Phenobarbital Versus Benzodiazepines for the Treatment of Severe Alcohol Withdrawal.

BACKGROUND: Phenobarbital may offer advantages over benzodiazepines for severe alcohol withdrawal syndrome (SAWS), but its impact on clinical outcomes has not been fully elucidated. OBJECTIVE: The purpose of this study was to determine the clinical impact of phenobarbital versus benzodiazepines for SAWS. METHODS: This retrospective cohort study compared phenobarbital to benzodiazepines for the management of SAWS for patients admitted to progressive or intensive care units (ICUs) between July 2018 and July 2022. Patients included had a history of delirium tremens (DT) or seizures, Clinical Institute Withdrawal Assessment of Alcohol-Revised (CIWA-Ar) >15, or Prediction of Alcohol Withdrawal Severity Scale (PAWSS) score ≥4. The primary outcome was hospital length of stay (LOS). Secondary outcomes included progressive or ICU LOS, incidence of adjunctive pharmacotherapy, and incidence/duration of mechanical ventilation. RESULTS: The final analysis included 126 phenobarbital and 98 benzodiazepine encounters. Patients treated with phenobarbital had shorter median hospital LOS versus those treated with benzodiazepines (2.8 vs 4.7 days; P < 0.0001); a finding corroborated by multivariable analysis. The phenobarbital group also had shorter median progressive/ICU LOS (0.7 vs 1.3 days; P < 0.0001), and lower incidence of dexmedetomidine (P < 0.0001) and antipsychotic initiation (P < 0.0001). Fewer patients in the phenobarbital group compared to the benzodiazepine group received new mechanical ventilation (P = 0.045), but median duration was similar (1.2 vs 1.6 days; P = 1.00). CONCLUSION AND RELEVANCE: Scheduled phenobarbital was associated with decreased hospital LOS compared to benzodiazepines for SAWS. This was the first study to compare outcomes of fixed-dose, nonoverlapping phenobarbital to benzodiazepines in patients with clearly defined SAWS and details a readily implementable protocol.

Impact of Initial Warfarin Dosing on Time in Therapeutic Range for Postoperative Left Ventricular Assist Device Patients.

ABSTRACT: Initial warfarin dosing and time in therapeutic range (TTR) are poorly characterized for early post-operative left ventricular assist device (LVAD) patients. This study evaluated TTR after LVAD implantation compared between patients receiving low-dose (<3 mg) and high-dose (≥3 mg) warfarin. This single-center, retrospective analysis included 234 LVAD patients who received warfarin within 5 days of implantation. The primary outcome was TTR during the 5 days following first international normalized ratio (INR) ≥2 compared between low-dose and high-dose groups. Secondary outcomes were hospital and intensive care unit length of stay, time to first INR ≥2, TTR after first INR ≥2, and reinitiation of parenteral anticoagulation. No difference in TTR was detected between warfarin groups (57.2% vs. 62.7%, P = 0.13). Multivariable analysis did not detect any factors predictive of TTR during the primary outcome timeframe, but age and body mass index were associated with the warfarin dose. The low-dose group received a mean warfarin dose of 1.9 mg (±0.64 mg), and the high dose group received 4.34 mg (±1.38 mg). Cohort TTR during the primary outcome timeframe was 60.5% and 56.5% for hospitalization. The low-dose group had longer intensive care unit length of stay, shorter time to therapeutic INR, and more frequently reinitiated parenteral anticoagulation. Patients with recent LVAD implantation are complex and have diverse warfarin sensitivity factors, which did not allow for optimal warfarin dose detection, although half of all patients received doses between 2.04 mg and 4.33 mg. Individualized dosing should be used, adjusting for patient-specific factors such as age, body mass index, and drug interactions.

Nebulized Heparin for Adult Patients With Smoke Inhalation Injury: A Review of the Literature.

Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.

Warfarin-Induced Rapid Rise in INR Post-Cardiac Surgery Is Not Associated With Increased Bleeding Risk.

Background: Post-cardiac surgery bleeding can have devastating consequences, and it is unknown if warfarin-induced rapid international normalized ratio (INR) rise during the immediate postoperative period increases bleed risk. Objective: To determine the impact of warfarin-induced rapid-rise INR on post-cardiac surgery bleeding. Methods: This was a single-center, retrospective chart review of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester. Patients were grouped based on occurrence or absence of rapid-rise INR (increase ≥1.0 within 24 hours). The primary outcome compared bleed events between groups. Secondary outcomes assessed hospital length of stay (LOS) and identified risk factors associated with bleed events and rapid rise in INR. Results: During the study period, 2342 patients were included, and 56 bleed events were evaluated. Bleed events were similar between rapid-rise (n = 752) and non-rapid-rise (n = 1590) groups in both univariate (hazard ratio [HR] = 1.22; P = 0.594) and multivariable models (HR = 1.24; P = 0.561). Those with rapid-rise INR had longer LOS after warfarin administration (discharge HR = 0.84; P = 0.0002). The most common warfarin dose immediately prior to rapid rise was 5 mg. Risk factors for rapid-rise INR were low body mass index, female gender, and cross-clamp time. Conclusion and Relevance: This represents the first report to assess warfarin-related rapid-rise INR in post-cardiac surgery patients and found correlation to hospital LOS but not bleed events. Conservative warfarin dosing may be warranted until further research can be conducted.

Impact of initial fluid resuscitation volume on clinical outcomes in patients with heart failure and septic shock.

Background: Fluid resuscitation is a key treatment for sepsis, but limited data exists in patients with existing heart failure (HF) and septic shock. The objective of this study was to determine the impact of initial fluid resuscitation volume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with septic shock. Methods: This multicenter, retrospective, cohort study included patients with known HF (LVEF ≤50%) presenting with septic shock. Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h; <30 mL/kg or ≥30 mL/kg. The primary outcome was a composite of in-hospital mortality or renal replacement therapy (RRT) within 7 days. Secondary outcomes included acute kidney injury (AKI), initiation of mechanical ventilation, and length of stay (LOS). All related data were collected and compared between the two groups. A generalized logistic mixed model was used to assess the association between fluid groups and the primary outcome while adjusting for baseline LVEF, Acute Physiology and Chronic Health Evaluation (APACHE) II score, inappropriate empiric antibiotics, and receipt of corticosteroids. Results: One hundred and fifty-four patients were included (93 patients in <30 mL/kg group and 61 patients in ≥30 mL/kg group). The median weight-based volume in the first 6 h was 17.7 (12.2-23.0) mL/kg in the <30 mL/kg group vs. 40.5 (34.2-53.1) mL/kg in the ≥30 mL/kg group (P <0.01). No statistical difference was detected in the composite of in-hospital mortality or RRT between the <30 mL/kg group compared to the ≥30 mL/kg group (55.9% vs. 45.9%, P=0.25), respectively. The <30 mL/kg group had a higher incidence of AKI, mechanical ventilation, and longer hospital LOS. Conclusions: In patients with known reduced or mildly reduced LVEF presenting with septic shock, no difference was detected for in-hospital mortality or RRT in patients who received ≥30 mL/kg of resuscitation fluid compared to less fluid, although this study was underpowered to detect a difference. Importantly, ≥30 mL/kg fluid did not result in a higher need for mechanical ventilation.

The impact of serum zinc normalization on clinical outcomes in severe burn patients.

INTRODUCTION: Patients with thermal burns become zinc deficient due to exudative losses, increased urinary excretion, and reduction of carrier proteins which results in impaired immunity, wound healing and glucose control. Previous trials have demonstrated improved wound healing utilizing fixed zinc supplementation, but none have assessed the potential benefits associated with normalizing serum zinc concentrations. The objective of this study was to compare the impact of zinc normalization on clinical outcomes in patients with severe thermal burns. METHODS: This retrospective, single-center study of patients with at least 10% total body surface area (TBSA) burn and three serum zinc concentrations compared the ratio of hospital length of stay (LOS) over TBSA burned (LOS/TBSA index) between those with normal (≥60 mcg/mL) and non-normal (<60 mcg/mL) serum zinc concentrations; delineated by the third measurement. Secondary outcomes were time to 90% epithelialization, infection incidence, and percentage of blood glucose values greater than 180 mg/dL. Data are reported as median [25-75% interquartile range] for continuous variables and frequency (percent) for categorical variables. RESULTS: A total of 56 patients were included for evaluation (11 normal and 45 non-normal). Burn size was 20.5% TBSA [11-29] for those with normal zinc and 27.3% [22-36] for non-normal; number of grafts for each group was 1 [0-1] vs 2 [1-3] respectively. LOS/TBSA index did not differ significantly between groups (1.10 normal vs. 1.21 non-normal, unadjusted p = 0.69; p = 0.75 adjusting for number of grafts). Time to 90% epithelialization was reduced in the normal group (27.5 vs. 57 days, p = 0.02), but this did not remain statistically significant after adjustment for %TBSA and number of grafts (p = 0.18). The groups did not differ significantly in incidence of infection or hyperglycemia in either unadjusted or adjusted analyses. CONCLUSIONS: This was the first study, to our knowledge, to assess the clinical impact of normalizing serum zinc levels in patients with severe burns. Our results suggest the normalization of serum zinc levels through individualized zinc supplementation is not associated with improvement in clinical outcomes during hospitalization and therefore fixed-dose zinc supplementation without acquisition of serum zinc measurements should be considered.

Quantitative Assessment of Trace-Element Contamination in Parenteral Nutrition Components.

BACKGROUND: Trace-element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace-element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace-element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace-element prescribing in PN. METHODS: A total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace-element contamination. RESULTS: Trace-element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace-element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively. CONCLUSION: Trace-element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.

Comparison of Warfarin Requirements in Post-cardiac Surgery Patients: Valve Replacement Versus Non-valve Replacement.

INTRODUCTION: Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients. METHODS: This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries. RESULTS: A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions. CONCLUSIONS: This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.