Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT02825056 |
| Other study ID # |
NK/2676/DM/397 |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
Early Phase 1
|
| First received |
June 19, 2016 |
| Last updated |
July 1, 2016 |
| Start date |
July 2016 |
| Est. completion date |
June 2017 |
Study information
| Verified date |
July 2016 |
| Source |
Postgraduate Institute of Medical Education and Research |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is paucity of literature on the effects of intrathecal morphine on the postoperative
hemodynamics in the cardiac-surgical patients.We planned this study to compare the
post-operative hemodynamic effects (particularly the incidence of vasoplegia in the two study
groups) and outcome of combined general anesthesia + high spinal block, with or without
intrathecal morphine in patients undergoing cardiac-surgical procedures in our set up.
Description:
Introduction Currently various strategies are being developed for fast tracking in cardiac
anaesthesia that includes use of shorter acting opioids , combined thoracic epidural or high
spinal anaesthesia with GA, awake cardiac surgery along with normothermic or mild hypothermic
cardiopulmonary bypass (CPB) and off pump surgeries. The aim of fast tracking is early
extubation, early mobilization, decreased length of ICU and overall hospital stay, not only
to reduce costs and human resource utilisation but also to reduce the postoperative morbidity
and mortality while enhancing the quality of health care.
Traditionally high dose opioid anaesthesia has been used to abolish this stress response,
however, some studies have shown that this technique of anaesthesia only relatively minimizes
the stress response and does not completely block it.
Regional anaesthesia in the form of thoracic epidural anaesthesia (TEA) alone (awake cardiac
anaesthesia) or combined with general anaesthesia (GA) has been used in cardiac surgical
patients. One of the useful alternatives to TEA would be high spinal anaesthesia as the risk
of haematoma associated with this procedure is much less than the epidural in cardiac
surgical patients. The use of spinal anaesthesia in cardiac patients, particularly patients
with stenotic valvular lesions has been for long viewed with much apprehension, primarily due
to the perceived risk of hypotension as a result of sympatholysis. However, various studies
using high spinal up to T1 level have proved such apprehensions to be invalid in the setting
of cardiac surgery where patients are monitored intensively with invasive monitors and the
hypotension managed at the earliest with the use of small aliquots or continuous infusion of
vasoactive agents such as phenylephrine, norepinephrine, epinephrine, mephentermine as per
the requirements of underlying cardiac lesion.
Although thoracic epidural anaesthesia has been studied and practiced, there is paucity of
literature on the effects of intrathecal morphine on the postoperative hemodynamics in the
cardiac-surgical patients.Hence, the investigators planned this study to compare the
post-operative hemodynamic effects and outcome of combined light general anesthesia + high
spinal block, with or without intrathecal morphine in patients undergoing cardiac-surgical
procedures in our set up.
Null Hypothesis Addition of intrathecal morphine in high spinal anesthesia does not affect
postoperative hemodynamics.
Aims and objectives A. Primary end point
1. To look for incidence of Vasoplegia (defined by MAP < 60mmHg with cardiac index >
2.2L/min/m2 or requirement of vasopressors to maintain the MAP > 60 mmHg in presence of
cardiac index > 2.2L/min/m2) in the study groups.
B. Secondary end point 1. Mechanical ventilation duration, time to extubation, requirement of
postoperative analgesia based on VAS, spirometry performance and incidence of awareness under
anesthesia.
Materials and Methods After obtaining ethics committee approval and informed written consent
of the patients, this study will be conducted in 60 adult patients with valvular heart
disease and coronary artery disease of New York Heart Association class II-III aged 18 to 60
years undergoing elective cardiac surgery. All patients will receive their usual
cardiovascular medications except angiotensin - converting enzyme inhibitors, digoxin and
diuretics on the morning of surgery as per our institutional practice. On arrival inside
operating room and after securing peripheral venous access with 16 G catheter, continuous
monitoring will be instituted that will include 5-lead electrocardiogram, pulse oximetry,
end-tidal capnometry, and invasive arterial blood pressure through a 20-G catheter inserted
in a radial artery. A central venous catheter will be inserted before induction of
anaesthesia under local anaesthesia and mild sedation with midazolam 0.04mg/kg body weight.
ANESTHESIA PROTOCOL:
Spinal anesthesia - All study patients will receive spinal anaesthesia prior to induction of
GA. Patient will be placed in lateral position, parts painted and draped under strict aseptic
precautions. Heavy bupivacaine 40 mg will be administered in all patients at the level of
L2-3 or L3-4 intervertebral space in the Spinal group. Heavy bupivacaine (Anawin heavy 0.5%,
Neon laboratories LTD, Thane, India) 40 mg mixed with preservative free morphine sulphate 250
mcg (VERMOR 15,Verve health care limited, Delhi, India) will be given in L2-3 or L3-4 space
to all patients in the Opioid group. The patient will be then turned to supine position and a
30 degree Trendelenburg position will be maintained till sensory loss to a level of T1 is
achieved. The sensory level will be assessed by loss of sensation to cold stimulation (Spirit
swab), all the while administering 100% oxygen through a breathing system. Patient will
receive 100% oxygen by mask for 10 minutes and in case of respiratory depression will be
gently assisted in respiration. Once desired level is achieved, GA in both groups will be
induced with midazolam 1-2 mg, ketamine 20-30 mg plus lignocaine 2mg/kg and propofol 20-40 mg
titrated to maintain hemodynamics and to loss of eyelash reflex. Inj. Vecuronium bromide
0.1mg/kg will be used as muscle relaxant to facilitate tracheal intubation and lignocaine
spray (LOX 10% spray, Neon laboratories LTD, Thane, India) will be used over vocal cords
prior to intubation to blunt the sympathetic stimulation.
Subsequent anaesthesia will be maintained in all the patients in both the groups with
isoflurane inhalation to maintain BIS values between 40-60 or end-tidal isoflurane of 1-MAC.
Patients will be mechanically ventilated with 50% oxygen-air mixture and minute ventilation
will be adjusted to achieve normocapnia till sternotomy. Vasoactive drug phenylephrine
100ug/ml will be prepared and boluses (1-2 ug/kg) given to all patients to maintain MAP > 60
mmHg (stable haemodynamics) on CPB. Normothermic CPB will be carried in all cases. Hematocrit
of > 24% will be maintained in all patients on CPB. Total dose of phenylephrine received
before and on bypass will be recorded in both the groups. Anesthesia and hemodynamics on
cardiopulmonary bypass (CPB) will be maintained with isoflurane in oxygen-air mixture
connected to the CPB machine and anesthesia post CPB period will be maintained with
isoflurane in oxygen-air mixture. All patients will receive fentanyl 1ug/kg atleast 5-minutes
before sternal closure.
Baseline pre-CPB TEE evaluation of LVOT diameter and LVOT area in ME-AV long axis view
(average of three readings) will be recorded and used as a standard for subsequent
calculation of cardiac output and cardiac index post-CPB and in ICU. Intra-operative TEE will
be used to calculate the LVOT VTI (mean of three values) either in the transgastric long axis
view or the deep transgastric long axis view (which ever gives better alignment) 15 minutes
after separation from CPB and before transfer to ICU with simultaneous recording of systemic
pressures (SBP,DBP and MAP). Vasoplegia in our study will be defined by mean arterial blood
pressure < 60 mmHg with cardiac index ≥ 2.2 l/min/m2 or requirement for vasopressors to
maintain MAP > 60 mmHg in presence of cardiac index ≥ 2.2 l/min/m2 65.
The mean of three reading taken five minutes apart before anaesthesia induction (prior to
administration of spinal anaesthesia in spinal group) in both groups will be taken as
baseline values.
Ionotropes will be used according to the underlying cardiac pathology. A combination of
milrinone and norepinephrine will be used in patients with right ventricular dysfunction and
pulmonary arterial hypertension ; a combination of dobutamine and norepinephrine/epinephrine
will be used in patients with LV dysfunction ; in patients with biventricular dysfunction
milrinone and norepinephrine/epinephrine will be used and low dose norepinephrine will be
used in patients with diastolic dysfunction. Total dose of vasoactive drugs used in the
postoperative period in the both the groups will be recorded in first 48 hours and analysed.
In the ICU, following parameters will be recorded:
- Hemodynamic parameters (HR, SBP, DBP, MAP, CVP) will be recorded 4 hourly for 48 hours.
- Additional hemodynamic readings will be recorded at any point hemodynamic instability
(defined by MAP < 60 mmHg).
- LVOT VTI will be measured in apical 5-chamber view and used to calculate SV. LVOT VTI
derived will be multiplied with LVOT area (derived already on TEE) to calculate SV which
will be multiplied by the HR of the patient at that point of time to calculate CO and CI
every 4 hourly for 48 hours.
- Uniform rescue analgesia will be given to all the patients as per ICU protocol when the
value on the Visual analog scale (VAS) is more than.
. Postoperative Hb (gm/dl)
- Presence of residual sensory and motor blockade and occurrence of new onset motor
blockade
- Duration of ventilation and time to extubation
- Record of complications (nausea,vomiting,pruritis) if any.
- Intra-operative awareness.
- Post-operative spirometry.
Statistical analysis
This will be taken as an open end, pilot feasibility study, that is, more of subjects will be
added if the desired number (30) in each group is reached within less than the stipulated
time period for thesis desertion submission.
Statistical analysis will be done using the SPSS software. All the parametric data such as
hemodynamic parameters, time to extubation, and time to transfer to step down post
anaesthesia care unit will be analysed using Unpaired t-tests. Chi-square (χ2) test will be
used to analyse the requirement of vasoactive agents and the requirement of rescue analgesia.
Residual sensory and motor blockade will be analysed using Mann-Whitney test
Proforma
Baseline demographics :Age(in years)/Sex (M/F)/Height (in meters)/Weight(in Kg`s)/BSA(m2)/BMI
(kg/m2).
Diagnosis :
Preoperative transthoracic echo findings:
LV EDD- LV ESD- LVEF-
Other findings:
Systemic illness:
Medication:
Laboratory results:
Hb: TLC: DLC: Platelet count:
PT: PTI: aPTT: INR:
Blood urea: Serum creatinine:
Serum bilirubin: SGOT/SGPT:
Time of spinal drug administration:
Time of tracheal intubation:
Time of incision:
Time of sternotomy:
LVOT Diameter = LVOT Area = Post-CPB LVEF TEMPERATURE MAINTAINED ON CPB = BASE EXCESS ON CPB
= CPB TIME = AXC TIME = PONV = Y/N Hemodynamic Parameters: including HR,BP,CVP,LVOT
VTI,CO,CI,LVEF and vasopressor dose will be recorded 4 hourly unto 48 hours in postoperative
period.
Intravenous drugs given:All anesthetic drugs and ionotropes required to maintain stable
hemodynamics during surgical procedure shall be recorded.
Requirement of vasoactive agent: over 48 hours in postoperative period shall be recorded
Time of shifting to PACU:
Postoperative parameters:
Requirement of analgesia- total dose of opioid and or non-opioid analgesics used over
postoperative 48 hours shall be recorded Residual sensory blockade(Modified Bromage score):
shall be recorded 4 hourly for 48 hours in postoperative period Residual motor blockade
(Modified Bromage score):shall be recorded 4 hourly for 48 hours in postoperative period New
onset motor blockade- Duration of ventilation- Time of extubation- Time of transfer to step
down ICU- No of ICU hours- Post- extubation Volume achieved on incentive spirometry
1 hour 24 hours Awareness under Anaesthesia using Structured Brice and Bauer questionnaire
shall also be recorded.
