ANAESTHESIA FOR RENAL

TRANSPLANT PATIENT FOR

NON-TRANSPLANT

SURGERY

MOD : DR. KAUMUDI

Dr.Arun

INTRODUCTION

n POST TRANSPLANT PATIENT

n INCREASED SURVIVAL• BETTER IMMUNOSUPPRESSIVE REGIMES,

• SURGICAL TECHNIQUES

• POSTOPERATIVE CARE.

n After successful kidney transplantation,

most patients are classified as having

National Kidney Foundation stage 2 or 3 CKD

with usual GFRs more than 30 mL/min.

n GFR typically deteriorates by 1.4 to 2.4

mL/min/yr in renal transplant recipients

PRE ANAESTHETIC

CONSIDERATIONS

1. IDENTIFICATION OF COMPLICATIONS &

THEIR ANAESTHETIC IMPLICATIONS

2. TOXICITY OF IMMUNOSUPPRESSANTS

3. RELEVANT DRUG INTERACTIONS WITH

IMMUNOSUPPRESSANTS

4. REJECTIONS

5. INFECTIONS

CONCERNS IN A

TRANSPLANT RECIPIENT1) ALTERED FUNCTION/ PHYSIOLOGY RELATED

TO TRANSPLANTED ORGAN

2) ALTERED FUNCTION DUE TO IMMUNO SUPPRESSION

1) INFECTIONS

2) MALIGNANCIES

3) TOXICITY OF IMMUNOSUPPRESSIVE DRUGS

4) POTENTIAL INTERACTION OF IMMUNOSUPPRESSIVE DRUGS WITH OTHER DRUGS

5) POTENTIAL FOR REJECTIONOF TRANSPLANTED ORGAN

n Progression of preexisting CAD as

immunosuppression contributes to the

development of de novo hyperlipidemia,

hypertension, and diabetes.

n Cardiovascular disease is the most common

cause of death in kidney transplant patients.

n GFR -usually reduced,(despite normal

creatinine) -electrolyte abnormalities and

altered drug metabolism

COMPLICATIONS AFTER

RENAL TRANSPLANTATION

n EARLY

• HEMORRHAGIC CYSTITIS

• CAPILLARY LEAK

• AGVHD

• PANCYTOPENIA

• CARDIOMYOPATHY

• VENO OCCLUSIVE LIVER DISEASE

• INTERSTITIAL PNEUMONITIS

COMPLICATIONS AFTER

RENAL TRANSPLANTATION

n LATE

• CGVHD

• LEUKO ENCEPHALOPATHY

• INFECTION

• SECONDARY MALIGNANCIES

• OBSTRUCTIVE/ RESTRICTIVE LUNG DISEASE

• HYPOTHYROIDISM

• CATARACT

IMMUNOSUPPRESSIVE

THERAPY FOR

TRANSPLANT RECIPIENTS

TRIPLE DRUG REGIMEN

1) CYCLOSPORIN / TACROLIMUS

2) GLUCOCORTICOIDS – METHYL

PREDNISOLONE

3) MYCOPHENOLATE MOFETIL/

AZATHIOPRINE

CYCLOSPORIN : started 7 days before transplantation of living donor kidney

1 day after for cadaver kidney

8mg/kg in 2 div doses

then tapered to 3 – 4 mg/kg

TACROLIMUS : starting 1 day after transplantation of both living & cadaver kidney transplantation

METHYL PREDNISOLONE : 250 mg IV 1hr before & 6 hrs after surgery

Tapered & maintained for 6 mths

MYCOPHENOLATE MOFETIL : 1 gm iv BD starting 1 day before Sx & continue for 6 mths

TOXICITY RELATED TO

IMMUNOSUPPRESSIVE

DRUGS

CYCLOSPORIN A

WATER SOLUBLE

ORAL ABSORPTION UNPREDICTABLE

IV DOSE 1/3 ORAL DOSE

TOXICITY

NEPHROTOXICITY

• RENAL VASC. RESISITANCE

• RBF

• APPARENT WITHIN A WEEK OF

INITIATION OF THERAPY

• CHRONIC TOXICITY

• AMINOGYCOSIDE + C/c Cs A THERAPY

POTENTIATE NEPHROTOXICITY OF Cs A

CYCLOSPORIN A

NEUROTOXICITY

• HEADACHE

• PARESTHESIAS

• TREMOR

• CONFUSION

• FLUSHING

• NEUROPATHIES

• GENERALISED SEIZURES

CYCLOSPORIN A

VASCULAR EFFECTS

• HYPERTENSION (INCIDENCE 42-100%)

• DIABETOGENIC

• TOTAL CHOLESTEROL

CORONARY ARTERY DISEASE

CYCLOSPORIN A

METABOLIC EFFECTS• HYPERKALEMIA

• HYPOMAGNESEMIA

HIRSUITISM

GUM HYPERPLASIA

ANOREXIA

LYMPHOPROLIFERATIVE DISEASES

INFECTIOUS DISEASES

TACROLIMUS

INHIBIT T CELL PROLIFERATION

100 TIMES POTENT THAN CYCLOSPORINE

ADVERSE EFFECTS:-• NEPHROTOXIC

• DM

• NEUROLOGIC – TREMOR, HEADACHE

• ALOPECIA

• BONE MARROW SUPPRESSION

• LYMPHOPROLIFERATIVE DISEASES

• INFECTIOUS DISEASES

TACROLIMUS

USED IF NOT TOLERATING Cs A

Cs A STOPPED ONLY AFTER 24 HRS OF

STARTING TACROLIMUS

STERIODS

USED IN ALL TRANSPLANT FOR A PERIOD

OF TIME

USED TO PREVENT REJECTION AND AS

PULSE THERAPY FOR TREATMENT OF

ACUTE REJECTION

STERIODS

OBESITY

GLUCOSE INTOLERANCE

SERUM LIPID LEVELS

ACCELERATE CARDIOVASCULAR

DISEASE

MARKED SKIN FRAGILITY

• MINIMISE ADHESIVE TAPES

• PADDED BP CUFFS

• EYES LUBRICATED

STERIODS

DELAYED WOUND HEALING

RISK OF OSTEOPOROSIS

• CAREFUL MOVEMENT & POSITIONING

IRRITATE GASTRIC MUCOSA

ANTIMETABOLITES

AZATHIOPRINE

MYCOPHENOLATE MOFETIL

• ANTI-NUCLEOTIDE ANTIMETABOLITES

• INHIBIT LYMPHOCYTE PROLIFERATION &

ANTIBODY PRODUCTION

AZATHIOPRINE

• BONE MARROW DEPRESSION

• HEPATOTOXICITY

MYCOPHENOLATE

• NO INTERACTION WITH CsA &

PREDNISOLONE

• NEPHROTOXICITY

• HEPATOTOXICITY

• BM DEPRESSION

ANTIMETABOLITES

AZATHIOPRINE

MYCOPHENOLATE MOFETIL

• ANTI-NUCLEOTIDE ANTIMETABOLITES

• INHIBIT LYMPHOCYTE PROLIFERATION &

ANTIBODY PRODUCTION

DRUGS AFFECTING Cs A &

TACROLIMUS BLOOD

LEVELS

BLOOD LEVELS• METOCLOPRAMIDE

• VERAPAMIL

• NICARDIPINE

• CIMETIDINE

• DILTIAZEM

• BROMCRIPTINE

• ERYTHROMYCIN

• KETOCONAZOLE

• CHLOROQUINE

DRUGS AFFECTING Cs A &

TACROLIMUS BLOOD

LEVELS BLOOD LEVELS

• CARBAMAZEPINE

• PHENOBARBITAL

• PHENYTOIN

• RIFAMPICIN

• OCTREOTIDE

• TICLOPIDINE

DRUGS THAT MAY CAUSE

RENAL DYSFUNCTION

WHEN GIVEN WITH Cs A &

TACROLIMUSNSAIDs

RANITIDINE

CIMETIDINE

AMPHOTERICIN

COTRIMOXAZOLE

GENTAMICIN

MELPHALAN

TACROLIMUS/ Cs A

INFECTIONS IN

IMMUNOSUPPRESSEDMAJOR CAUSE OF MORBIDITY & MORTALITY

1ST MONTH - BACTERIAL INFECTIONS • WOUND INFECTION - STAPH. AUREUS

• URINARY CATHETER – E. COLI

• PNEUMONIA – PNEUMOCOCCI

OPPURTUNISTIC INFECTIONS MOST COMMON 30-180 DAYS AFTER SURGERY• CMV - COMMONEST

• HERPES

• VARICELLA ZOSTER

• PNEUMOCYSTIS CARINII

MYCOBACTERIAL INFECTIONS

SYSTEMIC MYCOSES

NOCARDIOSES

PARASITIC INFECTIONS

• STRONGYLOIDES

• ENTAMEBA

• ACANTHAMEBA

ANESTHETIC

CONSIDERATION

The main anesthetic goal is to maintain

renal perfusion and prevent harm to the

already compromised renal function by

avoiding hypoxia, hypovolemia and

hypotension.

Pre op Evaluation

History: Establish the cause of renal

failure and duration of treatment.

Need for dialysis postoperatively.

Enquire about fluid restriction if any and

daily urine output.

H/O comorbidities (Hypertension,

diabetes, IHD, connective tissue

disorders) and whether controlled and on

what treatment (dose, frequency).

Pre op Evaluation

Enquire about

Exercise Tolerance, Anemia, LVF, Electrolyte

Disturbance, Medications), Gastroesophageal

reflux.

Seek nephrology opinion regarding need for

dialysis in the postoperative period

ExaminationMeasure the patient’s blood pressure in

standing and in sitting position to R/O

autonomic neuropathy.

Flow murmur secondary to anemia and

pericardial rub due to uremic pericarditis.

Look for ankle or sacral edema which may

indicate either right ventricular failure or

hypoproteinemia or both.

Patient’s who are fluid overloaded may

have crepitations

REJECTION

MAIN CAUSE OF LATE MORTALITY

PROGRESSIVE DETERIORATION IN

ORGAN FUNCTION TESTS

• AZOTEMIA

• PROTEINURIA

• HYPERTENSION

REJECTION

SURGERY DURING PERIOD OF

REJECTION HAVE HIGHER MORBIDITY

REJECTION

PRESENTATION:-

PROGRESSIVE DETERIORATION OF ORGAN FUNCTION

OR

WITH MINIMAL SYMPTOMS FROM TRANSPLANTED ORGAN &

WITH NON SPECIFIC SYMPTOMS• POOR APPETITE

• IRRITABILITY

• FATIGUE

REJECTION

TIMING :-

MAJORITY WITHIN 3 MONTHS

PEAK TIME – 4-6 WEEKS POST TRANSPLANT

TREATMENT :-

INCREASING IMMUNOSUPPRESSIVE TREATMENT• ADDING ADDL. DRUGS LIKE METHOTREXATE

• AUGMENTATION OF STEROID USE

REJECTION

ADEQUATE LEVELS OF

IMMUNOSUPPRESSIVE AGENTS SHOULD

BE MAINTAINED THROUGHOUT THE

PERIOPERATIVE PERIOD

InvestigationsFull blood count: Normochromic, normocytic anemia

and infection are likely.

Clotting studies: are required if the uraemia is

severe.

Renal function tests (BUN, serum creatinine,

Electrolytes)

ECG: Look for ischemia, arrhythmia, LVH,

conduction blocks or hyperkalemia.

Chest radiograph: Pleural effusions, cardiomegaly,

pulmonary edema

ABG to evaluate the acid base status

LFT if a major surgery is planned; as a baseline value

Preoperative

optimization/preparationIf infection / rejection suspected postpone

elective surgery

Continue immunosuppressants

antihypertensive

Adjust dosage according to drug blood levels

For elective surgery, it is prudent to optimize

blood pressure, serum potassium level.

Preoperative

optimization/preparation

Avoid unnecessary blood transfusion

because of anemia to avoid sensitization

for future transplantation.

Metoclopramide and H2 receptor

antagonists should be administered if

patient has gastroesophageal reflux.

GENERAL ANAESTHETIC

CONSIDERATIONS

Induction of anesthesia

Preoxygenate

Administer induction drugs slowly to minimize

hemodynamic disturbances. If hypotension occurs

despite above, vasopressors can be given titrated

to mean arterial pressure.

If rapid sequence induction is necessary,

suxamethonium can be used if the serum

potassium is < 5.5 mEq/ L,

modified rapid sequence induction can be done

with rocuronium

If difficult airway is anticipated;

inhalational induction is a safer option.

.f there is any doubt regarding airway

adequacy, always intubate.

Regional anesthesia can be administered

after weighing the risks and the benefits.

Concern with epidural anesthesia is

platelet dysfunction; increasing the risk of

epidural hematoma.

Maintenance of anesthesia

Nitrous oxide can be administered

safely as it does not affect the renal

function.

Isoflurane is the inhalational agent of

choice as only 0.2% undergoes

metabolism and produces low levels of

fluoride ions.

Ventilation should be controlled for

long procedures.

Maintenance of anesthesia

Atracurium is preferable as it undergoes Hoffman’s

elimination.

Vecuronium and rocuronium can be used but

smaller top-up doses are required less frequently.

Neuromuscular blockade should be monitored using

a nerve stimulator and top-up doses administered

accordingly.

Fentanyl can be administered safely; half life may be

prolonged particularly if used as an infusion.

Morphine can be used with care as clearance is

reduced

If morphine is administered patient should

be monitored for respiratory depression in

the postoperative period.

It should never be used as a continuous

infusion

Cs A potentiate :-

• Barbiturates

• Fentanyl

• NDMRs esp. atrac/ vec

So smaller doses & recovery time

prolonged

AZATHIOPRINE

• antagonise NDMR

– Use larger dose

• It may prolong SCh effect

Seizure threshold reduced in patients

treated with Cs A & Tacrolimus

• Avoid hyperventilation

Massive fluid infusion periop.

• Dilute Cs A / Tacrolimus

NSAIDs avoided

• Risk of GI hge, nephrotoxicity, hepatic

dysfn

Regional techniques :-

• If coagulation status & Platelet count normal

• Azathioprine can cause Thrombocytopenia

SPECIFIC ANAES.

CONSIDERATIONSRENAL FUNCTION SHOULD BE ASSESSED• ESP IN PTS ON Cs A / TACROLIMUS

IF IMPAIRED• PROLONG DRUG ACTION EXCRETED BY

RENAL ROUTE

RISK OF CARDIOVASCULAR DISEASE• ESP IN DM/ ELDERLY

HIGH INCIDENCE OF HYPERTENSION• ON C/c ANTIHYPERTENSIVES

ADEQUATELY FUNCTIONING KIDNEY

RECIPIENTS

• NORMAL Cr. LEVELS

• GFR lower

CHOOSE DRUGS INDEPENDENT OF

KIDNEY FOR EXCRETION

AVOID NEPHROTOXIC DRUGS

MONITORING

Monitor ECG, BP, end-tidal capnometry, pulse

oximetry, temperature and neuromuscular

monitoring.

If large fluid shifts or blood loss is anticipated;

invasive monitoring (central venous pressure

and invasive arterial BP) should be established

to guide fluid replacement.

A urinary catheter should be passed to

monitor urine output hourly and should be

maintained at 0.5–1 mL/kg/hr.

If the urine output is low despite good

hydration and BP; mannitol should be

administered as first line treatment

followed by frusemide

.IV fluids should be administered

cautiously,

central venous monitoring may be done to

guide volume replacement.

Starches should be avoided in these

patients as it can accumulate and worsen

the renal impairment, gelatine is safe.

Ringer’s lactate can be used if serum

potassium is within the normal limits.

..

Forced air warmer and fluid warmer

should be used mandatorily to maintain

normothermia.

Over transfusion of blood to correct

anemia should be avoided as increase in

hematocrit can decrease renal perfusion

and further compromise the renal

function.

.NSAID’s are contraindicated in these

patients, paracetamol can be administered

safely

Reversal of neuromuscular

block

Neuromuscular blockade can be reversed

with neostigmine.

Recurarization can occur in the postop and

the recovery staff should be warned about

the same.

Inadequate reversal -it is safer to ventilate

the patient for short-term till complete

neuromuscular recovery occurs

POST OPERATIVE CARE.Oxygen

. ECG, BP and SPO2

ANALGESIA.

WITH ACETAMINOPHEN AVOID NSAIDs

EPIDURAL BLOCK

WOUND INFILTRATION

PERIPHERAL NERVE BLOCK

Early mobilization and physiotherapy

POST OP. CARE

Dosages of medications should administered

as per creatinine clearance. :

Cockcroft–Gault equation (eCCr = estimated

creatinine clearance)

eCCr = (140 - Age) × Mass (inkilograms) [0.85

if female] /72 × Serumcre atinine (inmg/dL)

AVOID PREGNANCY FOR A PERIOD OF

2 YRS AFTER TRANSPLANTATION.

Contraceptive counselling should begin immediately

after transplantation, (ovulatory cycles may begin within

1–2 months of transplantation )

Low dose oestrogen–progesterone OCP.

The risk of infection from the use of intrauterine devices

is increased in immunocompromised patients.

EFFECT OF PREG. ON ALLOGRAFT

MINIMAL BUT FETAL OUTCOME LESS

FAVOURABLE

45% PREG. BEYOND 28 WKS – ADVERSE OUTCOME

LIMIT NUMBER OF PREGNANCIES

PREGNANCY

Factors that are associated with favorable pregnancy outcomes

include the following:

Good general health for about 2 years after

transplantation

No graft rejection in the last year

Adequate and stable graft function

No acute infections that might affect the fetus

Maintenance immunosuppression at stable doses

Patient compliance with treatment and follow-up

Normal blood pressure or blood pressure that is well

controlled with one medication

Normal allograft ultrasonography results

Factors that may worsen

pregnancy outcomesEtiology of the original disease

Chronic allograft dysfunction

Renal insufficiency

Cardiopulmonary diseases

Hypertension

Diabetes mellitus

Obesity

Maternal infection with hepatitis B (HBV) or C

(HCV) or cytomegalovirus (CMV)

EFFECT OF PREGNANCY

ON RENAL ALLOGRAFT

Pregnancy does not appear to cause

excessive or irreversible problems

with graft function if the function of

transplant organ is stable prior to

pregnancy

EFFECT ON FETUS

GOOD PROGNOSIS SEEN WITH:-1. GOOD GENERAL CONDITION FOR 2 YRS

AFTER SURGERY

2. STATURE COMPATIBLE WITH GOOD OBSTETRICAL OUTCOME

3. NO PROTEINURIA

4. NO SIGNIFICANT HYPERTENSION

5. NO e/o GRAFT REJECTION

6. NO e/o PELVICALYCEAL DISTENSION

7. DRUG THERAPY– PREDISOLONE 15 mg/d or less

– AZATHIOPRINE 2mg/kg/d or less

Immunosuppressive drugs in

pregnancy

Glucocorticoids : Adrenal insufficiency and thymic

hypoplasia cleft palate or mental retardation in infants.

(unlikely if the dose of prednisone has been decreased

to 15 mg ).

MOTHER : PROM,infections,aggrevate hypertension.

Azathioprine : low birth weights, prematurity,

jaundice, respiratory distress syndrome and aspiration

,myelosuppression in the fetus.

leukopenia is not usually a problem in the neonate if the

maternal white blood count is maintained at values

higher than 7500/mm3

Immunosuppressive drugs in

pregnancycyclosporin low birth weights and a higher incidence of

maternal diabetes, hypertension and renal allograft dysfunction.

Cyclosporin metabolism increased during pregnancy -higher

doses may be required.

pregnancies in cyclosporin‐treated women were complicated by

pre‐eclampsia.

Tacrolimus:premature labour,renal dysfunction

FEW DETAILS AVAILABLE WITH USE OF OTHER

DRUGS.

Patient self-monitoring of daily blood pressure

Aggressive management of hypertension:

DOC methyldopa

Second-line agents i:clonidine and calcium

channel ,alpha blockers.

contraindicated drugs : angiotensin-converting

enzyme inhibitors and angiotensin receptor

blockers.

Close monitoring of graft function; if rejection is

suspected, consider biopsy .

In cases of acute rejection, steroids are the

preferred drugs

SHOULD CONTINUE

• PREDNISOLONE

• AZATHIOPRINE

• Cs A

• FEAR OF ACUTE REJECTION

REQT. OF Cs A INCREASED DURING PREGNANCY

• INCREASED METABOLISM

GUIDELINES FOR MX

Obstetric management of

pregnant transplant recipients Frequent evaluations, preferably every 2 weeks

Vaginal delivery (preferred): Usually delayed until

labor onset unless maternal/fetal indications for

induction exist

Cesarean delivery is only indicated for obstetric

reasons .

Avoid injury to the allograft by knowing its exact

location

Antibiotic prophylaxis for all surgical procedures [1]

Increased steroid dose at labor onset to overcome

the stress of labor and prevent postpartum transplant

rejection

EMERGENCY SURGERY

WITH ACUTE GRAFT

REJECTION

SPECIAL PREANAESTHETIC

CONSIDERATIONS ARE :-

1. RISK OF ASPIRATION

-GI HGE/PERFORATION

2. TOXICITY OF IMMUNOSUPPRESSANTS

& RELEVANT DRUG INTERACTIONS

3. RISK OF INFECTIONS

4. AVOIDANCE & CURTAILMENT OF

NEPHROTOXIC INSULT

EVALUTE FOR CAD

• Cs A – HYPERTENSION,HYPERGLYCEMIA &

HYPERLIPIDEMIA

PTS ON C/c STEROID THERAPY

• STRESS DOSE OF STEROIDS

INTRAOPERATIVELY

STRICT ASEPSIS FOR INVASIVE

PROCEDURES

BROAD SPECTRUM ANTIBIOTICS

Anesthesia for patients after liver

transplantationGraft function must be assessed

PT-INR excellent marker of synthetic

function

Sterile techniques should be used

Complications due to immunosupressants.

Regional anesthesia is an option if clotting

status is acceptable

A stress dose of corticosteroids may be

needed.

Hepatic blood flow should be maintained.

Anesthesia for patients after

lung transplantation Recipients may require months to achieve peak

pulmonary function.

Transplanted lung is especially susceptible to

infection and rejection as a result of its unique

exposure to the external environment.

Careful preoperative evaluation with PFTs

Postponement of elective surgical procedures

when allograft rejection or infection is suspected.

OTHER CONSIDERATIONS

Airway hyper responsiveness,

Loss of the cough reflex,

Potential for injury to the airway anastomosis

with intubation.

Increased risk for pulmonary edema, D/T

disruption of the lymphatic drainage in the

transplanted lung

Anesthesia for patients after

HEART transplantation

Most issues relate to the absence of autonomic

innervation in the transplanted heart.

Denervation has multiple physiologic effects,

Higher than normal resting HR (from absence of

vagal tone);

Absence of cardiac baroreflexes;

Lack of response to carotid sinus massage,

Valsalva maneuver, laryngoscopy, or tracheal

intubation. .

Anesthesia for patients after

HEART transplantation

Denervation also affects responses to

medications;

the allograft demonstrates a normal or

augmented response to direct-acting

drugs (e.g., epinephrine),

A blunted response to indirect-acting

agents (e.g., ephedrine),

And no response to vagolytic agents.

Chronic allograft rejection

Manifest as accelerated coronary heart disease

and as both systolic and diastolic dysfunction.

Allograft denervation causes any myocardial

ischemia to be silent.

Typical manifestations of chronicrejection

include fatigue, ventricular dysrhythmias,

congestive heart failure, and silent MI on the

ECG.

Patient’s recent cardiac testing must be reviewed.

Anesthesia for patients after

HEART transplantation Routine periodic evaluation for CAD (stress

testing or coronary angiography) and cardiac

function (echocardiogram or radionuclide

angiography).

PreoperativeECGs often reveal conduction

abnormalities and may show two P waves (a non

conducted P wave from the native atria and a

conducted P wave from the donor atria).

Many heart transplant recipients also require

permanent pacemakers, and pacemaker function

should be confirmed during the preoperative

assessment.

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