Shock Moritz Haager, PGY-4 Dr. Lisa Campfens July 29, 2004.

ShockShock

Moritz Haager, PGY-4Moritz Haager, PGY-4

Dr. Lisa CampfensDr. Lisa Campfens

July 29, 2004July 29, 2004

ObjectivesObjectives

Develop an approach to the shock patientDevelop an approach to the shock patient Are there any novel diagnostic tools?Are there any novel diagnostic tools?

Review the DDx of shockReview the DDx of shock Discuss specific controversies and new Discuss specific controversies and new

therapies for specific shock statestherapies for specific shock states Primary focus on Hypovolemic & septic shockPrimary focus on Hypovolemic & septic shock Other shock etiologies covered elsewhereOther shock etiologies covered elsewhere

The common threadThe common thread

Shock is not a disease but a symptom of Shock is not a disease but a symptom of numerous possible underlying etiologiesnumerous possible underlying etiologies

Best defined as a state where supply of oxygen Best defined as a state where supply of oxygen & nutrients is inadequate for metabolic demand & nutrients is inadequate for metabolic demand resulting in tissue ischemiaresulting in tissue ischemia

Time is moneyTime is money The longer the time spent in the shock state the more The longer the time spent in the shock state the more

irreversible the damageirreversible the damage

Combined mortality tends to be >20% Combined mortality tends to be >20%

Initial ApproachInitial Approach

Triage to resus bayTriage to resus bay OO22, monitors, IV’s x2, help, monitors, IV’s x2, help

ABC’sABC’s Intubate these pts earlyIntubate these pts early

• Be prepared for their BP to crashBe prepared for their BP to crash Paralyze to decrease metabolic demandsParalyze to decrease metabolic demands Fluid resuscitationFluid resuscitation

• Which fluid? How fast? How much?Which fluid? How fast? How much?• Choice of fluid, rate, and amount will depend on Choice of fluid, rate, and amount will depend on

your DDx for underlying causeyour DDx for underlying cause

Initial ApproachInitial Approach

D – Disability & NeuroD – Disability & Neuro E – Environment, Exposure, Every vital signE – Environment, Exposure, Every vital sign

There are 6 vitals – don’t forget Temp & C/SThere are 6 vitals – don’t forget Temp & C/S F – Find an underlying causeF – Find an underlying cause

How to get a good HxHow to get a good Hx• EMS, CPS, Bystanders, Family, Roommates, Medical EMS, CPS, Bystanders, Family, Roommates, Medical

records – the earlier the betterrecords – the earlier the better Actively look for possible causes on your DDxActively look for possible causes on your DDx

• Focused physical including DREFocused physical including DRE• ABG, ECG, CXRABG, ECG, CXR• Echo, ED U/S for AAA, free fluid, tamponadeEcho, ED U/S for AAA, free fluid, tamponade

DDx: Mechanistic ApproachDDx: Mechanistic ApproachSHOCK

Vasculature Pump Volume

Cardiogenic:•MI / ischemia•Arrhythmias

•Cardiomyopathies•Myocarditis

•Trauma•Wall rupture

•Drug (BB, CCB, TCA) OD

Obstructive:•PE

•Tamponade•Valves

(Stenosis, thrombosis, rupture)•PTX

•Congenital defects(Coarctation & other

ductus-dependant lesions)

Decreased vascular tone:•Neurogenic shock

•Septic shock•Endocrine shock

Increased Permeability:•Anaphylaxis

•Sepsis & SIRS

Hypovolemia:GI losses

HemorrhageThird spacing / inflammation

AnaphylaxisBurns

Insensible losses

Metabolic

Endocrinological Causes:•Addison's

•CAH•Adrenal infarct

•Chronic steroids

Cellular Poisons:

•Carbon monoxide •Methemoglobinemia

•Hydrogen sulfide •Cyanide

DDx: Empiric ApproachDDx: Empiric Approach S - S - septicseptic S - S - spinal (neurogenic)spinal (neurogenic) H - H - hypovolemichypovolemic H - H - hemorrhagichemorrhagic O - O - obstructive (PE, PTX, HTX, Tamponade)obstructive (PE, PTX, HTX, Tamponade) C - C - cardiogenic (rate, contractility, cardiogenic (rate, contractility,

obstruction, valve)obstruction, valve)

C - C - cellular toxins (CN, CO, HS, ASA, Fe)cellular toxins (CN, CO, HS, ASA, Fe) K - K - anaphylaCTicanaphylaCTic E - E - endocrine/adrenal crisisendocrine/adrenal crisis

Having a good DDx in the back of you head is absolutely KEY to Having a good DDx in the back of you head is absolutely KEY to providing appropriate subsequent careproviding appropriate subsequent care

Pediatric Shock:Pediatric Shock: SS -- septicseptic SS -- spinal (neurogenic)spinal (neurogenic) HH - - hypovolemic: gastro, abdo surgicalhypovolemic: gastro, abdo surgical

emergency, DKAemergency, DKA HH - - hemorrhagichemorrhagic OO - - obstructive (PE, pthrx, hthrx, ct)obstructive (PE, pthrx, hthrx, ct) CC - - cardiogenic (cardiogenic (rate- SVTrate- SVT, contractility, , contractility,

obstruction, valve, obstruction, valve, congenital heart congenital heart dzdz))

C - C - cellular toxins (CN, CO, HS, ASA, Fe)cellular toxins (CN, CO, HS, ASA, Fe) KK -- anaphylaCTicanaphylaCTic E - E - endocrine: endocrine: adrenal crisis (CAH)adrenal crisis (CAH)

/hypoglcemia/metabolic defects/hypoglcemia/metabolic defects

Why is the DDx so important?Why is the DDx so important?

After primary survey & initial resus optimal After primary survey & initial resus optimal further Tx can be radically different further Tx can be radically different depending on etiologydepending on etiology E.g. fluid resus in sepsis vs. penetrating E.g. fluid resus in sepsis vs. penetrating

traumatrauma Epi for anaphylactic vs. cardiogenic shockEpi for anaphylactic vs. cardiogenic shock

Re-emphasizes point that shock is a Re-emphasizes point that shock is a symptom – not the diseasesymptom – not the disease

Empiric Criteria for Diagnosis of Empiric Criteria for Diagnosis of Circulatory ShockCirculatory Shock

Need any 4 of:Need any 4 of: Ill appearance or altered mental status Ill appearance or altered mental status Heart rate > 100 beats/min Heart rate > 100 beats/min RR > 22 breaths/min or PaCO2 < 32 mm Hg RR > 22 breaths/min or PaCO2 < 32 mm Hg Arterial base deficit < –5 mEq/L or lactate > 4 Arterial base deficit < –5 mEq/L or lactate > 4

mM mM Urine output < 0.5 ml/kg/hr Urine output < 0.5 ml/kg/hr Arterial hypotension > 20 minutes durationArterial hypotension > 20 minutes duration

• From Rosens Textbook of Emergency MedicineFrom Rosens Textbook of Emergency Medicine

Diagnosing ShockDiagnosing Shock

The dilemmaThe dilemma The more advanced the shock state, the easier it is to The more advanced the shock state, the easier it is to

identifyidentifybutbut Significant tissue hypoxia appears to exist prior to Significant tissue hypoxia appears to exist prior to

development of significant signs & symptomsdevelopment of significant signs & symptoms• Normal BP in face of hypovolemia means some organs are Normal BP in face of hypovolemia means some organs are

hypoperfused to maintain systemic BPhypoperfused to maintain systemic BP• Evidence suggests we are frequently underestimating Evidence suggests we are frequently underestimating

disease severity in pts w/ early shock (see Rivers study)disease severity in pts w/ early shock (see Rivers study) Early reversal of shock is key determinant of Early reversal of shock is key determinant of

preventing MODSpreventing MODS

Diagnostic AdjunctsDiagnostic Adjuncts Base deficit Base deficit

= amount of strong base required to be added to a liter of blood to = amount of strong base required to be added to a liter of blood to normalize the pH; should > –2 mEq/L; < -4 mEq/L predicts MOFnormalize the pH; should > –2 mEq/L; < -4 mEq/L predicts MOF

Shock indexShock index HR/systolic BP; should be less than 0.8 (more sensitive than HR/systolic BP; should be less than 0.8 (more sensitive than

either alone)either alone) LactateLactate

[lactate] > 4.0 mM predicts MOF[lactate] > 4.0 mM predicts MOF Lactate clearance indexLactate clearance index

Serial [lactate] should decrease by 50% 1 hour w/ resusSerial [lactate] should decrease by 50% 1 hour w/ resus Urine outputUrine output

Should be > 0.5 ml/kg/h; requires Foley & 30 min to be accurateShould be > 0.5 ml/kg/h; requires Foley & 30 min to be accurate SvOSvO2 2 (mixed venous O(mixed venous O22 sat) sat)

Should be >70%; limits of physiologic compensation at 50% Should be >70%; limits of physiologic compensation at 50%

Future Adjuncts?Future Adjuncts?

NIRS (Near-Infrared Spectroscopy) NIRS (Near-Infrared Spectroscopy) Same basic principle as SpOSame basic principle as SpO22 monitors except monitors except

measures tissue Omeasures tissue O22

Sublingual TonometrySublingual Tonometry• Uses sublingual vascular bed as marker for splanchnic Uses sublingual vascular bed as marker for splanchnic

perfusionperfusion

Thoracic bioimpedanceThoracic bioimpedance Similar to ECG; uses multiple electrodes to measure Similar to ECG; uses multiple electrodes to measure

impedance across thorax as estimate of COimpedance across thorax as estimate of CO None in common use yet; no outcome studies None in common use yet; no outcome studies

evaluating their utilityevaluating their utility

Case 1Case 1

39 M stabbed 39 M stabbed multiple times by multiple times by jealous loverjealous lover

O/E: 35O/E: 3555, 140, 80/p, , 140, 80/p, 22, 90% RA22, 90% RA

What do you do for What do you do for him?him?

ATLS Classification of ATLS Classification of Hemorrhagic ShockHemorrhagic Shock

Blood Products ASAP

Tx of Hypovolemic ShockTx of Hypovolemic Shock

ABC’sABC’s Direct pressure on any bleederDirect pressure on any bleeder

Estimated 20% of combat deaths in Vietnam Estimated 20% of combat deaths in Vietnam could have been prevented w/ pressure or could have been prevented w/ pressure or tourniquettourniquet

Up to 2 L of fluid – then blood…right?Up to 2 L of fluid – then blood…right? Depends on underlying etiologyDepends on underlying etiology

• Trauma: Blunt vs. penetratingTrauma: Blunt vs. penetrating• Dehydration etcDehydration etc

Fluid Resus in Hemorrhagic ShockFluid Resus in Hemorrhagic Shock

Multiple ControversiesMultiple Controversies Which fluid?Which fluid?

• Crystalloids: NS, Ringers lactate (RL)Crystalloids: NS, Ringers lactate (RL)• Colloids: Colloids: AlbuminAlbumin, , Starches, Starches, Dextrans, Gelatins Dextrans, Gelatins • Hypertonic saline +/- dextranHypertonic saline +/- dextran• Oxygen carrier substitutesOxygen carrier substitutes• Blood productsBlood products

How much fluid? How fast?How much fluid? How fast?• Blunt vs. penetrating traumaBlunt vs. penetrating trauma

What end-points should be used?What end-points should be used?

Historical OverviewHistorical Overview

Moore FA, McKinley BA, Moore EE. The next generation in shock resuscitation. Lancet 2004; 363: 1988–96

Crystalloids or Colloids?Crystalloids or Colloids?Theoretical Pro’s & Con’sTheoretical Pro’s & Con’s

CrystalloidsCrystalloids Resuscitate both intra- & Resuscitate both intra- &

extravascular compartment extravascular compartment Improve organ functionImprove organ function Minimal risk of Minimal risk of

anaphylactoid reactions anaphylactoid reactions InexpensiveInexpensive Reduce colloid oncotic Reduce colloid oncotic

pressure -- may predispose pressure -- may predispose to pulmonary and to pulmonary and peripheral edemaperipheral edema

• Decrease gas exchange Decrease gas exchange

• Delayed wound healingDelayed wound healing

ColloidsColloids Require less volume Require less volume Work fasterWork faster Improve organ functionImprove organ function Risk of anaphylaxis Risk of anaphylaxis Risk of infectionRisk of infection Risk of coagulopathyRisk of coagulopathy

• Dextrans > starches > Dextrans > starches > gelatinsgelatins

ExpensiveExpensive

Rizoli, SB. Crystalloids and Colloids in Trauma Resuscitation: A BriefOverview of the Current Debate. J Trauma. 2003;54:S82–S88.

Crystalloids or Colloids?Crystalloids or Colloids?What is the Evidence?What is the Evidence?

Meta-analysis of 16 RCT’s of isotonic crystalloids vs. Meta-analysis of 16 RCT’s of isotonic crystalloids vs. colloidscolloids

Primary outcomes of mortality & pulmonary edemaPrimary outcomes of mortality & pulmonary edema Results:Results:

No statistically significant differences found for mortality, No statistically significant differences found for mortality, pulmonary edema, or LOSpulmonary edema, or LOS

Subgroup AnalysesSubgroup Analyses• Trend Trend in favor of crystalloids (RR 0.64, 95% CI: 0.17 to 2.42) for in favor of crystalloids (RR 0.64, 95% CI: 0.17 to 2.42) for

decreasing pulmonary edema in trials with well-described decreasing pulmonary edema in trials with well-described randomization methods randomization methods

• TrendTrend to decreased mortality w/ crystalloids in trauma pts (RR 0.39, to decreased mortality w/ crystalloids in trauma pts (RR 0.39, 95% CI: 0.17 to 0.89)95% CI: 0.17 to 0.89)

Analysis underpowered to detect small but imp differencesAnalysis underpowered to detect small but imp differences Concluded:Concluded:

Results equivocal; unable to argue for or against either fluid due Results equivocal; unable to argue for or against either fluid due to lack of power & study heterogeneityto lack of power & study heterogeneity

Choi PTL, et al. Crystalloids vs. colloids in fluid resuscitation: A systematic review. Crit Care Med. 1999; 27: 200-10


Meta-analysis of 18 RCT’s Meta-analysis of 18 RCT’s Primary outcome: all cause mortalityPrimary outcome: all cause mortality ResultsResults

Albumin or plasma protein fraction: 7 RCTs RR1.52 (1.08 to Albumin or plasma protein fraction: 7 RCTs RR1.52 (1.08 to 2.13). 2.13).

Hydroxyethylstarch: 7 RCTs RR 1.16 (0.68 to 1.96). Hydroxyethylstarch: 7 RCTs RR 1.16 (0.68 to 1.96). Modified gelatin: 4 RCTs RR 0.50 (0.08 to 3.03). Modified gelatin: 4 RCTs RR 0.50 (0.08 to 3.03). Dextran: 8 RCTs RR 1.24 (0.94 to 1.65). Dextran: 8 RCTs RR 1.24 (0.94 to 1.65). Colloids in hypertonic crystalloid compared to isotonic Colloids in hypertonic crystalloid compared to isotonic

crystalloid: crystalloid: • albumin and hypertonic saline vs. isotonic crystalloid: 1 RCT RR of albumin and hypertonic saline vs. isotonic crystalloid: 1 RCT RR of

death 0.50 (0.06 to 4.33) death 0.50 (0.06 to 4.33) • dextran in hypertonic crystalloid vs. isotonic crystalloid: 8 RCTs RR dextran in hypertonic crystalloid vs. isotonic crystalloid: 8 RCTs RR

0.88 (0.74 to 1.05) 0.88 (0.74 to 1.05) Conclusions:Conclusions:

No benefit for colloids; should not be usedNo benefit for colloids; should not be usedAlderson, P; Schierhout, G; Roberts, I; Bunn, F. Colloids versus crystalloids for

fluid resuscitation in critically ill patients . 2004; 2. The Cochrane Database of Systematic Reviews


Analyzing the meta-analysesAnalyzing the meta-analyses 6 meta-analyses to date on crystalloids vs. 6 meta-analyses to date on crystalloids vs.

colloidscolloids All fail to show statistical differenceAll fail to show statistical difference All indicate trend towards increased mortality All indicate trend towards increased mortality

w/ colloids in trauma ptsw/ colloids in trauma pts Many limitations in primary studiesMany limitations in primary studies



Rizoli. 2003 cont’dRizoli. 2003 cont’d

ConcludedConcluded ““The first limitation of a meta-analysis is that it can The first limitation of a meta-analysis is that it can

only be as good as the quality of the individual RCTs only be as good as the quality of the individual RCTs it includes”it includes”

““meta-analysis should be interpreted cautiously and meta-analysis should be interpreted cautiously and …viewed as hypothesis generating given the …viewed as hypothesis generating given the limitations in both study design and limitations of the limitations in both study design and limitations of the primary RCTs”primary RCTs”

Large well done trial is needed but evidence suggests Large well done trial is needed but evidence suggests trauma pts should continue to be resuscitated w/ trauma pts should continue to be resuscitated w/ crystalloidscrystalloids


Crystalloids or Colloids?Crystalloids or Colloids?

ConclusionConclusion No real conclusive data to firmly support one No real conclusive data to firmly support one

over the other but trend towards harm w/ over the other but trend towards harm w/ colloids in traumacolloids in trauma

Lots of limitations in primary studies limits Lots of limitations in primary studies limits utility of meta-analyses utility of meta-analyses

Given cost, ease of use, and familiarity Given cost, ease of use, and familiarity crystalloids should continue to be our primary crystalloids should continue to be our primary fluid in the EDfluid in the ED

Hypertonic SalineHypertonic Saline

Hypertonic SalineHypertonic Saline HTS = 7.5% saline +/- 6% dextran (HTS-D)HTS = 7.5% saline +/- 6% dextran (HTS-D) Dose: 4 ml/kg or 250 cc as initial bolus over 5-10 Dose: 4 ml/kg or 250 cc as initial bolus over 5-10

minmin MOA:MOA:

shifts water 1shifts water 1stst out of RBCs & endothelium into out of RBCs & endothelium into plasma, & then out of interstitium & tissue cellplasma, & then out of interstitium & tissue cell

• a rapid but transient improvement in intravascular volume & a rapid but transient improvement in intravascular volume & hemodynamicshemodynamics

• hemodilution and endothelial cell shrinkage hemodilution and endothelial cell shrinkage decreased decreased capillary hydraulic pressure capillary hydraulic pressure improved perfusion. improved perfusion.

Hypertonic SalineHypertonic Saline AdvantagesAdvantages

Improves hemodynamics, Improves hemodynamics, lowers subsequent fluid and lowers subsequent fluid and blood requirements, and blood requirements, and improves DOimproves DO22

• Many animal studies and Many animal studies and clinical trials demonstrate thisclinical trials demonstrate this

Decreased inflammatory Decreased inflammatory response response

• may limit ischemia / may limit ischemia / reperfusion injury and thus reperfusion injury and thus decrease MOFdecrease MOF

May be neuroprotective May be neuroprotective Small fluid volume requiredSmall fluid volume required

DisadvantagesDisadvantages Primarily theoretical: Primarily theoretical:

• Rare to non-existent reports Rare to non-existent reports in literaturein literature

• Primarily related to Primarily related to hypernatremia, rapid volume hypernatremia, rapid volume expansion, & dextranexpansion, & dextran

Central pontine myelinolysis Central pontine myelinolysis Worsened bleedingWorsened bleeding

• Shown in animals but not Shown in animals but not observed in human trialsobserved in human trials

Interference w/ X-matchingInterference w/ X-matching Anaphylactoid reactions Anaphylactoid reactions

(dextran)(dextran)

Orlinsky, M. Current controversies in shockand resuscitation.Surg Clin North Am 2001; 81(6): 1217-62

Cochrane ReviewCochrane Review MethodsMethods

Systematic review of mortality in17 studies of HTS or Systematic review of mortality in17 studies of HTS or HTS-D vs. isotonic crystalloids in trauma, burn, & HTS-D vs. isotonic crystalloids in trauma, burn, & surgical ptssurgical pts

Only 6 were adequate methodology (5/6 trauma trials)Only 6 were adequate methodology (5/6 trauma trials) Results:Results:

Trauma: RR for death w/ HTS 0.84 (0.61-1.16)Trauma: RR for death w/ HTS 0.84 (0.61-1.16) Burns: RR for death w/ HTS 1.49 (0.56-3.95)Burns: RR for death w/ HTS 1.49 (0.56-3.95) Surgery: RR for death w/ HTS 0.62 (0.08-4.57)Surgery: RR for death w/ HTS 0.62 (0.08-4.57)

Conclusions:Conclusions: Data too limited to exclude or prove benefit from HTSData too limited to exclude or prove benefit from HTS Need more & larger trials to narrow CI’sNeed more & larger trials to narrow CI’s

• Bunn, F et al. Hypertonic versus isotonic crystalloid for fluid Bunn, F et al. Hypertonic versus isotonic crystalloid for fluid resuscitation in critically ill patients. Cochrane Database of resuscitation in critically ill patients. Cochrane Database of Systematic Reviews. 2004Systematic Reviews. 2004

Is dextran confounding?Is dextran confounding?

Meta-analysis of 12 RCT’sMeta-analysis of 12 RCT’s Analyzed HTS & HTS-D separately in hypotensive trauma ptsAnalyzed HTS & HTS-D separately in hypotensive trauma pts

ResultsResults 4/6 HTS trials “positive” but non-significant pooled OR 0.98 (0.71 4/6 HTS trials “positive” but non-significant pooled OR 0.98 (0.71

- 1.36)- 1.36) 7/8 HTS-D trials “positive” but non-significant pooled OR 1.20 7/8 HTS-D trials “positive” but non-significant pooled OR 1.20

(0.94 - 1.57)(0.94 - 1.57)• Only 1/8 trials reached statistical significanceOnly 1/8 trials reached statistical significance

ConcludedConcluded HTS-D appears better than HTS, and both may be better than HTS-D appears better than HTS, and both may be better than

isotonic crystalloids (but fails to reach significance)isotonic crystalloids (but fails to reach significance)• Wade, CE et al. Efficacy of hypertonic 7.5% saline and 6% Wade, CE et al. Efficacy of hypertonic 7.5% saline and 6%

dextran-70 in treating trauma: A meta-analysis of controlled dextran-70 in treating trauma: A meta-analysis of controlled clinical studies. Surgery 1997;122:609-16.clinical studies. Surgery 1997;122:609-16.

HTS: ConclusionHTS: Conclusion

Looks promising, lots of theoretical Looks promising, lots of theoretical benefits, but so far no convincing evidence benefits, but so far no convincing evidence its better (or worse) than isotonic its better (or worse) than isotonic crystalloidscrystalloids

Data limitedData limited Small studiesSmall studies Heterogeneous populationsHeterogeneous populations Different solutions usedDifferent solutions used Virtually all adult studies – unable to Virtually all adult studies – unable to

extrapolate to pedsextrapolate to peds

Oxygen-carriersOxygen-carriers

3 basic types3 basic types Hemoglobin-basedHemoglobin-based

• Surface-modified hemoglobins Surface-modified hemoglobins • Intramolecular cross-linked hemoglobinsIntramolecular cross-linked hemoglobins• Polymerized hemoglobinsPolymerized hemoglobins

PolyHeme – promising; in Phase III trialsPolyHeme – promising; in Phase III trials Hemopure – approved in S. Africa; trials ongoingHemopure – approved in S. Africa; trials ongoing Hemolink – promising; trials ongoingHemolink – promising; trials ongoing

PerfluorocarbonsPerfluorocarbons• Work by allowing large amts of OWork by allowing large amts of O22 to dissolve in them but studies to dissolve in them but studies

disappointing to datedisappointing to date Liposome-encapsulated HemoglobinLiposome-encapsulated Hemoglobin

• Costly, potential RES overloadCostly, potential RES overload

Jury is still out on these but they are comingJury is still out on these but they are coming

Delayed vs. Early Fluid Delayed vs. Early Fluid ResuscitationResuscitation

The Golden HourThe Golden Hour

PerspectivePerspective Hypotension occurs after ~1/3 loss of blood Hypotension occurs after ~1/3 loss of blood

volume (~1.5 L in 70 kg adult)volume (~1.5 L in 70 kg adult) Death occurs after ~50% loss of blood volumeDeath occurs after ~50% loss of blood volume Rate of bleeding determines “golden hour”Rate of bleeding determines “golden hour”

• 25 cc/min – hypotensive at 1 hr; dead at 2 hrs e.g. 25 cc/min – hypotensive at 1 hr; dead at 2 hrs e.g. liver lacerationliver laceration

• 100 cc/min – hypotensive at 15 min, dead at 30 100 cc/min – hypotensive at 15 min, dead at 30 min e.g. vascular injurymin e.g. vascular injury

Delayed vs. Early Fluid ResusDelayed vs. Early Fluid ResusPro’s and Con’sPro’s and Con’s

DelayedDelayed Bleeding from injured Bleeding from injured

vessels will decrease vessels will decrease due to clot formation, due to clot formation, vasoconstriction etcvasoconstriction etc

Fluid resus may Fluid resus may increase hemorrhage:increase hemorrhage:

• Raises BP increasing Raises BP increasing hydraulic pressurehydraulic pressure

• VasodilateVasodilate• Dilute clotting factorsDilute clotting factors

Early Early Fluid resus increases Fluid resus increases

perfusion & DOperfusion & DO22 to to

end organs end organs Prolonged Prolonged

hypoperfusion leads to hypoperfusion leads to MODSMODS

• = main cause of post-= main cause of post-traumatic death after traumatic death after immediate immediate exsanguination or head exsanguination or head injuryinjury

Historical BackgroundHistorical Background

Early 1900’s fluid resus was frowned uponEarly 1900’s fluid resus was frowned upon Canon in 1910 pointed out that increasing BP prior to achieving Canon in 1910 pointed out that increasing BP prior to achieving

hemostasis could “pop the clot”hemostasis could “pop the clot” 50’s -60’s: Popularity of fluid resus 50’s -60’s: Popularity of fluid resus

based on animal data where rapid reversal of shock induced by based on animal data where rapid reversal of shock induced by controlled blood loss (e.g. through phlebotomy) w/ IV fluids controlled blood loss (e.g. through phlebotomy) w/ IV fluids improved survivalimproved survival

Subsequent studies of uncontrolled blood loss (e.g. razor Subsequent studies of uncontrolled blood loss (e.g. razor wire into aorta) found decreased survival w/ aggressive wire into aorta) found decreased survival w/ aggressive fluid resusfluid resus

Raising BP caused more bleedingRaising BP caused more bleeding Limited resus targeting lower BP’s improved survival the mostLimited resus targeting lower BP’s improved survival the most

Bickell, WH et al.Bickell, WH et al. Immediate versus Delayed Fluid Immediate versus Delayed Fluid Resuscitation for Hypotensive Patients with Penetrating Resuscitation for Hypotensive Patients with Penetrating

Torso InjuriesTorso Injuries. NEJM . NEJM 1994; 331: 1105-091994; 331: 1105-09

RCT of 598 pts >16 yo w/ penetrating torso RCT of 598 pts >16 yo w/ penetrating torso trauma in urban settingtrauma in urban setting

Odd/even day randomization into early Odd/even day randomization into early (prehospital ATLS protocol) or delayed (no fluids (prehospital ATLS protocol) or delayed (no fluids until in OR) fluid resuscitationuntil in OR) fluid resuscitation

ResultsResults Sig increased survival in delayed group (70% vs. Sig increased survival in delayed group (70% vs.

62%, P = 0.04) 62%, P = 0.04) Significantly prolonged PT/PTT in immediate resus Significantly prolonged PT/PTT in immediate resus

group -- ?clinical significancegroup -- ?clinical significance

CriticismsCriticisms

Odd / even day randomizationOdd / even day randomization Rapid transport times (12-13mins)Rapid transport times (12-13mins)

How does this change in rural setting?How does this change in rural setting?

Not analyzed in Intention-to-treat fashionNot analyzed in Intention-to-treat fashion ITT analysis of data failed to show sig benefitITT analysis of data failed to show sig benefit

Relatively small volumes of fluids usedRelatively small volumes of fluids used High mortality rates in both groupsHigh mortality rates in both groups Most of the benefit appeared to occur in pts w/ Most of the benefit appeared to occur in pts w/

tamponadetamponade

Cochrane ReviewCochrane Review

Systematic review of RCT’s looking atSystematic review of RCT’s looking at Early vs. delayed fluid resusEarly vs. delayed fluid resus Large vs. small volume fluid resusLarge vs. small volume fluid resus

Found 4487 potential papers – only 6 met Found 4487 potential papers – only 6 met the inclusion criteriathe inclusion criteria

Unable to combine the results Unable to combine the results quantitatively due to heterogeneity quantitatively due to heterogeneity

Kwan I, Bunn F, Roberts I. Timing and volume of fluid administration for patients with bleeding. (Cochrane Review). In: The Cochrane Library, Vol 2; 2004

Cochrane ReviewCochrane Review Early versus delayed fluids:Early versus delayed fluids:

Bickel 1994: Bickel 1994: • 598 hypotensive penetrating torso trauma pts598 hypotensive penetrating torso trauma pts• Mortality 116/309 (38%) vs. 86/289 (30%)Mortality 116/309 (38%) vs. 86/289 (30%)• RR for death w/ early fluids was 1.26 (95% CI 1.00-1.58) RR for death w/ early fluids was 1.26 (95% CI 1.00-1.58)

Blair 1986: Blair 1986: • 50 hypotensive pts w/ UGIB50 hypotensive pts w/ UGIB• Mortality 2/24 (8%) vs. 0/26 (0%) Mortality 2/24 (8%) vs. 0/26 (0%) • RR for death w/ early blood transfusion was 5.4 (95% CI 0.3-RR for death w/ early blood transfusion was 5.4 (95% CI 0.3-

107.1) 107.1) Turner 2000: Turner 2000:

• 1309 trauma pts1309 trauma pts• Mortality 73/699 (10.4%) vs. 60/610 (9.8%) Mortality 73/699 (10.4%) vs. 60/610 (9.8%) • RR for death with early fluids was 1.06 (95% CI 0.77-1.47). RR for death with early fluids was 1.06 (95% CI 0.77-1.47).



Large vs. small volume fluid resusLarge vs. small volume fluid resus Dunham 1992: Dunham 1992:

• 36 hypotensive trauma pts.36 hypotensive trauma pts.• Mortality 5/20 (25%) vs. 5/16 (31%) Mortality 5/20 (25%) vs. 5/16 (31%) • RR for death for large volume was 0.80 (95% CI 0.28-2.29) RR for death for large volume was 0.80 (95% CI 0.28-2.29)

Dutton 2002: Dutton 2002: • 110 hypotensive blunt & penetrating trauma pts110 hypotensive blunt & penetrating trauma pts• Mortality 4/55 (7.3%) vs. 4/55 (7.3%)Mortality 4/55 (7.3%) vs. 4/55 (7.3%)• The RR for death w/ large volume was 1.00 (95% CI 0.26-The RR for death w/ large volume was 1.00 (95% CI 0.26-

3.81). 3.81). Fortune 1987Fortune 1987

• 25 pts; No mortality data25 pts; No mortality data



““This review found insufficient evidence for This review found insufficient evidence for or against the use of early or larger or against the use of early or larger volume fluid resuscitation in the treatment volume fluid resuscitation in the treatment of uncontrolled haemorrhage. While of uncontrolled haemorrhage. While vigorous fluid resuscitation may be life-vigorous fluid resuscitation may be life-saving in some patients, results from saving in some patients, results from clinical trials are inconclusive.”clinical trials are inconclusive.”


So give fluids…Don’t give fluids?So give fluids…Don’t give fluids?

Best study to date (Bickel 1994)Best study to date (Bickel 1994) Suggests we should limit pre-OR fluid resus in penetrating Suggests we should limit pre-OR fluid resus in penetrating

traumatrauma Tons of variables & unanswered questionsTons of variables & unanswered questions

At what time point does reversal of benefit occur? i.e. when does At what time point does reversal of benefit occur? i.e. when does the wait become too long?the wait become too long?

How does this apply to blunt trauma?How does this apply to blunt trauma? In pigs there appears to be a middle ground – is there an ideal In pigs there appears to be a middle ground – is there an ideal

SBP at which we should maintain pts?SBP at which we should maintain pts? Different etiologies of shock likely need different approachesDifferent etiologies of shock likely need different approaches How does choice of resus fluid figure in all of this?How does choice of resus fluid figure in all of this?

Limiting resus to attain SBP ~90 mm Hg Limiting resus to attain SBP ~90 mm Hg makes intuitive sense, and is recommended by some authorities makes intuitive sense, and is recommended by some authorities

BUT at this point has not been adequately studiedBUT at this point has not been adequately studied

Experimental Treatments in Experimental Treatments in Hemorrhagic ShockHemorrhagic Shock

VasopressinVasopressin Promising in porcine modelsPromising in porcine models

Oxygen carriersOxygen carriers No large clinical trials yetNo large clinical trials yet

FVIIa concentrateFVIIa concentrate No conclusive evidence yet – stops bleeding No conclusive evidence yet – stops bleeding

but also appears to cause thrombotic but also appears to cause thrombotic complicationscomplications

Case 2Case 2

65 M presents w/ fever & AMS65 M presents w/ fever & AMS PMHx: DM, HTN, PMHx: DM, HTN, O/E: 39O/E: 3922, 122, 100/45, 24, 90% RA, , 122, 100/45, 24, 90% RA,

GCS14GCS14 CXR: bilateral pulm infiltratesCXR: bilateral pulm infiltrates What do you want to do for him?What do you want to do for him?

Septic ShockSeptic Shock

EpidemiologyEpidemiology

Incidence variable but on the riseIncidence variable but on the rise ~ 1/1000 – 260/1000 pts days~ 1/1000 – 260/1000 pts days Larger # of elderly, HIV, chemotherapy, organ Larger # of elderly, HIV, chemotherapy, organ

transplant, and dialysis pts in addition to diabetics, transplant, and dialysis pts in addition to diabetics, alcoholics etcalcoholics etc

Mortality ranges from 3% for pts w/ no SIRS Mortality ranges from 3% for pts w/ no SIRS criteria to 46% for septic shock criteria to 46% for septic shock

Locally ~250 ICU admissions for sepsis per yearLocally ~250 ICU admissions for sepsis per year

Latest ACCP/SCCM Consensus Latest ACCP/SCCM Consensus DefinitionsDefinitions

Infection = invasion of organ system(s) by Infection = invasion of organ system(s) by microorganismsmicroorganisms

Sepsis = systemic host response to infection Sepsis = systemic host response to infection requiring requiring >> 1 signs & symptoms of sepsis 1 signs & symptoms of sepsis

Severe sepsis = sepsis w/ organ failureSevere sepsis = sepsis w/ organ failure Septic shock = severe sepsis w/ Septic shock = severe sepsis w/

cardiovascular failure requiring vasoactive cardiovascular failure requiring vasoactive medicationsmedications

• Vincent & Jacobs. Curr Opin Infect Dis 16: 309-13. 2003Vincent & Jacobs. Curr Opin Infect Dis 16: 309-13. 2003

Vincent & Jacobs. Curr Opin Infect Dis 16: 309-13. 2003

Classifications reflect disease Classifications reflect disease severityseverity

Diagnostic categoryDiagnostic category Mortality (%)Mortality (%)

SIRS criteriaSIRS criterianonenone 3322 7733 101044 1717

SepsisSepsis 1616Severe sepsisSevere sepsis 2020Septic shockSeptic shock 4646

• McCoy & Matthews. Drotrecogin Alfa (Recombinant Human McCoy & Matthews. Drotrecogin Alfa (Recombinant Human Activated Protein C) for the treatment of severe sepsis. Clin Ther Activated Protein C) for the treatment of severe sepsis. Clin Ther 2003; 25: 396-4212003; 25: 396-421

SEPSIS

INFLAMMATION PATHOGENS

TF EXPOSURE ENDOTHELIAL INJURY

ANTI-COAGULANTSYSTEM INHIBITON

ACTIVATIONOF CLOTTING CASCADE

FIBRINOLYTICSYSTEM INHIBITION

PRO-COAGULANT EFFECT

MICROVASCULAR THROMBOSIS

MULTI ORGAN DYSFUNTION SYNDROME

TNF-α, IL-1, IL-6, IL-7,Proteases, Leukotrienes, ProstaglandinsBradykinin, Platelet activating factorsFree oxygen radicals

Endotoxins, ExotoxinsDirect endothelial invasion

↓ AT III, ↓ aPC, ↓ pS↓ thrombomodulin

↑ PAI-1

SCCM Guidelines for Treatment SCCM Guidelines for Treatment of Septic Shockof Septic Shock

UtilizeUtilize EGDT in 1EGDT in 1stst 6 hrs 6 hrs Cultures before AbxCultures before Abx Source controlSource control Aggressive rehydration Aggressive rehydration

with colloid or crystalloidwith colloid or crystalloid Use dopamine or Use dopamine or

norepinephrine for norepinephrine for refractory shockrefractory shock

Give stress dose steroidsGive stress dose steroids

Give rhAPC when Give rhAPC when appropriateappropriate

Keep Hb 70-90Keep Hb 70-90 Use low TV’s & minimal Use low TV’s & minimal

peak pressure & PEEP peak pressure & PEEP vent strategyvent strategy

Use insulin therapyUse insulin therapy

AvoidAvoid Supranormal oxygenationSupranormal oxygenation BicarbBicarb

• Dellinger et al. Surviving sepsis Dellinger et al. Surviving sepsis campaign guidelines for management campaign guidelines for management of severe sepsis and septic shock. Crit of severe sepsis and septic shock. Crit Care Med. 2004; 32: 858-73Care Med. 2004; 32: 858-73

Early Goal Directed Early Goal Directed TherapyTherapy

Rationale behind EGDTRationale behind EGDT

Time is survival:Time is survival: Goal is to achieve balance b/w OGoal is to achieve balance b/w O22 delivery & delivery &

consumptionconsumption

Standardized approaches to ED Tx have Standardized approaches to ED Tx have improved outcomes in other Dz (e.g. MI)improved outcomes in other Dz (e.g. MI)

Traditional parameters of perfusion appear to be Traditional parameters of perfusion appear to be too insensitive for ongoing tissue hypoxiatoo insensitive for ongoing tissue hypoxia

Early observational trials found survivors to have Early observational trials found survivors to have supranormal hemodynamic parameterssupranormal hemodynamic parameters

Earlier TrialsEarlier Trials

No consistent benefit from using goal-directed No consistent benefit from using goal-directed therapy to optimize oxygen delivery in ICU therapy to optimize oxygen delivery in ICU patients patients Gattinoni et al. A trial of goal-directed hemodynamic therapy in critically ill Gattinoni et al. A trial of goal-directed hemodynamic therapy in critically ill

patients. N Eng J Med 1995; 333: 1025-32patients. N Eng J Med 1995; 333: 1025-32 Hayes et al. Elevation of systemic oxygen delivery in the treatment of Hayes et al. Elevation of systemic oxygen delivery in the treatment of

critically ill patients. N Eng J Med 1994; 330: 1717-22critically ill patients. N Eng J Med 1994; 330: 1717-22 Yu et al. Effect of maximizing oxygen delivery on morbidity and mortality Yu et al. Effect of maximizing oxygen delivery on morbidity and mortality

rates in critically ill patients: a prospective randomized controlled study. rates in critically ill patients: a prospective randomized controlled study. Crit Care Med. 1993; 21: 830-8Crit Care Med. 1993; 21: 830-8

Boyd et al. A randomized clinical trial of the effect of deliberate Boyd et al. A randomized clinical trial of the effect of deliberate perioperative increase of oxygen delivery on mortality in high-risk perioperative increase of oxygen delivery on mortality in high-risk surgical patients. JAMA. 1993; 270: 2699-707surgical patients. JAMA. 1993; 270: 2699-707

Tuchschmidt et al. Elevation of cardiac output and oxygen delivery Tuchschmidt et al. Elevation of cardiac output and oxygen delivery improves outcome in septic shock. Chest 1992; 102: 216-20improves outcome in septic shock. Chest 1992; 102: 216-20

Shoemaker et al. prospective trial of supranormal values of survivors as Shoemaker et al. prospective trial of supranormal values of survivors as therapeutic goals in high-risk surgical patients. Chest 1988; 94: 1176-86therapeutic goals in high-risk surgical patients. Chest 1988; 94: 1176-86

Earlier Trials Earlier Trials

Limitations:Limitations: Heterogeneous study populationsHeterogeneous study populations Small sample sizes & wide CI’sSmall sample sizes & wide CI’s Enrollment after ICU admissionEnrollment after ICU admission Tended to focus on one intervention in Tended to focus on one intervention in

isolationisolation Most used PA cathetersMost used PA catheters

Rivers et al. Rivers et al. Early goal-directed therapy in the Early goal-directed therapy in the treatment of severe sepsis and septic shock. N treatment of severe sepsis and septic shock. N

Eng J Med. 2001; 345: 1368-77Eng J Med. 2001; 345: 1368-77 Prospective RCT of 263 adult pts with sepsis Prospective RCT of 263 adult pts with sepsis

treated either with traditional care or a treated either with traditional care or a standardized resuscitation protocol in the EDstandardized resuscitation protocol in the ED

All had arterial & central venous lines placed – All had arterial & central venous lines placed – the EGDT group got a catheter capable of the EGDT group got a catheter capable of continuous Ocontinuous O22 sat measurement sat measurement

EGDT discontinued once transferred to ICU – all EGDT discontinued once transferred to ICU – all ICU staff blinded to pts assignmentsICU staff blinded to pts assignments

Primary endpoint was mortalityPrimary endpoint was mortality

EGDT Protocol

Edwards PreSep Central Edwards PreSep Central Venous Oximetry Catheter Venous Oximetry Catheter

Rivers et al. 2001 (cont’d)Rivers et al. 2001 (cont’d)

Found that EGDT did significantly betterFound that EGDT did significantly better In-hospital mortality 30.5% vs. 46.5%, In-hospital mortality 30.5% vs. 46.5%, ARR 16%, NNT = 6; OR 0.58 (95%CI 0.38 – 0.87)ARR 16%, NNT = 6; OR 0.58 (95%CI 0.38 – 0.87) 60d mortality 44.3% vs. 56.9%60d mortality 44.3% vs. 56.9%

• Primarily explained by reduction in sudden CVS collapse Primarily explained by reduction in sudden CVS collapse deaths (10.3% vs. 21.0%)deaths (10.3% vs. 21.0%)

Various secondary outcomes (labs & severity Various secondary outcomes (labs & severity scores) significantly better in EGDT groupscores) significantly better in EGDT group EGDT pts spent longer time in the EDEGDT pts spent longer time in the ED EGDT survivors spent less time in hospital than standard EGDT survivors spent less time in hospital than standard

Tx survivors (14.6 d vs. 18.4 d)Tx survivors (14.6 d vs. 18.4 d) Baseline SVOBaseline SVO22 was 48% despite only 50% ventilated was 48% despite only 50% ventilated

Rivers et al. 2001 (cont’d)Rivers et al. 2001 (cont’d)

Differences in EGDT groupDifferences in EGDT group More fluid More fluid early early (4.9 L vs. 3.5L)(4.9 L vs. 3.5L) More transfusions (64.1% vs. 18.5%)More transfusions (64.1% vs. 18.5%) More inotropic support (13.7% vs. 0.8%)More inotropic support (13.7% vs. 0.8%) Less use of pulmonary artery catheters Less use of pulmonary artery catheters

later in ICU stay (18% vs. 31.9%)later in ICU stay (18% vs. 31.9%)

ControversiesControversies

Above average mortality in both Tx armsAbove average mortality in both Tx arms Liberal use of transfusionLiberal use of transfusion Use of SvOUse of SvO2 2 never thoroughly studied as resus never thoroughly studied as resus

end point – is it equivalent to SmOend point – is it equivalent to SmO22??

Conflicts with earlier studies showing lack of Conflicts with earlier studies showing lack of benefit from using hemodynamic goalsbenefit from using hemodynamic goals

• Hayes et al. N Eng J Med 1995; 330: 1717-22Hayes et al. N Eng J Med 1995; 330: 1717-22

• Gattinoni et al. N Eng J Med 1995; 333: 1025-32Gattinoni et al. N Eng J Med 1995; 333: 1025-32

Different time points – all prior studies in ICU settingDifferent time points – all prior studies in ICU setting More heterogeneous patient populationsMore heterogeneous patient populations

ControversiesControversies

Transfusion practiceTransfusion practice How does this fit with the TRICC trial?How does this fit with the TRICC trial?

Need for IJ or SC linesNeed for IJ or SC lines Which part of protocol accounts for benefit?Which part of protocol accounts for benefit? How will this affect department flow?How will this affect department flow? Does this protocol have any applicability to Does this protocol have any applicability to

other shock etiologies?other shock etiologies?

Why the TRICC trial does not Why the TRICC trial does not contradict Rivers et alcontradict Rivers et al

Different patient populationDifferent patient population Euvolemic ptsEuvolemic pts Enrolled within 72 hrs of ICU admissionEnrolled within 72 hrs of ICU admission Only 6% had Dx of sepsis, and only 26.5% Only 6% had Dx of sepsis, and only 26.5%

had any infection at allhad any infection at all

Supporting dataSupporting data

Success of hemodynamic optimization Success of hemodynamic optimization appears time-dependentappears time-dependent Meta-analysis of ICU ptsMeta-analysis of ICU pts Studies instituting PAC goal-directed therapy Studies instituting PAC goal-directed therapy

later than 12 hrs or after onset of organ failure later than 12 hrs or after onset of organ failure failed to show benefitfailed to show benefit

Studies that intervened early found to result in Studies that intervened early found to result in significant mortality reduction of 23% (95%CI significant mortality reduction of 23% (95%CI 16-30)16-30)

• Kern et al. Meta-analysis of hemodynamic optimization in Kern et al. Meta-analysis of hemodynamic optimization in high-risk patients. Crit Care Med 2002; 30: 1686-92high-risk patients. Crit Care Med 2002; 30: 1686-92

Fluids in SepsisFluids in Sepsis

How much fluid?How much fluid?

Till they froth at the mouth!!Till they froth at the mouth!! These pts need a ton of fluid – average of These pts need a ton of fluid – average of

6L in Rivers study6L in Rivers study Note difference compared to approach to Note difference compared to approach to

penetrating trauma penetrating trauma

VasopressorsVasopressorsJust need a little squeeze..Just need a little squeeze..

Vasopressors:Vasopressors:

Dopamine: Dopamine: Dose:Dose:

• 1-5 ug/kg/min: 11-5 ug/kg/min: 10ly0ly dopaminergic effectdopaminergic effect

• 5-10 ug/kg/min :15-10 ug/kg/min :10ly 0ly beta effectbeta effect

• 10-20 ug/kg/min : 110-20 ug/kg/min : 10ly0ly alpha effectalpha effect

Levophed:Levophed: Dose:Dose:

• 0.01 – 3 ug/kg/min0.01 – 3 ug/kg/min MOA:MOA:

• 110ly0ly potent alpha agonist potent alpha agonist• Some beta effectSome beta effect

ControversiesControversies• Used to be thought that Used to be thought that

it worsened tissue it worsened tissue perfusionperfusion

• More recent studies More recent studies contradict thiscontradict this

Norepinephrine or Dopamine 1Norepinephrine or Dopamine 1stst in septic shock?in septic shock?

Tons of animal data; very few clinical studiesTons of animal data; very few clinical studies Decreased mortality w/ norepinephrine vs. dopamine Decreased mortality w/ norepinephrine vs. dopamine

in one NON-randomized trialin one NON-randomized trial Theoretical benefits w/ norepinephrineTheoretical benefits w/ norepinephrine

• Less tachycardiaLess tachycardia• No effect on HPA or cerebral perfusion pressureNo effect on HPA or cerebral perfusion pressure• Increased GFRIncreased GFR• Decreased lactate levelsDecreased lactate levels• Improved splanchnic blood flowImproved splanchnic blood flow

• Vincent & de Backer. Crit Care 2003; 7: 6-8Vincent & de Backer. Crit Care 2003; 7: 6-8 On the other hand dopamine is quickly available and On the other hand dopamine is quickly available and

familiarfamiliar Bottom line = either will do as an initial pressorBottom line = either will do as an initial pressor

Antibiotics Antibiotics

SCCM GuidelinesSCCM Guidelines

Draw appropriate cultures firstDraw appropriate cultures first Give antibiotics within 1 hr of recognition of Give antibiotics within 1 hr of recognition of

septic syndromeseptic syndrome Antibiotics should be broad-spectrum & chosen Antibiotics should be broad-spectrum & chosen

to cover most likely organisms based on to cover most likely organisms based on presentation & local resistance patternspresentation & local resistance patterns

Arrange for further diagnostic studies to rule out Arrange for further diagnostic studies to rule out surgically correctable foci of infection once surgically correctable foci of infection once appropriateappropriate

Remove lines & tubes if appropriateRemove lines & tubes if appropriate

GIVE ABX EARLYGIVE ABX EARLY

““Autopsy studies in persons Autopsy studies in persons who died in the intensive who died in the intensive care unit show that failure care unit show that failure to diagnose and to diagnose and appropriately treat appropriately treat infections with antibiotics or infections with antibiotics or surgical drainage is the surgical drainage is the most common avoidable most common avoidable error”error”

• Hotchkiss & Karl. The Hotchkiss & Karl. The pathophysiology and treatment of pathophysiology and treatment of sepsis. N Eng J Med. 2003; 348: sepsis. N Eng J Med. 2003; 348: 138-50138-50

Local ID recommendations: Local ID recommendations: Quick reference guide Quick reference guide

Undifferentiated febrile Undifferentiated febrile shocky pt w/ no focusshocky pt w/ no focus CeftriaxoneCeftriaxone

Respiratory Respiratory Ceftriaxone + macrolide or Ceftriaxone + macrolide or

resp quinoloneresp quinolone Urinary tractUrinary tract

Gentamicin or quinoloneGentamicin or quinolone MeningitisMeningitis

Ceftriaxone +/- vancomycin Ceftriaxone +/- vancomycin +/- ampicillin+/- ampicillin

IntraabdominalIntraabdominal Ancef + flagyl + gentamicin Ancef + flagyl + gentamicin

(24 hr dosing)(24 hr dosing) Ceftriaxone + flagylCeftriaxone + flagyl Pip-tazoPip-tazo CarbapenemCarbapenem

Necrotizing fasciitisNecrotizing fasciitis IVIG + penicillin + IVIG + penicillin +

clindamycin + surgeryclindamycin + surgery Dr. Dan Gregson personal Dr. Dan Gregson personal

communicationcommunication

A Plea from Dr. KortbeekA Plea from Dr. Kortbeek

When inserting When inserting central lines, chest central lines, chest tubes etctubes etc Wear a sterile gownWear a sterile gown Wear a maskWear a mask Prep & drape a huge Prep & drape a huge

areaarea Communicate potential Communicate potential

‘dirty’ lines to admitting ‘dirty’ lines to admitting serviceservice

Ventilatory StrategiesVentilatory Strategies

BackgroundBackground

Traditional vent parametersTraditional vent parameters TV 10 – 15 ml/kg, minimal PEEP to maintain TV 10 – 15 ml/kg, minimal PEEP to maintain

normal PCOnormal PCO22, PO, PO2 2 & pH & pH ARDS mortality as high as 90% in the 70’s ARDS mortality as high as 90% in the 70’s

(currently 30-40%)(currently 30-40%)• Gattinoni et al. Physiologic rationale for ventilator setting in Gattinoni et al. Physiologic rationale for ventilator setting in

acute lung injury / acute respiratory distress syndrome acute lung injury / acute respiratory distress syndrome patients. Crit Care Med. 2003; 31(S): S300-04patients. Crit Care Med. 2003; 31(S): S300-04

ARDS-Net trialARDS-Net trial

Multicenter RCT of 861 adults with ARDSMulticenter RCT of 861 adults with ARDS Randomized within 36 hrs of intubation to:Randomized within 36 hrs of intubation to:

Control groupControl group• Vt 12 ml/kg predicted body wt on AC mode Vt 12 ml/kg predicted body wt on AC mode • Adjusted Vt to keep plateau pressure b/w 45-50 cm Adjusted Vt to keep plateau pressure b/w 45-50 cm

HH22OO Low Vt groupLow Vt group

• Vt 6-8 ml/kg predicted body wt on AC modeVt 6-8 ml/kg predicted body wt on AC mode• Adjusted Vt to keep plateau pressure b/w 25-30 cm HAdjusted Vt to keep plateau pressure b/w 25-30 cm H2200

Followed for 180 daysFollowed for 180 days

Acute Respiratory Distress Syndrome Network.Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute as compared with traditional tidal volumes for acute lung injury and the acute

respiratory distress syndromerespiratory distress syndrome. . N Eng J Med. 2000; 342: 1301-8N Eng J Med. 2000; 342: 1301-8

ARDS-Net trial (cont’d)ARDS-Net trial (cont’d)

Primary outcomesPrimary outcomes In hospital mortalityIn hospital mortality Ventilator-free days in first 28 daysVentilator-free days in first 28 days

Secondary outcomesSecondary outcomes Organ failureOrgan failure BarotraumaBarotrauma Plasma IL-6 levelsPlasma IL-6 levels

ARDS-Net trial (cont’d)ARDS-Net trial (cont’d)

Results: Low Vt group hadResults: Low Vt group had Sig decreased mortalitySig decreased mortality

• 31.0% vs. 39.8%31.0% vs. 39.8%• ARR 8.8% (95%CI 2.4-15.3%); NNT = 11ARR 8.8% (95%CI 2.4-15.3%); NNT = 11

Numerous improved secondary outcomesNumerous improved secondary outcomes

ConclusionsConclusions

General consensus in the literature that ARDS General consensus in the literature that ARDS trial results are valid, and that trial results are valid, and that • VVTT should be 6-8 ml/kg should be 6-8 ml/kg

• Plateau pressures should be kept to < 30 cm HPlateau pressures should be kept to < 30 cm H22OO

• PEEP should be used to minimize alveolar collapse PEEP should be used to minimize alveolar collapse at pressures as low as possible (start 5-10 cm Hat pressures as low as possible (start 5-10 cm H22O)O)

SteroidsSteroids

BackgroundBackground Anti-inflammatory effectsAnti-inflammatory effects

Basis for large dose (primarily methylprednisolone 30 Basis for large dose (primarily methylprednisolone 30 mg/kg followed by 5 mg/kg }steroid trials in 80’smg/kg followed by 5 mg/kg }steroid trials in 80’s

2 large RCT’s failed to show benefit2 large RCT’s failed to show benefit• Veterans administration. Effect of high-dose glucocorticoid Veterans administration. Effect of high-dose glucocorticoid

therapy on mortality in patients wit clinical signs of systemic therapy on mortality in patients wit clinical signs of systemic sepsis. N Eng J Med. 1987; 317: 659-65sepsis. N Eng J Med. 1987; 317: 659-65

• Bone et al. A controlled clinical trial of high dose Bone et al. A controlled clinical trial of high dose methylprednisolone in the treatment of severe sepsis and septic methylprednisolone in the treatment of severe sepsis and septic shock. N Eng j Med. 1987; 317: 653-58shock. N Eng j Med. 1987; 317: 653-58

Meta-analysis of 9 RCT’s found no benefit, and Meta-analysis of 9 RCT’s found no benefit, and possibly increased mortality w/ large dose steroids RR possibly increased mortality w/ large dose steroids RR 1.13, 95%CI 0.99 – 1.291.13, 95%CI 0.99 – 1.29

• Cronin et al. Corticosteroid treatment for sepsis: A critical Cronin et al. Corticosteroid treatment for sepsis: A critical appraisal and meta-analysis of the literature. Crit Care Med. appraisal and meta-analysis of the literature. Crit Care Med. 1995; 23: 1430-391995; 23: 1430-39

BackgroundBackground Concept of adrenal insufficiencyConcept of adrenal insufficiency

Stress steroid response essentialStress steroid response essential• Taking out adrenals increases septic & hemorrhagic Taking out adrenals increases septic & hemorrhagic

shock mortality in animals -- reversible with exogenous shock mortality in animals -- reversible with exogenous steroidssteroids

• Bilateral adrenal necrosis or infarction noted in ~30% of Bilateral adrenal necrosis or infarction noted in ~30% of septic pts at autopsyseptic pts at autopsy

• Multiple factors affect HPA axis during stressMultiple factors affect HPA axis during stress• Studies of sepsis pts have shown that up to 42% have Studies of sepsis pts have shown that up to 42% have

adrenal or HPA dysfunction which correlates w/ adrenal or HPA dysfunction which correlates w/ increased mortalityincreased mortality

• Multiple studies document improved catecholamine Multiple studies document improved catecholamine response in steroid-treated septic shockresponse in steroid-treated septic shock

• Prigent et al. Clinical review: Corticotherapy in sepsis. Crit Care Prigent et al. Clinical review: Corticotherapy in sepsis. Crit Care 2004; 8: 122-292004; 8: 122-29

Annane et alAnnane et al. Effect of treatment with low doses of . Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in hydrocortisone and fludrocortisone on mortality in

patients with septic shock. JAMA 2002; 288: 862-71patients with septic shock. JAMA 2002; 288: 862-71

Multicenter DBRCT of 300 adult septic shock pts Multicenter DBRCT of 300 adult septic shock pts tested with short corticotropin test & randomized tested with short corticotropin test & randomized toto PlaceboPlacebooror Hydrocortisone 50 mg q6h IV & fludrocortisone 50 ug Hydrocortisone 50 mg q6h IV & fludrocortisone 50 ug

PO OD for 7 daysPO OD for 7 days Primary outcomePrimary outcome

28d survival28d survival

Annane et al cont’dAnnane et al cont’d

ResultsResults No significant difference in mortality for all ptsNo significant difference in mortality for all pts Non-responders treated w/ steroids had Non-responders treated w/ steroids had

decreased 28d mortality decreased 28d mortality 53 vs. 63%; ARR 10%, OR 0.54 (95%CI 0.31-0.97) NNT = 1053 vs. 63%; ARR 10%, OR 0.54 (95%CI 0.31-0.97) NNT = 10

Less reliance on vasopressorsLess reliance on vasopressors Non-responders: Median time to withdrawal 7 vs. 10 d; HR Non-responders: Median time to withdrawal 7 vs. 10 d; HR

1.91 (95%CI 1.29-2.84)1.91 (95%CI 1.29-2.84) All pts: Median time to withdrawal 7 vs. 9 d; HR 1.54 (95%CI All pts: Median time to withdrawal 7 vs. 9 d; HR 1.54 (95%CI

1.10-2.16)1.10-2.16)

No significant differences in adverse eventsNo significant differences in adverse events

CriticismsCriticisms

Possible inclusion of true adrenal insufficiencyPossible inclusion of true adrenal insufficiency High mortality rate in placebo groupHigh mortality rate in placebo group

Use of fludrocortisone in addition to hydrocortisoneUse of fludrocortisone in addition to hydrocortisone Not widely practicedNot widely practiced CORTICUS trial ongoing to evaluate hydrocortisone CORTICUS trial ongoing to evaluate hydrocortisone

alone in septic shockalone in septic shock Underpowered to detect harm in respondersUnderpowered to detect harm in responders

Trend towards harm in responders needs clarificationTrend towards harm in responders needs clarification Avoid steroids for all approachAvoid steroids for all approach

Change of entry criteria during studyChange of entry criteria during study No analysis of pts recruited before & afterNo analysis of pts recruited before & after

DX of adrenal insufficiencyDX of adrenal insufficiency

What is a normal serum cortisol during stress?What is a normal serum cortisol during stress? Most controversial area -- Nobody knowsMost controversial area -- Nobody knows No clear cut normal range: No clear cut normal range:

• Serum cortisol levels variable & poorly reflective of biologic action Serum cortisol levels variable & poorly reflective of biologic action during stressduring stress

• Elevated and depressed cortisol levels are both associated w/ Elevated and depressed cortisol levels are both associated w/ increased morbidity & mortalityincreased morbidity & mortality

Current approach to Dx based on consensus opinion & limited Current approach to Dx based on consensus opinion & limited literatureliterature

• Cooper & Stewart. Corticosteroid insufficiency in acutely ill patients. N Cooper & Stewart. Corticosteroid insufficiency in acutely ill patients. N Eng J Med. 2003; 348: 727-34Eng J Med. 2003; 348: 727-34

Serum free cortisol measurements appear to be more predictive Serum free cortisol measurements appear to be more predictive & may become new standard& may become new standard

• Harnrahian et al. Measurement of serum free cortisol in critically ill Harnrahian et al. Measurement of serum free cortisol in critically ill patients. N Eng J Med 2004; 350: 1629-38patients. N Eng J Med 2004; 350: 1629-38

Suggested diagnostic approachSuggested diagnostic approach

Draw a random cortisol levelDraw a random cortisol level Perform a ACTH stim testPerform a ACTH stim test

Administer 250 ug of cosyntropin IVAdminister 250 ug of cosyntropin IV Draw serum cortisol levels at 0, 30, and 60 minDraw serum cortisol levels at 0, 30, and 60 min

Give dexamethasone 2-4 mg in ED Give dexamethasone 2-4 mg in ED Does not interfere w/ ACTH stim testDoes not interfere w/ ACTH stim test Treatment should be stopped if test negative Treatment should be stopped if test negative

• Serum cortisol levels >1242 nmol/L have been found to Serum cortisol levels >1242 nmol/L have been found to be associated w/ significantly greater mortalitybe associated w/ significantly greater mortality

• Suggests that exogenous steroids could be harmfulSuggests that exogenous steroids could be harmful• Sam et al. Cortisol levels and mortality in severe sepsis. Clin Sam et al. Cortisol levels and mortality in severe sepsis. Clin

Endo. 2004; 60: 29-35Endo. 2004; 60: 29-35

Interpreting resultsInterpreting results

Random cortisolRandom cortisol < 414 nmol/L (15 ug/dL) – suggestive of adrenal < 414 nmol/L (15 ug/dL) – suggestive of adrenal

insufficiency – start steroidsinsufficiency – start steroids >938 nmol/L (34 ug/dL) – suggestive of steroid >938 nmol/L (34 ug/dL) – suggestive of steroid

resistance – replacement unlikely to helpresistance – replacement unlikely to help 414 – 938 nmol/L – base decision on ACTH stim test 414 – 938 nmol/L – base decision on ACTH stim test

resultresult ACTH stim testACTH stim test

>250 nmol/L (9 ug/dL) change >250 nmol/L (9 ug/dL) change adrenal insufficiency adrenal insufficiency unlikelyunlikely

<250 nmol/L (9 ug/dL) change <250 nmol/L (9 ug/dL) change suggestive of adrenal suggestive of adrenal insufficiency – start steroidsinsufficiency – start steroids

• Cooper & Stewart. Corticosteroid insufficiency in acutely ill patients. Cooper & Stewart. Corticosteroid insufficiency in acutely ill patients. N Eng J Med. 2003; 348: 727-34N Eng J Med. 2003; 348: 727-34

Steroid conclusionsSteroid conclusions

Think of steroids in pts w/ apparent septic Think of steroids in pts w/ apparent septic shock refractory to standard treatmentshock refractory to standard treatment

Draw baseline cortisol levels & do ACTH Draw baseline cortisol levels & do ACTH stim teststim test

Use dexamethasone in the EDUse dexamethasone in the ED Do NOT give steroids card blancheDo NOT give steroids card blanche Await trials on use of free cortisolAwait trials on use of free cortisol

Recombinant Human Recombinant Human Activated Protein CActivated Protein C

(rhAPC = Drotrecogin alfa = Xigiris(rhAPC = Drotrecogin alfa = Xigiris® ® aka superdrug)aka superdrug)

BackgroundBackground No pharmacologic agent shown to reduce in No pharmacologic agent shown to reduce in

sepsis mortality in phase III trials….sepsis mortality in phase III trials…. IbuprofenIbuprofen NACNAC Anti-TNF-Anti-TNF-αα mAb vs. placebo mAb vs. placebo (NORASEPT II) (NORASEPT II) IL-1 receptor antagonist vs. placeboIL-1 receptor antagonist vs. placebo PAF receptor antagonist vs. placebo PAF receptor antagonist vs. placebo High dose steroidsHigh dose steroids Bradykinin antagonist (Deltibant)Bradykinin antagonist (Deltibant) Tissue factor pathway inhibitorTissue factor pathway inhibitor AT III vs. placebo (KYBERSEPT)AT III vs. placebo (KYBERSEPT) Etc, etcEtc, etc

……until now (maybe)until now (maybe)

PROWESS TrialPROWESS Trial: Bernard et al. Efficacy and safety : Bernard et al. Efficacy and safety of recombinant human activated protein C for severe of recombinant human activated protein C for severe

sepsis. N Eng J Med 2001; 344: 699-709sepsis. N Eng J Med 2001; 344: 699-709

Multicenter DBRCT of 1690 adult pts w/ Multicenter DBRCT of 1690 adult pts w/ severe sepsissevere sepsis

Randomized toRandomized to rhAPC infusion @ 24 ug/kg/h for 96 hrsrhAPC infusion @ 24 ug/kg/h for 96 hrs PlaceboPlacebo

Primary outcomePrimary outcome All-cause mortality at 28dAll-cause mortality at 28d

Bernard et al. cont’dBernard et al. cont’d

ResultsResults rhAPC significantly reduced mortalityrhAPC significantly reduced mortality

• 28d mortality 24.7% APC vs. 30.8% placebo28d mortality 24.7% APC vs. 30.8% placebo• ARR 6.1% (95% CI 1.9-10.4); NNT = 16ARR 6.1% (95% CI 1.9-10.4); NNT = 16

rhAPC had non-significant increase in risk of rhAPC had non-significant increase in risk of serious bleedingserious bleeding• 3.5% vs. 2.0% (p=0.06), NNH = 673.5% vs. 2.0% (p=0.06), NNH = 67

Sounds great, but don’t forget to Sounds great, but don’t forget to read the fine print…read the fine print…

Post hoc analysesPost hoc analyses

Pts w/ APACHE II scores <25 did worse Pts w/ APACHE II scores <25 did worse w/ rhAPC than w/ placebow/ rhAPC than w/ placebo

Benefit dec’d w/ less organ dysfunctionBenefit dec’d w/ less organ dysfunction ARR single organ system 1.7%ARR single organ system 1.7% ARR multi-organ failure 7.4%ARR multi-organ failure 7.4%

More benefit in pts w/ septic shock rather More benefit in pts w/ septic shock rather than sepsisthan sepsis

Pts not in DIC did worse w/ rhAPC than w/ Pts not in DIC did worse w/ rhAPC than w/ placeboplacebo

CostCost $335 Cdn per 5 mg vial$335 Cdn per 5 mg vial

0.024 mg x 70g kg x 96 hrs = ~161 mg or 32 vials = 0.024 mg x 70g kg x 96 hrs = ~161 mg or 32 vials = $10, 800 Cdn per treatment$10, 800 Cdn per treatment

Is it cost-effective? Yes, if used selectively.Is it cost-effective? Yes, if used selectively. Cost per life-year gainedCost per life-year gained

• APACHE II <25 $19, 723 USDAPACHE II <25 $19, 723 USD• APACHE II >25 $575,054 USDAPACHE II >25 $575,054 USD

Total cost to our systemTotal cost to our system• CHR ICU pharmacy budget 2001: $1.6 million USDCHR ICU pharmacy budget 2001: $1.6 million USD• Cost if rhAPC was used in pts w/ APACHE II > 25: Cost if rhAPC was used in pts w/ APACHE II > 25:

$482,800 USD$482,800 USD• Manns et al. An economic evaluation of activated protein C for Manns et al. An economic evaluation of activated protein C for

severe sepsis. N Eng J Med. 2002; 347: 993-1000severe sepsis. N Eng J Med. 2002; 347: 993-1000

The FutureThe Future

ADDRESS TrialADDRESS Trial Placebo-controlled trial of rhAPC in lower-risk Placebo-controlled trial of rhAPC in lower-risk

pts w/ severe sepsispts w/ severe sepsis Trials in pediatric populationsTrials in pediatric populations Trials examining use of heparin in Trials examining use of heparin in

conjunction w/ rhAPCconjunction w/ rhAPC Development of more defined criteria for Development of more defined criteria for

selecting pts likely to benefit from rhAPCselecting pts likely to benefit from rhAPC

Septic Shock SummarySeptic Shock Summary

Mortality reduction strategies:Mortality reduction strategies: EGDT:EGDT: ARR 16.0%ARR 16.0% ARDSNet vent strategyARDSNet vent strategy ARR 8.8%ARR 8.8% SteroidsSteroids ARR 10.0%ARR 10.0% rhAPCrhAPC ARR 6.1%ARR 6.1% InsulinInsulin ARR 3.4%ARR 3.4% Dex in MeningitisDex in Meningitis ARR 8.0%ARR 8.0% Early appropriate AbxEarly appropriate Abx Source controlSource control

Case 3Case 3

56F w/ SOB & pleuritic CP & syncope56F w/ SOB & pleuritic CP & syncope PMHx: Breast CA, Hx of DVTPMHx: Breast CA, Hx of DVT O/E: 37O/E: 3700, 110, 80/40, 86% RA, big fat red , 110, 80/40, 86% RA, big fat red

legleg ECG: deep S in I, Q in III, inverted T in III, RV ECG: deep S in I, Q in III, inverted T in III, RV

strain patternstrain pattern CXR: Hampton’s hump, Westermark signCXR: Hampton’s hump, Westermark sign Echo: high right-sided pressures, RV dilationEcho: high right-sided pressures, RV dilation D-dimer: 7.0D-dimer: 7.0

Are you going to Are you going to thrombolyse her?thrombolyse her?

Obstructive Shock: PEObstructive Shock: PE

25% mortality for shock 225% mortality for shock 2oo to PE to PE 2/3 of pts w/ fatal PE die within 1 hr of presentation2/3 of pts w/ fatal PE die within 1 hr of presentationBUT BUT Only a few pts w/ “massive” PE exhibit shock – many more Only a few pts w/ “massive” PE exhibit shock – many more

exhibit RV dysfunction but never deteriorate into shockexhibit RV dysfunction but never deteriorate into shock Indications for thrombolysis Indications for thrombolysis

Very controversialVery controversial Shock is the one indication most experts agree onShock is the one indication most experts agree on

• Based only on hemodynamic improvements Based only on hemodynamic improvements • No good mortality dataNo good mortality data

• Wood. Wood. The presence of shock defines the threshold to initiate thrombolytic therapy in patients with pulmonary embolism. Crit Care Med. 2002. 28:1537–1546

PE + Shock: Thrombolyze?PE + Shock: Thrombolyze? Meta-analysisMeta-analysis

9 RCT’s of 461 pts: lytics vs. heparin9 RCT’s of 461 pts: lytics vs. heparin Only 1 study (n=8) demonstrated mortality benefit (all Only 1 study (n=8) demonstrated mortality benefit (all

pts in shock)pts in shock) No statistically sig benefit for 1No statistically sig benefit for 100 outcomes: outcomes:

Pooled RR for death w/ lytics: 0.63 (0.32-1.23)Pooled RR for death w/ lytics: 0.63 (0.32-1.23)• No sig difference in shock subset analysisNo sig difference in shock subset analysis

Pooled RR for recurrence : 0.59 (0.30 – 1.18)Pooled RR for recurrence : 0.59 (0.30 – 1.18) Statistically sig increase in serious bleedsStatistically sig increase in serious bleeds

RR 1.76 (1.04 – 2.98), NNH = 17RR 1.76 (1.04 – 2.98), NNH = 17• Thabut et al. Thabut et al. Thrombolytic Therapy of Pulmonary

Embolism: A Meta-Analysis J Am Coll Cardiol 2002;40:1660 –7

Conclusion:Conclusion:

No good literature support for thrombolysis No good literature support for thrombolysis in PE butin PE but Small studies (underpowered)Small studies (underpowered) No good studies looking at shock exclusivelyNo good studies looking at shock exclusively Good physiologic and observational data to Good physiologic and observational data to

support use in PE + shocksupport use in PE + shock Most experts agree it should be given in Most experts agree it should be given in

shockshock

OK, So what is the dose?OK, So what is the dose?

Standard regimen: Standard regimen: Alteplase: Alteplase:

• 10 mg IV bolus, then 90 mg over 2 hours10 mg IV bolus, then 90 mg over 2 hours

Rapid regimen:Rapid regimen: Alteplase: Alteplase:

• 0.6 mg/kg over 15 min0.6 mg/kg over 15 min

Case 4Case 4

48 yo Male w/ crushing RSCP radiating to L 48 yo Male w/ crushing RSCP radiating to L arm & jaw while shoveling snowarm & jaw while shoveling snow PMHx: DM, HTN, Chol, Smoker, ObesePMHx: DM, HTN, Chol, Smoker, Obese FHx: 3 brothers, 6 sisters, 2 fathers, 2 mothers FHx: 3 brothers, 6 sisters, 2 fathers, 2 mothers

all w/ MI’s in their 40’sall w/ MI’s in their 40’s Pale, diaphoretic, vomiting, GCS 8, SOBPale, diaphoretic, vomiting, GCS 8, SOB 373733, 120, 75/palp, 22, 89% RA, 120, 75/palp, 22, 89% RA ECG: tombstones in V2-4 w/ reciprocal ECG: tombstones in V2-4 w/ reciprocal

changeschanges What do you want to do with him?What do you want to do with him?

Approach to Cardiogenic ShockApproach to Cardiogenic Shock ABC’sABC’s Consider DDx & identify etiologyConsider DDx & identify etiology

MI, myocarditis, dissection, arrhythmia, LV wall MI, myocarditis, dissection, arrhythmia, LV wall rupture, cardiomyopathy, PE, valve, tamponade, rupture, cardiomyopathy, PE, valve, tamponade, OD’s, etcOD’s, etc

Your Tx plan is CRRRAPYour Tx plan is CRRRAP C – Contractility (inotropes, IABP)C – Contractility (inotropes, IABP) R – Rate controlR – Rate control R -- Rhythm controlR -- Rhythm control R – Reperfusion strategies (PTCA, lytics)R – Reperfusion strategies (PTCA, lytics) A – Afterload reductionA – Afterload reduction P – Preload (fluids)P – Preload (fluids)

ManagementManagement

Are you going to cath him? Lyse Are you going to cath him? Lyse him? Anything else?him? Anything else?

Reperfusion StrategiesReperfusion Strategies

PTCA or Lytics? – The SHOCK TrialPTCA or Lytics? – The SHOCK Trial RCT of 302 pts w/ AMI & shock randomized to RCT of 302 pts w/ AMI & shock randomized to

surgical (PTCA or CABG) vs. medical (lysis) Txsurgical (PTCA or CABG) vs. medical (lysis) Tx No significant mortality difference at 30dNo significant mortality difference at 30d

• ARR 9.3% (20.5 to -1.9%)ARR 9.3% (20.5 to -1.9%) Sig dec in mortality at 6 mo in surgical groupSig dec in mortality at 6 mo in surgical group

• ARR 12.8% (23.2 – 0.9%)ARR 12.8% (23.2 – 0.9%) Benefit sustained at 1 yearBenefit sustained at 1 year

Important ConsiderationsImportant Considerations

PTCA appears to be slightly better than PTCA appears to be slightly better than thrombolysis for all comersthrombolysis for all comers

• Keeley et al. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13–20

No trial has ever shown benefit of reperfusion alone in shock pts – IABP appears to be essential

Case 5Case 5

49 F w/ fever, AMS, N&V, abd pain49 F w/ fever, AMS, N&V, abd pain PMHx: HTN, Asthma, RA PMHx: HTN, Asthma, RA O/E: 38O/E: 3844, 125, 85/30, 24, 87% RA, 125, 85/30, 24, 87% RA CXR: RLL pneumoniaCXR: RLL pneumonia Fluids, Abx, pressors – still hypotensiveFluids, Abx, pressors – still hypotensive What is going on?What is going on?

Don’t forget about medsDon’t forget about meds

Pt is on prednisone 50 mg PO OD for last Pt is on prednisone 50 mg PO OD for last 20 years!!!!20 years!!!!

Etiology of Adrenal CrisisEtiology of Adrenal Crisis Pre-existing or Pre-existing or

New Adrenal New Adrenal InsufficiencyInsufficiency

AddisonsAddisons Chronic steroidsChronic steroids SepsisSepsis Adrenal Adrenal

infarcts / infarcts / hemorrhagehemorrhage

Pituitary infarct / Pituitary infarct / hemorrhagehemorrhage

AdrenalCrisis

Acute Precipitant

•Surgery•Anesthesia•Procedures

•Infection•MI/CVA/PE

•Alcohol/drugs•Hypothermia

Tx: As for sepsis…Tx: As for sepsis…

Draw a random cortisol levelDraw a random cortisol level Perform a ACTH stim testPerform a ACTH stim test

Administer 250 ug of cosyntropin IVAdminister 250 ug of cosyntropin IV Draw serum cortisol levels at 0, 30, and 60 minDraw serum cortisol levels at 0, 30, and 60 min

Give dexamethasone 2-4 mg in ED Give dexamethasone 2-4 mg in ED Does not interfere w/ ACTH stim testDoes not interfere w/ ACTH stim test Treatment should be stopped if test negative Treatment should be stopped if test negative

• Serum cortisol levels >1242 nmol/L have been found to Serum cortisol levels >1242 nmol/L have been found to be associated w/ significantly greater mortalitybe associated w/ significantly greater mortality

• Suggests that exogenous steroids could be harmfulSuggests that exogenous steroids could be harmful• Sam et al. Cortisol levels and mortality in severe sepsis. Clin Sam et al. Cortisol levels and mortality in severe sepsis. Clin

Endo. 2004; 60: 29-35Endo. 2004; 60: 29-35

Case 6Case 6

32 yo M mountain biking – goes over 32 yo M mountain biking – goes over handlebars & lands on his headhandlebars & lands on his head

PMHx: nonePMHx: none O/E: 37O/E: 3700, 45, 80/60, 12, 95% RA, GCS 15, 45, 80/60, 12, 95% RA, GCS 15 Tx?Tx? Why is he bradycardic?Why is he bradycardic? Why is he hypotensive?Why is he hypotensive?

Neurogenic ShockNeurogenic Shock

Differentiate b/w:Differentiate b/w: Spinal shock:Spinal shock:

• Loss of all cord function below level of injury Loss of all cord function below level of injury occuring in first 24 hrs (occ several days) occuring in first 24 hrs (occ several days)

Neurogenic hypotension:Neurogenic hypotension:• Part of spinal shock – get disruption of sympathetic Part of spinal shock – get disruption of sympathetic

innervation & unopposed vagal toneinnervation & unopposed vagal tone No reflex tachycardia (No reflex tachycardia (>>T4) & peripheral vasodilation T4) & peripheral vasodilation

((>>T6)T6)

• Dx of exclusionDx of exclusion in trauma in trauma areflexia, flaccid paralysis, vasodilation, bradycardia areflexia, flaccid paralysis, vasodilation, bradycardia

Neurogenic Shock: TxNeurogenic Shock: Tx

R/O other causes of shock 1R/O other causes of shock 1stst Tends to respond toTends to respond to

TrendelenburgTrendelenburg FluidsFluids

May requireMay require Atropine 0.5 – 1.0 mg IVAtropine 0.5 – 1.0 mg IV

• NB: Pre-Tx prior to intubation to avoid unopposed vagal NB: Pre-Tx prior to intubation to avoid unopposed vagal stimulation stimulation bradyarrest bradyarrest

Pressors: dopaminePressors: dopamine Generally should not require aggressive Tx: Generally should not require aggressive Tx:

consider other causes consider other causes

Key PointsKey Points

Shock is a symptom, not a diseaseShock is a symptom, not a disease General approach (ABC’s), thenGeneral approach (ABC’s), then DDx is KEY!! DDx is KEY!!

• SSHHOCCKE mnemonic or mechanistic approachSSHHOCCKE mnemonic or mechanistic approach Empiric investigations & treatment is indicatedEmpiric investigations & treatment is indicated

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Shock Moritz Haager, PGY-4 Dr. Lisa Campfens July 29, 2004.

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