Jamie L Miller

Oklahoma City University, Oklahoma City, Oklahoma, United States

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Publications (25)37.84 Total impact

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    ABSTRACT: Objective: To review the role of ketamine continuous infusions (CINs) in critically ill children for sedation and analgesia, withdrawal, and bronchospasm. Data Sources: Relevant articles were identified using MEDLINE (1946 to December 2015), EMBASE (1988 to December 2015), International Pharmaceutical Abstracts (1970 to December 2015), and the Cochrane Library (1996 to December 2015) using the terms ketamine, children, and CIN. Study Selection and Data Extraction: All English-language articles in humans identified from data sources were evaluated. Three studies and 8 case reports/series representing 74 patients were included. Data Synthesis: Ketamine is an N-methyl-d-aspartate (NMDA) receptor antagonist that blocks glutamate in the limbic system, resulting in sedation and analgesia. Additionally, it provides bronchodilation by increasing catecholamine transmission and stimulation of β2 receptors. The majority of reports evaluated ketamine for bronchospasm in children with status asthmaticus or bronchospasm refractory to conventional treatments. A total of 72 patients (97.3%) received a loading dose ranging from 0.2 to 2 mg/kg prior to CIN initiation. The CIN dosing range was 0.2 to 3.6 mg/kg/h. Children who received ketamine for sedation or opioid withdrawal received a lower dose than children initiated on it for bronchospasm: 0.24 to 0.9 versus 0.2 to 3.6 mg/kg/h, respectively. Duration of use ranged from 1 to 96 hours. Six of the reports mentioned that the ketamine CIN was tapered prior to discontinuation. Approximately 10.8% of patients included in the analysis experienced adverse events, with only 3 children (4.1%) experiencing emergence phenomenon. Conclusions: Limited evidence was noted, so ketamine CINs could be considered an adjunct therapy at this time. Further prospective studies should be conducted to determine ketamine’s role in sedation and analgesia, withdrawal treatment, and bronchospasm treatment.
    No preview · Article · Jan 2016 · Annals of Pharmacotherapy
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    ABSTRACT: Background: There are no definitive guidelines regarding the management of iatrogenic opioid abstinence syndrome (IOAS), but methadone tapers are one common approach. Methadone tapers can be complex for caregivers to manage, and there is a paucity of data about caregiver experiences administering medication tapers postdischarge. Objective: The primary objective was to describe caregiver perception, self-efficacy, and knowledge of administering methadone tapers. Secondary objectives included an assessment of the change in self-efficacy and knowledge of methadone and IOAS before and after discharge as well as clinical outcomes occurring postdischarge. Methods: This was an exploratory, descriptive, institutional review board–approved study surveying caregivers of children receiving methadone tapers for IOAS. Caregivers were included if they had a child ≤12 years of age discharged to home on a methadone taper. The study consisted of 2 phases: a questionnaire and observation/counseling session predischarge and a telephone interview after taper completion. Univariate descriptive statistics were utilized for data analysis. Results: Phase 1 of the study was completed by 12 caregivers, and only 5 completed phase 2. The majority of caregivers were completely confident predischarge (83.3%) and postdischarge (80%) in administering methadone as prescribed. However, some caregivers were confused about the purpose of the taper and experienced difficulty in measuring oral solutions. Conclusions: Despite high self-efficacy, caregivers experienced difficulties in understanding taper management and during the observation session. The results of this study suggest presenting information to caregivers utilizing minimal medical jargon, conducting a counseling/observation session predischarge, and utilizing the teach-back method with caregivers to assess for understanding.
    No preview · Article · Dec 2015 · The Journal of pharmacy technology: jPT: official publication of the Association of Pharmacy Technicians
  • Amber Thomas · Jamie L. Miller · Kevin Couloures · Peter N. Johnson
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    ABSTRACT: OBJECTIVES: The purpose of this study was to describe the method of delivery, dosage regimens, and outcomes of sedatives administered by extravascular route for imaging procedures in children. METHODS: Medline, Embase, International Pharmaceutical Abstracts, and Cochrane Database of Systematic Reviews were searched using keywords "child", "midazolam", "ketamine", dexmedetomidine", "fentanyl", "nitrous oxide", and "imaging." Articles evaluating the use of extravascular sedation in children for imaging procedures published in English between 1946 and March 2015 were included. Two authors independently screened each article for inclusion. Reports were excluded if they did not contain sufficient details on dosage regimens and outcomes. RESULTS: Twenty reports representing 1,412 patients ranging in age from 0.33 to 19 years of age were included for analysis. Due to discrepancies in doses and types of analyses, statistical analyses were not performed. Oral midazolam was the most common agent evaluated; other agents included intranasal (IN) ketamine, IN midazolam, IN fentanyl, IN and transmucosal dexmedetomidine, and N2O. Most agents were considered efficacious compared with placebo. CONCLUSIONS: Most agents showed efficacy for sedation during imaging when delivered through an extra-vascular route. Selection of agents should be based on onset time, duration, patient acceptability, recovery time, and adverse events. More robust studies are necessary to determine the optimal agent and route to utilize for imaging procedures when sedation is needed.
    No preview · Article · Nov 2015
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    ABSTRACT: Colleges of pharmacy provide varying amounts of didactic and clinical hours in pediatrics resulting in variability in the knowledge, skills, and perceptions of new graduates toward pediatric pharmaceutical care. The Pediatric Pharmacy Advocacy Group (PPAG) endorses the application of a minimum set of core competencies for all pharmacists involved in the care of hospitalized children.
    No preview · Article · Nov 2015

  • No preview · Article · Dec 2014 · American Journal of Health-System Pharmacy
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    ABSTRACT: Purpose. The results of a study to determine the frequency of pseudohyperphosphatemia in a sample of pediatric patients treated with i.v. liposomal amphotericin B are reported. Methods. A single-site retrospective study was conducted to identify evidence of pseudohyperphosphatemia in the medical records of patients 18 years of age or younger who received at least five doses of amphotericin B liposome; the maximum dose was calculated for each regimen and categorized as either <= 5 or >5 mg/kg/day. The primary objective was to ascertain the rate of pseudohyperphosphatemia (i.e., abnormally high serum phosphate without elevated serum calcium). The secondary objective was to compare rates of pseudohyperphosphatemia at the higher and lower amphotericin B dosage levels. A multivariate generalized estimating equation (GEE) regression model was used to identify potential predictors of pseudohyperphosphatemia. Results. Data were collected on 72 courses of amphotericin B liposome administered during a 13-month period to 47 patients; based on a review of chart notations and clinical data, it was determined that 36 regimens (50%) involved pseudohyperphosphatemia. The GEE model revealed no significant association between pseudohyperphosphatemia and any evaluated variable, including age, weight, duration of therapy, and concurrent use of medications known to alter serum phosphorus. Conclusion. In children receiving amphotericin B liposome, half of the regimens were associated with pseudohyperphosphatemia. Although no factors were found to predict pseudohyperphosphatemia, on average, patients who developed the abnormality were significantly older and heavier and received a significantly higher absolute initial dosage of amphotericin B liposome than those who did not develop the condition.
    No preview · Article · Sep 2014 · American Journal of Health-System Pharmacy
  • Jamie L Miller · Amber N Thomas · Peter N Johnson
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    ABSTRACT: Loop diuretics are commonly used in critically ill children to achieve appropriate fluid balance. They are often administered as a continuous intravenous infusion (CI) in hemodynamically unstable children because of fewer alterations in central venous pressure, oxygen saturation, and heart rate compared with scheduled intermittent dosing. During the past few years, however, drug shortages have been reported for bumetanide, torsemide, and furosemide. Therefore, to explore the use of alternative agents for CI, we performed a literature search to identify articles evaluating the use of furosemide, bumetanide, ethacrynic acid, and torsemide CI in critically ill children. The search was limited to English-language articles in the MEDLINE (1946-December 2013), EMBASE (1980-December 2013), and International Pharmaceutical Abstracts (1970-December 2013) databases and the Cochrane Database of Systematic Reviews (2005-December 2013). Reference citations from relevant articles were also reviewed. A total of 10 reports representing 173 pediatric patients were included in the analysis. Most of the reports provided evidence for furosemide, and no reports with torsemide were identified. Wide variability in CI dosing was reported in these studies. When selecting the loop diuretic CI for critically ill patients, clinicians should consider their adverse-event profiles, compatibility with other concomitant intravenous infusions, and pharmacoeconomics. Fluid balance and urine output should be monitored routinely to ensure appropriate response. The lowest initial dose should be used to achieve an appropriate fluid balance and target urine output of 1-3 ml/kg/hour while limiting the likelihood of toxicity.
    No preview · Article · Aug 2014 · Pharmacotherapy
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    ABSTRACT: The purpose of this study was to describe dosage regimens and treatment outcomes in critically ill children receiving ethacrynic acid continuous infusions (CI). This retrospective cross-sectional study evaluated patients less than 18 years of age who received ethacrynic acid CI with a duration exceeding 12 hours, from January 1, 2007, through January 31, 2012. The primary objective was to determine the mean/median doses of ethacrynic acid CI. Secondary objectives were to assess surrogate efficacy markers (e.g., urine output [UOP], fluid balance) and the number of patients with electrolyte abnormalities or metabolic alkalosis. Descriptive statistics were used. A series of repeated measures analyses of variance were conducted to assess differences in surrogate efficacy markers and in adverse events that occurred pre-, mid-, and posttherapy. Nine patients were included. The mean ± SD initial and maximum doses (mg/kg/hr) were 0.13 ± 0.07 (median 0.1; range, 0.08-0.3) and 0.17 ± 0.08 (median, 0.16; range 0.09-0.3), respectively. The median UOP (mL/kg/hr) pre-, mid-, and postinfusions (interquartile range [IQR]) were 2.4 (1.8-3.2), 4.2 (3.5-6), and 4 (3.4-5.3), respectively. The median fluid balance (mL; IQR) was 189 (90-526), -258 (-411.7 to 249) and -113.5 (-212.5 to 80.2), respectively. There were statistically significant differences in UOP and fluid balance pre- versus mid-therapy (0.014) and pre- versus posttherapy (p=0.010). No significant differences were noted with magnesium and potassium. Five children (55.6%) developed metabolic alkalosis. This study provides preliminary evidence for ethacrynic acid CI in children. The median initial dose and maximum dose in this cohort were 0.13 mg/kg/hr and 0.17 mg/kg/hr, respectively. Larger prospective studies are needed to confirm these findings.
    No preview · Article · Apr 2014
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    ABSTRACT: Opioids are commonly used in the neonatal intensive care unit (NICU). Negative neurodevelopmental effects in the short-term setting have been associated with opioids ; however, long-term studies have been limited. The primary objective was to determine if there is a dose relationship between fentanyl and neurodevelopmental outcomes, as measured by Bayley Scales of Infant and Toddler Development (Bayley-III) composite scores for language, cognition, and motor skills. Secondary objectives included comparison of Bayley-III scores and neurodevelopmental impairment classification based on fentanyl exposure. A retrospective evaluation of 147 very-low-birth-weight infants with Bayley-III scores obtained at a chronological age of 6 months to 2 years at clinic follow-up was conducted. Univariate and multivariable linear regression analyses were used to determine if there was a dose-related association between fentanyl and neurodevelopmental outcomes. To evaluate secondary outcomes, patients were divided based on cumulative fentanyl dose ("high-dose" versus "low/no-dose"). The univariate analysis found a statistically significant decrease in cognition (P = .034) and motor skills scores (P = .006). No association was found in the multi-variable regression between fentanyl cumulative dose and Bayley-III scores. There was a significant decrease in the motor skills score between the high-dose versus low/no-dose group, 94 ± 20 versus 102 ± 15, respectively (P = .026); however, no statistical differences were noted for language or cognition scores or neurological impairment classification. When controlling for other variables, the cumulative fentanyl dose did not correlate with neurodevelopmental outcomes. Further evaluation of benefits and risks of opioids in premature infants are needed.
    No preview · Article · Dec 2013 · Annals of Pharmacotherapy
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    ABSTRACT: Methadone is commonly prescribed for children with opioid abstinence syndrome (OAS) as a taper schedule over several days to weeks. The Medication Taper Complexity Score (MTCS) was developed to evaluate outpatient methadone tapers. To further validate the MTCS and determine if it is a reliable tool for clinicians to use to assess the complexity of methadone tapers for OAS. An expert panel of pediatric clinical pharmacists was convened. Panel members were provided 9 methadone tapers (ie, "easy," "medium," and "difficult") to determine construct and face validity of the MTCS. The primary objective was to further establish reliability and construct/face validity of the MTCS. The secondary objective was to assess the reliability of the MTCS within and between tapers. Instrument reliability was assessed using a Pearson correlation coefficient; with 0.8 as the minimum acceptable coefficient. Construct (divergent) validity was assessed via a repeated-measures ANOVA analysis (Bonferroni post hoc analyses) of the mean scores provided by panel members. Six panel members were recruited from various geographical locations. Panel members had 18.3 ± 5.5 years of experience, with practice expertise in general pediatrics, hematology/oncology, and the pediatric and neonatal intensive care unit. The MTCS had a reliability coefficient of .9949. There was vivid discrimination between the easy, medium, and difficult tapers; P = .001. The panel recommended minor modifications to the MTCS. The MTCS was found to be a reliable and valid tool. Overall, the panel felt that the MTCS was easy to use and had potential applications in both practice and research.
    No preview · Article · Nov 2013 · Annals of Pharmacotherapy
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    ABSTRACT: Background: Acetazolamide is an option for hypochloremic metabolic alkalosis, but there are limited reports in children. Objective: To describe the acetazolamide regimen and outcomes in critically ill children with metabolic alkalosis. Methods: This was a descriptive, retrospective study of patients <18 years of age who received ≥3 doses of acetazolamide for metabolic alkalosis (ie, pH > 7.45 and bicarbonate [HCO3] > 26 mEq/L). Patients receiving other treatments for metabolic alkalosis within 24 hours of acetazolamide were excluded. The primary objective was to identify the mean dose and duration of acetazolamide. Secondary objectives were to determine the number of patients with treatment success (ie, serum HCO3 22-26 mEq/L) and occurrence of adverse events. Results: Thirty-four patients were included for analysis, the median age was 0.25 years (range = 0.05-12 years). The acetazolamide regimen included a mean dose of 4.98 ± 1.14 mg/kg for a mean number of 6.1 ± 5.3 (range = 3-24) doses. The majority (70.6%) received acetazolamide every 8 hours. Treatment success was achieved in 10 (29.4%) patients. Statistically significant differences were noted between the pre-acetazolamide and post-acetazolamide pH and HCO3, 7.51 ± 0.05 versus 7.37 ± 0.05 (P < .001) and 39.4 ± 6.1 mEq/L versus 31.4 ± 7.5 mEq/L (P < .001), respectively. Conclusions: This is the first study to evaluate acetazolamide dosing for metabolic alkalosis in children with and without cardiac disease. Acetazolamide treatment resulted in improved HCO3, but the majority of patients did not achieve our definition of treatment success. Future studies should elucidate the optimal acetazolamide regimen.
    Full-text · Article · Sep 2013 · Annals of Pharmacotherapy
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    ABSTRACT: To determine whether patients receiving higher doses of caffeine have increased alkaline phosphatase (ALP) levels, as a biomarker for osteopenia. This descriptive, retrospective study included 152 extremely low-birth-weight infants (ie, <1 kg) admitted from January 1, 2007, to September 30, 2009, who received caffeine for >2 weeks. Patients were divided into a low-dose (<7.5 mg/kg/day) and high-dose (≥7.5 mg/kg/day) group based on maximum caffeine dose received. The primary objective was to compare peak ALP levels between groups. Secondary objectives included a comparison of caffeine regimens and risk factors for osteopenia between groups and identification of factors significantly related to increase in ALP. Between-group analysis was performed using the chi-squared or Fisher exact test and Wilcoxon Mann-Whitney median test or t-tests where appropriate. A linear regression model was used, with peak ALP as the dependent variable. A majority of the patients (n=122) were included in the high-dose caffeine group. No significant difference in maximum ALP level between groups (median, 599.5, versus 602.5 units/L, p=0.72). Gestational age and birth weight were inversely related to ALP, whereas parenteral nutrition duration was directly related. No significant relationship between caffeine dose and ALP was identified. In this preliminary study, using ALP as a biochemical marker for bone turnover, there does not appear to be a dose-related effect between ALP and caffeine dose.
    Full-text · Article · Nov 2012
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    Peter N Johnson · Jamie L Miller · Tracy M Hagemann
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    ABSTRACT: The interplay of pain, discomfort, and fear can cause agitation in critically ill children. Therefore, sedation and analgesia are essential components in the intensive care unit setting and are best managed with a multidisciplinary team approach. No one standard approach exists to assess and manage pain and anxiety. Many tools are available for the assessment of pain and sedation, but each tool has its advantages and disadvantages. Clinicians should consider adopting a validated tool for routine continuous assessment. Multiple pharmacological therapies are available to manage pain, anxiety, fear, and agitation. Dosing of these agents can be influenced by age-related pharmacokinetic and pharmacodynamic changes. Agents should be selected on the basis of the child's disease state, desired level of sedation, and cardiac and respiratory status.
    Preview · Article · Oct 2012 · AACN Advanced Critical Care

  • No preview · Article · Sep 2012 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
  • Peter N Johnson · Krystal A Boyles · Jamie L Miller
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    ABSTRACT: Iatrogenic opioid abstinence syndrome (IOAS) is a common complication in critically ill infants and children receiving prolonged exposure to continuous infusions of opioids. Although no guidelines are available regarding management of IOAS in children, several treatment options are available, including clonidine, morphine, and methadone. Methadone is commonly prescribed due to its long half-life and antagonism of the N-methyl-d-aspartate receptor. Different approaches, such as weight-based and formula-based methods, have been used to determine the initial methadone dosing regimen. Because of the vast differences in the recommended dosing regimen from these sources, we conducted a literature search to identify articles evaluating the initial methadone dosing regimen for prevention and/or treatment of IOAS in children. Specifically, we evaluated the reported frequency of withdrawal and oversedation after initiation of methadone treatment. Our literature search was limited to English-language articles in the MEDLINE (1950-March 2011), EMBASE (1988-March 2011), International Pharmaceutical Abstracts (1970-March 2011), and Cochrane Library (1996-March 2011) databases. Relevant abstracts and reference citations were also reviewed. A total of eight reports representing 183 patients were included in the analysis. There was wide discrepancy in the initial methadone dosing regimen. Approximately one-third of all patients experienced withdrawal after starting methadone, and there did not appear to be a difference between weight-based and formula-based regimens. Seven patients experienced oversedation; however, not all articles reported this complication. It appears that a standard approach to initial methadone dosing does not exist because withdrawal occurred despite the regimen started. Therefore, it seems best to begin with the lowest dose possible and titrate to the child's response to avoid complications such as oversedation. Routine monitoring should be performed in all patients to guide clinicians in the management of IOAS.
    No preview · Article · Feb 2012 · Pharmacotherapy
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    ABSTRACT: Methadone is often prescribed as a taper schedule to prevent/treat opioid abstinence syndrome (OAS) or neonatal abstinence syndrome (NAS). The objective of this study was to determine the percentage of children discharged home on methadone tapers and to develop, assess, and implement an instrument for measuring the complexity of the methadone regimens. This study used a descriptive retrospective design to examine patients younger than 18 years from January 1, 2008, to December 31, 2008, administered methadone for prevention/treatment of OAS/NAS and discharged home on a methadone taper. Data collection included demographics and characteristics of methadone regimen. The primary objective was to determine the percentage of children discharged on methadone. Secondary objectives included characterization (ie, number of dosage and interval changes), duration, and complexity of the methadone taper. Descriptive statistics were performed using Stata v10 (StataCorp LP, College Station, TX). Complexity was evaluated using the medication taper complexity score (MTCS) between 4 raters. Reliability of the MTCS was established using interrater correlation analyses of the regimen complexity scores. Thirty-three patients (41.8%) were discharged on methadone. The median (range) age was 0.42 (0-12) years, with most patients (75.8%) initiated on methadone for prevention of OAS. Thirty-one patients were included for further analysis of medication complexity. The median (range) duration of the home taper was 8 days (2-48), which included a median (range) of 4 (1-11) dose changes and at least 1 (0-2) change in the interval. MTCS ranged from 7 to 42, with the tool demonstrating 95% interrater reliability. More than one-third of patients were discharged home on methadone. The median taper duration was 8 days and included a median of 5 adjustments in either the dose or interval. The MTCS demonstrated very good interrater reliability to measure wide variability in the complexity of individual tapers. Future studies should determine the construct validity of the MTCS and the applicability of this tool for further research and clinical application.
    No preview · Article · Jan 2012 · Research in Social and Administrative Pharmacy
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    ABSTRACT: Vancomycin dosages in overweight and obese children were evaluated. This retrospective study evaluated data for children who were age 2-17 years, received i.v. vancomycin, and were admitted to a children's hospital from September 1, 2007, through October 31, 2009. Patients were then stratified into two groups: normal-weight patients and overweight or obese patients. The primary objective was to compare the number of vancomycin regimens between groups with a trough concentration of 5-15 μg/mL. Secondary objectives included a comparison of dosage changes and toxicities. Multivariate, conditional logistic regression was performed to assess the relationship between attaining optimal vancomycin concentrations (5-15 μg/mL) and independent variables. Data were collected for 232 courses of vancomycin, representing 187 patients. The mean ± S.D. initial dose for the normal-weight and overweight or obese groups differed significantly (461.3 ± 303.1 mg and 658.4 ± 389.6 mg, respectively; p < 0.01); the milligram-per-kilogram initial vancomycin dose did not. The multivariate analysis revealed that every-eight-hour regimens had increased odds of achieving therapeutic concentrations (p < 0.001), while obese children had decreased odds of achieving therapeutic concentrations (p = 0.037). A study of prescribing behavior in one hospital revealed no significant difference in the size of vancomycin doses (in milligrams per kilogram) given to normal-weight children compared with overweight or obese children. Regimens using every-eight-hour dosing were significantly more likely than other regimens to result in a vancomycin trough concentration of 5-15 μg/mL, and regimens for obese children, compared with regimens for nonobese children, were less likely to produce trough concentrations in the same range of 5-15 μg/mL.
    No preview · Article · Nov 2011 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
  • Jamie L Miller · Tracy M Hagemann
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    ABSTRACT: Published reports on placebo-controlled clinical trials and other studies investigating the use of pure opioid antagonists for the prevention and treatment of opioid-induced pruritus (OIP) were evaluated. OIP is a common adverse effect of therapeutic use of opioid medications that can have a major impact on patients' comfort, quality of life, and willingness to continue opioid therapy. A literature search identified more than a dozen published reports on the use of pure opioid antagonists (naloxone, naltrexone, methylnaltrexone) for the management of OIP in pediatric and adult patients. Of the studies included in this review, most investigated the effects of naloxone administered by various parenteral routes for the prevention of OIP. Some of those studies indicated a significant reduction in the frequency or severity of pruritus with use of naloxone (a low-dose, continuous i.v. infusion of naloxone appeared to be the most effective treatment). A significant diminution of analgesia requiring increased cumulative doses of morphine was also observed in some studies. A number of studies evaluating the use of orally administered naltrexone for the management of OIP yielded generally less favorable results. Evidence from one small study suggested a potential role for orally administered methylnaltrexone in the prevention of OIP. Based on the existing data, a low-dose, continuous i.v. infusion of naloxone has the largest body of evidence supporting its use for prevention of OIP in adult and pediatric patients.
    No preview · Article · Aug 2011 · American journal of health-system pharmacy: AJHP: official journal of the American Society of Health-System Pharmacists
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    Emily C Gish · Jamie L Miller · Brooke L Honey · Peter N Johnson
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    ABSTRACT: To review the pharmacology, toxicology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines for lofexidine, an alpha(2)-agonist, for opioid detoxification. Primary literature was identified through a MEDLINE search (1950-September 2009), EMBASE (1988-July 2009), International Pharmaceutical Abstracts (1970-September 2009), and the Cochrane Library (1996-September 2009) using the key words lofexidine and opioid withdrawal. Abstracts were included in the absence of published results of studies. Studies published in English-language literature reporting on animal and human pharmacology, toxicology, and pharmacokinetics were included in addition to clinical trials using lofexidine for opioid detoxification in comparison to placebo or active controls. Lofexidine is an alpha(2)-agonist structurally related to clonidine. It is not an effective antihypertensive agent; however, it decreases the sympathetic outflow responsible for many opioid withdrawal symptoms. Nine clinical studies were reviewed representing 354 patients receiving lofexidine including a recent Phase 3 clinical trial. Eight studies involved comparisons of lofexidine to an opioid receptor agonist or clonidine for opioid detoxification. In these trials, lofexidine dosing was titrated to a maximum of 1.6-3.2 mg/day in divided doses for a total of 5-18 days. The data suggest that lofexidine has positive efficacy in reducing opioid withdrawal symptoms and is at least as effective as the opioid receptor agonists utilized for detoxification. Not all withdrawal symptoms are alleviated by alpha(2)-agonists, with many patients complaining of insomnia and aching. The most common adverse event with lofexidine in the Phase 3 trial was insomnia. Hypotension was also reported; however, the studies comparing clonidine with lofexidine suggest decreased incidence and severity of adverse events with lofexidine. Lofexidine appears to be a promising agent for opioid detoxification. If approved, it would be the first nonopioid agent approved for this indication. Further large-scale controlled studies are needed to identify the safest, most effective dosage regimen required to achieve opioid detoxification.
    Preview · Article · Feb 2010 · Annals of Pharmacotherapy
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    Jamie L Miller · Christine Allen · Peter N Johnson
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    ABSTRACT: Dexmedetomidine is a α(2)-adrenergic agonist which possesses sedative, analgesic, and anxiolytic properties. It is approved for short-term use in adults to provide sedation while mechanically ventilated and for noninvasive procedural sedation. An increased number of anecdotal reports describe the use dexmedetomidine in children. Cardiovascular withdrawal symptoms have been reported in the literature. However, there have been few published reports of neurologic withdrawal symptoms following discontinuation of prolonged infusions of dexmedetomidine. We describe a 2 year-old child who received a prolonged continuous infusion (263 hours) of dexmedetomidine as an adjunctive sedative agent. Following abrupt discontinuation of dexmedetomidine, the patient presented with symptoms suggestive of neurological withdrawal. The symptoms gradually resolved over two days without further intervention, and the patient had full resolution of symptoms and was discharged home with no further neurologic sequelae.
    Preview · Article · Jan 2010