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

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

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

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.

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

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

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

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

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

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

patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 48 hours postoperatively

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"

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"

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"

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"

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"

patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 6 hours postoperatively

patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 12 hours postoperatively

patients will be followed for cumulative morphine consumption through patient-controlled analgesia device for 24 hours postoperatively

satisfaction from postoperative analgesia on a four-point Likert scale with 1 marked as minimal satisfaction and 4 as maximal satisfaction

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

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

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

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

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.

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.

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.

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.

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.

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.