• Open Access

Use of an Implanted Sacral Nerve Stimulator to Restore Urine Voiding in Chronically Paraplegic Dogs

Authors


  • Some of the data have been presented in abstract form at the 24th Annual Symposium of the European Society of Veterinary Neurology and European College of Veterinary Neurology, Trier, Germany, 2011

Corresponding author: Nick D. Jeffery, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, 1600 South 16th Street, Ames, IA 50011; e-mail: njeffery@iastate.edu.

Abstract

Background

Loss of urinary control after spinal cord injury increases risk of urinary tract disease and is problematical for owners of affected dogs.

Objectives

To design, implant, and test a sacral nerve stimulating device for controlling urine voiding in paraplegic dogs.

Animals

Nine pet dogs with severe thoracolumbar spinal cord injury causing paraplegia, loss of hindquarter sensation, and incontinence for more than 3 months. The procedure was offered prospectively to owners of suitable candidates after the irreversibility of the incontinence had been ascertained.

Methods

Open label clinical study. Surgically implantable electrode “books” were designed for insertion and retention of mixed sacral nerves. Sacral nerves were accessed via laminectomy and stimulated to test their ability to elicit detrusor contraction and then inserted into the electrode book, which was attached to a subcutaneously implanted, externally activated receiver.

Results

In 8/9 dogs, S2 nerves elicited the largest increases in intravesicular pressure with minimum stimulation and were placed in electrode books. Voiding efficiency was >90% in 8 of the 9 implanted dogs. No important detrimental effects of the procedure were observed.

Conclusions and Clinical Importance

This sacral nerve stimulating implant is a simple and apparently effective neuroprosthetic device that restores urine voiding in paraplegic dogs.

Abbreviations
SCI

spinal cord injury

SARS

sacral anterior root stimulator

UMN

upper motor neuron

T, L, S

thoracic, lumbar, sacral

SNS

sacral nerve stimulator

Loss of control over urine voiding is a common complication after spinal cord injury (SCI) or other disorders of the nervous system, and may be permanent. The most commonly encountered are upper motor neuron (UMN) deficits associated with thoracolumbar (T3-L3) spinal cord lesions because of the frequency with which SCI occurs within this segment. Typically, because of loss of supraspinal regulation, incoordination of detrusor and sphincter contraction (termed “dyssynergia”) develops. This causes a functional obstruction that reduces the ability to void urine[1] and impairs emptying of the bladder by manual expression.[2] Management of overflow incontinence consequent to dyssynergia can be difficult in dogs, and each of the currently available options—intermittent catheterization, manual expression, and indwelling catheterization—is associated with risk of urinary tract infections[3, 4] and demanding on owner time and attention to detail.

For many years a “sacral anterior root stimulator” has been available to paraplegic humans which permits bladder emptying on demand through electrical stimulation of the sacral spinal nerves.[5, 6] This system functions through poststimulus voiding by exploiting the different physiological responses of smooth muscle (detrusor) and the sphincter mechanism (striated muscle).[7] Electrical stimulation of the sacral nerves increases tone in both the detrusor and the sphincter mechanism, but during the poststimulus period the smooth muscle of the detrusor continues to contract, whereas the striated muscle of the sphincter relaxes, thus resulting in a sufficient pressure gradient for urine to flow from the bladder. Previous studies have shown that it would also be feasible to drive micturition in paraplegic dogs, using stimuli applied extradurally to one or more pairs of sacral nerves,[8-10] although these procedures have not previously been applied to canine clinical cases. Recently, a custom-built device has been made available for dogs through a collaboration between veterinarians and neuroscientists in a large bioengineering project. In this article we describe our experience with the implantation technique, postoperative monitoring of efficacy, and discuss the value of this implant for paraplegic canine patients.

Materials and Methods

This study was carried out on client-owned dogs with therapeutic intent and approved by the Ethical Committee of the Department of Veterinary Medicine, University of Cambridge, UK.

Implant Design

We dissected the cauda equina of canine cadavers to measure the dimensions of the caudal lumbar and sacral vertebral canal, the sacral spinal nerves, and their dorsal and ventral roots. These measurements were used to design 2 sizes of custom-built nerve interfaces, termed electrode books, to fit within the vertebral canal. Each book was designed to accommodate a mixed sacral spinal nerve root (ie, dorsal and ventral components, which in dogs are tightly encased in fibrous tissue) within each of 2 slots, each containing 3 platinum electrodes situated at intervals along their long axis (Fig 1). Two sizes of electrode books were fabricated: small—7 mm long × 0.6 mm wide × 0.9 mm deep slots; large—10 mm long × 1 mm wide × 1.5 mm deep slots; to provide implants for small and medium-large sized dogs, respectively.

Figure 1.

Smaller sized electrode designed for implantation. (A, B) Platinum electrodes are supported by a silicon rubber “book” design based on a stiff silicon rubber base, which contains fabric filaments. Cooper cable (C) supplies electrical input and is glued to the base. The lid (l) is transparent silicon rubber with a rim of white rubber for additional strength and can be reflected to place the nerves within the slots. Parallel arrows indicate open end of slots into which sacral nerves are placed. (c) The Cooper cable has a plug (arrow) that permits connection to the receiver coil (rc) after electrode implantation. The receiver coil is positioned subcutaneously.

The electrode books were attached, with Cooper cable,1 as for similar implants in humans, to a receiver device implanted under the skin of the dog close to the lumbosacral junction. Activation of the receiver was via radiofrequency induction emanating from a hand-held transmitter box placed on the external surface of the dog adjacent to the implanted receiver. The transmitter box (external stimulator) requires charging approximately every 3 months, depending on stimulus characteristics; the surgical implant does not contain a battery.

Dogs

Potential candidates for the procedure were dogs that had suffered a severe SCI, including loss of behavioral response to painfully noxious stimuli applied to the hindquarters (ie, loss of “deep pain”[11]) plus loss of conscious control of urination. The owners of these cases were managing bladder emptying by manual expression or intermittent catheterization, but had encountered difficulties with fully expressing the bladder and recurrent urinary infections.

Neurologic examination and cystometry were used to fully determine the suitability of each dog for the procedure. For inclusion, each dog had to have a chronic spinal lesion, of at least 3 months duration since the initial incident and intact sacral segment reflexes, including bulbocavernosus, perineal and pelvic limb flexor reflexes. Each dog was assessed with urodynamic equipment2 while conscious and unsedated, similarly to a previously reported method.[12] Briefly, a dual lumen catheter was introduced into the bladder and the pressure response to bladder filling at a defined rate (10–20 mL/min depending on dog size), controlled by an electric pump, was determined. A reference pressure balloon was placed in the rectum to correct for abdominal pressure variation during bladder pressure assessment. This analysis enabled determination of the bladder compliance (pressure change per unit infused saline volume corrected for the dog's body weight) and (i) whether each dog was able to elicit involuntary detrusor contractions during preoperative cystometry (defined as a rise of bladder pressure >5 cmH2O that did not occur simultaneously with a similar pressure rise on the abdominal pressure); and, or, (ii) a rise in detrusor pressure ≥20 cmH2O from start to end of the cystometry (Fig 2). Dogs in which there was not evidence of a sufficiently strong detrusor response, as defined above, were excluded from the study because the implant could not be expected to function properly if the detrusor mechanism was incompetent or atonic.

Figure 2.

Preoperative cystometry in dog 5. (A) Changes in bladder pressure (cmH2O) during infusion of sterile saline; (B) changes in colo-rectal pressure (cmH2O) during the same period (controls for abdominal pressure changes during infusion). The solid arrows indicate the effect of external abdominal palpation. The dashed arrow indicates the start of bladder leaking (cystometry end-point); at this stage the peak intravesicular pressure was 26 cmH2O, rising from 3cmH2O at commencement of the study.

Dogs were excluded from consideration if they had an intercurrent disease that might threaten their survival for more than 12 months or if they had a temperament that was unsuitable.

Surgical Procedure

Before surgery a dual lumen catheter (6 or 7 FG according to individual dog size) was placed into the bladder of each dog and the pressure response to bladder filling was measured with urodynamic equipment2, to ensure correct catheter positioning. The reference pressure balloon was placed at the level of the anal sphincter to record anal sphincter (striated muscle) activity as a surrogate measure of urethral sphincter activity.

The caudal lumbar and sacral vertebrae were exposed using a modification of the standard dorsal approach to the lumbosacral junction[13] and the laminae removed to open the vertebral canal from caudal L5 to the midsacrum ensuring sufficiently adequate lateral exposure to allow placement of the electrode book. The extradural L7 mixed spinal nerve was identified by its location in the lateral recess of L7 vertebra and observing its exit from the canal through the L7/S1 foramen. S1, S2, and S3 spinal nerve roots were then identified through their subsequent craniocaudal exits from the dural sac.

The bladder was partially filled with sterile saline using the infusion pump and then a stimulus of variable intensity (from 0.5 to 10 V at 30 Hz) was applied to each of the exposed sacral nerves in turn, via hook electrodes3 to elevate and isolate the stimulated nerve from the remainder of the cauda equina. During stimulation we observed the effect on bladder pressure and anal sphincter pressure through urodynamic recordings and also determined visually whether there was contraction of pelvic and pelvic limb musculature. This process was used to identify the sacral nerve efferents that (i) stimulated a response in the bladder without unwanted stimulation of the pelvic musculature or undue increase in anal sphincter pressure; and (ii) elicited the maximal increase in bladder pressure during minimal stimulation. After determining which sacral spinal nerve root(s) were most appropriate for implantation into the stimulator device they were identified by tagging with a loose (4/0 PDS) suture, which also allowed more gentle handling during subsequent surgical manipulation. In human patients, the dorsal roots containing the bladder afferents are routinely sectioned (ie, “rhizotomized”) to prevent reflex incontinence and sphincter dyssynergia,[7] and therefore the analogous procedure was planned for these canine cases. Through our experience with the procedure (see 'Animals') this approach was modified in later cases, so that in only 6 of 9 dogs was the dural sac opened to identify the dorsal root of the relevant sacral spinal nerve for complete or partial rhizotomy (Supplementary Table S1).

When the appropriate spinal nerve roots on each side of the body had been identified the electrode book was implanted into the vertebral canal, ventral to the caudal part of the dural sac and the roots were eased into the slots of the book. The lid was closed and sutured into position, with 5/0 polypropylene (Prolene; Ethicon) sutures, to enclose the relevant spinal nerve roots and exclude the remainder of the cauda equina.

The cable exiting the stimulator was then loosely sutured to the spinous process of L5 vertebra with 2/0 Polypropylene (Prolene; Ethicon) and tunneled into the subcutis dorsolateral to the lumbosacral junction. The plug at the end of the cable was then joined with the socket on the internal receiver unit and sealed with silicone glue.4 The receiver was implanted into a pocket made in the subcutaneous tissue. The remaining closure was routine.

Postoperative Monitoring and Adjustments

After surgery each dog received injectable opiate analgesics (methadone or morphine combined with fentanyl dermal patch) at standard dosage and intervals for at least 48 hours, combined with nonsteroidal drugs or other analgesics for 7 days. On the 2nd postoperative day, the bladder of each dog was catheterized with the dual lumen catheter to allow bladder pressure responses to externally driven nerve stimulation to be recorded (Fig 5). The bladder pressures in response to electrical sacral spinal nerve root stimulation were recorded and the stimulation parameters on the external stimulating device were varied to achieve an “on”/“off” stimulus pattern that generated sufficient bladder pressure to empty the bladder to an appropriate residual volume (ideally <0.2 mL/kg[1]) while avoiding excessive intravesicular pressure (ie, not >120 cmH2O). Four factors were available for altering the stimulus parameters: amplitude of stimulation, pulse width, pulse repetition frequency, and the total duration of stimulating and relaxing epochs.

The residual volume was measured once after the external stimulating device was correctly programmed (ie, between 3 and 8 days postoperatively) and the dogs were returned to the owners with instructions for using it 3 times daily. The residual volume was then measured once at 3 weeks postoperatively during a recheck visit. The residual volume of urine was measured after stimulated bladder emptying by inserting a catheter into the bladder and completely emptying the bladder with a syringe. The volume of urine obtained after each stimulated bladder emptying was recorded 3 times a day while the dogs were hospitalized (between 3 and 8 days) and 3 times a day up to 3 weeks postoperatively while the dogs were at home (ie, for 12–17 days). The urine produced during each emptying was collected (see Supplementary Online Material) and the volume obtained was measured with a syringe. The daily urine volume for each dog was calculated by adding the values of the three measures obtained on each day. The mean voided volume was obtained by dividing the daily urine volume by the number of days of measurements. The “voiding efficiency” (%) was calculated at 1 and 3 weeks postoperatively, using the formula: mean voided volume/(mean voided volume + residual volume) × 100.[7]

The owners were asked to return dogs after 3 weeks and to inform the clinic of any problems in the meantime. Subsequent follow-up was by telephone or visits as required by each owner and dog. Urine of dogs in which there was evidence of urinary tract infection (hematuria, urine cloudiness, or foul smell) was routinely analyzed (with urine dipstick and cytology), cultured for bacterial growth and antibiotic sensitivity as required, and treatment with appropriate antibiotics administered for 3 weeks when needed.

Results

Implanted Cases

A total of 9 dogs were included in this study. The age range of the implanted dogs was 3–8 years old (mean = 6.3, SD = 1.5). Time between spinal cord injury and date of implantation ranged from 3 to 11 months (mean = 7.7, SD = 3.7). Each dog was unable to voluntarily void urine, and presented with long-term urine retention and overflow that had been managed by manual expression. Preoperatively cystometric recordings in each dog were obtained to document bladder compliance and detrusor responses (Fig 2). Preoperative bladder compliance was 0.8 ± 0.5 cmH2O/mL (mean, SD). In accordance with inclusion criteria a detrusor response was detected in response to bladder filling in each dog. Involuntary detrusor contractions were recorded in dogs 1, 2, 5, 6, 7; in the remaining dogs there was a rise in detrusor pressure ≥20 cmH2O during cystometry, implying an intact detrusor contractile capability.

Intraoperative Recordings

In all cases we recorded the greatest increase in bladder pressure (ie, greatest contraction of the detrusor muscle) upon stimulation of the S2 and S1 spinal nerves (Fig 3). However, S1 stimulation also elicited simultaneous pelvic limb muscle contraction and was therefore not placed into the electrode book. In all cases we detected weak increases in bladder pressure upon stimulation of S3 spinal nerve, except in case 5 in which stimulation of the left S3 spinal nerve elicited higher bladder pressure than S2 (and was therefore placed in the book in preference). The selected nerves for implantation produced a pressure of 88 ± 34.2 cmH2O during stimulation at the lowest stimulator setting of 5 V. Stimulation of all three sacral nerves elicited rectal contractions (Fig 3); although not the main purpose of placing the stimulator, such an effect can be helpful in stimulating defecation.

Figure 3.

Intraoperative measurements (dog 2) of (A) intravesicular and (B) anal sphincter pressures (cmH2O) with the bladder containing 30 ml sterile saline and unilateral (left) stimulation of individual mixed sacral nerves. Vertical lines indicate stimulation of (i) S1 nerve at 0.5 V, producing a pressure increase in the bladder and the rectum; (ii) S2 nerve at 0.5 V, producing rectal response only; (iii) S2 nerve at 1 V, which produces a large response in both bladder (attaining 50 cmH2O) and rectum; (iv) S3 nerve at 10 V, which produces only a moderate response, despite increased intensity. All stimulations were done at 30 Hz. Similar results were obtained on the right-side nerve roots.

In all cases but one (case 5 in which the left S3 nerve and right S2 were placed in the electrode book) the paired (right and left) S2 spinal nerves were slotted into a single electrode book positioned ventral to the dural sac. A small size book was used in 6 dogs (cases 2, 3, 4, 5, 7, and 9) and the large size in 3 dogs (cases 1, 6, and 8).

In dogs 1, 2, 3, and 4, the dorsal roots of the S2 sacral nerves (and no others) were identified intradurally (where they can be atraumatically separated from their ventral pair) and sectioned completely. In dogs 5 and 6, it was difficult to identify which nerve roots unequivocally contained only afferent fibers (because intravesicular pressure increased during stimulation) and so only a part of what had tentatively been identified anatomically as the dorsal root was sectioned, here we term that “partial rhizotomy”. In subsequent re-evaluations, bladder emptying after electrical stimulation appeared no different in dogs that had undergone partial rather than complete rhizotomy, therefore the S2 dorsal root was left intact in the last 3 dogs of the series (cases 7, 8, and 9).

The total time for surgical implantation was not formally measured (because other data recordings were being made concurrently and required extra surgical time), but was estimated at approximately 120 minutes. Figure 4 illustrates implant position.

Figure 4.

Lateral (A) and ventrodorsal (B) postoperative radiographs illustrating placement of the electrode book (black arrows) within the vertebral canal (dog 4). The receiver device (u) is located subcutaneously.

Postoperative Recordings and Adjustments

Postoperative bladder emptying was achieved through the external triggering device that simultaneously stimulated the (right and left side) implanted sacral nerves (Fig 5). At post-operative follow-up, higher voiding pressures, 102 ± 19.6 cmH2O, were reached during sacral nerve stimulation than were obtained intraoperatively. Adjustments to stimulus parameters were made to allow maximal bladder emptying but prevent retrograde urine flow through the ureters, according to the manufacturer's programming manual.1 Typically the procedure consisted of several steps; first the stimulus amplitude was altered to produce bladder contraction and urine flow, but without bladder pressure exceeding 120 cmH2O (monitored by cystometry); increased duration of “on” periods was used to increase bladder pressure if needed. After removing the catheter the “on” and “off” periods of stimulation were then varied to achieve a smooth flow of urine during the “off” periods (see Supplementary Online Material). Finally, the pulse width was adjusted according to the patient's subcutaneous fat thickness (which affects the penetration of the stimulus from the transmitter box).

Figure 5.

External stimulator device. (A) The external stimulator consisted of a control box (arrow) attached to the transmitter block (arrow head) by conventional cable. The 4 “mode” buttons allow adjustment of stimulus strength and duration and “on” and “off” times. (B) To initiate bladder emptying the stimulator pad is placed over the subcutaneous receiver coil and activated, causing current to flow from the receiver to the electrodes (dog 2).

At 2 days after surgery the stimulator in all dogs was able to elicit poststimulus urine voiding with an increasingly powerful urine flow with increasing number of stimulus bursts (Fig 6; and see Supplementary Online Material). The stimulus parameters were adjusted at this time to keep maximal intravesicular pressure less than 120 cmH2O but produce near-complete bladder emptying. At 1 week after implantation, the voiding efficiency ranged 30–99% (median = 23%); the stimulus parameters were adjusted again for dogs 2 and 9 with an unsatisfactory degree of bladder emptying (78 and 85% voiding efficiency, respectively).

Dog 3 which had a voiding efficiency of 30% at 1 week, was not presented for readjustment. At 3 weeks after implantation, the remaining 8 dogs had a voiding efficiency ranging 92–99% (median = 99%).

Figure 6.

Effects of S2 nerve stimulation postoperatively (dog 5). (A) Bladder and anal sphincter pressure (cmH2O) variation with time and bilateral S2 nerve stimulation. Black arrows indicate effect of manual palpation to check system, black bars on x-axis indicate “on” periods of stimulation (periods of 2 seconds each). Bladder pressure increases after each stimulation but does not return immediately to normal, as opposed to the anal sphincter pressure (a surrogate for urethral sphincter pressure) that immediately relaxes; therefore urine flows during “off” period. (B) Urine flow in response to stimulation. The line indicates voided urine volume, which flows in pulses, corresponding to the “off” periods of stimulation.

There were minor, transient complications suspe-cted to be associated with surgical implantation in 2 of the 9 dogs. These were reduced tail and anal tone for approximately 3 weeks (dog 4), and penile protrusion and decreased anal tone for 2 weeks (dog 1). In dog 9, a seroma developed over the receiver implant site but resolved within 2 weeks; microbial culture of the fluid was negative. Three dogs (cases 2, 7, and 8) were diagnosed with urinary tract infections, 2 of these were present before surgery (cases 2 and 8) and 1 developed postoperatively (case 7); all resolved with appropriate antibiotic therapy. In dog 2 that had a urinary tract infection before surgery, a large amount of urinary crystals were detected during bladder ultrasound. The crystals (magnesium ammonium phosphate) caused repeated urethral obstruction during bladder emptying with the sacral nerve stimulator. Treatment of the infection, plus dietary management, resolved the clinical difficulties within 10 days. Dogs 1, 4, and 9 each developed a single episode of urinary tract infection in the year after implantation.

In 5 dogs (cases 1, 3, 6, 7, and 8) bladder emptying was accompanied by (slightly delayed) defecation (as observed during the hospitalization periods and rechecks). In the remaining 4 dogs (cases 2, 4, 5, and 9), defecation was inconsistently associated with bladder emptying. For dogs 3, 7, and 8, the owners reported that pre-existing fecal incontinence also resolved with continued stimulator use (defecation was only associated with stimulator use).

Subjective Outcome Assessment

In 8 of the 9 dogs the sacral nerve stimulator system provided excellent bladder emptying from the clinician's point of view. In the remaining dog (case 3), preoperative bladder wall damage had been suspected preoperatively, which limited the increase in bladder pressure that could be generated with the stimulator, although fecal expulsion was improved (suggesting integrity of the neural structures). Unfortunately the stimulus parameters could not be adjusted in this dog because it was not returned for follow-up beyond 1 week. At long-term follow-up of 6 months (dogs 7, 8, 9), 11 months (dogs 5 and 6), 14 months (dogs 4), and 17 months (dogs 1 and 2), 7 of 8 dogs were reported by the owners to have stopped the leakage of urine in the house that had been apparent before stimulator implantation. Dog 3 could not be followed up further because the owners did not return. Dog 8 had urinary tract infections during the follow-up period that led to urine leakage in the house but this resolved after treatment.

Discussion

The implant is a simple neuroprosthetic device that can be used in dogs to overcome a persistent neurologic deficit. This study suggests that the use of a sacral spinal nerve stimulator is an effective method to manage bladder emptying disorders in paraplegic dogs. The implantation surgical time is relatively short (approximately 2 hours) and the owners managed the dogs without difficulty at home. Owner satisfaction with the procedure was generally excellent, although one dog was lost to follow-up; no owner reported urine leakage in the house, except during periods associated with urinary tract infection in one individual (dog 8).

In this study we examined the effects of sacral nerve stimulators (SNS) to aid management of dogs with a very specific type of incontinence disorder (retention and overflow) and these dogs also had no apparent pain sensation caudal to their thoracolumbar spinal lesions. Both of these factors simplify the implementation of the SNS device as there is little risk of painful complications resulting from the implantation or stimulation protocol. However, the external stimulator has very flexible stimulation parameters and could therefore be used in future to aid management of many other canine incontinence or urine retention disorders, provided these have not caused detrusor atony, nor are associated with sacral motoneuron destruction. Therefore conditions such as reflex dyssynergia in male dogs or even spay-related incontinence in female dogs might be candidates for this approach.

In human patients the use of SARS devices has previously been limited because of the perceived need for concomitant dorsal rhizotomy so as to prevent reflex activation of the detrusor and sphincter mechanisms.[6] In particular, male human patients object to deafferentation because it implies loss of penile erectile function, so reducing the desirability of SARS implantation. This consideration is not important in paraplegic dogs and so renders the implant more widely applicable in this species. In fact, our experience that omission of deafferentation does not inhibit bladder emptying even suggests the possibility that it may not be as essential to efficient functioning of the human SARS device as previously thought. Furthermore, omission of dorsal rhizotomy, as we describe here, renders the procedure much less invasive and quicker to perform than the comparable procedure in human patients, as there is no need to open the dura.

Acknowledgments

We are grateful for the assistance provided by the anesthetic, technical, and nursing staff at Oncovet, Lille, France and the Department of Veterinary Medicine, University of Cambridge.

Conflict of Interest: One of the authors, Peter Fairhurst, is employed by Finetech Medical. This company developed the implants that were originally used for the SARS implant in humans and helped to develop the new implants for use in dogs. The company is considering manufacturing devices for commercial use in dogs based on the results of this currently submitted study.

Financial Support: A grant from the Engineering and Physical Sciences Research Council of Great Britain (EPSRC).

Footnotes

  1. 1

    Finetech Medical Ltd, Welwyn Garden City, UK

  2. 2

    Lifetech, Stafford, TX

  3. 3

    Extradural surgical probe, Finetech Medical Ltd

  4. 4

    Sterile surgical adhesive, Finetech Medical Ltd

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