The PONV Problem

The PONV Problem
JBL
PONV
PDNV
OIE
MINV
[email protected]
The PONV Problem:
Frequent – Predictable – Evaluable –
Expensive – Dissatisfying – Avoidable
John B. Leslie, MD, MBA
Professor
Department of Anesthesiology
Mayo Clinic College of Medicine
Rochester, Minnesota
Consultant in Anesthesiology
Mayo Clinic Arizona, Scottsdale, AZ
Professor of Clinical Anesthesia
University of Arizona, Tucson, AZ
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PONV “Terminology”
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Air the diced carrots
Barf - Boot - Blow - Brack
Bark at the moon
Blow foam, chunks, or bile
Bring it up for a vote
Burpin’ solid
Call Uncle Earl or Ralph
Call Europe
Call on great white telephone
Call up the beasties
Chumming
Chunder and Chunks
Clean house
Core dump
Drive the porcelain bus
Drive the Buick
Emit with a food fountain
Empty your bucket
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Fertilize the carpet
Growl at the ground
Hurl - Hack - Heave - Huey
Liquid laugh or yawn
Lunch re-run
Laugh at the carpet
Make an inventory
Make a pavement pizza
Private exorcism (AKA LB)
Produce the liquid laugh
Puke - Spew - Retch - Urp
Park the tiger
Protein spill
Shout at your shoes
Sick-up and spew
Technicolor yawn
Toss your cookies
Vomit or Un-eat
Have we solved the PONV
“little big problem” ?
3 decades of clinical trials
Risk Stratification
Multiple combination therapies
Guidelines & Updated Guidelines
“Breakthrough medications”
“Break-the-Bank Expenses”
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Many Patients Experience
PONV Beyond the PACU
Incidence of PONV/PDNV/OIE
• Overall range: 25% to 30%
•
• High-risk patients: 70% to 80%
• 35% to 67% of patients may experience PDNV
• PONV may persist for 5 days after surgery
• Opioid-induced emesis (OIE): 10% to 60%
• No 1 or No 2 adverse outcome following routine
outpatient surgery!
Gan TJ, et al Guidelines for the Management of PONV; Anesth Anal, Vol 105, December, 2007. Kovac. Drugs. 2000;59:213243; Natof et al. In: Wetchler, ed. Anesthesia for Ambulatory Surgery. 2nd ed. 1991:437-474; Carroll et al. Anesth Analg.
1995;80:903-909; Gan et al. Anesth Analg. 2002;94:1199-2000; Gan. JAMA. 2002;287:1233-1236; Leslie and Bash. Poster
presented at: NYSSA 57th Postgraduate Assembly; December 13, 2003; New York, NY; Gan et al. Anesth Analg. 2003;97:6271; Chung et al. Eur J Anaesthesiol. 1999;16:669-677; Hirayama et al. Yakugaku Zasshi. 2001;121:179-185.
John B Leslie, MD MBA
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Initial Experience of PONV
Among Affected Patients, %
• Outpatient range: 20% to 80%, depending on the patient
population
Overall: 41% had PONV and … of patients who experienced PONV, nearly
80% initially did so in the PACU and/or within 48 hours after discharge.
78%
80
60
40
36%
20
0
Initial PONV
in the PACU
(21/58)
Initial PONV in the PACU and/or
Within 48 Hours After PACU Discharge
(45/58)
Study Design: Data from a study examining patients’ experiences with PONV following discharge from outpatient
surgery centers. Incidence of PONV was measured in the recovery room, by telephone the day after discharge, and by a
questionnaire that patients were instructed to complete 5 days after discharge. A total of 143 outpatients (aged ≥18
years) who received general anesthesia and underwent 1 of 4 selected surgeries (laparoscopy, dilation and curettage,
arthroscopy, or hernia repair) provided complete data. Some patients who initially experienced PONV within 48 hours
after PACU discharge continued to experience PONV for up to 5 days after PACU discharge.
Carroll NV et al. Anesth Analg. 1995;80:903–909.
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The PONV Problem
PONV Remains a Problem
Despite Current Therapies
1.
2.
3.
4.
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The Real Value of Guidelines?
Overall
Up to 30% for all surgeries and patient populations.1–3
Outpatient
About 40% of patients with PONV treated at
outpatient
surgery centers.4
Breakthrough
More than 30% of patients with PONV were receiving
prophylactic antiemetics.3
— No significant differences among ondansetron,
dexamethasone, and droperidol
Kovac AL. Drugs. 2000;59:213–243.
Habib AS, Gan TJ. Can J Anesth. 2004;51:326–341.
Apfel CC et al. N Engl J Med. 2004;350:2441–2451.
Carroll NV et al. Anesth Analg. 1995;80:903–909.
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PONV vs PDNV: Under-Recognized Problem
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PONV vs PDNV: Under-Recognized Problem
Prospective Study of 2170 Outpatients in 12 USA Centers
C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009
C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009
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PONV vs PDNV: Under-Recognized Problem
Conclusion: The results of this 12-center multicenter cohort
study showed a substantial incidence of PDNV in the US.…
Clinical trials that address this patient population with a long
acting antiemetic strategy are needed
What does failure to prevent
PONV actually cost?
Patient Risk
Patient discomfort
Patient dissatisfaction
Economic burden
C Apfel, S Shi, A Kovac, A Shilling, J Leslie, B Philip, on behalf of the PDNV Study Group: IARS Annual Mtg. 2009
John B Leslie, MD MBA
The PONV Problem
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PONV: #1 Patient Problem
Potential Consequences of PONV
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Emesis is the postoperative outcome least preferred by patients
Medical Consequences PONV
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Can cause electrolyte abnormalities and dehydration
Can cause tension on suture lines1,2
Venous hypertension2
Can cause hematomas (increased bleeding) beneath surgical
flaps,1 vascular anastomosis, aneurysm clipping, etc
—
Can place the patient at risk for pulmonary aspiration of vomit if
airway reflexes are depressed from lingering effects of anesthetic
and analgesic drugs1,2 (esp increased risk with jaw wired closed)
1
Postoperative Outcomes Least Preferred by Patients
Rank
Practical Consequences of PONV
—
—
Delayed Discharge after out-patient surgery2
Unanticipated hospital admission1
Postoperative Outcomes
1
Vomiting
2
Gagging on endotracheal tube
3
Incisional pain
4
Nausea
5
Recall without pain
6
Residual weakness
7
Shivering
8
Sore throat
9
Somnolence
Data from a survey of adult patients (N=101) conducted at Stanford University Medical Center. Patients were eligible if they were scheduled to
undergo surgery at the center. Patients were asked to rank-order 10 possible postoperative outcomes from most to least desirable. F-test <0.01.
1. Golembiewski J, et al Am J Health-Sys Pharm; Vol 62 Jun, 2005
2. Watcha MF, White PF. Anesthesiology. 1992;77:162–184.
Adapted from Macario A et al. Anesth Analg. 1999;89:652–658. © 1999. With permission from Lippincott Williams & Wilkins.
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Cost Components in PONV Episodes
What do Surgical Patients Most Want to Avoid?
Cost Components for an Episode of Emesis
“… avoiding Post-Operative Nausea and Vomiting
seems to be a high priority for most Patients”1
(% total median management cost per patient)
Hospital
admission
PACU
10%
delay
4%
Ranking and Relative Values ($100) of Patient Outcomes*
$20
n=62
$18.05
$17.86
$16.96
$13.82
$15
Materials*
0.2%
$11.82
$10
$7.99
MD/CRNA
5%
Personnel
83%
PACU
nurses
78%
$7.60
$5
$3.04
Antiemetic cost
3%
$Vomiting
Gagging on ET
Tube
Pain
Recall w/out
Pain
Nausea
Residual
Weakness
Shivering
Sore Throat
*Per item of basin, gloves, paper, linen, and gown
*Patients were asked to distribute $100 among 10 outcomes, with proportionally more money being allocated
to the more undesirable outcomes (eg, patients assigned $18.05 of $100 to avoid vomiting).
Hill RP et al. Anesthesiology. 2000;92:958-967.
Macario, A, et al Which Clinical Anesthesia Outcomes; Anesth Anal, 1999; 89;652-8
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PONV Incurs Higher Cost$
• In a study conducted in 2000, PONV was associated
with increased cost*
— A single episode of emesis costs an average of $305
— A single episode of nausea costs an average of $82
• PONV is a major factor limiting early discharge
of ambulatory surgical patients (1st or 2nd all major studies)
• PONV is a leading cause of unanticipated hospital
admissions (24% primary reason)
• Preventing PONV can be cost-effective
* PACU personnel costs are biggest component:
NOT PHARMACEUTICALS
Hill RP et al. Anesthesiology. 2000;92:958-967
Lau H & Brooks DC. Arch Surg (2001) 136:1150-53.
John B Leslie, MD MBA
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The PONV Problem
PONV
PDNV
OIE
MINV
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“Volatile anaesthetics may be the main cause of early but
not delayed postoperative vomiting: a randomized
controlled trial of [5x] factorial design.”
750 combinations:
Gender, Surgery,
Opioids, Maintenance,
PONV Prophylaxis
1180 patients
50% pediatric
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Apfel BJA 2002;88:659
Why do patients develop PONV?
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PONV Risk Prediction Tool?
PONV Risk Factors
PONV Risk Factors (cont)
• Patient related1-7
• Surgery related1-5
—Duration of surgery
—Operative procedure (e.g., gynecologic,
laparoscopic, eye, plastic, abdominal)
—Female gender
—History of PONV and/or motion sickness
—Nonsmokers
—Younger age
—Anxiety
—Underlying disease (e.g., GI obstruction,
neuromuscular disorders, gastric hypomotility)
• Anesthesia related1-3,6-8
—Volatile anesthetics
—General anesthesia
—Duration of anesthesia
—Postoperative opioids
—Muscle relaxant antagonists (e.g., neostigmine)
1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Kovac AL. Drugs. 2000;59:213-243. 3. Apfel CC, et al. Acta Anaesthesiol Scand.
1998;42:495-501. 4. Apfel CC, et al. Anesthesiology. 1999;91:693-700. 5. Koivuranta M, et al. Anaesthesia. 1997;52:443-449. 6.Apfel CC, Roewer N.
Int Anesthesiol Clin. 2003;41:13-32. 7. Apfel CC. Anesthesiology News Special Edition. 2006:71-76.
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John B Leslie, MD MBA
1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Kovac AL. Drugs. 2000;59:213-243. 3. Apfel CC, et al. Br J Anaesth. 2002;88:659-668. 4.
Cohen MM, et al. Anesth Analg. 1994;78:7-16. 5. Koivuranta M, et al. Anaesthesia. 1997;52:443-449. 6. Apfel CC, et al. Anaesthesia. 2004;59:10781082. 7. Roberts GW, et al. Anesth Analg. 2005;101:1343-1348. 8. Apfel CC, et al. Anesthesiology. 1999;91:693-700.
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The PONV Problem
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PONV Risk Factors (cont)
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Comparison of predictive models for PONV
• Most predictive1-3
Apfel
Koivuranta
Palazzo
Sinclair
—Female gender
—Nonsmokers
—History of PONV/motion sickness
—Postoperative opioid analgesics
• Multiple (≥3) risk factors2
—60%–80% of patients may experience PONV
1. Kovac AL. Drugs. 2000;59:213-243. 2. Apfel CC, et al. Anesthesiology. 1999;91:693-700. 3. Apfel CC. Anesthesiology News Special Edition.
2006:71-76.
“A risk score to predict the probability of
postoperative vomiting in adults.”
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Apfel et al. Br J Anaesth 2002;88:234-40
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SAMBA Algorithm Factors for PONV
1137 ENT patients split into an evaluation set (533) and a validation set (584)
•
POV Risk (probability) =
Adult Risk Factors
1
1 + e-z
Children Risk
Factors
Surgery > 30 min
Patient Related
• Where: Z = (no=0, yes=1)
+ 1.28*(female gender)
- 0.029*(age)
- 0.74*(smoking)
+ 0.63*(history motion sickness or PONV)
+ 0.26*(duration)
- 0.92
Environmental
History of PONV or
Motion Sickness
Postop Opioids
Age > 3 years
Female Gender
Emetogenic surgery
(type & duration)
Strabismus surgery
Non-Smoker
History of POV or
relative with PONV
Gan et al. Anesth Analg. 2007;105:1615-28.
Apfel et al. Acta Anaesthesiol Scand 1998;42:495-501
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Simplified Risk Score to Predict PONV in Adults1
PONV
PDNV
OIE
MINV
JBL
When either 1, 2, 3 or 4 of the independent PONV predictors are present,
the corresponding risk for PONV increases
Risk Factors
Points
100
Female Gender
1
80
Non-Smoker
1
60
History of PONV**
1
40
Percent Risk for PONV
80
60
40
20
Postoperative Opioids
1
20
Sum =
0, 1, 2, 3, 4
0
** or motion sickness?
10
0 Risk
Factor
1 Risk
Factor
2 Risk
3 Risk
4 Risk
Factors Factors Factors
For example (YELLOW BOX), if a patient is a “female” “non-smoker”
she has 2 risk factors and there is a 40% chance of her experiencing PONV
1. Gan TJ, et al Guidelines for the Management of PONV; Anesth Anal, Vol 105, December, 2007
John B Leslie, MD MBA
Where are we in the development
and implementation of “best
practices” PONV guidelines?
The PONV Problem
JBL
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Strategies to Reduce Baseline
PONV Risk
PONV Patient-At-Risk “Game Plan”
• Avoidance of general anesthesia by the use of
regional anesthesia (RCT)
• Use of propofol for induction and maintenance of
anesthesia (RCT/SR)
• Avoidance of nitrous oxide (RCT/SR)
• Avoidance of volatile anesthetics (RCT)
• Minimization of intraoperative and postoperative
opioids (RCT/SR)
• Minimization of neostigmine (SR)
• Adequate hydration (RCT)
Gan et al. Anesth Analg. 2007;105:1615-28.
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Guidelines for Antiemetic Prophylaxis for PONV
Receptor Site Affinity
Drug
ASA 20021
ASPAN 20062
• Prophylaxis with:
—5-HT3 RA
—Droperidol
—Dexamethasone
—Metoclopramide
—5-HT3 RA +
dexamethsone
• If required, rescue
with 5-HT3 RA
FDA
Approved
SAMBA 20073
• Prophylaxis with 1 or more:
—5-HT3 RA
—Droperidol
—Dexamethasone
—H1 receptor blocker
—Transdermal scopolamine patch
Prochlorperazine
• Assess patient risk
• Reduce baseline risk factors
• Prophylaxis with 1-2
interventions for patients at
moderate risk:
—5-HT RA
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PONV Treatment Team
9
Receptor Site Affinity
Serotonin
Dopamine
Histamine
Muscarinic
+
++++
++
++
++++
+
+
Haloperidol
3
• Give adequate IV hydration
—Droperidol, haloperidol
• Use total IV anesthesia
—Dexamethasone
—H1 receptor blocker
• If patient fails in PACU, then
—Transdermal scopolamine
administer another category of
patch
agent
—Promethazine,
• If required, rescue with
prochlorperazine, perphenazine
promethazine, prochlorperazine,
—Ephedrine
or metoclopramide
• High-risk multimodal
approach
• If patient fails, then administer
another category of agent
ASA=American Society of Anesthesiologists; ASPAN=American Society of PeriAnesthesia Nurses; SAMBA=Society for Ambulatory Anesthesia.
1. ASA Task Force on Postanesthetic Care. Anesthesiology. 2002;96:742-752. 2. ASPAN PONV/PDNV Strategic Work Team. J Perianesth Nurs.
2006;21:230-250. 3. Gan TJ, et al. Anesth Analg. 2007;105:1615-1628.
Droperidol
9
+
++++
Metoclopramide
9
++
+++
Scopolamine
9
Dimenhydrinate
Hydroxyzine
9
Promethazine
9
Aprepitant
9
Dolasetrron
9
++++
Granisetron
9
++++
Ondansetron
9
++++
Palonosetron
9
++++
Dexamethasone
+
++++
++
+
++++
++++
++
++
++++
++
1. Watcha MF, White PF. Anesthesiology. 1992;77:162-184. 2. Scuderi PE. Int Anesthesiol Clin. 2003;41:41-66. 3. Prommer E. J Pain Palliat Care
Pharmacother. 2005;19:31-39.
SAMBA Treatment Algorithm Options for
PONV
Surgeons
Anesthesiologists &
Nurse Anesthetists
John B Leslie, MD MBA
+
+
+
Antagonism of prostaglandins and release of endorphins
Peri-Anesthesia Nurse
Gan TJ, et al Guidelines for the Management of PONV; Anesth Analgesia, Vol 105, December, 2007
Neurokinin
++++
The Consensus Guidelines for the management of PONV was written
by a multi-disciplinary panel that included such clinicians as …
Pharmacist
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PONV Antiemetics
Gan et al. Anesth Analg. 2007;105:1615-28.
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The PONV Problem
SAMBA Treatment Algorithm Options for
PONV
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Gan et al. Anesth Analg. 2007;105:1615-28.
SAMBA Treatment Algorithm Options for
PONV
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Gan et al. Anesth Analg. 2007;105:1615-28.
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Increasing the Number of Antiemetics Reduces the
Incidence of PONV (n=5161 patients at high risk for PONV)
Selecting “Best Shot” PONV/PDNV Drugs?
60
52% chance of PONV
% Incidence of PONV
95% Confidence Interval
52
50
37% chance of PONV
37
40
28% chance of PONV
22% chance of PONV
28
30
22
20
10
0
No Antiemetic
1 Antiemetic
2 Antiemetics
3 Antiemetics
0 Antiemetics
1 Antiemetic
2 Antiemetics
3 Antiemetics
IV Ondansetron
IV Dexamethasone
IV Droperidol
IV Ond + IV Dex
IV Ond + IV Dro
IV Dro + IV Dex
Adapted from Apfel et al. N Engl J Med. 2004;350:2241-2251.
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Estimated Incidence of PONV as a function of Baseline Risk
Assumption: Each Intervention Reduces risk by 26%1
n=5161 patients at risk for PONV
80% baseline risk
4 Risk Factors
The baseline risk levels 0f 10%, 20%, 40%, 60% and 80% reflect the presence of
0,1,2,3 and 4 risk factors respectively, according to a simplified score
80
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Despite multiple combinations with
current drugs, we fail…yes, we fail!
Estimated PONV incidence as a function of baseline risk, assuming
each intervention reduces relative risk by 26%
60% baseline risk
3 Risk Factors
Number of interventions
Percenatage
60
50
Baseline risk
(no intervention)
40% baseline risk
2 Risk Factors
40
30
20
10
20% baseline risk
1 Risk Factor
10% baseline risk
0 Risk Factors
0
Baseline Risk
with No
Intervention
One
Intervention
Two
Interventions
Three
Interventions
Four
Interventions
1
2
3
10%
7%
5%
4%
3%
20%
15%
11%
8%
6%
40%
29%
22%
16%
12%
60%
44%
33%
24%
18%
80%
59%
44%
32%
24%
26% reduction in relative risk of PONV for each additional antiemetic used
Adapted from Apfel et al. N Engl J Med. 2004;350:2241-2251.
John B Leslie, MD MBA
4
Apfel CC, Korttila K, Abdalla M, et al. A factorial trial of six interventions for the prevention of
postoperative nausea and vomiting. N Engl J Med 2004;350:2441-51.
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The PONV Problem
Selecting the Ideal Antiemetic? Pathway?
The Numbers are In. We Are Failing ;-(
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Current & Future Antiemetic Therapy for
PONV Prophylaxis in Adults
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• Serotonin (5-HT3) antagonists • Diphenhydramine (Benadryl®)
— Ondansetron (Zofran®)
• Nonpharmacologic
— Dolasetron (Anzemet®)
techniques*
— Granisetron (Kytril®)
— Tropisetron (Navoban®)*
— Palonosetron (Aloxi®)
• Dexamethasone (Decadron®)*
• Droperidol (Inapsine®)†
— Haloperidol (Haldol®)*
•
•
•
•
—
—
—
—
Acupuncture* (Acupressure)*
Hypnosis*
Aromatherapy*
Music therapy*
• Dimenhydrinate (Dramamine®)
• Neurokinin-1 Antagonists
Scopolamine (Transderm Scop®)
— Aprepitant (Emend®)
— Casopitant (Rezonic)* 5-20-09
Promethazine (Phenergan®)
Prochlorperazine (Compazine®) • Cannabinoid
— Nabilone (Cesamet®)*
Ephedrine*
— Dronabinol (Marinol®)*
*Currently not FDA-approved for PONV in the United States; †Note package insert black box warning.
Modified from Gan et al. Anesth Analg. 2003;97:62-71.
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PONV Summary and Conclusions
• Understanding of emetic pathways continues to evolve
— 30% overall incidence 2
— PONV incidence increases with each additional risk factor, thus
underscoring need for assessment and preventative intervention 3
• Risk assessment helps identify patients who would benefit
from prophylactic antiemetics
• Effective PONV prevention strategy incorporates risk
assessment that reflects its multifactorial etiology 2
— Peripheral versus central emetogenic triggers 1,2
— Peripheral versus central neurotransmitter/receptor pathways 3.4
• Involvement of different emetic neurotransmitter
pathways may impact treatment strategies
— Source of emetic stimuli impacts effectiveness of
pharmacologic antiemetic intervention 5
— Multiple receptor approach probably logical and effective
• Ideal combination unproven: Consider 5-HT3 + steroid +
droperidol/haloperidol + SCOP + “special needs” + techniques
2
— New pharmacology 5HT3 antagonist palonosetron
— First substance P/NK1 antagonist now available for prevention
of troublesome PONV and PDNV: Aprepitant 40 mg
— Patient-related characteristics
— Surgery-related characteristics
— Anesthesia-related characteristics
1. Kovac. Drugs. 2000;59:213-243. 2. Nelson TP. J PeriAnesthesia Nursing 2002;17:178-189. 3. Saito R., et
al. J Pharmacol Sci 2003;91:87-94. 4. Hornby PJ. Amer J Med 2001;111:106S-112S. 5. Diemunsch P.,
Grelot L. Drugs 2000;60:533-546
1. Macario A., et al. Anesth Analg 1999;89:652-658. 2. Kovac. Drugs. 2000;59:213-243. 3. Apfel CC et al.
Anesthesiology 1999;91:693-700
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SCOAP PONV Challenge
Risk stratification can and should be done.
Prevention measures should be implemented.
Outcome benefits should be producible and
measurable.
Benefits should include patient satisfaction and
reduced costs.
The PONV initiative should be widely applicable.
John B Leslie, MD MBA
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(cont)
• PONV: Ranked as most undesirable consequence of
surgery 1
• Global risk assessment includes evaluation of:
PONV Summary and Conclusions
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Questions?
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