Behandling av PONV samt interaktioner

Prediktion, profylax och
behandling av PONV
Jan Jakobsson
Leg. Läk., Med. Dr., Docent
Karolinska Institutet
Sabbatsberg Närsjukhus
Jan.jakobsson@ki.se

PONV
the little
big or
big little
PROBLEM

Physiology - PONV

The
pathophysiology
in PONV

PONV
PREDICTION
Emtogena faktorer
Patient relaterade faktorer
Kirurgi relaterade faktorer
Anestesi relaterade faktorer
Läkemedel relaterade faktorer
PROFYLAX/
”Rescue BEHANDLING
Antiemetika
Icke farmakologiska
Farmakologloska

PONV
PREDICTION
Emtogena faktorer
Patient relaterade faktorer
Kirurgi relaterade faktorer
Anestesi relaterade faktorer
Läkemedel relaterade faktorer
PROPHYLAX/
BEHANDLING
Antiemetika
Då ingen profylax givits
Icke farmakologiska
Farmakologloska

PONV
PREDICTION
Emtogena faktorer
Patient relaterade
faktorer
Kirurgi relaterade faktorer
Anestesi relaterade
faktorer
Läkemedel relaterade
faktorer
PROPHYLAX/
”Rescue BEHANDLING
Antiemetika
Icke farmakologiska
Farmakologlska

Patients “at risk” for PONV
kvinna > man
anamnes på ”rörelsesjuka”
tidigare PONV
icke-rökare
menstruationcykel
postoperativa opioider
M. Koivuranta. A survey of postoperative nausea and
vomiting Anaesthesia 1997;52:443-9

PONV risk factors
This literature shows that;
female gender post-puberty,
nonsmoking status,
history of PONV or motion sickness,
childhood after infancy and younger adulthood,
increasing duration of surgery,
use of volatile anesthetics, nitrous oxide,
large-dose neostigmine,
intraoperative or postoperative opioids
Are all well-established PONV risk factors

PONV
Possible risk factors include
history of migraine,
history of PONV or motion sickness in a child's parent or
sibling,
better ASA physical status,
intense preoperative anxiety,
certain ethnicities or surgery types,
decreased perioperative fluids,
crystalloid versus colloid administration,
increasing duration of anesthesia,
general versus regional anesthesia or sedation,
balanced versus total IV anesthesia,
use of longer-acting versus shorter-acting opioids.

Early-phase menstruation, obesity and lack of
supplemental oxygen are disproved risk
factors.
..tid under menstrationscykel ringa
betydelse

“Högrisk” kirurgi - PONV
Bröstkirurgi
Ögonkirurgi
ÖNH
Gynekologisk kirurgi
Abdominell kirurgi
…..
..typiska
dagkirurgiska
ingrepp
M. Koivuranta. A survey of postoperative nausea and
vomiting Anaesthesia 1997;52:443-9

Kirurgi
bröst
ÖNH
buk
”invasive”
Duration

Anestesival
Generell anestesi ≥ Regional anestesi
Inhalionsanestesi ≥ Intravenös anestesi
lyftväg?
Ventilationsteknik
Mask vs intub
Kontrollerad vs spontan
anestesidjup, area under the curve
BIS
Puls/blodtryck

Läkemedel
Opioids
Tramadol
Neostigmine
Nitrous oxide
Halogenated inhaled anaesthetics
Differences inbetween?

Läkemedel
Opioider
Tramadol
Neostigmin
Lustgas ??
De vanliga narkosgasrena?!?!

PONV
PREDICTION
Emtogena faktorer
Patient relaterade faktorer
Kirurgi relaterade faktorer
Anestesi relaterade faktorer
Läkemedel relaterade faktorer
PROFYLAX
”Rescue”
BEHANDLING
Behandling -
”naiv”
Antiemetika

Vad eftrestävar vi; no PONV
initial frekvens
kirurgi
anestesiteknik
Hur länge följer vi patienten;
”UVA”
utskrivning,
24 h - 48 h
patientens eller ”Observes” bedömning
Analgetikastrategi!

Vad eftrestävar vi; no PONV
initial frekvens
surgical procedure
anesthetic technique
Hur länge följer vi patienten;
”UVA”
utskrivning,
24 h - 48 h
patientens eller ”observes” bedömning
Analgetikastrategi!

Smärtbehandling inom Dagkirurgi
Opiod iv.
Kodein/
dextropropoxyphene
po
NSAID
Paracetamol
Lokalbedövning

Kirurgi
Multi-modal approach
Opioids
Anaesthesia
Local anaesthesia
Peripheral
analgesics/
NSAIDs

Pain therapy
Opioid iv
oral opioid
oralt NSAID
oralt paracetamol 2 gr (30mg/kg)
Marcain innan man syr
Xylo före

”hur bra är antiemetika”
Minskad förekomst avs ymtomen
kontroll patienter - 60 % PONV
study group - 40 % PONV
20 % förre upplever PONV
en 33 % sökning av PONV
..men 40 % har fortfarande PONV

”hur bra är antiemetika”
Minskad förekomst avs ymtomen
kontroll patienter - 60 % PONV
study group - 40 % PONV
20 % förre upplever PONV
en 33 % sökning av PONV
..men 40 % har fortfarande PONV
Detta är ungefär så bra som de
flesta av våra antiemetika är
”även” Zofran

PONV
PREDICTION
Emtogenic factors
Patient related factors
Surgery related factors
Anaesthesia related
factors
Drug related factors
PROPHYLAXIS/
TREATMENT
Antiemetika
Icke-farmakologiska
tekniker

Antiemetika
DOPA-agonister
droperidol
metoclopramide
cyclicine
antikolinergika
5-HT 3 blockerare
Steroider
Propofol
midazolam

Antiemetika
DOPA-agonister
droperidol
metoclopramide
cyclicine
anti-cholinergika
propofol
5-HT 3 blockare
steroider

The 5-HT 3 -blocking agents
ondansetron
tropisetron
granisetron
dolasetron
ropasetron

Cytochrome P450 2D6 metabolism and 5hydroxytryptamine
type 3 receptor antagonists for
postoperative nausea and vomiting.
Janicki PK Med Sci Monit. 2005 Oct;11(10):RA322-8.

5-HT3 receptor antagonists for prevention of late
acute-onset emesis.
Constenla M. Ann Pharmacother. 2004 Oct;38(10):1683-91.

5-HT3 receptor antagonists for prevention of late
acute-onset emesis.
Constenla M. Ann Pharmacother. 2004 Oct;38(10):1683-91.

5-HT3 receptor antagonists for prevention of late
acute-onset emesis.
Constenla M. Ann Pharmacother. 2004 Oct;38(10):1683-91.

5-HT3 receptor antagonists for prevention of late
acute-onset emesis.
Constenla M. Ann Pharmacother. 2004 Oct;38(10):1683-91.

Cytochrome P450 2D6 metabolism and 5hydroxytryptamine
type 3 receptor antagonists for
postoperative nausea and vomiting.
Janicki PK Med Sci Monit. 2005 Oct;11(10):RA322-

100
90
80
70
60
50
40
30
20
10
0
Dose effect for ondansetron
Helmers H. et al Can J Anaesth 1993;40:1155-61
80
74
placebo 1 mg ond. 8 mg ond. 16 mg ond.
59
72
PONV

Dose effect for tropisetron
Capouet V. et al Br J Anaesth 1996;76:54-60
60
50
40
30
20
10
0
44
31
placebo 0.5 mg
trop
26
2 mg
trop
30
5 mg
trop
PONV
rescue

Granisetron and ondansetron for prevention of
nausea and vomiting in patients undergoing
modified radical mastectomy.
In a randomized, double-blind, placebo-controlled
trial, sixty female patients received;
• ondansetron 4 mg,
• granisetron 1 mg
• saline intravenously
just before induction of anaesthesia A standardized
general anaesthetic technique was employed.
The incidence of PONV and adverse events were
recorded for the first 24h postoperatively.
The incidence of PONV was;
• 25% with ondansetron,
• 20% with granisetron
• 70% with saline Dua N, et al
Anaesth Intensive Care. 2004 Dec;32(6):761-4.

Dexamethasone 8 mg in combination with
ondansetron 4 mg appears to be the optimal dose
for the prevention of nausea and vomiting after
laparoscopic cholecystectomy.
Elhakim M, Nafie M, Mahmoud K, Atef A.
Can J Anaesth. 2002 Nov;49(9):922-6.

Combination of 5-HT 3 blockers with steroids
or droperiodol
Pueyo F. et al Anasth Analg 1996;83:117-22
80
70
60
50
40
30
20
10
0
72
40
placebo drop ond. ond. +
drop.
44
8
PONV

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.
Gan T. et al Can J Anaesth. 2004 Apr;51(4):311-9.

PONV
Prophylaxis
More than 1 risk factor
Treatment
Following prophylaxis
In a naive patient

PONV
Prophylaxis
More than 1 risk factor
Treatment
Following prophylaxis
In a naive patient

Prophylaxis
iv, oral,
pre op
at end of surgery
effective dos
Repeated administration -
combination

Superior prolonged antiemetic prophylaxis with a
four-drug multimodal regimen - comparison with
propofol or placebo.
Hammas B, Thorn SE, Wattwil M.
Patients in the M group received dexamethasone 4 mg
and three antiemetics, ondansetron 4 mg, droperidol 1.25
mg and metoclopramide 10 mg i.v.
Acta Anaesthesiol Scand. 2002 Mar;46(3):232-7.

Superior prolonged antiemetic prophylaxis with a four-drug
multimodal regimen - comparison with propofol or placebo.
Hammas B, Thorn SE, Wattwil M.
CONCLUSION: The incidence of PONV is very high in
patients undergoing breast and abdominal surgery. In the
present study antiemetic prophylaxis with a combination of
droperidol, ondansetron, metoclopramide and
dexamethasone was more effective in preventing PONV,
especially vomiting, than a postoperative low-dose infusion of
propofol, which had a short lasting effect.
…alla 4 tillsammans
är ännu bättre
Acta Anaesthesiol Scand. 2002 Mar;46(3):232-7.

PONV
Prophylaxis
More than 1 risk factor
Treatment
Following prophylaxis
In a naive patient

PONV
Prophylaxis
More than 1 risk factor
Treatment
Following prophylaxis
In a naive patient

Treatment
Intravenous
drug
Dose

Om patienten fått
5-HT-3 blockare
Promethazine 25 mg !!!
metoclopramide 10 mg!

…om patienten fått dridol
eller steroid
5-HT-3 blockerare

15 – 20 µg/kg = ca 1 mg
Clin Ther. 2004 Jul;26(7):1055-60.

PONV
the little
big or
big little
PROBLEM

Comparative efficacy of acustimulation (ReliefBand) versus
ondansetron (Zofran) in combination with droperidol for
preventing nausea and vomiting.
White PF, Issioui T, Hu J, Jones SB, Coleman JE, Waddle JP, Markowitz SD, Coloma M, Macaluso AR, Ing CH.
CONCLUSIONS: The ReliefBand compared favorably to
ondansetron (4 mg intravenously) when used for prophylaxis
against postoperative nausea and vomiting. Furthermore, the
acustimulation device enhanced the antiemetic efficacy of
ondansetron after plastic surgery.
…ett “acupressband är lika
effektivt som “zofran”…

PONV
Multi modal approach
Avoid opioids
…keep something for rescue
None pharmacological techniques
……………

Hur skall man göra …
BP!
Bltr
Acupressor
behandling
1mg. granisitron iv.
droperidol 1 mg iv.
metoclopramide 10-20 mg
FiO2
dexamethason 8 mg iv så tidigt som möjlligt

Cost effective multi-modal
approach
BP!
Bltr
Acupressor
Treatment
1mg. granisitron iv.
droperidol 1 mg iv. at end
metoclopramide 10-20 mg at end
FiO2
dexamethason 8 mg iv as early as possible
Oralt promethazine som premed

Den Dubbla Multimodala Tekniken
T.Paracetamol (30 mg/mg)
T.NSAID/Coxib
Xylo före
Marcain Efter
“innan/
under”
op
Små långsamma doser
“morfin” VAS < 4
preop
T.Postafen
Betapred så fort som nål
Dridol 1 mg +
Primperan 10 mg
under op då du har tid
postop
Behandla med 5-HT-3
blockare;
Kytril ½ - 1 mg iv.

Multi-modal approach
BP!
Bltr
Drug rotation
Acupressor
Behandling
1mg. granisitron iv.
droperidol 1 mg iv.
metoclopramide 10-20 mg
FiO2
dexamethason 8 mg iv så tidigt som möjligt