Multimodal Analgesia Versus Traditional Opiate Based Analgesia

Multimodal Analgesia Versus Traditional Opiate Based Analgesia and Cardiac Surgery Outcome

Pain after cardiac surgery can be moderate to severe with incisions to the sternum and lower extremities, and also the placement of chest tubes. Postoperative pain may contribute to delirium, stress, myocardial oxygen demand supply imbalance, etc. Traditionally postoperative pain management after cardiac surgery has been based on opiate analgesics. However, opiates have many deleterious side effects including nausea/vomiting, ileus, bladder dysfunction, and respiratory depression, which substantially influence patient recovery and may delay discharge after surgery.

The current study is designed to evaluate if an opiate sparing multimodal regimen of tylenol, gabapentin, ketamine, lidocaine and dexmedetomidine provided better analgesic effect (pain score, postoperative PCA opioid dose), less side effects (PONV) and improved cardiac surgery outcome (delirium, a-fib, AKI, dysglycemia) compared to a traditional fentanyl and hydromorphine regimen after cardiac surgery. Additionally, it aims to investigate if the benefit of multimodal regimen is achieved by combination of all drugs or all drugs except dexmedetomodine by introducing third group of study patients who will be randomized to all interventions except saline placebo instead of dexmedetomodine infusion.

Study Overview

• Status: Unknown
• Conditions: Cardiac Surgery
• Intervention / Treatment: Drug: Ketamine; Drug: Lidocaine; Drug: Dexmedetomidine; Drug: Gabapentin; Drug: Tylenol; Drug: Gabapentin Pill; Drug: Tylenol Pill

• Study Type: Interventional
• Enrollment (Anticipated): 225
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA II-III Grade
• BMI 18-31kg/m2
• Adult patients presenting for on-pump cardiac surgery through median sternotomy

Exclusion Criteria:

• Cardiac surgery without sternotomy
• emergency surgery
• h/o allergy to any of the medications in the research protocol
• hepatic disease with elevated liver enzymes (preoperative SGPT and SGOT elevated to 1.5 times maximum normal value)
• pregnancy
• unable to give consent
• preoperative mental disorders

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: T; traditional opioid based regimen
Active Comparator: MD; multimodal group with dexmedetomidine	Drug: Ketamine; Intraoperatively use. 0.5 mg/kg with induction bolus, followed by 5mcg/kg/min infusion after induction. Continue up to 1 hour prior to extubation. maximum total dose 3mg/kg.; Drug: Lidocaine; Intraoperatively use. start lidocaine infusion at 2mg/min after anesthesia induction, and continue up to 1 hour prior to extubation.; Drug: Dexmedetomidine; Intraoperatively use. start dexmedetomidine infusion at 0.5 mcg/kg/min after anesthesia induction, and continue up to 1 hour prior to extubation.; Drug: Gabapentin; Postoperatively use. 300 mg PO TID starting POD1 until discharge Use lower dose for >65y or if patient having significant sedation/dizziness; Drug: Tylenol; Postoperatively use. 1000 mg PO Q8hr starting POD0 until discharge (max 3000 mg in 24hrs) Reduce to 650 mg PO Q6h if <70kg; Drug: Gabapentin Pill; Pre-operatively use. 300mg PO up to 1 hour before OR time Reduce to 100 mg PO in patients >65y or with GFR < 50 Consider dose reduction in patients with sleep apnea; Drug: Tylenol Pill; Pre-operatively use. 1000 mg PO up to 1 hour before OR time Reduce to 650 mg PO if <70kg Don't use if h/o liver disease or anticipated liver injury (right heart failure, pulmonary hypertension, etc leading to systemic venous congestion)
Placebo Comparator: M; multimodal with saline placebo	Drug: Ketamine; Intraoperatively use. 0.5 mg/kg with induction bolus, followed by 5mcg/kg/min infusion after induction. Continue up to 1 hour prior to extubation. maximum total dose 3mg/kg.; Drug: Lidocaine; Intraoperatively use. start lidocaine infusion at 2mg/min after anesthesia induction, and continue up to 1 hour prior to extubation.; Drug: Gabapentin; Postoperatively use. 300 mg PO TID starting POD1 until discharge Use lower dose for >65y or if patient having significant sedation/dizziness; Drug: Tylenol; Postoperatively use. 1000 mg PO Q8hr starting POD0 until discharge (max 3000 mg in 24hrs) Reduce to 650 mg PO Q6h if <70kg; Drug: Gabapentin Pill; Pre-operatively use. 300mg PO up to 1 hour before OR time Reduce to 100 mg PO in patients >65y or with GFR < 50 Consider dose reduction in patients with sleep apnea; Drug: Tylenol Pill; Pre-operatively use. 1000 mg PO up to 1 hour before OR time Reduce to 650 mg PO if <70kg Don't use if h/o liver disease or anticipated liver injury (right heart failure, pulmonary hypertension, etc leading to systemic venous congestion)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of analgesic effect	Evaluation of analgesic effect by Visual Analogue Scale	Within 3 months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional opioid consumption	assessed by daily sufentanil PCIA dose	Within 3 days after operation
postoperative delirium	evaluated by CAM-ICU criteria	Within 3 days after operation

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Investigators: Principal Investigator: Lin Jin, PHD, Fudan University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2018
• Primary Completion (Anticipated): May 1, 2019
• Study Completion (Anticipated): December 30, 2019

Study Registration Dates

• First Submitted: April 12, 2018
• First Submitted That Met QC Criteria: April 27, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): May 11, 2018
• Last Update Submitted That Met QC Criteria: April 27, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Antipyretics; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Hypnotics and Sedatives; Anti-Anxiety Agents; Anticonvulsants; Anesthetics, Local; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Antimanic Agents; Ketamine; Dexmedetomidine; Lidocaine; Gabapentin; Acetaminophen
• Other Study ID Numbers: MAvsTOBA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No