The Transplanted Patients: Can We Improve Outcomes of Non-transplant Surgery?

© Springer International Publishing AG 2018
Jean-Luc Fellahi and Marc Leone (eds.)Anesthesia in High-Risk

18. The Transplanted Patients: Can We Improve Outcomes of Non-transplant Surgery?

Christopher P. R. Walker1, Paul Harris1, Janos Fazakas2, Janos Gal3 and Nandor Marczin1, 2, 4  

Department of Anaesthetics, The Royal Brompton and Harefield NHS Foundation Trust, Harefield, UK

Department of Transplantation and Anaesthesia and Intensive Therapy, Semmelweis University, Budapest, Hungary

Department of Anaesthesia and Intensive Therapy, Semmelweis University, Budapest, Hungary

Imperial College London, London, UK



Nandor Marczin

18.1 Introduction

Recipients of solid organ transplantation represent some of the most unique cohort of patients who have experienced, survived and adopted to the most extensive physical, medical and psychological traumas on the transplant waiting lists, and during and after transplantation. They accept the reality that the transplant implantation may be followed by subsequent transplant-related surgical procedures such as a series of biopsies. Perhaps it is less recognised that the transplant status and immunosuppression predispose for additional surgical need especially trauma and malignancies more often than for the general population [14].

For the medical and surgical teams, these represent additional demands with variable expertise and comfort level in different settings ranging from the transplant centre or a teaching hospital with close partnership with the transplant centre or in a district general hospital. Elective procedures even in a general hospital setting should be quite straightforward as there is sufficient time for full planning and consultations with the transplant centres. With major emergency admission, however, senior expertise may not be readily available, and there may not be sufficient time for in-depth consultations [5].

In this review, we focus on new emerging information on the prevalence and outcomes of these operations and conclude that outcomes of high-risk patients and emergency operations are poor. To overcome these negative trends, we aim to arrive at recommendations on how modern anaesthetic management could be refocused and improved. We will provide a detailed analysis for heart transplant recipients and highlight special aspects of lung, renal and liver transplantation.

18.2 Quality of Life, Physical and Exercise Capacity After Transplantation

A successful transplant enables patients with end-stage organ failure to live a high quality of productive life and physical conditions exceeding many in the normal population. Some patients regularly compete in the national and worldwide transplant games and Olympics demonstrating what can be achieved on an individual and team level. Our heart and lung transplant patients have participated in an expedition to take on the volcano climb challenge in South America and completed an epic two-week adventure, which is thought to have been the highest ever climb made by a group of transplant patients.

While such extraordinary achievements do not apply to all heart transplant recipients, the majority will transform into an active person with a potentially excellent quality of life [6]. However, unique physiological changes after heart transplantation limit exercise performance in general. Cystic fibrosis patients, single-lung transplant recipient, older patients and those developing bronchiolitis obliterans syndrome also show significantly decreased physical ability ratings following lung transplantation [7].

These findings have important implications to the physical conditioning of patients presenting for non-transplant surgery. Those without frequent episodes of infections and free of limitations from chronic rejection are comparable in their daily activities and exercise abilities to their normal counterparts in the non-transplant population. Those with moderate to severe chronic rejection will present with important limitations related to graft function and general health status. While these patients can walk independently and pursuing an autonomous life, they may be considered high risk for noncardiac and non-transplant-related surgical outcomes.

18.3 The Spectrum and Complications of Non-transplant Surgery

Marzoa and colleagues have provided a relatively recent account on late noncardiac surgeries (mainly malignancies) in their heart transplant population [8]. The major interventions were elective (85%) comprising of urologic (30%), abdominal (25%), vascular (12%), ENT (11%), skin and soft tissue (9%) and orthopaedic (6%). Mortality was 1% in the overall elective procedures but more than 16% in the emergent setting. A preoperative risk stratification to the middle−/low-risk cohort exhibited low (0%) mortality, whereas 16% of patients died with preoperative high-risk scores. The most frequent complication was related to postsurgical infection (6.9%), while none of the patients displayed allograft dysfunction or an acute rejection episode perioperatively.

Zeyneloglu et al. have also demonstrated the relative safe conduct of non-transplant surgery after liver transplantation [9]. In their series 22 patients underwent more than 30 surgical procedures. General and regional anaesthesia was associated with preserved liver and renal function with all patients surviving the predominantly low-risk surgical interventions.

A recent systematic review of more than 70,000 transplant recipients identified emergency abdominal surgery for graft-unrelated acute diseases in 2.5% of patients [10]. The solid organs transplanted in these patients were the heart in 66% of patients, the lung in 22%, the kidney in 9% and the liver in 3%. Gallbladder diseases, gastrointestinal perforations, complicated diverticulitis, small bowel obstructions and appendicitis were the main indications. Such surgery was associated with high morbidity in one third of patients with mortality rates close to 20%. These further emphasise the particularly challenging perioperative management of transplanted patients in the emergency setting.

Transplant recipients on long-term immunosuppression have various bone complications and require orthopaedic procedures for accelerated osteoarthritis and fractures [11, 12]. Klatt et al. observed 17% infection rates following total knee arthroplasty with another 20% additional overall complication rate potentially related to immunosuppression [13]. Reid et al. found very high rates of medical complications within 90 days after lower limb fractures, with 40% of patients having acute renal failure, a quarter developing urinary tract infection, 8% having a superficial surgical site infection and as much as 8% suffering from non-orthopaedic sepsis [12].

18.4 Anaesthetic Implications: A Framework for Quality Improvement

Our overall interpretation of the outcome data is that in most elective situations, there is sufficient anaesthetic and surgical attention and care dedicated to the transplanted organ and general haemodynamic stability to ensure optimal allograft and vital organ function. However, this is not achieved with the higher-risk subset of patients or during the emergency presentation of surgical disease. Moreover, we do not successfully negate the multiple negative side effects of chronic immunosuppression, and in general, we tend to err on too much immunosuppression and pay the price by postoperative infections.

There could be multiple contributing mechanisms to such failures including (1) gaps in our understanding and defining high-risk populations, (2) mismanaging critical events by not recognising negative trends due to inappropriate monitoring and/or missing opportunities to intervene effectively and (3) staging imbalance between immunosuppression and microbial surveillance especially unrecognising “endogenous” postoperative immunosuppression [1416].

We strongly believe that anaesthesia management of the transplanted patient should go beyond “routine” anaesthetic practice. A new ambitious mission and a significant paradigm change in our practice are required that demand a systematic quality improvement in every domain of our engagement from preoperative assessment through intraoperative management to postoperative recovery. The emphasis should be on integration of protecting the allograft and managing comorbidities and perioperative risks together by:

  • Recognising the high-risk patient preoperatively.

  • Understanding the reduced physiological and functional reserve of these patients and the importance of reduced critical time window for optimisation.

  • Comprehensive intra- and postoperative monitoring to detect even subtle changes in homeostasis.

  • Precise maintenance of homeostasis by aggressive therapeutic modalities.

  • Taking ownership of assessing, monitoring and optimising perioperative immunosuppression in its globality.

  • Meticulous attention to infection prevention and control.

18.5 Heart Transplant Recipients

18.5.1 Physiology of the Transplanted Heart

The transplanted heart rarely provides the recipient with completely normal cardiac function. The organ’s intrinsic muscle function may be preserved, but its altered physiology results from denervation and the anatomical consequences of surgical implantation [1, 4, 17].

Electrophysiology. Both sympathetic and parasympathetic efferent nerve fibres are severed during surgical implantation as well as sensory afferents. Reinnervation may occur, in some cases detectable as early as 5 months post-implantation, though more usually is not physiologically significant [1820]. Denervation will result in symptomless ischaemia (no angina pectoris), increase in body water and left atrial pressures and elevated resting heart rate (approx. 90–110 bpm). The denervated heart will not mount a tachycardia as part of any reflex sympathetic response. Thus, any increase in cardiac output will be dependent on increasing heart rate and increasing circulating volume. The cardiovascular responses to surgical stimulation are lost. Carotid sinus massage and the Valsalva manoeuvre do not affect heart rate.

A significant fraction of patients exhibit conduction defects, especially right bundle branch block and implantation of a permanent pacemaker. Dysrhythmias are common and likely contributing factors include absent vagal tone, rejection (previous or active episodes) and raised endogenous catecholamines.

Cardiac performance. Exercise function may be reduced to 60–70% of that of normal subjects due to the absence of reflex tachycardia to exercise, increasing preload-related filling pressures and coexistent diastolic dysfunction [3, 4, 17].

The neuroendocrine response to heart transplantation may include elevation of plasma renin, natriuretic peptides, vasopressin and noradrenaline. This may contribute to diastolic dysfunction and the exaggerated hypertensive disease seen in patients and limit the heart’s response to the demands of exercise.

Skeletal muscle mass and function may be diminished by poor preoperative condition, as end-stage cardiac failure progresses, and the need for corticosteroids postoperatively as part of the immunosuppressive regime.

Cardiac allograft vasculopathy. CAV is a diffuse, nonfocal concentric thickening of the donor coronary arteries [21, 22]. The predominant pathological feature is concentric intimal hyperplasia as opposed to the discrete endothelial lipid core seen in atherosclerotic coronary arterial disease. The final common pathway is one of the immune activation leading to intimal hyperplasia most likely due to the cumulative injury from ischaemia-reperfusion injury, mechanical damage, cytomegalovirus infection and inherent endothelial damage (hypertension, diabetes, immunosuppression, hyperlipidaemia). The diffuse and extensive nature of the disease reduces the chances of successful revascularisation treatments significantly. Within 5 years of transplantation, only 70% of patients are CAV-free and this drops to 40% by 10 years.

Pharmacology. Due to denervation, vagolytic drugs such as atropine and glycopyrrolate have no effect unless a degree of reinnervation has occurred. There is lack of reflex tachycardia in response to glyceryl trinitrate, sodium nitroprusside and local anaesthetic neuraxial blocks. The effect of beta-blockers may be exaggerated due to up-regulation of beta-adrenoceptors and due to the risk of excessive bradycardia; their use is not recommended.

Conversely, direct chronotropes and pressors are required to increase heart rate and systemic vascular resistance. Isoprenaline, dobutamine, metaraminol, adrenaline and noradrenaline all exert a direct adrenoceptor action. Ephedrine may be less effective as at least some of its activity is presynaptic, and myocardial catecholamine storage is chronically depleted.

Most antiarrhythmic drugs remain effective, but their potent negative inotropy may be revealed, as the heart is unable to initiate any reflexes to counter this. Amiodarone is the most widespread antiarrhythmic used following heart transplant and is effective in treating acute arrythmias. Chronic amiodarone use is avoided as cyclosporine levels are affected. Digoxin is less effective at delaying AV conduction in the denervated heart. Adenosine is effective at blocking AV nodal conduction but exhibits a supersensitivity response. Thus, the initial dose should be reduced to 1 mg.

Denervation will affect the activity of some anaesthesia drugs [1, 3, 4]. Tachycardia associated with pancuronium is not seen, and bradycardia in response to succinylcholine, neostigmine and with some synthetic opioids (e.g. fentanyl) is absent. The advent of sugammadex has offered an alternative for reversing neuromuscular blockade with rocuronium, and it has been used without adverse effect in heart transplant patients [23].

18.5.2 Preoperative Assessment

This must be extensive and should provide a detailed picture on the individual patients existing limitations and assessment of the implications of these to intraoperative and postoperative functions [1, 3, 4]. In the elective setting, this is best done by directly accessing the last comprehensive transplant review (cardiac transplant “MOT”). Transplant physicians methodically review heart transplant patients at least annually or more frequently pending complications. Thus, the patients have regular assessment of cardiac function and any associated organ dysfunction that may exist (e.g. renal function with cyclosporine use). The transplant team is an invaluable source of information and should be in regular contact when a patient presents for a noncardiac procedure.

Transthoracic echocardiography imaging provides a good snapshot of biventricular systolic function, diastolic performance, existence of valvular comorbidities and frequent information on pulmonary pressures. Coronary artery imaging is paramount given the silent nature of any myocardial ischaemia. Electrophysiology evaluation should include a current ECG to uncover ischaemia and arrhythmias, and pacemaker advice should be thought if present ensuring an up-to-date pacemaker check is available.

Cardiac history is also informative regarding any lasting symptoms of the original heart failure condition with residual cardiorenal alterations and hepatic dysfunction due to end-stage RV failure [24]. Patient journey, especially significant complications of cardiac allograft implantation, primary graft failure, bridging or salvage mechanical support, frequent rejections and documented development of accelerated atherosclerosis, should ring alarm bells for concerns.

All patients should be carefully assessed for any significant change in performance status or the occurrence of any new symptoms covering the period from the last transplant review. Should these generate any suspicion for change of status, elective procedures should be postponed and patient referred back to the transplant unit.

Review and plans for immunosuppression should constitute a central part of preoperative workup [25]. Review of rejection episodes should provide an indication for compliance with and efficiency of immunosuppressive regimes. Up to date report and advice should be directly sought from the principal transplant physician taking into consideration the extent of surgery, suitability of oral or intravenous administration and multiple factors that may influence plasma levels and depth of immunosuppression [1, 2]. The signs of chronic complications attributable to chronic immunosuppression such as worsening hypertension, diabetes, renal function, neurotoxicity with calcineurine inhibitors or bone marrow depression with azathioprine and MMF resulting in anaemia/leucopenia and reduced platelet counts should be carefully acknowledged [1, 3, 4]. Not only these side effects bare direct relevance to the conduct of anaesthesia, but also they may indicate the patient’s heightened response to normal immunosuppression or overzealous immunosuppressed state. A detailed plan for continuing or temporarily suspending some immunosuppression medications, monitoring drug levels and provisions for the postoperative period with different scenarios have to be documented.

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Dec 18, 2017 | Posted by in Uncategorized | Comments Off on The Transplanted Patients: Can We Improve Outcomes of Non-transplant Surgery?
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