The process of kidney transplantation (KT) involves successful execution of multiple protocolized steps in a sequential manner1 starting with optimal recipient-donor selection, immunological matching, and preoperative patient optimization, followed by surgical intervention and perioperative care, including optimal fluid management, immunosuppression, and monitoring for postoperative complications.
Kidney transplantation has traditionally been performed by open surgery,2 but recently, a few groups including our own have described a minimally invasive approach.3-8 The benefits of minimally invasive surgery have been demonstrated across multiple surgical subspecialties and have led to its widespread adoption,9-13 including in the transplant community,14,15 such that today laparoscopic surgery is the preferred modality for performing live donor nephrectomy. We have previously described our technique of robotic KT (RKT) with regional hypothermia in a detailed step-by-step manner,7 and have highlighted the important technical differences that exist between our approach and the minimally invasive techniques described by Giulianotti et al,3 Boggi et al,4 and Modi et al.5 However, information on perioperative issues surrounding minimally invasive KT is lacking in these reports. Accordingly, in this report, we aim to focus on perioperative considerations in minimally invasive KT and seek if tweaking of standard perioperative protocols is required in these patients. Further, we describe key 6-month outcomes in patients undergoing RKT at our center.
MATERIALS AND METHODS
Patient Cohort, Institutional Review Board Approval, and Patient Consent
Between January 2013 and June 2014, 152 patients with end-stage renal disease (ESRD) underwent RKT, using previously published technique7 at 2 tertiary care centers (Medanta Hospital, India [n = 67] and Institute of Kidney Disease and Research Center [IKDRC], India [n = 85]). Patients were inducted into the study if they expressed the desire to undergo minimally invasive surgery and satisfied the selection criteria described previously (Table 1).6,7 Outcomes in patients with a minimum follow-up of 6 months (i.e., patients enrolled between January 2013 and January 2014) from Medanta Hospital are presented here (n = 54; for logistical reasons the data from IKDRC could not be presented in the current report [the institutional institutional review board did not grant access to publish data without long-term follow-up]). Study approval was obtained, and the technical and data collection protocols were registered with the institutional review board of Medanta Hospital and IKDRC, prospectively. Informed consent was obtained in each case.6,7
Preoperative Evaluation of Recipient
Preoperative assessment was similar to OKT and included gathering information regarding etiology and duration of ESRD, comorbidity status, and evaluation of ongoing renal replacement therapy (see below, Table 3). Cardiorespiratory and serological evaluations were performed in all patients as per standard transplant protocols.
As in OKT patients, triple immunosuppression therapy was used in patients undergoing RKT. Tacrolimus (0.1 mg/kg) and mycophenolate mofetil/sodium (1 g/720 mg twice daily) were started on the day before the surgery, and Prednisone (40mg/day) was started on the day of operation. An induction agent, Basiliximab or Thymoglobulin, was administered after discussion with the patient regarding HLA match status and affordability.
Operating Room Setup
Ideal OR setup is shown in Figure 1. Though not crucial, it is helpful to set up the OR in a manner similar to that depicted in the illustration because it promotes good conversation among the console surgeon, bedside assistant, and the anesthesia team.
Invasive Monitoring and Anesthesia Protocol in Tandem With Key Surgical Steps
Patients undergoing RKT were induced, maintained, and monitored similarly as those undergoing OKT. Specifically, patients were premedicated with intravenous (IV) Midazolam (1 mg on-table) and induced with Propofol (2 mg/kg), Atracurium (0.5 mg/kg), and Fentanyl (2 μg/kg). Anesthesia was maintained with a volatile anaesthetic agent (e.g., Sevoflurane) and air-oxygen mixture. Intraoperative analgesia was maintained by boluses of Fentanyl. Monitoring included pulse oximetry, electrocardiogram, end tidal CO2, end tidal gas concentrations, minimum alveolar concentration, central venous pressure (CVP), input-output and core/graft temperature measurements. Central venous access, an integral part of our transplant anesthesia protocol, was secured in all patients. Although reserved only for OKT patients with severe comorbidities, an arterial line was placed in all RKT patients, keeping in mind the initial learning phase, for continuous blood pressure (BP) monitoring and blood gas analysis, performed post-induction, during vascular anastomosis and 30 minutes after anastomoses in all RKT patients. Patients were kept paralyzed with continuous infusion of Atracurium (0.25 mg/kg/hour) till the undocking of robot and return to supine position. Methyl prednisone bolus was administered slow IV just before graft reperfusion and a bolus Injection of Lasix 100 mg IV was given soon after. After extubation, a careful note was made of any head and neck or eye changes, like edema or haemorrhages. Nasopharyngeal airway was routinely used in all patients immediately postoperatively.
Intraoperative Fluid Management
A fluid restriction policy was followed during the initial part of the operation, in contrast to OKT. Robotic KT recipients received 10 mL/kg/hour of 0.9% normal saline (roughly 1200–1500 mL) from the start of the procedure till graft reperfusion, whereas OKT patients were infused at a consistent rate of 30 mL/kg/hour throughout the surgery. Liberal hydration, however, was started after reperfusion of the graft and a total of 2.5 to 3 L of fluid were infused by the time the patient was extubated and shifted to the intensive care unit. The mean arterial pressure was maintained above baseline (approximately 20% over) from graft reperfusion onward.
Coordination of Donor and Recipient Surgery and Preparation of Graft
Both donor and recipient surgeries were started simultaneously in a twin operating room. Donor nephrectomy was performed laparoscopically in all cases. Of note, the graft was retrieved only after the recipient team was ready, to minimize cold ischemia time. This coordination is especially important during the initial potentially longer cases to minimize the “overall” ischemia time. Back-bench preparation was done in a standard manner and included defatting and cold perfusing the graft kidney, preparing an ice-gauze jacket,7 and tying of small capsular and perforator vessels.
We have previously described our surgical technique in a detailed step-by-step manner.7 Briefly, surgical steps include patient positioning and port placement in a manner typical for robotic radical prostatectomy.16 The operation starts with skeletonization of external iliac vessels, followed by dropping down of bladder and ureterovesicostomy site preparation on its right anterolateral wall. Subsequently, a transverse incision is made in the peritoneum, 2 to 3 cm distal to the cecum, extending from iliac vessels to lateral abdominal wall, and peritoneal flaps are raised, to be utilized later for extraperitonealization of the graft. This concludes recipient-bed preparation, and next, the iliac fossa is cooled with ice slush introduced through the GelPOINT, and the graft kidney wrapped in ice gauze jacket is introduced. Graft vessels are anastomosed to external iliac vessels in an end-to-side fashion using 5-0 Gore-Tex suture. Specifically, a venotomy is made in the external iliac vein with the monopolar scissors, and then the graft renal vein is anastomosed to the external iliac vein in an end-to-side continuous manner. Next, in a similar fashion, the graft artery is anastomosed to the external iliac artery. After reperfusion, the graft is extraperitonealized using the peritoneal flaps prepared previously. Stented ureterovesicostomy is performed using the modified Lich-Gregoir technique. An immediate on-table Doppler ultrasound of the graft is performed in all patients before transportation to recovery room.
In cases with multiple renal graft vessels, if minor upper or lower polar arteries were encountered (∼ ≤ 20% parenchymal supply), they were anastomosed to the inferior epigastric artery (IEA) separately (6 cases; the IEA stump was prepared previously at the time of vessel bed preparation),7 while, in cases with major arteries, they were anastomosed on bench to create a single stump which was then anastomosed with external iliac artery (5 cases) (Note: For information regarding the learning curve and approximate number of cases a surgeon must perform to achieve competency in RKT, please refer to Sood et al.17
Table 2 summarizes the key steps of our technique and provides a comparative narrative of other described techniques of RKT.
Other Intraoperative Considerations
- (A) Ventilation strategy: pressure control rather than volume control ventilation was used in RKT cases, in accordance with previously published evidence of its superiority in patients undergoing minimally invasive procedures in Trendelenburg position.18 The addition of positive-end expiratory pressure in a titrating manner was used as a recruitment manoeuvre.
- (B) Management of pneumoperitoneum: pneumoperitoneum was kept at 15 mm Hg during initial part of the procedure till vascular anastomoses completion, subsequently reduced to 10 to 12 mm Hg post-vessel unclamping to allow adequate graft perfusion.19,20
- (C) Temperature monitoring: core body temperature was monitored continuously using a transesophageal probe. Graft surface temperature was measured just before reperfusing the graft using a sterile temperature probe.7 Bair hugger and fluid warmers were used to prevent potential systemic hypothermia secondary to use of ice slush in pelvis.
Postoperative Care and Follow-up
Postoperative hemodynamic monitoring of the patients included blood pressure, heart rate, CVP, urine output, and oxygen saturation monitoring in the transplant intensive care unit for the first 48 hours, as is the case in OKT patients. Serum biochemistry and hematologic investigations were repeated twice daily for the first 2 days, and daily thereafter till discharge. A follow-up graft Doppler Ultrasound was performed on postoperative day (POD) 1.
Central neuraxial pain management with epidural/paravertebral catheter, standard for our OKT cases, was not required after RKT. Rather, postoperative pain was comfortably managed by continuous infusion of Fentanyl (0.5 μg/kg/hour) with morphine as rescue (patient-controlled analgesia).
Postoperative fluid management was identical to OKT. Patients were kept well hydrated and had a CVP line for the first 48 hours. Specifically, for the first 24 hours, we administered 90% to 100% normal saline or half normal saline replacement per previous hours’ urine output, which was reduced to 70% to 80% replacement over the next 24 hours. Abdominal drains were removed on POD 2 or 3, once the drain output was serous and fluid creatinine was normal. Foley catheter was removed on POD 4.
After discharge, patients were followed up twice weekly during the first month, once weekly during the second month, once every 2 weeks during the third month, monthly thereafter till the end of first year, and every 2 to 3 months subsequently. The maintenance immunosuppression protocol was similar to OKT. Specifically, Tacrolimus dosing was determined by frequent Tac levels (target 8–12 ng/mL during first 3 months, 6–8 ng/mL for next 3 months, and 3–6 ng/mL afterward). Prednisone was tapered to 20 mg at discharge, 10 mg at 2 months, and 7.5 mg to 5 mg at 3 months. Mycophenolate was reduced to 1 g/720 mg daily by 3 months. Mycophenolate levels were not monitored. All recipients with postoperative renal dysfunction underwent ultrasound-guided percutaneous biopsy, regardless of the operative approach, for histopathological diagnosis to aid guide therapy. The ureteral stent was removed 3 weeks after the surgery.
Sixty-seven patients underwent RKT with regional hypothermia between January 2013 and June 2014. Outcomes in 54 patients, with a minimum follow-up of 6 months, are reported here.
Tables 3 and 4 summarize baseline recipient and donor/graft characteristics, respectively. Diabetes and hypertension were the 2 most common causes of ESRD (64.8%). Mean preoperative creatinine was 9.1 mg/dL (SD = 3.6 mg/dL). Eight (14.8%) patients underwent preemptive transplantation. Basiliximab induction, in addition to triple immunosuppression, was used in 41 patients (75.9%). Mean Charlson comorbidity score was 3.7 (range = 3–10). All grafts were harvested laparoscopically; 9 grafts (16.6%) were right-sided, and 11 (20.4%) had multiple renal arteries.
Using the anesthesia protocol outlined above, all 54 patients successfully underwent RKT with regional hypothermia without the need for conversion to open. Mean operative time was 201.1 min (Table 5). Mean warm, cold and rewarming ischemia times were 2.3, 27.7, and 42.9 minutes, respectively. Average graft surface temperature, measured just before reperfusion, was 19.2°C, whereas the mean drop in core body temperature was 0.7°C. None of the patients developed systemic hypothermia. All anastomoses, including anastomosis of polar graft vessels to recipient IEA (n = 6), could be accomplished robotically.
Seven patients required nitroglycerin to manage intraoperative hypertension. Minimally invasive intraoperative cardiac output monitoring was used in 3 patients with ejection fraction less than 50%. Arterial blood gas analysis did not reveal any adverse findings in any of the cases. Average intraoperative fluid infusion volume was 3.37 L. All robotic transplant patients could be extubated on table despite presence of significant head and neck edema in 3 patients. No significant eye changes were observed except conjunctival edema in the same 3 patients. None of the patients developed subcutaneous emphysema or nerve palsies (Tables 5 and 6).
Postoperative Course and Follow-up
Observed head and neck edema in the 3 patients subsided within 48 hours. No patient required reintubation. All patients, except one, remained hemodynamically stable. Hypotension was successfully managed with inotropes in that patient. All graft functioned immediately, and no patient required dialysis within the first week. Mean serum creatinine was 1.4 mg/dL at discharge and 1.2 mg/dL at 6 months (Figure 2). Graft biopsy was needed in 11 (20.3%) cases with diagnosis of acute rejection in 7 (12.9%) and patchy acute tubular necrosis in 3 patients and calcineurin toxicity in 1 patient.
There was no 30-day mortality. However, within a median follow-up of 13.4 months, 2 patients died with functioning grafts, 1 at 6 weeks secondary to acute congestive heart failure, and the other at 7 months after a fatal myocardial infarction. Patient and death-censored graft survival at a median follow-up of 13.4 months was 96.3% and 100%, respectively (Table 6).
Robotic KT with regional hypothermia is safe, feasible, and reproducible. Tweaking of the standard OKT protocols is necessary considering the altered anatomy and physiology during Trendelenburg positioning, pneumoperitoneum, pelvic cooling, and transperitoneal approach of graft placement to obtain optimal outcomes.
Trendelenburg position predisposes to head and neck edema, including cerebral, tracheal, and optic edema (ranging from conjunctival edema to retinal detachment and ischemic optic neuropathy).21-23 Thus, in RKT patients, intraoperative fluid infusion needs to be carefully titrated, so as to neither jeopardize graft function secondary to poor graft perfusion24 nor compromise neurological safety. Similarly, it is important to avoid airway edema because early extubation and nondependence on mechanical ventilation have been associated with improved survival outcomes in transplant patients.25 With our protocol of initial fluid restriction, all patients had optimal graft function, and facial/conjunctival edema occurred only in 3 (5.6%) patients, which resolved itself within 48 hours. Moreover, none of these patients suffered from neurological deficits nor required mechanical ventilation. These findings are corroborated by the previous study of robotic prostatectomy by Kalmar et al,26 where the authors demonstrated the safety of steep Trendelenburg (40°) with regards to cerebral blood flow and function. Further, the authors also reported no compromise in cardiac function in their patients. We also did not note any perioperative cardiac complications in our patients; however, given the increased risk for postsurgical cardiac complications in ESRD patients secondary to uremic cardiomyopathy, we do recommend careful screening and intraoperative cardiac monitoring (FloTrac/Vigileo, Irvine, CA) in patients with poor ejection fraction. Other Trendelenburg-associated complications, such as lower limb ischemia and nerve palsy,27 which might be accentuated in ESRD patients due to a uremic state (peripheral vascular disease, neuropathy, etc.), were not observed in the current study.
Pneumoperitoneum beyond 10 mm Hg has been shown to reduce renal blood flow and glomerular filtration rate. An intra-abdominal pressure of 20 mm Hg can reduce the glomerular filtration rate by almost 25%.19,20 The graft kidney suffers a second pneumoperitoneum insult during recipient surgery, having already been exposed to prolonged pneumoperitoneum during donor nephrectomy (laparoscopic). Fortunately, the duration/degree of pneumoperitoneum during RKT impacts only the graft after reperfusion. Accordingly, we routinely bring down the pneumoperitoneum to 10 to 12 mm Hg, after release of vascular clamps, just enough to perform ureterovesicostomy. Another complication associated with pneumoperitoneum and the use of GelPOINT device is increased risk for subcutaneous emphysema, as demonstrated by Park et al.28 We did not observe this complication in our cohort, most likely because we used the GelPOINT for graft and ice-slush delivery rather than for single site surgery. Park et al in their study of renal surgery noted that Laparoendoscopic Single Site Surgery required more aggressive instrument movements and torquing, in comparison to standard multiport laparoscopic surgery, potentially leading to greater amounts of insufflation gas escaping between the port and the peritonotomy causing subcutaneous emphysema.
As mentioned previously, the transplanted kidney requires good perfusion for early recovery of function after ischemia.24 Proper intravascular volume and mean arterial pressures greater than 80 mm Hg are necessary to achieve this. Loss of autoregulatory capacity of the denervated graft kidney in the face of varying systemic BP are cited as the reasons behind the requirement for higher BP for proper renal perfusion. Central venous pressure has been used as a surrogate marker of intravascular volume; however, its use is controversial because it does not correlate well with fluid balance.29 This problem is further compounded by the Trendelenburg positioning and pneumoperitoneum, which lead to false elevation in CVP. Hence, we use multiple checkpoints to ensure adequate perfusion of the graft. First, we measure the baseline CVP at the start of the procedure both in supine and Trendelenburg position with and without pneumoperitoneum. This gives us an estimate of the effect of Trendelenburg positioning and pneumoperitoneum on the baseline CVP, and we can alter the target value for CVP accordingly (normal target value is >15 mm Hg in supine patients without pneumoperitoneum, after vascular clamp release). Second, we use clinical signs of graft well-being, including a pink, turgid kidney, and onset of adequate on-table diuresis. Third, we perform on-table Doppler ultrasound at the end of each case to visualize graft perfusion and note resistive indices.
Finally, in our technique, we use ice slush pelvic hypothermia and place the graft via a transperitoneal approach. Wickham, many years ago, observed that the ideal temperature for maximal renal protection was about 20°C.30 We, on average, achieved a graft surface temperature of 19.2°C. Accordingly, we noted quicker graft function recovery in our series, in contrast to previously published reports of laparoscopic and robotic transplants which had been performed under warm ischemia.31,32 None of the patients developed systemic hypothermia. In addition to cooling the graft intracorporeally, every effort should be made to coordinate donor and recipient surgeries because this would help offset the prolonged anastomoses times during the initial learning phase of RKT by keeping in check the “overall” ischemia time. Lastly, KT has conventionally been a retroperitoneal approach, and there have been concerns about a transperitoneal approach. In fact, Oberholzer et al32 required open/laparoscopic visualization under anesthesia to perform postoperative graft biopsies secondary to intraperitoneal position of the grafts. Modi et al31 reported graft torsion and loss after leaving the graft intraperitoneally. To avoid these complications, we routinely exptraperitonealize the graft, and so far, we have been able to perform all graft biopsies percutaneously under USG guidance and have noted no graft torsion within a median follow-up of 13.4 months, and death-censored graft survival rate has been 100%.
In conclusion, RKT with regional hypothermia is a safe and effective operation. Preoperative screening and immunosuppression protocols are the same as for OKT; however, tweaking of standard intraoperative protocols, including monitoring and fluid management strategies, is necessary for a successful surgery without compromise in patient outcomes. There is an obvious need for replication of these results by other centers/groups to substantiate these early encouraging findings.
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