Article Type : Research Article
Authors : Banerjee A, SenDasgupta C and Goswami A
Keywords : Continuous infusion; levobupivacain; Clonidine; Median sternotomy
The
International Association for the Study of Pain (IASP) defines pain as an
unpleasant sensory and emotional experience associated with actual or potential
tissue damage, or described in terms of such damage. Most of the cardiac
surgeries are performed through median sternotomy, it is associated with a
significant amount of pain which patients describe as burning, aching or
shooting unrelieved perioperative pain translates into uninhibited surgical
stress response [1]. This may have detrimental effects on major organ systems
which may lead to substantial postoperative morbidity and adverse hemodynamic,
metabolic, immunologic, and hemostatic alterations [2-4]. There may be intense
pain after cardiac surgery. It originates from many sources, such as the incision
site, from intraoperative tissue retraction and dissection, vascular
cannulation sites, vein-harvesting sites and site of insertion of chest tubes
[5]. Adequate pain relief is essential because it results in better patient
comfort, decreased morbidity and reduced duration of stay in hospital and hence
reduced costs. Patient satisfaction has a direct link to adequate pain relief.
It is an essential element that influences clinical activity of
Anaesthesiologists. Fast tracking in cardiac surgery has led to adoption of
multimodal analgesia, in order to maximize analgesia and limit the side-effects
of any one particular method of pain relief. Various methods have been used for
pain relief after cardiac surgery. They include intravenous opioids, NSAIDs, intrathecal
and epidural techniques, nerve blocks and local anaesthetic infiltration [6].
Opioids are the commonest agents used for alleviating postoperative pain after
cardiac surgery. They are usually delivered using either patient controlled
analgesia or nurse controlled analgesia. However, opioids are notorious for
causing sedation and respiratory depression, causing delayed tracheal extubation. They have other adverse effects such as nausea, vomiting,
constipation and urinary
retention. Limiting their use results in better adherence to fast-track
discharge protocols [7]. Non-steroidal analgesics have been shown to be effective in reducing pain after median sternotomy
[8]. However, they are sparingly
used in patients after cardiac surgery. These groups of patients
commonly have associated co-morbidities such as diabetes, hypertension and underlying nephropathy. Non-steroidal analgesics are known to cause renal dysfunction and bleeding
tendencies.Cyclooxygenase-2 (COX-2) inhibitors possess analgesic (opioid-sparing)
effects and lack deleterious effects on coagulation (in contrast with nonselective nonsteroidal anti-inflammatory drugs), because they spare the constitutive COX 1 system
that confers protective effect. However,
current evidence does not suggest
that COX-2 inhibitors provide major advantages over traditional
NSAIDs. Furthermore, potential links between this class of drugs and
cardiovascular complications, sternal wound infections, and thromboembolic
complications need to be fully
evaluated [9]. Paracetamol infusion
as an adjunct to opioids
has shown equivocal results in treating
postoperative pain after cardiac surgery [10]. Central neuraxial block using opioids
and local anaesthetic infusions have proved
to be efficacious in reducing postoperative pain after cardiac surgery
[11]. Placement of needle and catheters in the presence of systemic
anticoagulation requires strict vigilance. Other adverse effects associated with neuraxial blockade are
hypotension, bradycardia, local site infection, catheter breakage etc. Continuous wound catheters have
consistently demonstrated analgesic efficacy as evident by reduced opioid requirement and decreased pain scores after all types of surgery [12]. Studies of local
anaesthetic infusion at the wound site after median sternotomy have produced variable
results Paul F white and his colleagues demonstrated significantly
reduced pain scores and earlier return
of bowel sounds and removal
of urinary catheter
in patients receiving
local infusion of 0.25%
and 0.5% bupivacaine for 48 hours postoperatively after cardiac surgery [13].
The present study is designed to find the efficacy of local anaesthetic infusion at the wound site in reducing postoperative pain measured by the amount of rescue opioid required
, its effect on duration
of tracheal intubation, patient mobilization, discharge
from ICU, patient satisfaction , bio-chemical
markers of stress response and development of chronic pain.
This double-blinded,
randomized, prospective study was carried out in the Department of
Cardiothoracic and Vascular Surgery of a tertiary care hospital. After
obtaining institutional ethics committee approval and written informed consent
from the patients, 84 patients of age group 18 to 75 years posted for cardiac
surgery via median sternotomy were included in the study. Patients with
Modified Parsonnet Score > 10, known allergy to local anaesthetics,
significant liver disease, severe renal dysfunction, any neurological
dysfunction or insulin dependent diabetes mellitus or unable to comprehend
Visual Analogue Scale were excluded from the study. Patients with active
bacterial infection or those in whom the duration of postoperative positive
pressure ventilation was more than 24 hours were also excluded from the study.
All the patients underwent a thorough preoperative examination before surgery
and all of them were explained meticulously regarding the procedure and were
familiarised with the Visual 1 Analogue Scale. After patient was shifted to
operation theatre, five lead ECG, non-invasive blood pressure and saturation
probe were attached. An arterial line was inserted in the left radial artery
under local anesthesia and invasive arterial blood pressure monitoring
commenced from then on. Induction of anaesthesia was done using intravenous
injections of fentanyl (5- 10 mcg/kg), midazolam (0.05-0.1 mg/kg) and sleep
dose of thiopentone sodium (0.5-1 mg/kg). Endotracheal intubation was
facilitated using IV inj rocuronium (1 mg/kg). After securing the airway, the
patient was adequately positioned and a central venous catheter was inserted in
right internal jugular vein under strict aseptic precaution. Continuous
monitoring included 5 lead ECG, pulse oximetry, capnography, invasive arterial
blood pressure, central venous pressure, urine output, temperature. At the end
of surgery, two epidural catheters were inserted at either end of sternotomy
wound just after sternal closure with all aseptic precautions, by the surgeon.
One catheter was placed in the sub-fascial plane just above the sternal wound
after apposition of sternal wires. A second epidural catheter was placed just
below the skin incision. The wound was closed and the patients were shifted to
ICU. The patients were randomized into two groups by a computer generated
randomization chart. Group I received 0.25% levobupivacaine at a rate of 2ml/
hour through each of the catheters. Group II received 0.25% levobupivacaine and
2 mcg/kg of clonidine at 2 ml per hour through each of the catheters. All the
study drugs and syringes were prepared by a second anaesthesiologist blinded to
study design. After shifting the patients to ICU, infusions were started after
negative aspiration of blood and were delivered through the conventional
bacterial filter present in the epidural kit. The infusions were delivered
through an elastomeric pump set at 2ml/ hour. There was no provision for bolus
dose because such doses would not be effective and would increase the chance of
local anaesthetic toxicity. The mechanism of this modality of analgesia is
presumed to be by the action 1 of cumulative dose of local anaesthetic on the
nerves carrying afferent pain impulses from incision site. All the infusions
were continued till 48 hours after shifting to the Intensive Care Unit. In the
ICU, hemodynamic parameters including heart rate, invasive blood pressure,
oxygen saturation, central venous pressure were monitored continuously for a
period of 48 hours. Pain scores using Visual Analogue scale were noted 5 at 6,
12, 24, 36 and 48 hours after surgery [14]. The patients who were on ventilator
support at the time of recording of VAS, were asked to nod their head at the
number on a scale of 1 to 10, which indicated the severity of their pain. Sedation
score using Ramsay Sedation Scale were noted 8 at 6,12,24,36 and 48 hours after
tracheal extubating [15]. Levels of blood glucose, lactate and cortisol were
measured just after shifting the patient to ICU, at 24 hours and at 48 hours of
stay in ICU. The time required for first rescue analgesic was noted. The
patients were administered morphine at a dose of 0.05mg/ kg intravenously, when
the VAS score was more than or equal to 4. It was delivered using a PCA pump.
No background infusion was used to preclude accumulation of active metabolite
Morphine 6 glucuronide. The lock out interval between the boluses was 30
minutes and a maximum of four doses were allowed over a period of 24 hours.
Overall patient satisfaction as described on a 100-point scale with a score of
1 meaning very dissatisfied and 100 meaning fully satisfied. Incidence of
chronic pain 3 months after surgery were noted. During discharge, the patients
were asked to attend the Anaesthesia clinic at the end of three months. They
were interrogated about any burning or shooting pain at the site of sternal
wound.
Out of 84 patient’s one patient in group I and two patients in group II had sternal wound dehiscence. There was accidental catheter removal in one patient in group I. One patient was lost to follow up at the end of three months. There was no significant difference in between the two groups in terms of their age (p=0.44), sex, modified Parsonnet score (p=0.18) 6, type of surgery, baseline parameters, aortic cross clamp times (p=0.25) and cardiopulmonary bypass duration (p=0.52). There were no significant arrhythmias or hypotension during 48 hours of infusion [16] (Figures 1 and 2) (Table 1).
Table 1: Demographic Profile.
Pre
OP |
Group
1 n = |
Group
2 n = 2 |
Group 1 Mean + SD |
Group 2 Mean + SD | |
Age |
42 |
42 |
38.64 + 15.62 |
41.12 + 13.71 | |
Sex |
Male |
25 |
23 |
|
|
Female |
17 |
19 | |||
Weight |
42 |
41 |
50.36 + 11.15 |
49.1 + 8.29 | |
Modified Personnet Score |
42 |
42 |
8.33 + 1.2 |
8.62 + 0.62 | |
Surgery |
OPCAB |
9 |
6 |
|
|
MVR |
6 |
7 |
|
| |
AVR |
7 |
5 |
|
| |
LA Myxoma |
2 |
1 |
|
| |
RA Myxoma |
0 |
1 |
|
| |
DVR |
3 |
6 |
|
| |
ASD |
6 |
6 |
|
| |
VSD |
3 |
4 |
|
| |
On Pump CABG |
0 |
1 |
|
| |
Ebsteins Anomaly |
0 |
1 |
|
| |
DCRV |
1 |
1 |
|
| |
Pericardiectomy |
0 |
1 |
|
| |
ACxcl Time § |
42 |
41 |
37.7 + 31.94 |
46.6 + 37.51 |
|
CPB Time ¶ |
42 |
42 |
50.38 + 39.35 |
56.24 + 42.95 |
|
Baseline HR ? |
42 |
42 |
88.71 + 21.5 |
99 + 14.92 |
|
Baseline MAP ? |
42 |
42 |
93.29 + 15.8 |
107.74 + 16.89 |
|
Baseline SpO2 |
42 |
42 |
98.19 + 1.27 |
97.26 + 1.38 |
|
Baseline RR ? |
42 |
42 |
16.76 + 2.65 |
20.29 + 2.89 |
|
§ Aortic
Cross Clamp Time;
¶ Cardiopulmonary Bypass
; ? Heart Rate
; ? Mean Arterial Pressure ; ˜ Respiratory Rate |
Table 2: Total postoperative morphine requirement (in mg).
|
Group |
Mean |
Std Dev |
Minimum |
Maximum |
Median |
p-value |
DOSE MORPHINE |
Group I |
11.2262 |
1.7455 |
8.0000 |
15.0000 |
11.0000 |
<0.0001 |
Group II |
4.8714 |
2.4111 |
0.0000 |
10.0000 |
5.0000 | ||
Total
dose of Morphine required in 48 hours ( in mg) |
Pain scores were
significantly less in group II as compared to group I during the postoperative
6 hours (3.5 ± 0.9 vs 5.3 ± 1.6,
p< 0.0001),12 hours (3.4 ± 0.63 vs
4.8 ± 0.9, p<0.0001) and 24 hours (2.7 ± 0.7 vs 4 ± 0.8, p<0.0001). Thenceforth the intensity of pain as
measured by VAS decreased and was found to be similar between the two groups
(Figure 3) (Table 2).
Figure 1: Heart rate variation in the postoperative period.
Figure 2: Mean arterial pressure variation in postoperative period.
Figure 3: Pain Scores in the postoperative period.
The bio chemical markers for stress response at the end of 48 hours were significantly lower in group II than in group I. Serum lactate was 1.79 ± 0.7 mmol/L in group I vs 1.38 ± 0.61 in group II (p=0.034). Serum cortisol in group I was 30.7310 ± 15.6662µg/dl vs 22.07 ± 9.04 (p=0.003) (Figure 4).
Figure 4: Serum biochemical markers (Cortisol and Lactate) in postoperative period.
The patient satisfaction
score was found to be significantly higher in group II than in group I (78.3 ±
8.46 vs 72.52 ± 5.220, p=0.0003). One
patient in group I was lost to follow up. Two (n=41) patients developed chronic
pain in group I (7.14%) 1 whereas 3/42 (7.32%) patients developed chronic pain
in group II. None of the patients had 2 catheter breakage, wound dehiscence or
sternal wound infection requiring re-exploration.
Pain after cardiac surgery remains a challenge
for cardiac anaesthesiologists. Postoperative pain is an important concern
after cardiac surgery because it is associated with adverse hemodynamic changes
which may be detrimental in these patients. Undertreated severe pain may have
physiological consequences increasing the stress response to surgery, seen as a
cascade of endocrine-metabolic and inflammatory events that ultimately may
contribute to organ dysfunction, morbidity, increased hospital stays and
mortality. The pain often causes the patient to remain immobile, thus becoming vulnerable
to deep venous thrombosis, pulmonary atelectasis, and muscle wasting and
urinary retention. Besides, restlessness caused by severe pain may contribute
to postoperative hypoxemia. The peripheral neural activation, together with
central neuroplastic changes, associated with postoperative pain may in some
patients continue into a chronic pain state [17-19]. Also, unrelieved pain
after cardiac surgery is associated with major organ dysfunction. Patients
undergoing surgery are usually petrified of postoperative pain and it is listed
as one of the main concerns of the patients before surgery [20]. Pain is
neglected in the postoperative period especially because of inadequate
reporting and recording. There are reservations about administering pain medication
especially opioids because of fear of development of physical dependence,
tolerance and side-effects. Pain after cardiac surgery may be multifactorial in
origin. The commonest cause’s incisions, intraoperative tissue retraction and
dissection, multiple intravascular cannulations and chest tube insertion sites.
The most excruciating pain is felt on the first two postoperative days. The
intensity of pain decreases as the distance from the operation increases [21].
The nature of pain also changes from sharp localized pain to dull
osteo-articular pain. Efficacy of a continuous wound catheters delivering local
anaesthetics has been documented in different group of surgical patients [22].
Similar studies conducted in cardiac surgery, have shown variable results. The
results of our study are in accordance to those of Paul F White and his
colleagues who used continuous infusion of 0.25% and 0.5% of bupivacaine and
found decreased pain scores and better patient satisfaction scores in the
postoperative period. They did not find any significant decrease in the
duration of tracheal intubation and ICU stay [13]. Their study on 37 patients
undergoing cardiac surgery. They used a continuous infusion of ropivacaine for
a period of 4 days and reported a persistently low pain scores (0-3), faster
recovery time and lesser duration of hospital stay [23]. In a similar study
conducted a series of intercostal blocks along with continuous infusion of
presternal 0.25% bupivacaine was used. They showed lower morphine consumption
over 48 hours (8.6 ± 0.94 vs 18.83 ±
3.4 mg, p<0.02), earlier time for extubation and better respiratory
parameters [24]. Levobupi vacaine is L enantiomer of upivacaine with better
safety profile. The effect of parasternal block and local anesthetic infiltration
with levobupivacaine after cardiac surgery with desflurane was evaluated.
Patients in the levobupivacaine group used significantly less morphine in the
first 4 h after surgery (20.8 +/-6.2 mg versus 33.2 +/- 10.9 mg in the placebo
group; P=0.013); they also had better oxygenation at the time of extubation.
The incidence of chronic pain was found to be similar in the two groups.
Petsikas and his colleagues found that unrelieved pain after cardiac surgery
may lead to chronic post sternotomy pain in as high as 30% of cases [25,26]. In
the present study it was found to be around 8% which is significantly less.
However, since this was studied as a secondary outcome measure, larger
population groups need to be considered to establish the actual reduction in incidence
of chronic pain. Thus, in this study we found that the intensity of pain was
significantly lower in patients receiving levobupivacaine plus clonidine
(p<0.0001) which led to a significantly lower requirement of morphine
(p<0.0001) required in postoperative period. These patients also had lower
levels of biochemical markers of stress as evident by significantly lower
lactate (p=0.034) and cortisol levels (p<0.0003). Also, they were more
satisfied with their postoperative care (p<0.0003). However, the duration of
tracheal intubation and time required for first mobilization with assistance
were similar in both groups. One limitation of the study was not being able to
measure blood levobupivacaine levels as high performance liquid chromatography
for estimation was not available.
Subcutaneous and
subfascial infiltration of 0.25% levobupivacaine and 2 µg/ ml of clonidine
produced lesser pain scores, decreased postoperative opioid requirements ,
decreased surgical stress response and led to better patient satisfaction in
cardiac surgical patients Clonidine was found to have analgesic sparing effects
when combined with levobupivacaine. It is a simple method which can be easily
used and is not associated with any adverse effect.