Vardenafil decreases bladder afferent nerve activity in unanesthetized, decerebrate, spinal cord-injured rats

Background

Phosphodiesterase type 5 inhibitors (PDE5-Is) improve storage symptoms in benign prostatic hyperplasia patients, despite a lack of effect on peak urinary flow rate. Moreover, vardenafil improves urodynamic parameters in spinal cord-injured (SCI) patients with neurogenic detrusor overactivity (NDO). SCI rats also display NDO characterized by nonvoiding contractions (NVCs) during bladder filling, resulting in an increased bladder afferent nerve firing (BANF).

Objective

We postulated that vardenafil could improve urodynamic parameters by reducing BANF. The effect of vardenafil has been investigated on intravesical pressure by cystometry experiments while recording BANF in response to bladder filling.

Design, setting, and participants

Complete T7–T8 spinalization was performed in 15 female adult Sprague-Dawley rats (250–275 g).

Measurements

At 21–29 d postspinalization, fine filaments were dissected from the L6 dorsal roots and placed across a bipolar electrode. Bladder afferent nerve fibers were identified by electrical stimulation of the pelvic nerve and bladder distension. SCI rats were decerebrated before cystometry experiments. Bladders were filled to determine the maximal bladder filling volume (BFV) for each rat. Then, after bladder stabilization at 75% of maximal BFV, saline (n = 7) or vardenafil 1 mg/kg (n = 8) was delivered intravenously. NVCs and BANF were recorded for 45 min.

Results and limitations

In all SCI rats, BANF was already present and regular at resting conditions (26.2 ± 4.1 spikes per second). During bladder filling, intravesical pressure (IVP) slowly increased with transient NVCs superimposed. Concomitantly, BANF progressively increased up to 2.4-fold at maximal BFV (2.08 ± 0.24 ml). After stabilization at submaximal BFV, BANF was increased by 186 ± 37%. Vardenafil injection induced an immediate decrease in NVCs compared to saline (p < 0.001) and BANF (52% decrease vs 28% in saline after 45 min; p < 0.001).

Conclusions

Systemic vardenafil reduced both NVCs and BANF in unanesthetized, decerebrate, SCI rats. These findings provide new insights into the mechanism of action by which PDE5-Is improve storage symptoms in SCI patients.     

Mortality and prognostic factors of the cirrhotic patients with hepatic encephalopathy admitted to medical intensive care unit

Objective

To assess mortality and to identify variables that could predict it in cirrhotic patients hospitalized to the medical intensive care unit (MICU) for hepatic encephalopathy (HE).

Study design

Retrospective cohort study.

Patients and methods

From January 1995 to December 2004, the cirrhotic patients admitted consecutively in MICU were screened and those with altered level of consciousness were included. The MICU mortality rate was assessed. Nearly 80 variables were analyzed and compared between survivors and non-survivors. Statistical analysis: t test, χ² or Fisher exact tests, Kaplan-Meier and log rank, Cox regression analysis.

Results

A total of 180 patients (42 women - 138 men, mean age: 59 ± 10 years) were admitted (incidence: 2.6%). The SAPS II was 30.1 ± 11, Acute Physiology Age and Chronic Health Evaluation II (APACHE II): 16.5 ± 5.3, Child-Pugh score: 9.1 ± 1.9 and GCS: 11 ± 2.8. The causes of liver cirrhosis was identified in 41.2% of cases (viral: 35.6%, alcohol: 5.6%). Nearly 18% of patients had an antecedent of HE. The causes of HE were: infection (65.6%), upper gastrointestinal bleeding (32.2%), drugs (5%) and metabolic cause (5%). MICU mortality rate was 33.3% and seemed higher in gastrointestinal bleeding. Eighteen variables were significantly associated with poor prognosis in univariate analysis. Only three variables remained significant in multivariate analysis: systolic blood pressure < 90 mmHg (RR = 4; IC95% = 2–8.1), total WBC > 12 000 n/mm³ (RR = 3.1; IC95% = 1.8–5.3) and use of mechanical ventilation (RR = 3.1; IC95% = 1.7–5.6).

Conclusion

The MICU mortality of cirrhotic patients with HE was high and significantly associated with haemodynamic instability, hyperleucocytosis and mechanical ventilation.     

Prevention of recurrent urinary tract infections by intravesical administration of hyaluronic acid and chondroitin sulphate: a placebo-controlled randomised trial

Background

Urinary tract infection (UTI) is a prevalent condition in women during their lifetime with a high rate of recurrence within 3–6 mo.

Objectives

Our aim was to investigate the efficacy and tolerability of the intravesical administration of combined hyaluronic acid (HA) and chondroitin sulphate (CS) in female patients with a history of recurrent UTI.

Design, setting, and participants

We conducted a prospective, randomised, double-blind, placebo-controlled study comparing the intravesical instillation of HA-CS with placebo in women with recurrent UTI.

Intervention

Participants were randomised to receive 50 ml of sterile sodium HA 1.6% and CS 2.0% solution (IALURIL^®) weekly for 4 wk and then monthly for 5 mo.

Measurements

The primary end point of the study was defined as the mean number of UTI per patient per year. Participants were evaluated addressing UTI status/urinary symptoms and with a general health-related quality-of-life (QoL) questionnaire at baseline and after 3, 6, 9, and 12 mo.

Results and limitations

In the intention-to-treat analysis, 57 women were randomly allocated to HA-CS (n = 28) or placebo (n = 29). The UTI rate per patient per year at the end of the study (12 mo) (mean ± SD: −86.6% ± 47.6 vs −9.6% ± 24.6; mean difference: 77%; 95% confidence interval, 72.3–80.8; p = 0.0002) and the mean time to UTI recurrence (52.7 ± 33.4 vs 185.2 ± 78.7 d; p < 0.001) were significantly reduced after treatment with HA-CS compared with placebo. Overall urinary symptoms and QoL measured by questionnaires significantly improved compared with placebo (Pelvic Pain and Urgency/Frequency questionnaire symptom score: 14.53 ± 4.32 vs 9.88 ± 6.77; p = 0.004; SF-36 QoL score: 78.6 ± 6.44 vs 53.1 ± 4.72; p < 0.001). No serious adverse event was reported.

Conclusions

Compared with placebo, HA-CS intravesical instillations significantly reduced UTI rate without severe side effects while improving symptoms and QoL over a 12-mo period in patients with recurrent UTI.

Trial registration

ISRCTN 76354426.     

Prospective study of the role of transurethral resection of the prostate in patients with an elevated prostate-specific antigen level, minor lower urinary tract symptoms, and proven bladder outlet obstruction

Background

Deciding on strategy for patients with minor lower urinary tract symptoms (LUTS), elevated prostate-specific antigen (PSA) levels, unsuspicious digital rectal examination (DRE) and/or transrectal ultrasound (TRUS), and multiple negative extended prostate biopsies is complex.

Objectives

To define the role and clinical significance of transurethral resection of the prostate (TURP) in these patients.

Design, settings, and participants

Thirty-three patients with elevated PSA; minor LUTS, as assessed by the International Prostate Symptoms Score (IPSS); no suspicion for prostate cancer on DRE and/or TRUS; and negative extended prostate biopsies were prospectively enrolled in a cohort study at a tertiary care institution.

Intervention

After full urodynamic investigation showing all patients to be bladder outlet obstructed, TURP was performed.

Measurements

Resected tissue was histologically examined for presence of prostate cancer. Within 6 mo after TURP, patients were clinically reevaluated by means of IPSS and PSA level.

Results and limitations

Preoperatively, mean PSA and IPSS values were 8.2 ng/ml and 6.8, respectively. Mean detrusor pressure at maximum flow was 80.3 cm H₂O. Histological examination after TURP revealed benign prostate hyperplasia in 81.8% (subgroup 1) and aggressive prostate cancer in 6.1% of patients (subgroup 2). In 12.1% of patients, only a few chips of nonaggressive prostate cancer (T1a) were detected. In patients without signs of aggressive prostate cancer (93.9% = 12.1% + 81.8%, subgroup 3), mean postoperative PSA and IPSS values were 0.6 ng/ml and 2.4, respectively, while these values were 0.6 ng/ml and 2.5 ng/ml in subgroup 1 (p < 0.0001). This study is limited in sample size, requiring more research to confirm these results.

Conclusions

This prospective study shows that, in patients with minor LUTS and no suspicion for prostate cancer, bladder outlet obstruction can result in elevated PSA levels. These patients will benefit from TURP regarding symptomatology and supernormalisation of PSA levels. Moreover, albeit in few cases, histological examination will reveal aggressive prostate cancer.     

Timing of tracheostomy and outcome of patients requiring mechanical ventilation

Objectives

To assess the impact of tracheostomy timing on outcome of critically ill patients requiring mechanical ventilation (MV).

Study design

Retrospective clinical study in a twelve beds intensive care unit (ICU).

Patients and methods

From January 2001 to June 2005, patients under MV who received tracheostomy were divided into 2 groups: early tracheostomy group when tracheostomy was performed before or on day 7 and late tracheostomy group when it was performed thereafter. We compared prevalence of nosocomial pneumonia, length of sedation, lengths of MV, length of stay in ICU, weaning from MV and mortality rates between the 2 groups.

Results

During this period of 4 years and half, 112 patients underwent tracheostomy, 62 of whom had early tracheostomy and 50 had late tracheostomy. Early tracheostomy was associated with significant reduction of length of sedation (10 ± 3 vs 17 ± 5 days, P < 0.001), length of MV (21 ± 19 vs 29 ± 17 days, P = 0.02) and length of stay in ICU (33 ± 22 vs 42 ± 18 days, P = 0.042). There were no differences in prevalence of pneumonia (21% for early tracheostomy group vs 31% for late tracheostomy group, P = 0, 13), weaning from MV (50 vs 36%, P = 0.19), and mortality rates between the 2 groups (38 vs 54%, P = 0.15).

Conclusion

This study demonstrated that early tracheostomy (≤ 7 days), was associated with shorter length of sedation, shorter duration of MV and shorter ICU length of stay, without affecting weaning from MV, prevalence of nosocomial pneumonia or survival.     

Influence of nerve transsections and combined bladder filling on intravesical electrostimulation-induced bladder contraction in the rat

Background

The exact mechanisms of action of intravesical electrical stimulation (IVES) are not yet fully understood.

Objective

To gain more insight into the underlying mechanism(s) of the direct detrusor response during IVES by transsecting the dorsal roots and the pelvic nerve consecutively at different levels and to determine whether the efficiency of IVES to induce contraction could be enhanced by simultaneous bladder filling and IVES and by changing the bladder-filling grade.

Design, Setting, and Participants

Eighteen Sprague-Dawley rats underwent IVES (square-wave pulses at 10 Hz, 20-ms pulse duration).

Measurements

In seven rats, IVES-induced bladder-pressure development was studied after the bladder nerves were consecutively sectioned bilaterally at four different levels: no lesion, L6 dorsal roots, L6 ventral roots, pelvic nerve, and major pelvic ganglion with surrounding nerves. Bladder-pressure development induced by IVES with simultaneous bladder filling, by bladder filling alone, and by IVES alone was recorded in seven other rats, and bladder-pressure development induced by IVES with different grades of bladder filling was recorded in four rats.

Results and Limitations

Contraction during IVES was significantly weaker after consecutive section of more nerves (all p < 0.001), but a small contraction (19 ± 17% of baseline) could be elicited even after total decentralization. In the neurologically intact rats, separate stimulation and bladder filling gave contraction strengths similar to those of simultaneous bladder filling and stimulation, but the latter gave contraction after a significantly shorter stimulation time (both p < 0.015).

Conclusions

IVES-induced contraction is, for the major part, a nerve-mediated process. However, a small bladder-pressure rise was induced by direct bladder-wall stimulation after all nerves were cut. Simultaneous electrical stimulation and bladder filling needed much shorter stimulation times than bladder filling alone or stimulation alone. If confirmed in humans, this could shorten IVES sessions substantially without altering the contractile results and could indicate that summation of afferent potentials from different triggers is possible.     

Duloxetine for mild to moderate postprostatectomy incontinence: preliminary results of a randomised, placebo-controlled trial

Background

Duloxetine is effective in the management of stress urinary incontinence (SUI) in women but has been poorly evaluated in the treatment of SUI following radical prostatectomy (RP).

Objective

To establish the superiority of duloxetine over placebo in SUI after RP.

Design, setting, and participants

We conducted a prospective, randomised, placebo-controlled, double-blind, monocentric superiority trial. After a placebo run-in period of 2 wk, patients with SUI after RP were randomised to receive either 80 mg of duloxetine daily or matching placebo for 3 mo.

Measurements

The primary outcome measure was the relative variation in incontinence episodes frequency (IEF) at the end of study compared to baseline. Secondary outcomes included quality of life (QoL) measures (Incontinence Impact Questionnaire Short Form [IIQ-SF], Urogenital Distress Inventory Short Form [UDI-SF], Incontinence Quality of Life [I-QoL]), symptom scores (Urinary Symptom Profile [USP] questionnaire, International Consultation on Incontinence/World Health Organisation Short Form questionnaire [ICIQ-SF], the Beck Depression Inventory [BDI-II] questionnaire), 1-h pad test, and assessment of adverse events.

Results and limitations

Thirty-one patients were randomised to either the treatment (n = 16) or control group (n = 15). Reduction in IEF was significant with duloxetine compared to placebo (mean ± standard deviation [SD] variation: −52.2% ± 38.6 [range: −100 to +46] vs +19.0% ± 43.5 [range: −53 to +104]; mean difference: 71.2%; 95% confidence interval [CI] for the difference: 41.0–101.4; p < 0.0001). IIQ-SF total score, UDI-SF total score, SUI subscore of the USP questionnaire, and question 3 of the ICIQ-SF questionnaire showed improvement in the duloxetine group (p = 0.006, p = 0.02, p = 0.0004, and p = 0.003, respectively). Both treatments were well tolerated throughout the study period.

Conclusions

Duloxetine is effective in the treatment of incontinence symptoms and improves QoL in patients with SUI after RP.     

Anatomic Bladder Neck Preservation During Robotic-Assisted Laparoscopic Radical Prostatectomy: Description of Technique and Outcomes

Background

Robotic-assisted laparoscopic radical prostatectomy (RALP) has been rapidly adopted despite a daunting learning curve with bladder neck dissection as a challenging step for newcomers.

Objective

To describe an anatomic, reproducible technique of bladder neck preservation (BNP) and associated perioperative and long-term outcomes.

Design, settings, and participants

From September 2005 to May 2009, data from 619 consecutive RALP were prospectively collected and compared on the basis of bladder neck dissection technique with 348 BNP and 271 standard technique (ST).

Surgical procedure

RALP with BNP.

Measurements

Tumor characteristics, perioperative complications, and post-operative urinary control were evaluated at 4, 12 and 24 months using (1) the Expanded Prostate Cancer Index (EPIC) urinary function scale scored from 0–100; and (2) continence defined as zero pads per day.

Results and limitations

Mean age for BNP versus ST was 57.1 ± 6.6 yr versus 58.9 ± 6.7 yr (p = 0.033), while complication rates did not vary significantly by technique. Estimated blood loss was 183.7 ± 95.8 ml versus 224.6 ± 108 ml (p = 0.938) in men who underwent BNP versus ST. The overall positive margin rate was 12.8%, which did not differ at the prostate base for BNP versus ST (1.4% vs. 2.2%, p = 0.547). Mean urinary function scores for BNP versus ST at 4, 12, and 24 mo were 64.6 versus 57.2 (p = 0.037), 80.6 versus 79.0 (p = 0.495), and 94.1 versus 86.8 (p < 0.001). Similarly, BNP versus ST continence rates at 4, 12, and 24 mo were 65.6% versus 26.5% (p < 0.001), 86.4% versus 81.4% (p = 0.303), and 100% versus 96.1% (p = 0.308).

Conclusions

BNP versus ST is associated with quicker recovery of urinary function and similar cancer control.     

Minimal effective dose of dysport and botox in a rat model of neurogenic detrusor overactivity

Background

Two botulinum toxins A have been evaluated for the treatment of refractory neurogenic detrusor overactivity (NDO) in humans: Dysport (abobotulinumtoxinA) and Botox (onabotulinumtoxinA). However, these two distinct commercialized products have different potency units and are not interchangeable.

Objective

Assessment of the dose response and determination of minimal effective dose (MED) for Dysport and Botox in spinal cord–injured (SCI) rats with NDO.

Design, setting, and participants

Female, adult, Sprague-Dawley rats (n = 98) underwent T8-T9 spinal cord transection. Nineteen days after spinal cord injury, rats received intradetrusor injections (25 μl injected, eight sites) of vehicle (V); Dysport 2, 5, 7.5, 10, and 12.5 U; and Botox 0.8, 2, 5, 7.5, and 10 U. Two days after injection, continuous cystometry was performed in conscious rats.

Measurements

Voiding contractions (VC) were assessed by duration of VC, intercontraction interval, voided volume, maximal pressure, pressure threshold change, and intravesical baseline pressure (BP), while nonvoiding contractions (NVC) were evaluated by amplitude, frequency, and volume threshold to elicit NVC. MEDs for Dysport and Botox were determined by analysis of variance step-down trend test.

Results and limitations

MEDs for Dysport and Botox were 10 U and 7.5 U, respectively. Regarding VC, only BP significantly decreased after 10 U Dysport and 7.5 U Botox compared to V (from 3.7 ± 0.6 to 1.5 ± 0.1 and 1.4 ± 0.3 mm Hg, respectively; p < 0.01 and p < 0.001, respectively). Dysport (10 U) and Botox (7.5 U) significantly inhibited NVC by decreasing their amplitude (from 7.4 ± 1.1 to 5.8 ± 0.5 and 5.4 ± 0.6 mm Hg, respectively; p < 0.05); frequency (from 2.2 ± 0.4 to 1.5 ± 0.2 and 1.3 ± 0.3 NVC per minute, respectively; p < 0.01); and increasing volume threshold to elicit NVC (from 29.8 ± 3.7 to 47.6 ± 6.9 and 47.7 ± 6.3%, respectively; p < 0.05 and p < 0.001, respectively).

Conclusions

This is the first preclinical dose-ranging study with Dysport and Botox under standardized conditions showing similar inhibiting effects on NDO, albeit at different MEDs. It highlights the importance of distinguishing each preparation for predicted outcomes and doses to be used. Further studies in patients with NDO are warranted to confirm these experimental results.     

Tension-free vaginal tape for the treatment of urodynamic stress incontinence: efficacy and adverse effects at 10-year follow-up

Background

One of the most effective and popular current procedures for the surgical treatment of stress urinary incontinence (SUI) is tension-free midurethral slings.

Objective

To evaluate the outcomes of women with retropubic tension-free vaginal tape (TVT) for urodynamic stress incontinence (USI) after 10-yr follow-up.

Design, setting, and participants

This was a prospective observational study. Consecutive women with proven USI were treated with TVT. Patients with mixed incontinence and/or anatomic evidence of pelvic organ prolapse were excluded.

Intervention

Standard retropubic TVT.

Measurements

Patients underwent preoperative clinical and urodynamic evaluations. During follow-up examinations, women were assessed for subjective satisfaction and objective cure rates. Multivariable analyses were performed to investigate outcomes.

Results and limitations

A total of 63 women were included. After 10 yr, 5 patients (8%) were lost or no longer evaluable. The 10-yr subjective, objective, and urodynamic cure rates were 89.7%, 93.1%, and 91.4%, respectively. These rates were stable across the whole study period (p > 0.99). De novo overactive bladder was reported by 30.1% and 18.9% of patients at 3-mo and 10-yr follow-up, respectively (p for trend = 0.19). A total of 84.2% of women with detrusor overactivity received antimuscarinic drugs, but 43.8% were nonresponders 12 wk later. At multivariable analysis, maximum detrusor pressure during the filling phase >9 cm H₂O (hazard ratio [HR]: 16.2; p = 0.01) and maximum detrusor pressure during the voiding phase ≤29 cm H₂O (HR: 8.0; p = 0.01) were independent predictors for the recurrence of SUI, as well as obesity was for the recurrence of objective SUI (HR: 17.1; p = 0.01) and of USI (HR: 8.9; p = 0.02), respectively. Intraoperatively, bladder perforation occurred in two cases; no severe bleeding or other complications occurred.

Conclusions

The 10-yr results of this study seem to demonstrate that TVT is a highly effective option for the treatment of female SUI, recording a very high cure rate with low complications after a 10-yr follow-up.     

Real-time MRI of orthotopic ileal neobladder voiding: preliminary findings

Objectives

The purpose of this preliminary study was to analyze the dynamic changes in the configuration of the neobladder and naïve bladder during voiding using real-time MRI.

Methods

This study included 10 male patients who had a radical cystectomy and an ileal orthotopic neobladder due to organ-confined bladder cancer and had good urinary function, and 5 male control volunteers. With the subjects in the lateral decubitus position, real-time MRI was performed during micturition. A sagittal slice orientation was used to depict the bladder and the entire length of the urethra; individual movements along the X-axis and Y-axis of the bottom and top of the neobladder and the naïve bladder were recorded and analyzed. Urodynamic studies (UDS) and video voiding cystourethrography were performed in patients.

Results

Five of the 10 neobladder patients could void in the lateral decubitus position. In normal controls and patients who could void, the bladder outlet bladder moved ventrocranially during micturition. The ileal bladder outlet moved a significantly longer distance than the naïve bladder during micturition (X-axis, −13.4 ± 1.5 vs. −3.6 ± 4.3 cm, p = 0.0014; Y-axis, −10.6 ± 0.5 vs. −2.0 ± 6.5 cm, p = 0.0187). The distance that the bladder top moved between the naïve bladders and the neobladder did not differ. UDS did not show a difference between patients who could and could not void at lateral position.

Conclusions

During micturition, the neobladder was found to rotate and move more dynamically than the naïve bladder. Real-time MRI is useful for assessing dynamic voiding function of orthotopic neobladders.     

Effect of whole body vibration on leg muscle strength after healed burns: A randomized controlled trial

Objective

To investigate the effects of eight weeks whole body vibration training program on leg muscle strength (force-producing capacity) in adults after healed burns.

Design

Randomized controlled trial.

Setting

Faculty of Physical Therapy, Cairo University.

Subjects

Thirty-one burned patients participated in the study and were randomized into whole body vibration group and control group. Non-burned healthy adults were assessed similarly to burned subjects and served as matched healthy controls.

Methods

The whole body vibration group performed an eight weeks vibration program three times a week on a vibration platform; the control group received home based physical therapy program without vibration training.

Main measures

Assessment of knee extensors and ankle planter flexor strength by isokinetic dynamometer at 150°/s were performed at the beginning of the study and at the end of the training period for both groups.

Results

Subjects with burns more than 36% TBSA produced significantly less torque in the quadriceps and calf muscle than non-burned healthy subjects. Patients in whole body vibration group showed a significant improvement in knee extensor and ankle planter flexor strength as compared with those in the control group. Knee extensor strength and percent improvement was 233.40 ± 5.74 (64.93 ± 3.03 change score) and 38.54% for the vibration group and 190.07 ± 3.99 (21.66 ± 4.41 change score) and 12.86% for the control group, ankle plantar flexor strength and percent improvement was 156.27 ± 5.95 (54.53 ± 6.16 change score) and 53.70% for the vibration group and 116.13 ± 3.24 (14.66 ± 2.71 change score) and 14.52% for the control group.

Conclusions

Participation in whole body vibration program resulted in a greater improvement in quadriceps and calf muscle strength in adults with healed thermal burn compared to base line values; a WBV program is an effective for strength gain in rehabilitation of burned patients.     

Secondary abdominal compartment syndrome in patients with toxic epidermal necrolysis

Introduction

Secondary abdominal compartment syndrome (ACS) is a severe complication in patients admitted to burn intensive care units (BICUs). Unlike patients with thermal burns, patients with toxic epidermal necrolysis (TEN) present with a different pathophysiology and usually require less fluid.

Patients and methods

We reviewed our registry of adult patients presenting with TEN in our 8-bed BICU over the course of 11 years and identified and analyzed patients treated for ACS and decompressive laparotomy (DL).

Results

From a total of 29 patients with bioptic confirmed TEN, 5 underwent DL due to ACS with a mean age of 57 years, mean percentage of total body surface area (TBSA) affected of 54 ± 25%, complete epidermolysis of 28 ± 24% TBSA, a mean severity of illness score (SCORTEN) of 3.8 ± 0.8, and a mean intra-abdominal pressure before DL of 33 ± 7 mmHg. Mortality was 100% in patients with ACS versus 33% without ACS.

Conclusion

An ACS that requires DL worsens the already critical condition of a TEN patient considerably. TEN-related impaired intestinal functionality and increasing intestinal edema due to systemic capillary leakage warrant early initiation of intra-abdominal pressure monitoring to identify patients at high risk of ACS.     

Efficacy, Tolerability and Safety of Propiverine Hydrochloride in Children and Adolescents with Congenital or Traumatic Neurogenic Detrusor Overactivity—A Retrospective Study

Objectives

Anticholinergic treatment combined with intermittent catheterisation is the cornerstone of the conservative treatment strategy in children with neurogenic detrusor overactivity, which in most cases is due to congenital causes. Efficacy, tolerability and safety of propiverine hydrochloride were evaluated retrospectively in these children.

Methods

At four specialized outpatient clinics, all children's records were scrutinized for first-line propiverine hydrochloride treatment, or second- or third-line treatment after failure of a non-selective alpha-blocker (phenoxybenzamine) and/or other anticholinergics (oxybutynin, trospium chloride). The primary efficacy outcomes were urodynamic parameters, with clinical symptoms as secondary outcomes. Statistical analysis was performed by paired t-tests (significance level p < 0.05).

Results

Altogether 74 children and adolescents (40 boys, 34 girls; age range 11 months–19 years) were treated with propiverine hydrochloride (average duration 2 years and approximately 4 months; individual dose range 5–75 mg). The primary efficacy outcome parameters improved significantly: maximum cystometric capacity 161.2 [standard deviation (SD) 97.3] to 252.2 ml (SD 117.2), p < 0.001; maximum detrusor pressure 43.8 (SD 39.2) to 27.1 cm H₂O (SD 26.4), p = 0.002; bladder compliance 7.6 (SD 6.4) to 17.0 ml/cm H₂O (SD 16.2), p < 0.001. Phasic detrusor overactivity was abolished by 63%; incontinence resolved by 54%. One patient spontaneously reported a typical anticholinergic adverse event, which resolved after dose reduction. No safety concerns were documented.

Conclusions

Propiverine hydrochloride is effective in neurogenic detrusor overactivity in children and adolescents, even in some of those cases unresponsive to other anticholinergics. The low incidence rate (<1.5%) of adverse events evidences a favourable risk-benefit profile of propiverine hydrochloride, considering in particular the total documented treatment and surveillance period of 171 patient years and nine months.     

Effects of music therapy in intensive care unit without sedation in weaning patients versus non-ventilated patients

Objectives

Music has been found to be an effective nonpharmacologic adjunct for managing anxiety and promoting relaxation in limited trials of critically ill patients. However, its effects have not been compared in intubated patients during weaning from mechanical ventilation with non-intubated patients spontaneously breathing.

Study design

A cross-over randomized experimental design.

Patients and Methods

Thirty patients were studied (intubated group n?=?15, non-intubated group n?=?15). Patients were randomized to receive either 20 minutes of uninterrupted rest or then 20 minutes of music therapy or the music therapy first and then the uninterrupted rest period. Patients selected a relaxing music of their choice from a selection including different types of music. Heart rate (HR), systolic blood pressure (SAP), respiratory rate (RR) and bispectral index (BIS score) were recorded each 5-min intervals throughout both periods (rest and music). Agitation/sedation state and pain were evaluated by the Richmond-Agitation-Sedation-Scale (RASS) and the Numerical-Rating-Scale (NRS) respectively, before and after each studied periods. Music have not been performed in five patients (5/35?=?14%).

Results

Music significantly decreased HR (88 ± 15 vs 82 ± 15, P < 0.05), SAP (137 ± 17 vs 128 ± 14, P < 0.05), RR (25 ± 3 vs 22 ± 4, P < 0.05), BIS (94 ± 5 vs 81 ± 10, P < 0.01), RASS (+0.1 ± 0.7 vs –0.7 ± 0.9, P < 0.05) and NRS (4.4 ± 1.7 vs 1.9 ± 1.3, P < 0.01) in both intubated and non-intubated groups whereas no significant change was observed during the rest period. The variations level studied parameters induced by music were comparable for the two groups.

Conclusion

A single music therapy session was found to be effective for decreasing anxiety and promoting relaxation, as indicated by decreases in heart rate, blood pressure, BIS and respiratory rate over the intervention period in intubated patients during weaning phase.     

Dopexamine Test in septic shock with hyperlactatemia

Objective

To evaluate the 6 hours haemodynamic effects of dopexamine (DPX) infusion in septic shock patients with persistent hyperlactatemia treated with high dose of norepinephrine (NE).

Study design

Preliminary, prospective, uncontrolled study.

Patients

Twenty-one septic shock with NE > 0.5 μg/kg/min, venous mixed oxygen saturation (ScvO₂/SvO₂) > 70%, cardiac index (CI) > 3.5 l/min/m² and lactate > 3 mmol/l.

Interventions

Infusion of DPX at 0.5 μg/kg/min. After 6 hours, patients were classified as DPX-responders or DPX-non-responders according to the presence or not of a decrease ≥ 20% in lactatemia.

Measurement

DPX-responders and DPX-non-responders were compared with MAP, CI, central venous pressure (CVP), heart rate (HR) before infusion of DPX (h0), 30 minutes (h0.5) and 6 hours later (h6); and with NE infusion rate at h0 and h6.

Results

Eleven (52%) patients were DPX-responders and 10 (48%) DPX-non-responders. At H0.5, DPX-responders increased MAP more than DPX-non-responders (+21% versus +7%, P = 0.01) with no change in CI, CVP and HR in both groups. At h0.5, an increase in MAP higher than 14%, compared to h0, could predict lactate clearance at h6 (sensitivity 91%, specificity 90%). From h0 to h6, increase in MAP (80 ± 7 versus 70 ± 8 mmHg, P < 0.01) in DPX-responders allowed reduction in NE infusion (from 1.6 ± 0.3 to 0.4 ± 0.3 μg/kg/min, P < 0.01); 28-day mortality was lower in DPX-responders than in DPX-non-responders (7 versus 90%, P < 0.01).

Conclusion

This study suggests that DPX did induce a decrease in lactatemia in 52% of septic shock, that could be predict by an increase in MAP (> 14% within 30 minutes). Controlled studies are needed to confirm those preliminary results.     

Near-infrared spectroscopy: a novel, noninvasive, diagnostic method for detrusor overactivity in patients with overactive bladder symptoms--a preliminary and experimental study

Background

Near-infrared spectroscopy (NIRS) is an optical technology. It detects the hemodynamic changes in tissues via noninvasive measurement of changes in the concentration of tissue chromophores such as oxyhemoglobin (O₂Hb) and deoxyhemoglobin (HHb). Involuntary bladder contractions may cause changes detectable by NIRS.

Objective

To address the accuracy and reproducibility of NIRS to detect the hemodynamic effects of detrusor overactivity (DO).

Design, setting, and participants

A prospective cohort study was carried out on 41 patients with overactive bladder symptoms.

Measurements

Forty-one patients underwent one or more filling cystometries with simultaneous NIRS of the bladder. The separated graphs representing both tests were presented to three urodynamicists on two occasions, 3 wk apart. The graphs showed curves with and without DO episodes with the bladder sensations marked. Thirteen of 47 graphs (28%) with DO and 16 of 58 graphs (28%) without DO were excluded due to motion artifacts. The urodynamicists marked pressure changes suggestive of DO on the cystometry curves. For NIRS curves they marked definite deviations from baseline. The sensitivity and specificity of NIRS for DO were determined. The inter- and intraobserver agreements were determined.

Results and limitations

Valid data from 33 of 41 patients (80%) were included in the analysis. The interobserver agreement to trace the effect of DO on NIRS curves was “substantial” (κ_f > 0.6). The sensitivity of the Hb_sum (O₂Hb + HHb) curves for DO was 62–97% with a specificity of 62–79% (area under the curve [AUC]: 0.80–0.82; p < 0.001). O₂Hb curves had 79–85% sensitivity and 82–91% specificity for DO (AUC: 0.80–0.85; p < 0.001). The sensitivity and specificity of the HHb curves for DO were 71–82% and 77–82%, respectively (AUC: 0.73–0.84; p < 0.001). These values represent the performance of NIRS in the data sample that is not contaminated with motion artifacts; they are not representative of a general clinical setting.

Conclusion

NIRS is a potential noninvasive, reproducible, diagnostic method to detect DO.     

Endoscopic Combined Intrarenal Surgery in Galdakao-Modified Supine Valdivia Position: A New Standard for Percutaneous Nephrolithotomy?

Background

Percutaneous nephrolithotomy (PCNL), the gold standard for the management of large and/or complex urolithiasis, is conventionally performed with the patient in the prone position, which has several drawbacks. Of the various changes in patient positioning proposed over the years, the Galdakao-modified supine Valdivia (GMSV) position seems the most beneficial. It allows simultaneous performance of PCNL and retrograde ureteroscopy (ECIRS, Endoscopic Combined Intra-Renal Surgery) and has unquestionable anaesthesiological advantages.

Objective

To prospectively analyse the safety and efficacy of endoscopic combined intrarenal surgery (ECIRS) in GMSV position for the treatment of large and/or complex urolithiasis.

Design, setting, and participants

From April 2004 to December 2007, 127 consecutive patients who were followed in our department for large and/or complex urolithiasis were selected for surgery (American Society of Anesthesiologists [ASA] score 1–3, no active urinary tract infection [UTI], any body mass index [BMI]).

Intervention

All the patients underwent ECIRS in GMSV position. Technical choices about percutaneous access, endoscopic instruments and accessories, and postoperative renal and ureteral drainage are detailed.

Measurements

Patients’ mean age plus or minus standard deviation (± SD) was 53.1 yr ± 14.2. Of the 127 patients, 5.5% had congenital renal abnormalities, 3.9% had solitary kidneys, and 60.6% were symptomatic for renal colics, haematuria, and recurrent UTI. Mean stone size ± SD was 23.8 mm ± 7.3 (range: 11–40); 33.8% of the calculi were calyceal, 33.1% were pelvic, 33.1% were multiple or staghorn, and 4.7% were also ureteral.

Results and limitations

Mean operative time ± SD was 70 min ± 28, including patient positioning. Stone-free rate was 81.9% after the first treatment and was 87.4% after a second early treatment using the same percutaneous access during the same hospital stay (mean ± SD: 5.1 d ± 2.9). We registered overall complications at 38.6% with no splanchnic injuries or deaths and no perioperative anaesthesiological problems.

Conclusions

ECIRS performed in GMSV position seems to be a safe, effective, and versatile procedure with a high one-step stone-free rate, unquestionable anaesthesiological advantages, and no additional procedure-related complications.     

30 microg intrathecal clonidine prolongs labour analgesia, but increases the incidence of hypotension and abnormal foetal heart rate patterns

Objective

To assess the efficacy of spinal clonidine combined with bupivacaine and sufentanil and its effects on maternal and foetal outcome.

Study design

Prospective double-blind randomized study.

Patients and methods

One hundred and five patients requesting labour analgesia had combined spinal epidural analgesia with intrathecal bupivacaine 2.5 mg and were randomly assigned to receive in addition either sufentanil 5 μg (S5), sufentanil 5 μg and clonidine 30 μg (C30), or sufentanil 10 μg (S10). Onset time, duration of analgesia, visual analogue scores, blood pressure, ephedrine requirements, heart rate, nausea, pruritus, sedation, motor block, foetal heart rate abnormalities, mode of delivery and Apgar scores were recorded.

Results

Mean duration of spinal analgesia was significantly longer in patients receiving spinal clonidine compared to patients in S5 group (144 ± 61 min versus 95 ± 37 min). The onset time of analgesia was significantly shorter in S10 group (3 ± 1 min) versus C30 group (4 ± 1 min) and S5 group (4 ± 1 min) (P = 0.002). Hypotension was significantly more frequent in C30 group (29 versus 3% and 3% in S5 and S10 groups) (p = 0,001). Foetal heart rate abnormalities and sedation were also significantly more frequent in C30 group. Mode of delivery (spontaneous, instrumental or caesarean delivery) and Apgar scores were unaffected by clonidine treatment.

Conclusion

Intrathecal clonidine 30 μg prolongs analgesia. However, it increases the incidence of hypotension, and abnormal foetal heart rate patterns. Thus, this study confirms that the use of 30 μg intrathecal clonidine for labour analgesia is not recommended.