Neurourology and Urodynamics 36:171–175 (2017)
Risk Factors to Develop Autonomic Dysreflexia During Urodynamic Examinations in Patients With Spinal Cord Injury rrez-Martın,3 Manuel de la Marta-Garcıa,1 Miguel Vırseda-Chamorro,1* Jesus Salinas-Casado,2 Pablo Gutie 1 Antonio Lopez-Garcıa-Moreno, and Manuel Esteban Fuertes1 1
2
Department of Urology, Paraplegics National Hospital, Toledo, Spain Department of Urology, Hospital Clınico de San Carlos, Universidad Complutense, Madrid, Spain 3 Department of Urology, Hospital Virgen del Prado, Talavera, Toledo, Spain
Aims: The risk factors for developing autonomic dysreflexia (AD) during urodynamic (UD) examination in patients with spinal cord injury (SCI) above Th6 still remain unclear. The main goal of our study is to investigate the risk factors that could be associated with AD in these particular patients. Design: Cross sectional survey. Subject and methods: The study was carried out in 83 patients with SCI above Th6 who were submitted to our center for a UD examination. AD was defined as a rise in systolic blood pressure above 15 mm Hg with a pulse rate below 60 beats per minute. Results: The prevalence rate of AD among our patients was 54%. Univariate analysis of our study showed the following risk factors: patient’s age, SCI completeness, traumatic etiology, indwelling catheter, presence of chills or sweating, anticholinergic treatment, maximum detrusor voiding pressure, detrusor pressure at maximum flow rate, detrusor external sphincter dyssynergia, and bladder outlet obstruction. Using multivariate logistic regression, we found that there are only two independent risk factors: patient’s age equal to or above 45 years of age (OR ¼ 10.995) and maximum detrusor voiding pressure equal to or above 31 cm H2O (OR ¼ 3.879). Conclusions: According to our results, the patient’s age and maximum detrusor voiding pressure should be considered at the time of performing a UD examination in order to prevent the sudden onset of AD in patients with SCI above Th6. Neurourol. Urodynam. 36:171–175, 2017. # 2015 Wiley Periodicals, Inc. Key words: autonomic dysreflexia; risk factors; spinal cord injuries; urodynamics INTRODUCTION
MATERIALS AND METHODS
Autonomic dysreflexia (AD) is a condition that results in paroxysmal hypertension (HT) from a severe, unopposed sympathetic discharge, balanced by the activation of the vagus nerve via the baroreceptor reflex, which leads to concurrent bradycardia. This condition afflicts spinal cord injury (SCI) patients with a lesion above the Th6 level as a consequence of a stimulus below the level of the injury, and is potentially life threatening.1 Several stimuli can lead to AD, but the most common triggering factor is bladder distension, which accounts for up to 85% of cases.2 Urodynamic (UD) examination is used to describe the status of the lower urinary tract and to diagnose neurogenic lower urinary tract dysfunction (NLUTD) in patients with SCI. However, because of the bladder distension that this examination provokes, there is a risk of triggering AD. Therefore, assessment of blood pressure is advisable during UD study.3 The proportion of patients with SCI above Th6 presenting with AD during UD examinations is around 40%.4,5 Some authors have reported that AD is more frequent in complete SCIs,6 but other authors have not found out any relation between the completeness of SCI and AD.4 On the other hand, we should not forget that only a percentage of patients with complete SCI above Th6 suffer from AD during UD, indicating that there are some other factors contributing to the onset of AD. Knowledge about and awareness of these risk factors is crucial for treating AD early during UD. The aim of our study is to investigate which risk factors can predict the onset of AD in patients with SCI above Th6 during UD.
We carried out a cross-sectional study in patients with SCI who were submitted to our center for UD examination. Inclusion criteria were as follows: patients above 18 years of age and a stable SCI above Th6 level. Exclusion criteria were as follows: history of neurological diseases other than SCI, previous diseases of the genitourinary tract, urinary tract infections, or cardiovascular diseases (coronary heart disease, arrhythmias, or hypertension). The required sample size was calculated in accordance with Curt et al.6 These authors observed that the percentage of AD in patients with complete SCI above Th6 was 91% compared to 27% in patients with incomplete SCI above Th6. After having established an alpha error of 5% and a statistical power of 80%, the minimum number of patients required was 31 in each group. We reviewed 1,075 patients in our center between July 2014 and February 2015, and 83 patients fulfilled the criteria for inclusion in our study (Fig. 1). The level and degree of SCI are shown in Table I. The ethic committee of our center approved the study, and all patients signed an informed consent. A clinical history was taken for all patients, including the age, gender, level and
#
2015 Wiley Periodicals, Inc.
Dr. Hashim Hashim led the peer-review process as the Associate Editor responsible for the paper. Potential conflicts of interest: Nothing to disclose. Correspondence to: Miguel Chamorro Virseda, Department of Urology, Paraplegics National Hospital, Finca la Peraleda s/n, Toledo 45071, Spain. E-mail:
[email protected] Received 20 June 2015; Accepted 25 September 2015 Published online 19 October 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/nau.22906
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Vırseda-Chamorro et al. into intermittent and continuous. Urethral resistance was measured by URA and detrusor contractility by WF parameters Wmax and W80-20. Both parameters were calculated automatically by the computer, but checked manually looking for artefacts by the urologist. Bladder outflow obstruction (BOO) was considered in males when the URA was at 29 cm H2O or above, and at the level of 20 cm H2O or above in females. When patients were unable to void, the BOO was considered positive if maximum detrusor pressure was 40 cm H2O or above in males, and 30 cm H2O or above in females. Blood pressure and pulse rate were measured by means of an automatic sphygmomanometer with an inflatable cuff wrapped around the forearm, before examinations, during bladder filling after every 50 ml infused, and after examinations. AD was defined as an increase of systolic blood pressure above 15 mm Hg, its basal level, associated with a pulse rate below 60 beats per minute.10 The data obtained were stored in a Microsoft Access database and later exported to the statistical package SPSS version 12 (SPSS Inc., Chicago, IL) for statistical analysis. The statistical tests used were as follows: Kolmogorov–Smirnov test to assess the normal distribution of quantitative data; Fisher’s exact test for dichotomous variables; Pearson’s chi-squared test for categorical variables; lineal association test for ordinal variables; and the Student’s t comparison of means test for parametric variables. We also used a receiver operating characteristic curve analysis to calculate the best cut-off point (i.e., maximal value of sensitivity plus specificity) of parametric variables. Additionally, we performed a multivariate analysis by step-wise logistic regression in order to assess the risk factors that independently could influence the likelihood of developing AD. The significance level was set at a two-sided 95% level. The data are represented by their means standard deviation.
Fig. 1. Flow diagram of included/ excluded patients.
degree of SCI according to ASIA criteria,7 antiquity and cause of SCI, urological surgical background, specific oral treatment for the lower urinary tract, mechanism of bladder emptying, and medical history of urinary incontinence. The UD examination was performed with a Solar polygraph MMS, (Enschede, The Netherlands), following the standards of the International Continence Society.8 The patients were placed in a supine position. The bladder was filled using a double lumen catheter inserted transurethrally with continuous filling of saline solution at a rate of 20 ml/min. The abdominal pressure was recorded using a rectal balloon. A perineal electromyogram (EMG) was obtained using surface electrodes. The filling phase was defined as ending when either there was an involuntary detrusor contraction (neurogenic overactivity) or blood pressure rose to a dangerous level i.e, systolic blood pressure: 180 mm Hg or diastolic blood pressure: 110 mm Hg. In this case, according to our protocol,9 if the elevated blood pressure does not start to decline after 1 min, we start medical treatment with sublingual captopril. If the high blood pressure persists, the patient is admitted in the intensive care unit. Detrusor external sphincter dyssynergia (DESD) was classified TABLE I. Level and Grade of Spinal Cord Injury
High cervical (C1–C4) Low cervical (C5–C8) Thoracic (Th1–Th5) Total
Complete
Incomplete
Total
7 29 12 48
9 23 3 35
16 52 15 83
Neurourology and Urodynamics DOI 10.1002/nau
RESULTS Descriptive Statistics
All quantitative variables were normally distributed. The patient’s mean age was 45 14.7 years. The distribution by gender was 67 men (81%) and 16 women (19%). The prevalence rate of AD was 54% (45 patients). One of the patients showed AD only during the filling phase and the other patients during voiding. The average duration of spinal cord injury was 177 135.6 months. The etiology of the SCI was traumatic in 69 cases (83%), myelitis in two cases (2%), tumoral in five cases (6%), vascular in four cases (5%) and vertebral disc-related in three cases (4%). The mechanism of bladder evacuation was clean intermittent catheterization (CIC) in 36 cases (43%), reflex voiding in 20 cases (24%), indwelling catheter (IC) in 22 cases (26%), sacral anterior roots stimulation (SARS) in one case (1%), and finally, voluntary micturition in four cases (5%). Thirty-seven (45%) patients were not actively taking any lower urinary tract medications, whereas 43 (52%) were taking anticholinergics, two patients (2%) were taking alpha-blocking agents, and one patient (1%) was taking mirabegron. Regarding surgical background, we found that no surgical procedures were performed in 61 cases (73%). Regarding clinical symptoms, 51 (61%) patients did not have any during UD examination, 10 patients (12%) suffered from chills, three patients (4%) had sweating, 18 patients (22%) reported a sensation of abdominal fullness, and just one patient (1%) developed suprapubic pain.
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Neurogenic detrusor overactivity (NDO) was demonstrated in 73 patients (88%) and stress urinary incontinence (SUI) in three patients (4%). Abdominal straining during voiding was demonstrated in 20 patients (20%), and detrusor external sphincter dyssynergia (DESD) in 70 patients. Dyssynergia was intermittent in 60 cases (72%) and continuous in 10 cases (12%). BOO was shown in 41 patients (49%).
off point for maximum detrusor pressure was 31 cm H2O (86% sensitivity and 45% specificity). The logistic regression analysis results are shown in Table IV. The independently prognostic variables of AD appearance during UD examinations were maximum detrusor pressure at a level of or above 31 cm H2O and age at the level of or above 45 years.
Inferential Statistics
DISCUSSION
The relationship between clinical data and AD is shown in Table II. The variables significantly related to AD are as follows: age, SCI completeness, traumatic etiology, indwelling catheter, onset of AD symptoms (chills or sweating), and anticholinergic treatment. The best cut-off point for age was 45 years (80% sensitivity and 71% specificity). Table III shows the relationship between UD data and AD. A statistically significant association was found between AD and NDO, detrusor maximum pressure during voiding, detrusor pressure at maximum flow rate, DESD, and BOO. The best cut-
According to our results, we can conclude that there are some clinical and UD factors that could predict the onset of AD in patients with SCI above Th6 during UD. The clinical factors include the patient’s age (patients with AD were younger), completeness of injury (AD was more frequent in patients with complete injury), the etiology of SCI (more frequent in traumatic SCI), indwelling catheter (less frequent in patients who were subject to indwelling catheter), the presence of chills or sweating during the examination, and anticholinergic treatment (more frequent in patients who received these
TABLE II. Relationship Between Clinical Data and Autonomic Dysreflexia
Age (full years)a Age of injury (months)a Sex (women/men)b Injury level (high cervical/low cervical/thoracic)b Injury completeness (incomplete/complete)b Injury cause (traumatic/other)b Incontinence device (none/condom/napkin)b Indwelling catheter (yes/no)b Dysreflexia symptoms (yes/no)b Anticholinergics (yes/no)b Sphincterotomy (yes/no)b
With dysreflexia
Without dysreflexia
38 10.6 188 122.2 20%/80% 16%/69%/16% 31%/69% 93%/ 7% 51%/42%/7% 16%/84% 27%/73% 69%/31% 25%/75%
53 15.0 165 150.7 18%/82% 24%/55%/21% 55%/45% 71%/29% 55%/26%/18% 39%/ 61% 3%/97% 32%/68% 55%/45%
Significance 0.000 0.468 1.000 0.436 0.044 0.009 0.141 0.024 0.002 0.001 0.332
Mean standard deviation. Percentage. Significant. a
b
TABLE III. Relationship Between Urodynamic Data and Autonomic Dysreflexia
Cystometric capacity (ml)a Bladder compliance (ml/cm H2O)a Detrusor overactivity (yes/no)b Bladder capacity to first IC (ml)a Maximum detrusor pressure during IC (cm H2O)a Urinary incontinence during IC (yes/no)b Urgency during IC (yes/no)b Stress urinary incontinence (yes/no)b Voided volume (ml)a Maximum flow rate (ml/sec)a Maximum detrusor pressure (cm H2O)a Detrusor pressure at maximum flow (cm H2O)a Maximum abdominal pressure (cm H2O) Post void residual (ml)a DESD (no/intermittent/continuous)b URA (cm H2O) Bladder outlet obstruction (yes/no)b Wmax (W/M2)a W80-20 (W/M2)a
With dysreflexia
Without dysreflexia
Significance
350 224.3 244 211.2 98%/2% 247 164.3 54 28.0 59%/41% 11%/89% 2%/98% 71 125.8 3 4.8 56 25.4 42 18.7 37 22.5 338 527.5 7%/78%/16% 32 17.9 60%/40% 37 128
314 220.5 191 182.3 76%/24% 234 161.8 43 21.9 80%/20% 23%/77% 5%/95% 54 92.7 3 4.5 35 26.9 31 17.2 37 25.5 278 219.6 26%/66%/8% 27 15.6 37%/63% 7 7.4
0.463 0.233 0.005 0.741 0.068 0.078 0.218 0.591 0.501 0.650 0.001 0.038 0.965 0.514 0.019 0.288 0.048 0.270
IC, involuntary contraction; DESD, detrusor external sphincter dysynergia. a Mean standard deviation. b Percentage. Significant.
Neurourology and Urodynamics DOI 10.1002/nau
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Vırseda-Chamorro et al.
TABLE IV. Multivariate Analysis Results Variables Age 45 years Pmax 31 cm H2O Constant
b
OR
P
R
2.534 1.355 2.167
10.995 3.879 0.115
0.000 0.032 0.001
0.429
2
Pmax 31 cm H2O: maximum detrusor pressure during voiding 31 cm H2O. b, multivariate logistic regression coefficient; OR, odds ratio; P, significance level (Wald).
drugs). The UD factors include neurogenic detrusor overactivity (more frequent in patients with this dysfunction), maximum detrusor voiding pressure and detrusor pressure at maximum flow (both higher in patients with AD), detrusor external sphincter dyssynergia (more frequent in patients with AD), and the diagnosis of BOO (more frequent in patients with AD). However, multivariate analysis showed that there were only two independent factors: the patient’s age and maximum detrusor pressure during voiding. Detrusor pressure seems to be a trigger for AD in patients with bladder distension (not the bladder volume). Wallin et al.11 have shown that in patients with SCI above T4, changes in bladder pressure correlate positively with changes in blood pressure and inversely with changes in pulse rate, whereas in control subjects without SCI, these changes are not shown. Furthermore, Yoshizawa et al.12 used an experimental model in rats with SCI above Th5. Their study reached two different conclusions. Firstly, that increase of blood pressure, in response to bladder distension, is detrusor pressure dependent. Secondly, they found a significant reduction in blood pressure as a response to an intravesical application of resinferatoxin, which works by C-fiber desensitization. The results of our study also confirm this relationship, as all 45 patients with AD during UD examinations had detrusor pressure increase: 44 patients during the voiding phase, and one during the filling phase. In this latter case, detrusor pressure was increased because bladder compliance was reduced at 5 ml/cm H2O. As Huang et al.4 point out, a diminished compliance in patients with SCI above Th6 can also cause an increase in blood pressure. Patients with AD during the voiding phase showed a significantly higher maximum detrusor pressure than those without AD (56 cm H2O vs. 35 cm H2O). Multivariate analysis demonstrated that if maximum detrusor pressure is 31 cm H2O or above, the risk of having AD will be 5.072 times higher. Nevertheless, the response to increasing detrusor pressure was not the same in all patients. Twenty-one patients in our study did not suffer from AD in spite of a detrusor pressure above 31 cm H2O. On the other hand, eight patients with detrusor pressure below 31 cm H2O had AD. Most biological responses need both an external stimulus and host susceptibility. The central nervous system of patients with SCI above Th6 could react differently to the same pressure stimulus. It can be hypothesized that completeness of injury is pivotal. In fact, univariate analysis showed a significant relationship between this factor and AD. However, multivariate analysis demonstrated that this factor was not an independent variable. The other independent variable found in our multivariate analysis was the patient’s age. AD was more frequent in younger patients (mean age 38 years vs. 53 years). Huang et al.5 also found that patients with symptomatic AD (with headache, flushing, chills, or sweating) were significantly younger (mean age 40 years) than those with asymptomatic AD (49 years). An Neurourology and Urodynamics DOI 10.1002/nau
explanation could be that aging decreases baroreceptor sensitivity.13 The aim of our study was to investigate the risk factors that may be connected to the onset of AD in patients with SCI above Th6 during UD. However, our results may also be useful for managing patients with AD. Increasing detrusor voiding pressure, which may trigger AD, can be due either to an increased urethral resistance (bladder outlet obstruction) or detrusor contractility.14 The criteria for diagnosis of BOO in SCI patients are not yet defined. In our study, we used a URA value of 29 cm H2O15 for men and a value of 20 cm H2O for women as a cut-off value for BOO.16 Unfortunately, there were several patients who could not void, therefore we used 40 cm H2O for men17 and 30 cm H2O for women18 as cut-off point for maximum detrusor pressure. Although these criteria have been developed for patients without SCI, they were useful in our study as a risk factor for AD. Moreover, if these criteria were also applicable to SCI patients, it would mean that 18 patients in our series were diagnosed with AD without BOO. The development of AD in these patients can either be due to increased detrusor contractility or increased baroreceptor sensitivity. Some authors propose sphincterotomy to control AD in SCI,19 but if these patients are not obstructed, sphincterotomy will not benefit. On the other hand, according to our results, patients with SCI above Th 6 below 45 years of age or with maximum detrusor voiding pressure above 31 cm H2O are at the highest risk of developing AD. If other studies supported our data, it would imply that such patients should avoid reflex micturition, replacing it, for example, by a regimen of clean intermittent catheterization and anticholinergics. A limitation of our study is that the classical diagnosis of AD is based on an increase in blood pressure associated with at least one of the following signs (sweating, piloerection, facial flushing, cold peripheries), or symptoms (headache, blurred vision, stuffy nose, chest tightness, chills) but, surprisingly, sometimes there are no clinical symptoms when blood pressure is elevated, a condition referred to as silent AD.5 Our criteria for AD included, besides the rise in blood pressure, the presence of bradycardia. Although bradycardia is commonly considered as accompanying AD, pulse rate response is still a controversial issue.4 However, AD results from a spinal mechanism reflex that generates a generalized sympathetic response, which in turn results in widespread vasoconstriction that causes a sudden increase in blood pressure, and following this hypertension crisis, intact baroreceptors stimulate the parasympathetic nervous system in an attempt to lower blood pressure causing bradycardia.10 Hence, in our opinion, we consider bradycardia as a necessary condition for AD diagnosis. CONCLUSIONS
Our study concludes that there are two main factors that give rise to AD during UD examinations: the patient’s age and the detrusor maximum voiding pressure. These factors should be considered in order to prevent the onset of AD. REFERENCES 1. Shergill IS, Arya M, Hamid R, et al. The importance of autonomic dysreflexia to the urologist. BJU Int 93:923–6. 2. Gunduz H, Binak DF. Autonomic dysreflexia: An important cardiovascular complication in spinal cord injury patients. Cardiol J 2012;19:215–9. 3. St€ ohrer M, Blok B, Castro-Diaz D, et al. EAU guidelines on neurogenic lower urinary tract dysfunction. Eur Urol 2009;56:81–8. 4. Huang YH, Bih LI, Chen GD, et al. Autonomic dysreflexia during urodynamic examinations in patients with suprasacral spinal cord injury. Arch Phys Med Rehabil 2011;92:1450–4.
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