UMEM Educational Pearls - Critical Care

Question

You decide to do a R.U.S.H. exam on your hypotensive patient and perform an apical four-chamber view.You see one of the two clips below; are there any tricks to figure out which is the left ventricle and which is the right ventricle?

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  • A recent meta-analysis found that non-invasive ventilation can improve survival in acute care settings.
  • Consider using NIPPV in:
    • COPD exacerbation
    • Obesity hypoventilation syndrome
    • Asthma
    • Hypoxemic respiratory failure
    • Cardiogenic pulmonary edema
    • ARDS
  • Make sure to reassess your patients for improvement within one hour of applying NIPPV. If gas exchange has not significantly improved then endotracheal intubation and mechanical ventilation should be considered.
  • Adverse effects:
    • Gastric distension
    • Pressure ulcers on the face
    • Can be uncomfortable
  • In cardiogenic pulmonary edema there are cardiac performance benefits:
    • Decreases preload
    • Decreases left ventricular afterload
    • Improved cardiac ouput

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Mechanical Ventilation in the ED

  • Emergency physicians (EPs) intubate patients on a daily basis.  Due to prolonged lengths of stay for many of these patients, the EP must manage the ventilator during the crucial early hours of critical illness.
  • Despite the marked increase in critically ill patients, emergency medicine residents receive very little training in mechanical ventilation (MV).1
  • In addition, recent literature has demonstrated some common themes regarding MV in the ED.2,3
    • Use of higher than recommended tidal volumes
    • Infrequent use of lung protective ventilation strategies
    • Infrequent monitoring of plateau pressures
  • Take Home Points
    • Pay attention to tidal volume
    • Monitor and maintain plateau pressures < 30 cm H2O

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Category: Critical Care

Title: Stop looking for the "Best PEEP", aim for a "Better PEEP"

Keywords: mechanical ventilation, ARDS, PEEP (PubMed Search)

Posted: 3/24/2015 by John Greenwood, MD (Updated: 3/28/2024)
Click here to contact John Greenwood, MD

 

Stop looking for the “Best PEEP”, aim for a “Better PEEP”

Mechanical ventilation settings in the patient with acute respiratory distress syndrome (ARDS) need to provide adequate gas exchange and prevent ventilator induced lung injury (VILI). Positive end-expiratory pressure (PEEP) is often prescribed with consideration of the patient’s FiOrequirement, estimated chest wall compliance, and hemodynamic tolerance. 

So what is the best strategy for PEEP prescription?

In a recent review, Gattinoni & colleagues analyzed a number of the recent studies examining PEEP optimization.  In this paper, the authors conclude that there is no “Best PEEP,” and regardless of the level chosen there will be some degree of intratidal recruitment-derecruitment and VILI.  They go on to recommend a PEEP prescription strategy that reflects the severity of ARDS using the patient’s PaO2/FiO2 or P/F ratio.  

  • Mild ARDS (P/F 200 – 300): 5-10 cm H2O
  • Moderate ARDS (P/F 100 – 200): 10-15 cm H2O
  • Severe ARDS (P/F < 100): 15-20 cm H2O
     

Bottom line: There is no “Best PEEP” however, a “Better PEEP” is one that is primarily tailored to the severity of the patient’s ARDS, but also compensates for chest wall resistance and minimizes hemodynamic compromise.    

 

References

  1. Gattinoni L, Carlesso E, Cressoni M. Selecting the 'right' positive end-expiratory pressure level. Curr Opin Crit Care. 2015;21(1):50-7.
  2. ARDSnet PEEP table: http://www.ardsnet.org/system/files/Ventilator%20Protocol%20Card.pdf

 

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Category: Critical Care

Title: The results are in! The ProMISe Trial

Posted: 3/17/2015 by Haney Mallemat, MD (Emailed: 3/18/2015) (Updated: 3/18/2015)
Click here to contact Haney Mallemat, MD

The results of a multi-center trial from the UK, the ProMISe trial, were just released and it confirms what two prior studies (i.e., ProCESS and ARISE) have already shown; there does not appear to be any difference in mortality when septic patients are treated with a strategy of early-goal directed therapy as compared to usual care.

Patients were included in the ProMISe trial if they were in septic shock and were then randomized to either the EGDT group (630 patients) or the usual care group (630 patients); a total of 1,260.

The primary end-point was all cause mortality at 90 days and there was no difference shown in the primary outcome. There were no differences found in the measured secondary outcomes (e.g., serious adverse events)

This trial adds to the evidence that septic patients may not benefit from protocolized (i.e., EGDT) care versus usual care. One explaination why, is that our "usual care" in 2015 has significantly changed since the introduction of EGDT in 2001.

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Category: Critical Care

Title: Transfusion in Major Trauma: The PROPPR Trial

Keywords: massive transfusion, trauma, bleeding, critical care, severe trauma, PROPPR (PubMed Search)

Posted: 3/10/2015 by Feras Khan, MD
Click here to contact Feras Khan, MD

Transfusion in Major Trauma: The PROPPR Trial

What should we be transfusing in major trauma?

  • Should we aim towards 1:1:1 ratios or is that unnecessary? Most trauma centers have gone towards a 1:1:1 ratio or a 1:1:2 ratio with a greater percentage of RBCs transfused in the latter
  • Our strategy should be to avoid coagulopathy, acidosis, and hypothermia
  • This trial looks at transfusion of Plasma, Platelets, and RBCs in a 1:1:1 vs a 1:1:2 ratio
  • Is it safe to give 1:1:1 ratios?

The Trial

  • RCT, Non-blinded
  • 12 Trauma Centers in North America
  • 15 years or older; highest level trauma activation
  • Predicted to receive massive transfusion
  • Transfusions stopped when clinically indicated

Results

  • 24 hour or 30 day mortality no significant difference
  • Post-hoc analysis: death by exsanguination (9% vs 15%) in the 1st 24hrs was significantly decreased in the 1:1:1 group
  • Achieved hemostatis (86% vs 78%; p = 0.006) greater in the 1:1:1 group

Conclusions

  • Was not powered to detect a difference of less than 10% in mortality
  • There was less mortality from exsanguination in the 1:1:1 ratio.
  • Worth noting that platelets given first in 1:1:1 group (in control group 6 U and 3 FFP given prior to platelets)
  • There was some "catch up" in the 1:1:2 group (after the initial transfusions, these patients got more than expected plasma and platelets based on INR/Plt counts)
  • TEG was used in the majority of the patients and TXA was used in a majority of patients (but similar in both groups)

How does this affect my practice?

A 1:1:1 transfusion practice is safe and can decrease mortality from hemorrhage in major trauma

Other points: control bleeding, permissive hypotension, avoid crystalloids, use TEG to guide therapy (TXA etc)

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High-Flow Nasal Cannula for Apneic Oxygenation

  • In recent years, much has been written about the use of apneic oxygenation for patients who require endotracheal intubation (ETI).
  • Critically ill patients often have little cardiopulmonary reserve and can rapidly desaturate during ETI.
  • High-flow nasal cannula (HFNC) devices can deliver heated, humidified O2 up to 60 L/min and can provide a modest amount of positive pressure.
  • A recent study evaluated the use of a HFNC device for apneic oxygenation in ICU patients requiring ETI:
    • Prospective, quasi-experimental, before-after study
    • 101 patients in a single ICU in France
    • Compared NRB + nasal cannula to HFNC for preoxygenation/apneic oxygenation
    • Prevelance of severe hypoxemia (SpO2 < 80%) was significantly lower in the HFNC group
  • Clinical Application: Consider using HFNC for apneic oxygenation in critically ill patients with mild-to-moderate hypoxemia who require ETI.

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The Role of the CVP in a Post- “7 Mares” Era
 

The role for using central venous pressure (CVP) as a measure of volume responsiveness has largely fallen out of favor over the years.1 There are certainly better indices for fluid responsiveness, but don’t be fooled – the CVP isn’t a one trick pony.  In fact, a high or rapidly rising CVP should raise a significant concern for impending cardiovascular collapse.

Consider the following differential diagnosis in the patient with an abnormally high or rising CVP ( >10 cm H2O).

  • Excessive pressures outside of the heart or impediments to venous return (juxta-cardiac pressures)
    • Cardiac tamponade
    • Auto PEEP or breath stacking during mechanical ventilation
    • Tension pneumothorax
  • Venous return that’s more than the right ventricle can handle
    • RV failure
    • Severe tricuspid valve disease
    • Massive increase in pulmonary vascular resistance (massive PE, pulmonary hypertension, ARDS, LV failure)

Bottom Line: In a time where the utility of the CVP has been largely dismissed, remember that an abnormal CVP offers great deal of information beyond a simple measure of volume status.

 

References

  1. Marik PE, Baram M, Vahid B. Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest. 2008;134(1):172-8.
  2. Berlin DA, Bakker J. Starling curves and central venous pressure. Critical Care. 2015;19(1):55.

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As the cold and snow rips through the United States, hypothermia is a major concern because each year approximately 1,300 Americans die of hypothermia.

Classification of hypothermia:

  • Mild (32-35 Celsius): shivering, hyperventilation, tachycardia, but patients are usually hemodynamically stable.
  • Moderate (28-32 Celsius): CNS depression, hypoventilation, loss of shivering, risk of arrhythmias, and paradoxical undressing
  • Severe (<28 degrees Celsius): increased risk of ventricular tachycardia/fibrillation, pulmonary edema, and coma

The risk of cardiac arrest increases when the core temperature is less than 32 Celsius and significantly rises when the temperature is less than 28 Celsius. Rapid rewarming is required as part of resuscitation should cardiac arrest occur.

A rescue therapy to consider (when available) is extra corporeal membrane oxygenation (ECMO). ECMO not only provides circulatory support for patients in cardiac arrest, but allows re-warming of patients by 8-12 Celsius per hour.

Some studies quote survival rates of 50% with hypothermic cardiac arrest patients receiving ECMO versus 10% in similar patients who do not receive ECMO.

As winter lingers in the United States, consider speaking to your cardiac surgeons now to plan an Emergency Department protocol for hypothermic patients that may require ECMO.

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Category: Critical Care

Title: Updates in preventative strategies in the ICU

Keywords: VAP, chlorhexidine baths, subglottic suctioning (PubMed Search)

Posted: 2/10/2015 by Feras Khan, MD
Click here to contact Feras Khan, MD

Updates in preventative strategies in the ICU

Preventing Ventilator Associated Pneumonia (VAP)

  • Traditionally ICUs use techniques such as head of bed elevation> 30 degrees, chlorhexidine mouth rinses, reduced sedation, and controlling cuff pressure between 20-30 cm H2O to reduce VAP
  • A new trial confirms that subglottic suctioning also reduces VAP
  • Endotracheal tubes are made with a suction line along the edge with fenestrations below the vocal cords and above the cuff
  • This is hooked to wall suction removing secretions before they are aspirated
  • VAP rates are very low in the US (most likely due to under-reporting)
  • It is reported at around 15 VAPs/ 1000 ventilator days in Europe

The trial

  • 5 ICUs in Belgium; 352 total patients with suctioning vs control were randomized
  • Reduced incidence of confirmed VAP 9% vs 18%, decrease ventilator days 10 vs 20 and antibiotic use 7% absolute reduction

Bottom Line

  • More expensive around $20 or more vs $1 for a regular ETT
  • NNT around 11 to prevent one VAP: it is cost efficient
  • Use them in patients who will remain intubated for > 48hrs (not elective surgical patients)

Daily bathing with chlorhexidine does not reduce health care associated infections

  • It is believed that daily bathing with chlorhexidine antibiotic washes decrease rates of infection in the ICU; this is debatable

The trial

  • One center, 5 ICUs, 9340 patients
  • 10 week cleaning period followed by a two week washout then crossover to the alternate treatment (non-antibiotic washes)
  • Looking for CLABSIs, CAUTIs, VAP and C. diff infections
  • 55 infections occurred in the chlorhexidine group; 60 in the control goup.
  • 2.86 per 1000 patient days (chlorhexidine group) vs 2.9 per 1000 patient days (control)

Bottom Line

  • Does not appear to be helpful (perhaps specific patient groups such as bone marrow units may benefit)
  • More expensive to use these washes and can lead to resistance
  • Very well designed study with a variety of ICUs used (although one center)

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Hypertensive Emergency Pearls

  • It is well known that a hypertensive emergency is not defined by an arbitrary blood pressure reading.  Rather, it is characterized by the presence of end-organ dysfunction, often due to a sudden increase in sympathetic activation.
  • When treating patients with a hypertensive emergency, consider the following:
    • Many are hypovolemic due to a pressue-induced natriuresis - give them fluids and avoid diuretics.
    • BP should be reduced in a controlled manner using short-acting titratable intravenous agents. Rapid reductions in BP can lead to organ hypoperfusion.
    • Avoid oral, sublingual, and transdermal medications until end-organ dysfunction has resolved.
    • Clevidipine is the newest agent
      • A third-generation dihydropyridine
      • Relaxes arteriolar smooth muscle
      • Rapid onset (2-4 min) and short acting (5-15 min)
      • Compares favorably with nicardipine in available studies

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Category: Critical Care

Title: Extracorporeal Treatment Strategies for Acute Methanol Poisoning (When to Dialyze)

Keywords: Methanol, toxicology, methanol toxicity, critical care (PubMed Search)

Posted: 1/20/2015 by John Greenwood, MD (Emailed: 1/27/2015) (Updated: 1/30/2015)
Click here to contact John Greenwood, MD

 

Extracorporeal Treatment Strategies for Acute Methanol Poisoning (When to Dialyze)

 

Methanol toxicity is classically included in the differential for the intoxicated patient presenting to the ED. Add a negative EtOH level, anion/osmolar gap, blindness and you have yourself a slam dunk diagnosis. The goal is to stop the liver from metabolizing methanol to formic acid. Outside of fomepizole (or old school ethanol therapy), dialysis is often discussed, but when should you actually get the nephrologist on the phone?

This month the Extracorporeal Treatments in Poisoning Workgroup released a systematic review and consensus statement to help clinicians decide when to pull the HD trigger. Their suggestions are below.

When to start HD:

  1. Neurologic dysfunction: Coma, seizures, new vision deficits
  2. Metabolic acidosis: blood pH ≤7.15 or persistent metabolic acidosis despite adequate supportive measures & antidotes
  3. Serum anion gap higher than 24 mmol/L
  4. Serum methanol concentration:
    • > 700 mg/L (21.8 mmol/L) if fomepizole therapy is given
    • > 600 mg/L or 18.7 mmol/L if ethanol treatment is given
    • > 500 mg/L or 15.6 mmol/L in the absence of an alcohol dehydrogenase blocker

Which Modality: Intermittent HD (IHD) should be used over continuous renal replacement therapies (CRRT), as you can clear the toxin faster with higher HD flows.

When to stop HD: Extracorporeal treatment can be terminated when the methanol concentration is less than 200 mg/L or 6.2 mmol/L and a clinical improvement is observed.

Bottom Line:  Consider early hemodialysis in most patients presenting with methanol toxicity.  Clinical exam and routine lab testing will likely provide enough information to determine the need for IHD, but specific methanol levels can be helpful to guide adjunctive treatment options.

 

Reference

Roberts DM, Yates C, Megarbane B, et al. Recommendations for the Role of Extracorporeal Treatments in the Management of Acute Methanol Poisoning: A Systematic Review and Consensus Statement. Crit Care Med. 2015;43(2):461-472.

 

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  • Intraosseous (IO) is well-recognized as a venous line for delivering a variety of medications, including vasopressors. However, there is not a wealth of literature to support the use of IOs when administering medications for rapid sequence intubation (RSI).
  • This prospective observational study was conducted to determine whether an IO can be used to reliably and rapidly administers medications during RSI in trauma patients.
  • Thirty-four trauma patients were enrolled in the study and patients had a variety of traumatic mechanisms; blunt, penetrating, burns, and blast. The primate study outcome was the success rate of first-pass intubations using direct laryngoscopy.
  • The authors demonstrated a first pass success rate of 97% with a grade I view on 91% of attempts.
  • Bottom-line: This is yet another study demonstrating that when rapid and reliable access is needed, IO is an excellent option for venous access.

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Category: Critical Care

Title: Diaphragm weakness and its significance

Keywords: diaphragm weakness, respiratory failure (PubMed Search)

Posted: 1/13/2015 by Feras Khan, MD
Click here to contact Feras Khan, MD

Diaphragm weakness and its significance

  • Acute respiratory failure is partially due to respiratory muscles inability to meet the demands of respiration that is strained by a medical condition
  • Ventilation can have an adverse effect on respiratory muscles even after just 5-6 days (atrophy)

There are several ways to monitor diaphragm strength and function

  • Airway pressure and flow waveforms
  • Occlusion pressure
  • Esophageal pressure waveforms
  • Sniff maneuvers
  • Ultrasound
  • Diaphragm EMG
  • Chest xray

Clinical Relevance

  • Goal is to use these devices to limit the development of respiratory muscle atrophy because of disuse
  • Prevent "overassist" from the ventilator
  • Potential use in weaning trials to evaluate for respiratory muscle performance
  • This is a new area of intensive care research that could lead to improvements in outcomes

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"PQRST" - Capnography in Cardiac Arrest

  • Resuscitation of the patient in cardiac arrest can be stressful, chaotic, and variable depending on the setting.
  • Capnography is a valuable tool in the management of patients in cardiac arrest.
  • Heradstveit, et al. published a pneumonic for the use of capnography during cardiac arrest:
    • P - Position of the tube
      • The sensivity and specificity of capnography for endotracheal tube confirmation is superior to auscultation and capnometry.
    • Q - Quality of CPR
      • Early detection of poor-quality compressions.
    • R - ROSC
      • A sudden increase in end-tidal CO2 can indicate ROSC without interrupting CPR for pulse checks.
    • S - Strategy
      • May assist clinicians in determining underlying etiology of cardiac arrest.
    • T - Termination
      • An end-tidal CO2 value < 10 mm Hg after 20 min of resuscitation has been shown to be very accurate in predicting death.

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Cartoons Kill: A new high-risk patient for critical illness & death

This past month, the BMJ published an impressive retrospective review that analyzed nearly 80 years of data to find that animated characters in children’s films are in fact at a very high-risk for death when compared to characters in adult dramas.

Films ranged from 1937 (Snow White) to 2013 (Frozen) and were compared against the two highest gossing dramatic films in that same year.  The authors found that nearly two thirds of the children’s animated films contained an on-screen death of an important character compared to only half in adult dramas. 

Fatalities were most commonly the result of:

  • Defenestration/falls (11%)
  • Animal attacks (11%)
  • Drowning (6.7%)
  • Gunshot wounds (6.7%)
  • Other mystical causes (6.7%)

Other high-risk animated characters include the parents of the protagonist (17.8% mortality) and nemeses (28.9% mortality).  Median survival time was approximately 90 minutes (much less than the usual ED LOS!)

Notable early on-screen deaths included Nemo’s mother being eaten by a barracuda 4 minutes into Finding Nemo, Tarzan’s parents being killed by a leopard 4 minutes into Tarzan, and Cecil Gaines’ father being shot in front of him 6 minutes into The Butler.

The author’s intention  was to point out the psychological impact of death on young children, but I think the authors also highlight an important, high-risk patient population that could present to your ED.

 

Bottom Line: Animated characters should be aggressively resuscitated and strongly considered for admission to a higher level of care should they present to your ED, as they appear to be at high-risk for death and rapid decompensation.

May all of you have a happy and safe 2015!

 

Reference

1. Colman I, Kingsbury M, Weeks M, et al. CARTOONS KILL: casualties in animated recreational theater in an objective observational new study of kids' introduction to loss of life. BMJ. 2014;349:g7184.

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Treating ischemic strokes with interventional therapies (e.g., clot retrievers, stents, intra-arterial tPA, etc.) is nothing new, but there has never been a randomized control trial demonstrating benefit until recently.

The prospective MR CLEAN trial evaluated whether interventional therapies (i.e., either mechanical intervention or intra-arterial tPA) would confer benefit; patients were included if there was an acute occlusion within the proximal intracranial portion of the anterior cerebral circulation.

90% of patients received alteplase prior to randomization; there were 233 patients in the intervention group (alteplase + intraarterial intervention) and 267 patients in the usual care care arm (alteplase only); all patients were treated within 6 hours of symptoms onset

The primary outcome was functional independence at 90 days; an absolute difference of 13.5 percentage points favoring the intervention group was found. There were no significant differences in mortality or symptomatic intracerebral hemorrhage.

Despite these exciting results, we must pause and ask why this was this the first randomized trial demonstrating benefit when previous trials could not? Here are three blogs posts that deep dive this question and raise even more questions:

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How does it present?

  • Fever, cough, sore throat, runny nose, muscle aches, headaches, fatigue, diarrhea (in children especially)

Who cares…I got my vaccine! Does the vaccine work this year?

  • There has been some antigenic drift this year in the influenza A (H3N2) type virus.
  • 52% are anti-genically different than the H3N2 vaccine virus.
  • So the vaccine is less effective this year but it can give some cross-protection (in addition to protection against the other strains used in the vaccine)
  • CDC recommends still getting the vaccine  (http://www.cdc.gov/flu/protect/vaccine/vaccines.htm)
  • 91% of samples reported to the CDC have been influenza A this year

Can I test for this?

  • Rapid influenza diagnostic tests check for antigen detection
  • Pooled sensitivity of 62%; specificity of 98%
  • False negatives are common
  • Good technique during sample collection is important

The CDC is recommending treatment...wait I thought we were done with Tamiflu?

  • Benefits: shortens the duration of symptoms (day or less), reduces the risk of complications, reduces the risk of death among hospitalized patients
  • Risks: side effects (see below)
  • A recent Cochrane review revealed that treatment did not really help reduce complications and most of the data on anti-viral agents is biased (Roche funded) and hotly debated

Who is at risk/who deserves consideration for treatment?

  • Hospitalized patients with influenza 
  • Old people (>65)
  • Children
  • Pregnant women
  • Chronic medical conditions (asthma, COPD, diabetes, or heart disease)
  • American Indians and Alaskan natives
  • Chronic immunosuppression
  • Institutional outbreaks (nursing homes, correctional facilities)

Pearls of treatment

  • Treat as early as possible (<48hours from symptom onset)
  • 5 days of treatment; twice daily dosing. Wt based for children. Renally dosed.
  • Oseltamivir: used for more severe influenza cases
  • Zanamivir: 7 years or older; IV Zanamivir is currently in Phase III clinical trials

What are the side effects of anti-viral agents?

  • Don’t use zanamivir in patients w/ pulmonary disease
  • Transient neuropsychiatric events for oseltamivir
  • Nausea, vomiting, diarrhea are common both both

 

Show References



The Critically Ill Patient with Ebola Virus Disease

  • The current outbreak of Ebola Virus Disease (EVD) is the largest ever recorded and has been declared "a public health emergency of international concern" by the WHO.
  • Pearls regarding critically ill patients within the current EVD outbreak include:
    • Clinical Features
      • Tachycardia, tachypnea, oliguria, and alterations in mental status are common and generally seen about 7-12 days after symptom onset.
      • Shock is often due to profound hypovolemia from GI losses.
      • Hemorrhage is a late finding and most often manifests as lower GIB.
    • Labs
      • Common lab abnormalities include hypokalemia, hypocalcemia, hypoalbuminemia, and lactic acidosis.
    • Treatment
      • The mainstay of treatment is aggressive fluid resuscitation and electrolyte repletion (especially potassium).
      • Blood products can be administered for those with coagulopathy and hemorrhage.
      • Empiric antibiotics and antimalarial medications should be considered while awaiting confirmatory testing for EVD.

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Dynamic Measures of Intravascular Volume Assessment

The resuscitation of a patient in shock often requires the administration of intravenous fluid.  Excessive fluid resuscitation can lead to worsening pulmonary edema, systemic edema, acid-base disturbances, as well as many other complications. There are a myriad of techniques to try and figure out if the patient needs more intravascular volume, but each has it’s pitfalls.

Recently, experts have recommend that we move away from using static measures of preload assessment such as central venous pressure (CVP) and instead focus on using dynamic measures for volume responsiveness.

Volume Responsiveness Defined: An increase of stroke volume of 10-15% after a 500 mL IV crystalloid bolus over 10-15 minutes.

Below is a chart describing key values, requirements, and contraindications for each of these dynamic measures of non-invasive intravascular volume assessment. 

Important notes:  PPV and SVV require the patient to be intubated with controlled tidal volumes.  Arrhythmias and right heart failure make many of these measures invalid (except for PLR).  Other methods of assessment not discussed include systolic pressure variation, left ventricular outflow track velocity time integral (LVOT VTI), and end-expiratory occlusion pressure (EEO).

Bottom Line: None of these measures are perfect and shouldn't be used in isolation to determine if the patient’s “tank is full”.  Combine clinical judgment with these measures to get a best estimate of whether or not to give that next fluid bolus.  

 

Reference

1. Enomoto TM, Harder L. Dynamic indices of preload. Crit Care Clin. 2010;26(2):307-21, 

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