Moira Bruintjes

The aim of this thesis was to explore strategies to improve the quality of recovery following kidney transplantation (KTX), in both living donors and KTX recipients. We assessed anaesthesiological and surgical innovations to optimise the postoperative recovery, including deep neuromuscular blockade (NMB) and double J (JJ) ureteral stenting.

Chapter 1 provides the general introduction and outline of this thesis. The importance of living kidney donation for patients with end stage renal disease (ESRD) is highlighted and the term postoperative recovery is explained. In addition, the concepts of deep NMB and JJ ureteral stenting are introduced.

PART I - OPTIMISING RECOVERY IN LIVING KIDNEY DONATION

Chapter 2 includes a systematic review and meta-analysis, in which we compared the influence of deep NMB and moderate NMB on the surgical space conditions during laparoscopy. Our search yielded 12 studies on the effect of deep NMB on the surgical space conditions. The meta-analysis showed that the use of deep NMB during laparoscopic surgeries improves the surgical space conditions when compared to moderate NMB, with a mean difference of 0.65 [0.47-0.83] on a scale of 1-5. Furthermore, we found a reduction of postoperative pain scores in the PACU in the group with deep NMB, with a mean difference of -0.52 [-0.71- -0.32].

Chapter 3 describes the study protocol of the RELAX-study, a randomised controlled trial in 96 patients, scheduled for laparoscopic donor nephrectomy (LDN), comparing the efficacy of deep versus moderate NMB in enhancing postoperative recovery after LDN. The primary outcome was the early quality of recovery, measured by the Quality of Recovery-40 (QoR-40) questionnaire. Secondary outcomes were adverse events (AE’s), postoperative pain, analgesic consumption and length-of-stay. The results of the RELAX-study are described in chapter 4. The intention-to-treat analysis did not show a difference with regard to the quality of recovery, pain scores, analgesic consumption and length-of-stay. However, less intraoperative AE’s occurred in patients allocated to deep NMB (1/48 versus 6/48). Furthermore, the RELAX-study showed that - in clinical practice - it can be difficult to achieve and maintain an adequate deep NMB. Five patients allocated to a deep NMB received a moderate block and in two patients neuromuscular monitoring failed. Therefore, an additional as-treated analysis was performed, which revealed a higher QoR-40 score on postoperative day 2 and significant lower postoperative pain scores, in the group allocated to deep NMB.

In chapter 5, we explored the prevalence of chronic postsurgical pain (CPSP) following LDN. This cross-sectional cohort study revealed a mean prevalence of CPSP of 5.7% within 512 living kidney donors with a mean follow-up time of 6 years. Severe early postoperative pain, previous abdominal surgery and pre-existing pain problems were identified as possible predictors for CPSP following LDN. Furthermore, the RAND SF-36 questionnaire showed an impaired health-related quality of life (HRQoL) in patients with CPSP when compared to those without CPSP. Our unique data indicate that CPSP following LDN is a highly relevant issue and that potential living kidney donors should be well informed in the preoperative phase about the risk of CPSP.

PART II - OPTIMISING RECOVERY IN KIDNEY TRANSPLANTATION RECIPIENTS

Chapter 6 provides an update on the incidence of major urological complications (MUCs), including urinary leakage and ureteral obstruction, following living donor and deceased donor KTX. Within a Dutch cohort of 3329 KTX recipients between January 2005 and December 2015, 208 patients (6.2%) developed MUCs within 3 months after surgery. There were no significant differences in complication rates between recipients from living donors and deceased donors. An older donor age and previous cardiac events of the recipient were revealed as predictors for the development of urological complications. The occurrence of early MUCs did not affect graft or patient survival. An additional sub-study showed that preservation of peri-ureteric tissue within living donor KTX was not independently associated with urological complications.

In chapter 7, we investigated the influence of JJ stents versus externally draining percutaneous (PC) stents on the postoperative recovery in living donor KTX. A prospective cohort study was performed in two consecutive cohorts of 40 patients who underwent living donor KTX. Patients with a JJ stent scored significantly better on the Quality of Recovery score, when compared to patients in the PC cohort, on the third postoperative day (191.0 versus 185.0; p=0.019) and the fifth postoperative day (193.0 versus 189.5; p=0.021). Furthermore, patients with a JJ stent were earlier mobilising and independent in daily activities, in comparison to patients with a PC stent, resulting in a shorter length of hospital stay. The number of postoperative urological complications was comparable between the two groups.

Chapter 8 provides a general discussion on the research presented in this thesis and our view on the future perspectives of deep NMB and JJ stenting.