Shock, Ischemia, CPR Papers

Lascarrou et al, 2019

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm

Objective: The objective of the Therapeutic Hypothermia after Cardiac Arrest in Nonshockable Rhythm (HYPERION) trial was to assess whether moderate therapeutic hypothermia at 33*C as compared with targeted normothermia (37*C) would improve neurologic outcome in patients with coma who had been successfully resuscitated after cardiac arrest with nonshockable rhythm

Results:

• From January 2014-January 2018, a total of 584 patients from 25 ICUs underwent randomization and 581 were included in the analysis

• On day 90 a total of 29/284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17/297 (5.7%) in the normothermia group

• Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively)

• Moderate therapeutic hypothermia improved the neurologic prognosis but not survival at 90 days whereas the opposite has been reported for epinephrine

  • The number needed to treat for one additional patient to survive with a CPC score of 1 or 2 is 22 with hypothermia as compared with a number needed to treat to prevent one death of 15 with bystander CPR and 112 with epinephrine

• The incidence of prespecificed adverse events did not differ significantly between groups

Conclusion: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypthermia at 33*C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia

Delivery of Oxygen (DO2) Equation

DO2 = CO x CaO2

Arterial Oxygen Content (CaO2) Equation

(1.36 x [Hb] x SaO2) + (0.03 x PaO2)

Oxygen Consumption (VO2) Equation

CO x (CaO2 - CmvO2) DO2 x O2ER

Oxygen Extraction Ratio Equation (O2ER)

(VO2/DO2)

or

(CaO2-CmvO2)/CaO2

Under aerobic conditions, what is total oxygen consumption (VO2) proportional to?

The metabolic rate and dependent on the body’s energy requirements (supply indpendent)

Fick Principle

The amount of oxygen going into an organ minus the amount of that oxygen coming out of the organ, is equal to the oxygen utilization rate (VO2)

What % of the delivered oxygen does the body normally use?

About 20-30%

What happens as delivery of oxygen declines?

VO2 is initially maintained by increases in oxygen extraction (flow or supply-independent VO2)

With continued losses in effective circulating volume CO2 eventually decreases beyond a critical point (DO2crit) where compensatory increases in O2ER are no longer able to adequately maintain VO2 (flow-dependent VO2)

• Usually occurs when O2ER reaches 0.6-0.7

Cellular Response to Reaching DO2crit

Cellular hypoxia ensues, resulting in mitochondrial respiratory dysfunction and transition from aerobic to anaerobic metabolism with lactate formation and development of metabolic acidosis

Eventually cellular ATP becomes depleted, jeopardizing the cell’s ability to maintain the electrical gradient across its cell membrane due to failure of membrane-associated ion transport pumps, particularly sodium and calcium

Loss of the membrane electrical gradient and integrity allows an influx of Na, Ca, and water into the cell, causing cell swelling and eventually cellular lysis and necrosis

Cellular acidosis, oxygen-free radical generation, and loss of cellular adenine nucleotides also contribute to irreversible injury and cell death

Transfusion Recommendations in Humans

Studies have demonstrated that a restrictive transfusion polity (eg, [Hb] <7 g/dL) is at least as effective and possibly superior to a liberal transfusion policy ([Hg] > 10 g/dL)

How does isovolemic anemia change cardiac output?

Increases cardiac output due to restoration of preload and left ventricular stroke volume

Hemodilution of circulating RBCs reduced blood viscosity and therefore resistance to blood flow so the body experiences an overall increase in RBC velocity with subsequent increases in venous return and preload

Volume resuscitation restores systemic mean arterial pressures which further increases RBC velocity and promotes venous return and CO

ATLS Class 1 Hemorrhage

Up to 15% loss

Clinical symptoms of volume loss are not readily observed

ATLS Class 2 Hemorrhage

15-30% loss

Tachycardia and subtle changes in mentation are observed

Blood pressure remains within normal limits

ATLS Class 3 Hemorrhage

30-40% loss

Marked tachycardia

Impaired mentation

Measurable hypotension

ATLS Class 4 Hemorrhage

>40% loss

Vital signs are further deranced and may lead to a complete loss of consciousness

Massive Hemorrhage Definition

A loss of total blood volume within a 24 hour period or loss of half of the total blood volume in a 3 hour period

Systemic Response to Acute Hemorrhage

Marked decreases in effective circulatory volume decrease venous return, cardiac output, and eventually MAP

With progressively declining intravascular volume, the body’s compensatory mechanisms are activated to maintain CO and MAP in an effort to achieve adequate effective circulatory volume, vital organ perfusion, and DO2

Immediate Phase Compensatory Mechanisms

Occurs within minutes following an insult and typically involves baroreceptor-mediated stimulation of the sympathetic nervous system, leading to increased HR, myocardial contractility, and selective vasoconstriction

At slow rates and lower magnitudes of hemorrhage, and in absence of concurrent trauma, patients may experience a depressor reflex where vagal-mediated bradycardia and vasodilation predominate over the baroreceptor reflex in order to preserve blood flow while minimizing bloo dloss

Baroreceptor Response

Baroreceptor stimulation leads to preferential arterial vasoconstriction and venoconstriction of capacitance vessels within the skin, skeletal muscles, and splanchnic circulation, allowing for blood to be shunted to the more vital organs (heart, brain, lungs)

Heart rate increases and CO is maintained despite decreased preload

Chemoreceptor Response

The presence of metabolic acidosis due to hypoperfusion-induced anaerobic metabolism stimulates peripheral and central chemoreceptors, resulting in increased ventilatory drive and respiratory rate in order to induce a compensatory respiratory alkalosis

Intermediate Compensatory Phase

Charcterized by transcapillary fluid shifts (Starling’s law of the capillary) pulling fluids from interstitial and intracellular compartments into the vasculature

• Transcapillary fluid shifts alone have been shown to return plasma volume up to 50% of the original volume and arterial blood pressure up to ~75% of its original value

Second arm of the intermediate phase involves activation of RAAS

• Angiotensin II mediates vasomotor tone and water retention through stimulating:

  • Norepinephrine release from adrenal medulla and sympathetic nerve termines

  • Vasopressin and aldosterone release

  • Thirst

  • Sodium reabsorption in the proximal tubule by activating Na+/H+ antiporter in the proximal tubules

  • Preferential efferent arteriole vasoconstriction

Vasopressin release is stimulated by an increase in osmolality or a decrease in effective circulating volume

• Binds to V1 receptors causing vsoconstriction

• When bound to V2 receptors in the collecting ducts of the kidneys, induces insertion of aquaporin channels and reabsorption of water

Late or Long-Term Compensatory Mechanisms

Promote a net positive fluid balance in patients 1-48 hours after survival of the initial insult

Primarily influence the renal control system involving the RAAS and influence of ANP

Continued intravascular losses cause compensatory mechanisms to eventually become exhausted and fail to adequately maintain adequate CO, MAP and subsequently tissue perfusion and oxygenation

Compensated Hemorrhagic Shock

Represents the initial physiological responses to hypovolemia and blood loss in which the animal is capable of maintaining its MAP and metabolic needs through compensatory mechanisms

Vasoconstriction results in pale mucous membranes and prolonged CRT in spite of “normotension”

Respiratory rates increase due to decreases in CaO2 and the preceived oxygen debt

What is the first recognizable clinical sign of acute compensatory shock?

Tachycardia with a narrowing pulse pressure (due to decreases in CO with increases in peripheral vasoconstriction)

Decompensated Hemorrhagic Shock

Classified into early/acute decompensated shock and late decompensated shock

Peripheral pulses become unpalpable, the patient becomes stuporous to comatose, systolic cardiac function fails, and respiratory failure and hypoventilation ensues

Irreversible shock is characterized as systemic vasodilation with decreased cardiac filling pressures, myocardial systolic depression, and widespread evidence of cell dysfunction

What are the hallmark findings of decompensated hemorrhagic shock?

A precipitous drop in MAP and systemic hypotension

Post-Hemorrhage Dysrhythmias

May be due to sympathetic activation leading to enhanced myocardial automaticity, ectopic pacemaker activity, or reperfusion

Acute Traumatic Coagulopathy (ATC)

Develops within 20-30 minutes post-injury and is considered unrelated to the actual loss, consumption, inhibition, or dilution of hemostatic factors or platelets

Six Proposed Precipitants of Acute Traumatic Coagulopathy

Tissue injury

Hypoperfusion (shock)

Systemic inflammation

Metabolic acidosis

Hypothermia

Hemodilution

What are the two main drivers of acute traumatic coagulopathy?

Shock due to ongoing tissue hypoperfusion and severity of tissue injury

• Tissue injury activates both clotting and fibrinolytic systems

• Hemodilution, metabolic acidosis, and hypothermia that develop subsequent to liberal fluid resuscitation and that persist throughout the resuscitative period potentiate ATC and hinder therapeutic efforts

Trauma Induced Coagulopathy (TIC)

Extension of ATC due to resuscitation-induced acidosis, hypothermia, and hemodilution

Lethal Triad or Trauma Triad of Death

Coagulopathy

Acidosis

Hypothermia