SHOCK

Core Rounds August 7, 2003

Dr. Rob Hall PGY4

Dr. Gil Curry MD, FRCPC

JOHN-WEST

john-west.qt

Shock Talk:outline

• A few cases

• Approach to and ddx of shock

• Detailed review of major causes

• Focus on septic, hypovolemic, cardiogenic shock for literature review

• Controversies in management of sepsis, hypovolemic shock, cardiogenic shock

“ Shock is the transition between illness and

death”

Definitions of Shock

• Clinical manifestations of the inability of the circulatory system to adequately supply tissues with nutrients and remove toxic waste

• Inadequate blood flow secondary to decreased cardiac output or mal-distributed output that results in irreversible tissue damage

Rosen’s Empiric Cirteria for the Diagnosis of Shock:

4 out of 6 criteria• Ill appearance or

decreased LOC

• HR > 100

• RR > 22 or PC02 < 32

• Base deficit < -5 or lactate > 4

• Urine output < 0.5 ml/kg/hr

• Hypotension > 20 minute duration

• NOTES• Can be in shock

without being hypotensive

• Base deficit = amount of base required to neutralize the pH (normal is > -2)

Classification of Shock: find your own way to classify shock and

remember the ddx

• Pre - heart• hypovolemia, venous

pooling

• Heart• contractility, arrythmias,

mech obstruction

• Post - heart• loss of vascular tone,

inability to deliver to tissues, inability of tissues to utilize

• Quantitative• hypovolemic,

hemorrhagic, obstructive, myocardial dysfunction

• Qualitative• sepsis, anaphylaxis,

neurogenic, dyshemoglobinemia, cellular poisons

Etiological Classification: man this guy looks SSHHOCCKE…

• S - septic• S - spinal (neurogenic)• H - hypovolemic• H - hemorrhagic• O - obstructive (PE, pthrx, hthrx, ct)• C - cardiogenic (rate, contractility,

obstruction, valve)

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

Pathophysiology

• Common final pathway = cellular injury

• FIVE unifying features of shock• intracellular calcium overload

• intracellular hydrogen ion

• cellular and interstitial edema

• catabolic metabolism

• inflammation

Undifferentiated Shock: Thorough history, complete physical, shot gun

investigations………ya, but what are some tips?

• History• Paramedics, caregivers, witnesses, family, and old chart

are keys to give you historical clues• Get someone on the phone EARLY (ie: in resusc bay)

who can tell you what was going on

• Physical• Don’t forget the chemstrip, rectal, AAA exam

• Investigations• STAT echo can be very useful• Emerg ultrasound will soon be available

Shock Trivia• Patient in shock but is bradycardic: why?

• Elderly, medications, neurogenic shock, intraabdominal pathology (vagal tone)

• Shock index• HR/SBP > 0.9 suggest shock

• Lactate clearance index• Patient is under – resuscitated if lactate has not

decreased by 50% since last measurement

• Gastric/Rectal Tonography• Balloon probe measure mucosal pH as an indicator of

gut perfusion

Septic Shock

Definitions:Consensus conference on definitions for sepsis: Critical

Care Medicine 2000. Volume 28 (1): 232 - 235

• SIRS (Systemic Inflammatory Response Syndrome)• temp > 38 or < 36

• HR > 90

• RR > 20 or PaC02 < 32

• wbc > 12, < 4, or > 10% bands

• Sepsis = SIRS + documented infection

• Severe Sepsis = Sepsis + MODS (Mulitorgan dysfuntion)

• Septic Shock = Sepsis + Hypotension refractory to volume resuscitation (requiring vasopressors)

Management of Septic Shock

• Intubate/ventilate• Control airway• Decrease work of breathing

• Fluids• Boluses of NS or RL• Adults: bolus 1-2 L and repeat• Peds: bolus 20 ml/kg and repeat• Pressors after 2-3 boluses but keep fluids running• Require a lot of fluid

• Absolute hypovolemia: increase incensibles, poor intake• Relative hypovolemia: vasodilation and decreased SVR

Vasopressors:Most common choices

• Dopamine: • 1-5 ug/kg/min ~

dopaminergic• 5-10 ug/kg/min ~ beta

activity• >10 ug/kg/min ~ alpha

activity

• Preferred agent for many• Effects well established• Physicians comfortable

with use

• Levophed:• 0.01 – 3 ug/kg/min• Potent alpha agonist• Some beta

propertiesConcern with levophed worsening end organ hypoperfusion

• Older studies: levophed used as last resort and thus poor outcomes• Hesselvik JF, et al., Crit

Care Med 1989

Norepinephrine

• Norepinephrine improves renal blood flow and tissue oxygenation in patients with septic shock:• Desjars et al., Crit Care Med 1989

• Rendl-Wenzel et al., Intensive Care Med 1993.

• Meadows et al., Crit Care Med 1988

• Martin C., et al., Crit Care Medicine 2000

Dopamine versus norepinephrine

• Martin et al., Chest 1993 and Marik et al., JAMA 1994• Many small studies (n=20) like these two that showed a

benenfit in physiological markers with norepinephrine

• Levophed has favourable effect on hemodynamics and end organ perfusion as compared to dopamine

• A mortality benefit for levophed over dopamine has never been shown

Pressor summary

• Make sure the pump is full first

• Dopamine/Levophed first line agents

• Levophed may be the superior agent in septic shock

• Titrate up doses fast (q 5-10 min to effect)

• Add second agent if needed

• Invasive monitoring required

Sepsis and Antibiotics

• Bochud et al., Intensive Care Medicine 2001: reviewed 4 retrospective studies of septic patients and abx choice

• N=1190

• Appropriate Abx mort rate~28%

• Inappropriate Abx mot rate~49%

• P<0.001

• Early ED antibiotics have also shown to decrease mortality in many disease subgroups (pneumonia, meningitis, urosepsis)

EARLY and APPROPRIATE initiation of antibiotic coverage

are CRUCIAL emergency department interventions in the

patient with septic shock

Empirical antibiotic choices

• Target suspected source of infection• Refer to SANDFORD’s recommendations • Use maximum doses of antibiotics• Broad spectrum = grm +ves, grm –ves, anaerobes• Amp + Gent + Flagyl• Piperacillin/Tazobactam being used more often• Imipenum as monotherapy (big gun)• Neutropenic: cover pseudomonas (ceftazidime,

cipro, tobramycin)

Newer approaches to septic shock:

• Vasoactive mediators• vasopressin, nitric oxide

• Coagulation Cascade• protein C, protein S, antithrombin III

• Inflammatory mediators• anti TNF antibodies, anti LPS, TFPI,

interleukins, IVIG

Question: how to get an intensivist talking at a wine and

cheese party?

Answer: just say……

(i) There is NO evidence for steroid use in septic shock

(ii) Recombinant activated Protein C is killing patients

Steroids in septic shock

Rationale:

• Anti-inflammatory• Relative adrenal insufficiency in many of

cases of refractory shock

• Upregulates catecholamine receptors

• Hopefully immunosuppression and bleed risk did not counter benefits

Steroids and Sepsis

• Early mega-dose steroid trials • “supraphysiologic” doses• Solumedrol 30/mg/kg x

3-4 doses• Trend towards increased

mortality• Increase incidence of GI

bleeding• Increased incidence of

secondary infections

• 1990’s trial’s with lower dose steroids• “physiologic doses”• aimed to replace

steroids for a “Relative adrenal insufficiency”

• Researchers hoped get catecholamine sensitivity and anti-inflammatory effects still

Steroids and Sepsis:Bollaert et al.,Critical Care Medicine 1998

• Double-blind, placebo controlled, small study • Solu-cortef 100mg IV q 8hrs x 5days vs. placebo • Outcome Steroid group Placebo

• Shock reversal @7d: 68% 21% p=.007• Mortality 32% 63% p=.09

• No increase adverse outcomes• Showed more shock reversal at 7 days with low

dose steroids

Steroids and Sepsis: Briegel et al., Crit Care Med 1999.

• Another small RCT (n=40)

• Randomized to solu-cortef 100mg IV then low dose infusion vs placebo

• Outcome Steroid group Placebo• Time to shock reversal 2 days 7 days

(p=.005)

• No increase adverse outcomes, no diff in mortality

• Showed earlier shock reversal with low dose steroids

Steroids and Sepsis:Annane. JAMA 2002.

• Largest prospective trial of low dose steroids• RCT, blinded, N = 300• Randomized to low dose hydrocortisone (50 mg iv

q6hr) + fluticasone vs placebo• Did ACTH stim test on everyone• Mortality decreased 10% in “non-responders”

• 63% -> 53% (p = 0.02)

• Criticisms of their definitions of non-responders and how they did the stim test exist

Steroids and Sepsis:Review article in Chest May 2003

• High dose steroids clearly shown to increase mortality

• There is some evidence for benefit from low dose steroids in sepsis

• Current debate over low dose steroids unresolved and needs further study

Steroids and Sepsis:Take home message

• There is no current indication for the ED initiation of low dose steroids in sepsis unless adrenal crisis is suspected

• You should be aware that ICU will likely do an ACTH stim test and may give steroids

Activated Protein C and Sepsis

• Antithrombotic

• Profibrinolytic

• Anti-inflammatory

Activated Protein C and Sepsis:drotrecogion (Zigris)

• PROWESS TRIAL (Bernard. NEJM 2001)

• Multicentered RCT, N = 1690

• Mortality 30.8% in placebo, 24.7% in treatment group (p= 0.005)

• ARR 6.1% for NNT 16

• RRR of 19%

• Serious bleeding 3.5% vs 2.0% (p=0.06)

• Enrollement criteria changed ½ way through!

Activated Protein C and Sepsis

• The FDA is confused• Study stopped early because of “remarkable effect”,

FDA approved the drug• Further discussion and controversy: FDA limited its use

to only sicker patients (based on APACHE score) and asked for further study

• Critical Care Medicine. 31(1). S85-96• Recent review on rhAPC• Highlights problems with PROWESS study and FDA

approval --------- calls for further study

Activated Protein C and Sepsis

• Take home messages:• rhAPC is expensive (10,000 per course)

• rhAPC has been shown to decrease mortality although the effect is modest (ARR 6%)

• There is NO role for ED initiation of rhAPC

• May be used in ICU

Case

• 15 yo male

• Attempted hanging

• Cut down from tree

• HR 75, BP 85/30

• Why is he in shock?

Neurogenic Shock:Definitions

• Spinal Shock• initial loss of spinal cord function following

SCI including motor, sensory, and sympathetic function

• Neurogenic Shock• loss of sympathetic autonomic function due to

spinal cord injury

Neurogenic Shock: Pathophysiology

• Hypotension• Due to loss of sympathetic tone thus vasodilation and

decreased SVR• Usually only occurs with lesions at or above T6 because

lower lesions leave enough of the body with intact sympathetics that the BP doesn’t drop

• Bradycardia (absolute or relative)• Due to unopposed parasympathetic (VAGAL) tone to the

heart• Usually only occurs with lesions at or above T4 because

sympathetic innervation to heart is at T4

Neurogenic Shock:Management

• Fluids

• Atropine 0.5 mg – 1.0 mg iv• NOTE: may see bradycardia or bradyasystolic arrest

due to stimulation from laryngoscopy so have atropine ready if intubating

• Vasopressors• Epinephrine 1:10,000 (1ml prn to effect)

• Phenylephrine: 10 mg in 100ml NS (1ml is 100 ug)

• Ephedrine

Hemorrhagic Shock

Hemorrhagic Shock:Classification

Class I Class II Class III Class IV

Volume <750ml 750 – 1500 1500-2000 > 2000

% < 15% 15-30% 30-40% > 40%

HR < 100 100 - 120 120 – 140 > 140

PP N or incrd decreased decreased decreased

BP normal normal decreased decreased

LOC anxious anxious confused lethargic

Hemorrhagic Shock:Definition

• Hemorrhage vs Hemorrhagic shock?

• Rosen’s definition of hemorrhagic shock = Requires 4 out of 6 empiric criteria for shock

• Ill or decreased LOC

• U/o < 0.5 ml/kg/hr

• HR > 100

• RR > 22 or PC02 < 32

• BD < -5 or lactate > 4

• Hypotension > 20 minutes

Hemorrhagic Shock: Management

• V: vascular access, crystalloid bolus X 2, blood transfusion prn, identify and treat cause

• Controversies• Which fluid?• When to fluid resuscitate?• How fast should fluid be given?• Optimal endpoints of resuscitation?• Blunt versus penetrating trauma

Hemorrhagic Shock

Which fluid to give?

Colloids

• Albumin, protoplasm protein fraction, hydroxyethylstarch, pentastarch, gelatin, dextran

• Advantages• less fluid required, more volume in vascular

space, potential to draw fluid in from tissues

• Disadvantages• expensive, allergic reactions, coagulopathies

Colloids

• Cochrane Database of Systematic Reviews. BMJ 1998: 317:235-40.• Objective: effect of albumin on mortality

• Study: 30 RCTs total 1419 patients

• Results: RR of death 1.46 hypovolemia, 2.40 burns, 1.69 hypoalbuminemia

• Pooled RR of death 1.68 (1.26,2.23)

• Conclusion: albumin increases mortality

Colloids

• Cochrane Database 2003. Colloids versus crystalloids for fluid resuscitation.• Albumin: 18RCTs RR1.52 (1.08,2.13)

• HES: 7 RCTs RR 1.16 (0.68,1.96)

• Gelatin: 4 RCTs RR 0.50(.08,3.03)

• Dextran: 8 RCTs RR 1.24 (.94,1.65)

• Conclusion: No evidence that colloids reduce risk of death in trauma, burns, or surgery

Colloids:Summary

• There is NO evidence that colloids decrease mortality in the resuscitation of critically ill patients.

Hypertonic Saline

• Advantages• less volume, stays in vascular space, draws fluid

• Disadvantages• hypernatremia, hyperosmolarity, seizures,

coagulopathy, anaphylactoid rxns with dextran

• Details• Hypertonic saline (7.5% NaCl) +/- 6% dextran

• Most often given as a 250 cc bolus (~ 4ml/kg) over 5-10 min

Hypertonic Saline

• Animal evidence • improved hemodynamics and mortality

• Human evidence: Wade et al 1997: • HS and HSD in trauma patients• Metanalysis of 8 RCTS of HSD and 6 HS• HS (7.5% saline): no difference in mortality• HSD (+6%dextran): decreased mortality in 7/8

trials overall 3.5%; trend only ---> Not stat sign

Hypertonic Saline

• Cochrane Database 2003. Alderson P. Colloids vs crystalloids for fluid resuscitation. • Part of this systemic review looked at Hypertonic

Saline + Dextran and effect on mortality

• Study: metanalysis of 8 RCTs

• Results: pooled RR of 0.88 (0.74, 1.05)

• Conclusion: there is a trend toward reduction in mortality with HSD although not statistically significant

Hypertonic Saline

• Cochrane Database: 2003. Bunn F. Hypertonic vs Isotonic Crystalloid• 17 RCTs with total N = 869 (small trials!)

• 12/17 reported on mortality rates

• Trauma: RR death 0.84 (.61 – 1.16)

• Trend that favors hypertonic saline

Hypertonic Saline:Conclusions

• There is evidence of TRENDS toward lower mortality in resuscitation with hypertonic saline but statistical significance has not been demonstrated in large studies

• More RCTs are needed………..

Hemorrhagic Shock

When to give fluids?

How much?

How fast?

Controlled Fluid Resuscitation:Rationale

• Also called hypotensive resuscitation or permissive hypotension

• Elevation of BP before hemorrhage control may be harmful

• Reasons• Hydraulic pressure• Dislodgement of soft clots • Dilution of clotting factors

Controlled Fluid Resuscitation:Evidence

• Early anmimal studies of fluid replacement were in CONTROLLED hemorrhage models showed benefit for fluids

• Recent animal studies of fluid replacement in UNCONTROLLED hemorrhage models show increased mortality with early and aggressive fluids (especially if BP is elevated)

Controlled Fluid Resuscitation:Evidence

• Review articles:• Emerg Med Clinics: 123(4). Nov 2002

• Journal of Trauma supplement Vol 54(5S). May 2003.

Bickell et al and Controlled Fluid Resuscitation - “here

piggy,piggy”

Bickell et al 1990The Detrimental Effects of Intravenous Crystalloid after

Aortotomy in Swine. Surgery 110: 529-36.

• Objective: does rapid volume replacement inc mortality?

• Study: 16 pigs, 8 controls (no fluid), 8 tx (RL 80 ml/kg )

• Results Mortality

• Controls 0/8

• RL tx grp 8/8

• Then repeated the study with hypertonic saline + dextran

• Bickell et al 1992. HSD vs RL after Aortotomy

• HSD tx grp 5/8

Bickell et al. NEJM 1994.Immediate versus Delayed Fluid Resuscitation for

Hypotensive Patients with Penetrating Torso Trauma

• Study: 598 patients SBP<90, odd/even day randomization, immediate fluids vs none until OR

• Immediate fluids - mortality 110/303 (38%)• Delayed fluids - mortality 86/289 (30%)• Statistically significant p = 0.04• Concln: delayed fluid resuscitation reduces

mortality in hypotensive patients with penetration• Comments: even/odd day randomization, significant

cross over between groups, note short transport times

Controlled Fluid Resuscitation:What about blunt trauma?

• Turner. Health Technol Assess 2000. Prehospital fluid replacement in serious truama.• RCT, immediate resuscitation vs no

prehospital fluids in blunt trauma• N = 1309• No diff in mortality, complications• Hard to draw conclusions -> MAJOR protocol

violations

Controlled Fluid Resuscitation:What about blunt trauma?

• Sampalis. J Trauma 1997• Retrospective evidence of increased mortality

with IV therapy (? Due to longer scene time)

• Dutton. Resuscitation 1996• Retrospective evidence of increased mortality

of rapid iv infusion compared to historical controls

Controlled Fluid Resuscitation:What about blunt trauma?

• Dutton RP. J. Trauma 2002. Hypotensive Resuscitation During Active Hemorrhage: Impact on in Hospital Mortality• RCT, N=40, target SBP >70 or > 100

• ½ penetrating and ½ blunt trauma

• No difference in survival

• Small study, heterogenous patients, low mortality

Controlled Fluid Resuscitation

• Cochrane Database 2001. Kwan I. Timing and volume of fluid administration for patients with bleeding following trauma.• 3 RCTs for early vs delayed fluids

• 3 RCTs for large vs small volume

• NO evidence for early or large volume fluid replacement and trends toward increased mortality

• But only 6 studies thus not a valid systemic review

Controlled Fluid Resuscitation: Take home messages

• Early, aggressive fluid resuscitation increases mortality in penetrating trauma.

• Controlled fluid resuscitation probably better (target SBP 70 – 90)

• Delayed fluid resuscitation (until hemmorrhage controlled) may be better

• Further study needed especially in blunt trauma• Unknown if this applies to long transport times• Pour it in for arrested or near-arrested patients

Where will trauma resuscitation be in 2010?

My prediction: small volume of hypertonic saline + dextran for target

SBP 90 and to OR ASAP!

Cardiogenic Shock

Cardiogenic shock

• Definition• decreased cardiac output and evidence of tissue

hypoxia in presence of adequate intravascular volume

• Criteria• hypotension (SBP < 90) x 30 min, or 30mmHG below

baseline, cardiac index < 2.2 L/min/m2, PCWP > 15 mmHg

• Rosen’s: 4 out of 6 criteria for empiric shock

• Pathologically• Will have lost 40% of myocardium

Cardiogenic Shock

B radyT achy

R a te

Isch em iaM yo ca rd it is

-v e ion o tropeC M o r C H D

C on tra c ti li ty

A cu te ru p tu reC r i tica l A S

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P ET a m po na de

T u m or

O b stru ction

E tio log y o f C ard iog en icS h o ck

Cardiogenic Shock:Approach

• Stabilize the ABCs

• Identify etiology of cardiogenic shock

• Small fluid bolus (250cc)

• Don’t be shy on fluids if RV infarct

• Ionotropic/vasopressor support

• Manage infarct

Cardiogenic shock: Pressor choices

• Dobutamine: beta adrenergic • positive B1 ionotrope; may drop BP b/c of vasodilation• SBP 70 - 100 without signs of hypoperfusion a/f fluids

• Dopamine: dopaminergic, beta , alpha adrenergic• SBP 70 - 100 with signs of hypoperfusion after fluids

• Norepinephrine: alpha agonist• SBP < 70 after fluids

• Others• Amrinone, milrinone

MI + Cardiogenic shock:How to manage the MI?

• Options• Thrombolysis

• Get BP up with ionotropes then thrombolyse

• Stabilize with IABP then thrombolyse

• PTCA

• Emergency CABG

• What does the literature tell us?

MI + Cardiogenic shock:How to manage the MI?

• Thrombolysis in cardiogenic shock• GISSI (N=280) 30day mortality

• streptokinase 70.1%

• medical mx 69.6%

• NO trial has shown reduction mortality with cardiogenic shock with thrombolysis

MI + Cardiogenic shock:How to manage the MI?

• Intra-Aortic Balloon Pump• Gusto I: early IABP + lysis showed trend

towards lowered 30d and one year mortality

• SHOCK trial: IABP + lysis mortality 17% versus medical mx alone 32%

• Temporizing with IABP then lysis is an option

Cardiogenic: the SHOCK trial Hochman JS. NEJM 1999; vol 341 (9): 625-34.

• RCT of AMI + cardiogenic shock• 152 early revascularization (PTCA or CABG) or

150 initial medical mx only (lysis initially, some had PTCA/CABG after 52hrs)

• End Point early revasc. Med Mx stats

• 30d mortality 46.7% 56%p=.11

• 6m mortality 50.3% 63.1%p=.027

Cardiogenic Shock:the SHOCK trial

• Hochman JS. One year survival following early revascularization for cardiogenic shock. JAMA 2001.

• End Point early revasc. Med Mx stats

• 1yr survival 46.7% 33.6% p=.03

MI + Cardiogenic shock:How to manage the MI?

• Conclusions …….• Patients with AMI complicated by cardiogenic

shock, especially those < 75yo, should undergo emergent revascularization (PTCA or CABG)

Anaphylactic Shock

• You’d better know this!• Airway management

• Epinephrine

• Benadryl

• Fluids

• Steroids

• Racemic epinephrine and ventolin nebs

• Ranitidine

• Glucagon

Etiology of Adrenal Crisis

Underlying Adrenal Insufficiency

(Addision’s and Chronic Steriods)

Acute Precipitant

AdrenalCrisis

Acute adrenal crisis?

• Underlying Adrenal insufficiency• Addison’s disease• Chronic steroids

• No underlying Adrenal insufficiency• Adrenal infarct or

hemorrhage• Pituitary infarct or

hemorrhage

• Precipitants of Adrenal crisis• Surgery

• Anesthesia

• Procedures

• Infection

• MI/CVA/PE

• Alcohol/drugs

• Hypothermia

Key Features of Adrenal Crisis

• Nonspecific• Nausea, vomiting,

abdominal pain

• Shock• Distributive shock not

responsive to fluids or pressors

• Laboratory (variable)• Hyponatremia,

hyperkalemia, metabolic acidosis

• Known Adrenal insufficiency

• Features of undiagnosed adrenal insufficiency• Weakness, fatigue,

weight loss, anorexia, N/V, abdo pain, salt craving, hyperpigmentation

Features of Adrenal Insufficiency

H yperp igm en ta tionH ypona trem iaH ype rka lem ia

M e tabo lic A c idos is

PRIMARYADRENAL INSUFF

N O H ype rpigm en ta tionM ild hypona trem iaN O hyperka lem iaN O m e t ac idos is

SECONDARY /TERTIARY ADRENAL

INSUFFIC IENCY

Adrenal Crisis

•Consider on the differential diagnosis of SHOCK NYD

Management of Adrenal Crisis

• Corticosteroid replacement• Dexamethasone 4mg iv q6hr is the drug of choice

(doesn’t affect ACTH stim test)

• Hydrocortisone 100 mg iv is an option

• Mineralocorticoid not required in acute phase

• Other• Correct lytes, fluid resuscitation (2-3L)

• Glucose for hypoglycemia

• Pressors

Conclusions

• Shock is the transition between illness and death

• Shock has many different causes but the end result is the same

• The diagnosis and management of shock is essential knowledge in emergency medicine