Browsing by Author "Wischmeyer, Paul E"
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Item Open Access A randomized trial of supplemental parenteral nutrition in underweight and overweight critically ill patients: the TOP-UP pilot trial.(Crit Care, 2017-06-09) Wischmeyer, Paul E; Hasselmann, Michel; Kummerlen, Christine; Kozar, Rosemary; Kutsogiannis, Demetrios James; Karvellas, Constantine J; Besecker, Beth; Evans, David K; Preiser, Jean-Charles; Gramlich, Leah; Jeejeebhoy, Khursheed; Dhaliwal, Rupinder; Jiang, Xuran; Day, Andrew G; Heyland, Daren KBACKGROUND: Nutrition guidelines recommendations differ on the use of parenteral nutrition (PN), and existing clinical trial data are inconclusive. Our recent observational data show that amounts of energy/protein received early in the intensive care unit (ICU) affect patient mortality, particularly for inadequate nutrition intake in patients with body mass indices (BMIs) of <25 or >35. Thus, we hypothesized increased nutrition delivery via supplemental PN (SPN) + enteral nutrition (EN) to underweight and obese ICU patients would improve 60-day survival and quality of life (QoL) versus usual care (EN alone). METHODS: In this multicenter, randomized, controlled pilot trial completed in 11 centers across four countries, adult ICU patients with acute respiratory failure expected to require mechanical ventilation for >72 hours and with a BMI of <25 or ≥35 were randomized to receive EN alone or SPN + EN to reach 100% of their prescribed nutrition goal for 7 days after randomization. The primary aim of this pilot trial was to achieve a 30% improvement in nutrition delivery. RESULTS: In total, 125 patients were enrolled. Over the first 7 post-randomization ICU days, patients in the SPN + EN arm had a 26% increase in delivered calories and protein, whereas patients in the EN-alone arm had a 22% increase (both p < 0.001). Surgical ICU patients received poorer EN nutrition delivery and had a significantly greater increase in calorie and protein delivery when receiving SPN versus medical ICU patients. SPN proved feasible to deliver with our prescribed protocol. In this pilot trial, no significant outcome differences were observed between groups, including no difference in infection risk. Potential, although statistically insignificant, trends of reduced hospital mortality and improved discharge functional outcomes and QoL outcomes in the SPN + EN group versus the EN-alone group were observed. CONCLUSIONS: Provision of SPN + EN significantly increased calorie/protein delivery over the first week of ICU residence versus EN alone. This was achieved with no increased infection risk. Given feasibility and consistent encouraging trends in hospital mortality, QoL, and functional endpoints, a full-scale trial of SPN powered to assess these clinical outcome endpoints in high-nutritional-risk ICU patients is indicated-potentially focusing on the more poorly EN-fed surgical ICU setting. TRIAL REGISTRATION: NCT01206166.Item Open Access American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.(Anesth Analg, 2018-01-23) Wischmeyer, Paul E; Carli, Franco; Evans, David C; Guilbert, Sarah; Kozar, Rosemary; Pryor, Aurora; Thiele, Robert H; Everett, Sotiria; Grocott, Mike; Gan, Tong J; Shaw, Andrew D; Thacker, Julie KM; Miller, Timothy E; Hedrick, Traci L; McEvoy, Matthew D; Mythen, Michael G; Bergamaschi, Roberto; Gupta, Ruchir; Holubar, Stefan D; Senagore, Anthony J; Abola, Ramon E; Bennett-Guerrero, Elliott; Kent, Michael L; Feldman, Liane S; Fiore, Julio F; Perioperative Quality Initiative (POQI) 2 WorkgroupPerioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.Item Open Access American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Patient-Reported Outcomes in an Enhanced Recovery Pathway.(Anesthesia and analgesia, 2018-06) Abola, Ramon E; Bennett-Guerrero, Elliott; Kent, Michael L; Feldman, Liane S; Fiore, Julio F; Shaw, Andrew D; Thacker, Julie KM; Gan, Tong J; Miller, Timothy E; Hedrick, Traci L; McEvoy, Matthew D; Mythen, Michael G; Bergamaschi, Roberto; Gupta, Ruchir; Holubar, Stefan D; Senagore, Anthony J; Wischmeyer, Paul E; Carli, Franco; Evans, David C; Guilbert, Sarah; Kozar, Rosemary; Pryor, Aurora; Thiele, Robert H; Everett, Sotiria; Grocott, Mike; Perioperative Quality Initiative (POQI) 2 WorkgroupPatient-reported outcomes (PROs) are measures of health status that come directly from the patient. PROs are an underutilized tool in the perioperative setting. Enhanced recovery pathways (ERPs) have primarily focused on traditional measures of health care quality such as complications and hospital length of stay. These measures do not capture postdischarge outcomes that are meaningful to patients such as function or freedom from disability. PROs can be used to facilitate shared decisions between patients and providers before surgery and establish benchmark recovery goals after surgery. PROs can also be utilized in quality improvement initiatives and clinical research studies. An expert panel, the Perioperative Quality Initiative (POQI) workgroup, conducted an extensive literature review to determine best practices for the incorporation of PROs in an ERP. This international group of experienced clinicians from North America and Europe met at Stony Brook, NY, on December 2-3, 2016, to review the evidence supporting the use of PROs in the context of surgical recovery. A modified Delphi method was used to capture the collective expertise of a diverse group to answer clinical questions. During 3 plenary sessions, the POQI PRO subgroup presented clinical questions based on a literature review, presented evidenced-based answers to those questions, and developed recommendations which represented a consensus opinion regarding the use of PROs in the context of an ERP. The POQI workgroup identified key criteria to evaluate patient-reported outcome measures (PROMs) for their incorporation in an ERP. The POQI workgroup agreed on the following recommendations: (1) PROMs in the perioperative setting should be collected in the framework of physical, mental, and social domains. (2) These data should be collected preoperatively at baseline, during the immediate postoperative time period, and after hospital discharge. (3) In the immediate postoperative setting, we recommend using the Quality of Recovery-15 score. After discharge at 30 and 90 days, we recommend the use of the World Health Organization Disability Assessment Scale 2.0, or a tailored use of the Patient-Reported Outcomes Measurement Information System. (4) Future study that consistently applies PROMs in an ERP will define the role these measures will have evaluating quality and guiding clinical care. Consensus guidelines regarding the incorporation of PRO measures in an ERP were created by the POQI workgroup. The inclusion of PROMs with traditional measures of health care quality after surgery provides an opportunity to improve clinical care.Item Open Access American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an Enhanced Recovery Pathway for Elective Colorectal Surgery.(Anesthesia and analgesia, 2018-06) Hedrick, Traci L; McEvoy, Matthew D; Mythen, Michael Monty G; Bergamaschi, Roberto; Gupta, Ruchir; Holubar, Stefan D; Senagore, Anthony J; Gan, Tong Joo; Shaw, Andrew D; Thacker, Julie KM; Miller, Timothy E; Wischmeyer, Paul E; Carli, Franco; Evans, David C; Guilbert, Sarah; Kozar, Rosemary; Pryor, Aurora; Thiele, Robert H; Everett, Sotiria; Grocott, Mike; Abola, Ramon E; Bennett-Guerrero, Elliott; Kent, Michael L; Feldman, Liane S; Fiore, Julio F; Perioperative Quality Initiative (POQI) 2 WorkgroupThe primary driver of length of stay after bowel surgery, particularly colorectal surgery, is the time to return of gastrointestinal (GI) function. Traditionally, delayed GI recovery was thought to be a routine and unavoidable consequence of surgery, but this has been shown to be false in the modern era owing to the proliferation of enhanced recovery protocols. However, impaired GI function is still common after colorectal surgery, and the current literature is ambiguous with regard to the definition of postoperative GI dysfunction (POGD), or what is typically referred to as ileus. This persistent ambiguity has impeded the ability to ascertain the true incidence of the condition and study it properly within a research setting. Furthermore, a rational and standardized approach to prevention and treatment of POGD is needed. The second Perioperative Quality Initiative brought together a group of international experts to review the published literature and provide consensus recommendations on this important topic with the goal to (1) develop a rational definition for POGD that can serve as a framework for clinical and research efforts; (2) critically review the evidence behind current prevention strategies and provide consensus recommendations; and (3) develop rational treatment strategies that take into account the wide spectrum of impaired GI function in the postoperative period.Item Open Access Are we creating survivors…or victims in critical care? Delivering targeted nutrition to improve outcomes.(Curr Opin Crit Care, 2016-08) Wischmeyer, Paul EItem Open Access Assessments of frailty in bladder cancer.(Urologic oncology, 2020-05-22) Grimberg, Dominic C; Shah, Ankeet; Molinger, Jeroen; Whittle, John; Gupta, Rajan T; Wischmeyer, Paul E; McDonald, Shelley R; Inman, Brant ABACKGROUND AND AIMS:The incidence of frailty is increasing as the population ages, which has important clinical implications given the associations between frailty and poor outcomes in the bladder cancer population. Due to a multi-organ system decline and decreased physiologic reserve, frail patients are vulnerable to stressors of disease and have poorer mortality and morbidity rates than their nonfrail peers. The association between frailty and poor outcomes has been documented across multiple populations, including radical cystectomy, creating a need for frailty assessments to be used preoperatively for risk stratification. We aim to provide a review of the common frailty assessments and their relevance to radical cystectomy patients. FINDINGS:A variety of assessments for frailty exist, from short screening items to comprehensive geriatric assessments. The syndrome spans multiple organ systems, as do the potential diagnostic instruments. Some instruments are less practical for use in clinical practice by urologists, such as the Canadian Study of Health and Aging Frailty Index and Comprehensive Geriatric Assessment. The tool most studied in radical cystectomy is the modified Frailty Index, associated with high grade complications and 30-days mortality. Frailty often coexists with malnutrition and sarcopenia, stressing the importance of screening for and addressing these syndromes to improve patient's perioperative outcomes. CONCLUSIONS:There is no universally agreed upon frailty assessment, but the most studied in radical cystectomy is the modified Frailty Index, providing valuable data with which to counsel patients preoperatively. Alterations in immune phenotypes provide potential future diagnostic biomarkers for frailty.Item Open Access Brief Glutamine Pretreatment Increases Alveolar Macrophage CD163/Heme Oxygenase-1/p38-MAPK Dephosphorylation Pathway and Decreases Capillary Damage but Not Neutrophil Recruitment in IL-1/LPS-Insufflated Rats.(PLoS One, 2015) Fernandez-Bustamante, Ana; Agazio, Amanda; Wilson, Paul; Elkins, Nancy; Domaleski, Luke; He, Qianbin; Baer, Kaily A; Moss, Angela FD; Wischmeyer, Paul E; Repine, John EBACKGROUND: Glutamine (GLN) attenuates acute lung injury (ALI) but its effect on alveolar macrophages is unknown. We hypothesized that GLN pretreatment would induce the anti-inflammatory CD163/heme oxygenase (HO)-1/p38-MAPK dephosphorylation pathway in alveolar macrophages and reduce ALI in rats insufflated with interleukin-1 (IL-1) and lipopolysaccharide (LPS). METHODS: Male Sprague-Dawley rats were randomized to the following groups: GLN-IL-1/LPS-, GLN+IL-1/LPS-, GLN-IL-1/LPS+, and GLN+IL-1/LPS+. GLN pretreatment was given via gavage (1 g/kg L-alanyl-L-glutamine) daily for 2 days. ALI was subsequently induced by insufflating 50 ng IL-1 followed by 5mg/kg E.coli LPS. After 24h, bronchoalveolar lavage (BAL) protein, lactate dehydrogenase (LDH) and neutrophil concentrations were analyzed. BAL alveolar macrophage CD163+ expression, HO-1 and p38-MAPK concentrations were measured, as well as alveolar macrophage tumor necrosis factor (TNF)-α and interleukin (IL)-10 concentrations. Histology and immunofluorescence studies were also performed. RESULTS: Following IL-1/LPS insufflation, GLN pretreated rats had significantly decreased BAL protein and LDH concentrations, but not BAL neutrophil counts, compared to non-GLN pretreated rats. The number of alveolar macrophages and the number of CD163+ macrophages were significantly increased in GLN pretreated IL-1/LPS-insufflated rats compared to non-GLN pretreated, IL-1/LPS-insufflated rats. GLN pretreatment before IL-1/LPS also significantly increased HO-1 concentrations and dephosphorylated p38-MAPK levels but not cytokine levels in alveolar macrophages. Immunofluorescence localized CD163 and HO-1 in alveolar macrophages. CONCLUSION: Short-term GLN pretreatment activates the anti-inflammatory CD163/HO-1/p38-MAPK dephosphorylation pathway of alveolar macrophages and decreases capillary damage but not neutrophil recruitment in IL-1/LPS-insufflated rats.Item Open Access Change to Mixed-Lipid Emulsion From Soybean Oil-Based Lipid Emulsion in Pediatric Patients.(JAMA network open, 2023-09) Haines, Krista L; Ohnuma, Tetsu; Hornik, Chi Dang; Grisel, Braylee; Leraas, Harold; Trujillo, Charles N; Krishnamoorthy, Vijay; Raghunathan, Karthik; Wischmeyer, Paul EImportance
Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes.Objective
To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes.Design, setting, and participants
Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023.Exposure
In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil-based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group).Main outcomes and measures
Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin).Results
A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant.Conclusions and relevance
In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy-LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.Item Open Access Clinical review: Optimizing enteral nutrition for critically ill patients--a simple data-driven formula.(Crit Care, 2011) Hegazi, Refaat A; Wischmeyer, Paul EIn modern critical care, the paradigm of 'therapeutic nutrition' is replacing traditional 'supportive nutrition'. Standard enteral formulas meet basic macro- and micronutrient needs; therapeutic enteral formulas meet these basic needs and also contain specific pharmaconutrients that may attenuate hyperinflammatory responses, enhance the immune responses to infection, or improve gastrointestinal tolerance. Choosing the right enteral feeding formula may positively affect a patient's outcome; targeted use of therapeutic formulas can reduce the incidence of infectious complications, shorten lengths of stay in the ICU and in the hospital, and lower risk for mortality. In this paper, we review principles of how to feed (enteral, parenteral, or both) and when to feed (early versus delayed start) patients who are critically ill. We discuss what to feed these patients in the context of specific pharmaconutrients in specialized feeding formulations, that is, arginine, glutamine, antioxidants, certain ω-3 and ω-6 fatty acids, hydrolyzed proteins, and medium-chain triglycerides. We summarize current expert guidelines for nutrition in patients with critical illness, and we present specific clinical evidence on the use of enteral formulas supplemented with anti-inflammatory or immune-modulating nutrients, and gastrointestinal tolerance-promoting nutritional formulas. Finally, we introduce an algorithm to help bedside clinicians make data-driven feeding decisions for patients with critical illness.Item Open Access Current Landscape of Nutrition Within Prehabilitation Oncology Research: A Scoping Review(Frontiers in Nutrition) Gillis, Chelsia; Davies, Sarah J; Carli, Francesco; Wischmeyer, Paul E; Wootton, Stephen A; Jackson, Alan A; Riedel, Bernhard; Marino, Luise V; Levett, Denny ZH; West, Malcolm ABackground: Prehabilitation aims to improve functional capacity prior to cancer treatment to achieve better psychosocial and clinical outcomes. Prehabilitation interventions vary considerably in design and delivery. In order to identify gaps in knowledge and facilitate the design of future studies, we undertook a scoping review of prehabilitation studies to map the range of work on prehabilitation being carried out in any cancer type and with a particular focus on diet or nutrition interventions.Objectives: Firstly, to describe the type of prehabilitation programs currently being conducted. Secondly, to describe the extent to which prehabilitation studies involved aspects of nutrition, including assessment, interventions, implementation, and outcomes.Eligibility Criteria: Any study of quantitative or qualitative design that employed a formal prehabilitation program before cancer treatment (“prehabilitation” listed in keywords, title, or abstract).Sources of Evidence: Search was conducted in July 2020 using MEDLINE, PubMed, EMBASE, EMCARE, CINAHL, and AMED.Charting Methods: Quantitative data were reported as frequencies. Qualitative nutrition data were charted using a framework analysis that reflects the Nutrition Care Process Model: assessment, intervention, and monitoring/evaluation of the nutrition intervention.Results: Five hundred fifty unique articles were identified: 110 studies met inclusion criteria of a formal prehabilitation study in oncology. prehabilitation studies were mostly cohort studies (41%) or randomized-controlled trials (38%) of multimodal (49%), or exercise-only (44%) interventions that were applied before surgery (94%). Nutrition assessment was inconsistently applied across these studies, and often conducted without validated tools (46%). Of the 110 studies, 37 (34%) included a nutrition treatment component. Half of these studies provided the goal for the nutrition component of their prehabilitation program; of these goals, less than half referenced accepted nutrition guidelines in surgery or oncology. Nutrition interventions largely consisted of counseling with dietary supplementation. The nutrition intervention was indiscernible in 24% of studies. Two-thirds of studies did not monitor the nutrition intervention nor evaluate nutrition outcomes.Conclusion: Prehabilitation literature lacks standardized and validated nutritional assessment, is frequently conducted without evidence-based nutrition interventions, and is typically implemented without monitoring the nutrition intervention or evaluating the intervention's contribution to outcomes. We suggest that the development of a core outcome set could improve the quality of the studies, enable pooling of evidence, and address some of the research gaps identified.Item Open Access Diet and Exercise Are not Associated with Skeletal Muscle Mass and Sarcopenia in Patients with Bladder Cancer.(European urology oncology, 2021-04) Wang, Yingqi; Chang, Andrew; Tan, Wei Phin; Fantony, Joseph J; Gopalakrishna, Ajay; Barton, Gregory J; Wischmeyer, Paul E; Gupta, Rajan T; Inman, Brant ABackground
There is limited understanding about why sarcopenia is happening in bladder cancer, and which modifiable and nonmodifiable patient-level factors affect its occurrence.Objective
The objective is to determine the extent to which nonmodifiable risk factors, modifiable lifestyle risk factors, or cancer-related factors are determining body composition changes and sarcopenia in bladder cancer survivors.Design, setting, and participants
Patients above 18 yr of age with a histologically confirmed diagnosis of bladder cancer and a history of receiving care at Duke University Medical Center between January 1, 1996 and June 30, 2017 were included in this study.Outcome measurements and statistical analysis
Bladder cancer survivors from our institution were assessed for their dietary intake patterns utilizing the Diet History Questionnaire II (DHQ-II) and physical activity utilizing the International Physical Activity Questionnaire long form (IPAQ-L) tools. Healthy Eating Index 2010 (HEI2010) scores were calculated from DHQ-II results. Body composition was evaluated using Slice-O-Matic computed tomography scan image analysis at L3 level and the skeletal muscle index (SMI) calculated by three independent raters.Results and limitations
A total of 285 patients were evaluated in the study, and the intraclass correlation for smooth muscle area was 0.97 (95% confidence interval: 0.94-0.98) between raters. The proportions of patients who met the definition of sarcopenia were 72% for men and 55% of women. Univariate linear regression analysis demonstrated that older age, male gender, and black race were highly significant predictors of SMI, whereas tumor stage and grade, chemotherapy, and surgical procedures were not predictors of SMI. Multivariate linear regression analysis demonstrated that modifiable lifestyle factors, including total physical activity (p=0.830), strenuousness (high, moderate, and low) of physical activity (p=0.874), individual nutritional components (daily calories, p=0.739; fat, p=0.259; carbohydrates, p=0.983; and protein, p=0.341), and HEI2010 diet quality (p=0.822) were not associated with SMI.Conclusions
Lifestyle factors including diet quality and physical activity are not associated with SMI and therefore appear to have limited impact on sarcopenia. Sarcopenia may largely be affected by nonmodifiable risk factors.Patient summary
In this report, we aim to determine whether lifestyle factors such as diet and physical activity were the primary drivers of body composition changes and sarcopenia in bladder cancer survivors. We found that lifestyle factors including dietary habits, individual nutritional components, and physical activity do not demonstrate an association with skeletal muscle mass, and therefore may have limited impact on sarcopenia.Item Open Access Early propranolol treatment induces lung heme-oxygenase-1, attenuates metabolic dysfunction, and improves survival following experimental sepsis.(Crit Care, 2013-09-10) Wilson, Joel; Higgins, David; Hutting, Haley; Serkova, Natalie; Baird, Christine; Khailova, Ludmila; Queensland, Kelly; Vu Tran, Zung; Weitzel, Lindsay; Wischmeyer, Paul EINTRODUCTION: Pharmacological agents that block beta-adrenergic receptors have been associated with improved outcome in burn injury. It has been hypothesized that injuries leading to a hypermetabolic state, such as septic shock, may also benefit from beta-blockade; however, outcome data in experimental models have been contradictory. Thus, we investigated the effect of beta-blockade with propranolol on survival, hemodynamics, lung heat shock protein (HSP) expression, metabolism and inflammatory markers in a rat cecal ligation and puncture (CLP) model of sepsis. METHODS: Sprague-Dawley rats receiving either repeated doses (30 minutes pre-CLP and every 8 hours for 24 hours postoperatively) of propranolol or control (normal saline), underwent CLP and were monitored for survival. Additionally, lung and blood samples were collected at 6 and 24 hours for analysis. Animals also underwent monitoring to evaluate global hemodynamics. RESULTS: Seven days following CLP, propranolol improved survival versus control (P < 0.01). Heart rates in the propranolol-treated rats were approximately 23% lower than control rats (P < 0.05) over the first 24 hours, but the mean arterial blood pressure was not different between groups. Metabolic analysis of lung tissue demonstrated an increase in lung ATP/ADP ratio and NAD+ content and a decreased ratio of polyunsaturated fatty acids to monounsaturated fatty acids (PUFA/MUFA). Cytokine analysis of the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) demonstrated decreased expression of TNF-alpha in both lung and plasma at 24 hours post CLP induced sepsis. Finally, propranolol led to a significant increase in lung hemeoxygenase-1 expression, a key cellular protective heat shock protein (HSP) in the lung. Other lung HSP expression was unchanged. CONCLUSIONS: These results suggest that propranolol treatment may decrease mortality during sepsis potentially via a combination of improving metabolism, suppressing aspects of the inflammatory response and enhancing tissue protection.Item Open Access Extracorporeal membrane oxygenation postcardiotomy: "With great power comes great responsibility".(J Thorac Cardiovasc Surg, 2017-01) Arora, Rakesh C; Wischmeyer, Paul E; Singal, Rohit KItem Open Access Frailty in the End-Stage Lung Disease or Heart Failure Patient: Implications for the Perioperative Transplant Clinician.(Journal of cardiothoracic and vascular anesthesia, 2019-05) Bottiger, Brandi A; Nicoara, Alina; Snyder, Laurie D; Wischmeyer, Paul E; Schroder, Jacob N; Patel, Chetan B; Daneshmand, Mani A; Sladen, Robert N; Ghadimi, KamrouzThe syndrome of frailty for patients undergoing heart or lung transplantation has been a recent focus for perioperative clinicians because of its association with postoperative complications and poor outcomes. Patients with end-stage cardiac or pulmonary failure may be under consideration for heart or lung transplantation along with bridging therapies such as ventricular assist device implantation or venovenous extracorporeal membrane oxygenation, respectively. Early identification of frail patients in an attempt to modify the risk of postoperative morbidity and mortality has become an important area of study over the last decade. Many quantification tools and risk prediction models for frailty have been developed but have not been evaluated extensively or standardized in the cardiothoracic transplant candidate population. Heightened awareness of frailty, coupled with a better understanding of distinct cellular mechanisms and biomarkers apart from end-stage organ disease, may play an important role in potentially reversing frailty related to organ failure. Furthermore, the clinical management of these critically ill patients may be enhanced by waitlist and postoperative physical rehabilitation and nutritional optimization.Item Open Access Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre–post-comparative study(Critical Care) Haines, Krista L; Ohnuma, Tetsu; Trujillo, Charles; Osamudiamen, Obanor; Krishnamoorthy, Vijay; Raghunathan, Karthik; Wischmeyer, Paul EAbstract Introduction Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. Methods We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. Results We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95–0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87–0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82–0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (− 1.6, 95% CI − 2.8 to − 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26–0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. Conclusion 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.Item Open Access Immediate Post-operative Enterocyte Injury, as Determined by Increased Circulating Intestinal Fatty Acid Binding Protein, Is Associated With Subsequent Development of Necrotizing Enterocolitis After Infant Cardiothoracic Surgery.(Frontiers in pediatrics, 2020-01) Watson, John D; Urban, Tracy T; Tong, Suhong S; Zenge, Jeanne; Khailova, Ludmilla; Wischmeyer, Paul E; Davidson, Jesse AObjectives: 1 Measure serial serum intestinal fatty acid binding protein levels in infants undergoing cardiac surgery with cardiopulmonary bypass to evaluate for evidence of early post-operative enterocyte injury. 2 Determine the association between immediate post-operative circulating intestinal fatty acid binding protein levels and subsequent development of necrotizing enterocolitis. Design: Observational cohort study. Intestinal fatty acid binding protein was measured pre-operatively, at rewarming, and at 6 and 24 h post-operatively. Percent of goal enteral kilocalories on post-operative day 5 and episodes of necrotizing enterocolitis were determined. Multivariable analysis assessed for factors independently associated with clinical feeding outcomes and suspected/definite necrotizing enterocolitis. Setting: Quaternary free-standing children's hospital pediatric cardiac intensive care unit. Patients: 103 infants <120 days of age undergoing cardiothoracic surgery with cardiopulmonary bypass. Interventions: None. Results: Median pre-operative intestinal fatty acid binding protein level was 3.93 ng/ml (range 0.24-51.32). Intestinal fatty acid binding protein levels rose significantly at rewarming (6.35 ng/ml; range 0.54-56.97; p = 0.008), continued to rise slightly by 6 h (6.57 ng/ml; range 0.75-112.04; p = 0.016), then decreased by 24 h (2.79 ng/ml; range 0.03-81.74; p < 0.0001). Sixteen subjects (15.7%) developed modified Bell criteria Stage 1 necrotizing enterocolitis and 9 subjects (8.8%) developed Stage 2 necrotizing enterocolitis. Infants who developed necrotizing enterocolitis demonstrated a significantly higher distribution of intestinal fatty acid binding protein levels at both 6 h (p = 0.005) and 24 h (p = 0.005) post-operatively. On multivariable analysis, intestinal fatty acid binding protein was not associated with percentage of goal enteral kilocalories delivered on post-operative day 5. Higher intestinal fatty acid binding protein was independently associated with subsequent development of suspected/definite necrotizing enterocolitis (4% increase in odds of developing necrotizing enterocolitis for each unit increase in intestinal fatty acid binding protein; p = 0.0015). Conclusions: Intestinal fatty acid binding protein levels rise following infant cardiopulmonary bypass, indicating early post-operative enterocyte injury. Intestinal fatty acid binding protein was not associated with percent of goal enteral nutrition achieved on post-operative day 5, likely due to protocolized feeding advancement based on clinically observable factors. Higher intestinal fatty acid binding protein at 6 h post-operatively was independently associated with subsequent development of necrotizing enterocolitis and may help identify patients at risk for this important complication.Item Open Access Impact of early postoperative oral nutritional supplement utilization on clinical outcomes in colorectal surgery.(Perioperative medicine (London, England), 2020-01) Williams, David GA; Ohnuma, Tetsu; Krishnamoorthy, Vijay; Raghunathan, Karthik; Sulo, Suela; Cassady, Bridget A; Hegazi, Refaat; Wischmeyer, Paul EBackground:Small randomized trials of early postoperative oral nutritional supplementation (ONS) suggest various health benefits following colorectal surgery (CRS). However, real-world evidence of the impact of early ONS on clinical outcomes in CRS is lacking. Methods:Using a nationwide administrative-financial database (Premier Healthcare Database), we examined the association between early ONS use and postoperative clinical outcomes in patients undergoing elective open or laparoscopic CRS between 2008 and 2014. Early ONS was defined as the presence of charges for ONS before postoperative day (POD) 3. The primary outcome was composite infectious complications. Key secondary efficacy (intensive care unit (ICU) admission and gastrointestinal complications) and falsification (blood transfusion and myocardial infarction) outcomes were also examined. Propensity score matching was used to assemble patient groups that were comparable at baseline, and differences in outcomes were examined. Results:Overall, patients receiving early ONS were older with greater comorbidities and more likely to be Medicare beneficiaries with malnutrition. In a well-matched sample of early ONS recipients (n = 267) versus non-recipients (n = 534), infectious complications were significantly lower in early ONS recipients (6.7% vs. 11.8%, P < 0.03). Early ONS use was also associated with significantly reduced rates of pneumonia (P < 0.04), ICU admissions (P < 0.04), and gastrointestinal complications (P < 0.05). There were no significant differences in falsification outcomes. Conclusions:Although early postoperative ONS after CRS was more likely to be utilized in elderly patients with greater comorbidities, the use of early ONS was associated with reduced infectious complications, pneumonia, ICU admission, and gastrointestinal complications. This propensity score-matched study using real-world data suggests that clinical outcomes are improved with early ONS use, a simple and inexpensive intervention in CRS patients.Item Open Access Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19(Journal of Cardiovascular Translational Research) Fudim, Marat; Qadri, Yawar J; Ghadimi, Kamrouz; MacLeod, David B; Molinger, Jeroen; Piccini, Jonathan P; Whittle, John; Wischmeyer, Paul E; Patel, Manesh R; Ulloa, LuisItem Open Access Lipid emulsions in parenteral nutrition: does it matter?(Current opinion in critical care, 2023-06) Haines, Krista; Grisel, Braylee; Gorenshtein, Laura; Wischmeyer, Paul EPurpose of review
Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse outcomes related to high Omega-6 content in soybean oil (SO) ILE's. This review summarizes recent literature on improved clinical outcomes with new Omega-6 lipid-sparing ILE's in PN management.Recent findings
Although there is a paucity of large-scale studies directly comparing Omega-6 lipid sparing ILE's with SO-based lipid emulsion use in PN in ICU patients, there is strong translational and meta-analysis evidence to suggest that lipid formulations containing fish oil (FO) and/or olive oil (OO) have favorable effects on immune function and improve clinical outcomes in ICU populations.Summary
More research is needed to directly compare omega-6-sparing PN formulas with FO and/or OO versus traditional SO ILE's. However, current evidence is promising for improved outcomes using newer ILE's including reduced infections, shorter lengths of stay, and reduced costs.Item Open Access Novel approaches to metabolic assessment and structured exercise to promote recovery in ICU survivors(Current Opinion in Critical Care, 2020-06-19) Molinger, Jeroen; Pastva, Amy M; Whittle, John; Wischmeyer, Paul E