Introduction:
Renal transplant is the best long term replacement therapy for any end stage renal failure. As science is evolving day by day since the first ever transplant done in 1954, Anaesthesiologists play a pivotal role in making the transplant successful. One has to understand the renal failure and its consequences well to administer anaesthesia for the transplant surgery.
Challenges:
Understanding the pathophysiology and the co-morbid conditions of end-stage renal failure will make you to take up the challenges comfortably. The challenges are many, from optimization of the patient to the conduct of anaesthesia and perioperative management. Though there are a few absolute contraindications, all are based on patient selection and legal issues in which we may not have much say.
Absolute contraindications to renal transplantation:

• Predicted patient survival of less than 5 years
• Predicted risk of graft loss greater than 50% at 1 year
• Patients unable to comply with immunosuppressant therapy
• Immunosuppression predicted to cause life threatening complications

Optimization:
The optimization based on the underlying causes of CKD (Chronic kidney disease), systems affected and the co-morbid conditions (Table 1).
Table 1

 
Since renal transplantation is done by a team of experts and is an elective procedure, it gives us the opportunity to go through and revise the case history before visiting the patient. The periodical assessment and the investigations are recorded chronologically so that we will have a thorough understanding of the patient status. The pre-anaesthetic assessment has to be carried out twice at least prior to the surgery; one, couple of weeks before and the other just prior to surgery. It will be wise to optimize the patient well ahead and do only minimal changes just before to the procedure.
Cardiovascular system:
Since the cardiovascular disease is the commonest cause of death among dialysis patients, one needs to evaluate the system thoroughly. Presence of hypertension, ischaemic heart disease or cardiac failure makes the fluid status and volume assessment more difficult. ACC/AHA guidelines published in 2012 may facilitate the evaluation.
A thorough history and physical examination are recommended to identify active cardiac conditions before transplantation. Routine investigations like chest X-Ray, ECG and Echocardiography are mandatory for all patients.
The 2012 AHA Scientific statement says that non-invasive stress testing may be considered for those who are not having active cardiac conditions on the basis of the presence of multiple CAD risk factors regardless of functional status. However, symptomatic patients are supposed to undergo invasive and strenuous evaluation as cardiac ailment happened to be the primary cause of death in most of the single organ transplants.
Pulmonary:
Respiratory system as such is not affected primarily in ESRD, whereas the fluid distribution and accumulation causes pulmonary oedema and hypoxia. Patients on regular haemodialysis may not have many problems as long as the fluid management is taken care off. Regular chest X-Ray is needed to rule out pulmonary deceleration and pleural effusion. Poor compliance due to pleural effusion may be a big concern in case we contemplate central neuraxial blockade as a sole anaesthetic technique. Pre-operative blood gas analysis may be useful to find out the status of gas exchange in addition to the acid-base abnormalities.
Gastrointestinal:
Uraemia per se in addition to the co-morbid disease like diabetes can cause gastro paresis. It is wise to take precautions against aspiration and treat them as full stomach since there will be delayed gastric emptying. Some patients may have gastric ulceration which may get exacerbated due to starvation prior to surgery. Gastric bleed may further decrease the Hb which is already debilitated due to decreased production in CRF.
Renal & Metabolic:
Patients on dialysis often encounter electrolyte and acid-base abnormalities due to various reasons. The status may vary vastly in patient to patient, based on the type of dialysis and fluid replacement protocol. Routine preoperative check-up of electrolytes and blood gas are mandatory. ECG findings may not be consistent with all electrolyte changes though it could be handy to have baseline ECG findings. Wide range of electrolyte abnormalities needs to be corrected well ahead. However the one prior to anaesthesia after the last dialysis needs to be corrected appropriately to avoid or reduce complications in perioperative period.
Patients are bound to be acidotic due to inability of excreting acid load. Initially it may be non-anion gap acidosis and later may encounter a highly anion-gap acidosis due to retained sulphates and phosphates. It is easy to correct during dialysis, however acid-base status has to be corrected prior to induction if it is deranged vastly.
Haematological:
Many factors attribute to anaemia in ESRD patients. An impaired erythropoiesis secondary to decreased erythropoietin synthesis and decreased red cell life span are being the main causes for anemia. Patient on hemodialysis with AV fistula bound to have depleted volume status and thus results in chronic anemia. Pre-operative correction is not warranted unless there is an active loss of blood from gastric ulcers or the Hb value is very low. Use of biosynthetic erythropoietin and darbopoietin reduces blood transfusion in perioperative period.  
Though the platelet count is in normal limits the platelet activity may be deranged with decreased adhesiveness and aggregation. Desmopressin or cryoprecipitate may be useful to certain extent.
Endocrine:
The risk of cardiovascular disease is high in ESRD individuals those who are diabetic when compare to non-diabetic.  A good glycaemic control prior and after transplant is essential to avoid complications. Secondary hyperparathyroidism in these individuals are also a big concern.

Nervous:
Nervous system is affected in all uremic individuals. CNS manifestations such as fatigue, malaise and seizures may be present. Autonomic neuropathy either due to the primary disease or co-existing conditions is the main concern for the anaesthesiologists. Orthostatic hypotension and silent ischaemia are not uncommon.
Pre-emptive transplants
Pre-emptive transplants are bigger challenge for anaesthesiologist as these patients are not on dialysis which makes the fluid, electrolyte and acid-base management more difficult. Though they are more vulnerable for pulmonary oedema, the ill effect of long term dialysis may not exist. One or two dialysis just before surgery makes the perioperative management much easier and is fully recommended.
Altered pharmacology:

Majority of the anaesthetic drugs are metabolised by kidney and hence the pharmacodynamics and pharmacokinetics are altered vastly. In addition to this hypoprotenemia makes more unbound fraction of drugs available for action. The blood brain barrier allows the free drugs to cross and exacerbate the action in uraemia.
Pre-anaesthetic Medications: Relatively unchanged distribution and metabolism of Midazolam makes it as the choice of anxiolytic prior to surgery. Aspiration prophylaxis includes H2 receptor antagonists are useful.
Induction agents: Propofol and thiopentone are the drugs of choice as etomidate interfere in adrenal secretion and might cause fatal cardiac arrest. A titrated dose of thiopentone, probably a lesser volume than the calculated amount will be sufficient to put the patient to sleep. In case of propofol we might have to give a slightly larger dose from the calculated volume.
Inhalational Agent:
Isoflurane can be used along with nitrous-oxide safely. Compound A which is a NEPHROTOXIC, should be kept in mind when we use sevoflurane with circle absorber.
Analgesic:
Fentanyl analogues are the best choice among the opiates as morphine sulphate gives rise to morphine-6-glucuronite which may accumulate in ESRD and cause myocardial depression. Adjuvants like paracetamol can be supplemented in addition to opiates in post-operative period.
Muscle Relaxant: Intubation on non-depolarising muscle relaxants is the standard practice unless the patient is very obese or difficult airway is predicted. In these situations rapid sequence induction using suxamethonium is preferred provided the potassium levels are within the limits. Atracurium and sis-atracurium are the drugs preferred among the non-depolarising agents as it is excreted via Hoffman degradation. However, laudanosin which is an end product of atracurium metabolism is excreted through the kidneys may cause convulsion. Rocuronium is the next choice as it can be used and reversed safely in ESRD.
Reversing Agent:
Acid-Base status influences the reversal of non-depolarising agents vastly in transplant surgery. Measures should be taken to manage the acid-base abnormalities prior to the reversal. Neostigmine with glycopyrolate is the regular preference as atropine interferes with blood brain barrier. Since these patients are on immunosuppressant it is better to reverse at the end of the procedure and avoid post-operative ventilation.

Table 2:

Monitoring:
Standard monitoring with 5 lead ECG, pulse oximetry, temperature probe, capnography and central venous pressure is enough for most of the patients. Internal jugular venous cannulation with triple lumen catheters is useful to give immunosuppressant and other drugs separately.  Invasive arterial pressure monitor and pulmonary capillary wedge pressure may be required for those who are having low cardiac ejection or post myocardial infarction. Neuromuscular monitoring will be an additional cushion for reversal from muscle relaxants.
Controversies:
Choice of anaesthesia: General anaesthesia with controlled ventilation is the choice in many patients. An epidural anaesthesia in addition to General anaesthesia may be helpful in post-operative pain relief. Epidural anaesthesia can be used as a sole anaesthetic technique in patients with compromised respiratory system.
Fluid management: Studies have proved that over use of normal saline might increase hyperchloraemic acidosis which could be avoided by using half normal saline or ringer lactate in patients with normal electrolyte levels. Volume management might vary between centres and individuals. Volume has to be challenged with the guidance of central venous pressure which could be maintained around 14 to 16 cm of H2O in patients with normal cardiac function. No inotropes has shown better out come over other when used to improve blood pressure.  Monitoring pulmonary capillary wedge pressure may be useful in low cardiac output status. Since the graft function depends on multiple factors, it is unwarranted to overload the patient beyond a limit with fluids over enthusiastically.

Post- operative care:
It is better to isolate the transplanted patients in a separate room in order to avoid unnecessary infection. The vital signs and the function of the kidney have to be monitored continuously. Acid-base, electrolytes and fluid management are to be monitored intensively.
Re-exploration:
Re-exploration might be required sometimes to reposition the graft. Anaesthesiologist should take a survey on acid-base, electrolyte and fluid status. Care must be given to maintain hemodynamic stability while inducing as any change in that may jeopardise the graft function further. Haemoglobin level has to be checked and blood may be reserved as the patient might lose more blood during re-exploration.
Summary:
Anaesthesia for renal transplant surgery is a challenging field for the anaesthesiologist. The outcome and wellbeing of the patient is very much dependent on the anaesthesia as well. The anaesthesiologist should be well versed with the patho-physiological changes of end stage renal disease and co-morbid conditions to anaesthetize the patient for renal transplant surgery.
Reference:

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