Aminoglycosides in Critically Ill Patients

• Aminoglycosides remain an important class of antibiotics in critically ill patients, especially those infected with multidrug-resistant organisms (i.e., Klebsiella  and Pseudomonas spp.).
• Importantly, aminoglycosides are concentration-dependent antibiotics and a greatly affected by the increased volume of distribution and altered elimination commonly seen in the critically ill.
• As a result, recommended doses are often too low to be effective. 
• Initial doses of aminoglycosides should, therefore, be higher in critically ill patients.
  • Amikacin: 25-30 mg/kg
  • Gentamicin: 7-9 mg/kg
  • Tobramycin: 7-9 mg/kg
• Subsequent doses are based on drug level monitoring.

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Back 2 Basics Series: Your Simple RSI Checklist - SOAP ME

The use of a checklist during high stress medical procedures is often recommended.  Rapid sequence intubation (RSI) is a classic situation where having a checklist can ensure adequate preparation however, if you don’t have a checklist – this simple mnemonic will make sure you are well prepared for a successful intubation.

The SOAP ME mnemonic is a quick and useful technique to remember only the basics of airway management and preparation.  Always remember to also assign roles to team members and communicate clearly to maximize your chances of success.  

Choosing Wisely in the ICU

• There is a general overuse of medical tests and treatments
• This wastes healthcare resources
• The Choosing Wisely Campaign was developed to have providers of different specialties choose medical services that should be questioned

The Critical Care Societies Collaborative came up with this list for ICU providers

1.     Don’t order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions. Do you really need a daily INR check or CBC check in all ICU patients? Really?

2.     Don’t transfuse red blood cells in hemodynamically stable, non-bleeding ICU patients with a hemoglobin concentration greater than 7 g/dl. See last week’s Pearl!

3.     Don’t use parental nutrition in adequately nourished critically ill patients within the first seven days of an ICU stay. TPN is the Cinnamon Toast Crunch of fungi.

4.     Don’t deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation. Use as little as possible when you can.

5.     Don’t continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort. Engage families early in the hospital stay regarding aggressive life-sustaining treatments. Get palliative care involved in the ED!

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Hemoglobin Threshold in Septic Shock

• Numerous trials have demonstrated the benefit of lower hemoglobin thresholds for blood transfusion in critically ill patients.
• The recently published Transfusion Requirements in Septic Shock (TRISS) trial evaluated the effects on mortality of a lower versus higher hemoglobin threshold in ICU patients with septic shock.
• The TRISS trial randomized 1005 patients to a lower hemglobin threshold (7 g/dL) or a higher hemoglobin threshold (9 g/dL). 
• Overall, there was no difference in 90-day mortality between groups.
• Patients randomized to the lower threshold received significantly fewer units without any increase in ischemic or adverse events.
• Take Home Point: A hemoglogin threshold of 7 g/dL for blood transfusion appears effective for most patients with septic shock.

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The ARISE Trial

Early, aggressive resuscitation and attention to detail are essential element of managing critically ill patients.  This past week the ARISE trial was published - a 2nd large, randomized control study to examine the benefit of protocolized vs. usual care in patients with severe sepsis and septic shock. 

What were the main findings?  After enrolling 1,600 patients who presented to the ED in severe sepsis or septic shock:

• They found no difference in mortality between the control (usual care) and treatment arm (early goal-directed therapy)
• Mortality was 18.6% vs. 18.8% at 90 days
• No evidence that continuous ScVO2, Hgb target > 10 mg/dL (check out the TRISS trial), or use of inotropes with a normal cardiac index improved mortality

Bottom Line:  Resuscitation goals for the patient with septic shock should include:

• Early antibiotics (source control)
• Adequate volume resuscitation (preferably balanced, crystalloid solution)
• End-organ perfusion (lactate normalization)

Additional therapeutic goals should be made on a patient by patient basis.  Reassess your patient frequently, pay attention to the details, and you will improve your patient’s mortality.

Suggested Reading

1. The ARISE Investigators and the ANZICS Clinical Trials Group.  Goal-Directed Resuscitation for Patients with Early Septic Shock. N Engl J Med. 2014. [PubMed Link]
2. Wessex ICS: The Bottom Line Review

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The last Back to the Basics post discussed the use of vasopressors to improve hemodynamics by increasing arterial (and venous) tone. This time we’ll discuss the use of agents to increase inotropy for patients with severe systolic dysfunction / failure.

Dobutamine: a direct b1 and b2-receptors agonist. It has no peripheral vasoconstrictor properties, so if blood pressure increases it occurs secondary to increased cardiac output. Unfortunately, blood pressure may be decreased in some patients due to its peripheral vasodilatory effects; in these cases it may need to be used with a vasopressor.

Milrinone: augments contractility by increasing intracellular Ca levels via cellular phosphodiesterase inhibition. Because it does not work on beta-receptors, it might be preferred for patients taking beta-blockers requiring inotropic support. It may cause peripheral vasodilation and hypotension, but this may be a benefit if pulmonary artery pressure is elevated as reductions in pulmonary artery pressure lead to improvements in right ventricular function. It has a long-half life and should be avoided in patients with renal impairment.

Dopamine: chemical precursor to norepinephrine and technically a vasopressor. At moderate doses (3-10 mcg/kg/min) it works on beta-receptors to increase myocyte contractility. At higher doses works primarily as a vasopressor, which may reduce cardiac output due to higher afterload.

Norepinephrine/epinephrine: has alpha and beta properties that lead to increased peripheral vasoconstriction, but also increases inotropy and chronotropy (faster heart rate)

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What is a massive transfusion?

• Can be institution dependent but usually means greater than 10 Units of blood products transfused within 24hrs.
• Most hospitals have this as a protocol that a physician can order to notify the blood bank that a large volume of blood products may be required rapidly.

When would I use this?

Indications:

-Systolic Blood pressure < 100

-Unable to obtain blood pressure

AND

-Penetrating torso trauma

-Positive FAST

-External blood loss

-Plans to go to the OR

How do I give it?

• The transfusion ratio is usually 1:1:1 or 2:1:1
• Give 1 unit PRBC, then 1 U FFP, and alternate until 6 units of each have been given and then 1 bag of apheresis platelets (6 equivalent units). Can repeat as needed.

Does this apply for just traumatic bleeding?

• Although this data was based on soldiers in the recent Iraq Wars, it has been used for medical patients as well.
• Therefore, consider using in upper GI bleeds, post-partum hemorrhage, etc.

Are there other agents I can use?

• There is some data to give tranexamic acid early (less than three hours from injury) in trauma patients who are hypotensive and are having severe bleeding.

What am I trying to do with this protocol?

• Control hemorrhage
• Use the best products possible
• Prevent hypothermia
• Prevent hemodilution
• Treat coagulopathy

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Infectious Risks Associated with TTM

• Targeted temperature management (TTM) is commonly used in the care of patients resuscitated from cardiac arrest.
• Despite improving neurologic outcomes, TTM can increase the risk of infection, bleeding, coagulopathy, arrhythmias, and electrolyte derangements.
• Infectious complications of TTM are associated with increases in ICU length of stay, along with increases in the duration of mechanical ventilation.
• Pneumonia and bacteremia are the two most common infectious complications of TTM, with S.aureus the most common single pathogen isolated in cases of infection.
• Since TTM may suppress normal signs of infection, it is important to be vigilant for these two infectious complications.
• At present, evidence does not support prophylactic antibiotics for all patients receiving TTM.

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Goal-Directed Resuscitation During Cardiac Arrest

Focusing on high-quality CPR is by far one of the most effective methods to ensure your arrested patient has the best chance to survive.  However, emerging evidence suggests that there are additional goals that we should try and accomplish during our resuscitation.

 As we continue to move toward goal-directed resuscitation strategies, optimizing coronary perfusion pressure (CPP) may be our next target in “personalizing” the care we provide to those in cardiac arrest.

A recent AHA consensus statement recommended the following physiologic goals during cardiac arrest care:

• CPP > 20 mmHg: Estimated by diastolic BP [DBP] – [CVP] using an arterial line & central line.
• DBP > 25 mmHg: When an a-line is present without an appropriate CVC.
• EtCO₂ > 20 mmHg: When an a-line & CVC are not present.

Each of these variables can give the provider valuable feedback about how their patient is responding to their resuscitation.  Some argue that the DBP target should be much higher (>35 mmHg), with the caveat that pharmacologic optimization can only occur once high quality CPR is confirmed.  The goal should always be to minimize the use of epinephrine whenever possible!

Bottom Line:  During your next cardiac arrest resus, consider using a goal-directed strategy by monitoring the patient’s CPP, DBP, & EtCO₂ to determine the effectiveness of your resuscitation.

Suggested Reading

1. Meaney PA, Bobrow BJ, Mancini ME, et al. Cardiopulmonary resuscitation quality: [corrected] improving cardiac resuscitation outcomes both inside and outside the hospital: a consensus statement from the American Heart Association. Circulation. 2013;128(4):417-35.
2. Sutton RM, Friess SH, Maltese MR, et al. Hemodynamic-directed cardiopulmonary resuscitation during in-hospital cardiac arrest. Resuscitation. 2014;85(8):983-6.

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Vasopressors are used in shock-states to increase mean arterial pressure (MAP) and improve distal tissue perfusion. Additionally, some agents have effects on the heart to augment cardiac output.

Receptors that vasopressors work on include: 

• Alpha-1: increase arterial tone (increases MAP) and venous tone to reduce venous pooling and augment cardiac preload 
• Beta-1: increase inotropy and chronotropy on heart muscle; also increases arterial tone
• Beta-2 and Dopamine: cause vasodilation but may actually be beneficial because this increases perfusion to cardiac, renal, and GI tissues.
• V1: arterial vasoconstriction to increase MAP
• The chart below is a summary; please note that quoted receptor effects vary depending on the source reviewed

Norepinephrine (NE): excellent vasopressor for most types of shock and recommended as a first-line agent in the Surviving Sepsis Guidelines.

• Works on alpha-1, beta-1, and beta-2 receptors. 
• Initial dosing 0.05 mcg/kg/min with a maximum dose often cited as 0.5 mcg/kg/min (though there is technically no maximum dose).

Epinephrine (a.k.a. Adrenaline): in several countries the first-line agent for shock (including sepsis).

• Works similarly to NE on alpha-1, beta-1 and beta-2; it is a more potent inotrope than NE.
• One downside is the production of lactic acid, which can sometimes lead to confusion when following serial lactates during resuscitation. 

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Background

• Artificial nutrition is a staple of critical care
• Patients who are unable to eat, require enteral nutrition (preferred over parental nutrition)
• There are some formulas that are called "immunonutrition" which try to alter the inflammatory response seen in critical illness
• They may contain omega-3 fatty acids and essential amino acids such as arginine or glutamine, and anti-oxidants.

Data

• A recent trial (MetaPlus) was designed to see if immunonutrition could decrease the development of infections in the critically ill
• Compared to regular high protein formulas, there was no difference in mortality, duration of ventilation, or hospital length of stay

What to do

• Immuno-nutrition formulas cannot be routinely recommended
• Use regular high protein formulas
• Start within 48 hours of identifying a need

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Sepsis Pearls from the Recent Literature

• Sepsis remains one of the most common critical illnesses managed by emergency physicians and intensivists.
• Recent publications and meta-analyses (i.e., ProCESS, ALBIOS, SEPSISPAM) have further refined the management of these complex patients.
• A few pearls from the recent literature:
  • Early broad-spectrum antibiotics remains the most important factor in reducing morbidity and mortality.
  • Appropriate fluid resuscitation with a balanced crystalloid solution targeting 30 ml/kg. Use a dynamic measure of volume responsiveness to determine if additional fluid needed (i.e., PLR with a minimally invasive or noninvasive cardiac output monitor)
  • Maintain adequate tissue perfusion with IVFs and vasopressors (norepinephrine) targeting a MAP > 65 mm Hg.  Patients with chronic HTN may benefit from a higher MAP goal.  If the diastolic BP is < 40 mm Hg upon presentation, start vasopressors concurrent with IVF resuscitation.

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Should I Give My Patient with Septic Cardiomyopathy Fluids? 

The incidence of acute LV dysfunction in septic shock is estimated to occur in 18 - 46% of patients within the first 24 hours of shock.  Unlike the "classic" pattern of cardiogenic shock where LV filling pressure is high, in septic shock there are normal or low LV filling pressures.

Three therapeutic options should be strongly considered in the patient with a septic cardiomyopathy [CM]:

• FLUIDS:  Most patients with septic CM need fluids to restore adequate preload/afterload.  Severe vasoplegia requires volume resuscitation - even if the bedside ECHO suggests reduced contractility. Give fluids generously.
• Vasopressors: Catecholamine supplementation (norepi) improves patient's preload & afterload, but can often unmask septic CM. Consider epinephrine as a second line agent (over vasopressin) for inotropic support.
• Inotropes: Consider adding epinephrine (1 to 5 mcg/min) or dobutamine (start at 1-5 mcg/kg/min) to target an improved cardiac index (>2.5 L/min/m2) or ScVO2 > 70%.

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There are many ventilator modes to choose from, but almost every mode can be distilled down to its basic principles by understanding the “Three T's of Mechanical Ventilation”

Trigger: You must determine whether the vent or patient will trigger a mechanical breath. For example, machine-triggered breaths (a.k.a. control mode of ventilation) are used for paralyzed patients and will deliver a breath after a period of time has elapsed (e.g., if RR is 10/min, then a breath is given every 6 seconds). On the other hand, if a patient’s respiratory drive is intact (a.k.a. assist-mode) than the patient triggers the breath when the vent detects a patient induced change in airflow or airway pressure. These two modes can also be mixed together.

Target: Mechanical breaths must have a specific target, either a target airway pressure or a tidal volume. Because pressure and volume are directly related, pick the variable you want to target and the other parameter will vary depending on the patient’s intrinsic physiology. For example, if you choose to target a specific tidal volume, we may get one plateau pressure in a patient with normal lungs, but a higher plateau pressure in another patient with stiffer lungs.

Terminate: You must decide when the mechanical breath (i.e., inspiration) terminates and expiration begins. Termination occurs: 1) after a set inspiratory time has elapsed in certain pressure-targeted modes, 2) when a predefined target volume has been achieved (i.e., volume-cycled modes), or 3) when airflow has been reduced by a certain percentage (as in pressure-support ventilation; to be discussed separately)

Let’s put this all together by looking at an example: pressure control ventilation (rate = 12/min and target pressure 20cm H20). Trigger: Because this is a “control”, not assist mode, the machine will trigger a breath 12 times per minute or every 5 seconds. Target: Here we chose to have pressure be the target, so when the ventilator triggers a breath it will deliver a constant airway pressure of 20 cmH2O until we tell the vent terminate that breath. Terminate: the constant airway pressure will be turned off after a fixed period of time has elapsed; for this example we will set the inspiratory time as 1 second, then expiration begins. Now, after a few vent breaths we will observe the results of our settings and reassess; if the resulting tidal volume is lower than what we wanted, we will increase the target pressure to increase the tidal volume. If the tidal volume is higher than what we wanted, we will reduce the target pressure to reduce the tidal volume. We can also tweak the inspiratory time to manipulate the tidal volume, but this does so to a lesser degree.

Try to break down your favorite modes of ventilation using the Three T’s and see if this helps you understand vent modes better. 

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Observation after giving IM Epi for allergic reactions or anaphylaxis

Background

• Common practice is to observe patients who receive epinephrine for allergic reactions or anaphylaxis for several hours post-administration
• This can be from 4-24 hours depending on the institution
• This is to monitor for a biphasic reaction

Question

• Do we need to observe these patients?
• And if so, for how long?

Meta-analysis

• 2 urban Canadian EDs
• 5 year period
• Primary outcome was the amount of patients with a clinically important biphasic reaction
• Secondary outcome was mortality

Results

• 2819 encounters: 496 anaphylactic + 2323 allergic reactions
• 5 clinically important biphasic reactions (0.18%; 95% CI 0% to 0.17%)
• No fatalities
• Biphasic reactions tended to happen several hours (>24hrs) after ED discharge

Limitations

• If patients did not return to an ED in the region, then they would not be identified as a possible biphasic reaction

What to do?

• You can probably discharge most patients whose symptoms have resolved without a prolonged observation period (<4hrs)
• Patients with ongoing anaphylaxis and allergic reaction, should be observed longer or admitted
• Biphasic reactions are very rare

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Predicting Neurologic Outcome in Patients Treated with TTM

• Whether you target 36^oC or 33^oC, targeted temperature management (TTM) improves survival and long-term neurologic oucome in survivors of out-of-hospital cardiac arrest.
• TTM, however, can affect the accuracy and timing of commonly used tests to predict poor neurologic outcome.
• Golan, et al just published a meta-analysis evaluating the accuracy of select diagnostic tests to predict outcome in patients treated with TTM.
  • 20 studies (1,845 patients)
  • Most accurate tests to predict poor neurologic outcome were:
    • Bilaterally absent pupillary reflex (LR 10.45)
    • Bilaterally absent somatosensory-evoked potentials (LR 12.79)
  • Specificity of tests improved when testing was delayed > 72 hours
  • Other commonly used tests (i.e., corneal reflexes, GCS motor score, unfavorable EEG readings) had higher false positive rates and lower LRs

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Patient Positioning During Mechanical Ventilation

In any patient with acute respiratory failure, it is extremely important to consider patient positioning after initiating mechanical ventilation.  Both ventilation (V) and perfusion (Q) of the lungs can be significantly altered by manipulating the way you position your patient.  

• Routine Care: A good rule of thumb is to alays keep the patient's head of bed > 30 degrees whenever possible to maximize diaphragmatic excursion, increase lung expansion, and prevent downstream incidence of ventilator associated pneumonias.
   
• Lateral Decubitus Positioning: Severe unilateral lung disease may warrant alternative patient positiong.
  • Good lung DOWN: In general, the good lung should be placed in the dependent position to improve V/Q matching.
  • Good lung UP: Exceptions where the patient should be placed so the bad lung is in the dependent position include massive hemoptysis (prevent blood from filling the good lung), large pulmonary abscesses (prevent pus from filling the good lung), & unilateral emphysema (prevent hyperinflation)
     
• Reverse Trendelenburg:  In the morbidly obese patient, or those who must remain flat in bed, a trick of the trade to achieve a pseudo-semirecumbent position is to utilize reverse trendelenburg to > 30 degrees.

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• When considering starting a patient on non-invasive ventilation (NIV), ask yourself whether the patient is having a problem of oxygenation (Type I respiratory failure) or a problem of CO2 removal or ventilation (i.e., Type II respiratory failure); don’t forget both types can be present, simultaneously
• Examples of Type I problems are pneumonia and pulmonary edema; examples of Type II problems are COPD, drug overdose, and neuromuscular disease (e.g., myasthenia gravis). Once the underlying problem is identified, selecting the type of NIV is straight-forward. 
• There are only two interventions for type I disorders: 1) increase fio2 and/or 2) increase mean airway pressure (positive end-expiratory pressure; a.k.a. PEEP). There are only two interventions for type II disorders: 1) increase tidal volume and/or 2) increase respiratory rate 
• Continuous positive airway pressure (CPAP) only provides support for type I problems (i.e., can titrate FiO2 and PEEP); CPAP does not provide a tidal volume or a respiratory rate (needed for type II support)
• Bi-level positive airway pressure (BPAP) provides support for type II problems; tidal volume can be titrated by increasing the pressure support and a respiratory rate can be dialed in.

Editors note: The new Back 2 Basic series will review essential critical care concepts on the first Tuesday of each month. Want a specific topic reviewed? Contact us by email or Twitter.

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Risk of infection from Blood transfusions

• We are already moving to decreasing transfusions in general for most of our hospital patients
• But now there is evidence that more transfusions can lead to an increase in nosocomial infections

JAMA Meta-Analysis

• 18 randomized trials with 7,593 patients
• All tested higher vs lower transfusion thresholds in a variety of inpatient settings
• Hospital-acquired infections were the outcome

What they found

• Absolute risk for nosocomial infection was 17% among patients with a higher hemoglobin target compared to 12% with a lower target
• NNT to avoid an infection was 38 using a restrictive transfusion strategy

Bottom Line

• Potential cost savings to the healthcare industry with less transfusions
• For most patients, a hemoglobin > 7 g/dL is just fine

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Prophylactic FFP for Procedures?

• FFP is commonly transfused to correct abnormal coagulation studies prior to performing procedures in nonbleeding critically ill patients.
• Despite common practice, there is little to no supportive evidence to demonstrate a clinical benefit to transfusing FFP in this patient population.
• Muller, et al recently evaluated the use of FFP before invasive procedures in critically ill patients.  Brief highlights include:
  • Prospective, randomized, open-label study at 4 sites in the Netherlands
  • 76 adult ICU patients with INRs between 1.5 and 3.0
  • Procedures: central line placement, thoracentesis, percutaneous tracheostomy
  • Result: no difference in major bleeding events between those who received FFP and those randomized to no FFP
• Take Home Point: In the nonbleeding critically ill patient, routine transfusion of FFP to correct lab abnormalities prior to procedures is not indicated.

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