1. Circulatory shock Vasopressors

2. Shock: definition
Shock is the physiologic state characterized by significant reduction of systemic tissue perfusion, resulting in decreased tissue oxygen delivery.
This creates an imbalance between oxygen delivery and oxygen consumption.
Prolonged oxygen deprivation leads to cellular hypoxia and derangement of critical biochemical processes at the cellular level, which can progress to the systemic level

3. Shock: Stages
Preshock = warm or compensated shock: rapid compensation for diminished tissue perfusion by various homeostatic mechanisms (↑HR, peripheral vasoconstriction, ↑or↓ in BP)
Shock: the compensatory mechanisms become overwhelmed and signs and symptoms of organ dysfunction appear (↑HR, dyspnea, oliguria, acidosis).
End-organ dysfunction: progressive end-organ dysfunction leads to irreversible organ damage and patient death.

4. Pathogenesis
Impairment in tissue perfusion and vasomotor paralysis that could become irreversible
Mechanisms for the vasodilatation
1. Opening of ATP-Sensitive Potassium Channels→ hyperpolarization of Vascular Smooth Muscle→↓Ca entry
→persistent vasodilation
2. Increased Synthesis of Nitric Oxide
3. Generation of free radicals
4. Deficiency of Vasopressin due to exhaustion of hypophyseal stores and rapid degradation of vasopressin in plasma

5. Classification of Circulatory Shock
HYPOVOLEMIC
Hemorrhagic
Trauma
Gastrointestinal
Retroperitoneal
Fluid depletion (nonhemorrhagic)
External fluid loss
- Dehydration
- Vomiting
- Diarrhea
- Polyuria

6. Classification of Circulatory Shock
CARDIOGENIC
Myopathic (myocardial infarction, nonischemic cardiomyopathy, septic or pharmacologic myocardial depression)
Mechanical (valvular failure, hypertropic cardiomyopathy ventricular septal defect)
Arrhythmic

7. Classification of Circulatory Shock
EXTRACARDIAC OBSTRUCTIVE
Impaired Diastolic Filling
Direct venous obstruction (obstructive tumor)
Increased intrathoracic pressure(tension pneumothorax, status asthmaticus)
Decreased cardiac compliance (constrictive pericarditis, cardiac tamponade)
Impaired Systolic Contraction
Right ventricle ( massive PE, acute PAH)
Left Ventricle ( aortic dissection)

8. Classification of Circulatory Shock
DISTRIBUTIVE
Septic (bacterial, fungal, viral, rickettsial)
Toxic shock syndrome
Anaphylactic, anaphylactoid
Neurogenic (spinal shock)
Endocrinologic( Adrenal crisis, thyroid storm)
Toxic (nitroprusside, bretylium)

9. Shock: Clinical presentation
Cardinal findings
- hypotension
- oliguria
- cool and clammy skin
- abnormal mental status
- metabolic acidosis
Suggestive findings suggest a particular type of shock

10. Shock: Evaluation
History: including medications, allergies, procedures, comorbidities, immunocompromised state
Physical examination: JVP, left S3, S4, gallop, new murmurs, arrhythmia, rub, pulsus paradoxus,peripheral edema, fever, rigors, infection focus, abdominal tenderness, GI bleeding, neurological exam, rashes
Laboratory data: Blood work (CBC, Chem, LFT, Amylase/lipase, coags, lactate, ABG), EKG, imaging (Chest/abdominal Xray, CT, Echo), toxicology

11. Pulmonary artery catheter
Diagnosis
PCWP = preload CO
SVR =
afterload
Tissue perf = sVO2
Hypovolemic ↓ ↑
Cardiogenic
Distributive
↓or↔
↑or↔
Obstructive
↔or↓
↑PVR

12. A Clinical Approach to Shock Diagnosis and Management
Immediate Goals in Shock
Hemodynamic support MAP > 60mmHg PAOP = mmHg Cardiac Index > 2.2 L/min/m Maintain oxygen delivery Hemoglobin > 9 g/dL Arterial saturation > 92% Supplemental oxygen and mechanical ventilation Reversal of oxygen dysfunction Decreasing lactate (< 2.2 mM/L) Maintain urine output Reverse encephalopathy Improving renal, liver function tests

13. Shock: Management Hypovolemic Cardiogenic Distributive Obstructive
Rapid volume replacement (saline, blood products)
Idenify source of loss
-Endoscopy
-Angiography
-MRI/CTscan
LV infarct
-IABP
-revascularize
RV infarct
-fluids/inotropes
Valve problem
-surgery
Septic
-Antibiotics
- Fluids, pressors, inotropes
- Goals:
SV02 > 70% improving organ function
decreasing lactate levels
Pericardial tamponade
pericardiocentesis
surgical drainage
Pulmonary embolism
Heparin
VQ scan/CTA
Consider tPA/embolectomy

14. Shock: Management Fluids ▪Crystalloids, isotonic (NS)
▪20 mL/kg fluid challenge in hypovolemic or septic shock with re-challenges of mL/kg
▪ mL challenges in cardiogenic shock

15. Vasopressors
induce vasoconstriction and elevate mean arterial pressure
few controlled clinical trials have directly compared these or documented improved outcomes
adrenergic receptors relevant to vasopressor activity
▪ ά-1 in vascular walls, induces vasoconstriction. Also in the heart and can ↑ the duration of contraction but no ↑ chronotropy
▪ β-1 in the heart, mediate ↑ in inotropy and chronotropy with minimal vasoconstriction
▪ β-2 in blood vessels induce vasodilation
▪ dopa in renal, splanchnic, coronary, and cerebral vascular beds; stimulation leads to vasodilation. A second subtype causes vasoconstriction by inducing norepinephrine release (high doses of medication)

16. Dopamine Precursor of norepinephrine and epinephrine
Increases MAP and CO due to increase in SV and to a lesser extent to a HR. Increases CI
Increases oxygen delivery but effects on oxygen consumption mixed (microcirculatory flow)
Dose dependent effects
<5 mcg/kg/min→dopa receptors →vasodilation in renal and mesenteric beds
5-10 mcg/kg/min →β1 receptors →increase in cardiac contractility and heart rate
>10 mcg/kg/min →ά1 receptors→vasoconstriction and increase in BP

17. Norepinephrine
Potent ά-adrenergic agent with less pronounced β-agonist effect
Increases MAP by vasoconstriction, 10-15% increase in CO and SV
More potent than Dopamine
Dose range: start with mcg/min, increase up to 30 mcg/min
Improves tissue oxygenation
Effect on renal hemodynamics- !adequate volume resuscitation prior to norepi start
Effect on splanchnic blood flow - mixed results

18. Phenylephrine
Selective ά-1 adrenergic agonist, increases BP by vasoconstriction.
Rapid onset of action, short duration, primary vascular effect
Concerns for potential reduction in CO
Dose range: start with mcg/min and increase to mcg/min until BP stable.
Second line agent
Consider in tachyarrhythmias limiting therapy with other vasopressors.

19. Vasopressin
Peptide hormone, synthesized in the hypothalamus, stored in pituitary gland. Released in response to decreased intravascular volume, increased osmolarity
Constricts vascular smooth muscle via V1 receptors
Increases vessel responsiveness to catecholamines
Low steady dose vasopressin Units/min
Vasopressin (0.03 Units/min) + Norepinephrine safe
No effect on mortality

20. Dominant clinical effect
Drug ά1 β1 β2
dopa
Dominant clinical effect
Phenylephrine
+++
SVR ↑↑, CO↔/↑
Norepinephrine ++
Epinephrine
CO↑↑, SVR↓(low dose),
SVR ↑ (higher dose)
Dopamine
mcg/kg/min + CO
5-10 mcg/kg/min
CO↑, SVR ↑
10-20mcg/kg/min
SVR ↑↑
Dobutamine
0/+
CO↑, SVR↓
Isoproterenol
Vasopressin
SVR ↑↑, CO↔

21. Vasopressors: complications of use
Hypoperfusion
Dysrhythmias
Myocardial ischemia
Local effects
Hyperglycemia
NO STUDY HAS DEMONSTRATED A SURVIVAL BENEFIT DUE TO ONE VASOPRESSOR COMPARED TO ANOTHER