Adjuvant Analgesics Research Articles

Interdisciplinary approach in a patient diagnosed with prostate cancer and spine metastases

Prostate cancer is one of the malignant tumours in which treatment of bone metastases is a significant clinical problem. In this article 66-year-old patient diagnosed with prostate cancer and multiple metastases to all parts of the spine with accompanying neuropathic pain of severe intensity, which disabled self-moving of a patient is presented. The patient was not qualified for surgery during neurosurgeon consultation. During palliative care provision for the patient by an interdisciplinary team of Home Hospice composed pharmacology treatment of pain was introduced using oxycodone/naloxone, ketoprofen and adjuvant analgesics: zoledronate acid with calcium and vitamin D supplementation, pregabalin and dexamethasone. Stability of the spine was provided through high trunk orthosis in order to minimize the risk of spine damage associated with rehabilitation. A significant decrease in pain, constipation and anxiety intensity was achieved with an improvement of overall performance status and quality of life, which enabled a further anticancer treatment and palliative radiotherapy. The submitted case indicates on a necessity of palliative care provided by the interdisciplinary team for patients diagnosed with prostate cancer and dissemination to bones and severe pain intensity, which significantly increases a chance for obtaining satisfactory analgesia, improvement in the quality of life and a possibility of continuing anticancer and symptomatic treatment. Palliat Med Pract 2018; 12, 4: 207–213

Antipsychotics for patients with pain.

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D2 receptor bindings with strong binding to the 5-HT2A receptor, while typical antipsychotics block long-lasting, tight D2 receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.

Opioidni i adjuvantni analgetici u savremenom lečenju bola

Opioidni i adjuvantni analgetici u savremenom lečenju bola

Pharmacokinetic and pharmacodynamic studies of pregabalin suppositories based on pharmacological research.

As commercially available pregabalin preparations are limited to oral administration, it is impossible to use it as an adjuvant analgesic for neuropathic cancer-related pain in terminally ill cancer patients with oral feeding difficulties. The objective of this study was to develop a pregabalin suppository to be available at hospitals. Pregabalin suppositories were prepared using bases comprising six different compositions of Witepsol H-15, Witepsol S-55, and Witepsol E-75. The suppository release test and stability test were performed invitro. The pharmacokinetics and pharmacodynamics of the suppositories were assessed in rats. In the invitro releasing test, the pregabalin suppositories with H-15, H-15:S-55=1:1, H-15:S-55=2:1, H-15:S-55=1:2 released approximately 100% of the pregabalin within 180min. Among these pregabalin suppositories, only the suppository with H-15:S-55=2:1 demonstrated an equivalent AUC0-∞ with the oral administration group. Consistent with the results of the pharmacokinetic study, the pregabalin suppository with H-15:S-55=2:1 exhibited antinociceptive effects. In addition, the pregabalin suppository with H-15:S-55=2:1 was stable for 12weeks when refrigerated with light shielding. The pregabalin suppositories prepared in this study may be applicable for pain control for terminally cancer ill patients with oral feeding difficulties.

Rebound pain after regional anesthesia in the ambulatory patient.

Regional anesthesia is popular in ambulatory setting allowing safe and fast recovery. The problem of 'rebound pain', that is very severe pain when peripheral nerve block (PNB) wears off represents a clinically relevant problem and a cause of increased healthcare resource utilization. This review tries to make the point on a not so rare, unwanted and often neglected side effect of PNB. The major finding is the lack of large prospective studies. Incidence of rebound pain is unknown but could reach 40% of patients at PNB resolution. To date, pathophysiological mechanisms remain debated: mechanical and chemical (proinflammatory effect of local anesthetics) nerve insult caused by PNB in predisposed patients (with severe preoperative pain, younger patients). Effective preventive strategies also are missing (e.g. role of analgesic adjuvants in PNB). Long-term consequences in term of functional recovery and persistent pain have not been demonstrated. Interview of patients has underlined the need of information and education about PNB and postoperative analgesia. Patients' report of excruciating pain and major distress when PNB wears off questions the quality of current anesthesia practice in ambulatory setting. Rebound pain unanswered questions are challenging in the area of perioperative medicine.

Analgesic Potentials of Preoperative Oral Pregabalin, Intravenous Magnesium Sulfate, and their Combination in Acute Postthoracotomy Pain.

The objective of this study was to investigate the effects of the preoperative combination of oral Pregabalin and intravenous (IV) magnesium sulfate as analgesic adjuvants in postthoracotomy pain. One hundred twenty patients with American Society of Anesthesiologists physical status II were allocated randomly into 1 of 4 groups. Group MP received 300 mg pregabalin orally and an IV infusion of magnesium sulfate 50 mg/kg mixed with 200 mL normal saline (NS); group P received 300 mg pregabalin orally and 200 mL NS infusion; group M received an IV infusion of magnesium sulfate 50 mg/kg mixed with 200 mL NS and a placebo capsule; and group C received placebo capsule and an IV infusion of 200 mL NS. All medications were given 1 hour before surgery in all groups. In the first 24 hours postoperatively, total morphine consumption, the Visual Analog Scale (0 to 10)-used as a pain measurement tool-and postoperative nausea and vomiting were assessed. The total morphine consumption in the first 24 hours postoperatively decreased significantly in group MP (28.47±5.76 mg) compared with group P (33.97±6.34 mg), group M (40.87±4.4 mg), and group C (42.2±6.1 mg), respectively. VAS scores were in the accepted range (≤4) in the 4 groups throughout the first 24 hours, as all patients were on patient-controlled analgesia. However, there was a statistically significant difference at 0 and 4 hours postoperatively in favor of groups MP and P. Postoperative nausea and vomiting decreased significantly in groups MP, P, and M in comparison with group C (P<0.001). The combined preoperative single dose of pregabalin and magnesium sulfate is an effective method for attenuating postoperative pain and total morphine consumption in patients undergoing thoracotomy.

Parturient on Magnesium Infusion and Its Effectiveness as an Adjuvant Analgesic after Cesarean Delivery: A Retrospective Analysis.

Background Perioperative use of intravenous magnesium as part of multimodal analgesia has been increasing in recent years in an effort to decrease the use of opioids. The aim of this study was to evaluate the effectiveness of magnesium sulfate infusion in lowering analgesic requirement and decreasing the intensity of pain score after cesarean delivery. Methods Sixty-four patients who underwent cesarean delivery under spinal anesthesia were included in this medical record review: 32 patients received magnesium infusion after cesarean delivery for treatment of mild preeclampsia (Mg group); 32 patients received routine post-cesarean delivery care (control group). Primary outcome was total analgesic consumption and secondary was visual analogue scores (VAS) of pain in each group during the first 24 hours following delivery. These measures were compared using Student's t-tests and Mann-Whitney U-tests. Results Our study found that patients in the Mg group had significantly less requirement for analgesia than the control group. In the 24 h after cesarean delivery, the Mg group received significantly less intravenous ketorolac (the standard initial rescue analgesic agent) when compared to the control group (79 ± 23 mg vs. 90 ± 0 mg; P = 0.008). The Mg group also received significantly less intravenous morphine equivalents than the control group (median 5.0 (IRQ: 0.0 – 10.0) vs. 9.3 (IRQ: 6.0 – 21.1); P = 0.001) during the first 24 h after cesarean delivery. The Mg group also had significantly lower VAS pain scores than the control group (median 1.75 (IRQ: 0.4 – 2.6) vs. median 3.2 (IRQ: 2.3 – 4.5); P < 0.001). Conclusions Our results suggest that magnesium sulfate infusion decreases total analgesic requirements and lowers VAS pain scores during the first 24 h after cesarean delivery.

Change in Pain Score after Administration of Analgesics for Lower Extremity Fracture Pain during Hospitalization

BackgroundEffective acute pain management following injury is critical to improve short-and long-term patient outcomes. Analgesics can effectively reduce pain intensity, yet half of injury patients report moderate to severe pain during hospitalization. PurposeThe primary aim of this study was to identify the analgesic, different analgesic combinations, or analgesic and adjuvant analgesic combination that generated the largest percent change from pre- to post-analgesic pain score. DesignThis was a descriptive retrospective cohort study of 129 adults admitted with lower extremity fractures to a trauma center. MethodsName, dose, and frequency of analgesics and adjuvant analgesics administered from admission to discharge were collected from medical records. Percent change was calculated from pain scores documented on the 0-10 numeric rating scale. ResultsThe analgesic with largest percent change from pre- to post-administration pain score was hydromorphone 2 mg IV (53%) for the emergency department and morphine 4 mg IV (54%) for the in-patient unit. All analgesics administered in the emergency department and ∼50% administered on the in-patient unit produced a minimal (15%) decrease in pain score. ConclusionsThis study revealed that few analgesics administered in the emergency department and the in-patient unit to patients with lower extremity fractures provide adequate pain relief. In the emergency department, all analgesics administered resulted in at least minimal improvement of pain. On the in-patient unit 13 analgesic doses resulted at least minimal improvement in pain while nine doses did not even reach 20% change in pain. Findings from this study can be used guide the treatment of fracture pain in the hospital.

Opioid responsiveness of nociceptive versus mixed pain in clinical cancer patients

ObjectiveTo investigate whether clinical cancer patients with mixed nociceptive–neuropathic pain are less responsive to opioids than patients with nociceptive pain. BackgroundPain is common in advanced cancer patients. Pain driven by neuropathic mechanisms is considered to be resistant to opioids. This hypothesis is mainly based on animal studies and single-dose opioid studies in humans but has not been confirmed in clinical practice. MethodsData were prospectively collected from 240 clinical cancer pain patients using opioids. Multiple linear regression was used for assessing the associations between the logarithm of the morphine equivalent dose (MED) at three days after admission (T = 3d) relative to admission (T = 0d) (logRMED) and type of pain (nociceptive versus mixed pain), corrected for gender, age, primary cancer site and use of non-opioid and adjuvant analgesics. As secondary outcome measures, associations between logMED and logPFent (fentanyl plasma level) at T = 3d and type of pain were assessed. ResultsPain intensity between T = 0d and T = 3d was significantly and evenly reduced in patients with nociceptive pain (n = 173) and mixed pain (n = 67). Median (interquartile range) MED was 20 (10–52) and 20 (20–80) mg (T = 0d), 40 (10–67) and 40 (20–100) mg (T = 3d), median PFent (T = 3d) was 1.59 (0.58–3.19) and 1.38 (0.54–4.39) ng/ml, none of them significantly different, in patients with nociceptive and mixed pain, respectively. Neither logRMED, logMED (T = 3d), or logPFent (T = 3d) was significantly associated with type of pain, after correction for confounding factors. ConclusionsWe conclude that, at least in clinical cancer patients, mixed pain is as responsive to opioids as nociceptive pain.

Role and Advantageousness of Ketamine in Obese and Non-Obese Patients: Peri-Interventional Considerations

Obese and morbidly obese patients are a growing group of individuals that generates medical, social and economicproblems worldwide. They undergo various interventions that require anesthesia and/or analgesia. Despite theirhealthy look, these individuals are graded at high ASA physical status, mainly because of their impaired respiratoryand cardiovascular conditions, and the metabolic changes their body undergoes. Opioids are the default drugsfor perioperative analgesia. Nevertheless, their use has reached a frightening epidemic-like condition worldwide.Multimodal analgesia regimens have been recommended as a perioperative standard of care, particularly useful in theobese. These regimens employ combinations of opioids and non-opioid compounds that reciprocate each analgesicpotencies, thus providing superior pain relief at rest, movement, or on effort, while reducing opioid consumption andtheir concerned adverse effects. The most important perioperative IV adjuvant currently employed is ketamine thatsees resurgence among physicians from diverse medical specialties. After summarizing obese patients’ perioperativedrawbacks, this review will illustrate ketamine’s neuropharmacology, and will describe its therapeutic usefulness asan analgesic adjuvant. Since data regarding the use of the drug in obese patients is scarce, brief exemplifications ofits benefits in non-obese cohorts will be portrayed as well.

Differences between Transdermal Fentanyl and Buprenorphine in the Elderly Hospice Patients.

Introduction Opioids are the most important drugs in treating pain in palliative care patients. Transdermal formulations are especially useful due to their noninvasive nature and minimal interference in daily life. However, studies have shown a controversial relationship of opioids to survival and a rise in deaths associated with the use of transdermal opioids. Although applying precise doses is paramount, we have no clear recommendations for the exact equianalgesic ratio for buprenorphine patch and no recommendation for the type of transdermal opioid to use in hospice. Methods We analyzed the differences between the transdermal fentanyl and buprenorphine group by analyzing patient characteristics and evaluating the differences in survival in hospice patients over the age of 65, from 2013 to 2017. Results A total of 292 patients (75.8%) used fentanyl patch and 93 (24.1%) were on buprenorphine patch. Patients had virtually the same characteristics in both groups. However, when using a 1:100 buprenorphine equianalgesic ratio, there were significant differences in initial and final doses, and it seems that a 1:80 conversion rate is more accurate for elderly hospice patients. Finally, there was no difference in survival between the two groups using transdermal opioids, with or without adjuvant analgesics. Discussion There were no differences in survival between the group using transdermal fentanyl and the group using buprenorphine in the elderly hospice population. Although adjuvant NSAIDs could be useful in the treatment of pain in terminal cancer, they do not affect survival or reduce the opioid doses, while a 1:80 equianalgesic ratio of buprenorphine might be the most appropriate in this population.

Intravenously Administered Lidocaine and Magnesium During Thyroid Surgery in Female Patients for Better Quality of Recovery After Anesthesia.

Although systemic lidocaine and magnesium have been widely studied as perioperative analgesic adjuvants, they have been rarely evaluated with respect to recovery quality under the same conditions. We compared the quality of recovery 40 (QoR-40) scores of female patients who received intravenous lidocaine, magnesium, and saline during thyroidectomy to investigate their effects on comprehensive recovery from anesthesia. In this prospective, double-blind trial, 135 female patients scheduled for open thyroidectomy were randomly assigned to the lidocaine group (group L), magnesium group (group M), or control group (group C). Immediately after induction, lidocaine (2 mg/kg for 15 minutes followed by 2 mg/kg/h) was administered in group L and magnesium sulfate (20 mg/kg over 15 minutes followed by 20 mg/kg/h) was administered in group M. Group C received an equivalent volume of saline. The QoR-40 survey was conducted on postoperative days 1 and 2. The mean global QoR-40 scores on postoperative day 1 were 186.3 (standard deviation, 5.5) in group L, 184.3 (4.7) in group M, and 179.4 (17.8) in group C, and there was a significant difference only between group L and group C (mean difference, 6.9; adjusted P = .018). Among the 5 dimensions of QoR-40, emotional state, physical comfort, and pain were superior in group L compared to group C. Lidocaine administered intravenously during anesthesia led to better quality of postoperative recovery measured by QoR-40 compared with the group C. Magnesium was found to be insufficient to induce any significant improvement with the dose used in the present study.

Effects of Ketamine on Postoperative Pain After Remifentanil-Based Anesthesia for Major and Minor Surgery in Adults: A Systematic Review and Meta-Analysis.

Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been postulated as an adjuvant analgesic for preventing remifentanil-induced hyperalgesia after surgery. This systematic review and meta-analysis aims to assess the effectiveness of ketamine [racemic mixture and S-(+)-ketamine] in reducing morphine consumption and pain intensity scores after remifentanil-based general anesthesia. We performed a literature search of the PubMed, Web of Science, Scopus, Cochrane, and EMBASE databases in June 2017 and selected randomized controlled trials using predefined inclusion and exclusion criteria. To minimize confounding and heterogeneity, studies of NMDA receptor antagonists other than ketamine were excluded and the selected studies were grouped into those assessing minor or major surgery. Methodological quality was evaluated with the PEDro and JADA scales. The data were extracted and meta-analyses were performed where possible. Twelve RCTs involving 156 adults who underwent minor surgery and 413 adults who underwent major surgery were included in the meta-analysis. When used as an adjuvant to morphine, ketamine reduced postoperative morphine consumption in the first 24 h and postoperative pain intensity in the first 2 h in the minor and major surgery groups. It was also associated with significantly reduced pain intensity in the first 24 h in the minor surgery group. Time to the first rescue analgesia was longer in patients who received ketamine and underwent major surgery. No significant differences in the incidence of ketamine-related adverse effects were observed among patients in the intervention group and controls. This systematic review and meta-analysis show that low-dose (≤0.5 mg/kg for iv bolus or ≤5 μg/kg/min for iv perfusion) of ketamine reduces postoperative morphine consumption and pain intensity without increasing the incidence of adverse effects.

Prevalence and Characteristics of Moderate to Severe Pain among Hospitalized Older Adults.

To investigate the prevalence, characteristics, and management of pain in older hospitalized medical patients. Medical record aggregate review. Tertiary care hospital. Individuals aged 65 and older admitted to the medicine service between November 28, 2014, and May 28, 2015. Demographic characteristics, comorbidity burden, pain characteristics, and analgesics during index hospitalization were assessed in individuals with moderate to severe pain (≥4 on 0-10 Numeric Pain Rating Scale). Of 1,267 patients admitted to the medicine service, 248 (20%) had moderate to severe pain on admission (mean age 75 ± 8, 57% female, 50% white). During hospitalization, most participants received opioids (80%) and acetaminophen (74%), and few received nonsteroidal antiinflammatory drugs (9%). Participants with chronic pain had less reduction in pain intensity score from admission to discharge than those without a history of chronic pain (mean change score 3.7 vs 4.9, p=.002) and were more likely to receive opioids, adjuvant analgesics, and other analgesics (all p<.05). Twenty percent of older adults admitted to a general medicine service had moderate to severe pain. Further research about optimal pain management in hospitalized older adults, particularly those with chronic pain, is necessary to improve care in this population.

PC-FACS

PC-FACS

Dexmedetomidine as a sedative and analgesic adjuvant in spine surgery: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis appraise the clinical evidence on efficacy and safety of dexmedetomidine (DEX), as a sedative and analgesic adjunct in adult patients undergoing spine surgery. A database search was conducted to identify randomized clinical trials (RCTs) pertinent to the perioperative use of DEX in spine surgery. Sedative and analgesic efficacy of DEX constituted the primary outcomes, whilst the incidence of hemodynamic changes, quality of recovery and occurrence of adverse events served as secondary ones. Fifteen studies enrolling a total of 913 patients were selected for qualitative analysis, among which eight RCTs incorporating a placebo comparison group were included in the meta-analysis. Most of the retrieved studies were of moderate to good quality and demonstrated an acceptable risk of bias. DEX-treated patients showed a significant reduction of both propofol [mean difference (MD), -214.47mg; 95%CI, -253.16 to -175.78; P < 0.001] and morphine equivalents consumption both intraoperatively and postoperatively (MD, -2.69; 95% CI, -3.05 to -2.33; P < 0.001 and MD, -4.36mg; 95%CI, -6.93 to -1.79; P < 0.001, respectively) compared to those assigned to placebo. Postoperative nausea and vomiting incidence were comparable between DEX and placebo groups, whilst other adverse events were not consistently reported. DEX emerges as an attractive alternative to standard sedative and analgesic modalities applied in spine surgery, by attaining a notable sedative and opioid-sparing effect, which goes with an enhanced safety profile. Yet, no definite conclusion can be drawn due to the considerable heterogeneity of available data. PROSPERO CRD42015029537.

P.117 A systematic review on opioid free analgesic techniques for supratentorial craniotomies

Background: Post-craniotomy pain can be severe and undermanaged. While opioids are the mainstay treatment, they have the potential to interfere with neurological monitoring. The objectives of this review are: 1) to identify measures to provide opioid-free analgesia 2) to compare the effectiveness of non-opioid to opioid analgesia in post-craniotomy pain. Methods: A comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases was conducted for RCTs evaluating the effect of opioid vs non-opioid pain control strategies in patients undergoing supratentorial craniotomy. Results: The literature search yielded 462 citations, 5 RCTs that met the inclusion criteria for a total of 250 patients. Scalp infiltration/block was found to provide equivalent analgesia to morphine1 and fentanyl.2 Morphine was associated with slightly higher postoperative nausea and vomiting. Paracetamol was less likely to induce nausea and vomiting,3,4 but provided inadequate pain relief compared to nalbuphine,3 tramadol,3 morphine4 and sufentanil.4 Dexmedetomidine5 provided similar analgesia to remifentanil but did delay the time to first dose of rescue analgesia with similar side effects. Conclusions: Based on the limited number of RCTs comparing opioid to non-opioid techniques, no definite recommendations can be made with regards to the optimal management of post-craniotomy pain. Considerations should be made for use of multimodal analgesia-including adjuvant analgesics.

Dexmedetomidine infusion as an analgesic adjuvant during laparoscopic \u0441holecystectomy: a randomized controlled study

BackgroundDexmedetomidine (DEX) has sedative, sympatholytic and analgesic effects and might be beneficial if used as an adjuvant to: improve analgesia; modulate haemodynamic responses to intubation and pneumoperitoneum and; reduce the number of opioid-associated adverse events. The aim of this study was to evaluate the efficacy and safety of DEX infusion during elective laparoscopic cholecystectomy (LC).MethodsA randomized, single-centre, parallel-group, placebo-controlled study was carried out between May 2016 and June 2017. Adult patients (18–79 years) with American Society of Anesthesiology (ASA) physical status I–II were randomly assigned to 0.5 μg/kg/h DEX infusion from induction of anaesthesia to extubation (Group D; n = 30) or normal saline infusion (Group C; n = 30). The primary efficacy outcomes were postoperative morphine consumption. Secondary efficacy outcomes included: time to first use of rescue analgesia; postoperative morphine consumption; intraoperative fentanyl consumption; time from end of surgery to extubation; lengths of intensive care unit (ICU) and general ward stay; degree of postoperative pain 3, 6, 12 and 24 h after surgery; incidence of persistent post-surgical pain.ResultsDEX infusion was associated with a decrease in postoperative morphine consumption (p = 0.001), lower incidence of severe postoperative pain (odds ratio [OR] 9, 95% confidence interval [CI] 1.1–77, p = 0.04) and significantly longer time to first use of rescue analgesia (p = 0.001). Group D also had significantly lower fentanyl consumption both intraoperatively (p = 0.001) and in the time from end of surgery to extubation (p = 0.001) plus decreased incidence of persistent post-surgical pain (OR 14.5, 95% CI 1.7–122, p = 0.005). The incidence of postoperative nausea and vomiting was lower in Group D than Group C (OR 5, 95% CI 1.1–26, p = 0.005). Median pain intensity did not differ between the groups 3, 6, 12 or 24 h after surgery and there were no inter-group differences in the lengths of ICU stay or overall hospital stay between groups. The incidence of hypertension was significantly higher in Group C (OR 13.8, 95% CI 4–48, p < 0.0001); there were no inter-group differences in incidences of hypotension and bradycardia.ConclusionsIntraoperative DEX infusion is safe and effective for improving analgesia during and after elective LC. DEX appears to significantly reduce the number of patients with severe postoperative pain, postoperative morphine consumption and prolong time to first use of rescue analgesia.Trial registrationClinicalTrials.gov: Retrospectively registered on July 7, 2017, NCT03211871.

The Development of Transdermal Ketamine Patch

Objective We prepared the transdermal ketamine patch, determined the size of the patch to yield proper plasma ketamine level due to human skin permeability and the amount of residual ketamine in the patch, and estimated the utility of this ketamine transdermal patch when it will be applied to patients. Methods A ketamine patch was prepared with ketamine hydrochloride intramuscular solution (3.0mg/cm2). The ketamine patch was put on the skin samples taken from the human. The solutions of the diffusion cell were examined every two hours after the application until 30 hours. The amount of ketamine that has penetrated into the skin was measured by using HPLC system, and Flux of transdermal ketamine patch was defined. Results The cumulative ketamine permeation amount was found to be 785.6 mg/cm2 at the 30-hour sampling, showing a stable Flux of 30.1 mg/cm2/hr during the period from 10 to 30 hours of sampling. Conclusion We have been attempting to formulate transdermal ketamine patches at a size of 155 cm2 to yield a plasma ketamine level of 50 ng/mL for use in the clinical practice setting. The patch may become a formulation of choice as an analgesic adjuvant for combined use with opioids.

Ketamine as an Analgesic Adjuvant in Adult Trauma Intensive Care Unit Patients With Rib Fracture.

Rib fracture associated pain is difficult to control. There are no published studies that use ketamine as a therapeutic modality to reduce the amount of opioid to control rib fracture pain. To examine the analgesic effects of adjuvant ketamine on pain scale scores in trauma intensive care unit (ICU) rib fracture. This retrospective, case-control cohort chart review evaluated ICU adult patients with a diagnosis of ≥1 rib fracture and an Injury Severity Score >15 during 2016. Patients received standard-of-care pain management with the physician's choice analgesics with or without ketamine as a continuous, fixed, intravenous infusion at 0.1 mg/kg/h. A total of 15 ketamine treatment patients were matched with 15 control standard-of-care patients. Efficacy was measured via Numeric Pain Scale (NPS)/Behavioral Pain Scale (BPS) scores, opioid use, and ICU and hospital length of stay. Safety of ketamine was measured by changes in vital signs, adverse effects, and mortality. Average NPS/BPS, severest NPS/BPS, and opioid use were lower in the ketamine group than in controls (NPS: 4.1 vs 5.8, P < 0.001; severest NPS: 7.0 vs 8.9, P = 0.004; opioid use: 2.5 vs 3.5 mg morphine equivalents/h/d, P = 0.015). No difference was found between the cohort's length of stay or mortality. Average diastolic blood pressure was higher in the treatment group versus the control group (75.3 vs 64.6 mm Hg, P = 0.014). Low-dose ketamine appears to be a safe and effective adjuvant option to reduce pain and decrease opioid use in rib fracture.