Fluid Resuscitation

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Dr. Dan Howes Queens University
Controversies and Progress in Resuscitation 2009
Dr. Jason Lord University of Calgary
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Declaration of potential conflict of interest

• Dr. Lord has received honoraria from
• Eli Lilly
• Bristol Myers Squibb
• Dr. Howes has received research funding from Life
  Recovery Systems, but so far no one is willing to
  pay for his opinion.

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Topics

• Advances in transfusion resuscitation
• Controversies with Massive Submassive PE
• Cognitive Psychology gets practical

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Advances in Transfusion Medicine
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Case 1

• 54 YO cyclist strikes the side of a car at a high
  rate of speed
• Injuries include multiple orthopedic injuries,
  hemothorax, splenic and liver lacerations, pelvic
  fracture.
• Conscious, responding appropriately gtgt
• decreasing level of consciousness

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• BP 85/30
• HR 135
• RR 16
• IV access, 2.3 L N/S has infused on route.
• You decide to administer blood products

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• Red blood cells?
• Frozen Plasma?
• Platelets?

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution

• Reduces activity of clotting factors by 50 at 34
  C
• Platelet activation almost eliminated at
• 30 C

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution

• Xa-Va complex activity reduced
• pH
• 7.2 50
• 7.o 70
• 6.8 90

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution

• Once thought to be the major cause
• Late
• Iatrogenic

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution
• Consumption
• Fibrinolysis

• Was thought to be DIC
• (late)
• Now recognized as local (early)

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution
• Consumption
• Fibrinolysis

• With consumption of thrombin, Thrombin Activated
  Thrombolysis Inhibitor secretion deminished
• Low flowgtgtTPA secretion

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COST Coagulopathy of Severe Trauma

• Hypothermia
• Acidosis
• Dilution
• Consumption
• Fibrinolysis

• Severe Trauma victims arrive coagulopathic, even
  if they arent cold or acidotic.

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Whole Blood Administration
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• COST
• coagulopathy of
• severe trauma

• Success of Whole Blood transfusion

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• COST
• coagulopathy of
• severe trauma

• Success of Whole Blood transfusion

More Aggressive Blood Transfusion Ratios 111(?)
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111 is not the same as Whole Blood

• If you recombine
• 1 unit pRBCs
• 1 unit of FFP
• 1 unit platelets

• You get
• Hb 100
• Plts 88
• 65 coagulation factors

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111 is not the same as Whole Blood

• If you recombine
• 1 unit pRBCs
• 1 unit of FFP
• 1 unit platelets

• You get
• Hb 100 gtgt 90
• Plts 88 gtgt 61
• 65 coagulation factors

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What we are doing

• Avoid blood transfusion in most trauma patients
• If you do need to transfuse
• 11 pRBCs plasma
• After 5 units, add 1 dose platelets (Buffy Coat)

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Buffy Coat platelets

• Ordering platelets has changed
• 1 adult dose
• Equivalent to 5 units of plts
• 4 donors in the plasma of 1 male donor

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What if our patient is on coumadin?

• Prothrombin Complex Concentrate
• Octaplex

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Octaplex
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Octaplex

• Recommended for warfarinized patients with
• Major bleeding
• Need for urgent (lt6 hours) surgical procedure.
• Contraindicated in patients with HIT
• 20 mL vial give 40 mL over 15 minutes

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Controversies with Pulmonary Emboli
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Clinical Case

• 56 yr healthy male presents to ER with swollen
  right leg, RSCP and SOB
• Requiring 60 FiO2
• Stable BP
• Tachycardic

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Pulmonary Embolism

• CT shows bilateral thrombus with saddle
  formation and persistent R leg clot
• ECHO in the ED reveals hypokinetic,
  dysfunctional RV

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Common Questions

• Should I start thrombolytics in the ED?
• Should I arrange for an IVC filter?

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Clinical Case

• Heparin bolus and infusion started
• Resp/ICU consulted for opinions re thrombolysis
  /- filter insertion
• ICU decision to transfer to unit for observation
• Prior to bed coming available - acute
  deterioration
• SBP drops to 70 despite additional fluids

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Clinical Case

• CVC inserted and Levophed started
• tPA infusion in the ER
• Gradual resolution over 90 min
• BP 125/70, HR 95 NSR, O2 Sat 90 2L
• Pressors weaned
• Near complete symptom resolution

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Clinical Case

• Complications
• Sigmoid intramural hemorrhage perforation
• IVC filter insertion
• Bowel resection complicated by perforation and
  re-bleed
• Intraabdominal abscess Gram - sepsis
• 8 wk hospital stay prior to death from MODS

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Classification of Acute PE

• Minor PE with normal RV function
• Major PE with isolated RV dysfunction
• Major PE with shock

Goldhaber. Intern Med. 1999 Nass. Am J Cardiol.
1999
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Impact of Clinical Instability at Presentation
Mortality
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The Evidence for Thrombolysis

• Only randomized study comparing lytic to heparin
  alone in patients with shock
• 8 patients with MPE and Shock
• Randomized to 1 hr SK infusion vs Heparin
• All 4 treated with SK lived
• All 4 treated with Heparin died
• Trial stopped prematurely for ethical reasons
  (intended n40)

Jerjes-Sanchez et al., J Thromb Thrombolysis, 1995
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Thrombolytic Administration

• Similar outcomes
• Type of thrombolytic
• Duration of infusion
• Bolus vs infusion
• Local vs systemic infusion

UKEP investigators, Eur Heart J, 1987 Levine et
al., Chest, 1990 Goldhaber et al., Chest,
1994 Goldharber et al., Lancet 1993
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What About Submassive PE?

• 80 of pts have normal BP at time of dx
• 27-55 of have ECHO evidence of RV dysfunction

Kasper et al, Heart, 1997 Ribeiro et al, Am Heart
J, 1997
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Prognostic Importance of RV Dysfunction
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Stevinson et al, Eur Heart J, 2007
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Prognostic Importance of RV Dysfunction

• Prospective study of 205 patients with
  sub-massive PE
• Identified a subgroup of 127 previously healthy
  patients
• Primary Outcome at 6 months
• ECHO, 6 min walk distance (6MWD), and a
  quality-of-life survey
• 5 pts had inadequate echos, nine lost to
  follow-up, and four died

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Prognostic Importance of RV Dysfunction

• Of 109 remaining patients, 45 (41) had
  cardiopulmonary problems at 6 months
• 18 (17) abnormal RV on ECHO
• 18 of 109 (17) functional limitation (NYHA gt2)
• 9 of 109 (8) had both
• 22 patients (20) indicated at least one index of
  poor quality-of-life
• health status worse
• not currently shopping
• perceived need for oxygen at home.

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Thrombolysis for Submassive PE?

• SoRV dysfunction adversely impacts prognosis and
  probably affects long-term QOL in a number of
  patients
• Does this mean that normotensive pts with
  submassive PE actually benefit from thrombolysis?

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Do Thrombolytics Improve Outcomes?

• Retrospective cohort registry study in France
• 128 stable pts with RV dysfunction
• 64 lysed pts matched to 64 pts treated with
  heparin alone
• All short term physiologic benefits lost by 1 wk
• In-hosp mortality 6.3 lytic vs 0 heparin
• ICH 4.7 lytic vs 0 heparin
• No difference in recurrent PE

Hamel et al, Chest, 2001
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Convincing Evidence?

• Prospective RCT 256 pts with submassive PE
• IV Heparin vs tPA
• Primary end point death or escalation of
  treatment (need for pressors, secondary rescue
  thrombolysis, endotracheal intubation, CPR or
  emergency catheter or surgical embolectomy)
• At 30d 32 (24.6) vs 9 (11.0) difference
• Low incidence mortality in both groups (4 vs 2)
• No difference in complications or recurrence

Konstantidides et al, NEJM, 2002
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Convincing Evidence?

• Inconsistent inclusion criteria
• Large numbers of patients in the control arm who
  received secondary thrombolysis (vague and
  subjective indications)
• Investigators could break the randomization code
  if clinical deterioration
• No difference btw groups for pressors, ETT, CPR
  or embolectomy
• No difference between groups in mortality or PE
  recurrence

Konstantidides et al., NEJM, 2002
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PEITHO Pulmonary Embolism Thrombolysis Study

• Comparison Trial Evaluating Efficacy and Safety
  of Single IV Bolus Tenecteplase (TNK) Plus
  Heparin as Compared With Heparin Alone in
  Normotensive Patients (with ECHO and Tn evidence
  of RV dysfunction)
• Primary Outcome
• 7d All cause mortality or hemodynamic collapse
• Estimated enrollment 1000 pts
• Completion Nov 2010

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Does This Patient Need an IVC Filter?

• Indications
• Contraindications to anticoagulation
• Major bleeding complications during
  anticoagulation
• Recurrent embolism despite adequate
  anticoagulation therapy
• Massive PE when it is believed that additional
  emboli might be lethal

Tapson, NEJM, 2009
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• Single best trial assessing effectiveness of IVC
  filters
• Multicentre RCT at 44 centers in France
• 2 x 2 trial comparing permanent IVC filter with
  no filter and fixed dose sc heparin vs IV
  unfractionated heparin (200 pts per arm)
• Primary outcome was occurrence of PE within 12
  days post randomization
• Secondary outcomes PE, recurrent DVT, death,
  filter complications and major bleeding at 2 years

Decousus et al., NEJM, 1998
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IVC Filters

• No patients receiving IVC filters died of acute
  PE, while 80 of early deaths in the non-IVC
  filter group (4/5) was due to PE
• Filters do not prevent death - they prevent
  death due to pulmonary embolism

Decousus et al, NEJM, 1998 Flinn et al, Arch
Surg, 1996
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IVC Filters

• When your best clinical judgment suggests that
  the risk of acute, fatal PE in your patient would
  be significantly reduced by placement of an IVC
  filter, you are probably right
• Dr. William Flinn

Flinn, J Int Care Med, 2003
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Conclusions

• Clinical severity depends on clot burden
  hemodynamic reserve
• Pts with RV dysfunction do poorly
• Inc mortality, dec QOL and dec functional scores
• Thrombolytics
• Stable PE NO
• MPE with shock YES
• Submassive PE (RV dysfunction but no shock) NO
• Consider an urgent IVC filter in selected pts

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Applications of Cognitive Psychology
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Play to your strengths
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Play to your strengths

• 234 x 567.4

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Decision Making
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Questions?
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Rapid Induction of Therapeutic Hypothermia
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Case 2

• 62 yo man, sudden collapse at a mall
• Bystander CPR x 4 minutes
• Shocked by firefighters with AED, return of pulse
• Second arrest on arrival in ED, V.fib
• 15 minute resuscitation, ROSC

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• BP 110/85, HR 111
• Unresponsive
• Therapeutic Hypothermia?
• Where? When? How?

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Rapid induction of hypothermia

• Significant efforts being made to shorten cooling
  times

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Thrombolytics in CA

• First Case report 1974
• Bolus SK to 35 yr woman 4 days post-partum
• Successfully resuscitated and d/c 2/52 later
• Nearly 100 case reports in literature
• All retrospective, selection bias
• All report satisfactory outcomes with relatively
  uncommon adverse effects

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Thrombolytics in CACase Reports
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Thrombolytics in Cardiac Arrest

• Review in Critical Care Medicine 2001
• Possible benefit
• Evidence in reducing hemodynamic instability
• Possible reduction in mortality
• Low incidence of severe complications
• Support the empiric use of thrombolytics when
  high suspicion of MPE in cardiac arrest

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Elevated Troponins Correlate with Increased
Mortality
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4.8
0
Mortality
La Vecchia, Heart, 2004
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BNP as a Predictor of Outcome

• Low median BNP levels may also predict benign
  clinical outcome in PE
• No correlation between RVSP and BNP
• Low positive predictive value
• A cut-off of lt 50 pg/mL identified 95 of
  patients with a benign clinical course

Kucher et al, Circulation, 2003 ten Wolde et al,
Circulation, 2003
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Catheter Embolectomy in PE

• Indications
• Contraindication to thrombolytics
• Persistent hypotension despite thrombolysis
• Ongoing/Intermittent cardiac arrest
• Various devices available
• Fragmentation (Pigtail, Clot Buster)
• Rheolytic (Angiojet, Hydrolyser)
• Aspiration (Meverovitz, Greenfield)

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Catheter Fragmentation

• Prospective Interventional Study
• 10 pts with massive PE
• Rotatable pigtail fragmentation systemic
  thrombolytics
• Successful recanalization hemodynamic
  improvement in 70 pts
• Mortality 20 - No significant complications

Schmitz-Rode et al., Chest 1998
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Surgical Embolectomy in MPE

• Several retrospective case reports
• Contraindication/Failure of thrombolytics
• Interventional radiology unavailable
• Most suffered CA before or during surgery
• Major predictive factor is need for CPR

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Surgical Embolectomy in MPE
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Surgical Embolectomy in Submassive PE

• 29 pts with submassive PE and moderate to severe
  RV dysfunction
• Surgical technique without aortic crossclamp or
  cardioplegia
• IVC Filters in all patients
• 11 30d mortality
• 26/29 pts survival

Aklog et al, Circulation 2002