Case 3—1996 unusual cause of hypotension after cardiopulmonary bypass

CASE CONFERENCE Alan J. Schwartz, MD Frederick A. Hensley, Jr, MD Section Editors

CASE 3m1996 Unusual Cause of Hypotension After Cardiopulmonary Bypass Norman G. Zavela, MD, Glenn P. Gravlee, MD, Daniel H. Benckart, MD, Sang B. Park, MD, and Viwan Gahtan, MD

Case Presentation A 60-year-old 120-kg woman with severe aortic stenosis presented for aortic valve replacement. She presented with progressive exertional dyspnea, paroxysmal nocturnal dyspnea, and two-pillow orthopnea. Other pertinent conditions included hypertension, morbid obesity, and chronic phlebitis. Peak systolic pressure gradient was 75 mmHg, and the calculated aortic valve area was less than 1 cm 2. Cardiac catheterization also showed mild coronary atherosclerosis and normal left ventricular function. Preoperative medications included methyldopa, hsinopril, and warfarin. Warfarin was discontinued 6 days before surgery. Physical examination showed a grade III/VI systolic ejection murmur at the right upper sternal border that radiated to the carond arteries. Her chest x-ray showed mild interstitial fibrosis but was otherwise normal. Electrocardiogram (ECG) showed sinus rhythm, left ventrlcular hypertrophy, an old inferior myocardial infarction, and mtraventricular conduction delay. Laboratory results included a white blood cell count of 6,200/ixL, Hgb 13.5 g/dL, hematocrit 40.3%, and prothrombin time 13.4 seconds (normal range 11.0 to 12.0 seconds). After premedicatlon with morphine, 6 nag intramuscularly, the patient was brought to the operating room and placed supine on the operating room table. Routine monitors (ECG, nonmvaswe blood pressure (BP); pulse oxlmeter) were applied, and a pulmonary artery catheter was placed without difficulty via the right internal jugular vein. After several unsuccessful attempts at placing a 20-G right femoral arterial catheter, a 20-G 15-cm left femoral arterial catheter was placed with some difficulty. The right femoral artery had been successfully punctured with a Seldinger needle, but difficulties in advancing a guideline precluded successful cannulahon. General anesthesia was induced using etomidate, 0.1 mg/kg, fentanyl, 8 Ixg/kg, midazolam, 30 ixg/kg, and succinylcholine, 1.2 mg/kg. General anesthesia was maintained using fentanyl, 30 txg/kg, and isoflurane, up to 0.8 minimum alveolar concentration for BP control. Hemoglobin concentration after anesthetic reduction was 12.3 g/dL. The prebypass period was uneventful with mlmmal blood loss, and 1,500 mL of lactated Ringer's solution was administered intravenously before cardiopulmonary bypass (CPB). Anticoagulataon was achieved with 300 U/kg of heparin, and the activated clotting time was maintained at greater than 400 seconds throughout CPB for a total heparln dose of 40,000 units. Representatwe h e m o -

dynamics before CPB were BP 95/55, pulmonary artery (PA) pressure 26/16, right atrial pressure (CVP) 11, and cardiac index (CI) 1.8 L/min/m 2. The extracorporeal circuit was primed with 1,500 mL of balanced salt solution, 500 mL of 5% mannmtol solution, and 5,000 units of heparin. The initial hemoglobin concentration during CPB was 7.3 g/dL, which was increased to 8.8 g/dL by the end of CPB with 2 units of packed red blood cells (RBCs). An additional 1,200 mL of Plasmalyte was administered during bypass. Blood loss during CPB was conserved by a Haemonetics Cell Saver (Haemonetics, Inc, Bramtree, MA) device and did not appear excessive. The patient separated easily from bypass with a central venous pressure (CVP) of 3 mmHg and PA pressures of 28/13 mmHg. CI was 2.5 L/min/m 2, and protamine, 350 mg, was administered over 15 minutes. Soon after the protamine infusion was completed, the patient's systolic blood pressure (SBP) decreased to 64 mmHg. Intravenous hetastarch 6% was administered to maintain adequate CVP and PA diastolic pressures. However, even after 1,000 mL of hetastarch, hypotensmon continued. PAL pressure remained around 28/15 mmHg, while CVP remained less than 5 mmHg. CI was 4 to 4.5 L/min/m 2, whereas systemic vascular resistance (SVR) was 500 to 600 dyne/s/cm -5. With SBP m the 60s (mmHg) and mean arterial pressure (MAP) m the high 40s (mmHg), an anaphylactic or anaphylactoid reaction to protamine was presumed to be causing the hypotension. Diphenhydramine, 50 mg, and hydrocortisone, 120 rag, were administered intravenously, an epinephrine bolus (100 Ixg) was administered, and an epinephrine infusion was begun at 8 ixg/min. This therapy increased SBP into the 80s (mmHg), which was maintained by repeated 100-1xg boluses of epinephrine and by increasing the epinephrine infusion rate to 10 to 20 ~g/min. ABG

From the Departments of Anesthestology and Surgery, Allegheny Campus (Pzttsburgh, PA), and the Dtvtston of Vascular Surgery (Phdadelphla, PA), The Medmal Collegeof Pennsylvama and Hahnemann Untverstty Address repnnt requests to Glenn P. Gravlee, MD, Department of Anesthestology, Allegheny General Hospttal, 320 E North Ave, Ptttsburgh, PA 15212. Copyrtght© 1996 by W B Saunders Company 1053-0770/96/1004-002353 00/0 Key words protamme reactton, hypotenston, femoral arterypuncture

Journal of Cardlothoracm and VascularAnesthesla, Vo110, No 4 (June), 1996 pp 553-556

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analysis showed PaO2 487 mmHg, PaCO2 32 mmHg, pH 7.40, on an FIO2 of 1.0, potassium 3.9 meq/L, ionized calcium 0.86 mmol/L, sodium 137 meq/L, and hemoglobin 7.8 g/dL. Calcium chloride, 1.0 g, 3 units of allogenelc RBCs, and 500 mL of 5% albumin were administered. Hemostasis in the mediastinum was considered very good. SBP remained in the 80s (mmHg) despite the addition of a norepinephrine infusion ranging from 8 to 30 ~g/min and dobutamine, 5 ~g/kg/min. The possibility of abdominal distention was considered, but the patient's preexisting abdominal protuberance rendered this evaluation difficult. The abdomen did not feel tense to palpation. The final mtraoperative hemoglobin was 6.5 g/dL after 5 units of RBCs. The patient's wound was closed, and she was transferred to the intensive care umt (ICU), where two additional units of RBCs, 1 g of calcium chloride and 4 g of magnesium sulfate were administered intravenously. The patient remained unstable with an SBP in the 70s (mmHg). Naloxone, 0.4 mg, and flumazenil, 1 rag, were administered by the surgeon to reverse the effects of fentanyl and midazolam. The first set of laboratory values in the ICU showed a hemoglobin of 5.5 g/dL, with PaO2 315 mmHg, PaCO2 32.9 mmHg, and pH 7.24, base excess -13, with an FIO2 of 1.0. SBP remained in the 70s (mmHg). Drainage from the medlastinal tubes was minimal. The patient's abdomen was believed to be distended, so a consultant general surgeon performed a diagnostic peritoneal lavage that showed gross blood. An additional 5 units of RBCs were transfused as well as 4 units of fresh frozen plasma, and the patient was transferred to the operating room for an emergency exploratory laparotomy. A tear on a side branch of the right external lliac artery was found and repaired, and approximately 2.5 L of gross blood were found in the abdomen. Subsequent recovery was largely uneventful, and the patient was discharged from the hospital 10 days postoperatively. DISCUSSION*

When the patient's blood pressure first decreased after CPB, protamine-induced vasodilation was suspected. Cardmc output was high, and SVR was low. Protamine commonly causes self-limiting vasodflation that can be reduced by infusing it slowly3 Protamine-lnduced anaphylaxls is rare, characterized by systemic hypotension with decreased SVR, and may be accompanied by urticaria or bronchospasm. Anaphylaxis reqmres previous protamine exposure, often via chronic use of NPH insulin. 2-4 Although most patients undergoing cardiac surgery have been exposed to protamine at least once, the nsk for protamine-lnduced anaphylaxis is well below 1%. For patients receiving an insulin preparation that contains protamine, the risk for anaphylaxis may be as high as 3%. 5 A diagnosis of protamine-mduced anaphylaxls was considered even in the absence of urticaria or bronchospasm. Although epinephrine and norepinephrlne were aggres*Norman G Zavela, MD, Glenn P. Gravlee, MD, Daniel H. Benckart, MD, and Sang B. Park.

sively administered, hypotension persisted. In retrospect, the problem was hemorrhagic shock resulting from retroperitoneal and intraperltoneal bleeding. This diagnosis was obscured by the relatively sustained high cardiac output state with low SVR, a condition that may have been enhanced by the epinephrine infusion. Even the addition of an aggressive norepinephrine infusion did not materially alter the low-SVR high-output state, but this was the only intervention that appeared to sustain BP above 80 mmHg. During cardiac surgery with CPB, the need for continuous blood pressure monitoring and frequent blood sampiing makes an intra-arterial catheter essential. Soderstrom et al 6 found that femoral artery catheters used in critically ill patients remained functional nearly twice as long (7.25 days) as radial artery catheters (3.78 days). Both sites exhibited a 5% occurrence rate for the most common complication, local hematoma. 6 Hemorrhagic complication rates range from 0.25% to 5% in other reports of femoral artery catheterization. 7-I~ Most often the hematoma is clinically insigmficant, but occasionally hemorrhage can track retroperitoneally to induce hypotension and abdominal distention and discomfort. In the authors' practice, femoral arterial catheters are placed for cardiac surgical procedures because of the improved representation of central arterial pressure versus radial artery catheters ~2-15 and because this permits a ready access site for intra-aomc balloon pump placement if that should become necessary. In the case presented, the femoral artery catheter and previous puncture sites were covered w~th sterile drapes. Having these sites accessible for examination would not have facilitated diagnosis, because the puncture was intraperitoneal. Owing to the patient's large girth, abdominal distention was not easdy recognized. Additionally, abdominal examination is unreliable for detecting sigmficant hematomas that have extended from a femoral artery puncture site into the abdominal cavity, n The arterial injury in this patient erupted into the peritoneum. Femoral artery puncture site injuries can also dissect retroperitoneally to the pararenal spaces, abdominal wall, or flank or be confined to the groin and thigh regions. Intra-abdominal bleeding can be readily identified by diagnostic peritoneal lavage (DPL), but this technique does not reliably diagnose retroperitoneal bleeding. In the latter case, either a high clinical index of suspicion leading to laparotomy or computerized tomography may be necessary for diagnosis. Groin and abdominal wall hematomas should be evident from the localized distention and ecchymosis. Fortunately, in this case, the bleeding was intraperltoneal and the diagnosis was readily made by the gross blood found during DPL. In retrospect, it is surprising that major problems sustaining intravascular volume did not occur during the intense anticoagulation used for CPB. The need for 2 units of RBCs during CPB and the hemoglobin concentration response to transfusion did not seem unusual. When the patient was placed on CPB, hemoglobin concentration decreased from 12.3 to 7.3 g/dL. The blood volume was estimated to be 7,800 mL (mesomorphic woman with 65 mL/kg blood volume), therefore, the 2,000

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mL CPB prime plus 1,500 mL of lactated Ringer's solution administered before bypass (assuming 1,000 mL remained intravascular) should have theoretically produced an initial CPB hemoglobin level of 9.4 g / d E The postbypass hemoglobin values were attributed to dilutional effects from the intravenous fluids administered while the patient was being treated for presumed anaphylactic shock. The final intraoperative hemoglobin concentration of 6.5 g/dL and the initial postoperative value of 5.5 g/dL strongly suggested the correct diagnosis of acute blood loss. This case presents an unusual cause of hypotension after CPB. Although this patient ultimately did well, the unusual complication she experienced was nearly fatal. At least in the early stages of her life-threatening occult hemorrhage, the diagnosis was obscured by high cardiac output and low SVR, both of which are atypical for hemorrhagic shock. During cardiac surgery, occult intra-abdominal or retropentoneal bleeding should be considered when intravascular volume is difficult to maintain, even in the presence of a hemodynamic picture more consistent with anaphylaxis. COMMENTARY1

The case presented demonstrates that, although femoral artery catheterization is a commonly performed minor procedure, clinically significant complications can occur. These untoward events include hemorrhage, thrombosis, pseudoaneurysm formation, arteriovenous fistula development, distal embolization, and infection. For arterial complications, hemorrhage has the most frequent occurrence (6.18%), with the others having an incidence of 1% or less. 16 Several factors that place the patient at higher risk for complications include coagulopathy, plaque formation, arterial wall calcification, small vessel size, multiple puncture sites, excessive manipulation, hypertension, and obesity. When entering the vessel, the arteriotomy should be in the anterior position. The femoral artery should be punctured below the inguinal ligament to minimize the risk of hemorrhage in an incompressible location and thereby avoiding uncontrolled bleeding m the retroperitoneum and, in rare cases, the peritoneal cavity. Identifying the inguinal hgament can be more difficult in obese patients. On failed catheterization after arterial puncture or removal of an arterial catheter, direct pressure must be applied to minimlze the risk of hemorrhage and/or pseudoaneurysm formation. Once a significant hematoma forms, it is difficult to achieve adequate compression. The incidence of hemorrhage can also be minimized by having a normal prothrombin, partial thromboplastin, and bleeding time for both

tVivian Gahtan, MD

cannulation and catheter removal. A larger catheter size can also increase the risk of a complication. Sterile technique also is important to avoid infection. It is essential to identify problems early to avoid the potentially devastating sequelae of acute hemorrhage or ischemia. The diagnosis of hemorrhage can be straightforward observing local bleeding from the skin puncture site and/or obvious hematoma formation. When hemorrhage is retroperitoneal, there may be flank ecchymosis, or for intra-abdominal hemorrhage, abdominal distention. However, hemorrhage may be obscure and often first presents with signs of shock, such as tachycardia, hypotension, and oliguria. Diagnostic aids for retroperitoneal hemorrhage include ultrasound or computed tomography. For pseudoaneurysm formation, a widened pulse is often appreciated as well as a bruit. For arteriovenous fistula formation, a palpable thrill and bruit are the most common early signs. Duplex scanning has become the most common method of diagnosis for the latter two problems. Thrombosis and distal embollzation are evident by signs of limb ischemia, and occasionally angiography may be helpful for both diagnosis and therapeutic management. Once a problem is identified, timely intervention is important. Hemorrhage, for the most part, is a self-limited process. A coagulopathy, if present, should be corrected whenever possible. Localized groin hematoma, the most common complication, usually does not require intervention other than direct compression. Retroperitoneal hemorrhage usually stops without intervention, but sometimes arterial repair is necessary. Intraperitoneal hemorrhage, when present, will generally require direct arterial repam Pseudoaneurysms can sometimes be treated with ultrasound-guided compression but generally require surgical repair. For an arteriovenous fistula, surgical repair of the artery and vein is performed. For thrombosis and/or distal embolization, thromboembolectomy is performed with or without patch angioplasty. Major complications of femoral artery catheterization are relatively uncommon. By following the principles mentioned previously, risks can be minimized but not completely avoided. Although there was evidence of hypovolemic shock in the case presented, the rest of the climcal picture confounded the appropriate diagnosis. Given that there was no local evidence of bleeding, the rare incidence of mtraperitoneal hemorrhage, large body habitus, and the focus on the patient's cardiac procedure, it is not surprising that the complication was not &scovered until much later. Anticoagulation for the operative procedure probably added to the risk of hemorrhage. The significance of early recognition and prompt intervention in cases of retroperitoneal and intraperitoneal bleeding cannot be overemphasized.

REFERENCES

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3. Holland CL, Slngh AK, McMaster PRB, et al: Adverse reactions to protamme sulfate following cardiac surgery. Clime Cardlol 7 157-162, 1984 4 Doolan L, McKenzle I, Krafchek J, et al' Protamine sulfate hypersensitivity. Anesth Intens Care 9:147-149, 1981 5 Gottschhch GM, Gravlee GP, Georgitis JW: Adverse reac-

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tlons to protamme sulfate during cardiac surgery in &abetlc and non-diabetic patients Ann Allergy 161'277-281, 1988 6 Soderstrom CA, Wasserman DH, Dunham CM. et al: Superiority of the femoral artery for momtorlng Am J Surg 144'309-312, 1982 7 Russell JA, Joel M, Hudson RJ, et al: A prospectwe evaluation of radial and femoral artery catherlzatlon sites in critically dl patients Crlt Care Med 9.144, 1981 8. Illescas FF, Baker ME, McCann R, et al' CT evaluation of retroperltoneal hemorrhage associated with femoral arterlography. Am J Roentgenol 146:1289-1292, 1986 9 Kaufman JL. Pelvic hemorrhage after percutaneous femoral angiography. Am J Roentgenol 143"335-336, 1984 10 Trerotola SO, Kuhlman JE, Flshman EK: Bleeding complications of femoral catheterization' CT evaluation. Radiology 174:37-40, 1990

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11 Slgstedt B, Lunderqmst A Complications of anglographlc examinations. Am J Roentgeno1130:455-460, 1978 12. Gravlee GP, Wong AB, Adklns TG, et al: A comparison of radial, brachlal, and aortic pressures after cardlopulmonary bypass. J Cardlothorac Anes 3'20-26, 1989 13. Stern DH, Gerson JI, Allen FB, et al. Can we trust the direct radial artery pressure immediately following cardlopulmonary bypass? Anesthesiology 62:557-561, 1985 14. Pauca AL, Meridlth JW' Possibility of A-V shunting upon cardiopulmonary bypass discontinuation. Anesthesiology 67'91-94, 1987 15 Mohr R, Lavee J, Goor DA. Inaccuracy of radial artery pressure measurement after cardiac operations. J Thorac Cardiovasc Surg 94:286-290, 1987 16 Waugh JR, Sacharlas N: Arteriographlc comphcatlons in the DSA era Radiology 182:243-246, 1992