Foundations of a life support equipment exchange platform.

Background: The Extracorporeal Life Support Organization Supplies Platform (https://Supplies.ELSO.org) was created out of Extracorporeal Membrane Oxygenation (ECMO) disposable product shortage prior to and during the Coronavirus Disease 2019 (COVID-19) pandemic. This novel Platform supports Centers in obtaining disposables from other Centers when alternative avenues are exhausted. Methods: Driven by the opportunity for increased patient care by using the product availability of the 962 ELSO centers worldwide was the motivation to form an efficient online supply sharing Platform. The pandemic created by COVID-19 became a catalyst to further recognize the magnitude of the supply disruption on a global scale, impacting allocations and guidelines for institutions, practice, and patient care. Conclusions: Records kept on the Platform website are helpful to the industry by providing insights into where difficulties exist in the supply chain for needed equipment. Yet, the common thread is awareness, of how critical situations can stretch resources and challenge our resolve for the best patient care. ELSO is proud to support member centers in these situations, by providing a means of attaining needed ECMO life support products to cover supply shortages.

Human factors in ECLS - A keystone for safety and quality - A narrative review for ECLS providers.

INTRODUCTION: Although the technology used for extracorporeal life support (ECLS) has improved greatly in recent years, the application of these devices to the patient is quite complex and requires extensive training of team members both individually and together. Human factors is an area that addresses the activities, contexts, environments, and tools which interact with human behavior in determining overall system performance. HYPOTHESIS: Analyses of the cognitive behavior of ECLS teams and individual members of these teams with respect to the occurrence of human errors may identify additional opportunities to enhance safety in delivery of ECLS. RESULTS: The aim of this article is to support health-care practitioners who perform ECLS, or who are starting an ECLS program, by establishing standards for the safe and efficient use of ECLS with a focus on human factor issues. Other key concepts include the importance of ECLS team leadership and management, as well as controlling the environment and the system to optimize patient care. CONCLUSION: Expertise from other industries is extrapolated to improve patient safety through the application of simulation training to reduce error propagation and improve outcomes.

Determining optimal donor heart ischemic times in adult cardiac transplantation.

OBJECTIVES: Unsupervised statistical determination of optimal allograft ischemic time (IT) on heart transplant outcomes among ABO donor heart types. METHODS: We identified 36,145 heart transplants (2000-2018) from the United Network for Organ Sharing database. Continuous and categorical variables were analyzed with parametric and nonparametric testing. Determination of IT cutoffs for survival analysis was performed using Contal and O'Quigley univariable method and Vito Muggeo multivariable segmented modeling. RESULTS: Univariable and multivariable IT threshold determination revealed a cutoff at about 3 h. The hourly increase in survival risk with ≥3 h IT is asymmetrically experienced at the early 90 days (hazard ratio [HR] = 1.29, p < .001) and up to 1-year time point (HR = 1.16, p < .001). Beyond 1 year the risk of prolonged IT is less impactful (HR = 1.04, p = .022). Longer IT was associated with more postoperative complications such as stroke (2.7% vs. 2.3, p = .042), dialysis (11.6% vs. 9.1%, p < .001) and death from primary graft dysfunction (1.8% vs. 1.2%, p < .001). O blood type donor hearts with IT ≥ 3 h has significantly increased hourly mortality risk at 90 days (HR = 1.27, p < .001), 90 days to 1 year (HR = 1.22, p < .001) and >1 year (HR = 1.05, p = .041). For non-O blood types with ≥3 h IT hourly mortality risk was increased at 90 days (HR = 1.33, p < .001), but not at 90 days to 1 year (HR = 1.09, p = .146) nor ≥1 year (HR = 1.08, p = .237). CONCLUSIONS: The donor heart IT threshold for survival determined from unbiased statistical modeling occurs at 3 h. With longer preservation times, transplantation with O donor hearts was associated with worse survival.

Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest (EROCA): Results of a Randomized Feasibility Trial of Expedited Out-of-Hospital Transport.

STUDY OBJECTIVE: Outcomes of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest depend on time to therapy initiation. We hypothesize that it would be feasible to select refractory out-of-hospital cardiac arrest patients for expedited transport based on real-time estimates of the 911 call to the emergency department (ED) arrival interval, and for emergency physicians to rapidly initiate ECPR in eligible patients. METHODS: In a 2-tiered emergency medical service with an ECPR-capable primary destination hospital, adults with refractory shockable or witnessed out-of-hospital cardiac arrest were randomized 4:1 to expedited transport or standard care if the predicted 911 call to ED arrival interval was less than or equal to 30 minutes. The primary outcomes were the proportion of subjects with 911 call to ED arrival less than or equal to 30 minutes and ED arrival to ECPR flow less than or equal to 30 minutes. RESULTS: Of 151 out-of-hospital cardiac arrest 911 calls, 15 subjects (10%) were enrolled. Five of 12 subjects randomized to expedited transport had an ED arrival time of less than or equal to 30 minutes (overall mean 32.5 minutes [SD 7.1]), and 5 were eligible for and treated with ECPR. Three of 5 ECPR-treated subjects had flow initiated in less than or equal to 30 minutes of ED arrival (overall mean 32.4 minutes [SD 10.9]). No subject in either group survived with a good neurologic outcome. CONCLUSION: The Extracorporeal Cardiopulmonary Resuscitation for Refractory Out-of-Hospital Cardiac Arrest trial did not meet predefined feasibility outcomes for selecting out-of-hospital cardiac arrest patients for expedited transport and initiating ECPR in the ED. Additional research is needed to improve the accuracy of predicting the 911 call to ED arrival interval, optimize patient selection, and reduce the ED arrival to ECPR flow interval.

Fate of preoperative moderate mitral regurgitation following left ventricular assist device implantation.

OBJECTIVE: We examined for improvements in preoperative moderate mitral regurgitation following continuous-flow left ventricular assist device (cfLVAD) implantation. METHODS: From 2006 to 2020, 190 patients with moderate MR underwent cfVLAD implant without concomitant mitral valve (MV) surgery. Cardiac dimensions and contractility, as well as valve function, were assessed with an echocardiogram (echo) pre-cfLVAD, and at approximately 1 month post-cfLVAD. Outcomes were determined by retrospective chart review. RESULTS: Median echo follow-up was 0.94 (0.53, 1.38) months. Residual significant moderate or greater MR was present in 30/190 (15.8%) on follow-up. Patients with significant residual MR had larger preoperative left ventricular internal diameters in diastole (74.4 ± 8.7 vs. 71.1.0 ± 9.1 mm, p = .034). Significant residual MR was associated with higher preoperative mean pulmonary artery pressures (OR = 1.055, p = .035) and pulmonary capillary wedge pressures (OR = 1.060, p = .034). Significant residual MR on echo was not associated with any survival difference (p = .325). The 1, 5, and 10 year survival were 89.9%, 55.2%, and 34.2%, respectively. CONCLUSIONS: For patients with moderate MR undergoing LVAD implantation, the likelihood of significant residual MR is low and mitral intervention in this population is not recommended. However, select patients with larger preoperative left heart dimensions and pulmonary vascular pressures may be at risk for persistent residual MR.

Risk factors for heart transplant survival with greater than 5 h of donor heart ischemic time.

OBJECTIVE: Implantation of donor hearts with prolonged ischemic times is associated with worse survival. We sought to identify risk factors that modulate the effects of prolonged preservation. METHODS: Retrospective review of the United Network for Organ Sharing database (2000-2018) to identify transplants with >5 (n = 1526) or ≤5 h (n = 35,733) of donor heart preservation. In transplanted hearts preserved for >5 h, Cox-proportional hazards identify modifiers for survival. RESULTS: Compared to ≤5 h, transplanted patients with >5 h of preservation spent less time in status 1B (76 ± 160 vs. 85 ± 173 days, p = .027), more commonly had ischemic cardiomyopathy (42.3% vs. 38.3%, p = .002), and less commonly received a blood type O heart (45.4% vs. 50.8%, p < .001). Longer heart preservation time was associated with a higher incidence of postoperative stroke (4.5% vs. 2.5%, p < .001), and dialysis (16.4% vs. 10.6%, p < .001). Prolonged preservation was associated with a greater likelihood of death from primary graft dysfunction (2.8% vs. 1.5%, p < .001) but there was no difference in death from acute (2.0% vs. 1.7%, p = .402) or chronic rejection (2.0% vs. 1.9%, p = .618). In transplanted patients with >5 h of heart preservation, multivariable analysis identified greater mortality with ischemic cardiomyopathy etiology (hazard ratio [HR] = 1.36, p < 0.01), pre-transplant dialysis (HR = 1.84, p < .01), pre-transplant extracorporeal membrane oxygenation (ECMO, HR = 2.36, p = .09), and O blood type donor hearts (HR = 1.35, p < .01). CONCLUSION: Preservation time >5 h is associated with worse survival. This mortality risk is further amplified by preoperative dialysis and ECMO, ischemic cardiomyopathy etiology, and use of O blood type donor hearts.

Evaluating Changes in del Nido Cardioplegia Practices in Adult Cardiac Surgery.

There has been a rapid adoption of the use of del Nido cardioplegia (DC) among adults undergoing cardiac surgery. We leveraged a multicenter database to evaluate differences over time in the choice and impact of cardioplegia type (DC vs. blood) among patients undergoing cardiac surgery. We evaluated 26,373 patients undergoing non-emergent coronary artery bypass and/or valve surgery between 2014-2015 (early period) and 2017-2018 (late period) at 31 centers. DC was compared with blood-based cardioplegia (BC: 1:1, 2:1, 4:1, 8:1, and variable ratio). We evaluated whether treatment choice differed across prespecified patient characteristics, procedure type, and perfusion practices by time period. We evaluated increased DC use with clinical outcomes (major morbidity and mortality, prolonged intubation, and renal failure), after adjusting for baseline characteristics, procedure type, center, and year. DC use increased from 19.6% in 2014-2015 to 41.5% in 2017-2018, p < .001. Increased DC use occurred among coronary artery bypass grafting (CABG), valve, and CABG + valve procedures, all p < .001. Differences in median procedural duration increased over time (DC vs. BC): 1) bypass duration was 11.0 minutes shorter with DC in the early period and 27.0 minutes shorter in the late period, and 2) cross-clamp duration was 7.0 minutes shorter with DC in the early period and 17.0 minutes shorter in the late period, all p < .001. There were no statistical differences in adjusted odds of major morbidity and mortality (odds ratio [OR]adj: 1.01), prolonged intubation (ORadj: .99), or renal failure (ORadj: .80) by DC use (p > .05). In this large multicenter experience, DC use increased over time and was associated with reduced bypass and ischemic time absent any significant differences in adjusted outcomes.

Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications after Cardiac Surgery.

BACKGROUND: Compared with historic ventilation strategies, modern lung-protective ventilation includes lower tidal volumes (VT), lower driving pressures, and application of positive end-expiratory pressure (PEEP). The contributions of each component to an overall intraoperative protective ventilation strategy aimed at reducing postoperative pulmonary complications have neither been adequately resolved, nor comprehensively evaluated within an adult cardiac surgical population. The authors hypothesized that a bundled intraoperative protective ventilation strategy was independently associated with decreased odds of pulmonary complications after cardiac surgery. METHODS: In this observational cohort study, the authors reviewed nonemergent cardiac surgical procedures using cardiopulmonary bypass at a tertiary care academic medical center from 2006 to 2017. The authors tested associations between bundled or component intraoperative protective ventilation strategies (VT below 8 ml/kg ideal body weight, modified driving pressure [peak inspiratory pressure - PEEP] below 16 cm H2O, and PEEP greater than or equal to 5 cm H2O) and postoperative outcomes, adjusting for previously identified risk factors. The primary outcome was a composite pulmonary complication; secondary outcomes included individual pulmonary complications, postoperative mortality, as well as durations of mechanical ventilation, intensive care unit stay, and hospital stay. RESULTS: Among 4,694 cases reviewed, 513 (10.9%) experienced pulmonary complications. After adjustment, an intraoperative lung-protective ventilation bundle was associated with decreased pulmonary complications (adjusted odds ratio, 0.56; 95% CI, 0.42-0.75). Via a sensitivity analysis, modified driving pressure below 16 cm H2O was independently associated with decreased pulmonary complications (adjusted odds ratio, 0.51; 95% CI, 0.39-0.66), but VT below 8 ml/kg and PEEP greater than or equal to 5 cm H2O were not. CONCLUSIONS: The authors identified an intraoperative lung-protective ventilation bundle as independently associated with pulmonary complications after cardiac surgery. The findings offer insight into components of protective ventilation associated with adverse outcomes and may serve as targets for future prospective interventional studies investigating the impact of specific protective ventilation strategies on postoperative outcomes after cardiac surgery.

Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary Bypass Surgery.

A new portable gas phase nitric oxide (NO) generator is described for potential applications in inhaled NO (INO) therapy and during cardiopulmonary bypass (CPB) surgery. In this system, NO is produced at the surface of a large-area mesh working electrode by electrochemical reduction of nitrite ions in the presence of a soluble copper(II)-ligand electron transfer mediator complex. The NO generated is then transported into gas phase by either direct purging with nitrogen/air or via circulating the electrolyte/nitrite solution through a gas extraction silicone fiber-based membrane-dialyzer assembly. Gas phase NO concentrations can be tuned in the range of 5-1000 ppm (parts per million by volume for gaseous species), in proportion to a constant cathodic current applied between the working and counter electrodes. This new NO generation process has the advantages of rapid production times (5 min to steady-state), high Faraday NO production efficiency (ca. 93%), excellent stability, and very low cost when using air as the carrier gas for NO (in the membrane dialyzer configuration), enabling the development of potentially portable INO devices. In this initial work, the new system is examined for the effectiveness of gaseous NO to reduce the systemic inflammatory response (SIR) during CPB, where 500 ppm of NO added to the sweep gas of the oxygenator or to the cardiotomy suction air in a CPB system is shown to prevent activation of white blood cells (granulocytes and monocytes) during extracorporeal circulation with cardiotomy suction conducted with five pigs.

Outcome of Adult Respiratory Failure Patients Receiving Prolonged (≥14 Days) ECMO.

OBJECTIVE: To examine the outcomes of prolonged (≥14 days) extracorporeal membrane oxygenation (P-ECMO) for adult severe respiratory failure and to assess characteristics associated with survival. BACKGROUND: The use of ECMO for treatment of severe respiratory adult patients is associated with overall survival rates of 50% to 70% with median ECMO duration of 10 days. No prior multi-institutional studies have examined outcomes of P-ECMO for severe respiratory failure. METHODS: Data on all adult (≥18 years) patients who required P-ECMO for severe respiratory failure from 1989 to 2013 were extracted from the Extracorporeal Life Support Organization international multi-institutional registry. We examined outcomes over 23 years and compared the 2 more recent time periods of 1989 to 2006 versus 2007 to 2013. RESULTS: Up to 974 patients, mean age 40.2 (18-83) years, had ECMO duration of mean 25.2 days/median 21.0 days (range: 14-208 days). Venovenous ECMO support was most common (venovenous: 79.5%, venoarterial: 9.9%). Reason for ECMO discontinuation included native lung recovery (54%), organ failure (23.7%), family request (6.7%), hemorrhage (2.7%), and diagnosis incompatible with life (5.6%). Forty patients (4.1%) underwent lung transplant with 50% postoperative in-hospital mortality. Increased prevalence of P-ECMO was noted with 72% (701/974) of all cases reported since 2008. Survival to hospital discharge was 45.4% (443/974) and did not vary with ECMO duration. Multivariate logistic regression analysis confirmed that P-ECMO patients 2007 to 2013 had a lower risk of death [odds ratio (OR): 0.650; 95% confidence interval (CI), 0.454-0.929; P = 0.010] compared with 1989 to 2006. Factors independently associated with survival were younger age (OR: 0.983; 95% CI, 0.974-0.993; P < 0.001) and lower PaCO2 (OR, 0.991; 95% CI, 0.986-0.996; P < 0.001). CONCLUSIONS: Prolonged ECMO use for adult respiratory failure was associated with a lower (45.4%) hospital survival rate, compared with prior reported survival rates of short duration ECMO. Prolonged ECMO survival significantly increased in recent years, and increasing ECMO duration did not alter the survival fraction in the 1989 to 2013 study cohort. Although P-ECMO survival rates are less than short ECMO runs, P-ECMO support is justified.

Conditions and procedures for in-hospital extracorporeal life support (ECLS) in cardiopulmonary resuscitation (CPR) of adult patients.

The use of extracorporeal life support (ECLS) in cardiopulmonary resuscitation (CPR; ECPR) has been repeatedly published as non-randomized studies, mainly case series and case reports. The aim of this article is to support physicians, perfusionists, nurses and extracorporeal membrane oxygenation (ECMO) specialists who regularly perform ECPR or are willing to start an ECPR program by establishing standards for safe and efficient ECPR procedures. This article represents the experience and recommendations of physicians who provide ECPR routinely. Based on its survival and outcome rates, ECPR can be considered when determining the optimal treatment of patients who require CPR. The successful performance of ECLS cannulation during CPR is a life-saving measure and has been associated with improved outcome (including neurological outcome) after CPR. We summarize the general structure of an ECLS team and describe the cannulation procedure and the approaches for post-resuscitation care. The differences in hospital organizations and their regulations may result in variations of this model.

Percutaneous Extraction of Embolized Intracardiac Inferior Vena Cava Filter Struts Using Fused Intracardiac Ultrasound and Electroanatomic Mapping.

This report describes the percutaneous extraction of embolized intracardiac inferior vena cava (IVC) filter struts using fluoroscopy and fused intracardiac echocardiography and three-dimensional electroanatomic mapping. Six patients with indwelling IVC filters placed at outside institutions 5 months to 14 years previously presented with cross-sectional imaging of the chest demonstrating fractured IVC filter struts embolized to the myocardial free wall (four patients) or interventricular septum (two patients). All embolized filter struts were successfully retrieved, and open heart surgery was avoided.

Practice Patterns in Sternal Closure and Evaluation of Adoption of a Novel Sternal Closure Device.

OBJECTIVE: The technique for sternal closure has remained largely unchanged owing to the efficacy, simplicity, and low cost of stainless-steel sternal wires. Despite their ubiquity, several other closure devices designed to address the complications associated with sternal wires such as sternal bleeding and dehiscence have become popular. We have developed a novel sternal closure device that reduces sternal bleeding and dehiscence. This study quantifies the use of currently available sternal closure devices and determines predicted uptake of the novel device. METHODS: An electronic survey, designed to determine practice patterns for sternal closure, was distributed to 70 US cardiac surgeons. The survey included a discrete choice section in which surgeons evaluated relative value of device attributes including cost, ease of emergent sternal reentry, and dehiscence risk. RESULTS: There were 70 surgeons from 30 states who completed the survey. The most frequent means of sternal closure was straight sternal wires (35.8%), followed by straight sternal wires plus figure-of-8 sternal wires (18.1%), double wires (10.9%), plates (10.2%), and other (25%). The relative utilization shifted from sternal wires to sternal plates as the risk for dehiscence increased. The adoption of the novel closure device was estimated at 34.6%. CONCLUSIONS: The standard stainless-steel sternal wire remains the most common means of sternal reapproximation, but its utilization is lower in patients at high risk for sternal dehiscence. Based on this survey, there is acceptance in the community for a novel sternal closure device designed to address the limitations of traditional sternal closure methods.

Mechanical Analysis of a Novel Sternal Closure System in Static Tensile Loading.

The most common means of sternal closure after sternotomy is stainless steel wire cerclage. These wires, while inexpensive and simple in design, are known to be associated with low strength and sternal dehiscence. In this biomechanical analysis, we compare single sternal wires, double sternal wires, and a novel sternal closure device we have designed to mitigate sternal dehiscence. The device uses polymer grommets at the sternal interfaces to distribute load over a large surface area of bone. Samples of each closure device were installed in a bone model and distracted at a rate of 10 mm/min while tensile forces were continuously measured and compared. Single wires generated the lowest stiffness and strength values, followed by the double wires. The novel device demonstrated significantly higher stiffness and strength at all displacements compared with the single and double wires. Clinical use of this device may result in meaningful reduction in complications associated with the use of standard sternal wires such as sternal separation and fracture.

Gastrointestinal bleeding following Heartmate 3 left ventricular assist device implantation: The Michigan Bleeding Risk Model.

BACKGROUND: Gastrointestinal bleeding (GIB) results in frequent hospitalizations and impairs quality of life in durable left ventricular assist device (LVAD) recipients. Anticipation of these events before implantation could have important implications for patient selection and management. METHODS: The study population included all adult HeartMate 3 (HM3) primary LVAD recipients enrolled in the STS Intermacs registry from January 2017 to December 2020. Using multivariable modeling methodologies, we investigated the relationships between preimplantation characteristics and postimplant bleeding, bleeding and death, and additional bleeding episodes on subsequent bleeding episodes and created a risk score to predict the likelihood of post-LVAD GIB based solely on preimplantation factors. RESULTS: Of 6,425 patients who received an HM3 LVAD, 1,010 (15.7%) patients experienced GIB. Thirteen preimplantation factors were independent predictors of post-LVAD GIB. A risk score was created from these factors and calculated for each patient. By 3 years postimplant, GIB occurred in 11%, 26%, and 43% of low-, medium- and high-risk patients, respectively. Experiencing 1 post-LVAD GIB event was associated with an increased risk for further GIB events, with 33.9% of patients experiencing at least 1 recurrence. While post-LVAD GIB was associated with mortality, there was no relationship between number of GIB events and death. CONCLUSIONS: The Michigan Bleeding Risk Model is a simple tool, which facilitates the prediction of post-LVAD GIB in HM3 recipients using 13 preimplant variables. The implementation of this tool may help in the risk stratification process and may have therapeutic and clinical implications in HM3 LVAD recipients.

Determinants of survival following heart transplantation in adults with congenital heart disease.

BACKGROUND: Adult patients surviving with congenital heart disease (ACHD) is growing. We examine the factors associated with heart transplant outcomes in this challenging population with complex anatomy requiring redo-surgeries. METHODS: We reviewed the United Network for Organ Sharing-Standard Transplant Analysis and Research database and analyzed 35,952 heart transplants from January 1st, 2000, to September 30th, 2018. We compared transplant characteristics for ischemic cardiomyopathy (ICM) (n = 14,236), nonischemic cardiomyopathy (NICM) (n = 20,676), and ACHD (n = 1040). Mean follow-up was 6.20 ± 4.84 years. Kaplan-Meier survival curves and Cox-proportional hazards analysis were used to analyze survival data. RESULTS: Multivariable analysis confirmed that ACHD was associated greater in-hospital death compared to ICM (HR = 0.54, P < 0.001) and NICM (HR = 0.46, P < 0.001). Notable factors associated with increased mortality were history of cerebrovascular disease (HR = 1.11, P = 0.026), prior history of malignancy (HR = 1.12, P = 0.006), pre-transplant biventricular support (HR = 1.12, P = 0.069), postoperative stroke (HR = 1.47, P < 0.001) and postoperative dialysis (HR = 1.71, P < 0.001). ACHD transplants had a longer donor heart ischemic time (P < 0.001) and trend towards more deaths from primary graft dysfunction (P = 0.07). In-hospital deaths were more likely with ACHD and use of mechanical support such as use of right ventricular assist device (HR = 2.20, P = 0.049), biventricular support (HR = 1.62, P < 0.001) and extracorporeal membrane oxygenation (HR = 2.36, P < 0.001). Conditional survival after censoring hospital deaths was significantly higher in ACHD (P < 0.001). CONCLUSION: Heart transplant in ACHD is associated with a higher post-operative mortality given anatomical complexity but a better long-term conditional survival. Normothermic donor heart perfusion may improve outcomes in the ACHD population by reducing the impact of longer ischemic times.

Open Surgical Treatment of Acute and Chronic Pulmonary Embolism.

Acute pulmonary embolism (PE) is a common cause of death and morbidity in the United States and the prevalence of chronic thromboembolic pulmonary hypertension (CTEPH), a possible sequela of PE, has increased during the past decade. The mainstay treatment of CTEPH is open pulmonary endarterectomy, a procedure performed under hypothermic circulatory arrest, which entails endarterectomy of the branch, segmental and subsegmental pulmonary arteries. Acute PE may be similarly be treated with an open embolectomy in certain select circumstances.

Modeling and estimating a threshold effect: An application to improving cardiac surgery practices.

Estimating thresholds when a threshold effect exists has important applications in biomedical research. However, models/methods commonly used in the biomedical literature may lead to a biased estimate. For patients undergoing coronary artery bypass grafting (CABG), it is thought that exposure to low oxygen delivery (DO2) contributes to an increased risk of avoidable acute kidney injury. This research is motivated by estimating the threshold of nadir DO2 for CABG patients to help develop an evidence-based guideline for improving cardiac surgery practices. We review several models (sudden-jump model, broken-stick model, and the constrained broken-stick model) that can be adopted to estimate the threshold and discuss modeling assumptions, scientific plausibility, and implications in estimating the threshold. Under each model, various estimation methods are studied and compared. In particular, under a constrained broken-stick model, a modified two-step Newton-Raphson algorithm is introduced. Through comprehensive simulation studies and an application to data on CABG patients from the University of Michigan, we show that the constrained broken-stick model is flexible, more robust, and able to incorporate scientific knowledge to improve efficiency. The two-step Newton-Raphson algorithm has good computational performances relative to existing methods.