Goal-directed Therapy Research Articles

Early experience with baroreflex activation therapy from a vascular surgery perspective

Baroreflex activation therapy (BAT) is an emerging device-based treatment for patients with heart failure with a reduced ejection fraction refractory to maximally tolerated goal-directed medical therapy. Currently, there is sparse literature on the critical role that vascular surgeons serve in the delivery of this novel therapy. This single-institution series describes the creation of a BAT program and elaborates on the function of vascular surgeons in the multidisciplinary heart failure team. The preoperative evaluation, perioperative care, and postoperative course of patients receiving BAT from March 2022 to August 2023 were retrospectively analyzed. Eleven patients were evaluated by a dedicated heart failure cardiologist for medical eligibility and assessed by a vascular surgeon for technical feasibility. Of the 11 patients, 7 were men (63.6%). The median age was 60.5 years (range, 44-73 years). No patient (0.00%) had existing carotid artery disease, and one patient (9.1%) had undergone previous neck radiation therapy. All 11 patients (100%) had an existing cardiac implantable electronic device, and BAT implantation was performed on the same side as the cardiac implantable electronic device in two patients (18.1%). Four patients (36.4%) required preoperative hospital admission for medical optimization before surgery. The median length of surgery was 82 minutes (range, 58-113 minutes), and the median length of stay in the hospital after surgery was 1 day (range, 0-6 days). No major adverse neurologic or cardiovascular events, cranial nerve injuries, device complications requiring reintervention, or heart failure-related mortality at 6 months occurred. Three patients (27.3%) experienced extraneous stimulations, which affected BAT tolerability. Within 6 months after BAT implantation, no significant improvements were observed for several heart failure disease burden markers compared with 6 months before BAT implantation. Our early results demonstrate that BAT implantation is a safe procedure with rare complications. Vascular surgeons play an important role in the multidisciplinary delivery of this novel device-based therapy. More data are needed to understand whether BAT is beneficial in the treatment of heart failure with a reduced ejection fraction refractory to maximally tolerated goal-directed medical therapy.

Perioperative Fluid Management in Colorectal Surgery: Institutional Approach to Standardized Practice

The present review discusses restrictive perioperative fluid protocols within enhanced recovery after surgery (ERAS) pathways. Standardized definitions of a restrictive or liberal fluid regimen are lacking since they depend on conflicting evidence, institutional protocols, and personal preferences. Challenges related to restrictive fluid protocols are related to proper patient selection within standardized ERAS protocols. On the other hand, invasive goal-directed fluid therapy (GDFT) is reserved for more challenging disease presentations and polymorbid and frail patients. While the perfusion rate (mL/kg/h) appears less predictive for postoperative outcomes, the authors identified critical thresholds related to total intravenous fluids and weight gain. These thresholds are discussed within the available evidence. The authors aim to introduce their institutional approach to standardized practice.

Can perioperative pCO2 gaps predict complications in patients undergoing major elective abdominal surgery randomized to goal-directed therapy or standard care? A secondary analysis

The difference between venous and arterial carbon dioxide pressure (pCO2 gap), has been used as a diagnostic and prognostic tool. We aimed to assess whether perioperative pCO2 gaps can predict postoperative complications. This was a secondary analysis of a multicenter RCT comparing goal-directed therapy (GDT) to standard care in which 464 patients undergoing high-risk elective abdominal surgery were included. Arterial and central venous blood samples were simultaneously obtained at four time points: after induction, at the end of surgery, at PACU/ICU admission, and PACU/ICU discharge. Complications within the first 30 days after surgery were recorded. Similar pCO2 gaps were found in patients with and without complications, except for the pCO2 gap at the end of surgery, which was higher in patients with complications (6.0 mmHg [5.0–8.0] vs. 6.0 mmHg [4.1–7.5], p = 0.005). The area under receiver operating characteristics curves for predicting complications from pCO2 gaps at all time points were between 0.5 and 0.6. A weak correlation between ScvO2 and pCO2 gaps was found for all timepoints (ρ was between − 0.40 and − 0.29 for all timepoints, p < 0.001). The pCO2 gap did not differ between GDT and standard care at any of the selected time points. In our study, pCO2 gap was a poor predictor of major postoperative complications at all selected time points. Our research does not support the use of pCO2 gap as a prognostic tool after high-risk abdominal surgery. pCO2 gaps were comparable between GDT and standard care. Clinical trial registration Netherlands Trial Registry NTR3380.

Good Performance of Revised Scoring Systems in Predicting Clinical Outcomes of Aeromonas Bacteremia in the Emergency Department: A Retrospective Observational Study.

Aeromonas species, Gram-negative, non-sporulating, facultative, and anaerobic bacilli, widely distributed in aquatic environments, derive various infections, including bacteremia. Most of these infections were opportunistic and found in patients with predisposing conditions. Among the infections, bacteremia remains with notable mortality, reported from 15% to 45%. However, predicting systems for assessing the mortality risk of this disease have yet to be investigated. We aimed to validate the performance of specific predictive scoring systems to assess the clinical outcomes of Aeromonas bacteremia and applied the revised systems to predict mortality risk. A retrospective observational study reviewed patients with bacteremia caused by Aeromonas spp. based on at least one positive blood culture sample collected in the emergency department from January 2012 to December 2020. The outcome was in-hospital mortality. We used seven predictive scoring systems to predict the clinical outcome. According to the effectiveness in predicting mortality, we revised three of the seven predictive scoring systems by specific characteristics to refine their risk-predicting performances. We enrolled 165 patients with bacteremia caused by Aeromonas spp., including 121 males (73.3%) and 44 females (26.7%), with a mean age of 66.1 ± 14.9 years and an average length of hospital stay of 12.4 ± 10.9 days. The overall mortality rate was 32.7% (54/165). The non-survivors had significantly higher scores in MEDS (6.7 ± 4.2 vs. 12.2 ± 3.3, p < 0.001), NEWS (4.0 ± 2.8 vs. 5.3 ± 3.0, p = 0.008), and qSOFA (0.3 ± 0.6 vs. 0.6 ± 0.7, p = 0.007). Regarding mortality risk prediction, the MEDS demonstrated the best predictive power with AUC of ROC measured up to 0.834, followed by NEWS (0.626) and qSOFA (0.608). We revised the MEDS, NEWS, and qSOFA by hemoglobin and lactate. We found that the revised scores had better powerful performance, including 0.859, 0.767, and 0.691 of the AUC of ROC, if the revised MEDS ≥10, revised NEWS ≥8, and revised qSOFA ≥2, respectively. MEDS, NEWS, and qSOFA were good tools for predicting outcomes in patients with Aeromonas spp. bacteremia. The revised MEDS, NEWS, and qSOFA demonstrated more powerful predicting performance than the original scoring systems. We suggested that patients with higher scores in revised MEDS (≥10), revised NEWS (≥8), and revised qSOFA (≥2) received early goal-directed therapy and appropriate broad-spectrum antibiotic treatment as early as possible to reduce mortality.

Goal-directed therapy guided by the FloTrac sensor in major surgery: a systematic review and meta-analysis.

To provide insights into the potential benefits of goal-directed therapy guided by FloTrac in reducing postoperative complications and improving outcomes. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate goal-directed therapy guided by FloTrac in major surgery, comparing goal-directed therapy with usual care or invasive monitoring in cardiac and noncardiac surgery subgroups. The quality of the articles and evidence were evaluated with a risk of bias tool and GRADE. We included 29 randomized controlled trials with 3,468 patients. Goal-directed therapy significantly reduced the duration of hospital stay (mean difference -1.43 days; 95%CI 2.07 to -0.79; I2 81%), intensive care unit stay (mean difference -0.77 days; 95%CI -1.18 to -0.36; I2 93%), and mechanical ventilation (mean difference -2.48 hours, 95%CI -4.10 to -0.86, I2 63%). There was no statistically significant difference in mortality, myocardial infarction, acute kidney injury or hypotension, but goal-directed therapy significantly reduced the risk of heart failure or pulmonary edema (RR 0.46; 95%CI 0.23 - 0.92; I2 0%). Goal-directed therapy guided by the FloTrac sensor improved clinical outcomes and shortened the length of stay in the hospital and intensive care unit in patients undergoing major surgery. Further research can validate these results using specific protocols and better understand the potential benefits of FloTrac beyond these outcomes.

Intraoperative goal-directed fluid therapy in neurosurgical patients: A systematic review.

Perioperative fluid management is critical in neurosurgery as over perfusion can lead to brain edema whereas under perfusion may lead to brain hypoperfusion or ischemia. We aimed to determine the effectiveness of intraoperative goal-directed fluid therapy (GDFT) in patients undergoing intracranial surgeries. We searched MEDLINE, Cochrane, and PubMed databases and forward-backward citations for studies published between database inception and February 22, 2024. Randomized controlled trials where intraoperative GDFT was performed in neurosurgery and compared to the conventional regime were included in the study. GDFT was compared with the conventional regime as per primary outcomes - total intraoperative fluid requirement, serum lactate, hemodynamics, brain relaxation, urine output, serum biochemistry, and secondary outcomes - intensive care unit and hospital length of stay. The quality of evidence was assessed with the Cochrane risk of bias tool. This study is registered on PROSPERO (CRD42024518816). Of 75 records identified, eight were eligible, the majority of which had a low to moderate risk of overall bias. In four studies, more fluid was given in the control group. No difference in postoperative lactate values was noted in 50% of studies. In the remaining 50%, lactate was more in the control group. Three out of four studies did not find any significant difference in the incidence of intraoperative hypotension, and four out of six studies did not find a significant difference in vasopressor requirement. The majority of studies did not show significant differences in urine output, brain relaxation, and length of stay between both groups. None found any difference in acid base status or electrolyte levels. GDFT, when compared to the conventional regime in neurosurgery, showed that the total volume of fluids administered was lesser in the GDFT group with no increase in serum lactate. There was no difference in the hemodynamics, urine output, brain relaxation, urine output, length of stay, and biochemical parameters.

Successful Anesthetic Management in a Viable 26-week Extrauterine Abdominal Pregnancy

ABSTRACT Extrauterine abdominal pregnancies occur when the fertilized ovum implants directly into the peritoneal cavity. They are rare, with its incidence being just 1 in 10,000 live births worldwide, and only 0.43% of all documented ectopic pregnancies in the Philippines. This poses a challenge in anesthesia because of the risk of massive hemorrhage the abnormal implantation brings about. This case report presents the anesthetic management of a 29-year-old G3P2 (2002) diagnosed case of 26-week and 5-day gestation viable abdominal pregnancy who underwent abdominal fetal extraction under combined general and epidural anesthesia. Along with the utilization of a multidisciplinary approach, goal-directed fluid therapy, and massive transfusion protocol, this management has been shown to be successful and safe for both the mother and the fetus.

Intraoperative Goal-Directed Perfusion in Cardiac Surgery with Cardiopulmonary Bypass: The Roles of Delivery Oxygen Index and Cardiac Index.

Goal-directed perfusion (GDP) refers to individualized goal-directed therapy using comprehensive monitoring and optimizing the delivery of oxygen during cardiopulmonary bypass (CPB). This study aims to determine whether the intraoperative GDP protocol method has better outcomes compared to conventional methods. We searched the PubMed, Central, and Scopus databases up to October 12, 2023. We primarily examined the GDP protocol in adult cardiac surgery, using CPB with oxygen delivery index (DO2I) and cardiac index (CI) as the main parameters. In all, 1128 participants from seven studies were included in our analysis. The results showed significant differences in the duration of intensive care unit (ICU) stays (p = 0.01), with a mean difference of -0.33 (-0.59 to 0.07), and hospital length of stay (LOS) (p = 0.0002), with a mean difference of -0.84 (-1.29 to -0.39). There was also a notable reduction in postoperative complications (p <0.00001), odds ratio (OR) of 0.43 (0.32-0.60). However, there was no significant decrease in mortality rate (p = 0.54), OR of 0.77 (0.34-1.77). Postoperative acute kidney injury and ICU and hospital LOS are significantly reduced when GDP protocols with indicators of flow management, oxygen delivery index, and CI are used in intraoperative cardiac surgery using CPB.

Personalized Predictive Hemodynamic Management for Gynecologic Oncologic Surgery: Feasibility of Cost-Benefit Derivatives of Digital Medical Devices.

Intraoperative hypotension is associated with increased perioperative complications, hospital length of stay (LOS) and healthcare expenditure in gynecologic surgery. We tested the hypothesis that the adoption of a machine learning-based warning algorithm (hypotension prediction index-HPI) might yield an economic advantage, with a reduction in adverse outcomes that outweighs the costs for its implementation as a medical device. A retrospective-matched cohort cost-benefit Italian study in gynecologic surgery was conducted. Sixty-six female patients treated with standard goal-directed therapy (GDT) were matched in a 2:1 ratio with thirty-three patients treated with HPI based on ASA status, diagnosis, procedure, surgical duration and age. The most relevant contributor to medical costs was operating room occupation (46%), followed by hospital stay (30%) and medical devices (15%). Patients in the HPI group had EURO 300 greater outlay for medical devices without major differences in total costs (GDT 5425 (3505, 8127), HPI 5227 (4201, 7023) p = 0.697). A pre-specified subgroup analysis of 50% of patients undergoing laparotomic surgery showed similar medical device costs and total costs, with a non-significant saving of EUR 1000 in the HPI group (GDT 8005 (5961, 9679), HPI 7023 (5227, 11,438), p = 0.945). The hospital LOS and intensive care unit stay were similar in the cohorts and subgroups. Implementation of HPI is associated with a scenario of cost neutrality, with possible economic advantage in high-risk settings.

A multicomponent intervention program to Prevent and Reduce AgItation and phySical rEstraint use in the ICU (PRAISE): study protocol for a multicenter, stepped-wedge, cluster randomized controlled trial

BackgroundPhysical restraints remain to be commonly used in agitated intensive care unit (ICU) patients worldwide, despite a lack of evidence on efficacy and safety and reports of detrimental short and long-term consequences, such as prolonged delirium and a longer ICU length of stay. Physical restraint minimization approaches have focused mainly on educational strategies and other non-pharmacological interventions. Combining these interventions with goal-directed light sedation therapy if needed may play an important contributory role in further reducing the use of physical restraints. The aim of the study is to determine the effectiveness of a multicomponent intervention (MCI) program, combining person-centered non-pharmacological interventions with goal-directed light sedation, compared to physical restraints.MethodsA multicenter stepped-wedge cluster randomized controlled trial will be conducted in six Dutch ICUs. A power calculation based total of 480 (expected to become) agitated adult patients will be included in 26 months with a subsequent 2-year follow-up. Patients included in the control period will receive standard care with the current agitation management protocol including physical restraints. Patients included in the intervention period will be treated with the MCI program, consisting of four components, without physical restraints: education of ICU professionals, identification of patients at risk for agitation, formulation of a multidisciplinary person-centered care plan including non-pharmacological and medical interventions, and protocolized goal-directed light sedation using dexmedetomidine. Primary outcome is the number of days alive and outside of the ICU within 28 days after ICU admission. Secondary outcomes include length of hospital stay; 3-, 12-, and 24-month post-ICU quality of life; physical (fatigue, frailty, new physical problems), mental (anxiety, depression, and post-traumatic stress disorder), and cognitive health; and 1-year cost-effectiveness. A process evaluation will be conducted.DiscussionThis will be the first multicenter randomized controlled trial determining the effect of a combination of non-pharmacological interventions and light sedation using dexmedetomidine compared to physical restraints in agitated ICU patients. The results of this study, including long-term patient-centered outcomes, will provide relevant insights to aid ICU professionals in the management of agitated patients.Trial registrationNCT05783505, registration date 23 March 2023.

Goal-directed fluid therapy using stroke volume variation on length of stay and postoperative gastrointestinal function after major abdominal surgery-a randomized controlled trial

Background and objectiveThe effectiveness of goal-directed fluid therapy (GDFT) in promoting postoperative recovery remains unclear, the aim of this study was to evaluate the effect of GDFT on length of hospital stay and postoperative recovery of GI function in patients undergoing major abdominal oncologic surgery.MethodsIn this randomized, double- blinded, controlled trial, adult patients scheduled for elective major abdominal surgery with general anesthesia, were randomly divided into the GDFT protocol (group G) or conventional fluid therapy group (group C). Patients in group C underwent conventional fluid therapy based on mean arterial pressure (MAP) and central venous pressure (CVP) whereas those in group G received GDFT protocol associated with the SVV less than 12% and the cardiac index (CI) was controlled at a minimum of 2.5 L/min/m2. The primary outcomes were the length of hospital stay and postoperative GI function.ResultsOne hundred patients completed the study protocol. The length of hospital stay was significantly shorter in group G compared with group C [9.0 ± 5.8 days versus 12.0 ± 4.6 days, P = 0.001]. Postoperative gastrointestinal dysfunction (POGD) occurred in two of 50 patients (4%) in group G and 16 of 50 patients (32%) in the control group (P < 0.001). GDFT significantly also shorten time to first flatus by 11 h (P = 0.009) and time to first tolerate oral diet by 2 days (P < 0.001).ConclusionsGuided by SVV and CI, the application of GDFT has the potential to expedite postoperative recovery of GI function and reduce hospitalization duration after major abdominal surgery.Trial registrationThis study was registered on www.clinicaltrials.gov on 07/05/2019 with registration number: NCT03940144.

Fluid therapy for emergent and critical cases: hypovolaemia vs dehydration

Intravenous fluid therapy is commonly used in emergent and critical patients. Water is a nutrient that is vital to the survival of patients, but one that must be replenished daily. Fluid in the body can be subdivided into intracellular and extracellular portions, with extracellular being further divided into interstitial and intravascular compartments. Fluid loss from all compartments is called dehydration – this is not immediately life threatening. Hypovolaemia is fluid loss from the intravascular compartment – this is life-threatening and requires immediate treatment. Prompt patient assessment and identification of these conditions is essential in selecting the right treatment for the patient. Goal-directed therapy is the gold standard approach for patients receiving intravenous fluid therapy and the veterinary nurse has a key role to play in patient monitoring.

Effect of Somatostatin on hepatic blood flow: preliminary results

Background: Somatostatin (SOMATO) administration affects hepatic blood flow (HBF); however, its clinical effect remains ill-defined. The aim of this study is to assess the clinical effects of SOMATO administration on HBF during major abdominal surgery by comparing HBF in patients with and without intra-operative SOMATO admin-istration. Methods: This retrospective analysis used data from two separate prospective studies including patients undergoing pancreaticoduodenectomy and was approved by the Ghent University Hospital ethical committee. All patients received total intravenous an-esthesia, using target-controlled infusion, and guided by a depth of anesthesia monitor. Schnider model was used for propofol, and Minto model was used for remifentanil. All patients received goal-directed hemodynamic therapy guided and recorded by Pul-sioFlex monitoring (Getinge Group). Portal vein blood flow and arterial hepatic blood flow were measured using ultrasound transit time flow measurements (Medi-Stim®). Both PVF and HAF were indexed using cardiac index. Patients were divided in two groups, receiving SOMATO (group S) versus control group not receiving SOMATO (group C). The Shapiro-Wilk test was used for testing normal distribution. Statistical testing was done using a Welch T-test or a Wilcoxon test. Results: From 6/2017 to 10/2020, a total of thirty-seven patients were analyzed. Twenty-five patients received SOMATO (group S) whereas twelve patients did not (group C). In Group S, PVFi was significantly reduced in patients receiving SOMATO compared to the control group (p = 0.005). HAFi was similar in both groups. The net effect on total HBFi was significantly lower in group S (p = 0.027). Hemodynamic parameters did not differ between both groups. Conclusions: SOMATO significantly reduced PVFi in the surgical patients while HAFi remained similar in both groups. As a result, total HBFi was significantly lower in SO-MATO-treated patients.

Restrictive versus goal-directed fluid replacement strategy in ovarian cancer cytoreductive surgery (RiGoROCS): A randomised controlled trial.

Although goal-directed fluid therapy (GDFT) is associated with reduced morbidity and length of stay (LOS) in the hospital after major surgery, it has not been widely studied in ovarian cancer cytoreductive surgery (CRS). The primary objective of the study was post-operative LOS. In this double-blind, randomised controlled trial, ovarian cancer patients undergoing elective CRS were randomised to receive either GDFT or restrictive fluid therapy after pre-randomisation stratification for primary debulking surgery or interval debulking surgery. The primary objective was to measure post-operative LOS in the hospital. Secondary outcome measures were the cost of surgical treatment episode and post-operative morbidity assessed by post-operative morbidity survey (POMS) on the 1st, 3rd, 5th, and 7th post-operative day and at discharge. Clavien-Dindo (CD) classification was used to assess the 30-day morbidity/mortality rate. Median LOS was 7 days (interquartile range (IQR): 5-10; P = 0.282) in both groups. Median POMS at day 3 was 3 (IQR: 2-5) in the GDFT and 4 (IQR: 2.25-2.75) in the control groups (P = 0.625). The cost of treatment was INR 310907 (IQR: INR 211,856-427,490) in the GDFT group and INR 342,468 (IQR: INR 270,179-454,122) in the control group (P = 0.100). Grade 3-5 CD morbidity was 7 (12%) in GDFT and 9 (16%) in the control group (P = 0.790). GDFT did not confer significant benefit over restrictive fluid therapy in ovarian cancer CRS regarding hospital LOS.

Utilising patient-reported outcomes for goal-directed therapy of hip fracture patients: a sequential controlled trial

BackgroundHip fracture patients (HFPs) frequently have multiple underlying conditions, necessitating that agreed-upon goals take these complications into consideration. Communication regarding goals between medical-personnel and patients is not always effective. Patient-reported...

Effect of using hypotension prediction index versus conventional goal-directed haemodynamic management to reduce intraoperative hypotension in non-cardiac surgery: A randomised controlled trial

Study objectiveIt remains unclear whether it is the hypotension prediction index itself or goal-directed haemodynamic therapy that mitigates intraoperative hypotension. DesignA single centre randomised controlled trial. SettingSapporo Medical University Hospital. PatientsA total of 64 adults patients undergoing major non-cardiac surgery under general anaesthesia. InterventionsPatients were randomly assigned to either group receiving conventional goal-directed therapy (FloTrac group) or combination of the hypotension prediction index and conventional goal-directed therapy (HPI group). To investigate the independent utility of the index, the peak rates of arterial pressure and dynamic arterial elastance were not included in the treatment algorithm for the HPI group. MeasurementsThe primary outcome was the time-weighted average of the areas under the threshold. Secondary outcomes were area under the threshold, the number of hypotension events, total duration of hypotension events, mean mean arterial pressure during the hypotension period, number of hypotension events with mean arterial pressure < 50 mmHg, amounts of fluids, blood products, blood loss, and urine output, frequency and amount of vasoactive agents, concentration of haemoglobin during the monitoring period, and 30-day mortality. Main resultsThe time-weighted average of the area below the threshold was lower in the HPI group than in the control group; 0.19 mmHg (interquartile range, 0.06–0.80 mmHg) vs. 0.66 mmHg (0.28–1.67 mmHg), with a median difference of −0.41 mmHg (95% confidence interval, −0.69 to −0.10 mmHg), p = 0.005. Norepinephrine was administered to 12 (40%) and 5 (17%) patients in the HPI and FloTrac groups, respectively (p = 0.045). No significant differences were observed in the volumes of fluid and blood products between the study groups. ConclusionsThe current randomised controlled trial results suggest that using the hypotension prediction index independently lowered the cumulative amount of intraoperative hypotension during major non-cardiac surgery.

Tranexamic Acid in Trauma Management: A Review of Evidence

Hemorrhage is the leading cause of death in trauma patients and trauma induced coagulopathy (TIC) is a major contributor to bleeding mortality. TIC has a diverse pathophysiology triggered by injury and hypoperfusion, including platelet dysfunction, endotheliopathy, fibrinogen or thrombin abnormalities, and dysregulated fibrinolysis. Early fluid resuscitation, appropriate blood transfusion, and definitive control of bleeding are essential components of initial management for TIC. Additionally, tranexamic acid (TXA), an antifibrinolytic agent, has emerged as a potential adjunctive therapy following the 2010 landmark trial that demonstrated the benefit of early administration of TXA in reducing trauma patient mortality (CRASH-2). This review provides an analysis of the current literature on the use of TXA in trauma patients. It critically evaluates the evidence on the effect of TXA on TIC and other clinical outcomes, emphasizing the time-sensitive nature of TXA administration and the variation of its effect depending on the severity and location of injury. It also discusses the optimal dosage, timing, and safety of TXA, as well as the challenges and limitations of existing studies. Furthermore, it highlights the importance of individualized treatment approaches based on the fibrinolysis status of TIC and the value of goal-directed therapy guided by viscoelastic hemostatic assays for the appropriate use of TXA.

Permissive Cardiotoxicity As a Guiding Principle to CAR-T Therapy with Reduced Ejection Fraction Heart Failure

Introduction: Pivotal CAR-T registrational trials for the six CAR-T therapies currently FDA approved have excluded those with heart failure (HF), defined either by low ejection fraction (EF) or clinical symptoms of HF (NYHA functional classification). This has created a real-world dilemma for clinicians desiring to treat this patient population. There is concern that those with HF may not tolerate the physiologic and hemodynamic stressors associated with cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) and thus have increased risk of severe morbidity or death. The emerging concept of permissive cardiotoxicity seeks to allow for an acceptable level of cardiac toxicity to allow for treatment with highly efficacious but potentially cardiac toxic treatments like CAR-T therapy. To that end, in this study, we provide our real-world, single-institution experience with CAR-T therapy in patients with medically optimized HF with reduced EF (HFrEF) prior to date of apheresis. Methods: This was a retrospective review of 168 (100 B-cell lymphoma and 68 multiple myeloma) CAR-T therapy patients, with 20 (12%) identified with HFrEF of ≤50% prior to apheresis by two-dimensional transthoracic echocardiogram as part of the standard CAR-T screening process and without clinical symptoms of HF at time of apheresis. 19/20 patients received standard of care CAR-T products. This study was conducted following IRB approval. Statistical analysis was done using R version 4.2.3. Kaplan-Meier curves were used to calculate progression free survival(PFS) and overall survival(OS). Results: Twenty patients with HFrEF prior to CAR-T infusion were identified with median EF of 44.1% (range 25-50%) (see Table 1, Baseline Characteristics). The median age was 63.5 (37-82) years-old, predominately male gender (80%), Caucasian (70%), with ECOG of 1 (95%), and 10 patients (50%) received axicabtagene ciloleucel (axi-cel). Most patients received CAR-T for B-cell lymphoma (80%). Cardiac history included 5 (25%) with previous CAD, 1 (5%) with previous PAD, and 4 (20%) with history of atrial fibrillation/flutter. Cardio-Oncology was consulted prior to CAR-T therapy in 10 (50%) and 12 (60%) were optimized on goal-directed therapy (GDT). CKD was pre-existing in 4 (20%) patients. Where measured, all patients had a pre-CAR-T troponin within normal institutional limits (&amp;lt;0.05ng/mL). NT-BNP at baseline was only measured in 6 (30%) patients with a median value of 110pg/mL (49-3200, upper limit of normal 125pg/mL). Longitudinal strain prior to CAR-T was measured in 5 (25%) patients with median value of -16% (-19 to -10%, &amp;lt;-17% normal). There were no cases of grade ≥3 CRS with 3 (15%) grade 1 and 12 (60%) grade 2 CRS (see Table 1, Safety Outcomes). There were 4 (20%) with grade 3 ICANS, although most patients 12 (60%) did not experience ICANS. Compared to ZUMA-1, the 10 patients receiving axi-cel did not have significantly higher rates of CRS or ICANS. Tocilizumab was administered in 15 (75%) of patients and steroids given in 10 (50%) of patients. Following CAR-T infusion, 11 (55%) of patients required ICU admission, no patients required vasopressors, 6 (30%) experienced an AKI, 2 (10%) had LFT abnormalities, 4 (20%) had an arrhythmia, and 5 (25%) had further decline in EF with recovery occurring in most cases where measured. Only 2 (10%) of patients had an HF exacerbation within 30 days of CAR-T infusion. PFS and OS were 11.3 and 26 months, respectively. Conclusion: Given that all registrational CAR-T trials excluded HF, notable reservation exists among clinicians in the use of CAR-T therapy in patients with a history of HF and particularly HFrEF. In our institutional experience of 20 patients with good performance status and medically optimized on GDT, we demonstrate that CAR-T therapy can be given safely with rates of CRS and ICANS similar to that expected in the non-HF population. Additionally, while ICU utilization was high, the incidence of arrhythmias, renal or hepatic toxicity as indicators of end organ dysfunction, non-recovering EF decline, and heart failure exacerbation following CAR-T infusion were quite low. It is thus our practice to consider CAR-T therapy on a case by case basis in those with a history of HFrEF. The key to success being maximal cardiac optimization achieved through early engagement of our Cardio-Oncology colleagues based upon the concept of permissive cardiotoxicity.

Cost-Effectiveness of Early Goal-Directed Therapy Using the FloTrac/EV1000 Platform in Patients Undergoing Coronary Artery Bypass Graft with Cardiopulmonary Bypass: A Retrospective Analysis

Background: Coronary artery bypass graft (CABG) with cardiopulmonary bypass (CPB) is a high-risk surgery with significant morbidity resulting in a prolonged stay in the intensive care unit (ICU) at an increased cost. Early goal-directed therapy (EGDT) using the FloTrac/EV1000 platform improved outcomes in these patients with shorter ICU stay but with extra cost for a FloTrac transducer. Objective: To assess the cost-effectiveness of implementing the FloTrac/EV1000 in these patients. Materials and Methods: The present study was a retrospective study. Sixty adult patients who underwent CABG with CPB were included and divided into two groups: the EV1000 and the Control group. The EV1000 group was managed with EGDT protocol using FloTrac/EV1000 platform. The Control group was managed using a standard protocol. The ICU and hospital stay of both groups were compared. Then, the authors assessed the daily ICU cost by including another 62 patients admitted to the cardiovascular and thoracic (CVT) ICU. Finally, the extra cost of a FloTrac transducer was compared with the saved CVT ICU cost. Results: The EV1000 group had a shorter CVT ICU stay, with mean difference of –23.7 h (95% CI –34.5 to –12.9, p&lt;0.001). The EV1000 group had a shorter ventilator time, as well as a shorter hospital stay. The average daily CVT ICU cost was 10,020.05 Baht. The extra cost of a FloTrac sensor was 5,000 Baht. The saved cost of CVT ICU exceeds the cost of a FloTrac by 5,020.05 Baht. Conclusion: The implementation of EGDT using the FloTrac/EV1000 platform in patients undergoing CABG with CPB improved patients’ outcomes resulting in less CVT ICU cost and better resource management of CVT ICU beds. The extra cost of the FloTrac sensor was offset by the larger amount of CVT ICU cost that was saved. Keywords: Cost-effectiveness; Early goal-directed therapy; FloTrac; Intensive care unit; ICU stay

Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial.

Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice. The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery. With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 μg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively. Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up. CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high. Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172.