Noncardiac surgery in heart transplant recipients in the cyclosporine era

Noncardiac

Surgery

in Heart Transplant

Recipients

in the Cyclosporine

Era

Jose A. Melendez, MD, Ellise Delphin, MD, Joanne Lamb, RN, CCRN, and Eric Rose, MD As survival and quality of life continue to improve for cardiac transplant recipients, there is an ever-increasing possibility that these patients will present for elective and/or emergency surgery outside of a transplantation center. Cyclosporine therapy has been a major factor in extending homograft survival, but recent studies have suggested that cyclosporine administration increases the duration of action of some anesthetics. The authors evaluated the influence on anesthetic management of cardiac transplantation and chronic

T

HE FREQUENCY of cardiac transplantation has increased markedly since the introduction of cyclosporine therapy in 1983. As the duration of posttransplant survival has improved and the incidence of intercurrent infection has decreased, there is an increasing likelihood that some of these patients will require elective and/or emergency operations outside of major transplantation institutions. Recent animal studies have suggested that a single dose of cyclosporine may result in an increased duration of action of both barbiturates and narcotics.’ Because there are no clinical studies addressing the issue, this review had the following goals: (1) to present the authors’ experience in the perioperative management of these patients, and (2) to attempt to identify differences in the response of these patients to general and regional anesthesia. MATERIALS

AND METHODS

The anesthetic records of all heart recipient patients who subsequently underwent noncardiac surgery between March 1983 and January 1988 at this institution were reviewed. Particular attention was paid to the dosages of intravenous and inhalation anesthetics administered scrutinizing charts for evidence of delayed awakening (unusually prolonged emergence) or unplanned postoperative ventilation. In addition, the physiological monitors used were tabulated. Cyclosporine levels determined at the time of surgery were also recorded. RESULTS

Twenty-eight of the 124 heart transplant recipients grafted at the study hospital between March 1983 and January 1988 subsequently underwent 35 noncardiac operative procedures requiring an anesthetic. The surgical procedures are listed in Table 1. All operations were performed between 4 months and 4 years following transplantation, and all patients had been maintained on chronic immunosuppression with cyclosporine for a minimum of 1 month prior to surgery. Cyclosporine levels were followed weekly and all patients had therapeutic levels perioperatively. Endomyocardial biopsies were performed within 2 weeks of operaFrom the Departments of Anesthesiology and Cardiac Surgery, College of Physicians and Surgeons. Columbia University, and Presbyterian Hospital, New York, NY. Presented in abstract form at the 1988 Annual Meeting of Intemational Anesthesia Research Society San Diego, CA. Reprints not available. Copyright B 1991 by W.B. Saunders Company 1053.077019110503-0005$03.00l0 218

cyclosporine therapy in a retrospective review of all postcardisc transplant patients who presented for noncardiac surgery at the study institution. The data suggest that a number of commonly used anesthetic techniques can be administered safely to these patients when no evidence of graft rejection is present. No clinically significant prolongation of anesthetic effect was encountered following the doses of anesthetics described. Copyright o 1991 by W.B. Saunders Company

tion; no patient was acutely rejecting at the time of examination. Additional “stress” doses of corticosteroids were uniformly administered perioperatively. Intraoperative monitoring included electrocardiography (ECG), blood pressure (BP) by oscillometric technique. esophageal stethoscope, temperature, pulse oximetry, and end-tidal CO?. Strict sterile precautions were maintained in the insertion of all intravascular devices. Invasive central monitoring and intraarterial cannulation were used in only three patients. Two patients, both undergoing thoracotomy for septic abscesses, had central venous catheter insertion preoperatively; one patient underwent pulmonary artery catheterization for resection of a thoracic aortic aneurysm. Thirty-three operations were performed under general anesthesia. Two inhalation inductions with 70% NzO in 0, and 2.5% halothane were performed in one j-year-old child, once for a lymph node biopsy and once for a herniorrhaphy. There was no hypotension or dysrhythmia. In all other patients, anesthesia was induced with either intravenous (IV) sodium thiopental, sodium thiopental and narcotic, or midazolam. When used as the sole induction agent, the amount of sodium thiopental administered to produce unconsciousness was 4 to 5 mg/kg. When used in combination with IV fentanyl. 2 to 3 p&kg, as m 50% of the cases, the dose of sodium thiopental was reduced to 2 to 3 mgikg. Three patients received IV midazolam, 0.15 mg/kg, for induction of anesthesia. There was no evidence of a BP reduction greater than 20% following induction of general anesthesia. Anesthesia was maintained with morphine (2 patients) or fentanyl (4 patients), plus relaxant and a nitrous oxide,; oxygen mixture. Inspired NZO concentrations ranged from 50% to 70% in OZ. The most commonly used narcotic was fentanyl, in a dose range of 3 to 5 ug,kg/h. Twenty-seven patients received isoflurane in combination with fentanyl: nitrous oxide/oxygen. The most common concentration of isoflurane used was 0.5% to l%, inspired. The dosage of fentanyl used in conjunction with N,O/O,/isoflurane ane\thesia ranged from 1 to 3 kg/kg/h. Muscle relaxants used for intubation included succinylcholine, 1 mgikg, in 3 patients; metacurine, 3 mg/kg, in 1tJ patients; pancuronium, 0.1 mgikg, in 2 patients; atracurium, 0.5 mg/kg, in 2 patients; and vccuronium, 0.1 mg/kg, in 10 patients. The need for additional doses of muscle relaxants was continually assessed with the use of a peripheral nerve stimulator. Paralysis was easily reversed in all patients at

Journalof Card/othoraoc and VascularAnesthes/a,

Vol 5, No 3 (June), 1991: pp 218.220

NONCARDIAC SURGERY IN TRANSPLANT

219

RECIPIENTS

Table 1. Surgical Procedures Performed in Heart Transplant Recipients on Cyclosporine

Procedure

No. of Cases

Type of Anesthetic

Pacemaker insertion

3

MAC

Open lung resection

2

GA

Sternal wound debridement

2

GA

Pleural abrasion

GA

Thoracic aortic aneurysm resection

GA

Exploratory laparotomy

GA GA

Iliac artery exploration Cholecystectomy

8

GA

2

1 SP. 1 GA

Drainage of rectal abscesses lnguinal herniorrhaphy

GA GA

Ventral herniorrhaphy

MAC

Cataract surgery Lymph node biopsy

GA 1 SP, 1 GA

Resection aspergilloma thigh Therapeutic abortion

GA GA

Bilateral hip replacement Bilateral core reversal

2

GA

Arthroscopy

2

GA

Abbreviations: MAC, monitored anesthetic care; GA, general anesthesia; SP, spinal anesthesia.

the termination of surgery after a single dose of neostigmine, 2.5 mg, IV, and glycopyrrolate, 0.6 mg, IV. Spinal anesthesia with tetracaine was used for two procedures: a hernia repair and drainage of a thigh abscess. Both patients received 1 L of lactated Ringer’s solution prior to administration of the spinal local anesthetic. The calculated dose of tetracaine was based on the patient’s height and location of the planned surgical incision. In one case, 8 mg of tetracaine achieved a T, anesthetic level that lasted for 4.5 hours. In the other, 10 mg of tetracaine with epinephrine (0.1 mL of l:l,OOO solution) reached a T, anesthetic level that persisted for 9 hours. In both cases the dose provided excellent motor and sensory blockade. Both BP and heart rate (HR) remained stable without vasopressor therapy following the onset of anesthesia. Hemodynamic instability was not a problem in any case. The preoperative HR of between 90 and 105 beats/min remained unchanged throughout surgery without clinically troublesome dysrhythmias. There was little variation in BP, remaining between 100 and 150 mm Hg systolic in all cases. There were few variations greater than 10 to 15 mm Hg in any individual’s record. Particularly noteworthy was the absence of an immediate sympathetic response either to endotracheal intubation or to surgical incision. Prolonged duration of anesthesia did not occur in the postoperative period. Delayed awakening was not evident and there was no required reintubation or unplanned postoperative ventilation. The duration of recovery room stay ranged from 1.5 to 7.5 hours (mean, 2.6 2 1.8 hours). DISCUSSION

Cardiac transplant recipients present the anesthesiologist with the twin problems of chronic immunosuppression and myocardial denervation. Interestingly, this survey suggests that these patients may have similar monitoring and

anesthetic requirements to patients who have not undergone cardiac transplantation. A variety of agents was administered safely, both for induction and maintenance of anesthesia. Of particular interest was that halothane, a potent myocardial depressant used for one pediatric induction, was tolerated in relatively high inspired concentrations without untoward effect. This, although an interesting observation, should not lead to the belief that all patients would react similarly. The incidence of infectious etiologies as the primary diagnosis leading to surgery in this series was 25%, markedly reduced from the prior estimate of greater than 50%.2 This is most likely a result of changing immunosuppressive therapy with the addition of cyclosporine and reduction in steroid use. However, infection is still the leading cause of morbidity and mortality in this patient population. Accordingly, it is imperative that these patients be handled with extreme sterile precautions, particularly when placing intravascular catheters and airway equipment. Despite prior recommendations for the use of central venous pressure monitoring for maintenance of euvolemia in these patients,’ this review demonstrated a minimal amount of invasive monitoring use, clearly reducing infection sources. This failed to have deleterious effects on patient care. These patients do not seem to require any additional monitoring than that which would have been used in nontransplant patients undergoing similar procedures. The inability of the denervated heart to mount a rapid tachycardic response requires particular attention with regard to maintenance of intravascular volume status. To prevent intraoperative hypotension, adequate preload must be available. This is particularly true for patients receiving spinal anesthesia. Remarkable hemodynamic stability was found in these patients after they had received 1 L of lactated Ringer’s solution prior to administration of the spinal local anesthetic. In patients receiving general anesthesia, the perioperative hemodynamic profiles were most interesting. There were minimal HR and BP responses to endotracheal intubation and surgical incision, presumably a result of the denervation of the heart following transplantation. Gradual increases in both HR and BP were observed during surgery, and these changes have been attributed to increasing circulating catecholamine levels occurring with prolonged surgical stimulation.’ It has been suggested that graft rejection markedly increases intraoperative morbidity.’ Thus, it is crucial that endomyocardial biopsy information be available prior to elective surgery and that adequate levels of cyclosporine be maintained throughout the perioperative period. It is believed that the excellent outcomes observed in this series of patients are related to the absence of rejection at the time of surgery. Despite the salutary effects of cyclosporine, alterations in drug activity have been observed in animals after receiving a single dose of this immunosuppressant. Cirella et al’ showed an increase in the hypnotic effect of barbiturates and an increased analgesic effect of fentanyl. Increased drug availability was excluded as a causative factor; therefore, it was suggested that cyclosporine altered central

MELENDEZ

nervous system sensitivity to these agents. Similar studies by Gramstad et al demonstrated enhanced neuromuscular blockade by vecuronium and atracuriumP However, in the clinical setting, it does not appear that patients chronically maintained on cyclosporine have much of a decreased requirement for nondepolarizing neuromuscular blocking agents. Other immunosuppressive agents have been implicated in the antagonism of muscle relaxants, ie, azathioprine. This was not of concern because the present patients only received prednisone as adjuvant immunosuppression to cyclosporine. The authors are not aware of muscle relaxant potentiation attributed to steroids. Although acutely administered cyclosporine clearly potentiates the effect of some anesthetics, chronically, it may increase their metabolism and/or alter their volume of distribution resulting in no overall clinical effect. In summary, this patient population was found to be within the normal range of dose requirement for IV and inhalational agents, muscle relaxants, and local anesthetics.

ET AL

There was no apparent instance of prolonged action with any of the anesthetics administered. However, the study is a retrospective chart review; a well-controlled prospective trial, in which patients are matched by operation and anesthetic, would be required to ultimately address the question of the clinical relevance of cyclosporine on anesthetic requirements. In conclusion, it was found that cardiac transplant recipients can be safely anesthetized using carefully titrated routine doses of anesthetic agents as long as there is no evidence of active graft rejection. Particular attention must be addressed to maintenance of intravascular volume status and meticulous attention to sterile technique in these immunocompromised patients. Although it was not possible to rule out a potentiating effect of chronic cyclosporine on anesthetic dose requirements, no clinically significant prolongation of action of any drugs administered in the perioperative period was observed.

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