Anesthesia Aspects of Multivisceral Transplantation: A Case Series Study

Background Multi-visceral transplantation (MVTx) usually refers to the transplantation of more than three intra-abdominal organs. A successful MVT procedure requires strong multidisciplinary teamwork of transplant surgeons, anesthesiologists, and intensivists.

intubation, midazolam 50micro /kg,and morphin 0.1 mg/kg were maintained with propofol infusion (0.1-0.2 mg /kg/min) and oxygen/air. In these cases, the following information is addressed: demographic data (age, BMI, and sex), comorbidity disease, the etiology of intestinal failure and MVT indications, outpatient department parenteral nutrition, time on the waiting list (WL), ABO compatibility, length of hospitalization before transplantation (days), length of TPN (days), preoperative laboratory data such as hemoglobin, albumin, total and direct bilirubin, and serum creatinine ( Table 1).
Information on intraoperative anesthesia such as the number of bleedings, blood products transfusion, albumins and uids administration, operation time, mean Cold Ischemia Time (CIT), Warm Ischemia Time (WIT) are shown in Table 1.
Postoperative complications like acute and chronic rejection rates, their causes, antibody-mediated rejection, infection (site/pathogens), CMV infection, and other complications that occurred during a 6-months followup, were also recorded. Moreover, survival rates were also considered (Table S.1).

Case 1:
She was a 44-year-old woman diagnosed with a well-differentiated neuroendocrine tumor (NET, grade one, Carcinoid Tumor); she had undergone multiple operations, colectomy, and small bowel resection anastomosis at another center. She developed small bowel tumor recurrence, single liver metastasis, short bowel syndrome, and enterocutaneous stula. The patient was referred to the center while complaining about food intolerance and bowel obstruction symptoms as gastric outlet obstruction. She was admitted and received gastrointestinal rest and TPN for two months. She underwent classic MVT and had a good postoperative period. She survived the event.

Case 2:
She was a 52-year-old woman known as a case of celiac and superior mesenteric arteries (SMA) aneurysm admitted to our center. She suffered from severe abdominal pain after the diagnosis. SMA and celiac artery aneurysm reconstructions were performed using saphenous vein interposition graft, but graft thrombosis occurred post-operation. The patient underwent immediate classic MVT. She survived for three months, afterward, she died of GVHD (graft-versus-host disease) and pneumonia in the hospital.

Case 3:
She was a 35-year-old woman had undergone laparoscopic right hemicolectomy due to the colonic polyp and subsequent GI bleeding. She was discharged from the hospital; however, a few days later, she presented with abdominal pain, leukocytosis, and thrombocytosis in the laboratory data. Doppler ultrasonography showed the portal vein thrombosis (PVT), and exploratory laparotomy revealed extensive bowel gangrene. Small bowel resection and anastomosis failed three times in the local hospital.
She was admitted with short bowel syndrome, TPN-associated liver failure, and stula. She received some TPN and then established a GI continuity by deudeno-colic anastomosis surgery. TPN continued, and MVT was performed 79 days later. Klebsiella pneumonia and severe sepsis deteriorated her condition during her hospital stay; unfortunately, she died two months after MVT.

Case 4:
She was a 39-year-old woman, known case of diabetes mellitus, opium-addicted, non-cirrhotic portal hypertension, and protein C de ciency developed with extensive Porto mesenteric thrombosis. She was admitted to the hospital with severe abdominal pain, food intolerance, lack of response to band ligation, and repeated upper gastrointestinal bleeding. She received TPN for 25 days and was then scheduled for classic MVT. She had one episode of acute graft rejection on the 8 th days post-operation which was resolved with high-dose steroids; she was nally discharged from the hospital 25 days after MVT, and she was well at the follow-up 6 months later.

Case 5:
A 47-year-old man who was suffering from a klatskin tumor with obstructive jaundice admitted to the hospital. PTBD (percutaneous transhepatic biliary drainage) was inserted, and a left hepatectomy was performed. He received an entire course of adjuvant chemotherapy and then returned with recurrent tumor and GOO (Gastric outlet obstruction) one year later. TPN started, and metastatic workup revealed no distant metastasis. Afterwards, Cluster MVT was performed, and he had an uneventful postoperative period until he had a high-output stula. TPN, octreotide, and GI rest decreased his stula drain to <1100cc in 24 hours.
Finally, he developed pneumonia, severe sepsis and died two months later in the hospital.

Discussion
Multivisceral transplantation (MVTx) have gained acceptance as therapeutic modalities for patients with: intestinal failure with life-threatening complications of parenteral nutrition (PN), rare cases of vascular abdominal catastrophes and some cases of low-grade neoplastic tumors and desmoids involving the mesenteric root. This prolonged procedure, associated with signi cant blood loss, metabolic abnormalities, temperature uctuations, uid and electrolyte shifts, and coagulopathy. Malnutrition, dehydration, reduced physiologic reserves due to long-standing intestinal failure, and liver dysfunction make these challenges more di cult to overcome (3). These pathophysiologic considerations underpin the anesthetic plan for the patients undergoing multi-visceral transplantation (4). In this case series, the anesthetic aspects of ve MVT cases at a referral single center were discussed.
Patients' monitoring: In addition to peripheral access, a large-bore introducer should be embedded in the right internal jugular vein for uid resuscitation, blood products transfusion and vasopressor infusion. Patients presenting for multi-visceral transplantation are critically ill, and long-term parenteral nutrition increases the risk of prior venous thrombosis. Therefore, using bedside ultrasound is recommended to identify the target vein (5). A radial arterial catheterization is suggested for the beat-to-beat evaluation of mean arterial blood pressure, measurement of systolic pressure variations in estimating intravascular volume status, and the continuous evaluation of blood gasses, hemoglobin, and electrolytes (6, 7). During MVT, wide temperature uctuations secondary to prolonged exposure of the viscera is common, so the maintenance of normothermia is essential, which prevents coagulopathy and cardiac instability followed by hypothermia (5,8). Accordingly, we measured core body temperature through the esophageal probe and considered prewarming of resuscitation uids. Blood glucose (BS) monitoring is necessary in all cases recently had undergone TPN, and supplemental dextrose is required to prevent hypoglycemia following abrupt discontinuation of TPN.

Intraoperative concerns
Fluid resuscitation is crucial because of the prolonged operation time, signi cant blood loss, and excessive third-space losses. Therefore, conservative uid management and application of a pulse counter cardiac output (PICCO) system are the recommended uid management strategies to restore intravascular volume (9). In this study, PICCO was used to evaluate pulse pressure variation (PPV) and stroke volume variation (SVV) which predict the preload volume and uid responsiveness.
Colloid solutions are more effective plasma volume expanders than crystalloids and reduce the severity of bowel edema. Studies suggest that the optimal crystalloid-to-colloid volume ratio is approximately 60:40. A balanced uid strategy is a well-directed technique to maintain mean arterial pressure (MAP) > 60 mm Hg and target CVP >10-12 mm Hg), it aims to stabilize hemodynamic status and improve organ perfusion (10). To prevent bowel edema, we considered a conservative uid strategy that maintains the target CVP < 10 mm Hg with the concomitant administration of vasopressor infusions (norepinephrine, vasopressin, and/or epinephrine) if the MAP was < 60 mmHg. It should be noted that the mean ±SD of total volume administration was 15±1 cc/kg/h which were given as normal saline solution 0.9% /albumin 20% (60%/40%).
Some researchers have suggested that Rotational thromboelastometry (ROTEM) can be applied for the evaluation of coagulation status in MTX (6). Using intra-operative ROTEM analysis in our center revealed that the majority of patients were in a 'hypercoagulable status' and there was no need for fresh frozen plasma (FFP), cryoprecipitate ,and platelet except the fourth case, whom we transfused FFP, cryoprecipitate ,and platelet to correct microvascular bleeding after massive transfusion.
Bleeding during the MVTx procedure would be either surgical or coagulopathic or both. It might be more severe in patients with adhesions from previous abdominal surgeries, portal hypertension, or portal vein thrombosis (PVT) (11).We had an average of 2600 cc blood loss during these MVTx procedure. To achieve adequate tissue oxygenation, the hemoglobin level should be maintained at the range of 7-10 g/dl. On the other hand, overcorrection of hemoglobin may enhance the risk of vascular graft thrombosis and should be avoided (12). In our study, the average Hb level was 10.62 g/dl and the average transfusion of packed red blood cells was 4±1 bag in the series. About 47% of patients undergoing small bowel transplants experience post-reperfusion syndrome (PRS) (13).
PRS is the largest hemodynamic disorder due to the amount of reperfused organs. It is characterized by marked decreases in MAP, and systemic vascular resistance, as well as moderate increases in pulmonary arterial pressure and central venous pressure. This syndrome may also develop when the mean arterial pressure (MAP) is less than 60 mm Hg or 30% below the pre-unclamping baseline value, lasting for at least 1 min, within 10 min after unclamping (8, 14,15). The PRS occurred among all these ve cases but severe PRS which needed continuous vasopressin and norepinephrine infusion happened in only one case. It is welldocumented that several factors contribute to PRS development (i.e., hyperkalemia, acidosis, sudden hypothermia, vasoactive substances like free radicals, endotoxin, inflammatory cytokines, and acidotic compounds produced by the graft or intestine) (15) Aortic cross clump and PRS may also contribute to renal injury. Studies suggested that the risk of post-transplant renal failure was 50% in MVTx (16). We did not observe any case of CRRT or dialysis-requiring acute kidney injury. It might be related to maintaining MAP > 60 mmHg and improving kidney perfusion pressure with infusion minimum dose of vasopressor during the clumping and unclamping phase (16, 17).
Indeed, TPN supplement contain potassium, on the other hand, concomitant liver graft reperfusion may enhance the intensity of hyperkalemia. Serial measurements of plasma potassium have suggested to keep the potassium level below 4 mmol/L before un-clumping phase and revascularization (18). Treatment options for hyperkalemia include the simultaneous administration of insulin and hypertonic-glucose, calcium gluconate, insulin, sodium bicarbonate, and diuretics (19)(20)(21).
In this study, methylprednisolone was administered simultaneously in the beginning of vascular Consent for publication: Written informed consent was obtained from the patient or the patient's next of kin for publication of this Case report and any accompanying images. A copy of the written consent is available for review by the Editor of this journal Availability of data and materials: All data will be available on request.  Figure 1 Recovered organs before implantation.

Figure 2
Implanted organs after reperfusion