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Pelvic Floor Muscle Activity During Coughing: Altered Pattern in Women with Stress Urinary Incontinence
Adult Urology Pelvic Floor Muscle Activity During Coughing: Altered Pattern in Women with Stress Urinary Incontinence Xavier Deffieux, Katelyne Hubeaux, Raphael Porcher, Samer Sheikh Ismael, Patrick Raibaut, and Gérard Amarenco OBJECTIVES METHODS
RESULTS
CONCLUSIONS
To assess the relationship between bladder pressure (BP) and pelvic floor muscle activity during coughing in women with stress urinary incontinence (SUI). External anal sphincter integrated electromyographic activity (EAS-EMGi) was recorded in 21 women using pregelled surface electrodes. The relationship between BP and EAS-EMGi activity was assessed during four successive coughs at 0, 200, and 400 mL of filling. We also compared this relationship in 6 women presenting with SUI and 4 continent women. Among the considered models, a sigmoid relationship between EAS-EMGi and BP best described the data: EMGi ⫽ exp[a ⫻ (BP ⫺ b)]/(1 ⫹ exp[a ⫻ (BP ⫺ b)]). This relationship between EAS-EMGi and BP was significantly altered in women presenting with SUI (P ⬍0.0001). Women with SUI exhibited an altered pattern of the pelvic floor muscle response during successive coughing efforts. The lack of this modulation of pelvic floor muscle response to stress might be one of the pathophysiologic factors of SUI. UROLOGY 70: 443– 448, 2007. © 2007 Elsevier Inc.
T
he physiology of urinary continence during stress is complex, and the respective role of passive and active mechanisms remains unclear. Coughing leads to a contraction of the pelvic floor muscles (PFMs). This PFM contraction is a major factor in urinary continence, because it increases the urethral pressure, allowing the maintenance of a positive urethral-bladder pressure (BP) gradient during stress.1– 4 Few studies have focused on the quantification of this PFM contraction during coughing. It has previously been demonstrated that the PFM contraction increases with the amount of intraabdominal pressure generated during stress, reflecting a graduate adaptation of the PFMs to stress.5 The present study was conducted to (a) determine the type and reproducibility of the relationship between BP and PFM electromyographic (EMG) activity during coughing; (b) assess the influence of bladder volume on this relationship; and (c) assess the pattern of this relationship in patients presenting with stress urinary incontinence
From the Université Pierre et Marie Curie, Paris 6, Faculté de Médecine; Service de Rééducation Neurologique et d’Explorations Périnéales, AP-HP, Groupe Hospitalier Universitaire Est, Hôpital Rothschild; INSERM; and Raphael Porcher, Département de Biostatistiques et d’Informatique Médicale, AP-HP, Groupe Hospitalier Universitaire Est, Hôpital Saint Louis, Paris, France Reprint requests: Xavier Deffieux, MD, PhD, Laboratoire d’Urodynamique et de Neurophysiologie, Service de Rééducation Neurologique, Hôpital Rothschild, Assistance Publique, Hôpitaux de Paris, 33 boulevard de Picpus, Paris 75571 Cedex 12 France. E-mail: [email protected] Submitted: July 18, 2006; accepted (with revisions): March 1, 2007
© 2007 Elsevier Inc. All Rights Reserved
(SUI) compared with a control group without incontinence.
MATERIAL AND METHODS Subjects The study group consisted of 21 women (mean age, 49 ⫾ 15.9 years) referred for urodynamic investigation in 2005. Of these 21 women, 4 suffered from urgency and/or frequency without incontinence (mean age, 39 years; range, 24 to 53 years), 6 had isolated SUI according to the International Continence Society classification,6 and 11 had mixed incontinence. The subjects were excluded if they had a history of neurologic or respiratory abnormalities or an associated anorectal disorder. All 21 women underwent the cough stress test in a supine position at a common bladder volume (400 mL). The cough stress test was positive (urine loss) in all patients with SUI or mixed incontinence and negative in the remaining subjects. The national ethical committee approved the research procedure. All patients were informed of the aims and progress of the trial. All subjects provided written informed consent, and all procedures adhered to the Declaration of Helsinki.7 BP Recording The patients underwent urodynamic investigation according to the laboratory’s standard procedure and in agreement with International Continence Society rec0090-4295/07/$32.00 doi:10.1016/j.urology.2007.03.084
443
ommendations.8 The urinary bladder was filled with normal saline solution at a rate of 50 mL/min with the patient in the supine position. None of the patients had exhibited detrusor contractions during cystomanometry (no overactive detrusor). We assessed the intraabdominal pressure with a catheter positioned within the bladder (instead of the rectal cavity), because the urinary bladder is a cavity allowing good-quality pressure recordings when a perfused catheter is used. Therefore, a doublelumen 8F catheter was introduced through the urethra to record the BP (Model No. 9021P5081, Medtronic; Minneapolis, MN). We chose to use a double-lumen perfused catheter, because we use it routinely and it is well tolerated. On the basis of the recommendations of the International Continence Society, before the insertion, the catheters were positioned at the level of the pubic symphysis and zeroed to the atmospheric pressure. The temporal resolution of the pressure measurement was checked and allowed good recordings of the cough efforts. Electromyography In all subjects, EMG recordings were made from a pair of pregelled disposable surface self-adhesive electrodes (Model No. 9013S0221, Medtronic) that were positioned on the perineal skin, attached laterally to opposite sides of the external anal sphincter (EAS). These electrodes are considered to make recordings primarily from the EAS and from the distal fibers of the levator ani muscles. We used pregelled disposable surface electrodes for the EMG recordings, instead of concentric needle electrodes, because they are painless and not dislodged by movement. Furthermore, contact electrodes are better adapted to obtain accurate measurements of whole muscle EMG activity. The surface electrodes can record a greater EMG volume than can needle electrodes, which assess only a small number of muscular fibers. EMG and pressure data were recorded using Duet equipment (Medtronic) and the EMG signal was immediately integrated. The sampling rate was 50 Hz for pressure and EMG recordings. The digital values were exported to be processed within an Excel Microsoft spreadsheet. It was chosen to analyze the percentage of maximal integrated EMG (EMGi) to eliminate bias resulting from the differences in intrinsic EAS strength among the subjects. It is known that the absolute PFM strength development is greater in continent than in incontinent women.9 At 0, 200, and 400 mL, the patient was asked to cough four times successively. Four successive voluntary coughs of increasing intensity were required: gentle, moderate, strong, and very strong. Modeling The relationship between BP and EAS-EMGi was analyzed using different mathematical models (nonlinear mixed modeling10,11). Such modeling allows for correla444
tion between parameters measured repeatedly in the same subject (repeatability assessment). Several competing models were consecutively considered (eg, sigmoid, linear, parabolic) and compared using the Bayesian information criterion model.12 This included determination of the random effects and the residual variance correlation structures that best modeled the data. The models were fitted using the restricted maximum likelihood.10 However, comparisons of the models involving different fixed effects were based on maximum likelihood estimates, because likelihood comparisons between restricted maximum likelihood fits with different fixed effects are not valid.11 Specific hypotheses regarding fixed effects were tested using Wald or likelihood ratio tests. Among the considered models, a sigmoid relationship between EAS-EMGi (expressed as a percentage of the maximal value of each subject) and BP (similarly expressed as a percentage) best described the data. The model is expressed as EAS-EMGi ⫽ exp[a ⫻ (BP ⫺ b)]/(1 ⫹ exp[a ⫻ (BP ⫺ b)]), with EAS-EMGi and BP in percentages. The model parameters a and b represent the inflection of the curve (curvature) and the inflection point (position of the change in curvature). These parameters were estimated at 6.11 (standard error 0.24; P ⬍0.0001) and 0.532 (standard error 0.013; P ⬍0.0001) for a and b, respectively. Repeatability The repeatability of the relationship between BP and EAS-EMGi activity was checked using the graphic method of Bland and Altman13 (average for both measurements did not differ, P ⫽ 0.26, paired Student’s t test) and the intraclass coefficient correlation estimation14 (intraclass coefficient correlation estimation 0.654, 95% confidence interval 0.487 to 0.775), comparing two repeated measures at 0, 200, and 400 mL in the series of 21 subjects. Influence of Continence Status and Bladder Filling Volume The influence of continence status and bladder filling volume was evaluated in a series of 10 subjects: 4 continent women (with urgency and/or frequency, without neurologic disease) and 6 women presenting with isolated SUI. Statistical Analysis The data were analyzed using R software (a statistical software program). Descriptive statistics are expressed as the mean ⫾ standard deviation.
RESULTS All patients understood the requirements and were able to vary their coughing effort at each level of bladder filling volume. The average relationship corresponding to the estimation of the relationship between BP and EAS-EMGi is given UROLOGY 70 (3), 2007
and BP in continent subjects (P ⫽ 0.10, likelihood ratio test; Fig. 2). The relationship between EAS-EMGi and BP was significantly different between the continent and incontinent (SUI) groups (P ⬍0.0001, likelihood ratio test). Furthermore, the effect of continence status on this relationship was different according to the bladder filling volume (P ⬍0.0001, likelihood ratio test). More precisely, the EAS-EMGi for a given BP value was lower for SUI patients than for the control group (continent patients), except in the case of the larger bladder filling volume (400 mL; P ⫽ 0.027, Wald test corrected for multiple testing). This is clearly illustrated in Figure 3.
COMMENT
Figure 1. Average relationship between percentage of EASEMGi and percentage of BP in whole study group for PFM activity during coughing. Sigmoid relationship best described data. Model expressed as EAS-EMGi ⫽ exp [a ⫻ (BP ⫺ b)]/(1 ⫹ exp [a ⫻ (BP ⫺ b)]), with EAS-EMGi and BP in percentages. Model parameters a and b represent inflection of curvature and inflection point, respectively. Solid line represents average estimated curve with point-wise 95% confidence interval (shaded region). Circles give individual observed values.
Figure 2. Average relationship between percentage of EASEMGi and BP in continent women for PFM activity during coughing. Bladder filling volume did not significantly modify relationship between EAS-EMGi and BP in continent subjects (P ⫽ 0.10, likelihood ratio test).
Figure 1. In the continent group the bladder filling volume did not significantly modify this relationship (Fig. 2). The bladder filling volume was shown not to significantly modify the relationship between the EAS-EMGi UROLOGY 70 (3), 2007
Urinary continence is maintained by a positive urethral/BP gradient.15 The generation of the urethral pressure increase during stress, such as coughing, is presumed to result from a combination of active contractions of the periurethral and intraurethral striated muscles and passive transmission of the intraabdominal pressure.16 Active contractions can be voluntary (anticipatory contraction preceding a “planned” effort) or a reflex mechanism (anticipatory reflex-mediated contractions). The failure of the PFMs to adequately resist increases in intraabdominal pressure is thought to underlie the pathophysiology of SUI.16,17 The pathophysiology of SUI is complex, and the respective roles of these passive and active mechanisms remain unclear. Incontinent women should have incontinence during different types of effort (eg, sudden efforts such as coughing and progressive efforts such as the Valsalva maneuver). In a previous study, we demonstrated that PFM contractions (EAS-EMGi) increase with the importance of the intraabdominal pressure/BP generated during coughing.5 That preliminary study, performed in continent patients, demonstrated that the PFM response to cough is not a univocal response (response or nonresponse after coughing), but a modulated response. We have hypothesized that this gradual adaptation of the PFMs is probably one of the main factors contributing to urinary continence during stress in women. Thus, to demonstrate a specific mechanism of SUI, we wanted, in the present study, to assess the relationship between BP and EAS-EMGi during coughing in continent women and women with SUI. Our method provided a reasonable estimate of the pattern of PFM activity during coughing. During nonvoluntary contractions, the PFMs (periurethral muscles, levator ani muscles, and EAS) behave as one muscle determining a global contraction (synchronously contraction).3,18 –20 We verified that the coughs were appropriately graded: the successive BPs obtained were proportionally graded, with statistical significance. Furthermore, the cough intensity was significantly related to the EAS-EMGi activity, confirming a significant, increasing relationship between both parameters. Among the considered models, the relationship between BP and 445
Figure 3. Average relationship between percentage of EAS-EMGi and percentage of BP was lower for SUI patients than for continent group (P ⬍0.0001), except in the case of larger bladder filling volumes (400 mL). Solid line represents data concerning continent women (n ⫽ 4), and dashed lines represent data concerning women with SUI (n ⫽ 6).
EAS-EMGi was best described by a sigmoid relationship. The repeatability of the measurements were checked using the graphic method of Bland and Altman13 and the intraclass coefficient correlation estimation.14 This nonlinear modeling of the motor unit activity of PFM during coughing illustrates that the generation of the urethral pressure increase during stress, such as coughing, is presumed to be caused by a combination of passive and active (reflex and/or preprogrammed) mechanisms, including urethral tone, contraction of the urethral rhabdomyosphincter, and contraction of the periurethral striated muscles (levator ani muscles, pubococcygeus, and bulbocavernosus muscles). We have an hypothesis concerning the pattern observed for low-cough efforts (part 1 of the sigmoid curve illustrated in Fig. 1). It can be explained by a predominant role of passive mechanisms (urethral tone) associated with moderate action of striated muscle contractions. At the opposite, for very strong coughing efforts, the contraction capacity of the PFMs seems to reach its limit (spatial and temporal recruitment), indicating involvement of other associated mechanisms of continence (part 3 of the sigmoid curve). A strict and linear relationship was observed between BP and EAS-EMGi at the intermediate part of the sigmoid curve (part 2). Although the comparisons between continent women and patients with SUI were made of a relatively small number of subjects, the results have consistently indicated that the relationship between EAS-EMGi and BP was significantly altered in women presenting with SUI (P ⬍0.0001). The difference was observed in both model parameters a and b, representing the inflection of the curve and the inflection point, respectively (Fig. 3). Thus, it is our hypothesis that, in various conditions, a lack of the modulation of the PFM contraction with the amount of the exercise can lead to SUI. This lack of modulation is probably rarely isolated, but it might be an important cofactor of SUI. Future studies could be conducted to evaluate the influence of different stress and 446
fatigue conditions on this modulation of the PFM response. The pattern observed in SUI women at 400 mL (no difference was found compared with continent women) could possibly have resulted from several factors, including the limited number of patients. It could also be because the measurement was less stable with large bladder volumes. However, we have also hypothesized that this pattern observed at 400 mL is related to increased voluntary PFM activity as the desire to void increases. This voluntary contraction is difficult to distinguish from nonvoluntary activity. Miller et al.21 have shown that women’s ability to accomplish a conscious contraction diminishes if the normal mechanisms generating it during a cough have been lost. Another point is that the control group was not a healthy group, but a group of continent women presenting with overactive bladder syndrome (“dry”). Therefore, additional studies are needed to assess this relationship in healthy volunteers and to investigate the evolution of the modulation of the PFM response to coughing, before and after the sensation of a desire to void, which determine the increase in reflex and voluntary contractions, and for different bladder volumes (300, 500, and 600 mL). Regarding the potential influence of bladder volume on this relationship, previous studies have shown that the striated sphincter activity increases with bladder volume (guarding reflex)22,23 and that the bladder volume might modify detrusor activity.24 On the basis of these findings, we assessed whether the relationship between BP and EAS-EMGi correlated with the bladder filling volume. Previous studies have shown that basic EAS-EMG activity is not modified by the bladder filling volume.25 This is probably because the BP adapts to slow bladder filling with no pressure increase, but does not for greater intravesical volumes. However, these studies did not concern modulation of the EAS response during coughing. In the present study, which excluded women with diminished UROLOGY 70 (3), 2007
bladder compliance, in the group of continent women, bladder filling did not significantly modify the relationship between BP and EAS-EMGi during coughing (Fig. 2). Our results might illustrate, at each bladder volume level, an adequate adaptation of PFM contractions to provide adequate urethral closure and prevent urine leakage during coughing. Finally, our hypothesis is that the altered modulation of PFM contractions during coughing contributes to SUI, at least in some women. Additional studies should assess the frequency of this kind of neuromuscular dysfunction in women presenting with SUI. If confirmed, the theory of an altered neuromuscular mechanism in SUI could lead to reflection concerning conservative management of SUI, especially for programs of pelvic floor physiotherapy. It has been hypothesized that physiotherapy treatment might be more efficient in women presenting with altered PFM neuromuscular function. Therefore, the determination of neuromuscular dysfunction might represent a predictive factor of physiotherapy treatment. It should be very interesting to assess the evolution of such a neuromuscular dysfunction before and after physiotherapy.
CONCLUSIONS Our data have consistently indicated that women affected with SUI exhibit an altered pattern of PFM response during coughing. This altered pattern in women with SUI, with a lack of PFM muscular modulation, could be suggestive of one of the physiopathologic mechanisms of urinary incontinence in women. The method described in this study could provide additional information on the modulation of the PFM response to stress, thereby contributing to a better understanding of the pathogenesis of SUI.
References 1. Parks AG, Porter NH, and Melzak J: Experimental study of the reflex mechanism controlling the muscle of the pelvic floor. Dis Colon Rectum 5: 407– 414, 1962. 2. Bo K, Kvarstein B, Hagen R, et al: Pelvic floor muscle exercise for the treatment of female stress urinary incontinence: II. Validity of vaginal pressure measurements of pelvic floor muscle strength and the necessity of supplementary methods for control of correct contraction. Neurourol Urodyn 9: 479 – 487, 1990. 3. Sapsford RR, and Hodges PW: Contraction of the pelvic floor muscles during abdominal maneuvers. Arch Phys Med Rehabil 82: 1081–1088, 2001. 4. Neumann P, and Gill V: Pelvic floor and abdominal muscle interaction: EMG activity and intra-abdominal pressure. Int Urogynecol J 13: 125–132, 2002. 5. Amarenco G, Ismael SS, Lagauche D, et al: Cough anal reflex: strict relationship between intravesical pressure and pelvic floor muscle electromyographic activity during cough— urodynamic and electrophysiological study. J Urol 173: 149 –152, 2005. 6. Abrams P, Cardozo L, Fall M, et al: The standardisation of terminology of lower urinary tract function: report from the Standardisation Sub-Committee of the International Continence Society. Am J Obstet Gynecol 187: 116 –126, 2002.
UROLOGY 70 (3), 2007
7. Shapiro HT, and Meslin EM: Ethical issues in the design and conduct of clinical trials in developing countries. N Engl J Med 345: 139 –142, 2001. 8. Schafer W, Abrams P, Liao L, et al: for the International Continence Society: Good urodynamic practices: uroflowmetry, filling cystometry, and pressure-flow studies. Neurourol Urodyn 21: 261– 274, 2002. 9. Verelst M, and Leivseth G: Are fatigue and disturbances in preprogrammed activity of pelvic floor muscles associated with female stress urinary incontinence? Neurourol Urodyn 23: 143–147, 2004. 10. Davidian M, and Giltinan DM: Nonlinear Models for Repeated Measurement Data. Monographs on Statistics and Applied Probability, 62. Boca-Raton, Florida, Chapman & Hall/CRC, 1995, pp 359. 11. Pinheiro J, and Bates D: Mixed-Effects Models in S and S-Plus. Statistics and Computing Series. New York, Springer-Verlag, 2000, pp 528. 12. Schwartz G: Estimating the dimension of a model. Ann Stat 6: 461– 464, 1978. 13. Bland JM, and Altman DG: Statistical methods for assessing agreement between two methods of clinical measurement. Lancet 1: 307–310, 1986. 14. Bartko JJ: The intraclass correlation coefficient as a measure of reliability. Psychol Rep 19: 3–11, 1966. 15. Enhorning G: Simultaneous recording of intravesical and intraurethral pressure. A study on urethral closure in normal and stress incontinent women. Acta Chir Scand Suppl 276: 1– 68, 1961. 16. Constantinou CE, and Govan DE: Spatial distribution and timing of transmitted and reflex generated urethral pressures in healthy women. J Urol 127: 964 –969, 1982. 17. DeLancey JO: Anatomy and physiology of urinary continence. Clin Obstet Gynecol 33: 298 –307, 1990. 18. Lose G, Tanko A, Colstrup H, et al: Urethral sphincter electromyography with vaginal surface electrodes: a comparison with sphincter electromyography recorded via periurethral coaxial, anal sphincter needle and perianal surface electrodes. J Urol 133: 815– 818, 1985. 19. Bo K, and Stien R: Needle EMG registration of striated urethral wall and pelvic floor muscle activity patterns during cough, Valsalva, abdominal, hip adductor, and gluteal muscle contractions in nulliparous healthy females. Neurourol Urodyn 13: 35– 41, 1994. 20. Shafik A: A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation: mass contraction of the pelvic floor muscles. Int Urogynecol J Pelvic Floor Dysfunct 9: 28 –32, 1998. 21. Miller JM, Perucchini D, Carchidi LT, et al: Pelvic floor muscle contraction during a cough and decreased vesical neck mobility. Obstet Gynecol 97: 255–260, 2001. 22. Blaivas JG, and Olsson CA: Stress incontinence: classification and surgical approach. J Urol 139: 727–731, 1988. 23. McGuire EJ: Physiology of the lower urinary tract. Am J Kidney Dis 2: 402– 408, 1983. 24. Carbone A, Palleschi G, Parascani R, et al: Modulation of viscerosomatic H-reflex during bladder filling: a possible tool in the differential diagnosis of neurogenic voiding dysfunctions. Eur Urol 42: 281–288, 2002. 25. Shafik A: The effect of vesical filling and voiding on the anorectal function with evidence of a “vesico-anorectal reflex.” Neurogastroenterol Mot 11: 119 –124, 1999.
EDITORIAL COMMENT I have read this article with interest. The objective of this study was to assess the relationship between BP and PFM activity during coughing in women with SUI. Shafik,1,2 Amarenco et al.,3 and others have previously described this relationship in women with urgency/frequency syndrome but without urgency urinary incontinence or SUI. In that sense, this topic is not new, as Shafik4 has also reported. In this study, the new impor447
RESULTS
CONCLUSIONS
To assess the relationship between bladder pressure (BP) and pelvic floor muscle activity during coughing in women with stress urinary incontinence (SUI). External anal sphincter integrated electromyographic activity (EAS-EMGi) was recorded in 21 women using pregelled surface electrodes. The relationship between BP and EAS-EMGi activity was assessed during four successive coughs at 0, 200, and 400 mL of filling. We also compared this relationship in 6 women presenting with SUI and 4 continent women. Among the considered models, a sigmoid relationship between EAS-EMGi and BP best described the data: EMGi ⫽ exp[a ⫻ (BP ⫺ b)]/(1 ⫹ exp[a ⫻ (BP ⫺ b)]). This relationship between EAS-EMGi and BP was significantly altered in women presenting with SUI (P ⬍0.0001). Women with SUI exhibited an altered pattern of the pelvic floor muscle response during successive coughing efforts. The lack of this modulation of pelvic floor muscle response to stress might be one of the pathophysiologic factors of SUI. UROLOGY 70: 443– 448, 2007. © 2007 Elsevier Inc.
T
he physiology of urinary continence during stress is complex, and the respective role of passive and active mechanisms remains unclear. Coughing leads to a contraction of the pelvic floor muscles (PFMs). This PFM contraction is a major factor in urinary continence, because it increases the urethral pressure, allowing the maintenance of a positive urethral-bladder pressure (BP) gradient during stress.1– 4 Few studies have focused on the quantification of this PFM contraction during coughing. It has previously been demonstrated that the PFM contraction increases with the amount of intraabdominal pressure generated during stress, reflecting a graduate adaptation of the PFMs to stress.5 The present study was conducted to (a) determine the type and reproducibility of the relationship between BP and PFM electromyographic (EMG) activity during coughing; (b) assess the influence of bladder volume on this relationship; and (c) assess the pattern of this relationship in patients presenting with stress urinary incontinence
From the Université Pierre et Marie Curie, Paris 6, Faculté de Médecine; Service de Rééducation Neurologique et d’Explorations Périnéales, AP-HP, Groupe Hospitalier Universitaire Est, Hôpital Rothschild; INSERM; and Raphael Porcher, Département de Biostatistiques et d’Informatique Médicale, AP-HP, Groupe Hospitalier Universitaire Est, Hôpital Saint Louis, Paris, France Reprint requests: Xavier Deffieux, MD, PhD, Laboratoire d’Urodynamique et de Neurophysiologie, Service de Rééducation Neurologique, Hôpital Rothschild, Assistance Publique, Hôpitaux de Paris, 33 boulevard de Picpus, Paris 75571 Cedex 12 France. E-mail: [email protected] Submitted: July 18, 2006; accepted (with revisions): March 1, 2007
© 2007 Elsevier Inc. All Rights Reserved
(SUI) compared with a control group without incontinence.
MATERIAL AND METHODS Subjects The study group consisted of 21 women (mean age, 49 ⫾ 15.9 years) referred for urodynamic investigation in 2005. Of these 21 women, 4 suffered from urgency and/or frequency without incontinence (mean age, 39 years; range, 24 to 53 years), 6 had isolated SUI according to the International Continence Society classification,6 and 11 had mixed incontinence. The subjects were excluded if they had a history of neurologic or respiratory abnormalities or an associated anorectal disorder. All 21 women underwent the cough stress test in a supine position at a common bladder volume (400 mL). The cough stress test was positive (urine loss) in all patients with SUI or mixed incontinence and negative in the remaining subjects. The national ethical committee approved the research procedure. All patients were informed of the aims and progress of the trial. All subjects provided written informed consent, and all procedures adhered to the Declaration of Helsinki.7 BP Recording The patients underwent urodynamic investigation according to the laboratory’s standard procedure and in agreement with International Continence Society rec0090-4295/07/$32.00 doi:10.1016/j.urology.2007.03.084
443
ommendations.8 The urinary bladder was filled with normal saline solution at a rate of 50 mL/min with the patient in the supine position. None of the patients had exhibited detrusor contractions during cystomanometry (no overactive detrusor). We assessed the intraabdominal pressure with a catheter positioned within the bladder (instead of the rectal cavity), because the urinary bladder is a cavity allowing good-quality pressure recordings when a perfused catheter is used. Therefore, a doublelumen 8F catheter was introduced through the urethra to record the BP (Model No. 9021P5081, Medtronic; Minneapolis, MN). We chose to use a double-lumen perfused catheter, because we use it routinely and it is well tolerated. On the basis of the recommendations of the International Continence Society, before the insertion, the catheters were positioned at the level of the pubic symphysis and zeroed to the atmospheric pressure. The temporal resolution of the pressure measurement was checked and allowed good recordings of the cough efforts. Electromyography In all subjects, EMG recordings were made from a pair of pregelled disposable surface self-adhesive electrodes (Model No. 9013S0221, Medtronic) that were positioned on the perineal skin, attached laterally to opposite sides of the external anal sphincter (EAS). These electrodes are considered to make recordings primarily from the EAS and from the distal fibers of the levator ani muscles. We used pregelled disposable surface electrodes for the EMG recordings, instead of concentric needle electrodes, because they are painless and not dislodged by movement. Furthermore, contact electrodes are better adapted to obtain accurate measurements of whole muscle EMG activity. The surface electrodes can record a greater EMG volume than can needle electrodes, which assess only a small number of muscular fibers. EMG and pressure data were recorded using Duet equipment (Medtronic) and the EMG signal was immediately integrated. The sampling rate was 50 Hz for pressure and EMG recordings. The digital values were exported to be processed within an Excel Microsoft spreadsheet. It was chosen to analyze the percentage of maximal integrated EMG (EMGi) to eliminate bias resulting from the differences in intrinsic EAS strength among the subjects. It is known that the absolute PFM strength development is greater in continent than in incontinent women.9 At 0, 200, and 400 mL, the patient was asked to cough four times successively. Four successive voluntary coughs of increasing intensity were required: gentle, moderate, strong, and very strong. Modeling The relationship between BP and EAS-EMGi was analyzed using different mathematical models (nonlinear mixed modeling10,11). Such modeling allows for correla444
tion between parameters measured repeatedly in the same subject (repeatability assessment). Several competing models were consecutively considered (eg, sigmoid, linear, parabolic) and compared using the Bayesian information criterion model.12 This included determination of the random effects and the residual variance correlation structures that best modeled the data. The models were fitted using the restricted maximum likelihood.10 However, comparisons of the models involving different fixed effects were based on maximum likelihood estimates, because likelihood comparisons between restricted maximum likelihood fits with different fixed effects are not valid.11 Specific hypotheses regarding fixed effects were tested using Wald or likelihood ratio tests. Among the considered models, a sigmoid relationship between EAS-EMGi (expressed as a percentage of the maximal value of each subject) and BP (similarly expressed as a percentage) best described the data. The model is expressed as EAS-EMGi ⫽ exp[a ⫻ (BP ⫺ b)]/(1 ⫹ exp[a ⫻ (BP ⫺ b)]), with EAS-EMGi and BP in percentages. The model parameters a and b represent the inflection of the curve (curvature) and the inflection point (position of the change in curvature). These parameters were estimated at 6.11 (standard error 0.24; P ⬍0.0001) and 0.532 (standard error 0.013; P ⬍0.0001) for a and b, respectively. Repeatability The repeatability of the relationship between BP and EAS-EMGi activity was checked using the graphic method of Bland and Altman13 (average for both measurements did not differ, P ⫽ 0.26, paired Student’s t test) and the intraclass coefficient correlation estimation14 (intraclass coefficient correlation estimation 0.654, 95% confidence interval 0.487 to 0.775), comparing two repeated measures at 0, 200, and 400 mL in the series of 21 subjects. Influence of Continence Status and Bladder Filling Volume The influence of continence status and bladder filling volume was evaluated in a series of 10 subjects: 4 continent women (with urgency and/or frequency, without neurologic disease) and 6 women presenting with isolated SUI. Statistical Analysis The data were analyzed using R software (a statistical software program). Descriptive statistics are expressed as the mean ⫾ standard deviation.
RESULTS All patients understood the requirements and were able to vary their coughing effort at each level of bladder filling volume. The average relationship corresponding to the estimation of the relationship between BP and EAS-EMGi is given UROLOGY 70 (3), 2007
and BP in continent subjects (P ⫽ 0.10, likelihood ratio test; Fig. 2). The relationship between EAS-EMGi and BP was significantly different between the continent and incontinent (SUI) groups (P ⬍0.0001, likelihood ratio test). Furthermore, the effect of continence status on this relationship was different according to the bladder filling volume (P ⬍0.0001, likelihood ratio test). More precisely, the EAS-EMGi for a given BP value was lower for SUI patients than for the control group (continent patients), except in the case of the larger bladder filling volume (400 mL; P ⫽ 0.027, Wald test corrected for multiple testing). This is clearly illustrated in Figure 3.
COMMENT
Figure 1. Average relationship between percentage of EASEMGi and percentage of BP in whole study group for PFM activity during coughing. Sigmoid relationship best described data. Model expressed as EAS-EMGi ⫽ exp [a ⫻ (BP ⫺ b)]/(1 ⫹ exp [a ⫻ (BP ⫺ b)]), with EAS-EMGi and BP in percentages. Model parameters a and b represent inflection of curvature and inflection point, respectively. Solid line represents average estimated curve with point-wise 95% confidence interval (shaded region). Circles give individual observed values.
Figure 2. Average relationship between percentage of EASEMGi and BP in continent women for PFM activity during coughing. Bladder filling volume did not significantly modify relationship between EAS-EMGi and BP in continent subjects (P ⫽ 0.10, likelihood ratio test).
Figure 1. In the continent group the bladder filling volume did not significantly modify this relationship (Fig. 2). The bladder filling volume was shown not to significantly modify the relationship between the EAS-EMGi UROLOGY 70 (3), 2007
Urinary continence is maintained by a positive urethral/BP gradient.15 The generation of the urethral pressure increase during stress, such as coughing, is presumed to result from a combination of active contractions of the periurethral and intraurethral striated muscles and passive transmission of the intraabdominal pressure.16 Active contractions can be voluntary (anticipatory contraction preceding a “planned” effort) or a reflex mechanism (anticipatory reflex-mediated contractions). The failure of the PFMs to adequately resist increases in intraabdominal pressure is thought to underlie the pathophysiology of SUI.16,17 The pathophysiology of SUI is complex, and the respective roles of these passive and active mechanisms remain unclear. Incontinent women should have incontinence during different types of effort (eg, sudden efforts such as coughing and progressive efforts such as the Valsalva maneuver). In a previous study, we demonstrated that PFM contractions (EAS-EMGi) increase with the importance of the intraabdominal pressure/BP generated during coughing.5 That preliminary study, performed in continent patients, demonstrated that the PFM response to cough is not a univocal response (response or nonresponse after coughing), but a modulated response. We have hypothesized that this gradual adaptation of the PFMs is probably one of the main factors contributing to urinary continence during stress in women. Thus, to demonstrate a specific mechanism of SUI, we wanted, in the present study, to assess the relationship between BP and EAS-EMGi during coughing in continent women and women with SUI. Our method provided a reasonable estimate of the pattern of PFM activity during coughing. During nonvoluntary contractions, the PFMs (periurethral muscles, levator ani muscles, and EAS) behave as one muscle determining a global contraction (synchronously contraction).3,18 –20 We verified that the coughs were appropriately graded: the successive BPs obtained were proportionally graded, with statistical significance. Furthermore, the cough intensity was significantly related to the EAS-EMGi activity, confirming a significant, increasing relationship between both parameters. Among the considered models, the relationship between BP and 445
Figure 3. Average relationship between percentage of EAS-EMGi and percentage of BP was lower for SUI patients than for continent group (P ⬍0.0001), except in the case of larger bladder filling volumes (400 mL). Solid line represents data concerning continent women (n ⫽ 4), and dashed lines represent data concerning women with SUI (n ⫽ 6).
EAS-EMGi was best described by a sigmoid relationship. The repeatability of the measurements were checked using the graphic method of Bland and Altman13 and the intraclass coefficient correlation estimation.14 This nonlinear modeling of the motor unit activity of PFM during coughing illustrates that the generation of the urethral pressure increase during stress, such as coughing, is presumed to be caused by a combination of passive and active (reflex and/or preprogrammed) mechanisms, including urethral tone, contraction of the urethral rhabdomyosphincter, and contraction of the periurethral striated muscles (levator ani muscles, pubococcygeus, and bulbocavernosus muscles). We have an hypothesis concerning the pattern observed for low-cough efforts (part 1 of the sigmoid curve illustrated in Fig. 1). It can be explained by a predominant role of passive mechanisms (urethral tone) associated with moderate action of striated muscle contractions. At the opposite, for very strong coughing efforts, the contraction capacity of the PFMs seems to reach its limit (spatial and temporal recruitment), indicating involvement of other associated mechanisms of continence (part 3 of the sigmoid curve). A strict and linear relationship was observed between BP and EAS-EMGi at the intermediate part of the sigmoid curve (part 2). Although the comparisons between continent women and patients with SUI were made of a relatively small number of subjects, the results have consistently indicated that the relationship between EAS-EMGi and BP was significantly altered in women presenting with SUI (P ⬍0.0001). The difference was observed in both model parameters a and b, representing the inflection of the curve and the inflection point, respectively (Fig. 3). Thus, it is our hypothesis that, in various conditions, a lack of the modulation of the PFM contraction with the amount of the exercise can lead to SUI. This lack of modulation is probably rarely isolated, but it might be an important cofactor of SUI. Future studies could be conducted to evaluate the influence of different stress and 446
fatigue conditions on this modulation of the PFM response. The pattern observed in SUI women at 400 mL (no difference was found compared with continent women) could possibly have resulted from several factors, including the limited number of patients. It could also be because the measurement was less stable with large bladder volumes. However, we have also hypothesized that this pattern observed at 400 mL is related to increased voluntary PFM activity as the desire to void increases. This voluntary contraction is difficult to distinguish from nonvoluntary activity. Miller et al.21 have shown that women’s ability to accomplish a conscious contraction diminishes if the normal mechanisms generating it during a cough have been lost. Another point is that the control group was not a healthy group, but a group of continent women presenting with overactive bladder syndrome (“dry”). Therefore, additional studies are needed to assess this relationship in healthy volunteers and to investigate the evolution of the modulation of the PFM response to coughing, before and after the sensation of a desire to void, which determine the increase in reflex and voluntary contractions, and for different bladder volumes (300, 500, and 600 mL). Regarding the potential influence of bladder volume on this relationship, previous studies have shown that the striated sphincter activity increases with bladder volume (guarding reflex)22,23 and that the bladder volume might modify detrusor activity.24 On the basis of these findings, we assessed whether the relationship between BP and EAS-EMGi correlated with the bladder filling volume. Previous studies have shown that basic EAS-EMG activity is not modified by the bladder filling volume.25 This is probably because the BP adapts to slow bladder filling with no pressure increase, but does not for greater intravesical volumes. However, these studies did not concern modulation of the EAS response during coughing. In the present study, which excluded women with diminished UROLOGY 70 (3), 2007
bladder compliance, in the group of continent women, bladder filling did not significantly modify the relationship between BP and EAS-EMGi during coughing (Fig. 2). Our results might illustrate, at each bladder volume level, an adequate adaptation of PFM contractions to provide adequate urethral closure and prevent urine leakage during coughing. Finally, our hypothesis is that the altered modulation of PFM contractions during coughing contributes to SUI, at least in some women. Additional studies should assess the frequency of this kind of neuromuscular dysfunction in women presenting with SUI. If confirmed, the theory of an altered neuromuscular mechanism in SUI could lead to reflection concerning conservative management of SUI, especially for programs of pelvic floor physiotherapy. It has been hypothesized that physiotherapy treatment might be more efficient in women presenting with altered PFM neuromuscular function. Therefore, the determination of neuromuscular dysfunction might represent a predictive factor of physiotherapy treatment. It should be very interesting to assess the evolution of such a neuromuscular dysfunction before and after physiotherapy.
CONCLUSIONS Our data have consistently indicated that women affected with SUI exhibit an altered pattern of PFM response during coughing. This altered pattern in women with SUI, with a lack of PFM muscular modulation, could be suggestive of one of the physiopathologic mechanisms of urinary incontinence in women. The method described in this study could provide additional information on the modulation of the PFM response to stress, thereby contributing to a better understanding of the pathogenesis of SUI.
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EDITORIAL COMMENT I have read this article with interest. The objective of this study was to assess the relationship between BP and PFM activity during coughing in women with SUI. Shafik,1,2 Amarenco et al.,3 and others have previously described this relationship in women with urgency/frequency syndrome but without urgency urinary incontinence or SUI. In that sense, this topic is not new, as Shafik4 has also reported. In this study, the new impor447