Sacral neuromodulation blocks pudendal inhibition of reflex bladder activity in cats: insight into the efficacy of sacral neuromodulation in Fowler's syndrome.

This study tested the hypothesis that sacral neuromodulation, i.e., electrical stimulation of afferent axons in sacral spinal root, can block pudendal afferent inhibition of the micturition reflex. In α-chloralose-anesthetized cats, pudendal nerve stimulation (PNS) at 3-5 Hz was used to inhibit bladder reflex activity while the sacral S1 or S2 dorsal root was stimulated at 15-30 Hz to mimic sacral neuromodulation and to block the bladder inhibition induced by PNS. The intensity threshold (T) for PNS or S1/S2 dorsal root stimulation (DRS) to induce muscle twitch of anal sphincter or toe was determined. PNS at 1.5-2T intensity inhibited the micturition reflex by significantly ( P < 0.01) increasing bladder capacity to 150-170% of control capacity. S1 DRS alone at 1-1.5T intensity did not inhibit bladder activity but completely blocked PNS inhibition and restored bladder capacity to control level. At higher intensity (1.5-2T), S1 DRS alone inhibited the micturition reflex and significantly increased bladder capacity to 135.8 ± 6.6% of control capacity. However, the same higher intensity S1 DRS applied simultaneously with PNS, suppressed PNS inhibition and significantly ( P < 0.01) reduced bladder capacity to 126.8 ± 9.7% of control capacity. S2 DRS at both low (1T) and high (1.5-2T) intensity failed to significantly reduce PNS inhibition. PNS and S1 DRS did not change the amplitude and duration of micturition reflex contractions, but S2 DRS at 1.5-2T intensity doubled the duration of the contractions and increased bladder capacity. These results are important for understanding the mechanisms underlying sacral neuromodulation of nonobstructive urinary retention in Fowler's syndrome.

An excitatory reflex from the superficial peroneal nerve to the bladder in cats.

This study in α-chloralose-anesthetized cats discovered an excitatory peroneal nerve-to-bladder reflex. A urethral catheter was used to infuse the bladder with saline and record bladder pressure changes. Electrical stimulation was applied to the superficial peroneal nerve to trigger reflex bladder activity. With the bladder distended at a volume ~90% of bladder capacity, superficial peroneal nerve stimulation (PNS) at 1-3 Hz and threshold (T) intensity for inducing muscle twitching on the posterior thigh induced large-amplitude (40-150 cmH2O) bladder contractions. PNS (1-3 Hz, 1-2T) applied during cystometrograms (CMGs) when the bladder was slowly (1-3 ml/min) infused with saline significantly (P < 0.01) reduced bladder capacity to ~80% of the control capacity and significantly (P < 0.05) enhanced reflex bladder contractions. To determine the impact of PNS on tibial nerve stimulation (TNS)-induced changes in bladder function, PNS was delivered following TNS. TNS of 30-min duration produced long-lasting poststimulation inhibition and significantly (P < 0.01) increased bladder capacity to 140.5 ± 7.6% of the control capacity. During the post-TNS inhibition period, PNS (1-3 Hz, 1-4T) applied during CMGs completely restored bladder capacity to the control level and significantly (P < 0.05) increased the duration of reflex bladder contractions to ~200% of control. The excitatory peroneal nerve-to-bladder reflex could also be activated by transcutaneous PNS using skin surface electrodes attached to the dorsal surface of the foot. These results raise the possibility of developing novel neuromodulation therapies to treat underactive bladder and nonobstructive urinary retention.

Glutamatergic Mechanisms Involved in Bladder Overactivity and Pudendal Neuromodulation in Cats.

The involvement of ionotropic glutamate receptors in bladder overactivity and pudendal neuromodulation was determined in α-chloralose anesthetized cats by intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder produced bladder overactivity. In the first group of 5 cats, bladder capacity was significantly (P < 0.05) reduced to 55.3±10.0% of saline control by AA irritation. Pudendal nerve stimulation (PNS) significantly (P < 0.05) increased bladder capacity to 106.8 ± 15.0% and 106.7 ± 13.3% of saline control at 2T and 4T intensity, respectively. T is threshold intensity for inducing anal twitching. MK801 at 0.3 mg/kg prevented the increase in capacity by 2T or 4T PNS. In the second group of 5 cats, bladder capacity was significantly (P < 0.05) reduced to 49.0 ± 7.5% of saline control by AA irritation. It was then significantly (P < 0.05) increased to 80.8±13.5% and 79.0±14.0% of saline control by 2T and 4T PNS, respectively. CP465022 at 0.03-1 mg/kg prevented the increase in capacity by 2T PNS and at 0.3-1 mg/kg prevented the increase in capacity by 4T PNS. In both groups, MK801 at 0.3 mg/kg and CP465022 at 1 mg/kg significantly (P < 0.05) increased the prestimulation bladder capacity (about 80% and 20%, respectively) and reduced the amplitude of bladder contractions (about 30 and 20 cmH2O, respectively). These results indicate that NMDA and AMPA glutamate receptors are important for PNS to inhibit bladder overactivity and that tonic activation of these receptors also contributes to the bladder overactivity induced by AA irritation.

Role of cannabinoid receptor type 1 in tibial and pudendal neuromodulation of bladder overactivity in cats.

The role of cannabinoid type 1 (CB1) receptors in tibial and pudendal neuromodulation of bladder overactivity induced by intravesical infusion of 0.5% acetic acid (AA) was determined in α-chloralose anesthetized cats. AA irritation significantly (P < 0.01) reduced bladder capacity to 36.6 ± 4.8% of saline control capacity. Tibial nerve stimulation (TNS) at two or four times threshold (2T or 4T) intensity for inducing toe movement inhibited bladder overactivity and significantly (P < 0.01) increased bladder capacity to 69.2 ± 9.7 and 79.5 ± 7.2% of saline control, respectively. AM 251 (a CB1 receptor antagonist) administered intravenously at 0.03 or 0.1 mg/kg significantly (P < 0.05) reduced the inhibition induced by 2T or 4T TNS, respectively, without changing the prestimulation bladder capacity. However, intrathecal administration of AM 251 (0.03 mg) to L7 spinal segment had no effect on TNS inhibition. Pudendal nerve stimulation (PNS) also inhibited bladder overactivity induced by AA irritation, but AM 251 at 0.01-1 mg/kg iv had no effect on PNS inhibition or the prestimulation bladder capacity. These results indicate that CB1 receptors play an important role in tibial but not pudendal neuromodulation of bladder overactivity and the site of action is not within the lumbar L7 spinal cord. Identification of neurotransmitters involved in TNS or PNS inhibition of bladder overactivity is important for understanding the mechanisms of action underlying clinical application of neuromodulation therapies for bladder disorders.

Effect of a concomitant urologic procedure on outcomes following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND AND OBJECTIVES: To evaluate whether urologic procedures during cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) are associated with adverse postoperative outcomes. METHODS: We identified patients who underwent CRS-HIPEC at our institution from 2001 to 2012 and compared outcomes between operations that did and did not include a urologic procedure. RESULTS: A total of 938 CRS-HIPEC procedures were performed, 71 of which included a urologic intervention. Urologic interventions were associated with longer operative times (547 vs. 459 min, P < 0.001) and greater length of stay (15 vs. 12 days, P = 0.003). Major complications (Clavien III and IV) were more common in the urologic group (31% vs. 20%, P = 0.028). On multivariable analysis, urologic procedures were associated with a low anterior resection (OR: 2.25, 95%CI 1.07-4.74, P = 0.033) and a greater number of enteric anastomoses (OR: 1.83, 95%CI 1.31-2.56, P < 0.001). At a median follow up of 17 months (IQR 5.6-35 months), addition of a urologic procedure did not significantly impact overall survival for appendiceal or colorectal cancers. CONCLUSION: Urologic surgery at the time of CRS-HIPEC is associated with longer operative times, length of stay and increased risk of major complications, but not with decreased overall survival. J. Surg. Oncol. 2016;113:218-222. © 2016 Wiley Periodicals, Inc.

Physicians' decision-making roles for an acutely unstable critically and terminally ill patient.

OBJECTIVES: There is substantial variation in use of life sustaining technologies in patients near the end of life but little is known about variation in physicians' initial ICU admission and intubation decision making processes. Our objective is to describe variation in hospital-based physicians' communication behaviors and decision-making roles for ICU admission and intubation decisions for an acutely unstable critically and terminally ill patient. DESIGN: We conducted a secondary analysis of transcribed simulation encounters from a multi-center observational study of physician decision making. The simulation depicted a 78-year-old man with metastatic gastric cancer and life threatening hypoxia. He has stable underlying preferences against ICU admission and intubation that he or his wife will report if asked. We coded encounters for communication behaviors (providing medical information, eliciting preferences/values, engaging the patient/surrogate in deliberation, and providing treatment recommendations) and used a previously-developed framework to classify subject physicians into four -mutually-exclusive decision-making roles: informative (providing medical information only), facilitative (information + eliciting preferences/values + guiding surrogate to apply preferences/values), collaborative (information + eliciting + guiding + making a recommendation) and directive (making an independent treatment decision). SETTING: Simulation centers at 3 US academic medical centers. SUBJECTS: Twenty-four emergency physicians, 37 hospitalists, and 37 intensivists. MEASUREMENTS AND MAIN RESULTS: Subject physicians average 12.4 years (SD 9.0) since graduation from medical school. Of 98 physicians (39%), 38 physicians sent the patient to the ICU, and 9 of 98 (9%) ultimately decided to intubate. Most (93 of 98 [95%]) provided at least some medical information, but few explained the short-term prognosis with (26 of 98 [27%]) or without intubation (37 of 98 [38%]). Many (80 of 98 [82%]) elicited the patient's intubation preferences, but few (35 of 98 [36%]) explored the patient's broader values. Based on coded behaviors, we categorized 1 of 98 (1%) as informative, 48 of 98 (49%) as facilitative, 36 of 98 (37%) as collaborative, and 12 of 98 (12%) as directive; 1 of 98 (1%) could not be placed into a category. No observed physician characteristics predicted decision-making role. CONCLUSIONS: The majority of the physicians played a facilitative or collaborative role, although a greater proportion assumed a directive role in this time-pressured scenario than has been documented in nontime-pressured ICU family meetings, suggesting that physicians' roles may be context dependent.