Clinical trial NCT02734940
Conditions: Heart Diseases
Sponsor: Virginia Commonwealth University
Start date: 2016-07-11; Completion date: 2017-02-01
Enrollment: 3 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The investigators objective is to assess the effectiveness of an opioid sparing multimodal approach for enhancing the recovery in Cardiac Surgical patients. This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs.

Detailed description:
Cardiac surgery is associated with significant acute pain and a proportion of these patients will develop chronic pain.

Opioids are the main stay of analgesia in cardiac surgery because of the safer hemodynamic profile and sedation. However high dose narcotic use is associated with a variety of unwanted side effects prolonging postoperative recovery. There is growing evidence for the effectiveness of multimodal approach utilizing opiate sparing techniques for enhancing patient recovery following surgery. Early extubation has been associated with improved patient outcome and cost effectiveness in cardiac surgery. The investigators objective is to assess the effectiveness of an opioid sparing multimodal approach for enhancing the recovery in Cardiac Surgical patients. This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs. All of the above anesthetic drugs have opioid sparing effect in surgical Patients.

Dexmedetomidine use has been associated with decreased cardiac arrhythmias and improved neurological outcome in cardiac surgical patients. Ketamine has been linked with attenuation of postoperative cognitive dysfunction after cardiac surgery. Both intravenous lidocaine and spinal morphine have been shown to reduce opioid consumption in the perioperative period.

Arms: arm 1: Will receive injection of sterile saline (2cc) in lower back area (to minimize participant bias) and unrestricted amount of intraoperative opioids (fentanyl) at the discretion of the Anesthesiologist.

Both groups will receive General Anesthesia with volatile agents and single dose of iv Tylenol intraoperatively. Both groups of patients will be transported to Intensive Care Unit (ICU) on Dexmedetomidine (dose range 0.25 - 0.7 mcg/kg/hr). Dose titration is based on sedation level and hemodynamic goals set by Cardiac Anesthesiologist. arm 2: Will receive pre-operative spinal duramorph (4mcg/kg up to max dose of 300mcg), intra-operative intravenous (iv) infusion of Ketamine (0.4 mg/kg/hr), Lidocaine (20 mcg/kg/min) and Dexmedetomidine (0.25 mcg/kg/hr) started after induction of General Anesthesia and maintained through the Cardiopulmonary Bypass (CPB) towards the end of surgery. At this point all infusions will be turned off except Dexmedetomidine. The total intraoperative fentanyl dose will be limited to \<250mcg (or 3mcg/kg) and total midazolam to ≤ 2mg in the study group.
Interventions: intervention 1: Lidocaine intervention 2: Unrestricted Fentanyl intervention 3: Ketamine intervention 4: Precedex intervention 5: Duramorph
Intervention descriptions: intervention 1: This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs. intervention 2: No changes to current practices, using unlimited narcotic medications intraoperatively. intervention 3: This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs. intervention 4: This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs. intervention 5: This model would use a combination of intravenous (Dexmedetomidine, Ketamine, Lidocaine) and Spinal (Morphine) drugs.

Protocol documents:
Prot_SAP_000.pdf: 
Cardiac surgery is associated with significant acute pain and a proportion of 
these patients will develop chronic post sternotomy pain (Ref 1, 2)  
 
Opioids are the main stay of analgesia in cardiac surgery because of the safer 
hemodynamic profile and sedation (3). However high dose narcotic use is 
associated with a variety of unwanted side effects prolonging postoperative 
recovery. There is growing evidence for the effectiveness of multimodal 
approach utilizing opiate sparing techniques for enhancing patient recovery 
following surgery (4, 5, 6, 7). Early extubation has been associated with 
improved patient outcome and cost effectiveness in cardiac surgery (8, 9, 10). 
 
Our objective is to assess the effectiveness of an opioid sparing multimodal 
approach for enhancing the recovery in Cardiac Surgical patients. This model 
would use a combination of intravenous (Dexmedetomidine, Ketamine, 
Lidocaine) and Intrathecal (Morphine) drugs. 
 
All of the above anesthetic drugs have opioid sparing effect in surgical patients 
(11, 12,13).  
Dexmedetomidine use has been associated with decreased atrial arrhythmias 
and improved neurological outcome in cardiac surgical patients (14, 15).  
Ketamine has been linked with attenuation of postoperative cognitive 
dysfunction after cardiac surgery (16,17).  
Both intravenous lidocaine and intrathecal morphine has been shown to reduce 
narcotic consumption in the perioperative period (18, 19, 20) 
 
Hypotheses 
Primary hypothesis– multimodal analgesia would improve pain scores at 24hr 
post extubation  
 
Secondary hypothesis – multimodal approach would decrease opioid 
requirement in the first 24 hrs and enhance organ function recovery in the 
postoperative period 
 
Methods: 
Assuming mean pain score = 5 in control (21); test =3 (2 point difference); 
stdev=2.5; n = 26/group (56 total subjects assuming a 8% drop out rate).  
 
Prospective randomized trial with blinding at the stage of data analysis. 
 
Study group: will receive pre-operative intrathecal duramorph (4mcg/kg up to 
max dose of 300mcg), intra-operative infusion of Ketamine (0.4 mg/kg/hr), 
Lidocaine (20 mcg/kg/min) and Dexmedetomidine (0.25 mcg/kg/hr) started 
after induction and maintained through the CPB towards the end of surgery. At 
this point all infusions will be turned off except Dexmedetomidine (0.25 
mcg/kg/hr) which will be continued until the patient is extubated.  The total 
intraoperative fentanyl dose will be limited to <250mcg (or 3mcg/kg).  
Control group: will receive unrestricted amount of intraoperative opioids at the 
discretion of the Anesthesiologist 
 


Both groups will receive volatile agents and single dose of iv Tylenol 
intraoperatively and total midazolam to <2mg. 
Postoperatively both groups will receive PRN iv Tylenol and PRN iv Opioids.  
 
Inclusion criteria: Elective CABGs and/or Valve replacements 
  
Exclusion criteria: Re-do cardiac surgery, Acute endocarditis, Circulatory arrest, 
Emergent cases, Shock, LVADs, Transplantation, TAVR, contraindications for 
neuraxial including coagulopathy and Clopidogrel <7days, psychosis, known 
allergy to any of the study drugs, Preoperative liver dysfunction (AST/ALT > 2 
times normal) and Renal dysfunction (Cr > 2 mg/dL)  
 
Drop outs: If a patient in the study group appears to require more narcotics than 
250mcg of Fentanyl or midazolam >2mg, the patient will receive so and be 
dropped from the trial. Circumstances where the study protocol is not followed 
will lead to dropping out of those patients from the trial. 
 
 
Outcome Measures 
 
Primary outcomes - Pain score at 24hr after extubation 
Secondary outcomes - Postoperative opioid consumption (in first 24 hrs), 
Extubation time, ICU Length of stay, Delirium scores, Inotropic requirement, 
patient satisfaction scores (in first 24 hrs) 
 
Data collection  
 
(Post op - Pain scores, sedation, nausea, vomiting, itching, hemodynamics, and 
respiratory parameters will be measured at 2, 4, 8, 12, 24, 48 & 72 hrs post 
extubation) 
 
Pain scores – starting from 2hr post extubation, 11 point verbal rating scale, 
timing as above 
 
Opioid consumption – first 12 hrs, thereafter daily and total (iv and PO) 
 
Time of Extubation 
 
Lengths of stay:  ICU LOS, In-hospital LOS, 30 day readmission rate 
 
Delirium: CAM-ICU measured at 24, 48 and 72 hrs 
 
Inotrope requirement – Intraop, postoperative, total 
 
Patient satisfaction with pain management score: in the first 24 hrs measured at 
above intervals 
 
 
 


Complications: 
 
Cardiac complications: Atrial fibrillation on EKG, Arrhythmias requiring 
treatment, CHF (requiring 2 or more inotropes or use of IABP >24 hrs), MI (new 
Q waves in EKG or elevation of Troponins) 
 
Respiratory complications – Mechanical ventilation >24hrs, desaturations, 
reintubations 
 
Neurological complications – CVA, TIA, Post-operative delirium (measured by 
Delirium scores: CAM-ICU) 
 
Renal complications: acute increase in Creatinine >50% of baseline or the need 
for dialysis  
 
Gastrointestinal complications: Ileus (Measured as time of return of bowel 
function - POD to first oral liquid/flatus/stool) 
 
Infectious complications: Surgical site infections, other organ infection, sepsis 
 
Opioid related Side effects: Nausea, vomiting, pruritus, sedation (RASS score), 
urinary retention – measured as above 
 
Other Perioperative and postoperative data collected: Anesthesia time, CPB time, 
Cross clamp time, Fluids, PRBC, FFP, Platelets, Cryoppt, Urine output, Electrical 
defibrillation, No of defibrillations, Pacing, Time of ventilation weaning  
 
 
 
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