Category: Critical Care Literature Update
Keywords: hydrocortisone, corticosteroids, insulin, sepsis (PubMed Search)
Since all of us are taking care of critically ill patients for longer periods of time, I think it is important to be familar with current critical care literature. Often, we are the first "intensivist" a patient sees when they arrive to the hospital. To keep us up to date, I am going to be sending out critical care literature updates every couple of weeks similar to Amal's cardiology updates. Please email me with any questions, comments, or feedback.
Recent Articles from the 2008 Critical Care Literature
Hydrocortisone therapy for patients with septic shock.
Sprung CL, Annane D, Keh D,
Corticosteroid therapy for patients with septic shock seems to change favor every couple of years. In the first publication of the Surviving Sepsis Campaign Guidelines, steroids were given a favorable recommendation based largely upon the results of one multicenter, randomized, controlled trial. (Annane, et al. JAMA 2002;288:862-71) In this study, Annane reported a reduction in the likelihood of death in patients who did not respond to the corticotropin stimulation test and were given steroids (hydrocortisone and fludrocortisone).
The current study is from the CORTICUS Study Group and is a multicenter, randomized, double-blind, placebo-controlled study conducted in 52 ICUs from March 2002 to November 2005. Enrolled patients had to have clinical evidence of infection, a systemic response to infection, organ dysfunction attributable to sepsis, and the onset of shock within 72 hours (SBP < 90 mmHg despite fluids or vasopressors). Patients were randomized to receive either hydrocortisone or placebo for 5 days. Doses were then tapered over the next 6 days for a total duration of therapy of 11 days. A lack of response to corticotropin was defined as an increase in cortisol of no more then 9 mcg/dL. The primary end point of the study was the rate of death from any cause at 28 days in “non-responders”. Some important secondary end-points included the rate of death at 28 days in “responders”, time to reversal of shock, duration of ICU and hospital stay, and rates of death at 1 year.
Four-hundred ninety nine patients were enrolled in the study. Of these, 233 were identified as “non-responders”. In this group, 125 were randomized to receive hydrocortisone and 108 received placebo. The demographic and clinical characteristics of patients in each group were similar. Over 90% of patients in each group were vented and all were receiving vasopressors, the most common being norepinephrine. With respect to the primary outcome, there was no significant difference in the rate of death at 28 days between the study groups. For the secondary end points, there was also no significant difference in the rate of death in “responders”, duration of ICU or hospital length of stay, or death at 1 year. The only difference that was found in those receiving hydrocortisone was a reduction in the time to reversal of shock. Importantly, this did not translate into improved mortality. Lastly, the authors reported an increase in new episodes of sepsis and septic shock in those receiving hydrocortisone but the absolute numbers are small.
Things to Consider: Investigators had planned to enroll 800 patients but stopped at 499 due to slow recruitment, termination of funding, and expiration of the study drug. In addition, the mortality rate in the placebo group was lower than what would be expected. As a result, the study is inadequately powered. In contrast to the Annane study, enrollment of patients could be up to 72 hours after the onset of shock, raising the question of timing of steroids administration. Furthermore, the majority of patients in this study were older, Caucasian males who required emergency surgery – not typical of the septic shock population at UMMC. Importantly, patients who were receiving long-term corticosteroids within the past 6 months, or short-term steroids within the past 4 weeks, were excluded – the patients we would typically give stress dose steroids to during refractory shock.
Take Home Point: Although CORTICUS is underpowered, it is one of the largest trials to date on corticosteroids in patients with septic shock. The results indicate that corticosteroid therapy in this patient population of “non-responders” had no effect on mortality. Based upon this study, the latest version of the Surviving Sepsis Campaign Guidelines has downgraded their recommendation on corticosteroids. It appears that the pendulum regarding steroids may now be swinging back in the negative direction.
Intensive insulin therapy and pentastarch resuscitation in severe sepsis.
Brunkhorst FM, Engel C, Bloos R, Meier-Hellmann A, Ragaller M, et al. NEJM 2008;358:125-139.
The concept of “tight glucose control” in critically ill patients primarily began with the Van de Berghe study in 2001. In this study, investigators found a reduction in mortality in critically ill patients whose glucose was maintained between 80 – 110 mg/dL. (Van de Berghe G, et al. NEJM 2001;345:1359-67.) The benefit was primarily seen in cardiac surgery patients who had multiple organ failure from sepsis. Furthermore, these patients were given a high glucose challenge immediately after surgery – not a common practice. More recently, the same investigators evaluated MICU patients who had not undergone surgery nor received a glucose challenge. (Van de Berghe G, et al. NEJM 2006;354-449-61.) In this latter study there was no benefit to intensive insulin therapy.
The current study is a multicenter, randomized, open-label study of both intensive insulin therapy and hydroxyethyl starch in patients with severe sepsis. The study was conducted from April 2003 to June 2005 in 18 multidisciplinary ICUs at academic tertiary hospitals in
The insulin arm of the study compared intensive insulin therapy to conventional insulin therapy. In the conventional group, insulin was given when glucose values were > 200 mg/dL, with the goal of maintaining glucose between 180 – 200 mg/dL. In the intensive insulin group, insulin was given when glucose values were > 110 mg/dL, with the goal of maintaining glucose between 80 – 110 mg/dL. Treatment ended at either discharge from the ICU, death, or a total of 21 days of therapy were reached.
Five hundred thirty seven patients were enrolled, 290 in the conventional insulin group and 247 in the intensive insulin group. Baseline patient characteristics including age, pre-existing co-morbidities, sites of infection, lab values, and hemodynamic variables were similar between the groups. Total nutritional intake, including glucose, was similar in both groups. Interestingly, the majority of patients had nosocomial acquired infections and over 60% in both groups were given hydrocortisone. Overall, there was no significant difference in the rate of death between the intensive and conventional insulin therapy groups. Furthermore, there was no significant difference in morbidity between the two groups. As one might expect, there was significantly more hypoglycemic episodes in the intensive insulin therapy group (17% vs. 4.1%). Although no deaths were attributable to hypoglycemia, there were more “life threatening” episodes of hypoglycemia in the intensive insulin group. As a result of the increase in hypoglycemic episodes the study was stopped early.
Take Home Point: In this patient population with severe sepsis, intensive insulin therapy, using a continuous infusion, to maintain glucose between 80 – 110 mg/dL did not improve mortality. It did, however, result in significantly more hypoglycemic episodes (glucose < 40 mg/dl). Many EDs across the country are now developing and implementing sepsis protocols primarily based upon the SSC Guidelines. Based upon this study, intensive insulin therapy may not be a necessary component to the ED management of patients with severe sepsis or septic shock.
Keywords: zolpidem, benzodiazepines, eszopiclone (PubMed Search)
Both dealing with the adverse effects from therapeutic administration, like when you order it on the floors or take yourself - to the overdose setting. Here is a brief list of the common sleep aids, MOA and toxicity. (Zolpidem or Ambien gets the award for most entertaining adverse effect of "Sleep Eating")
Keywords: dizzy, head and neck examination, heent (PubMed Search)
Be sure to perform a thorough head and neck examination in the dizzy patient, as the etiologic source is often due to ear, nose, and throat pathology, such as structural abnormalities, some of which may even signal a more widespread process
Such common physical examination findings may include the following:
Category: Critical Care
Keywords: d-dimer (PubMed Search)
D-Dimer in the Critically Ill
Crowther MA, et al. Neither baseline tests of molecular hypercoagulability nor D-dimer levels predict deep venous thrombosis in critically ill medical-surgical patients. Intensive Care Med 2005;31(1):48-55.
Keywords: BP, Hypertension, Angioedema (PubMed Search)
Direct Renin Inhibitor-Aliskiren (Tekturna)
This drug is the 1st in a new class of antihypertensives called direct renin inhibitors-1st approved in 2007. This drug, along with three others being developed, inhibits the entire Renin-Angiotensin-Aldosterone System (RAAS) which has been shown to lead to definitive 24 hour blood pressure control.
Why should emergency physicians care, you ask?
J Hypertension March 2007
Keywords: acute myocardial infarction, stress test (PubMed Search)
Just a reminder, after a recent case of a patient that had a large AMI the day after a negative dobutamine stress test...
Neither stress testing nor coronary angiography are definitive for ruling out unstable/vulnerable plaques. If the HPI for your patient is very concerning, don't obviate your concern just because of a recent negative stress test or angiography. These tests are good at identifying large occlusions, but they tell us nothing about recent rupture or about composition of the plaques, and we now know that it is the composition that determines plaque instability. Size doesn't always matter...
Category: Obstetrics & Gynecology
Keywords: Ultrasound, ectopic, pregnancy (PubMed Search)
Ultrasound in Pregnancy
A full bladder is needed for Transabdominal Ultrasound and an empty bladder for transvaginal ultrasound.
Keywords: DKA, Cerebral Edema, Mannitol, Risk Factors (PubMed Search)
Cerebral Edema in Patients with DKA
Keywords: influenza, tamiflu, oseltamivir (PubMed Search)
Keywords: Romberg Test, proprioception, dorsal columns, balance (PubMed Search)
Category: Critical Care
Keywords: central venous pressure (PubMed Search)
Category: Airway Management
Keywords: Asthma (PubMed Search)
Care of the Crashing Asthma Patient
Several things should be considered in the crashing asthmatic:
Keywords: adenosine, ventricular tachycardia (PubMed Search)
Adenosine should never be used in the setting of a wide complex regular tachycardia as a diagnostic maneuver. Adenosine will convert some types of VT, and this may mislead the health care provider into thinking that the WCT is an SVT. The electrophysiology literature is rife with reports of "adenosine-sensitive VT," and these patients are often young and without prior history of CAD...the very patients that we'd most be inclinded to assume have SVT.
The bottom line is that one should always assume that a regular WCT (without obvious evidence of sinus tachycardia) is VT, and treat the tachydysrhythmia as such.
Category: Infectious Disease
Keywords: Dermatology, Rash, (PubMed Search)
Most of use remember that Fifth disease is a viral infection presenting with a distinctive rash (slapped check) caused by Parvovirus B19. But do you know the numbering of the other six Contagious Illnesses that are associated with rashes:
Keywords: Ferbrile Seizures, Bacteremia, Fever (PubMed Search)
Here are a couple of herbals touted as aphrodesiac's and the toxcity associated with them (the price of love):
Chan Su or "Love Stone" - A chinese herbal that is suppose to be topically applied, unfortunately all of the instructions are in chinese and those who ingest it will die a digoxin-like death. It has a compound that is essentially a potent digoxin-like substance.
Yohimbine - herbals that contain this can cause priapism - shocker
Keywords: brainstem, cranial nerves (PubMed Search)
Category: Critical Care
Keywords: spontaneous pneumomediastinum (PubMed Search)
Keywords: AAA, aneurysm (PubMed Search)
AAA...be afraid, be very afraid
Abdominal Aortic Aneurysm (AAA) is known as the great masquerader in the elderly for good reason....
Keywords: acute coronary syndrome, history (PubMed Search)
The 5 most important factors at predicting the presence of ACS in a patient presenting with chest pain (in order of importance):
1. nature of anginal symptoms (i.e. the HPI)
2. prior history of CAD
3. male gender
4. older age
5. increasing number of traditional risk factors
Notice this means that the MOST important factor is the HPI...the OLDCAAAR. If the patient has a concerning HPI, NEVER drop your concerns just because the patient is young or has minimal other risk factors.