BACKGROUND
The world's demand for open heart surgery as well as in Viet Nam is huge. Early extubation trend after cardiac
surgery was born based on balance anesthesia and selecting opioid with short duration of action. At the moment,
opioid dose is lower than before to meet the needs of the increasing number of open-heart surgery, to reduce the
cost of treatment and complications of mechanical ventilation, so the pain after surgery is very important
(Roediger, 2004). The effective pain management after heart surgery not only reduces the harmful effects on the
cardiovascular, respiratory, immune and coagulation but also helps patients recover faster, and is an indispensable
mental care. Effective treatment of acute pain may reduce the incidence of chronic pain, improve quality of life
(Wu, 2000; MacIntyre, 2010).
The discovery of opioid receptors in the dorsal horn opened a new pain control method. Morphine is less
lipophilic, has slow onset of action, reaching the maximum analgesic effect of the chest after lumbar injection in
4-7 hours, duration of effect lasts up to more than 24 hours so they're suitable for reducing postoperative pain.
Sufentanil is more lipophilic, has rapid onset of action, less than 5 minutes, the duration of effect lasting 2-6 hours
is suitable for pain in surgery. The meta-analysis study showed that morphine dose more than 0.3 mg had not
increased the analgesic effects but increased undesirable effects (Gehling, 2009). Bettex and Swenson used
intrathecal sufentanil of 50 mcg. The combination of morphine and intrathecal sufentanil may provide both intra-
and postoperative analgesia and help patients recover "no pain" and reduce chronic pain after surgery. In the
1
world, there are few studies with limited objects, no study has been done on this issue in Viet Nam. We conducted
this study with the following objectives:
2
1. To compare the intraoperative analgesia of single intrathecal morphine dose of 0.3 mg, intrathecal morphine
0.3 mg combined without or with sufentanil doses of 25 mcg or 35 mcg dose before induction in patients
receiving general anesthesia for open heart surgery.
2. To compare postoperative analgesia of the above methods.
3. To assess the effects on respiration and some undesirable effects of the methods above.
THE NEW FINDINGS OF THE THESIS
- Intrathecal sufentanil attenuates intraoperative fluctuations of mean blood pressure and heart rate, reduces
significantly intraoperative intravenous sufentanil consumption and the intrathecal sufentanil dose of 25 microgram
is appropriate to reduce pain during open heart surgery.
- The intrathecal morphine dose of 0.3 mg combined with or without sufentanil reduces postoperative pain,

longer than normal may cause depression. Postoperative pain if not treated effectively is the risk of chronic pain,
affecting the quality of life (Wu, 2002).
Activation of the sympathetic nervous system in response stress or inadequate analgesia may cause heart
rate, myocardial contractility increase and hypertension leading to increased myocardial oxygen consumption,
loss oxygen demand - supply balance, leading to an increased risk of myocardial ischemia or infarction that this
phenomenon peaks in the postoperative period.
Influence on respiratory function occurs in the first 24 hours following surgery and returns to the preoperative
values in 2 weeks thoracic or big abdominal surgery. Reduction is to 40% vital capacity after upper abdominal
surgery. Besides, There is postoperative increased coagulation status, immunosuppression and gastrointestinal
disorders.
1.2. Pain assessment
1.2.1. Intraoperative pain assessment
Analgesia (pain relief) amnesia (loss of memory) and immobilisation are the three major components of
anaesthesia. The perception of pain, and the need for analgesia are individual, and the monitoring of analgesia
is indirect and, in essence, of the moment. Under general anaesthesia, analgesia is continually influenced by
external stimuli and the administration of analgesic drugs, and cannot be really separated from anaesthesia: the
interaction between analgesia and anaesthesia is
5
inescapable. There is no stool or method to directly mesure intraoperative pain.
Autonomic reactions, such as tachycardia, hypertension, sweating and lacrimation, although non-specific,
having been proposed by Evans, using the PRST (blood Pressure, heart Rate, Sweating, Tears) score of
responsiveness are always regarded as signs of nociception or inadequate analgesia.
The authors used this score to assess intraoperative pain in their studies (Stomberg 2001; Turker, 2005;
Guignard, 2006).
1.2.2. Postoperative pain assessment
There are numerous scales to to assess postoperative pain. Currently, there are three types of scale used
clinically to assess postoperative pain (Viel, 2007).
Visual Analogue Scale (VAS): VAS is a reference scale in assessing the degree of pain and the effectiveness
of the treatment
Verbal Numeric Rating Scale (VNRS): Scale consists of a sequence of numbers, 0 corresponding to "no

Duration 2 - 6 hours 20,5 - 40 hours
1.3.3. Intrathecal opioid analgesia studies in cardiac surgery
In 1979, Wang reported the effect of intrathecal morphine in postoperative and cancer analgesia.
Mathews and Abrahams were the first ones who applied intrathecal morphine on the heart surgery patients.
The studies before 1990’s used high-dose intrathecal morphine. When early extubation was applied in
cardiac surgery, the authors have used lower doses of intrathecal morphine so as not to prolong the duration of
mechanical ventilation after surgery, the authors used doses from 6 - 10 mcg/kg or 0.5 mg (Jacobsohn, 2006;
Roediger, 2006; Yapici, 2008).
The recent meta-analysis studies recommended dose of intrathecal morphine ≤ 0.3 mg to reduce undesirable
effects.
In Vietnam, the study by Nguyen Phu Van combined 7 mcg/kg morphine with 1.5 mcg/kg fentanyl
intrathecally, Nguyen Van Minh, morphine 0.3 mg combined with sufentanil before induction for open heart
surgery shows the effective pain relief. Some authors used intrathecal sufentanil dose of 50 mcg. The randomized
prospective studies on combination of morphine and intrathecal sufentanil are needed.
8
CHAPTER 2
SUBJECTS AND METHODS
2.1. Subjects
2.1.1. Selection criteria: Patients were planned open heart surgery to repair or replace valves, to repair
congenital abnormalities; Early extubation prediction; Aged 18 - 60; ASA II - III; NYHA I - III; agree to
participate in research; No allergy to opioids.
2.1.2. Exclusion criteria: Patients with chronic diseases such as chronic lung diseases, liver failure, kidney
failure, systolic pulmonary artery pressure > 70 mmHg; previous heart surgery; history of addiction or opioid
dependence, taking pain medication before surgery; abnormal spinal anatomy; Local infection or sepsis at the
site of lumbar punctur; left ventricular ejection fraction (LVEF) < 50%; history of abnormal bleeding
prothrombin ratio < 70%, bleeding disorders, platelet count <100 x 109/l; EuroScore ≥ 6 points.
2.1.3. Removed from the study criteria: More than 3 attempts at needle insertion; Bleeding during insertions;
Complications of anesthesia, surgery; Ventilation over 24 hours due to other causes such as heart failure, low
cardiac output or the intra-aortic balloon counterpulsation; the renal replacement therapy after surgery.
2.2. Methods

3.1.1. General characteristics
Age, height, weight average and male/female ratio of the four study groups did not differ significantly (p >
0.05), the lowest age is 18 and the oldest 59 years old. Average weight was 49.4 ± 6.8 kg (p > 0.05), women in
each group dominated.
11
3.1.2. Anesthesia, cardiopulmonary bypass, surgery characteristics: early extubation anesthesia applied by
etomidate, sufentanil, vecuronium, isofluran, and propofol during cardiopulmonary bypass. Patients undergoing
valve replacement or repair surgery accounted for about 70% of patients in the group. The rest was atrial and
ventricular septal closure.
3.2. Intraoperative analgesia
3.2.1. Intraoperative sufentanil consumption and anesthesia time
*, † p < 0,05: Versus group 1 and 2
Figure 3.1. Intraoperative sufentanil consumption and anesthesia time
12
†
*
Anesthesia time did not differ significantly between the groups, the amount of intravenous sufentanil used in
surgery in group 1 and 2 higher groups 3 and 4 in a statistically significant manner (p < 0.05), butno statistically
significant difference between groups 1, 2 and 3, 4.
3.2.2. Intraoperative mean blood pressure and heart rate stability
13
†*
* p < 0,05: Group 3 versus group 1, 2;
† p < 0,05: Group 4 versus group 1, 2
Graph 3.1. Mean blood pressure at different surgical time
Mean blood pressure at skin incision in group intrathecal sufentanil (group 3 and 4) was lower than the
group without sufentanil (group 1 and 2) (p < 0.05).
Table 3.12. Patients with mean blood pressure increase
Group
Time

(n = 40)
Group 3
(n = 40)
Group 4
(n = 40)
P
Postintubation 22,5% 20% 12,5% 15% > 0,05
Post incision 35%* 32,5%) 15% 12,5% < 0,05
Poststernotomy 17,5% 12,5% 15% 10% > 0,05
* p < 0,05: Group 1 versus group 3 and 4
† p < 0,05: Group 2 versus group 3 and 4
The percentage of patients with heart rate increase after skin incision in intrathecal sufentanil groups ( 3, 4)
was lower than in no sufentanil groups (1, 2) in a statistically significant manner (p <0,05).
3.3. Postoperative analgesia
3.3.1. Postoperative morphine consumption
16
* p < 0,05: Versus group 2, 3 and 4
† p < 0,05: Versus group 3 and 4
*
*
*
*
*
*
*
Figure 3.4. Postoperative cumulative morphine consumption
High postoperative morphine group 1 than group 2, 3, 4 at all time points evaluated statistically
significant (p < 0.05). The amount of morphine in the second group higher in the first 4 hours of group 3 and
group 4 was statistically significant (p < 0.05).
Table 3.16. Intravenous morphine consumption (mg) day 1, 2, 3

3,2 7,6
±
4,1 < 0,05
48 - 72 hour 6,2
±
2,9 6,4
±
4,9 5,9
±
3,5 5,5
±
2,8 > 0,05
72 hours 37,8
±
12,5
*
22,9
±
11,5 19,7
±
5,2 19,6
±
7,6 < 0,05
* p < 0,05: Versus group 2, 3 and 4
17
*
*
†
Intravenous morphine consumption on the first and second day in group 1 was significantly higher than in group
2, 3 and 4 (p < 0.05), morphine consumption on the first day in group 2 higher than group3 and group 4, but the

0,96 < 0,05
H8 3,60
±
0,81* 2,13
±
0,76 2,20
±
0,79 2,15
±
0,74 < 0,05
H12 3,30
±
0,69* 2,25
±
0,81 2,03
±
0,66 2,23
±
0,70 < 0,05
H16 2,85
±
0,66* 2,23
±
0,70 2,03
±
0,66 2,23
±
0,69 < 0,05
H20 2,53
±

±
0,61 2,00
±
0,68 > 0,05
H42 2,20
±
0,65 2,20
±
0,65 2,18
±
0,75 2,15
±
0,77 > 0,05
H48 2,03
±
0,83 1,85
±
0,80 1,78
±
0,97 1,73
±
0,72 > 0,05
H60 1,80
±
0,72 1,93
±
0,83 1,78
±
0,80 1,70
±

3.4. Respiratory changes and other undesirable effects
21
Table 3.26. Mechanical ventilation and extubation time (hour)
Group
Time
Group 1
(n = 40)
Group 2
(n = 40)
Group 3
(n = 40)
Group 4
(n = 40)
p
Ventilation
(min - max)
4,98
±
3,55
(0,5 - 16,0)
4,26
±
2,29
(1,0 - 12,0)
4,66
±
2,46
(1,5 - 12,0)
4,54
±


Mechanical ventilation and extubation time did not differ significantly between groups (p > 0,05).
Table 3.32. Other undesirable effects
Group
Variable
Group 1
(n = 40)
Group 2
(n = 40)
Group 3
(n = 40)
Group 4
(n = 40)
P
Nausea 9 (22,5%) 10 (25%) 9 (22,5%) 8(20%) > 0,05
Vomiting 7 (17,5%) 5 (12,5%) 6(15%) 7 (17,5%) > 0,05
22
Pruritus 3 (7,5%) 2 (5%) 3 (7,5%) 4 (10%) > 0,05
Headache 2 (5%) 1 (2,5%) 2 (5%) 3 (7,5%) > 0,05
The difference of nausea, vomiting, pruritus, headache incidence between groups was not statistically
significant (p > 0.05). The rate of nausea incidence in the range of 20 - 22%, nausea 12.5 - 17.5%, pruritus 5 -
10%, headache 2.5 - 7.5%.
23
CHAPTER 4
DISCUSSION
4.1. Patient, anesthesia and surgery characteristics
4.1.1. General characteristics
Age, gender, height, weight, ASA and NYHA between groups were not significantly different, which
proves the identity of the participants in the study group.
4.1.2. Anesthesia, surgery and cardiopulmonary bypass characteristics