The Effect of Ketamine on Interleukin-6 Synthesis in Hepatic Resections Requiring Temporary Porto-arterial Occlusion

2014-08-27 03:19:17 | BioPortfolio


The purpose of this study is to determine whether ketamine is effective to inhibit interleukin 6 synthesis in hepatic resections requiring temporary porto-arterial occlusion.


Introduction: Many complications in liver resection surgery, such as post-operative hepatic insufficiency, sepsis, and multi-organ liver failure, have been attributed to ischemia-reperfusion injury and the release of pro-inflammatory agents. Previous studies had shown that ketamine inhibited the synthesis of interleukin 6 (IL-6) in some cardiac surgeries, and that IL-6 levels had a direct correlation with mortality in critically ill patients.

Goal: The purpose of our study was to determine the effect of ketamine on IL-6 levels in patients undergoing liver resections with temporary porto-arterial occlusion (Pringle maneuver).

Material and Methods: Our prospective, controlled, randomized, and blinded study was approved by the Research Ethics Committee of the Hospital Italiano of Buenos Aires (CEPI). All procedures were carried out according to the Declaration of Helsinski. All patients voluntarily consented to the study and signed the appropriate informed consent approved by the CEPI.

Inclusion criteria were age of 21 years or older and planned liver resection with Pringle maneuver lasting 30-60 minutes. Those with chronic illness requiring corticosteroids, cirrhosis, hemodynamic instability prior to the surgery, diabetes, sepsis, surgical interventions or chemotherapy treatments within the past 30 days, pregnancy, illnesses that could potentially affect the hepatic circulation, arterial or ocular hypertension (contraindications for the use of ketamine), ketamine allergy, preoperative portal embolization / radiofrequency ablation, or requiring emergency surgeries were not considered. From March 2002 to June 2008, 44 consecutive patients agreed to participate and were enrolled in the study. Those who did not require the Pringle maneuver during the resection, who did not undergo the planned procedure, or whose hematocrit was less than 20% for over 30 minutes were excluded.

Patients were assigned to one of two groups according to a computer generated randomization.

The study group received ketamine 0.25 mg/kg, while the control group was administered an identical volume of saline. Syringes containing 10 ml of either ketamine or saline were delivered by the hospital pharmacy personnel to the corresponding anesthesiologist, who was blinded to their contents. In order to calculate the correct dose that was administered immediately after induction of anesthesia, the ketamine and placebo concentration was established at 10 mg/ml. Both anesthesia and surgical teams were the same in all cases. Members of both teams, as well as all personnel involved with blood collection remained blinded at all times.

All patients were transported to the operating room with an intravenous line in place and premedicated with midazolam 0.04 mg/Kg. Once in the operating room, they received intravenous antibiotics, non-invasive cardiac monitoring, blood pressure monitoring, and pulse oxymetry.

Remifentanil 0.25 micrograms/kg/min was administered prior to induction with sodium thiopental 2-2.5 mg/Kg. Vecuronium 0.1 mg/Kg was used for muscle relaxation. After waiting approximately 3 minutes, patients were intubated endotracheally and a nasogastric tube was placed. Remifentanil 0.5 micrograms/kg/min, ibuprofen 10 mg/Kg, and morphine 0.15 mg/kg were administered during the case.

Anesthesia was maintained with Sevorane in the setting of an FiO2 of 0.70. Mechanical ventilation was adjusted to allow an EtCO2 of 25-30 mmHg and a plateau pressure < 30 cmH2O. An arterial line was placed after induction of anesthesia to serve for invasive monitoring as well as for blood sampling. A central line was placed in the right internal jugular vein to monitor intra-operative central venous pressure (CVP). All patients received body warmers and warmed fluids. We aimed for a CVP < 5 cm H2O at the time of resection to diminish bleeding. Intravenous fursemide at doses of 10-20 mg as well as fluid restriction were employed when necessary in order to reach the desired value. Potassium levels were kept at or above 3.5 mmol/lt. Phenylephrine was used when necessary to maintain a median arterial pressure of at least 70 mmHg.

Patients who underwent extensive resections were admitted to the Intensive Care Unit (ICU) and maintained on mechanical ventilation for 6-8 hours prior to extubation. In all other cases patients were extubated at the end of the procedure, observed in the post anesthesia care unit (PACU) for at least 8 hours, and subsequently transferred to the floor if hemodynamically stable. Pain management in patients extubated intraoperatively was with synthetic opioids (dextropropoxifen 1 mg/kg and dipyrone 2.5 mg. In cases of persistent pain (4 or more in a visual scale of 10), analgesia was supplemented with 2 mg of morphine every 20 minutes until relief of symptoms, somnolence, or a respiratory rate of 8 or less per minute was observed.

Blood samples for IL-6 levels were obtained prior to surgery upon placement of the first intravenous line, and at 4, 12, 24, 72 and 120 hours after the Pringle maneuver, on the postoperative period. In all cases peripheral venous blood was sampled at a site where no contamination with any of the infused fluids could occur. Immediately after obtaining the sample, the blood was centrifuged, the plasma isolated, and frozen to -70 degrees centigrades. In all cases, two plasma tubes of each sample were individually labeled and stored.

IL 6 was quantified by means of the IL 6 EASIA (BIOSOURCE, Europe Belgium) based on oligoclonal antibodies coupled with monoclonal antibodies to various IL 6 epitopes. This method showed sensitivity for both low and standard IL 6 ranges. The results expressed in our manuscript represent the mean of both samples obtained for each time point of the study.

Statistical analysis Based on previous studies that reported a > 100 picograms/mL difference among both groups with a SD < 50 picograms/mL, we based our calculations on a predicted difference among both groups of 50 picograms/mL with a SD of 50 picograms/mL (17). Based on the fact that since sixteen patients in each group would allow rejection of the null hypothesis with an 80% confidence in the setting of a difference >50 picograms/mL among both groups, a total of 36 patients were randomized. P<0.05 was considered significant.

Study Design

Allocation: Randomized, Control: Placebo Control, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment




Ketamine, Placebo


Hospital Italiano de Buenos Aires
Ciudad Autonoma de Buenos Aires




Hospital Italiano de Buenos Aires

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:19:17-0400

Clinical Trials [436 Associated Clinical Trials listed on BioPortfolio]

Ketamine, Lidocaine and Combination for Postoperative Analgesia in Open Liver Resection

Lidocaine and ketamine both are being used for perioperative analgesia. Perioperative lidocaine infusion has been shown to reduce postoperative pain and opioid consumption. Perioperative l...

Ketamine and Neuropathic Pain

The primary outcome is to compare the analgesic efficacy of intravenous ketamine treatment to that of a placebo in patients with refractory neuropathic pain. The secondary outcomes are: ...

Lidocaine and Ketamine in Abdominal Surgery

This study is being done to determine if combined infusions of lidocaine and ketamine is better than a lidocaine or ketamine infusion alone, or to placebo in improving recovery after abdo...

Reducing Ketamine-Induced Agitation, by Midazolam or Haloperidol Premedication After Adult Procedural Sedation

Ketamine is the cornerstone of procedural sedation in emergency department but ketamine induced agitation has limited its usage by many physicians. As a solution, some propose using midazo...

Ketamine for Reduction of Alcoholic Relapse

96 recently detoxified alcoholics will be randomized to receive either 3 sessions ketamine (0.8 mg/kg IV over 45 minutes) or placebo plus manualised psychological therapy, or 3 sessions of...

PubMed Articles [1129 Associated PubMed Articles listed on BioPortfolio]

Repeat-dose ketamine augmentation for treatment-resistant depression with chronic suicidal ideation: A randomized, double blind, placebo controlled trial.

Several studies indicate that ketamine has rapid antidepressant effects in patients with treatment-resistant depression (TRD). The extent to which repeated doses of ketamine (versus placebo) reduce de...

Lamotrigine attenuates the motivation to self-administer ketamine and prevents cue- and prime-induced reinstatement of ketamine-seeking behavior in rats.

Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. A case report has demonstrated that a ketamine addict experienced a significant reduction in craving and k...

An update on ketamine and its two enantiomers as rapid-acting antidepressants.

Depression is one of the most disabling diseases worldwide. Approximately one-third of depressed patients are treatment-resistant to the currently available antidepressants and there is a significant ...

Laparoscopic hepatectomy versus open hepatectomy for hepatocellular carcinoma in 157 patients: A case controlled study with propensity score matching at two Chinese centres.

The aim of this study was to investigate the long-term outcomes and perioperative outcomes of laparoscopic hepatectomy (LH) versus open hepatectomy (OH) for hepatocellular carcinoma (HCC) between well...

Ketamine in electroconvulsive therapy for depressive disorder: A systematic review and meta-analysis.

Electroconvulsive therapy (ECT) is one of the most effective treatments for depressive disorder. Sub-anesthetic dose of ketamine exerts a rapid and robust antidepressive effect. However, it is still u...

Medical and Biotech [MESH] Definitions

A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.

A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.

Excision of all or part of the liver. (Dorland, 28th ed)

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

An effect usually, but not necessarily, beneficial that is attributable to an expectation that the regimen will have an effect, i.e., the effect is due to the power of suggestion.

More From BioPortfolio on "The Effect of Ketamine on Interleukin-6 Synthesis in Hepatic Resections Requiring Temporary Porto-arterial Occlusion"

Quick Search


Relevant Topics

Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Sepsis, septicaemia and blood poisoning
Septicaemia (another name for blood poisoning) refers to a bacterial infection of the blood, whereas sepsis can also be caused by viral or fungal infections.  Sepsis is not just limited to the blood and can affect the whole body, including the organ...

Searches Linking to this Trial