Acta Anaesthesiol Scand 2007; 51: 1354–1367 # 2007 The Authors

Printed in Singapore. All rights reserved Journal compilation # 2007 Acta Anaesthesiol Scand

ACTA ANAESTHESIOLOGICA SCANDINAVICA

doi: 10.1111/j.1399-6576.2007.01447.x

Anaesthesia for renal transplant surgery

H. SARINKAPOOR1, R. KAUR1 and H. KAUR2

Departments of 1Anaesthesiology and Intensive Care and 2Nephrology, Fortis Hospital, Amritsar, India

Renal transplantation is the preferred therapeutic option for patients Accepted for publication 25 June 2007
with end-stage renal disease. Survival rates are much higher in
patients who receive a transplant. Patients with renal failure have
significant concomitant medical conditions, such as cardiovascular Key words: Anaesthesia; kidney transplant; renal transplant.
disease. This article provides an overview of the important issues to
be considered in patients undergoing renal transplant, and discusses # 2007 The Authors
the anaesthetic management of these patients. Journal compilation # 2007 Acta Anaesthesiol Scand

I N recent years, tremendous strides have been

made in the general care of patients with end-
stage renal disease (ESRD). By definition, ESRD
marginal quality (7–9). Ojo et al. (10) found that, on
average, recipients of marginal kidney transplants
lived 5 years longer than transplant candidates who
begins when renal replacement therapy is initiated. remained on dialysis, whereas ideal cadaveric trans-
Once the kidneys fail, the patient has three manage- plant recipients had a 13-year survival benefit.
ment options: haemodialysis (HD), peritoneal dialy- Rabbat et al. (11) have also shown a long-term
sis (PD) or transplantation. Over the past decade, survival advantage associated with cadaveric renal
improvements in immunosuppressive medication, transplantation over dialysis. This difference was
organ procurement, patient preparation and surgical found to be more striking in patients in whom end-
techniques have resulted in a significant increase in stage renal failure was caused by diabetes and
survival rates after renal transplantation (1, 2). Fur- glomerulonephritis.
thermore, renal transplantation has been shown to Dialysis is considered to be one of the costliest
confer a greater survival benefit than maintenance treatment modalities in medicine. In a study by Joyce
dialysis. The estimated number of additional life- et al. (12), the annual per-patient cost was found to
years gained from renal transplantation have been increase by 150% in diabetics and 140% in those
found to vary from 8 years in a 60-year-old diabetic without diabetes following the onset of ESRD. In the
recipient to 31 years in a non-diabetic recipient aged same study, it was shown that 5% of Medicare
between 20 and 44 years (3, 4). Moreover, in dialysis programme expenditure in the USA was for ESRD
patients, the left ventricular function tends to deteri- patients, although they constituted only 0.5% of the
orate with time (5). Valvular disease, in particular beneficiaries. In another study in Greece, the average
aortic stenosis, has also been shown to progress cost of a single dialysis session was estimated to be
markedly over the years in dialysis patients (6). 240 euros, and the aggregate economic impact was
Therefore, earlier transplantation is advantageous to calculated to exceed 250 million euros per annum
ESRD patients on dialysis. (13). Furthermore, in this study, it was reported that
The kidney donor pool has been expanded to dialysis was more expensive than renal transplant,
include those who might have been deemed unsuit- the cost of which was calculated to be 22,500 euros
able in earlier times. The presence of certain pre- according to the estimate of the Hellenic National
transplant correlates of diminished graft survival, Transplant Organization in 2003. Thus, it is more
such as advanced donor age, long-standing donor economically feasible to perform a renal transplant in
hypertension or diabetes mellitus, non-heart-beating patients with ESRD.
cadaver donor and prolonged cold preservation time, The aims of this review are to provide an overview
has been used to characterize an organ as being of of the pre-operative considerations involved in

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 Anaesthesia for renal transplant surgery

patients undergoing renal transplant, and to discuss Table 1

the anaesthetic management of these patients. Important pre-operative considerations prior to renal transplant.

Cardiovascular disease
Pre-operative assessment Ischaemic heart disease
Congestive cardiac failure
Patients with end-stage renal failure suffer from Hypertension
various concomitant medical diseases. Their medical Diabetes mellitus
history is complex and many systems are likely to be Anaemia
Hyperparathyroidism and elevated calcium and phosphate
affected. Diabetes is the most common cause of Dyslipidaemias
ESRD, followed by hypertension (Fig. 1). Hence, it Infections
is important to take a full pre-operative history and Hepatitis B
Hepatitis C
also to evaluate the medications taken by the pa- Newer cardiovascular risk factors
tients. The important medical and other issues to be C-reactive protein
considered in patients with ESRD, prior to trans- Homocysteine
Duration of end-stage renal disease
plant, are summarized in Table 1 and explained in Centre effect
detail below.

Cardiovascular disease risk of cardiovascular disease is 10–30 times higher in

Cardiovascular disease is the major cause of dialysis patients than in the normal population.
increased morbidity and mortality in dialysis pa- Following renal transplantation, the risk is decreased
tients, and accounts for over 50% of deaths (14). The to twice that in normal subjects (15, 16). Several
factors contribute to the development and progres-
sion of cardiovascular disease in patients on renal
9 10 replacement therapy. These include both the tradi-
8 tional cardiovascular risk factors recognized in the
7 general population and additional risk factors
6 particular to chronic renal failure, such as volume
overload with consequent hypertension (17, 18),
anaemia (19) and disturbance of calcium phosphate
metabolism (20).
All patients should be investigated for cardiovas-
1 cular disease when they are accepted onto the trans-
plant waiting list. Various angiographic studies have
demonstrated a high prevalence of clinically silent
5
ischaemic heart disease in these patients, especially in
those with concomitant diabetes mellitus (21–23). As
the resting electrocardiogram (ECG) is often abnor-
mal in these patients, standard treadmill tests are
difficult to interpret (24). Hence, dobutamine stress
echocardiography or thallium dipyridamole stress
tests should be considered (23, 25). Coronary angi-
4 ography should be carried out in patients showing
3 2 reversible ischaemia.
Congestive cardiac failure is also more prevalent in
Fig. 1. Incidence of end-stage renal disease (ESRD) by primary
dialysis patients. When ESRD patients with conges-
diagnosis [data from US Renal Data System (USRDS) 2006
Annual Data Report: Atlas of End-Stage Renal Disease in United tive heart failure as a result of reduced left ventricular
States. Bethesda, MD: National Institutes of Health, National ejection fraction (LVEF) present for kidney trans-
Institute of Diabetes, Digestive and Kidney Diseases, 2006]. 1, plantation evaluation, they are generally considered
Diabetes mellitus (44.9%); 2, glomerulonephritis (8.2%); 3, secondary to be at high risk for surgery. However, Wali et al. (26)
glomerulonephritis/vasculitis (2.1%); 4, interstitial nephritis/ demonstrated that kidney transplantation could be
pyelonephritis (4.1%); 5, hypertension/large vessel disease (26.6%);
6, cystic/congenital/hereditary disease (3.4%); 7, neoplasms/tumours performed safely in ESRD patients with decreased
(2.1%); 8, miscellaneous (4.6%); 9, aetiology uncertain (4.1%); LVEF, advanced heart failure and without inducible
10, missing (1.1%). ischaemia. In their study, renal transplantation

1355
H. SarinKapoor et al.

resulted in an increase in LVEF in more than 86% of heart failure. Calcium antagonists can be given in
patients, and was associated with an improvement in the elderly, but short-release preparations should
New York Heart Association (NYHA) functional sta- be avoided.
tus in more than two-thirds of patients. Furthermore,
they reported that the duration of dialysis therapy
before kidney transplantation was the only significant
Diabetes
Diabetic nephropathy is the most common cause of
factor that predicted the normalization of LVEF.
ESRD in Europe, Japan and the USA. Patients with
However, subjects in this study were relatively young.
diabetic nephropathy and ESRD are known to have
Hence, all dialysis patients with reduced LVEF
higher mortality rates than those with other causes
must be initially evaluated for underlying ischaemia,
of ESRD. Diabetic patients with renal failure have
and their medications for heart failure [b-blocker,
an increased risk of cardiovascular disease. Hence,
angiotensin-converting enzyme (ACE) inhibitor or
screening and treatment of coronary artery disease
angiotensin receptor blocker] should be optimized.
are essential in diabetic patients undergoing trans-
These patients can then be assessed for kidney trans-
plantation. Good glycaemic control is also important
plantation, especially those in the younger age
before and during transplant, and is associated with
groups.
a lower mortality.
Norio et al. (32) studied the peri-operative ECGs
and invasive haemodynamic and oxygenation pa-
Hypertension
rameters in patients undergoing renal transplanta-
Hypertension is a common clinical problem in renal
tion. They reported an increased incidence of QT
transplant recipients, and plays an important role in
dispersion in the pre-operative ECG and a higher
causing cardiac damage by producing left ventricular
pre-operative heart rate and mean arterial pressure
hypertrophy, which predisposes the patient to ischae-
in diabetics than in non-diabetics. Following pre-
mia (27). The impairment of coronary perfusion in
anaesthetic volume loading, hyperdynamic circula-
a hypertrophic heart results in regional impairment
tion was noted in all patients, which subsided during
of left ventricular contraction and left ventricular
anaesthesia. Although intra-operative cardiac dys-
dilatation, leading to systolic dysfunction (28). The
rhythmias were not noted in any of the diabetics in
risk of cardiovascular death in patients on dialysis
this study, it is suggested that ECG monitoring
has been reported to be 2.2 times greater in those
should be performed intra-operatively in all diabetics
with a pre-dialysis blood pressure of 130/80 mmHg
for arrhythmias.
or greater than in those with a blood pressure of less
Diabetic patients undergoing renal transplant are
than 130/80 mmHg (18). Foley et al. (17) have
susceptible to accelerated peripheral vascular dis-
reported that, after adjusting for age, diabetes,
ease (33). Diabetic foot disease can be troublesome
ischaemic heart disease, haemoglobin and serum
post-transplant. Post-transplant diabetes mellitus is
albumin, each 10-mmHg rise in mean arterial blood
also known to develop as a complication of immu-
pressure is associated with concentric left ventricular
nosuppression, specifically steroids and calcineurin
hypertrophy and the development of ischaemic heart
inhibitors.
disease and cardiac failure. An inverse relationship
has been shown to exist between the severity of
hypertension and graft survival (29). Anaemia
A blood pressure of 140/90 mmHg has been Anaemia is a known complication of ESRD and is
shown to minimize the occurrence of left ventricular also linked to cardiovascular morbidity and mortal-
hypertrophy and death in dialysis patients (17). ity. In chronic renal failure, decreased left ventricular
Hence, a value of 140/90 mmHg or less should be capillary supply increases the critical oxygen diffu-
set as the target blood pressure (30). Ambulatory sion distance in the myocardium (which is hypertro-
blood pressure monitoring is not strictly necessary phic in renal failure), predisposing it to ischaemia
for routine monitoring in HD patients. and, consequently, failure. In a study by Harnett et al.
For the control of high blood pressure, ACE (19), the independent relative risk of mortality in
inhibitors should be used, as these agents have been dialysis patients was calculated to be 1.18 per 1.0-g/dl
found to confer a better prognosis in patients with decrease in haemoglobin level. Mix et al. (34) reported
a high risk of cardiovascular events (31). Angioten- that the prevalence of anaemia (haematocrit <36%)
sin-II receptor antagonists should be used when an was 76% at transplantation and fell to 21% 1 year post-
ACE inhibitor-induced cough is present, and also in transplant.

1356
 Anaesthesia for renal transplant surgery

The correction of anaemia with erythropoietin mortality in both the general and ESRD population.
increases oxygen transport and decreases cardiac CRP has been found to be chronically elevated in
output, pulse rate and cardiac workload, which leads one-third to two-thirds of dialysis patients (46, 47).
to a decrease in left ventricular hypertrophy, thereby Oh et al. (48) have demonstrated that CRP strongly
improving cardiac status (35). Furthermore, it also correlates with coronary calcifications in young
improves exercise capacity, cognitive and brain func- ESRD patients, not only undergoing dialysis but also
tion and quality of life, and also reduces mortality after renal transplantation. In chronic renal failure
(36, 37). However, erythropoietin therapy has been patients, CRP levels have been found to be associated
found to increase blood pressure in up to 30% of with malnutrition and increased cardiovascular risk
dialysis patients (38). The correction of anaemia has and mortality (49). Furthermore, increased levels of
also been found to improve uraemic coagulopathy, pro-inflammatory cytokines, such as interleukin-1
increase blood viscosity and decrease erythrocyte (IL-1), tumour necrosis factor-a, IL-6 and IL-13, have
deformability, thus predisposing to thrombus forma- also been found to be associated with higher rates of
tion (39). Hence, a gradual correction of anaemia mortality in HD patients (50).
with a target haemoglobin level of around 12 g/dl Homocysteine is another cardiovascular risk factor
should be considered for all patients. that is elevated in chronic renal failure and remains
so even after kidney transplantation. Homocysteine
Parathyroid hormone, calcium and phosphate has been found to predict cardiovascular mortality
Elevated serum calcium and phosphate, secondary in ESRD patients and morbidity after transplanta-
hyperparathyroidism and the administration of phos- tion (51, 52). Oh et al. (48) have reported that
phate-chelating agents may play a role in the patho- hyperhomocysteinaemia contributes significantly to
genesis of cardiovascular disease in chronic renal coronary artery calcification, independent of CRP,
failure. A high degree of fibrosis and myocardial parathyroid hormone and calcium phosphate load.
calcium content can lead to the development of Asymmetric dimethylarginine (ADMA) is an
myocardial hypertrophy and diastolic dysfunction of endogenous competitive inhibitor of nitric oxide
the left ventricle (40). Secondary hyperparathyroidism (NO) synthase. It has been hypothesized that ADMA
and increased calcium
phosphate product have accumulation in renal failure inhibits NO-induced
been found to be associated with calcification of the vasodilatation, and thus could contribute to hyper-
cardiac valves and coronary arteries (41, 42). It has tension and cardiovascular disease (53).
been suggested that hyperphosphataemia is mainly
responsible for cardiac valve calcification, and hence
should be efficiently controlled (43). Calcium-based Hepatitis C
chelators are widely used for phosphate control; Hepatitis C virus (HCV) infection is linked to chronic
however, high doses are required, which can lead to renal disease. Chronic infection with HCV is associ-
frequent episodes of hypercalcaemia, thus contribut- ated with membranous nephropathy and membra-
ing further to metastatic calcification. noproliferative glomerulonephritis with or without
cryoglobulinaemia (54). Patients on chronic HD are at
an increased risk of acquiring HCV infection as
Dyslipidaemia a result of frequent blood transfusions and HCV-
The prevalence of dyslipidaemia in chronic renal contaminated dialysis equipment. Various studies
failure is higher than that in the general population. have reported that the relative risk for death in
Higher levels of serum lipoprotein-A seen in chronic anti-HCV-antibody-positive patients is significantly
renal failure have been found to contribute to ath- higher than that in anti-HCV-antibody-negative pa-
erosclerosis, leading to an increased incidence of tients after adjusting for age, transplantation, dura-
cardiac events (44). Hence, serum lipid levels should tion of dialysis and race (55, 56). Hepatocellular
be decreased using a strategy combining dietary carcinoma and liver cirrhosis are serious complica-
modifications and lipid-lowering agents. tions of HCV infection and could contribute to the
high mortality in the HCV-positive group (57, 58).
Other cardiovascular risk factors Sepsis has been shown to be another significant cause
In the last decade, evidence has been increasing that of death in HCV-positive patients with renal trans-
atherosclerosis is an inflammatory disorder (45). plantation (59).
C-reactive protein (CRP), a marker of micro-inflam- There is considerable debate about the effect of
matory state, is a potent predictor of cardiovascular recipient HCV infection on renal allograft loss and

1357
H. SarinKapoor et al.

acute rejection in kidney transplantation. Numerous include ophthalmological examination to rule out
studies have reported a deleterious effect, with higher CMV retinitis, and cervical and anal smears for
rates of acute rejection and allograft loss (60, 61). By human papillomavirus-associated cervical and anal
contrast, an equal number of studies have reported intraepithelial neoplasia.
outcomes that are comparable with those seen in
recipients who are not infected with HCV (62, 63).
The differences may possibly be the result of the Duration of ESRD and renal transplant outcome
influence of confounding factors, other than HCV Increased duration of pre-transplant ESRD is associ-
infection, on renal allograft outcomes. ated with poor graft and recipient outcome (67, 68).
Goldfarb-Rumyantzev et al. (69) found that a longer
duration of ESRD was associated with a worsening
Human immunodeficiency virus (HIV) infection graft outcome; however, the association only became
The number of HIV-positive patients having ESRD significant after 6 months of dialysis therapy, and,
has increased over the last couple of years. The after 3 years, no significant change in risk was
various factors contributing to this increase are evident. In the same study, a longer duration of
HIV-associated nephropathy, increased duration of ESRD was reported to be associated with a worsening
survival of HIV-positive patients and increased sur- recipient survival when calculated from the time of
vival of HIV-positive patients on dialysis. transplant, becoming significant after 1 year of ESRD
The presence of HIV type 1 has traditionally been duration.
considered a contraindication for transplantation Kidney transplantation is associated with a sig-
because of concerns that immunosuppression could nificant improvement in azotaemia. By contrast,
increase viral load, and a stable patient could decom- prolonged exposure to uraemic toxins has been
pensate. However, the introduction of highly active demonstrated to affect myocardial contractility.
antiretroviral therapy (HAART) has markedly Although the exact nature of such toxins has yet to
improved the survival of HIV-infected patients be ascertained, various studies have demonstrated
because of excellent control of the viral load and numerous potentially negative inotropic and chro-
fewer infections (64). Furthermore, because of the notropic factors in the uraemic plasma (70, 71).
extremely low HIV viral load (<50 copies/ml), fresh Amann et al. (72) have reported that a prolonged
T cells can be generated prior to transplantation (65). exposure to these uraemic toxins can result in my-
Bhagani et al. (66) have compiled guidelines for ocyte fibrosis and death. A longer duration of dialysis
renal transplantation in HIV-infected patients. A life therapy results in a prolonged exposure of myocytes
expectancy of at least 5 years is considered to be to these uraemic toxins, and hence may decrease the
appropriate before planning transplantation. Fur- likelihood of improvement in LVEF in the post-
thermore, the patients should have been on a stable transplant period. Similarly, Eknoyan et al. (73) have
HAART regimen for at least 6 months (CD4 count demonstrated that a longer duration of dialysis and
>200 cells/ml; HIV viral load <50 copies/ml). There decreased clearance of middle molecules (a compon-
should be no current acquired immunodeficiency ent of the uraemic toxin) are associated with an
syndrome (AIDS)-defining illness. Infections with increased risk of death from cardiac causes. Further-
resistant fungi and bacteria and untreated active more, increased atherogenesis during chronic renal
chronic infections with cytomegalovirus (CMV) and failure and dialysis treatment may cause deteriora-
Mycobacterium are considered as contraindications to tion in the cardiovascular status of all potential
transplantation. Advanced cardiopulmonary disease, transplant recipients, and of diabetic patients in
a history of neoplasms, except adequately treated particular (74).
solid tumours with a disease-free period of more than
5 years, pregnancy and human T-cell lymphotropic The centre effect
virus type-1 positivity are also considered as contra- Various studies have shown that centres performing
indications to transplantation. lower numbers of transplants over a designated
Before transplant, all patients should be vaccinated period of time show lower graft and patient survival
with pneumococcal, meningococcal and Haemophilus rates. The centre effect in renal transplantation has
influenzae B vaccines. Patients should also be vacci- been defined as the variation in centre-specific renal
nated with varicella, hepatitis A and B vaccines if allograft outcomes beyond that which can be ex-
they do not possess antibodies to these infections. plained by random variation and adjustments for
Furthermore, routine pre-transplant assessment should factors known to impact on these outcomes (75, 76).

1358
 Anaesthesia for renal transplant surgery

Although some studies have shown that the centre Neuromuscular blocking agents
effect is most significant only within the first year Succinylcholine is frequently used in general anaes-
after transplantation (77), others have reported the thesia to facilitate tracheal intubation because of its
persistence of the centre effect at 1 year post-trans- rapid onset and brief duration of action. However, it
plantation and beyond (75, 76, 78). The centre effect may increase serum potassium concentration, which
has been reported to be lower in living donor trans- can result in cardiac arrhythmias and even cardiac
plants and negligible in human leucocyte antigen arrest (85). Patients with renal failure may have
(HLA)-identical transplants. The degree of HLA associated uraemic polyneuropathy, and repeated
matching has been reported to account for some of doses of succinylcholine can trigger hyperkalaemia
the variation seen between centres (79, 80). Physician
in such patients (86). Therefore, succinylcholine
and surgeon experience and careful and well-
should be used cautiously in patients with end-stage
organized clinical management have been found to
renal failure. Its use is not recommended in patients
be important factors in determining a centre’s success
with end-stage renal failure who have concomitant
in renal transplantation (77, 81).
hyperkalaemia.
Long-acting non-depolarizing neuromuscular
Anaesthetic management blocking agents are largely eliminated by renal
Anaesthetic drugs excretion. Hunter (87) found that, in patients with
The most important risk factor for post-operative end-stage renal failure, the effects of long-acting non-
renal failure is poor pre-operative renal function (82). depolarizing neuromuscular blocking agents were
As subjects with ESRD have impaired renal function, significantly prolonged, with a high rate of residual
it is important to avoid potentially nephrotoxic blockade at the end of surgery and a notable cumu-
substances when anaesthetizing these high-risk pa- lative effect with repetitive administration. Therefore,
tients (Table 2). Hepatic drug metabolism is also in patients with ESRD, muscle relaxants whose
influenced by renal failure, either through induction excretion is not primarily dependent on renal func-
or inhibition of hepatic enzymes or by alteration of tion should be used for general anaesthesia.
protein binding and protein denaturation. Changes The onset time of various muscle relaxants in
in body fluid distribution and circulatory volume patients with end-stage renal failure has been re-
also affect drug disposition. This causes changes in ported by different studies to be similar or prolonged
hepatic blood flow, which alter the production and when compared with controls (88, 89). A slower
elimination of metabolites (83, 84). onset time may be seen in patients with water
intoxication as a result of the increased volume of
distribution, whereas a more rapid onset time may be
observed in patients with dehydration caused by
Table 2
dialysis therapy as a result of a smaller volume of
Safety profile of drugs for anaesthesia. distribution.
The duration of action of muscle relaxants is
Neuromuscular Inhalational
blockers agents dependent on the excretory route of the agents.
Succinylcholine þ (K <5.5 mEq/l) Isoflurane þ Excretion of atracurium is via Hofmann elimination
Atracurium þ Sevoflurane þ
Cisatracurium þ Desflurane þ
and hydrolysis by esterase, and hence renal failure
Mivacurium þ/– Enflurane – does not alter its elimination. The duration of action
Vecuronium þ/– Induction agents and recovery time of initial and incremental doses of
Rocuronium þ/– Propofol þ
Pancuronium þ/– Pentothal þ atracurium in patients with end-stage renal failure
Intra-operative Post-operative are similar to those in controls (90, 91). However, the
opioids analgesics metabolite of atracurium, laudanosine, is partially
Fentanyl þ Morphine þ
Alfentanil þ Fentanyl þ eliminated through the kidney, resulting in a pro-
Sufentanil þ Paracetamol – longed elimination half-life of this metabolite in
Remifentanil þ NSAIDs –
Morphine – COX-2 inhibitors –
patients with renal failure (92). The concentration of
Meperidine – laudanosine required to produce convulsions in dogs
is more than 20 mg/ml; the concentrations found
COX-2, cyclo-oxygenase-2; NSAIDs, non-steroidal anti-inflamma-
tory drugs. after the clinical use of atracurium are between 2 and
þ, can be used; –, cannot be used; þ/– could be used. 14 mg/ml.

1359
H. SarinKapoor et al.

Cisatracurium is approximately four times as that neither the duration of action nor the recovery
potent as atracurium. Its principal mode of break- after an initial dose, or even three subsequent incre-
down is also Hofmann elimination, and laudanosine mental doses, was prolonged in patients with chronic
is one of its breakdown products. There is no direct renal failure who were given rocuronium. Neuro-
metabolism by esterases. As it is more potent, smaller muscular function can recover spontaneously with-
amounts of cisatracurium are required, and therefore out an antagonist after the use of rocuronium in
less laudanosine is formed. Even in patients with patients with renal failure (97, 101).
renal failure or those receiving prolonged infusions,
the highest plasma levels of laudanosine are well Inhalational agents
below the toxic threshold, about one-fifth of the level All potent inhalational agents cause a decrease in the
found with atracurium. The duration of action is, renal blood flow and glomerular filtration rate in
however, slightly prolonged in renal disease, sug- proportion to the dose. The association between the
gesting that it may normally undergo slightly more metabolic production of inorganic fluoride ions and
renal excretion than atracurium. high-output renal failure has been known for years.
Mivacurium is eliminated by hydrolysis by plasma Serum fluoride levels of 50 mmol/l are needed to
cholinesterase at a hydrolytic rate of 70–80% of that produce nephrotoxicity, but significant decreases in
of succinylcholine. The proportion of elimination of the maximum urine-concentrating ability can occur
mivacurium by the kidney is minimal. Cook et al. when serum fluoride levels are on the order of
(93) found no significant difference in the pharma- 20 mmol/l.
cokinetics or pharmacodynamics of mivacurium Enflurane is metabolized to a small extent, and
between patients with renal failure and controls, occasional cases of renal failure have been reported
but others (94, 95) found that the no-response period following its use. With enflurane, maximal serum
of mivacurium was significantly prolonged in pa- fluoride levels are on the order of 25 mmol/l. It
tients with end-stage renal failure, probably because should not be used in patients with renal impair-
of the decreased plasma cholinesterase activity in ment. Although fluoride is also the major metabolite
patients on long-term dialysis therapy. of isoflurane, the extent of its metabolism is so small
The elimination of vecuronium and rocuronium is (0.2%) that the amount of fluoride produced is
relatively independent of kidney function. Both unlikely to cause renal damage.
drugs are mainly metabolized by the liver, but their Sevoflurane is degraded to fluoromethyl-2,2-
metabolites and partial prototypes are excreted by difluoro-1-trifluoromethyl vinyl ether (compound-A)
the kidney. The duration of action of vecuronium and by carbon dioxide absorbers of standard anaesthesia
rocuronium in patients with renal failure has been re-breathing systems. A decrease in fresh gas flow is
reported to be prolonged (96–98), and a cumulative known to increase compound-A production within
effect has been noted with repetitive administration the circuit, thereby increasing compound-A levels
(99, 100). This is caused by the accumulation of an (102). Compound-A has been shown to be nephro-
active metabolite that is produced in the liver by the toxic in rats (103, 104). However, studies performed to
removal of the acetyl group. In a case report, a patient assess the safety of sevoflurane in patients with pre-
with chronic renal insufficiency had complete neuro- existing renal disease have reported that renal dys-
muscular blockade for more than 3 h after an initial function is not enhanced by compound-A (105, 106).
dose of 0.09 mg/kg vecuronium (100). Sevoflurane is metabolized by hepatic cytochrome
Ma and Zhuang (94) reported that, in patients P450 to hexafluoroisopropanol and inorganic fluo-
undergoing dialysis 1 day before transplantation, ride. Peak serum inorganic fluoride levels greater
no difference in the no-response period or the time than 30 mmol have been reported after sevoflurane
to 25% recovery after an initial dose of vecuronium or anaesthesia (107, 108). Although such high levels of
rocuronium twice the ED95 (dose required to pro- inorganic fluoride are known to produce transient
duce 95% suppression of twitch responce to nerve renal damage after enflurane anaesthesia, a similar
stimulation) value was noted when compared with deterioration has not been found after sevoflurane
controls. However, after repetitive incremental doses, anaesthesia, even in patients with pre-existing renal
the no-response period and the time to 25% recovery disease (105–108). Conzen et al. (109) did not find any
were prolonged. Renal failure leads to decreased correlation between serum inorganic fluoride and
plasma clearance and a prolonged elimination half- compound-A levels and the markers of renal function
life of vecuronium and rocuronium, as discussed after low-flow sevoflurane anaesthesia in patients
earlier. However, Khuenl-Brady et al. (101) found with co-existing renal disease.

1360
 Anaesthesia for renal transplant surgery

Bito et al. (110) have demonstrated that low-flow Thiopental is another inducing agent that is almost
sevoflurane anaesthesia does not cause renal injury entirely metabolized in the liver. Its breakdown
when compared with high-flow sevoflurane or low- products are excreted by the kidneys and the alimen-
flow isoflurane anaesthesia. In their study, blood urea tary tract. Traces are excreted unchanged in the urine.
nitrogen and creatinine concentrations did not No permanent effects of this agent on kidney func-
increase, and creatinine clearance did not decrease, tion have been recorded.
when compared with values before anaesthesia, The use of glycopyrronium is contraindicated in
although there was an insignificant increase in the uraemic patients. Kirvela et al. (120) reported severe
urinary excretion of the kidney-specific enzymes impairment of glycopyrronium elimination in uraemic
N-acetyl-b-D-glucosaminidase and alanine amino- patients undergoing renal transplantation. In their
peptidase. Similarly, Conzen et al. (109) reported that study, the 24-h renal excretion of glycopyrronium was
low-flow sevoflurane anaesthesia was safe and did 7% (0–25%) in uraemic patients and 65% (30–99%) in
not alter kidney function in patients with pre-existing ASA I control patients undergoing general surgery.
renal disease. Hence, low-flow sevoflurane anaesthe-
sia can be safely used in renal transplant recipients. Opioids
Furthermore, sevoflurane has been shown to have The effect of morphine is prolonged in patients with
an anti-inflammatory effect that protects against chronic renal failure as a result of the accumulation of
ischaemia–reperfusion injury (111). Lee et al. (112) its active metabolite morphine-6-glucuronide (121).
demonstrated anti-inflammatory and anti-necrotic Similarly, the administration of high or repeated
effects of sevoflurane in cultured kidney proximal doses of meperidine in these patients is known to
tubule cells. produce seizures as a result of the accumulation of
Similarly, desflurane is not contraindicated in pa- normeperidine (122). The elimination of oxycodone is
tients with renal dysfunction (113, 114). Litz et al. also impaired in uraemic patients undergoing renal
(114) found no deterioration in renal function in transplant. Kirvela et al. (123) reported a prolonged
patients with pre-existing renal disease who were mean elimination half-life of oxycodone in patients
given 2.2  1.8 minimum alveolar concentration with end-stage renal failure. They found higher
(MAC) hours of desflurane. In another study, Obal concentrations of its metabolite noroxycodone in
et al. (115) examined the effects of post-conditioning plasma. Furthermore, uraemic patients were found
by desflurane on renal function and morphology in to excrete significantly smaller quantities of oxy-
rats. Post-conditioning involves the administration of codone and its metabolites, noroxycodone and oxy-
anaesthetics during early reperfusion, and has been morphone. However, the pharmacokinetics of
found to have a protective effect on several organs. fentanyl, alfentanil and sufentanil are not altered in
They administered 1 MAC of desflurane during post- chronic renal failure, because the metabolites are
conditioning and found that it protected renal func- inactive and are unlikely to contribute to the opioid
tion and tissue. effect even if they accumulate.
Remifentanil is metabolized in the peripheral tis-
Induction agents and other drugs sues by an esterase enzyme. Its principal metabolite,
Propofol is extensively used as an intravenous agent GR90291, possesses about 1/4600th the potency of
for the induction and maintenance of general anaes- remifentanil, and is eliminated primarily by the
thesia. Propofol is mainly metabolized in the liver kidneys (124). Hoke et al. (125) studied the pharma-
and its metabolites do not possess pharmacological cokinetics and pharmacodynamics of remifentanil in
activity (116). Studies have shown that propofol can patients with chronic renal failure. In their study,
be safely used for the induction and maintenance of blood pressure elevations were noted before and after
anaesthesia in patients with renal failure (117, 118). the termination of remifentanil infusion in patients
Uraemia requiring HD has not been shown to affect who had dialysis fistulae or grafts. Dialysis fistulae
significantly the pharmacokinetics of propofol. Infu- are known to produce hyperdynamic circulation.
sion dose requirements have been found to be similar They also found that the adverse effects were mild
in ESRD patients and patients with normal renal and were the result of typical micro-opioid effects,
function (118). Shorter emergence times have been including dyspnoea, somnolence, nausea, vomiting
noted in ESRD patients when compared with pa- and chills. However, the maximum concentration and
tients with normal renal function (118, 119). No plasma half-life of GR90291 were markedly increased.
adverse effects have been reported following inter- In another study, Bower and Sear (126) found no
mittent injections of propofol. correlation between alfentanil binding and plasma

1361
H. SarinKapoor et al.

albumin, total plasma proteins, plasma urea or (135). Furthermore, they do not have adverse effects
plasma creatinine clearance in patients with chronic on the reticuloendothelial system or renal function,
renal failure. However, in these patients, total drug nor do they have bleeding complications. In one
clearance and the volume of distribution were sig- study, immediate renal function was found to be
nificantly increased. impaired in renal transplant recipients whose donors
were infused with HES (136). However, another
Intravenous fluid therapy retrospective study concluded that HES given at
Normal saline is routinely used for intra-operative a maximum dosage of 15 ml/kg/day to the donor
intravenous fluid therapy in renal transplant recip- had no detrimental effect on renal function in the
ients. Electrolyte imbalance, especially hyperkalae- recipient (137). Sufficient amounts of crystalloids
mia, is frequently seen in patients with renal failure. should, however, be infused together with HES.
Potassium-containing fluids, such as lactated Ring-
er’s solution, are thus avoided in such patients
Central venous pressure (CVP)
in order to minimize the risk of development of
In the immediate post-transplant period, CVP invari-
hyperkalaemia.
ably declines despite positive fluid balance and
Metabolic acidosis has been reported to develop
vigorous fluid resuscitation. Various explanations
following the administration of large volumes of
have been offered for this phenomenon: hypovolae-
normal saline (127, 128). Various possible explana-
mia in chronic dialysis patients; vasodilatation from
tions for this metabolic derangement have been
anaesthetic drugs; altered vascular permeability or
suggested. The rapid administration of fluids con-
response to factors liberated from the perfused
taining near-physiological concentrations of sodium
kidney. Reperfusion is known to produce oxygen-
and anions (other than bicarbonate) dilutes the
derived free radicals (138). These produce tissue
extracellular bicarbonate, resulting in dilutional aci-
damage, resulting in increased vascular permeability
dosis (129). Furthermore, normal saline could cause
and alterations in vascular tone. The redistribution of
metabolic acidosis as a result of its chloride content,
fluids in different compartments as a result of pre-
according to Kellum (130). He suggested that,
existing vascular permeability may lead to a decrease
although the proportion of sodium and chloride is
in CVP. The excretion of NO synthase inhibitor by the
similar in normal saline, it is not so in the plasma.
transplanted kidneys, leading to increased NO levels,
Hence, the administration of large volumes of normal
has also been implicated in the decrease in CVP (139).
saline has a greater effect on total body chloride than
However, concomitant vasodilatation as a result of
on total body sodium, leading to the development of
NO has not been noted in recipients.
metabolic acidosis (130). Hyperchloraemic metabolic
Acute tubular necrosis has been reported to be
acidosis further leads to an extracellular potassium
lower in patients who are profoundly hydrated (140,
shift, producing hyperkalaemia (131).
141). Hyperhydration is known to dilate the atria,
Although normal saline may have a potential det-
leading to the release of atrial natriuretic peptide
rimental effect on renal function, as described, it is still
(142). It also leads to increased renal perfusion.
commonly used in patients undergoing transplanta-
Ferris et al. (143) have shown a lack of correlation
tion. O’Malley et al. (132) have shown that normal
between the decrease in CVP and fluid balance. In their
saline does not adversely affect renal function.
study, although the fluid balance of recipients corre-
Colloids should only be considered in recipients
lated strongly with immediate post-operative function,
with severe intravascular volume deficits who
no correlation was detected between the absolute value
require high-volume restoration (133). Artificial col-
of CVP intra-operatively or the post-operative decrease
loids, such as gelatin and dextran, are known to
in CVP and the incidence of acute tubular necrosis.
adversely affect the kidney (134). Albumin is a nor-
Furthermore, they found that the maximum decrease
mal endogenous colloid with a wide safety margin,
in CVP occurred between the operating theatre and
and hence should be used. Furthermore, albumin
intensive care unit. This could be the result of the
also protects the kidney by scavenging reactive
prompt redistribution of fluids, or the fact that patients
oxygen species and inhibiting apoptosis (134).
with ESRD have a different post-anaesthetic response.
Hydroxyethyl starch (HES) solutions are being
used instead of albumin. Medium molecular weight
HES solutions have been found to have the lowest Anaesthesia procedure
in vivo molecular weight above the threshold for Adequate monitoring is a prerequisite for renal
renal elimination and are also easily degradable transplantation. A central venous line is essential

1362
 Anaesthesia for renal transplant surgery

for the assessment of volume status. Intra-arterial References

blood pressure monitoring is useful for patients with
1. Hariharan S, Johnson CP, Bresnahan BA, Taranto SE,
significant cardiovascular disease. McIntosh MJ, Stablein D. Improved graft survival after renal
Both epidural anaesthesia and general anaesthesia transplantation in the United States, 1988 to 1996. N Engl J
are used for providing anaesthesia during renal Med 2000; 342: 605–12.
transplantation. Haemodynamics and renal function 2. US Renal Data System. 1999 Annual Data Report. Am J
Kidney Dis 1999; 34: S1.
have not been reported to differ significantly in 3. Port FK, Wolfe RA, Mauger EA, Berling DP, Jiang K.
the two techniques (144). Dahaba et al. (145) found Comparison of survival probabilities for dialysis patients
no difference in haemodynamic responses to peri- vs cadaveric renal transplant recipients. J Am Med Assoc
operative events and recovery parameters when using 1993; 270: 1339–43.
4. Wolfe RA, Ashby VB, Milford EL et al. Comparison of
total intravenous anaesthesia with remifentanil, pro- mortality in all patients on dialysis, patients on dialysis
pofol and cisatracurium in patients with end-stage awaiting transplantation, and recipients of a first cadaveric
renal failure and those with normal renal function. transplant. N Engl J Med 1999; 341: 1725–30.
Kirvela et al. (146) found no advantage of using total 5. Middleton RJ, Parfrey PS, Foley RN. Left ventricular hyper-
trophy in the renal patient. J Am Soc Nephrol 2001; 12:
intravenous anaesthesia with propofol and alfentanil 1079–84.
over balanced anaesthesia with isoflurane–nitrous 6. Malergue MC, Urena P, Prieur P. Incidence and development
oxide–fentanyl. of aortic stenosis in chronic hemodialysis. An ultrasono-
graphic and biologic study of 112 patients. Arch Mal Coeur
Vaiss 1997; 90: 1595–601.
Post-operative pain relief 7. Plotkin JS, Ridge L, Kuo PC, Lim J, Njoku MJ, Johnson LB.
Post-operative pain relief is essential after renal Extending the boundaries of acceptable organ donors:
transplantation, as inadequately controlled pain a means of expanding the donor pool for liver transplanta-
tion. Transplant Proc 1997; 29: 3288.
can lead to agitation, tachycardia, hypertension and
8. Vromen MA, Leunissen KM, Persijn GG, Kootstra G. Short-
an increased risk of pulmonary complications. Mor- and long-term results with adult non-heart-beating donor
phine or fentanyl delivered by patient-controlled kidneys. Transplant Proc 1988; 20: 743–5.
analgesia is known to provide sufficient pain relief. 9. Shenoy S, Lowell JA, Flye MW, Brennan DC, Ceriotti C,
Howard TK. Use of extended donors in high-risk renal
Post-operative epidural analgesia has been found to
transplant recipients: a 2-year single-center experience.
be more effective than intravenous tramadol (144). Transplant Proc 1996; 28: 95.
However, the use of paracetamol and non-steroidal 10. Ojo AO, Hanson JA, MeierKriesche HV et al. Survival in
anti-inflammatory drugs (NSAIDs) should be recipients of marginal cadaveric donor kidneys compared
with other recipients and wait-listed transplant candidates.
avoided. Martin et al. (147) demonstrated an altered
J Am Soc Nephrol 2001; 12: 589–97.
disposition of paracetamol in renal transplant recipi- 11. Rabbat CG, Thorpe KE, Russel JD, Churchill DN. Compar-
ents. The clearance of paracetamol from plasma and ison of mortality for dialysis patients and cadaveric first
the renal elimination of its glucuronide and sulphate renal transplant recipients in Ontario, Canada. J Am Soc
Nephrol 2000; 11: 917–22.
conjugates were prolonged. Furthermore, the elimi-
12. Joyce AT, Iacoviello JM, Nag S et al. End-stage renal
nation of its conjugates was found to correlate disease-associated managed care costs among patients with
negatively with serum creatinine levels. The use of and without diabetes. Diabetes Care 2004; 27: 2829–35.
high-dose NSAIDs in patients with chronic kidney 13. Kontodimopoulos N, Niakas D. Overcoming inherent prob-
lems of preference-based techniques for measuring health
disease has been shown to increase the risk of
benefits: an empirical study in the context of kidney trans-
rapid progression of the disease in the elderly age plantation. BMC Health Serv Res 2006; 6: 3.
group (148). Cyclo-oxygenase-2 enzyme inhibitors 14. US Renal Data System. 1998 Annual Data Report. Bethesda,
have also been reported to be nephrotoxic in trans- MD: National Institutes of Health, National Institute of
Diabetes, Digestive and Kidney Diseases.
plant recipients and in patients with impaired renal
15. Foley RN, Parfrey PS, Sarnak MJ. The clinical epidemiology
function (149). of cardiovascular disease in chronic renal disease. Am J
Kidney Dis 1998; 32: 112–9.
16. Levey AS, Beto JA, Coronado BE et al. Controlling the
Conclusions epidemic of cardiovascular disease in chronic renal disease.
What do we know? What do we need to learn? Where do we
Kidney transplantation is the preferred treatment go from here? Am J Kidney Dis 1998; 32: 853–906.
modality for patients with ESRD. A successful out- 17. Foley RN, Parfrey PS, Harnett JD, Kent GM, Murray DC,
come after transplant is influenced by appropriate Barre PE. Impact of hypertension on cardiomyopathy, mor-
pre-operative assessment and drug treatment, close bidity and mortality in end-stage renal disease. Kidney Int
1996; 49: 1379–85.
intra-operative monitoring, optimization of intravas- 18. Charra B, Calemard E, Laurent G. Importance of treatment
cular fluid volume and the appropriate use of anaes- time and blood pressure control in achieving long-term
thetic agents. survival on dialysis. Am J Nephrol 1996; 16: 35–44.

1363
H. SarinKapoor et al.

19. Harnett JD, Kent GM, Foley RN, Parfrey PS. Cardiac 38. Brunkhorst R, Nonnast-Daniel B, Koch KM, Frei U. Hyper-
function and hematocrit level. Am J Kidney Dis 1995; 25: tension as a possible complication of recombinant human
S3–7. erythropoietin therapy. Contrib Nephrol 1991; 88: 118–25.
20. Amann K, Gross ML, London GM, Ritz E. Hyperphospha- 39. Eckardt KU. Cardiovascular consequences of renal anaemia
taemia – a silent killer of patients with renal failure? Nephrol and erythropoietin therapy. Nephrol Dial Transplant 1999; 14:
Dial Transplant 1999; 14: 2085–7. 1317–23.
21. Ramos EL, Kasiske BL, Alexander SR et al. The evaluation 40. London GM, De Vernejoul MC, Fabiani F et al. Secondary
of candidates for renal transplantation. The current prac- hyperparathyroidism and cardiac hypertrophy in hemodi-
tice of US transplant centers. Transplantation 1994; 57: alysis patients. Kidney Int 1987; 32: 900–7.
490–7. 41. London GM, Pannier B, Marchais SJ, Guérin AP. Calcifica-
22. Philipson J, Carpenter B, Itzkoff J et al. Evaluation of tion of the aortic valve in the dialysed patient. J Am Soc
cardiovascular risk for renal transplantation in diabetic Nephrol 2000; 11: 778–83.
patients. Am J Med 1986; 81: 630–4. 42. Goodman WG, Goldin J, Kuizon BD et al. Coronary-artery
23. Dahan M, Viron BM, Faraggi M et al. Diagnostic imaging calcification in young adults with end-stage renal disease
and prognostic value of combined dipyridamole-exercise who are undergoing dialysis. N Engl J Med 2000; 342:
thallium imaging in haemodialysis patients. Kidney Int 1998; 1478–83.
54: 255–62. 43. Urena P, Malergue MC, Goldfarb B, Prieur P, Guédon-
24. Rutsky EA, Rostand SG. The management of coronary artery Rapoud C, Pétrover M. Evolutive aortic stenosis in haemo-
disease in patients with end stage renal disease. In: Parfrey dialysis patients: analysis of risk factors. Nephrologie 1999; 20:
PS, Harnett JD (eds). Cardiac Dysfunction in Chronic 217–25.
Uremia. Boston/Basle: Kluwer Academic Publishers, 1992: 44. Cressman MD, Heyka RJ, Paganini EP. Lipoprotein (a) is an
233–5. independent risk factor for cardiovascular disease in hemo-
25. Reis G, Markovitz P, Leichtman AB et al. Usefulness of dialysis patients. Circulation 1992; 86: 475–82.
dobutamine stress echocardiography in detecting coronary 45. Ross R. Atherosclerosis – an inflammatory disease. N Engl J
artery disease in end stage renal disease. Am J Cardiol 1995; Med 1999; 340: 115–26.
75: 707–10. 46. Arici M, Walls J. End-stage renal disease, atherosclerosis and
26. Wali RK, Wang GS, Gottlieb SS et al. Effect of kidney cardiovascular mortality: is C-reactive protein the missing
transplantation on left ventricular systolic dysfunction and link? Kidney Int 2001; 59: 407–14.
congestive heart failure in patients with end-stage renal 47. Lagrand WK, Visser CA, Hermens WT et al. C-reactive
disease. J Am Coll Cardiol 2005; 45: 1051–60. protein as a cardiovascular risk factor: more than an
27. London G, Parfrey PS. Cardiac disease in chronic uremia: epiphenomenon? Circulation 1999; 100: 96–102.
pathogenesis. Adv Renal Replace Ther 1997; 4: 194–211. 48. Oh J, Wunsch R, Turzer M et al. Advanced coronary and
28. Parfrey PS, Foley RN, Harnett JD, Kent GM, Murray DC, carotid arteriopathy in young adults with childhood-onset
Barre PE. Outcome and risk factors for left ventricular chronic renal failure. Circulation 2002; 106: 100–5.
disorders in chronic uraemia. Nephrol Dial Transplant 1996; 49. Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-reactive
11: 1277–85. protein predicts all-cause and cardiovascular mortality in
29. Opelz G, Wujciak T, Ritz G. Association of chronic kidney hemodialysis patients. Am J Kidney Dis 2000; 35: 469–76.
graft failure with recipient blood pressure. Collaborative 50. Kimmel PL, Phillips TM, Simmens SJ et al. Immunologic
Transplant Study. Kidney Int 1998; 53: 217–22. function and survival in haemodialysis patients. Kidney Int
30. Locatelli F, Bommer J, London GM et al. Cardiovascular 1998; 54: 236–44.
disease determinants in chronic renal failure. Clinical 51. Ducloux D, Motte G, Challier B, Gibey R, Chalopin JM.
approach and treatment. Nephrol Dial Transplant 2001; 16: Serum total homocysteine and cardiovascular disease in
459–68. chronic, stable renal transplant recipients: a prospective
31. Heart Outcomes Prevention Evaluation (HOPE) Study In- study. J Am Soc Nephrol 2000; 11: 134–7.
vestigators. Effects of an angiotensin-converting enzyme 52. Moustapha A, Naso A, Nahlawi M et al. Prospective study
inhibitor, ramipril, on cardiovascular events in high-risk of hyperhomocysteinemia as an adverse cardiovascular
patients. N Engl J Med 2000; 342: 145–53. risk factor in end-stage renal disease. Circulation 1998; 97:
32. Norio K, Makisalo H, Isoniemi H, Groop Ph, Pere P, Lidgren 138–41.
L. Are diabetic patients in danger at renal transplantation? 53. Kielstein JT, Böger RH, Bode-Böger SM et al. Asymmetric
An invasive perioperative study. Eur J Anaesthesiol 2000; 17: dimethylarginine plasma concentrations differ in patients
729–36. with ESRD. relationship to treatment method and athero-
33. Marsh J, Andrews PA. Management of the diabetic patient sclerotic disease. J Am Soc Nephrol 1999; 10: 594–600.
approaching end-stage renal failure. Br J Diabetes Vasc Dis 54. Pouteil-Noble C, Maiza H, Dijoud F, MacGregor B. Glomer-
2002; 2: 121–6. ular disease associated with hepatitis C virus infection in
34. Mix TCH, Kazmi W, Khan S et al. Anemia: a continuing native kidneys. Nephrol Dial Transplant 2000; 15: 28–33.
problem following kidney transplantation. Am J Transplant 55. Stehman-Breen CO, Emerson S, Gretch D, Johnson RJ. Risk
2003; 4: 1426–33. of death among chronic dialysis patients infected with
35. Fellner SK, Lang RM, Neumann A, Korcarz C, Borow KM. hepatitis C virus. Am J Kidney Dis 1998; 32: 629–34.
Cardiovascular consequences of correction of anaemia of 56. Nakayama E, Akiba T, Marumo F, Sato C. Prognosis
renal failure with erythropoietin. Kidney Int 1993; 44: 1309–15. of anti-hepatitis C virus antibody-positive patients on
36. Mayer G, Thum J, Cada EM, Stumwoll HK, Graf H. Working regular hemodialysis therapy. J Am Soc Nephrol 2000; 11:
capacity is increased following recombinant human eryth- 1896–902.
ropoietin treatment. Kidney Int 1998; 34: 525–8. 57. Kiyosawa K, Sodeyama T, Tanaka E et al. Interrelation of
37. Marsh JT, Brown WS, Wolcott D et al. rHuEPO treatment blood transfusion, non-A, non-B hepatitis and hepatocellular
improves brain and cognitive function of anaemic dialysis carcinoma: analysis by detection of antibody to hepatitis
patients. Kidney Int 1991; 39: 155–63. C virus. Hepatology 1990; 12: 671–5.

1364
 Anaesthesia for renal transplant surgery

58. Takahashi M, Yamada G, Miyamoto R, Doi T, Endo H, Tsuji 79. Ogura K, Cecka JM. Center effects in renal transplantation.
T. Natural course of chronic hepatitis C. Am J Gastroenterol In: Terasaki, PI, ed. Clinical Transplants 1991. Los Angeles,
1993; 88: 240–3. CA: UCLA Tissue Typing Laboratory, 1991: 245–56.
59. Periera BJ, Wright TL, Schmid CH, Levey AS. The impact of 80. Cho YW, Cecka JM. Centre effect in the UNOS Renal
pretransplantation hepatitis C infection on the outcome of Transplant Registry. In: Terasaki, PI, Cecka, JM, eds. Clinical
renal transplantation. Transplantation 1995; 60: 799–805. Transplants 1992. Los Angeles, CA: UCLA Tissue Typing
60. Gonzalez-Roncero F, Gentil MA, Valdivia MA et al. Outcome Laboratory, 1992: 333–46.
of kidney transplant in chronic hepatitis C virus patients: 81. Evans RW, Manninen DL, Dong F. The center effect in kidney
effect of pretransplantation interferon-alpha2b monother- transplantation. Transplant Proc 1991; 23: 1315–7.
apy. Transplant Proc 2003; 35: 1745–7. 82. Novis BK, Roizen MF, Aronson S, Thisted RA. Association of
61. Meier-Kriesche HU, Ojo AO, Hanson JA, Kaplan B. Hepatitis preoperative risk factors with postoperative acute renal
C antibody status and outcomes in renal transplant recipi- failure. Anesth Analg 1994; 78: 143–9.
ents. Transplantation 2001; 72: 241–4. 83. Elston AC, Bayliss MK, Park GR. Effect of renal failure on
62. Rao KV, Ma J. Chronic viral hepatitis enhances the risk of drug metabolism by the liver. Br J Anaesth 1993; 71: 282–90.
infection but not acute rejection in renal transplant recipi- 84. Reidenberg MM. Biotransformation of drugs in renal failure.
ents. Transplantation 1996; 62: 1765–9. Am J Med 1977; 62: 482–5.
63. Breitenfeldt MK, Rasenack J, Berthold H et al. Impact of 85. Yentis SM. Suxamethonium and hyperkalaemia. Anaesth
hepatitis B and C on graft loss and mortality of patients after Intensive Care 1990; 18: 92–101.
kidney transplantation. Clin Transplant 2002; 16: 130–6. 86. Welton JD, Farman JV. Suxamethonium hyperkalaemia in
64. Ahuja TS, Borucki M. Highly active antiretroviral therapy uraemic neuropathy. Anaesthesia 1973; 28: 666–8.
improves survival of HIV-infected hemodialysis patients. 87. Hunter JM. Muscle relaxants in renal disease. Acta Anaes-
Am J Kidney Dis 2000; 36: 574–80. thesiol Scand 1994; 38: 2–5.
65. Ahuja TS, Zingman B. Long-term survival in an HIV- 88. Head-Rapson AG, Devlin JC, Parker CJ, Hunter JM. Phar-
infected renal transplant recipient. Am J Nephrol 1997; 17: macokinetics and pharmacodynamics of the three isomers of
480–2. mivacurium in health, in end-stage renal failure and in
66. Bhagani S, Sweny PI, Brook G. Guidelines for kidney trans- patients with impaired renal function. Br J Anaesth 1995;
plantation in patients with HIV disease. HIV Med 2006; 7: 75: 31–6.
133–9. 89. Hunter JM, Jones RS, Utting JE. Comparison of vecuronium
67. Bleyer AJ, Burkart JM, Russell GB, Adams PL. Dialysis and tubocurarine in normal patients and in patients with no
modality and delayed graft function after cadaveric renal renal function. Br J Anaesth 1984; 56: 941–51.
transplantation. J Am Soc Nephrol 1999; 10: 154–9. 90. Fahey MR, Rupp SM, Fisher DM et al. The pharmacokinetics
68. Cosio FG, Alamir A, Yim S et al. Patient survival after renal and pharmacodynamics of atracurium in patients with and
transplantation. I. The impact of dialysis pre-transplant. without renal failure. Anesthesiology 1984; 61: 699–702.
Kidney Int 1998; 53: 767–72. 91. Lepage JY, Malinge M, Cozian A, Pinaud M, Blanloeil Y,
69. Goldfarb-Rumyantzev A, Hurdle JF, Scandling J, Wang Z, Souron R. Vecuronium and atracurium in patients with
Baird B, Barenbaun L. Duration of end-stage renal disease end-stage renal failure. A comparative study. Br J Anaesth
and kidney transplant outcome. Nephrol Dial Transplant 2005; 1987; 59: 1004–10.
20: 167–75. 92. Parker CJ, Jones JE, Hunter JM. Disposition of infusions of
70. Vanholder R, Glorieux G, Lameire N. Uraemic toxins and atracurium and its metabolite, laudanosine, in patients in
cardiovascular disease. Nephrol Dial Transplant 2003; 18: renal and respiratory failure in an ITU. Br J Anaesth 1988; 61:
463–6. 531–40.
71. Zoccali C, Bode-Böger S, Mallamaci F et al. Plasma concen- 93. Cook DR, Freeman JA, Lai AA et al. Pharmacokinetics of
tration of asymmetrical dimethylarginine and mortality in mivacurium in normal patients and in those with hepatic or
patients with end-stage renal disease: a prospective study. renal failure. Br J Anaesth 1992; 69: 580–5.
Lancet 2001; 358: 2113–7. 94. Ma H, Zhuang X. Selection of neuromuscular blocking
72. Amann K, Breitbach M, Ritz E, Mall G. Myocyte/capillary agents in patients undergoing renal transplantation under
mismatch in the heart of uremic patients. J Am Soc Nephrol general anaesthesia. Chin Med J 2002; 11: 1692–6.
1998; 9: 1018–22. 95. Phillips BJ, Hunter JM. Use of mivacurium chloride by
73. Eknoyan G, Beck GJ, Cheung AK et al. Effect of dialysis dose constant infusion in the anephric patient. Br J Anaesth 1992;
and membrane flux in maintenance hemodialysis. N Engl J 68: 492–8.
Med 2002; 347: 2010–9. 96. Lynam DP, Cronnelly R, Castagnoli KP et al. The pharma-
74. Rostand SG. Coronary heart disease in chronic renal insuf- codynamics and pharmacokinetics of vecuronium in pa-
ficiency: some management considerations. J Am Soc Nephrol tients anesthetized with isoflurane with normal renal
2000; 11: 1948–56. function or with renal failure. Anesthesiology 1988; 69:
75. Opelz G, Mickey MR, Terasaki PI. Comparison of kidney 227–31.
transplant survival among transplant centers. Transplanta- 97. Cooper RA, Maddineni VR, Mirakhur RK, Wierda JM, Brady
tion 1975; 19: 226–9. M, Fitzpatrick KT. Time course of neuromuscular effects and
76. Gjertson DW, Terasaki IP, Cecka JM, Takemoto S. Reduction pharmacokinetics of rocuronium bromide (Org 9426) during
of the center effect by HLA matching. Transplant Proc 1993; isoflurane anaesthesia in patients with and without renal
25: 215–6. failure. Br J Anaesth 1993; 71: 222–6.
77. Taylor RM, Ting A, Briggs JD. Renal transplantation in the 98. Beauvoir C, Peray P, Daures JP, Peschaud JL, D’Athis F.
United Kingdom and Ireland – the centre effect. Lancet 1985; Pharmacodynamics of vecuronium in patients with and
1: 798–803. without renal failure: a meta-analysis. Can J Anaesth 1993;
78. Terasaki PI, Cecka JM. The center effect: is bigger better? In: 40: 696–702.
Cecka, JM, Terasaki, PI, eds. Clinical Transplants 1999. Los 99. Bevan DR, Donati F, Gyasi H, Williams A. Vecuronium in
Angeles, CA: UCLA Immunogenetics Center, 1991: 317–24. renal failure. Can Anaesth Soc J 1984; 31: 491–6.

1365
H. SarinKapoor et al.

100. Hackl W, Plainer B, Mauritz W. Protracted action of vecuro- haemodynamic changes during induction of anaesthesia in
nium in a patient with chronic renal insufficiency treated by uraemic patients. Br J Anaesth 1992; 68: 178–82.
dialysis. Anaesthetist 1988; 37: 598–600. 118. Ickx B, Cockshott ID, Barvais L et al. Propofol infusion for
101. Khuenl-Brady KS, Pomaroli A, Pühringer F, Mitter- induction and maintenance of anaesthesia in patients with
schiffthaler G, Koller J. The use of rocuronium (Org 9426) end-stage renal disease. Br J Anaesth 1998; 81: 854–60.
in patients with chronic renal failure. Anaesthesia 1993; 48: 119. Nathan N, Debord J, Narcisse F et al. Pharmacokinetics of
873–5. propofol and its conjugates after continuous infusion in
102. Bito H, Ikeda K. Effect of total flow rate on the concentration normal and in renal failure patients: a preliminary study.
of degradation products generated by reaction between Acta Anaesthesiol Belg 1993; 44: 77–85.
sevoflurane and soda lime. Br J Anaesth 1995; 74: 667–9. 120. Kirvela M, Ali Melkkila T, Kaila T, Iisalo E, Lindgren L.
103. Gonsowski CT, Laster MJ, Eger EI, Ferrell LD, Kerschmann Pharmacokinetics of glycopyrronium in uraemic patients.
RL. Toxicity of compound A in rats: effect of a 3-hour Br J Anaesth 1993; 71: 437–9.
administration. Anesthesiology 1994; 80: 556–65. 121. Osborne R, Joel S, Grebenik K, Trew D, Slevin M. The
104. Keller KA, Callan C, Prokocimer P et al. Inhalation toxicity pharmacokinetics of morphine and morphine glucuronides
study of a haloalkene degradant of sevoflurane, Compound in kidney failure. Clin Pharm Ther 1993; 54: 158–67.
A (PIFE), in Sprague-Dawley rats. Anesthesiology 1995; 83: 122. Szeto HH. Accumulation of normeperidine, an active metab-
1220–32. olite of meperidine, in patients with renal failure or cancer.
105. Conzen PF, Nuscheler M, Melotte A et al. Renal function and Ann Intern Med 1977; 86: 738–41.
serum fluoride concentrations in patients with stable renal 123. Kirvela M, Lindgren L, Seppala T, Olkkola KT. The phar-
insufficiency after anesthesia with sevoflurane or enflurane. macokinetics of oxycodone in uremic patients undergoing
Anesth Analg 1995; 81: 569–75. renal transplantation. J Clin Anesth 1996; 8: 13–8.
106. McGrath BJ, Hodgins LR, DeBree A, Frink EJJ, Nossaman 124. Hoke JF, Cunningham F, James MK, Muir KT, Hoffman WE.
BD, Bikhazi GB. A multicenter study evaluating the effects Comparative pharmacokinetics and pharmacodynamics of
of sevoflurane on renal function in patients with renal remifentanil, its principle metabolite (GR90291) and alfenta-
insufficiency. J Cardiovasc Pharmacol Ther 1998; 3: 229–34. nil in dogs. J Pharmacol Exp Ther 1997; 281: 226–32.
107. Frink EJJ, Ghantous H, Malan TP et al. Plasma inorganic 125. Hoke JF, Shlugman D, Dershwitz M et al. Pharmacokinetics
fluoride with sevoflurane anesthesia: correlation with indi- and pharmacodynamics of remifentanil in patients with
ces of hepatic and renal function. Anesth Analg 1992; 74: renal failure compared with healthy volunteers. Anesthesiol-
231–5. ogy 1997; 87: 533–41.
108. Frink EJJ, Malan TPJ, Isner RJ, Brown EA, Morgan SE, Brown 126. Bower S, Sear JW. Disposition of alfentanil in patients receiv-
BRJ. Renal concentrating function with prolonged sevoflur- ing a renal transplant. J Pharm Pharmacol 1989; 41: 654–7.
ane or enflurane anesthesia in volunteers. Anesthesiology 127. Scheingraber S, Rehm M, Sehmisch C, Finsterer U. Rapid
1994; 80: 1019–25. saline infusion produces hyperchloremic acidosis in patients
109. Conzen PF, Kharasch ED, Czerner SF et al. Low-flow undergoing gynaecologic surgery. Anesthesiology 1999; 90:
sevoflurane compared with low-flow isoflurane anesthesia 1265–70.
in patients with stable renal insufficiency. Anesthesiology 128. Williams EL, Hildebrand KL, McCormick SA, Bedel MJ. The
2002; 97: 578–84. effect of intravenous lactated Ringer’s solution versus 0.9%
110. Bito H, Ikeuchi Y, Ikeda K. Effects of low-flow sevoflurane sodium chloride solution on serum osmolality in human
anesthesia on renal function: comparison with high-flow volunteers. Anesth Analg 1999; 88: 999–1003.
sevoflurane anesthesia and low-flow isoflurane anesthesia. 129. Prough DS, White RT. Acidosis associated with perioper-
Anesthesiology 1997; 86: 1231–7. ative saline administration: dilution or delusion? Anesthesi-
111. Loop T, Scheiermann P, Doviakue D et al. Sevoflurane ology 2000; 93: 1167–9.
inhibits phorbol-myristate-acetate-induced activator pro- 130. Kellum JA. Determinants of blood pH in health and disease.
tein-1 activation in human T lymphocytes in vitro: potential Crit Care 2000; 4: 6–14.
role of the p38-stress kinase pathway. Anesthesiology 2004; 131. Halperin ML, Kamel KS. Potassium. Lancet 1998; 352:
101: 710–21. 135–40.
112. Lee HT, Ota-Setlik A, Fu Y, Nasr SH, Emala CW. Differential 132. O’Malley CM, Frumento RJ, Hardy MA et al. A randomized
protective effects of volatile anaesthetics against renal is- double-blind comparison of lactated Ringer’s solution and
chaemia-reperfusion injury in vivo. Anesthesiology 2004; 101: 0.9% NaCl during renal transplantation. Anesth Analg 2005;
1313–24. 100: 1518–24.
113. Zaleski L, Abello D, Gold MI. Desflurane versus isoflurane 133. Schnuelle P, Johannes van der Woude F. Perioperative fluid
in patients with chronic hepatic and renal disease. Anesth management in renal transplantation: a narrative review of
Analg 1993; 76: 353–6. the literature. Transpl Int 2006; 19: 947–59.
114. Litz RJ, Hübler M, Lorenz W, Meier VK, Albrecht D, Michael 134. Davidson IJ. Renal impact of fluid management with colloids:
MD. Renal responses to desflurane and isoflurane in patients a comparative review. Eur J Anesthesiol 2006; 23: 721–38.
with renal insufficiency. Anesthesiology 2002; 97: 1133–6. 135. Treib J, Baron JF, Grauer MT, Strauss RG. An international
115. Obal D, Rascher K, Favoccia C. Post-conditioning by a short review of hydroxyethyl starches. Intensive Care Med 1999; 25:
administration of desflurane reduced renal reperfusion 258–68.
injury after different ischaemia times in rats. Br J Anaesth 136. Cittanova ML, Leblanc I, Legendre C, Mouquet C, Riou B,
2006; 97: 783–91. Coriat P. Effect of hydroxyethylstarch in brain-dead kidney
116. Simons PJ, Cockshott ID, Glen JB, Gordon EA, Knott S, donors on renal function in kidney-transplant recipients.
Ruane RJ. Disposition and pharmacology of propofol glu- Lancet 1996; 348: 1620–2.
curonide administered intravenously to animals. Xenobiotica 137. Deman A, Peeters P, Sennesael J. Hydroxyethyl starch does
1992; 22: 1267–73. not impair immediate renal function in kidney transplant
117. Kirvela M, Olkkola KT, Rosenberg PH, Yli-Hankala A, recipients: a retrospective, multicentre analysis. Nephrol Dial
Samela K, Lindgren L. Pharmacokinetics of propofol and Transplant 1999; 14: 1517–20.

1366
 Anaesthesia for renal transplant surgery

138. Weinberg JM. The cell biology of renal ischaemic injury. 145. Dahaba AA, von Klobucar F, Rehak PH, List WF. Total
Kidney Int 1991; 39: 476–500. intravenous anesthesia with remifentanil, propofol and cis-
139. Kang ES, Miles DE, Tevlin MT, Cates TB, Acchiardo SR. atracurium in end-stage renal failure. Can J Anaesth 1999; 46:
Reversible sequestration of nitric oxide by haemoglobin 696–700.
during haemodialysis in end-stage renal disease. Am J Med 146. Kirvela M, Yli-Hankala A, Lindgren L. Comparison of
Sci 2001; 321: 113–23. propofol/alfentanil anaesthesia with isoflurane/N2O/fen-
140. Thomsen HS, Lokkegaard H, Munck O. Influence of normal tanyl anaesthesia for renal transplantation. Acta Anaesthesiol
central venous pressure on onset of function in renal Scand 1994; 38: 662–6.
allografts. Scand J Nephrol Urol 1987; 21: 143–5. 147. Martin U, Temple RM, Venkat-Raman G, Prescott LF. Para-
141. Carlier M, Squifflet JP, Pirson Y, Gribomont B, Alexandre GP. cetamol disposition in renal allograft recipients. Eur J Clin
Maximal hydration during anaesthesia increases pulmonary Pharmacol 2002; 57: 853–6.
arterial pressures and improves early function of human 148. Gooch K, Culleton BF, Manns BJ et al. NSAID use and
renal transplants. Transplantation 1982; 34: 201–4. progression of chronic kidney disease. Am J Med 2007; 120:
142. Hestin D, Mertes PM, Hubert J et al. Relationship between 280 e1–7.
blood pressure and renin, angiotensin II and atrial natri- 149. Woywodt A, Schwarz A, Mengel M, Haller H, Zeidler H,
uretic factor after renal transplantation. Clin Nephrol 1997; Kohler L. Nephrotoxicity of selective COX-2 inhibitors.
48: 98–103. J Rheumatol 2001; 28: 2133–5.
143. Ferris RL, Kittur DS, Wilasrusmee C, Shah G, Krause E,
Ratner L. Early hemodynamic changes after renal trans-
plantation: determinants of low central venous pressure in Address:
the recipients and correlation with acute renal dysfunction. Dr H. SarinKapoor
Med Sci Monit 2003; 9: CR61–6. Fortis Hospital
144. Dauri M, Costa F, Servetti S, Sidiropoulou T, Fabbi E, Sabato Ranjit Avenue
AF. Combined general and epidural anesthesia with ropi- Amritsar 143001
vacaine for renal transplant. Minerva Anestesiol 2003; 69: India
873–84. e-mail: h_sarinkapoor@hotmail.co.uk

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