Morphine Versus Ketamine as Adjuvants in Paravertebral Blocks

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: local anesthetic-morphine
* Drug: local anesthetic-ketamine
* Drug: local anesthetic


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: local anesthetic and morphine group<br>paravertebral block with local anesthetic and morphine, followed by a continuous infusion of local anesthetic and morphine in the paravertebral space | Drug: local anesthetic-morphine<br>* 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<br>* Other names: local anesthetic and morphine administered paravertebrally;|
| Active Comparator: local anesthetic and ketamine group<br>paravertebral block with local anesthetic and ketamine, followed by a continuous infusion of local anesthetic and ketamine in the paravertebral space | Drug: local anesthetic-ketamine<br>* 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<br>* Other names: local anesthetic and ketamine administered paravertebrally;|
| Active Comparator: local anesthetic group<br>paravertebral block with local anesthetic only, followed by a continuous infusion of local anesthetic only in the paravertebral space | Drug: local anesthetic<br>* 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<br>* Other names: local anesthetic administered paravertebrally;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| morphine consumption in Post-Anesthesia Care Unit (PACU) | mg of morphine requested during patient PACU stay | 24 hours postoperatively | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| side effects postoperatively | patients will be monitored for side-effects of the administered agents postoperatively | 96 hours postoperatively | 
| 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 | 
| morphine requirement during surgery | dose of required morphine administered intraoperatively | intraoperatively | 
| 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 | 
| hospitalization time | duration of hospital stay after surgery in days | 7 days postoperatively | 
| 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 | 
| 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 |