Clinical trial NCT04852484: Morphine Versus Ketamine as Adjuvants in Paravertebral Blocks
Official title: Morphine Versus Ketamine as Adjuvants in Ultrasound-guided Paravertebral Thoracic Blocks in Elective Thoracic Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Pain, Postoperative
Pain, Acute
Pain, Chronic
Pain, Neuropathic
Morphine
Ketamine
Analgesia
Lead sponsor: Aretaieion University Hospital
Sponsor class: OTHER
Collaborators: name: KAT General Hospital
First posted: 2021-04-21
Enrollment: 90
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: morphine consumption in the first 48 hours
timeFrame: 48 hours postoperatively
Secondary outcomes:
measure: morphine consumption in Post-Anesthesia Care Unit (PACU)
timeFrame: 24 hours postoperatively
measure: pain score on arrival to Post-Anesthesia Care Unit (PACU)
timeFrame: immediately postoperatively
measure: pain score 6 hours postoperatively
timeFrame: 6 hours postoperatively
measure: pain score 12 hours postoperatively
timeFrame: 12 hours postoperatively
measure: pain score 24 hours postoperatively
timeFrame: 24 hours postoperatively
measure: pain score 48 hours postoperatively
timeFrame: 48 hours postoperatively
measure: morphine consumption in the first 6 hours
timeFrame: 6 hours postoperatively
measure: morphine consumption in the first 12 hours
timeFrame: 12 hours postoperatively
measure: morphine consumption in the first 24 hours
timeFrame: 24 hours postoperatively
measure: side effects postoperatively
timeFrame: 96 hours postoperatively
measure: satisfaction from postoperative analgesia
timeFrame: 48 hours postoperatively
measure: morphine requirement during surgery
timeFrame: intraoperatively
measure: time to first request for analgesia
timeFrame: during stay in Post-Anesthesia Care Unit, 24 hours postoperatively
measure: hospitalization time
timeFrame: 7 days postoperatively
measure: incidence of chronic pain 3 months after surgery
timeFrame: 3 months after surgery
measure: incidence of chronic pain 6 months after surgery
timeFrame: 6 months after surgery
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Aretaieion University Hospital
city: Athens
country: Greece
facility: KAT General Hospital of Athens
Study officials:
affiliation: Aretaieion University Hospital
name: Kassiani Theodoraki, PhD, DESA
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.