Five Centers of Nausea. Linda Tavel, MD Program Medical Director VistaCare Hospice

Transcription

1 Five Centers of Nausea Linda Tavel, MD Program Medical Director VistaCare Hospice

2 Objectives Prevalence of nausea and vomiting Anatomic and physiologic paths to nausea Evaluation of nausea Treatment of nausea Case Studies

3 Nausea Subjective sensation Often multifactorial Other symptoms occur: Sweating Salivation Tachycardia Most unpleasant of symptoms

4 It s great to be a cow. Vomiting absent in rats, rabbits, cows Rare in horses, ungulates

5 Vomiting Matter is ejected from GI tract Aka emesis (Gr.( Emein and Indo. wem ) wem Usually accompanied by nausea

6 What is vomiting? Three different actions: Salivation (from parasympathetic nervous system) Retroperistalsis,, from mid small intestine, pushing contents from digestive tract, into stomach, through relaxed pyloric sphincter Glottis closes, reducing aspiration risk Increase in abdominal pressure as muscles contract, propel stomach contents into esophagus, through relaxed lower esophageal sphincter

7 Prevalence Cancer 62% terminally ill patients--at least 40% last 6 weeks life Common in end stage heart disease Frequently seen in HIV/AIDs Liver failure Renal failure

8 Prevalence Chemotherapy Radiation therapy Opiates Medications Anorexia/cachexia syndrome

9 Causes Can be determined in most patients Up to 75% Medications Metabolic Infections Gastric slowing Constipation Always look for reversible/treatable causes first

10 Five centers. Important to determine which etiologies are involved Since multifactorial, may require more than one medication/strategy But, shotgunning not optimal Treatment aimed at underlying cause Assessment vital!

11 Assessment of Nausea and Vomiting Nausea intensity (0-10), duration, description Aggravating or activating factors QUality of life impact of N,V Symptoms accompanying N,V Emetic episodes per 24 hrs (+ timing) Alleviating factors Dahlin,, Management of Symptoms Other than Pain 2006

12 Pathophysiology of nausea / vomiting Chemoreceptor Trigger Zone (CTZ) Vomiting center Neurotransmitters Serotonin Dopamine Acetylcholine Histamine Neurokinin Cortex Vestibular apparatus GI tract

13 Where are the receptors?

14 Cortical causes of nausea Meningitis Increased intracranial pressure Anxiety (conditioning) Visual stimulus Olfactory stimulus Pain Cerebral edema due to metastases

15 Treatment of cortical pathway GABA neurotransmitter Benzodiazepines Lorazepam mg po q 4 hrs Clonazepam--longer longer acting 0.25 mg po q 12 hrs scheduled, increase q 3 days, 4 mg/d max Alprazolam--rapid rapid onset, burns off quickly mg po (panic) Treat the underlying cause!

16 Case study 41 y/o female with metastatic rectal adenocarcinoma,, multiple admissions to hospital with intractable nausea and vomiting. Resolves somewhat with hydration. Ondansetron 8 mg q 8 hrs is ineffective. Not currently receiving chemo. Patient also with fungating wound of perineum. Significant odor. Patient reports with peri- care and dressing changes the nausea worsens significantly.

17 Pathophysiology of nausea / vomiting Chemoreceptor Trigger Zone (CTZ) Vomiting center Neurotransmitters Serotonin Dopamine Acetylcholine Histamine Neurokinin Cortex Vestibular apparatus GI tract

18 Case 1 continued How would you treat her? What are the possible causes of her nausea and vomiting? Topical flagyl to wound reduced odor Lorazepam 0.5 mg po q 4 hours prn anxiety, administered prior to dressing change Dietician consult for strategies to maintain hydration

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20 Vestibular causes of nausea Tumor at base of skull Medications Motion sickness Conflicting signals visual vs. other input

21 What are the receptors?

22 Treatment of Vestibular pathway Receptors are muscarinic and histaminergic Work through decreasing excitability of labyrinths and block conduction of vestibular-cerebellar pathway Antihistamines are sedating Anticholinergics are exciting!!! (primarily due to all those side effects) Agitation, urinary retention, constipation

23 Medications Antihistamines Diphenydramine 25-50mg 50mg po/sc/pr q 4 hr prn Hydroxyzine (Atarax)(Atarax Promethazine (Phenergan) Weak dopamine antagonist Meclizine (Antivert)(Antivert

24 Medications Anticholinergics antimuscarinics Hyoscyamine (Levsin) mg po/sl q 4 hrs prn or scheduled Atropine 1% ophthalmic drops drops sl q hrs prn Scopolamine transdermal patches 1 patch q 72 hrs Glycopyrrolate (Robinul) mg po/sc q 8 hrs

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26 Chemoreceptor Trigger Zone Area postrema on floor of 4th ventricle Lies outside blood-brain brain barrier Medications: digoxin opiates Clonidine anticonvulsants antiretrovirals Antibiotics NSAIDs Metabolic: hypercalcemia,, uremia

27 Chemoreceptor Trigger Zone Chemotherapeutic agents Serotonin released by dying cells Immediate emetogenicity versus delayed Bacterial toxins Mechanoreceptors from increased ICP Following radiation therapy Whole body, mediastinal,, upper abdomen

28 Emetogenicity

29 Emetogenicity

30 Anatomy of CTZ

31 What are the receptors?

32 Treatment for CTZ nausea Dopamine antagonists Haloperidol 0.5 mg q hrs prn, titrate up in dose Pills, liquid, may give SQ Prochlorperazine (Compazine) ) mg po/pr q 4 hr prn Metoclopramide (Reglan)--also also 5HT4, at higher doses, 5HT3 More commonly for prokinetic action in gut 5-10 mg po/sc/pr QID, up to 100 mg/d (GI)

33 Treatment for CTZ nausea Setrons --Serotonin Setrons -- Serotonin antagonists Ondansetron (Zofran) po or IV 4-88 mg po q hrs/single IV dose (4-32mg) Granisetron (Kytril) mg po daily 4-32 mg IV once Dolasetron (Anzemet) Palonosetron (Aloxi)(Aloxi

34 Treatment for CTZ nausea Setrons --Serotonin Setrons -- Serotonin antagonists Prophylactically or routinely scheduled Very expensive!!!! Kytril or Zofran about $90 per day Others much more.

35 Treatment for CTZ nausea Substance P/NeuroKinin-1 1 receptor antagonist Aprepitant (Emend) Only for chemotherapy induced nausea 3 day regimen, po $300/3 days For delayed nausea as well T1/2 about 3 days

36 GI causes for nausea Peripheral Teeth to tail!!!!!! Biliary obstruction Constipation Gastric distension Gastroparesis Liver disease

37 GI causes for nausea Bowel obstruction Partial or complete Pharyngeal lesions Esophagitis Mucositis Visceral Pain

38 What are the receptors?

39 Treatment of GI pathway Assess fully!!! Treat the underlying condition Constipation, esophagitis,, mucositis

40 Treatment of GI pathway Prokinetic agents For gastric emptying Metoclopramide (Reglan) 5-20 mg po/pr/sq q 6 hrs Antidopaminergic at higher doses Dystonic reactions with higher doses and if combined with 5HT3 receptor antagonists, antidepressants, antipsychotics

41 Treatment of GI pathway AntiAcid agents Proton pump inhibitors Omperazole (OTC) mg/d po Lansoprazole,, mg/d Pantaprazole 40 mg/d Esmeprazole mg/d

42 Vomiting Center The final common pathway!!! Lateral medullary reticular formation in the pons Multiple receptors Histaminic, muscarinic cholinergic, 5HT2

43 What are the receptors?

44 Treatment of Vomiting Center Treat underlying cause Antihistamines Diphenydramine 25-50mg 50mg po/sc/pr q 4 hr prn Hydroxyzine (Atarax)(Atarax Promethazine (Phenergan) Weak dopamine antagonist Meclizine (Antivert)(Antivert

45 Treatment of Vomiting Center Anticholinergics antimuscarinics Hyoscyamine (Levsin) mg po/sl q 4 hrs prn or scheduled Atropine 1% ophthalmic drops drops sl q 2-44 hrs prn Scopolamine transdermal patches 1 patch q 72 hrs Glycopyrrolate (Robinul) mg po/sc q 8 hrs

46 Treatment of Vomiting Center Multireceptor antagonist: Olanzapine (Zyprexa) Antagonist D2, H1, 5HT2, Muscarinic cholinergic 5-20 mg po daily 2.5 mg SC up to 4 times daily This is off label use, but gaining favor

47 Treatment of Vomiting Center Multireceptor antagonist: Mirtazapine (Remeron) Antagonist for 5HT3, 5HT4, H1 15mg po BID Often used for anorexia off label

48 Miscellaneous treatments of nausea, vomiting Steroids Adjunctive therapy Emesis prevention in chemotherapy and radiation therapy Helpful in edema from brain metastases Also used in bowel obstruction We don t t know how steroids work..eduardo.. Bruera,MD Feb 25, 2008

49 Miscellaneous treatments of nausea, vomiting Steroids continued Dexamethasone mg po/sc 1-21 times daily Prednisone mg po daily Anti-inflammatory, inflammatory, promotes sense of well being, increases appetite

50 Miscellaneous treatments of nausea, vomiting Cannabinoid receptor antagonists Tetrahydrocannabinol (Marinol)/(Dronabinol) Indication chemotherapy related n,v HIV anorexia 2.5 mg BID po up to 20mg/day Euphoria, dysphoria 30 day supply= $284. 5HT3/metoclopramide/dexamethasone more in favor for chemotx related n,v

51 Alternative therapies Accupressure P6 best known Hypnosis Ginger Ginger ale, ginger tea, ginger candies Ginger root more effective than placebo mg ginger root qid Aromatherapy not ideal due to conditioning

52 Remember Case 1? 41 y/o with metastatic rectal cancer, Fungating rectal wound Nausea controlled fairly well with topical antibiotics and anxiolytic therapy. Continued to have low grade nausea. Why might she have nausea?

53 Where are the receptors?

54 What would you add to regimen? What tests? What interventions?

55 Pathophysiology of nausea / vomiting Chemoreceptor Trigger Zone (CTZ) Vomiting center Neurotransmitters Serotonin Dopamine Acetylcholine Histamine Neurokinin Cortex Vestibular apparatus GI tract

56 Malignant Bowel Obstruction Symptom management NG tubes occasional helpful short term Opioids for pain Anticholinergics to reduce secretions and reduce peristalsis (levsin)(levsin ( Haloperidol for nausea (concern about metoclopramide in complete obstn) Dexamethasone to reduce inflammation and?edema

57 Malignant Bowel Obstruction Octreotide Somatostatin analog Reduces gastrointestinal motility Reduces gastric, pancreatic, small intestine secretions Improves water and electrolyte absorption micrograms BID-TID SC/IV

58 Summary Five Pathways in nausea, vomiting Multiple receptors Multiple mechanisms Good assessment Treat underlying condition Add layers of medications I.e. dopaminergic,, steroid, 5HT3 Hydration

59 Case 2 UNIPAC-Selena Selena 58 y/o widow with advanced breast cancer, PPS 40%. S/P chemotherapy and radiation to chest wall, right arm, hip. Principal complaint pain in right arm and severe nausea. Meds: piroxicam (Fedlene)(Fedlene ) 20mg daily, morphine extended release 30 mg BID, theophylline slow release 300 mg BID

60 Where are the receptors?

61 Case 2 continued Nausea has been mild, chronic, increased over last 2 days when MD changed Selena from Tylenol #3 (codeine 30 mg) 1 q 4 hr prn to Morphine ER 30 mg BID. No BM for 4 days, increasing nausea at mealtime Piroxicam 20 mg for OA, now for bony mets Bronchitis,, but no hx asthma?

62 Case 2 continued What would you do? What medication changes would you make? Discontinue piroxicam Discontinue theophylline Change Morphine ER back to shorter acting opiate (oxycodone) Laxative

63 Case 2 continued Oxycodone, antacids, laxatives, and albuterol inhaler are effective Over time, escalating doses of oxycodone ER Nauseated much of the day and vomiting after eating, still with regular BMs Increased arm pain, weakness, nausea

64 Case 2 continued What medications or treatments would you offer now? Dexamethasone 4 mg Metaclopramide Haloperidol

65 Case 2 After the interventions aforementioned, Selena improves for awhile Selena experiences increasing confusion and sedation At this point, what tests or interventions?

66 Bibliography Module 3p Symptoms-Nausea/Vomiting EPEC- Oncology National Cancer Institute to order copy Storey, P. Nausea and Vomiting. UNIPAC Four: Management of Selected Non-pain Symptoms in the Terminally Ill. American Academy of Hospice and Palliative Medicine Twycross,, R Wilcock,, A. Hospice and Palliative Care Formulary USA. Palliativedrugs.com, Ltd. 2006

67 Bibliography Dahlin,, C Lynch, M et al. Management of Symptoms Other Than Pain. Anesthesiology Clin N Am 2006;(24): Montagnini,, M Moat, M. Non-Pain Symptom Management in Palliative Care. 2004;6(2): Wood, G Shega,, J Lynch, B Von Roenn,, J. Management of Intractable Nausea and Vomiting in Patients at the End of Life. JAMA. 2007;208(10): Chemotherapy-Related Nausea and Vomiting.Interactive Textbook on Clinical Symptom Research. Accessed 3/4/08