Current Controversies in the
Management of PONV
T. J. Gan, M.D., M.B.A., F.R.C.A., M.H.S.
Mildred M. Oppenheimer Distinguished Endowed Chair
Head, Anesthesiology, Critical Care and Pain Medicine
UT Texas MD Anderson Cancer Center
Houston, Texas
Division of Anesthesiology, Critical Care and Pain Medicine
Disclosures
Honoraria from Baxter, Haisco, Masimo and Vertex
Outline
Incidence of PONV
Baseline risks for PONV
Antiemetic choices and side effects
Effective strategies to reduce baseline risks
PONV management in ERAS protocol
5th Consensus Guidelines on PONV Management
Functional Interference
Due to Nausea and/or Vomiting
27 26
31
52
44
50
31
23
35
19
11
22
47
37
56
35
24
41
8711
34
26
41
22 18
33
0
20
40
60
80
100
0-6 h 6-24 h 24-72 h 0-6 h 6-24 h 24-72 h 0-6 h 6-24 h 24-72 h
% of Patients That Experience:
1 antiemetic 2 antiemetic 3+ antiemetics
0-6 h
6-24 h 24-72 h 0-6 h 6-24 h 24-72 h 0-6 h 6-24 h 24-72 h
1 antiemetic 2 antiemetic 3 antiemetic
Emesis Nausea Functional Interference
White et al. Anesth Analg 2008;107:452-8
TJ Gan
Patients Perceive PONV To Be
Worse Than Pain
1. Eberhart LH, et al. Anesthesiology. 2002;89(5):760-761. 2. Hill RP, et al.
Anesthesiology. 2000;92:958-967. 3. Gan TJ, et al. Br J Anaesth. 2004;92(5):681-688.
11%
13%
27%
49%
Relative Importance of Patient Postoperative
Recovery Concerns (%) (N=220)1
PONV
Pain
Alertness
Additional cost
PONV
The most common reason for
poor patient satisfaction during
the perioperative period2
A greater concern for some
patients than pain, alertness, or
additional cost1,3
Zhang GS & Mathura JR. NEJM 2005;352;17
Loss of Vision After Vomiting Retching Following Blepharoplasty
Boerhaave Syndrome
Previously healthy 59-year-old man presented
to the ED with a 5-hour history of severe,
pleuritic chest pain.
Half an hour before the onset of symptoms,
he had vomited a large amount of gastric
contents after eating street food.
On physical examination, his breathing was
found to be rapid and shallow.
Emergency thoracoscopic repair of the
esophageal perforation
Hospitalized for 35 days
Air in the
mediastinum
extending into
the neck
DOI: 10.1056/NEJMicm2500300
extravasation of the contrast
material into the mediastinum
TJ Gan
The Use of Olive Oil to Prevent or Relieve
Postanesthetic Vomiting
“The oil was administered by
mouth immediately after partial
restoration of consciousness.
The oil in the stomach absorbed
any ether that might be there.”
Ferguson RH. New York Medical Journal 1912;95:1359-61.
Costs per Episode of Nausea and Emesis
0
50
100
150
200
250
300
350
Nausea Vomiting
Antiemetic
PACU delay
Hospital admission
Personnel
Total
US$
Hill et al., Anesthesiology 2000;92:958-67
Each episode of PONV prolongs PACU stay by about 30 min
Cost of PACU : $15/min, Cost of OR: $34/min
Number of Publications on PONV
0
2000
4000
6000
8000
10000
12000
14000
16000
18000
1st (2003) 2nd (2007) 3rd (2014) 4th (2020) 5th (2026)
PubMed Search: Postoperative Nausea, Vomiting
PONV Consensus Guidelines
TJ Gan
15,539 to Oct 4, 2023
4th PONV Consensus Guidelines
Endorsed by 23 professional organizations
American Society for Enhanced
Recovery
American Society of Health Systems
Pharmacists
American Society of Peri Anesthesia
Nurses
American Society of
Anesthesiologists
American Academy of
Anesthesiologist Assistants
American Association of Nurse
Anesthetists
American College of Clinical
Pharmacy Perioperative Care Practice
and Research Network
Australian Society of Anesthetists
Brazilian Society of Anesthesiology
Chinese Society of Anesthesiology
European Society of Anesthesiologists
Indian Society of Anesthesiologists
Japanese Society of Anesthesiologists
Korean Society of Anesthesiologists
Malaysian Society of Anesthesiologists
Royal College of Anesthesiologist
Thailand
Singapore Society of Anesthesiologists
Society for Ambulatory Anesthesia
Society for Pediatric Anesthesia
South African Society of
Anesthesiologists
Taiwan Society of Anesthesiologists
Society of American Gastrointestinal &
Endoscopic Surgeons
TJ Gan
5th PONV Consensus Guidelines
Endorsed by 25 Professional Societies
TJ Gan
American Society for Enhanced Recovery
American Academy of Anesthesiologist Assistants
American Association of Nurse Anesthesiology
American Academy of Ambulatory Care Nursing
American College of Clinical Pharmacy
American Society of Health Systems Pharmacists
American Society of Peri Anesthesia Nurses
Australian and New Zealand College of Anesthetists
Australian Society of Anesthetists
Canadian Anesthesiologists' Society
College of Anesthesiologists of Ireland
European Society of Anesthesiology
German Society of Anesthesiology
Hong Kong College of Anesthesiologists
Indian Society of Anesthesiology
Indonesian Society of Anesthesiologists and Intensive
Therapy
Japanese Society of Anesthesiologists
Korean Society of Anesthesiologists
Malaysian Society of Anesthesiologists
Royal College of Anesthesiologist Thailand
Royal College of Anaesthetists United Kingdom
Singapore Society of Anesthesiologists
Society for Ambulatory Anesthesia
Society for Pediatric Anesthesia
South African Society of Anesthesiologists
Gan et al. Fifth Consensus Guidelines for the Management of PONV. Anesth Analg 2025 (In press)
PONV Risk Factors in Adults
Evidence
Positive overall
Conflicting
Disproven or of limited clinical
relevance
Gan TJ et al. Anesth Analg 2025 (In press)
Adult PONV Risk Factors
Gan TJ et al. Anesth Analg 2025 (In press)
Pediatric PONV Risk Factors
Gan TJ et al. Anesth Analg 2025 (In press)
Multiple Neurotransmitters and Their Receptors in CTZ
21
ReceptorAntagonistNeurotransmitter
Cholinergic muscarinic
M3/M5 receptor
D2/D3 receptors
H1 receptor
5-HT3 receptor
NK-1 receptor
Acetylcholine
Dopamine
Histamine
Substance P/NK-1
Serotonin
CTZ
D3=dopamine-3. H1=histamine. M3=muscarinic 3. M5=muscarinic 5. NK-1=neurokinin-1.
1. Watcha MF, et al. Anesthesiology. 1992;77(1):162-184. 2. Shaikh SI, et al. Anesth Essays Res. 2016;10(3):388-396. 3. Kovac AL. In: Gan TJ, Habib A. eds.
Postoperative Nausea and Vomiting: A Practical Guide. Cambridge, UK: Cambridge University Press; 2016:13-22. 4. Darmani NA, et al. J Neural Transm.
1999;106:1045-1061.
Serotonin (5HT-3) Antagonists
Ondansetron Tropisetron Granisetron Palonosetron
Dose (mg) 4 2 mg 0.1–1.0 0.075
Half-life (h) 3–5 6–8 5–840
Route of Adm IV, Tab, ODT Solution, IV, oral IV, Tab, Patch, Solution IV, oral
Metabolism
Primarily hepatic
(CYP1A2, CYP2D6,
CYP3A4),
Primarily hepatic
via CYP2D6
significant
variability based on
genetic
polymorphism.
Primarily metabolized
by CYP3A4, with no
involvement of
CYP2D6.
• 50% metabolized in
the liver by CYP2D6,
CYP3A4, and CYP1A2.
• 40% excreted
unchanged by the
kidneys.
• Clinical effects are
not significantly
impacted by CYP2D6
genetic variations.
QT Prolongation Effect Yes Yes Yes No
https://doi.org/10.1016/j.anclin.2017.01.003; Individual drugs prescribing information
Palonosetron vs. Ondansetron
Early and Late Vomiting
Xiong C. Can J Anesth 2015;62:1268-78
Popovic M. Support Care Cancer 2014;22:1685e97
Less QTc prolongation than ondansetron and granisetron 2.45 versus 5.13 ms,p= 0.002
Dexamethasone – Doses and Efficacy
Dexamethasone 4-5 mg:
NNT = 3.7 (3, 4.7)
OR: 0.312 (0.235, 0.415)
Dexamethasone 8-10 mg:
NNT = 3.8 (3, 4.3)
OR 0.274 (0.215, 0.350)
De Oliveira Jr GS. Anesth Analg 2013;116:58-74
(95 % CI)
Dexamethasone
(4372)
Placebo (4353)
Risk Ratio/Median
Difference
SSI at 30 days
8.1% 9.1% 0.89 (0.77 – 1.03)
Deep or organ space
SSI at 90 days
1.9 2.0 0.94 (0.55 – 1.60)
PONV (24h)
42.2% 53.9% 0.78 (0.75 – 0.82)
Hyperglycemia events
(without diabetes)
0.6% 0.2%
QoR
15 (day 1) 109 (93 – 123) 104 (87 – 118) 5.0 (3.8 – 6.2)
New
-onset chronic
postsurgical pain at 6
months
8.7% 7.1% 1.23 (1.06 – 1.42)
TJ Gan
Dexamethasone and Surgical Site Infection
Corcoran TB et al. N Engl J Med 2021;384:1731-41
Jones IA et al. Analg 2024;139:479–89
NK-1 / Tachykinin Receptors
Discovered in 1931 by Von Euler and Gaddum from horse
intestine and brain
G-Protein coupled receptors
Selective affinity to tachykinins
Subsptance P
Neurokinin A and Neurokinin B
NK-1 antagonists
Oral: Aprepitant, Rolapitant, Casopitant
IV: Fosaprepitant (CINV)
IV: aprepitant – APONVIE (PONV indication)
Aprepitant vs. Ondansetron
Gan, et al. Anesth Analg 2007;104:1082-9
1154 high risk patients
Laparoscopic GI surgery
Dexamethasone 5 mg
and palonosetron 0.075
mg were given in both
groups.
The primary outcome:
incidence of PONV
(defined as nausea,
retching, or vomiting)
during the first 24 h
TJ Gan Huang et al. British Journal of Anaesthesia 2023; 131: 673-681
Genetic Factor - 2D6 Polymorphism
Incidence of Vomiting
0
5
10
15
20
25
30
35
40
45
50
Poor Intermediate Extensive Ultrarapid
%
Candiotti KA, et al. Anesthesiology. 2005 Mar;102:543-9
** p<0.05
Genetic factors Associated with Increased Risk of PONV
Polymorphism /genetic
factors studied
PONV rate (with allele/without
allele)
Observation period Relative Risk (95% Confidence interval)
CHRM3
G
(38.1%/46.2%)
24 h
1.39 (1.07
-1.81)
CHRM
3
GG/GA/AA
(28.8%/ 42.5%/ 46.4%)
2, 6, (24)h
AA vs GA: 1.3 (1
-1.7)
AA vs GG: 1.2 (1.1
-1.4)
CHRM
3
GG
ref
GA
AA
(not
reported)
2, 6, 24 h
2 (1.3
-3.1) 2.2 (1.1-4.1)
KCNB
2
33
.5%/44/5% (TC/CC)
2, 6, 24 h
1.6 (1.1
-2.4)
5
HTR2C
G
= 57.5%, C = 30.2%
6, 12, 24 h
01.652 (0.003
-2.723)
5
HT3BR
85
.7%/39.7% (with/without
AAG
deletion)
2, 24 h
2.2 (1.5
-3.0)
5
HTTLPR
60
%/49.5% (SS/LL+SL)
24 h
Cohort A 1.5 (1.1
-2.1)
Cohort B 1.8 (1.4
-2.3)
MIR
4300HG
26
.6%/16.5% (major/minor)
24 h
0.16 (0.05
-0.51)
PTPRD
25
.6%/16/8%
24 h
0.48 (0.16
-1.44)
CARMN
20
.3%/26/6%
24 h
Not on MVA
CYP
2D6
45
.5%/14.7% (3 or more alleles/
1
or
2 alleles)
24 h
3.6 (1.4
-9.2)
DRD
2 Taq IA
51
.2%/48.8% (IA/A1A2 + A1A1)
6, 24 h
1.6 (1.1
-2.4)
Gan TJ et al. Anesth Analg 2025 (In press)
Outcome
Relative Risk (RR)
p value
PONV
0.61 (0.53
– 0.69)
<0.00001
Pain Score
-
0.51 (-0.81 – -0.20)
0.001
PACU Stay
-
2.9 (-5.47 – -0.35)
0.03
Patient Satisfaction
Score
1.06 (1.01
– 1.10)
0.02
Schraag et al. BMC Anesthesiology 2018;18:162
Meta-analysis on 229 RCTs
20,911 patients
The addition of propofol infusions to volatile-based anesthesia is
Associated with a dose-dependent reduction in the need for
rescue antiemetics in the PACU regardless of the number of
prophylactic antiemetics, duration of procedure, and type of
volatile agent used.
Sprung J et al. Anesth Analg 2024;139:26–34
Gan et al. Anesthesiology 1996;85:1036-1042
Propofol Administration Techniques for PONV Reduction
Simulations of Plasma
Propofol Concentrations
PP: Propofol induction and maintenance
PIP: Propofol – Inhalational – Propofol
PI: Propofol induction - Inhalational
TJ Gan
TJ Gan Gan et al. Anesthesiology 1999;90:1564-70
Nitrous Oxide and PONV
Placebo N2O 50% N2O 70%
PONV n(%) 15 (33) 21 (46) 28 (62)*
Nausea n(%) 12 (26) 16 (35) 25 (56)*
Nausea Score 10.9±20.5 12.7±19.5 20.5±21.8*
Mraovic et al. Anesth Analg 2008;107:818-23
* p<0.05
TJ Gan
Amisulpride for Prophylaxis: Complete Response Over Time
Placebo + another
antiemetic
Amisulpride 5 mg
+ another antiemetic
Time From Wound Closure (Hours)
Probability of Patient Continuing to Meet
Criteria for Complete Response
0
1.0
0.8
0.6
0.4
0.2
024
14 15 16 17 18 19 20 21 22 23
3 4 5 6 7 8910 11 12 13
12
HR (95% CI): 0.70
(0.59, 0.83) P<0.001
58%
47%
Kranke P, et al. Anesthesiology. 2018;128(6):1099-1106
Patients With
Complete Response
Gan et al. Anesthesiology 2017; 126:268-75
Successful Treatment of PONV Over Time
Candiotti K et al. Anesth Analg 2019;128:1098–105
P6
PC6
Acupuncture and Incidence of PONV
RR 95% CI
Nausea 0.71 0.61 to 0.83
Vomiting 0.7 0.59 to 0.83
Rescue Antiemetic 0.69 0.57 to 0.83
Vs. antiemetic (nausea) 0.82 0.60 to 1.13
Vs. antiemetic (vomiting) 1.01 0.77 to 1.31
•Cochrane Review
•40 trials involving 4858 participants
•Efficacy no different between acupuncture and antiemetics
•Similarly effective in adults and children
•Side effects minimal
Lee A, Fan LTY. Stimulation of the wrist acupuncture point P6 for preventing postoperative nausea and vomiting. Cochrane
Database of Systematic Reviews 2009, Issue 2. Art. No.: CD003281. DOI: 10.1002/14651858.CD003281.pub3.
TJ Gan Chen J et al. https://doi.org/10.1016/j.ijsu.2019.10.036
TJ Gan Ergezen FD et al. Journal of PeriAnesthesia Nursing 37 (2022) 717−727
Music interventions significantly reduced postoperative vomiting (95% CI: 0.01 to 0.63) but had
no statistical significant effect on postoperative nausea (95% CI: -0.13 to 0.70).
Wallenborn et al. Prevention of postoperative nausea and vomiting by metoclopramide combined with
dexamethasone: randomised double blind multicentre trial BMJ 2006; 333(7563): 324.
Metoclopramide
Dose-response Metoclopramide 10 mg is under-dosed.
Baseline risk low (PONV incidence in controls only 20.6%) – due to Dex
RCT: 1. Meto 10 mg IV (783)
2. Meto 25 mg IV (781)
3. Meto 50 mg IV (788)
4. No treatment (788)
PONV at 24h: 10 mg: NNT 30 25 mg: NNT 16 50 mg: NNT 11
Dyskinesia or extrapyramidal symptoms:
Controls: 0.1%; 10 mg: 0.4%; 25 and 50 mg: 0.8% (NNH with 25 or 50 mg: 140)
All patients received dex 8 mg IV 30-60
minutes before end of surgery
Antiemetic Doses and Timing for Prevention of
PONV in Adults
Gan TJ et al. Anesth Analg 2025 (In press)
Antiemetic Doses and Timing for Prevention of
PONV in Children
Gan TJ et al. Anesth Analg 2025 (In press)
Combination Antiemetics
5HT-3 antagonists
Dexamethasone
Aprepitant
Dopamine antagonists
Transdermal scopolamine
Propofol
Acupuncture
Gan TJ et al. Anesth Analg 2020;131:411–48
TJ Gan
23 RCTs with 1304 patients
Opioid Opioid Free Risk Ratio p value
Pain Scores (2 h) VAS
3.6 (2.7–4.5) 3.4 (2.5–4.4) -0.2 (-0.5 to 0.2) ns
Morphine equivalent (24 h) mg
0.9 (-1.1 to 2.9) ns
PONV (%)
24 19 0.77(0.61–0.97) 0.03
PACU Stay (min)
0.6 (-8.2 to 9.3) ns
Frauenknecht J et al. Anaesthesia 2019;74:651–662
TJ Gan
Naloxone and Opioid Side Effects
0
10
20
30
40
50
60
70
80
Nausea Vomiting Rescue
antiemetic
Pruritus
Placebo Low Dose High Dose
*
* *
* p<0.05
0.25 mcg/kg/h 1 mcg/kg/h
Gan et al. Anesthesiology 1997;87:1075-81
%
TJ Gan
TDS – PONV Efficacy
Apfel et al. Clin Thera 2010;32:1987-2002
Pyridoxine (Vitamin B6) - Prevention of
Postoperative Nausea andVomiting
PONV Nausea Vomiting
Both groups received Dex 10 mg and Ondansetron 8 mg
Zhang Q et al. Anesthesiology 2025; 142:655–65
Chewing Gum to
Treat PONV
Darvall et al. Anesthesiology 2025; 142:454–64
2 Groups
15 min of chewing gum
4 mg intravenous ondansetron
Prophylaxis
2-3 RF - 4 mg dexamethasone
4 RF - 4 mg dexamethasone and
droperidol up to 0.625 mg
ERAS
Preadmission
counseling &
education
Selected
bowel
preparation
Carbohydrate
loading
Goal
directed fluid
therapy
Avoidance of
Sodium/fluid
overload
Non-opiate
analgesics
Epidural
anesthesia/
analgesia
Prevention of
nausea and
vomiting
Short acting
anesthetic
agents
Laparoscopic,
No drains
No naso-
gastrtic
tubes
Warm air
body heating
Early
removal of
catheters
Early
mobilization
Early oral
nutrition
Audit of
compliance
PONV Risk
Reduction
Minimally Invasive
Surgical Techniques
Multimodal Analgesia ±
Regional Techniques
Minimize Preoperative
Fasting
Avoid Routine
Nasogastric Intubation
Prevent Postoperative
Ileus with Caffeine,
Chewing gum,
laxatives, etc.
Maintain Euvolemia ±
Goal-Directed Fluid
Therapy
Preoperative
Carbohydrate Loading
Standardized
Anesthetic Protocol ±
TIVA
Opioids, Pain
Bowel edema or
hypoperfusion
Unclear: Gastric volume,
mobilize bowel edema
Opioids, Pain
Unclear: Hypovolemia bowel
perfusion at induction
Unclear: Metabolic Stress,
Insulin resistance, Patient
wellbeing Opioids
Unclear: Patient discomfort,
Vomiting, earlier return of bowel
function
Volatile and N2O use
Schwartz J and Gan TJ. Best Pract Res Clin Anaesthesiol. 2020;34:687-700
The Role of
ERAS in
PONV Risk
Reduction
TJ Gan
Shortened Preoperative Fasting and PONV
Xu D et al. Journal of International Medical Research 2017, Vol. 45(1) 22–37
TJ Gan
Sugammadex vs Neostigmine – Risk of Adverse Events
PONV - RR (95%CI) 0.52 (0.28–0.97), n = 389, NNT: 16, GRADE: low quality
Hristovska AM et al. Anaesthesia 2018, 73, 631–641
TJ Gan
Combination Prophylaxis in Patients at Moderate
or High Risk May Reduce Incidence of PONV
Monotherapy
Combination prophylaxis
with 3 antiemetics
PONV Incidence
Therapy Type
52%
Combination prophylaxis
with 2 antiemetics
No antiemetic
0123
Number of Antiemetics
PONV Incidence
37%
28%
22%
Apfel CC, et al. N Engl J Med. 2004;350:2441-2451
TJ Gan
Antiemetics – Efficacy and
Adverse Events
TJ Gan Weibel S et al. Anaesthesia 2021, 76, 962–973
Efficacy Adverse
Events
PONV Treatment
Algorithm for Adults
Two antiemetics now recommended
for prevention in patients with 1-2 risk
factors
3-4 antiemetics + risk mitigation for ≥3
RF
For rescue, administering repeated
doses from the same class within 6 hrs
does not confer additional benefit
If more than 6 hours, administer a 2nd
dose of 5HT-3 RA is acceptable
If no prophylaxis, a 5HT-3 RA remain
1st line
TJ Gan Gan TJ et al. Anesth Analg 2025 (In press)
PONV Treatment Algorithm
for Pediatric Patients
No risk factor – 1 antiemetic
2 antiemetics in patients with 1-2 risk
factors
2 antiemetics + risk mitigation for ≥3
RF
Use different anti-emetic class than
prophylactic drug for rescue
If no prophylaxis, a 5HT-3 RA remain
1st line
Gan TJ et al. Anesth Analg 2025 (In press)
Reduce Baseline Risks
Regional anesthesia (A1)
Use of propofol for induction and maintenance of anesthesia (A1)
Avoidance of nitrous oxide in surgeries (A1)
Avoidance of volatile anesthetics (A2)
Minimization of intraoperative (A1) and postoperative opioids (A1)
Adequate hydration (A1)
Goal directed fluid therapy in major surgery (A3)
Using sugammadex instead of neostigmine for the reversal
of neuromuscular blockade (A1)
Gan TJ et al. Anesth Analg 2020;131:411–48
Treatment of PONV - Ondansetron
Retreatment Study
0
20
40
60
80
100
Prophylactic Treatment
OO O
OPP
O=Ondansetron (4 mg, IV)
P=Placebo
02 h
024 h
02 h
NS 024 h
NS
Kovac AL. J Clin Anesth 1998;11:453–459
Not Significantly Different From Placebo
n=2199 n=214 n=214
n=2199 n=214 n=214
% Complete Response
TJ Gan
Take Home Messages
PONV are common and preventable
PONV decrease patient satisfaction and increase costs
Establish risk factors
Use combination antiemetic strategy
Implement PONV protocol in ERAS strategy
Prompt treatment following failure of prophylaxis
Use antiemetic from different class in the PACU
TJ Gan
TJ Gan
Questions?
Gan TJ et al. Anesth Analg 2020;131:411–48