Unexplained intraoperative hypotension, acute ischemic hepatitis, and pancreatitis associated with aortorenal bypass surgery

Unexplained Intraoperative Hypotension, Acute Ischemic Hepatitis, and Pancreatitis Associated With Aortorenal Bypass Surgery Pavel J. Levy, MD, Juraj Sprung, MD, PhD, Aldo H. Tabares, MD, Andrew C. Novick, MD, and Jerome F. O'Hara, Jr, MD URGICAL revascularization of the kidneys is beneficial in patients with poorly controlled hypertension who are in the early stages of chronic renal insufficiency secondary to renal arterial stenosis. 1,2 Aortorenal saphenous vein grafting, a commonly used procedure in these patients, t is safe with relatively low morbidity and mortality rates) A transient intraoperative visceral organ ischemia that occurred in a patient with severe atherosclerotic visceral disease and who required potent vasopressor treatment for unexplained intraoperative hypotension is reported. Such hypotension could have resulted from visceral organ ischemia not recognized intraoperatively. Alternatively, the primary hypotension may have exacerbated visceral organ hypoperfusion associated with the atherosclerotic visceral disease to cause ischemic injury of the liver and pancreas. The possible pathogenesis of this rare complication is discussed.

S

CASE REPORT A 69-year-old male smoker who had severe atherosclerotic renovascular disease associated with progressive deterioration of kidney function, poorly controlled hypertension, and a 5-cm solid fight renal mass was scheduled for partial nephrectomy and hepatorenal bypass. He had no history of other cardiovascular disease or prior abdominal surgery. The physical examination was unremarkable except for a blood pressure of 170/90 mmHg. Laboratory studies included normal white blood cell count, hematocrit, platelet count, liver function tests, and clotting characteristics. The blood urea nitrogen concentration was 25 mg/dL (normal, 8 to 25 mg/dL); creatinine, 2.2 mg/dL (normal, 0.7 to 1.4 mg/dL); and creatinine clearance, 25 mL/min. Carbon dioxide arteriography was performed 1 month before the surgery and showed bilateral proximal 80% renal artery stenosis. A lateral aortogram showed a mild proximal celiac trunk stenosis with patent splenic, hepatic, and superior mesenteric arteries, and occluded inferior mesenteric artery. The right hepatic artery originated from the superior mesenteric artery and had a 50% to 60% osteal stenosis. The preoperative electrocardiogram and thallium stress test were normal; a carotid duplex ultrasound showed a 40% to 59% stenosis of the fight internal carotid artery. Under general endotracheal anesthesia (induction and endotracheal intubation with 150 mg of propofol and 10 mg of vecuronium, and maintenance with oxygen, nitrous oxide, and isoflurane), a bilateral subcostal incision was made, and a Bookwalter retractor was positioned. At exploration, a decreased pulse was noted in the porta hepatis area; therefore, an aortorenal rather than a hepatorenal bypass was performed. After resection of the kidney mass under cold ischemia (duration, 45 minutes), the anterolateral side of the aorta was clamped, and an aortorenal bypass with a reversed greater saphenous vein graft was performed with warm ischemia time of 25 minutes. The patient received no systemic heparinization and only regional arterial heparin flushes (up to 1,000 U) were used during the revascularization. The operation lasted about 4 hours. During the first 2 hours, the systolic blood pressure was

Journal of Cardiothoracic and Vascular Anesthesia,

between 100 and l l 0 mmHg, and a continuous intravenous dopamine drip (dose, 1 to 3 ~tg/kg/min) was administered. The central venous pressure was 15 to 18 mmHg. During the last 2 hours of the surgery, the systolic blood pressure was maintained between 90 to 100 mmHg (despite relatively low blood loss and light anesthesia with 0.2% to 0.3% isoflurane) with increased fluid administration, and dopamine and epinephrine infusions at 12 ~g/kg/min and 0.03 to 0.07 pg/kg/min, respectively. The estimated blood loss during the entire operation was 1,500 mL, and the patient received 2 U of packed red blood cells. In addition, the patient received 8,000 mL of crystalloid solution and 500 mL of 5% albumin. Two hours after the beginning of the operation, the blood gas measurements indicated metabolic acidosis (pH 7.22; PaCO2, 40 mmHg, HCO3, 16 mmol/L, base deficit - 1 0 retool/L). During the rest of the surgery a base deficit of - 7 to - 1 4 mmol/L existed despite repeated administration of sodium bicarbonate. Immediate postoperative laboratory results (Table 1) revealed markedly elevated liver transaminase and pancreatic enzymes (lipase and amylase), excessive leukocytosis, thrombocytopenia, and severe lactic acidemia. The patient tested positive for heparin-dependentplatelet antibodies (platelet aggregation test). Screening tests for hepatitis A, B, and C viruses were negative. During the first 5 postoperative days, the patient remained in the intensive care unit, was afebrile, hemodynamically stable, had good urinary output (with 1 to 3 gg/kg/min of dopamine), and had no evidence of myocardial ischemia. The patient's trachea was extubated on postoperative day 2. A technetium renal scan showed prompt uptake and excretion by both kidneys. On postoperative day 6, the patient had massive rectal bleeding, secondary to severe distal erosive esophagitis and gastritis. This episode was followed by bleeding episodes requiring multiple transfusions and reintubation. Later, he developed pneumonia (day 8), bacteremia (first documented positive blood culture on postoperative day 11), and had laboratory and clinical evidence of disseminated intravascular coagulation (day 11). Computerized tomography of the abdomen (day 9) suggested pancreatitis. There was no evidence of hydronephrosis or fluid collection. The patient died on postoperative day 20. Autopsy revealed an extensive retroperitoneal abscess involving the right perinephric, periduodenal, and peripancreatic spaces, diffuse septic vasculitis, and accelerated autolysis of the splanchnic viscera; the aortorenal bypass graft was patent.

From the Departments of General Anesthesiology, Urology, and Vascular Medicine, The Cleveland Clinic Foundation, Cleveland OH. Address reprint requests to Juraj Sprung, MID, PhD, The Cleveland Clinic Foundation, Department of General Anesthesiology, E-31, 9500 Euelid Ave, Cleveland, OH 44195. Copyright © 1997 by W.B. Saunders Company 1053-0770/97/1106-001753.00/0 Key words: acute ischemic hepatitis, acute pancreatitis, aortorenal bypass.

Vo[ 11, No 6 (October),1997:pp 767-770

767

768

LEVY ET AL

Table 1. Perioperative Laboratory Findings Laboratory Findings

Variables

Preoperative

Postoperative Day

Day of Surgery

1

2

3

4

5

6

8

White blood c o u n t (1,000/pL)

10.4

36.3

36.4

36.0

31.4

30.3

23.5

20.9

20.2

Hematocrit (%)

42

33

36

33

32

30

26

20

30.2

244

111

90

63

66

119

142

136

Platelets (1,000/pL) Creatinine (mg/dL)

2.2

--

2.8

3.9

4.7

5.1

5.1

4.8

Bilirubin (mg/dL)

0.5

--

0.6

0.6

0.7

0.7

0.6

0.7

AST (IU/L) Alkaline phosphatase (IU/L)

14

--

1452

1212

490

125

51

36

112 5.0 0.7 22

65

--

37

41

51

43

42

35

37

167

--

2694

1530

856

676

606

516

412

A m y l a s e (IU/L)

--

--

--

1892

769

213

54

--

--

Lipase (IU/L)

--

--

--

567

159

59

28

--

--

Lactic acid (mmol/L)

--

13,4

CPK (MB%) (IU/L)

--

436 (1)

LDH (IU/L)

5.1 .

. .

. .

. .

.

2.7 .

.

--

.

Abbreviations: AST, aspartate a m i n o transaminase; LDH, lactic dehydrogenase; CPK, creatine phosphokinase.

DISCUSSION

The majority of patients undergoing surgical renal revascularization have generalized atherosclerosis involving the abdominal aorta, which may contribute to operative morbidity and mortality and create technical problems during the operation. 1,2 Although aortorenal bypass is the most common surgical method for revascularizing atherosclerotic renal arteries, various extra-anatomical techniques have been successfully used to avoid handling of diseased aorta. 4 Based on the authors' literature search, transient visceral organ ischemia, ie, acute ischemic hepatitis, pancreatitis, and mesenteric hypoperfusion, has not been reported after aortorenal bypass. The early postoperative changes in liver enzymes suggested a diagnosis of acute ischemic hepatitis based on established biochemical criteriaS: a transient marked increase (at least 20-fold) of serum transaminases and hepatic lactate dehydrogenase (isoenzyme LDHs) concentrations that peaked during the first and second postoperative days and declined significantly 3 to 5 days later. Microscopically, acute ischemic hepatitis (AIH) is characterized by multiple areas of centrilobular liver necrosis. 6 This condition has been reported mainly in association with systemic hypotension and low cardiac output. 6 Early autopsy series mentioned that fewer than half the cases have been diagnosed antemortem. 7 The authors have recently reported AIH and disseminated intravascular coagulation that developed in two patients during elective abdominal aortic aneurysm repair. 8 Several mechanisms could be involved in the development of AIH in the presented case. The arteriographic evidence of osteal stenosis of the right hepatic artery suggests preexisting hepatic hypoperfusion that could have been potentiated by prolonged relative intraoperative hypotension. Recently, Valentine et al9 showed an increased prevalence of significant celiac artery stenosis in patients with greater than 75% renal artery stenosis. Intraoperative use of potent vasopressors might further perpetuate visceral organ hypoperfusion and metabolic acidosis. A previous study 6 showed that at least one-third of hepatic infarction cases were not associated with vascular occlusions; however, all these patients had recently undergone abdominal surgeries with prolonged shock. By using an echo-Doppler, Nishihara et al 1° showed reversal of portal flow in 10 patients

undergoing abdominal surgeries other than portosystemic shunt procedures, and nine of them died. The liver is the only organ that depends for 80% of its blood supply via the portal vein from other organ systems, such as intestine, spleen, and pancreas, u The lack of valve mechanisms within the portal system permits bidirectional flow. Arterial and portal systems are not linked by connections in the liver. I1 If splanchnic outflow diminishes, the liver can compensate for it directly only through the rise of its arterial flow.11 This, however, could be limited in a patient with significant underlying visceral arteriosclerosis. In addition to splanchnic hypoperfusion associated with prolonged hypotension, a direct inadvertent compression of the portal triad during the operation could further limit portal blood flow. Insufficient oxygen supply and accumulation of metabolites may contribute to hepatic cell injury during the ischemic period. 12 There is growing evidence that reperfusion is the most harmful factor in producing cell necrosis after temporary hepatic ischemia.t3 This could be attributed to a nonreflow phenomenon, probably caused by hepatocyte swelling, which was observed after ischemia. 13Dysfunctional hepatocytes may contribute to further alteration of hepatic flow resulting from secondary intrahepatic hypercoagulability due to their inability to clear plasminogenactivator inhibitors. 14The clinical course, together with the time sequence and extensive change in the liver function tests, make a transfusion reaction, sepsis, or acute viral hepatitis unlikely causes of acute hepatic dysfunction in this patient. The early postoperative increase of serum amylase and lipase concentrations suggested acute pancreatitis, which was later confirmed by computerized tomography. Postoperative pancreatitis has been reported in patients with shock after cardiac surgery 15 or aortic aneurysmectomy. I6 Although postoperative pancreatitis is frequently subclinical, severe cases are typically associated with high mortality. 17Several mechanisms have been proposed, including systemic hypotension, manipulation of the bile ducts, direct trauma to the pancreas, atheromatous embolization, or colonic ischemia. Other causes are vascular in origin, and these have been gaining attention. Warshaw and O'Hara 18 found that the pancreas is prone to ischemic injury after abdominal aortic aneurysmectomy or cardiac surgery. Robert et a119 demonstrated persistently diminished flow in superior

AORTORENAL BYPASS, HEPATITIS, PANCREATIS

769

pancreaticoduodenal artery during the shock, whereas the flow in the superior mesenteric artery increased. This finding of relative spoliation in pancreatic blood supply as shock proceeds may support an ischemic etiology of acute pancreatitis. Recently, Gullo et al 2° showed that supraceliac aortic cross-clamping during the repair of thoracoabdominal aneurysm causes increase in serum pancreatic enzyme concentrations starting after declamping, with the peak levels around 24 hours postoperatively. Also, pathologically significant acinar cell necrosis developed 6 to 24 hours after experimental ischemic pancreatic insult. 21 Mithofer et a121 showed that temporary pancreatic hypoperfusion contributed to early increases in ectopic trypsinogen activation, with subsequent tissue injury characteristic of acute pancreatitis. In addition, complete occlusion of pancreatic venous outflow was shown to induce hemorrhagic necrosis of the pancreas, edema, and focal pancreatic necrosis. 22 Ranson et a123 demonstrated marked changes in coagulation parameters early during acute pancreatitis and suggested that enzymerelated intravascular coagulation plays a role in this condition. This could further induce liberation and activation of lysosomal and secretory enzymes with eventual autodigestion of the pancreas. 22 Castelman et a124 demonstrated atheroembolic debris in pancreatic microcirculation in patients who died after abdominal aortic aneurysm repair. In this case, however, no biliary tract damage was evident during the operation. Protracted intraoperative metabolic acidosis, as well as a high plasma-lactic acid level detected immediately postoperatively and the increased white blood cell count, suggest that mesenteric ischemia occurred early intraoperatively in this patient. Lactic acidemia predicts mesenteric ischemia with a sensitivity of 100% and specificity of 42% in patients with acute abdominal diseases. 25 The low specificity may be related to the elevated

lactic acid concentrations in patients with shock, acute pancreatitis, kidney failure, or liver failure. Gonce et a126 recently Showed that experimental portal triad occlusion can cause circulatory collapse. Combination of cardiovascular collapse and acute portal hypertension, resulting from portal triad occlusion, may limit arterial inflow to the visceral organs resulting in ischemic injury. Autopsy showed that the longer the duration of portal triad occlusion, the greater the degree of ischemic injury to the splanchnic organs (stomach, pancreas, and intestine). In addition, in an animal study, Liu et a127 showed that multisystem organ failure results from ischemiareperfusion injury after continuous hepatic inflow interruption. It has been shown that hepatic inflow interruption that lasted more than 90 minutes resulted in sharp decline in arterial blood pressure, severe microscopic damage to the myocardium and lungs, interstitial pancreatitis, severe gastrointestinal tract edema, and high mortality. 27 Therefore, it is possible that unexplained intraoperative hypotension in this patient was a harbinger of unrecognized visceral organ hypoperfusion. In summary, a patient who developed hypotension and acute transient visceral organ ischemia during aortorenal bypass is described. Protracted hypotension was present in the absence of apparent bleeding and required vasopressor support. Possibly, the hypoperfusion of the liver, pancreas, and intestine during surgery had a cause-effect relationship with hypotension. Therefore, close intraoperative monitoring of blood gases, lactic acid, and serum transaminases may help in early detection of visceral organs hypoperfusion. Because the perfusion through atherosclerotic vessel may be pressure-dependent, the intraoperative blood pressure in patients with severe renovascular disease should be maintained near preoperative values.

REFERENCES

1. Novick AC, Pohl MA, Schreiber M, et al: Revascularization for preservation of renal function in patients with atherosclerotic renovascular disease. J Urol 129:907-912, 1983 2. Hansen KJ, Starr SM, Sands E, et al: Contemporary surgical management of renovascular disease. J Vasc Surg 16:319-331, 1992 3. Novick AC, Straffon RA, Stewart RH, et al: Diminished operative morbidity and mortality in renal revascularization. JAMA 246:749-753, 1981 4. Fergany A, Kolettis R Novick AC: The contemporary role of extra-anatomical revascularization in patients with atherosclerotic renal artery disease. J Urol 153:1798-1802, 1995 5. Gibson PR, Dudley FJ. Ischemic hepatitis: Clinical features, diagnosis and prognosis. Aust NZ J Med 14:822-825, 1990 6. Seely TT, Blumenfield CM, Ikeda R, et al: Hepatic infarction. Human Pathol 3:265-276, 1972 7. Wooling KR, Baggenstoss AH, Weir JF: Infarcts of the liver. Gastroenterology 17:479-493, 1951 8. Sprung J, Levy R Tabares A, Gottlieb A: Perioperative hepatic dysfunction in two patients during elective aortic aneurysm repair. Anesthesiology 83:1347-1351, 1995 9. Valentine RJ, Martin JD, Myers SI, et al: Asymptomatic celiac and superior mesenteric artery stenoses are more prevalent among patients with unsuspected renal artery stenoses. J Vasc Surg 14:195-199, 1991 10. Nishihara K, Yagyu T, Sakata K, et al: Echo-Doppler evaluation of reverse flow sign in the intrahepatic portal branches after surgery. Ann Surg 223:370-376, 1996

11. Charbon GA, Anderson MF: Hepatic hemodynamics as related to blood flow through the gut, spleen, and pancreas. Gut 30:265-278, 1989 12. Hasselgren PO: Prevention and treatment of ischemia of the liver. Surg Gynecol Obstetr 164:187-196, 1987 13. Parks, DA, Granger DN: Ischemia-reperfusion injury: A radical view. Hepatology 8:680-682, 1988 14. Dinbar A, Rangel DM, Fonkalsrud EW: Effects of hepatic ischemia on coagulation in primates. Application to liver transplantation. Surgery 68:269-276, 1970 15. Fernandez-del Castillo C, Harringer W, Warshaw AL, et al: Risk factors for pancreatic cellular injury after cardiopulmonary bypass. N Engl J Med 325:382-387, 1991 16. McIntyre KE, Bernhard VM: Gastrointestinal problems after aortic surgery, in Bergan JJ, Yao JST, (eds): Reoperative arterial surgery. New York, NY, Grnne & Stratton, 1986, pp 207-211 17. Thompson JS, Bragg LE, Hodgson PE, Rikkers LF: Postoperative pancreatitis. Surg Gynecol Obstet 167:377-380, 1988 18. Warshaw AL, O'Hara PJ: Susceptibility of the pancreas to ischemic injury in shock. Ann Surg 188:197-201, 1978 19. Robert JH, Toledano AE, Toth LS, et al: Hypovolemic shock, pancreatic blood flow, and pancreatitis. Int J Pancreatol 3:283-292, 1988 20. Gullo L, Cavicchi L, Tomaseni P, et al: Effects of ischemia on the human pancreas. Gastroenterology 111:1033-1038, 1996 21. Mithofer K, Fernandez-del Castillo C, Frick TW, et al: Increased intrapancreatic trypsinogen activation in ischemia-induced experimental pancreatitis. Ann Surg 221:364-371, 1995

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22. Waldner H: Vascular mechanisms to induce acute pancreatitis. Eur Surg Res 24:62-67, 1992 23. Ranson JHC, Lackner H, Berman IR, Schinella R: The relationship of coagulation factors to clinical complications of acute pancreatitis. Surgery 81:502-511, 1977 24. Castelman B, Scully RE, McNelly BU: Case records of Massachusetts General Hospital (case #8-1972). N Engl J Med 277:703-709, 1972

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25. Lange H, Jackel R: Usefulness of plasma lactate concentration in the diagnosis of acute abdominal disease. Eur J Surg 160:381-384, 1994 26. Gonce ME, Brackett DJ, Squires RA, et al: Development of circulatory and metabolic shock following transient portal triad occlusion. J Surg Res 59:534-543, 1995 27. Liu DL, Jeppsson B, Hokansson CI-I, Odselius R: Multi-system organ damage resulting from prolonged hepatic inflow interruption. Arch Surg 131:442-447, 1996