5 Primary afferent pathways involved in vomiting stimulation:
Chemoreceptor Trigger Zone (CTZ)
Vagal mucosal pathway in the GI system
Neuronal pathways from the vestibular system (Inner Ear)
Reflex afferent pathways from the cerebral cortex
Midbrain afferents
Stimulation of the afferent pathways stimulating vomiting can be activated by four receptor types
Cholinergic (muscarinic)
Dopaminergic
Histaminergic
serotonergic
Vomiting center is located
It is located within the reticular formation of the brainstem
Vomiting center can also be stimulated by
gut, oropharynx, movement, pain, hypoxemia, and hypotension
Efferent signals are directed to the following nerves:
Glossopharyngeal (IX) Hypoglossal (XII) Trigeminal (V) Accessory(XI) Spinal segmental Flood states V, VII, IX, X, XII
Outside the BBB
Has contact with CSF and allows substances in blood and CSF to interact.
Toxins and/or drugs in the blood can stimulate the____causing n/v
This stimulation may send emetogenic triggers to the vomiting center activating the vomiting reflex
CTZ
Vomiting is associated with marked vagal and sympathetic activity causing:
Sweating
Pallor
Bradycardia
PONV is influenced by multiple factors that are r/t:
Patient
Surgery
Anesthesia
PONV: PATIENT FACTORS
Sex: Women > Men (strongest predictive factor)
Motion Sickness: Previous history motion sickness or PONV from previous surgeries
Smoking: Nonsmokers > Smokers due to gradual desensitization of the CTZ
Age: < 50 years of age is a significant factor
Obesity: recent studies demonstrate BMI is not a factor
Delayed Gastric Emptying:
MD
Hypothyroidism
Pregnancy
Increased ICP
Swallowing blood
Full stomach
PONV:
PRE-OP AND INTRA-OP FACTORS
Surgical: ______________
During Surgery: _______________
Surgical: Type of surgery: cholecystectomy, gynecological and lap surgeries have high incidents of PONV
During Surgery: Long duration; Increasing by surgery time by 30 minutes may increase PONV risk by 60%
Significant decrease in vomiting when avoided in lap procedures.
Nitrous oxide
_________ and ________ cause higher PONV d/t increase in endogenous catecholamines
Ether and Cyclopropane
_________, _______, _______, ______. and _______ are associated with lesser degree of PONV
Sevoflurane, Enflurane, Desflurane, and Halothane
Continuous infusion markedly increases post-op emesis
Etomidate
When used for induction, its been known to delay D/C d/t vivid dreams, hallucinations, and higher incidence of PONV (20 to endogenous catecholamine release) when compared to giving barbiturates and nitrous oxide
Ketamine
reduced PONV
Propofol
increase incident of PONV d/t directly stimulating the CTZ
Nitrous-Opioid-relaxant technique
Emesis caused by stimulation of opioid receptors in the CTZ. Using intraoperative ______ shows a weak contribution to PONV
opioids
Incidence of PONV is uncertain
Neuromuscular Reversal Agents
Risk for PONV is 9 times less than with ______than with general anesthesia
regional
Nausea after epidural may be less with ______ ________ opioids such as _______ and ________d/t less rostral spread from lumbar epidural injection site to CTZ and vomiting center than the less lipid soluble such as morphine
lipid soluble, fentanyl and sufentanil
______ or _____ is common cause of post op emesis
Visceral or pelvic pain
Sudden motion, changes in position, and/or transport from PACU to patient floor can precipitate n/v after receiving ______
opioids
Post-op opioids ______ risk for PONV in dose dependent manners. This effect can last as long as opioids are used in the post op period
increase
________ can be used perioperatively to reduce need for opioids.
Non-steroidal
__________ is no longer recommended for PONV prevention
Supplemental O2
Genes/receptors regarded as r/t PONV or opioid induced N/V:
5-HT3 Muscarinic type-3 Dopamine type 2 Catechol-o-methyl transferase Alpha-2 adrenoceptor Adenosine triphosphate binding cassette subfamily B member Cytochrome P450 superfamily enzyme Uridine 5’-diphospho-glucuronosyltransferae
5-hydroxytryptamine subtype 3 receptor antagonists:
Ondansetron Dolasetron (ban d/t concerns of QT prolongation and torsade's de pointes)
Blocks muscarinic receptors in the cerebral cortex and pons to induce antiemetic effects
Anticholinergic/Antimuscarinic
Transdermal Scopolamine
Histamine Receptor Antagonists: Blocks acetylcholine receptors in the vestibular apparatus and histamine receptors in the nucleus tractus solitaries
Dimenhydrinate (Dramamine)
Meclizine: Has longer during of PONV effect than ondansetron
Promethazine
Dopamine Antagonist:
Metoclopramide: Strong D2-receptor antagonist and blocks H1 and 5-HT3 receptors as well.
Neurokinin-1 Receptor Antagonists: New group of drugs used for PONV thought to prevent both acute and delayed emesis. Act mainly at nucleus tractus solitaries and areas of reticular formation blocking NK-1 receptors. More effective in inhibiting emesis than nausea.
Aprepitant (Emend [PO], Cinvanti [IV]):
Aprepitant (Emend [PO], Cinvanti [IV]): NK-1 receptor antagonist with a ____hours half life. Significantly more effective than ondansetron for preventing vomiting at 24 and 48 hour after surgery and in reducing nausea severity in the first 48 hours after surgery
40
Blocks synthesis of prostaglandins which sensitized nerves to other commonly involved neurotransmitters in emesis control.
May have central effect by antagonizing 5-HT3 receptors or corticosteroid receptors in the nucleus tractus solitaries
Corticosteroids:
Dexamethasone:
effective for late PONV prevention
Methylprednisolone:
Butryphenones
Droperidol
Haldol
Relatively selective D2 receptor antagonist. Use was stopped in 2001 due to black box warning related to CV events. A recent meta-analysis demonstrated at low doses of <1 mg or 15 mcg/kg IV there is significant antiemetic efficacy with low risk of adverse reactions.
Droperidol
Haldol
< 2 mg reduces the risk of side effects and QT prolongation. Not DFA approved
Phenothiazines
Perphenazine
Chlorpromazine
Used to treat schizophrenia and n/v
Perphenazine
a D2 receptor antagonist at CTZ. May treat schizophrenia; used to treat mental illness, behavioral disorders, tetanus, blood disorders such as porphyria and severe n/v. Severe sedation
Chlorpromazine
Used in TIVA can reduce baseline risk of PONV
Propofol
Has direct antiemetic effect along with opioid sparing effect. Clonidine and Dexmedetomidine (alpha-2-adrenceptor agonists) demonstrated a significant but weak and short lived antinausea effect (meta-analysis)
Alpha-2-agonists
Antidepressant (specific serotonergic an noradrenergic antidepressant). The combination of _______30 mg PO and dexamethasone 8 mg decreases incidence of late PONV > 50%.
mirtazapine (remeron)
_____600 mg 2 hours prior to surgery effectively decreases PONV. An hour before surgery ________ 800 mg PO is as effective as dexamethasone 9 mg IV and the combination is better than either drug given alone
Gabapentin
_______: 2 mg 30 before end of surgery is as effective as ondansetron 4 mg. 2 mg 30 min before end of surgery is more effective against PONV than 35 mcg/kg premedication
Midazolam
Effective for reducing the baseline risk for PONV.
IV Fluids:
Strategies that do not work:
Music therapy Isopropyl alcohol inhalation Intraoperative gastric decompression The proton pump inhibitor esomeprazole (Nexium) Ginger root Nicotine patch to nonsmokers Cannabinoids
Serotonin (5-hydroxytryyptamine subtype 3) antagoist examples
ondansetron, granisetron, dolasetron, ramosetron, palonsetron, tropistron, corticosteroids
Antcholinergics. antimuscarinics (M)
Scopolamine
Histamine (H1) antagonist
promethazine, perphenazine, dimenhdrinate, diphenhydramine, meclizine, chlorpromazine
Dopamine (D2) antagonist
Domperidone, chlorpromazine, metoclopramide, drperidol, haloperidol
Neurokinin-I antagonist
Apreitant, cospitant, rolapitant