Ketamine and Pain Relief

Dr. Shannon Granger                   

August 21, 2012

Estimation of the Contribution of Norketamine to Ketamine-induced Acute Pain Relief and Neurocognitive Impairment in Healthy Volunteers

Summary:          

                Ketamine is an NMDA receptor antagonist that is metabolized in the liver to an active metabolite, norketamine. The goal of this study was to assess norketamine’s role in analgesia and cognitive effects as no study to date has been performed elucidating these points. 

                12 healthy male volunteers aged 18-37 were selected and given rifampicin or placebo pretreatment to assess the effects of ketamine versus norketamine. Previous to the study, researchers showed that pretreatment with the antibiotic rifampicin caused a 10% reduction in ketamine and a 50% reduction of norketamine, thus the effect of norketamine could be deduced. It was hypothesized that norketamine contributed 20% to the ketamine induced effects such as analgesia. Subjects underwent three days of testing at three week intervals, one day 6 subjects took rifampicin and 6 took the placebo pill and received on normal saline infusion, on day 2 all 12 took the rifampicin and received an infusion of ketamine, on the third occasion all patients took the placebo pill and all received treatment with ketamine. Patients underwent a heat tolerance test in which heat pain was induced and pain was scored by the visual analogue scoring system, drug high was scored form 0-10 meaning maximal effect, and cognition was measured using a neurocognitive battery test.

                A descriptive analysis showed that ketamine produced greater analgesia, psychotropic effects and impaired cognition than did placebo. Additionally, norketamine had a negative contribution to pain intensity and appreciation when testing patients for heat sensitivity (meaning that norketamine had an opposing effect on ketamine). When norketamine levels were low, such as after rifampicin administration the VAS response was reduced and no hyperalgesia was observed. Norketamine also showed fewer effects on cognitive abilities in this study. Further studies are needed to confirm this study’s findings; however this study suggests that norketamine produces opposing effects to ketamine.

TAP Blocks and Same Day Lap Choli Surgery

Jeff Halonen, DO

The Beneficial Effects of Transverse Abdominid Plane Block After Laparoscopic Cholecystectomy in Day-Case Durgery: A Randomized Clinical Trial. Premillennialism Lykke Petersen, MD et al. Anesthesiology. September 2012- Vol 115- Number 3, p 527-533.

Summary

Patients generally have moderate pain in the early postoperative period following. There have been RCT's that suggest the use of transversal abdominis block following abdominal surgeries for analgesia. The purpose of this trial was to see of this TAP block could decrease the pain with rest and coughing, decrease opioid use and side effects after laparoscopic cholecystectomies in day-case surgery.

This trial put patients into one of two categories. One received bilateral TAP block with Ropivicaine while the other received a placebo block. Their goal was then to see if there was a difference in the above measures.

What was found was that there was a difference in the pain scores when coughing and total opioid consumption. These differences were thought to only be a small difference however.

Gabapentin/Ketamine in post-hysterectomy acute and chronic pain

Dr. Dong

A Comparison of Gabapentin and Ketamine in Acute and Chronic Pain following Hysterectomy

Sen, Sizlan et al. Anesthesia and analgesia. 2009 nov. 109(5). 1645-1650

One of the main objectives and roles of an anesthesiologist is to investigate individual agents or combinations of agents that can alter the perception of post operative pain and allow ones return to baseline functioning. This specific study analyzes two drugs with differing analgesic mechanisms and how they can individually alter post operative opioid use, improve results on subjective pain scores and decrease chronic incisional pain levels. Sixty patients whom were scheduled for abdominal hysterectomy were randomly assigned to either a control group, a ketamine group (received 0.3mg/kg IV bolus followed by 0.05mg/kg IV continuous infusion) and a gabapentin group (received 1.2g PO). Following random assignment, standard anesthetic practice was utilized and patients were assessed immediately post op for acute measures and at 1, 3 and 6 months for chronic changes. The study utilized various modes of statistical analysis and concluded that immediate post operative pain scores were reduced in the gabapentin group, amount of pca morphine use was higher in the control group vs the ketamine and gabapentin groups and chronic surgical site incisional pain was decreased in the gabapentin group. Based on the findings of this study it demonstrates the power of multimodal pain strategies by utilizing agents of various mechanisms and the importance of exploring different methods of improving patient care.

Preoperative Anxiety and Pain Sensitivity, Dr. Tada

Troy Tada, D.O

PGY-4 Resident at RCRMC who will do a Pain Management Fellowship at Rush University upon graduation

Preoperative Anxiety and Pain Sensitivity are Independent Predictors of Propofol and Sevoflurane Requirements in General Anaesthesia

H. K. Kil; W. O. Kim; W. Y. Chung; G. H. Kim; H. Seo; J.-Y. Hong; British Journal of Anesthesia

Psychological factors are thought to drive inter-patient variations in anesthetic and analgesic requirements. This was a cross-sectional study that investigated whether preoperative psychological factors can predict anesthetic requirements and postoperative pain.  One hundred consecutive women completed the Spielberger's State–Trait Anxiety Inventory (STAI) and the pain sensitivity questionnaire (PSQ) prior to their scheduled total thyroidectomy. Target-controlled propofol was administered for induction of anesthesia, and sevoflurane–oxygen–air was given to maintain equal depths of anesthesia, as determined by bispectral index (BIS) monitoring.  This study revealed that patients with higher anxiety scores (state and trait) required greater amounts of propofol to reach light (BIS=85) and moderate (BIS=75) levels of sedation, but only trait anxiety was significantly associated with propofol requirements in reaching a deep level of sedation (BIS=65). The MAC-hour of sevoflurane was significantly correlated only with PSQ scores and postoperative pain intensity was significantly correlated with both STAI and PSQ.  Thus, this study shows that preoperative anxiety and pain sensitivity are independent predictors of propofol and sevoflurane requirements in general anesthesia.

Low Dose Ketamine in outpatient knee surgery, Dr. Dong

Erik Dong, D.O.

Article:
Intraoperative Small-Dose Ketamine Enhances Analgesia

After Outpatient Knee Arthroscopy

Christophe Menigaux, MD, Bruno Guignard, MD, Dominique Fletcher, MD,

Daniel I. Sessler, MD, Xavier Dupont, MD, and Marcel Chauvin, MD

(AnesthAnalg 2001;93:606–12)

Summary:

            Ketamine is a NMDA channel blocker that has been increasingly analyzed for its uses within the multimodal approach to preemptive analgesia and post operative narcotic use. This double blinded, randomized study aims to correlate the use of ketamine at the time of induction, to post op pain, necessity for additional pain medication and ability to ambulate in patients undergoing outpatient knee arthroscopy with meniscal repair. Patients were subjected to similar inclusion and exclusion criteria and placed into groups of 25 (control vs ketamine 0.15mg/kg) with similar management of general anesthesia and surgical technique.

            The findings demonstrated that the ketamine experimental group required less post operative morphine in the PACU and less Di-Antalvac (400 mg acetaminophen and 30 mg dextropropoxyphene; Aventis, Inc., Montrouge, France) in the ambulatory setting, further distances with ambulation with minimal to no direct adverse affects attributed to ketamine. Unlike previous ketamine studies, this particular one suggests that ketamine may aid in post operative analgesia for long durations, as its beneficial effects were seen for up to three days post surgery.

            It has been suggested by the authors that ketamine preemptively blocks analgesia by various mechanisms. First it works by prevention of the development of neuronal hyperexcitability within the central nervous system, distinct and independent of peripheral opiod receptors. Another potential method being potentiation and synergism between the NMDA antagonist and NSAIDS. Overall this a well designed study which shows the benefit of small doses of ketamine in a multimodal approach to surgical analgesia.

Celiac Plexus Block and end of life care, Dr. Chon

 Chang-Ho Chon, DO

Article:
Effect of Neurolytic Celiac Plexus Block on Pain Relief, Quality of Life, and Survival in Patients with Unresectable Pancreatic Cancer

Wong, Gilbert Y., et al. JAMA. Mar 3, 2004 – Vol 291 – No. 2, pp 1092-9

Summary:

Pancreatic cancer is an aggressive malignancy associated with high mortality and often severe upper abdominal pain. Previous studies by Lillemoe, et al. and Kelsen, et al. suggested pancreatic cancer patients to have decreased pain following intraoperative chemical splanchnicectomy and decreased survival when pain was out of control, respectively. This double-blinded, randomized control trial, which was conducted at Mayo Clinic, aimed to test the hypothesis that neurolytic celiac plexus block (NCPB) vs opioids alone can improve pain relief, quality of life (QOL), and survival in patients with unresectable pancreatic cancer.

100 eligible patients were enrolled and randomly assigned to receive either NCPB or systemic analgesic therapy (SAT) with a sham injection. All patients were allowed to receive additional opioids managed by a clinician blinded to the treatment assignment.

At week 1, the mean pain intensity decreased for each group from baseline, but the pain relief was much greater in the NCPB group (53% vs 27%, P=0.005). After week 1, pain intensity decreased gradually and was significantly lower for NCPB than for SAT (P=0.01). Opioid consumption increased over time with no evidence of difference between the groups. Following week 1, QOL gradually declined and did not differ between groups (P=0.46). At 1 year, 16% of NCPB patients and 6% of SAT patients were alive, but survival did not differ significantly (P=0.26).

The study concludes, then, that although NCPB improves pain in this patient population, it does not affect QOL or survival.