As a general rule, special equipment is not needed and anesthesia should be performed using standard American Society of Anesthesiology’s monitoring guidelines. The decision to use invasive hemodynamic monitors, placement of central venous access, pulmonary artery catheters or other procedures such as transesophageal echocardiography should be made on a case by case basis. This decision should be guided by consideration of the patient’s comorbidities, hemodynamic stability, the expertise of the anesthesiologist in placing the invasive device and interpreting the data, the inherent risk of the surgery, and the overall risk to benefit ratio of the proposed monitor [15]. It is important to consider that central venous access may be difficult as many of these patients have had long-standing illnesses with the need for central venous catheters for parenteral nutrition, hemodialysis, esophageal variceal hemorrhage, sepsis, and other clinical problems that required central venous access. These may have been complicated by thrombosis, stenosis, and infection making reaccessing these veins difficult or impossible [14]. Meticulous hygiene practice and aseptic technique are of utmost importance to minimize exposure to infectious organisms and bacteremia when attempting any invasive procedures in this population [4,8,16].

Airway management of transplant patients may pose a concern for several reasons. Many patients may have preexisting diabetes mellitus before transplant or acquire diabetes after transplant (PTDM). Diabetic patients can develop limitations in joint mobility caused by glycosylation of the connective tissue within their joints. Several retrospective and prospective evaluations performed at transplant institutions in patients with diabetes mellitus undergoing kidney and/or pancreas transplantation report increased rates of difficult laryngoscopy, including a retrospective analysis from our institution [17,19]. The airway management plan should be formulated after careful airway examination and review of previous anesthetic records. If recent records are not available locally, they may be obtained from the transplant center keeping in mind that if extended time has elapsed since the last anesthetic, the ongoing effects of diabetes on the mandibular and atlanto-occipital joints may result in a difficult intubation not previously reported. Graft-versus-host disease can also create limited joint mobility creating a similar scenario. This population is also at increased risk for lymphoproliferative disorders secondary to immune-suppressant drugs, and lymphoproliferative growth may compromise any part of the airway or mediastinum and cause life-threatening airway obstruction during sedation and anesthesia. Aspiration risk may be increased in transplanted patients as a result of delayed gastric emptying and gastropathy [4,8]. These potential problems should all be taken into consideration when constructing the anesthetic plan for airway management.

Oral endotracheal tubes are preferred over nasal tubes because of the increased potential for infection from the nasal route in this immune-compromised population. Early postoperative extubation is preferred if possible to prevent the development of nosocomial or ventilator-associated pneumonia.

Antibiotic prophylaxis has not been studied extensively in transplant recipients undergoing nontransplant surgery. Although transplant patients are considered at-risk hosts for infection because of their immune status, there is no evidence to suggest different bacteriology of surgical site infections than for the general population. However, the use of prophylaxis even for clean cases in this higher risk population is advocated and has some supporting evidence [20,21]. It is recommended that the guidelines for surgical antibiotic prophylaxis from the National Surgical Infection Project be followed and should be given before incision.(Table 3). Antimicrobial coverage need not be expanded to include atypical or opportunistic organisms as long as active infection with such an organism is not present or suspected [7,21,22].

Table 3 Antimicrobial prophylaxis for selected surgical procedures

Abbreviations: ACOG, American College of Obstetricians and Gynecologists; ASHP, American Society of Health-System Pharmacists.

Data from Bratzler DW, Houck PM. Antimicrobial prophylaxis for surgery: an advisory statement from the National Surgical Infection Prevention Project. Clin Infect Dis 2004;38:1706–15.

All inhalational and intravenous anesthetics have been used with success in transplant recipients. The choice of anesthetics and adjunctive drugs should be determined by the type of surgery and condition of the patient. As a general guideline, if hepatic and renal functions are normal, all standard anesthetic medications and adjuncts may be used. Some special considerations for each type of organ transplant are discussed in the section on organ-specific considerations.

Premedication with benzodiazepines is acceptable, keeping in mind that most are metabolized by the liver and may have active metabolites that are cleared via the kidneys. Caution should be used in patients with hepatic or renal insufficiency as effects may be prolonged. Benzodiazepines should be avoided in patients who are somnolent or if there is a concern of respiratory depression or obstruction, as with any anesthetic that is performed. Some centers avoid them to facilitate extubation, but this is probably not justified in most surgeries. The intended effect of anxiolysis augments a smooth and more tolerated anesthetic.

The selection and administration of intravenous anesthetics should be guided by the patient’s hemodynamic status, the drug’s cardiovascular effects and pharmacokinetic properties, especially the biotransformation and elimination profiles of the drug. Drugs that undergo primarily hepatic metabolism, such as barbiturates, should be dose adjusted if administered to avoid prolonged effects in patients with hepatic insufficiency. Care should be taken when using barbiturates as cardiac output and mean arterial pressures can decrease precipitously as a result of venous pooling and loss of cardiac preload. Propofol is extensively metabolized by the liver to inactive glucuronic acid metabolites that are excreted by the kidneys. Despite the known mechanisms of biotransformation, there seems to be no need for dose adjustments in patients with hepatic or renal failure indicating an extrahepatic route of elimination as well [23]. Care should be used in patients with cardiovascular compromise as propofol can worsen cardiac contractility, compromise cardiac preload, cause bradycardia, and lower systemic vascular resistance culminating in diminished cardiac output and mean arterial pressure. Etomidate does not have the cardiac depressant effect of barbiturates and propofol. Etomidate is metabolized rapidly by hydrolysis within the liver and by plasma esterases, and also does not require dosage adjustment in renal or hepatic disease. One unique characteristic of etomidate is its ability to inhibit the 11-β-hydroxylase, an enzyme necessary for the synthesis of cortisol, for 5 to 8 hours after administration. The clinical significance in patients who already have adrenal suppression as a result of exogenous steroid use is unclear, but heightened attention should be paid to the need for perioperative stress-dose corticosteroids [23]. Ketamine is metabolized via the hepatic cytochrome P-450 system to norketamine, which has approximately one-third of the clinical activity of its parent and therefore the clinical effects of ketamine are prolonged in the presence of hepatic insufficiency. The metabolites of norketamine are excreted by the kidneys. The usual cardiac stimulating effects caused by central stimulation of the sympathetic system are not present in the denervated heart, but ketamine can still increase systemic vascular tone. Ketamine has neuroexcitatory effects and is known to cause myoclonic activity, although its ability to actually cause seizures is debated [23]. However, there are case reports of seizures after its administration in patients who have previously had liver transplant and in the presence of cyclosporine, an immunosuppressant drug with the potential for neurotoxicity [24]. Table 4 is an abbreviated list of drugs commonly used in the perioperative period that have active metabolites that require renal excretion and accumulate in patients with renal insufficiency.

Table 4 Drugs with renally excreted active metabolites and their actions

Data from Littlewood K. The immunocompromised adult and surgery. Best Pract Res Clin Anaesth 2008;22(3):585–609.

All inhaled anesthetics have been used in transplanted patients with success. Among the inhaled anesthetics currently used, only halothane requires a truly cautionary note given its potential for hepatotoxicity and direct cardiac depressant effects. Of the most commonly used volatile anesthetics in the United States today, isoflurane, desflurane, and sevoflurane, there does not seem to be a significant clinical advantage or disadvantage of one over the others. The choice of inhaled anesthetic can be dictated by the anesthesiologist’s preference, experiences, and comfort with the anesthetic [25]. The decision whether or not to use a volatile anesthetic need not be imposed by the presence of a transplanted organ, but should be guided by other patient factors, such as hemodynamic stability and history or risk of malignant hyperthermia. The theoretic risk of nephrotoxicity caused by the liberation of free fluoride and Compound A following sevoflurane metabolism does not seem to be a true clinical concern outside of laboratory animals [4,25]. The decision to use nitrous oxide (N₂O) as part of the anesthetic should be considered with caution. Whether or not to use N₂O as part of the anesthetic should be based on clinical findings of the patient and type of surgical procedure, such as the potential for postoperative nausea and for expanding air-filled cavities such as pneumothorax, intestinal obstruction, and tympanic membrane grafts. It is probably prudent to avoid prolonged use of N₂O because of the potential risk of bone marrow suppression and the potential for altered immunologic response (impaired chemotaxis and motility of polymorphonuclear leukocytes) [25]. Although these effects were seen in laboratory animals receiving N₂O for more than 24 hours, they may be potentiated in immune-compromised patients. N₂O can also worsen preexisting pulmonary hypertension, which may be present in patients who have undergone lung, heart, or liver transplant, by increasing pulmonary vascular resistance and potentiating hypoxemia. N₂O is best avoided in patients who have known or suspected pulmonary hypertension. Although there is little data on the use of N₂O in the transplanted population, the brief use of N₂O during induction or emergence is probably acceptable and without clinical consequence but may be best avoided if there are alternatives [25,26].

The decision to use neuromuscular blockade should be based on the type of surgery and actual need for muscle relaxation during the procedure or the need to optimize intubating conditions. The choice of specific neuromuscular blocking agent to be used should be dictated by length of surgery, underlying medical illnesses such as myasthenia or other neuromuscular disorders, history of malignant hyperthermia, and the functional state of the patient’s kidney and liver. Of the nondepolarizing agents, the metabolism and clearance of mivacurium, a short-acting agent, and cisatracurium and atracurium, intermediate-acting agents, are independent of kidney and liver function (Table 5). In the presence of a normally functioning kidney or liver graft, other nondepolarizing agents, such as vecuronium, rocuronium, and pancuronium, exhibit normal clinical activity, but can have prolonged effects in the face of hepatic or renal insufficiency and require dose adjustments and close neuromuscular monitoring and evidence of full reversal before extubation [27]. Some immune-suppressant drugs can have effects on neuromuscular blockade. Azathioprine can increase the dose required to achieve and maintain muscle relaxation and cyclosporine can prolong the action of the neuromuscular blocking agents [28]. Succinylcholine, the only depolarizing agent available in the United States currently, is used frequently in this population given the need for rapid sequence intubation and rapid airway control. There are no contraindications in patients who have undergone organ transplant with the possible exception of previous cardiac transplant, in which its actions can be complex. Otherwise, succinylcholine should be avoided only if there are other clinical reasons, such as hyperkalemia, muscular dystrophy, or history of malignant hyperthermia [27,28].

Table 5 Drugs not solely dependent on renal and/or hepatic elimination

There are few contraindications to performing a regional or neuraxial anesthetic in previously transplanted patients. The consideration of spinal or epidural anesthesia is appropriate in this population as long as there is no increased risk for bleeding complications. There may be several advantages to choosing a neuraxial or regional technique in this population. Superior analgesia over systemic opioids, especially in patients who may have narcotics tolerance as a result of long-term opioid use, reduced pulmonary complications, decreased incidence of graft occlusion, and improved joint mobility are just a few of the benefits of regional and neuraxial anesthesia [29]. Clinically relevant doses of bupivicaine and ropiviciane, which are commonly used local anesthetics for neuraxial anesthesia, do not seem to result in toxic levels or increased risk of toxic effects in renal and liver transplant recipients [8,14]. However, it is important to be prepared for the risk of hypotension because of preexisting autonomic neuropathy and cardiac denervation in this population when performing a neuraxial anesthetic [9,29]. Concurrent hemodynamic monitoring is imperative during the procedure. Direct and indirect-acting adrenergic agonists should be readily available along with emergency airway supplies. Cautious correction of hypovolemia before epidural or spinal anesthesia may help to attenuate the hypotension.

Although the risk of epidural abscess complicating epidural anesthesia is low (about 1 in 2000 or less), there seems to be a very slight increase of the incidence in immunocompromised patients in many epidemiologic series. Staphylococcus aureus is isolated in approximately two-thirds of the epidural abscesses indicating infection from normal skin flora. Meningitis after spinal anesthesia seemingly does not have a greater disposition for immunocompromised hosts compared with healthy patients. When meningitis occurs after spinal anesthesia, the organism cultured is usually an oropharyngeal bacteria implying iatrogenic infection from the proceduralist [29,30]. Therefore, if a neuraxial block is included in the anesthetic plan, it is imperative that strict aseptic technique is practiced and a mask should be worn. Although the risk of infectious complications is very low, it is important to be highly vigilant when monitoring these patients after a neuraxial anesthetic as the attenuated inflammatory response may diminish the typical signs and symptoms of epidural abscess or meningitis [29].

There is limited information available on the incidence of infectious complications after peripheral nerve block procedures in immunocompromised patients, other than a few case reports and series. Overall, the incidence of infectious complications seems to be extremely low, even in immune-suppressed patients. When they do occur, the organisms cultured are similar to those found in infections after neuraxial anesthesia, Staphylococcus aureus and mouth organisms, indicating skin or mouth flora from the anesthesiologist or patient as the source [31]. Again, aseptic technique and a mask should be considered essential when performing these procedures.

There may be other, albeit less well understood benefits of using a neuraxial or regional anesthetic technique in this population. There is consistent evidence that surgical stress suppresses both cellular and humoral immune function for several days after surgery. This effect may be exaggerated or prolonged in patients with preexisting immune dysfunction. General anesthetics alone do not diminish the surgical stress response [20,29]. Neuraxial anesthesia and postoperative analgesia are associated with some preservation of cell-mediated immunity and attenuated inflammatory response. Local anesthetics themselves lessen the inflammatory response to stress and injury [20,32]. The risk to benefit ratio of neuraxial anesthesia or regional block may, therefore, be altered in previously transplanted patients. The decision to perform a regional or neuraxial anesthetic technique in a previously transplanted patient must be made on an individual basis. Anesthetic alternatives, the risks of the technique that may be increased, balanced with the potential for greater benefit should all be carefully considered when constructing the anesthetic plan in this population.