Elizabeth A. Paesch, MD

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Physicians are exposed to a wide variety of cases that pique our interest. Cases that make you go home and read just a little bit more. Cases that prompt you to seek out your classmates and colleagues for further discussion, or trigger a call to someone from your past. Residents and students often ask, “Should I write this case up?” Our answer is, “Yes!”

Why do we recommend that you write the case up? Much of medical education is a clinical- or case-based exercise. Clinical cases provide context for the principles being taught. We use real cases to point out the nuance in a presentation of a particular illness or the management of a disease.

In clinical conferences, such as morning report or clinical-pathologic conferences (CPCs), we highlight the choices we make as physicians to provide the best care. Respected physicians and master clinicians at our own institutions often lead these discussions, which form the building blocks for how many of us will practice in our careers.

At grand rounds, the best speakers start with a case. These vignettes grab our attention, making us realize the importance of what the speaker teaches us.

Writing up a vignette will give you a skill set you need. You learn how to select a case, create a “teachable moment,” or hone a series of teaching points. You develop your skills in searching and critically appraising the literature. You become a content expert among your peers. This activity helps you to develop and master the academic skills that will drive your career and will be pivotal in your success.

Follow these eight steps to produce successful clinical vignette submissions:

click for large version

Step 1

Be a good doctor and make the correct diagnosis: Interesting cases will come to you. Don’t chase a zebra on every cough. Don’t send autoimmune panels for every rash. Read about each patient’s case that you see. Use the time to build your clinical acumen and develop your own illness scripts. Through the process of being a thoughtful student of medicine, you will come to distinguish the fascinoma from the merely fleeting infatuation with a diagnosis.

Step 2

Recognize the good case: The best way to recognize a good case is appreciate when it excites people locally. If you present it at morning report or CPC, are you inundated with requests to speak more after the conference has finished? Did it stump your colleagues (usually a pretty bright group)? Do you find that the consultants ask for others in their division to come and see the case? Clinically, did it take the team a while to come to the end diagnosis? If any of these are true, then you should move forward.

Step 3

Perform a literature search: How often does a similar situation arise? Is it 1 in 10,000, 1 in a million, or less? Even a case of 1 in 10,000 can be impactful to read about when you consider how long it may take a physician to see that many patients.

Step 4.

Develop two or three teaching points: Most abstracts for national and regional meetings have a restrictive word limit. When you consider all the information required of a thorough case presentation and adequate discussion, it can seem almost impossible to fit it all in. Start early, at least a month before the deadline if you can, and start big. Determine two or three key teaching points you wish to make. These will serve as your roadmap for the write-up.

Next, write down everything you want to say. Then cut the verbiage and descriptions that are not needed to tell your story. Focus on two or three take-home points. Each fact included or statement made should help to guide the reader to these lessons. As readers and authors, we also like to see prevalence and incidence of disease findings, or how good a test is with specificity and sensitivity values. Make sure the readers know what you want them to learn.

click for large version

Step 5

Keep the case concise, and focus on the discussion: The best write-ups keep the case description short and focused. Avoid trying to tell your readers everything about your case. Highlight what makes your case different without including extraneous information that does not support your teaching points. This leaves more room to focus on your discussion and explain to the reader the importance of your case. The discussion is where you create the “teachable moment” by elaborating on your teaching points.

Step 6

Keep your drafts and proofread your work carefully: The process of writing a clear and concise vignette will take many drafts. To do a great job, plan for at least three or four versions. Through the process of revisiting every word you use, you will start to hone your mastery of the topic; you will see the case in a new way with each draft.

As you do this, keep each edit as a separate file. You will inevitably edit something out early on that you will want to put back in later. Keeping your drafts will make this much easier.

At the final version, proofread carefully! Most reviewers will deduct points for poor grammar and misspellings. If it looks sloppy, then a reader will assume it represents sloppy thoughts.

Step 7

Get feedback: Have others read your work. It is always hard to put your writing out there for critique, particularly when it is such a personal representation of your own clinical thought. Hopefully, you have collaborated with others involved in the case; however, to avoid any “group think” about the work, it is best to have uninvolved individuals (e.g., trusted faculty member, program director, division chief) review your work before submission. The point of these vignettes is to help you develop skills as an author and academician. Since most meetings do not provide any feedback on the review of your submission, outside of “accepted” or “rejected,” it is important to get this from your own institution. It will also heighten your chances of acceptance. Take their suggestions openly, and use them to refine your abstract.

Step 8

Consider the following keys to a poster or oral presentation: The presentation at the meeting should be an expansion on the abstract. Remember, you have described the situation, but now you have the opportunity to use a picture. The old adage that a picture is worth a thousand words really rings true here.

Avoid copying and pasting your text. Concise statements will grab people’s eyes and leave you more space for charts and images. Visuals grab the reader’s eye better than small-font text.

Conclusion

Your first clinical vignette can be a truly great experience. Although it is a lot of hard work, presenting clinical thought is a skill that you must learn. Once you do this, you might find that you have “caught the bug,” and will find yourself well on your way to a role in medical education. You might even start a larger project based on this experience.

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Beth Israel Medical Center and assistant dean and assistant professor of medicine at Albert Einstein College of Medicine, both in New York City. Dr. Paesch is a comprehensive care physician in the section of hospital medicine at the University of Chicago, and assistant professor at the University of Chicago Pritzker School of Medicine. Dr. Miller is director of student programs, associate program director, residency, and associate professor of medicine in the Department of Medicine at Tulane Health Sciences Center in New Orleans.

click for large version

Physicians are exposed to a wide variety of cases that pique our interest. Cases that make you go home and read just a little bit more. Cases that prompt you to seek out your classmates and colleagues for further discussion, or trigger a call to someone from your past. Residents and students often ask, “Should I write this case up?” Our answer is, “Yes!”

Why do we recommend that you write the case up? Much of medical education is a clinical- or case-based exercise. Clinical cases provide context for the principles being taught. We use real cases to point out the nuance in a presentation of a particular illness or the management of a disease.

In clinical conferences, such as morning report or clinical-pathologic conferences (CPCs), we highlight the choices we make as physicians to provide the best care. Respected physicians and master clinicians at our own institutions often lead these discussions, which form the building blocks for how many of us will practice in our careers.

At grand rounds, the best speakers start with a case. These vignettes grab our attention, making us realize the importance of what the speaker teaches us.

Writing up a vignette will give you a skill set you need. You learn how to select a case, create a “teachable moment,” or hone a series of teaching points. You develop your skills in searching and critically appraising the literature. You become a content expert among your peers. This activity helps you to develop and master the academic skills that will drive your career and will be pivotal in your success.

Follow these eight steps to produce successful clinical vignette submissions:

click for large version

Step 1

Be a good doctor and make the correct diagnosis: Interesting cases will come to you. Don’t chase a zebra on every cough. Don’t send autoimmune panels for every rash. Read about each patient’s case that you see. Use the time to build your clinical acumen and develop your own illness scripts. Through the process of being a thoughtful student of medicine, you will come to distinguish the fascinoma from the merely fleeting infatuation with a diagnosis.

Step 2

Recognize the good case: The best way to recognize a good case is appreciate when it excites people locally. If you present it at morning report or CPC, are you inundated with requests to speak more after the conference has finished? Did it stump your colleagues (usually a pretty bright group)? Do you find that the consultants ask for others in their division to come and see the case? Clinically, did it take the team a while to come to the end diagnosis? If any of these are true, then you should move forward.

Step 3

Perform a literature search: How often does a similar situation arise? Is it 1 in 10,000, 1 in a million, or less? Even a case of 1 in 10,000 can be impactful to read about when you consider how long it may take a physician to see that many patients.

Step 4.

Develop two or three teaching points: Most abstracts for national and regional meetings have a restrictive word limit. When you consider all the information required of a thorough case presentation and adequate discussion, it can seem almost impossible to fit it all in. Start early, at least a month before the deadline if you can, and start big. Determine two or three key teaching points you wish to make. These will serve as your roadmap for the write-up.

Next, write down everything you want to say. Then cut the verbiage and descriptions that are not needed to tell your story. Focus on two or three take-home points. Each fact included or statement made should help to guide the reader to these lessons. As readers and authors, we also like to see prevalence and incidence of disease findings, or how good a test is with specificity and sensitivity values. Make sure the readers know what you want them to learn.

click for large version

Step 5

Keep the case concise, and focus on the discussion: The best write-ups keep the case description short and focused. Avoid trying to tell your readers everything about your case. Highlight what makes your case different without including extraneous information that does not support your teaching points. This leaves more room to focus on your discussion and explain to the reader the importance of your case. The discussion is where you create the “teachable moment” by elaborating on your teaching points.

Step 6

Keep your drafts and proofread your work carefully: The process of writing a clear and concise vignette will take many drafts. To do a great job, plan for at least three or four versions. Through the process of revisiting every word you use, you will start to hone your mastery of the topic; you will see the case in a new way with each draft.

As you do this, keep each edit as a separate file. You will inevitably edit something out early on that you will want to put back in later. Keeping your drafts will make this much easier.

At the final version, proofread carefully! Most reviewers will deduct points for poor grammar and misspellings. If it looks sloppy, then a reader will assume it represents sloppy thoughts.

Step 7

Get feedback: Have others read your work. It is always hard to put your writing out there for critique, particularly when it is such a personal representation of your own clinical thought. Hopefully, you have collaborated with others involved in the case; however, to avoid any “group think” about the work, it is best to have uninvolved individuals (e.g., trusted faculty member, program director, division chief) review your work before submission. The point of these vignettes is to help you develop skills as an author and academician. Since most meetings do not provide any feedback on the review of your submission, outside of “accepted” or “rejected,” it is important to get this from your own institution. It will also heighten your chances of acceptance. Take their suggestions openly, and use them to refine your abstract.

Step 8

Consider the following keys to a poster or oral presentation: The presentation at the meeting should be an expansion on the abstract. Remember, you have described the situation, but now you have the opportunity to use a picture. The old adage that a picture is worth a thousand words really rings true here.

Avoid copying and pasting your text. Concise statements will grab people’s eyes and leave you more space for charts and images. Visuals grab the reader’s eye better than small-font text.

Conclusion

Your first clinical vignette can be a truly great experience. Although it is a lot of hard work, presenting clinical thought is a skill that you must learn. Once you do this, you might find that you have “caught the bug,” and will find yourself well on your way to a role in medical education. You might even start a larger project based on this experience.

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Beth Israel Medical Center and assistant dean and assistant professor of medicine at Albert Einstein College of Medicine, both in New York City. Dr. Paesch is a comprehensive care physician in the section of hospital medicine at the University of Chicago, and assistant professor at the University of Chicago Pritzker School of Medicine. Dr. Miller is director of student programs, associate program director, residency, and associate professor of medicine in the Department of Medicine at Tulane Health Sciences Center in New Orleans.

click for large version

Physicians are exposed to a wide variety of cases that pique our interest. Cases that make you go home and read just a little bit more. Cases that prompt you to seek out your classmates and colleagues for further discussion, or trigger a call to someone from your past. Residents and students often ask, “Should I write this case up?” Our answer is, “Yes!”

Why do we recommend that you write the case up? Much of medical education is a clinical- or case-based exercise. Clinical cases provide context for the principles being taught. We use real cases to point out the nuance in a presentation of a particular illness or the management of a disease.

In clinical conferences, such as morning report or clinical-pathologic conferences (CPCs), we highlight the choices we make as physicians to provide the best care. Respected physicians and master clinicians at our own institutions often lead these discussions, which form the building blocks for how many of us will practice in our careers.

At grand rounds, the best speakers start with a case. These vignettes grab our attention, making us realize the importance of what the speaker teaches us.

Writing up a vignette will give you a skill set you need. You learn how to select a case, create a “teachable moment,” or hone a series of teaching points. You develop your skills in searching and critically appraising the literature. You become a content expert among your peers. This activity helps you to develop and master the academic skills that will drive your career and will be pivotal in your success.

Follow these eight steps to produce successful clinical vignette submissions:

click for large version

Step 1

Be a good doctor and make the correct diagnosis: Interesting cases will come to you. Don’t chase a zebra on every cough. Don’t send autoimmune panels for every rash. Read about each patient’s case that you see. Use the time to build your clinical acumen and develop your own illness scripts. Through the process of being a thoughtful student of medicine, you will come to distinguish the fascinoma from the merely fleeting infatuation with a diagnosis.

Step 2

Recognize the good case: The best way to recognize a good case is appreciate when it excites people locally. If you present it at morning report or CPC, are you inundated with requests to speak more after the conference has finished? Did it stump your colleagues (usually a pretty bright group)? Do you find that the consultants ask for others in their division to come and see the case? Clinically, did it take the team a while to come to the end diagnosis? If any of these are true, then you should move forward.

Step 3

Perform a literature search: How often does a similar situation arise? Is it 1 in 10,000, 1 in a million, or less? Even a case of 1 in 10,000 can be impactful to read about when you consider how long it may take a physician to see that many patients.

Step 4.

Develop two or three teaching points: Most abstracts for national and regional meetings have a restrictive word limit. When you consider all the information required of a thorough case presentation and adequate discussion, it can seem almost impossible to fit it all in. Start early, at least a month before the deadline if you can, and start big. Determine two or three key teaching points you wish to make. These will serve as your roadmap for the write-up.

Next, write down everything you want to say. Then cut the verbiage and descriptions that are not needed to tell your story. Focus on two or three take-home points. Each fact included or statement made should help to guide the reader to these lessons. As readers and authors, we also like to see prevalence and incidence of disease findings, or how good a test is with specificity and sensitivity values. Make sure the readers know what you want them to learn.

click for large version

Step 5

Keep the case concise, and focus on the discussion: The best write-ups keep the case description short and focused. Avoid trying to tell your readers everything about your case. Highlight what makes your case different without including extraneous information that does not support your teaching points. This leaves more room to focus on your discussion and explain to the reader the importance of your case. The discussion is where you create the “teachable moment” by elaborating on your teaching points.

Step 6

Keep your drafts and proofread your work carefully: The process of writing a clear and concise vignette will take many drafts. To do a great job, plan for at least three or four versions. Through the process of revisiting every word you use, you will start to hone your mastery of the topic; you will see the case in a new way with each draft.

As you do this, keep each edit as a separate file. You will inevitably edit something out early on that you will want to put back in later. Keeping your drafts will make this much easier.

At the final version, proofread carefully! Most reviewers will deduct points for poor grammar and misspellings. If it looks sloppy, then a reader will assume it represents sloppy thoughts.

Step 7

Get feedback: Have others read your work. It is always hard to put your writing out there for critique, particularly when it is such a personal representation of your own clinical thought. Hopefully, you have collaborated with others involved in the case; however, to avoid any “group think” about the work, it is best to have uninvolved individuals (e.g., trusted faculty member, program director, division chief) review your work before submission. The point of these vignettes is to help you develop skills as an author and academician. Since most meetings do not provide any feedback on the review of your submission, outside of “accepted” or “rejected,” it is important to get this from your own institution. It will also heighten your chances of acceptance. Take their suggestions openly, and use them to refine your abstract.

Step 8

Consider the following keys to a poster or oral presentation: The presentation at the meeting should be an expansion on the abstract. Remember, you have described the situation, but now you have the opportunity to use a picture. The old adage that a picture is worth a thousand words really rings true here.

Avoid copying and pasting your text. Concise statements will grab people’s eyes and leave you more space for charts and images. Visuals grab the reader’s eye better than small-font text.

Conclusion

Your first clinical vignette can be a truly great experience. Although it is a lot of hard work, presenting clinical thought is a skill that you must learn. Once you do this, you might find that you have “caught the bug,” and will find yourself well on your way to a role in medical education. You might even start a larger project based on this experience.

Dr. Burger is associate program director of internal medicine residency in the Department of Medicine at Beth Israel Medical Center and assistant dean and assistant professor of medicine at Albert Einstein College of Medicine, both in New York City. Dr. Paesch is a comprehensive care physician in the section of hospital medicine at the University of Chicago, and assistant professor at the University of Chicago Pritzker School of Medicine. Dr. Miller is director of student programs, associate program director, residency, and associate professor of medicine in the Department of Medicine at Tulane Health Sciences Center in New Orleans.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.

In This Edition

Literature At A Glance

A guide to this month’s studies

1. Initial trophic feedings effective for patients with acute lung injury
2. IM vs. IV benzodiazepines in status epilepticus
3. CDI risk following antibiotic cessation
4. Acid suppression associated with increased complications in CDI patients
5. Perioperative statins and cardiac events in surgical patients
6. Enoxaparin vs. unfractionated heparin during PCI
7. Optimal serum potassium levels for AMI patients
8. PPIs superior to H2-blockers for lowering UGI bleeding following ACS and STEMI

Initial Lower-Volume Enteral Feeding Better Tolerated, but Has No Mortality Benefit

Clinical question: In mechanically ventilated patients with acute lung injury, do initial lower-volume enteral feedings (trophic feedings) improve clinical outcomes when compared with full enteral feedings?

Background: Malnutrition in critically ill patients is associated with poor outcomes, but conflicting data exist regarding the best timing, amount, and formulation of enteral nutrition to initiate. Initiation of lower-volume enteral feeding with periodic assessment of gastric residual volume is common practice, but the effects of this practice are unknown.

Study design: Multicenter randomized controlled open-label study.

Setting: Forty-four hospitals in the National Heart, Lung, and Blood Institute (NHLBI) Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network.

Synopsis: One thousand patients with acute lung injury receiving mechanical ventilation for longer than 72 hours were randomized using a Web-based system to receive either trophic or full enteric feedings for the first six days of mechanical ventilation. After the sixth day, a full enteric feeding protocol was used in all patients. All analyses were by intention-to-treat.

There was no significant difference between the trophic and full enteral feeding groups with regard to the primary outcome of ventilator-free days through Day 28 (14.9% vs. 15.0%, P=0.89). There were also no significant differences between groups in secondary outcomes, which included 60-day mortality, ICU-free days, organ-failure-free days, or the incidence of new infections. However, gastrointestinal intolerances occurred less often in the trophic feeding group, and these patients received fewer anti-diarrheal and prokinetic agents. The full feeding group gained 2.1 liters of fluid by Day 7, but this fluid gain did not cause significant differences in measures of circulatory or pulmonary physiology.

Limitations include open-label study design and inclusion of only critically ill adult medical patients with acute lung injury.

Bottom line: Initial lower-volume tube feedings in mechanically ventilated patients with acute lung injury did not improve clinical outcomes compared with full enteral feedings, but they were associated with fewer instances of gastrointestinal intolerance.

Citation: National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network. Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA. 2012;307:795-803.

Intramuscular Benzodiazepines as Good as IV Benzodiazepines in Status Epilepticus

Clinical question: Is intramuscular (IM) midazolam noninferior to intravenous lorazepam in patients in status epilepticus?

Background: Studies have shown that IV benzodiazepines, particularly lorazepam, are effective for patients in status epilepticus. Studies have not evaluated IM benzodiazepines. However, many emergency medical service (EMS) agencies use IM midazolam because IM administration is easier than IV administration, and midazolam has a longer nonrefrigerated shelf life than lorazepam does.

Study design: Randomized, double-blinded clinical trial.

Setting: Thirty-three EMS agencies across the United States.

Synopsis: Based on the 893 adults and children in status epilepticus included in this double-blind study, the researchers found IM midazolam to be noninferior to, and in fact superior to, IV lorazepam for treating seizures prior to arrival at EDs. Specifically, they found 10% more (95% CI 4.0% to 16.1%; P<0.001 for noninferiority and P<0.001 for superiority) seizure-free patients arriving at EDs when IM midazolam was administered. Seizures ceased in patients given IM midazolam in less time on average than it took for paramedics to administer IV lorazepam.

Hospitalists might be less inclined than EMS personnel to use IM midazolam because their patients have established IV access and refrigerated drugs are readily available. However, since IM midazolam was superior to IV lorazepam in this prehospital study, a similar trial in hospitalized patients is warranted. In subsequent trials, it would be useful to administer both midazolam and lorazepam via IM and IV routes, and IM injections by an autoinjector could be compared with the conventional manner.

Bottom line: In the prehospital setting, IM midazolam is at least as good as IV lorazepam in treating status epilepticus in children and adults.

Citation: Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366:591-600.

Clostridium Difficile Infection Risk Remains High at Least Three Months after Antibiotics Are Stopped

Clinical question: How long are patients at higher risk for Clostridium difficile infection (CDI) after completing antibiotics?

Background: Studies have shown that patients given antibiotics are at higher risk for CDI than those who are not, particularly if they take multiple antibiotics at high doses for a prolonged period of time. However, it is not known how long a patient remains at high risk for CDI after completing antibiotic therapy.

Study design: Case-control study.

Setting: Nine hospitals in Netherlands.

Synopsis: The study compared 337 hospitalized patients who had CDI with 337 nondiarrheal controls and 227 non-CDI diarrheal controls. The study showed a seven- to tenfold increased risk for CDI during antibiotic treatment and in the 30 days following cessation of antibiotics. A 2.7-fold increased risk of CDI was seen in the one- to three-month period after antibiotic treatment was stopped.

Because researchers only obtained information about antibiotic use in the three months preceding the onset of diarrhea, it is unknown if CDI risk remains elevated longer than three months after antibiotics are stopped. Also of note, the enzyme immunoassays used in this study to diagnose C. diff had sensitivities of between 60% and 85%.

As hospitalists, this information can be used to advise patients about their continued risk for CDI after cessation of antibiotics. Further studies are needed to determine the risk after three months.

Bottom line: Patients are at highest risk for CDI up to one month after stopping antibiotics but continue to be at higher risk for at least two additional months.

Citation: Hensgens MPN, Goorhuis A, Dekkers OM, Kuijper EJ. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742-748.

Acid Suppression and Poor Outcomes in C. Diff Patients

Clinical question: What are potential modifiable risk factors associated with increased complications and mortality in patients hospitalized with C. diff infection (CDI)?

Background: CDI is a growing cause of morbidity and mortality in hospitalized patients. Evidence is growing for the association of acid suppression, among other modifiable risk factors, with complications and mortality in patients with CDI.

Study design: Retrospective case review.

Setting: Naval medical center.

Synopsis: A laboratory, medical record, and pharmacy database query found 485 patients with CDI. Complications of CDI were defined as ICU admission, surgery, and megacolon. Factors significantly associated with CDI complications and mortality were admission for CDI, corticosteroid use >5 mg per day, age ≥80 years, and prescription acid suppression (including H2-blockers and proton-pump inhibitors).

The latter two risk factors were associated with mortality alone. In multivariable regression, the odds of mortality among patients on acid suppression was more than four times the odds of those not on acid suppression (OR 4.74, 95% CI, 1.57 to 14.36).

Although this is a retrospective cohort study and cannot prove a causal relationship, the data add to a growing body of evidence supporting the risk of CDI complications and mortality for those on acid suppression.

Bottom line: In hospitalized patients with CDI, acid suppression is associated with increased complications and mortality and should be discontinued in this population when possible.

Citation: Morrison RH, Hall NS, Said M, et al. Risk factors associated with complications and mortality in patients with Clostridium difficile infection. Clin Infect Dis. 2011;53:1173-1178.

Perioperative Statins Reduce Cardiac Events for Surgical Patients

Clinical question: Does perioperative statin use improve cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay) in statin-naive patients undergoing cardiac or non-cardiac surgery?

Background: Statins have been hypothesized to reduce perioperative cardiac complications because they reduce vascular and systemic inflammation caused by surgery, and several meta-analyses have demonstrated their efficacy. To date, no meta-analyses have specifically evaluated the benefits of perioperative statins in non-cardiac surgery from randomized controlled trials.

Study design: Systematic review of the literature and meta-analysis.

Setting: Fifteen randomized controlled trials of hospitalized surgical patients.

Synopsis: A systematic review examined the effects of statins on a variety of perioperative cardiac outcomes (death, myocardial infarction, atrial fibrillation, and ICU and hospital lengths of stay); 11 of the 15 patients were undergoing cardiac surgery.

Perioperative statins decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (RR 0.56; 95% CI 0.45-0.69; number needed to treat [NNT], 6). In both cardiac and non-cardiac surgical patients, statins reduced the risk of myocardial infarction (RR 0.53; 95% CI 0.38 to 0.74; NNT 23). Statin treatment also reduced the mean length of hospital stay (in days, mean difference -0.32; 95% CI, -0.53 to -0.11) but did not reduce the length of ICU stay (mean difference -0.08; 95% CI, -0.25 to 0.10). Risk of death was not reduced with statin treatment (RR 0.62; 95% CI, 0.34 to 1.14).

Bottom line: Perioperative statins reduce the risk of postoperative atrial fibrillation in cardiac surgical patients, the risk of postoperative MI in cardiac and non-cardiac surgical patients, and the mean length of hospital stay.

Citation: Chopra V, Wesorick DH, Sussman JB, et al. Effect of perioperative statins on death, myocardial infarction, atrial fibrillation, and length of stay: a systematic review and meta-analysis. Arch Surg. 2012;147:181-188.

Enoxaparin Safe and Effective during Percutaneous Coronary Intervention

Clinical question: Is enoxaparin safe and efficacious compared with unfractionated heparin during percutaneous coronary intervention (PCI)?

Background: Despite problems with the use of unfractionated heparin during PCI, current guidelines give it a Class 1 recommendation for PCI in ST-elevation myocardial infarction (MI). There is growing evidence that enoxaparin can provide predictable, effective anticoagulation during PCI. Although several trials have examined this issue, none have been sufficiently powered to evaluate mortality.

Study design: Systematic review and meta-analysis.

Setting: Twenty-three trials or registries of patients undergoing PCI.

Synopsis: A systematic review found 23 trials representing 30,966 patients that examined the effects of enoxaparin versus unfractionated heparin on risk of mortality, MI, complications of MI, and major bleeding. Of these, 10,243 (33.1%) patients underwent primary PCI for ST elevation MI, 8,750 (28.2%) underwent PCI after fibrinolysis, and 11,973 (38.7%) patients had either scheduled PCI or PCI for non-ST elevation acute coronary syndrome.

Of all the patients, 13,943 (45%) received enoxaparin and 17,023 (55%) received unfractionated heparin. Enoxaparin was associated with significant reductions in all-cause mortality (RR 0.66; 95% CI, 0.57 to 0.76), composite of death or MI (RR 0.68; 95% CI, 0.57 to 0.81), and complications of MI (RR 0.75; 95% CI, 0.6 to 0.85). For patients who received primary PCI for ST elevation MI, enoxaparin reduced the risk of complications of MI by 44% (RR 0.56; 95% CI, 0.42 to 0.76). Enoxaparin also reduced the risk of major bleeding (RR 0.80, 95% CI, 0.68 to 0.95) with even more striking results for the 14 studies that compared intravenous enoxaparin to unfractionated heparin (RR 0.66; 95% CI, 0.52 to 0.83).

Bottom line: Enoxaparin is safe and efficacious when used during PCI. Patients who receive enoxaparin during PCI have reduced risk for death, MI, complications of MI, and major bleeding when compared with patients who receive unfractionated heparin.

Citation: Silvain J, Beygui F, Barthelmy O, et al. Efficacy and safety of enoxaparin versus unfractionated heparin during percutaneous coronary intervention: systematic review and meta-analysis. BMJ. 2012;344:e553.

Serum Potassium Levels and Mortality in Acute Myocardial Infarction

Clinical question: What is the relationship between serum potassium levels and mortality in acute myocardial infarction (AMI) patients?

Background: Several smaller studies in the pre-beta-blocker and pre-reperfusion era recommended maintaining serum potassium levels between 4.0 mEq/L and 5.0 mEq/L in AMI patients. However, current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.

Study design: Retrospective cohort study.

Setting: Multicenter study involving 67 hospitals in the U.S.

Synopsis: Using the Cerner Health Facts database, which included 38,689 patients with biomarker-confirmed AMI, this study showed there was a U-shaped relationship between mean post-admission serum potassium level and in-hospital mortality.

Compared with the reference group of 3.5 mEq/L to less than 4.0 mEq/L (mortality rate 4.8%; 95% CI, 4.4% to 5.2%), mortality was comparable for those with mean post-admission potassium of 4.0 mEq/L to less than 4.5 mEq/L (5.0%; 95% CI, 4.7% to 5.3%). Mortality was twice as great for potassium of 4.5 mEq/L to less than 5.0 mEq/L (10.0%; 95% CI, 9.1% to 10.9%), and even greater for higher potassium strata. Similarly, mortality rates were higher for potassium levels of less than 3.5 mEq/L. Rates of ventricular fibrillation or cardiac arrest were higher among patients with potassium levels of less than 3.0 mEq/L or more than 5.0 mEq/L.

Bottom line: For inpatients with AMI, serum potassium levels of 3.5 mEq/L to 4.5 mEq/L should be maintained for the best outcomes. Repletion of serum potassium to levels greater than 4.5 mEq/L is associated with increased mortality and should be avoided.

Citation: Goyal A, Spertus JA, Gosch K, et al. Serum potassium levels and mortality in acute myocardial infarction. JAMA. 2012;307:157-164.

Proton-Pump Inhibitors Better than H2-Blockers in ACS and STEMI

Clinical question: Are proton-pump inhibitors (PPIs) better than H2-blockers at preventing UGI bleeding in patients after acute coronary syndrome (ACS) or ST-elevation myocardial infarction (STEMI)?

Background: It is not definitively known if PPIs are the same or better than H2-blockers in preventing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and anticoagulants) after ACS or STEMI.

Study design: Randomized double-blinded controlled trial.

Setting: Single hospital.

Synopsis: Patients with ACS or STEMI were treated with aspirin, clopidogrel, and enoxaparin or thrombolytics. They were then randomized to either esomeprazole 20 mg or famotidine 40 mg, both administered nightly. They were followed throughout their hospital stay and were then followed between four and 52 weeks after discharge (mean duration: 19 weeks for esomeprazole, 18 weeks for famotidine). The primary end point was time to a composite outcome, consisting of UGI bleeding, obstruction, or perforation. Overall, 313 patients were randomized (164 to esomeprazole and 149 to famotidine).

The treatment groups were equivalent in baseline characteristics, and compliance in both groups was excellent (>98%). The primary endpoint occurred in three patients in the esomeprazole group and in 12 patients in the famotidine group (hazard ratio 0.21; 95% CI, 0.06 to 0.75; P=0.008).

Bottom line: PPIs are superior to H2-blockers in reducing UGI bleeding in patients on high-risk medications (aspirin, clopidogrel, and enoxaparin or thrombolytics) after ACS and STEMI. This confirms the recommendations of the 2010 ACCF/ACG/AHA Expert Consensus that PPIs should be used in those on dual antiplatelet therapy on anticoagulants.

Citation: Ng FH, Tunggal P, Chu WM, et al. Esomeprazole compared with famotidine in the prevention of upper gastrointestinal bleeding in patients with acute coronary syndrome or myocardial infarction. Am J Gastroenterol. 2012;107:389-396.