ST.

LIDETA LEMARYAM TENA SCIENCES AND BUSINESS COLLEGE

Department of Pharmacy
THERAPY 2 ASSIGNMENT
Group 2
Section E
GROUP MEMBERS ID NO

1. Beza Abebe………………………………………475/14
2. Yanet Ashebir…………….......…………….......467/14
3. Feven Amare…...………………………………...428/14
4. Husniya Abdi.…………………………………….443/14
5. DemekeBasazin….……….………...……….….499/14
6. Alferid Delgeba…………………………………..935/14
7. Zakir Nasir………………………………………...486/14
SHOCK
 CONTENTS
 Introduction
 EPIDEMIOLOGY
 ETIOLOGY

 PATHOPHYSIOLOGY

 CLINICAL PRESENTATION

 DIAGNOSIS AND MONITORING

 GOAL Of TREATMENT

 General Approach to Treatment

 Non-Pharmacologic Therapy

 Pharmacologic Therapy

 EVALUATION OF THERAPEUTIC OUTCOMES

INTRODUCTION

 Shock is a broad term for a heterogeneous group of syndromes that cause

an acute, generalized form of circulatory failure.
 associated with inadequate oxygen utilization by the cells.
 Circulatory shock is a medical emergency
 If not addressed promptly, it can quickly lead to serious consequences
 Typically, shock is characterized as:

 a systolic blood pressure (SBP) <90 mm Hg (or acute reduction of at least

40 mm Hg from baseline) or

 mean arterial blood pressure (MAP) <70 mm Hg with tachycardia

 organ perfusion abnormalities.

 The key feature of all shock syndromes is inadequate tissue and organ
perfusion.
:
 EPIDEMIOLOGY
 Shock is not a reportable category by state and federal agencies that track
causes of death and, thus, the true incidence is unknown.

 Reported mortality of patients with shock in clinical studies from the 1980s

exceeded 70%, but now ranges from 20% to 55%.

 However, estimates of deaths due to shock are complicated by

differences in definitions and classification systems.

 ETIOLOGY
• Shock is typically classified into one of four etiologic mechanisms:

(1) hypovolemic, are both encountered in about 16% of cases

(2) Cardiogenic,

(3) obstructive……….. rarely encountered (about 2% of cases).

(4) Vasodilatory /distributive….the most common (about two-thirds of all shock cases requiring
vasopressors.
• Notably, patients may have more than one shock syndrome on presentation
• The categories are not mutually exclusive and patients can transition from one shock type to another

• (e.g., a patient with cardiogenic shock may subsequently develop septic shock, or a patient with
septic shock may develop cardiogenic shock from a myocardial infarction).
• Hypovolemic, cardiogenic, and obstructive shock are all characterized by

 Low cardiac output (CO), but the mechanism for low CO is different in each shock state

• Hypovolemic shock

 is caused by inadequate venous return

 from internal or external loss of intravascular fluids

 (eg, trauma, surgery, or haemorrhage), resulting in insufficient cardiac preload and

• decreased stroke volume.

• Cardiogenic shock

results from a loss in pump function, either through decreased cardiac

contractility (eg, myocardial infarction), acute valvular abnormality, or
an arrhythmia (eg, ventricular tachycardia).

• Obstructive shock

results from an extra-cardiac obstruction to blood flow into or out of the

heart, such as tension pneumothorax, cardiac tamponade, or pulmonary
embolism
• Vasodilatory/distributive shock

 is distinctly different from other three forms of shock because it is characterized by a

loss of vascular tone.

 is a general term that describes tissue hypo-perfusion due to a decrease in SVR (or

hypo-perfusion despite a normal or elevated CO).

• Distributive shock

 is a subset of vasodilatory shock characterized by misdistribution of blood flow in the

microcirculation (consisting of arterioles, capillaries, and venules) or at the organ level.

 Septic shock causes vasodilatory/distributive shock in 96% of cases,

 It can also be caused by a number of conditions, including

 neurogenic shock (typically secondary to acute spinal cord injury),

 immune-mediated (ie, anaphylactic) or

 nonimmunologic (ie, anaphylactoid) reactions,

 adrenal insufficiency,

acute liver failure, or as a component of ischemia-reperfusion injury (eg, after

cardiopulmonary bypass or return of spontaneous circulation after cardiac arrest).
 PATHOPHYSIOLOGY

• Each shock syndrome has a different etiology and resultant

pathophysiology.

• Shock results in failure of the circulatory system to deliver sufficient

oxygen (O2) to tissues despite normal or reduced O2 consumption.

• Shock may be caused by intravascular volume deficit (hypovolemic

shock), myocardial pump failure (cardiogenic shock), or peripheral
vasodilation (septic, anaphylactic, or neurogenic shock).
• Hypovolemic shock is characterized by acute intravascular volume deficiency due to
external losses or internal redistribution of extracellular water.

• It can be precipitated by hemorrhage; burns; trauma; surgery; intestinal

obstruction; and dehydration from considerable insensible fluid loss,
overaggressive diuretic administration, and severe vomiting or diarrhea.

• Relative hypovolemia leading to hypovolemic shock occurs during significant

vasodilation, which accompanies anaphylaxis, sepsis, and neurogenic shock.
• Fall in blood pressure (BP) is compensated by increased sympathetic
outflow, activation of the renin–angiotensin system, and other factors
that stimulate peripheral vasoconstriction.
• Compensatory vasoconstriction redistributes blood away from skin,
skeletal muscles, kidneys, and gastrointestinal (GI) tract toward vital
organs (eg, heart and brain) in attempt to maintain oxygenation, nutrition,
and organ function.
• Severe lactic acidosis often develops secondary to tissue ischemia
and causes localized vasodilation, which further exacerbates the
impaired cardiovascular state.
Shock syndromes: differentiated based on evaluation of preload, cardiac
output & afterload
 CLINICAL PRESENTATION

• Patients with hypovolemic shock may have thirst, anxiousness, weakness, light-
headedness, dizziness, decreased urine output, and dark yellow urine.

• Signs of more severe volume loss include

 Tachycardia (>120 beats/min),

 Tachypnea (>30 breaths/min),

 Hypotension (SBP <90 mm Hg),

 Mental status changes or unconsciousness, agitation, and

Normal or low body temperature (in the absence of

infection) with cold extremities
• Serum Na+ and Cl- concentrations are usually high with acute volume
depletion.

• BUN : creatinine ratio may be elevated initially, but the creatinine increases with
renal dysfunction.

• Metabolic acidosis results in elevated base deficit and lactate concentrations with
decreased bicarbonate and PH.
• Complete blood cell count (CBC) is normal in absence of infection.
• In haemorrhagic shock, the RBCs, Hgb, and Hct will decrease.
• Urine output is decreased to less than 0.5 to 1 mL/kg/h.
 DIAGNOSIS AND MONITORING

• Evaluation of medical history, clinical presentation, and laboratory findings

• Findings include

• hypotension (SBP <90 mm Hg)

• depressed cardiac index (CI <2.2 L/min/m2)

• tachycardia (heart rate >100 beats/min)

• low urine output (<20 mL/h).

• Pulmonary artery (Swan–Ganz) catheter can be used to determine central venous pressure
(CVP), pulmonary artery pressure (PAP), cardiac output (CO), and pulmonary artery
occlusion pressure (PAOP).
• Renal function can be assessed grossly by hourly measurements of urine output, but
estimation of creatinine clearance based on isolated serum creatinine values may be
inaccurate.

• Decreased renal perfusion and aldosterone release result in sodium retention and thus
low urinary sodium (<30 mEq/L).
TREATMENT

Goals of Treatment

• The goal during resuscitation for shock is to achieve and maintain mean arterial
pressure (MAP) consistently above 65 mm Hg while ensuring adequate perfusion to
critical organs.

• The ultimate goals are to prevent further disease progression

• To reverse organ dysfunction that has already occurred.

Treatment of the patient with circulatory shock can be divided into four phases,

• 1. Salvage: a minimum perfusion pressure and CO must be obtained to

ensure the patient’s survival.
 Concomitant treatment of the underlying etiology of the shock state
 Examples of these treatments include surgical/interventional hemostasis,
antimicrobials and source control for sepsis, and coronary revascularization for
acute myocardial infarction.

• 2. Optimization: to ensuring adequate organ perfusion and DO2.

• 3. Stabilization: the goal is preventing (further) end-organ dysfunction.
•
4. De-escalation: facilitation of patient recovery is targeted where goals
include weaning (or cessation) of vasoactive medications and fluid
elimination.
 General Approach to Treatment

• Initiate supplemental O2 at the earliest signs of shock, beginning with 4 to 6 L/min

via nasal cannula or 6 to 10 L/min by face mask.

• Fluid resuscitation to maintain circulating blood volume is essential.

• If fluid administration does not achieve desired end points, pharmacologic support is
necessary with inotropic and vasoactive drugs.

• Supportive care measures include assessment and management of pain, anxiety,

agitation, delirium, immobility, sleep disturbances, nutrition, glycemic control, and
thromboembolism prophylaxis.
 Non-Pharmacologic Therapy
• Non-Pharmacologic therapy for shock is dependent on the inciting event

• Basic life support measures such as a secure airway with appropriate oxygenation apply
to all patients.

• For patients with hypovolemic shock,

 surgery (including stabilization of fractures),

 control of blood loss by physical compression, endoscopic, or surgical control,

 blood component transfusion, and

prevention of heat loss since hypothermia may aggravate other problems such as

coagulopathy and bleeding.

 Cardiogenic shock secondary to acute myocardial infarction
 Coronary revascularization and
 CO augmentation via mechanical device (eg, intra-aortic balloon pump or
extracorporeal life support).
 Obstructive shock
 including pericardiocentesis or surgical evacuation of fluid for cardiac tamponade, and
needle decompression and/or chest tube thoracostomy for tension pneumothorax.
 Surgical or catheter thrombectomy (for obstructive shock secondary to pulmonary
embolism).
 Vasodilatory/distributive shock secondary to septic shock
 Fever control via external cooling.

 Immune-mediated shock
 discontinued the potentially offending agent(s) and,
 Pharmacologic Therapy
Intravenous Fluids and Blood Products
• The goal is to increase venous return in order to subsequently increase stroke
volume, cardiac output, DO2, and blood pressure.
Crystalloid solutions
• Isotonic crystalloid solutions (0.9% sodium chloride or lactated Ringer solution)
are the initial fluids of choice.
• The choice between normal saline and lactated Ringer solution is based on clinician
preference and adverse effect concerns.
• Crystalloids can be rapidly and easily administered, are compatible with most
drugs, and have low cost.
• Their disadvantages include the need to use large fluid volumes and the possibility
that dilution of oncotic pressure may lead to pulmonary edema.
• Crystalloids are administered at a rate of 500 to 2000 mL/h, depending on severity
of the deficit, degree of ongoing fluid loss, and tolerance to infusion volume.
Colloids

• Albumin, hydroxyethyl starch, and dextran possess the theoretical advantage of prolonged
intravascular retention time compared with crystalloid solutions.

• However, colloids are expensive and have been associated with fluid overload, renal dysfunction, and
bleeding.

Blood products

• Some patients require blood products (whole blood, packed red blood cells, fresh frozen plasma, or
platelets) to ensure maintenance of O2-carrying capacity, as well as clotting factors and platelets for
blood hemostasis.

• Blood products may be associated with transfusion-related reactions, virus transmission(rare),

hypocalcemia resulting from added citrate, increased blood viscosity from supranormal hematocrit
 Vasopressors and Inotropes
Hypovolemic shock:

• Inotropic agents and vasopressors are generally not indicated in initial treatment of
hypovolemic shock (if fluid therapy is adequate), because the body’s compensatory
response is to increase CO and peripheral resistance to maintain BP.

• Use of vasopressors in lieu of fluids may exacerbate this resistance to the point
that circulation is stopped.
• Therefore, vasoactive agents that dilate peripheral vasculature such as
dobutamine are preferred if blood pressure is stable and high enough to
tolerate the vasodilation.

• Vasopressors are only used as a temporizing measure or last resort when other
measures fail to maintain perfusion.
Septic shock

• Initial hemodynamic therapy for septic shock is administration of IV fluid

(30 mL/kg of crystalloid)

• More than 30 mL/kg of crystalloid fluids may be needed to obtain goal MAP,
reverse global hypoperfusion, or achieve clinical indication of regional

organ-specific perfusion (eg, urine production).

• Therefore, dynamic fluid response and clinical assessment should occur

frequently after each fluid challenge.
• Current recommendations are to measure serum lactate and administer 30 mL/kg
of crystalloid for hypotension within 3 hours of presentation and obtain MAP ≥65
mmHg with vasopressors, reassess volume status, and re- measure serum lactate if
the initial lactate was elevated within 6 hours of presentation.

• Although crystalloids and colloids are arguably considered equivalent for shock
resuscitation, crystalloids are generally preferred over colloids (because of ready
availability and lower cost) unless patients are at risk for adverse events from
redistribution of IV fluids to extravascular tissues or are fluid restricted.
• Norepinephrine is the preferred initial vasopressor in septic shock not
responding to fluid administration.
• Epinephrine may be added in cases where there is suboptimal hemodynamic response
to norepinephrine.
• Phenylephrine may be tried as the initial vasopressor in cases of severe
tachydysrhythmias, when CO is known to be high, or as salvage therapy when
combination vasopressors including low-dose vasopressin fail to achieve goals.
• Dobutamine is used in low CO states despite adequate fluid resuscitation
pressures or ongoing signs of global or regional hypoperfusion despite adequate
resuscitation.
• Vasopressin 0.03 units/min may be considered as adjunctive therapy in patients who
are refractory to catecholamine vasopressors despite adequate fluid resuscitation.
Doses of 0.04 units/min or less increase SVR and arterial BP to reduce the dose
requirements of catecholamine adrenergic agents.
• Norepinephrine is first-line therapy for septic shock because it effectively
increases MAP.
• It has strong α1-agonist activity and less potent β1-agonist effects while
maintaining weak vasodilatory effects of β2-receptor stimulation.
• Norepinephrine infusions are initiated at 0.05 to 0.1 mcg/kg/min and rapidly titrated to
pre-set goals of MAP (usually at least 65 mm Hg), improvement in peripheral
perfusion (to restore urine production or decrease blood lactate), and/or achievement
of desired oxygen transport variables while not compromising cardiac index.

• Norepinephrine 0.01 to 2mcg/kg/min improves hemodynamic parameters to “normal”

values in most patients with septic shock.

• As with other vasopressors, norepinephrine dosages exceeding those

recommended by most references frequently are needed in critically ill patients
with septic shock to achieve predetermined goals.
• Phenylephrine is a pure α1-agonist; in sepsis, it improves MAP by
increasing cardiac index through enhanced venous return to the heart
(increase in CVP and stroke index) and by acting as a positive inotrope.
• Phenylephrine 0.5 to 9 mcg/kg/min, used alone or in combination
with dobutamine or low doses of dopamine, improves blood
pressure and myocardial performance in fluid-resuscitated septic
patients.
• Adverse effects, such as tachydysrhythmias, are infrequent,
particularly when it is used as a single agent or at higher doses,
because it does not have β1-adrenergic agonist activity.
• Phenylephrine may be a useful alternative in patients who cannot
tolerate tachycardia or tachydysrhythmias from dopamine or
norepinephrine and in patients who are refractory to dopamine or
norepinephrine.
• Epinephrine has combined α- and β-agonist effects; it is an acceptable choice for
hemodynamic support of septic shock because of its combined vasoconstrictor and
inotropic effects, but it is associated with tachydysrhythmias and lactate elevation.
• As a result, it is considered second-line or as adjunctive therapy to norepinephrine.
Infusion rates of 0.04 to 1 mcg/kg/min alone increase hemodynamic and
oxygen transport variables to supranormal values without adverse effects in septic
patients without coronary artery disease.
• Large dosages (0.5–3 mcg/ kg/min) often are required.
• Smaller dosages (0.10–0.50 mcg/kg/min) are effective when epinephrine is
added to other vasopressors and inotropes.
• Younger patients appear to respond better to epinephrine, possibly because of
greater β-adrenergic reactivity.
• Based on current evidence, epinephrine may be used as a second-line
vasopressor
as added on to norepinephrine in patients with septic shock refractory to fluid
administration.
• Although it effectively increases CO and DO2, it has deleterious effects on the
• Dopamine is generally not as effective as norepinephrine and
epinephrine for achieving goal MAP in patients with septic shock.
• Dopamine doses of 5 to 10 mcg/kg/min increase cardiac index by
improving contractility and heart rate, primarily from its β1 effects.
• It increases MAP and SVR as a result of both increased CO and,
at higher doses (>10 mcg/kg/min), its α1 agonist effects.
• The clinical utility of dopamine is limited because large
dosages are frequently necessary to maintain CO and MAP.
• At dosages exceeding 20 mcg/kg/min, further improvement in
cardiac performance and regional hemodynamics is limited.
• Its clinical use frequently is hampered by tachycardia
and tachydysrhythmias, which may lead to
myocardial ischemia.
• Use dopamine with caution in patients with elevated preload
• Dobutamine is an inotrope with vasodilatory properties (an
“inodilator”).
• It is used to increase the cardiac index, typically by 25% to 50%.
• Dobutamine should be started at dosages ranging from 2.5 to 5
mcg/kg/min.
• Although a dose response may be seen, dosages greater than 5
mcg/kg/min may provide limited beneficial effects on oxygen transport
values and hemodynamics and may increase adverse cardiac effects.
• If given to patients who are intravascularly depleted, dobutamine will result
in hypotension and a reflexive tachycardia.
• Vasopressin produces rapid and sustained improvement in hemodynamic
parameters at dosages not exceeding 0.04 units/min.
• Doses above 0.04 units/min are associated with negative changes in CO and
mesenteric mucosal perfusion.
• It should be used with extreme caution in septic shock patients with cardiac
dysfunction.
• Cardiac ischemia appears to be a rare occurrence when low doses are used;
therefore, use of
higher doses in septic shock patients with cardiac dysfunction
warrants extreme caution.
• In order to minimize adverse events and maximize beneficial effects,
use
vasopressin as add-on therapy to catecholamine adrenergic agents
rather than as firstline
• Vasopressin should be used when response to one or two adrenergic agents
is inadequate or as a method for reducing the dosage of those therapies.
• Increased arterial pressure should be evident within the first hour of vasopressin therapy,
at which time the dose(s) of adrenergic agent(s) should be reduced while maintaining
goal MAP.
• Attempt to discontinue vasopressin when the dosage(s) of adrenergic agent(s) has been

Corticosteroids can be initiated in septic shock when adrenal insufficiency is suspected

(eg, patients receiving long-term corticosteroid therapy for other indications prior to the
onset of shock), when vasopressor dosages are escalating, or when weaning of
vasopressor therapy proves futile.
• Assessment of adrenal function to guide therapy is not recommended.
• Adverse events are few because corticosteroids are administered for a short time,
usually 7 days.

• Acutely, elevated BUN, white blood cell count, glucose, and sodium may occur.
• In general, treatment of septic shock with corticosteroids improves hemodynamic
variables and lowers catecholamine vasopressor dosages with minimal to no adverse
effect on patient safety.
 EVALUATION OF THERAPEUTIC OUTCOMES
• The initial monitoring of a patient with suspected volume depletion
should include:
• Vital signs,
• Urine output,
• Mental status, and
• Physical examination.
• Laboratory tests(electrolytes and renal function tests (BUN and serum
creatinine); CBC, PT and a PTT; and lactate concentration and base
deficit to detect inadequate tissue perfusion.