Study
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Intervention
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Outcome
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Conclusion
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Bradshaw et al.5
RCT- double blinded
Performed in United Kingdom
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IV Morphine + placebo (n = 136)
IV Morphine + metoclopramide 10 mg (n = 123)
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N/V between the two groups was not statistically significant (p = 0.3).
Overall incidence of N/V was low in both treatment groups (3.7% in placebo and 1.6% metoclopramide)
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Determined pre-treating patients with metoclopramide was not necessary.
Overall N/V associated with IV morphine was very low and recommended using antiemetics for patients who develop N/V
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Bhowmik et al. 8
RCT- double blinded
Performed in India
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IV Morphine + placebo (n = 53)
IV Morphine + promethazine (n = 54)
IV Morphine + ramosetron (n = 54)
IV Morphine + metoclopramide (n=54)
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Overall incidence of N/V was low in all treatment groups (9.4% ramosetron, 18.5% metoclopramide, 10.2% in promethazine and 6.2% in placebo)
Rate of N/V was not statistically significant between any of the groups.
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Incidence of N/V in patients was low in all treatment groups. Trial concluded that patients should receive antiemetic therapy only if experience N/V and not as a prophylactic agent with IV opiates.
Per results patients that received placebo + morphine had less N/V compared to other treatment groups; however, NOT statistically significant.
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Sussan et al 9
Randomized Double masked multicenter trial
Performed in 9 countries
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Investigated 2574 patients that received IV opiates and randomized 520 patients that developed N/V associated with IV opiates.
Group 1: placebo (n = 94)
Group 2: ondansetron 8 mg (n = 214)
Group 3: ondansetron 16mg (n = 211)
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Resolution of N/V was statistically more significant (p < 0.001) when comparing ondansetron therapy with placebo.
Group 1: 45.7% N/V resolved
Group 2: 62.3% N/V resolved
Group 3: 68.7% N/V resolved
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Concluded the best practice would be to treat patients’ N/V after development in patients that receive IV opiates.
Trial determined the prevalence of N/V is minimal and exposing patients to medication they do not need puts them at risk for additional adverse drug reactions.
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Month: November 2015
The Dark Arts of Pharmacokinetics
Single, double or triple? In terms of vancomycin dosing kinetics, it’s an important question. Pharmacokinetic teachings tell us to select the simplest model and fewest compartments necessary to describe the data adequately. Thus the single compartment model is frequently used in initial dosing of vancomycin. For the most part, vancomycin dosing teachings include solving patient cases using one compartment pk formulas such as the Sawchuck-Zaske.1
A two compartment model acknowledges the distribution of vancomycin from plasma into tissues.
Troughs as a surrogate for AUC 0-24/MIC is a debate for another post, but in the real world the practice is to follow trough.6-8
Population: This was a prospective analysis of the divided vancomycin loading protocol in consecutive patients weighing > 137% IBW (mean weight: 111 + 31 kg) and admitted to a single community hospital (Marin General Hospital). Patients were excluded if they had long-term paralysis, pregnant, receiving some other vancomycin protocol or had monitoring errors.
Intervention: Divided load protocol was dependent on the IBW, % over IBW and CrCl. Most patients received 1g IV q6 x 4 doses unless they were a) very tall or b) low CrCl.
Within 12 hours:
- Trough 10-20, n = 48 (89%); mean 14.5 + 3.2
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Trough > 10, n = 51 (94%); including the above 48 patients, with the other 3 (6%) having troughs > 20 (20.5 – 22.5)
Within 24 hours: 31 patients had troughs drawn at 24 hours. 19 patients had dosing interval changes that moved the trough draw beyond 24 hours (unclear why, i.e. change in protocol, poor follow up, clinical event (AKI), etc.)
- Trough 10-20, n = 30/32 (97%); mean 15.0 + 3.1
“The biphasic, divided-load obese protocol described here achieved vancomycin trough concentrations in the range of 10-20 within the first 12 hours of treatment for 89% of patients weighing up to 245.2kg, and 97% of trough concentrations sampled during maintenance dosing for the patients were within target range.”
Small sample, although met its predefined power at 12 hours.
Then there is whether it should be taken to a three compartment model.
We’re still between a rock and a hard place when it comes to dosing vancomycin in obese patients. This new approach seems logical and in this limited study and appears to achieve the desired outcome, but not necessarily improved patient oriented outcomes. Clearly more evidence is needed to hash out how to dose vancomycin in obese patients, but this protocol could have a role in the future.
References:
1. Winter ME. Basic Clinical Pharmacokinetics. 3rdedition. Edited by Mary Anne Koda-Kimble, Applied Therapeutics Inc. Vancouver, WA. Copyright 1996
2. Matzke GR et al. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother 1984:25;433-7
3. Rybak MJ, Lomaestro BM, Rotschafer JC et al. Therapeutic monitoring of vancomycin in adults summary of consensus recommendations from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Pharmacotherapy. Nov 2009;29(11):1275–1279
4. Wesner AR, Brackbill ML, Coyle LL, Kidd RS. Prospective trial of a novel nomogram to achieve updated vancomycin trough concentrations. Interdiscip Perspect Infect Dis. 2013;2013:839456. doi:10.1155/2013/839456
5. Reynolds DC, Waite LH, Alexander DP, DeRyke CA. Performance of a vancomycin dosage regimen developed for obese patients. Am J Health Syst Pharm. 2012;69:944-950
6. Brown J, Brown K, Forrest A. Vancomycin AUC24/MIC ratio in patients with complicated bacteremia and infective endocarditis due to methicillin-resistant Staphylococcus aureus and its association with attributable mortality during hospitalization. Antimicrob Agents Chemother. 2012;56:634-638. doi:10.1128/AAC.05609-11
7. Lodise TP, Drusano GL, Butterfield JM, Scoville J, Gotfried M, Rodvold KA. Penetration of vancomycin into epithelial lining fluid in healthy volunteers. Antimicrob Agents Chemother. 2011;55:5507-5511
8. Skhirtladze K, Hutschala D, Fleck T, et al. Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. Antimicrob Agents Chemother. 2006;50: 1372-1375
9. Denetclaw TH, Yu MK, Moua M, Dowling TC, Steinke D. Performance of a divided-load intravenous vancomycin dosing strategy for obese patients. Ann Pharmacother 2015;49(8): 861-868
Vanishing Vasopressin
Vasopressin has gone by the way of atropine in the updated ACLS guidelines.1 But is this a reason to sachet into your next resuscitation/critical care meeting and suggest vasopressin be removed from your hospital’s crash carts? No. Don’t do it. Don’t just read the guidelines; read the primary literature.
2010 Guidelines
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2015 Guidelines
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What the What?
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Lindner KH, et al.Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation. Lancet. 1997;349:535–537
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Not included in 2010… perhaps it was in the review article they cite below.
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Wenzel V, et al; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105–113
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Wenzel V, et al; European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004;350:105–113
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Stiell IG, et al. Vasopressin versus epinephrine for inhospital cardiac arrest: a randomised controlled trial. Lancet. 2001;358:105–109
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Not sure where this one went.
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Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med. 2005;165:17–24
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Review article, shouldn’t have been included
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Callaway CW, et al. Usefulness of vasopressin administered with epinephrine during out-of-hospital cardiac arrest. Am J Cardiol. 2006;98:1316–1321
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Callaway CW, et al. Usefulness of vasopressin administered with epinephrine during out-of-hospital cardiac arrest. Am J Cardiol. 2006;98:1316–1321
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Gueugniaud PY, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21–30
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Gueugniaud PY, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21–30
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Mukoyama T, Kinoshita K, Nagao K, Tanjoh K. Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation. Resuscitation. 2009;80:755–761
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Mukoyama T, Kinoshita K, Nagao K, Tanjoh K.Reduced effectiveness of vasopressin in repeated doses for patients undergoing prolonged cardiopulmonary resuscitation. Resuscitation. 2009;80:755–761
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Ducros L, et al. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans. J Emerg Med. 2011;41:453–459
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Published after 2010
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Ong ME, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83:953–960
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Published after 2010
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References:
1. 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132(18) supplement 2.
2. Hagihara A et al. Prehospital Epinephrine Use and Survival Among Patients with OHCA. JAMA 2012; 307(11):1161-68.
3. Nakahara S et al. Evaluation of pre-hospital administration of adrenaline (epinephrine) by emergency medical services for patients with out of hospital cardiac arrest in Japan: controlled propensity matched retrospective cohort study. BMJ December 2013.
4. Olasveengen TM, Sunde K, Brunborg C, et al. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA 2009; 302:2222–2229.
5. Jacobs IG, Finn JC, Jelinek GA, et al. Effect of adrenaline on survival in out-of hospital cardiac arrest: a randomised double-blind placebo-controlled trial. Resuscitation 2011; 82:1138–1143.
6. Mentzelopoulos S, Zakynthinos S, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med 2009;169:15-24. PMID: 19139319
7. Mentzelopoulos S, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013;310(3):270-9. PMID: 19139319
8. Varvarousi G, Stefaniotou A, Varavaroussis D, et al. Glucocorticoids as an emergency pharmacologic agent for cardiopulmonary resuscitation. Cardiovasc Drugs Ther. 2014;28:477-88. PMCID: PMC4163188
9. Ong ME, et al. A randomised, double-blind, multi-centre trial comparing vasopressin and adrenaline in patients with cardiac arrest presenting to or in the Emergency Department. Resuscitation. 2012;83:953-960.
10. Mayr V, et al. Developing a vasopressor combination in a pig model of adult asphyxia cardiac arrest. Circulation, 2001;104:1651-1656.
11. 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science. Circulation. 2010; 122(18) supplement 3.
12. Ducros L, et al. Effect of the addition of vasopressin or vasopressin plus nitroglycerin to epinephrine on arterial blood pressure during cardiopulmonary resuscitation in humans. J Emerg Med. 2011;41:453-459.
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