horrible hiccups sarah wilcox spr palliative medicine york hospital. may 2005
TRANSCRIPT
Horrible Hiccups
Sarah Wilcox
SpR Palliative Medicine
York Hospital. May 2005.
Case History
72 yr old manJuly 2004 admitted with painless
jaundice/itch/malaise.USS Mass head of pancreasWhipple’s procedurePost-op: non-functioning
gastrojejunostomy and onset of hiccupsUnderwent further laparotomy/gastrectomy
Persistent non-functioning and ongoing hiccups, therefore 3rd laparotomy in 8 weeks and revision gastojejunostomy. Unfortunately had adhesions ++ and accidental perforation of bowel resulted in R hemi-colectomy
Declined oncology input and discharged after 3 months in surgical ward
Progress
Reviewed in clinic with ongoing hiccupsTried:-
metoclopramide – no help
haloperidol – felt awful on it. Hand shaking uncontrollably, drooling, confused. Discontinued by patient.
chlorpromazine (prn only) – no help
Further Progress
By Jan 2005 hiccups had become intolerable. Unable to sleep, eat. Low in mood.
Admitted by the surgical team and commenced baclofen
First contact with PCT “help!”
Initial Assessment
PMH: micturition syncope 2001
Rh fever as a child
BUT!
Retired 6 years early due to shaking r hand
Handwriting shaky and becoming illegible
Mental slowing – poor concentration
Falls at home and unsteady on feet
Low mood due to above and hiccups
Drugs: lansoprazole 30mg od
metoclopramide 10mg tds
baclofen 5mg bd
Social: married, no children
retired carpet fitter
Examination
Paucity of voluntary speech (bradyphrenic)Lack of facial expressionPsychomotor retardationNo tremor at rest but tremulous on exertionNo cogwheeling or pill-rollingHandwriting small and spideryFestinant gait
Conclusion
New diagnosis of ParkinsonismPlan: collateral history from wife/GP
neurology opinion ? Idiopathic vs drug-induced
stop metoclopramide
avoid haloperidol/neuroleptics
But what to do for hiccups???
In view of low mood and case report in Psychosomatics, decided to try sertraline 50mg od
Seen by Consultant Neurologist the following day– Confirmed likely Parkinson’s– Commenced madopar
Next Day
Crash call. Found unresponsive on the floor after trying to mobilise to bathroom
BP 80/40mmHg with postural dropMedical Reg. stopped baclofen and
madopar (both thought to lower BP)Hiccups worsened over weekend
By Monday
Very low – physically exhausted and lack of sleep due to continuous hiccuping
Team planned to CT thorax and abdomen to check for a subdiaphragmatic collection and arrange OGD
What to do for hiccups?
Neurology advice
Not to rechallenge with madopar, even half dose
Possible options for Parkinson’s amantadine or selegiline (but would have to stop sertraline with the later)
Palliative Care Advice
Hiccups likely largely due to a mechanical cause following extensive surgery
May have nothing else to offer but we can’t say nothing to offer
? Benzodiazepines?nifedipine (but hypotensive)Dr Wilcox to do a lit search
Literature Review
Single case report of using amantadine in longstanding hiccups in a patient with newly diagnosed Parkinson’s
DW Neurology – worth a try as relatively few side effects and unlikely to worsen BP
Prescribed amantadine 100mg od
Response
4 days later hiccups much improved – less frequent episodes and shorter duration “manageable”
Nursing staff also commenting on increased facial expression – now able to smile and make a joke
Plan to increase amantadine to 100mg bd after 1 week
CT shows progressive intra-abdominal disease – to discuss options with Oncology
Next Problem
Serum Na has gradually dropped over two weeks coincides with starting sertraline ?SIADHSerum osm 267 (275-95) and urine osm 210
(300-900)However, reluctant to disrupt the status quo as
asymptomaticDischarged home with plan for Oncol review as
OP
Progress at home
Quiet for several weeksPhone contact with wife – opted against
chemotherapy in case it sets off his hiccupsDistress calls from wife – hiccups
returned. Seen in clinic – to stop sertraline as ?low Na now contributing to hiccups
Things settle again over several days
Terminal Stages
Admitted with likely CVA. Reduced conscious level and unable to swallow safely
All oral medication discontinuedNo return of hiccupsDied three weeks later on S/D diamorphine
and midazolam. Hiccups never recurred
Learning Points
Safe use of drugs in Parkinson’s patient? Successful use of amantadine for hiccupsSIADH associated with TCAsNever give up!
Hiccups Literature
Lots of case reports/review articlesLittle hard evidence-baseOnly one RCT for baclofen (see later)Case series for chlorpromazine,
metoclopramide, valproate and nifedipine all showed some benefit
Case reports for lots of varied drugs
Hiccups Overview
Caused by an abrupt reflex closure of the glottis after contraction of the inspiratory muscles
Also called hiccough or singultusPersistent >48hrs or recur at frequent intervals Intractable – continuous for weeks/months/years.
Significant morbidityPrimitive reflex ?functional or behavioural roleRecord: every 1.5 secs for 69 years and 5 months
Hiccup Reflex Arc
Afferent: vagus and phrenic nerves and sympathetic chain T6-T12
Hiccup centre in cervical cord (C3-C5)Efferent: phrenic nerve, glottic nerves,
nerves to accessory muscles of respirationUsually stop during sleep
Causes of Hiccups
Anything that interrupts the reflex pathway (structural, metabolic, inflammatory, neoplastic or infectious)
Underlying organic cause in 90% of men (but fewer women)
More than 100 listed causes Commonest is gastric distensionPrevalence of 19 cases in 942 palliative care
patients in 1 setting
Hiccup treatments - physical
Plato recommended a slap on the backSneezing/Valsalva’s manoeuvre/breath
holding/hyperventilating/paper bag may help benign hiccups
Granulated sugar/ice water/peanut butterForced gastric emptyingForcible tongue traction!Drinking from the far side of a glass?
Hiccup treatments – drugs 1
GI tract agents
1. Metoclopramide 10-20mg tds reduces gastric distension + ? DA action
2. Asilone 10ml qds – defoaming anti-flatulent
3. Lansoprazole 30mg od – gastric irritation is a common cause of hiccups
Hiccup treatments – drugs 2
Antipsychotics: 1. Chlorpromazine 25-50mg iv rptd after 2-
4hrs relieved hiccups in 41/50 patients w/o recurrence. Can then continue oral dose for 7-10 days. Thought to act via DA blockade in hypothalamus
2. Haloperidol 1.5mg tds starting dose3. ?levomepromazine
Hiccup treatments – drugs 3
Anticonvulsants1. Sodium valproate – case series of 5
showed some benefit but side effects troublesome
2. Phenytoin – iv bolus followed by oral therapy not consistently effective
3. Carbamazepine – case reports only4. Benzos – not helpful. May cause hiccups.
Hiccup treatments – drugs 4
Antispasticity agentsBaclofen – thought to decrease hiccup reflex excitability. One double-blind, placebo controlled crossover RCT in only 4 men with resistant hiccups. Symptomatic improvement seen using 5mg tds increased to 10mg tds but no elimination of hiccups. Caution in elderly, renal impairment and withdraw gradually
Nifedipine – relaxes smooth muscle. Ltd efficacy
Hiccup treatments – drugs 5
Amantadine – dopamine agonistCase report in NEJM: women with
persistent hiccup for 35 years thought to be due to fibrotic lung changes and chronic gastritis developed clinical features of Parkinson’s. Rx amantadine 100mg od which dramatically interrupted her hiccups and remained hiccup free after 1 year of Rx
Hiccup treatment – drugs 6
Anti-depressants
1. Amitriptyline. 1 case report in NEJM of 17yr old with hiccups for 1 year. Known type 1 DM and epilepsy. Rx 10mg tds and hiccups resolved
2. Sertraline. 1 case report using 150mg od in a depressed patient who coincidentally had 3 years of intractable hiccups. Hiccups ceased and did not recur until attempted dose reduction
Other Treatments
Electrical stimulation or chemical/surgical disruption of the phrenic nerve
Temporary measures e.g bilateral phrenic nerve block/crush procedures not always successful and can result in resp. failure
? Glossopharyngeal nerve blocks – less invasive
Pray to St Jude (patron saint of lost causes)
Hyponatraemia/SIADH and anti-depressants
EPIDEMIOLOGYCan be caused by any class of anti-
depressant (SSRIs > TCAs, MAOIs and others)
Incidence approx 5 per 1000 per year in all patients prescribed SSRIs
5-7% of all acute admissions to hospital have hyponatraemia (often SIADH)
Risk factors
Increased risk in >65 years, women, summertime (?increased sweating), first few weeks of Rx
Mean time to onset 4-28 days with SSRIs (most hospitalised within 12 days of starting)
Recent dose increase is also associatedDiuretics increase risk of developing
hyponatremia in elderly patients on SSRI
Mechanism
Unknown! ? Increased ADH secretion from posterior
pituitary or potentiating the effect of ADH on the kidney
DA/5-HT/cholinergic and noradrenergic activity can all affect ADH secretion
Management
In general stop offending drug (and/or fluid restrict)However, hyponatraemia may settle while
continuing medication, especially if mild. Average time was 7 days in 1 study of SSRIs (?correction of ADH level)
Average time for correction of hyponatraemia from stopping drug was 15 days in one study
Rechallenge with a drug from the same or a different class of anti-depressants usually results in recurrence of hyponatraemia
References
1. Hiccups and their cures, Lewis JH, Clinical Perspectives in Gastroenterology, 2000; 3(5): 277-83.
2. Hiccups a treatment review, Friedman NL, Pharmacotherapy, 1996; 16(6): 986-95.
3. Smith HS and Busracamwongs A. Management of hiccups in the palliative care population. American Journal of Hospice and Palliative Care, 2003; 20(2): 149-53
4. Askenasy JJM. Persistent hiccup cured by amantadine. NEJM, 1988; 318(11): 711.
References
5. Stalnikowicz et al. Amitriptyline for intractable hiccups. NEJM, 1986; 315(1): 64-5.
6. Vaidya V. Sertraline in the treatment of hiccups. Psychosomatics, 2000; 41(4): 353-5.
7. Bogunovic OJ. Hyponatraemia secondary to anti-depressants. Psychiatric Annals, 2003; 35(5): 333-9.