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As bupivacaine is eliminated almost entirely by hepatic meta-
 Glucose intolerance
bolism, impairment of hepatic function in conjunction with
repeated drug doses could result in drug accumulation, with the
 Gastrointestinal tract complaints, hepatotrophic
risk of central nervous system (CNS) and cardiovascular toxicity.
Repeated bilateral intercostal injections of bupivacaine have
 Infection and neoplastic risk
been used immediately following liver transplantation to provide
analgesia, limiting the need for the systemic administration of
 Bone marrow depression (lymphopenia,
opioids. Pharmacokinetic studies reveal prolonged elimination of
thrombocytopenia, anemia) and synergy with
both enantiomers of bupivacaine with no tendency for accumu-
other marrow suppressants
lation, even upon repeated dosing.206
 Hepatic dysfunction and jaundice
During the reperfusion phase of liver transplantation, there is
 Hypersensitivity reactions, rashes
progressive recovery of cytochrome P-450-dependent microso-
 Gastrointestinal manifestations, pancreatitis
mal enzyme activity starting immediately after unclamping the
 Infection and neoplastic risk
portal vein and inferior vena cava.207 Therefore, neuromuscular
 Drug interactions: potentiation of depolarizing
blocking agents that are eliminated by the liver (e.g. vecuronium,
and antagonism of nondepolarizing
rocuronium, pipecuronium) are suitable for use in patients with
neuromuscular blockade
normal liver graft function.207,208 Plasma concentrations and the
 Psychological effects (mood changes to psychosis)
neuromuscular effect of atracurium are not influenced by the
 Hypertension, salt and water retention,
absence of hepatic function or circulation, although an accumu-
accelerated atherosclerosis
lation of its metabolite, laudanosine, has been reported.207,209
 Obesity and cushingoid features
In all liver transplant patients, large-bore i.v. access is essential
 Adrenal insufficiency
for the rapid administration of fluids and blood products, as
 Hyperglycemia, hypokalemia
required. The patient may be at risk for intraoperative hemor-
 Osteoporosis, compression fractures, aseptic
rhage from excessive surgical blood loss due to the presence of
necrosis, skin fragility, short stature

5 Other disorders

hypersensitivity to catecholamines.198,214 Supraventricular dys-
residual portal-systemic collaterals, a mild to moderate coagulo-
pathy, and the clinical impression of a decreased capacity of the rhythmias occur frequently, possibly due to surgical trauma of
denervated hepatic vasculature to compensate for systemic the sino-atrial node, ischemia, or as a consequence of a rejection
episode.215 These dysrhythmias respond to treatment with stan-
dard antidysrhythmic drugs, cardioversion where appropriate,
and correction of an underlying rejection episode with large
Heart and heart“lung(s)
doses of immunosuppressive drugs.216 For treatment of tachy-
In the heart or heart“lung(s) transplant patient, invasive hemody- dysrhythmias, some evidence suggests adenosine supersensitiv-
ity of the denervated human heart.217
namic monitoring may be useful to assess the balance between
peripheral vasodilatation and volume loading. Indications include: Only direct-acting pharmacologic agents will have predictable
a suspicion of cardiac decompensation during an acute rejection inotropic or chronotropic responses. Any maneuver or drug that
episode; preexisting marginal cardiac reserve from chronic rejec- relies solely on reflex autonomic neural pathways for its chrono-
tion; myocardial ischemia; or if large fluid volume shifts are antici- tropic effect will not produce a change in HR, i.e. M-muscarinic-1
pated. Additional indications include oliguria unresponsive to and M2 agonist (fentanyl, phenylephrine), M1 and M2 antagonist
fluids; respiratory compromise; and the need for short-acting (atropine, glycopyrrolate, meperidine), M2 antagonist (pancuro-
vasoactive medications (e.g. sodium nitroprusside).196 In most nium) or cholinergic, M2 agonist (neostigmine, edrophonium,
instances, a minimum amount of monitoring is needed for these pyridostigmine). However, peripheral actions on vascular tone
patients.210 The left internal jugular, antecubital, or subclavian are maintained.218
veins are preferred for central venous cannulation to keep the Sodium thiopental may produce greater hypotension than
right side of the neck available for rejection surveillance using expected, due to its intrinsic myocardial depressant action, and
serial endomyocardial biopsies of the right ventricle.198 Radial absence of reflex increase in HR. Opioids may not be as effective in
artery lines are preferable to femoral artery lines, wherever poss- the treatment of ˜˜light anesthesia™™ because of their inability to
ible.112 Transesophageal echocardiography may provide the least decrease HR and BP via vagal mechanisms.219 Nitrous oxide can
invasive method to evaluate ventricular filling and contractility. produce unanticipated hypotension because of the lack of its
Infective endocarditis is a rare complication;211 however, routine sympathetic stimulating properties to offset its direct myocardial
depressant effect.220 Isoflurane can also produce exaggerated
administration of standard endocarditis prophylaxis according to
the American Heart Association guidelines is recommended on the hypotension due to an absence of reflex increases in HR in
response to vasodilation.219 Reflex tachycardia, often seen with
basis of the immunocompromised condition of the patients and
the theoretical risk of suture-line infection.75 vasodilator drugs used to treat preeclampsia (hydralazine, gly-
In the absence of reflex vasoconstriction following hypovole- cerin trinitrate, and sodium nitroprusside), is absent and hypoten-
sion may be exaggerated.110 Caution should be exercised in the
mia, these patients are exquisitely sensitive to changes in preload
and as such require attention to left-sided uterine displacement administration of ergonovine or PGF2-alpha for uterine hypoto-
and volume loading. Before instituting spinal or epidural nia. Although no cases of angina pectoris have been reported in
anesthesia for C/S, preloading the ˜˜compromised™™ patient with a pregnant transplant patient, EKG monitoring for coronary ische-
a colloid solution is felt by some authors to be more efficacious mia during labor and delivery is essential. Three years post heart
than a crystalloid preload in preventing hypotension.196 Cautious transplant, at least 30% of patients will have significant single or
multivessel coronary artery disease in the transplanted heart.100
titration of drugs is imperative, with the avoidance or judicious
use of myocardial depressants. The anesthetized patient with Use muscle relaxants with minimal histamine-releasing and
ganglionic-blocking properties (see Table 22.17).219 Neostigmine
a heart transplant may show exaggerated responses to hypovole-
mia, orthostatic hypotension, or decreases in SVR.110 Treatment has been reported to produce bradycardia and sinus arrest in
of hypotension includes adequate volume loading and the heart transplant patients, which could be explained by cholinergic
availability of an infusion of isoproterenol, epinephrine, or dobu- receptor hypersensitivity, direct activation of cardiac ganglionic
tamine to increase the HR rapidly and improve cardiac contrac- cells, vagal reinnervation, or sinus node dysfunction from surgical
trauma, ischemia, or rejection.221,222 If muscle relaxants are
tility. Most reports indicate that despite both direct and indirect
cardiac effects, the clinical actions of ephedrine and dopamine required, recommendations include administration of short- or
are apparently unchanged.212,213 Depth of anesthesia or intermediate-acting agents (cisatracurium, mivacurium) with ven-
responses to noxious stimuli may be difficult to assess due to tilation of the patient until spontaneous recovery of muscular
a normally elevated baseline HR and delayed CO and HR function occurs without attempting reversal of neuromuscular
blockade.221 Both external and internal pacemakers, atropine,
responses. Therefore, BP responses may provide a more accurate
guide to anesthetic requirements. Both atrial and ventricular and beta-adrenergic agonists (isoproterenol or epinephrine),
dysrhythmias are common findings in the recently transplanted should be readily available to treat bradydysrhythmias in heart
transplant patients undergoing general anesthesia.222
heart, due to: (1) the presence of coronary artery disease; (2)
episodes of acute rejection; and (3) as an incidental finding The immediate sympathetic response to laryngoscopy and
in the long-term heart transplant patient. Ventricular dysrhyth- intubation should be absent. Other maneuvers such as externali-
mias may be due also to a lack of suppressant vagal tone, zation of the uterus producing vagal stimulation and reflex bra-
dycardia with hypotension, would not be expected to occur.196
increased endogenous catecholamine concentrations, and/or

Chapter 22

Table 22.17 General anesthesia for cesarean section: Table 22.18 Regional anesthesia for cesarean section:
a suggested technique for heart transplant patients a suggested technique for heart transplant patients

External and internal pacemakers, atropine, and b-adrenergic agonists 1. Administer aspiration prophylaxis.
such as isoproterenol or epinephrine, should always be readily 2. Volume load with 1 to 2 liters of dextrose-free crystalloid
available. (or colloid) solution.
1. Administer aspiration, steroid, and antibiotic prophylaxis 3. Administer supplemental oxygen, apply hemodynamic monitors
2. Volume preload with dextrose-free crystalloid (or colloid) solution, (blood pressure cuff, EKG, pulse oximetry), and position patient.
preferably two indwelling intravenous catheters NOTE: Resuscitation equipment and drugs must be readily available
3. Position supine (left uterine displacement), surgical preparation, for use.
and draping Epidural anesthesia
4. Noninvasive monitors: EKG, automatic blood pressure cuff, pulse Local anesthetic solutions:
oximetry, neuromuscular blockade (invasive monitoring for renal, 1. 0.5% bupivacaine or 0.5% ropivacaine
respiratory, or cardiac compromise) 2. 2% lidocaine
5. Preoxygenation (O2 > 6 liters/min) 3. 3% chloroprocaine
 Addition of epinephrine to a concentration of 1:200 000 for the
6. Assistant readiness to apply cricoid pressure, surgeon poised
7. Rapid sequence induction with cricoid pressure: thiopental test dose (15 mg) and fractionated incremental doses up to 20 ml is
4 mg/kg or propofol 2 mg/kg and succinylcholine 1.5 mg/kg, controversial.
 Availability of a titratable infusion of esmolol and observation of
careful intubation of trachea within 60 seconds, verify cuffed
endotracheal tube placement with end-tidal CO2 monitor heart rate with EKG monitoring is essential.
 Adjustment for rapid onset with sodium bicarbonate (8.4%):
and chest auscultation prior to releasing cricoid pressure.
Do not precurarize the patient, due to interaction potential of 1:10 ml with lidocaine or chloroprocaine and 0.1:10 ml with
magnesium, CyA, and nondepolarizing muscle relaxants bupivacaine/ropivacaine.
 Addition of epidural narcotics for intraoperative analgesia
8. Maintenance: nitrous oxide 50%, isoflurane <0.75%
 Choice of muscle relaxants: no additional relaxant, mivacurium, recommended (fentanyl 50 to 100 mg) and morphine 3 mg fol-
or cisatracurium (do not administer reversal dose of lowing delivery.
neostigmine and atropine, document sustained head lift for 4. Position patient supine with left uterine displacement.
five seconds prior to extubation and again in recovery room) 5. Monitor arterial blood pressure every minute until delivery of the
9. Hypotension (systolic blood pressure <100 mmHg or decreased baby, then every five minutes for the duration of the block.
by 30%): determine etiology, ensure LUD, administer fluids, 6. Anxiety or ˜˜patchy™™ anesthesia may be treated with: fentanyl
ephedrine 5“15 mg i.v., isoproterenol (avoid maternal 1 mg/kg, ketamine 0.25 mg/kg, midazolam 1“2 mg or nitrous oxide
hyperventilation and high peak inspiratory pressures) 40%, with additional intravenous narcotic following delivery.
10. With delivery of the baby, deepen anesthesia with narcotics and Spinal anesthesia
benzodiazepines, continue isoflurane <0.50%/N2O/O2, limit FiO2 Local anesthetic solutions:
to 40% in heart“lung transplant patients 1. Bupivacaine 10 to 12.5 mg (0.75% with 8.25% dextrose solution)
 Avoid hyperbaric lidocaine solutions.
11. Extubate with the patient fully awake; demonstrate adequate
 Optional addition of intrathecal narcotics including fentanyl 10
ventilation, oxygenation and recovery from residual muscle
relaxant to 15 ug or preservative-free morphine 0.1 to 0.2 mg for post-
operative pain relief.

Epidural analgesia is preferred for labor and delivery as incre-
mental injection of local anesthetics and titration of the level of report intact alpha- and beta-adrenoreceptors in the denervated
sympathetic blockade will allow time for volume loading and heart responding normally to circulating catecholamines without
physiologic compensation by the patient (see Tables 22.18 and evidence of denervation hypersensitivity to exogenous and endo-
genous catecholamines.213,224
22.19). One should be aware of the additional infection risk to the
CNS when choosing epidural and spinal anesthesia.87 The epi- Postpartum monitoring includes: assessment of cardiovascular
dural catheter should not be left in situ for more than two days, as and renal status, temperature, fluid balance, evaluation of ven-
the incidence of infection increases after this time.199 Complete tricular function with serial EKGs, echocardiography, and cardiac
sympathetic denervation implies that levels of regional anesthe- isoenzymes, plus cardiac biopsy if acute rejection is suspected.
sia above T4 would not be expected to result in bradycardia.223 All equipment used directly on the heart“lung(s) or lung trans-
Epidural injection of an epinephrine-containing local anesthetic plant patients should be sterile and a disposable circuit with
a bacterial filter should be used on the anesthetic machine.110
in a patient with a transplanted heart produced a profound tachy-
cardia, which has the risk of precipitating myocardial ischemia. Careful placement of the endotracheal tube with monitoring of
The proposed mechanism for this exaggerated response was sys- FiO2, arterial blood gases, (pulse oximetry, capnography, or inva-
temic absorption of epinephrine in the face of exquisite sensitiv- sive monitoring), peak airway pressures, and fluid infusions
ity of the transplanted heart to b-adrenergic agonists.223 Others should minimize the risk of oxygen toxicity, barotrauma, or stress

5 Other disorders

pulmonary leakage.112 Monitoring of RV function is essential if
Table 22.19 General considerations for management of the there is evidence of residual pulmonary hypertension or cardiac
transplant recipient during labor and delivery decompensation.
1. Mandatory strict adherence to aseptic techniques
2. Augmentation of steroids for labor-induced stress Summary
3. Minimizing invasive monitoring techniques
During the past two decades organ transplantation has become
4. Essential antibiotic prophylaxis for all invasive monitoring and
widely accepted as an established therapeutic option for patients
suffering from end-stage organ failure. The ultimate goal for these
5. Assessment and optimization of graft function
patients is not purely survival at all costs, but rather the resump-
6. Anticipation of altered physiologic and pharmacologic responses in
tion of a normal life style, which for many young women includes
the denervated organ
childbearing. Despite early concerns, at least 14 000 births among
7. Continuation of immunosuppressive therapy
women with transplanted organs have been reported worldwide.7
For patients not permitted oral intake, the oral to intravenous
Pregnancy is now an expected part of the benefits afforded
conversion factors for immunosuppressive drugs are:
to women by organ transplantation. Important advancements
 Prednisone po: methylprednisolone i.v. “ 1:0.8
in organ preservation and immunosuppressive therapy have dras-
 Azathioprine po: azathioprine i.v. “ 1:1
tically improved patient and graft survival, and as such it is inevi-
 CyA po bid: CyA i.v. bid “ 1:0.25, infused over 6 hours twice daily
table that with increasing frequency the anesthesiologist will be
8. Maintain surveillance and optimization of renal function, blood
requested to participate in the care of the pregnant transplant
pressure, and fluid balance
recipient during labor and delivery. This chapter has been com-
9. Identify maternal problems related to the pregnancy,
piled from a review of the literature, discussion among colleagues,
immunosuppressive therapy, transplant surgery, or coexisting
and my personal experience as a transplant anesthesiologist.
systemic illness
10. Vaginal delivery is recommended, but cesarean section may be
required in at least 50% of women
1. Murray, J. E., Reid, D. E., Harrison, J. H. & Merrill, J. P. Successful pregnan-
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on the tracheal/bronchial anastomosis, excessive increases in
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Am. J. Kidney Dis. 1992; 19: 173“6.
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Chapter 22

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