Morphine Versus Ketamine as Adjuvants in Paravertebral Blocks

Pain, Postoperative Clinical Trial

— Annie-Dimitr  

Official title:

Morphine Versus Ketamine as Adjuvants in Ultrasound-guided Paravertebral Thoracic Blocks in Elective Thoracic Surgery

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04852484
• Other study ID #: 307/26-03-2021
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 16, 2021
• Est. completion date: April 16, 2024

Study information

• Verified date: May 2023
• Source: Aretaieion University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study will be to compare the effects of morphine versus ketamine when they are used as adjuvants to the local anesthetic in paravertebral nerve blocks performed with the aid of ultrasound. Furthermore, a group of local anesthetic without an adjuvant, will also be compared to the two groups

Description:

Elective thoracotomies are usually performed for removal of pathological masses in the mediastinum, lung parenchyma and upper gastrointestinal system. They are considered to be painful operations, related to both acute and chronic pain (post- thoracotomy pain syndrome), the latter lasting for a minimum period of 2 months. Post-operative thoracic pain is associated often with diaphragmatic dysfunction, which can also lead to atelectasis and pneumonia and post-operative pulmonary complications in general. Several techniques have been tried in order to minimize such events. Thoracic epidural analgesia, intravenous analgesia, intercostal blocks, local infiltration of local anesthetics by the surgeon are some of them. Paravertebral thoracic blocks have become increasingly popular in recent years since they are less likely to cause neurologic complications than thoracic epidural analgesia. Moreover, bleeding disorders, and use of anti-coagulant and anti- thrombotic medications, which are considered as contraindications to an epidural procedure, are not strict contraindications in the performance of paravertebral blocks, especially when they are performed under ultrasonographic guidance. Ropivacaine and Levobupivacaine are the most popular local anesthetics that have been used. Moreover, several adjuvants have been added to them in order to enhance the effects of those blocks. Dexamethasone, Morphine, Dexmedetomidine, Clonidine, Ketamine, Magnesium Sulphate are some of them. Results are variable. The rationale behind adjuvants used to enhance effects of local anesthetics is the fact that some seem to act directly in the spinal cord receptors and the central nervous system. The effect of morphine on the dorsal horns of the spinal cord has been extensively studied in the past. Due to its limited lipophilicity, it is assumed that administering the specific drug to the paravertebral space could lead to its transfer and action on the dorsal horns. On the other hand, the action of ketamine seems to be by blocking N-Methyl-D-Aspartate (NMDA) receptors in the spinal cord. It is also considered to have an effect on voltage sensitive Ca2+ channels, opioid receptors, and monoaminergic receptors. Therefore, it is considered overall to affect nociception. Overall, it is assumed that morphine might have an effect on the dorsal horns of the spinal cord, and ketamine on NMDA receptors at "higher pain centers". It is also assumed that there will be some degree of systemic absorption due to the rich vascular supply of the specific area. The investigators aim to compare the effects of those two when they are used as adjuvants to the local anesthetic in paravertebral nerve blocks performed with the aid of ultrasound. Furthermore, a group of local anesthetic without an adjuvant, will also be compared.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: April 16, 2024
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

Inclusion Criteria:

• patients undergoing elective thoracotomy for any cause
• American Society of Anesthesiologists class I-III (ASA I-III)

Exclusion Criteria:

• known allergy to local anesthetic
• local inflammation
• paravertebral tumor
• severe respiratory distress ( breathing dependence on accessory muscles)
• severe spinal deformities
• severe ipsilateral diaphragmatic paresis
• morbid obesity (BMI>35 kg/m2)
• blood coagulation disorders
• known contraindication for administration of ketamine or morphine
• psychiatric disorders
• severe cardiovascular disease
• systematic use of opioids due to chronic pain
• renal or hepatic failure
• patients who refuse to participate

Related Conditions & MeSH terms

• Acute Pain
• Analgesia
• Chronic Pain
• Ketamine
• Morphine
• Neuralgia
• Pain, Acute
• Pain, Chronic
• Pain, Neuropathic
• Pain, Postoperative

Intervention

Drug:
• local anesthetic-morphine
Before the operation, 19 mL of 0.5% Ropivacaine + 2 mg of morphine (20 mL in total) will be injected in the paravertebral space. Afterwards, there will be a pump of 500 ml of 0.2 % ropivacaine + 6 mg of morphine connected to the catheter after the end of the surgery, administered continuously at a rate of 10 mL/hr
• local anesthetic-ketamine
Before the operation, 19 mL of 0.5% Ropivacaine + 50 mg of ketamine (20 mL in total) will be injected in the paravertebral space. Afterwards, there will be a pump of 500 ml of 0.2 % ropivacaine + 200 mg of ketamine connected to the catheter after the end of the surgery, administered continuously at a rate of 10 mL/hr
• local anesthetic
Before the operation, 19 mL of 0.5% Ropivacaine + 1 mL of normal saline (20 mL in total) will be injected in the paravertebral space. Afterwards, there will be a pump of 500 ml of 0.2 % ropivacaine connected to the catheter after the end of the surgery, administered continuously at a rate of 10 mL/hr

Locations

Country	Name	City	State
Greece	Aretaieion University Hospital	Athens
Greece	KAT General Hospital of Athens	Athens

Sponsors (2)

Lead Sponsor	Collaborator
Aretaieion University Hospital	KAT General Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (7)

Ahmed MJ, Ur Rehman A, Arshad RM, Amjad MWA, Khan Z, Furqan A. Efficacy of Dexmedetomidine vs Morphine as an Adjunct in a Paravertebral Block with Bupivacaine in Postoperative Analgesia Following Modified Radical Mastectomy. Cureus. 2020 May 22;12(5):e8231. doi: 10.7759/cureus.8231. — View Citation

D'Ercole F, Arora H, Kumar PA. Paravertebral Block for Thoracic Surgery. J Cardiothorac Vasc Anesth. 2018 Apr;32(2):915-927. doi: 10.1053/j.jvca.2017.10.003. Epub 2017 Oct 4. — View Citation

El Mourad MB, Amer AF. Effects of adding dexamethasone or ketamine to bupivacaine for ultrasound-guided thoracic paravertebral block in patients undergoing modified radical mastectomy: A prospective randomized controlled study. Indian J Anaesth. 2018 Apr;62(4):285-291. doi: 10.4103/ija.IJA_791_17. — View Citation

Gerner P. Postthoracotomy pain management problems. Anesthesiol Clin. 2008 Jun;26(2):355-67, vii. doi: 10.1016/j.anclin.2008.01.007. — View Citation

Kathirvel S, Sadhasivam S, Saxena A, Kannan TR, Ganjoo P. Effects of intrathecal ketamine added to bupivacaine for spinal anaesthesia. Anaesthesia. 2000 Sep;55(9):899-904. doi: 10.1046/j.1365-2044.2000.01472.x. — View Citation

Mao Y, Zuo Y, Mei B, Chen L, Liu X, Zhang Z, Gu E. Efficacy of perineural dexamethasone with ropivacaine in thoracic paravertebral block for postoperative analgesia in elective thoracotomy: a randomized, double-blind, placebo-controlled trial. J Pain Res. 2018 Sep 11;11:1811-1819. doi: 10.2147/JPR.S164225. eCollection 2018. — View Citation

Maruyama Y, Shimoji K, Shimizu H, Sato Y, Kuribayashi H, Kaieda R. Effects of morphine of human spinal cord and peripheral nervous activities. Pain. 1980 Feb;8(1):63-73. doi: 10.1016/0304-3959(80)90090-1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	morphine consumption in the first 48 hours	patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 48 hours postoperatively	48 hours postoperatively
Secondary	morphine consumption in Post-Anesthesia Care Unit (PACU)	mg of morphine requested during patient PACU stay	24 hours postoperatively
Secondary	pain score on arrival to Post-Anesthesia Care Unit (PACU)	pain score by the use of Numeric Rating Scale (NRS) on arrival to PACU, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	immediately postoperatively
Secondary	pain score 6 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 6 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	6 hours postoperatively
Secondary	pain score 12 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 12 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	12 hours postoperatively
Secondary	pain score 24 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 24 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	24 hours postoperatively
Secondary	pain score 48 hours postoperatively	pain score by the use of Numeric Rating Scale (NRS) 48 hours postoperatively, ranging from 0 to 10, where 0 means "no pain" and 10 means "worst pain imaginable"	48 hours postoperatively
Secondary	morphine consumption in the first 6 hours	patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 6 hours postoperatively	6 hours postoperatively
Secondary	morphine consumption in the first 12 hours	patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 12 hours postoperatively	12 hours postoperatively
Secondary	morphine consumption in the first 24 hours	patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 24 hours postoperatively	24 hours postoperatively
Secondary	side effects postoperatively	patients will be monitored for side-effects of the administered agents postoperatively	96 hours postoperatively
Secondary	satisfaction from postoperative analgesia	satisfaction from postoperative analgesia on a four-point Likert scale with 1 marked as minimal satisfaction and 4 as maximal satisfaction	48 hours postoperatively
Secondary	morphine requirement during surgery	dose of required morphine administered intraoperatively	intraoperatively
Secondary	time to first request for analgesia	the time for the first patient request for analgesia will be noted	during stay in Post-Anesthesia Care Unit, 24 hours postoperatively
Secondary	hospitalization time	duration of hospital stay after surgery in days	7 days postoperatively
Secondary	incidence of chronic pain 3 months after surgery	occurrence of chronic pain at the site of the operation 3 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	3 months after surgery
Secondary	incidence of chronic pain 6 months after surgery	occurrence of chronic pain at the site of the operation 6 months after surgery, with the use of the Numeric Rating Scale (NRS), at rest and during movement	6 months after surgery