Morphine Versus Ketamine as Adjuvants in Paravertebral Blocks (Annie-Dimitr)

Aretaieion University Hospital

Status: Active, not recruiting

Conditions: Morphine; Pain, Acute; Ketamine; Pain, Postoperative; Pain, Chronic; Pain, Neuropathic; Analgesia

Treatments: Drug: local anesthetic; Drug: local anesthetic-ketamine; Drug: local anesthetic-morphine

Study type: Interventional

Funder types: Other

Identifiers

NCT04852484

307/26-03-2021

Details and patient eligibility

About

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

Full 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.

Enrollment: 90 estimated patients

Sex: All

Ages: 25 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

90 participants in 3 patient groups

local anesthetic and morphine group

Active Comparator group

Description:

paravertebral block with local anesthetic and morphine, followed by a continuous infusion of local anesthetic and morphine in the paravertebral space

Treatment:

Drug: local anesthetic-morphine

local anesthetic and ketamine group

Active Comparator group

Description:

paravertebral block with local anesthetic and ketamine, followed by a continuous infusion of local anesthetic and ketamine in the paravertebral space

Treatment:

Drug: local anesthetic-ketamine

local anesthetic group

Active Comparator group

Description:

paravertebral block with local anesthetic only, followed by a continuous infusion of local anesthetic only in the paravertebral space

Treatment:

Drug: local anesthetic