luan an tom tat (eng) nghiên cứu tác dụng giảm đau của các liều morphin tiêm trước mổ vào khoang dưới nhện và PCA morphin tĩnh mạch sau mổ tầng bụng trên

MINISTRY OF EDUCATION AND TRAINING

MINISTRY OF DEFENSE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL
SCIENCES

----------

DO KHAC HUNG

STUDY ON ANALGESIC EFFECT OF MORPHINE DOSAGES INJECTED
BEFORE SUBARACHNOID SPACE OPERATION COMBINED WITH IV-PCA
MORPHINE INJECTED AFTER UPPER ABDOMINAL ONE

Specialism:
Code:

Anesthesia Reanimation
62.72.01.22

THE SUMMARY OF MEDICAL DOCTORAL THESIS

HANOI - 2018


THE THESIS HAS BEEN COMPLETED AT
108 INSTITUTE OF CLINICAL MEDICAL AND
PHARMACEUTICAL SCIENCES

Scientific supervisor:

Prof. Nguyen Thu
Associate Prof. PhD. Cong Quyet Thang
Opponent 1: .......................................................................................

Opponent 2: .......................................................................................

Opponent 3:........................................................................................

Doctoral thesis will be evaluated at thesis evaluation council at
108 Institute of Clinical Medical and Pharmaceutical Sciences
On: ………………, ……… /………./ 2018

You can find the thesis at:
1. The National Library
2. Library of 108 Institute
Pharmaceutical Sciences.

of

Clinical

Medical

and


1
INTRODUCTION

Pain affects the patients during and after surgery, causing many
side-effects in respiratory, circulatory, endocrine, inflammatory
process, prolonged hospital stay... The consequences of
postoperative pain greatly affect the recovery of health and patients’
psychology.
More pain caused after the upper abdominal operation,
therefore, effective pain-killer measures must be required. Using
Intrathecal morphine (ITM) injection is a direct injection of
morphine into the subarachnoid space and has been proved to be
good pain-relief in the first day postoperatively while Intravenous
Patient-Controlled Analgesia (IV-PCA) reduces pain effectively,
especially for surgeries cause little and moderate pain.
The combination of spinal cord morphine injection with IVPCA has been studied by several authors to provide good analgesic
effects after urological, obstetric, orthopedic surgery... To find the
effective dose of this combination and to meet patient’s pain-killer
need after upper abdominal operation, we studied the subject: “Study
on analgesic effect of morphine before subarachnoid space
operation combined with IV-PCA morphine injected after upper
abdominal one” for below purposes:
1. To evaluate the analgesic effect of morphine at 0.2 mg and
0.4 mg when it’s injected before subarachnoid space operation
combined intravenous PCA morphine injected after upper abdominal
operation.
2. To evaluate the unexpected effects of morphine at 0.2 mg
and 0.4 mg when it’s injected before subarachnoid space operation
combined intravenous PCA morphine injected after upper
abdominal operation.


2

SUMMARY OF THESIS’S NEW MAIN SCIENTIFIC
CONTRIBUTION
1. Injection of morphine into the spinal cord before operation
combined with PCA had a good analgesic effect after upper
abdominal surgery, reducing a statistically significant amount of
morphine (p <0.05) compared with using IV-PCA morphine. Patients
injected with morphine 0.4 mg into the spinal cord before operation
need titrated morphine and total IV- PCA morphine for
postoperative pain after 24h, 48h, 72h were lower and statistically
significant (p <0.05) compared with the group of patients with 0.2
mg into the spinal cord: 2.74 ± 1.88mg compared with 4.25 ±
2.12mg; 7.84 ± 6.14mg, 15.19 ± 9.51mg and 19.69 ± 11.71mg
compared with 14.6 ± 11.65mg, 26 ± 18.54mg and 34.53 ± 22.39mg,
respectively; the time to initiate using morphine IV- PCA after
surgery in the 0.4mg morphine group injected into the spinal cord
before surgery is longer and the A/D ratio in 72h is higher than that
one in the group injected with 0.2mg morphine into the spinal cord:
17.42 ± 17.34 hours versus 5.0 ± 5.34 hours and 99.05 ± 3.69%
versus 94.0 ± 9.56%.
2. Injection of morphine into the spinal cord before surgery
combined with IV-PCA for reducing postoperative pain in the upper
abdomen did not affect the patients’ hemodynamics and respiration.
The incidence of itching, nausea and sedation with the injection of
0.4 mg in comparison of the one with 0.2 mg morphine into the
spinal cord before surgery was not statistically significant (p> 0.05):
38.3%, 43.3% and 46.6% compared to 36.7%, 40% and 48.3%,
respectively.


3

THESIS STRUCTURE
The thesis has 124 pages, not including annexes and references,
2 pages of introduction. The thesis has four chapters:
 Chapter 1: Overview, 32 pages.
 Chapter 2: Research subjects and methods, 18 pages.
 Chapter 3: Research result, 24 pages.
 Chapter 4: Discussion, 45 pages; Conclusion and
recommendations, 3 pages.
The thesis has 30 tables, 3 charts, 10 images and 121 references.
Chapter 1
OVERVIEW
1.1 Pain definition.
According to International Association for Study of Pain IASP, “Pain is unpleasant sensory and emotional experience
associated with actual or potential tissue damage, or describe in
terms of such damage”.
1.2. Characteristics of pain after upper abdominal surgery
Pain after abdominal surgery has been proven by many authors
to be subject to severe pain group (both in intensity and duration) as
well as with thoracic and spine surgery and knee replacement and
postoperative pain management.
- Skin incision: the usual incision is above or below the navel,
which is a long incision and directly affects the respiratory muscles
(especially the diaphragm).
- Abdominal surgery usually involves the removal or cutting of
organs, mesentery or arteries, causing neurological damage, blood
vessels in the surgical area, or setting up drainage causes severe pain.
- Pain due to regional blood-shortage in the surgical site: When
the blood supply to the tissue is reduced, pain occurs within a few
minutes. Pain intensity is directly proportional to the level of tissue

4
metabolism. In particular, if the level of metabolism in the higher the
tissue, the anemia, the pain in that tissue will be more intense. The
cause of pain is the accumulation of large amounts of lactic acid in
the diseased tissue during anaerobic metabolism (without the
involvement of oxygen) which liberates the acid metabolite products,
bradykinin, Atrophy in the damaged cell stimulates the nociceptor
receptors at the nerve terminal.
- Pain due to the spasm of the hollow organs: contraction of the
stomach, colon, and gallbladder through mechanical stimulation of
the neurotransmitter receptor, and contraction also reduces tissue
perfusion in combination with increased transfusion of smooth
muscle causes the pain level to increase.
- Pain due to excessive stretching in the empty organs such as
intestines, stomach, colon after surgery can cause pain by stretching
the tissue. At the same time when the stretching of empty organs also
cracked or broken up, blood vessels around the body causes anemia
to nourish the pain increases.
- In addition, the cause of pain is due to chemical stimulation: it
can be leaked digestive fluid, pancreatic fluid in surgery into the
peritoneal cavity. These infections cause inflammation and the
destruction of the peritoneal mucus also creates intense racing
stimuli.
1.3. Effect of pain after abdominal surgery
- Pain aggravates the body's stress response to injury: adverse
reactions to stress affect many different organs including
cardiovascular, respiratory, immune, and blood clots.
- Pain causes immunosuppression by increasing cortisol and
epinephrine concentrations, increasing the risk of surgical site

infections and infection.


5
- Pain causes hormonal and metabolic disorders (especially
glucose metabolism) then this cause hyperglycemia and decrease the
anabolic hormones such as insulin, testosterone.
- Pain that slows recovery after surgery, increased
complications from hospitalization and increased costs.
- Pain at high risk of chronic pain despite the wound healed,
greatly affecting the life and work of the patient.
- Pain has a negative effect on patients’ psychology, sympathy
and hospital, especially children.
- Post-operative abdominal pain in patients with poor breathing
causes collapse of the lungs and may cause respiratory failure.
1.4. The rules of pain prevention after abdominal surgery
- Apply systematic preoperative and postoperative pain
management measures.
- The preparation of patients before surgery to help them have a
good psychological comfort and good coordination with the
physician to make the treatment of pain more effective.
- VAS pain assessment and pain management at the time of
patient discharge.
- Tacit assay for patients with VAS score ≥ 4 in the recovery
room before using other analgesia (e.g. IV-PCA).
- It should be based on the degree of pain of the surgery, the
existing equipment and the capacity of the treating staff to select
appropriate pain management techniques.
- For patients with severe pain, strategies for applying multi modal therapy are needed.
- Pain prevention should be performed concurrently with

vomiting and postoperative vomiting, especially when using
morphine. Vaginal suppositories should be used systemically in
surgery, such as steroids or 5-HT3 receptor antagonists
(ondansetron).


6
- Anti-pain patients should be monitored postoperatively to
ensure effective pain relief (VAS <4) by adjusting the dosage, even
by more appropriate methods, to ensure that there are no serious
complications (respiratory, circulatory, peripheral blood, infections)
and minimize unwanted effects such as paralysis, numbness,
vomiting, nausea, urinary retention, itching ...
- Catheter used in pain relief as well as other instruments,
should not save more than 3 days.
Chapter 2
RESEARCH SUBJECTS AND METHODS
2.1 Research subjects
The study was conducted in patients undergoing endotracheal
anesthesia for open surgery under the plan of upper abdominal
ailments at Department of Anesthesiology and Resuscitation - Bac
Ninh General Hospital. Study period from August 2012, to June 2016.
Criteria for choosing patients to study
- Age is over 18 regardless of gender.
- Health Status ASA I, II.
- No contraindication with spinal anesthesia.
- No contraindications to morphine.
- Patients know how to use PCA after being instructed.
- The patient agrees to cooperate with the physician to
participate in the study.

Criteria to exclude patients from the study.
- Patients with heart failure, respiratory failure, kidney failure.
- Patients with difficulty communicating, having a history of or
present with epilepsy or mental illness.
- Patients with a history of drug addiction.
- Patients with prostatic hypertrophy and cholecystitis.


7
- Patients who have had painkillers morphine before surgery
for 7 days or have chronic illness often have to use painkillers.
- Patients require other painkillers and / or tranquilizers.
2.2. Research methods
2.2.1. Study categories
Prospective study, randomized, controlled clinical trials and
compare.
2.2.2. Sample size and selection.
We apply the following formula to calculate the sample size:

Notes:
n: number of patients in each study group.
p1: According to research by Justin Sangwook Ko, the
postoperative satisfaction rate was 83%.
Assumptions in the study were: p2 = 55%
α Type I error
β: type II error
P = 1/2 (P1 + P2)
Z: coefficient of confidence
Assumption of selection in the study was: α = 0.05; β = 0.10
Apply to formulas:

P1 = 83%
P2 = 55%
P = 1/2 (P1 + P2) = 69.0%
Z1-a / 2 = 1.96; Z1-β = 1.28
Replace these numbers into the formula for calculating the
sample size, calculated as n = 54. Thus, each group was 54 patients.
We selected 60 patients each.


8
2.2.3. Proceeding way
180 patients were divided into 3 groups:
- Group 1 (N1): postoperative pain management with pure
morphine IV-PCA.
- Group 2 (N2): injection of 200 mcg morphine into the lower
spinal cavity before surgery with IV-PCA morphine postoperatively.
- Group 3 (N3): 400 mcg morphine injection into the lower
spine before surgery with IV-PCA morphine postoperatively.
2.2.7. Perform anesthesia, maintain anesthesia and withdraw the
NKQ following a unified procedure.
2.2.8. Facilities and research equipment.
- PCA: Bbraun - Germany.
- Blood gas meter: GEM Premier 3000 - Japan
- Top flow measuring instrument.
- Drugs and other necessary GMHS facilities.
2.3.9. Criteria for evaluation in the study: Data collection
2.3.9.1. Criteria related to pain effectiveness (1st Goal)
- VAS points (T: 0, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72 hours)
+ VAS rating at break time
+ Evaluate VAS scores at mobilization

- First time need pain relief
- Amount of morphine used (in milligrams):
+ The amount of morphine used when titling.
+ Amount of morphine consumed through IV-PCA after surgery.
- Results of peak supply: Before surgery, after surgery 24, 48
and 72 hours.
- A / D ratio (%)
- Patient satisfaction with analgesia; It is divided into three
levels: Very satisfied, satisfied and dissatisfied.


9
2.3.8.2. Criteria for undesirable effects and complications (2nd
Goal)
- Changes in circulation, respiration, sedation.
- Evaluate of vomiting and nausea, itching, urinary retention
2.6. Analysis and processing of data
The data was analyzed and processed by computer statistics on
computer using Stata software.
Chapter 3
RESEARCH RESULT
3.1 Studied patient’s characteristics
Table 3.1: Age, height, weight, sex and ASA of the three
groups were not significantly different from p> 0.05.
3.2. Analgesic effect
3.2.1. Wake up time, time to extubation and first postoperative pain
relief demand.
Table 3.8. Wake up time, time to extubation and first pain relief
demand.
Group 1

Group 2
Group 3
p
n = 60
n = 60
n = 60
Wake up time after surgery (minutes)
±SD

23,25 ± 13,3 26,5 ± 13,54 27,3 ± 15,52 >0,05
Min÷Max
5÷70
10÷80
5÷70
Time to extubation (minutes)
±SD

35,62 ± 18,04 34,73 ± 19,44 40,75 ± 19,0

Min÷Max
10÷110
First pain relief demand (hours)
±SD
Min÷Max

0,52 ± 0,34
0,08÷2

10÷120

5,0± 5,34
0,5÷20

>0,05

15÷90

17,42 ± 17,34 <0,05
1÷72


10
Evaluate: The wake up time and time to extubation are not
different. The start average time must use PCA to relief pain in group
1is lowest, next group 2 and the highest in group 3. The difference
among the three groups was statistically significant at p <0.05.
3.2.2. A/D ratio
Table 3.9. A/D ratio
Group 1
Group 2
Group 3
n
=
60
n
=
60
n = 60
Time
p

X + SD
X + SD
X + SD
4h
77,52 ± 12,63 91,55 ± 12,34 99,53 ± 1,92
<0,05
8h
75,45 ± 14,09 91,68 ± 12,43 98,5 ± 5,23
<0,05
12h
72,05 ± 14,54 91,27 ± 12,55 98,98 ± 2,93
<0,05
16h
72,52 ± 14,53 89,37 ± 13,21 99,15 ± 2,12
<0,05
24h
72,53 ± 13,81 89,67 ± 12,78 98,88 ± 2,43
<0,05
32h
72,52 ± 15
87,48 ± 13,84 98,57 ± 2,7
<0,05
40h
73,37 ± 14,66 87,1 ± 13,72
98,35 ± 3,38
<0,05
48h
73,55 ± 14,17 86,63 ± 13,8
98,57 ± 2,28
<0,05

56h
72,92 ± 13,88 90,33 ± 11,57 98,85 ± 2,15
<0,05
64h
74,23 ± 13,89 91,67 ± 10,88 99,18 ± 2,38
<0,05
72h
75,53 ± 13,51 94 ± 9,56
99,05 ± 3,69
<0,05
(p:compare among three groups in each evaluated time)
Evaluate: The differance of the median A/D ratio among 3
groups in each evaluated time was statistically significant at p <0.05.
3.2.3. Amount of morphine titration
Table 3.10. The average amount of morphine needed to titrate
The average amount of
Group 1 Group 2 Group 3
p
morphine titration (mg)
60
58
52
n
± SD
Min ÷ Max

6,28±2,16 4,25±2,12 2,74±1,88 <0,05
2÷10
2÷8
2÷6

11
Evaluate: The average amount of morphine needed to titrate is
highest in group 1, next in group 2 and lowest in group 3.
3.2.4. Total consumption of postoperative pain-killer Morphine at times.
Table 3.11. The consumption of pain-killer Morphine after 72
postoperative hours(mg)
Time Value
Group 1
Group 2
Group 3
p
n
60
55
43
24h
X + SD 27,67 ± 12,89 14,6 ± 11,65 7,84 ± 6,14 <0,05
Min÷Max
1÷62
1÷40
1÷26
n
60
58
52
42,3
±
16,96

26
±
18,54
15,19
± 9,51 <0,05
48h
X + SD
Min÷Max
6÷77
2÷68
2÷42
n
60
58
52
72h
X + SD 53,07 ± 21,9 34,53 ± 22,39 19,69 ± 11,71 <0,05
Min÷Max
9÷95
2÷76
3÷46
Evaluate: Morphine was used within 24 hours, 48 hours and 72
hours: group 1 was highest, then group 2 and lowest group 3, The
difference among 3 groups in each evaluated time was statistically
significant at p <0.05.
Table 3.12. Number of patients used morphine 72 postoperative
hours.
Morphine (mg)
Group 1 Group 2 Group 3
p

0
0
2
8
<0,05
≤ 10
2
7
14
11 - 30
10
24
29
31 – 60
18
16
9
>60
30
11
0
Total
60
60
60
(p: compare among three groups)


12
Evaluate:

- Patients with a total dose of ≤10 mg were significantly
different in the three groups
- Patients with a total dose of >60 mg were significantly
different in the three groups
3.2.5. Visual Analog Scale (VAS) pain at postoperative times.
Table 3.13. VAS pain scores in postoperative static sense

Time

Group 1

Group 2

Group 3

n = 60

n = 60

n = 60

X + SD

X + SD

X + SD

p

0h

3,6 ± 2,39

2,17 ± 1,88

1,82 ± 1,23

<0,05

4h

3,42 ± 1,52

2,4 ± 1,12

1,83 ± 0,94

<0,05

8h

3,28 ± 1,39

2,15 ± 0,86

1,85 ± 0,95

<0,05

12h

3,25 ± 1,36

2,13 ± 0,87

1,85 ± 0,95

<0,05

16h

2,92 ± 1,15

2,13 ± 0,87

1,87 ± 0,98

<0,05

24h

3,07 ± 1,18

2,13 ± 0,77

2 ± 0,94

<0,05

32h

2,82 ± 0,91

2,13 ± 0,75

1,95 ± 0,93

<0,05

40h

2,57 ± 0,93

2,2 ± 0,75

2,08 ± 0,89

<0,05

48h

2,47 ± 0,93

2,15 ± 0,78

2,13 ± 0,96

<0,05

56h

2,35 ± 0,94

2,05 ± 0,7

1,88 ± 0,8

<0,05

64h

2,18 ± 0,77

2,12 ± 0,85

1,77 ± 0,74

<0,05

72h

2,13 ± 0,72

1,95 ± 0,72

1,7 ± 0,74

<0,05

(p:compare among three groups in each evaluated time)

Evaluate: VAS scores were highest in group 1, followed by group 2
and lowest in group 3. The difference among the three groups was
statistically significant at p<0.05.


13
Table 3.14. VAS pain scores in postoperative dynamic sense
Group 1
Group 2
Group 3
n
=
60
n
=
60
n = 60
Time
p
X + SD
X + SD
X + SD
0h
4,79 ± 2,26
3,29 ± 2,15
2,58 ± 1,54 <0,05
4h
4,57 ± 1,53
3,57 ± 1,33
2,77 ± 1,16 <0,05

8h
4,38 ± 1,39
3,27 ± 1,16
2,83 ± 1,17 <0,05
12h
4,42 ± 1,37
3,25 ± 1
2,9 ± 1,13
<0,05
16h
3,98 ± 1,24
3,25 ± 1,02
3,05 ± 1,14 <0,05
24h
4,23 ± 1,21
3,35 ± 0,9
3,17 ± 1,04 <0,05
32h
4,08 ± 1,18
3,32 ± 0,85
3,08 ± 1,03 <0,05
40h
3,73 ± 1,04
3,33 ± 0,82
3,08 ± 1,01 <0,05
48h
3,65 ± 0,99
3,33 ± 0,99
3,12 ± 1,08 <0,05
56h

3,47 ± 1,07
3,07 ± 0,84
2,85 ± 0,88 <0,05
64h
3,25 ± 0,88
3,15 ± 0,99
2,7 ± 0,85
<0,05
72h

<0,05
3,15 ± 0,88
2,93 ± 0,88
2,6 ± 0,91
(p:compare among three groups in each evaluated time)
Evaluate: VAS scores were highest in group 1, followed by group 2
and lowest in group 3. The difference among the three groups was
statistically significant at p <0.05.
3.2.6. Patient Satisfaction level
Table 3.15. Patient Satisfaction Level
Level
Group 1 Group 2 Group 3
Total
p
n = 60
n = 60
n = 60
n=180
Extra
P<0,05

19(31,7%) 27(45%) 37(61,7%) 83(46,1%)
satisfied
p1,2<0,05
Satisfied
21(35%) 20(33,3%) 11(18,3%) 52(28,9%) p1,3<0,05
Unsatisfied 20(33,3%) 13(21,7%) 12(20%) 45(25%) p2,3>0,05
(p:compare among three groups)


14
Evaluate:
- The level of extra-satisfaction and satisfaction of group 2 is
higher than that of group 1. This difference was statistically
significant at p <0.05.
- The level of extra-satisfaction and satisfaction of group 3 is
higher than that of group 1. This difference was statistically
significant at p <0.05.
3.3. Indicators for monitoring complications, undesirable effects
3.3.1. Indicators of complications.
Heart rate: table 3.16; Mean arterial pressure: table 3.17; Systolic
arterial pressure: table 3.18; diastolic arterial pressures: table 3.19;
Respiratory rate: table 3.20; SpO2: table 3.21.
Evaluate: The difference among Heart rate mean arterial pressure,
systolic arterial pressure, diastolic arterial pressures, respiratory rate
and SpO2 was statistically significant at p <0.05.
3.3.2. Measurement result of ventilation function
Table 3.22. Measurement result of peak flow (liter/min)
Group 1
Group 2
Group 3

n
=
60
n
=
60
n = 60
Time
p
X
X
X
( + SD)
( + SD)
( + SD)
Prenursery 402,5 ± 62,86 413,67 ± 55,36 415,75 ± 55,21 >0,05
24h
178,0 ± 77,24 227,83 ± 49,58 247,67 ± 53,31 <0,05
48h
216,33 ± 66,31 267,08 ± 42,79 309,33 ± 43,49 <0,05
72h
248,25 ± 64,26 303,17 ± 33,42 353,17 ± 41,76 <0,05
(p:compare among three groups)
Evaluate:
- The preoperative peak flow of three groups was not
significantly different with p> 0,05.
- The postoperative peak flow of three groups was lower than
preoperative peak flow. These difference is statistically
signification at p<0,05.

15
3.3.3. Arterial blood gas test results
Table 3.23. PaO2 result (mmHg)
Group 1
n = 60

Group 2
n = 60

X + SD
Min ÷Max

95,4 ± 11,86
67÷118

93,28 ± 14,23
63÷119

94,82 ± 12,15 >0,05
65÷133

X + SD
Min ÷Max
X + SD
Min ÷Max
X + SD
Min ÷Max

82,42 ± 11,65

64÷112

80,03 ± 13,13
64÷115

83,43 ± 10,56 >0,05
63÷103

81,25 ± 11,51
63÷113

78,98 ± 11,78
65÷107

82,75 ± 8,83 >0,05
65÷99

81,13 ± 13,67
63÷120

80,88 ± 11,36
65÷110

84,58 ± 8,33 >0,05
68÷100

Time

Value

Prenursery

24h
48h
72h

Group 3
n = 60

p

(p:compare among three groups in each evaluated time)
Evaluate:
- At preoperative point, the difference among 3 groups was
not statistically signification with p> 0,05.
- After each postoperative point, the difference among 3
groups is not statistically signification at p>0,05.
- After each postoperative point, 3 groups compared with
preoperative point was statistically significant at p <0.05.
Table 3.24. PaCO2 result (mmHg)
Time
Prenursery

24h
48h
72h

Value

X + SD

Min ÷Max
X + SD
Min ÷Max
X + SD
Min ÷Max
X + SD
Min ÷Max

Group 1
n = 60

Group 2
n = 60

Group 3
n = 60

p

36,32 ± 4,05 35,6 ± 3,88 36,83 ± 3,69 >0,05
27÷44
28÷44
29÷45
36,42 ± 3,86 35,78 ± 3,76 36,3 ± 3,67 >0,05
29÷45
28÷45
28÷44
36,63 ± 3,6 36,85 ± 3,68 36,65 ± 3,66 >0,05
27÷43
27÷43

28÷43
38,13 ± 4,25 38,32 ± 3,71 38,17 ± 3,54 >0,05
27÷44
29÷43
30÷45

Evaluate: PaCO2 among three groups was not different at the
time of study with p> 0.05.


16
3.3.4. Unexpected side-effects
Table 3.27. Unexpected side-effects
Group 1
n = 60
Vomiting
n (%)
and nausea
Level 0
34(56,7%)
Level 1
15(25%)
Level 2
10(16,7%)
Level 3
1(1,7%)
Rash and Itching
Level 0
43(71,7%)
Level 1

16(26,7%)
Level 2
1(1,7%)
Level 3
0(0%)
Sedation
SS0
21(35%)
SS1
34(56,7%)
SS2
5(8,3%)
SS3
0(0%)
Respiratory effects
R0
48(80%)
R1
11(18,3%)
R2
1(1,7%)
R3
0(0%)
Retention

Group 2
n = 60

Group 3
n = 60

Total
n = 180

n (%)

n (%)

n (%)

36(60%)
19(31,7%)
3(5%)
2(3,3%)

34(56,7%)
20(33,3%)
3(5%)
3(5%)

104(57,8%)
54(30%)
16(8,9%)
6(3,3%)

>0,05

38(63,3%)
21(35%)
0(0%)

1(1,7%)

37(61,7%)
23(38,3%)
0(0%)
0(0%)

118(65,6%)
60(33,3%)
1(0,6%)
1(0,6%)

>0,05

31(51,7%)
27(45%)
2(3,3%)
0(0%)

32(53,3%)
26(43,3%)
2(3,3%)
0(0%)

84(46,7%)
p<0,05
87(48,3%) p1,3<0,05
p1,2<0,05
9(5%)
p2,3>0,05

0(0%)

53(88,3%) 53(88,3%)
7(11,7%)
7(11,7%)
0(0%)
0(0%)
0(0%)
0(0%)
Undetermined

154(85,6%)
25(13,9%)
1(0,6%)
0(0%)

p

>0,05

(p:compare among three group; p1,3:compare group 1 with group 3;
P2,3: compare group 2 with group 3; p1,2: compare group 1 with
group 2).
Evaluate:
- The unexpected side-effects such as vomiting and nausea,
rash and itching and respiratory effects was not different among 3
groups with p> 0.05.
- Sedation SS1 and SS2 on group 1 differ from group 2 and
group 3. These difference is statistically signification at p<0,05.

17
Chapter 4
DISCUSSION
4.1. Studied patients’ general characteristics.
As shown in Table 3.1, our patients in terms of age, sex, height,
weight and ASA were not significantly different from p <0.05,
similar to An Thanh Cong, Bui Ngoc Chinh and Nguyen Toan
Thang. Thus, our research patients are homogeneous.
4.2. Evaluate the results of pain relief.
4.2.1. Time of first pain relief request.
As shown in Table 3.8, the PCA start-up time in group 1 was
0.52 ± 0.34 hours, group 2 was 5.0 ± 5.34 hours and group 3 was
17.42 ± 17.34 hours. Group 1 was the lowest, followed by group 2
and the highest group 3, the difference between the three groups was
statistically significant at p <0.05. This demonstrates that the
administration of morphine into the spinal cord prior to surgery is
effective in preventing postoperative pain. In the study of Khaled
Mohamed, the PCA initiation time of group 1 (morphine 0.2 mg)
was 0.5 ± 0.66 hours; group 2 (morphine 0.5 mg) was 22.13 ± 5.21
hours; Group 3 (morphine 1mg) was 30.83 ± 4.89 hours. According
to Hala (2016), postoperative analgesia in large tumors of the
abdomen, resulting in a 0.5 mg spinal morphine injection, the initial
initiation of analgesia was 22, 13 ± 5.2 hours. Our time lower than
Khaled Mohamed and Hala is due to the lower morphology of our
spinal cord. In the study of An Thanh Cong using 0.3 mg spinal
morphology before surgery in the cases of abdominal surgery, found
the time to start the need for pain first is 4.59 ± 3.97 hours and The
authors also found that preoperative morphine injection was effective
in preventing postoperative pain.

Thus, the time needed to relieve pain after surgery is not only
dependent on the type of surgery, anesthesia and analgesia during


18
and after surgery, but also depends on the time and dose of morphine
injection in the spinal cord.
4.2.2. A /D ratio and need for painkillers.
As shown in Table 3.9, the mean A/D ratio of group 1 in each
postoperative period was lower than in group 2 and group 3, and the
difference was significant at p <0.05, suggesting that with upper
abdominal surgery Simply applied IV-PCA-morphine, pain relief
may not meet the need, so it should be combined with other methods
(such as spinal morphine injection) to support postoperative pain.
The results showed a good analgesic effect when combining ITM
with IV-PCA-morphine, especially in group 3 using ITM 0.4mg
injection before surgery. Our results in groups 2 and 3 had a higher A
/ D ratio than Nguyen Toan Thang with 24 hours 71.6 ± 7.7%, after
48 hours 76.3 ± 6.2%. The reason for this is that in group 2 and
group 3 we have used spinal morphology before surgery so that
postoperative pain relief is better and the need for postoperative
analgesia decreases significantly at p<0,05.
4.2.3. The amount of triturative pain-killer morphine after
operation
PCA pain-killer method is essentially maintenance therapy, so
the patient should achieve adequate analgesia (equivalent to VAS
<4) before putting the PCA. The results in Table 3.10, group 1 were
the highest, followed by group 2 and lowest group 3, significant
differences were found between groups at p<0,05. In the An Thanh
Cong’s study, the preoperative ITM group was 3.27 ± 3.30 mg

(maximum of 10 mg and at least 2 mg) and in the S group was 7.29 ±
3.38 mg (4-18 mg) and the difference between the two groups was
statistically significant at p <0.05. Thus, our titrated dose in group 1
was equivalent to postoperative ITM (S), group 2 was equivalent to
preoperative (T) and lower group (ITM).


19
The postoperatively titrative morphine pain after surgery for
abdominal surgery in the IV-PCA group (morphine) which Nguyen
Toan Thang used was 6.6 ± 1.8 mg. Thus, the authors' titratable
morphine is comparable to our 1st group, but more so than in group 2
and group 3, the reason being that these two groups used spinal
morphine injected prior to anesthesia, because after surgery, the need
for pain will reduce. Thus, for effective postoperative analgesia,
pain-level alignment with VAS <4 goals, on the other hand the use of
intraoperative spinal morphine for effective postoperative
prophylaxis, reduces the need for pain medication when titrated.
4.2.4. The dose of morphine used for analgesic after surgery.
As shown in table 3.11: Morphine was used for analgesic within 72
hours: group 1 was highest, then group 2 and lowest group 3, The
difference among 3 groups in each evaluated time was statistically
significant at p <0.05. According to the study of An Thanh Cong with a
dose of 0.3mg spinal morphine has result: 24 hours after morphine
consumption in group T (injection before surgery) was 9.12 ± 3.21mg
less significant than when compared with the S group (postoperative
injection) was 12.76 ± 2.96 at p<0,05. Thus, with a dose of 0.3 mg
spinal morphine, morphine consumption was less than in group 2 and
higher than in group 3, indicating that the spinal morphine dose was
critical to the need for postoperative pain relief. especially the first 24

hours. According to Palmer CM, ITM combinations of IV-PCA
compared with the IV-PCA alone group showed that morphine
consumption in the IV-PCA group was eight times higher than that in
the combined group, Very low (0.075mg or 0.1mg). Similar to Junyeol
Bae (2017), postoperative treatment (ITM 300mcg with IV-PCA)
reduced morphine morphine (IV-PCA) [5 (IQR 3-15) mg vs. 17 IQR
11-24) mg, p = 0.001]. On the other hand, according to Nuri Deniz
(2013), when applying ITM, the need for tramadol decreased
significantly with p <0.01 compared with control group.


20
Thus, the morphine consumption after surgery depends mainly
on the ITM dose and the authors also concluded that after surgery the
patient must be controlled for pain for at least 72 hours.
4.3. Unexpected side-effects
As results in Table 3.27, the incidence of itching was 34.5%
(grade 1 and 2, 33.9%, grade 3, 0.6%), nausea and vomiting (grade 1
and 2 were 38.9%; 3.3%), the proportion of each group was similar
and there was no difference with p> 0.05. The mild effects of KMM
are usually cured without treatment. This is equivalent to the authors
Suhattaya and Hyun-Chang Kim.
The results of Table 3.27, the sedation of group 1 were the
highest, and there was a difference between group 1 versus group 2
and 3 at p<0,05. As a result of Luciana's combination therapy with
IV-PCA-morphine, plasma concentrations of morphine in the
combination group were 4.08 ng / mL, IV-PCA alone was 15.87 ng /
ml and significant difference at p<0,05. Justin Sangwook Ko, also
found that the sedation rate in the cohort was also lower than that of
the cohort. Thus, with the combination of ITM and IV-PCA, the rate

and level of sedation was lower than that of IV-PCA alone, which
proved to be safe and effective.
In our study (Table 3.16 to Table 3.21), hemodynamic and
respiratory outcomes were stable compared to preoperative and
postoperative time and no significant difference was observed with
p> 0, 05. This result is comparable to that of Khaled Mohamed and
Hamid Kayalha, that is, when combined with analgesic,
hemodynamics and respiration are completely stable.
As shown in Table 3.22, the postoperative peak flow was lower
than before surgery, postoperative peak peak 1, then group 2 and
highest in group 3, significant difference with p <0, 05. This result is
similar to Mason and Luciana. This showed that group 3 had good


21
pain relief, so patients took a deep breath and was more effective
than the other two groups.
Results of Table 3.23, PaO2 were lower than before surgery and
PaCO2 increased after surgery but no difference with p> 0.05. This
indirectly demonstrates that postoperative hemodynamically stable,
respiratory and also homeostatic stability in the body. Equivalent to
Elif Kupeli and Ferguson.
4.4. Patient’s satisfaction with pain relief methods
Satisfaction is one of the objective criteria for assessing the
analgesic effect on a patient, which is also an important factor
reflecting the health care services and technical expertise of a
medical facility. Satisfaction with postoperative analgesia in addition
to the two important factors of quality of analgesia and KMM effects
depends on the attitudes of the medical staff, the effectiveness of the
surgery and the patient care services after surgery. In fact, many

studies have demonstrated amazing effects of pain relief in
combination ITM with IV-PCA. The geometry of the Luciana's
Research, the result of the group of inclusive is better of a IV-PCAmorphine plain, morphine concentration in the equivalent plasma
over the p <0,05 (p = 0,029), lower morphine is less than with
p <0,05 (p = 0,037), the other performance rate KMM low than this
so with a single IV-PCA group, over it is satisfied at the contract
group. Similarly, Hyun-Chang Kim, also noted in the combo group,
had a good analgesic effect, reduced postoperative painkillers and
mild KMM effects, which was seen as increased satisfaction.
As shown in Table 3.15, the rate of satisfaction and satisfaction
in group 1 is 66.7%, group 2 is 78.3% and group 3 is 80%, there is
difference in satisfaction rate and very harmonious between group 1
and group 2 or group 3 at p<0,05. This shows that the ITM method
combines IV-PCA with good efficacy and is accepted by the


22
majority of patients even if the KMM effects are present. The best
analgesic effect in group 3, good psychological, good pain relief,
patients can mobilize early, early recovery and thereby shorten
treatment time. This result was comparable to Justin Sangwood Ko,
in the ITM group of 0.4 mg with IV-PCA satisfaction rate of 83 ±
11.3 (%), while the IV-PCA group was 57.5 ± 7.8 (%). In Viet Nam,
studies on intra-abdominal patients: Nguyen Trung Kien, found that
in the IV-PCA group, the satisfaction rate was 56.2%. Our overall
satisfaction rate was 75% higher than Nguyen Trung Kien because
we combined ITM with IV-PCA for better pain relief.
Thus, good postoperative care and analgesia, will make patients
not only more satisfied, but also give patients a comfortable mind,
can mobilize early, early recovery, avoid the Postoperative

complications and possible early discharge.
CONCLUSION
In a study of 180 abdominal surgery patients, postoperative pain
relief by intravenous morphin injection in combination with intravenous
self-management, at general anesthesia department, general hospital Bac
Ninh province. We draw some conclusions as follows:
1. About pain relief effects:
- Postoperative morphine injection in the lower spine at a dose
of 0.4 mg had a better postoperative analgesic effect and was more
effective than the 0.2 mg group and the control group.
- When injecting in subarachnoid space with morphine 0.4 mg
combined VAS point both at rest and at exercise was lower than for the
other two groups, the difference was statistically significant at p <0.05.
- Morphometric titration: At least ITM 0.4 mg was 2.74 ± 1.88
mg, then ITM 0.2 mg was 4.25 ± 2.12 mg and the highest control group
6.28 ± 2.16 mg, the difference was statistically significant with p <0.05.


23
- The dose of ITM 0.4 mg had the longest duration of
anesthesia required at 17.42 ± 17.34 h, followed by the ITM 0.2 mg
at 5.0 ± 5.34 h, the lowest was the control group 0.52 ± 0.34 hours,
difference was statistically significant at p <0.05.
- The average amount of morphine was used 72 hours
postoperative: in the ITM group the lowest 0.4 mg was 19.69 ± 11.71
mg, followed by the ITM group with 0.2 mg was 34.53 ± 22.39 mg
and the highest was the control group 53.07 ± 21.9 mg, the
difference was statistically significant with p <0.05.
- The A / D ratio in 72 hours of the ITM group was 0.4 mg, the
highest was 99.05 ± 3.69%, followed by the ITM group at 0.2 mg, 94

± 9.56% and the lowest at 75 , 53 ± 13.51%, the difference was
statistically significant with p <0.05.
- The common satisfaction rate in the ITM group of 0.4 mg was
highest at 80%, followed by ITM 0.2 mg at 78.3% and lowest at the
certification group at 66.7%, with the difference between control
group compared with the other two groups with p <0.05.
2. About the unwanted effects.
- Arterial blood pressure and postoperative blood pressure at
the time of study were stable within the normal range and the change
was not statistically significant at p> 0.05.
- Respiratory: The respiratory rate and pulmonary oxygen
saturation (SpO2) postoperatively at the time of study were also
stable within the normal range and the change was not statistically
significant with p> 0.05.
- The itching rate was 28.4% in the first group, 36.7% in the
second group and 38.3% in the third group. The difference was not
significant at p> 0.05.
- Nausea and vomiting rate: group 1 was 43.4%; Group 2 is 40%;
Group 3 was 43.3%, the difference was not significant with p> 0.05.