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Percutaneous radiofrequency ablation is a commonly treatment for patients with liver cancer that cannot be surgically resected. During the procedure, patients need to keep awake and cooperate with the procedure, including deep breath and hold breath. However, intolerable pain generated during puncture and radiofrequency heating may cause body movements and interfere the procedure. Oxycodone is frequently used for analgesia but still insufficient. A recent study showed that dexmedetomidine-esketamine combination improves analgesia without increasing adverse events. After stopping infusion, the analgesic/sleep-promoting effects of dexmedetomidine-esketamine seemed to last for up to 24 hours.
The investigators hypothesize that dexmedetomidine-esketamine combination as a supplement to oxycodone will improve sedation and analgesia in patients undergoing radiofrequency liver ablation of the liver.
Ultrasound-guided percutaneous radiofrequency ablation is a new technique to treat liver cancer. Under ultrasound guidance, a radiofrequency electrode needle is inserted into the cancer through which local high temperature is generated to coagulate and necrose the cancer tissue. Percutaneous radiofrequency ablation is currently recognized as the best treatment for patients with liver cancer that cannot be surgically resected. During the procedure, patients need to keep awake and cooperate with the procedure, including deep breath and hold breath. However, intolerable pain generated during puncture and radiofrequency heating may cause body movements and interfere the procedure.
Oxycodone is a widely used opioid. It activates the μ and κ receptors and relieves pain including visceral pain, which makes it suitable for analgesia during radiofrequency ablation. However, due to the strong stimulation of radiofrequency liver ablation, supplemental analgesics are often required to improve patient cooperation. As a commonly used supplement, remifentanil is also a μ receptor agonist that quickly reaches blood-brain balance in about 1 minute in and is rapidly hydrolyzed in tissues and blood. The problems with remifentanil are the ultra-short action and pain allergy after stopping infusion. The burning pain after percutaneous liver radiofrequency ablation may last for up to 24 hours.
Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that has sedative, anxiolytic, and analgesic effects. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that is widely used in pediatric anesthesia and postoperative analgesia. Recent studies found that low-dose ketamine also has antidepressant and sleep promoting effects. Esketamine is the S-enantiomer of racemic ketamine with a higher affinity for NMDA receptors and is approximately twice as potent as racemic ketamine in analgesia. A recent study showed that dexmedetomidine-esketamine combination improves analgesia without increasing adverse events. After stopping infusion, the analgesic and sleep-promoting effects of dexmedetomidine-esketamine seemed to last for up to 24 hours.
The investigators hypothesize that dexmedetomidine-esketamine combination as a supplement to oxycodone will improve sedation and analgesia in patients undergoing radiofrequency liver ablation of the liver.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dexmedetomidine-esketamine combined with oxycodone | Experimental | Dexmedetomidine-esketamine combination will be infused in addition to oxycodone; the target is to maintain a Richmond Agitation and Sedation Scale between -2 and -1 during surgery. |
|
| Remifentanil combined with oxycodone | Active Comparator | Remifentanil will be infused in addition to oxycodone; the target is to maintain a Richmond Agitation and Sedation Scale between -2 and -1 during surgery. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dexmedetomidine-esketamine combination | Drug | Dexmedetomidine-esketamine mixture will be infused with doses adjusted to maintain a Richmond Agitation-Sedation Scale between -2 to -1 during surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Area under curve of Numerical Rating Scale of pain during and within 24 hours after surgery. | Numerical Rating Scale (NRS, an 11-point scale where 0=no pain and 10=the worst pain) of pain will be assessed after percutaneous liver puncture, start of radiofrequency-ablation, every 5±1 minutes during radiofrequency-ablation, end of radiofrequency-ablation, and 10 minutes after needle removal during surgery, as well as at 0.5, 1, 2, 3-8, >8-12h,and 24 hours after surgery. | During and within 24 hours after surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| The highest Numerical Rating Scale of pain during surgery. | Numerical Rating Scale (NRS, an 11-point scale where 0=no pain and 10=the worst pain) of pain will be assessed after percutaneous liver puncture, start of radiofrequency-ablation, every 2 minutes during radiofrequency-ablation, end of radiofrequency-ablation, and 10 minutes after needle removal during surgery | During surgery. |
| Measure | Description | Time Frame |
|---|---|---|
| Patients' evaluation on anesthesia. | Patients' evaluation will be performed using the Likert five-point scale: 1=very dissatisfied, 2=dissatisfied, 3=neutral, 4=satisfied, and 5=very satisfied. | Within 30 minutes after surgery. |
| Surgeons' evaluation on anesthesia. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Dong-Xin Wang, MD, PhD | Peking University First Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking University First Hospital | Beijing | Beijing Municipality | 100034 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 2185179 | Background | McGahan JP, Browning PD, Brock JM, Tesluk H. Hepatic ablation using radiofrequency electrocautery. Invest Radiol. 1990 Mar;25(3):267-70. doi: 10.1097/00004424-199003000-00011. No abstract available. | |
| 22424278 | Background | European Association for Study of Liver; European Organisation for Research and Treatment of Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. Eur J Cancer. 2012 Mar;48(5):599-641. doi: 10.1016/j.ejca.2011.12.021. No abstract available. |
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| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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Not provided
| ID | Term |
|---|---|
| D000077208 | Remifentanil |
| D010098 | Oxycodone |
| ID | Term |
|---|---|
| D011422 | Propionates |
| D000144 | Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
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| Remifentanil | Drug | Remifentanil will be infused with doses adjusted to maintain a Richmond Agitation-Sedation Scale between -2 to -1 during surgery. |
|
| Oxycodone | Drug | Oxycodone will be injected intravenously 10-15 min before puncture. |
|
| Number of intraoperative adjustment of study drug infusion rate. | Number of adjustment of study drug infusion rate during surgery. | During surgery. |
| Number of additional oxycodone or other analgesics during and within 24 hours after surgery. | Number of additional oxycodone or other analgesics during and within 24 hours after surgery. | During and within 24 hours after surgery. |
| Dose of analgesics during and within 24 hours after surgery. | Dose of opioids (excluding remifentanil administered as study drugs) will be converted to intravenous morphine equivalent. | During and within 24 hours after surgery. |
| Pain intensity and opioid consumption (PIOC) index during and within 24 hours after surgery. | Pain intensity will be calculated as area under curve (AUC) of Numerical Rating Scale (NRS, an 11-point scale where 0=no pain and 10=the worst pain) of pain during and within 24 hours after surgery. Opioid consumption (OC) during and within 24 hours after surgery will be calculated after excluding remifentanil administered as study drugs. Pain intensity and opioid consumption (PIOC) index will be calculated as: PIOC=[(AUCmean rank - AUCrank)/AUCmean rank] + [(OCmean rank - OCrank)/OCmean rank]. The range of the sum is -200% to +200%. Values above 0 indicate increased summed AUC and OC compared to the all patients. | During and within 24 hours after surgery. |
| Numeric Rating Scale of subjective sleep quality on the first and second nights after surgery. | Numerical Rating Scale (NRS, an 11-point scale where 0=the best sleep and 10=the worst sleep) of sleep quality on the first and second nights after surgery. | On the first and second nights after surgery. |
Surgeons' evaluation will be performed using the Likert five-point scale: 1=very dissatisfied, 2=dissatisfied, 3=neutral, 4=satisfied, and 5=very satisfied. |
| Within 30 minutes after surgery. |
| Postoperative recovery time. | Time interval between end of surgery and arrival of general ward. | Up to 2 hours after surgery. |
| Length of hospital stay after surgery. | Length of hospital stay after surgery. | Up to 30 days after surgery. |
| Incidence of postoperative complications during hospital stay. | Postoperative complications are defined as new-onset conditions after surgery that have adverse effects on postoperative recovery and require therapeutic interventions. | Up to 30 days after surgery. |
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| D008107 |
| Liver Diseases |
| D010880 |
| Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D003061 | Codeine |
| D009022 | Morphine Derivatives |
| D009019 | Morphinans |
| D053610 | Opiate Alkaloids |
| D000470 | Alkaloids |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D010616 | Phenanthrenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D011083 | Polycyclic Compounds |