UMEM Educational Pearls - By Mike Winters

Recent Articles from the Critical Care Literature

Efficacy and Safety of Recombinant Activated Factor VII for Acute Intracerebral Hemorrhage.

Does this Patient with Diabetes have Osteomyelitis?

• Diagnosis of lower extremity osteomyelitis in the diabetic patient remains challenging
• Bone biopsy with culture remains the gold standard for diagnosis but is not always obtainable
• What clinical features, therefore, raise the likelihood of osteomyelitis?
• In this review, an ulcer size > 2 cm² (LR 7.2), ability to probe to bone using a sterile stainless steel probe (LR 6.4), and an ESR > 70 mm/h were found to be useful in predicting the presence of osteomyelitis
• Clinical features NOT found to be useful included fever (sensitivity 19%), presence of erythema, swelling, or purulence (LR 1), elevated white blood cell count (sensitvity 14%-54%), and superficial swab culture
• A note about radiographic studies:
  • bony changes on plain films may take up to 2 weeks to develop
  • plain films alone are only marginally useful if positive (LR 2.3)
  • MRI is more accurate than bone scan or plain films
  • If you are going to order a radiographic study, your best bet is the MRI

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Passive Leg Raising (PLR)

• We have discussed that static measures of volume (CVP, PA wedge pressures) are not reliable markers of fluid responsiveness
• PLR has recently gained interest as a simple and transient way to assess fluid responsiveness in the critically ill
• Patients are placed in the horizontal position (not Trendelenburg) and the legs are raised to 45 degrees
• A hemodynamic response should be seen in 30 - 90 seconds
• Patients who have improvement in hemodynamics with PLR are said to be fluid responsive (i.e on the ascending portion of their Starling Curve) and require additional volume resuscitation

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Acinetobacter in the Critically Ill

• As all of us know, there has been an alarming increase in the incidence of acinetobacter infections
• At present, infections mostly occur in ICU/critically ill patients
• Important risk factors for colonization and infection include mechanical ventilation, recent surgery, tracheostomy, residents of long-term care facilities, central venous catheterization, and enteral feedings
• The most frequent clinical manifestations are ventilator associated pneumonia and bacteremia
• Susceptible strains can be treated with a broad-spectrum cephalosporin, carbapenem, or B-lactam-B-lactamase used alone or in combination with an aminoglycoside
• For resistant strains, the most active agent in vitro are the polymyxins
• The most common adverse effect of the polymyxins is nephrotoxicity (up to 36%)
• Tigecycline has been used but resistance rates are rapidly increasing

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Fluids in Acute Liver Failure

• Acute liver failure is often complicated by intravascular volume depletion - insensible losses, vomiting, poor oral intake
• Early and adequate fluid resuscitation is mandatory
• AVOID lactated Ringer's solution - exogenous lactate load is poorly tolerated by lack of hepatic function
• AVOID dextrose containing water solutions - will lead to hyponatremia and increase the risk of cerebral edema

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COPD and mechanical ventilation

• In some studies, the failure rate of non-invasive positive pressure ventilation (CPAP, BiPAP) in acute exacerbations of COPD has been as high as 50%
• When setting the ventilator in patients with COPD, keep in mind that the majority have chronic ventilatory failure with a chronic compensatory respiratory acidosis
• Pearl: Look at the serum bicarbonate level obtained from a recent period of stability
• A recent serum bicarbonate level can provide an indirect indication of the patient's baseline P_aCO₂ if you have no prior ABGs
• Rather than target a P_aCO₂ of 40 mm Hg, manipulate the ventilator to target the patient's baseline serum bicarbonate or a pH of 7.35 - 7.38.

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Acute Lung Injury (ALI) / Acute Respiratory Distress Syndrome (ARDS)

• ALI and ARDS are defined as:
  • bilateral pulmonary infiltrates on CXR
  • pulmonary capillary wedge pressure < 18 mm Hg (no heart failure)
  • P_aO₂ / F_iO₂ < 300 = ALI
  • P_aO₂ / F_iO₂ < 200 = ARDS  
• The current management for patients with ALI or ARDS is low tidal volume ventilation and a conservative fluid management strategy
• Two recent trials (EXPRESS and LOVS) evaluated different applications of PEEP in patients with ALI/ARDS
• Both studies evaluated lower levels of PEEP (5-10) vs. higher levels of PEEP titrated to plateau pressure
• Bottom line: different PEEP strategies did not influence survival, although higher levels did result in improved oxygenation.

Propofol Infusion Syndrome

• Many of us are now using propofol for sedation in our critically ill patients
• Although a great drug, it is important to be aware of "propofol infusion syndrome" (PIS)
• Risk factors for PIS include young age, severe CNS or pulmonary illness, and exogenous catecholamine administration
• Clinical features include: unexplained metabolic acidosis, rhabdomyolysis, hyperlipidemia, hepatomegaly, and cardiovascular instability
• Pearl: It is reported that the development of coved ST elevations in V1-V3 (similar to Brugada syndrome) may be the first sign of cardiac instability with PIS

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Intra-aortic balloon pump counterpulsation

• It is possible that at some point in your career you may need to place an intra-aortic balloon pump (IABP) to temporarily stabilize a patient wth cardiogenic shock
• Optimal performance of the IABP is dependent upon proper positioning in the thoracic aorta
• Traditional teaching has been to insert the IABP via the femoral artery and advance to the level of the aortic knob (via CXR)
• A recent study suggests that using the aortic knob to position the IABP may result in occlusion of the left subclavian artery in a substantial portion of patients (16% in the study)
• Placing the IABP 2 cm above the carina may be a more reliable landmark that using the aortic knob

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Bedside Glucometry in the Critically Ill

• Hyperglycemia is common in critically ill patients
• Depending on the underlying condition (e.g. DKA), you may be instituting an insulin drip and following frequent fingersticks in the ED
• A recent study indicates that bedside glucose values may not accurately reflect serum values in approximately 15% of critically ill patients
• This is more likely to occur in patients with poor peripheral perfusion
• Take Home Point: Interpret bedside glucose readings with caution especially in hypotensive critically ill patients

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Vasopressin for Sepsis

• The VASST trial was recently published in NEJM comparing vasopressin vs. norepinephrine for septic shock
• Unfortunately, there are some issues with the study which I will clarify/expand upon in the next Critical Care Literature Update
• There was a trend towards improved mortality in the vasopressin group receiving low doses of norepinephrine (5 - 14 mcg/min)
• Take Home Point: If you are thinking about adding vasopressin to norepinephrine in patients wtih refractory septic shock, do it early.  In other words, add vasopressin when you find yourself titrating norepinephrine doses to 6, 7, 8 mcg/min

ACTH Stimulation Test

• With the recent publication of the CORTICUS study (along with others), it is becoming clear that the ACTH stimulation test is not reliable in identifying patients with adrenal insufficiency
• In fact, the test is no longer recommended in the evaluation of patients with severe sepsis/septic shock
• Furthermore, if you decide to give steroids to the patient with severe sepsis/septic shock, there is no need to use dexamethasone for fear of "disrupting the ACTH stim test" (hydrocortisone is the preferred agent)

Dialysis Disequilibrium Syndrome (DDS)

• Although typically seen in ESRD patients who are being initiated on hemodialysis, DDS can be seen in the critically ill
• Critically ill patients at risk for DDS include recent CVA, head trauma, subdural hematoma, hyponatremia,, hypertensive emergency, and hepatic encephalopathy
• Mild cases are characterized by restlessness, nausea, vomiting, headache, disorientation, and tremors
• More severe symptoms include seizures and coma
• The exact pathogenesis is debated but centers around acute cerebral edema
• Treatment of DDS primarily centers around manipulation of hemodialysis
• For the EP: patients with DDS presenting with seizures can be treated by rapidly increasing plasma osmolality with either hypertonic saline or mannitol (12.5 gms)  

Guidewire length for central venous catheterization

• 18 cm should be considered the upper limit of guidewire insertion during internal jugular or subclavian central venous catheterization (16cm for right IJ)
• There is the Peres Nomogram for determining guidewire length, which is based on patient height
• However, height is less reliable in predicting safe guidewire length

Potassium Phosphate ("K-phos")

Over the weekend, I had a patient with Dr. Scott that had a phosphate of 0.8 mmol/L.  Phosphate < 1.0 mmol/L is an indication for IV repletion.  IV repletion involves giving potassium phosphate.  An important clinical question, therefore, is how much potassium does the patient actually get?

• 1 mmol of IV phosphate delivers 1.46 mEq of potassium
• Recommended infusion rate is 5 mmol/hr
• Rapid infusion may lead to severe hypocalcemia, hypotension, acute renal failure, hypomagnesemia, and hypernatremia

Coagulopathy and Trauma

• When resuscitating a trauma patient recall that the "lethal triad" consists of acidosis, hypothermia, and coagulopathy
• Coagulopathy is induced by the combination of direct loss of clotting factors, consumption in clot formation, dilutional due to crystalloid administration, acidosis, and hypothermia
• When giving PRBCs in trauma resuscitation, don't forget to give FFP
• The ratio to remember is 1U of FFP for every 2U PRBCs

Aspiration Pneumonitis

• Aspiration pneumonitis is an acute lung injury resulting from the aspiration of gastric contents
• It is an inflammatory condition rather than infectious
• Despite the inflammation, corticosteroids have been shown to have no effect on mortality
• Aspiration pneumonitis is self limited
• Antibiotics are generally held for 24 to 48 hours
• When to consider empiric broad spectrum antibiotics in the ED:  Gastric contents are sterile in most patients.  Patients who may have colonization/contamination of gastric contents are more likely to progress from pneumonitis to pneumonia.  Consider empiric antibiotics for aspiration pneumonitis in the patient with SBO, gastroparesis, those receiving enteral feeds through a G- or J-tube, and those on chronic PPI's/antacids.

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.

Mike

Recent Articles from the 2008 Critical Care Literature

Hydrocortisone therapy for patients with septic shock.

Sprung CL, Annane D, Keh D, Moreno R, Singer M, et al. NEJM 2008;358:111-24.

            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 Germany.  The study was designed to detect a decrease in mortality from 40% to 30% at 28 days.  Enrolled patients had to have the onset of severe sepsis or septic shock either 24 hours before ICU admission or less than 12 hours after ICU admission.  The primary end points were the rate of death from any cause at 28 days and morbidity.  Since we do not use HES in the ED for volume resuscitation, I will focus on intensive insulin therapy.

            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.

D-Dimer in the Critically Ill

• Diagnosis of VTE in the critically ill can be challenging and these patients are at high risk for the disease
• Only 3.6% - 16% of critically ill patients have a negative d-dimer, regardless of the presence or absence of VTE
• Even in patients with low pretest probability, d-dimer in the critically ill is of limited utility

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.

• The use of central venous pressure as a monitor of volume status remains very controversial in the critical care literature
• Remember that CVP can be affected by many conditions
• Important conditions that affect the accuracy of CVP include: 
  • right ventricular disease
  • tricuspid valve disease
  • pericardial disease
  • changes in intrathoracic pressure (PEEP, positive pressure ventilation) 
  • arrhythmias
  • reference level of the transducer