IMMUNOSUPPRESSIVE therapy with cyclosporine has been reported to increase the risk of cholelithiasis in cardiac transplant recipients. [1]This may increase the need for cholecystectomy in these patients. [2]During orthotopic cardiac transplantation, the cardiac plexus is divided, which leads to persistent denervation of the heart, causing abnormal responses to stress. [3,4]Because the posttransplantation cardiac function profile is different from normal innervated cardiac function, hemodynamic changes during laparoscopic cholecystectomy (LC) in these patients may differ from those observed in healthy patients. [5]We evaluated the hemodynamic changes associated with pneumoperitoneum and patient position changes during elective LC in 11 consecutive cardiac transplant recipients.

After receiving institutional review board approval, we enrolled in the study 11 consecutive consenting patients who had undergone orthotopic cardiac transplantation and who were scheduled for elective LC. On arrival at the operating room and after being fitted with routine monitoring devices, all patients received 1 to 2 mg intravenous midazolam. Before induction of anesthesia, the radial artery was cannulated using a 20-gauge catheter, and a 7.5 French thermodilution pulmonary artery catheter (model 131–74; Baxter Edwards, Irvine, CA) was introduced through the left internal jugular vein. General anesthesia was induced with administration of etomidate (0.1 to 0.2 mg/kg given intravenously) and alfentanil (75 to 200 micro gram given intravenously). Vecuronium (0.1 mg/kg given intravenously) was used to facilitate tracheal intubation and maintain muscle relaxation. General anesthesia was maintained with 0.5 to 1.5% isoflurane and intermittent doses of alfentanil (100 to 500 micro gram given intravenously). Patients' lungs were mechanically ventilated with 50% oxygen in air, and end-tidal carbon dioxide concentrations were maintained between 35 and 40 mmHg. The operation was performed by the same surgeon (M.L.F.) using a standard surgical technique. The intraabdominal pressure was automatically maintained at 15 mmHg with a carbon dioxide insufflator (WISAP insufflator; Semm Systems, Munchen, Germany).

Intraoperative monitoring included continuous electrocardiograms (leads II and V5), arterial blood pressure, pulse oximetry, capnography, body temperature, peak airway pressures, and neuromuscular function using a nerve stimulator. Hemodynamic variables, including heart rate, mean arterial pressure, pulmonary artery occlusion pressure, central venous pressure, and cardiac output, were recorded at predetermined intervals (T1= before induction of anesthesia; T2= 5 min after induction of anesthesia but before incision; T3= 5 min after peritoneal carbon dioxide insufflation and reverse Trendelenburg's position and left lateral tilt; T4-8 = every 10 min after reverse Trendelenburg's position; T9= after deflation of the abdomen and return to supine position; and T10= 10 min after attaining supine position). From these measured variables, cardiac index (CI), systemic vascular resistance (SVR), and pulmonary vascular resistance were calculated. The pressure transducers were located at the level of the right atrium and moved to the same level with changes in patient position. In addition, arterial blood gases were measured before and 20 min after carbon dioxide insufflation.

Data are presented as means +/- standard deviations. Data were analyzed using two-way analysis of variance with Tukey-Kramer correction or Kruskal-Wallis test as appropriate. A probability value less than 0.05 was considered statistically significant.

(Table 1) shows patients' demographic and clinical characteristics. All patients were classified as American Society of Anesthesiologists physical status 3. The CI decreased significantly after induction of anesthesia, but it returned to preinduction values after carbon dioxide insufflation and reverse Trendelenburg's positioning and did not change significantly thereafter (Table 2). The mean arterial pressure decreased significantly after induction of anesthesia, but it returned to preinduction values after insufflation and decreased again 10 min after patients were placed in the reverse Trendelenburg's position and remained significantly lower than baseline until the end of the study (Table 2). Compared with postinduction values, the central venous pressure and pulmonary artery occlusion pressure increased after carbon dioxide insufflation and reverse Trendelenburg's positioning and remained significantly high until 20 min and 40 min after reverse Trendelenburg's positioning, respectively. Pulmonary vascular resistance increased after induction of anesthesia and remained significantly high until 20 min after reverse Trendelenburg's positioning. No significant changes in the heart rate and SVR were observed throughout the study (Table 2). None of the patients exhibited any adverse effects requiring supportive treatment. The postoperative course was uncomplicated in all cases.

Table 1. Demographic and Clinical Data in Cardiac Transplant Patients Undergoing Laparoscopic Cholecystectomy

Table 1. Demographic and Clinical Data in Cardiac Transplant Patients Undergoing Laparoscopic Cholecystectomy
Table 1. Demographic and Clinical Data in Cardiac Transplant Patients Undergoing Laparoscopic Cholecystectomy

Table 2. Measured and Derived Data at Various Time Points during Laparoscopic Cholecystectomy in Cardiac Transplant Recipients

Table 2. Measured and Derived Data at Various Time Points during Laparoscopic Cholecystectomy in Cardiac Transplant Recipients
Table 2. Measured and Derived Data at Various Time Points during Laparoscopic Cholecystectomy in Cardiac Transplant Recipients

We found that the cardiac index does not change significantly during pneumoperitoneum in orthotopic cardiac transplant recipients. This is in contrast to previous reports of a significant decrease in CI during LC in healthy patients [5–7]and in those with significant cardiopulmonary dysfunction. [8,9]The differences in the hemodynamic responses may be due to persistent denervation of the heart and related pathophysiologic changes in the cardiovascular system after orthotopic cardiac transplantation [3,10]or due to differences in anesthetic techniques.

After orthotopic cardiac transplantation, the myocardial contractility and myocardial reserve are normal. [11–13]However, the interruption of the sympathetic and parasympathetic nerve fibers to the donor heart affects the regulation of the cardiovascular system. Adaptation to stress is altered as the heart responds primarily by increasing the stroke volume, which depends on venous return and the Frank-Starling mechanism. [10]In addition, there is a lag period in the hemodynamic response because the cardiac output is increased secondary to humoral reflexes (catecholamine release) rather than to neural reflexes. The absence of vagal tone results in a higher resting heart rate and a loss of normal responses to the Valsalva maneuver. Furthermore, exaggerated responses to catecholamines have been observed in cardiac transplant recipients, which is attributed to an increase in receptor density (upregulation). [14]Exaggerated responses may also be due to availability of a greater proportion of local catecholamines, which, because of cardiac denervation, are not removed by neuronal uptake. [15].

Hemodynamic changes during LC in patients with an innervated heart include increase in mean arterial pressure, decrease in CI, and increase in SVR. The possible causes of the hemodynamic changes observed during LC are complex, and it is difficult to distinguish the effects of increased intraabdominal pressure (from creation of pneumoperitoneum), systemic absorption of insufflated carbon dioxide, and reverse Trendelenburg positioning from those of neurohumoral responses. [16]This may explain the variability in the hemodynamic response observed by various investigators during LC. [5–7,17,18].

Previous studies have reported a biphasic change in CI (i.e., an initial reduction in CI followed by gradual restoration) after creation of pneumoperitoneum. [5,7]After pneumoperitoneum, the CI is reduced by approximately 50% of the baseline. [5]Cunningham and associates [6]reported that in healthy patients, the left ventricular function, as determined by transesophageal echocardiographic estimation of ejection fraction, was preserved after carbon dioxide insufflation and changes in patient position. The reported increase in mean arterial pressure may represent an increase in afterload (SVR), which is attributed to neurohumoral responses during LC. [16]A recent study reported a linear correlation between changes in mean arterial pressure and increases in plasma concentrations of renin and aldosterone. [19]The plasma concentrations of vasopressin increased significantly after pneumoperitoneum and paralleled the time course of increase in SVR. [20].

In contrast to previous reports, we did not observe an increase in mean arterial pressure and SVR or any decrease in CI in our patients with denervated hearts. It is possible, but remains to be demonstrated, that neurohumoral responses during LC in posttransplant patients may be different from those observed in healthy patients. [21–23]The cause-effect relationship between CI and SVR is unclear. The decrease in CI observed by previous authors may have increased the SVR. The initial decrease in CI observed in this study may be due to the myocardial depressive effects of the drugs used to induce anesthesia. The increase in the CI after insufflation may have resulted from an increase in venous return, as suggested by an increase in the central venous pressure and pulmonary artery occlusion pressure. The increase in central venous pressure and pulmonary artery occlusion pressure may be the result of an increase in the intravascular volume due to compression of the abdominal organs (liver and spleen) caused by increased intraabdominal pressure. Furthermore, a 15% increase in blood volume after cardiac transplantation may explain the maintenance of cardiac output. [24]Because the cardiac output in heart transplant recipients depends on the Frank-Starling mechanism, increased intravascular volume should improve cardiac output. On the other hand, measured increases in central venous pressure and pulmonary artery occlusion pressure only reflect transmitted intrathoracic pressures, and the reverse Trendelenburg's position and increased intrathoracic pressure may actually decrease venous return and cardiac filling pressures. Our results, however, seem to support the idea that the Frank-Starling mechanism is activated by increased filling pressures. As observed in this study, retrospective analyses of cardiac transplant patients undergoing noncardiac surgery found no significant adverse hemodynamic changes. [25].

The increased sensitivity of the transplanted heart to catecholamines, [14]compared with healthy patients, may help preserve cardiac performance by increasing myocardial contractility. In addition, the absence of increased afterload (SVR) also may have maintained the CI. [16]Furthermore, carbon dioxide insufflation in supine patients rather than in those in reverse Trendelenburg's position (as performed in the previous study [5]) may be responsible in part for the maintaining the CI. The lack of a Valsalva response to the pneumoperitoneum may also have played a role in maintaining the CI.

We evaluated the combined effects of carbon dioxide insufflation and reverse Trendelenburg's position because the time period between these two events is usually short. Carbon dioxide insufflation in supine patients and delay between carbon dioxide insufflation and change of position may further modify hemodynamic changes during LC. In addition, use of transesophageal echocardiography may have provided more information, such as left ventricular end systolic and end diastolic areas at every stage of the operation. Furthermore, measurement of the various humoral factors and transmural filling pressures may explain the differences in the hemodynamic changes in these patients.

This preliminary study shows that orthotopic cardiac transplant recipients anesthetized with isoflurane and alfentanil show minimal hemodynamic changes with carbon dioxide insufflation and reverse Trendelenburg's position during LC.

The authors thank the anesthesia residents and fellows for help in collecting these data. The authors would also thank C. T. Suit, Research Associate, Baylor University Medical Center at Dallas, for collating these data and Vicky Howard for secretarial help.

Spes CH, Angermann CE, Beyer RW, Schreiner J, Lehnert P, Kemkes BM, Theisen K: Increased incidence of cholelithiasis in heart transplant recipients receiving cyclosporine therapy. J Heart Transplant 1990; 9:404-7.
Sekela ME, Hutchins DA, Young JB, Noon GP: Biliary surgery after cardiac transplantation. Arch Surg 1991; 126:571-3.
Regitz V, Bossaller C, Strasser R, Schuler S, Hetzer R, Fleck E: Myocardial catecholamine content after heart transplantation. Circulation 1990; 82:620-3.
Bailey PL, Stanley TH: Anesthesia for patients with a prior cardiac transplantation. J Cardiothorac Anesth 1990; 4:38-47.
Joris JL, Noirot DP, Legrand MJ, Jacquet NJ, Lamy ML: Hemodynamic changes during laparoscopic cholecystectomy. Anesth Analg 1993; 76:1067-71.
Cunningham AJ, Turner J, Rosenbaum S, Rafferty T: Transoesophageal echocardiographic assessment of haemodynamic function during laparoscopic cholecystectomy. Br J Anaesth 1993; 70:621-5.
Westerband A, Van De Water JM, Amzallag M, Lebowitz PW, Nwasokwa ON, Chardavoyre R, Abou-Taleb A, Wang X, Wise L: Cardiovascular changes during laparoscopic cholecystectomy. Surg Gynecol Obstet 1992; 175:535-8.
Fox LG, Hein HAT, Gawey BJ, Hellman CL, Ramsay MAE: Physiologic alterations during laparoscopic cholecystectomy in ASA III & IV patients (abstract). ANESTHESIOLOGY 1993; 79:A55.
Safran D, Sgambati S, Orlando RI: Laparoscopy in high-risk cardiac patients. Surg Gynecol Obstet 1993; 176:548-54.
Clark DA, Schroeder JS, Griepp RB, Stinson EB, Dong E, Shumway NE, Harrison DC: Cardiac transplantation in man: Review of first three year's experience. Am J Med 1973; 54:563-76.
Von Scheidt W, Neudert J, Erdmann E, Kemkes BM, Gokel JM, Autenrieth G: Contractility of the transplanted, denervated human heart. Am Heart J 1991; 121:1480-8.
Stinson EB, Caves PK, Griepp RB, Oyer PE, Rider AK, Shumway NE: Hemodynamic observations in the early period after human heart transplantation. J Thorac Cardiovasc Surg 1975; 69:264-70.
Borow KM, Neumann A, Arensman FW, Yacoub MH: Left ventricular contractility and contractile reserve in humans after cardiac transplantation. Circulation 1985; 71:866-72.
Gilbert EM, Eiswirth CC, Mealey PC, Larrabu P, Herrick CM, Bristow MR: beta-adrenergic supersensitivity of the transplanted human heart is presynaptic in origin. Circulation 1989; 79:344-9.
Goldstein DS, Brush JE, Eisenhofer G, Stull R, Esler M: In vivo measurement of neuronal uptake of norepinephrine in the human heart. Circulation 1988; 78:41-8.
Wahba RWM, Beique F, Kleiman SJ: Cardiopulmonary function and laparoscopic cholecystectomy. Can J Anaesth 1995; 42:51-63.
Iwase K, Takenaka H, Yagura A, Ishizakz T, Ohata T, Takagaki M, Oshima S: Hemodynamic changes during laparoscopic cholecystectomy in patients with heart disease. Endoscopy 1992; 24:771-3.
Liu S-Y, Lieghton T, Davis I, Klein S, Lippmann M, Bongard F: Prospective analysis of cardiopulmonary responses to laparoscopic cholecystectomy. J Laparoendosc Surg 1991; 1:241-6.
O'Leary E, Hubbard K, Tormey W, Cunningham AJ: Laparoscopic cholecystectomy: Hemodynamic and neuroendocrine responses after pneumoperitoneum and changes in position. Br J Anaesth 1996; 76:640-4.
Joris J, Lamy M: Neuroendocrine changes during pneumoperitoneum for laparoscopic cholecystectomy (abstract). Br J Anaesth 1993; 70:A33.
Aoki T, Tanii M, Takahashi K, Tateda T, Miyazawa A: Cardiovascular changes and plasma catecholamine levels during laparoscopic surgery (abstract). Anesth Analg 1994; 78:S8.
Felber AR, Blobner M, Goegler S, Senekowitsch R, Jelen-Esselborn S: Plasma vasopressin in laparoscopic cholecystectomy (abstract). ANESTHESIOLOGY 1993; 79:A32.
Mealy K, Gallagher H, Lennon F, Traynor O, Hyland J: Physiological and metabolic responses to open and laparoscopic cholecystectomy. Br J Surg 1992; 79:1061-4.
Tamburino C, Corcos T, Feraco E, Leger P, Desrveness M, Vaissier E, Gandjbakhch I, Pavie A, Cabrol A, Cabrol C: Hemodynamic parameters one and four weeks after cardiac transplantation. Am J Cardiol 1989; 63:635-7.
Cheng DCH, Ong DD: Anaesthesia for non-cardiac surgery in heart-transplanted patients. Can J Anaesth 1993; 40:981-6.