Horrible Hiccups

1
Horrible Hiccups

• Sarah Wilcox
• SpR Palliative Medicine
• York Hospital. May 2005.

2
Case History

• 72 yr old man
• July 2004 admitted with painless
  jaundice/itch/malaise.
• USS Mass head of pancreas
• Whipples procedure
• Post-op non-functioning gastrojejunostomy and
  onset of hiccups
• Underwent further laparotomy/gastrectomy

3

• 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

4
Progress

• Reviewed in clinic with ongoing hiccups
• Tried-
• metoclopramide no help
• haloperidol felt awful on it. Hand shaking
  uncontrollably, drooling, confused. Discontinued
  by patient.
• chlorpromazine (prn only) no help

5
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!

6
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

7

• Drugs lansoprazole 30mg od
• metoclopramide 10mg tds
• baclofen 5mg bd
• Social married, no children
• retired carpet fitter

8
Examination

• Paucity of voluntary speech (bradyphrenic)
• Lack of facial expression
• Psychomotor retardation
• No tremor at rest but tremulous on exertion
• No cogwheeling or pill-rolling
• Handwriting small and spidery
• Festinant gait

9
Conclusion

• New diagnosis of Parkinsonism
• Plan collateral history from wife/GP
• neurology opinion ? Idiopathic vs
  drug-induced
• stop metoclopramide
• avoid haloperidol/neuroleptics
• But what to do for hiccups???

10

• 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 Parkinsons
• Commenced madopar

11
Next Day

• Crash call. Found unresponsive on the floor after
  trying to mobilise to bathroom
• BP 80/40mmHg with postural drop
• Medical Reg. stopped baclofen and madopar (both
  thought to lower BP)
• Hiccups worsened over weekend

12
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?

13
Neurology advice

• Not to rechallenge with madopar, even half dose
• Possible options for Parkinsons amantadine or
  selegiline (but would have to stop sertraline
  with the later)

14
Palliative Care Advice

• Hiccups likely largely due to a mechanical cause
  following extensive surgery
• May have nothing else to offer but we cant say
  nothing to offer
• ? Benzodiazepines
• ?nifedipine (but hypotensive)
• Dr Wilcox to do a lit search

15
Literature Review

• Single case report of using amantadine in
  longstanding hiccups in a patient with newly
  diagnosed Parkinsons
• DW Neurology worth a try as relatively few side
  effects and unlikely to worsen BP
• Prescribed amantadine 100mg od

16
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

17
Next Problem

• Serum Na has gradually dropped over two weeks
• coincides with starting sertraline ?SIADH
• Serum osm 267 (275-95) and urine osm 210
  (300-900)
• However, reluctant to disrupt the status quo as
  asymptomatic
• Discharged home with plan for Oncol review as OP

18
Progress at home

• Quiet for several weeks
• Phone contact with wife opted against
  chemotherapy in case it sets off his hiccups
• Distress calls from wife hiccups returned. Seen
  in clinic to stop sertraline as ?low Na now
  contributing to hiccups
• Things settle again over several days

19
Terminal Stages

• Admitted with likely CVA. Reduced conscious level
  and unable to swallow safely
• All oral medication discontinued
• No return of hiccups
• Died three weeks later on S/D diamorphine and
  midazolam.
• Hiccups never recurred

20
Learning Points

• Safe use of drugs in Parkinsons patient
• ? Successful use of amantadine for hiccups
• SIADH associated with TCAs
• Never give up!

21
Hiccups Literature

• Lots of case reports/review articles
• Little hard evidence-base
• Only 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

22
Hiccups Overview

• Caused by an abrupt reflex closure of the glottis
  after contraction of the inspiratory muscles
• Also called hiccough or singultus
• Persistent gt48hrs or recur at frequent intervals
• Intractable continuous for weeks/months/years.
  Significant morbidity
• Primitive reflex ?functional or behavioural role
• Record every 1.5 secs for 69 years and 5 months

23
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 respiration
• Usually stop during sleep

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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 distension
• Prevalence of 19 cases in 942 palliative care
  patients in 1 setting

25
Hiccup treatments - physical

• Plato recommended a slap on the back
• Sneezing/Valsalvas manoeuvre/breath
  holding/hyperventilating/paper bag may help
  benign hiccups
• Granulated sugar/ice water/peanut butter
• Forced gastric emptying
• Forcible tongue traction!
• Drinking from the far side of a glass?

26
Hiccup treatments drugs 1

• GI tract agents
• Metoclopramide 10-20mg tds reduces gastric
  distension ? DA action
• Asilone 10ml qds defoaming anti-flatulent
• Lansoprazole 30mg od gastric irritation is a
  common cause of hiccups

27
Hiccup treatments drugs 2

• Antipsychotics
• 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
• Haloperidol 1.5mg tds starting dose
• ?levomepromazine

28
Hiccup treatments drugs 3

• Anticonvulsants
• Sodium valproate case series of 5 showed some
  benefit but side effects troublesome
• Phenytoin iv bolus followed by oral therapy not
  consistently effective
• Carbamazepine case reports only
• Benzos not helpful. May cause hiccups.

29
Hiccup treatments drugs 4

• Antispasticity agents
• Baclofen 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

30
Hiccup treatments drugs 5

• Amantadine dopamine agonist
• Case 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 Parkinsons. Rx amantadine 100mg od
  which dramatically interrupted her hiccups and
  remained hiccup free after 1 year of Rx

31
Hiccup treatment drugs 6

• Anti-depressants
• 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
• 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

32
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)

33
Hyponatraemia/SIADH and anti-depressants

• EPIDEMIOLOGY
• Can be caused by any class of anti-depressant
  (SSRIs gt 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)

34
Risk factors

• Increased risk in gt65 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 associated
• Diuretics increase risk of developing
  hyponatremia in elderly patients on SSRI

35
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

36
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

37
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.

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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.