Introduction of an enhanced recovery protocol into a laparoscopic living donor nephrectomy programme

Abstract

Introduction

Living-donor renal transplantation is the optimal treatment for patients with end-stage renal disease. The rate of living donation in the UK is sub-optimal, and potential donor concerns regarding postoperative recovery may be contributory. Enhanced recovery programmes are well described for a number of surgical procedures, but experience in living-donor surgery is sparse. This study reports the impact of introducing an enhanced recovery protocol into a living-donor renal transplant programme.

Materials and methods

All consecutive patients undergoing laparoscopic living-donor nephrectomy over a 25-month period were included. The principles of enhanced recovery were fluid restriction, morphine sparing and expectation management. Outcome measures were postoperative pain scores and complications for donor and recipients.

Results

Standard care was provided for 24 (30%) patients and 57 (70%) followed an enhanced recovery pathway. The latter group received significantly less preoperative intravenous fluid (0ml vs 841ml p < 000.1) and opiate medication (14.83mg vs 23.85mg p = 0.001). Pain scores, postoperative complications and recipient transplant outcomes were comparable in both groups.

Conclusions

Enhanced recovery for living-donor nephrectomy is a safe approach for donors and recipients. Application of these techniques and further refinement should be pursued to enhance the experience of living donors.

Introduction

Renal transplantation from either a deceased or a living donor is the optimal form of renal replacement therapy for suitable patients with end-stage renal disease. It is also significantly less costly than maintenance dialysis therapy. Transplantation from a living donor has a number of further advantages, most notably prolonged graft and patient survival.^1,2 It also provides an opportunity for transplantation for some individuals who are unsuitable for emergency surgery and increases the options for others with an incompatible living donor (either directly or through paired exchange programmes).

Despite the benefits to recipients and to society at large, the rate of living-donor transplantation in the UK (16 per million population per annum) is lower than in some comparable countries and at present substantially less than the aspiration of a mean living-donor rate of 26 per million population per annum by 2020.³

Living donors derive no physical benefit from donating. It is therefore imperative that the process from initial contact to donation to long-term follow-up is made as straightforward, safe and acceptable as possible. Initiatives to improve the acceptability of the donation procedure itself should be welcomed. We report the impact of introducing an enhanced recovery protocol to laparoscopic living-donor nephrectomy in one UK region.

Materials and methods

Patients and procedure

All consecutive patients who underwent transperitoneal laparoscopic living-donor nephrectomy at Belfast City Hospital between 17 April 2013 and 20 May 2015 were included. The surgical procedure was performed by three surgeons and was the same for all patients. All patients up to 8 October 2013 received standard perioperative care (standard care group) and, subsequently, all donors followed an enhanced recovery protocol (enhanced recovery group). For logistical reasons, the latter group were also admitted the day before surgery.

Standard care

Preoperatively, these patients were fasted overnight and received intravenous 0.9% physiological saline. On induction, bilateral transversus abdominis plane blocks were placed using 0.25% levobupivacaine. Intraoperatively, intraperitoneal insufflation pressure was set to 12mmHg. Postoperatively, intravenous fluid was administered until the day following surgery, and the urinary catheter was removed after 24 hours. Analgesia was provided with six-hourly intravenous paracetamol and patient-controlled morphine administration as required.

Enhanced recovery protocol

Preoperatively, these donors received counselling at surgical assessment, including expectation management and agreement of postoperative physical therapy goals. They were given a carbohydrate drink (Nutricia Pre-op™) 800ml at eight hours and 400ml at two hours preoperatively. No intravenous fluid was administered.

On induction, bilateral transversus abdominis plane blocks were placed using 0.25% levobupivacaine. Intraoperatively, intraperitoneal insufflation pressure was limited to 12mmHg. Following extraction and closure of the parietal peritoneum with a continuous suture (3/0 Polydioxanone suture), a 65mm multi-holed ON-Q™ silver-soaker wound infiltration catheter (Halyard Health, Alpharetta, GA) was tunnelled into a preperitoneal, retrorectus position. A bolus of 30ml 0.25% levobupivacaine was administered (total transversus abdominis plane dose and catheter loading dose 2mg/kg), followed by continuous infiltration of 0.125% levobupivacaine at 10ml/hour via a pump (CADD-Solis 2110, Smiths Medical ASD, St Paul, MN).

Postoperatively, intravenous fluid was not administered and the urinary catheter was removed in theatre prior to arrival in the post-anaesthetic care unit. Donors were allowed to eat a full unrestricted diet and were mobilised on the night of surgery. Analgesia was six-hourly intravenous paracetamol with oral oxycodone administration for breakthrough pain as required. The wound infiltration catheter was allowed to remain in place for 24 hours postoperatively. At this time, the patient was given a choice of trial removal of catheter (stop catheter infusion and restart if necessary after six hours or remove if comfortable) or to continue for a further 24 hours, at which stage the catheter was removed.

Discharge

All patients were discharged to their own homes. Our donors all receive the telephone number of the living-donor coordinator and the transplant ward for 24-hour advice or access for readmission should it be required. They are advised to communicate with us about any problem, whether they perceive this to be major or minor. All donors are assessed at two weeks (living-donor coordinator), six weeks (operating surgeon) and 12 months (living-donor coordinator) post-donation. They are then enrolled in a lifelong annual surveillance programme.

Outcomes

Data recorded included age, sex, body mass index, intravenous fluid administered, surgical time, time in the post-anaesthetic care unit, nausea scores, pain scores, morphine requirements, length of postoperative hospital stay, pre- and post-donation renal function, albumin and haematocrit, plus recipient outcomes. Nausea scores using a numerical rating scale (0–3; 0 = no nausea, 3 = severe nausea) were recorded at 24 and 48 hours. Resting and dynamic pain scores were recorded at the same time points also using a numerical rating scale (0–10; 0 = no pain, 10 = worst pain imaginable). The requirement for postoperative dialysis was prospectively recorded for all recipients, together with serial creatinine levels.

Statistics

Frequency, mean plus or minus standard deviation was used to summarise the variables. Independent sample t-test or the non-parametric alternative was used to compare the distribution of continuous variables. Chi-square test or Fisher’s exact test was used to compare categorical variables. Data were analysed using Stata/IC 12.1. and p-values of less than 0.05 were considered significant.

Results

There were 81 patients in the study, 39 (48%) male, and the mean age was 45 years (range 23–72 years). Twenty-four donors (30%) received standard care and 57 (70%) followed the enhanced recovery protocol. There were no deviations from protocol in the enhanced recovery group in terms of preoperative fluids, intraoperative wound infiltration catheter placement, postoperative urinary catheter removal and analgesia regimen.

Preoperative

Demographic parameters were comparable between the two groups (Table 1). The enhanced recovery group received significantly less preoperative fluid (0ml vs 841ml; p < 0.0001).

Table 1.

Demographic and preoperative data.

	Enhanced recovery (n = 57)	Standard care (n = 24)	p-value
Age, years, mean (SD)	46.2 (12.2)	44.2 (12.2)	0.51
Sex (M/F)	27/30	12/12	1.00
Body mass index (kg/m2), mean (SD)	26.6 (3.2)	25.9 (4.8)	0.44

Perioperative

There was no significant difference between the enhanced recovery and standard care groups, respectively, in administered intraoperative fluid volume (2298ml vs 2563ml, p = 0.131), operating time (222 minutes vs 212 minutes; p = 0.33) or time spent in the post-anaesthetic care unit (104 minutes vs 115 minutes; p = 0.45).

Postoperative

The median numerical rating scale score for pain at rest at 24 and 48 hours was 2.7 and 1.8 in the enhanced recovery group compared with 2.9 and 1.9 in the standard care group (not significant). The median numerical rating scale score for pain on movement at 24 and 48 hours was 3.3 and 2.4 in the enhanced recovery group as compared with 3.0 and 2.2 in the standard care group (not significant). The scores for nausea were minimal and therefore comparable in both groups (data not shown). The On-Q system remained in place for a mean of 1.4 days.

There was a marked morphine-sparing effect in the group undergoing enhanced recovery surgery compared with the standard care group. A significant reduction of morphine requirement was observed at all time points and in overall requirements at 48 hours postoperatively, despite equivalent pain scores (Table 2).

Table 2.

Analgesic requirements.

Morphine	Enhanced recovery group		Standard care group		p-value
	(mg)	(SD)	(mg)	(SD)
Hours of use:
0–6	6.68	6.2	13.13	6	< 0.001
6–12	0.81	1.86	2.41	2.45	< 0.001
12–24	0.57	1.48	3.67	3.57	< 0.001
24–48	0.12	0.93	1.65	3.12	< 0.001
Cumulative equivalents (hours):
0–24	11.59	10.1	21.1	8.55	< 0.001
24–48	14.83	13.76	23.85	10.85	0.001

There were no significant differences between the groups in postoperative length of stay, change in donor creatinine concentration, markers of haemodilution or transplant recipient outcomes (Table 3).

Table 3.

Donor and recipient outcomes.

Outcome	Enhanced recovery group		Standard care group		Mean difference (95% CI)	p-value
	(mean)	(SD)	(mean)	(SD)
Donor
Length of hospital stay (days)	2.58	1.02	2.96	1.20	0.38 (–0.14 to 0.90)	0.15
Postoperative day 1:
Percentage albumin drop (g/l)a	16.6	6.6	17.2	5.9	0.6 (3.3 to 4.6)	0.76
Percentage haematocrit drop a	10.1	6.1	10.8	5.6	0.7 (2.1 to 3.6)	0.60
Creatinine change (μmol/l)	63.1	18.8	60.1	21.1	–3.0 (–12.5 to 6.4)	0.26
Recipient
Postoperative day 0:
Mean creatinine (μmol/l):	558	218	578	202	20 (–88 to 128)	0.72
Postoperative day 3:
Mean creatinine (μmol/l):	179	111	135	59	44 (–94 to 5)	0.13
Mean percentage creatinine drop	66.5	19.0	73.3	16.0	6.8 (–1.6 to 15.2)

^a Average change in relation to preoperative assessment

Discussion

The introduction of laparoscopic techniques to living kidney donor nephrectomy (first described in 1995) was a positive factor in increasing the number of living-donor kidney transplants;⁴ the substantial reduction in procedure-associated morbidity and time to resumption of normal activities made the process much more acceptable to potential donors.⁵ Further incentives to improve tolerability are unlikely to be as dramatic, however they do need to be considered to provide the best possible donor experience and encourage more people to consider kidney donation.

Our philosophy is to make it as easy as possible for people to donate, and Northern Ireland currently has the highest rate of living-donor kidney transplantation in Europe (37 pmp in 2015). This reflects a sustained interest among the 1.8 million population in the concept of living kidney donation and altruism, the mean living-donor rate 2010–2015 was 32.7 per million population per annum. Reports of positive and negative donor experiences travel rapidly within the community, having great potential to influence the donor rate. Our programme therefore places extreme importance on a positive donor experience.

Enhanced recovery protocols bring together aspects of care which minimise the stress response to surgery and the associated postoperative organ dysfunction, with the goal of achieving a faster return to normality for patients.⁶ We have concentrated on improving a number of individual elements of perioperative care and combined them into an enhanced recovery protocol for our laparoscopic live-donor nephrectomy patients. We place an emphasis on the use of morphine sparing techniques in the postoperative period and by introducing the concept of fluid sparing to donor nephrectomy, also challenge the notion that aggressive fluid administration regimens are necessary for optimal donor and recipient outcome. Our belief is that these changes have resulted in an overall measurable improvement in donor experience with no detriment in outcome to either donor or transplant recipient.

The enhanced recovery protocol is employed for all donors, who now complete three questionnaires throughout their journey (after assessment, inpatient stay, and 12 months after donation). In terms of pain control, 100% of donors rated this as excellent, 91% reported excellence also for the overall inpatient stay with the remaining 9% rating it as good.

Perioperative fluid management

It is increasingly recognised that the perioperative fluid prescription may influence postoperative outcome. Lobo and others have described the dangers of excessive fluid administration in terms of subsequent complications including postoperative ileus, an increased time to mobilisation, and delayed hospital discharge.^7–9

With the aim of avoiding fluid and sodium excess, and in contrast to the standard care group, our enhanced recovery group did not receive any pre- or postoperative intravenous fluids. Importantly, from a safety point of view, this approach did not have a detrimental impact on graft function. Recipient serum creatinine decreased equally across both groups, which suggests that the need for aggressive preoperative diuresis in donors is unnecessary. There was one instance of delayed graft function requiring dialysis in the control group.

Pain management

Potential kidney donors consistently identify both postoperative pain and the time taken to return to normal activity as barriers to donation.⁵ Strategies to allay the pain of surgery have largely relied on the use of parenteral opiate medication. Such regimens are successful at controlling pain but are associated with undesirable advese effects.¹⁰

Attempts to manage pain in opiate-sparing regimens have excited interest in the 2010s, particularly within enhanced recovery protocols. Current gastrointestinal enhanced recovery pathways are exploring the role of intravenous lidocaine infusion, lipoidal bupivacaine and intrathecal analgesia. Outcomes of programmes using these strategies will be viewed with interest when they are reported.¹⁰

Local use of a wound infiltration catheter is one such technique that has reduced opiate consumption and length of stay in hand-assisted retroperitoneoscopic and retroperitoneal living-donor nephrectomies.^11,12 We have shown in our series that, as a component of enhanced recovery for transperitoneal laparoscopic living-donor nephrectomy, the use of the wound catheter reduced morphine consumption without impacting on postoperative pain.

Our study shows that integration of the wound catheter into our protocol is feasible. It is simple to implement, it does not add to operating time and, additionally, both nursing staff and patients subjectively report high levels of satisfaction with its use. Minor leakage from the catheter insertion site occurred in four patients and this was easily managed with extra dressings. In keeping with the low incidence of reported infection with such devices, there were no instances of wound infection in the catheter group; no catheters were displaced and there were no patient readmissions.

We do not demonstrate a difference in length of postoperative stay between our two groups; however, a median postoperative length of stay of two to three days compares favourably with other published results, which report postoperative lengths of stay between two and days.¹³ The postoperative length of stay may not have been improved due to perioperative shoulder tip pain (discussed below) or social reasons, such as concern about their recipient’s postoperative course. A limitation of our study is that we did not record the time taken to return to normal activities, which would be the most useful outcome measure of any enhanced recovery programme.

Unfortunately, shoulder tip pain secondary to pneumoperitoneal insufflation was not substantially impacted by the enhanced recovery protocol. This pain is occasionally severe and is extremely debilitating. It is frequently the reason that additional opioid-based analgesia is required by our patients. Length of stay over two days was usually as a result of prolonged discomfort from shoulder tip pain. The phenomenon is widely reported in the field of laparoscopic surgery, but it is difficult to define subjectively and comparison between programmes is similarly difficult. There appear to be no specific factors that will accurately predict which patient is likely to suffer from this pain or to what severity. There is no specific pattern of distribution of the pain; either shoulder can be affected, as can the epigastrium. The pain lasts up to 36 hours postoperatively and then dissipates. Techniques such as local infiltration of the peritoneum with local anaesthesia, insertion of indwelling nerve catheters left in proximity to the left hemidiaphragm and the presence of suction drains to remove any residual carbon dioxide have been attempted, but without consistent success. More recently, we have attempted to use ultra-low pneumoperitoneal insufflation pressures (8mm H₂O) and performing prolonged anaesthetic recruitment manoeuvres prior to closure of port sites. These techniques may yield success, but they require further elucidation in the setting of a structured, prospective trial.

Conclusion

We have demonstrated that enhanced recovery within a laparoscopic living-donor nephrectomy programme, concentrating on fluid restriction and morphine sparing, is safe to both donor and recipient. Further efforts to improve the experience of living kidney donors, in particular minimising pain related to pneumoperitoneal insufflation, should be considered.