Shock and Resuscitation

A good reference for this: the Guyton model https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20028/cardiac-output-curves-and-vascular-function-curves

Somewhat controversial validity and applicability to shock physiology, FWIW.

Thinking: in normal states, venous return limits CO. However, with severe heart failure, this can not be true. Discussed 7-9 minutes here:

Goal: deliver more oxygen (Increased DO2)

Variables to optimize: Hgb, CO (=SV, HR), SaO2

Remember: DO2 = delivery of O2. VO2 = consumption of O2.

DO2:VO2 ratio is normally 4:1-5:1 ish (meaning, the body pumps 4-5x as much o2 to body as needed at any given moment, provides a buffer for instantaneous increase in demand; said another way - A normal Oxygen extraction ratio (SaO2-SvO2) / SaO2 is ~20-25%. ). When DO2 < VO2, anaerobic threshold has been reached (usually doesn't occur for whole body at once).

DO2:VO2 = SaO2 / (SaO2 - SvO2). Thus, SvO2 50% with SaO2 ~100% = 2:1 ratio, which has empirically been shown to be near the anaerobic threshold.

Consider this: why do we care so much about blood pressure? If perfusion is the end-goal, and the conductance of ALL the tissues increased (e.g. resistance decreased) - the delivery of oxygen would be UNCHANGED even if the map lowered.

Is it related to imbalances in changes in conductance? (e.g. some areas remain adequately perfused, others do not), or to the stressed vs unstressed volume (e.g. relaxed venous circulation lowers preload, discussed below).

Determinants of Cardiac Output: Venous Circuit

Refs: 2 part series

DOI: 10.1097/CCM.0b013e3182772ab6
DOI: 10.1097/CCM.0b013e31827bfc25

Ways to start. Imagine you have somebody with a cardiac output of zero. His blood pressure also zero? No. Consider this, for that person what would happen if you gave them a liter of fluid? Or 10 L of fluid? Clearly blood pressure would go up some because the volume contained in the distensible vessels would become under pressure much like inflating a balloon.

Another thing to consider, in the classic cardiac output equals stroke volume times heart rate, why is it that pressers increase delivery of oxygen? Or do they? It's not easy to answer because this model

Is incomplete in describing those mechanics. Keep in mind our models or just maps of the territory and don't always explain all the relevant factors. A better model is that a venous return

Classically, CO depends on HR, Contractility, Preload, Afterload (Left Ventricle / Cardiac Function centered). However, in critically ill patient's it is often not just (or primarily) the LV that is malfunctioning - it often makes more sense to view from venous circuit function (because conceptually, at steady state CO must equal Venous return) - dependent on vascular volume, tone, and intrathoracic pressure.

(Formalized: since VR and CO must equal in a closed system and the only way LH functioning can influence PRA (not stressed blood volume, vessel capacitance, or resistance) - under most pathophysiological conditions the LV will not be the limiting function)

Think about the myriad of ways LV function fails to explain observed physiology in the ICU: why don't we give inotropes to increase DO2? What of these parameters do vasopressors modify? Why do cirrhotics crump? etc. - the model is incomplete. Time to paint a more complete map.

Role of venous system = 1.) act as a conduit of blood return and 2.) serve as a reservoir to circulating blood volume

systemic veins are 30x more distensible than arteries, thus 70% of intravascular volume is in the veins (mostly small veins and venules - 20-33% is in the splanchnic circulation) - thus veins are termed capacitance vessels.

Why would it be designed this way? need to be able to maintain RV filling despite changes in blood volume.

Venous return = (P_inlet aka Pmcf - P_outlet aka PRA) / Resistance_to_venous_return.

This can be represented by the Guyton Diagram

[this is analagous to CO = (MAP - PRA) / SVR, an application of Hagen-Poiseulle's law]

Of note, if the Pressure outside the vessels is higher than in the vessels, it will function like a starling resistor and flow will go to 0.

Mean circulatory filling pressure (Pmcf): pressure in vascular system in the absence of flow. = degree vascular system is stretched by contained volume. During flow, post-capillary venules are thought to most closely approximate Pmcf. In normal times, 12 mmHg. With normal stressed volume (see below), 1L of blood volume would raise by 5.3 mmHg

(Note, venous return and cardiac output in a steady state are, by definition, the same)

Consider, a heart starts and the arterial pressure increases while the venous pressure decreases (because the blood left as it was pumped). The artery pressure increases more than the venous pressure decrease because it is arteries are stiffer.

alt

P_mcf - P_RA = flow resistive pressure drop for venous return to the heart. RA pressure roughly = Mean Central Venous Pressure, RVEDP)

Thus, if PRA increases, EDV increases but Venous Return decreases (because P_mcf - PRA is smaller = less flow resistive pressure drop).

Also of note: the Right Atrial filling pressure = PRA - P_pleural (because this is the tension on the wall of the atrium). This varies by the respiratory cycle (and whether a patient is intubated/has pleural disease). When P_pleural is below atmospheric, extrathoracic veins will collapse and venous return goes to 0.

Qt = CO = Venous return depends on:

Right atrial pressure
Mean Circulatory Filling Pressure
Wall tension of the venous circuit

MCFP depends on:

vascular capacitance (decreasing capacity by increasing neural tone e.g. vasopressors. Functionally, this converts unstressed volume to stressed volume)
stressed blood volume (Vt, changable by giving crystalloid, or by giving pressors to mobilize unstressed volume into stressed volume)

Ross, Linhart Braunwald: Effect of Changing Heart Rate in Man by Electrical Stimulation Right Atrium -> paced heart rate from 60 to 120 with no change in cardiac output. Why?

From venous circuit stand-point: Venous return per second(= cardiac output) depends on (Pcmf - RA pressure) / flow resistance. PCMF = f(vessel elastance, blood volume), neither of which changed. Thus, though the HR went up, the preload likely decreased in kind (because there is less volume filling in to heart for each beat).

####Stressed vs Unstressed Volume:

Unstressed volume = the volume in the venous vasculature where if you added more, pressure (in the venous system) would not increase because the vessels would distend to accomodate. AKA volume in circ system when P_transmural = 0. E.g. taking a collapsed band and inflating it. 70-85%

Stressed volume = more volume leads to more pressure. (P_transmural > 0). E.g. stretching the elastic band. The amount the transmural pressure increases depends on the vascular compliance. Empirically, 15-30% of total blood volume is stressed volume.

Total Vascular Volume = Stressed + Unstressed Volume.

alt

Hypovolemic

In terms of venous return: the initial insultleads to loss of stressed volume and therefore P_mcf decreases. (A->B below)

Response (b->c->d->e): catecholamines move unstressed volume into stressed volume. Also, acute phase reactants increase oncotic pressure to draw more fluid into stressed volume (a few hundred cc's in 6-12 hours)

alt

Why would intubation before resuscitation be particularly problematic in hypovolemic shock?

induction agents = increase venous capacitance, much of compensation from catecholamines that moved unstressed->stressed volume is undone
positive intrathoracic pressure will decrease mean resistive pressure drop of venous return.

####Hemorhagic shock

hemorrhage over 15-30%... = 750-1500+ cc blood loss
control the bleeding
replace the volume (blood > crystalloid if in shock: Transfuse 1:1:1 rbcs, plasma, platelets. Consider CaCl, Abx redose, TXA, DDAVP, Vit K vs PCC) via 18g peripheral (resistance proportional to length / radius to 4th. PICC has 30x the resistance, CVC has 6-16x the resistance. Mac introducer has 0.35x the resistance. IO is the same.)

####Volume losses (insensible, diarrhea, excessive UOP)

Distributive

Stressed volume moves to unstressed volume as a result of increased vascular capacitance (vasodilation). Additionally, total volume decreases from increased permeability (from inflammatory response / "3rd spacing"). Thus, there is often a component of "hypovolemia" to initial distributive shock physiology. Takes .5-2L to reverse this (to move from point B to points C & D). Often, some degree of myocardial depression is accompanied (in septic shock anyway)

alt

Sepsis

Consider: how does infusing fluid that has no oxygen carrying capacity increase oxygen delivery? (A: in improving pump and pipe dynamics)
Historically EGDT (2001 ED-based): crystalloid for CVP 8-12, Pressors for MAP 65-90, Transfuse to hct 30 then inotrope for ScvO2 70+%
Q = HR * SV = change in pressure / resistance. In systemic circulation, MAP - CVP = change in pressure.
CVP (off IVC, central line, PICC - all same. no valves) is surrogate RVEDP. However, RVEDP and RVEDV are not linearly related (not perfectly elastic). At IMC, ~23% of fluid boluses increase cardiac output by 15+%(retrospective). Dynamic > static measures.. but have to be sure that R heart preload = L heart aka no obstructive shock.
Colloid vs Crystalloid: SAFE, CRISTAL trials = no difference in mortality.
PROMISE, PROCESS, ARISE: more recent, no difference to EGDT vs usual care (had changed to less fluid given).
Positive fluid balance may be harmful (retrospective, confounding by indication? CLOVERS trial will answer). Early diuresis may be helpful (FACTT trial)

also neurogenic, anaphylactic, pancreatitis

Obstructive

PE, Tamponade, Tension pneumothorax

In tension PTX, the flat portion of the venous return curve shifts to the right, as the increased pleural pressure leads to collapse of the IVC (ie. functioning like a starling resistor) at a higher pressure (when P_outside is over P_inside).

alt

Note: importantly, this change in the curves also occurs with mechanical ventilation, where the pleural pressure is positive.

Cardiogenic

alt

CHF - frank starling flatter

Acute MI

How do you assess adequate DO2?

SvO2 (or surrogate, ScVO2) and assessing the O2 extraction ratio as it approaches 50%... however, this does not account for unequal distribution of oxygen delivery to different tissue beds. Hence, lactate's appeal (though, it should be noted, the idea that lactate is predominantly generated by hypoperfusion is controversial:

As it turns out, lactate is not generally produced as a result of tissue ischemia as much as increased pyruvate production (and subsequent shunting to lactate to be used as brain/CV fuel) during stress. Thus improvement in lactate = lessening physiologic stress, not restoration of perfusion.

Therefore, UOP, mentation, cap refill are often equally important to integrate (and SvO2 & lactate clearance are not goals in themselves)

Causes of high S[c]Vo2? delivery of o2 in excess of demands, impaired cellular oxygen use, microcirculatory shutning

Causes of low S[c]VO2? inadequate oxygen delivery to meet metabolic demands.

Note: there is some thought that CO2 gap (the difference between mixed venous Co2 and arterial CO2) might be a better marker for poor microvascular perfusion - https://journals.lww.com/ccmjournal/Fulltext/2020/12000/The_Use_of_Central_Venous_to_Arterial_Carbon.22.aspx

#Vasopressors Vasopressors

#Fluid

D5W = 1000 ml -> 100 ml intravascular
NS / LR = 1000 ml -> 250-300 ml after 30 minutes. (note, more stays intravascular if hypovolemic)
7.5% saline = 250 ml -> 1000 ml

#CVP How and when are CVP and Preload different?

CVP measures the transmural pressure between the RA and the atmosphere (where the catheter is zeroed). Preload measures the pressure from the inside of the heart to the outside of the heart (e.g. intrathoracic pressure aka pleural pressure, equilibrates with esophageal pressure. "Filling pressure of the heart at the end of diastole" - right before the v-wave).

Thus, if you switch breathing/intrathoracic pressure from spontaneous respiration to positive pressure ventilation (e.g. BiLevel or entracheal intubation), you'd expect CVP to increase, despite preload decreasing.

Can CVP be negative (with the IVC not collapsed)?

Yes - if intrathoracic pressure is below atmospheric (the usual state in healthy, spontaneously breathing adults), then the transmural pressure of the walls of the IVC / Right atrium can still be positive yet the measured pressure (zero'ed to atmosphere) can be negative.

What measure of pressure is the CVP given in? How does it convert to physical exam?

mmHg = measured. cmH2O = observed. 10 cmH2O = 7.5 mmHg

CVP is determined by Venous Volume and Caval Compliance (usually ignored) - The venous volume is the relationship between venous return and CO. If CO drops and venous return is the same, CVP goes up.

CVP is NOT an indicator of volume status.

alt

https://pulmccm.org/review-articles/icu-physiology-1000-words-defense-central-venous-pressure/

Of note: volume status (=where the \ angled line is on the Guyton diagram) and volume responsiveness (whether or not you're on the flat portion of the starling curve) are not synonymous - if you have depressed cardiac function, you can be both hypovolemic and not fluid responsive.

###IVC Collapse IVC collapsability? Gives marker of CVP as compared to abdominal pressure (collapses when it drops below). There is no "Thoracic IVC" - as soon as it enters the thorax from the abdominal cavity, it enters the RA.

RA Pressure will drop from: a decrease in pleural pressure (spontaneous breaths with higher effort), a leftward shift in the venous return curve (less stressed volume due to volume loss or loss of venous tone), or an increase in the RV function

Abd pressure will increase if belly breathing or decreased abdominal compliance.

PEEP's influence? Increases the pressure at which the IVC will begin to function as a Starling resistor - and will thus increase the CVP at which the IVC will collapse. https://pulmccm.org/critical-care-review/icu-physiology-1000-words-ivc-collapse-revisited-part-1/

##Venous Oxygen SvO2 vs ScvO2?

SvO2: measured via pulmonary artery catheter, contains IVC and SVC blood. 0.5 or less = extraction occuring to a point where tissue dysoxia is likely. 0.8+ = high flow state (sepsis via microvascular shunting, hyperthyroidism, severe liver disease)
ScvO2: measured via a central line, reflects blood from SVC. Used in Rivers/EGDT study as a surrogate for SvO2. Slightly lower than (5%) SVo2 because the brain extracts relatively more oxygen

Uses: can calculate CO and CI by Fick (decision to add inotrope)

Septic/distributive shock: Vaso(veno)dilation leads to an increase in the unstressed volume, and thus a decrease in the forward flow / venous return to the heart. Can either: add vasopressors to decrease the unstressed volume, or can add volume to fill up the unstressed volume.

Hemorrhagic shock: unstressed volume remains constant, but the overall volume is lost - thus the only correct strategy is to refill the unstressed volume.

References

https://derangedphysiology.com/main/cicm-primary-exam/required-reading/cardiovascular-system/Chapter%20028/cardiac-output-curves-and-vascular-function-curves

https://heart-lung.org/modules-2

Physiology chalk talk

Explain the relationship between static pressures measured within the right atrium and cardiac pre-load, and the factors that might disrupt that relationship.

CVP vs Preload

Preload definition (https://journals.physiology.org/doi/full/10.1152/advan.00050.200): myocardial sarcomere length just prior to contract (functionally, end-diastolic volume) or myocardial sarcomere tension (functionally, end-diastolic pressure)

Determinants? -Pressure filling the ventricle (intrathoracic pressure, CVP, resistance to return) -Compliance of the ventricle (pericardial compliance, ventricular wall compliance)

Why intrathoracic pressure? RV and RA are thin walled. When you take spontaneous breaths, intrapleural pressure is negative and this equilibrates with RV and RA

Scenario 1: why do people pass out, or feel light headed, during or after a big deadlift? (https://onlinelibrary-wiley-com.ezproxy.lib.utah.edu/doi/epdf/10.1111/apha.12639) Phase 1: increase in MAP as intrathoracic pressure increase from valsalva is transmitted to the arterial tree (increase in MAP parallels increase in pleural pressure - think of this pushing aorta out). Of note, the pressure goes backward into the venous circulation into the valves - maintaining some forward flow). In a weird way, venous valves might make it so that we don't die whenever we valsalva. Of note, intraabdominal pressure also increases.

Estimates of degree: esophageal pressure ~200 mmHg, https://doi.org/10.1016/S0140-6736(73)90974-4

Leads to transient BP of

Phase 2: 3s in, atrial filling declines and stroke volume / MAP declines, HR increases Phase 3: strain released, thoracic pressure drops, and MAP temporarily drops Phase 4: the elevated cardiac output pics up the slack (temporary increase in MAP, can lead to passing out)

(Note some people say to use the forced exhalation maneuver instead of VM to avoid black out after)

Scenario: “Why does my fellow think that the blood pressure of my patient with ARDS and hypotension might increase with a liter of crystalloid even though his right atrial pressure is already 10 mm Hg?

Are they intubated and passively ventilated (with normal compliance vs super stiff lungs vs very obese)? Are they intubated and not passively ventilated? Are they not intubated and spontaneously breathing? Are they not intubated and on BiPAP/Helmet? Do they have RV failure because they're day 45? Pericardial tamponade/restrictive pericarditis? Tricuspid Stenosis? Submerged in water by 20cm and breathing through a snorkel?

Can the IVC collapse in the scenario?

Note: PEEP does, empirically, raise the upper abdominal pressure.

TTE estimations of CVP when intubated.

CVP determined by (the place where the venous return curve and the cardiac function curve cross paths.)

VR - increases CVP with increased venous return. depends in MCFP: volume and capacitance of venous beds, and venous resistance to flow
Cardiac function - increases CVP with decreased function
Intra-thoracic pressure - spontaneous inspiration = negative, positive pressure ventilation = positive. Intubated PEEP but breathing spontaneously -> depends on Pmus vs Pvent

How much does PEEP increase intrathoracic pressure? Depends on compliance of lungs and chest wall... in health, it's about 50/50. However, horrible ARDS? Most of that PEEP will be used in expanding the lungs, relatively less for the chest wall -> smaller increase in intrapleural pressure.

---> changes in PEEP and how they transmit to the CVP seem like they could also approximate chest wall vs lung compliance, though you'd have other heart-lung interactions that would complicate things.

IVC collapses whenever CVP < Abdominal pressure. Thus, PEEP/ intrabdominal pressure (or ascites, obesity) could also.

Note: 1 other place this could fall apart: tricuspid stenosis (OR afib, less pressure)