UCONN Emergency Medicine Interest Group

Posts Tagged ‘RCT’

Journal Article Synopsis: Apixaban and ACS

In JOURNAL CLUB on October 30, 2011 at 7:00 AM

Summary of “Apixaban with Antiplatelet Therapy after Acute Coronary Syndrome” by John Alexander et. al, New England Journal of Medicine ePub ahead of print: July 24th 2011: pp. 1-10

What is already known on this topic:
Patients with acute coronary syndromes frequently have recurrent ischemic events despite the use of currently recommended antiplatelet therapy, revascularization procedures, and other evidence based secondary preventative measures. Anticoagulation therapy with oral vitamin K antagonists reduces the recurrence of ischemic events following MI however, when added to aspirin or aspirin and clopidogrel combined it increases the risk of bleeding. Previous studies of the use of the factor Xa inhibitor apixiban were conducted in patients who had recent acute coronary syndrome and were receiving aspirin or aspirin and clopidogrel. Treatment with apixiban resulted in dose related increase in bleeding with a trend towards fewer ischemic events.

What question this study addressed:
Does the benefit of adding apixiban to standard acute coronary treatment outweigh the increased risk of bleeding in high-risk patients?

What was the study design:
The Apixiban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial was a double blind, placebo-controlled, randomized clinical trial conducted at 858 sites in 39 countries. Patients included in this study must have had an acute coronary syndrome (myocardial infarction, with or without ST-segment elevation, or unstable angina) within the previous 7 days, with symptoms of myocardial ischemia lasting more than 10 minutes with the patient at rest plus either elevated cardiac biomarkers or dynamic ST-segment elevation or depression of 0.1mV or more. Patients meeting these criteria were eligible for the study if their condition was clinically stable and they were receiving standard treatment for acute coronary syndrome, including aspirin or aspirin and any P2Y12-receptor antagonist. Eligible patients were also required to have two high-risk characteristics which included: an age of at least 65 years, diabetes mellitus, MI within the previous 5 years, cerebrovascular disease, peripheral vascular disease, clinical heart failure or a left ventricular ejection fraction of less than 40% in association with the index event, impaired renal function with a calculated creatinine clearance of less than 60ml per minute, and no revascularization after the index event.

What this study adds to our knowledge:
Administration of apixiban at a dose of 5mg twice daily in high risk patients taking either aspirin or aspirin plus clopidogrel significantly increases bleeding events, including events of fatal and intracranial bleeding, without significant reduction in recurrent ischemic events.

How this is relevant to clinical practice:
The current standard of care for patients after acute coronary syndrome includes dual antiplatelet therapy, usually with aspirin and clopidogrel. Even with this aggressive antiplatelet therapy patients still frequently experience recurrent ischemic events. Newer P2Y12 antagonists are more potent and provide additional reductions in ischemic events and mortality but at the cost of increased risk of bleeding. The combination of antiplatelet and anticoagulant therapy seems attractive, yet it may pose an unacceptable risk of bleeding.

Other considerations:
The population included in the study comprised only high-risk patients, with large proportions of those patients having diabetes, heart failure, or renal insufficiency. The lack of significant reduction in recurrent ischemic events could partially be a product of such a high-risk population. As the authors noted, there may be other patient populations for which the results may be different.

Journal Article Synopsis: Vascular Access during Out-of-Hospital Cardiac Arrest

In JOURNAL CLUB on October 16, 2011 at 8:00 AM

Summary ofJournal Article Synopsis: Intraosseous Versus Intravenous Vascular Access During Out-of-Hospital Cardiac Arrest: A Randomized Controlled Trial,” Reades, Rosalyn, MD; Studnek, Jonathan R., PhD, NREMT-P; Vandeventer, Steven, EMT-P; Garret, John, MD.  Annals of Emergency Medicine. 2011 Aug 17. [Epub ahead of print]

What is already known on this topic:
Intraosseous vascular access was originally used mainly in children.  However, it has recently been shown that this method is also a rapid and effective way to obtain vascular access in the adult population, especially when a peripheral intravenous line fails.  Therefore, this technique is used commonly in out-of-hospital settings when rapid vascular access is needed during cardiac arrest.  Emergency Medical Services (EMS) protocols in the US list sternal, humeral, and tibial locations as available sites for intraosseous vascular access.

What question this study addressed:
The humeral and tibial locations are better sites during cardiac arrest due to constant chest compressions.  However, data regarding the effectiveness of the humeral site versus the tibial site are limited.  This study assessed the frequency of first-attempt success between humeral intraosseous, tibial intraosseous, and peripheral intravenous routes during out-of hospital cardiac arrest.

What was the study design:
This study was a prospective, nonblinded, triple-arm, randomized control trial of 182 adult patients over 18 years of age experiencing a non-traumatic out-of-hospital cardiac arrest in which resuscitation was initiated.  Patients were randomized to one of 3 vascular access routes: tibial intraosseous, humeral intraosseous, or peripheral intravenous.  Paramedics received extensive training in each method.  The outcome measure was first-attempt success, defined as secure needle position in the marrow cavity or a peripheral vein with normal fluid flow.  If a needle dislodged, it was considered a failure.

What this study adds to our knowledge:
Tibial intraosseous vascular access was determined to be the optimal method with regards to highest success rate and fastest time to access.  However, peripheral intravenous access was associated with a higher volume of infused fluid.

How this is relevant to clinical practice:
Tibial intraosseous vascular access is beneficial for patients in who are in cardiac arrest or unconscious and who are unlikely to need large-volume fluid resuscitation.  Its location is more removed from the primary site of resuscitation efforts, and is generally not beneath large amounts of soft tissue.

Other considerations:
The cost of intraosseous vascular access is much greater than the cost of peripheral intravenous vascular access.  Further studies should be conducted to determine the cost effectiveness of tibial intraosseous over peripheral intravenous access.

Journal Article Synopsis: Ibuprofen and Acetazolamide as Prophylaxis for High Altitude Headache

In JOURNAL CLUB on May 18, 2011 at 5:50 PM

Summary for “Prospective, Double-Blind, Randomized, Placebo-Controlled Comparison of Acetazolamide Versus Ibuprofen for Prophylaxis Against High Altitude Headache: The Headache Evaluation at Altitude Trial (HEAT) by Jeffery Gertsch, MD, et al. in Wilderness and Environmental Medicine vol 21 pp: 236-243.

What is already known on this topic:
Headaches are one of the most common complaints from those who venture into high altitudes. Termed High Altitude Headaches (HAH), these can occur as benign incidents but are also considered a sentinel symptom of the development of Acute Mountain Sickness (AMS). AMS is defined at altitudes above 2500m with the presence of headache and one other symptom (anorexia, fatigue, insomnia, or dizziness).  Left untreated, AMS can lead to High Altitude Cerebral Edema (HACE) which is associated with a significant mortality rate. Ibuprofen was widely been used in the treatment of HAH through its inhibition of the inflammatory pathway. Acetazolamide, a diuretic and carbonic anhydrase inhibitor, has also been documented in the prevention of altitude headaches. The mechanisms of AMS prevention include renally induced metabolic acidosis resulting in diuresis and increased ventilation and inhibition of CSF production.

What questions this study addressed:
Despite the frequency with which HAH occur, there is a relative lack of literature pertaining to its prevention. This study was designed to compare the effects of treatment with ibuprofen with acetazolamide while also better establishing clinical standards for HAH prevention.

What was the study design:
This study was a prospective, double-blind, randomized, placebo-controlled trial.

What this study adds to our knowledge:
Both ibuprofen and acetazolamide proved effective in the prevention of HAH and can be recommended for prophylaxis at altitude with the inference that acetazolamide may prevent more severe headaches. The clinical efficacy of low-dose acetazolamide in the prevention of AMS has been reconfirmed and ibuprofen was also found to be effective against symptoms of AMS.

How this is relevant to clinical practice:
The use of these drugs in high altitude situations may help lower the incidence of AMS and thus prevent the onset of HACE and decrease the incidence of HACE-related mortality.

Other considerations:
Would other NSAIDs provide the same or similar protection? Is the action of ibuprofen simply masking the pain of a true underlying HAH? The participants were already at a high altitude before they began the study. What then, would be the effect of ibuprofen and acetazolamide on people going from low altitude to high. Are these drugs really preventing HAPE/HACE or are they simply preventing one of the symptoms?

Journal Article Synopsis: Prewired Electrodes for ECG

In JOURNAL CLUB on May 11, 2011 at 5:42 PM

Summary for “Comparison of the Use of Conventional and Prewired Electrodes for Electrocardiography in an Emergency Setting: The Spaghetti Study” by Frederic Lapostolle et al. in Annals of Emergency Medicine Vol 57 (4); pp 357 -361

What is already known on this topic:
ECG’s are a routine procedure commonly encountered in the Emergency Department and integral to the diagnosis and disposition of a wide variety of patients. The two most important factors in the usefulness of an ECG are its quality and the duration of time it takes to be performed. A poorly done ECG done promptly can be just as useless as a well-done ECG received too late. Therefore, improvements in the speed and quality of ECG recording are highly sought after.

The quality and promptness of an ECG are heavily influenced by the user. It is not uncommon for errors to occur in the placement of ECG leads, in particular reversal of the leads. These types of mistakes can lead to a significant loss in time and accuracy of interpretation of ECG’s. Unfortunately, these types of errors are more common in the acute settings, such as those often seen in Emergency Departments. This study involved the use of pre-wired electrodes, rather than conventional electrodes that are placed and then hooked up to the series of wires. These prewired electrodes are disposable, pre-wired, pre-gelled, and numbered for ease and elimination of ambiguity in placement.

What questions this study addressed:
Is there a difference in the quality of ECG recordings obtained with conventional versus prewired electrodes ? How easy is the use of the prewired electrodes in an emergency setting?

What was the study design:
Prospective, randomized, open comparison study including 105 patients undergoing ECG’s. Time to make recordings was measured, and both a prewired and conventional recording was performed. These were then analyzed and scored by 3 blinded reviewers, on the basis of artifacts and baseline instability.

What this study adds to our knowledge:
The ECG’s performed with the prewired electrodes took 20% less time than those done with conventional electrodes (average 118 seconds versus 144 seconds). Signal noise and baseline instability were significantly reduced with prewired electrodes regardless of the endpoint considered (whether number of unstable leads, max signal noise, baseline instability score, etc). There was no significant difference found in the prevalence of p-wave or QRS complex abnormalities.

How this is relevant to clinical practice:
The recordings done with prewired electrodes were accomplished significantly faster than those with conventional – and this did not include the time necessary to disinfect and untangle the lead wires (a daunting task, at times). In addition, recordings with prewired electrodes were significantly better than those made with conventional electrodes. The number of artifact-free recordings was nearly twice as high, and the level of signal noise and baseline instability was significantly lower.

Other considerations:
It would be interesting to examine this from a cost-benefit perspective. Although prewired electrodes are faster and provide better recordings, they are also more expensive – would they pay for themselves with faster and better quality care?

Journal Article Synopsis: Ketamine vs. Ketofol, an RCT

In JOURNAL CLUB on May 1, 2011 at 4:15 PM

Summary for “A Blinded, Randomized Controlled Trial to Evaluate Ketamine/Propofol Versus Ketamine Alone for Procedural Sedation in Children” by Amit Shah et al. in Annals of Emergency Medicine Vol 57 (5); pp 425 -433

What is already known on this topic:
Ketamine is a well-established agent used for procedural sedation of children in the Emergency Department.   However, ketamine recovery times can be lengthy and have been shown to range from 25-108 minutes.  Recently, the use of propofol for procedural sedation has become more popular given its favorable pharmokinetics and adverse events profile.  The disadvantage of propofol is the risk of dose-dependent respiratory depression.

Recent studies have demonstrated the safety of administering ketamine and propofol together.  The premise behind administering both medications together, is that it allows for a dose reduction in each medication and thus decreases the risk of respiratory depression.  In addition, ketamine and propofol exhibit several opposite qualities, which may complement each other for a more favorable side effect profile (i.e.  ketamine is emetogenic while propofol has antiemetic properties; ketamine often produces post procedural agitation, while propofol has anxiolytic properties; ketamine maintains respiratory drive, while propofol depresses repiratory drive; ketamine provides an element of analgesia which propofol is lacking)

What question this study addressed:
Is there a clinically significant decrease in total sedation time (10 minutes or more) when using ketamine plus propofol compared to the use of ketamine alone for pediatric procedural sedation?

Secondarily, is there a significant difference in time to recovery, adverse events, efficacy, or satisfaction scores between ketamine plus propofol or ketamine alone?

What was the study design:
Blinded, randomized, controlled trial including 136 pediatric patients requiring procedural sedation for an isolated orthopedic injury.

What this study adds to our knowledge:
The use of ketamine plus propofol compared to the use of ketamine alone reduced the total sedation time by 3 minutes (p=0.04).  In addition, ketamine plus propofol demonstrated a 10% reduction in vomiting compared to ketamine alone (95% CI  -18% to -2%).  Finally, satisfication scores were higher with the ketamine/propofol group (p<0.05).  There was no statistical difference between the two groups with respect to efficacy or airway complications.

How this is relevant to clinical practice:
The combination of ketamine plus propofol for procedural sedation only minimally reduces total sedation time (3 minutes) making it questionable as to whether or not this is clinically significant.  However, ketamine plus propofol does decrease the incidence of vomiting and has a higher rate of satisfaction among patients, nurses, and physicians.

Other considerations:
It would be interesting to compare ketamine plus propofol to propofol alone for pediatric procedural sedation.

%d bloggers like this: