Fixed, Dilated, and Cannulated - Medical Management of Elevated Intracranial Pressures due to a Large Intracranial Hemorrhage in a Patient on Veno-Venous Extracorporeal Membrane Oxygenation: Case Report.

A 40-year-old woman presented with mediastinitis, necrotizing pancreatitis, and severe acute respiratory distress syndrome with refractory acidemia (pH 7.14) and hypercapnia (PaCO2 115 mmHg), requiring veno-venous extracorporeal membrane oxygenation (ECMO). Eight hours after cannulation, and rapid correction of PaCO2 to 44 mmHg, she was found to have bilaterally fixed and dilated pupils. Imaging showed a 60 mL left-sided temporoparietal intracranial hemorrhage with surrounding edema, 8 mm midline shift, intraventricular hemorrhage, and impending herniation. Decompressive hemicraniectomy was not offered due to concern for medical instability. After receiving a dose of mannitol, her pupillary and motor exam improved. An intracranial pressure (ICP) monitor was placed to guide hyperosmolar therapy administration, hemodynamic targets, and sweep gas titration. On hospital day (HD) 5, her ICP monitor was removed. Follow-up imaging revealed resolution of mass effect and no brainstem injury. She was subsequently extubated (HD 9) and discharged home (HD 40). One year after hospitalization, she is living at home with minimal residual deficits. This case highlights the utility of targeted, medical ICP management and importance of assessing response to conservative therapies when considering prognosis in patients on ECMO with severe acute brain injury.

Variable Practice, Variable Results: Impact of Postinterview Communication Practices Among Critical Care Medicine/Pulmonary and Critical Care Medicine Fellowship Applicants and Program Directors.

BACKGROUND: Although postinterview communication (PIC) guidelines exist, adherence is voluntary. There are no studies of PIC practices in critical care medicine (CCM) and pulmonary and critical care medicine (PCCM) fellowship recruitment. RESEARCH QUESTION: What is the frequency, format, goals, and content of PIC between CCM/PCCM applicants and program directors? What is the impact of PIC on applicant and program rank order lists (ROLs)? STUDY DESIGN AND METHODS: CCM/PCCM applicants and program directors were separately surveyed after the 2022-2023 National Resident Matching Program Specialty Match. Surveys included multiple-choice, Likert-scale, and two free text questions. Thematic content analysis of free text responses was performed. RESULTS: One-third of eligible participants responded (applicants: n = 373 [34%]; program directors: n = 86 [32%]). Applicant respondents applied to CCM (19%), PCCM (69%), or both (12%). Program directors represented CCM (17%), PCCM (57%), or both (26%) programs. Applicant (66%) and program director (49%) respondents reported initiating PIC. PIC did not impact ROL decision for most applicants (73%) or program directors (83%), though 21% of applicants and 17% of program directors moved programs or applicants up on their ROL in response to PIC. One-quarter (23%) of applicants strongly agreed or agreed that PIC was helpful in creating their ROL, 27% strongly disagreed or disagreed, and 29% were neutral. PIC challenges identified by both groups included time; lack of uniformity; peer pressure; misleading language; and uncertainty about motives, rules, and response protocols. INTERPRETATION: PIC is common among CCM/PCCM applicants and program directors. About 50% of applicants and 20% of program directors share ranking intentions via PIC. Although PIC did not impact ROL for most applicants and program directors, a minority of applicants and program directors moved programs up on their ROL after receiving PIC from the other party. Applicants have mixed perspectives on PIC value. Applicants and program directors alike desire clear guidance on PIC to minimize ambiguous and misleading communication.

Novel non-invasive assessment of upper airway inflammation in obstructive sleep apnea using positron emission tomography/magnetic resonance imaging.

PURPOSE: To develop a novel non-invasive technique to quantify upper airway inflammation using positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with obstructive sleep apnea (OSA). METHODS: Patients with treatment naïve moderate-to-severe OSA underwent [18F]-fluoro-2-deoxy-D-glucose (FDG) PET/MRI. Three readers independently performed tracings of the pharyngeal soft tissue on MRI. Standardized uptake values (SUV) were generated from region of interest (ROI) tracings on corresponding PET images. Background SUV was measured from the sternocleidomastoid muscle. SUV and target-to-background (TBR) were compared across readers using intraclass correlation coefficient (ICC) analyses. SUV from individual image slices were compared between each reader using Bland-Altman plots and Pearson correlation coefficients. All tracings were repeated by one reader for assessment of intra-reader reliability. RESULTS: Five participants completed our imaging protocol and analysis. Median age, body mass index, and apnea-hypopnea index were 41 years (IQR 40.5-68.5), 32.7 kg/m2 (IQR 28.1-38.1), and 30.7 event per hour (IQR 19.5-48.1), respectively. The highest metabolic activity regions were consistently localized to palatine or lingual tonsil adjacent mucosa. Twenty-five ICC met criteria for excellent agreement. The remaining three were TBR measurements which met criteria for good agreement. Head-to-head comparisons revealed strong correlation between each reader. CONCLUSIONS: Our novel imaging technique demonstrated reliable quantification of upper airway FDG avidity. This technology has implications for future work exploring local airway inflammation in individuals with OSA and exposure to pollutants. It may also serve as an assessment tool for response to OSA therapies.

Postrenal transplant infection: What is the effect of specific immunosuppressant agents?

BACKGROUND: Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections. METHODS: A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed. RESULTS: The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; P = .020) were protective. CONCLUSION: Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.

Acetylcholinesterase and butyrylcholinesterase in cardiosurgical patients with postoperative delirium.

BACKGROUND: Patients in intensive care units (ICU) are often diagnosed with postoperative delirium; the duration of which has a relevant negative impact on various clinical outcomes. Recent research found a potentially important role of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in delirium of critically ill patients on non-surgical ICU or in non-cardiac-surgery patients. We tested the hypothesis that AChE and BChE have an impact on patients after cardiac surgery with postoperative delirium. METHODS: After obtaining approval from the local ethics committee, this mechanistic study gathered data of all 217 patients included in a randomized controlled trial testing non-pharmacological modifications of care in the cardiac surgical ICU to reduce delirium. Delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and the Nursing Delirium Screening Scale (Nu-DESC) twice a day for the first 3 days after surgery. Further outcome variables were somatic laboratory parameters and variables regarding surgery, anesthesia, and postsurgical recovery. 10 µl venous or arterial blood was drawn and AChE and BChE were determined with ChE check mobile from Securetec. RESULTS: Of 217 patients, 60 (27.6%) developed postsurgical delirium (POD). Patients with POD were older (p = 0.005), had anemia (p = 0.01), and worse kidney function (p = 0.006). Furthermore, these patients had lower intraoperative cerebral saturation (NIRS) (p < 0.001) and higher intraoperative need of catecholamines (p = 0.03). Delirious patients showed more inflammatory response (p < 0.001). AChE and BChE values were mainly inside the norm. Patients with values outside the norm did not have POD more often than others. Regarding AChE and BChE patients did not differ in having delirium or not (p > 0.10). CONCLUSIONS: Postoperative measurement of AChE and BChE did not discern between patients with and without POD. The effect of the cardiac surgical procedure on AChE and BChE remains unclear. Further studies with patients in cardiac surgery are needed to evaluate a possible combination of delirium and the cholinergic transmitter system. There might be possible interactions with AChE/BChE and blood products and the use of cardiopulmonary bypass, which should be investigated more intensively. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00006217.

Racial Disparity in Renal Transplantation: Alemtuzumab the Great Equalizer?

OBJECTIVES: Racial disparity as a barrier to successful outcomes in renal transplants for African Americans has been well described. Numerous unsuccessful attempts have been made to identify specific immunologic and socioeconomic factors. The objective of our study was to determine whether alemtuzumab (AL) induction abolishes this discrepancy and improves allograft survival in African American recipients. METHODS: A retrospective chart review of consecutive adult renal transplants was conducted between 2006 and 2014. Kaplan-Meier analysis and hazard ratios were calculated for the African Americans (AA) and white groups. Multiple linear regressions were performed to assess independent variables (race, retransplant, sex, donor type, induction agent) on allograft survival. RESULTS: A significant difference in allograft survival was identified between whites (n = 272) and AA (n = 445), with AA experiencing more graft losses (18.2% vs 12.1%, P = 0.0351). Induction with AL improved outcomes in all transplant recipients. Multiple linear regression identified that the strongest predictor of allograft failure was induction without AL (P < 0.0001). The data for a subset analysis matched for follow-up length demonstrated that whites compared with AA (n = 157, 67 whites and 90 AA) had lower rates of allograft failure in the absence of AL induction (14.9% vs 44.4%, P = 0.0156, hazard ratio = 2.077). In contrast, AL induction (n = 275, 105 whites and 170 AA) eliminated the racial disparity in allograft failure (5.7% vs 9.4%, P = 0.8248, hazard ratio = 1.504). CONCLUSIONS: This is the first study to describe the effects of AL induction therapy on AA renal transplant recipients beyond the first posttransplant year. Our early results suggest that AL induction therapy abolishes the disparity in renal allograft failure.

Generics: are all immunosuppression agents created equally?

BACKGROUND: The Affordable Care Act initiated innumerable cost-containment measures, including promoting generic conversion from brand medications and directing the Food and Drug Administration to decrease requirements for generic approvals. Despite this mandate, few data existed on generic conversion of immunosuppressant medications with narrow therapeutic troughs. METHODS: A retrospective analysis of our initial experience with generic tacrolimus (n = 39) was performed using a control cohort from our renal transplant database. A rejection and cost analysis was performed using a consecutive 2-year prior cohort (n = 159) as a control to determine the effect of generic conversion on tacrolimus a narrow therapeutic index immunosuppressant medication. RESULTS: During the first year after transplantation, the generic group had a greater drug variability (20% ± change in trough levels) that required more dosage adjustments (5.42 vs 3.59 drug dosage changes; P = .038) to obtain a stable dose, required increased number of intravenous magnesium infusions (4.95 vs 1.68 infusions; P = .001), and incurred a greater incidence of rejection (23.1% vs 10.2%; P = .024). A yearly institutional cost was evaluated against a negotiated $18,000/yearly central pharmacy cost savings compared with a $652,862 institutional cost to treat unanticipated rejections. CONCLUSION: Programmatic conversion from brand to generic tacrolimus resulted in increased drug variability, a greater incidence of magnesium wasting, and more episodes of rejection, leading to increases in institutional costs of care. This government-driven attempt at cost containment may be applicable to noncritical medications such as antibiotics and antihypertensives, but this policy should be reconsidered for narrow therapeutic index medications, such as tacrolimus and other immunosuppressant medications.

A method of comparison of different regimens for dialyzing single-pool solutes.

Many points of reference have been used to compare and rationalize extracorporeal end-stage renal disease therapy. We address a specific part of the subject: the effect of the delivery schedule on a predetermined dose of dialysis, e.g., weekly Kt/V. Steady (time-invariant) application of dialysis absolutely minimizes time-averaged and peak concentrations of any extractable solute. However, such dosing is often impractical; we assess the effectiveness of achievable slow regimens relative to steady dosing, using the single-pool approximation, applicable to slow regimens. Dose scheduling has been previously considered. We combine and discuss prior observations and establish continuous dosing as an easily quantifiable reference point, and we emphasize fundamental patterns common to different schedules. Thus, we enable rapid comparison of the many "slow" dialysis regimens presently under consideration using two intuitive parameters to encompass dialysis dosing: intermittency and intensity. These parameters define any repetitive dialysis pattern. A method for evaluating any combination of them is given with formulae, graphically, and with examples. Intermittency increases average solute concentration only slightly, but the frequency and spacing of intermittent treatments strongly affect peak solute concentrations. With steadier solute removal, cycling of solvent (water) stores is likely to remain the dominant source of disequilibrium in patients.