Vomiting IAGH monthly meeting

Transcription

1 Vomiting IAGH monthly meeting D A R V I S H M O G H A D A M K E R M A N M E D I C A L U N I V E R S I T Y 29 M E H R

2 Sources UpTodate 18.2 Yamada Principles of Clinical Gastroenterology 2008 Sleisenger GI Liver disease 2006 Annals of Oncology 2009; 20 (Suppl 4): , Anesthesiology Clin 2010; 28: Neurogastroenterol Motil 2008; 20: CVS Gastroenterol Clin N Am 2007; 36: GP

3 Vomiting - Approach Duration: acute vs chronic Identify and correct the complications: fluid depletion, K, metabolic alkalosis Determine the etiology Rx: Symptomatic Targeted: Correct the correctable

4 Vomiting - Approach Carful Hx P/E duration, frequency, severity morning vomiting associated symptoms: Abdominal pain, distension, pyrosis, fever, ichter Character: malodor retained food, feculent, bloody Medications Blurred vision Vertigo, nystagmus Neurogenic: positional, projectile, with headache, Bulimia behavior LOC Asterixis papilledema Neck mass Abd. exam

5 Vomiting Approach Lab CBC FBS, BUN, Cr Ca, P, Na, K ABG TFT, LFT Amylase, Lipase Pregnancy test Cortisol U/A Structural Abdominal X- Ray GI Barium studies TUS GI Endoscopy CT: brain, chest, abdomen Angiography: CT, MR MRI: brain

6 Vomiting Approach: GI motor tests Gasric emptying: gastroparesis, cyclic vomiting synd Gastric Scintigraphy (Tc 99) TUS: liquid meal; useful in Nl GI & pregnancy 13 C breath test MRI emptying test: comparable to scintigraphy Single photon emission computed tomography (SPECT) IV 99 Tc: accumulates in gastric wall indicating volume, fundic accommodation, high radiation Electrogastrography (EGG) Manometry: stomach, small bowel

7 Vomiting - treatment Drugs Gastric electrical stimulation Surgery Based on clinical experience, costs, safety

8 Vomiting- pathogenesis 5 neurotransmitter receptors in vomiting M1 muscarinic D2 dopamine H1 histamine 5-hydroxytryptamine (HT)-3 serotonin μ opioid Neurokinin 1 (NK1) substance P area postrema: site of M1, D2, 5-HT3, NK1 receptors vestibular nucleus: H1 receptors vagal afferent neurons: 5-HT3

9 DDW 2010

10 Antiemetic drugs Class Antihistamine (H1) Anticholinergic (M1) Anti-dopamine (D2) Anti-serotonin Anti-Neurokinin (NK1) Type Dimenhydrinate Promethazine meclizine Hyoscine Scopolamine Metoclopramide Domperidone Ondansetron Granisetron Aprepitant

11 Antiemetic drugs Class Antidepressants Cannabinoids Type Amitriptyline Nortriptyline Dronabinol Coticosteroid Dexamethasone Benzodiazepine Lorazepam

12 Anticholinergic drug M1-muscarinic receptor antagonist Scopolamine: the major antiemetic prophylaxis against motion sickness Used: oral, transdermal, 1.5 mg q 72 h Side effects: dry mouth, drowsiness, blurred vision

13 Antihistamines (H1) Diphenhydramine(Benadryl): mg PO q 6 h or mg IV or IM Dimenhydrinate (Dramamine): 50 mg PO q 4 h Cyclizine (Marezine): 50 mg PO or IM q 4 h Meclizine (Antivert): mg PO q 24 h Promethazine (Phenergan): mg PO, IM q 4 h Effective for motion sickness Common side effect: Sedation New anti H1: cetrizne, fexofenadeine, astemizole are less antiemetic

14 DDW 2010

15 Dopamine receptor antagonists 3 classes: Phenothiazines Butyrophenones Benzamides Phenothiazines antagonizing D2- in area postrema & have anti- M1- & H1 effect Prochlorperazine: Dose: 5-10 mg q 6-8 h PO, IM, IV Chlorpromazine: 25 mg q 4-6 h, PO, IV Side effects: extrapyramidal Dystonia, tardive dyskinesia Hypotension

16 Dopamine receptor antagonists Butyrophenones: major tranquilizers, potentiate the opioids actions Have antiemetic effect when used alone primarily used as a preanesthetic agent or for procedural sedation also effective for postoperative NV and used in other settings Droperidol: short-acting drug, mg IM Haloperidol: long half-life (18 h) limits its use Side effect & antiemetic efficacy: similar to phenothiazines 2nd line of Rx prior to the advent of the 5-HT3 RA In recent years used occasionally

17 Benzamides Dopamine receptor antagonists Metoclopramide: has modest antiemetic effect central & peripheral D2 RA at low doses weak 5-HT3 RA blockade at high doses stimulates cholinergic receptors on gastric muscles enhances acetylcholine release tone in the LES speeds gastric emptying in gastroparesis can be used for CINV but replaced by 5-HT3 RA Crosses BBB: so causes akathisia, dystonia, tardive dyskinesia (black box warning from FDA)

18 Dopamine receptor antagonists Benzamides Domperidone (Motilium):D2-blocker with selective peripheral activity in upper GI does not cross BBB so lacks neurologic side effects Trimethobenzamide: no better than placebo in one study on variety of illnesses

19 5-HT3 receptor antagonists Ondansetron Granisetron Dolasetron No difference in efficacy - tolerability between theme Palonosetron has higher receptor binding affinity & longer half-life superior to older 5-HT3 RA in CINV control

20 DDW 2010

21 5-HT3 receptor antagonists Most useful class of antiemetics in acute CINV Also useful in: post Op, radiation, pregnancy Oral formulation have comparable efficacy to IV Side effects: well tolerated mild headache: most frequent, 15 20% Asthenia Constipation Dizziness 5 10% each No cognitive, psychomotor, affective disturbances

22 neurokinin-1 (NK1) receptor antagonists Substance P: the neuropeptide in brainstem nucleus tractus solitarius and the area postrema inducing vomiting NK1 RA: Aprepitant: oral form Fosaprepitant: parenteral version new class of antiemetics for CINV Effective in both acute & delayed CINV work best in conjunction with 5HT3 RA & Dexa.

23 DDW 2010

24 Corticosteroids Effective in CINV Mechanism of action: to be elucidated Side effects: insomnia, increased energy, mood changes, cleft palate in early gestation, Dexamethasone: the most extensively used drug Useful in acute & delayed CINV Combined with 5-HT3 RA & NK1 antagonist

25 DDW 2010

26 Cannabinoids Marijuana derivative Modest antiemetic activity Useful as adjunctive therapy Dronabinol: purified synthetic tetrahydrocannabinol Dose: 5-10 mg q 8 h Nabilone: 1-2 mg q 12 h Side effects: vertigo, xerostomia, hypotension, sedation, euphoria

27 Benzodiazepines weak antiemetics Lorazepam, alprazolam: most commonly used Adjunctive Rx for anxiety with Dexa akathisia with metoclopramide useful in anticipatory emesis Side effect: sedation

28 nausea - vomiting of pregnancy Morning sickness: mild nausea ± vomiting: 50-90% in pregnancies onset of symptoms: 6 weeks of gestation, peaks at 9 w abating: w may continue until third trimester: 15 20% morning sickness is a lay term, but usually is persistent throughout the day: 80% these experience fewer miscarriages & stillbirths

29 Nausea - vomiting of pregnancy Hyperemesis gravidarum: severe persistent vomiting with > 5% weight loss and ketonuria Occurs in 0.3-2% improves in last half of pregnancy

30 Nausea - vomiting of pregnancy: Rx Fluid- nutrition Pyridoxine (Vit B6): coenzyme in metabolism of lipids, carbohydrates, amino acids improves mild to moderate nausea, but not reduce vomiting Mechanism: is unknown H1 antagonists: Doxylamine ± Vit B6, Diphenhydramine, Dimenhydrinate

31 Nausea - vomiting of pregnancy: Rx D2 RA: used occasionally Metoclopramide:No major risk of congenital malformations, low birth weight, preterm delivery, perinatal death 5- HT3 RA: Ondansetron Glucocorticoid: risk of oral clefts before 10 w of gestation Best is avoided d in the first trimester Methylprednisolone: 16 mg orally or iv q 8 h Should be reserved for refractory NV

32 Chemotherapy induced nausea vomiting CINV: important adverse effect of Rx the most severe & most distressing Definition Acute: 5HT3 dependent Delayed: substance P Anticipatory Time of onset Initial 24 h after Rx After 24 h Days to hrs before Rx risk of emesis % High Moderate Low Minimal > 90 > < 10 Ann Oncol (Supplement 4): 2009 ASCO

33 CINV: level of risk Level Minimal ChemoRx drug - dose Rituximab Bevacizumab Bleomycin Busulfan Fludarabine Vinblastine Vincristine Medium Cytarabine 1000 mg/m 2 Cetuximab Docetaxel Paclitaxel Etoposide Fluorouracil Gemcitabine Methotrexate* Mitomycin Before Rx None Dexamethasone or prochlorperazine Antiemetic After Rx None None

34 CINV: level of risk Level Moderate ChemoRx drug - dose Carboplatin Cyclophosphamide <1.5 g/m 2 Cytarabine >1 g/m 2 Daunorubicin Doxorubicin Irinotecan Oxaliplatin Alemtuzumab Gemtuzumab Antiemetic Before Rx For cyclo+ Dauno 5-HT 3 -RA, Dexamethasone, & aprepitant For others 5-HT 3 -RA & Dexamethasone After Rx Aprepitant on days 2 & 3 or Dexa on days 2 &3 5-HT 3 -RA or Dexa on days 2 & 3 High Carmustine Cisplatin Cyclophosphamide 1.5g/ m 2 Dacarbazine Dactinomycin Mechlorethamine Streptozotocin 5-HT 3 -RA Dexamethasone, and aprepitant Dexamethasone on days 2-4 and aprepitant on days 2 & 3

35 CINV: non pharmacologic Rx Conventional antiemetics more successful at preventing emesis than nausea Ginger (Zingiber officinale) aids to reduce nausea Doses 0.5, 1.0 g bid limited evidence support for other methods Cognitive distraction: playing video games during Rx Learned relaxation, exercise Hypnosis Acupuncture

36 Antiemetic drugs - YAMADA 2008 Class Type Clinical use Side effects Antihistamine (H1) Dimenhydrinate Promethazine meclizine Motion sickness Labyrinthitis Uremia Post Op Sedation Dry mouth Anticholinergic (M1) Hyoscine Scopolamine Motion sickness Sedation Dry eye, mouth U. Retention, Anti-dopamine (D2) Metoclopramide Domperidone GE, Post Op Radiation Anxiety, sedation Dystonia,. Anti-serotonin Ondansetron Granisetron CINV, Post Op Pregnancy Constipation Headache Anti-Neurokinin (NK1) Aprepitant CINV Anorexia, diarrhea Constipation

37 Antiemetic drugs - YAMADA 2008 Class Type Clinical use Side effects Antidepressants Amitriptyline Nortriptyline Functional CVS Gastroparesis Sedation Constipation Cannabinoids Dronabinol CINV Ataxia Hallucination Corticosteroid Dexamethasone CINV Post Op Depression BS BP Benzodiazepine Lorazepam Anticipatory Sedation

38 Situation Migraine headache Vestibular Pregnancy-induced Postoperative Antiemetics clinical use Associated neurotransmitters Dopamine Histamine, acetylcholine Unknown Dopamine, serotonin Rx metoclopramide or prochlorperazine serotonin antagonists Antihistamines and anticholinergics nausea: ginger, vit B6 HG: 1- promethazine 2- ondansetron +corticosteroids Prevention: ondansetron, droperidol, dexamethason Rx: metoclopramide, ondansetron, dexamethasone

39 Situation Migraine headache Vestibular Pregnancy-induced Postoperative Antiemetics clinical use Associated neurotransmitters Dopamine Histamine, acetylcholine Unknown Dopamine, serotonin Rx metoclopramide or prochlorperazine serotonin antagonists Antihistamines and anticholinergics nausea: ginger, vit B6 HG: 1- promethazine 2- ondansetron +corticosteroids Prevention: ondansetron, droperidol, dexamethason Rx: metoclopramide, ondansetron, dexamethasone

40 Vomiting - Refractory Gastroparesis Cyclic vomiting syndrome Functional NV Anorexia nervosa Bulemia GI obstruction Hypercalcemia Certain antibiotics: erythromycin Cancer related High-dose chemotherapy Use of opiate analgesics CNS metastases Abdomino- pelvic Radio-Rx

41 Gastroparesis Causes: DM Scleroderma SLE DM/PM Amyloidosis Vagotomy HIV/AIDS Pancreatic Ca Lung small cell Ca Gastric ischemia Pseudo-obstruction Idiopathic

42 Gastroparesis Gastric retention with delayed gastric emptying without mechanical obstruction Classification: Grade 1 mild: intermittent symptoms with maintained weight and nutrition Rx: dietary modification Grade 2 - compensated moderate severity, maintain nutrition, hospitalize infrequently Rx: combination of prokinetic and antiemetic Grade 3 - gastric failure medication-refractory symptoms, unable to maintain nutrition, and frequent hospitalizations Rx: intermittent IV fluids, enteral or parenteral nutrition, endoscopic or surgical Rx Gastroenterol Clin N Am 2007; 36:

43 Gastroparesis - prokinetics Medication action Dose Metoclopramide Anti -D2, 5-HT3 antago. 5-HT4 agonist 5 20 mg qid Erythromycin Motilin agonist mg qid Domperidone Anti -D mg qid Bethanechol M1 agonist 25 mg qid Pyridostigmine Acetylcholinesterase inhibitor mg tid

44 Gastroparesis - Endoscopic Rx Botulinum toxin Injection into pylorus reverses the pylorospasm Accelerates the gastric emptying Pylorus pneumatic dilation reported anecdotal benefits; efficacy not proved

45 Gastroparesis - Surgical Rx Gastric electrical stimulation Better in DM gastroparesis Worse in idiopathic, pain, bloating opioid use, absent ICC on Bx Gastric resection subtotal gastrectomy gastroenteric anastomosis (Billroth I or II)

46 DDW 2010

47 Cyclic vomiting syndrome Periodic vomiting with normal intervals More in children, but not rare in adults Rome III criteria: all of the followings Stereotypical episodes of vomiting acute and duration < 1 w > 3 episodes in the prior year No NV between episodes criteria fulfilled for the last 3 m with symptoms onset x 6 m Supportive criteria: Hx or FHx of migraine headaches

48 CVS - pathogenesis remains unknown consistently associated with migraine headaches also linked to: food allergy Mitochondrial Metabolic Endocrine disorders

49 CVS and migraines CVS linked to migraine headaches & abd. migraine This connection is based on: progression from cyclic vomiting to migraine: 75% strong FHx of migraine headaches: 80% response to antimigraine in 80% CVS may lead to abd. migraines migraine headache Abdominal migraine core symptom: abd. pain CVS symptom: vomiting Both may have headache and respond to antimigraine Rx

50 CVS - manifestations Hx or FHx of migraine self-limited nature of attacks associated symptoms: nausea, abd. pain, headache, motion sickness, photophobia, lethargy associated signs: fever, pallor, diarrhea, dehydration, salivation, social withdrawal pattern of vomiting episodes: variable among patients but stereotypical for an individual episodes begin in early morning (2:00 to 7:00 AM)

51 CVS - manifestations In children, the attacks last an average of 1-2 d 50% of children have regular attacks at 2-4 w (12/ y) 2/3 have a trigger: URTI or psychological In adults: episodes are longer 3-6 d intervening intervals longer: 3 m (4/ y) Dx of CVS from functional nausea & vomiting CVS: normal health in intervening intervals Functional: continuous symptoms

52 CVS - diagnosis Based on Rome III criteria North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN) criteria: At least 5 attacks in any interval, or a minimum of 3 attacks in 6 m Episodic NV lasting 1 h - 10 d, occurring at least one week apart Vomiting occurs at least 4 times / h for at least 1 h Stereotypical pattern and symptoms in individual patient Return to baseline health between episodes Not attributed to another disorder

53 CVS - Warning signs Consider alternative Dx in the presence of severe headaches altered mental status gait disturbances any new "neurological signs GIB unilateral abdominal pain weight loss failure to respond to Rx progressive worsening prolonged episodes requiring hospitalization change in pattern or symptoms

54 CVS - approach to exclude other disorders of recurrent vomiting CBC Electrolytes Glucose ALT, GGTP, amylase, lipase U/A Upper GI series & small bowel follow-through Brain CT/MRI GI endoscopy

55 CVS - Treatment No specific Rx, can be considered as Abortive Prophylactic Supportive Antimigraine Rx even in the absence of a personal or FHx of migraines if Dx of CVS seems certain

56 CVS - Treatment Prophylactic Sumatriptan Erythromycin Carnitine Propranolol Cyproheptadine Amitriptyline Abortive 10% dextrose solution Ondansetron Diphenhydramine Lorazepam Quiet, dark room

57 Functional Vomiting Rome III criteria Must include all of the following: 1. One or more episodes of vomiting / w 2. No eating disorder, rumination, or major psychiatric disease 3. No self-induced or any co-morbid diseases *symptom for 3 m with onset at 6 m

58 Eating disorders Epidemiology Anorexia nervosa: in women 0.3 1% Bulimia nervosa: 1 1.5%, lower in men Pathogenesis: combination of Psychological, decreased self-esteem or self-control Biological Family Genetic Environmental, social factors

59 Anorexia nervosa- Dx 4 diagnostic criteria: DSM-IV Refusal to maintain normal weight Fear of weight gain despite being underweight Severe body image disturbance In postmenarch females: absent menstrual cycle, or amenorrhea (> 3 cycles)

60 Anorexia nervosa- Dx 15% below ideal body weight 2 subtypes: Restricting restriction of intake to reduce their weight binge eating/purging (vomiting, laxatives, diuretics)

61 Bulimia nervosa - Dx DSM-IV criteria: Periodic binge eating with a sense of loss of control Compensatory behavior: 2 type Purging: self-induced vomiting, laxative, diuretic abuse Nonpurging: excessive exercise, fasting, strict diets The behavior must occur a minimum of 2 times/ W x 3 m Dissatisfaction with body shape and weight

62 Anorexia nervosa: pathogenesis Neurotransmitters: levels of norepinephrine bradycardia, BP Serotonin controls brain appetite & satiety centers may account for neuropsychiatric changes and loss of appetite Brain MRI: volumes of gray and white matter CSF volume The significance of these findings is unclear

63 Eating disorders - evaluation Hx, P/E: PR, BP Specially to R/O other diseases skin for dryness, bruising, lanugo, lesions on the fingers to induce vomiting (Russell's sign) parotid gland hypertrophy Cardiac: bradycardia, arrhythmia, MVP Abdomen: abdominal mass Neurologic: R/O brain tumor

64 Eating disorders - evaluation To determine complications & R/O other diseases CBC FBS, BUN, Cr, Na, K, Ca, P, Mg, B-HCG TFT, prolactin, FSH

65 Eating disorders - complications Osteopenia or osteoporosis Growth delay Cardiac impairment Cognitive changes psychological malfunction GI dysfunction: nausea, bloating Dental erosion K, met. alkalosis ALT,AST Early mortality Endocrinologic changes: AN serum LH, FSH RT3: sick euthyroid synd serum DHEA insulin-like growth factor-i (IGF-I) leptin serum cortisol GH Infertility

66 Eating disorders - treatment interdisciplinary team approach: medical provider dietitian mental health professional nutritional rehabilitation medical monitoring Psychological Rx