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... To
Trang 1The world's demand for open heart surgery as well as in Viet Nam is huge Early extubation trend after cardiacsurgery 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 thecost 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 thecardiovascular, respiratory, immune and coagulation but also helps patients recover faster, and is an indispensablemental 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 lesslipophilic, has slow onset of action, reaching the maximum analgesic effect of the chest after lumbar injection in4-7 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 notincreased the analgesic effects but increased undesirable effects (Gehling, 2009) Bettex and Swenson usedintrathecal 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
Trang 2world, there are few studies with limited objects, no study has been done on this issue in Viet Nam We conductedthis study with the following objectives:
Trang 31 To compare the intraoperative analgesia of single intrathecal morphine dose of 0.3 mg, intrathecal morphine0.3 mg combined without or with sufentanil doses of 25 mcg or 35 mcg dose before induction in patientsreceiving 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, reducessignificantly 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,manifested by the decrease in morphine consumption during the first 30 hours, VAS at rest during the first 16 hours andVAS at deep breath after extubation At this dose of intrathecal morphine, no changes in FEV1 and FVC, in theundesirable effects, in the duration of mechanical ventilation and extubation time are found
- The combination of intrathecal morphine and sufentanil before induction in open heart surgery provideseffective analgesia per and post-operatively
Layout of the thesis: The thesis has 117 pages
Chapter 2 Subjects and Methods 16 pages
Trang 4Chapter 3 Results 26 pages
References: 169 (16 Vietnamese, 136 English, 17 French)
CHAPTER 1 OVERVIEW 1.1 Postoperative pain affects the body
1.1.1 Factors affecting postoperative pain
Surgery is the main factor to decide the importance and duration of postoperative pain Thoracic and bigabdominal surgeries are the most painful In addition to surgical factors, cultural factors, the threshold of pain,previous pain experience, the emotional, cognitive, situations, behaviors and attitudes, age and gender alsoaffect the nociception (Serrie, 2002)
1.1.2 The impact of pain during and after surgery on the body
Trauma caused by the surgery causes neuroendocrine response, a combination of the local inflammatoryresponse (due to cytokine and leukotriene) and neuroendocrine metabolic factors causes catabolisme, increase incatabolic hormones such as catecholamines, cortisol, renin, aldosterone and glucagon, decrease in anabolichormones such as insulin and testosterone On the way to the cortex, pain impulses going to the hypothalamus
Trang 5trigger the behavior, emotion, mood changes and general feeling such as anxiety, sleep disorders When pain lastslonger 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 heartrate, 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 thisphenomenon peaks in the postoperative period
Influence on respiratory function occurs in the first 24 hours following surgery and returns to the preoperativevalues in 2 weeks thoracic or big abdominal surgery Reduction is to 40% vital capacity after upper abdominalsurgery Besides, There is postoperative increased coagulation status, immunosuppression and gastrointestinaldisorders
1.2 Pain assessment
1.2.1 Intraoperative pain assessment
Analgesia (pain relief) amnesia (loss of memory) and immobilisation are the three major components ofanaesthesia 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 byexternal stimuli and the administration of analgesic drugs, and cannot be really separated from anaesthesia: theinteraction between analgesia and anaesthesia is
Trang 6inescapable 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 ofresponsiveness 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 usedclinically 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 "nopain" and 10 being "unbearable pain" Patients were asked to evaluate and reply with the number corresponding
to their level of pain This assessment may not need tools VNRS scale is suitable for elderly patients
Categorical rating Scale (CRS): This scale consists of five numbers in ascending order of intensity of pain,each number corresponding to a description; 0 - no pain, 1 - mild, 2 - moderate, 3 - severe, 4 - unbearable pain.This method is a quick, simple, low rate of incorrect response This method is especially suitable for patientsunable to use VNRS or VAS scale (children and elderly)
Trang 7The authors divide the pain intensity into three degrees: low, VAS ≤ 3 cm, moderate, VAS 3 - 7 cm andsevere VAS > 7 cm.
At the recovery room, patients with limited oral expression, the VAS is the appropriate scale to assess painand evaluate treatment response and morphine is used if VAS ≥ 4 cm VAS score ≤ 3 cm at rest and ≤ 5 cm atmovement are defined as effective pain relief
1.3 Intrathecal opioid for pain management after cardiac surgery
1.3.1 Pain in cardiac surgery
In cardiac surgery, the pain is caused by skin incision in the chest, sternotomy, field extension, themediastinal dissection, vascular canuyn, the subxiphoid drain and blood in pleural cavity This painful stimuli areconveyed mainly by the intercostal nerves from T1 to T11, innervating the chest wall, by diaphragmaticinnervating diaphragmatic pleura and by X nerve innervating mediastinal pleura In addition, the cutaneousbranches from the cervical superficial plexus coming down to innervate skin upper part of the chest wall (Morgan,2005) The neural axial (spinal, epidural) and paravertebral techniques may not affect the diaphragmatic nerve, thevagus nerve, which is also the basis for the application of multimodal analgesic method after thoraco-cardiacsurgery
1.3.2 Intrathecal opioid analgesia
Table 1.5 Pharmacodynamic parameters of intrathecal morphine and sufentanil
Trang 8Peak action < 30 min 4 - 7 hoursDuration 2 - 6 hours 20,5 - 40 hours1.3.3 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 incardiac surgery, the authors have used lower doses of intrathecal morphine so as not to prolong the duration ofmechanical 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 undesirableeffects
In Vietnam, the study by Nguyen Phu Van combined 7 mcg/kg morphine with 1.5 mcg/kg fentanylintrathecally, Nguyen Van Minh, morphine 0.3 mg combined with sufentanil before induction for open heartsurgery shows the effective pain relief Some authors used intrathecal sufentanil dose of 50 mcg The randomizedprospective studies on combination of morphine and intrathecal sufentanil are needed
Trang 9CHAPTER 2 SUBJECTS AND METHODS 2.1 Subjects
2.1.1 Selection criteria: Patients were planned open heart surgery to repair or replace valves, to repaircongenital abnormalities; Early extubation prediction; Aged 18 - 60; ASA II - III; NYHA I - III; agree toparticipate in research; No allergy to opioids
2.1.2 Exclusion criteria: Patients with chronic diseases such as chronic lung diseases, liver failure, kidneyfailure, systolic pulmonary artery pressure > 70 mmHg; previous heart surgery; history of addiction or opioiddependence, taking pain medication before surgery; abnormal spinal anatomy; Local infection or sepsis at thesite 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
2.2.1 Study Design
Trang 10Prospective, clinical intervention, single-blind, randomized study was conducted in the Department ofthoraco-cardiovascular Anesthesiology, Cardiovascular Center, Hue Central Hospital
From 01/2010 to 07/2012
2.2.2 The sample size
Applying the formula for calculating the sample size, we selected a group of 40 patients
Group 1 - control group, did not use intrathecal opioids
Group 2: Group injected intrathecal morphine 0.3 mg
Group 3: intrathecal morphine 0.3 mg plus sufentanil 25 mcg
Group 4: intrathecal morphine 0.3 mg plus sufentanil 35 mcg
2.2.3 The main criteria for assessment
2.2.3.1 Intraoperative analgesia: Intravenous sufentanil consumption; Intraoperative hemodynamic stability:Mean blood pressure, heart rate changes at intubation and the most painful time in surgery, the percentage ofpatients with mean blood pressure and heart rate increase
2.2.3.2 Postoperative analgesia: Postoperative intravenous morphine consumption by PCA; Visual analoguescale (VAS) during the first 3 days after surgery at rest and at deep breath; FVC, FEV1; Hemodynamicstability: Mean blood pressure, heart rate after extubation and during the first 3 days
Trang 112.2.3.3 The effects on respiration and undesirable effects: Duration of mechanical ventilation and extubationtime; Respiratory rate, SpO2 and blood gases after extubation and the first day after surgery; Respiratory rate,SpO2 in the first 3 days after surgery (oxygen via nasal inhalation of 4 l/min); Undesirable effects: Sedation,nausea, vomiting, pruritus, urinary retention, respiratory depression, epidural hematoma.
2.2.4 Procedure: Selecting randomly the patients to the group, setting up monitoring, inserting spinal needle 27 G(B/braun company) (groups 2, 3, 4), using medications, depending on the group Anesthesia, cardiopulmonarybypass and postoperative care follow the same protocol in the four groups
CHAPTER 3 RESULTS
Data processing of 160 patients with open heart surgery, the following results are obtained
3.1 Anesthesia and surgery characteristics
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 ineach group dominated
Trang 123.1.2 Anesthesia, cardiopulmonary bypass, surgery characteristics: early extubation anesthesia applied byetomidate, sufentanil, vecuronium, isofluran, and propofol during cardiopulmonary bypass Patients undergoingvalve replacement or repair surgery accounted for about 70% of patients in the group The rest was atrial andventricular septal closure.
3.2 Intraoperative analgesia
3.2.1 Intraoperative sufentanil consumption and anesthesia time
*, † p < 0,05: Versus group 1 and 2Figure 3.1 Intraoperative sufentanil consumption and anesthesia time
†
*
Trang 13Anesthesia time did not differ significantly between the groups, the amount of intravenous sufentanil used insurgery in group 1 and 2 higher groups 3 and 4 in a statistically significant manner (p < 0.05), butnostatistically significant difference between groups 1, 2 and 3, 4
3.2.2 Intraoperative mean blood pressure and heart rate stability
Post-intubation Pre-incision Post-incision sternotomyPre- sternotomy
Post-Group 1 Group 2 Group 3 Group 4
†
*
Trang 14* 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 timeMean blood pressure at skin incision in group intrathecal sufentanil (group 3 and 4) was lower than thegroup without sufentanil (group 1 and 2) (p < 0.05)
Table 3.12 Patients with mean blood pressure increaseGroup
Time
Group 1(n = 40)
Group 2(n = 40)
Group 3(n = 40)
Group 4(n = 40) pPostintubation 32,5% 30% 22,5% 25% > 0,05
Post incision 55% 52,5% 25%* 27,5%† < 0,05
Poststernotomy 17,5% 15% 10% 7,5% > 0,05
*, † p < 0,05: Versus group 1, 2
Trang 15The percentage of patients with mean blood pressure increase after incision in intrathecal sufentanil groups(groups 3, 4) was significantly lower than in no sufentanil groups (group 1, 2) (p < 0.05).
* p < 0,05: Group 3 versus group 1, 2;
† p < 0,05: Group 4 versus group 1, 2
Graph 3.2 Heart rate at the most painful time points Heart rate at skin incision in group intrathecal sufentanil (group 3, 4) was lower than the group withoutsufentanil (group 1, 2) (p < 0.05)
Post-Pre-incision
Post-incision
sternomy
Pre- sternomy
Post-Group 1 Group 2 Group 3 Group 4
†
*
Trang 16Table 3.14 The percentage of patients with heart rate increaseGroup
Time
Group 1(n = 40)
Group 2(n = 40)
Group 3(n = 40)
Group 4(n = 40) PPostintubation 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 4The 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)
Group 1 Group 2 Group 3 Group 4
* p < 0,05: Versus group 2, 3 and 4
† p < 0,05: Versus group 3 and 4
Trang 17Figure 3.4 Postoperative cumulative morphine consumptionHigh postoperative morphine group 1 than group 2, 3, 4 at all time points evaluated statisticallysignificant (p < 0.05) The amount of morphine in the second group higher in the first 4 hours of group 3 andgroup 4 was statistically significant (p < 0.05).
Table 3.16 Intravenous morphine consumption (mg) day 1, 2, 3Group
Intervals
Group 1(n = 40)
Group 2(n = 40)
Group 3 (n = 40)
Group 4(n = 40) P