Simon Colah

Successful Extracorporeal Membrane Oxygenation Support After Pulmonary Thromboendarterectomy

BACKGROUND Pulmonary thromboendarterectomy (PTE) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension. However, some patients develop severe cardiorespiratory compromise soon after separating from cardiopulmonary bypass, either from early reperfusion pulmonary edema or right ventricular failure secondary to residual pulmonary hypertension. Since 2005 we have used venoarterial extracorporeal membrane oxygenation (ECMO) support in this group that has no other therapeutic option. We review our experience of early ECMO support in the severely compromised patients post-PTE. METHODS We conducted a retrospective review of all patients undergoing PTE from a single national referral center between August 2005 and August 2007. RESULTS One hundred twenty-seven consecutive patients underwent PTE surgery. Seven patients (5.5%) had extreme cardiorespiratory compromise in the immediate postoperative period and required venoarterial ECMO support. Their mean age was 51.3 years with 3 males. When compared with patients not requiring ECMO, these patients had significantly poorer hemodynamic indices before the operation with mean pulmonary artery pressure of 62 mm Hg versus 51 mm Hg (p = 0.02) and pulmonary vascular resistance of 907 dynes/sec/cm(-5) versus 724 dynes/s(-1)/cm(-5) (p < 0.02). Mean duration of support was 119 hours (49 to 359 hours). Five patients were successfully weaned from ECMO support (73%) and 4 left the hospital alive, giving a salvage rate of 57%. For those who did not require ECMO support, hospital mortality was 4.2%. CONCLUSIONS Early venoarterial ECMO support has a role as rescue therapy post-PTE in patients with severe compromise who would probably otherwise die.

Functional assessment and transplantation of the donor heart after circulatory death

BACKGROUND After a severe shortage of brain-dead donors, the demand for heart transplantation has never been greater. In an attempt to increase organ supply, abdominal and lung transplant programs have turned to the donation after circulatory-determined death (DCD) donor. However, because heart function cannot be assessed after circulatory death, DCD heart transplantation was deemed high risk and never adopted routinely. We report a novel method of functional assessment of the DCD heart resulting in a successful clinical program. METHODS Normothermic regional perfusion (NRP) was used to restore function to the arrested DCD heart within the donor after exclusion of the cerebral circulation. After weaning from support, DCD hearts underwent functional assessment with cardiac-output studies, echocardiography, and pressure-volume loops. In the feasibility phase, hearts were transported perfused before evaluation of function in modified working mode extracorporeally. After the establishment of a reliable assessment technique, hearts with demonstrable good function were then selected for clinical transplantation. RESULTS NRP was instituted in 13 adult DCD donors, median age of 33 years (interquartile range [IQR], 28-38 years), after a median ischemic time from withdrawal to perfusion of 24 minutes (IQR, 21-29; range, 17-146 minutes). Two of 4 hearts in the feasibility phase were unsuitable for transplantation after functional assessment. Nine DCD hearts were transplanted in the clinical phase, with 100% survival. The median intensive care duration was 5 days (IQR, 4-5 days), with 2 patients requiring mechanical support. There were no episodes of rejection (total, 1,436 patient-days; range, 48-297). During the same period, we performed 20 standard heart transplants using brain-dead donors. CONCLUSIONS NRP allows rapid reperfusion and functional assessment of the DCD donor heart, ensuring only viable hearts are selected for transplantation. This technique minimizes the risk of primary graft dysfunction and maximizes confidence in DCD heart transplantation, realizing a 45% increase in our heart transplant activity.

A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death

BACKGROUND Ex vivo heart perfusion (EVHP) has been proposed as a means to facilitate the resuscitation of donor hearts after cardiocirculatory death (DCD) and increase the donor pool. However, the current approach to clinical EVHP may exacerbate myocardial injury and impair function after transplant. Therefore, we sought to determine if a cardioprotective EVHP strategy that eliminates myocardial exposure to hypothermic hyperkalemia cardioplegia and minimizes cold ischemia could facilitate successful DCD heart transplantation. METHODS Anesthetized pigs sustained a hypoxic cardiac arrest and a 15-minute warm ischemic standoff period. Strategy 1 hearts (S1, n = 9) underwent initial reperfusion with a cold hyperkalemic cardioplegia, normothermic EVHP, and transplantation after a cold hyperkalemic cardioplegic arrest (current EVHP strategy). Strategy 2 hearts (S2, n = 8) underwent initial reperfusion with a tepid adenosine-lidocaine cardioplegia, normothermic EVHP, and transplantation with continuous myocardial perfusion (cardioprotective EVHP strategy). RESULTS At completion of EVHP, S2 hearts exhibited less weight gain (9.7 ± 6.7 [S2] vs 21.2 ± 6.7 [S1] g/hour, p = 0.008) and less troponin-I release into the coronary sinus effluent (4.2 ± 1.3 [S2] vs 6.3 ± 1.5 [S1] ng/ml; p = 0.014). Mass spectrometry analysis of oxidized pleural in post-transplant myocardium revealed less oxidative stress in S2 hearts. At 30 minutes after wean from cardiopulmonary bypass, post-transplant systolic (pre-load recruitable stroke work: 33.5 ± 1.3 [S2] vs 19.7 ± 10.9 [S1], p = 0.043) and diastolic (isovolumic relaxation constant: 42.9 ± 6.7 [S2] vs 65.2 ± 21.1 [S1], p = 0.020) function were superior in S2 hearts. CONCLUSION In this experimental model of DCD, an EVHP strategy using initial reperfusion with a tepid adenosine-lidocaine cardioplegia and continuous myocardial perfusion minimizes myocardial injury and improves short-term post-transplant function compared with the current EVHP strategy using cold hyperkalemic cardioplegia before organ procurement and transplantation.

Comparison between cellular and acellular perfusates for ex vivo lung perfusion in a porcine model

BACKGROUND Ex vivo lung perfusion with acellular solutions is an established technique for assessing marginal donor lungs. We evaluated the utility of a blood-based lung preservation fluid as an alternative perfusate. METHODS Donor lungs from 50-kg donation after cardiac death pigs (n = 24) were randomized into 3 groups: acellular, commercial blood-based, and Papworth-Blood. Physiologic function was evaluated using conventional markers of pulmonary vascular resistance, pulmonary compliance, lactate excretion, partial pressure of oxygen/fraction of inspired oxygen, and wet-to-dry ratios. The immunologic profile was assessed by fluorescence-activated cell sorting analysis of bronchoalveolar lavage and cells entrapped in the leucocyte filter. Cytokines were quantified using a commercial platform. RESULTS No significant difference was noted in pulmonary vascular resistance (p = 0.26), compliance (p = 0.12), partial pressure of oxygen/fraction of inspired oxygen (p = 0.06) and wet-to-dry ratios (p = 0.26) between groups. There was no difference between the percentages of lymphocytes (p = 0.51), macrophages (p = 0.87), monocytes (p = 0.68), and dendritic cells (p = 0.65) in the leukocyte filters. Interleukin (IL)-1β (p = 0.36), IL-6 (p = 0.08), IL-8 (p = 0.64), and IL-18 (p = 0.14) were elevated in all groups. In bronchoalveolar lavage, IL-8 was significantly higher in the acellular group (p = 0.04). Electron microscopy cell characteristics were similar among the groups. CONCLUSIONS This study demonstrated no significant difference in the physiologic, immunologic, or ultrastructural parameters between lungs perfused with cellular or acellular solutions. The Papworth-Blood solution is a potential alternative perfusate for ex vivo lung perfusion.

Ex vivo perfusion of the swine heart as a method for pre-transplant assessment.

We describe a cost-effective, reproducible circuit in a porcine, ex vivo, continuous warm-blood, bi-ventricular, working heart model that has future possibilities for pre-transplant assessment of marginal hearts donated from brain stem dead donors and hearts donated after circulatory determination of death (DCDD). In five consecutive experiments over five days, pressure volume loops were performed. During working mode, the left ventricular end systolic pressure volume relationship (LV ESPVR) was 23.1±11.1 mmHg/ml and the LV preload recruitable stroke work (PRSW) was 67.8±7.2. (Standard PVAN analysis software) (Millar Instruments, Houston, TX, USA) All five hearts were perfused for 219±64 minutes and regained normal cardiac function on the perfusion system.They displayed a significant upward and leftward shift of the end systolic pressure volume relationship, a significant increase in preload recruitable stroke work and minimal stiffness. These hearts could potentially be considered for transplantation. The circuit was effective during reperfusion and working modes whilst proving to be successful in maintaining cardiac function in excess of four hours. Using an autologous prime of approximately 20% haematocrit (Hct), electrolytes and blood gases were easy to control within this period using standard perfusion techniques.

A lipopolysaccharide adsorber in adult cardiopulmonary bypass: a single centre randomised controlled pilot trial

OBJECTIVES The aim of this study was to describe the biochemical effects and safety of selective removal of endotoxin from whole blood using a lipopolysaccharide adsorber during complex cardiac surgery. METHODS We carried out a single centre prospective randomised controlled pilot trial in patients undergoing elective cardiac surgery using cardiopulmonary bypass (CPB) at a large UK cardiothoracic institution. Seventeen patients were randomly allocated to one of two groups: with or without an adsorber included in the CPB circuit. Fourteen patients were included in a complete case analysis. Blood samples were taken at the time of consent, immediately following anaesthesia, at 60, 180 and 360 min after the institution of CPB, and the morning following surgery. Primary outcomes were plasma levels of endotoxin, IL-6, IL-8 and TNF-alpha. Secondary outcomes were measures of patient safety including blood chemistry and coagulation parameters, length of stay, and adverse events. RESULTS No differences were seen in endotoxin or cytokine levels between adsorber and control groups at any of the measured time-points. No difference between groups was detected in measures of patient safety following the intervention. Haemoglobin and haematocrit were significantly lower in the intervention group pre-bypass, P=0.02 in both instances. CONCLUSION There was no effect of the adsorber on endotoxin levels or inflammatory response in this study, we have demonstrated the device to be safe in a complex cardiac surgery setting.

Coagulopathy associated with massive cell salvage transfusion following aortic surgery

Cell saver blood is used within the peri-operative setting of cardiothoracic surgery to reduce the need for transfusion of allogenic blood products. Several meta-analyses have proven a significant decrease in allogenic transfusion with the use of cell salvage techniques. Washing of red cells by the cell saver and subsequent transfusion of suspended red cells can occasionally cause coagulopathy, particularly when using high concentration heparin saline to wash the spilled blood. We present the case of a 74-year-old female who underwent complicated aortic surgery and was transfused large volumes of cell-saved blood due to post-operative bleeding, which subsequently led to coagulopathy.

The effect of retrograde autologous priming on intraoperative blood product transfusion in coronary artery bypass grafting

Introduction: Retrograde autologous priming (RAP) of the cardiopulmonary bypass (CPB) circuit could reduce the degree of haemodilution associated with priming with acellular solutions. However, there is no strong evidence to prove that the practice of RAP reduced intraoperative packed red cell (PRC) or blood product transfusion. Objective: To evaluate the effect of RAP on intraoperative PRC usage in coronary artery bypass grafting (CABG). Methods: This study is a prospective, observational study on patients who underwent first-time, isolated CABG using CPB between April 2012 and July 2012. Two groups of patients were identified: 1. Non-RAP group (n=128) and 2. RAP group (n=73). The primary outcome for the study was the amount of PRC and blood product usage between the induction of anaesthesia and the cessation of CPB. Results: Use of PRC and blood products in the operating room was comparable in both groups. Univariate logistic regression showed that RAP was not an independent predictor of PRC or blood product transfusion (p=0.43). Multivariate logistic regression showed that CPB time, preoperative haemoglobin (Hb) levels and creatinine clearance were independent predictors of blood product transfusion. Conclusion: Practising RAP with mean volumes of 300 ml does not necessarily reduce PRC and other blood product transfusion requirements during CABG. In our practice, RAP was performed, aiming at displacing CPB circuit prime volume with which the perfusionist felt comfortable and dictated by haemodynamic parameters prior to commencing CPB. We presume this is the case in many units around the world. This practice, in our opinion, is not enough to achieve the benefits of RAP, if any, in the form of a reduction of packed red cell transfusion requirements. The true advantages of RAP in cardiac surgery need to be studied in a prospective, randomized, controlled trial.

Human heart transplantation from donation after circulatory-determined death donors using normothermic regional perfusion and cold storage

Heart transplantation from donation after circulatory-determined-death (DCD) donors is emerging as an additional avenue to increase heart transplant activity. Previous methods of DCD heart retrieval include direct procurement and cold storage, direct procurement, and machine perfusion and normothermic regional perfusion, followed by machine perfusion during transportation. Herein we report a further technique resulting in successful DCD heart transplantation utilizing normothermic regional perfusion and permitting functional assessment followed by cold storage.

Cardiopulmonary bypass and deep hypothermic circulatory arrest in a massively obese patient

As a consequence of the rising global prevalence and magnitude of obesity, a greater proportion of patients presenting for cardiac surgery is morbidly obese. Being overweight (body mass index; BMI 25-29.9 kg/m2) or obese (BMI 30-35 kg/m2) appears to confer some survival benefit following cardiac surgery. By contrast, morbid obesity (BMI >40 kg/m2) is associated with an increased likelihood of postoperative complications and prolonged intensive care unit and hospital length of stay. The physical difficulties encountered when managing this group of patients is exemplified by those undergoing complex, multiple procedures requiring prolonged cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). We present the successful management of a massively obese 19-year-old male (BMI 45 kg/m2) with Marfan’s syndrome who required aortic root and arch replacement under DHCA. The selection of extracorporeal circuit components to accommodate a large circulating volume and permit high CPB flow rates (>9 l/min) is discussed.