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Symptom management in patients with established renal failure managed without dialysis.

Increasing numbers of patients with chronic kidney disease Stage 5 (GFR <15ml/minute) are being managed without dialysis, either through their own preference or because dialysis is unlikely to benefit them. This growing group of patients has extensive health care needs. Their overall symptom burden is high, and symptom prevalence matches or exceeds that in other end of life populations, both with cancer and other non-cancer diagnoses. These symptoms may often go unrecognised and under-treated. Regular symptom assessment is necessary, together with pro-active management of identified symptoms. Pain can be managed using the principles of the World Health Organisation analgesic ladder. Not all opioid medications are recommended for these patients. Paracetamol, tramadol, and fentanyl are the most appropriate medications for steps 1, 2 and 3 respectively. There is limited evidence on the use of buprenorphine, oxycodone and hydromorphone. Methadone is safe but should only be prescribed by a clinician experienced in its use. Morphine and diamorphine are not recommended because of metabolite accumulation. Pruritus is also challenging to manage. The evidence for pharmacological interventions to alleviate pruritus is summarized, and a pragmatic approach to management suggested. Emollients, capsaisin cream, antihistamines, thalidomide and ondansetron may be helpful, according to the extent and pattern of pruritus. Symptoms may frequently be due to co-morbid conditions, not renal disease itself, and managing them is difficult because of the constraints on the use of medication which kidney failure imposes. Collaboration between renal and palliative specialists can help identify ways to achieve best care for these patients.

Analgesics↗

Synergy between mu opioid ligands: evidence for functional interactions among mu opioid receptor subtypes.

Pharmacological differences among mu opioid drugs have been observed in in vitro and in vivo preclinical models, as well as clinically, implying that all mu opioids may not be working through the same mechanism of action. Here we demonstrate analgesic synergy between L-methadone and several mu opioid ligands. Of the compounds examined, L-methadone selectively synergizes with morphine, morphine-6beta-glucuronide, codeine, and the active metabolite of heroin, 6-acetylmorphine. Morphine synergizes only with L-methadone. In analgesic assays, D-methadone was inactive alone and did not enhance morphine analgesia when the two were given together, confirming that L-methadone was not acting through N-methyl-D-aspartate mechanisms. Both L-methadone and morphine displayed only additive effects when paired with oxymorphone, oxycodone, fentanyl, alfentanyl, or meperidine. Although it displays synergy in analgesic assays, the L-methadone/morphine combination does not exhibit synergy in the gastrointestinal transit assay. This analgesic synergy of L-methadone with selective mu opioid drugs and the differences in opioid-mediated actions suggest that these drugs may be acting via different mechanisms. These findings provide further evidence for the complexity of the pharmacology of mu opioids.

Analgesics, Opioid↗

Controlled comparison of the efficacy of fourteen preparations in the relief of postoperative pain.

Thirteen analgesic drugs, four of them at two dose levels, four analgesics in combination with antagonist or neuroleptic agents, and saline have been evaluated simultaneously in the relief of postoperative pain. The method of assessment was designed to favour drugs which provided freedom from pain with minimum depression of consciousness. Only levorphanol 2 mg proved significantly superior to pethidine 100 mg, which was used as the standard reference drug. Oxycodone 10 mg, pentazocine 20 mg, and the morphine 10 mg and cyclizine 50 mg combination were the most successful of the remaining drugs. None of the drug combinations was significantly better than the analgesic drug given alone.

Abdomen↗

The management of postherpetic neuralgia.

Postherpetic neuralgia is defined as pain persisting, or recurring, at the site of shingles at least three months after the onset of the acute rash. Thus defined, at least half of shingles sufferers over the age of 65 years develop postherpetic neuralgia. In addition to increasing age, less important risk factors for postherpetic neuralgia are pain severity of acute shingles and trigeminal distribution. Postherpetic neuralgia accounts for 11-15% of all referrals to pain clinics and would, in fact, be far more effectively dealt with in primary care. Effective treatment of acute shingles by systemic antivirals at the appropriate time may have some effect in reducing the incidence of postherpetic neuralgia, making it easier to treat with tricyclics and greatly reducing scarring (25% of all cases affect the face). Pre-emptive treatment with low-dose tricyclics (ami- or nor-triptyline 10-25 mg nocte) from the time of diagnosis of acute shingles reduces the incidence of postherpetic neuralgia by about 50%. Established postherpetic neuralgia should be vigorously treated with adrenergically active tricyclics in a dose rising over two or three weeks from 10-25 mg to 50-75 mg. Positive relaxation should also be used. Carbamazepine, like conventional analgesics, is of little or no value. Failure of tricyclics to effect relief within eight weeks calls for specialist treatment. North American practitioners in particular believe that some opioids (e.g., oxycodone) may be helpful in otherwise intractable cases.

Acyclovir↗

Pain control requirements for percutaneous ablation of renal tumors: cryoablation versus radiofrequency ablation--initial observations.

PURPOSE: To retrospectively compare the pain control requirements of patients undergoing computed tomography (CT)-guided percutaneous radiofrequency (RF) ablation with those of patients undergoing CT-guided percutaneous cryoablation of small (< or = 4-cm) renal tumors. MATERIALS AND METHODS: The study was HIPAA compliant and received institutional review board exemption; informed consent was not required. Medical and procedure records of patients who underwent RF ablation and cryoablation of renal tumors from June 19, 2003, to February 28, 2004, were retrospectively reviewed for clinical data, tumor characteristics, and anesthesia information. During the study period, 10 men (mean age, 66.5 years) underwent cryoablation of 11 renal lesions, and 14 patients (11 men, four women; mean age, 68.1 years) underwent RF ablation of 15 renal tumors. Analgesic and sedative requirements during the procedure were compared. Standard anesthesia consisted of 5 mL of 1% lidocaine injected locally, and conscious sedation consisted of 50 microg of fentanyl and 1 mg of midazolam administered intravenously. The Fisher exact test and Student t test were used to compare clinical factors and drug requirements between the two groups. RESULTS: There was no difference in terms of patient demographics, tumor diameter, or distribution of central versus noncentral lesions between the two groups. Cryoablation was associated with a significantly lower dose of fentanyl (165.0 microg [RF group] vs 75.0 microg [cryoablation group]; P < .001) and midazolam (2.9 mg [RF group] vs 1.6 mg [cryoablation group]; P = .026). In the RF group, one patient required general anesthesia, one patient required supplemental narcotics (5 mg of oxycodone) and sedatives (1 mg lorezapam), and one patient became apneic for a brief interval after receiving additional narcotics for pain during the procedure. An additional RF session was terminated early in one patient because of pain, and further medication could not be administered owing to bradycardia. No patients in the cryoablation group required any additional or alternate anesthetics. CONCLUSION: Image-guided percutaneous cryoablation of small (< or = 4-cm) renal lesions appears to require less analgesia than RF ablation. Prospective trials with validated pain scales are needed to examine this further.

Aged↗

Characterization of cough associated with angiotensin-converting enzyme inhibitors.

Chronic cough is a side effect of the angiotensin-converting enzyme (ACE) inhibitor class of antihypertensives. The cough is thought to be a result of inhibition of the enzymes that break down some of the mediators of inflammation, such as the bradykinins and tachykinins. We report 20 patients with chronic cough caused by ACE inhibitors and some of the characteristics of the cough. The cough is typically dry, nonproductive, and worse at night. Interference with sleep is common and was severe in three patients. Women outnumbered men in this series: urinary stress incontinence developed in five, rectal and vaginal prolapse developed in one. Three patients felt they were incapacitated by the cough. Most had been on multiple medications; only oxycodone was reported to be effective in controlling the cough, and four patients thought they were addicted to that. All coughs resolved with withdrawal of the ACE inhibitor. Chronic cough is common among individuals taking ACE inhibitors. It may be severe and associated with complications. The incidence and potential severity is understated in drug information sources, and patients and physicians often fail to recognize cough as a drug side effect.

Adult↗

Acute pain management pharmacology for the patient with concurrent renal or hepatic disease.

The clinical utility of most analgesic drugs is altered in the presence of patients with impaired renal or hepatic function not simply because of altered clearance of the parent drug, but also through production and accumulation of toxic or therapeutically active metabolites. Some analgesic agents may also aggravate pre-existing renal and hepatic disease. A search was performed, taking in published articles and pharmaceutical data to determine available evidence for managing acute pain effectively and safely in these two patient groups. The resulting information consisted mainly of small group pharmacokinetic studies or case reports, which included a large variation in degree of organ dysfunction. In the presence of renal impairment, those drugs which exhibit the safest pharmacological profile are alfentanil, buprenorphine, fentanyl, ketamine, paracetamol (except with compound analgesics), remifentanil and sufentanil. none of these deliver a high active metabolite load, or suffer from significantly prolonged clearance. Amitriptyline, bupivacaine, clonidine, gabapentin, hydromorphone, levobupivacaine, lignocaine, methadone, mexiletine, morphine, oxycodone and tramadol have been used in the presence of renal failure, but do require specific precautions, usually dose reduction. Aspirin, dextropropoxyphene, non-steroidal anti-inflammatory drugs and pethidine, should not be used in the presence of chronic renal failure due to the risk of significant toxicity. In the presence of hepatic impairment, most drugs are subject to significantly impaired clearance and increased oral bioavailability, but are poorly studied in the clinical setting. The agent least subject to alteration in this context is remifentanil; however the drugs' potency has other inherent dangers. Other agents must only be used with caution and close patient monitoring. Amitriptyline, carbamazepine and valproate should be avoided as the risk of fulminant hepatic failure is higher in this population, and methadone is contraindicated in the presence of severe liver disease.

Analgesics↗

Utilization of psychotropic drugs in Saskatchewan: 1977-1980.

Psychotropic drug use in Saskatchewan during 1977, 1978, 1979 and 1980 was determined. Approximately one in five prescriptions dispensed was for a psychotropic. About 20% of the population received psychotropic drugs in each year but use has declined slightly, especially that of tranquilizers. Psychotropic use increased with the patient's age and nearly two-thirds were women. Considerable caution should be exercised in making comparisons with other drug utilization studies. There may be substantial differences in the drugs selected for study, the categorization of these drugs, and the methodology used to analyze drug use. Also, most studies are based on data that is from a decade old or older. Moreover, most if not all other studies on drug use are based on sample surveys (from different sampling universes), whereas the present study is based on the entire population. Nevertheless, some generalizations may be valid. Since non-formulary drugs are excluded, the findings should be regarded as conservative. Examples of non-formulary drugs considered to be psychotropic include antispasmodic/tranquilizer/sedative combinations (example: Librax, Donnatal), combination hypnotics (example: Tuinal, Mandrax), and some combination analgesics (example: propoxyphene compounds, pentazocine compound, oxycodone compound).

Adolescent↗

Postpericardiotomy syndrome.

Postpericardiotomy syndrome, a frequent complication of open-heart surgery, is characterized by fever, chest pain, and pericardial and pleural effusions. These signs may develop 1 to 12 weeks after intracardiac surgery in approximately 30 percent of patients. Although the etiology of the syndrome is unknown, evidence points to a viral and/or autoimmune cause. Postpericardiotomy syndrome is diagnosed after excluding other conditions such as endocarditis and pneumonia. In many cases, the syndrome is self-limiting and occurs only once, but in other cases the symptoms have recurred as many as eight times. When the symptoms recur, management is more difficult because optimal pharmacologic treatment is not known. Antiinflammatory agents, such as salicylates and steroids, represent the drugs most commonly used. Although analgesics with codeine or oxycodone are important for the patients' symptomatic relief, early recognition of the syndrome is the key to limiting the discomfort and possible complications associated with this condition.

Analgesics↗

Gastric retention of enteric-coated magnesium chloride tablets.

OBJECTIVE: To describe a patient with gastric retention of enteric-coated magnesium chloride tablets. Potential drug and disease etiologies accounting for failure to empty this dosage form are discussed. DESIGN: Single case report. CASE SUMMARY: A seriously ill patient with metastatic small-cell lung cancer accumulated 21 enteric-coated magnesium chloride tablets in his stomach during a four-day administration period. The patient had gastroscopic evidence of mild pylorospasm and suspected gastric motor dysfunction. The latter may have been the result of several factors including concurrent use of oxycodone, vagal dysfunction from chronic alcoholism and cisplatin-based chemotherapy, and possibly a paraneoplastic neuromuscular syndrome involving the gastrointestinal tract. CONCLUSIONS: Enteric-coated tablets are indigestible solids, often of considerable size. Strong antral contractions, associated with phase 3 of the interdigestive migrating myoelectric complex, are usually required to carry such dosage forms through a normal pyloric channel and into the duodenum. Seriously ill patients who may have gastric hypomotility or pyloric channel narrowing are probably not good candidates for therapy with large enteric-coated dosage forms.

Aged↗

Associations between (pharmaco-)genetic markers and postoperative pain after inguinal hernia repair - a prospective study protocol.

BACKGROUND: Postoperative pain is a common complication following surgery, with severity and duration varying between patients. Chronic postoperative pain after inguinal hernia surgery has an incidence rate of approximately 10%. Risk factors for acute and chronic pain following hernia surgery include age, sex, psychosocial factors, and demographic background. Additionally, genetic polymorphisms in enzymes involved in pain mechanisms, as well as the metabolism of analgesics might influence pain perception, pain development, and response to pain medications. Key enzymes include the catechol-o-methyltransferase (COMT), the &#xb5;-opioid receptor 1 (OPRM1), and the cytochrome P450 2D6 (CYP2D6). CYP2D6 plays a crucial role in metabolizing analgesics such as tramadol, codeine, and oxycodone. It is also suspected to be involved in the synthesis of catecholamines and endogenous morphines suggesting a potential role in pathophysiology of pain. We hypothesize that the CYP2D6 activity influences the development of postoperative pain after hernia surgery. METHODS: This study is a prospective, observational, multicenter association study investigating adult patients scheduled for inguinal hernia surgery using a robotic-assisted (rTAPP) approach. Patients are enrolled during the preoperative surgical consultation. A buccal swab is collected for genetic testing at this time. Pain at the site of the hernia is assessed using the validated EuraHSQoL score preoperatively and at 2, 4, and 6&#xa0;weeks postoperatively. Additionally, information on co-medication and details of the surgery will be collected. The planned number of participants is 350 patients. The primary objective is to analyze the association between different genotype-predicted CYP2D6 phenotypes and patient-reported pain intensity 6&#xa0;weeks after surgery. Secondary objectives include the association between further genetic variants, such as the COMT rs4680 and OPRM1 rs1799971 genotype, and pain severity. Additionally, the potential of pharmacogenetic panel testing to optimize analgesic therapy in hernia surgery patients will be explored. DISCUSSION: The findings of this study are expected to provide valuable insights into identifying patients at higher risk for postoperative pain before surgery. This knowledge could pave the way for tailored interventions during and after surgery for these specific patients. TRIAL REGISTRATION: Deutsches Register Klinischer Studien https://www.drks.de/DRKS00034796 Registered on August 07, 2024.

Genetic Association Studies↗

Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network.

The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n = 855), step II (n = 509) and step III (n = 1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used non-opioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or co-analgesics used by >1% of the patients were corticosteroids (39%), tricylic antidepressants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; i.v. or s.c. morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses.

Adolescent↗

Preincisional treatment to prevent pain after ambulatory hernia surgery.

UNLABELLED: We designed this study as a randomized comparison of postoperative pain after inguinal hernia repair in patients treated with triple preincisional analgesic therapy versus standard care. Triple therapy consisted of a nonsteroidal antiinflammatory, a local anesthetic field block, and an N-methyl-D-aspartate inhibitor before incision. The treatment group (n = 17) received rofecoxib, 50 mg PO, a field block with 0.25% bupivacaine/0.5% lidocaine, and ketamine 0.2 mg/kg IV before incision; controls (n = 17) received a placebo PO before surgery. The anesthetic protocol was standardized. Postoperative pain was treated by fentanyl IV and oxycodone 5 mg/acetaminophen 325 mg PO as required for pain. Pain scores (0-10) and analgesic were recorded for the first 7 days after surgery. Pain scores were 47% lower in the treatment group before discharge (3.1 +/- 0.6 versus 5.9 +/- 0.6, P = 0.0026) (mean +/- SE) and 18% less in the first 24 h after discharge (5.6 +/- 0.4 versus 6.8 +/- 0.5, P = 0.05); oral analgesic use was 34% less in the treatment group (4.6 +/- 0.8 doses versus 7.1 +/- 0.7 doses, P = 0.02) in the first 24 h after surgery. We conclude that triple preincisional therapy diminishes pain and analgesic use after outpatient hernia repair, and encourage further evaluation of this technique. IMPLICATIONS: Outpatients undergoing inguinal hernia repair under general anesthesia report moderate-to-severe pain after surgery. Triple preincisional therapy that included rofecoxib, 50 mg PO, ketamine, 0.2 mg/kg IV, and local anesthetic field block reduced pain scores and analgesic use in the first 24 h after discharge.

Adolescent↗

Perioperative rofecoxib plus local anesthetic field block diminishes pain and recovery time after outpatient inguinal hernia repair.

In this study, we compared pain scores after inguinal herniorrhaphy in patients treated by preincisional local anesthetic field block (PL), or PL combined with perioperative rofecoxib, with controls who received standard care. Seventy-five patients having herniorrhaphy under general anesthesia were randomly assigned to receive a placebo pill preoperatively, and for 5 days postoperatively (CONT); preoperative bupivacaine field block and perioperative placebo (PL); preoperative field block plus rofecoxib, 50 mg preoperatively and for 5 days postoperatively (PLR). Bupivacaine infiltration in the wound at closure, IV fentanyl and acetaminophen/oxycodone were administered postoperatively to all. Discharge time, pain scores (0-10), analgesic use, and satisfaction scores (1-6) were compared using analysis of variance. PLR patients had lower maximum pain scores (worst pain) in the postanesthesia care unit (3.7 versus 5.3, P = 0.02) and at 24 h (5.3 versus 6.8, P = 0.03), were discharged 38 min sooner (P = 0.01), required 28% less oxycodone 0-24 h after discharge (P = 0.04), and reported higher satisfaction scores compared with CONT. Pain in PL was less than CONT for 30 min. There were no differences among the 3 groups after 24 h postoperatively. We conclude that perioperative rofecoxib with PL reduces in-hospital recovery time, decreases pain scores and opioid use, and improves satisfaction scores in the first 24 h after surgery.

Adolescent↗

The effect of single-injection femoral nerve block versus continuous femoral nerve block after total knee arthroplasty on hospital length of stay and long-term functional recovery within an established clinical pathway.

Total knee arthroplasty (TKA) may result in severe pain, and single-injection femoral nerve blocks (SFNB) have been demonstrated to have a limited duration of analgesia. Continuous femoral nerve blocks (CFNB) can prolong the analgesic duration of SFNB. We prospectively randomized 36 patients undergoing TKA to CFNB versus SFNB and evaluated the effect on hospital length of stay (LOS) as the primary outcome within a standardized clinical pathway. Secondary outcomes included visual analog scale (VAS) pain scores, opioid consumption, and long-term functional recovery at 12 wk. Mean VAS resting scores were significantly lower among patients who received CFNB versus SFNB: first day (1.7 vs 3.3 [P = 0.002]) and second day (0.9 vs 3.2 [P < 0.0001]) after surgery. Mean maximal VAS scores during physical therapy were significantly lower among patients who received CFNB versus SFNB: first day (4.7 vs 6.3 [P = 0.01]) and second day (3.9 vs 6.1 [P = 0.0005]) after surgery. Mean oxycodone consumption was significantly lower among patients who received CFNB versus SFNB: 15 mg versus 40 mg (P = or < 0.0001) on the first day after surgery; 20 mg versus 43 mg (P = 0.0004) on the second day after surgery. There was no difference in hospital LOS (3.8 vs 3.9 days) or long-term functional recovery (117 degrees versus 113 degrees knee flexion at 12 wk) between the two groups. The lack of effect provided by increased duration of analgesia (from CFNB) after TKA may now have minimal impact on hospital LOS and long-term functional recovery in the contemporary healthcare environment within the United States.

Aged↗

The prevention of emergence agitation with tropisetron or clonidine after sevoflurane anesthesia in small children undergoing adenoidectomy.

Postoperative agitation is a common problem after sevoflurane anesthesia in children. In the present study, we evaluated if tropisetron or clonidine could reduce the incidence of postoperative agitation after day case adenoidectomy in small children. We included 75 unpremedicated children aged 1-7 yr who were randomly assigned to receive either placebo, tropisetron (0.1 mg/kg) or clonidine (1.5 microg/kg) after anesthesia induction. Anesthesia was induced and maintained with sevoflurane. Patients also received alfentanil (20 microg/kg) and diclofenac (1 mg/kg). Postoperative pain was treated with IV oxycodone (0.05 mg/kg). Time to achieve discharge criteria was recorded. Modified pain/discomfort scale was used assess the postoperative behavior. The incidence of postoperative agitation was significantly less (32%, 8/25 patients) in the tropisetron group compared with placebo (62%, 16/26 patients), P < 0.05). Clonidine could not prevent agitation (incidence 54%, 13/24). No adverse effects were noted during the study. Discharge times were similar between the groups (between 80 and 99 min on average). In conclusion, tropisetron 0.1 mg/kg significantly reduced the incidence of postoperative agitation after sevoflurane anesthesia. Clonidine 1.5 microg/kg did not differ from placebo with respect to postoperative agitation.

Adenoidectomy↗

A four-drug pain regimen for head and neck cancers.

Twenty patients with end-stage head and neck cancer, unresponsive to either acetaminophen with codeine or oxycodone hydrochloride, were placed on a four-drug analgesic regimen consisting of methadone hydrochloride, Trilisate or acetaminophen, a tricyclic antidepressant, and, in most cases, hydroxyzine. All drugs could be delivered through a feeding tube, making this regimen appropriate for dysphagic patients. The efficacy of this nonparenteral regimen was assessed by structured pretreatment and posttreatment interviews that addressed pain intensity, activity, and sleep levels. All of the patients showed improvement in their pain levels and 16 of the 20 had a > or = 50% improvement in all of their pain ratings (P < .01) that persisted until death (2 to 10 months later). Excellent results and ease of administration make this regimen a good choice for analgesia in terminal patients.

Acetaminophen↗

Overview of oral modified-release opioid products for the management of chronic pain.

OBJECTIVE: To evaluate pharmaceutical and pharmacotherapeutic differences in oral opioid modified-release products used in the management of chronic pain. DATA SOURCES: Searches of MEDLINE (1966-May 2006) and an extensive review of peer reviewed journals were conducted using the key search terms opioid, morphine, hydromorphone, and oxycodone. Supplemental information was gathered through the American Pain Society, and limited but relevant information was obtained from manufacturers' labeling. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated. Information deemed relevant was included for this review if it introduced new or well supported concepts or clarified clinical practice issues. DATA SYNTHESIS: The recognition and treatment of pain has become a major focus of healthcare professionals. The Joint Commission on Accreditation of Healthcare Organizations mandates compliance with recommended standards, outcome measures, and other initiatives. A general review of pain management and pharmacokinetic parameters are included. CONCLUSIONS: Oral modified-release products have enabled patients to better maintain pain control due to convenient dosing intervals and sustained blood concentrations. The differences between available oral modified-release products are half-life, cost, and formulation (excipients and drug-release properties).

Administration, Oral↗