects meta-analysis. Risk of bias was assessed using the Cochrane RoB 2 (Risk of Bias 2) tool, heterogeneity was assessed using the I value and χ test for heterogeneity. Certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) methodology.
RESULTS
Four studies with 504 patients were included. 99% of included patients had chronic obstructive pulmonary disease. No trials recruited patients with obstructive sleep apnoea. 50% of trials recruited patients requiring mechanical ventilation. Risk of bias was overall low to some risk. There was no statistically significant difference with acetazolamide in mortality (relative risk 0.98 (95% CI 0.28 to 3.46); p=0.95; 490 participants; three studies; GRADE low certainty) or duration of ventilatory support (mean difference -0.8 days (95% CI -7.2 to 5.6); p=0.36; 427 participants; two studies; GRADE: low certainty).
CONCLUSION
Acetazolamide may have little impact on respiratory failure with metabolic alkalosis in patients with chronic respiratory diseases. However, clinically significant benefits or harms are unable to be excluded, and larger trials are required.
PROSPERO REGISTRATION NUMBER
CRD42021278757.
Topics: Humans; Acetazolamide; Obesity Hypoventilation Syndrome; Pulmonary Disease, Chronic Obstructive; Alkalosis; Respiratory Insufficiency
PubMed: 37217290
DOI: 10.1136/thorax-2023-219988 -
Annals of Thoracic Medicine 2021Acute mountain sickness (AMS) is a benign and self-limiting syndrome, but can progress to life-threatening conditions if leave untreated. This study aimed to assess the...
BACKGROUND
Acute mountain sickness (AMS) is a benign and self-limiting syndrome, but can progress to life-threatening conditions if leave untreated. This study aimed to assess the efficacy of acetazolamide for the prophylaxis of AMS, and disclose factors that affect the treatment effect of acetazolamide.
METHODS
Randomized controlled trials comparing the use of acetazolamide versus placebo for the prevention of AMS were included. The incidence of AMS was our primary endpoint. Meta-regression analysis was conducted to explore factors that associated with acetazolamide efficacy. Trial sequential analyses were conducted to estimate the statistical power of the available data.
RESULTS
A total of 22 trials were included. Acetazolamide at 125, 250, and 375 mg/bid significantly reduced incidence of AMS compared to placebo. TAS indicated that the current evidence was adequate confirming the efficacy of acetazolamide at 125, 250, and 375 mg/bid in lowering incidence of AMS. There was no evidence of an association between efficacy and dose of acetazolamide, timing at start of acetazolamide treatment, mode of ascent, AMS assessment score, timing of AMS assessment, baseline altitude, and endpoint altitude.
CONCLUSION
Acetazolamide is effective prophylaxis for the prevention of AMS at 125, 250, and 375 mg/bid. Future investigation should focus on personal characteristics, disclosing the correlation between acetazolamide efficacy and body mass, height, degree of prior acclimatization, individual inborn susceptibility, and history of AMS.
PubMed: 34820021
DOI: 10.4103/atm.atm_651_20 -
The American Journal of the Medical... May 2021Acute mountain sickness (AMS) is a benign and self-limiting syndrome but can progress to life-threatening conditions if leave untreated. This study aimed to assess the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute mountain sickness (AMS) is a benign and self-limiting syndrome but can progress to life-threatening conditions if leave untreated. This study aimed to assess the efficacy of acetazolamide for the prophylaxis of AMS and disclose potential factors that affect the treatment effect of acetazolamide.
MATERIALS AND METHODS
Randomized controlled trials comparing the use of acetazolamide versus placebo for the prevention of AMS were included. The incidence of AMS was the primary endpoint. Meta-regression analysis was conducted to explore potential factors associated with acetazolamide efficacy. Trial sequential analysis (TSA) was conducted to estimate the statistical power of the available data.
RESULTS
A total of 22 trials were included. Acetazolamide at 125, 250, and 375 mg/ twice daily (bid) significantly reduced incidence of AMS compared to placebo. TAS indicated that the current evidence was adequate confirming the efficacy of acetazolamide at 125, 250, and 375 mg/bid in lowering incidence of AMS. There was no evidence of an association between efficacy and dose of acetazolamide, timing at start of acetazolamide treatment, mode of ascent, AMS assessment score, timing of AMS assessment, baseline altitude, and endpoint altitude.
CONCLUSION
Acetazolamide is effective prophylaxis for the prevention of AMS in doses of 125, 250, and 375 mg/bid. Future investigations should focus on personal characteristics, disclosing the correlation between acetazolamide efficacy and body mass, height, degree of prior acclimatization, individual inborn susceptibility, and history of AMS.
Topics: Acetazolamide; Altitude Sickness; Carbonic Anhydrase Inhibitors; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 33587912
DOI: 10.1016/j.amjms.2020.12.022 -
The Cochrane Database of Systematic... Oct 2019Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the... (Review)
Review
BACKGROUND
Catamenial epilepsy describes a worsening of seizures in relation to the menstrual cycle and may affect around 40% of women with epilepsy. Vulnerable days of the menstrual cycle for seizures are perimenstrually (C1 pattern), at ovulation (C2 pattern), and during the luteal phase (C3 pattern). A reduction in progesterone levels premenstrually and reduced secretion during the luteal phase is implicated in catamenial C1 and C3 patterns. A reduction in progesterone has been demonstrated to reduce sensitivity to the inhibitory neurotransmitter in preclinical studies, hence increasing risk of seizures. A pre-ovulatory surge in oestrogen has been implicated in the C2 pattern of seizure exacerbation, although the exact mechanism by which this surge increases risk is uncertain. Current treatment practices include the use of pulsed hormonal (e.g. progesterone) and non-hormonal treatments (e.g. clobazam or acetazolamide) in women with regular menses, and complete cessation of menstruation using synthetic hormones (e.g. medroxyprogesterone (Depo-Provera) or gonadotropin-releasing hormone (GnRH) analogues (triptorelin and goserelin)) in women with irregular menses.Catamenial epilepsy and seizure exacerbation is common in women with epilepsy, and may have a significant negative impact on quality of life. Women may not be receiving appropriate treatment for their seizures because of uncertainty regarding which treatment works best and when in the menstrual cycle treatment should be taken, as well as the possible impact on fertility, the menstrual cycle, bone health, and cardiovascular health. This review aimed to address these issues in order to inform clinical practice and future research.
OBJECTIVES
To evaluate the efficacy and tolerability of hormonal and non-hormonal treatments for seizures exacerbated by the menstrual cycle in women with regular or irregular menses. We synthesised the evidence from randomised controlled trials of hormonal and non-hormonal treatments in women with catamenial epilepsy of any pattern.
SEARCH METHODS
We searched the following databases to 10 January 2019: Cochrane Register of Studies (CRS Web; includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE (Ovid: 1946 to 9 January 2019), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We used no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials (RCTs) of blinded or opeṉlabel design that randomised participants individually (i.e. cluster-randomised trials were excluded). We included cross-over trials if each treatment period was at least 12 weeks in length and the trial had a suitable wash-out period. Types of interventions included: women with any pattern of catamenial epilepsy who received a hormonal or non-hormonal drug intervention in addition to an existing antiepileptic drug regimen for a minimum treatment duration of 12 weeks.
DATA COLLECTION AND ANALYSIS
We extracted data on study design factors and participant demographics for the included studies. The primary outcomes of interest were: proportion seizure-free, proportion of responders (at least 50% decrease in seizure frequency from baseline), and mean change in seizure frequency. Secondary outcomes included: number of withdrawals, number of women experiencing adverse events of interest (seizure exacerbation, cardiac events, thromboembolic events, osteoporosis and bone health, mood disorders, sedation, menstrual cycle disorders, and fertility issues), and quality of life outcomes.
MAIN RESULTS
We identified 62 records from the databases and search strategies. Following title, abstract, and full-text screening, we included eight full-text articles reporting on four double-blind, placebo-controlled RCTs. We included two cross-over RCTs of pulsed norethisterone and two parallel RCTs of pulsed progesterone recruiting a total of 192 women aged between 13 and 45 years with catamenial epilepsy. We found no RCTs for non-hormonal treatments of catamenial epilepsy or for women with irregular menses.Meta-analysis was not possible for the primary outcomes, therefore we undertook a narrative synthesis. For the two RCTs evaluating norethisterone versus placebo (24 participants), there were no reported treatment differences for mean change in seizure frequency. Outcomes for the proportion seizure-free and 50% responders were not reported. For the RCTs evaluating progesterone versus placebo (168 participants), the studies reported conflicting results on the primary outcomes. One progesterone RCT reported no significant difference between progesterone 600 mg/day taken on day 14 to 28 and placebo with respect to 50% responders, seizure freedom rates, and change in seizure frequency for any seizure type. The other progesterone RCT reported that the decrease in seizure frequency from baseline in the progesterone group was significantly higher than the decrease in seizure frequency from baseline in the placebo group.Results of secondary efficacy outcomes showed no significant difference in terms of treatment withdrawal for any reason in the pooled progesterone RCTs when compared to placebo (pooled risk ratio (RR) 1.56, 95% confidence interval (CI) 0.81 to 3.00, P = 0.18, I = 0%) or for treatment withdrawals due to adverse events (pooled RR 2.91, 95% CI 0.53 to 16.17, P = 0.22, I = 0%). No treatment withdrawals from the norethisterone RCTs were reported. The RCTs reported limited information on adverse events, although one progesterone RCT reported no significant difference in the number of women experiencing adverse events (diarrhoea, dyspepsia, nausea, vomiting, fatigue, nasopharyngitis, dizziness, headache, and depression). No studies reported on quality of life.We judged the evidence from the included progesterone RCTs to be of low to moderate certainty due to risk of bias and from the included norethisterone RCTs to be of very low certainty due to serious imprecision and risk of bias.
AUTHORS' CONCLUSIONS
This review provides very low-certainty evidence of no treatment difference between norethisterone and placebo, and moderate- to low-certainty evidence of no treatment difference between progesterone and placebo for catamenial epilepsy. However, as all the included studies were underpowered, important clinical effects cannot be ruled out.Our review highlighted an overall deficiency in the literature base on the effectiveness of a wide range of other hormonal and non-hormonal interventions currently being used in practice, particularly for those patients who do not have regular menses. Further clinical trials are needed in this area.
PubMed: 31608992
DOI: 10.1002/14651858.CD013225.pub2 -
Journal of Nephrology Jan 2024Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are... (Review)
Review
BACKGROUND
Urine alkalization is one of the standard treatments to prevent acute kidney injury in patients receiving high-dose methotrexate. Carbonic anhydrase inhibitors are promising adjuvants/substitutes with advantages such as faster urine alkalization time and prevention of fluid overload. However, there is limited and contradictory evidence on its efficacy and safety. We aimed to compare the efficacy and safety of carbonic anhydrase inhibitors to standard treatments in adult patients receiving high-dose methotrexate.
METHODS
The protocol was registered at PROSPERO (CRD42022352802) in August 2021. We evaluated the use of carbonic anhydrase inhibitors in combination with standard treatment compared to standard treatment alone. We excluded articles irrelevant to the efficacy and safety of acetazolamide in patients receiving high dose methotrexate and/or did not provide sufficient data regarding doses, recruitment criteria, and follow-up period. Two authors performed the data extraction independently.
RESULTS
Among 198 articles retrieved, six observational studies met all eligibility criteria. Four studies with five datasets (totaling 558 patients/cycles) had enough data to be included in the meta-analysis. We independently report the results from the two remaining studies. The results did not show a significant difference between acetazolamide versus standard treatment in acute kidney injury (AKI) rate (OR = 0.79, 95% CI 0.48-1.29, P = 0.34, I = 0%). Regarding the time to urine pH goal, there was no significant time difference between the two groups (Mean Difference = 0.07, 95% CI - 1.9 to 2.04, P = 0.95, I = 25%). Furthermore, our meta-analysis showed that acetazolamide did not reduce length of stay (Mean Difference = 0.75, 95% CI - 0.8 to 2.31, P = 0.34, I = 0%). In one study, the only reported side effect of acetazolamide was hypokalemia (nearly 50% in the acetazolamide group).
CONCLUSIONS
This systematic review showed no significant difference between acetazolamide and standard care treatment regarding urine alkalinization time and AKI rate in adult patients receiving high dose methotrexate. We suggest performing a large blinded, randomized, controlled trial to evaluate the potential benefits of this low-cost medication.
PubMed: 38265601
DOI: 10.1007/s40620-023-01850-2 -
Brain Sciences Dec 2023Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the... (Review)
Review
BACKGROUND
Acetazolamide is a non-competitive inhibitor of carbonic anhydrase, an enzyme expressed in different cells of the central nervous system (CNS) and involved in the regulation of cerebral blood flow (CBF). The aim of this review was to understand the effects of acetazolamide on CBF, intracranial pressure (ICP) and brain tissue oxygenation (PbtO) after an acute brain injury (ABI).
METHODS
Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), we performed a comprehensive, computer-based, literature research on the PubMed platform to identify studies that have reported the effects on CBF, ICP, or PbtO of acetazolamide administered either for therapeutic or diagnostic purposes in patients with subarachnoid hemorrhage, intracerebral hemorrhage, traumatic brain injury, and hypoxic-ischemic encephalopathy.
RESULTS
From the initial search, 3430 records were identified and, through data selection, 11 of them were included for the qualitative analysis. No data on the effect of acetazolamide on ICP or PbtO were found. Cerebral vasomotor reactivity (VMR-i.e., the changing in vascular tone due to a vasoactive substance) to acetazolamide tends to change during the evolution of ABI, with the nadir occurring during the subacute stage. Moreover, VMR reduction was correlated with clinical outcome.
CONCLUSIONS
This systematic review showed that the available studies on the effects of acetazolamide on brain hemodynamics in patients with ABI are scarce. Further research is required to better understand the potential role of this drug in ABI patients.
PubMed: 38137126
DOI: 10.3390/brainsci13121678