Patrick Y. Wuethrich

Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study

Background:Recently published studies suggest that the anesthetic technique used during oncologic surgery affects cancer recurrence. To evaluate the effect of anesthetic technique on disease progression and long-term survival, we compared patients receiving general anesthesia plus intraoperative and postoperative thoracic epidural analgesia with patients receiving general anesthesia alone undergoing open retropubic radical prostatectomy with extended pelvic lymph node dissection. Methods:Two sequential series were studied. Patients receiving general anesthesia combined with epidural analgesia (January 1994–June 1997, n = 103) were retrospectively compared with a group given general anesthesia combined with ketorolac-morphine analgesia (July 1997–December 2000, n = 158). Biochemical recurrence-free survival, clinical progression-free survival, cancer-specific survival, and overall survival were assessed using the Kaplan–Meier technique and compared using a multivariate Cox-proportional-hazards regression model and an alternative model with inverse probability weights to adjust for propensity score. Results:Using propensity score adjustment with inverse probability weights, general anesthesia combined with epidural analgesia resulted in improved clinical progression-free survival (hazard ratio, 0.45; 95% confidence interval, 0.27–0.75, P = 0.002). No significant differences in the two groups were found for biochemical recurrence-free survival, cancer-specific survival, or overall survival. Higher preoperative serum values for prostate-specific antigen, specimen Gleason score of at least 7, non–organ-confined tumor stage, and positive lymph node status were independent predictors of biochemical recurrence-free survival. Conclusions:General anesthesia with epidural analgesia was associated with a reduced risk of clinical cancer progression. However, no significant difference was found between general anesthesia plus postoperative ketorolac-morphine analgesia and general anesthesia plus intraoperative and postoperative thoracic epidural analgesia in biochemical recurrence-free survival, cancer-specific survival, or overall survival.

Restrictive Deferred Hydration Combined with Preemptive Norepinephrine Infusion during Radical Cystectomy Reduces Postoperative Complications and Hospitalization Time: A Randomized Clinical Trial

Background:Anesthetics and neuraxial anesthesia commonly result in vasodilation/hypotension. Norepinephrine counteracts this effect and thus allows for decreased intraoperative hydration. The authors investigated whether this approach could result in reduced postoperative complication rate. Methods:In this single-center, double-blind, randomized, superiority trial, 166 patients undergoing radical cystectomy and urinary diversion were equally allocated to receive 1 ml·kg−1·h−1 of balanced Ringer’s solution until the end of cystectomy and then 3 ml·kg−1·h−1 until the end of surgery combined with preemptive norepinephrine infusion at an initial rate of 2 µg·kg−1·h−1 (low-volume group; n = 83) or 6 ml·kg−1·h−1 of balanced Ringer’s solution throughout surgery (control group; n = 83). Primary outcome was the in-hospital complication rate. Secondary outcomes were hospitalization time, and 90-day mortality. Results:In-hospital complications occurred in 43 of 83 patients (52%) in the low-volume group and in 61 of 83 (73%) in the control group (relative risk, 0.70; 95% CI, 0.55–0.88; P = 0.006). The rates of gastrointestinal and cardiac complications were lower in the low-volume group than in the control group (5 [6%] vs. 31 [37%]; relative risk, 0.16; 95% CI, 0.07–0.39; P < 0.0001 and 17 [20%] vs. 39 [48%], relative risk, 0.43; 95% CI, 0.26–0.60; P = 0.0003, respectively). The median hospitalization time was 15 days [range, 11, 27d] in the low-volume group and 17 days [11, 95d] in the control group (P = 0.02). The 90-day mortality was 0% in the low-volume group and 4.8% in the control group (P = 0.12). Conclusion:A restrictive-deferred hydration combined with preemptive norepinephrine infusion during radical cystectomy and urinary diversion significantly reduced the postoperative complication rate and hospitalization time.

Intraoperative Continuous Norepinephrine Infusion Combined with Restrictive Deferred Hydration Significantly Reduces the Need for Blood Transfusion in Patients Undergoing Open Radical Cystectomy: Results of a Prospective Randomised Trial

BACKGROUND Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringers maleate solution can reduce blood loss and the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. INTERVENTION Patients were randomly allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour until the bladder was removed, then to 3 ml/kg per hour of Ringers maleate solution (norepinephrine/low-volume group) or 6 ml/kg per hour of Ringers maleate solution throughout surgery (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. RESULTS AND LIMITATIONS Total median blood loss was 800 ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200 ml (range: 400-2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (±0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (±2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD.

Epidural Analgesia during Open Radical Prostatectomy Does Not Improve Long-Term Cancer-Related Outcome: A Retrospective Study in Patients with Advanced Prostate Cancer

Background A beneficial effect of regional anesthesia on cancer related outcome in various solid tumors has been proposed. The data on prostate cancer is conflicting and reports on long-term cancer specific survival are lacking. Methods In a retrospective, single-center study, outcomes of 148 consecutive patients with locally advanced prostate cancer pT3/4 who underwent retropubic radical prostatectomy (RRP) with general anesthesia combined with intra- and postoperative epidural analgesia (n=67) or with postoperative ketorolac-morphine analgesia (n=81) were reviewed. The median observation time was 14.00 years (range 10.87-17.75 yrs). Biochemical recurrence (BCR)-free, local and distant recurrence-free, cancer-specific, and overall survival were estimated using the Kaplan-Meier technique. Multivariate Cox proportional-hazards regression models were used to analyze clinicopathologic variables associated with disease progression and death. Results The survival estimates for BCR-free, local and distant recurrence-free, cancer-specific survival and overall survival did not differ between the two groups (P=0.64, P=0.75, P=0.18, P=0.32 and P=0.07). For both groups, higher preoperative PSA (hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.01-1.02, P<0.0001), increased specimen Gleason score (HR 1.24, 95% CI 1.06-1.46, P=0.007) and positive nodal status (HR 1.66, 95% CI 1.03-2.67, P=0.04) were associated with higher risk of BCR. Increased specimen Gleason score predicted death from prostate cancer (HR 2.46, 95% CI 1.65-3.68, P<0.0001). Conclusions General anaesthesia combined with epidural analgesia did not reduce the risk of cancer progression or improve survival after RRP for prostate cancer in this group of patients at high risk for disease progression with a median observation time of 14.00 yrs.

No benefit from perioperative intravenous lidocaine in laparoscopic renal surgery: a randomised, placebo-controlled study.

Context There is evidence that perioperative intravenous lidocaine administration can reduce analgesic requirement, improve recovery of bowel function and shorten the length of hospital stay. Its effect in laparoscopic renal surgery has not been investigated. Objective To evaluate the effect of systemic lidocaine on the length of hospital stay, readiness for discharge, opioid requirement, bowel function and inflammatory and stress response after laparoscopic renal surgery. Design Randomised, double-blind, placebo-controlled study. Setting Single tertiary centre where the study was carried out between July 2009 and February 2011. Participants Sixty-four patients completed the study. Inclusion criteria were laparoscopic renal surgery and American Society of Anesthesiologists physical status I to III. Exclusion criteria were steroid therapy, chronic opioid therapy, allergy to lidocaine, pre-existing bowel dysfunction and arrhythmia. Intervention Lidocaine was given as a 1.5 mg kg−1 bolus during induction of anaesthesia, followed by an intraoperative infusion of 2 and 1.3 mg kg−1 h−1 for 24 h postoperatively. Primary outcome was the length of hospital stay. Secondary outcomes were readiness for discharge, opioid consumption, sedation, incidence of postoperative nausea and vomiting (PONV), return of bowel function and inflammatory and stress responses. Main outcome measure Length of hospital stay. Results The length of hospital stay did not differ between the groups [6 days for the lidocaine group, interquartile range (IQR) 5 to 7, range 2 to 8 vs. 5 days for the placebo group, IQR 5 to 6, range 2 to 11; P = 0.24). Lidocaine had no effect on readiness for discharge [4 days for the lidocaine group (IQR 5 to 7, range 2 to 8) vs. 4 days for the placebo group (IQR 5 to 7, range 2 to 11); P = 0.26], opioid consumption, postoperative sedation, PONV, return of bowel function and plasma concentrations of C-reactive protein, procalcitonin and cortisol. Conclusion Systemic perioperative lidocaine administration over 24 h did not influence the length of the hospital stay, readiness for discharge, opioid consumption, return of bowel function or inflammatory and stress responses after laparoscopic renal surgery. Trial registration ClinicalTrials.gov identifier NCT00789620.

Effects of thoracic epidural analgesia on lower urinary tract function in women.

Aims: The need for an indwelling transurethral catheter in patients with postoperative thoracic epidural analgesia (TEA) is a matter of controversy. Subjective observations are ambivalent and the literature addressing this issue is scarce. As segmental blockade can be achieved with epidural analgesia, we hypothesized that analgesia within segments T4–T11 has no or minimal influence on lower urinary tract function. Thus, we evaluated the effect of TEA on lower urinary tract function by urodynamic studies. Methods: In 13 women with no preoperative lower urinary tract symptoms undergoing open kidney surgery by lumbotomy under TEA, we prospectively assessed changes in urodynamic parameters the day before and 2–3 days after surgery with the patients under TEA. Results: Before versus during TEA, there was a significant increase in postvoid residual (median, 5 ml vs. 220 ml, P < 0.001) and a significant decrease in maximum detrusor pressure (median, 23 cmH2O vs. 5 cmH2O, P = 0.001), detrusor pressure at maximum flow rate (median, 18 cmH2O vs. 5 cmH2O, P = 0.001), maximum flow rate (median, 12 ml/sec vs. 3 ml/sec, P < 0.001), and voided volume (median, 250 ml vs. 40 ml, P < 0.001). In addition, maximum urethral closure pressure at rest decreased significantly under TEA from median 75 cmH2O to 56 cmH2O (P = 0.002). Bladder sensation, maximum cystometric capacity, compliance, and functional profile length at rest were not influenced by TEA. Conclusions: TEA has a significant effect on bladder emptying with clinically relevant postvoid residual (PVR) necessitating (indwelling or intermittent) catheterization or monitoring of PVR. Neurourol. Urodyn. 30:121–125, 2011.

Detrusor activity is impaired during thoracic epidural analgesia after open renal surgery

Background:There are no data on lower urinary tract function during postoperative thoracic epidural analgesia (TEA). Because selected segmental blockade can be achieved with epidural analgesia, we hypothesized that lower urinary tract function remains unchanged during TEA within segments T4–T11 after open renal surgery. Methods:In a prospective, open, observational, follow-up study, 13 male patients with no preexisting lower urinary tract symptoms (International Prostate Symptom Score ≤7) and postvoid residual less than 100 ml underwent urodynamic investigations the day before open renal surgery (lumbotomy) and 2–3 days postoperatively during TEA. Primary outcome was the difference in postvoid residual before versus after surgery during TEA. Results:The median postvoid residual increased from 25 ml before surgery (range, 0–95) to 420 ml (15–1020) 2–3 days postoperatively (P = 0.002). Maximum detrusor pressure, detrusor pressure at maximum flow rate, and maximum flow rate were significantly reduced during TEA (37 [28–84] to 27 cm H2O [13–51], P = 0.004; 31 [27–52] to 19 cm H2O [0–33], P = 0.003; and 14 [4–35] to 4 ml/s [0–13], P = 0.001), respectively. Bladder capacity and sensation were not changed during TEA. All patients had a postvoid residual determined by ultrasound of less than 100 ml 1 day after removal of the epidural catheter. Conclusions:In contrast to our initial hypothesis, detrusor activity was significantly impaired during TEA after open renal surgery. This resulted in clinically relevant postvoid residuals.

Superior Functional Outcome after Radical Cystectomy and Orthotopic Bladder Substitution with Restrictive Intraoperative Fluid Management: A Followup Study of a Randomized Clinical Trial

PURPOSE Continuous intraoperative norepinephrine infusion combined with restrictive deferred hydration improves surgical field visibility, and significantly decreases intraoperative blood loss and postoperative complications in patients undergoing radical cystectomy and urinary diversion. We determined whether the intraoperative fluid regimen would affect functional results (continence and erectile function) 1 year after orthotopic ileal bladder substitution. MATERIALS AND METHODS We analyzed a subgroup of 93 patients who received an ileal orthotopic bladder substitute. The subgroup was part of a randomized trial in 167 patients initially allocated to continuous norepinephrine administration starting with 2 μg/kg per hour combined with 1 ml/kg per hour initially and 3 ml/kg per hour crystalloid infusion after cystectomy (norepinephrine/low volume group of 51) or a standard crystalloid infusion of 6 ml/kg per hour throughout surgery (42 controls). We prospectively assessed daytime and nighttime continence, and erectile function 1 year postoperatively in the 93-patient subgroup. RESULTS Daytime continence was reported by 44 of 51 patients (86%) in the norepinephrine/low volume group and by 27 of 42 controls (64%) (p = 0.016), and nighttime continence was reported by 38 (75%) and 25 (60%), respectively (p = 0.077). Erectile function recovery was reported by 26 of 33 preoperatively potent patients (79%) in the norepinephrine/low volume group and by 11 of 29 controls (38%) (p = 0.002). CONCLUSIONS Patients who undergo radical cystectomy and orthotopic bladder substitution with continuous norepinephrine infusion and restrictive hydration during surgery have significantly better daytime continence and erectile function 1 year postoperatively.

Influence of epidural mixture and surgery on bladder function after open renal surgery: a randomized clinical trial

Background:In a previous observational study, thoracic epidural analgesia (TEA) after open renal surgery resulted in clinically relevant postvoid residuals (PVRs). This study aimed to investigate the individual contribution of epidurally administrated drugs and surgery in bladder dysfunction. Methods:In this single-center, parallel-group, randomized (computer-generated list), double-blind superiority trial, 40 patients undergoing open renal surgery were equally allocated to receive epidural bupivacaine (0.125%) alone or with fentanyl (2 µg/ml). Patients underwent urodynamic investigations before TEA and during TEA preoperatively and postoperatively. Primary outcome was the difference (&Dgr;) in PVR between before TEA and postoperatively during TEA. Secondary outcomes were changes in detrusor pressure at maximum flow rate, bladder compliance, and &Dgr;PVR between different time points. Results:Median &Dgr;PVR (ml) from baseline to postoperatively was 180 (range, −85 to 645; P = 0.001) in the bupivacaine group and 235 (range, 0–580; P value less than 0.001) in the bupivacaine/fentanyl group, with no difference between groups (95% confidence interval, −167 to 103; P = 0.634). Detrusor pressure at maximum flow rate (cm H2O) from baseline was more pronounced in the bupivacaine/fentanyl than that in the bupivacaine group preoperatively (−10; range, −64 to −2; P value less than 0.001 vs. −3; range, −35 to 13; P = 0.397) (P = 0.045) and postoperatively (−18; range, −64 to 0; P value less than 0.001 vs. −12; range, −34 to 22; P = 0.006) (P = 0.135). Surgery did not affect PVRs, but a decreased bladder compliance was observed in both groups. No adverse events occurred. Conclusions:Thoracic epidurally administrated bupivacaine resulted in clinically relevant PVRs based on impaired detrusor function. The addition of fentanyl enhanced this effect without generating greater PVRs. After surgery, the voiding phase was not further impaired; however, bladder compliance was decreased.

Improved perioperative outcome with norepinephrine and a restrictive fluid administration during open radical cystectomy and urinary diversion

Intravenous fluid administration is fundamental in the perioperative period to replace the fluid lost during major surgery and to maintain physiological organ function. The optimal intraoperative fluid volume to be administered, however, is a matter of intense debate, and controversy persists in terms of how much fluid has to be infused, choice of fluids (crystalloids or colloids), concomitant administration of vasopressors, or a goal-directed hemodynamic therapy (GDT) aiming for an optimization or maximization of the stroke volume [1–6]. Intravenous fluids should be considered as drugs and consequently indication, timing, and dosage are relevant, regardless of the type of fluid.