class drug therapy of shock

Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

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Term “choc” – French for “push” or impact wasfirst published in 1743 by the physician LeDranBelief – symptoms arose from fear or someother form of altered cerebral functionInadequate oxygen delivery to meet metabolicdemandsResults in global tissue hypoperfusion andmetabolic acidosisShock can occur with a normal blood pressureand hypotension can occur without shock

• Inadequate systemic oxygen delivery activatesautonomic responses to maintain systemic oxygendelivery• Sympathetic nervous system

• NE, epinephrine, dopamine, and cortisol release•Causes vasoconstriction, increase in HR, and

increase of cardiac contractility (cardiac output)• Renin-angiotensin axis

• Water and sodium conservation andvasoconstriction

• Increase in blood volume and blood pressure

Progression of physiologic effects as shock ensuesCardiac depressionRespiratory distressRenal failureDIC

Result is end organ failure

• History• Recent illness• Fever• Chest pain,• Abdominal pain• Comorbidities• Medications• Toxins/Ingestions• Recent hospitalization or

surgery• Baseline mental status

• Physical examination• Vital Signs• CNS – mental status• Skin – color, temp, rashes,

sores• CV – heart sounds• Resp – lung sounds, RR,

oxygen sat, ABG• GI – abd pain, rigidity,

guarding, rebound• Renal – urine output

• Infectious sourceCardiorespiratory monitorPulse oximetrySupplemental oxygenIV accessABG, lab investigations-CBC, Chemistries, Lactate

Coagulation studies, CulturesFoley catheter

CT of head/sinusesLumbar punctureWound culturesAcute abdominal seriesAbdominal/pelvic CT or USCortisol levelFibrinogen, FDPs, D-dimer

HypovolemicSepticCardiogenicAnaphylacticNeurogenicObstructive

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Type Preload CO PVR SVR

Hemmorrhagic

Anaphylactic

Cardiogenic

Septic(Hyperdynamic)

Septic(Hypodynamic)

/

Non-hemorrhagicVomitingDiarrheaBowel obstruction,pancreatitisBurnsEnvironmental(dehydration)

HemorrhagicGI bleedTraumaMassive hemoptysisAbdominal AorticAneurysmrupture(AAA)Ectopic pregnancy,post-partum bleeding

Airway Breathing CirculationEstablish 2 large bore IVs or a central lineCrystalloids

Normal Saline or Lactate Ringers-Up to 3 litersPacked Red Blood CellsO negative or cross matchedControl any bleedingArrange definitive treatment

TBW (42 L) = 2/3 of body weight (70 kg).

ICF (28 L) = 2/3 of TBW.

ECF (14 L) = 1/3 of TBW.

Interstitial fluid (ISF, 10.5 L) = ¾ of ECF

Intravascular fluid (IVF, 3.5 L) = ¼ of ECF.

“Crystalloids”Normal saline (just NaCl).Lactated ringersPlasmalyte-balanced crystalloid solution withmultiple electrolye solutionNormosol-solution of balanced electrolytes in waterfor injection.Last 3 have K+ and other stuff (acetate, Mg++, etc.)

Crystalloids enter entire ECF: ISF (3/4 of ECF) and IVF(1/4 of ECF).3 or 4:1 for replacement of blood loss with crystalloidColloids only enter IVF (in short term– 16 hour half-time for entrance into ISF)1:1 replacement of blood loss with colloid

Blood trasfusionPacked red cells- increase O2 carrying capacityPlasma-fresh frozen plasma contains all stable

proteins-albumin, globulin and clotting factorsNormal human serum albumin-reduce edema,hypovolemic shock

DEXTRAN-isolated from beet rootInhibit rouleaux formationHYDROXYETHYL STARCH-resistant to hydrolysis byamylase, maintains blood volume longerPOLYVINYL PYROLIDINE (PVP)-synthetic water solublehydrophilic polymerGelatin polymers-HAEMACCEL-polypeptide dissolvedin electrolyteDEXTROSE-5% in water

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Vasoactive drugs are an important pharmacologicdefense in the treatment of shock.May be required to support BP in the early stages ofshock.These agents may be needed to:

Enhance CO through the use of inotropic agentsIncrease SVR through the use of vasopressors

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Epinephrine , β1, (β2) 2-10 µg/min

Norepinephrine , β1 0 - 2-20 µg/min

Dopamine β1, DR, (α ) 1 - 30

Dobutamine β1, β2 2 - 20

Phenylphrine 20-200µg/min

Vasopressin Angiotensin III 5 - 20

Amrinone PDI 2 -15

Drug Receptor CO SVR Dose Range

0 -

(µg/kg/min)

1

0

20

Nifedipine 0 - 0.5 - 10

Nitroglycerin 0 - 3 - 5

Nitroprusside 0 - 0.5 - 5

Prostacyclin 10 - 40

2

Drug CO SVR Dose Range

(µg/kg/min)

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An endogenous precursor of norepinephrine withmultiple dose-related effectsstimulates alpha, beta and dopaminergic receptors.Low Dose (0.5 - 3 µg/kg/min)

Predominantly dopaminergic (DR) effectsEnhanced blood flow to renal and splanchnic beds

Moderate Dose (5 -10 µg/kg/min)Positive inotropic effects (1)

High Dose (>10 µg/kg/min)a-actions (vasoconstriction)

DRUG Common UsesPhenylephrine Septic Shock, neurogenic

shock

Norepinephrine Septic shock

Epinephrine Anaphylaxis, ACLS, septicshock

Dopamine Renal Insufficeny, septicshock, cardiogenic shock

Dobutamine Cardiogenic shock (CS)

Isoproterenol bradycardia due to heartblock, effects HR

Milrinone Cardiogenic shock- in thosewho don’t respond todobutamine

Epinephrine—catecholamine. Low doses stimulatesbeta receptors (so increases CO), causesbronchodilation as well. Larger doses act on alphareceptors.

Drug of choice in anaphylaxis. Prevents release ofhistamine, so reverses vasodilation andbronchoconstriction.

Can be given IV, subcut or even via ETT.

Isoxsuprine(isoproterenol)—synthetic catecholamine.Works exclusively on beta receptors. Increases heartrate, myocardial contractility and variable BP effects.

Limited usefulness as vasopressor. Increases myocardialoxygen consumption and decreases coronary flow.Causes cardiac dysrhythmias.

Milrinone—used in combination with other agents incardiogenic shock.Increases cardiac output and decreases SVR withoutincreasing heart rate or myocardial oxygenconsumption.Improved CO then increases renal perfusion, thusurinary output with decrease in circulating volume anddecreased cardiac workload.

Norepinephrine—catecholamine.Primarily alpha 1 stimulation but also beta1 receptors.Useful in cardiogenic and septic shock.Does cause reduced renal blood flow so limits its longterm use.Phenylephrine—adrenergic that stimulates alphareceptors. Longer duration of action thanepinephrine. Reduction of renal and mesenteric bloodflow limits prolonged use.

Neosynephrine (phenyleprine)—adrenergic thatstimulates alpha receptors. Longer duration ofaction than epinephrine. Reduction of renal andmesenteric blood flow limits prolonged use.

Two or more of Criteria-Systemic InflammatoryResponse Syndrome (SIRS)

Temp > 38 or < 36 CHR > 90RR > 20WBC > 12,000 or < 4,000

Plus the presumed existence of infectionBlood pressure can be normal!

Sepsis plus refractory hypotensionAfter bolus of 20-40 mL/Kg patient still has one ofthe following:

SBP < 90 mm HgMAP < 65 mm HgMAP = [(2 x diastolic)+systolic] / 3

High feverDiffuse rash with desquamation on the palms andsoles over subsequent 1-2 weeksHypotension (may be orthostatic) and evidence ofinvolvement of 3 other organ systems

Streptococcal TSS more frequently presents with focalsoft tissue inflammation and less commonly isassociated with diffuse rash.Streptococcus pyogenes (group A Streptococcus)S aureus

• 2 large bore IVs• NS IVF bolus- 1-2 L wide open (if no

contraindications)• Supplemental oxygen• Empiric antibiotics, based on suspected source, as

soon as possibleAntibiotics- Survival correlates with how quickly thecorrect drug was givenCover gram positive and gram negative bacteria

Zosyn(piperacillin+ tazobactum) 3.375 grams IV andceftriaxone 1 gram IV orImipenem 1 gram IV

Add additional coverage as indicatedPseudomonas- Gentamicin or CefepimeMRSA- VancomycinIntra-abdominal or head/neck anaerobic infections-Clindamycin or MetronidazoleAsplenic- Ceftriaxone for N. meningitidis, H. infuenzaeNeutropenic – Cefepime or Imipenem

Vasoactive Drugs in Sepsis and Usual Hemodynamic Responses

Drug DoseCardiacOutput

BloodPressure

SystemicVascularResistance

Dopamine* 2.5-20 mcg/kg/min + + +

Norepinephrine† 0.05-2 mcg/kg/min + ++ ++

Epinephrine 0.05-2 mcg/kg/min ++ ++ +

Phenylephrine 2-10 mcg/kg/min - ++ ++

Dobutamine‡ 2.5-10 mcg/kg/min + +/- -

• Signs:• Cool, mottled skin• Tachypnea• Hypotension• Altered mental status• Narrowed pulse

pressure• Rales, murmur

• Defined as:• SBP < 90 mmHg• CI < 2.2 L/m/m2

• PCWP > 18 mmHg• Pulmonary Arterial

Wedge pressure

AMISepsisMyocarditisMyocardial contusionAortic or mitral stenosis, HCMAcute aortic insufficiency

Often after ischemia, loss of LV functionLose 40% of LV clinical shock ensues

CO reduction lactic acidosis, hypoxiaStroke volume is reduced

Tachycardia develops as compensationIschemia and infarction worsens

Goals- Airway stability and improving myocardialpump functionCardiac monitor, pulse oximetrySupplemental oxygen, IV accessIntubation will decrease preload and result inhypotension -fluid bolus

AMIAspirin, beta blocker, morphine, heparinIf no pulmonary edema, IV fluid challengeIf pulmonary edema

Dopamine – will ↑ HR and thus cardiac workDobutamine – May drop blood pressureCombination therapy may be more effective

PCI(Percutaneous Coronary Intervention) or thrombolyticsRV infarct

Fluids and Dobutamine (no NTG)Acute mitral regurgitation or VSD

Pressors (Dobutamine and Nitroprusside)

Correct hypotension:Fluid resuscitation to correct hypovolemiaInotropic or Vasopressor support:

DobutamineMilrinoneNorepinephrineDopamineEpinephrine

OxygenationIf MI – ASA, Heparin, and RevascularizationIf arrhythmia – correct arrhythmiaIf extracardiac abnormality – reverse or treat cause

Clinical Signs: Shock, Hypoperfusion, CHF, Acute Pulm EdemaMost likely major underlying disturbance?

Acute PulmonaryEdema

Hypovolemia Low-outputcardiogenic shock

Arrhythmia

AdministerFurosemideMorphine

Oxygen intubationNitroglycerin

DopamineDobutamine

AdministerFluids

Blood transfusionsCause-specificinterventions Check Blood Pressure

Bradycardia

Tachycardia

Check Blood Pressure

Systolic BP(>100 mm Hg)

Systolic BP(NO

signs/symptoms of shock)

Systolic BP(signs/symptoms

of shock)

Systolic BP (<70 mmHg + signs/symptoms

of shock)

See Sec. 7.7 inACC/AHA Guidelines

for patients withSTEMI

ACEInhibitors

Nitroglycerin Dobutamine Dopamine Norepinephrine

Systolic BP(>100 mm

Hg)

Further Diagnostic/Therapeutic Considerations (for non-hypovolemicshock)

Diagnostic / TherapeuticPulmonary artery catheter, Intra-aortic balloon pump,echo, angiography, etc Reperfusion revascularization 41

• Anaphylaxis – a severe systemic hypersensitivityreaction characterized by multisysteminvolvement• IgE mediated

• Anaphylactoid reaction – clinicallyindistinguishable from anaphylaxis, do notrequire a sensitizing exposure• Not IgE mediated

Pruritus, flushing, urticaria appear

Throat fullness, anxiety, chest tightness,shortness of breath and lightheadedness

Finally- Altered mental status, respiratorydistress and circulatory collapse

ABC’sAngioedema and respiratory compromise requireimmediate intubation

IV, cardiac monitor, pulse oximetryIVFs, oxygenEpinephrineSecond line

CorticosteriodsH1 and H2 blockers

Epinephrine0.3 mg IM of 1:1000Repeat every 5-10 min as neededCaution with patients taking beta blockers- cancause severe hypertension due to unopposedalpha stimulationFor CV collapse, 1 mg IV of 1:10,000If refractory, start IV drip

CorticosteroidsMethylprednisolone 125 mg IVPrednisone 60 mg PO

AntihistaminesH1 blocker- Diphenhydramine 25-50 mg IVH2 blocker- Ranitidine 50 mg IV

BronchodilatorsAlbuterol nebulizerAtrovent nebulizerMagnesium sulfate 2 g IV over 20 minutes

GlucagonFor patients taking beta blockers and with refractoryhypotension1 mg IV q5 minutes until hypotension resolves

• Occurs after acute spinal cord injury• Sympathetic outflow is disrupted leaving

unopposed vagal tone• Results in hypotension and bradycardia• Spinal shock- temporary loss of spinal reflex activity

below a total or near total spinal cord injury (not thesame as neurogenic shock, the terms are notinterchangeable)

Loss of sympathetic tone results in warm and dry skinShock usually lasts from 1 to 3 weeksAny injury above T1 can disrupt the entire sympatheticsystem

Higher injuries = worse paralysis

A,B,CsRemember c-spine precautions

Fluid resuscitationKeep MAP at 85-90 mm Hg for first 7 daysThought to minimize secondary cord injuryIf crystalloid is insufficient use vasopressors

Search for other causes of hypotensionFor bradycardia

AtropinePacemaker

MethylprednisoloneUsed only for blunt spinal cord injuryHigh dose therapy for 23 hoursMust be started within 8 hoursControversial- Risk for infection, GI bleed

Tension pneumothoraxAir trapped in pleural space with 1 way valve,air/pressure builds upMediastinum shifted impeding venous returnChest pain, SOB, decreased breath soundsConfirmation -CXRRx: Needle decompression, chest tube

Cardiac tamponadeBlood in pericardial sac prevents venous return toand contraction of heartRelated to trauma, pericarditis, MIBeck’s triad: hypotension, muffled heart sounds, JVDDiagnosis: large heart CXR, echoRx: Pericardiocentisis

Pulmonary embolismVirchow’s triad: Hypercoagulability. Hemodynamicchanges (stasis, turbulence) Endothelialinjury/dysfunction.Signs: Tachypnea, tachycardia, hypoxiaLow risk: D-dimerHigher risk: CT chestRx: Heparin, consider thrombolytics

Aortic stenosisResistance to systolic ejection causes decreasedcardiac functionChest pain with syncopeSystolic ejection murmurDiagnosed with echoVasodilators (NTG) will drop pressure!Rx: Valve surgery

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