**5.2 Hypotension: haemorrhage, sepsis and cardiac dysfunction**

Perioperative hypotension is common and may reflect inadequate intravascular volume, vasoplegia induced by anaesthetic or analgaesic agents or cardiac dysfunction. Management involves perioperative fluid status optimization with judicious administration of fluid boluses while excluding alternative causes of hypotension including haemorrhage, sepsis and cardiac dysfunction. Recipients with persistent hypotension, despite what appears to be adequate fluid replacement, may require temporary inotropic support. Hypovolaemia, even in the absence of hypotension, increases the risk of delayed graft function resulting in worse graft outcomes [75, 76]. As coronary artery disease is common in patients with ESKD, ruling out ischaemic myocardial damage with ECG review and cardiac enzyme assay measurements is essential (Section 5.3).

Haemorrhage is common in the early period of kidney transplantation, frequently occurring within 48 h of surgery with a reported incidence of 15% [77]. Apart from hypotension, bleeding may manifest clinically with increasing surgical drain output, pain or swelling at the site of the transplant or a falling haemoglobin on serial blood tests. Risk factors for perioperative bleeding include difficult bench surgery, uraemic platelet dysfunction and administration of antiplatelet agents or heparin (either as thromboprophylaxis or during haemodialysis). In a retrospective analysis, difficult bench surgery was identified as the most significant risk factor for post-operative haemorrhage with a 4-fold increased risk. The use of antiplatelet drugs pre-transplant conferred a 2-fold increased risk. Additionally, dialysis vintage was also a risk factor, and each year on dialysis was associated with a 2% increased bleeding risk [77].

In the early post-operative phase, clinical features suggestive of haemorrhage should prompt urgent review of haematology profile, and consideration of imaging in liaison with the transplant surgeon. Peri-nephric hematomas may be identified on ultrasound, but deep or retroperitoneal haemorrhage may be difficult to identify requiring computed tomography. The development of a peri-nephric haematoma may lead to allograft compression, which if significant, may impair graft perfusion with increased diastolic pressures despite normal, or near normal, arcuate artery blood flow indices.

Management of perioperative bleeding requires administration of crystalloid fluids together with judicious transfusion of packed red cells to maintain adequate haemodynamic and haemoglobin targets. Transfusions should be minimised as much as possible, as perioperative blood transfusion leads to recipient sensitization and can increase the likelihood of de novo DSA formation [78]. The decision to proceed to surgical drainage should be individualised, following discussion with the transplant surgeon. The presence of a large haematoma, ongoing haemodynamic instability or features suggesting compression of the allograft, would usually lead to surgical re-exploration.

Sepsis should also be considered in the setting of unexplained hypotension. A high index of suspicion for infection should be maintained at all times since transplant recipients may not develop a fever, leukocytosis or raised inflammatory markers because of their immunosuppressed state (Section 5.7).

#### **5.3 Cardiovascular complications**

Due to the significant cardiovascular disease burden and risk associated with chronic kidney disease, cardiovascular complications post-renal transplantation are common. In a retrospective cohort study, the most common perioperative cardiovascular complication was arrhythmia (53%), followed by myocardial infarction (26.4%) with congestive heart failure being relatively rare (1%) [79, 80].

Hypertension, although often overlooked as a perioperative complication, is common, occurring in 50–70% of recipients. It is likely driven by multiple factors including pre-existing hypertension associated with ESKD, cessation of previous antihypertensive therapy at the time of transplantation, iatrogenic fluid administration to optimise allograft perfusion, calcineurin inhibitor therapy (CNI) and corticosteroid-related fluid retention [81]. Modification of fluid status, diuretic therapy and administration of dihydropyridine calcium channel blockers are common initial strategies used to control BP in the early post-transplant period. The non-dihydropyridine agents (diltiazem and verapamil) may be used, but have significant interactions with CNI (cyclosporine > tacrolimus) increasing CNI exposure. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are usually avoided in the perioperative period to due to their potential to increase creatinine levels but can be introduced once allograft function has stabilised with appropriate monitoring of creatinine and potassium levels.

Despite pre-transplant screening for ischaemic heart disease, acute coronary syndromes (ACS) are still seen in the peri-transplant period, an indication of the limited sensitivity of non-invasive cardiac testing to detect clinically significant coronary disease in the ESKD population [82, 83]. ACS are a difficult complication to manage in the perioperative setting due to competing clinical priorities, and the potential benefits of antiplatelet and anticoagulant therapy need to be balanced against the risk of bleeding. Evaluation of the impact of the infarct on ventricular function can be assessed by echocardiography. Decisions on the optimal management including the potential need for angiography should be discussed with the local cardiology team.

Pre-existing congestive cardiac failure should be identified pre-transplantation and optimised through high-quality dialysis to control uraemia and volume overload as well as medical therapy. Large fluctuations in blood pressure and inter-dialytic weight gain will adversely affect myocardial function through cardiomyopathic remodelling and vasoactive humoral-mediated increases in vascular tone and damage. It is important to acknowledge controversies surrounding optimal blood pressure targets in dialysis patients and to individualise both blood pressure target and pharmacological hypertensive therapy [84, 85].

#### **5.4 Delayed graft function**

Delayed graft function (DGF) is a form of acute kidney injury and is usually defined as the need for dialysis post-transplant. DGF is associated with a higher incidence of acute rejection as well as poorer allograft survival, with a reported 40% greater risk of allograft loss and higher mean serum creatinine concentration [86, 87]. The reported frequency varies significantly (from 2 to 50%) due to heterogeneity of recipient and donor factors and definition of the event [75]. In Australia and New Zealand, nephrologist reported DGF is present in 19.5% of cadaveric renal transplants [ANZDATA 1997–2014].

Post-operative oliguria, failure of improvement of serum creatinine or the need for dialysis should prompt investigations to identify reversible causes of acute kidney injury, including assessment of risk factors for ATN, recipient hypotension or hypovolaemia, presence of post-surgical vascular or urological complications and rejection. In addition to a review of fluid status, haemodynamic parameters and the timing of a decrease in urine output, the following testing should be considered:

**23**

**Table 8.**

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*

the transplanted patient.

allograft function.

**Risk factor Relative impact**

Donor age > 55y 2× higher rate of DGF

Donation after circulatory

*Adapted from Perico et al. [75].*

*Risk factors for delayed graft function.*

death

• Repeat serum biochemistry and haematology profile to rule out pre-renal kidney injury from anaemia and sepsis, taking account of haemoglobin and haematocrit fluctuations with fluid status dilution and unpredictable inflam-

• Repeat CNI trough levels and review of CNI dosing and trends. These are nephrotoxic and may necessitate adjustment depending on the immune risk of

• Ultrasound duplex scan to rule out renovascular pathology. This also allows

• Functional nuclear medical imaging, such as a MAG3, scan will allow assess-

• A renal biopsy is usually undertaken if DGF persists at day 5 post-transplant to rule out rejection, and is repeated weekly until there are signs of improving

It is also helpful to consider risk factors associated with DGF in order to risk stratify and anticipate the clinical course of the transplanted patient (**Table 8**) [75]. In the setting of DGF, ongoing dialysis is often required. In haemodialysis patients, every effort should be made to preserve haemodialysis access. If haemodialysis is delivered through a central vascular catheter, this access should be preserved for this purpose alone and additional central access obtained as needed. If the peritoneum is breached in a peritoneal dialysis patient, alternative access for dialysis needs to be considered as peritoneal dialysis is less likely to be successful. Depending on the immunological risk of the patient, in the presence of DGF, a reduction in target tacrolimus levels can be contemplated. Many transplant centres target a tacrolimus level 8–10 μg/L in the peri-transplantation period. Provided the patient is not considered high immunological risk, reduction of the target range could be considered. The use of thymoglobulin in the setting of DGF is controversial in the absence of immunological risk factors advocating its use as an induction agent [15].

2× higher rate of ATN. No difference in outcome at 1 year

Donor on inotropes Early function 58% (vs. 83%). 1-year survival 73% (vs. 91%)

Higher PRA% Associated higher risk of requiring dialysis post-transplant

Other donor factors Poor reperfusion, death from stroke, presence of AKI associated with

Recipient hypovolaemia Lower pre-operative DBP, intra-operative albumin requirement and preoperative haemodialysis with UF Dialysis modality Higher rate of DGF in haemodialysis vs. peritoneal dialysis

Cold ischemia time 23% increase risk of DGF for every 6 h

Special circumstances Thrombophilia, previous transplant

increased risk

exclusion of peri-nephric collections and obstructive uropathy.

ment of perfusion, graft tracer uptake, and excretion.

matory response in the context of immunosuppression.

*Perioperative Care for Organ Transplant Recipient*

common. In a retrospective cohort study, the most common perioperative cardiovascular complication was arrhythmia (53%), followed by myocardial infarction

Hypertension, although often overlooked as a perioperative complication, is common, occurring in 50–70% of recipients. It is likely driven by multiple factors including pre-existing hypertension associated with ESKD, cessation of previous antihypertensive therapy at the time of transplantation, iatrogenic fluid administration to optimise allograft perfusion, calcineurin inhibitor therapy (CNI) and corticosteroid-related fluid retention [81]. Modification of fluid status, diuretic therapy and administration of dihydropyridine calcium channel blockers are common initial strategies used to control BP in the early post-transplant period. The non-dihydropyridine agents (diltiazem and verapamil) may be used, but have significant interactions with CNI (cyclosporine > tacrolimus) increasing CNI exposure. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are usually avoided in the perioperative period to due to their potential to increase creatinine levels but can be introduced once allograft function has stabilised with

Despite pre-transplant screening for ischaemic heart disease, acute coronary syndromes (ACS) are still seen in the peri-transplant period, an indication of the limited sensitivity of non-invasive cardiac testing to detect clinically significant coronary disease in the ESKD population [82, 83]. ACS are a difficult complication to manage in the perioperative setting due to competing clinical priorities, and the potential benefits of antiplatelet and anticoagulant therapy need to be balanced against the risk of bleeding. Evaluation of the impact of the infarct on ventricular function can be assessed by echocardiography. Decisions on the optimal management including the potential need for angiography should be discussed with the

Pre-existing congestive cardiac failure should be identified pre-transplantation

Delayed graft function (DGF) is a form of acute kidney injury and is usually defined as the need for dialysis post-transplant. DGF is associated with a higher incidence of acute rejection as well as poorer allograft survival, with a reported 40% greater risk of allograft loss and higher mean serum creatinine concentration [86, 87]. The reported frequency varies significantly (from 2 to 50%) due to heterogeneity of recipient and donor factors and definition of the event [75]. In Australia and New Zealand, nephrologist reported DGF is present in 19.5% of cadaveric renal

Post-operative oliguria, failure of improvement of serum creatinine or the need for dialysis should prompt investigations to identify reversible causes of acute kidney injury, including assessment of risk factors for ATN, recipient hypotension or hypovolaemia, presence of post-surgical vascular or urological complications and rejection. In addition to a review of fluid status, haemodynamic parameters and the timing of a decrease in urine output, the following

and optimised through high-quality dialysis to control uraemia and volume overload as well as medical therapy. Large fluctuations in blood pressure and inter-dialytic weight gain will adversely affect myocardial function through cardiomyopathic remodelling and vasoactive humoral-mediated increases in vascular tone and damage. It is important to acknowledge controversies surrounding optimal blood pressure targets in dialysis patients and to individualise both blood pressure

(26.4%) with congestive heart failure being relatively rare (1%) [79, 80].

appropriate monitoring of creatinine and potassium levels.

target and pharmacological hypertensive therapy [84, 85].

local cardiology team.

**5.4 Delayed graft function**

transplants [ANZDATA 1997–2014].

testing should be considered:

**22**


It is also helpful to consider risk factors associated with DGF in order to risk stratify and anticipate the clinical course of the transplanted patient (**Table 8**) [75].

In the setting of DGF, ongoing dialysis is often required. In haemodialysis patients, every effort should be made to preserve haemodialysis access. If haemodialysis is delivered through a central vascular catheter, this access should be preserved for this purpose alone and additional central access obtained as needed. If the peritoneum is breached in a peritoneal dialysis patient, alternative access for dialysis needs to be considered as peritoneal dialysis is less likely to be successful.

Depending on the immunological risk of the patient, in the presence of DGF, a reduction in target tacrolimus levels can be contemplated. Many transplant centres target a tacrolimus level 8–10 μg/L in the peri-transplantation period. Provided the patient is not considered high immunological risk, reduction of the target range could be considered. The use of thymoglobulin in the setting of DGF is controversial in the absence of immunological risk factors advocating its use as an induction agent [15].


#### **Table 8.** *Risk factors for delayed graft function.*

### **5.5 Renal vascular complication**

In transplant recipients who have established a good urine output post-operatively, the sudden development of oliguria or anuria should prompt a review of urinary catheter patency as well as raise the possibility of transplant vessel pathology. Early vascular pathology may be caused by structural or anatomical factors such as vessel kinking, anatomically disadvantageous configurations putting traction on the recipient vessels or thrombosis. Distinguishing between the various pathologies can be challenging clinically, with reliance on duplex ultrasound imaging and knowledge of donor vascular pathology through collaboration with transplant surgeons.

Renal transplant artery or vein thrombosis is a serious, although fortunately uncommon peri-transplant complication, with an incidence of 2–3%, classically occurring in the first week post-transplant [77]. Clinical features of transplant artery thrombosis are typically limited to the sudden onset of oligoanuria, while transplant vein thrombosis may cause allograft swelling, pain and frank haematuria in addition. Predisposing risk factors are decreased perfusion pressures and hypotension as well as donor factors—difficult bench surgery, multiple vessels, prolonged cold ischaemia time and vessel atherosclerosis [77, 88]. Rarer recipient risk factors, when present, can dramatically increase the risk of thrombosis, including in the transplant vessels. Recipients with thrombophilia, notably factor V Leiden mutation or anti-phospholipid antibodies, have been associated with higher risk (2.87 increased risk in one study) of adverse graft outcomes [89, 90]. Diagnosis of transplant vessel pathology may be obtained by urgent renal duplex ultrasonography; however, the abrupt onset of anuria in the early post-operative period is an indication for urgent surgical review and consideration of surgical re-exploration, due to the very short window after transplant arterial thrombosis before irretrievable graft loss occurs.

Renal transplant artery stenosis tends to be a later complication but can occasionally manifest in the perioperative period. The classical clinical features associated with stenosis of the transplant artery are hypertension, allograft dysfunction and fluid overload due to salt and water retention. Risk factors for early transplant artery stenosis tend to be donor related with atherosclerotic vessels or difficult bench surgery [77]. An association with acute rejection has also been described [91]. Diagnosis is by duplex scan showing increased velocity across the anastomotic sites and a flow differential between the aorta and transplant artery.

Intermittent vessel kinking caused by allograft nephroptosis can be diagnostically challenging due to the positional nature of the pathology [92]. Duplex scans may be non-diagnostic, and performing imaging in a non-prone position may assist in the diagnosis of positional vessel compression or kinking, and CT angiography may provide additional diagnostic information in this situation.

#### **5.6 Renal ureteric complications**

Ureteric pathology is more common than vascular pathology, but rarely affects graft survival [93]. The most common early urological complication is a urine leak with an estimated incidence of 8%, followed by ureteric stenoses with a similar incidence occurring later in the transplant course [77, 94]. Other complications of vesicoureteric reflux and urolithiasis are uncommon [95].

Ureteric leaks, like vascular pathology, typically occur in first few weeks post-transplant and may present with localised pain or swelling at the site of the allograft, increased surgical drain output or a peri-transplant collection seen on

**25**

*Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*

due to reabsorption of urinary creatinine and urea.

is beyond the scope of this chapter.

**5.7 Infection**

including [96]:

• haematology panel

• C-reactive protein

• chest X-ray

*5.7.1 Bacterial infection*

• blood culture and venous lactate

opportunistic infection screen

• urinalysis and urine culture

imaging [95]. Non-technical risk factors include recipient agent, pre-transplant urological pathology, immunosuppressive regimen and donor factors [94].

When there is a clinical suspicion for a urine leak due to increased surgical drain output, or if a peri-transplant collection is drained, the fluid should be sent for creatinine concentration analysis to differentiate serous or lymphatic fluid (which will have a similar creatinine concentration to the blood) from urine. Following drain removal, recipients with a urine leak may complain of pain due to fluid accumulation or if there is a significant urine leak, graft function will appear to deteriorate

The management of urine leaks can be complex and often requires liaison with a transplant urologist. It may be possible to manage minor urine leaks conservatively via bladder decompression with an indwelling catheter in addition to ureteric stenting to allow the distal anastomosis to heal. Larger leaks may require further investigation in contrast to enhanced computer tomography, insertion of a percutaneous nephrostomy or surgical repair [95]. A more detailed discussion of this topic

As a consequence of induction immunosuppression, transplant patients are particularly prone to infection in the perioperative phase. However, sepsis can be challenging to diagnose during this period because immunocompromised patients may not manifest the typical features of a systemic inflammatory response. Due to steroid therapy, most patients will exhibit a peripheral neutrophilia. In general, any change in physiological parameters, clinical deterioration or a temperature > 37.5°C should prompt consideration of sepsis, and a sepsis screen should be requested

• additional testing as appropriate—respiratory virus screen, lumbar puncture,

Although transplant recipients are susceptible to opportunistic pathogens such as CMV, EBV, mycobacteria, *Pneumocystis jiroveci* and fungi, these are unusual in the early post-transplant period. Infections occurring soon after transplantation are frequently nosocomial, associated with hospitalisation, intravenous and urinary catheters and intubation during surgery. In some instances, infection may be donor derived [97].

Urinary tract infections (UTI) are the most common cause of bacterial infection requiring hospitalisation in transplant patients, followed by pneumonia,

• empiric antibiotic therapy within 1 h of suspected sepsis diagnosis

#### *Perioperative Care for Kidney Transplant Recipients DOI: http://dx.doi.org/10.5772/intechopen.84388*

imaging [95]. Non-technical risk factors include recipient agent, pre-transplant urological pathology, immunosuppressive regimen and donor factors [94].

When there is a clinical suspicion for a urine leak due to increased surgical drain output, or if a peri-transplant collection is drained, the fluid should be sent for creatinine concentration analysis to differentiate serous or lymphatic fluid (which will have a similar creatinine concentration to the blood) from urine. Following drain removal, recipients with a urine leak may complain of pain due to fluid accumulation or if there is a significant urine leak, graft function will appear to deteriorate due to reabsorption of urinary creatinine and urea.

The management of urine leaks can be complex and often requires liaison with a transplant urologist. It may be possible to manage minor urine leaks conservatively via bladder decompression with an indwelling catheter in addition to ureteric stenting to allow the distal anastomosis to heal. Larger leaks may require further investigation in contrast to enhanced computer tomography, insertion of a percutaneous nephrostomy or surgical repair [95]. A more detailed discussion of this topic is beyond the scope of this chapter.
