1. Anaesthes ia Small Group Discussion Festejo, Katrina Marie Ho, Beverly Lorraine Hugo, Larimer Ignacio, Anna lore

2. Gen Data Vicky Bragais 59/F Married R-handed Roman Catholic Manila

3. Chief Complaint Low back pain

4. History 2 years PTA – Low back pain, hematuria, dysuria, fever No chills, lithuria – Consulted at Martinez Memorial Hospital A> Renal Calculi R>L P> Surgery – Patient opted to seek 2 nd opinion but was lost to follow up until…

5. History 1 year PTA – Still with hematuria, low back pain – No lithuria, no fever, no chills – Now with crampy abdominal pain VAS 9/10 – Rushed to Martinez Hospital UTZ: Non-obstructing nephrolithiasis, bilateral U/A: (+) sugar, RBC 10-15/hpf, PMN TNTC, EC occ, Bacteria many – Again, advised surgery but refused

6. History 1 month PTA – Persistence and progression prompted consult at Chinese General Hospital CT Stonogram: Bilateral staghorn calculi with hydronephrosis R>L – Admitted with the following working impression Urosepsis secondary to Staghorn Calculi – Discharged improved after 4 days

7. History Few days PTA – Recurrence of low back pain prompted consult at the Philippine General Hospital DFCM Clinic

8. Review of Systems (-) headache (-) BOV (-) nausea/vomiting (-) anorexia (-) weight loss (-) cough or colds (-) chest pain (-) dyspnea (-) orthopnea (-) constipation (-) muscle or joint pains (-) polyuria, polydipsia, polyphagia

9. Past Medical (+) Rheumatoid Arthritis, 2009 – Maintained on pain meds PRN basis

10. Family Medical (+) Rheumatoid Arthritis – father

11. Personal Social Married to fellow retiree Former school teacher No vices

12. Physical Examination Lying on a stretcher, conscious, coherent, oriented, not in cardio- respiratory distress Vital signs stable – BP 130/80 mmHg – HR 90 – RR 18 – Temperature

13. Physical Examination HEENT: anicteric sclerae, pink palpebral conjunctivae, no cervical masses or lymphadenopathy Chest and Lungs: symmetric chest expansion, no deformities, no retractions, clear breath sounds CVS: adynamic precordium, distinct heart sounds tachycardic, regular rhythm, no murmurs Abdomen: flabby, no direct tenderness, (+) CVA tenderness on R>L Extremities: full and equal pulses, no cyanosis, no clubbing, no edema

14. Neurologic Exam GCS 15, coherent, cooperative Oriented to time place and person No sensory and motor deficit

15. Assessment Nephrolithiasis, bilateral

16. Plan SAPOD Clearance Surgery: – Pelvolithotomy, L – Radial nephrolithotomy, R

17. Course Day 1 Admitted Referred to SAPOD Day 2 SAPOD cleared Day 3 OR Schedule

18. Anaesthesia Pre-op NPO 6 hours PTOR IVF D5NR 1L x 8 hours Meds 1 hour PTOR – Nalbuphine 10mg IM – Promethazine 25mg

19. Anaesthesia Intra-op X T – LLDS, SAAS – Local infiltration with lidocaine 2% – LP at L4-L5 using TNG18 2 attempts – 1 st attempt (+) CSF – 2 nd atttempt (+) LDLTH @ L3-L4 (-) blood (-) TD X 2 – Fentanyl 500, Propofol 10, Atracurium 30s Intraoperatively, NO hypotensive episodes, MINIMAL blood loss

20. Anaesthesia Post-op Ketorolac 30mg IV Q6 hours x 4 doses Morphine sulfate 0.03% 10cc/epidural Q12 hours

21. At the PACU Received with stable vital signs – BP 110/70, HR 88, RR 18, UO>0.5cc/hr 1 hour post-op – BP 110/70, HR 90, RR 18, UO>0.5cc/hr 2 hours post-op – (+) vomiting of yellowish clear liquid – BP 110/80, HR 92, RR 18, UO > 0.5cc/hr – Patient observed, reassured – (-) recurrence of vomiting The rest of her PACU stay was unremarkable

22. Vomiting

23. Pathophysiology coordination of the respiratory, gastrointestinal and abdominal musculature vomiting center: lateral reticular formation – in close proximity to the nucleus of the solitary tract in the brain stem – access to the motor pathways that are responsible for the visceral and somatic output involved in vomiting

24. Vomit Detectors gastrointestinal tract (GIT) – vagus nerve  mechanoreceptors - muscular wall of the gut, activated by contraction and distension of the gut  chemoreceptors - mucosa of the upper gut, sensitive to noxious chemicals chemoreceptor trigger zone (CTZ) – area postrema U-shaped structure a few millimeters long located on the dorsal surface of the medulla oblongata at the caudal end of the fourth ventricle Outside BBB and CSF barrier: can be activated by chemical stimuli received through the blood as well as the cerebrospinal fluid

25. CNS (cerebral cortex, labyrinthine, visual, vestibular apparatus) Oropharynx Mediastinum Peritoneum Genitalia CTZ Area Postrema CTZ Area Postrema GIT

26. Receptors vomiting center and vestibular nuclei: cholinergic receptors area postrema: dopamine (D2), opioid and serotonin (5HT3) receptors nucleus tractus solitarius: enkephalins, histaminic (H1), muscarinic cholinergic and NK-1 receptors dorsal motor nucleus of the vagus nerve: NK-1 receptors

28. Risk Factors Patient related factors – female – history of PONV or motion sickness – non-smoking status – High levels of anxiety and postoperative pain, (pelvic or visceral origin)

29. Risk Factors SURGERY - Adults: intra-abdominal surgery major gynecological surgery laparoscopic surgery breast surgery neurosurgery eye and ENT surgery SURGERY - Pediatrics: Strabismus adenotonsillectomy hernia repair orchidopexy penile surgery middle ear procedures

30. Risk factors Anesthesia related risk factors: – volatile agents – nitrous oxide – opioids – high doses of neostigmine (>2.5 mg) for the reversal of neuromuscular blockade

31. Risk Scoring Systems Palazzo and Evans – logit postoperative sickness = -5.03 + 2.24 (postoperative opioids) + 3.97 (previous sickness history) + 2.4 (gender) + 0.78 (history of motion sickness) – 3.2 (gender × previous sickness history) Koivuranta – Score=0.93 (if female) + 0.82 (if previous PONV) + 0.75 (if duration of surgery over 60min) + 0.61 (if nonsmoker) + 0.59 (if history of motion sickness) Apfel et al – four predictors: female gender, history of motion sickness or PONV, non-smoking status and the use of opioids for postoperative analgesia – none, one, two, three or four of these risk factors present, the incidences of PONV: 10, 21, 39, 61 and 79 %

32. Review of Anesthetic Meds

33. Nalbuphine Synthetic opioid used commercially as an analgesic SIDE EFFECTS – CNS effects: Nervousness, depression, restlessness, crying, euphoria, floating, hostility, unusual dreams, confusion, faintness, hallucinations, dysphoria, feeling of heaviness, numbness, tingling, unreality. The incidence of psychotomimetic effects, such as unreality, depersonalization, delusions, dysphoria and hallucinations – Cardiovascular: Hypertension, hypotension, bradycardia, tachycardia, pulmonary edema. – Gastrointestinal: Cramps, dyspepsia, bitter taste. – Respiration: Depression, dyspnea, asthma. – Dermatological: Itching, burning, urticaria.

34. Promethazine first-generation H 1 receptor antagonist SIDE EFFECTS: – confusion in the elderly; drowsiness, dizziness, fatigue, more rarely vertigo; dry mouth; respiratory depression; constipation; chest discomfort; euphoria (very rare, except with high IV doses and/or co-administration with opioids/CNS depressants); restless legs; paresthesia

35. Fentanyl Opioid – 100x more potent than morphine USE: Anaesthetic and analgesic SIDE EFFECTS – SERIOUS: weak, shallow breathing, severe weakness, drowsiness, or confusion; cold, clammy skin; or feeling light-headed or fainting. – LESS SERIOUS: nausea, vomiting, stomach pain, constipation; dizziness, drowsiness, headache; swelling; or pain or mouth sores where the tablet was placed.

36. Propofol short-acting, intravenously administered hypnotic agent SIDE EFFECTS: – Pain on injection – Low blood pressure – Transient apnea – (Rare) Dystonia

37. Atracurium intermediate-duration, nondepolarizing, skeletal muscle relaxant for intravenous administration

38. Ketorolac NSAID – Inhibits COX-1 and COX-2 thereby inhibiting PG production USE: short term management of severe to acute pain SIDE EFFECTS: – rash, ringing in the ears, headaches, dizziness, drowsiness, abdominal pain, nausea, diarrhea, constipation, heartburn, and fluid retention. stomach ulceration and intestinal bleeding renal impairment allergic reactions

39. Morphine Phenanthrene opioid receptor agonist – Interacts with μ-opioid receptor – Induces analegsia by mimicking endogenous endorphin release principal effect on CNS and GI – Analgesia, sedation, euphoria

40. Morphine SIDE EFFECTS Bradycardia, Cardiac arrest, Hypotension, Palpitation,syncope, Flushing of the face, Orthostatic hypotension, Pruritus or itching, Xerostomia or dry mouth, Intermittent blurring, miosis, Visual distortions, Constipation, Nausea and vomiting or emesis, Hepatotoxicity, Renal failure, Bradypnea, dyspnea or respiratory depression

41. Differentials for Post-op Nausea and Vomiting

42. Differentials Anaesthetic-induced – Opioid: fentanyl and morphine Hypotension – Secondary to anaesthetic agent or to blood loss during surgery – Highly unlikely

43. Opioid- induced Nausea and Vomiting

44. Opioids highly effective analgesics WHO's pain ladder – step-wise approach to the use of analgesics – third and final step for severe pain. Nausea and vomiting – undesirable side effects associated with the use of the opioid analgesics

45. Etiology & Risk Factors Medication with opioids is a major contributory factor to post-operative nausea and vomiting. – For example the incidence of nausea and vomiting in patients undergoing minor gynaecological surgery has been reported to increase from 18% in a control group to more than 60% in patients receiving morphine or pethidine Factors: type of opioid analgesic used, time course, route of administration; previous exposure to opioids

46. Cause Opioids have direct action on the CTZ thru the 3 receptors (kappa - κ, delta - δ and mu - μ)

48. Consequences When opioids are used post- operatively patients have little opportunity to develop tolerance to the emetic effects – compared to chronic opioid users i.e. cancer patients

49. Consequences Practical very distressing for patients when they are already feeling uncomfortable and anxious Medical powerful muscular contractions may damage stitches,  risk of bleeding, regurgitation of stomach contents, poss. aspiration pneumonia; e- imbalance and dehydration, if severe Economic personnel time in clearing up, material costs of disposable products, laundry, caring for patients, delayed discharged, unplanned admission leading to bed blocking, delayed surgical throughput and potential re-op costs *Audit Commission Report: most common cause for unplanned overnight hospiltalization after surgery is PONV

50. Management Anti-histamines Anti-muscarinics Dopamine receptor antagonists Opioid receptor antagonists – But will inhibit desired analgesic effect

52. Management

53. Novel Antiemetics Neurokinin-1 antagonist – Indirectly works on substance P, member of the tachykinin family of neuropeptides, an important neurotransmitter in afferent pathways of emesis – Works on NK1 receptor, a G-protein coupled receptor in the CNS, important in tachykinin peptide activity – potential NK 1 receptor blocking activity located deeper in the brain stem is thought to prevent both acute and delayed emesis

54. Novel Antiemetics Long Acting Serotonin Antagonist – Longest elimination half-life (40 hours) of all the currently available serotonin antagonists Its long – also has high binding affinity for 5-HT3 receptors

55. Recommendations: PONV prophylaxis No prophylaxis for low risk patients except if at risk for medical consequences from vomiting (e.g. wired jaw) Moderate to high risk : regional anesthesia High risk: combination antiemetics and multimodal therapy

56. Recommendations: treatment for established PONV paucity of data on the use of anti- emetics for the treatment of PONV in patients who failed prophylaxis or did not receive prophylaxis

57. Recommendations: treatment for established PONV 5-HT3 receptor antagonists were the most commonly tested drugs – small doses of these agents have been recommended for treatment ondansetron 1 mg dolasetron 12.5 mg granisetron 0.1 mg tropisetron 0.5 mg

58. Recommendations: treatment for established PONV Within 6 hours post-op: – a drug from a different class should be used for rescue Beyond 6 hours – may use any of the agents used for prophylaxis except dexamethasone and scopolamine, which are longer acting

59. History of PONV Regional anesthesia Adequate hydration Avoid nitrous oxide Avoid high dose neostigmine Female gender Postoperative opioid History of motion sickness Long duration of surgery Emetogenic surgery Non-smoke r - 5-HT3 antagonist + Dexamethasone - 5-HT3 antagonist + Droperidol* - 5-HT3 antagonist +Acupuncture ≥ 2 antiemetics PLUS TIVA with Propofol PONV reduction strategy A or3 factors in BA or/and <3 factors in B consider

60. Guidelines for management - Society of OBB-GYN in Canada Basically has the same recommendations Acupoint electrical stimulation may be used as an alternative or adjuvant therapy for prevention of PONV

61. Pharma Single Agent Combi Therapy Non-Pharma Accupuncture

62. Pharma Single Agent Combi Therapy Non-Pharma Accupuncture Single Agent

63. Metoclopramide: Pharmacodynamics Antagonist to dopamine D 2 receptors of the CTZ Mixed 5-HT 3 receptor antagonist/5-HT 4 receptor agonist. – Contribute to antiemetic effect at higher doses – prokinetic action

64. Metoclopramide: Pharmacokinetics rapidly and well absorbed absolute oral bioavailability of metoclopramide is 80% ± 15.5 peak plasma concentrations occur at about 1 to 2 hr after a single oral dose – similar time to peak is observed after individual doses at steady state.

65. Metoclopramide: Pharmacokinetics area under the drug concentration- time curve increases linearly with doses from 20 to 100 mg. peak concentrations increase linearly with dose whole body clearance is unchanged; elimination half-life in individuals with normal renal function is 5 to 6 hr

66. Metoclopramide: Pharmacokinetics 85% eliminated in the urine, – about half is present as free or conjugated metoclopramide. not extensively bound to plasma proteins (about 30%). HIGH whole body volume of distribution is high (about 3.5 L/kg) Renal impairment affects the clearance of metoclopramide. – kinetics of metoclopramide still linear – The reduction in clearance – Downward dose adjustment should be done

67. Pharma Single Agent Combi Therapy Non-Pharma Accupuncture Combi Therapy

68. Combination Antiemetic Therapy Based on the concept that least four major receptor systems are involved in PONV First introduced in 1988 Most of these studies suggest: two or more antiemetics acting on different receptors are better than monotherapy for prophylaxis

69. Combination Antiemetic Therapy Use two or more Acting at different receptors – 5-HT receptor antagonist + droperidol or dexamethasone: better PONV porphylaxis than 5-HT receptor antagonist alone – Habib AS, El-Moalem HE, Gan TJ. The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Canadian Journal of Anaesthesia 2004;51:311-9.

70. Combination Antiemetic Therapy Apfel CC, Korttila K, Abdalla M et al. A factorial trial of six interventions for the prevention of postoperative nausea and vomiting.[see comment]. New England Journal of Medicine 2004;350:2441-51. 3 antiemetic interventions – ondansetron 4 mg – droperidol 1.25 mg – dexamethasone 4 mg 3 anesthetic interventions – (TIVA with propofol, omitting nitrous oxide, and substituting remifentanil for fentanyl) for the prophylaxis of PONV

71. Combination Antiemetic Therapy Conclusion: – Antiemetics with different mechanisms of action have additive rather than synergistic effects on the incidence of PONV – Each antiemetic reduced risk by 25% – When combinations of interventions were used, the benefit of each subsequent intervention was always less than that of the first intervention – Efficacy depends on patient’s baseline risk

72. Multimodal Therapy Since PONV is multifactorial etiology, a multimodal therapy is also suggested Study by Scuderi et al: multimodal approach to the management of PONV in females undergoing outpatient laparoscopy – Multimodal management: 98% complete response rate (no PONV and no antiemetic rescue) in PACU. No patient in this group vomited before discharge, – Ondansetron group: 7 % of patients – Placebo group: 22 % of patients

73. Pharma Single Agent Combi Therapy Non-Pharma Accupuncture

74. Acupuncture and PONV stimulation at the Pericardium (P6) acupuncture point (acupoint) on the wrist will have a reduced risk of nausea and vomiting after surgery needle acupuncture, transcutaneous nerve stimulator, laser stimulation and acupressure wristbands

75. Acupuncture and PONV 4,500 patients from 1986 to 2008 – 32 studies: P6 acupoint stimulation vs placebo (3,385 patients) – 14 studies: P6 acupoint stimulation vs antiemetic treatment (1,036 patients) compared to placebo, stimulation of the P6 acupoint reduced the risk of nausea and vomiting after surgery, with fewer side-effects

76. Summary

77. Many opioids are very effective analgesics and they are frequently used for post-operative analgesia and in palliative care Nausea and vomiting are undesirable side effects associated with the use of opioids Medication with opioids is a major contributory factor to post-operative nausea and vomiting (PONV), though tolerance can develop when used chronically, for example in palliative care.

78. Summary Opioids are thought to induce nausea and vomiting by a direct action on the chemoreceptor trigger zone (CTZ). Opioid-induced nausea and vomiting can be distressing to patients, may have medical implications and has economic consequences Anti-histamines, anti-muscarinics and dopamine receptor antagonists have efficacy against opioid-induced nausea and vomiting.

79. Reference

80. Main Journal Gan TJ, Meyer T, Apfel CC, Chung F, Davis PJ, Eubanks S, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97;62–71.