Comparison of Alcohol Withdrawal Outcomes in Patients Treated with Benzodiazepines Alone versus Adjunctive Phenobarbital: a Retrospective Cohort Study

Background: For treatment of severe alcohol withdrawal syndrome, high dose benzodiazepines (BZDs) may cause delirium and over-sedation. Phenobarbital (PBT) is a long-acting barbiturate effective for the treatment of alcohol withdrawal. Given the potential benefits of PBT, we sought to investigate the effectiveness of PBT as adjunctive treatment for alcohol withdrawal. Methods: This was a retrospective cohort study on patients with a diagnosis of alcohol withdrawal who had a CIWA-Ar score > 10 treated with either BZDs alone (BZD alone group) or BZDs with adjunctive PBT (PBT-adjunct group). The patients received at least one dose of PBT in addition to BZDs (variable doses) in the PBT-adjunct group, and three doses of 20 mg diazepam equivalents within 6 hours in the BZD alone group. The primary endpoint was the proportion of patients with a CIWA-Ar score < 10 at 24 hours after initial treatment. Duration of withdrawal and cumulative dose of BZDs were also assessed. Results: Seven subjects in the adjunctive phenobarbital and 21 in the benzodiazepine group were included in the final analysis. Two patients (28.6%) in the PBT-adjunct group and 5 patients (23.8%) in the BZD only group achieved the primary endpoint, though the difference between the two groups was not statistically significant (P = 0.588). The median (IQR) duration of withdrawal symptoms was 44 (12-62) hours in the PBT-adjunct group compared to 53 (37-87) hours in the BZD only group, with no significant difference between the groups (P = 0.249). The median (IQR) cumulative BZD dose requirement (diazepam equivalent) in the PBT-adjunct group was significantly lower than BZD alone group (25 (20-226) vs. 326 (160-550) mg, P = 0.02). Conclusion: PBT appears to be a safe and effective alternative to BZDs for the treatment of alcohol withdrawal in non-critically ill patients and may be BZD sparing

Patiromer: a clinical review

Importance: Patiromer FOS (for oral suspension), formerly known as RLY5016, is pending FDA approval for the treatment of hyperkalemia. Once approved, patiromer, as well as a second agent known as sodium zirconium cyclosilicate (ZS-9), will be among the new therapeutic options available to treat hyperkalemia in over 50 years. Objective: The primary objective of this review is to analyze the efficacy and safety of patiromer to treat hyperkalemia and compare its pharmacokinetics to currently available sodium polystyrene sulfonate (SPS) therapy. Patiromer was studied in patients with chronic kidney disease and/or heart failure for both acute and chronic therapy. Evidence review: Studies of patiromer were obtained via a literature search of PubMed database and Google Scholar (2000 to the present) using ‘patiromer’, ‘RLY5016’, and ‘hyperkalemia management’ as keywords. Additional references were identified from fda.gov, clinicaltrials.gov, and the pharmaceutical manufacturer, Relypsa Inc. Findings: Three published clinical trials, ten posters, one clinical trial commentary, three editorials and one oral presentation were obtained. The materials discussed three main clinical trials (PEARL-HF, OPAL-HK and AMETHYST-DN) and examined the safety and efficacy of patiromer in patients with hyperkalemia or at risk for hyperkalemia who have chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), hypertension and/or heart failure (HF) while receiving renin–angiotensin–aldosterone system inhibitors (RAASis). All three studies achieved their primary endpoints and reduced serum potassium. The PEARL-HF study increased the proportion of patients able to titrate their spironolactone dose from 25 mg/day to 50 mg/day in patients with normokalemia who had a history of hyperkalemia or an estimated glomerular filtration rate of \u3c60 mL/min. The OPAL-HK study allowed patients receiving patiromer to remain on their RAASi therapy. The AMETHYST-DN study demonstrated that patiromer reduced and maintained mean serum potassium ≤5.0 mEq/L for up to 1 year, with a low rate of hypokalemia. Adverse events (AEs) were similar between studies. The most commonly reported adverse event was constipation. Conclusions and relevance: Patiromer is effective in decreasing serum potassium, preventing recurrence of hyperkalemia, and reducing RAASi discontinuation. Compared to current SPS therapy, patiromer may be the preferred option to treat hyperkalemia, once approved. Patiromer is well tolerated and is not associated with serious AEs