Alex Konstantatos Matthew Chan Margaret Angliss

A PROSPECTIVE COHORT OF OPIOID USE, A PROSPECTIVE COHORT OF OPIOID USE, EFFICACY AND SENSITIVITY IN A GROUP OF EFFICACY AND SENSITIVITY IN A GROUP OF

CHINESE AND AUSTRALIAN PATIENTS HAVING CHINESE AND AUSTRALIAN PATIENTS HAVING MAJOR SURGERYMAJOR SURGERY

Alex KonstantatosAlex Konstantatos

Matthew ChanMatthew Chan

Margaret AnglissMargaret Angliss

OPIOID COHORTOPIOID COHORT

HypothesisHypothesis People of Chinese Ethnicity have less

opioid requirement after major surgery compared to Caucasian Australians because of increased efficacy and increased sedation in Chinese

OPIOD COHORT: OPIOD COHORT: METHODOLOGYMETHODOLOGY

Prospective evaluation of two groups of Prospective evaluation of two groups of patients having elective major surgery patients having elective major surgery involving open abdominal incision:involving open abdominal incision:

68 Chinese patients (Prince of Wales 68 Chinese patients (Prince of Wales Hospital Hong Kong )Hospital Hong Kong )

68 Caucasian Australian patients (Alfred 68 Caucasian Australian patients (Alfred Hospital. Melbourne, Australia)Hospital. Melbourne, Australia)


INCLUSION CRITERIAINCLUSION CRITERIA Age 18-80 Age 18-80 Racial features (Asian or Caucasian)Racial features (Asian or Caucasian) Spent most of life in the relevant country Spent most of life in the relevant country

(Asians-Hong Kong/China, (Asians-Hong Kong/China, Caucasians/Australia) Caucasians/Australia)

Planned general anaesthesia +/- N2O, Planned general anaesthesia +/- N2O, intraoperative morphine and postoperative intraoperative morphine and postoperative PCA infusion therapy with morphinePCA infusion therapy with morphine

Able to understand principles of effective use Able to understand principles of effective use of PCAof PCA

No contraindication to NSAID or paracetamol No contraindication to NSAID or paracetamol


EXCLUSION CRITERIAEXCLUSION CRITERIA History Persistent PainHistory Persistent Pain Opioid use up to 2 weeks prior to Opioid use up to 2 weeks prior to

surgerysurgery Renal or Hepatic impairmentRenal or Hepatic impairment Strong preference for regional Strong preference for regional

analgesia or LA infiltrationanalgesia or LA infiltration Use of ketamineUse of ketamine


PREOPERATIVE SURVEY AND EDUCATION

Participants surveyed in native language about attitudes and understanding of opioids

Participants and Carers educated in native language about optimal use of PCA infusion for effective pain relief


PERIOPERATIVE ANALGESIAPERIOPERATIVE ANALGESIA All subjects administered Morphine plus single

dose of NSAID in theatre and prescribed Morphine PCA postoperatively for 72 hours

Patients with severe postoperative pain allowed paracetamol if prescribed by independent pain physician, data collection continued in this group

Opioid related side effects treated standardized therapies e.g. 5HT3 inh for PONV, antihistamine for itch


OUTCOME MEASURESOUTCOME MEASURESPRIMARY PRIMARY 72 hour postoperative opioid consumption, 72 hour postoperative opioid consumption,

including BMI adjusted opioid consumptionincluding BMI adjusted opioid consumption

SECONDARYSECONDARY Pain intensity ratings over 72 hours with Pain intensity ratings over 72 hours with

coughing (NRS)coughing (NRS) Incidence of sedation, PONV, itch, Incidence of sedation, PONV, itch,

respiratory rate respiratory rate


OTHER OUTCOME MEASURESOTHER OUTCOME MEASURES DemographicsDemographics Attitudes about opioids and Attitudes about opioids and

postoperative pain managementpostoperative pain management N2O use and effect N2O use and effect Educational attainmentEducational attainment Satisfaction RatingSatisfaction Rating Pharmacogenetics: OPRM1 statusPharmacogenetics: OPRM1 status

OPIOID COHORT: RESULTS 1OPIOID COHORT: RESULTS 1

CHINESE CAUCASIAN P VALUE

NO SUBJECTS 68 68

GENDER(M:FM) 36:32 38:30 0.37

AGE 59.6(11.9) 55.5(16.6) 0.18

BMI 23.4(4.6) 26.2(7.5) <0.0005

EDUCATION 2 2.5 <0.005

N2O(Y:N) 27:41 11:57 0.001

INCISION>10cm 53:15 47:21 0.3

DURATION OF PROCEDURE

218.1(121.2) 201.2(93.5) 0.71

SURGERY(CRS/GYNE) 58% 63%

SURGERY(HB/UPP GI) 38% 29%

SURGERY(UROL) 6% 8%

OPIOID COHORT: RESULTS IIOPIOID COHORT: RESULTS II

CHINESE CAUCASIAN

OPRM1 AA 38% 61%

OPRM1 GG 12% 33%

OPRM1 AG/GA 50% 6%

PARACETAMOL 26% 25%

OPIOID COHORT: RESULTSOPIOID COHORT: RESULTS Similar numbers of male/females, age, Similar numbers of male/females, age,

incision length, duration and classification incision length, duration and classification of procedure type, need for paracetamolof procedure type, need for paracetamol

Chinese participants had significantly Chinese participants had significantly lower BMI, greater exposure to lower BMI, greater exposure to intraoperative nitrous oxide, more upper intraoperative nitrous oxide, more upper abdominal surgeries, abdominal surgeries,

Caucasian Australians had higher Caucasian Australians had higher educational attainmenteducational attainment

OPIOID COHORT: RESULTSOPIOID COHORT: RESULTS Mean IVME consumption at Mean IVME consumption at

72 hrs significantly less in 72 hrs significantly less in Chinese Chinese 86.8 mg86.8 mg (71.8- (71.8-101.8) compared to 101.8) compared to Caucasian Australians Caucasian Australians 132.5 mg132.5 mg (115.3-149.7); (115.3-149.7); p<0.005p<0.005

Opioid consumption lower Opioid consumption lower in Chinese at 24, 48 hrsin Chinese at 24, 48 hrs

BMI adjusted opioid BMI adjusted opioid consumption was also consumption was also significantly less in significantly less in Chinese participants Chinese participants 3.83.8(3.1-4.5)versus (3.1-4.5)versus 4.9 4.9 (4.2-5.6) (p<0.029) (4.2-5.6) (p<0.029) 0

20

40

60

80

100

120

140

OPIOID COHORT: RESULTSOPIOID COHORT: RESULTS

NRS pain scores were significantly higher NRS pain scores were significantly higher in Chinese subjects in Chinese subjects * * RMANOVARMANOVA

NRS with NRS with coughingcoughing

ChineseChinese CaucasianCaucasian P ValueP Value

0.029 *0.029 *

24 hrs24 hrs 4.8(4.2-5.4)4.8(4.2-5.4) 3.2(2.6-3.8)3.2(2.6-3.8)

48 hrs48 hrs 3.6 (2.9-4.3)3.6 (2.9-4.3) 2.2 (1.7-2.7)2.2 (1.7-2.7)

72 hrs72 hrs 2.5(2.0-3.002.5(2.0-3.00 1.3(0.8-1.8) 1.3(0.8-1.8)


OPIOID RELATED SIDE EFFECTSOPIOID RELATED SIDE EFFECTS

SEDATIONSEDATION

Lower scoresLower scores in Chinese at: in Chinese at:

0-24hrs; p=0.020-24hrs; p=0.02

24-48 hrs; p=0.04924-48 hrs; p=0.049

48-72 hrs, p<0.00548-72 hrs, p<0.005



PONVPONVNo significant differenceNo significant difference between between

Chinese and Caucasian Australians at:Chinese and Caucasian Australians at:

0-24 hrs (P=0.94)0-24 hrs (P=0.94)

24-48 hrs (P=0.31)24-48 hrs (P=0.31)

48-72 hrs (P=0.35)48-72 hrs (P=0.35)



ITCHITCH

Chinese participants had Chinese participants had significantly significantly higher itchhigher itch at: at:

0-24 hrs (p=0.05)0-24 hrs (p=0.05)

24-48hrs (p=0.001)24-48hrs (p=0.001)

48-72hrs (p=0.001) 48-72hrs (p=0.001)


SATISFACTION RATINGSATISFACTION RATING

Chinese participants rated their Chinese participants rated their satisfaction with pain management satisfaction with pain management significantly highersignificantly higher than than Caucasian Australians; (p=0.009) Caucasian Australians; (p=0.009)

OPIOID COHORT: RESULTSOPIOID COHORT: RESULTS N2O identified as a significant covariate N2O identified as a significant covariate

influencing opioid consumption (p=0.001) i.e. it influencing opioid consumption (p=0.001) i.e. it accounted for part of the difference between accounted for part of the difference between Chinese and CaucasiansChinese and Caucasians

Significant difference in opioid consumption Significant difference in opioid consumption BETWEEN CHINESE and CAUCASIANS still present BETWEEN CHINESE and CAUCASIANS still present in those NOT exposed to N2O (p=0.008) in those NOT exposed to N2O (p=0.008)


PATTERNS WITHIN GROUPS EXPOSED TO N2OPATTERNS WITHIN GROUPS EXPOSED TO N2O 1) Caucasian Australians with N2O had SIMILAR opioid 1) Caucasian Australians with N2O had SIMILAR opioid

(p=0.76)and significantly LESS pain (p=0.04) (p=0.76)and significantly LESS pain (p=0.04) compared to NO N2O Caucasian Australianscompared to NO N2O Caucasian Australians

2) Chinese with N2O had SIMILAR opioid(p=0.68) and 2) Chinese with N2O had SIMILAR opioid(p=0.68) and MORE pain but non-significant (p=0.88) compared to MORE pain but non-significant (p=0.88) compared to NO N2O. i.e. pattern of low opioid, higher pain NO N2O. i.e. pattern of low opioid, higher pain intensity maintainedintensity maintained

Chinese having N2O reported greater incidence of Chinese having N2O reported greater incidence of vomiting which was non significant (p=0.2) vomiting which was non significant (p=0.2)

OPIOID COHORT: RESULTSOPIOID COHORT: RESULTSATTITUDE SURVEYATTITUDE SURVEY Chinese participants were Chinese participants were significantly more likelysignificantly more likely to to

expect severe pain after surgery and had a preference expect severe pain after surgery and had a preference for others to control their pain managementfor others to control their pain management

Chinese patient carers were significantly more likely to Chinese patient carers were significantly more likely to express preference for their patients to control their own express preference for their patients to control their own managementmanagement

Neither Chinese nor Caucasian Australian participants Neither Chinese nor Caucasian Australian participants nor their carers feared the subjects were at risk of nor their carers feared the subjects were at risk of opioid addiction opioid addiction

OPIOID COHORT: CONCLUSIONSOPIOID COHORT: CONCLUSIONS Chinese patients after major surgery use less Chinese patients after major surgery use less

opioid and rate their pain intensity higher opioid and rate their pain intensity higher compared with Caucasian Australians and are compared with Caucasian Australians and are more satisfied with their pain managementmore satisfied with their pain management

Chinese patients experienced less sedation in the Chinese patients experienced less sedation in the setting of using significantly less morphinesetting of using significantly less morphine

Explanations for this are multifactorial and are Explanations for this are multifactorial and are explained in part by greater susceptibility to itch, explained in part by greater susceptibility to itch, more frequent exposure to nitrous oxide, greater more frequent exposure to nitrous oxide, greater preoperative expectation of severe pain, and a preoperative expectation of severe pain, and a desire for less autonomy among the Chinese desire for less autonomy among the Chinese participants compared with Australian participants compared with Australian Caucasians.Caucasians.

OPIOID COHORT: CONCLUSIONSOPIOID COHORT: CONCLUSIONS

GENETICSGENETICS Complex and multifaceted, we did not have enough power Complex and multifaceted, we did not have enough power

to confidently analyse genetic factors but noted some to confidently analyse genetic factors but noted some trendstrends

OPRM1( mu receptor variation) OPRM1( mu receptor variation) GG variant present in good numbers in both populations.GG variant present in good numbers in both populations. Non-significant increase in opioid consumption among Non-significant increase in opioid consumption among

Chinese participants comparing AA and GG (p=0.05)Chinese participants comparing AA and GG (p=0.05) No significant differences in NRS pain among Chinese No significant differences in NRS pain among Chinese

participants comparing AA and GGparticipants comparing AA and GG No significant differences in opioid consumption or NRS No significant differences in opioid consumption or NRS

pain among Caucasian Australians pain among Caucasian Australians

OPIOID COHORT: CONCLUSIONSOPIOID COHORT: CONCLUSIONS

A patient’s experience of Pain after A patient’s experience of Pain after surgery is a balance between the surgery is a balance between the efficacy and side effects of therapy efficacy and side effects of therapy and is influenced by their beliefs and is influenced by their beliefs which can reflect ethnicity. which can reflect ethnicity. Clinicians too often focus on pain Clinicians too often focus on pain scores alone.scores alone.

THANKSTHANKS

Matthew ChanMatthew Chan

Marg AnglissMarg Angliss

Paul MylesPaul Myles

Documents

Alex Konstantatos Matthew Chan Margaret Angliss