Impact of One-Lung Ventilation on Oxygenation and Ventilation Time in Thoracoscopic Heart Surgery: A Comparative Analysis with Median Thoracotomy.

BACKGROUND One-lung ventilation is the separation of the lungs by mechanical methods to allow ventilation of only one lung, particularly when there is pathology in the other lung. This retrospective study from a single center aimed to compare 49 patients undergoing thoracoscopic cardiac surgery using one-lung ventilation with 48 patients undergoing thoracoscopic cardiac surgery with median thoracotomy. MATERIAL AND METHODS This single-center retrospective study analyzed patients who underwent thoracoscopic cardiac surgery based on one-lung ventilation (experimental group, n=49). Other patients undergoing a median thoracotomy cardiac operation were defined as the comparison group (n=48). The oxygenation index and the mechanical ventilation time were also recorded. RESULTS There was no significant difference in the immediate oxygenation index between the experimental group and comparison group (P>0.05). There was no significant difference for the oxygenation index between men and women in both groups (P>0.05). The cardiopulmonary bypass time significantly affected the oxygenation index (F=7.200, P=0.009). Operation methods (one-lung ventilation thoracoscopy or median thoracotomy) affected postoperative ventilator use time (F=8.337, P=0.005). Cardiopulmonary bypass time (F=16.002, P<0.001) and age (F=4.384, P=0.039) had significant effects on ventilator use time. There was no significant effect of sex (F=0.75, P=0.389) on ventilator use time. CONCLUSIONS Our results indicated that one-lung ventilation thoracoscopic cardiac surgery did not affect the immediate postoperative oxygenation index; however, cardiopulmonary bypass time did significantly affect the immediate postoperative oxygenation index. Also, one-lung ventilation thoracoscopic cardiac surgery had a shorter postoperative mechanical ventilation use time than did traditional median thoracotomy cardiac surgery.

Urinary L-FABP as an Early Biomarker for Pediatric Acute Kidney Injury Following Cardiac Surgery with Cardiopulmonary Bypass: A Systematic Review and Meta-Analysis.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in the early diagnosis and prediction of CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on 12 November 2023, using the MeSH terms "Children", "CPB", "L-FABP", and "Acute Kidney Injury". Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p < 0.05. Of 508 studies assessed, nine were included, comprising 1658 children, of whom 561 (33.8%) developed CPB-AKI. Significantly higher uL-FABP levels in AKI versus non-AKI patients first manifested at baseline to 6 h post-CPB. At 6 h, uL-FABP correlated with CPB duration (r = 0.498, p = 0.036), postoperative serum creatinine (r = 0.567, p < 0.010), and length of hospital stay (r = 0.722, p < 0.0001). Importantly, uL-FABP at baseline (AUC = 0.77, 95% CI: 0.64-0.89, n = 365), 2 h (AUC = 0.71, 95% CI: 0.52-0.90, n = 509), and 6 h (AUC = 0.76, 95% CI: 0.72-0.80, n = 509) diagnosed CPB-AKI earlier. Hence, higher uL-FABP levels associate with worse clinical parameters and may diagnose and predict CPB-AKI earlier.

Comparison between propofol and total inhalational anaesthesia on cardiovascular outcomes following on-pump cardiac surgery in higher-risk patients: a randomised controlled pilot and feasibility study.

OBJECTIVES: Myocardial revascularisation and cardiopulmonary bypass (CPB) can cause ischaemia-reperfusion injury, leading to myocardial and other end-organ damage. Volatile anaesthetics protect the myocardium in experimental studies. However, there is uncertainty about whether this translates into clinical benefits because of the coadministration of propofol and its detrimental effects, restricting myocardial protective processes. METHODS: In this single-blinded, parallel-group randomised controlled feasibility trial, higher-risk patients undergoing elective coronary artery bypass graft (CABG) surgery with an additive European System for Cardiac Operative Risk Evaluation ≥5 were randomised to receive either propofol or total inhalational anaesthesia as single agents for maintenance of anaesthesia. The primary outcome was the feasibility of recruiting and randomising 50 patients across two cardiac surgical centres, and secondary outcomes included the feasibility of collecting the planned perioperative data, clinically relevant outcomes and assessments of effective patient identification, screening and recruitment. RESULTS: All 50 patients were recruited within 11 months in two centres, allowing for a 13-month hiatus in recruitment due to the COVID-19 pandemic. Overall, 50/108 (46%) of eligible patients were recruited. One patient withdrew before surgery and one patient did not undergo surgery. All but one completed in-hospital and 30-day follow-up. CONCLUSIONS: It is feasible to recruit and randomise higher-risk patients undergoing CABG surgery to a study comparing total inhalational and propofol anaesthesia in a timely manner and with high acceptance and completion rates. TRIAL REGISTRATION NUMBER: NCT04039854.

The role of hemoadsorption in cardiac surgery - a systematic review.

BACKGROUND: Extracorporeal blood purification has been widely used in intensive care medicine, nephrology, toxicology, and other fields. During the last decade, with the emergence of new adsorptive blood purification devices, hemoadsorption has been increasingly applied during CPB in cardiac surgery, for patients at different inflammatory risks, or for postoperative complications. Clinical evidence so far has not provided definite answers concerning this adjunctive treatment. The current systematic review aimed to critically assess the role of perioperative hemoadsorption in cardiac surgery, by summarizing the current knowledge in this clinical setting. METHODS: A literature search of PubMed, Cochrane library, and the database provided by CytoSorbents was conducted on June 1st, 2023. The search terms were chosen by applying neutral search keywords to perform a non-biased systematic search, including language variations of terms "cardiac surgery" and "hemoadsorption". The screening and selection process followed scientific principles (PRISMA statement). Abstracts were considered for inclusion if they were written in English and published within the last ten years. Publications were eligible for assessment if reporting on original data from any type of study (excluding case reports) in which a hemoadsorption device was investigated during or after cardiac surgery. Results were summarized according to sub-fields and presented in a tabular view. RESULTS: The search resulted in 29 publications with a total of 1,057 patients who were treated with hemoadsorption and 988 control patients. Articles were grouped and descriptively analyzed due to the remarkable variability in study designs, however, all reported exclusively on CytoSorb® therapy. A total of 62% (18/29) of the included articles reported on safety and no unanticipated adverse events have been observed. The most frequently reported clinical outcome associated with hemoadsorption was reduced vasopressor demand resulting in better hemodynamic stability. CONCLUSIONS: The role of hemoadsorption in cardiac surgery seems to be justified in selected high-risk cases in infective endocarditis, aortic surgery, heart transplantation, and emergency surgery in patients under antithrombotic therapy, as well as in those who develop a dysregulated inflammatory response, vasoplegia, or septic shock postoperatively. Future large randomized controlled trials are needed to better define proper patient selection, dosing, and timing of the therapy.

Ac2-26 activated the AKT1/GSK3ß pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats. METHODS: Forty-eight rats were randomized into sham, CPB, Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups. Rats in sham group only received anesthesia and in the other groups received standard CPB surgery. Rats in the sham and CPB groups received saline, and rats in the Ac, Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups received Ac2-26 immediately after CPB. Rats in the Ac/AKT1, Ac/GSK3ßi and Ac/AKT1/GSK3ßa groups were injected with shRNA, inhibitor and agonist of GSK3ß respectively. The neurological function score, brain edema and histological score were evaluated. The neuronal survival and hippocampal pyroptosis were assessed. The cytokines, activity of NF-κB, S100 calcium-binding protein ß(S100ß) and neuron-specific enolase (NSE), and oxidative were tested. The NLRP3, cleaved-caspase-1 and cleaved-gadermin D (GSDMD) in the brain were also detected. RESULTS: Compared to the sham group, all indicators were aggravated in rats that underwent CPB. Compared to the CPB group, Ac2-26 significantly improved neurological scores and brain edema and ameliorated pathological injury. Ac2-26 reduced the local and systemic inflammation, oxidative stress response and promoted neuronal survival. Ac2-26 reduced hippocampal pyroptosis and decreased pyroptotic proteins in brain tissue. The protection of Ac2-26 was notably lessened by shRNA and inhibitor of GSK3ß. The agonist of GSK3ß recovered the protection of Ac2-26 in presence of shRNA. CONCLUSIONS: Ac2-26 significantly improved neurological function, reduced brain injury via regulating inflammation, oxidative stress response and pyroptosis after CPB. The protective effect of Ac2-26 primarily depended on AKT1/ GSK3ß pathway.

Hemadsorption to Contain Postoperative Cell-Free Hemoglobin and Haptoglobin Preservation for Extended Cardiopulmonary Bypass Time in Cardiac Surgery for Acute Kidney Injuries Prevention.

INTRODUCTION: Prevention of acute kidney injury during cardiopulmonary bypass (CPB) is still a challenge and has been the object of numerous studies. The incidence of acute kidney injury in the context of CPB is related to a multifactorial etiology. The role of hemadsorption in relation to cell-free hemoglobin and haptoglobin preservation is not well defined in the literature on CPB during cardiac surgery procedures. METHODS: This is a single-center pilot randomized report including 20 patients undergoing elective CPB procedures with an expected time > 120 minutes for each extracorporeal procedure. Patients were randomly allocated to either standard of care (n=10) or Jafron HA380 (n=10) during CPB. The primary outcome measured was the incidence of postoperative acute kidney injuries. RESULTS: The Jafron study group vs. control group reported postoperative values for cell-free hemoglobin at 10 minutes after CPB (mg/L) (11.6 ± 0.6 vs. 29.9 ± 0.3) (P-value 0.021), haptoglobin 10 minutes after CPB (mg/dl) (129.16 ± 1.22 vs. 59.17 ± 1.49) (P-value 0.017), creatinine peak after CPB (mg/dL) (0.92 ± 0.17 vs. 1.32 ± 0.9) (P-value 0.030), and acute kidney injury after 48 hours (number of patients) (one vs. four) (P-value 0.027). CONCLUSION: This pilot study suggested that the use of Hemoperfusion Cartridge HA380 Jafron for extended CPB time for complex cardiac surgery procedures was safe and effective and is associated with a better postoperative preservation of haptoglobin with a reduction of cell-free hemoglobin values and less incidence of acute kidney injury, though larger studies are warranted to confirm our result.

Comparison of outcomes between off-pump and on-pump coronary artery bypass graft surgery using collaborative targeted maximum likelihood estimation.

There are some discrepancies about the superiority of the off-pump coronary artery bypass grafting (CABG) surgery over the conventional cardiopulmonary bypass (on-pump). The aim of this study was estimating risk ratio of mortality in the off-pump coronary bypass compared with the on-pump using a causal model known as collaborative targeted maximum likelihood estimation (C-TMLE). The data of the Tehran Heart Cohort study from 2007 to 2020 was used. A collaborative targeted maximum likelihood estimation and targeted maximum likelihood estimation, and propensity score (PS) adjustment methods were used to estimate causal risk ratio adjusting for the minimum sufficient set of confounders, and the results were compared. Among 24,883 participants (73.6% male), 5566 patients died during an average of 8.2 years of follow-up. The risk ratio estimates (95% confidence intervals) by unadjusted log-binomial regression model, PS adjustment, TMLE, and C-TMLE methods were 0.86 (0.78-0.95), 0.88 (0.80-0.97), 0.88 (0.80-0.97), and 0.87(0.85-0.89), respectively. This study provides evidence for a protective effect of off-pump surgery on mortality risk for up to 8 years in diabetic and non-diabetic patients.

Effective Apixaban removal using hemoadsorption during emergent open-heart surgery: a case report and narrative literature review.

BACKGROUND: The management of hemostasis in patients medicated with apixaban (Eliquis) undergoing emergency cardiac surgery is exceedingly difficult. The body's natural elimination pathways for apixaban prove ineffective in emergency situations, and the impact of hemodialysis is limited. The application of Cytosorb® may attenuate the concentration of apixaban, thereby facilitating the stabilization of these patients. CASE PRESENTATION: An 84-year-old man treated with apixaban, underwent emergency ascending aorta replacement surgery due to an acute type A aortic dissection. To address the challenges induced by apixaban, we integrated Cytosorb® cartridge into the Cardiopulmonary bypass circuit. There was a 63.7% decrease in perioperative apixaban-specific anti-factor Xa activity. The patient's postoperative course was favourable. CONCLUSION: Hemoadsorption with Cytosorb® may offers a safe and feasible approach for reducing apixaban concentration in emergency cardiac surgery, thereby mitigating the risk of hemorrhagic complications.

Single-Lung Ventilation in Infants for Surgical Repair of Coarctation of The Aorta Without Cardiopulmonary Bypass.

OBJECTIVE: To investigate the effect of improving the operative field and postoperative atelectasis of single-lung ventilation (SLV) in the surgical repair of coarctation of the aorta (CoA) in infants without the use of cardiopulmonary bypass (CPB). METHODS: This was a retrospective cohort study. The clinical data of 28 infants (aged 1 to 4 months, weighing between 4.2 and 6 kg) who underwent surgical repair of CoA without CPB from January 2019 to May 2022 were analyzed. Fourteen infants received SLV with a bronchial blocker (Group S), and the other 14 infants received routine endotracheal intubation and bilateral lung ventilation (Group R). RESULTS: In comparison to Group R, Group S exhibited improved exposure of the operative field, a lower postoperative atelectasis score (P<0.001), reduced prevalence of hypoxemia (P=0.01), and shorter durations of operation, mechanical ventilation, and ICU stay (P=0.01, P<0.001, P=0.03). There was no difference in preoperative information or perioperative respiratory and circulatory indicators before SLV, 10 minutes after SLV, and 10 minutes after the end of SLV between the two groups (P>0.05). Intraoperative bleeding, intraoperative positive end-expiratory pressure (PEEP), and systolic pressure gradient across the coarctation after operation were also not different between the two groups (P>0.05). CONCLUSION: This study demonstrates that employing SLV with a bronchial blocker is consistent with enhanced operative field, reduced operation duration, lower prevalence of intraoperative hypoxemia, and fewer postoperative complications during the surgical repair of CoA in infants without the use of CPB.

The Efficacy of Tranexamic Acid in Reducing Perioperative Drainage in Cardiac Surgery with Cardiopulmonary Bypass.

INTRODUCTION: Although cardiopulmonary bypass procedures remain a critical treatment option for heart disease, they come with risks, including hemorrhage. Tranexamic acid is known to reduce morbidity and mortality in surgical hemorrhage. OBJECTIVE: This study aimed to evaluate the efficacy of tranexamic acid, which is routinely used to treat hemorrhage, in decreasing the amount of intraoperative and postoperative drainage. METHOD: A total of 80 patients who underwent cardiac surgery with cardiopulmonary bypass were included in this retrospective study. Forty patients who received tranexamic acid during the operation were assigned to Group 1, while 40 patients who did not receive tranexamic acid were assigned to Group 2. Patient data were collected from the hospital computer system and/or archive records after applying exclusion criteria, and the data were recorded. Statistical analyses were then performed to compare the data. RESULTS: Age, sex, height, weight, body surface area, flow, and ejection fraction percentages, preoperative hematological parameters, and intraoperative variables (except tranexamic acid) were similar between the groups (P>0.05). However, there were statistically significant differences between the groups in terms of intraoperative (through the heart-lung machine) and postoperative red blood cell transfusion rates, intraoperative and postoperative bleeding drainage amounts, as well as postoperative hematocrit, hemoglobin, platelet, and red blood cell levels (P<0.05). CONCLUSION: We concluded that intraoperative and postoperative use of tranexamic acid in patients who underwent coronary artery bypass grafting with cardiopulmonary bypass has positive effects on hematological parameters, reducing blood product use, and bleeding drainage amount.

[Research Progress on Influence of Centrifugal Blood Pump on Blood Injury].

Centrifugal blood pumps drive blood flow by regulating blood flow rate, and have been widely used in clinical applications, including extracorporeal membrane oxygenation (ECMO), cardiopulmonary bypass (CPB), and extracorporeal circulation carbon dioxide removal (ECCO2R). However, because different structures and different forms of centrifugal pumps have different requirements for blood extracorporeal circulation in clinical application scenarios, blood pumps face different application conditions in clinical use. In this study, the effects of different structures of centrifugal pumps and different working conditions on blood damage are summarized for reference by relevant institutions and R&D personnel.

Dexmedetomidine Pretreatment Confers Myocardial Protection and Reduces Mechanical Ventilation Duration for Patients Undergoing Cardiac Valve Replacement under Cardiopulmonary Bypass.

PURPOSE: The study aims to assess the effects of dexmedetomidine (Dex) pretreatment on patients during cardiac valve replacement under cardiopulmonary bypass. METHODS: For patients in the Dex group (n = 52), 0.5 µg/kg Dex was given before anesthesia induction, followed by 0.5 µg/kg/h pumping injection before aortic occlusion. For patients in the control group (n = 52), 0.125 ml/kg normal saline was given instead of Dex. RESULTS: The patients in the Dex group had longer time to first dose of rescue propofol than the control group (P = 0.003). The Dex group required less total dosage of propofol than the control group (P = 0.0001). The levels of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were lower in the Dex group than the control group at T4, 8 h after the operation (T5), and 24 h after the operation (T6) (P <0.01). The Dex group required less time for mechanical ventilation than the control group (P = 0.003). CONCLUSION: The study suggests that 0.50 µg/kg Dex pretreatment could reduce propofol use and the duration of mechanical ventilation, and confer myocardial protection without increased adverse events during cardiac valve replacement.

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

PURPOSE: 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. 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. RESULTS: 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). CONCLUSION: 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.

Probiotics may alleviate intestinal damage induced by cardiopulmonary bypass in children.

OBJECTIVES: Intestinal ischaemia-reperfusion injury induced by cardiopulmonary bypass causes intestinal epithelial barrier dysfunction, leading to dysbiosis and bacterial translocation. We conducted a randomized prospective study with 2 objectives: (i) to investigate epithelial barrier dysfunction and bacterial translocation induced by cardiopulmonary bypass and changes in the gut microbiota and (ii) to verify whether probiotics can improve these conditions. METHODS: Between 2019 and 2020, patients 0-15 years old scheduled to undergo cardiac surgery using cardiopulmonary bypass were enrolled and randomly allocated to 2 groups: the intervention group received probiotics and the control group did not receive probiotics. We analysed the microbiota in faeces and blood, organic acid concentrations in faeces, plasma intestinal fatty acid-binding protein and immunological responses. RESULTS: Eighty-two patients were enrolled in this study. The characteristics of the patients were similar in both groups. The total number of obligate anaerobes was higher in the intervention group than in the control group after postoperative day 7. We identified 4 clusters within the perioperative gut microbiota, and cluster changes showed a corrective effect of probiotics on dysbiosis after postoperative day 7. Organic acid concentrations in faeces, incidence of bacterial translocation, intestinal fatty acid-binding protein levels and immunological responses, except for interleukin -17A, were not markedly different between the 2 groups. CONCLUSIONS: Administration of probiotics was able to correct dysbiosis but did not sufficiently alleviate the intestinal damage induced by cardiopulmonary bypass. More effective methods should be examined to prevent disturbances induced by cardiac surgery using cardiopulmonary bypass. CLINICAL TRIAL REGISTRATION NUMBER: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037174 UMIN000035556.

Antithrombin supplementation attenuates heparin resistance in plasma spiked with Gla-domainless factor Xa S195A in vitro.

BACKGROUND: Andexanet alfa is a Gla-domainless mutant (S195A) factor Xa (GDXa) approved for acute reversal of oral factor Xa inhibitors. Cardiac surgery patients exposed to andexanet before cardiopulmonary bypass often exhibit severe heparin resistance. There is a paucity of data on the effectiveness and optimal dosage of antithrombin use in this setting. The objective of this study was to evaluate the in vitro effect of increased heparin with antithrombin levels on attenuating heparin resistance induced by GDXa. METHODS: Heparinised normal pooled plasma and cardiopulmonary bypass plasma were spiked with GDXa 4 µM. Tissue factor-activated thrombin generation was used to assess heparin reversal effects of GDXa and restoration of anticoagulation with additional heparin with and without antithrombin. Serum thrombin-antithrombin complex, antithrombin activity, and tissue factor pathway inhibitor were also measured in tissue factor-activated, recalcified cardiopulmonary bypass plasma spiked with GDXa. RESULTS: In normal pooled plasma, GDXa-induced heparin reversal was mitigated by maintaining a high heparin concentration (12 U ml-1) and supplementing antithrombin (1.5-4.5 µM) based on peak and velocity of thrombin generation. Heparin reversal by GDXa was also demonstrated in cardiopulmonary bypass plasma, but supplementing both heparin (8 U ml-1) and antithrombin (3 µM) attenuated GDXa-induced changes in peak and velocity of thrombin generation by 72.5% and 72.2%, respectively. High heparin and antithrombin levels attenuated thrombin-antithrombin complex formation in tissue factor-activated, GDXa-spiked cardiopulmonary bypass plasma by 85.7%, but tissue factor pathway inhibitor remained depleted compared with control cardiopulmonary bypass plasma. CONCLUSIONS: Simultaneous supplementation of heparin and antithrombin mitigate GDXa-induced heparin resistance by compensating for the loss of tissue factor pathway inhibitor.

Perfusion quality odds (PEQUOD) trial: validation of the multifactorial dynamic perfusion index as a predictor of cardiac surgery-associated acute kidney injury.

OBJECTIVES: The multifactorial dynamic perfusion index was recently introduced as a predictor of cardiac surgery-associated acute kidney injury. The multifactorial dynamic perfusion index was developed based on retrospective data retrieved from the patient files. The present study aims to prospectively validate this index in an external series of patients, through an on-line measure of its various components. METHODS: Inclusion criteria were adult patients undergoing cardiac surgery with cardiopulmonary bypass. Data collection included preoperative factors and cardiopulmonary bypass-related factors. These were collected on-line using a dedicated monitor. Factors composing the multifactorial dynamic perfusion index are the nadir haematocrit, the nadir oxygen delivery, the time of exposure to a low oxygen delivery, the nadir mean arterial pressure, cardiopulmonary bypass duration, the use of red blood cell transfusions and the peak arterial lactates. RESULTS: Two hundred adult patients were investigated. The multifactorial dynamic perfusion index had a good (c-statistics 0.81) discrimination for cardiac surgery-associated acute kidney injury (any stage) and an excellent (c-statistics 0.93) discrimination for severe patterns (stage 2-3). Calibration was modest for cardiac surgery-associated acute kidney injury (any stage) and good for stage 2-3. The use of vasoconstrictors was an additional factor associated with cardiac surgery-associated acute kidney injury. CONCLUSIONS: The multifactorial dynamic perfusion index is validated for discrimination of cardiac surgery-associated acute kidney injury risk. It incorporates modifiable risk factors, and may help in reducing the occurrence of cardiac surgery-associated acute kidney injury.

Point-of-care testing for tranexamic acid efficacy: a proof-of-concept study in cardiac surgical patients.

BACKGROUND: Low-dose tranexamic acid (TXA) has been recently recommended for cardiopulmonary bypass (CPB) to reduce associated complications. Although point-of-care laboratory tests for TXA concentrations are unavailable, a novel TPA-test on the ClotPro® system can measure TXA-induced inhibition of fibrinolysis. We evaluated the performance of the TPA-test in vitro and in patients undergoing surgery requiring CPB. METHODS: Blood samples were obtained from six volunteers for in vitro evaluation of tissue plasminogen activator (tPA)-triggered fibrinolysis and the effects of TXA. This was followed by an observational study in 20 cardiac surgery patients to assess clinical effects of TXA on the TPA-test. RESULTS: Hyperfibrinolysis induced by tPA was inhibited by TXA ≥2 mg L-1 in a concentration-dependent manner, and was completely inhibited at TXA ≥10 mg L-1. In patients undergoing CPB, antifibrinolytic effect was detectable on TPA-test parameters after a 0.1 g bolus of TXA at the end of CPB, and complete inhibition of fibrinolysis was obtained with TXA ≥0.5 g. The antifibrinolytic effects of 1 g TXA on TPA-test parameters were gradually attenuated over 18 h after surgery. However, the fibrinolytic inhibition continued in four patients with estimated glomerular filtration rate (eGFR) ≤30 ml min-1 1.73 m-2. The eGFR had strong correlations with TPA-test parameters at 18 h after surgery (r=0.86-0.92; P<0.0001). CONCLUSIONS: The TPA-test is sensitive to low concentrations of TXA and serves as a practical monitoring tool for postoperative fibrinolytic activity in cardiac surgery patients. This test might be particularly useful in patients with severe renal impairment.

Time-Varying Clearance in Milrinone Pharmacokinetics from Premature Neonates to Adolescents.

BACKGROUND AND OBJECTIVES: Milrinone is an inotrope and vasodilator used for prophylaxis or treatment of low cardiac output syndrome after weaning from cardiopulmonary bypass (CPB). It is renally eliminated and has an acceptable therapeutic range of 100-300 µg/L, but weight-based dosing alone is associated with poor target attainment. We aimed to develop a population pharmacokinetic model for milrinone from premature neonates to adolescents, and to evaluate how age, renal function and recovery from CPB may impact dose selection. METHODS: Fifty paediatric patients (aged 4 days to 16 years) were studied after undergoing cardiac surgery supported by CPB. Data from 29 premature neonates (23-28 weeks' postmenstrual age) treated for prophylaxis of low systemic blood flow were available for a pooled pharmacokinetic analysis. Population parameters were estimated using non-linear mixed effects modelling (NONMEM 7.5.1). RESULTS: There were 369 milrinone measurements available for analysis. A one-compartment model with zero-order input and first-order elimination was used to describe milrinone disposition. Population parameters were clearance 17.8 L/70 kg [95% CI 15.8-19.9] and volume 20.4 L/h/70 kg [95% CI 17.8-22.1]. Covariates included size, postmenstrual age and renal function for clearance, and size and postnatal age for volume. Milrinone clearance is reduced by 39.5% [95% CI 24.0-53.7] immediately after bypass, and recovers to baseline clearance with a half-time of 12.0 h [95% CI 9.7-15.2]. Milrinone volume was 2.07 [95% CI 1.87-2.27] times greater at birth than the population standard and decreased over the first days of life with a half-time of 0.977 days [95% CI 0.833-1.12]. CONCLUSION: Milrinone is predominately renally eliminated and so renal function is an important covariate describing variability in clearance. Increasing clearance over time likely reflects increasing cardiac output and renal perfusion due to milrinone and return to baseline following CPB.

Prevalence and clinical implications of heightened plastic chemical exposure in pediatric patients undergoing cardiopulmonary bypass.

BACKGROUND: Phthalate chemicals are used to manufacture plastic medical products, including many components of cardiopulmonary bypass (CPB) circuits. We aimed to quantify iatrogenic phthalate exposure in pediatric patients undergoing cardiac surgery and examine the link between phthalate exposure and postoperative outcomes. STUDY DESIGN AND METHODS: The study included pediatric patients undergoing (n=122) unique cardiac surgeries at Children's National Hospital. For each patient, a single plasma sample was collected preoperatively and two additional samples were collected postoperatively upon return from the operating room and the morning after surgery. Concentrations of di(2-ethylhexyl) phthalate (DEHP) and its metabolites were quantified using ultra high-pressure liquid chromatography coupled to mass spectrometry. RESULTS: Patients were subdivided into three groups, according to surgical procedure: (1) cardiac surgery not requiring CPB support, (2) cardiac surgery requiring CPB with a crystalloid prime, and (3) cardiac surgery requiring CPB with red blood cells (RBCs) to prime the circuit. Phthalate metabolites were detected in all patients, and postoperative phthalate levels were highest in patients undergoing CPB with an RBC-based prime. Age-matched (<1 year) CPB patients with elevated phthalate exposure were more likely to experience postoperative complications. RBC washing was an effective strategy to reduce phthalate levels in CPB prime. DISCUSSION: Pediatric cardiac surgery patients are exposed to phthalate chemicals from plastic medical products, and the degree of exposure increases in the context of CPB with an RBC-based prime. Additional studies are warranted to measure the direct effect of phthalates on patient health outcomes and investigate mitigation strategies to reduce exposure.

Routine External Iliac Artery Cannulation in Robotic Cardiac Surgery: Role of the Corona "Vitae" in Distal Limb Perfusion.

OBJECTIVE: Femoral artery cannulation is the most commonly used approach for cardiopulmonary bypass (CPB) in robotic cardiac procedures. However, without adding a distal perfusion cannula, leg ischemia can occur in up to 11.5% of patients. There is a well-described 2 to 4 mm size arterial branch that originates from the medial side of the external iliac artery or inferior epigastric artery, immediately above the inguinal ligament, and connects to the obturator artery. Therefore, it was historically named the corona mortis, which means "crown of death" in Latin. When peripheral cannulation is performed above this branch in the external iliac artery, we consider it a corona "vitae" because of its role as a limb-saving collateral. We report herein our standard technique of peripheral cannulation without the need of a distal perfusion cannula and preventing limb ischemia. METHODS: We included all patients who underwent robotic cardiac surgery with peripheral cannulation over a 16-month period at our institution. We cannulated just above the level of the inguinal ligament through a 2 to 3 cm transverse skin incision. The incidence of limb ischemia and vascular complications was recorded and analyzed. RESULTS: During the study period, 133 patients underwent robotic cardiac procedures with peripheral "external iliac" CPB. The size of the cannula was 21F or larger in 73% and 23F in 54% of the patients. No leg ischemia or femoral artery complications requiring additional intervention occurred. CONCLUSIONS: External iliac cannulation can be successfully performed in robot-assisted cardiac surgery using relatively large cannulas without the need of a distal limb perfusion catheter, with good results. In our view, given the importance of the corona mortis ("crown of death" in Latin) in perfusing the limb during CPB, we propose a new name for this artery in robotic cardiac surgery, namely, the corona vitae ("crown of life" in Latin).