1. Post Operative Nausea and Vomiting
Robert Ferrante
Pharmacy Candidate

2. Objectives
Discuss the prevalence of Post Operative Nausea and Vomiting (PONV) and why reducing PONV is so important to hospitals
Review the evolution of PONV treatment
Examine the current medications used for PONV

3. Post Operative Nausea and Vomiting (PONV)1
Up to 35% of ambulatory patients affected
70% of high risk patients
Number one concern of patients
… above pain, death, and MI
Patients often classified by risk

4. Risk Factors Younger Female “Large body habitus” History of:
PONV
Motion Sickness
Anxiety
Procedures:
Head/Neck
Intraabdominal
Larparoscopic
Gynecologic
Medications:
Opiods

5. Why So Important? Medical Consequences Patient satisfaction
Shorter PACU stays
More patients
MORE MONEY
Mo’ Problems?

6.
Emesis, or vomiting, is a physiologic response to the presence of irritating and potentially harmful substances in the gut or bloodstream. It sometimes occurs as a result of excessive vestibular stimulation (motion sickness) or psychological stimuli such as fear, dread, or obnoxious sights and odors. 
 The CTZ is outside the blood-brain- and cerebrospinal fluid-brain barriers and is extremely sensitive to emetic stimuli. Dopamine and 5-HT play an important role in the activity of the CTZ. 5-HT may play a large role in drug-induced emesis. 5-HT3 receptors appear to play an important part in the mediation of nausea and vomiting induced by high doses of cytotoxic agents. These receptors are located in the small intestine, the CTZ and the area postrema.

7. Antiemetics

8. Droperidol3 Potent D2 Receptor antagonist
PONV: mg IM/IV Q3-4h
Adjust for renal, hepatic, and age-related factors.
75% renal elimination
Extensive liver metabolism
T ½ mins
Discovered 1961

9. Droperidol Brief History1,2,3
Droperidol was the foundation for PONV
Effective and inexpensive
December 2001: FDA issue BBW
Arrhythmic-Effects
Heavily disputed.
Should be reserved for resistant patients
Requires excessive monitoring
ECG
Cost increase
277 cases of adverse effects associated with droperidol since its introduction to the market in Many of the reports were duplicates, leaving a total of 65 individual cases. Of these cases, only 2 described adverse effects possibly caused by droperidol in dosages commonly used in the United States. In addition to these reports, the results of two European studies prompted FDA to make the decision for the black-box warning. Both studies used droperidol doses times higher than those used in the United States.

10. Droperidol3 Contraindications Major drug interactions
First line treatment for anything but PONV
Known or suspected QT interval
Major drug interactions
Drugs that may cause QT prolongation
Including antiarrhythmics, opiods antipsychotics, and, diuretics

11. Reglan (Metoclopramide)4
MOA:
Peripheral dopamine receptor inhibiton
Sensitizes tissues to acetylcholine (does not stimulate).
Postoperative nausea and vomiting: 10 to 20 mg IV/IM every 4 to 6 hours as needed
CrCl < 40mL/min: 50% dose
Geriatric: Initiate at 50% dose
Adverse Effects:
Asthenia
Headache, Fatigue, Somnolence
N/V
Tardive dyskinesia – involuntary mvmnt, usually of lower face (EPS 0.02%)
Preg- B
T max IV 15 mins
Hepatic metab
85% renal excretion

12. Reglan (Metoclopramide)
BBW – Tardive dyskinesia
Contraindications:
Concomitant use with drugs likely to cause extrapyramidal reactions 
Epilepsy
Gastrointestinal hemorrhage, mechanical obstruction, or perforation.
REMS program required for other Indications
What causes EPS? Anti psychotics/ mood stabilizers (gen 1). Ach agonist

13. Reglan Efficacy5 Metoclopramide vs Ondansetron
According to a meta-analysis of 54 studies, metoclopramide is as effective as ondansetron in preventing postoperative nausea (59% vs 48%, respectively; p = 0.125)
Metoclopramide prevented postoperative vomiting in only 35% of patients compared with 50% of those using ondansetron (p < 0.001)
Metoclopramide vs Droperidol
Metoclopramide was inferior to droperidol in preventing both postoperative nausea and vomiting.
The incidence of nausea was 41% for droperidol and 52% for metoclopramide (p < 0.008);
The incidence of vomiting was 26% for droperidol versus 34% for metoclopramide (p < 0.001)

14. Aloxi (Palonosetron)6
PONV; Prophylaxis: mg IV as a single dose immediately before induction of anesthesia Major side effects
No Dose adjustments!
Contraindications?... Not really
Pregnancy Category B
Major drug interactions?... Not really…
Apomorphine

15. Aloxi (Palonosetron) Adverse Effects: One vial = about $400
Bradyarrhythmia (1-4%)
Constipation (5%)
Headache (9%)
One vial = about $400

16. Aloxi Vs. Ondansetron7
A Randomized, Double-blind Trial of Palonosetron Compared with Ondansetron in Preventing Postoperative Nausea and Vomiting after Gynaecological Laparoscopic Surgery.
Study design:
Induced with propofol
Intubated with rocuronium
NM blockade reversed with pyridostigmine and glycopyrolate

17. Aloxi Vs. Ondansetron7 0.075 mg Palonosetron , n = 45
8 mg Ondansetron, n = 45
Results:
Over 24 hours, overall PONV in 30 ondansetron patients, 19 in palonosetron
Rescue antiemetics were used in an equal number of patients
Adverse Events:
Headache, Dizziness, Constipation, Myalgia
Basically the same
Patient Satisfaction:
21 in ondansetron
30 in palonosetron

18. References
1.) Ting, P. Post-operative Nausea and Vomiting (PONV): An Overview. Available from
2.) Brenner GM, Stevens CW. Pharmacology. 4th Edition. Tulsa, OK. 2013
3.) Cherry W. Jackson, Amy Heck Sheehan, Jennifer G. Reddan. Evidence-Based Review of the Black-box Warning for Droperidol. Am J Health Syst Pharm. 2007;64(11):  
4.) Metoclopramide. In: DRUGDEX Evaluations [database on the Internet]. Greenwood Village (CO): Thompson Micromedex; [cited 18 Sep 2014].
5.) Domino KB, Anderson EA, Polissar NL, Posner KL. Comparative efficacy and safety of ondansetron, droperidol, and metoclopramide for preventing postoperative nausea and vomiting: a meta-analysis. Anesth Analg 1999;88:
6.) Palonosetron. In: DRUGDEX Evaluations [database on the Internet]. Greenwood Village (CO): Thompson Micromedex; [cited 18 Sep 2014].
7.)Park SK, Cho EJ. A Randomized, Double-blind Trial of Palonsetron Compared with Ondansetron in Preventing Postoperative Nausea and Vomiting after Gynaecological Lapaoscopic Surgery. J Int Med Res : 399

19. Questions?