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- Optimization and pharmacological characterization of a refined cisplatin-induced rat model of peripheral neuropathic pain. [JOURNAL ARTICLE]
- Behav Pharmacol 2014 Oct 16.
Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side-effect of many front-line anticancer drugs. This study was designed to establish and pharmacologically characterize a refined rat model of cisplatin-induced CIPN. Adult male Sprague-Dawley rats received four (n=18) or five (n=18) single intraperitoneal bolus doses of cisplatin at 3 mg/kg, or saline (control group), once-weekly. Body weight and general health were assessed over a 49-day study period. von Frey filaments and the Hargreaves test were used to define the time course for the development of mechanical allodynia and thermal hypoalgesia in the hindpaws and for efficacy assessment of analgesic/adjuvant agents. The general health of rats administered four cisplatin doses was superior to that of rats administered five doses. Mechanical allodynia was fully developed (paw withdrawal thresholds≤6 g) in the bilateral hindpaws from day 32 to 49 for both cisplatin dosing regimens. They also showed significant thermal hypoalgesia in the bilateral hindpaws. In cisplatin-treated rats with paw withdrawal thresholds of up to 6 g, single bolus doses of gabapentin and morphine produced dose-dependent analgesia, whereas meloxicam and amitriptyline lacked efficacy. We have established and pharmacologically characterized a refined rat model of CIPN that is suitable for efficacy profiling of compounds from analgesic discovery programmes.
- Indication of Adequate Transdermal Fentanyl Dose in Opioid Switching From Oral Oxycodone in Patients With Cancer. [JOURNAL ARTICLE]
- Am J Hosp Palliat Care 2014 Oct 16.
The present study aimed to examine affecting factors for conversion ratio and to predict adequate fentanyl dose for patients with cancer pain in opioid switching from oral oxycodone.Patient characteristics, biochemical parameters, daily oxycodone dose, and reasons for opioid switching were retrospectively collected. The effect of variables on the conversion ratio was analyzed by multiple regression analysis.Regression analysis for the data from 122 patients suggested that the typical conversion ratio was 95:1; however, this ratio was significantly reduced in patients taking a daily oral morphine-equivalent dose of <45 mg/d and in patients with poor pain control to 52:1 and 64:1, respectively.We should carefully and rapidly control pain in opioid switching based on the adequate dose indicated in this study.
- Intravenous lidocaine for the treatment of background or procedural burn pain. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2014 Oct 17.:CD005622.
This is an update of the review on "Lidocaine for pain relief in burn injured patients" first published in Issue 3, 2007, and first updated in 2012. Pain is a major issue for people with many different types of wounds, in particular those people with burn injuries. Prompt, aggressive use of opioid analgesics such as morphine has been suggested as critical to avert the cycle of pain and anxiety, but adverse effects are encountered. It has been proposed that newer agents such as lidocaine could be effective in reducing pain and alleviating the escalating opioid dosage requirements in people with burn injury.To assess the safety and effectiveness of intravenous lidocaine as a means of pain relief versus no therapy, placebo, other drugs, or a combination of these therapies in people with burn injury.For this third update, we searched the Cochrane Central Register of Controlled Trials (Issue 11, 2013), and Ovid MEDLINE, MEDLINE in Process and Ovid EMBASE (up to December 2013).We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs), published and unpublished, which assessed the efficacy of intravenous lidocaine in varying doses as a single-agent therapy with no therapy, placebo, other analgesics (such as opioids), lidocaine plus another drug, or a combination of these therapies as a means of pain relief in people with burn injury.Two review authors independently abstracted data and assessed the risk of bias of the studies identified.In this 2014 update, we found no new studies. The one small randomised double-blind placebo-controlled cross-over trial found in 2012, which included only 45 participants and compared intravenous lidocaine against placebo as a means of pain relief in people with burns still remains central to this review. We assessed this study as being at a high risk of bias due to its small size (fewer than 50 participants per treatment arm). Subjective pain ratings, as measured by the verbal rating scale, increased during procedures for both treatment arms; however, the increase was less in the lidocaine treatment group. There were no significant clinical or statistical differences regarding the effects of lidocaine and placebo on opioid requests and consumption, anxiety or level of satisfaction during a wound care procedure, but the small included study provided insufficient data to draw any conclusions.As current clinical evidence is based on only one RCT as well as case series and reports, intravenous lidocaine must be considered a pharmacological agent under investigation in burns care, the effectiveness of which is yet to be determined with further well-designed and conducted clinical trials.
- Dexamethasone versus a combination of dexamethasone and ondansetron as prophylactic antiemetic in patients receiving intrathecal morphine for caesarean section. [Journal Article]
- Afr Health Sci 2014 Jun; 14(2):453-9.
Intrathecal morphine for caesarean delivery provides excellent postoperative analgesia but it is commonly associated with nausea and vomiting. This prospective, randomized, double blind study was carried out to compare the effectiveness of a combination of dexamethasone and ondansetron with dexamethasone alone for prevention of postoperative nausea and vomiting (PONV) following intrathecal morphine injection for caesarean section.A total of 108 parturients aged 18-40 years for elective caesarean section were randomized into 2 groups (n=54) to receive either intravenous dexamethasone 8mg (Group A) or a combination of intravenous dexamethasone 8mg and ondansetron 4mg (group B). The study drug for each group consisted of 0.5% hyperbaric bupivacaine and 0.2mg morphine. The primary outcome variables were postoperative nausea and vomiting (PONV) which were assessed for a period of 24 hours. The patient's vital signs were monitored and documented.The incidence of nausea and vomiting was significantly reduced in patients who received a combination of dexamethasone and ondansetron compared with dexamethasone alone (9.3% Vs 37%, respectively, P = 0.003).This study showed that a combination of dexamethasone and ondansetron administered prophylactically significantly reduced the incidence of PONV in pregnant women on intrathecal morphine for caesarean section.
- Perioperative nonopioid agents for pain control in spinal surgery. [Journal Article]
- Am J Health Syst Pharm 2014 Nov 1; 71(21):1845-57.
Commonly used nonopioid analgesic agents that are incorporated into multimodal perioperative pain management protocols in spinal surgery are reviewed.Spinal procedures constitute perhaps some of most painful surgical interventions, as they often encompass extensive muscle dissection, tissue retraction, and surgical implants, as well as prolonged operative duration. Perioperative nonopioid analgesics frequently used in multimodal protocols include gabapentin, pregabalin, acetaminophen, dexamethasone, ketamine, and nonsteroidal antiinflammatory drugs (NSAIDs). There is evidence to suggest that gabapentin is safe and effective in reducing opioid consumption and pain scores at optimal doses of 600-900 mg orally administered preoperatively. Pregabalin 150-300 mg orally perioperatively has been shown to reduce both pain and narcotic consumption. Most reports concur that a single 1-g i.v. perioperative dose is safe in adults and that this dose has been shown to reduce pain and attenuate narcotic requirements. Dexamethasone's influence on postoperative pain has primarily been investigated for minor spinal procedures, with limited evidence for spinal fusions. Ketamine added to a patient-controlled analgesia regimen appears to be efficacious for 24 hours postoperatively when implemented for microdiskectomy and laminectomy procedures at doses of 1 mg/mL in a 1:1 mixture with morphine. For patients undergoing laminectomy or diskectomy, NSAIDs appear to be safe and effective in reducing pain scores and decreasing opioid consumption.Preemptive analgesic therapy combining nonopioid agents with opioids may reduce narcotic consumption and improve patient satisfaction after spinal surgery. Such therapy should be considered for patients undergoing various spinal procedures in which postoperative pain control has been historically difficult to achieve.
- Opioids prescription for symptoms relief and the impact on respiratory function: updated evidence. [JOURNAL ARTICLE]
- Curr Opin Support Palliat Care 2014 Oct 14.
Opioids are used for treating dyspnea and other symptoms in oncological and nononcological patients. The relief of respiratory fatigue and anxiety that these opioids offer is well known. One of the scarcely frequent, but very much feared, side-effects is respiratory depression. The purpose of this review is to determine whether or not the situation of an advanced-stage patient under palliative care and the use of opioids are risk factors for respiratory depression.Studies conducted on respiratory function and opioids have proliferated in the past 10 years, but there is no recent review that groups the results together and evaluates their safe use in end-stage patients.A bibliographic review found three randomized double-blinded placebo-controlled studies and five prospective studies, six of which showed that opioids significantly relieve dyspnea (P < 0.001). The use of morphine for symptomatic relief does not significantly change the level of saturation of oxygen in the blood. In addition, the functional studies do not indicate that the use of opioids for dyspnea relief causes high CO2 levels in blood (P = 0.05). The opioids used for treating dyspnea do not significantly compromise respiratory function; they are safe and effective.
- Modelling concentration-analgesia relationships for morphine to evaluate experimental pain models. [JOURNAL ARTICLE]
- Eur J Pharm Sci 2014 Oct 11.
The aim of this study was to develop population pharmacokinetic-pharmacodynamic models for morphine in experimental pain induced by skin heat and muscle pressure, and to evaluate the experimental pain models with regard to assessment of morphine pharmacodynamics. In a randomized, double-blind, placebo-controlled, crossover study, 39 healthy volunteers received an oral dose of 30 mg morphine hydrochloride or placebo. Non-linear mixed effects modelling was used to describe the plasma concentrations of morphine and metabolites, and the analgesic effect of morphine on experimental pain in skin and muscle. Baseline pain metrics varied between individuals and occasions, and were described with interindividual and interoccasion variability. Placebo-response did not change with time. For both pain metrics, morphine effect was proportional to baseline pain and was described with a linear model with interindividual variability on drug effect slope and linked to an effect compartment for muscle pressure. The models indicate that a steady-state morphine concentration of 21 ng/ml causes 33% and 0.84% increases in stimulus intensity from baseline for muscle pressure and skin heat, respectively. The population pharmacokinetic-pharmacodynamic models developed in this study indicate that mechanical stimulation of muscle is a more clinically relevant pain stimulus for the assessment of morphine pharmacodynamics than thermal stimulation of skin.
- A Survey of the Pain Management of Acute Painful Crisis among Patients with Sickle Cell Disease at Two Centres in Jamaica. [JOURNAL ARTICLE]
- West Indian Med J 2014 Jun 12; 63(3):256-261.
The aim of this survey was to establish the pain management approaches to acute painful crisis (APC) in sickle cell patients at two healthcare facilities and to compare with available guidelines.A multi-centre observational survey of the management of APC in sickle cell patients was conducted. Data were collected at the Sickle Cell Unit (SCU), Tropical Medicine Research Institute (TMRI) and Accident and Emergency Department (A&E), University Hospital of the West Indies.One hundred episodes of uncomplicated APC involving 81 patients managed at the SCU clinic and 64 episodes at the A&E in a total of 28 patients were included in the data set. Drugs used at the SCU included oral morphine, codeine and paracetamol and intramuscular diclofenac. At the A&E, parenteral morphine and pethidine were most commonly used. At the SCU, the mean time to initiation of analgesics was 38 minutes (IQR 25 to 50 minutes); at the A&E, this was 111 minutes (IQR 50 to 150 minutes). At the SCU, the mean duration of stay (DOS) was 2.9 hours (IQR 1.9 to 3.8 hours) with 94% of the patients being discharged home. At the A&E, the mean DOS was 13.0 hours (IQR 8.3 to 16.9 hours) with 93% of the patients being discharged home. The A&E patient group contained multiple high frequency presenters. Documentation of pain severity scores was inconsistent.The findings of the survey indicate that the management of APC at the two centres is substantially different. Further study is required to investigate patient satisfaction, centre preference and analgesic therapy efficacy.
- Assessing and responding to palliative care needs in rural sub-saharan Africa: results from a model intervention and situation analysis in Malawi. [Journal Article]
- PLoS One 2014; 9(10):e110457.
Palliative care is rarely accessible in rural sub-Saharan Africa. Partners In Health and the Malawi government established the Neno Palliative Care Program (NPCP) to provide palliative care in rural Neno district. We conducted a situation analysis to evaluate early NPCP outcomes and better understand palliative care needs, knowledge, and preferences.Employing rapid evaluation methodology, we collected data from 3 sources: 1) chart review of all adult patients from the NPCP's first 9 months; 2) structured interviews with patients and caregivers; 3) semi-structured interviews with key stakeholders.The NPCP enrolled 63 patients in its first 9 months. Frequent diagnoses were cancer (n = 50, 79%) and HIV/AIDS (n = 37 of 61, 61%). Nearly all (n = 31, 84%) patients with HIV/AIDS were on antiretroviral therapy. Providers registered 112 patient encounters, including 22 (20%) home visits. Most (n = 43, 68%) patients had documented pain at baseline, of whom 23 (53%) were treated with morphine. A majority (n = 35, 56%) had ≥1 follow-up encounter. Mean African Palliative Outcome Scale pain score decreased non-significantly between baseline and follow-up (3.0 vs. 2.7, p = 0.5) for patients with baseline pain and complete pain assessment documentation. Providers referred 48 (76%) patients for psychosocial services, including community health worker support, socioeconomic assistance, or both. We interviewed 36 patients referred to the NPCP after the chart review period. Most had cancer (n = 19, 53%) or HIV/AIDS (n = 10, 28%). Patients frequently reported needing income (n = 24, 67%) or food (n = 22, 61%). Stakeholders cited a need to make integrated palliative care widely available.We identified a high prevalence of pain and psychosocial needs among patients with serious chronic illnesses in rural Malawi. Early NPCP results suggest that comprehensive palliative care can be provided in rural Africa by integrating disease-modifying treatment and palliative care, linking hospital, clinic, and home-based services, and providing psychosocial support that includes socioeconomic assistance.
- Continuous Subcutaneous Use of Levetiracetam: A Retrospective Review of Tolerability and Clinical Effects. [JOURNAL ARTICLE]
- J Pain Palliat Care Pharmacother 2014 Oct 14.
ABSTRACT To evaluate the tolerability and clinical effects of subcutaneous (SC) levetiracetam for the treatment of epileptic seizures in a palliative care setting, we conducted a retrospective chart review of patients treated with subcutaneous levetiracetam in the Department of Palliative Medicine at the University Munich, between September 2006 and March 2013. The following parameters were extracted from the charts: reason for antiepileptic drug treatment, daily dose, concentration, infusion rate, co-administration of other drugs, and clinical effects. Furthermore, the charts were screened for signs of adverse drug reactions, e.g., irritation or pain at the infusion site. We identified 20 patients that were treated with levetiracetam SC in the inpatient (n = 7) and outpatient (n = 13) settings. Most patients (n = 17) tolerated the subcutaneous infusion well. Nineteen patients (95%) received levetiracetam in combination with other drugs. These were mainly metamizol (80%), midazolam (75%), and morphine (45%). The median dose of levetiracetam was 95.8 mg/h (SD 37 mg/h), median osmolarity of the infusion solution 2203 mOsmol/L (SD 717 mOsmol/L), and infusion rate 2 mL/h (SD 2.4 ml/h). In 16 patients (80%), seizures were controlled and status epilepticus were interrupted, respectively. We conclude that SC levetiracetam is an effective treatment and well tolerated in the palliative care setting.