Sean K. Gorman

Corticosteroid Treatment of Severe Community-Acquired Pneumonia

Objective: To assess the evidence for adjunctive corticosteroids for severe community-acquired pneumonia (CAP). Data Sources: MEDLINE (1966–February 2007) and EMBASE (1980–February 2007) were searched to identify English- and French-language publications that evaluated the use of corticosteroids for CAP in adults. Major search terms included community-acquired pneumonia, intensive care unit, steroids, glucocorticoids, and adrenal cortex hormones. Study Selection and Data Extraction: Clinical studies that evaluated the use of corticosteroids for CAP in adults were included. Clinical and surrogate markers of pneumonia were evaluated. Data Synthesis: Severe CAP is associated with an increase in pulmonary and circulatory cytokines such as interleukin-6 and tumor necrosis factor-α that may be associated with higher mortality. Corticosteroids suppress inflammatory reactions and prevent migration of inflammatory cells from the circulation to tissues by suppressing the synthesis of chemokines and cytokines. One observational comparative study and 2 randomized, controlled studies examined the effects of corticosteroid therapy at various doses on endpoints of pulmonary and systemic inflammation and clinical outcomes. One small observational pilot study revealed that methylprednisolone blunted some of the pulmonary and systemic markers of inflammation. One small, randomized, placebo-controlled study revealed that hydrocortisone had no significant effects on markers of pulmonary and systemic inflammation or clinical outcomes. Another small, randomized, placebo-controlled preliminary study with methodological limitations revealed improvements in oxygenation, organ dysfunction score, and markers of inflammation favoring hydrocortisone over placebo. Conclusions: Given the lack of proven benefit on clinically meaningful endpoints and adverse events, corticosteroids cannot be recommended for adjunctive treatment of severe CAP.

Valproic Acid Management of Acute Alcohol Withdrawal

Objective: To review the clinical evidence to determine the efficacy and safety of valproic acid in the management of alcohol withdrawal syndrome (AWS). Data Sources: MEDLINE (1966–February 2006), EMBASE (1980–February 2006), and PubMed (1966–February 2006) searches identified pertinent studies that were conducted in humans and published in English. Key words used for identification of articles included valproic acid, ethanol, alcohol, alcoholism, alcohol withdrawal delirium, alcohol withdrawal seizures, and substance withdrawal syndrome. References of identified articles were manually searched. Study Selection and Data Extraction: All controlled clinical trials that evaluated the use of valproic acid for the management of AWS in humans were included. Data Synthesis: Comparisons were made among various regimens of valproic acid and traditional therapy with benzodiazepine or nonbenzodiazepine agents. Only 2 of 6 trials reported a statistically significant difference in favor of valproic acid on endpoints of AWS. However, these differences were of marginal clinical significance. The number of patients included in these studies did not allow for adequate evaluation of safety. Conclusions: The existing limited efficacy and safety data suggest that valproic acid should not replace conventional therapy or be used as adjunct therapy for management of mild-to-moderate AWS.

Development of Clinical Pharmacy Key Performance Indicators for Hospital Pharmacists Using a Modified Delphi Approach

Background: Key performance indicators (KPIs) are quantifiable measures of quality. There are no published, systematically derived clinical pharmacy KPIs (cpKPIs). Objective: A group of hospital pharmacists aimed to develop national cpKPIs to advance clinical pharmacy practice and improve patient care. Methods: A cpKPI working group established a cpKPI definition, 8 evidence-derived cpKPI critical activity areas, 26 candidate cpKPIs, and 11 cpKPI ideal attributes in addition to 1 overall consensus criterion. Twenty-six clinical pharmacists and hospital pharmacy leaders participated in an internet-based 3-round modified Delphi survey. Panelists rated 26 candidate cpKPIs using 11 cpKPI ideal attributes and 1 overall consensus criterion on a 9-point Likert scale. A meeting was facilitated between rounds 2 and 3 to debate the merits and wording of candidate cpKPIs. Consensus was reached if 75% or more of panelists assigned a score of 7 to 9 on the consensus criterion during the third Delphi round. Results: All panelists completed the 3 Delphi rounds, and 25/26 (96%) attended the meeting. Eight candidate cpKPIs met the consensus definition: (1) performing admission medication reconciliation (including best-possible medication history), (2) participating in interprofessional patient care rounds, (3) completing pharmaceutical care plans, (4) resolving drug therapy problems, (5) providing in-person disease and medication education to patients, (6) providing discharge patient medication education, (7) performing discharge medication reconciliation, and (8) providing bundled, proactive direct patient care activities. Conclusions: A Delphi panel of hospital pharmacists was successful in determining 8 consensus cpKPIs. Measurement and assessment of these cpKPIs will serve to advance clinical pharmacy practice and improve patient care.

A critical appraisal of the quality of critical care pharmacotherapy clinical practice guidelines and their strength of recommendations

ObjectiveClinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations.MethodsMEDLINE (1966–February 2008), EMBASE (1980–February 2008), National Guideline Clearinghouse (February 2008) and personal files were searched to identify CPGs. Four appraisers evaluated each guideline using the appraisal of guidelines, research and evaluation (AGREE) instrument. AGREE assesses 23 items in six domains that include scope/purpose, stakeholder involvement, rigor of development, clarity, applicability and editorial independence. Standardized domain scores (0–100%) were determined to decide whether to recommend a guideline for use. One appraiser extracted strong pharmacotherapy recommendations and supporting evidence quality.ResultsTwenty-four CPGs were included. Standardized domain scores were clarity [69% (95% confidence interval (CI) 62–76%)], scope/purpose [62% (95% CI 55–68%)], rigor of development [51% (95% CI 42–60%)], editorial independence [39% (95% CI 26–52%)], stakeholder involvement [32% (95% CI 26–37%)] and applicability [19% (95% CI 12–26%)]. The proportion of guidelines that could be strongly recommended, recommended with alterations and not recommended was 25, 37.5 and 37.5%, respectively. High quality evidence supported 36% of strong pharmacotherapy recommendations.ConclusionVariation in AGREE domain scores explain why one-third of critical care pharmacotherapy CPGs cannot be recommended. Only one-third of strong pharmacotherapy recommendations were supported by high quality evidence. We recommend appraisal of guideline quality and the caliber of supporting evidence prior to applying recommendations.

Antidote stocking in British Columbia hospitals.

INTRODUCTION Previous studies have demonstrated that antidotes are insufficiently stocked in Canadian and US health care facilities. The purpose of this study was to determine the adequacy of antidote stocking in British Columbia hospitals based on the current guidelines. METHODS A written survey was mailed to hospital pharmacy directors at all 93 acute care facilities in BC. Availability of 14 essential antidotes was classified as sufficient or insufficient based on the current guidelines. Facilities were stratified into small (<50 beds), medium (50-250 beds) or large (>250 beds); teaching or non-teaching; trauma or non-trauma, urban or rural, and isolated or non-isolated. RESULTS Complete responses were received from 75 (81%) of 93 hospitals. No hospital had adequate stock of all 14 antidotes. Overall, the average number (+/- standard deviation) of antidotes adequately stocked was 4.2 +/- 2.9 per hospital. Urban hospitals had adequate stocks of 6.5 +/- 2.6 antidotes while rural centres had adequate stocks of 2.6 +/- 1.8 (p < 0.001). Corresponding figures were 9.0 +/- 1.8 for teaching hospitals vs. 3.7 +/- 2.4 for non-teaching hospitals (p < 0.001), 8.9 +/- 2.0 for trauma centres vs. 3.8 +/- 2.5 non-trauma centres (p < 0.001), and 2.5 +/- 2.1 for isolated hospitals vs. 4.6 +/- 2.9 for non-isolated hospitals (p = 0.018). Small, medium, and large hospitals adequately stocked 2.3 +/- 1.7, 5.7 +/- 2.2, and 7.7 +/- 3.0 antidotes, respectively (p < 0.001). The 4 antidotes most adequately stocked were sodium bicarbonate (77%), N-acetylcysteine (64%), ethanol (49%) and naloxone (47%). Digoxin immune Fab fragments, glucagon, pyridoxine and rattlesnake antivenin were poorly stocked with sufficient supplies of 5%, 7%, 7% and 13%, respectively. CONCLUSION BC hospitals do not have adequate antidote stocks. Provincial stocking guidelines and coordination of antidote purchasing and stocking are necessary to correct these deficiencies.

Rapid Imipenem/Cilastatin Desensitization for Multidrug-Resistant Acinetobacter Pneumonia

OBJECTIVE: To report a successful case of rapid imipenem desensitization in a critically ill patient with multidrug-resistant Acinetobacter baumannii ventilator-associated pnemonia (VAP). CASE SUMMARY: A 40-year-old white man who had a lengthy stay in the intensive care unit (ICU) following a motorcycle accident developed VAP caused by A. baumannii. Treatment with imipenem was necessary due to the bacterias resistance to all other antibiotics. However, this patient was diagnosed with an allergy to imipenem following exposure earlier in his hospitalization in addition to a positive penicillin skin test. Thus, we attempted rapid desensitization to imipenem using a continuous infusion protocol. The patient was desensitized within 4 hours and was successfully treated for 21 days with a continuous infusion of imipenem combined with daily amikacin. He experienced no adverse reaction during the desensitization process or the remainder of his treatment course. DISCUSSION: The protocol used in this case was modified from a previously reported case, and differed in the speed of desensitization and total daily dose. We assumed that a more gradual escalation of the dose in our modified protocol would prevent the occurrence of adverse events, thereby resulting in more rapid desensitization. Rapid desensitization was necessary in this patient due to the presence of a life-threatening infection. The lower total daily dose of imipenem was in response to impaired renal function. CONCLUSIONS: Therapeutic options for multidrug-resistant pneumonia in the ICU are significantly limited in the presence of imipenem allergy. An option of last resort is to desensitize the patient using a rapid administration protocol. Our modified rapid imipenem desensitization protocol was successful and allowed for effective treatment of life-threatening pneumonia.

Adequacy of antidote stocking in British Columbia hospitals: the 2005 Antidote Stocking Study

BACKGROUND Inadequate hospital stocking and the unavailability of essential antidotes is a worldwide problem with potentially disastrous repercussions for poisoned patients. Research indicates minimal progress has been made in the resolution of this issue in both urban and rural hospitals. In response to this issue the British Columbia Drug and Poison Information Centre developed provincial antidote stocking guidelines in 2003. We sought to determine the compliance with antidote stocking in BC hospitals and any factors associated with inadequate supply. METHODS A 2-part survey, consisting of hospital demographics and antidote stocking information, was distributed in 2005 to all acute care hospital pharmacy directors in BC. The 32 antidotes examined (21 deemed essential) and the definitions of adequacy were based on the 2003 BC guidelines. Availability was reported as number of antidotes stocked per hospital and proportion of hospitals stocking each antidote. For secondary purposes, we assessed factors potentially associated with inadequate stocking. RESULTS Surveys were completed for all 79 (100%) hospitals. A mean of 15.6+/-4.9 antidotes were adequately stocked per hospital. Over 90% of hospitals had adequate stocks of N-acetylcysteine, activated charcoal, naloxone, calcium salts, flumazenil and vitamin K; 71%-90% had adequate dextrose 50% in water (D50W), ethyl alcohol or fomepizole, polyethylene glycol electrolyte solution, protamine sulfate, and cyanide antidotes; 51%-70% had adequate folic acid, glucagon, methylene blue, atropine, pralidoxime, leucovorin, pyridoxine, and deferoxamine; and <50% had adequate isoproterenol and digoxin immune Fab. Only 7 (8.9%) hospitals sufficiently stocked all 21 essential antidotes. Factors predicting poor stocking included small hospital size (p < 0.0001), isolation (p = 0.01) and rural location (p < 0.0001). CONCLUSION Although antidote stocking has improved since the implementation of the 2003 guidelines, essential antidotes are absent in many BC hospitals. Future research should focus on determining the reasons for this situation and the effects of corrective interventions.

Corticosteroids in the Treatment of Severe Community-Acquired Pneumonia

Controversy surrounds the use of adjunctive corticosteroids in severe community acquired pneumonia (CAP) as current guidelines either do not address or discourage their use. Double-blind, placebo-controlled, randomized controlled trials examining systemic corticosteroids in the treatment of severe CAP were summarized and their impacts on patient-important outcomes assessed. Four trials describing systemic corticosteroid use in adults with severe CAP were identified. One trial had a significant mortality difference favoring corticosteroids. However, this may be the result of a CAP severity imbalance within the trial and the mortality benefit was not confirmed in a larger trial conducted in a similar critical care setting. Pneumonia severity, mortality assessment timing, comorbidities, corticosteroid and antibiotic choice and timing in the CAP disease course, and bias risks varied across the four trials. Because of the clinical heterogeneity of available studies and the unknowns pertaining to clinical efficacy and safety, we do not recommend the use of adjunctive corticosteroids in severe CAP.

Development of intervention-related quality indicators for renal clinical pharmacists using a modified Delphi approach

To develop a list of renal Quality Indicator Drug therapy problems (QI‐DTPs) that serve to advance renal pharmacy practice to improve patient care.