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Academic Emergency Medicine : Official... May 2024Alcohol withdrawal syndrome (AWS) is a commonly presenting condition in the emergency department (ED) and can have severe complications, including mortality.... (Review)
Review
OBJECTIVES
Alcohol withdrawal syndrome (AWS) is a commonly presenting condition in the emergency department (ED) and can have severe complications, including mortality. Benzodiazepines are first-line medications for treating AWS but may be unavailable or insufficient. This systematic review evaluates the direct evidence assessing the utility of phenobarbital for treating AWS in the ED.
METHODS
A systematic search was conducted and designed according to the patient-intervention-comparator-outcome (PICO) question: (P) adults (≥18 years old) presenting to the ED with alcohol withdrawal; (I) phenobarbital (including adjunctive); (C) benzodiazepines or no intervention; and (O) AWS complications, admission to a monitored setting, control of symptoms, adverse effects, and adjunctive medications. Two reviewers independently assessed articles for inclusion and conducted risk of bias assessments for included studies.
RESULTS
From 70 potentially relevant articles, seven studies met inclusion criteria: three retrospective cohort studies, two retrospective chart reviews, and two randomized controlled trials (RCTs), one examining phenobarbital monotherapy and one examining adjunctive phenobarbital. Across the retrospective cohort studies, treatment of AWS with phenobarbital resulted in lower odds of a subsequent ED visit. The retrospective chart reviews indicated that phenobarbital was associated with higher discharge rate compared to benzodiazepine-only treatments. For the two RCTs, phenobarbital did not differ significantly from benzodiazepine for most outcomes, although concomitant treatment with phenobarbital was associated with lower benzodiazepine use and intensive care unit admission. The heterogeneous designs and small number of studies prevented quantitative synthesis.
CONCLUSIONS
Relatively few studies provide direct evidence on the utility of phenobarbital for AWS in the ED, but the evidence that exists generally suggests that it is a reasonable and appropriate approach. Additional RCTs and other methodologically rigorous investigations are needed for more definitive direct evidence.
Topics: Phenobarbital; Humans; Emergency Service, Hospital; Substance Withdrawal Syndrome; Benzodiazepines; Hypnotics and Sedatives; Male; Adult; Female
PubMed: 37589203
DOI: 10.1111/acem.14788 -
The Cochrane Database of Systematic... Aug 2023Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental... (Review)
Review
Pharmacological pain and sedation interventions for the prevention of intraventricular hemorrhage in preterm infants on assisted ventilation - an overview of systematic reviews.
BACKGROUND
Germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) may contribute to neonatal morbidity and mortality and result in long-term neurodevelopmental sequelae. Appropriate pain and sedation management in ventilated preterm infants may decrease the risk of GMH-IVH; however, it might be associated with harms.
OBJECTIVES
To summarize the evidence from systematic reviews regarding the effects and safety of pharmacological interventions related to pain and sedation management in order to prevent GMH-IVH in ventilated preterm infants.
METHODS
We searched the Cochrane Library August 2022 for reviews on pharmacological interventions for pain and sedation management to prevent GMH-IVH in ventilated preterm infants (< 37 weeks' gestation). We included Cochrane Reviews assessing the following interventions administered within the first week of life: benzodiazepines, paracetamol, opioids, ibuprofen, anesthetics, barbiturates, and antiadrenergics. Primary outcomes were any GMH-IVH (aGMH-IVH), severe IVH (sIVH), all-cause neonatal death (ACND), and major neurodevelopmental disability (MND). We assessed the methodological quality of included reviews using the AMSTAR-2 tool. We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included seven Cochrane Reviews and one Cochrane Review protocol. The reviews on clonidine and paracetamol did not include randomized controlled trials (RCTs) matching our inclusion criteria. We included 40 RCTs (3791 infants) from reviews on paracetamol for patent ductus arteriosus (3), midazolam (3), phenobarbital (9), opioids (20), and ibuprofen (5). The quality of the included reviews was high. The certainty of the evidence was moderate to very low, because of serious imprecision and study limitations. Germinal matrix hemorrhage-intraventricular hemorrhage (any grade) Compared to placebo or no intervention, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (risk ratio (RR) 0.89, 95% confidence interval (CI) 0.38 to 2.07; 2 RCTs, 82 infants; very low-certainty evidence); midazolam may result in little to no difference in the incidence of aGMH-IVH (RR 1.68, 95% CI 0.87 to 3.24; 3 RCTs, 122 infants; low-certainty evidence); the evidence is very uncertain about the effect of phenobarbital on aGMH-IVH (RR 0.99, 95% CI 0.83 to 1.19; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in aGMH-IVH (RR 0.85, 95% CI 0.65 to 1.12; 7 RCTs, 469 infants; low-certainty evidence); ibuprofen likely results in little to no difference in aGMH-IVH (RR 0.99, 95% CI 0.81 to 1.21; 4 RCTs, 759 infants; moderate-certainty evidence). Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on aGMH-IVH (RR 1.17, 95% CI 0.31 to 4.34; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, morphine may result in a reduction in aGMH-IVH (RR 0.28, 95% CI 0.09 to 0.87; 1 RCT, 46 infants; low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on aGMH-IVH (RR 0.65, 95% CI 0.40 to 1.07; 1 RCT, 88 infants; very low-certainty evidence). Severe intraventricular hemorrhage (grade 3 to 4) Compared to placebo or no intervention, the evidence is very uncertain about the effect of paracetamol on sIVH (RR 1.80, 95% CI 0.43 to 7.49; 2 RCTs, 82 infants; very low-certainty evidence) and of phenobarbital (grade 3 to 4) (RR 0.91, 95% CI 0.66 to 1.25; 9 RCTs, 732 infants; very low-certainty evidence); opioids may result in little to no difference in sIVH (grade 3 to 4) (RR 0.98, 95% CI 0.71 to 1.34; 6 RCTs, 1299 infants; low-certainty evidence); ibuprofen may result in little to no difference in sIVH (grade 3 to 4) (RR 0.82, 95% CI 0.54 to 1.26; 4 RCTs, 747 infants; low-certainty evidence). No studies on midazolam reported this outcome. Compared to ibuprofen, the evidence is very uncertain about the effects of paracetamol on sIVH (RR 2.65, 95% CI 0.12 to 60.21; 1 RCT, 30 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.08, 95% CI 0.00 to 1.43; 1 RCT, 46 infants; very low-certainty evidence). Compared to fentanyl, the evidence is very uncertain about the effect of morphine on sIVH (grade 3 to 4) (RR 0.59, 95% CI 0.18 to 1.95; 1 RCT, 163 infants; very low-certainty evidence). All-cause neonatal death Compared to placebo or no intervention, the evidence is very uncertain about the effect of phenobarbital on ACND (RR 0.94, 95% CI 0.51 to 1.72; 3 RCTs, 203 infants; very low-certainty evidence); opioids likely result in little to no difference in ACND (RR 1.12, 95% CI 0.80 to 1.55; 5 RCTs, 1189 infants; moderate-certainty evidence); the evidence is very uncertain about the effect of ibuprofen on ACND (RR 1.00, 95% CI 0.38 to 2.64; 2 RCTs, 112 infants; very low-certainty evidence). Compared to midazolam, the evidence is very uncertain about the effect of morphine on ACND (RR 0.31, 95% CI 0.01 to 7.16; 1 RCT, 46 infants; very low-certainty evidence). Compared to diamorphine, the evidence is very uncertain about the effect of morphine on ACND (RR 1.17, 95% CI 0.43 to 3.19; 1 RCT, 88 infants; very low-certainty evidence). Major neurodevelopmental disability Compared to placebo, the evidence is very uncertain about the effect of opioids on MND at 18 to 24 months (RR 2.00, 95% CI 0.39 to 10.29; 1 RCT, 78 infants; very low-certainty evidence) and at five to six years (RR 1.6, 95% CI 0.56 to 4.56; 1 RCT, 95 infants; very low-certainty evidence). No studies on other drugs reported this outcome.
AUTHORS' CONCLUSIONS
None of the reported studies had an impact on aGMH-IVH, sIVH, ACND, or MND. The certainty of the evidence ranged from moderate to very low. Large RCTs of rigorous methodology are needed to achieve an optimal information size to assess the effects of pharmacological interventions for pain and sedation management for the prevention of GMH-IVH and mortality in preterm infants. Studies might compare interventions against either placebo or other drugs. Reporting of the outcome data should include the assessment of GMH-IVH and long-term neurodevelopment.
Topics: Infant, Newborn; Female; Humans; Ibuprofen; Acetaminophen; Midazolam; Analgesics, Opioid; Respiration, Artificial; Heroin; Perinatal Death; Systematic Reviews as Topic; Infant, Premature; Pain; Cerebral Hemorrhage; Phenobarbital
PubMed: 37565681
DOI: 10.1002/14651858.CD012706.pub2 -
JAMA Neurology Jul 2023Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy or...
IMPORTANCE
Super-refractory status epilepticus (SRSE) is defined as status epilepticus (SE) that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction/withdrawal of anesthesia. Current clinical knowledge of the disease and optimal treatment approach is sparse.
OBJECTIVE
To systematically assess clinical characteristics, causes, outcomes, prognostic factors, and treatment approaches for patients with SRSE.
DESIGN, SETTING, AND PARTICIPANTS
In this systematic review and meta-analysis, all studies reporting adult patients (18 years or older) diagnosed with nonanoxic SRSE were considered for inclusion, irrespective of study design. The databases used were MEDLINE, Cochrane Library, EMBASE, and ClinicalTrials.org (database inception through May 5, 2022).
DATA EXTRACTION AND SYNTHESIS
The study complied with the PRISMA guidelines for reporting, data extraction, and data synthesis. Different tools were used to assess risk of bias. All available data were extracted and missing data were neither imputed nor completed by contacting the study authors.
MAIN OUTCOME AND MEASURES
Successful treatment of SRSE, in-hospital mortality, and disability at discharge (estimated modified Rankin Scale).
RESULTS
The study team identified a total of 95 articles and 30 conference abstracts reporting 1200 patients with nonanoxic SRSE (266 individual patients were available for meta-analysis). They had a mean SRSE duration of 36.3 days, mean age of 40.8 years, and equal sex distribution. Patients with SRSE had a distinct pattern of etiologies where acute cerebral events and unknown etiologies accounted for 41.6% and 22.3% of all etiologies, respectively. Reports of SRSE caused by, eg, alcohol, drugs, or tumors were rare. At discharge, only 26.8% had none to slight disability (none, 16 [8.4%]; nonsignificant and slight disability, 35 [18.4%]). In-hospital mortality was 24.1%. Mortality stabilized after long-term treatment (more than 28 days) but with increased rates of seizure cessation and moderate to severe disability. Established prognostic factors, such as age and etiology, were not associated with in-hospital mortality. Reported treatment with ketamine, phenobarbital, other barbiturates, vagus nerve stimulator, and ketogenic diet were not associated with outcome.
CONCLUSION AND RELEVANCE
Patients with SRSE are distinct due to their pattern of care (eg, long-term treatment to younger patients without negative prognostic factors and unknown/nonmalignant etiologies) and their natural course of SE. Very long-term treatment was associated with lower mortality and high odds of cessation of SRSE but increased risk of moderate to severe disability.
PubMed: 37523161
DOI: 10.1001/jamaneurol.2023.2407 -
Journal of Research in Medical Sciences... 2023Febrile convulsion (FC) is the most common and preventable seizure in children. This study aimed to assess the effectiveness of the diazepam and phenobarbital for... (Review)
Review
Comparing the effect of intermittent diazepam and continuous phenobarbital in preventing recurrent febrile seizures among children under 6 years old: A systematic review and meta-analysis.
BACKGROUND
Febrile convulsion (FC) is the most common and preventable seizure in children. This study aimed to assess the effectiveness of the diazepam and phenobarbital for preventing recurrent FC.
MATERIALS AND METHODS
In this systematic review study, literature published in English language were carefully searched in biological databases (Cochrane Library, Medline, Scopus, CINHAL, Psycoinfo, and Proquest) by February 2020.Randomized clinical trials (RCTs) and Quasi randomized trial were included in the review. Two researchers checked the literature independently. The quality of studies was assessed using the JADAD score. The potential risk for publication bias was assessed by Funnel plot and Egger's test. Meta regression test and sensitivity analysis were used to identify the reasons for heterogeneity. Given the results of assessing heterogeneity, the random effect model in RevMan5.1 software was used for meta analysis.
RESULTS
Four out of 17 studies had compared the effect of diazepam and phenobarbital in preventing recurrent FC. The result of the meta analysis showed that the use of diazepam in comparison with phenobarbital reduces the risk of recurrence FC by 34% (risk ratio = 0.66, 95% confidence interval [CI] = [0.36-1.21]), but the relationship was not statistically significant. In assessing the effect of diazepam or phenobarbital versus placebo, the results showed that the use of diazepam and phenobarbital has reduced the risk of recurrent FC by 49% (risk ratio = 0.51, 95% CI = [0.32-0.79]) and 37% (risk ratio = 0.63, 95% CI = [0.42-0.96)]), respectively, and these relationships were statistically significant ( < 0.05). Results of the meta regression test showed that the follow up time can be a reason for the heterogeneity between trials with the comparison of diazepam versus phenobarbital ( = 0.047, = 0.049) and Phenobarbital versus placebo ( = 0.022, = 0.016). According to the results of Funnel plot and Egger's test, there was evidence of publication bias ( = 0.0584 for comparison of diazepam vs. phenobarbital; = 0.0421 for comparison of diazepam vs. placebo; = 0.0402 for comparison of phenobarbital vs. placebo).
CONCLUSION
The results of this meta analysis indicated that preventive anticonvulsants can be useful in preventing recurrent convulsions in cases of febrile seizures.
PubMed: 37213451
DOI: 10.4103/jrms.jrms_1114_21 -
The American Journal of Emergency... Jul 2023Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alcohol Withdrawal Syndrome (AWS) among patients with chronic and heavy alcohol consumption can range from mild to severe and is associated with high morbidity and mortality. Currently, treating AWS with benzodiazepines is the standard of care, but phenobarbital has also been hypothesized to be an effective first-line treatment due to its pharmacological properties and mechanism of action. We conducted a meta-analysis to review relevant literature and compare the clinical outcomes for patients diagnosed with AWS in ED and ICU settings.
METHODS
We performed a literature search in in the PubMed, Scopus, and Web of Science databases from inception to June 30, 2022. Randomized trials and observational (prospective or retrospective) studies were eligible if they included adult patients who presented in the ED and were treated in the ED and/or the intensive care unit (ICU) with a diagnosis of AWS. The primary outcome was the rate of intubation among patients who received phenobarbital, compared with benzodiazepines. Secondary outcomes such as rates of seizures, hospital, and ICU length of stay (LOS), also were included. The PROSPERO registration is CRD42022318862.
RESULTS
We included twelve studies (1934 patients) in our analysis. Of the 1934 patients in these studies, 765 (41.7%) were treated with phenobarbital and 1169 (58.3%) were treated with other modalities for alcohol withdrawal. Treating AWS patients with phenobarbital did not affect their risk for intubation, as the risk for intubation was similar between the phenobarbital and the control group (RR 0.70, 95% CI 0.36-1.38, P = 0.31). In addition, patients who were treated with phenobarbital were found to have similar rates of seizures (RR 0.73, 95% CI 0.29-1.89) and length of stay in the hospital (Standardized Mean Difference -0.02, 95% CI -0.26, 0.21) or the ICU (SMD -0.02, 95% CI -0.21, 0.25) when compared with patients receiving benzodiazepines.
CONCLUSIONS
Management of patients with AWS with phenobarbital is associated with similar rates of intubation, length of stay in the ICU, or length of stay in the hospital as treatment with benzodiazepines. However, due to the inclusion of mostly observational studies and a significant level of heterogeneity among the studies assessed in this review, additional trials with strong methodology are needed.
Topics: Adult; Humans; Substance Withdrawal Syndrome; Alcoholism; Retrospective Studies; Prospective Studies; Phenobarbital; Benzodiazepines; Seizures
PubMed: 37060631
DOI: 10.1016/j.ajem.2023.04.002 -
Neuropediatrics Oct 2023Autosomal dominant mutations of the gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE)....
BACKGROUND
Autosomal dominant mutations of the gene can cause two epileptic disorders: benign familial neonatal seizures (BFNS) and developmental epileptic encephalopathy (DEE). This systematic review aims to identify the best reported therapy for these patients, relating to phenotype, neurodevelopmental outcome, and an eventual correlation between phenotype and genotype.
METHODS
We searched on PubMed using the search terms "" AND "therapy" and "" AND "treatment"; we found 304 articles. Of these, 29 met our criteria. We collected the data from 194 patients. All 29 articles were retrospective studies.
RESULTS
In all, 104 patients were classified as DEE and 90 as BFNS. After treatment began, 95% of BFNS patients became seizure free, whereas the seizures stopped only in 73% of those with DEE. Phenobarbital and sodium channel blockers were the most used treatment in BFNS. Most of the DEE patients (95%) needed polytherapy for seizure control and even that did not prevent subsequent developmental impairment (77%).Missense mutations were discovered in 96% of DEE patients; these were less common in BFNS (50%), followed by large deletion (16%), truncation (16%), splice donor site (10%), and frameshift (7%).
CONCLUSION
Phenobarbital or carbamazepine appears to be the most effective antiseizure medication for children with a "benign" variant. On the contrary, polytherapy is often needed for DEE patients, even if it does not seem to improve neurological outcomes. In DEE patients, most mutations were located in S4 and S6 helix, which could serve as a potential target for the development of more specific treatment in the future.
Topics: Child; Infant, Newborn; Humans; Retrospective Studies; KCNQ2 Potassium Channel; Epilepsy, Benign Neonatal; Mutation; Seizures; Phenotype; Genotype; Phenobarbital
PubMed: 36948217
DOI: 10.1055/a-2060-4576 -
European Journal of Internal Medicine Jun 2023Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and...
BACKGROUND
Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and complications associated with alcohol withdrawal syndrome (AWS). However, the level of evidence, including appropriate dosing, is unclear. We aim to summarize the evidence regarding PB used in AWS and provide future agendas for research.
METHODS
Following the PRISMA guidelines, we searched MEDLINE, EMBASE, ClinicalTrials.gov, and WHO ICTRP for all peer-reviewed articles and clinical trials using keywords including"alcohol withdrawal", "delirium tremens", "phenobarbital," and "barbiturate" from their inception to September 18, 2022.
RESULTS
We included 20 articles, nine in the emergency department (ED) and 11 in the general floors or intensive care units (ICUs). Studies performed in the ED included two RCTs, although both suffered from a considerably small sample size. Six studies done in the general floors or ICUs compared PB and BZD monotherapy, while four compared the utility of adjunct PB in addition to BZD compared with BZD monotherapy and one was a database study without specific dosing information. Overall, there was considerable heterogeneity in PB dosing, measured outcomes, and AWS severity measurement scales.
CONCLUSION
This systematic review summarizes the current evidence related to PB use in AWS. While considerable heterogeneity exists among studies available, PB as monotherapy without BZD may be a safe and effective alternative in AWS treatment. Future prospective studies or trials should focus on the standardization of PB dosing and outcomes.
Topics: Humans; Substance Withdrawal Syndrome; Alcoholism; Alcohol Withdrawal Delirium; Prospective Studies; Retrospective Studies; Phenobarbital; Benzodiazepines
PubMed: 36935249
DOI: 10.1016/j.ejim.2023.03.006 -
The Cochrane Database of Systematic... Mar 2023Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus.... (Review)
Review
BACKGROUND
Intraventricular haemorrhage (IVH) is a major complication of preterm birth. Large haemorrhages are associated with a high risk of disability and hydrocephalus. Instability of blood pressure and cerebral blood in the newborn flow are postulated as causative factors. Another mechanism may involve reperfusion damage from oxygen free radicals. It has been suggested that phenobarbital stabilises blood pressure and may protect against free radicals. This is an update of a review first published in 2001 and updated in 2007 and 2013.
OBJECTIVES
To assess the benefits and harms of the postnatal administration of phenobarbital in preterm infants at risk of developing IVH compared to control (i.e. no intervention or placebo).
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, CINAHL and clinical trial registries in January 2022. A new, more sensitive search strategy was developed, and searches were conducted without date limits. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi-RCTs in which phenobarbital was given within the first 24 hours of life to preterm infants identified as being at risk of IVH because of gestational age below 34 weeks, birth weight below 1500 g or respiratory failure. Phenobarbital was compared to no intervention or placebo. We excluded infants with serious congenital malformations.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were all grades of IVH and severe IVH (i.e. grade III and IV); secondary outcomes were ventricular dilation or hydrocephalus, hypotension, pneumothorax, hypercapnia, acidosis, mechanical ventilation, neurodevelopmental impairment and death. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included 10 RCTs (792 infants). The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH of any grade compared with control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.84 to 1.19; risk difference (RD) 0.00, 95% CI -0.06 to 0.07; I² for RD = 65%; 10 RCTs, 792 participants; low certainty evidence) and in severe IVH (RR 0.88, 95% CI 0.64 to 1.21; 10 RCTs, 792 participants; low certainty evidence). The evidence is very uncertain about the effect of phenobarbital on posthaemorrhagic ventricular dilation or hydrocephalus (RR 0.62, 95% CI 0.31 to 1.26; 4 RCTs, 271 participants; very low certainty evidence), mild neurodevelopmental impairment (RR 0.57, 95% CI 0.15 to 2.17; 1RCT, 101 participants; very low certainty evidence), and severe neurodevelopmental impairment (RR 1.12, 95% CI 0.44 to 2.82; 2 RCTs, 153 participants; very low certainty evidence). Phenobarbital may result in little to no difference in death before discharge (RR 0.88, 95% CI 0.64 to 1.21; 9 RCTs, 740 participants; low certainty evidence) and mortality during study period (RR 0.98, 95% CI 0.72 to 1.33; 10 RCTs, 792 participants; low certainty evidence) compared with control. We identified no ongoing trials.
AUTHORS' CONCLUSIONS
The evidence suggests that phenobarbital results in little to no difference in the incidence of IVH (any grade or severe) compared with control (i.e. no intervention or placebo). The evidence is very uncertain about the effects of phenobarbital on ventricular dilation or hydrocephalus and on neurodevelopmental impairment. The evidence suggests that phenobarbital results in little to no difference in death before discharge and all deaths during the study period compared with control. Since 1993, no randomised studies have been published on phenobarbital for the prevention of IVH in preterm infants, and no trials are ongoing. The effects of postnatal phenobarbital might be assessed in infants with both neonatal seizures and IVH, in both randomised and observational studies. The assessment of benefits and harms should include long-term outcomes.
Topics: Infant, Newborn; Female; Humans; Infant; Infant, Premature; Phenobarbital; Cerebral Hemorrhage; Infant, Premature, Diseases; Hydrocephalus; Infant, Very Low Birth Weight
PubMed: 36924438
DOI: 10.1002/14651858.CD001691.pub4 -
Progress in Neuro-psychopharmacology &... Jun 2023Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a...
OBJECTIVE
Data on the ability of anticonvulsants and lithium to enter fetal and newborn circulation has become increasingly available; here we estimated penetration ratios in a series of matrices from combined samples of pregnant/breastfeeding women treated with anticonvulsants or lithium.
METHODS
We conducted a systematic literature search in PubMed/EMBASE for studies with concentrations of anticonvulsants/lithium from maternal blood, amniotic fluid, umbilical cord blood and/or breast milk. Penetration ratios were calculated by dividing the concentrations in amniotic fluid, umbilical cord plasma or breast milk by the maternal concentrations. When data from multiple studies were available, we calculated combined penetration ratios, weighting studies' mean by study size.
RESULTS
Ninety-one eligible studies for brivaracetam, carbamazepine, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, lithium, oxcarbazepine, perampanel, phenobarbital, phenytoin, pregabalin, primidone, topiramate, valproate, vigabatrin and zonisamide were identified. For amniotic fluid, the highest penetration ratios were estimated for levetiracetam (mean 3.56, range 1.27-5.85, n = 2) and lowest for valproate (mean 0.11, range 0.02-1.02, n = 57). For umbilical cord plasma, oxcarbazepine had the highest ratio (mean 1.59, range 0.11-4.33, n = 12) with clonazepam having the lowest (mean 0.55, range 0.52-0.59, n = 2). For breast milk, the highest ratios were observed for oxcarbazepine (mean 3.75, range 0.5-7.0, n = 2), whereas the lowest were observed for valproate (mean 0.04, range 0.01-0.22, n = 121).
DISCUSSION
We observed substantial variability between anticonvulsants and lithium regarding their ability to enter fetal/newborn circulation. Assessing concentrations of anticonvulsants and lithium in maternal samples can provide a surrogate of fetal/infant exposure, although patterns of concentration-dependent effects for maternal/neonatal safety are lacking.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Amniotic Fluid; Anticonvulsants; Fetal Blood; Lithium; Maternal-Fetal Exchange; Milk, Human
PubMed: 36805301
DOI: 10.1016/j.pnpbp.2023.110733 -
Cureus Jan 2023Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant... (Review)
Review
Alcohol withdrawal syndrome (AWS) is a complication frequently encountered among patients who are chronic alcohol abusers. It is considered to have a significant impact on the United States healthcare system. It not only has a toll on the healthcare spending but also contributes to significant morbidity and mortality. Benzodiazepines are considered first line in the treatment of AWS. Since patients with alcohol use disorder have downregulated gamma aminobutyric acid (GABA) receptors, this often leads to benzodiazepine resistance. Phenobarbital is also used in the management of alcohol withdrawal syndrome. Here we present a systematic review and meta-analysis of the efficacy and safety of the drug. We conducted an electronic database search for relevant studies published between the inception of the project and November 20, 2022, in three databases, including Medline/PubMed, Embase, and Cochrane Library. Our study included all original studies with prime focus on the baseline characteristics of patients admitted to the intensive care unit (ICU) for alcohol withdrawal syndrome and management/monitoring protocol implemented for its treatment. The primary outcomes that were the focus of our study consisted of changes in the length of hospital stay, length of ICU stay, and changes in scoring systems (for alcohol withdrawal assessment and monitoring) following the implementation of phenobarbital. The secondary outcomes included complications such as intubation and mortality. Based on our analysis, the mean difference in hospital stay was statistically significant at -2.6 (95% CI, -4.48, -0.72, P=0.007) for phenobarbital compared to the benzodiazepine group. We were unable to comment on the heterogeneity in our meta-analysis due to the standard deviation not being reported in one study. There was no statistically significant difference regarding the length of stay in the intensive care unit compared to the control/comparative arm, with a mean difference of -1.17 (95% CI, -1.17, 0.09, P=0.07), with considerable heterogeneity (I=77%, P=0.002). Our meta-analysis also investigated the risk of intubation between the phenobarbital and the control/comparative group. There was statistically significant difference in the incidence of intubation, relative risk (RR) 0.52 (95% CI, 0.25, 1.08, P=0.08), with considerable heterogeneity (I=80%, P=0.0001). Our study concludes that phenobarbital is an effective tool in the management of AWS in an ICU setting. However, various studies have reported contradictory results, and vital information appears to be lacking. Moreover, there is a lack of uniformity in terms of phenobarbital dosing. Drug administration should be adapted according to the severity of the symptoms. Further studies need to be conducted discussing the safety profile and adverse effects of the drug when it comes to the management of alcohol withdrawal syndrome.
PubMed: 36788902
DOI: 10.7759/cureus.33695