Acute cardiogenic shock secondary to blunt traumatic aortic valve injury.

Background: Blunt cardiac injuries rarely result in aortic valve cusp rupture, leading to acute aortic insufficiency and cardiogenic shock. This rare clinical entity carries a high mortality rate if left undiagnosed and not managed surgically, with few patients surviving beyond 24 h. It presents a diagnostic challenge in the polytrauma patient in shock, with multiple possible and complementary etiologies. Case presentation: We present a 56-year-old male with persistent hypotension, a wide pulse pressure, and elevated serum troponin levels suggesting blunt cardiac injury after a motor vehicle accident. Transthoracic and transesophageal echocardiography revealed normal biventricular function but severe aortic insufficiency due to prolapse of the left coronary cusp.He was taken emergently to surgery, where aortic valve exploration revealed complete left coronary cusp avulsion from the aortic annulus with a mid-cusp tear, requiring aortic valve replacement with a bioprosthetic valve. Postoperative echocardiography showed normal biventricular function with a well-seated bioprosthetic aortic valve with no insufficiency. Conclusions: Traumatic aortic valve injury can lead to torn or prolapsed cusps causing acute aortic insufficiency leading to cardiogenic shock, but early recognition with appropriate and targeted diagnostic imaging is vital to prevent rapid patient deterioration and demise.

Technical Considerations in Laparoscopic-Assisted Endoscopic Retrograde Cholangiography.

The use of endoscopic retrograde cholangiography (ERCP) for diagnostic and therapeutic interventions on the pancreaticobiliary system has steadily increased, but the standard approach through the oropharynx is prohibited after Roux-en-Y (RYGB) gastric bypass surgery. Laparoscopic access to the gastric remnant allows for the completion of ERCP using the standard side-viewing duodenoscope to facilitate the completion of standard and advanced endoscopic maneuvers. Here, we describe our experience with the technical aspects of safe and effective performance of laparoscopic-assisted ERCP.

A Daily Checklist Method Increases Documentation of Code Status in Trauma Patients.

OBJECTIVES: While insufficient code status documentation (CSD) is a longstanding challenge, all patients deserve the opportunity to participate in decision-making regarding code status, especially trauma patients with an unpredictable course. Prior interventions to increase CSD relied on reminder systems. We hypothesize that introducing a daily checklist will increase CSD for patients in the trauma ICU. METHODS: This quality improvement study examined the efficacy of a twice-daily checklist for improving CSD in trauma patients at a level I trauma center. A pre-intervention (PRE) and post-intervention (POST) daily census characterized the percentage of patients with CSD (primary outcome), time-to-code status (TTCS, secondary outcome) documentation, and information about patients who were discharged with no code status (DNCS, secondary outcome). RESULTS: Of 213 PRE and 207 POST, daily census CSD for all patients increased from a median of 50.0% PRE to 64.4% POST (P < .05). Time-to-code status was halved (PRE: 25.30 h, POST: 12.71 h, P < .05). Code status documentation within 12 h increased from 41.8% PRE to 60.9% POST (P < .05). Overall, the percentage of patients with CSD during their hospitalization increased 20% (PRE: 63.8%, POST: 83.6%, P < .05). Discharged with no code status patients decreased 20% (PRE: 35.2%, POST: 15.5%, P < .05). CONCLUSION: Including code status in a daily checklist involving key aspects of care for trauma patients is an effective method for improving code status documentation. Capturing code status for more patients in trauma allows us to provide patient-centered, goal-concordant care.

The Cost of Poverty: The Relationship Between Insurance Status, Length of Stay, and Discharge Disposition in Trauma Patients.

INTRODUCTION: Insurance status (IS) is known to be associated with length of stay (LOS). The impact of IS on excess LOS (ELOS), days between medical readiness and discharge date, has not been explored. METHODS: We conducted a retrospective study of patients with pelvic fractures at a level I trauma center. Outcomes included ELOS (primary), discharge disposition (secondary), and ELOS-associated complications (secondary). RESULTS: 185 patients were included. Uninsured patients were the youngest and had the least baseline comorbidities (31.3 years (median), Charlson Comorbidity Index (CCI) .1) while publicly insured patients were the oldest and had the most baseline comorbidities (58.4 years (median), CCI 2.32). Excess LOS and associated complications did not differ among groups. After regression analysis, UIPs had longer LOS than PRPs (2.07 days, 95% CI .28-3.85). UIPs were recommended to go to inpatient rehabilitation 51.6% of the time but were discharged home 93.6% of the time; 81.0% of these changes were attributed to insufficient financial resources. CONCLUSIONS: Excess LOS and complications associated with ELOS were not associated with IS. Although UIPs were younger and had fewer baseline comorbidities, they had longer LOS after regression analysis. While discharge recommendations differed based on insurance status, UIPs had limited access to rehabilitation due to financial disparities. Despite initial treatment team recommendations, UIPs had to be sent home as their lack of insurance precluded inpatient rehabilitation placement.

To Resect or Not to Resect: A Nationwide Comparison of Management of Sigmoid Volvulus.

INTRODUCTION: Despite the high recurrence rate of sigmoid volvulus, there is reluctance to perform a prophylactic colectomy in frail patients due to the operation's perceived risks. We used a nationally representative database to compare risk of recurrence in patients undergoing a prophylactic colectomy versus endoscopic detorsion alone. METHODS: We performed a retrospective cohort study using the National Readmission Database (2016-2019) including patients aged ≥18 y who had an emergent admission for sigmoid volvulus and underwent endoscopic detorsion on the day of admission. We performed a 1:1 propensity matching adjusting for patient demographics, frailty score comprising of 109 components, and hospital characteristics. Our primary outcome was readmission due to colonic volvulus and secondary outcomes included mortality, complications, length of stay (LOS), and costs during index admission and readmission. We performed a subgroup analysis in patients with Hospital Frailty Score >5. RESULTS: We included 2113 patients of which 1046 patients (49.5%) underwent a colectomy during the initial admission. In the matched population of 830 pairs, readmission due to colonic volvulus was significantly lower in patients undergoing endoscopy followed by colectomy than endoscopy alone. Patients undergoing a colectomy had higher gastric and renal complications, longer LOS, and higher costs but no difference in mortality. In the subgroup analysis of frail patients, readmission was significantly lower in patients with prophylactic colectomy with no significant difference in mortality in 439 matched patients. CONCLUSIONS: Prophylactic colectomy was associated with lower readmission, a higher rate of complications, increased LOS, and higher costs compared to sigmoid decompression alone.

Incidence of Endoscopic Retrograde Cholangiography after Subtotal Fenestrating and Reconstituting Cholecystectomy.

BACKGROUND: Laparoscopic subtotal cholecystectomy (SC) is used for the difficult cholecystectomy, but published experience with resource utilization for SC is limited. We hypothesized that the need for advanced resources are common after SC. STUDY DESIGN: Retrospective review of laparoscopic cholecystectomies between 2017 and 2021 at a large center. SC cases were identified using a medical record tool. Baseline characteristics were assessed with student's t-test and chi-squared. Primary outcome was ERC within 60-days. Secondary outcomes were reconstituted SC on post-op ERC and length of stay (LOS). Uni- and multivariable logistic regression were used for binary outcomes. Multiple linear regression was used for LOS. Covariates included age, sex, BMI, ASA class. RESULTS: A total of 1222 laparoscopic cholecystectomies were performed between 2017 and 2021. Of these, 87 (7%) were SC. Male (p<0.001) and older (p<0.001) patients were more likely to undergo SC. Odds of post-op ERC were higher in the SC group (OR 9.79 95% CI 5.90, 16.23 p<0.001). There was no difference in pre-op ERC (17% vs 21% p=0.38). Reconstituting SC had lower odds of post-op ERC (OR 0.12, 0.023-0.58, p=0.009). LOS was 1.81 times higher in the SC group(p=<0.001). Post-op ERC was not associated with LOS (p=.24). CONCLUSIONS: We present one of the largest single-center series of SC. SC patients are more likely to be male, older, have higher ASA class, and have increased LOS. SC should be performed when access to ERC and interventional radiology is available. Absent these adjuncts, reconstituting SC decreases the need for early ERC, but long-term outcomes are unknown.

The Importance of Early Femoral Access When REBOA Catheter Must Be Removed Prior to Hemorrhage Control.

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a tool for hemorrhage control. We describe a case where the REBOA Catheter needed to be removed prior to hemorrhage control. The patient is a 40-year-old man that presented following motor vehicle collision. A REBOA Catheter was placed via the right common femoral artery (CFA). CT scan demonstrated extravasation from the left inferior epigastric artery. The Interventional Radiology (IR) team would only be able to perform angioembolization via contralateral access where the REBOA Catheter was in place. Prior to removing the REBOA Catheter on the right, left CFA access was obtained in the event a new catheter needed to be deployed. Ultimately, IR performed angioembolization without a second REBOA Catheter. In gaining contralateral access prior to removing the REBOA Catheter, this case provides a strategy for expeditious replacement of REBOA Catheters in situations where the catheter interferes with hemorrhage control procedures.

Computed tomography scanning is feasible in select patients with REBOA catheter deployment.

BACKGROUND: Rapidly localizing and controlling bleeding is central to treating hemorrhagic shock. While REBOA allows temporary control, identifying the source of bleeding remains challenging. CT imaging with REBOA in place may provide information to direct hemorrhage control. The purpose of this study is to provide a descriptive summary of data comparing patients who did and did not undergo CT scan following REBOA deployment. Our hypothesis was that performing CT scan after REBOA placement in select patients is safe and can guide management of hemorrhagic shock. METHODS: We queried the AAST AORTA registry for patients receiving REBOA at our level 1 trauma center from May 2017 to December 2021. Clinical data was obtained through the Trauma Registry of the American College of Surgeons (TRACS). Comparison groups were those who underwent CT scan after REBOA deployment versus those who did not undergo CT scan after REBOA deployment. The primary outcome was inhospital mortality, and secondary outcomes included hospital-, ICU-, and ventilator-free days. RESULTS: 61 patients underwent CT scan with REBOA in place; 25 patients proceeded directly to hemorrhage control. Patients with REBOA prior to CT were more likely to have blunt mechanism, higher ISS, pelvic bleeding, and zone 3 REBOA placement. Mortality was not significantly different (51 % vs. 64 %). Patients who underwent CT with REBOA were more likely to undergo hemorrhage control in interventional radiology (43 % vs. 0 %). There was no difference in hospital-, ICU-, and ventilator-free days. DISCUSSION: We demonstrate the feasibility of performing CT in select trauma patients who undergo REBOA. We describe a pathway to enable expeditious workup and management of these patients. Optimal hemorrhage control management is impacted by CT scans when it can be performed. It is important to note that this is a severely injured patient population, and mortality is high even when hemorrhage is controlled. LEVEL OF EVIDENCE: III.

Zonisamide: A Comprehensive, Updated Review for the Clinician.

Purpose of Review: Zonisamide (ZNS) was first approved in the United States in 2000 for the adjunctive treatment of patients aged 16 years or older with partial (focal) seizures. Although ZNS has been proven to treat multiple seizure types, it has been largely underutilized in US clinical practice. Recent Findings: Published literature demonstrated that antiseizure medications (ASMs) acting on Na+ and Ca2+ channels may add beneficial effects in many seizure types by reducing seizure frequency and leading to overall improvements. In addition, effects of ZNS may lead to clinical improvements in Parkinson disease, alcohol and sleep disorders, pain, and migraine. ZNS is available in multiple formulations and is a safe and effective, broad spectrum ASM. Summary: The purpose of this review was to provide an update to what is known about the efficacy of ZNS and where it shows benefits in the treatment of patients with epilepsy and other CNS disorders through its many unique mechanisms of action.

UK adult ADHD services in crisis.

The UK's services for adult attention-deficit hyperactivity disorder (ADHD) are in crisis, with demand outstripping capacity and waiting times reaching unprecedented lengths. Recognition of and treatments for ADHD have expanded over the past two decades, increasing clinical demand. This issue has been exacerbated by the COVID-19 pandemic. Despite an increase in specialist services, resource allocation has not kept pace, leading to extended waiting times. Underfunding has encouraged growth in independent providers, leading to fragmentation of service provision. Treatment delays carry a human and financial cost, imposing a burden on health, social care and the criminal justice system. A rethink of service procurement and delivery is needed, with multiple solutions on the table, including increasing funding, improving system efficiency, altering the service provision model and clinical prioritisation. However, the success of these solutions hinges on fiscal capacity and workforce issues.

Vascular imaging immediately after tourniquet removal does not increase vasospasm risk.

BACKGROUND: Prehospital tourniquet use is now standard in trauma patients with diagnosed or suspected extremity vascular injuries. Tourniquet-related vasospasm is an understudied phenomenon that may confound management by causing erroneous arterial pressure indices (APIs) and abnormalities on computed tomography angiography (CTA) that do not reflect true arterial injuries. We hypothesized that shorter intervals between tourniquet removal and CTA imaging and longer total tourniquet times would be correlated with a higher likelihood of false positive CTA. MATERIALS AND METHODS: We performed a single-institution retrospective cohort study of patients presenting to a busy, urban Level 1 Trauma Center with prehospital tourniquets from 2019 to 2021. Patients who presented with a tourniquet disengaged upon arrival or who died prior to admission to the Trauma Unit were excluded. Tourniquet duration, time between tourniquet removal and CTA imaging (CTA interval), CTA findings, and management of extremity arterial injuries were extracted. The proportion of false positive injuries on CTA was assessed for correlation with increasing time interval from tourniquet removal to CTA imaging and correlation with increasing total tourniquet time using multivariable logistic regression. RESULTS: 251 patients were identified with prehospital tourniquets. 127 underwent CTA of the affected extremity, 96 patients had an abnormal CTA finding, and 57 (45% of total CTA patients) had false positive arterial injuries on imaging. Using multivariable logistic regression, neither the CTA interval nor the tourniquet duration was associated with false positive CTA injuries. Female sex was associated with false positive injuries on CTA (OR 2.91, 95% CI: 1.01 - 8.39). Vasospasm was cited as a possible explanation by radiologists in 40% of false positive CTA reports. CONCLUSIONS: Arterial vasospasm is a frequent finding on CTA after tourniquet use for extremity trauma, but concerns regarding tourniquet-related vasospasm should not alter trauma patient management. Neither the duration of tourniquet application nor the time interval since removal is associated with decreased CTA accuracy, and any delay in imaging does not appear to reduce the likelihood of vasospasm. These findings are important for supporting expedited care of trauma patients with severe extremity injuries.

Comparison of phenobarbital monotherapy to a benzodiazepine-based regimen for management of alcohol withdrawal syndrome in trauma patients.

BACKGROUND: Alcohol withdrawal syndrome (AWS) is associated with increased morbidity and mortality in the trauma population. Benzodiazepines (BZDs) are standard of care for AWS; however, given the risk of delirium with BZDs and reports of BZD-refractory withdrawal, phenobarbital (PHB) has emerged as an alternative therapy for AWS. Safety and efficacy studies of PHB for AWS in trauma patients are lacking. Our aim was to compare a BZD versus PHB protocol in the management of AWS in trauma patients. METHODS: We performed a retrospective cohort study at a level 1 trauma center of patients at risk for AWS managed with either a BZD or a low-dose oral PHB regimen. Patients were excluded if they were taking BZDs or barbiturates before admission, received propofol or dexmedetomidine before initiation of the study drug, presented with delirium tremens or seizures, or died or discharged within 24 hours of presentation. The primary outcome was complicated AWS (seizures or alcohol withdrawal delirium/delirium tremens). Secondary outcomes included uncomplicated AWS; therapy escalation; oversedation; delirium-, intensive care unit-, and ventilator-free days; and length of stay. RESULTS: A total of 411 patients were identified; 118 received BZD, and 293 received PHB. The odds of developing complicated AWS with PHB versus BZD-based therapy were not statistically significant (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.21-1.39); however, patients receiving PHB were less likely to develop uncomplicated AWS (OR, 0.08; 95% CI, 0.04-0.14) and less likely to require escalation of therapy (OR, 0.45; 95% CI, 0.24-0.84). The PHB group had a length of stay 3.1 days shorter than the BZD group ( p = 0.002). There was no difference in intensive care unit-, ventilator-, or delirium-free days. CONCLUSION: A PHB-based protocol for the management of AWS is a safe and effective alternative to BZD-based regimens in trauma patients. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The evolution of scientific literature as metastable knowledge states.

The problem of identifying common concepts in the sciences and deciding when new ideas have emerged is an open one. Metascience researchers have sought to formalize principles underlying stages in the life cycle of scientific research, understand how knowledge is transferred between scientists and stakeholders, and explain how new ideas are generated and take hold. Here, we model the state of scientific knowledge immediately preceding new directions of research as a metastable state and the creation of new concepts as combinatorial innovation. Through a novel approach combining natural language clustering and citation graph analysis, we predict the evolution of ideas over time and thus connect a single scientific article to past and future concepts in a way that goes beyond traditional citation and reference connections.

Rethinking protocolized completion angiography following extremity vascular trauma: A prospective observational multicenter trial.

BACKGROUND: Completion angiography (CA) is commonly used following repair of extremity vascular injury and is recommended by the Eastern Association for the Surgery of Trauma practice management guidelines for extremity trauma. However, it remains unclear which patients benefit from CA because only level 3 evidence exists. METHODS: This prospective observational multicenter (18LI, 2LII) analysis included patients 15 years or older with extremity vascular injuries requiring operative management. Clinical variables and outcomes were analyzed with respect to with our primary study endpoint, which is need for secondary vascular intervention. RESULTS: Of 438 patients, 296 patients required arterial repair, and 90 patients (30.4%) underwent CA following arterial repair. Institutional protocol (70.9%) was cited as the most common reason to perform CA compared with concern for inadequate repair (29.1%). No patients required a redo extremity vascular surgery if a CA was performed per institutional protocol; however, 26.7% required redo vascular surgery if the CA was performed because of a concern for inadequate repair. No differences were observed in hospital mortality, length of stay, extremity ischemia, or need for amputation between those who did and did not undergo CA. CONCLUSION: Completion angiogram following major extremity injury should be considered in a case-by-case basis. Limiting completion angiograms to those patients with concern for an inadequate vascular repair may limit unnecessary surgery and morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Analysis of Need for Intervention in Low-Grade Traumatic Splenic Injury.

BACKGROUND: Blunt splenic injuries are common traumatic injuries. Severe injuries may require blood transfusion, procedural, or operative intervention. Conversely, patients with low-grade injuries and normal vital signs frequently do not require intervention. The level and duration of monitoring required to safely manage these patients are unclear. We hypothesize that low-grade splenic trauma has a low rate of intervention and may not require acute hospitalization. METHODS: This retrospective descriptive analysis included patients admitted to a level I trauma center with low injury burden (injury severity score <15) and The American Association for the Surgery of Trauma (AAST) grade 1 (G1) and 2 (G2) splenic injuries between January 2017 and December 2019 using the Trauma Registry of the American College of Surgeons (TRACS). The primary outcome was the need for any intervention. Secondary outcomes included time to intervention and length of stay. RESULTS: 107 patients met inclusion criteria. 87.9% required no intervention . 9.4% required blood products, with a median time to transfusion of 7.4 hours from arrival. All patients receiving blood products had extenuating circumstances such as bleeding from other injuries, anticoagulant use, or medical comorbidities. 2 patients required splenic artery embolization, one presenting with return precautions 9 days post-injury and 1 with significant comorbidities. One patient with concomitant bowel injury required splenectomy. CONCLUSIONS: Low-grade blunt splenic trauma has a low rate of intervention, which typically occurs within the first 12 hours of presentation. This suggests that outpatient management with return precautions may be appropriate for select patients after a short interval of observation.

The Safe Cholecystectomy: Evaluating the Use of Laparoscopic Subtotal Cholecystectomy Between Junior and Senior Faculty.

BACKGROUND: Laparoscopic Subtotal Cholecystectomy (SC) is a technique for performing safe cholecystectomy when excessive inflammation prevents exposure of the Critical View of Safety. Studies have evaluated outcomes and complications of laparoscopic cholecystectomy (LC), with mixed results in terms of surgeon experience. It is unclear if the rate of SC is associated with experience. We hypothesized that the rate of SC would decrease as surgical experience increased. METHODS: We performed a retrospective review of LC performed at an academic medical center. Demographics were analyzed using descriptive statistics. We performed a multivariable logistic regression to examine the relationship between years in practice and performance of SC. We performed a sensitivity analysis comparing those in their first year on faculty with all others. RESULTS: Between November 1, 2017, and November 1, 2021, there were 1222 LC performed. 771 patients (63%) were female. 89 patients (7.3%) underwent SC. There were no bile duct injuries requiring reconstruction. Controlling for age, sex, and ASA class, there was no difference in the rate of SC by years of experience (OR .98, 95% CI .94-1.01). In a sensitivity analysis comparing first-year faculty to those beyond their first year, there was also no difference (OR .76, 95% CI 0.42-1.39). DISCUSSION: We find no difference in the rate of performance of SC between junior and senior faculty. This reflects consistency, in keeping with best practice guidelines. This could be confounded by junior faculty requesting assistance during difficult operations. Further investigation into factors affecting decision-making may clarify this.

Dispelling Dogma: American Association for Surgery of Trauma Prospective, Multicenter Trial of Index vs Delayed Fasciotomy after Extremity Trauma.

BACKGROUND: Surgical dogma states that "if you think about doing a fasciotomy, you do it," yet the benefit of this approach remains unclear. We hypothesized that early fasciotomy during index operative procedures for extremity vascular trauma would be associated with improved patient outcomes. STUDY DESIGN: This prospective, observational multicenter (17 level 1, 1 level 2) analysis included patients ≥15 years old with extremity vascular injury requiring operative management. Clinical variables were analyzed with respect to fasciotomy timing for correlation with outcomes, including muscle necrosis and limb amputation. Associated variables (p < 0.05) were input into multivariable logistic regression models evaluating these endpoints. RESULTS: Of 436 study patients, most were male (87%) with penetrating (57%), lower extremity (77%), arterial (73%), vein (40%), and bony (53%) injury with prolonged hospital length of stay (11 days). Patients who had index fasciotomy (66%) were compared with those who did not (34%), and no differences were appreciated with respect to age, initial systolic blood pressure, tourniquet time, "hard" signs of vascular injury, massive transfusion protocol activation, or Injury Severity Score (all p < 0.05). Of the 289 patients who underwent index fasciotomy, 49% had prophylactic fasciotomy, 11% developed muscle necrosis, 4% required an additional fasciotomy, and 8% required amputation, although only 28 of 147 (19%) required delayed fasciotomy in those without index fasciotomy. Importantly, forgoing index fasciotomy did not correlate (p > 0.05) with additional muscle necrosis or amputation risk in the delayed fasciotomy group. After controlling for confounders, index surgery fasciotomy was not associated with either muscle necrosis or limb salvage in multivariable models. CONCLUSIONS: Routine, index operation fasciotomy failed to demonstrate an outcome benefit in this prospective, multicenter analysis. Our data suggest that a careful observation and fasciotomy-when-needed approach may limit unnecessary surgery and its resulting morbidity in extremity vascular trauma patients.

Acquired Tracheomalacia Requiring Urgent Tracheostomy Exchange in Patients With COVID-19.

Tracheostomy for prolonged ventilation of patients with COVID-19 was often delayed due to high viral loads and persistent high ventilatory requirements. With prolonged intubation and significant dose corticosteroid use, patients with COVID-19 are at risk for tracheomalacia, and urgent tube exchange may be required to address persistent cuff leak and to maintain adequate mechanical ventilation. We sought to describe our single center experience with COVID-19 patients requiring tracheostomy and the tracheal complications that followed. We performed a review of patients with COVID-19 who underwent tracheostomy from June 2020 to October 2021. 45 patients were identified; 82.2% survived their index hospitalization. Tracheostomy was performed after 16.4 days of mechanical ventilation. 22.2% required urgent exchange to an extended length tracheostomy tube after 7.2 days from initial tracheostomy. Placement of an extended length tracheostomy tube can reduce cuff leak in ventilated COVID-19 patients and may be considered during initial tracheostomy placement.

Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.

INTRODUCTION: Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures. METHODS: A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided. RESULTS: We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy. CONCLUSION: The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.

Some people with epilepsy need to take more than one seizure medicine as part of their treatment. Taking more than one seizure medicine, however, can increase the risk of unwanted side effects. One approach to preventing side effects when adding a new seizure medicine is to lower the amount (dose) of existing seizure medicines. Cenobamate is a newer seizure medicine available in the USA for adults with focal seizures (also referred to as partial-onset seizures). Cenobamate, like many seizure medicines, must be titrated over time to a target dose. A group of epilepsy specialists met and developed recommendations for when and how to change the doses of existing seizure medicines when adding cenobamate. The goal of these recommendations is to prevent or reduce side effects like sleepiness or dizziness. The authors recommend that the dose of specific seizure medicines, including clobazam, lacosamide, phenytoin, and phenobarbital, be lowered as cenobamate is started or as cenobamate's dose is being increased (but before side effects occur). Regular doses of other seizure medicines can be lowered if a side effect occurs because reducing the dose of the other seizure medications can often stop the side effect. These recommendations may help patients successfully reach their optimal dose of cenobamate with fewer side effects, potentially improving their seizure control. Video Abstract: Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.

Balanced Crystalloid versus Saline in Adults with Traumatic Brain Injury: Secondary Analysis of a Clinical Trial.

Balanced crystalloids may improve outcomes compared with saline for some critically ill adults. Lower tonicity of balanced crystalloids could worsen cerebral edema in patients with intracranial pathology. The effect of balanced crystalloids versus saline on clinical outcomes in patients with traumatic brain injury (TBI) requires further study. We planned an a priori subgroup analysis of TBI patients enrolled in the pragmatic, cluster-randomized, multiple-crossover Isotonic Solutions and Major Adverse Renal Events Trial (SMART) (ClinicalTrials.gov: NCT02444988, NCT02547779). Primary outcome was 30-day in-hospital mortality. Secondary outcomes included hospital discharge disposition (home, facility, death). Regression models adjusted for pre-specified baseline covariates compared outcomes. TBI patients assigned to balanced crystalloids (n = 588) and saline (n = 569) had similar baseline characteristics including Injury Severity Score 19 (10); mean maximum head/neck Abbreviated Injury Score, 3.4 (1.0). Isotonic crystalloid volume administered between intensive care unit admission and first of hospital discharge or 30 days was 2037 (3470) mL and 1723 (2923) mL in the balanced crystalloids and saline groups, respectively (p = 0.18). During the study period, 94 (16%) and 82 (14%) patients (16%) died in the balanced crystalloid and saline groups, respectively (adjusted odds ratio [aOR], 1.03; 95% confidence interval [CI], 0.60 to 1.75; p = 0.913). Patients in the balanced crystalloid group were more likely to die or be discharged to another medical facility (aOR 1.38 [1.02-1.86]; p = 0.04). Overall, balanced crystalloids were associated with worse discharge disposition in critically injured patients with TBI compared with saline. The confidence intervals cannot exclude a clinically relevant increase in mortality when balanced crystalloids are used for patients with TBI.