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Horrible Hiccups

Horrible Hiccups. Sarah Wilcox SpR Palliative Medicine York Hospital. May 2005. Case History. 72 yr old man July 2004 admitted with painless jaundice/itch/malaise. USS Mass head of pancreas Whipple’s procedure Post-op: non-functioning gastrojejunostomy and onset of hiccups

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Horrible Hiccups

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  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 • Whipple’s 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 Parkinson’s • 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 Parkinson’s 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 can’t 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 Parkinson’s • 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 Parkinson’s 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 >48hrs 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

  24. 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/Valsalva’s 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 Parkinson’s. 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 > 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 >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 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.

  38. 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.

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