Emesis /CINV

brief presentation regarging basic causes of vomitting chemotherapy induced vomitting studies done for better control of vomitting

1. By Dr Tanveer alam Skmch.RC Emesis /CINV

2. Key points Definition How to approach a child with emesis Causes Excluding possible causes Investigation Management CINV Studies done

3. introduction Nausea : The unpleasant sensation of the imminent need to vomit, usually referred to the throat or epigastrium ; a sensation that may or may not ultimately lead to the act of vomiting . Vomiting: Forceful oral expulsion of gastric contents associated with contraction of the abdominal and chest wall musculature . Regurgitation : The act by which food is brought back into the mouth without the abdominal and diaphragmatic muscular activity that characterizes vomiting.

4. Differential diagnosis Clues on physical examination   —  Certain physical findings may offer diagnostic clues that can aid in narrowing the differential diagnosis: Gastroparesis / gastroenteritis. Constipation : Meningitis : A tense, bulging fontanels in neonates ,headache ,neck stiffness projectile vomiting level of suspicion for meningitis. Pyloric stenosis : Projectile vomiting in an infant three to six weeks of age suggests pyloric stenosis as a diagnosis . Acute appendicitis : Alvarado scoring( apgar scoring) CINV

5. Metabolic cause: An unusual odor emanating from the patient should be investigated for metabolic causes of vomiting. Obstruction Marked distension, visible bowel loops, absent bowel sounds, bile staining in the vomitus Trauma related Vomiting in association with trauma should leads to imaging studies to rule out intracranial or intraabdominal injury. Miscellaneous causes: Cholecystitis , uti ,motion sickness,pregnancyetc , sepsis, excessive feeding volume, pneumonia ,etc

6. How Vomitus helps in diagnosis

7. Clinical Approach

8. Referrels Patients should be referred to a pediatric gastroenterologist or other appropriate specialist ( eg , pediatric surgeon, neurologist) when there are symptoms or physical findings that are of particular concern. These include an abnormal neurologic exam, peritoneal signs on abdominal examination, severe abdominal pain, gastrointestinal bleeding, or significant weight loss. Immediate pediatric surgical consultation is warranted if appendicitis, bowel obstruction, or bowel perforation are suspected.

9. Laboratory Investigations

10. management Examination Vitals diagnosis IV fluids bolus (NS +R/L +dextrose) Antiemetic ( dimenhydrinate , metoclopramide , ( ondansetron , granisetron,palonosetron Serotonin (5-HT3 ) aprepitant , corticosteroide , domperidone Reassess ( vitals + exam +oral trial) Treat the cause

11. CINV: types & Definitions Acute (post-treatment) Occurs within first 24 hours after administration of cancer chemotherapy Delayed CINV that begins after first 24 hours May last for 120 hours Anticipatory Learned or conditioned response from poorly controlled nausea and vomiting associated with previous chemotherapy Breakthrough CINV that occurs despite prophylaxis and requires rescue Refractory Occurs during subsequent treatment cycles when prophylaxis and/or rescue has failed in previous cycles

12. Emetogenic Potential of Single Antineoplastic Agents HIGH Risk in nearly all patients (> 90%) MODERATE Risk in 30% to 90% of patients LOW Risk in 10% to 30% of patients MINIMAL Fewer than 10% at risk

13. 1 st Generation 5HT 3 RAs Are Therapeutically Equivalent Pts receiving MEC* (N=1,085) 80% of pts received prophylactic steroids * Cyclophosphamide 500 - 1200 mg/m 2 , carboplatin ≥300 mg/m 2 59.0 60.0 71.0 58.0 58.0 72.0 Total Nausea Emesis Oral granisetron 2 mg IV ondansetron 32 mg Complete Control (%) Highest Level Evidence & Not Debated MASCC 2004 NCCN 2009 ASCO 2006 1 st Generation Agents are Therapeutically Equivalent Dolasetron Ondansetron Granisetron 1 st Generation oral and IV doses equally effective Perez et al. J Clin Oncol 1998;16:754

14. 1 st vs 2 nd generation 5-HT 3 antagonist Pharmacologic differences from older 5-HT 3 antagonists prolonged half-life (~40 hours) enhanced receptor binding affinity (30-fold) Comparable tolerability 1 st Generation Oral 5HT 3 RAs Not Effective for Delayed CINV

15. Palonosetron vs. 1 st gen 5HT-3: Complete Response on Day of Chemo & Beyond Palonosetron 0.25 mg (n=378) Ondansetron/Dolasetron 32/100 mg (n=376) 46.8 42.0 * 57.7 * 64.0 * 72.0 60.6 20 40 60 80 100 Time (hr) Acute: 0-24 (Day 1) Delayed: 24-120 (Days 2-5) Overall: 0-120 (Days 1-5) Complete Response (CR) (% of Patients) * p <0.025 for pairwise difference (2-sided Fisher’s exact test) between palonosetron and ondansetron/dolasetron. Gralla R et al. Ann Oncol . 2003; Eisenberg P et al. Cancer . 2003. Rubenstein EB et al. Proc Am Soc Clin Oncol. 2003. Abstract 2932. CR = no emetic episodes or use of rescue medications

16. A JOURNAL OF PAKISTAN PAEDIATRIC ASSOCIATION ABSTRACT Objectives: The objective of the study is to evaluate gastrointestinal problems in cancer patients during treatment. Patients and methods: In a sample of 150 children having different childhood malignancies, the frequency, pattern and risk factors of gastrointestinal (GIT) symptoms were analyzed. Results : Almost 30% of pediatric cancer patients experienced one or more episode of GIT problems. Overall prevalence of anticipatory vomiting was 12%, acute vomiting was 51.33%; delayed vomiting was 26% that was highest on day 2 with 18% experiencing vomiting and decreased to 8% by day 5. Expectancy of nausea was found to be a strong predictor of subsequent occurrence of nausea and vomiting (P=0.047) as well as the chemotherapeutic regimen potentiality that significantly affected delayed vomiting (P=0.02).

17. continue Other predictive factors as age, gender , did not affect various forms of vomiting 40 % of the enrolled patient suffered from mucositis , ranging from grade 1 to 3 Clinical features of oral candidiasis werepresent in 10% of patients . 28% of the enrolled patients had attacks of diarrhea while 11.33% experienced constipation mostly due to vincristine opioids , 18% had altered perception of taste or smell. Conclusion : The gastrointestinal symptoms are common in cancer patients. Early recognition of GIT symptoms is essential for early intervention and guide nutritional support .

18. Clinical research of Olanzapine for prevention of chemotherapy-induced nausea and vomiting by journal of experimental & clinical research background This study was designed to mainly evaluate the activity and safety of olanzapine compared with 5-hydroxytryptamine3(5-HT 3 ) receptor antagonists for prevention of (CINV) + QOL Methods 229 patients receiving highly or moderately emetogenic chemotherapy were randomly assigned to the test group [ olanzapine (O) 10 mg p.o . plus azasetron (A) 10 mg i.v . and dexamethasone (D) 10 mg i.v . on day 1 ; Results In summary, this study demonstrated that olanzapine has obtained the better efficacy on being safely used for preventing the CINV. Olanzapine can improve the complete response of delayed nausea and vomiting in patients receiving the highly or moderately emetogenic chemotherapy comparing with the standard therapy of antiemesis , as well as improve the QoL of the cancer patients during chemotherapy. Olanzapine is a safe and efficient drug for prevention of CINV. Further study should be done to compare the efficacy of olanzapine with aprepitant or palonosetron on prevention of CINV through large sample study Pub med