MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics- PONV – insights Dr. S. Parthasarathy MD., DA., DNB, MD (Acu), Dip. Diab. DCA, Dip. Software statistics- PhD ( physiology), ( IDRA )

Some history One of the first extensive descriptions of this phenomenon was by Sir John Snow in 1848, within 18 months of chloroform introduction in anaesthesia. ether era, reported incidence of PONV was as high as 75–80% Olive oil oral on recovery – does it absorb ether ?

Some history Brown sequard – atropine to morphine – decreased PONV – still there 70 % to 50 % over the years to almost 20 % down now with proper prophylaxis comes down in single digit !?

Some definitions Nausea is an unpleasant and difficult to describe psychic experience in humans Retching ("dry heaves") refers to spasmodic respiratory movements conducted with a closed glottis Vomiting is a forceful expulsion of the contents of the stomach and sometimes the gut.

Nausea Nausea is derived from the Greek word naus denoting ‘ship’ and was used originally to describe the feeling of seasickness. Nausea is an unpleasant sensation referred to the upper gastrointestinal tract and pharynx. It is associated with dizziness and a strong urge to vomit. Score - not clear – assessment difficult

Retching Retching is the involuntary process of ‘unproductive vomiting’. It is characterized by the synchronous contraction of diaphragmatic and abdominal muscles against a closed mouth and glottis. Retching is extremely distressing

What is vomiting ?? Vomiting represents the final common pathway of a highly coordinated sequence of events involving gastrointestinal, abdominal, respiratory and pharyngeal muscles which results in the active and rapid expulsion of contents from the stomach and upper intestine. vomiting is easily identifiable and measurable!

Physiology of vomiting Chemoreceptor Trigger Zone (CTZ) Highly specialized are in the floor of the fourth ventricle Responds to chemicals Histamine. Serotonin, opioids, cholinergic , dopaminergic receptors When stimulated , it stimulates the vomiting centre

Vomiting center Medulla Final push Main sensory input is CTZ

GI tract Any threat to the integrity of the GI system, e.g. gastric distension, irritation, damage or toxins, triggers an ascending vagal activity which relays directly or indirectly to the vomiting centre Cholinergic (M1), serotoninergic (5-HT3 ) and dopaminergic D2 receptors are the principal mediators of signal transduction within the gut mucosa

Motion sickness is an unpleasant side-effect induced by aberrant vestibular or visual activity nausea may represent an important sign of underlying hypotension, particularly in patients who have just received regional nerve blockade. ? Retrograde autonomic signalling

Higher cortical centres (e. g Higher cortical centres (e.g. the limbic system) involved with initiation and modification of the vomiting reflex. Example: unpleasant sights, sounds or smells induce emetic responses

The act of vomiting Pre-Ejection Phase Nausea (not a prerequisite to vomiting). Gastric smooth muscle relaxes and retrograde peristalsis begins. Deep inspiration. Glottis closes (to avoid aspiration).

Ejection Phase Abdominal and diaphragmatic muscles contract. Lower and upper oesophageal sphincters relax. Intra-abdominal pressure increases. Mouth opens and gastric contents are forcefully expelled.

Post-Ejection Phase Autonomic and visceral nerves ‘recalibrate’ Lethargy and weakness. Increased autonomic activity results in salivation, pallor and tachycardia throughout all phases of the vomiting reflex.

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Incidence ?? The general incidence of vomiting is about 30%, the incidence of nausea is about 50% Big little problem ? Classify Early: 2-6 hours after surgery ( in PACU) Late: 6-24 hour period Delayed: Occurs beyond 24 hours in inpatient setting Why do we need to bother ??

Can it trigger to others ? Ps and Ds Can it trigger to others ?

Risk factors Patient related Anesthesia related Surgery related

Patient related Age : The incidence of PONV is 5% in infants, 25% below 5 years, 42-51% in the 6-16 age group and 14-40% in adults. b) Gender : Adult women are 2-4 times likely to suffer from PONV than men, may be - female hormones. c) Obesity : reported to have more PONV excessive adipose tissue - storage for anaesthetic - --excessive production of estrogen by adipose tissue. d) H/O motion sickness : -- predisposed to PONV.

Patient related e) Delayed gastric emptying : Patients with intraabdominal pathology, diabetes mellitus, hypothryoidism, pregnancy, increase ICT, h/o. swallowing blood and with full stomach are at increased risk of PONV f) Smokers : Non smokers are more prone to PONV

Anesthesia factors Opioids – intrathecal also 10 % 0f fentanyl dose is recovered in cervical spinal fluid in ten minutes N2O. Ether, cyclopropane –etomidate Movement of head on extubation Excessive fasting or recent food intake ?? Stress and anxiety ?? Nerve blocks < spinal < General Spinal hypotension

Volatile anaesthesia may increase PONV by decreasing serum levels of anandamide, an endogenous cannabinoid neurotransmitter that acts on cannabinoid-1 and transient receptor potential vanilloid-1 receptors to suppress nausea and vomiting.

Intrathecal ? Spinal = incidence = hypotension episodes Opioids Epinephrine increased Intrathecal clonidine – no role Epidural 10 – 20 % incidence Is there a role – parenteral opioid blunting pain and caused decreased PONV - because pain is potent stimulus for vomiting centre ??

Surgical factors Gynaec Squint ENT GIT patients with wired jaw !!?? Not increased but we cant allow even 10 %

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Receptors and drugs Anti Histaminergic : block histamine receptors in the nucleus tractus solitarius. Cyclizine & Meclizine 50 mg oral Dimenhydrinate Dose is 1–2 mg/kg IV. Sedation, dry mouth, urinary retention as side effects

Antimuscarinic -Transdermal scopolomine It is a competitive inhibitor at postganglionic muscarinic receptors in the parasympathetic nervous system and acts directly on the CNS by antagonizing cholinergic transmission in the vestibular nuclei--- applied as transdermal patch - 1.5 mg is secreted over 72 h applied the evening before surgery or 2–4 h before the start of anesthesia. Side effects are visual disturbances, dry mouth, and dizziness. Atropine as antiemetic in spinal !!

5‑hydroxytryptamine subtype 3 receptor antagonists These peripherally block gut vagal afferents and act centrally in area postrema. Ondan 4 mg IV Dolasetron – 12.5 mg Granisetron 3 mg IV At the end of surgery preferably Side effects are headache, mild sedation, dizziness prolongation of QT interval.

Ramosetron Dose 0.3 mg IV is most effective to prevent vomiting and decrease nausea for patients receiving fentanyl patient-controlled analgesia Palonosetron It is the second generation 5-HT3 receptor antagonist with a longer half-life of 40 h It provokes a conformational change of 5-HT3 receptor through allosteric binding. Most effective dose is 0.075 mg IV approved for 24 h Oral 0.5 mg two hours prior- personal experience

Metoclopramide It is a strong D2-receptor antagonist and blocks H1 and 5-HT3 receptors also Gastric transit time is increased !! Peripheral cholinergic agonist ? 10 mg IV IM or oral dyskinesia or extrapyramidal symptoms, headache, dizziness, and sedation.

NK 1 receptor antagonism new group of drugs used for PONV treatment thought to prevent both acute and delayed emesis. act mainly at nucleus tractus solitarius and areas of reticular formation blocking NK-1 receptors. ( No to substance P ) They are more effective in inhibiting emesis than nausea.

NK 1 receptor antagonism Antiemetic , antidepressant , anxiolytic Aprepitant Dose is 40 mg PO 1–2 h prior to surgery 40 hours half life ( late PONV ) Side effects are constipation, headache, pyrexia, pruritis. Cospitant Dose is 50–150 mg PO Rolapitant Dose is 70–200 mg Fosaprepitant - Intravenous use

Steroids Dexamethasone 4 – 8 mg on induction – slow onset Anti prostaglandin and anti serotonin Hyperglycemia at 6 - 12 hours later Insomnia Methyl prednisolone – 40 mg IV also effective

Butyrophenone low-dose droperidol (<1 mg or 15 µg/kg IV) in adults, there is still significant antiemetic efficacy with a low risk of adverse effects.. Sedation and hypotension Dopamine antagonism at CTZ

Phenothiazines Perphenazine It prevents PONV at doses between 2.5 and 5 mg IV or IM. Chlorpromazine It is a D2 receptor antagonist at CTZ and dosage is 10 mg IV; its side effect is severe sedation. Promethazine 25 mg IM (phenergan) Extrapyramidal side effects !! rare

Miscellaneous Propofol – subhypnotic doses Mirtazipine 30 mg oral Gabapentin 600 mg oral Alpha 2 agonists Midazolam 2 mg IV on induction

Manual electrical stimulation of the P-6 acupuncture point (Neiguan) by needle results in decrease in incidence of PONV upto 6 hours. Application of pressure on P-6 point every 2 hours is reported to produce effect for 24 hours.

Strategies not effective for PONV prevention music therapy, Supplemental oxygen isopropyl alcohol inhalation, intraoperative gastric decompression, the proton pump inhibitor ginger root, cannabinoids

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Drugs and side effects Serotonin antagonists Neurokinin inhibitors Steroids Antihistamines Butyrophenones Headache, diarrhoea, constipation, arrhythmia Dizziness, diarrhoea, headaches, weakness hyperglycemia mood changes, nervousness Confusion, drying of mucosal membranes, sedation, urinary retention Prolonged QT interval (at doses ≥0.1 mg kg), hypotension, tachycardia, extra-pyramidal symptoms

PDNV ?? Post discharge nausea and vomiting After Ambulatory – More with ambulatory lap scopy ? Upto 35 % Two drugs may be tried Dexa and ondansetron ( palonosetron !! )

Guidelines Guideline 1 : Identify Patients’ Risk for PONV individual risk and titrate for side effects

Guideline 2 – avoiding risk factors Avoidance of general anesthesia by the use of regional anesthesia Use of propofol for induction and maintenance of anesthesia Avoidance of nitrous oxide Avoidance of volatile anesthetics Adequate hydration Less opioids

Guideline 3 Administer PONV Prophylaxis Using 1 to 2 Interventions in Adults at Moderate Risk for PONV Guideline 4. Administer Prophylactic Therapy With Combination (≥2) Interventions/ Multimodal Therapy in Patients at High Risk for PONV

Guideline 5. Administer Prophylactic Antiemetic Therapy to Children at Increased Risk for POV; As in Adults, Use of Combination Therapy Is Most Effective Guideline 6. Provide Antiemetic Treatment to Patients With PONV who did not Receive Prophylaxis or in whom Prophylaxis Failed

Guideline 7. Ensure PONV Prevention and Treatment Is Implemented in the Clinical Setting- SOP Guideline 8 : form policies and implement

Drug prophylaxis for PONV No risk – not needed – low risk – one Moderate to high risk – risk removal with multimodal approach – non pharmacological also Vomits Don’t repeat Target Another receptor

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Summary History Physiology Risk score Drugs and side effects Guidelines

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