InnovAiT, 8(5), 291–297
DOI: 10.1177/1755738015578935
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Bladder problems
associated with
neurological disease
A
neurogenic bladder is defined as dysfunction of the bladder secondary to
known disease of, or injury to, the central, peripheral or autonomic nervous systems. Neurogenic bladder dysfunction can cause urinary symptoms for the patient as well as increasing the risk of developing recurrent
urinary tract infections, bladder calculi and potentially life-threatening complications including sepsis and renal failure. Therefore, it is important for GPs to have
a solid understanding of the aetiology, pathophysiology, assessment and management of this condition in order to improve patients’ symptom control and
attempt to prevent long-term complications.
The GP curriculum and bladder problems associated with neurological disease
There is currently no available data on the incidence or
prevalence of neurogenic bladder dysfunction in the
general population. However, given the prevalence of
the causative neurological conditions, the relative risk
of each of these for developing neurogenic bladder dysfunction, and the fact that once patients have neurogenic
bladder dysfunction they are likely to have it for a long
period of time, it is a condition that GPs will encounter on
a regular basis in primary care.
The symptoms and severity of bladder problems depend
upon the location and extent of pathology within the nervous system; however, there is no correlation between the
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Bladder problems associated with neurological disease are listed as a common and important condition forming part
of the knowledge- based Clinical example 3.18: Care of people with neurological problems. GPs should
be able to perform the following:
. Coordinate care with other primary care health professionals to enable chronic disease management and
rehabilitation
. Demonstrate empathy and compassion towards patients with disabling neurological conditions
. Understand the importance of continuity of care for patients with chronic neurological conditions
. Offer health education and accident prevention for people with chronic neurological disorders
. Know the functional anatomy of the nervous system relevant to diagnosis
. Perform and understand the limitations of a screening neurological examination
. Understand the principles of treatment for common conditions that are managed largely in primary care
. Make appropriate referrals on behalf of the patient for secondary care investigations and treatment
severity of symptoms and risk of long-term complications.
It is vital to identify patients suffering from neurogenic
lower urinary tract dysfunction early in order to assess
their level of risk, with the aim of both managing symptoms and preventing future complications.
Nerve supply to the
lower
urinary tract
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To understand and manage bladder problems associated
with neurological disease it is important to have a good
knowledge of the normal innervation of the lower urinary
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tract. This allows symptoms to be characterised better
and appropriate investigations and treatment initiated.
Motor innervation of the bladder
Motor innervation to the bladder is supplied by the autonomic nervous system. Parasympathetic nerves supply
excitatory input to the smooth muscle of the bladder
(detrusor), causing contraction. These parasympathetic
nerve fibres originate in spinal segments S2 to S4.
They leave the spinal cord through the anterior primary
rami and enter the pelvic plexus, where they travel to the
bladder and urethra.
Sympathetic nerves innervate the smooth muscle of the
bladder and exert inhibitory control on muscle contraction. The sympathetic nerve supply to the lower urinary
tract varies between males and females. In males, sympathetic nerves innervate the trigone, blood vessels of
the bladder, smooth muscle of the prostate and pre-prostatic sphincter. In females there is minimal innervation of
the bladder neck or urethra. Sympathetic nerves arise
from T10-L2, synapse in the sympathetic chain before
travelling to the bladder, urethra and prostate.
Afferent innervation of the bladder
Afferent neurons, arising from receptors throughout the
bladder and urethra, ascend with parasympathetic
nerves to the spinal cord, before travelling to the pontine
storage centre, micturition centre and cerebral cortex of
the brain. They sense bladder-filling.
Somatic motor innervation of the urethral
sphincter
There are two urethral sphincters (Fig. 1):
1. The bladder neck, which is under autonomic (nonvoluntary) control
2. A distal (external) urethral sphincter, which is under
voluntary control
The distal urethral sphincter is located in the mid-urethra
in females and just distal to the apex of the prostate in
males. This sphincter consists of three layers, extrinsic
skeletal muscle, smooth muscle within the wall and intrinsic striated muscle. The intrinsic striated muscle forms a
U-shape around the urethra and is absent posteriorly. It
produces urethral occlusion by kinking the urethra,
rather than circumferential compression and is supplied
by the pudendal nerve (S2-4). The smooth muscle within
the wall is tonically active. The extrinsic skeletal muscle
forms the outermost layer (the pubo-urethral sling) and is
part of the levator ani muscle.
Urine storage
The bladder is highly compliant. During filling, the pressure within the bladder remains low despite significant
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Figure 1. Nerve supply to the lower urinary tract.
Permission obtained from De Tijdstroom Uitgeverij ß Boon, T.
A. Basisboek Urologie (De Tijdstroom, Netherlands, 2001).
increases in volume. This is due to the elastic properties
of the connective tissues of the bladder and the ability of
detrusor smooth muscle cells to increase in length without any change in tension.
Micturition
Micturition is created by a spino-bulbar-spinal reflex
coordinated in the pontine micturition centre of the
brainstem. This reflex results in simultaneous detrusor
muscle contraction and urethral relaxation, allowing micturition. Receptors within the bladder wall sense increasing tension as the bladder fills. This information is relayed
by afferent neurons to the dorsal horn of the sacral cord.
Neurons then pass to the peri-aqueductal grey matter of
the pons. The peri-aqueductal grey matter and other
areas of the brain, such as the orbitofrontal cortex and
limbic system, input into the pontine micturition centre
and determine whether it is appropriate to start micturition. The system is a positive feedback loop such that
contraction is maintained until the bladder is empty.
Symptoms
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Symptoms of neurogenic bladder dysfunction will
depend upon the causative neurological pathology and
more specifically the site and severity of disease within
the nervous system. A summary of the causes of neurogenic bladder are listed in Table 1 and associated symptoms in Table 2.
Patients have abnormal bladder or sphincter function and
more commonly dysfunction of both. Both the bladder
and sphincter may be over- or underactive and any
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Table 1. Causes of a neurogenic bladder.
Site within nervous system
Causes
Examples
Peripheral nervous system
Peripheral neuropathy
Diabetes
Alcohol abuse
Vitamin B12 deficiency
Iatrogenic
Guillain Barré syndrome
Genital herpes
Porphyria
Syphilis
Heavy metal poisoning
Iatrogenic
Pelvic surgery
Regional spinal anaesthesia
Space-occupying
lesions
Brain tumours (24%)
Spinal cord tumours
Basal ganglia
pathology
Parkinson’s disease
Shy–Drager syndrome
Demyelination
Multiple sclerosis
Vascular
Stroke
Dementia
Alzheimer’s disease
Pick’s disease
Other
Spina bifida
Encephalitis
Cerebral palsy
Cauda equina syndrome
Central nervous system
Table 2. Symptoms associated with a neurogenic bladder.
Type of bladder dysfunction
Site of injury/disease
Symptoms
High pressure (spastic)
Central nervous system
Spinal cord injury/disease (above T12)
Retention
Incontinence
Nocturia
Frequency
Urgency
Leakage of urine (spasms)
Low pressure (hypotonic)
Peripheral nervous system
Spinal cord injury/damage (S2–S4)
Retention
Incontinence (overflow)
Hesitancy
Erectile dysfunction
Mixed
Central nervous system
Peripheral nervous system
Combinations of above
symptoms
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combination may co-exist. Symptoms will therefore
depend upon the balance between detrusor and sphincter function and activity.
Detrusor hyper-reflexia (high pressure)
Detrusor hyper-reflexia is bladder over-activity secondary to an underlying neurological problem and is most
commonly seen in patients suffering from a disease of
the central nervous system or a spinal cord injury above
the level of T12. In this group of patients, the bladder
intermittently contracts during filling, resulting in an
inappropriate high pressure. Symptoms commonly
include leakage of urine, urgency, frequency, retention
and incontinence.
Detrusor areflexia (low pressure)
Detrusor areflexia or underactive bladder is seen in
patients who have a disease of the peripheral nervous
system or a spinal injury at the level of S2–S4. In this
group of patients, the bladder is unable to generate high
pressures during voiding. Symptoms commonly include
retention, incontinence (overflow), hesitancy and erectile
dysfunction in men.
Detrusor external sphincter dyssynergia
Detrusor-external sphincter dyssynergia occurs when
involuntary contractions of the external urethral sphincter
occur during involuntary contractions of the detrusor
muscle and is caused by diseases of the central nervous
system.
Patients with detrusor over-activity combined with
detrusor sphincter dyssynergia are at significant risk
of vesicoureteric reflux and subsequent renal damage.
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It is therefore vital to identify such patients in order to
try and prevent long-term complications.
Diagnosis
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A thorough history and physical examination is vital in
diagnosing a neurogenic bladder. It is important to examine both the central and peripheral nervous systems and
the bladder itself. In most cases the diagnosis is suspected from the patient’s history and is often reinforced
by a large post-void residual volume or palpable bladder.
The bladder may be contractile, or there may be an outflow obstruction of the bladder. Both cases will most
likely result in urinary retention with overflow incontinence (Rackley, Vasavada, Firoozi, & Ingber 2011). If suspected, initial useful investigations in primary care
include urinalysis and routine blood tests, including
urea and creatinine levels. Urinary tract infection
must be considered and ruled out. An ultrasound of
the kidneys, ureters and bladder should be requested
to monitor for any hydronephrosis and a request made
at the same time for a post-micturition volume to be
measured.
Urgent referral to urology is recommended in cases of
patients with recurrent urinary tract infections, renal failure, obstructed urinary system on imaging, or simply
persistent symptoms which fail to resolve despite appropriate initial management (Pannek et al., 2011). For those
patients who are not severely debilitated (e.g. are able to
go to the bathroom or are able to self-catheterise) further
investigations in secondary care are usually endorsed.
Table 3 highlights common diagnostic procedures that
may then be used to further guide diagnosis and treatment (Rackley et al., 2011).
Table 3. Common investigations for suspected neurogenic bladder.
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Procedure
Benefits
Cystoscopy
Allows discovery of bladder lesions such as inflammation, cancer or bladder stones. May
influence treatment decisions according to the cause of incontinence.
Cystogram
Evaluates the capacity of bladder and detects vesicoureteral reflux. It can help confirm the
presence of stress incontinence and the degree of urethral motion.
Cystometrogram
A filling cystometrogram can determine the bladder volume and pressure. It can also help
evaluate detrusor functional capacity and assess the presence of phasic contractions of the
bladder (detrusor instability). A voiding cystometrogram can assess the bladder contractility
and the extent of a bladder outlet obstruction by simultaneously recording the rate of flow
and detrusor pressure.
Urodynamics
Shows whether there is coordination between bladder contraction and sphincter relaxation.
Allows accurate diagnosis of detrusor sphincter dyssynergia, which is common in spinal cord
injuries. Uncoordinated voiding occurs due to failure of urethral relaxation during contraction
of the bladder.
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Management
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Managing bladder problems associated with neurological
disease can be very challenging. The aim of treatment is
to protect the upper urinary tract, improve continence,
restore function and improve the patient’s quality of life.
Adequate support and education is required for both the
patient and his or her carers. As always, initial conservative management can often be attempted prior to implementing more definitive medical or surgical treatments.
Throughout treatment, it is essential to monitor a
patient’s symptoms regularly in addition to 6-monthly
renal function and annual ultrasound scan to monitor
the upper urinary tracts.
Conservative management
Conservative measures include controlling daily fluid
intake (drinking small amounts throughout the day
rather than a large quantity at one time) and managing
diet by avoiding spicy food, citrus fruit and caffeinated
drinks which can all irritate the bladder.
There is good evidence for recommending pelvic floor
exercises with the reported successful reduction on
incontinence ranging from 56-95% (Rickwood, 2002).
Strengthening the levator ani muscles maintains urinary
continence by preventing pelvic prolapse.
In addition, a voiding diary can be used to record the
patient’s daily bladder activity (National Institute for
Heath and Care Excellence (NICE), 2012). A pattern is
created by recording daily fluid intake and the number of
urination attempts. This can help the patient to know
when he or she should be near a toilet and when to
attempt urination next, gradually gaining better control
of bladder function.
Absorbent undergarments should be advised to help
prevent wetness and odours while protecting the skin
and clothes. Bed pads can protect sheets and mattresses
for patients who wet the bed. Patients should also be put
in contact with support groups and educated about the
symptoms of urinary tract infections so that they present
early should an infection develop. All patients should
have their renal function monitored regularly.
Medical management
If conservative measures fail to improve symptoms, the
next step that can be taken in primary care is the use of
medication to control bladder function (NICE, 2012).
Certain medications can reduce bladder spasms and tremors, effectively managing the symptoms of the patient.
Oxybutynin, tolterodine tartrate and trospium chloride
are anticholinergic medications that help relax the
smooth muscle of the bladder, preventing spasms.
These antispasmodics increase bladder capacity and
decrease urge incontinence. In patients with incomplete
emptying, clean intermittent self-catheterisation (CISC)
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should be commenced prior to starting anticholinergic
medication. Complete bladder emptying avoids residues
in the bladder and consequent risk of infection.
Antidepressants such as amitriptyline and imipramine
also have a similar effect, as they exhibit anticholinergic
and direct muscle relaxant effects on the bladder
(Pannek et al., 2011).
If a trial of these medications in combination with conservative measures fails to improve symptoms, the
patient should be referred to secondary care for a urology opinion (Pannek et al., 2011). Following further specialist assessment, alternative medication may be trialled,
such as Bethanecol, a parasympathomimetic choline carbamate that selectively stimulates muscarinic receptors. It
subsequently increases the contractility of the bladder
muscle, improving the ability to urinate.
Oestrogen derivatives such as Premarin can be used by
post-menopausal women with mild-to-moderate stress
incontinence. The up-regulation of alpha-adrenergic
receptors increases the tone of urethral muscles,
whereas the pelvic muscles are strengthened from the
enhanced alpha-adrenergic contractile response (Rackley
et al., 2011). The improved urethral mucosal-seal effect
prevents the intrinsic sphincter deficiency, which can
help alleviate the symptoms of incontinence in patients
with neurogenic bladder dysfunction.
The human bladder contains 3 beta-adrenoceptors, of
which 97% are beta3-adrenoceptors (B3-AR). The stimulation of these receptors inhibits detrusor contractions
from the urothelium. A number of clinical trials involving
various selective B3-AR agonists have shown promising
preliminary results for treating overactive bladders.
Catheterisation
Once referred to secondary care, catheters will often be
advised as an adjunct to conservative and medical treatments (NICE, 2012). In those patients with increased
post-residual volumes, CISC is often taught; it also
helps reduce the risk of urinary tract infections and
improves symptoms. However, patients must have the
dexterity to carry out the procedure, which they may
need to perform several times a day.
If physically or mentally impaired, occasionally a carer or
healthcare professional can perform the procedure for
the patient; however, these patients will usually require
an indwelling catheter (Buckley & Grant, 2009).
Indwelling catheters and suprapubic catheters are an
option to decompress the bladder in all patients; however, CISC is preferable due to a lower risk of urinary
tract infections, urethritis and prostatitis. Patients with
long-term urethral catheters will often develop traumatic
hypospadias or patulous urethras and therefore patients
with neuropathic bladders who require indwelling catheters are usually offered suprapubic catheter placement.
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It should be noted that a suprapubic catheter does not
reduce the risk of urinary tract infection compared with a
urethral catheter, however, is often beneficial to patient
comfort. In all patients with indwelling catheters, symptoms must be monitored closely. These patients are at
increased risk of urinary tract infection compared with
those without a catheter or performing CISC and any
symptomatic infection must be identified and treated
quickly. Indwelling catheters also increase the risk of
bladder calculus formation, which may cause patients
to present with increased bladder spasm or catheter
bypassing. Any suspicion of bladder calculi should
result in referral for a urology opinion.
Surgical management
Surgical treatment is the last resort if conservative and
medical measures fail. The choice of the surgical procedure to be performed will depend on patient symptoms
and performance status.
Overactive neurogenic bladders that are not responsive
to medical therapy can be treated with an intravesical
injection of botulinum toxin (BotoxÕ ) into the detrusor
muscle via a rigid or flexible cystoscope. This blocks postsynaptic muscarinic receptors to prevent involuntary
detrusor muscle contractions (Pannek et al., 2014). It is
vital to perform a full urodynamic evaluation prior to
treatment in order to confirm the diagnosis. If effective,
reinjection with botulinum toxin is needed every 9–12
months. There is a 5–10% risk of developing urinary
retention in the first 2 months, in which case urinary
catheterisation becomes necessary. This can become
problematic for patients with neuropathic bladders who
are trying to avoid CISC and indwelling catheters. The
risk of urinary retention must be discussed with the
patient before initiating intravesical botulinum toxin treatment. Other reported side effects of botulinum toxin
injection include haematuria, infection and allergic
reactions.
Other surgical procedures are available; however, they
do have a higher risk of complications. In men, external
urethral sphincterotomy can be performed to create an
open draining channel. This decreases the outlet resistance, which in turn lowers the intravesical pressure
removing the need for an indwelling catheter (Utohmo,
Groen, & Block, 2014).
Artificial sphincters and urethral slings can be beneficial
and bladder augmentation (cystoplasty) is occasionally
used. This involves increasing the bladder capacity
using sections of small or large bowel. Along with the
increased volume, the percentage of bladder involved in
contraction is also reduced, creating lower internal pressures in the bladder during urination (Ginsberg, 2013).
It is also possible to create urinary diversion through
either an ileal conduit or ureterostomy, whereas a
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neurosurgical procedure known as sacral rhizotomy can
effectively convert a spastic bladder to a flaccid one by
selectively destroying the S3 and S4 nerve roots of the
spinal cord.
Electrical stimulatory therapy in treating neurogenic bladder is a recent advance. Through a minor surgical procedure, a number of electrodes are placed near targeted
nerves and a small stimulator is implanted beneath the
skin. Painless electric shocks stimulate the levator ani
muscle causing contraction of the external urethral
sphincter while inhibiting bladder contraction
(Radziszewski, 2013). This act of neuro-modulation can
be trialled prior to more invasive procedures such as
cystoplasty or reconstructive surgery.
Considerations in primary care
Patients with neurogenic bladders are commonly seen in
primary care. Neurogenic bladder dysfunction causes
significant problems to patients with associated urinary
symptoms and complications that can reduce the
patient’s quality of life. It is vital for GPs to be able to
identify patients suffering from neurogenic lower urinary
tract dysfunction early in order to assess their level of risk
with the aim of both managing symptoms and preventing
future complications. Simple investigations and treatment
options can be undertaken in primary care with appropriate referrals to secondary care made when symptoms
fail to improve or complications develop.
Key points
. Patients with neurogenic bladder are often seen in
primary care
. Thorough history and examination are essential to
diagnosis
. Conservative measures and anticholinergic medication, if appropriate, should be started in primary
care
. At each review, assess for complications including
urinary tract infection, sepsis and renal failure
. If symptoms fail to improve or complications
develop, consider referral to secondary care
References and further information
. Bors, E., & Turner, R. D. (1960). History and physical examination in neurological urology. Journal of
Urology, 83, 759–767. Retrieved from www.ncbi.
nlm.nih.gov/pubmed/13802958
. Buckley, B., & Grant, A. M. (2009). What is the
most effective management of neurogenic bladder
dysfunction? British Medical Journal, 338, 659. doi:
10.1136/bmj.b659
. Ginsberg, D. (2013). Optimizing therapy and management of neurogenic bladder. American Journal
of Managed Care, 19(10), S197–S204. Retrieved
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.
.
.
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.
from
www.ajmc.com/publications/supplement/
2013/ace012_jul13_ngb/ace012_jul13_ngb_ginsberg2_s197/1
Igawa, Y., Aizawa, N., & Homma, Y. (2010). Beta3adrenoceptor agonists: Possible role in the treatment of overactive bladder. Korean Journal of
Urology, 51(12), 811–818. Retrieved from
www.ncbi.nlm.nih.gov/pmc/articles/PMC3016425
Madersbacher, H. (1990). The various types of
neurogenic bladder dysfunction: An update of current therapeutic concepts. Paraplegia, 28(4),
217–229. doi: 10.1038/sc.1990.28
NICE. (2012). Urinary incontinence in neurological
disease. Retrieved from www.nice.org.uk/guidance/CG148
Pannek, J., Blok, B., Castro-Diaz, D., del Popolo,
G., Groen, J., Karsenty, G.,. . .Stohrer, M. (2014).
European Association of Urology. Guidelines on
neuro-urology. Retrieved from www.uroweb.org/
gls/pdf/21%20Neuro-Urology_LR.pdf
Pannek, J., Stohrer, M., Blok, B., Castro-Diaz, D.,
del Popolo, G., Kramer, G.,. . .Wyndaele, J. J.
(2011). European Association of Urology.
Guidelines on neurogenic lower urinary tract dysfunction. Retrieved from www.uroweb.org/gls/
pdf/20_Neurogenic%20LUTD_LR.pdf
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. Rackley, R., Vasavada, S. P., Firoozi, F., & Ingber,
M. S. (2011). Neurogenic bladder. Retrieved from
www.emedicine.medscape.com/article/453539
. Radziszewski, K. (2013). Outcomes of electrical
stimulation of the neurogenic bladder: Results of
a two-year follow-up study. NeuroRehabilitation,
32(4), 867–873. Retrieved from www.ncbi.nlm.
nih.gov/pubmed/23867413
. RCGP. Clinical example 3.18: Care of people with
neurological problems. Retrieved from www.rcgpcurriculum.org.uk/pdf/curr_3_18_Neurological
_problems.pdf
. Rickwood, A. M. (2002). Assessment and conservative management of the neuropathic bladder.
Seminars in Pediatric Surgery, 11(2), 108–119.
Retrieved from www.ncbi.nlm.nih.gov/pubmed/
11973763
. Utomo, E., Groen, J., & Blok, B. (2014). Surgical
management of functional bladder outlet obstruction in adults with neurogenic bladder dysfunction.
Cochrane Database of Systematic Reviews, 5. art. no.:
CD004927. doi: 10.1002/14651858.CD004927.pub4
Mr Thomas J Smith, Dr Victoria Andrews, Dr Seok Cho, Mr Nicholas Drinnan and Mr William Dunsmuir
St Peter’s Hospital, Ashford and St Peters NHS Trust
Email: thomas.smith@doctors.org.uk
DOI: 10.1177/1755738015580701
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Single best answer question
You are seeing an 18-month-old boy at midnight while
doing an out-of-hours shift. The parents tell you that he
had a fever and barking cough all day. About 2 hours ago
he started to develop noisy breathing that is keeping him
awake. The child’s parents have tried paracetamol and
steaming with little effect. You feel that the most likely
diagnosis is croup and you find no signs of respiratory
distress on examination.
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AKT question relating to wheezy children
The most appropriate course of action is:
A. To explain the diagnosis to parents, reassure them
and discharge him home
B. To give the child a dose of oral prednisolone and
discharge him home with advice to see his own GP
in the morning
C. To give the child a dose of oral dexamethasone and
discharge him home with advice to see his own GP in
the morning
D. To refer him to the on-call paediatrician
E. To send him as an emergency to hospital with a blue
light ambulance
Answer DOI: 10.1177/1755738015580702
Dr Yasser Abdel Kerim
GP Partner, Banks and Bearwood Medical Centre, Bournemouth
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