Thrombelastography for Management of Non-Traumatic Hemorrhagic Shock

The use of thrombelastography (TEG, ROTEM) has traditionally been utilized and studied in the management of acute coagulopathy of trauma (ACoT) developed by patients in hemorrhagic shock secondary to trauma.

Functional coagulation tests such as the TEG may provide valuable information when resuscitating the hemorrhaging patient, especially if there is any concern for an underlying coagulopathy.  

The following is a TEG recently returned during the resuscitation of a 60 y/o male with a history of HCV cirrhosis presenting with hemorrhagic shock secondary to a massive upper GIB.  The University's Massive Transfusion Protocol was promptly activated and at this point, the patient had received approximately 4 units of PRBCs & FFP along with 1 liter of crystalloid.  His Hgb was 5, PT/PTT/INR were undetectable, and his fibrinogen was 80.

Below is a table that simplifies the treatment, based on the test's abnormalities:

• Prolonged R:  Fresh frozen plasma
• Prolonged K or reduced α angle: Cryoprecipitate
• Low MA: Platelets, desmopressin (DDAVP)
• Elevated LY 30%: Consider antifibrinolytics (aminocaproic acid, TXA)

After reviewing the initial TEG, all perameters were abnormal in addition to the presence of significant fibrinolysis.  The patient was given an additional 4 units of FFP, DDAVP, cryoprecipitate, a unit of platelets, and aminocaproic acid.  The patient still required significant resuscitation, however bleeding had significantly decreased as well has his pressor requirement.  Below is the patient's follow-up TEG 2 hours later.

There is growing enthusiasm for the use of functional coagulopathy testing in the patient with hemorrhagic shock.  Early resuscitation with blood products as your fluid of choice with limited fluid administration while arranging for definitive source control are critical, but also consider early thrombelastography to detect additional causes for uncontrolled hemorrhage.

References

1. Walsh M, Thomas SG, Howard JC, et al. Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography. Journal of Extra-Corporeal Technology. 2011 Sep; 43(3):162-7.
2. The Use of TEG & Goal Directed Blood Component Therapy.  MarylandCCProject.org

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email: johncgreenwood@gmail.com

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Emergent reversal of Dabigatran

What is it:

Direct thrombin inhibitor used for stroke prevention in non-valvular atrial fibrillation

When do I worry about reversal:

Patients can have clinically important bleeding (GI hemorrhage, or Intracranial bleeding) or need reversal for emergent surgery

Patients with renal failure can have a prolonged medication effect

What can I do:

1.     Activated charcoal: good for recent overdose or recent ingestion (within 2 hours)

2.     Hemodialysis:  around 60-65% can be removed within 2-4 hrs; putting in a dialysis line can be…bloody

3.     FFP: in rat studies, has been shown to reduce the volume of intracranial hemorrhage. Unknown in humans. No good evidence of use based on coagulation mechanisms. Still worth a try though. 

4.     Recombinant activated factor VII: Has been shown to correct the bleeding time in animal studies. Probably the best bet in severe bleeding

5.     Pro-thrombin complex concentrate: has been shown to decrease the bleeding time in animal studies

How do I monitor effect?

No great way here. Check aPTT and thrombin time (TT). At supra-therapeutic doses there is no good test. 

Coming attractions: Dabigatran-fab for emergent reversal (see previous pearl: https://umem.org/educational_pearls/2415/) 

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Are Intermediate Lactate Levels Concerning in Patients with Suspected Infection?

• It is well known that lactate levels > 4 mmol/L are associated with increased mortality in patients with suspected infection.
• What is unclear, however, is the prognostic value of intermediate lactate levels (2.0-3.9 mmol/L) in patients with suspected infection.
• Puskarich, et al. performed a systematic review to determine the risk associated with intermediate lactate levels.
  • 8 studies (> 11,000 patients) were included in the analysis
  • Mortality for patients with intermediate lactate levels but without hypotension was 15%
  • Mortality was > 30% for hypotensive patients with intermediate levels of lactate.
• Take Home Point: Patients with intermediate lactate levels have an increased risk of mortality.
• Though no current guidelines exist for the optimal care of these patients, aggressive care should continue until repeat levels demonstrate normalization.

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Carbapenem Resistant Organisms are HERE

We've all heard Dr. Bryan Hayes warn us that, "Vanc & Zosyn is NOT the Answer for Everything" but things just got a little more serious, on a whole 'nother level...

Within the past few months, 2 cases of NDM-producing carbapenem-resistant pseudomonas have been reported in the area - one in Delaware and one in Pennsylvania.  Previously, the only reported cases were found in Europe.  

It's important for EM physicians to be aware of carbapenem resistant organisms and infections because:

• They have been independently associated with an increase in mortality
•  Are increasing in frequency around the world
• Are a major threat to our antimicrobial armamentarium

Risk factors for carbapenem resistance 

• Stem cell transplant patients
• History of mechanical ventilation
• Recent ICU stay
• Previous exposure to antibiotics

Antimicrobial options

Few treatment options are currently available for carbapenem resistant organisms.  

• Polymixins (colistimethate & polymyxin B)
• Tigecycline
• Fosfomycin
• Some aminoglycosides (amikacin, gentamicin, & tobramycin)

Appear to have retained some in vitro activity against these organisms, but are generally used as, "drugs of last resort". 

What should you do about it?

Know it exists, take a good history, & know your local antibiogram.  Prior to selecting a broad spectrum antimicrobial regimen, try to obtain previous antimicrobial culture data for patients with resistant organism infectious risk factors.

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Prior literature has demonstrated the safety and feasibility of placing subclavian lines with ultrasound guidance; here's a link to a short educational video describing the technique. 

The literature has been varied, however, as to which approach is best for venous cannulation with ultrasound; the supraclavicular (SC) or infraclavicular (IC) approach (see references below)

A recent study evaluated both approaches in healthy volunteers in order to determine which approach is superior for cannulation using ultrasound.

98 patients were prospective evaluated by Emergency Medicine physicians with training in ultrasound. In each patient, both SC and IC views were evaluated on both the left and right sides; each view was given a grade for ease of favorability (no patients were actually cannulated)

Overall, it was found that the SC view was significantly more favorable compared to the IC view; the right SC was non-significantly preferred compared to the left SC.

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High Flow Nasal Cannula

What is it?

• High flow nasal cannula has been used in pediatrics for some time now
• It can be used in adults as well
• It is a simple nasal cannula setup with larger cannula sizes in both nares
• It is heated, humidified oxygen
• You can control your oxygen level and flow of oxygen

Benefits

• Small amount of PEEP provided to the patient (estimated 5-7 cm H20)
• Improves oxygenation (more reliable oxygenation than a non-rebreather face mask)
• Can provide some alveolar recruitment
• Increases FRC (functional residual capacity)
• Pharyngeal dead space washout

Who to use it on

• Acute hypoxemic respiratory failure
• Pre-intubation (can place before and during intubation in patients who have low oxygen saturation)
• Post-extubation
• Palliative care (DNI patients)

How to set it

• Flow rates: 0-60 L/min
• Spontaneously breathing patient with mild-moderate hypoxemia/respiratory distress:

            -15-30 L per minute

            -100% oxygen (wean as tolerated)

            -temp 35-40 C

            -when weaning decrease oxygen prior to flow

Bottom line: No evidence that it reduces intubation rates in patients with hypoxemic respiratory failure but may improve oxygenation issues while deciding on treatment options

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Antibiotic Timing in Severe Sepsis/Septic Shock

• Though the recent ProCESS trial has questioned the utility of central hemodynamic monitoring and protocol-based resuscitation, early antibiotic administration remains paramount in the care of patients with severe sepsis/septic shock.
• Retrospective studies have demonstrated that delays in antibiotic administration are associated with marked increases in hospital mortality.
• Notwithstanding, delays in antibiotic administration remain all too common.
• Ferrer et al, have just published the largest cohort to date analyzing the association of antibiotic timing to hospital mortality in patients with severe sepsis or septic shock.  The key findings include:
  • Retrospective cohort of 17,990 patients from the SSC database.
  • Hospital mortality rose linearly for each hour delay in antibiotic administration.
  • Odds ratio for hospital mortality increased from 1 to 1.52, as the delay increased from 0 to 6 hours after presentation.
• Key Point: Antibiotic timing matters!

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Direct vs. video laryngoscopy in the patient with an acute TBI

Hypoxia and hypotension are considered the "lethal duo" in patients with traumatic brain injury.  In a recent randomized control trial (by our own Dr. Dale Yeatts at the Shock Trauma Center) mortality outcomes were compared between 623 consecutive patients who were intubated with either direct laryngoscopy (DL) or video laryngoscopy (VL).  Here is what they found:

1. No significant difference in mortality for all comers (Primary Outcome)
2. In the subset of patients with severe head injuries, there was:

• A significantly higher mortality in patients with TBI if VL was used
• A significantly longer intubation duration for VL (74 sec) than DL (65 sec)
• A greater incidence of low oxygen saturations of 80% or less in the VL group (27 patients) than DL (15 patients) - objectively recorded data, not self reported.

There is a reasonable amount of literature that shows hypoxia and hypotension significantly contribute to morbidity & mortality in the TBI patient, and a growing body of literature that suggests intubation with VL takes longer than DL.

Bottom Line: When choosing a method of intubation for the TBI patient, remember the "Lethal Duo" and consider direct laryngoscopy with manual inline stabilization first.

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• Only 50% of hemodynamically unstable patients will improve their hemodynamics in response to a fluid bolus. However, because excessive fluid administration can lead to organ edema and dysfunction, it is important to give hemodynamically unstable patients only the necessary amount of fluids to improve their hemodynamics.

• There are two general categories of assessing a patient's response to volume administration; static and dynamic assessments (see referenced article below):

  • Static assessment (generally unreliable, but traditionally used):

    • Physical exam (dry mucus membranes, cool extremities, etc.)

    • Urine output

    • Blood pressure

    • Central venous pressure via central-line

  • Dynamic assessment (more reliable but more labor intensive)

    • Pulse Pressure Variation

    • IVC Distensibility Index

    • End-expiratory occlusion test

    • Passive Leg-Raise

• There is no simple way to accurately determine the need for a fluid bolus however the integration of the techniques above can help the clinician make better decisions.

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How low should you go? MAP Goals in Septic Shock

Background:

• Since Rivers’ Early-Goal Directed Therapy, a MAP of 65 mm Hg was been the standard goal for blood pressure in septic shock
• Some studies have suggested a higher target may be better for patients with hypertension
• Potentially less renal failure with a higher target

The Trial:

• 776 adult patients in France; Multi-center; randomized; non-blinded
• All patients had septic shock and on vasopressors
• MAP was maintained for 5 days or when the patient was weaned off pressors
• Primary outcome: Mortality at Day 28
• High target 65-70 mm Hg vs Low target 80-85 mm Hg

Outcome:

• No significant difference in mortality at 28 days: 36.6%  (high target) vs 34% (low target) (95 %CI; 0.84 to 1.38; P=0.57)
• No significant difference at 90 days: 43.8% (high target) vs 42.3% (low target) (95% CI; 0.83 to 1.30; P=0.74)
• Incidence of newly diagnosed atrial fibrillation was higher in the high-target group
• Patients with chronic hypertension: those in the higher target group required less renal-replacement therapy
• Significant percentage of patients in the high target group did not meet goal MAP BUT the trial mirrored actual clinical practice and allowed clinicians the ability to limit blood pressure and differences in actual MAP attained in both groups was significantly different

Bottom Line:

• A MAP goal of 65 is just fine in most patients
• Patients with chronic hypertension and atherosclerosis seem to benefit (less need for renal-replacement therapies) with a higher MAP: so aim higher in these patients or monitor renal function and increase MAP goals accordingly

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Coagulopathies in Critical Illness - DIC

• Disseminated intravascular coagulation (DIC) is an acquired syndrome of intravascular coagulation and is commonly encountered in critically ill patients.
• Think about DIC in the critically ill patient with oozing at vascular sites (or wounds) and the following lab abnormalities:
  • Thrombocytopenia
  • Prolonged PT and aPTT
  • Decreased fibrinogen
  • Elevated fibrin split products and D-dimer
• Guidelines for the management of DIC are primarily based on expert opinion and include:
  • Treat the underlying condition (i.e., sepsis)
  • Transfuse platelets if < 50,000 per mm³
  • Transfuse FFP to maintain PT and aPTT < 1.5 times normal control
  • Transfuse cryoprecipitate to maintain fibrinogen levels > 1.5 g/L
• The use of heparin remains controversial and cannot be routinely recommended.

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Nitric Oxide appears to have NO role in ARDS

Background: The use of inhaled nitric oxide (iNO) in acute respiratory distress syndrome (ARDS) & severe hypoxemic respiratory failure has been thought to potentially improve oxygenation and clinical outcomes.  It is estimated that iNO is used in up to 14% of patients, despite a lack of evidence to show improved outcomes. 

Mechanism: Inhaled NO works as a selective pulmonary vasodilator which has been found to improve P_aO₂/F_iO₂ by 5-13%, but is costly ($1,500 - $3,000 per day) and increases risk of renal failure in the critically ill.

Study: A recent systematic review analyzed 9 different RCTs (N=1142) and compared mortality between those with severe (P_aO₂/F_iO₂ < 100) and less severe (P_aO₂/F_iO₂ > 100) ARDS and found that iNO does not reduce mortality in patients with ARDS, regardless of the severity of hypoxemia.

Bottom Line: Inhaled NO is an intriguing option for the treatment of refractory hypoxemic respiratory failure, however there does not appear to be a mortality benefit to justify it's high cost and potentially negative side effects.  In the ED, it is important to focus on appropriate lung protective ventilation strategies (TV: 6-8 cc/kg IBW) and maintaining plateau pressures < 30 cm H₂O in the initial stages of ARDS to prevent ventilator induced lung injury while awaiting ICU admission.

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In 2001, Rivers et al. published a landmark article demonstrating an early-goal directed protocol of resuscitation that reduced mortality in septic Emergency Department patients.

Many questions have arisen throughout the years with respect to that trial; critics have complained about the overwhelming change in clinical practice based on this one single-center randomized trial.

Challenging Rivers data are the ProCESS (Protocolized Care for Early Septic Shock) investigators, who released the results from a multi-center randomized control trial of 1351 septic Emergency Department patients; the primary end-point was 60-day mortality. Click here for NEJM article.

Patients in this trial were randomized to one of three groups:

• Protocol-based EGDT

• Protocol-based standard (did not require central lines, inotropes, or blood transfusions

• Usual care (no specific protocol; care was left to the bedside clinicians)

Bottom-line: The investigators did not find any difference in mortality between patients in the three groups and comment that the most important aspects of managing the septic patient may be prompt recognition and early treatment with IV fluids and antibiotics.

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• “B-Lines” can be seen in patients with pulmonary edema (see attached image below)
• A “B-line” is a reverberation artifact defined by Lichtenstein as having several properties:

1.     A comet-tail artifact

2.     Arising from the pleural line

3.     Well defined

4.     Hyperechoic

5.     Long (does not fade)

6.     Erases A lines

7.     Moves with lung sliding

• A large amount of B-lines is pathologic
• These artifacts are also called “comet-tails” due to their appearance
• One or two B-lines can be seen in dependent lung zones in normal lungs
• AIS (Alveolar interstitial syndrome) describes a group of conditions including pulmonary edema, interstitial pneumonia, and pulmonary fibrosis that show similar findings on lung ultrasonography
• The most common presentation of this syndrome is from cardiogenic pulmonary edema and is characterized by B-lines in multiple lung zones
•  B lines correspond with interlobular septal thickening on CT scans, which represent pulmonary vascular congestion 

Technique

• B-mode is used with the micro-convex (cardiac) probe scanning in at least 8 lung zones
• Quantify the number of B-lines in each zone
• A lung zone is considered to be “positive” when three or more B-lines are present in a longitudinal plane between two ribs
• Two or more regions bilaterally are required to be defined as AIS
• Bilateral diffuse B-lines have a specificity of 95% and a sensitivity of 97% for the diagnosis of pulmonary edema

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Attachments

• 1403111625_Fig6.1BLINESFINAL.jpg (55 Kb)

Recruitment Maneuvers for ARDS

• Patients with ARDS who are ventilated with lung protective settings are at risk of derecruitment/collapse of lung units.
• Recruitment maneuvers are processes that transiently increase transpulmonary pressure to open collapsed units.
• These maneuvers can improve oxygenation and have been used in patients with ARDS and those with refractory hypoxemia.
• The various types of recruitment methods include:
  • Airway pressure-based maneuver: a continuous positive airway pressure of 35-45 cm H₂O is applied for 30-40 seconds
  • Ventilator modes: Airway pressure release ventilation (APRV) and high-frequency oscillatory ventilation (HFOV)
  • Prone positioning
• Adverse events can occur with recruitment maneuvers and include hypotension, hypoxia, and pneumothorax (rare).

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Intensive BP Control in Spontaneous Intracranial Hemorrhage

Managing the patient with hypertensive emergency in the setting of spontaneous intracerebral hemorrhage (ICH) is often a challenge.  Current guidelines from the American Stroke Association are to target an SBP of between 160 - 180 mm Hg with continuous or intermittent IV antihypertensives.  Continuous infusions are recommended for patients with an initial SBP > 200 mm Hg.
 

An emerging concept is that rapid and aggressive BP control (target SBP of 140) may reduce hematoma formation, secondary edema, & improve outcomes.
 

Recently published, the INTERACT 2 trial (n=2,829) compared intensive BP control (target SBP < 140 within 1 hour) to standard therapy (target SBP < 180) found:

• No difference in mortality (11.9% vs 12%, respectively)
• Improved functional status (secondary outcome) with intensive BP control
• Intensive lowering of BP in patients with acute ICH appears safe 

Study flaws: Patients treated with multiple drugs - combinations of urapadil, labetalol, nicardipine, nitrates, hydralazine, and diuretics.  Management variability away from protocol seemed high. (Interesting editorial)
 

A Post-hoc analysis of the INTERACT 2 published just this month suggests that large fluctuations in SBP (>14 mmHg) during the first 24 hours may increase risk of death & major disability at 90 days.

Bottom Line:  INTERACT 2 was a large RCT but not a great study (keep on the look out for ATACH II).  However, in patients with spontaneous ICH, consider early initiation of an antihypertensive drip (preferably nicardipine) in the ED to reduce blood pressure fluctuations early with a target SBP of 140 mmHg.

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• The well-known effects of cocaine toxicity include seizures, cardiac ischemia, and rhabdomyolysis. Abdominal pain, however, is a lesser known side-effect and may occur secondary to ischemia, infarction or perforation of the gastrointestinal tract; such cases tend to occur in younger people without known risk factors for ischemia.
• Ischemia may occur from the direct vasoconstrictive effects of cocaine, but may also occur from its pro-thrombotic effects on the mesenteric vessels; although any segment of the GI tract may be involved, the small bowel is most often affected.
• Symptoms may vary from mild abdominal pain to bloody diarrhea. Physical exam may reveal peritoneal signs if perforation occurs.
• CT scan of the abdomen may reveal the diagnosis although angiography may required for diagnosis or to guide revascularization.
• Management may vary from conservative (i.e., bowel rest and antibiotics) to surgical exploration and bowel resection in selected cases.

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A 50yo man found dow in the snow was brought into our ER last week in cardiac arrest with a bladder temperature of 21° C. Let’s warm him up!

• Passive external warming (good for mild hypothermia > 34° C):  remove all wet clothing, use warm blankets, hot chocolate.
• Active external rewarming (Used for temp between 30-34° C): Radiant heat, electric blankets, Bair-Hugger. Disadvantages: “core temperature after drop” theory: drop in core temp because of peripheral vasodilatation. Therefore, focus on warming the chest and torso area.  May not occur with certain warming techniques.
• Active core rewarming (<30 °C, above techniques and several other options):

1. Heated humidified oxygen via mechanical ventilation at 42-46°
2. IV normal saline warmed to 41-43° C
3. Cardio-pulmonary bypass: 1-2° C increase every 5 minutes
4. ECMO (best option in cardiac arrest): Up to 4-6° C/hr. VV or VA ECMO. Provides Cardio-pulmonary support. Can continue CPR while placing a cannula.
5. CVVH: less costly, more available, 1-4°C/hr. Case reports only. 
6. Artic Sun; external rewarming pads: used in hypothermia protocols. Easy to use. Case reports only.

• Other methods (use if other methods are unavailable):

1. Pleural irrigation: one chest tube in the mid-clavicular line w saline at 42° and another chest tube in the post-axillary line and connected to a pleurovac.
2. Peritoneal lavage: 8 Fr catheter into the peritoneum using a standard paracentesis method. Use 40-45° C dialysate.
3. Gastric, bladder, colonic irrigations

We were able to get ROSC with CPR and ACLS and then used Artic Sun to re-warm successfully.

Other tips/tricks:

• Continue CPR while rewarming (This is debatable: monitor ECG for new rhythms)
• How warm is “warm and dead”? Probably around 32°C
• How fast to rewarm?  Would warm quickly in cardiac arrest and then 1-2° C/hr thereafter; (No good evidence here)
• Arrhythmias corrected by rewarming (bradycardia etc); no need for pacing
• Up to three defibrillations for V. fib/V. tach; hold if no benefit
• Can give epinephrine per ACLS protocol but would be cautious with further dosing
• Pressors: can use epinephrine drip cautiously for hypotension
• Cisaturacurium for paralysis w/ sedation to prevent shivering
• Rule out hypoglycemia, adrenal insufficiency, hypothyroidism, sepsis if patient does not rewarm as expected!
• Avoid IJ lines or irritating the myocardium with a guidewire.
• K>12 mmol /L: consider termination of CPR

Attachments

• 1402111256_nejm_hypothermia2012.pdf (581 Kb)

Mechanical Ventilation During ECMO

• ECMO is a rapidly emerging therapy for critically ill patients with severe acute respiratory failure (VV-ECMO) and circulatory failure (VA-ECMO).
• Mechanical ventilation (MV) settings may have important effects on patients receiving either VV- or VA-ECMO.
• Though no large, randomized trials, consensus guidelines and expert opinion recommend the following initial settings for patients receiving VV-ECMO:
  • Tidal volume: < 4 ml/kg predicted body weight
  • Plateau pressure: < 25 cmH₂O
  • PEEP: 10-15 cmH₂O
  • F_iO₂: titrated to maintain sats > 85%
  • RR: 4 to 6 breaths per minute

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