HiccupsColleen Tallen M.D.

Palliative Care Lecture SeriesOctober 17, 2013

Objectives

•What are hiccups?

•Why do we hiccup?

•Who gets hiccups?

•How do we treat hiccups?

What is Hiccups?

• The term "hiccup" derives from the sound of the event. "Hiccough" erroneously implies an association with respiratory reflexes.

• The medical term, singultus (sing-guhl-tuhs), is thought to have originated from the Latin, singult, which translates roughly as "the act of catching one's breath while sobbing."

• Also called “synchronous diaphragmatic flutter”

What is Hiccups?• An involuntary, intermittent, spasmodic

contraction of the diaphragm and intercostal muscles accompanied by sudden inspiration that ends with abrupt closure of the glottis, making the classic hiccup sound.

• Persistent or protracted hiccups - lasting more than 48 hours

• Intractable hiccups - lasting more than one month

Who Hiccups?• Equal incidence between men and woman overall

• Higher incidence in men (82%) than women for protracted hiccups

• Organic cause identified in 93% of men and 8% of women

• Organic incidence is 80%. Psychogenic incidence is 20%

• More common in children

• Seen in utero

• More common in the evening (Circadian rhythm)

Why Hiccup?• Considered pathologic because serves no useful

function

• Unknown etiology

• Normally brainstem action that closes the glottis never activated when brainstem stops respirations (one inhibited/one activated). Abnormal when both activated

• Hypothesis based on

• Medulla controls both actions

• Damage to medulla can cause intractable hiccups

• May involve dopamine, serotonin, opioid, calcium channel, GABA pathways

Why Hiccups?• Reflex arch for hiccups

• Afferent pathway (periphery to central) - vagus, phrenic or thoracic sympathetic fibers (phrenic C3-5, anterior scalene C5-7, external intercostals T1-11, glottis- recurrent laryngeal component of vagus)

• Central connection -

• Phrenic nerve nuclei (neuron cell bodies located in the more medial portions of the anterior horn at cervical levels C3–C5 that innervate the diaphragm via the phrenic nerve)

• Inspiratory and glottis control centers in posterior lower medulla, reticular part of brainstem and hypothalamus

• Efferent pathway (center to periphery) - phrenic nerve to diaphragm. Involves the accessory respiratory muscles

WHY HICCUP?ETIOLOGY EXAMPLES

CNS

Vascular Stroke, infarct, SLE, vascular disorders, aneurysm, basilar artery insufficiency

Tumor Astrocytoma, carvenoma, brainstem tumors, glioblastomas, metastasis

Inflammation Neuromyelitis, multiple sclerosis, pneumonia, encephalitis, meningitis

Trauma Brain injury

Miscellaneous Seizure, cranial herpes infection, hydrocephalus,Parkinsons, tobacco use, multiple sclerosis

PERIPHERAL PATHWAY

Chest cavity Mediastinal diseases, lymphadenopathy/diaphragmatic tumors, mediastinal tumor, pleurisy, pulmonary edema

Heart Myocardial ischemia

GI Esophageal tumors, GERD & gastritis, Stomach volvulus, H. Pylori, hepatomegaly, pancreatitis, gastric distention,

Lower Abdomen Gynecologic tumors, prostate cancer, intra-abdominal tumors, bowel obstruction

Miscellaneous Cancers, nephrosis, UTI, psychological

EXTRINSIC CAUSES

Surgery Anesthetic agents, post-op disturbances

Chemotherapy Chemotherapeutics, steroids

Drugs Anti-parkinson treatment, psychiatric meds, azithromycin,bisphosphonates (hypocalcemia), morphine (hypocapnea), sulfonamides, steroids, methydopa, diazapam, barbiturates, Librium

Instrumental Atrial pacing, catheter ablation, central venous cath, esophageal stent, bronchoscopy, tracheostomy, shaving beards

Miscellaneous Electrolyte imbalance, ethanol users, TB, chronic renal failure, stress/anxiety/grief/psychogenic, anorexia

Understand the “why” will help with “how” to treat

• Injury to brain

• Ischemia/stroke - may improve with anticoagulants

• Inflammation (multiple sclerosis, encephalitis) - steroids

• Space occupying lesions(tumors, aneurysm)- resection, steroids

• Infection - meningitis - antibiotics. herpes zoster-acyclovir. H. pylori - antibiotics

Understand the “why” will help with “how” to treat

• Medications that may effect the hiccup reflex arch

• Bupivacaine epidural, propofol- interrupts inhibitory reflex of phrenic nerve and afferent visceral sensory pathway

• Chemotherapy - Cisplatin - releases 5-hydroxyltryptamine from vagal afferents and initiates the emetic reflex

• Steroids may cause hiccups by steroid receptors in the efferent limb of hiccup reflex (may also help when steroids decrease inflammation)

Understand the “why” will help with “how” to treat

• Instrumentation

• Atrial pacing/catheter ablation for atrial fibrillation (right phrenic nerve close to right atrium)

• Esophageal stenting/bronchoscopy/tracheostomy - irritate afferent pathway of hiccup reflex arc

• Shaving or stoking someone’s chin - chin innervated by C5 that projects to the medulla (centrally mediated hiccups)

• Psychogenic (consider if hiccups stop while sleeping)

Understand the “why” will help with “how” to treat

• GI causes

• Mechanical - gastric distention relieve source ie reglan for gastroparesis, NG tube, simethicone

• GERD - proton pump inhibitors, H2 - blockers

• Arrhythmia-induced syncope has been reported as both the cause and the effect of hiccups

• Peritoneal dialysis - may improve with change in pH of dialysis solution

How to treat hiccups?Non-pharmacologic

•Hold breath

•Hyperventilate (re-breath into paper bag)

• Sneeze

•Gargle

How to treat hiccups?Non-pharmacologic

• Food/drinks to ingest - Pineapple juice, lemon wedges with bitters, sugar, honey/vinegar

• Iced water - drink fast or on “wrong side” of glass

• Pressure on eyeballs or carotid sinus

• Chest compression by pulling knees to chest or leaning forward

How to treat hiccups?Non-pharmacologic

• Rubbing 5th cervical vertebrae

• Diaphragmatic pacing electrodes

• Acupuncture

•Massage or relaxation techniques

How to treat hiccups?• Dopamine antagonists

• Chlorpromazine (Thorazine) - central dopamine antagonist

• Approved for treating hiccups

• Blocks dopaminergic neurotransmission

• Oral/ IV/IM

• Recommended dose: 25-50 mg PO/IM q6-8 hours

• Personal dose: start at 3-6.25 mg IV/PO q4hours (titrate dose until hiccups resolved)

How to treat hiccups?• Dopamine antagonists

• Haloperidol - central dopamine antagonist

• Dopamine antagonist

• PO/IM/SL (use IV cautiously. Increased chance of QT interval prolongation)

• Recommended: 1-4mg PO/SL q8hour

• Personal: Start low and titrate until hiccups resolved. May start with 0.5 mg dose

• Droperidol

How to treat hiccups?

• Calcium Channel blockers (anti-spasmotic effect on smooth muscle?)

• Nifedipine (Adalat)

• nimodipine (Nimotop)

• Carvedilol - non-cardio selective beta blocker, Ca channel blocker and antioxident

• Amantadine (weak antagonist NMDA receptor)

• Zyprexa (serotonergic antagonist. Brain injury cases)

How to treat hiccups?

• Antiemetic with central anti-dopaminergic effect

• Metoclopramide (Reglan)

• Dopamine antagonist

• Helps with gastric distension

• Recommended: 5-10mg po/IV q8hours

How to treat hiccups?

• Anti-spasmotic

• Baclofen

• GABA(B) receptor agonist

• Acts primarily at the spinal cord level by inhibiting spinal afferent pathways

• Studied in double blind reandomized contolled study that showed effectiveness

• Cautious use in elderly, renal failure

How to treat hiccups?

• Anti-seizure medications

• Dilantin- 200 mg IV followed by 300 mg/day

• Tegretol

• Neurontin – normal titration

• Valproic acid

How to treat hiccups?• Ketamine

• Lidocaine

• Benzodiazapines

• Marijuana

• Combo - therapy ie COB (cisapride, omeprazole, baclofen) and COBG (add gabapentin)

• Sertraline (Zoloft) - Effects peripheral 5-HT4 receptors in GI tract reducing abnormal esophagus, gastric, diaphragm mobility

Sometimes I wrestle with my demons, sometimes we just snuggle