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PubMed2006

Comprehensive, integrative management of pain for patients with sickle-cell disease.

PURPOSES: The study was conducted to: (1) investigate both pharmacologic and complementary therapies used for pain management by caregivers of children with sickle cell disease (SCD), (2) investigate the prevalence and types of complementary therapies used for pain management by caregivers of children with SCD, and (3) explore caregivers' interests in using complementary therapies in the future. METHODS: A cross-sectional, descriptive design was used. Sixty-three caregivers of children with SCD were asked to complete a questionnaire while they visited a SCD clinic. Chi-square tests were performed to compare demographic variables, examine use of pharmacologic therapies for pain management between age groups, and compare use of pharmacologic and complementary therapies. RESULTS: The most frequently used pain medications for children with SCD (mean age 9 years) were ibuprofen (37.5%), acetaminophen with codeine (32.1%), and acetaminophen with oxycodone (14.5%). More than 70% of 63 caregivers (mean age 33 years) were using some form of complementary therapies (3.67 +/- 2.95, range: 0-9) for their child. The most commonly used therapies were prayer, spiritual healing by others, massage, and relaxation. Complementary therapy use was significantly higher among caregivers of children who were taking two or more analgesics compared to children taking no analgesics or one analgesic (chi (2) = 3.954, p = 0.047). Although no difference was found in nonopioid analgesic use, there was significant difference in opioid analgesic use (chi (2) = 14.736, p = 0.002) and total medication use (chi (2) = 11.025, p = 0.012) between children < or = 12 years and > or =13 years. CONCLUSIONS: Caregivers of children using greater numbers of conventional pain medications were more likely to be using complementary therapies as well. If offered in the future, many caregivers were willing to try various types of complementary therapies for pain management.

Adolescent↗

PubMed1992

Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl.

The effects of the new, highly selective alpha 2-adrenergic agonist, dexmedetomidine, were studied in a randomized, placebo-controlled, double-blind trial in 24 ASA I patients. Dexmedetomidine 0.6 micrograms kg-1 or saline was given i.v. 10 min before induction of anaesthesia. The required dose of thiopentone was significantly (P less than 0.001) smaller in the dexmedetomidine group (mean 4.4 (sd 0.9) mg kg-1) than in the control group (6.9 (1.6) mg kg-1), and the drug attenuated the cardiovascular responses to laryngoscopy and tracheal intubation. The concentration of noradrenaline in mixed venous plasma was smaller in the dexmedetomidine group during all phases of induction (P less than 0.01). During surgery, fentanyl was required in a dose of 0.5 (0.6) mg kg-1 and 2.8 (2.6) mg kg-1 in the dexmedetomidine and control groups, respectively (P less than 0.001). During 2 h postoperative follow-up, oxycodone 0.06 (0.06) mg kg-1 and 0.16 (0.1) mg kg-1 (P less than 0.05) was given to the two groups respectively.

Adrenergic alpha-Agonists↗

PubMed1999

Ketoprofen, diclofenac or ketorolac for pain after tonsillectomy in adults?

We have compared the analgesic and opioid sparing effect of three i.v. non-steroidal anti-inflammatory drugs with placebo in a randomized, double-blind, placebo-controlled study in 80 adult patients after elective tonsillectomy. A standard anaesthetic was used. After induction of anaesthesia, patients received ketoprofen 100 mg, diclofenac 75 mg or ketorolac 30 mg by i.v. infusion over 30 min. Patients in the placebo group received saline. Ketoprofen and diclofenac infusions were repeated after 12 h and ketorolac infusion at 6 h and 12 h. Oxycodone was used as rescue analgesic. Patients in the ketoprofen group requested 32% less opioid and patients in the diclofenac and ketorolac groups 42% less opioid than those in the placebo group (P < 0.05). There were one, two and six patients in the placebo, diclofenac and ketorolac groups, respectively, but none in the ketoprofen group, who did not request opioid analgesia during the study (P < 0.05, ketorolac vs placebo and ketoprofen). Visual analogue pain scores were similar in all groups. Visual analogue satisfaction scores were significantly higher in the diclofenac group compared with the placebo group. The incidence of nausea was 44-54%. There were no differences in the incidence of other adverse reactions. We conclude that all three non-steroidal anti-inflammatory drugs were superior to placebo after tonsillectomy.

Adolescent↗

PubMed2004

Small dose of clonidine mixed with low-dose ropivacaine and fentanyl for epidural analgesia after total knee arthroplasty.

BACKGROUND: We studied whether a small dose of clonidine added to a ropivacaine-fentanyl mixture improves epidural analgesia without provoking side effects typically related to larger amounts of epidural clonidine. METHODS: In this randomized, double-blinded study, patients (< or =85 yr, ASA I-III) underwent total knee arthroplasty (TKA) performed under spinal anaesthesia. After the operation, patients received an epidural infusion consisting of ropivacaine 2 mg ml(-1) and fentanyl 5 microg ml(-1) either without (Group RF, n=33) or with clonidine 2 microg ml(-1) (Group RFC, n=36). The infusion rate was adjusted within the range 3-7 ml h(-1). RESULTS: Average rate of infusion was slightly smaller in Group RFC than in Group RF (mean (sd) 4.7 (0.72) vs 5.2 (0.8) ml h(-1), P=0.004). Compared with the RF group, patients in the RFC group required significantly less rescue pain medication, that is i.m. oxycodone (median (25th, 75th percentile) 0 (0, 7) vs 7 (0, 12) mg, P=0.027). Arterial pressure and heart rate were slightly lower in Group RFC throughout the study period (mean difference between the groups 5 mm Hg (P<0.002) and 3 min(-1) (P=0.12), respectively). The groups did not differ statistically with respect to nausea, motor block, and sedation. CONCLUSIONS: The small amount of clonidine added to the low-dose ropivacaine-fentanyl mixture reduced the need for opioid rescue pain medication after TKA. Clonidine slightly decreased arterial pressure and heart rate without jeopardizing haemodynamics. Otherwise, the side effect profiles were comparable in both groups.

Adult↗

PubMed2005

Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.

Toxicity resulting from excessive intra-synaptic serotonin, historically referred to as serotonin syndrome, is now understood to be an intra-synaptic serotonin concentration-related phenomenon. Recent research more clearly delineates serotonin toxicity as a discreet toxidrome characterized by clonus, hyper-reflexia, hyperthermia and agitation. Serotonergic side-effects occur with serotonergic drugs, and overdoses of serotonin re-uptake inhibitors (SRIs) frequently produce marked serotonergic side-effects, and in 15% of cases, moderate serotonergic toxicity, but not to a severe degree, which produces hyperthermia and risk of death. It is only combinations of serotonergic drugs acting by different mechanisms that are capable of raising intra-synaptic serotonin to a level that is life threatening. The combination that most commonly does this is a monoamine oxidase inhibitor (MAOI) drug combined with any SRI. There are a number of lesser-known drugs that are MAOIs, such as linezolid and moclobemide; and some opioid analgesics have serotonergic activity. These properties when combined can precipitate life threatening serotonin toxicity. Possibly preventable deaths are still occurring. Knowledge of the properties of these drugs will therefore help to ensure that problems can be avoided in most clinical situations, and treated appropriately (with 5-HT(2A) antagonists for severe cases) if they occur. The phenylpiperidine series opioids, pethidine (meperidine), tramadol, methadone and dextromethorphan and propoxyphene, appear to be weak serotonin re-uptake inhibitors and have all been involved in serotonin toxicity reactions with MAOIs (including some fatalities). Morphine, codeine, oxycodone and buprenorphine are known not to be SRIs, and do not precipitate serotonin toxicity with MAOIs.

Analgesics, Opioid↗

PubMedDate not supplied

Morphine and etorphine: XIV. Detection by ELISA in equine urine.

We have raised antibodies to morphine and etorphine and developed one-step enzyme-linked immunosorbent assays (ELISA) for these drugs as part of a panel of post race tests for drugs in racing horses. These tests are simple, can be completed in 2 h, and can be read by visual inspection. The morphine ELISA has an I50 for morphine of about 1.5 ng/mL, while the etorphine ELISA has an I50 for etorphine of 250 pg/mL. Cross-reactivity studies show that the antimorphine antibody cross-reacts well with levorphanol, hydromorphone, and oxycodone, while the anti-etorphine antibody showed no cross-reactivity with buprenorphine, diprenorphine, oxymorphone, morphine, or thebaine. The morphine test readily detected parent morphine or its metabolites in equine urine for at least 8 h after administration of 50 mg/horse, while a 0.1 micrograms/kg dose of etorphine was detectable for up to 48 h post dosing. For each test the background activity in post-race urines was equal to or less than the I50 for the standard curves, making them useful equine forensic tests. Each of these tests has detected "positives" in post race urine samples and as such these tests are capable of substantially improving the speed and efficacy of both pre-race and post-race testing for morphine, etorphine, and their congeners in racing horses.

Animals↗

PubMed2002

Detection of cocaine analytes and opiates in nails from postmortem cases.

Postmortem fingernail and toenail specimens were utilized for the detection of cocaine analytes and opiates. Nail clippings were obtained from suspected overdoses and/or drug users. Nail clippings were washed with methanol and then solubilized in 0.1M potassium phosphate (pH 5.0). Analytes were isolated from the solubilized nails and methanolic washes by solid-phase or liquid-liquid extraction techniques. Quantitation was performed by gas chromatography-mass spectrometry. Clippings from each hand and foot were analyzed separately for comparison purposes. Concentrations of all the analytes were significantly higher in fingernails than in toenails. Cocaine analytes were detected in the nails of 15 cases with the following concentration ranges (ng/mg): cocaine (n = 15) 1.2-414.1; benzoylecgonine (n = 15) 1.4-170.3; ecgonine methyl ester (n = 14) 0.19-27.0; norcocaine (n = 12) 0.11-32.7; cocaethylene (n = 2) 0.08-2.93. Opiates were detected in 17 cases with the following concentration ranges (ng/mg): morphine (n = 15) 0.05-407.9; 6-acetylmorphine (n = 15) 0.04-504.0; codeine (n = 9) 0.06-8.84; hydromorphone (n = 4) 0.02-0.45. Oxycodone and hydrocodone were each detected in one case. The extent of drug incorporation due to external contamination was evaluated by comparing the differences in the amount of drugs detected in fingernails and toenails, along with the corresponding washes of those nails. These results demonstrate the usefulness of nails as postmortem specimens in detecting drugs of abuse.

Cocaine↗

PubMedDate not supplied

Postmortem distribution of tramadol, amitriptyline, and their metabolites in a suicidal overdose.

A case report involving a 34-year-old white male who was found dead at home by his roommate is presented. At the time of his death, he was being treated with tramadol/acetaminophen, metaxalone, oxycodone, and amitriptyline. The decedent's mother stated that he had been taking increasing amounts of pain medication in order to sleep at night. There were no significant findings at autopsy; however, toxicology results supported a cause and manner of death resulting from suicidal mixed tramadol and amitriptyline toxicity. This case reports the tissue and fluid distribution of tramadol, amitriptyline, and their metabolites in an acutely fatal ingestion in an effort to document concentrations of these analytes in 12 matrices with respect to one another to assist toxicologists in difficult interpretations.

Adult↗

PubMed2005

Direct analysis of opiates in urine by liquid chromatography-tandem mass spectrometry.

A method for the direct analysis of 10 opiate compounds in urine was developed using liquid chromatography-mass spectrometry-mass spectrometry (LC-MS-MS) with electrospray ionization interface (ESI). Opiates included were morphine-3-P-glucuronide, morphine-6--glucuronide, morphine, oxymorphone, hydromorphone, norcodeine, codeine, oxycodone, 6-monoacetylmorphine (6MAM), and hydrocodone. Urine samples were prepared by centrifugation to remove large particles and direct injection into the LC-MS-MS. Separation and detection of all compounds was accomplished within 6 min. Linearity was established for all opiates except 6MAM from 50 ng/mL to 10,000 ng/mL; 6MAM from 0.25 ng/mL to 50 ng/mL with all correlation coefficients (r) > 0.99. Interrun precision (%CV) ranged from 1.1% to 16.7%, and intrarun precision ranged from 1.3% to 16.3%. Accuracy (% bias) ranged from -7.3% to 13.6% and -8.5% to 11.8 for inter- and intrarun, respectively. Eighty-nine urine samples previously analyzed by gas chromatography-MS were re-analyzed by the LC-MS-MS method. The qualitative results found an 88% agreement for negative samples between the two methods and 94% for positive samples. The LC-MS-MS method identified 19 samples with additional opiates in the positive samples. Overall, the direct injection LC-MS-MS method performed well and permitted the rapid analysis of urine samples for several opiates simultaneously without extensive sample preparation.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

A comparative evaluation of the instant-view 5-panel test card with OnTrak TesTcup Pro 5: comparison with gas chromatography-mass spectrometry.

This study compared the ability of two on-site testing devices, Instant-View Test Card and OnTrak TesTcup Pro 5, to discriminate negative from positive urine samples for cannabinoids, cocaine metabolite, opiates, amphetamines, and benzodiazepines. The on-site devices were evaluated in a precision study with fortified urine samples and in a clinical study with samples submitted for forensic urine drug testing. For precision, seven stocks were prepared per device. Each stock had all five analytes added in a random fashion at 0, 25, 50, 75, 125, 150, or 175% of cutoff. Ten aliquots per stock were assigned random numbers and analyzed by two individuals. The respective accuracies (defined as "% below cutoff samples that were negative + % above cutoff samples that were positive") for Instant-View Test Card and TesTcup were 74.3 and 87.1 for amphetamines; 82.1 and 90.7 for benzoylecgonine; 88.6 and 90.7 for benzodiazepines; 83.6 and 94.3 for morphine; 82.1 and 87.9 for cannabinoids; and 82.1 and 90.1% overall. In contrast to the on-site testing devices, instrumental testing with OnLine reagents had perfect precision. For the clinical study, submitted samples that had reached their disposal date were rescreened for the five drug groups. Fifty that had absorbance changes near the negative control for all five drug groups were selected as "negatives"; 240 samples with positive or multi-positive results (some between the 75% control and cutoff) and confirmed by GC-MS were chosen as "positives" (at least 45 per drug group). The non-positive drug groups in these samples added 150 additional presumptively negatives per drug group. Samples were assigned random numbers, and two individuals tested each sample. The respective accuracies in respect to GC-MS results for Instant-View Test Card and TesTcup were 95.8 and 91.7 for amphetamines; 100 and 100 for benzoylecgonine; 96.7 and 96.5 for benzodiazepines; 98.8 and 99.2 for opiates; 94.4 and 95.0 for cannabinoids; and 97.1 and 96.5% overall. The clinical study revealed that the Instant-View Test Card had low cross-reactivity (i.e., false negatives) for samples with amphetamine only and oxycodone. TesTcup had low cross-reactivity for samples with amphetamine only and hydrocodone and/or hydromorphone; it also had more cross-reactivity towards (i.e., false positives) sympathomimetic amines. In summary, the Instant-View Test Card was less precise than the TesTcup at or near the cutoff; with clinical samples, however, the percent accuracies of the two devices were similar.

Forensic Medicine↗

PubMed2006

Pharmacogenomics for the forensic toxicologist.

Pharmacogenomics is the study of the linkage between an individual's genotype and the disposition of drugs in the body. The first association between adverse drug reactions and inherited variations was recognized in the 1950s, and since then, pharmacogenomics has come a long way. The importance of pharmacogenomics is accentuated by the incidence of adverse drug reactions, which may account for hospital expenditures of up to 5.6 billion dollars annually. Interindividual variations in drug metabolism are often the result of genetic variants or genetic polymorphisms, and polymorphisms have been known to alter the relationship between dose and plasma drug concentration. Drug disposition can be affected by polymorphisms in drug metabolizing enzymes, drug transport proteins, and drug targets. The cytochrome P450 (CYP) enzymes are responsible for the metabolism of a large number of drugs. Polymorphisms of the CYP enzymes have been well documented, and CYP2D6 is the most polymorphic CYP enzyme. However, there is a relative dearth of research on the role of transport proteins and drug targets. This review attempts to provide a brief synopsis of the pharmacogenomics of some common drug-metabolizing enzymes, transport proteins, and targets. The examples of tramadol, methadone, and oxycodone are used to illustrate the potential role of pharmacogenomics in forensic toxicology. Pharmacogenomics may present a practicable hypothesis in cases of incongruence between dose and plasma drug concentration, and the possibility of genotype-mediated drug plasma levels needs to be considered.

Biotransformation↗

PubMed2006

Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites.

Confirmation of opioids in urine samples of clinical patients requires liberation of opioids from their glucuronide conjugates. Both acid hydrolysis and enzyme hydrolysis using beta-glucuronidase from various sources have been reported, with the latter approach prevailing in most clinical toxicology laboratories. The goal of this study was to compare the efficiency of acid versus different enzyme hydrolysis methods in recovering morphine and common semisynthetic opioids from glucuronide standards and 78 patient urine samples that were screened positive for opioids as a class. Specimens were analyzed with a validated gas chromatography-mass spectrometry (GC-MS) procedure. With the exception of oxycodone, the results indicated that the majority of opioids tested were extensively glucuronide-conjugated in urine. Significantly, acid hydrolysis liberated > 90% of morphine and hydromorphone from their glucuronide standards but enzyme hydrolysis had lower and variable efficiency, depending on the opiate type and the enzyme source. In patient specimens, much higher concentrations of free codeine, morphine, hydromorphone, and oxymorphone were obtained with acid hydrolysis than with various enzyme methods. Incomplete hydrolysis using beta-glucuronidase could lead to false-negative results for many opioids when urine is tested for drugs of abuse. We conclude that acid hydrolysis is the method of choice for GC-MS confirmation of urine opioids.

Analgesics, Opioid↗

PubMedDate not supplied

Radioimmunological screening and gas chromatographic determination of morphine and related narcotic analgesics in post mortem blood.

A sensitive, reproducible, and relatively specific procedure is presented for the screening, identification, and quantitation of morphine, hydromorphone, codeine, oxycodone, and hydrocodone in autopsy blood. The drugs are isolated from whole blood by adsorption on an XAD-2 resin slurry and subsequent elution with an organic solvent mixture. Part of the resin extract is screened for morphine and related cross-reacting compounds by a commercially available radioimmunoassay (RIA) and the remainder of the same extract is analyzed by gas chromatography using a nitrogen/phosphorus detector (GC/NP). The procedure has been used frequently in forensic toxicological casework. Since toxic blood concentrations of hydrocodone have not been well documented, the results of toxicological examination of two fatalities involving this drug are presented.

Adult↗

PubMed2001

The preemptive analgesic effect of intraarticular bupivacaine and morphine after ambulatory arthroscopic knee surgery.

UNLABELLED: Intraarticular (IA) morphine provides effective postoperative analgesia after arthroscopic knee surgery. Some investigators have suggested that the preemptive administration of opioids may reduce postoperative analgesic requirements and hypersensitivity. We evaluated the analgesic effect of administering IA morphine either before or after surgical incision in patients undergoing arthroscopic knee surgery under local anesthesia. Forty patients undergoing arthroscopic meniscectomy were randomized into two groups. All patients received IA bupivacaine 0.25% before and after surgery together with IV sedation using midazolam and propofol. The Preemptive IA Morphine group received a single 3-mg dose of morphine with their preoperative bupivacaine. The Post-IA Morphine group received 3 mg of morphine at the completion of surgery with the postoperative bupivacaine. After surgery, pain scores, the time to first opioid use, and 24-h analgesic use were recorded. Analgesic duration, defined as the time from completion of surgery until first opioid use, was significantly longer in those patients receiving preoperative (953 +/- 209 min) versus postoperative (556 +/- 121 min) IA morphine. The 24-h acetaminophen and oxycodone use was less in the Preemptive group (2.2 +/- 1.2 pills) versus the Postoperative group (3.0 +/- 1.2 pills). We conclude that IA morphine provides a longer duration of postoperative analgesia with less 24-h opioid use when administered before surgery. IMPLICATIONS: The administration of intraarticular morphine 3 mg before arthroscopic knee surgery provides a longer duration of analgesia with less 24-h opioid use compared with the administration of the drug at the completion of surgery.

Aged↗

PubMed2002

An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children.

UNLABELLED: In this double-blinded, randomized, multicenter study, we examined analgesic efficacy and tolerability of tramadol in postoperative pediatric patients. Eighty-one postsurgical ASA physical status I and II patients ages 7-16 yr received oral tramadol (approximately 1 or 2 mg/kg) for postoperative analgesia when they were ready to transition from morphine patient-controlled analgesia to oral analgesics. Rescue analgesia consisted of morphine patient-controlled analgesia or an oral equivalent dose of oxycodone. Patients rated their pain just before the administration of tramadol and at regular intervals for 8 h afterwards using the Wong-Baker Faces Pain Rating Scale. The 2-mg/kg group required approximately half as much rescue analgesia as the 1-mg/kg group (P = 0.006). Parents rated the larger dose more favorably. Adverse events were generally mild to moderate in severity (vomiting [10%], nausea [9%], pruritus [7%], rash [4%]) and similar between the two treatment groups. There were no significant changes in hemodynamic variables, respiratory rate, or SpO(2) percentages between the two treatment groups or in all patients compared with pretreatment values. IMPLICATIONS: Oral tramadol 1-2 mg/kg is well tolerated and effective in postoperative children ready to transition from morphine patient-controlled analgesia. The group receiving 2 mg/kg required less rescue analgesic compared with those receiving 1 mg/kg.

Adolescent↗

PubMed2002

Cancer pain: an update of pharmacological approaches in pain therapy.

PURPOSE OF REVIEW: This review discusses clinically oriented data on advances in pharmacological research of cancer pain therapy carried out during the last year. The aim is to ascertain whether well known guidelines for cancer pain prove to be adequate or require modification. RECENT FINDINGS: There are alternatives to morphine, which is the standard drug, including oxycodone or methadone, with the problem of equivalence doses in the case of opioid rotation. Depending on the underlying pathophysiological mechanisms, adjuvant drugs are recommended, such as antidepressants and anticonvulsants for neuropathic pain, or bisphosphonates for metastasis bone pain. Current and future research will offer receptor-specific acting new drugs or old drugs under new indications. SUMMARY: The recommendations of the World Health Organization ladder remain the mainstay of cancer pain management. These recommendations, however, are based more on expert opinions than on evidence-based data.

Journal Article↗

PubMed1989

The prevalence and management of pain in patients with AIDS: a review of 134 cases.

In light of the lack of any prior systematic evaluations of the prevalence and types of pain syndromes and treatments found in patients with AIDS, a chart review study was undertaken to evaluate this issue. Fifty-two of 96 charts reviewed (54%) had at least one note on nonprocedural pain or analgesic prescription. Although chest pain was the most prevalent pain location (22%), presumably because of the high incidence of Pneumocystis carinii pneumonia, other possible AIDS-related entities, such as peripheral neuropathy and thrombophlebitis, were also found. No specific AIDS syndromes could be identified that were related to a higher incidence of pain. Nearly one-third of patients with pain received codeine (31%), others received acetaminophen (27%), and 17% of patients received acetaminophen and oxycodone HCl. Specific pain management interventions must be evaluated and applied to control the nontrivial occurrence of pain in patients who have AIDS symptoms that may be overlooked by the physician given the overwhelming disease process.

Acquired Immunodeficiency Syndrome↗

PubMedDate not supplied

Clinical pharmacology of opioids for pain.

The pharmacological effects of the opioid analgesics are derived from their complex interactions with three opioid receptor types (mu, delta, and kappa; morphine is an agonist at the mu opioid receptor). These receptors are found in the periphery, at presynaptic and postsynaptic sites in the spinal cord dorsal horn, and in the brain stem, thalamus, and cortex, in what constitutes the ascending pain transmission system, as well as structures that comprise a descending inhibitory system that modulates pain at the level of the spinal cord. The cellular effects of opioids include a decrease in presynaptic transmitter release, hyperpolarization of postsynaptic elements, and disinhibition. The endogenous opioid peptides are part of an endogenous pain modulatory system. A number of opioids are available for clinical use, including morphine, hydromorphone, levorphanol, oxymorphone, methadone, meperidine, oxycodone, and fentanyl, and their advantages and disadvantages for the management of pain are discussed. An understanding of the pharmacokinetic properties, as well as issues related to opioid rotation, tolerance, dependence, and addiction are essential aspects of the clinical pharmacology of opioids for pain.

Analgesics, Opioid↗