Fluids and blood Flashcards
Describe the distribution of body water
In the textbook 70 kg male, water represents 60% of the total body weight. This equals 42 L
TBW can be divided into:
* Intracellular volume = 40% of total body weight (28L)
* Extracellular volume= 20% of total body weight or (14L)
ECV can be further divided into:
* Interstitial fluid = 16% of total body weight (11L)
* Plasma fluid = 4% of total body weight or (3L)
Remember 60/40/20 (15/5) or (16/4)- either will work
Which populations tend to have a greater percentage of TBW% by weight? which have less?
Populations with higher TBW% by weight: Neonates
Populations with lower TBW% by weight: Females, obese, and elderly
what are the 2 most important determinants of fluid transfer between the capillaries and interstitial space?
The plasma is in direct contact with the interstitial fluid by way of pores in the capillaries. The movement of fluid between the intravascular space and the interstitial space is determined by:
* Starling forces
* The glycocalyx
Describe the Starling forces in the context of capillary fluid transfer
- Forces that move fluid from the capillary to the interstitium:
(c= capillary, if= interstitial fluid)
* Pc= capillary hydrostatic pressure (pushes fluid out of the capillary)
* (pie symbol) if = interstitial oncotic pressure (pulls fluid out of capillary) - Forces that move fluid from the interstitium into the capillary:
* Pif= Interstitial hydrostatic pressure (pushes fluid into capillary)
* (Pie symbol) c= capillary oncotic pressure (pulls fluid into capillary)
net filtration pressure= (Pc- Pif) - (pie c- pie if)
NFP >0= filtration (fluid exits capillary)
NFP <0= Reabsorption (fluid is pulled into capillary)
What is the glycocalyx, and what factors disrupt it?
The endothelial glycocalyx forms a protective layer on the interior wall of the blood vessel. It can be viewed as the gatekeeper that determines what can pass from the vessel into the interstitial space. It also contains anticoagulant properties.
Disruption of the glycocalyx contributes to capillary leak. Accumulation of fluid and debris in the interstitial space reduces tissue oxygenation. Conditions that impair the integrity of the glycocalyx include:
- Sepsis
- Ischemia
- Diabetes mellitus
- Major Vascular surgery
what is lymph and how does the lymphatic system work?
You can think of the lymphatic system as a fluid scavenger. It removes fluid, protein, bacteria, and debris that has entered the interstitium. It accomplishes this goal with a pumping mechanism that propels lymph through a vessel network line with one-way valves. This creates a net negative pressure in the interstitial space
Edema occurs when the lymphatic system is unable to do its job.
how is lymph returned to the systemic circulation?
Lymph is returned to the venous circulation by way of the thoracic duct at the juncture of the internal jugular and subclavian vein.
You can injure the thoracic duct during venous cannulation. Since the thoracic duct is larger on the left side, there is a greater risk of chylothorax (lymph in the chest) during left-sided IJ insertion.
What is the difference between osmosis and diffusion?
Osmosis is the net MOVEMENT of WATER across a semipermeable membrane, where the direction of water movement is driven by the difference in solute concentration on either side of the membrane (only the solvent moves)
Diffusion is the net Movement of MOLECULES from a region of high concentration to a region of low concentration (solvent AND solute move)
what is osmotic pressure, and what is its primary determinant?
Osmotic pressure is the pressure of a solution against a semipermeable membrane that prevents water from diffusing across that membrane
- osmotic pressure is a function of the number of osmotically active particles in a solution
- It is NOT a function of their molecular weights
what’s the difference between osmolarity and osmolality?
Both are measures of concentration- the amount of solvent within a defined space
* Osmolarity measures the number of osmoles per liter of solution
* osmolality measures the number of osmoles per kilogram of solvent
what is the reference value for plasma osmolarity, and what are the 3 most important contributors?
Plasma osmolarity is normally 280-290 mOsm/L
The 3 most important determinants are: sodium, glucose, and BUN
Plasma osmolarity= 2(Na) + Glucose/18 + BUN/2.8
from this equation, you can see that sodium is the most important determinant of plasma osmolarity
* you should also notice that hyperglycemia or uremia can increase plasma osmolarity
What is the difference between hypotonic and hypertonic solution?
Tonicity compares the osmolarity of a solution relative to the osmolarity of the plasma. Remember that plasma is the reference point we use to make the comparison.
Since plasma is isotonic to cells, we can think about tonicity another way. We can use it to compare the tonicity of a solution to the tonicity of the cells
Isotonic: 285 mOsm/L
Hypotonic: 255 mOsm/L - cells swell
Hypertonic: 315 mOsm/L- cells shrink
Think of all the IV fluids you can. Which are hypo-, iso-, and hypertonic to plasma? Bonus points if you can list osmolarity of each
Hypotonic solutions
NaCl 0.45% - 154 mOsm/L
D5W- 253
isotonic
NaCl 0.9%- 308
LR- 273
Plasmalyte A- 294
Albumin 5%- 300
Hespan 6%- 309
Hypertonic:
NaCl 3%- 1026
D5 NaCl 0.9%- 560
D5 NaCl 0.45%- 405
D5 LR- 525
Dextran 10%- 350
What is the relationship between the hypotonicity and hypertonicity of IV solutions and increased ICP?
Hypotonic solutions have a lower osmolarity than the plasma (or cells). These fluids are the same as giving free water, and this free water distributes throughout all of the body compartments.
This is why hypotonic solutions are poor expanders of intravascular volume and why you should never give hypotonic solution to a pt with increased ICP. It will cause these cells to swell, increase their volume, and increase ICP.
Instead, hypertonic saline is useful for treating cerebral edema (it pulls water out of cells, causing them to shrink)
how does dextrose affect the tonicity of IV fluids?
you may be thinkin that glucose in IVF (such as D5W) should be osmotically active. Well…you’re half right…
* you’re right because the glucose contributes osmotically active molecules to the plasma
* the other side of the story is that this glucose is metabolized to carbon dioxide and water. What’s left over? Water, and this water is, you guessed it… hypotonic.
how do isotonic IV fluids distribute in the patient?
Isotonic solutions have an osmolarity that is very close to the plasma (or cells). These solutions expand the plasma volume and the ECV.
Crystalloids tend to remain in the intravascular space for around 30 min, before moving the the ECF
what complication can result when hypertonic saline is administered too quickly?
Central pontine myelinolysis
Compare the advantages of colloids to the advantages of crystalloids
Crystalloids:
Replacement ration= 3:1
Expands the ECF
Restores 3rd space loss
* existence of the 3rd space is debatable
Colloids
Replacement ration= 1:1
Increases plasma volume (3-6hrs)
Smaller volume needed
less peripheral edema
Albumin has anti-inflammatory properties
Dextran 40 reduces blood viscosity
* improves microcirculatory in vascular surgery
Compare the disadvantages of colloids to the disadvantages of crystalloids.
Crystalloids:
Limited ability to expand plasma volume
* increases plasma volume (20-30 min)
* higher potential for peripheral edema
Large volume of NaCl-> hyperchloremic metabolic acidosis
* Increase Cl -> HCO3 excretion by the kidney
Dilutional effect on albumin
* reduces capillary oncotic pressure
Dilutional effect on coagulation factors
Colloids:
Natural colloids:
Albumin
* binds Ca -> hypocalcemia
synthetic colloids:
FDA black box on synthetic colloids
* risk of renal injury
coagulopathy
* Dextran > hetastarch > hextend
* Don’t exceed 20mL/kg
* not a problem with voluven
Anaphylactic potential
* Highest risk = Dextran
How does Hyperkalemia affect the EKG? (list the events in order of appearance)
Potassium= 5.5-6.5:
* Peaked T waves
Potassium= 6.5-7.5
* P wave flattening
* PR prolongation
Potassium 7-8:
* QRS prolongation
Potassium >8.5:
* QRS -> sine wave-> VF
How do you treat Hyperkalemia?
Cardiac membrane stabilization:
Calcium
Redistribution (shift K intracellularly):
* Insulin +D50
* Hyperventilation
* Bicarbonate
* Albuterol
Elimination
* Potassium wasting diuretics
* Kayexalate
* Dialysis
Discuss the presentation of hypocalcemia
Skeletal muscle cramps
Nerve irritability -> paresthesia and tetany
Chvostek sign
trousseau sign
Laryngospasm
Mental status changes -> seizures
Long QT interval and short PR
discuss the presentation of hypercalcemia
Nausea
Abdominal pain
HTN
Psychosis
Mental status changes -> seizures
Short QT interval and prolonged PR
What is the treatment of hypercalcemia
0.9% NaCl
Loop diuretic
Describe the presentation of hypermagnesemia
Hypermagnesemia complication is usually caused by excessive administration (Think OB and preeclampsia)
* Loss deep tendon reflex = 5.8-10 mEq/L or 7-12 mg/dL
* Respiratory depression = >10 mEq/L or >12 mg/dL
* cardiac arrest = >10 mEq/L or >12 mg/dL
What is the tx for hypermagnesemia
Calcium chloride or calcium gluconate -> directly antagonizes neuromuscular and cardiovascular effects of magnesium
how does hypermagnesemia affect neuromuscular blockade?
potentiates neuromuscular blockade (succ’s and nondepolarizers)
Compare and contrast the consequences of acidosis and alkalosis
what is the anion gap, and what does it tell you?
The anion gap helps us determine the cause of the acidosis
anion ion gap= Major cations - Major anions
or
Na- Cl +HCO3= 8- 12 mEq/L is considered normal
- accumulation of acid (AG>12) -> gap acidosis
- loss of bicarbonate or ECF dilution -> non-gap acidosis
list the possible causes of anion gap acidosis
Mnemonic: MUDPILES
- Methanol
- Uremia
- diabetic ketoacidosis
- Paraldehyde
- Isoniazid
- Lactate ( decreased DO2, sepsis, cyanide toxicity)
- Ethanol, ethylene glycol
- Salicylates (inhibits Krebs cycle)
List the possible causes of a non-gap acidosis
Mnemonic: HARDUP
* Hypoaldosteronism
* Acetazolamide
* Renal tubular acidosis
* Diarrhea
* Ureterosigmoid fistula
* Pancreatic fistula
Large volume resuscitation with NaCl solutions can cause a non-gap metabolic acidosis with hyperchloremia (think trauma)
Discuss the etiology of metabolic alkalosis
under normal conditions, why does blood remain a liquid?
blood exists as a viscous liquid. When there is no injury, blood remains a liquid because:
* coagulation proteins circulate in an inactive form
* the endothelium is smooth, and the glycocalyx repels clotting factors
* undamaged endothelium does not express tissue factor or collagen. This prevents the activation of platelets and the coagulation cascade
* Activated factors are removed by brisk blood flow through the vessels as well as anticoagulants in circulation
When there is a vascular injury, the blood plugs the damaged vessel by forming a clot (it solidifies). Over the next several days, the vessel repairs itself, ad the clot is reabsorbed
what are the 4 steps of hemostasis?
- Vascular spasm
- formation of the platelet plug (primary hemostasis)
- Coagulation and the formation of fibrin (secondary hemostasis)
- Fibrinolysis when the clot is no longer needed
Where are platelets formed? Where are they metabolized?
Platelets are:
* Formed by megakaryocytes in the bone marrow
* Cleared by macrophages in the reticuloendothelial system and the spleen
What is the normal value for platelets? what are the critical values?
Platelet count monitors the number of platelets, but not how well the platelets function. A normal count does not signify normal function.
* normal is 150,000- 300,000 mm^3
* <50,000mm^3 increases surgical bleeding risk
* <20,000mm^3 increases spontaneous bleeding risk
What are the 3 steps of platelet plug formation (primary homeostasis)?
After vascular injury occurs, platelets evolve into a platelet plug via a 3 step process:
1. Adhesion
2. Activation
3. Aggregation
The platelet plug is formed in about 5 minutes
list the 12 coagulation factors
there is no factor 6
Regarding the extrinsic pathway: what activates it? what lab tests measure it? what drug inhibits it?
The extrinsic pathway is activated by vascular injury (tissue trauma liberates tissue factor from the subendothelium).
* it’s measured by the PT and INR
* It’s inhibited by warfarin
Regarding the intrinsic pathway: What activates it? what lab tests measure it? what drug inhibits it?
The intrinsic pathway is activated by blood injury or exposure to collagen
* It’s measured by the PTT and ACT
* It’s inhibited by heparin
What factors are in the extrinsic pathway, intrinsic pathway, and final common pathway?
Extrinsic pathway: 3,7
* “…can be purchased for 37 cents”
Intrinsic pathway: 8, 9, 11, 12
* “ If you can’t buy the intrinsic pathway for $11.98, you can buy it for $12
Final common pathway: 1, 2, 5, 10, 13
* “…can be purchased at the 5 and dime (10) for 1 or 2 dollars on the 13th month”
Describe the process of fibrinolysis.
Since the clot is only a temporary fix while the vessel repairs itself, the body must have a way to break down the clot after it is no longer needed. This process is called fibrinolysis.
- Plasminogen is a proenzyme that is synthesized in the liver. It is incorporated into the clot as it’s being formed, but it lays dormant until it is activated.
- Plasmin is a proteolytic enzyme that degrades fibrin into fibrin degradation products
What are the 3 phases of the contemporary cell-based coagulation cascade?
The contemporary cell-based coagulation cascade attempts to explain how platelets, the extrinsic pathway, and the intrinsic pathway function in an interdependent manner. The idea is that coagulation takes place on the surface of a cell that expresses tissue factor.
the cascade consists of 3 phases:
1. initiation
2. Amplification
3. propagation
What are the components of the TEG?
The TEG provides a “real time” visual representation of disorders of coagulation and fibrinolysis.
Be able to identify TEG abnormalities
What is the mechanism of action of heparin?
Heparin inhibits the intrinsic and final common pathways.
Antithrombin III is a naturally occurring anticoagulant that circulates in the plasma. Heparin binds to antithrombin (AT) and greatly accelerates its anticoagulant ability 1000-fold. The heparin-AT complex neutralizes thrombin and activated factors 9, 10, 11, 12
How do you treat a patient with ATIII deficiency?
AT deficiency is a common cause for failure to achieve anticoagulation despite an adequate heparin dose prior to cardiopulmonary bypass.
Treatment: AT concentrate or FFP
Can a pregnant pt receive IV heparin?
Heparin does not cross the placenta and is safe in pregnancy
What is the normal ACT? What value should be achieved prior to transitioning to cardiopulmonary bypass?
Normal ACT is 90-120 seconds
* ACT should be >400 seconds before going on cardiopulmonary bypass
* ACT is measured before heparin administration, 3 minutes after it’s given, and every 30 minutes thereafter
What are the doses for heparin (for CPB) and protamine?
heparin dose = 300-400 U/kg
Protamine dose= 1 mg for every 100 U of heparin predicted to be in the circulation
how does protamine reverse heparin?
Heparin is a large, negatively charged, water-soluble compound.
Protamine is a highly alkaline compound with a strong positive charge.
The positive charge of protamine and the negative charge of heparin create a neutralization reaction and stop heparin’s anticoagulant activity
What are the side effects of protamine?
Hypotension:
Causes and considerations: Histamine release and administer > 5 minutes
Pulmonary HTN:
TxA2 and serotonin release
Allergic reaction
Previous sensitization to NPH insulin
Fish allergy
Vasectomy
Multiple drug allergies
MOA of warfarin
Inhibits the enzyme vitamin K epoxide reductase complex 1 (VKOR c1), which is responsible for converting inactive vitamin K to active vitamin K
It indirectly blocks the manufacturing of the vitamin K-dependent factors. These include: 2, 7, 9, and 10 and protein C and S
1972
List all of the antidotes for warfarin. When should each be used?
Vitamin K (10-20 mg PO, IM, or IV) may be used to reverse warfarin for non-emergent, minor surgical procedures. It requires 4-8 hours to restore the concentration of vitamin-K dependent clotting factors in the blood
Emergent or high-risk procedures, such as intracranial procedures, require reversal with FFP (1-2 units), recombinant factor VIIa, or prothrombin complex concentrate.
what conditions can cause vitamin K deficiency?
Vit K is a fat-soluble vitamin that requires the presence of fat and bile for absorption. It is also manufactured by bacteria in the gut.
Malabsorptive diseases, impaired GI flora, and decreased bile production can impair fat absorption and therefore create vitamin K deficiency
A deficiency of Vit K leads to coagulopathy
What is the risk associated with IV phytonadione?
Phytonadione (vit K) IV administration is associated with life-threatening anaphylaxis. IV administration is best avoided, however if given by this route, the rate should not exceed 1mg/min
why do neonates receive vit K after bith?
Healthy intestinal flora is required for the gut to synthesize vit K.
Neonates don’t have the intestinal flora that synthesizes vit k, so 0.5-1mg IM after delivery is common.
List 4 examples of ADP receptor inhibitors, and state how long each must be discontinued prior to surgery.
ADP receptor inhibitors prevent platelet aggregation and thrombus formation.
* Clopidogrel: 7 days
* Ticlopidine: 14 days
* Prasugrel: 2-3days
* ticagrelor: 5-7 days
List 3 examples of GIIb/IIIa receptor antagonists, and state how long each must be discontinued prior to surgery.
GIIb/IIIa antagonists inhibit platelet aggregation and thrombus formation.
- Abciximab: 3 days
- Eptifibatide: 1 day
- Tirofiban: 1 day
What drugs can be used to provide anticoagulation in a pt who is unable to receive heparin? How long must each be stopped prior to surgery?
Thrombin inhibitors can be used to provide anticoagulation in pts who are unable to receive heparin.
- Bivalirudin: 2-3 hours
- Argatroban: 4-6 hours
heparin should be stopped 6 hours prior to surgery
What is the MOA for COX inhibitors? What agents provide irreversible COX inhibition?
COX inhibitors prevent platelet aggregation by blocking cyclooxygenase 1 (COX-1). This stops the conversion of arachidonic acid to prostaglandins and ultimately thromboxane A2.
* Aspirin is irreversible- it lasts for the life of the platelet
* NSAIDs are reversible- their duration is shorter than the life of the platelet
Name 2 antifibrinolytics and 4 fibrinolytics
Antifibrinolytics stop the conversion of plasminogen to plasmin. They promote clot formation (reduces bleeding in cardiac and orthopedic surgery)
* tranexamic acid
* Aminocaproic acid
Fibrinolytics facilitate the conversion of plasminogen to plasmin. They break down clots (useful for myocardial infarction or embolic stroke)
* tPA
* Urokinase
* Streptokinase
* Reteplase
* Alteplase
where is vWF synthesized, and what is its function?
vWF is synthesized by the vascular endothelium and megakaryocytes. It serves two key functions:
- it anchors the platelet to the vessel wall at the site of vascular injury (platelet adhesion)
- It carries inactivated factor 8 in the plasma
what are the 3 types of Von Willebrand disease?
Von Willebrand disease is the most common inherited disorder of platelet function. As a qualitative platelet disorder, the platelet count is normal, but the platelets do not function properly.
- Type 1: mild-moderate reduction in the amount of vWF produced
- Type 2: the vWF that is produced doesn’t work well
- Type 3: Severe reduction in the amount of vWF produced
What lab results are consistent with Von Willebrand disease (PT/INR, PTT, platelet count, bleeding time, fibrinogen)?
What is the MOA of desmopressin? What is the dose?
DDAVP is a synthetic analogue of antidiuretic hormone. It stimulates the release of endogenous vWF and increases factor 8 activity.
- Patients with type 1 dx respond best to desmopressin
- Patients with Type 3 disease do not respond to ddavp because they do not produce vWF
Dose= 0.3-0.5 mcg/kg IV
Side effect= hypotension with rapid administration
Aside from desmopression, list 3 other treatments that can improve coagulopathy of Von Willebrand disease
Cryoprecipitate: Contains factors 8, 13, fibrinogen, and vWF. It can be used for Types 1, 2 ,or 3 dx
FFP: contains all of the clotting factors, so it too can be used for all 3 types
Purified 8-vWF concentrate: reduces the risk of transfusion related infection. It is the first line agent for the patient with type 3 disease.
Describe the pathophysiology of hemophilia A.
Hemophilia A is an X-linked chromosomal disorder (more common in males) that causes factor 8 deficiency.
Severe dx (factor 8 activity <1%) is associated with spontaneous bleeding into the joints, muscles and vital organs. These patients often require orthopedic surgery.
What lab results are consistent with hemophilia A (PT/INR, PTT, platelet count, bleeding time, fibrinogen)?
Factor 8 is part of the intrinsic. Therefore, the PTT will be prolonged with severe disease and only slightly prolonged with mild dx
What is the tx of hemophilia A?
Tx includes:
* Factor 8 concentrate prior to surgery.
* FFP and cryoprecipitate can also be used to replace factor 8, however, their use increases the risk of transfusion-related disease transmission.
* Antifibrinolytics (tranexamic acid and aminocaproic acid) can be used to minimize bleeding during dental procedures
* A type and crossmatch is required for any surgical procedure
How is hemophilia B different from Hemophilia A?
Hemophilia B is factor 9 deficiency
Labs and anesthetic management are similar to hemophilia A with 1 exception- instead of factor 8 replacement, factor 9 concentrate is indicated
What is the role of recombinant factor 7 in the management of hemophilia A and B?
Sometimes patients with hemophilia A or B develop inhibitors that prevent exogenous factor 8 or 9 from achieving their therapeutic goals.
For a clot to form, the missing coagulation factor must be replaced or “bypassed”. Recombinant factor 7 is a “bypass” agent, because it skips over factor 8 or 9 in patients with inhibitors, ultimately allowing the patient to form clot. The dose is 90-120 mcg/kg
Recombinant factor 7 can increase the risk of arterial thrombosis (MI and embolic stroke) as well as venous thrombosis (DVT, or pulmonary embolism), so the risk/benefit ratio must be considered in patients at risk for these complications.
Recombinant factor 7 is also used as a “last-ditch” treatment for bleeding without an identifiable cause (this is off label). The dose is 20-40 mcg/kg.
Describe the pathophysiology of disseminated intravascular coagulation.
DIC is characterized by disorganized clotting and fibrinolysis that lead to the simultaneous occurrence of hemorrhage and systemic thrombosis.
Generalized thrombin formation creates microvascular clots that impair tissue perfusion, resulting in tissue hypoxia and acidosis. The body attempts to break down clots by activating its anticoagulant system. However this leads to widespread consumption of its coagulation factors, fibrinogen, and platelets
Name 3 conditions that are associated with a high risk of developing DIC.
There are 3 conditions that you should associate with a high risk of developing DIC:
1. Sepsis (highest risk= gram-negative bacilli)
2. obstetric complications: (highest risk= preeclampsia, placenta abruption, and amniotic fluid embolism)
3. Malignancy: (highest risk= adenocarcinoma, leukemia, and lymphoma)
Describe the management for the patient with DIC.
DIC is not a disease in itself, but rather it’s manifestation of some other underlying problem. Indeed, the definitive treatment for DIC is reversing the underlying cause. Otherwise, treatment is supportive:
* Hypovolemia: treat with IV fluids
* Coagulopathy: replace consumed blood components with FFP, platelets, and cryoprecipitate (it’s ok to “feed the beast”)
* Severe microvascular thrombosis: IV heparin or LMWH
Compare ad contrast type 1 and type 2 heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia causes clot formation throughout the body! the platelet count falls because platelets are consumed faster than they are produced
Describe the pathophysiology and treatment of protein C and S deficiency
Protein C produces an anticoagulant effect by inhibiting factors 5a and 8a. This creates a feedback mechanism that prevents unnecessary clot formation.
- Protein S is a co-factor of protein C. Said another way, protein S helps C do its job.
- A deficiency of protein C or S can produce hypercoagulable state, increasing risk of thrombosis.
Treatment:
* A thromboembolism is treated with heparin that is transitioned to warfarin
* Patients may or may not require life-long anticoagulation with warfarin
Describe the pathophysiology and treatment of factor 5 Leiden mutation.
Factor 5 Leiden causes a resistance to the anticoagulant effect of protein C.
Treatment:
* Only patients with thromboembolism require anticoagulation
* Lifelong anticoagulation is unwarranted unless the patient experiences recurrent thrombotic events
Describe the pathophysiology of sickle cell anemia.
Sickle cell disease is an inherited disorder that affects erythrocytes. Amino acid substitution (valine substituted for glutamic acid) on the beta globulin chain alters RBC geometry. This affects RBC function in several ways:
* Deoxygenation of HgbS leads to sickling (a conformational change that alters the erythrocyte’s geometry)
* In severe cases, sickling causes the RBCs to clump together, which causes mechanical obstruction of the microvasculature in the vital organs and joints. This impairs tissue perfusion and causes intense pain (particularly in the bones and joints)
* Sickled cells are more prone to hemolysis and removal by the spleen ( Lifespan = 12-17 days vs normal RBC= 120 days)
List the triggers that cause sickling of HgbS.
- Pain
- Hypothermia
- Hypoxemia
- Acidosis
- Dehydration
Anesthetic management focuses on avoiding these triggers
What is the treatment of vaso-occlusive crisis?
Vaso-occlusive crisis:
* Sickled cells -> impaired tissue perfusion -> ischemic injury
* The most common manifestation of sickle cell disease
* Treatment: Analgesics (oral or IV) and hydration
* Hydroxyurea reduces the incidence and severity of vaso-occlusive crisis
Discuss the relationship between blood type, erythrocyte antigens, and plasma antibodies.
Blood type is determined by specific glycoproteins present on the erythrocyte cell membrane. These glycoproteins have an antigenic potential, so administering blood of the wrong type has catastrophic consequences. The most clinically important antigens are the ABO and Rh systems.
- if an antigen is expressed on the erythrocyte, then there will NOT be an antibody, against that specific antigen in the plasma
- If an antigen is NOT expressed on the erythrocyte, then there will be an antibody, against that specific antigen in the plasma
antigen equals ABO
What blood type is the universal donor for erythrocytes? How about the universal acceptor?
Universal RBC donor= O negative
Universal acceptor = AB positive
What blood type is the universal donor for FFP? how about universal acceptor?
universal donor: AB positive
Universal acceptor: O negative
What is the concern about an Rh- negative mother and pregnancy?
A person who is Rh-negative can be sensitized by exposure to Rh-positive blood during transfusion or pregnancy.
* An Rh-negative mother can be sensitized by her Rh-positive fetus. Transfer across the placenta, usually several days after delivery
* the mother receives Rhogam to prevent sensitization
* If the mother becomes sensitized and develops antibodies, a subsequent pregnancy with an Rh-positive fetus may result in erythroblastosis fetalis (hemolytic anemia of the fetus)
Compare and contrast type, screen, and crossmatch in terms of what each tests for and how long each takes.
A patient is suffering from acute hemorrhage and there is no time to wait for crossmatched blood. What is the next best option for this patient?
In the setting of acute hemorrhage, there may not be time to complete a full crossmatch (best option for transfusion)
Here is the recommended order of administering uncrossmatched blood (most to least favorable options):
1. Type-specific partially crossmatched blood
2. type specific uncrossmatched blood
3. Type O negative uncrossmatched blood (universal donor)
Can Type O positive blood ever be used for emergency transfusion?
If you don’t have time to obtain a type and crossmatch, type O negative is best for emergency transfusion, but…
Because 85% of the population is Rh-D positive, O positive can be used for emergency transfusion if the patient is NOT a woman of childbearing age and NOT received a previous transfusion
What is the indication to transfuse red blood cells?
RBC’s are transfused to increase CaO2
*Hgb > 10 g/dL: transfusion rarely required
* Hgb< 6g/dL: transfusion often required
* the decision to transfuse is guided by pt factors
What are the indications for FFP transfusion?
Coagulopathy (PT or PTT> 1.5x control)
Warfarin reversal (acute need)
Antithrombin deficiency
Massive transfusion
DIC
C1 esterase deficiency (hereditary angioedema)
*Conditions that can be treated with factor concentrates often carry less infectious risk
What are the indications for platelet transfusion?
Thrombocytopenia (<50,000/uL): invasive procedures, neuraxial blockade, or most surgeries
Thrombocytopenia (< 100,000/uL): eye and neurosurgery
Qualitative platelet defect
What is cryoprecipitate?
Fibrinogen
Factor 8
Factor 13
vWF
what are the indications for cryoprecipitate transfusion?
Fibrinogen deficiency (<80-100mg/dL)
vWB disease
Hemophilia
What is the dose for PRBC, FFP, platelets, and cryo?
PRBC:
* 1 unit increases HgB by 1g/dL
FFP
* Warfarin reversal = 5-8 mL/kg
* Coagulopathy= 10-20 mL/kg (increases factor concentration by 20-30%)
Platelets:
* 1 pack per 10kg/body weight
Cryo
* 5 bag pool increases fibrinogen by 50mg/dL
What is the estimated blood volume in preterm neonates, full term neonates, infants, and adults?
What is the formula for maximum allowable blood loss?
MABL= EBV x (starting Hgb - target Hgb)/ Starting Hgb
Name 4 substances that extend the shelf life of RBCs. What is the function of each?
Citrate: is an anticoagulant that inhibits calcium (factor 4). After transfusion of multiple units, the citrate load can cause hypocalcemia
Phosphate: is a buffer that combats acidosis
Dextrose: is the primary substrate for glycolysis
Adenine: is a substance that helps RBCs re-synthesize ATP. Extends storage time to 35 days.
Newer preservatives (adsol, nutricel, and optisol) extend storage time to 42 days
Discuss the RBC storage lesion
The red blood cell storage lesion leads to:
- Decreased 2,3 DPG -> Shifts oxyhemoglobin dissociation curve to the left (left = love -> Decreased O2 release)
- Decreased ATP -> shift to anaerobic metabolism
- Decreased pH (increased lactic acid)
- Increased potassium (caution in neonates and renal failure)
- impaired ability to change shape (important for capillary flow)
- Hemolysis
- increased production of proinflammatory mediators
What is leukoreduction, why is it used, and who does it benefit?
Leukoreduction removes WBCs from RBCs and platelets.
Since leukocytes are responsible for HLA alloimmunization, febrile nonhemolytic transfusion reactions and CMV transmission, it makes sense that removing them reduces these risks
What is washing, why is it uses, and who does it benefit?
Washing the blood products with saline removes any remaining plasma (and antigens) in the donor RBC’s (RBC’s antigens are not removed)
This process prevents anaphylaxis in IgA deficient patients
what is irradiation, why is it used, and who does it benefit?
Irradiation exposes units to gamma radiation. This disrupts WBC DNA in the donor cells-it destroys donor leukocytes. This process prevents graft-vs-host disease in the immunocompromised patients.
Populations who benefit from irradiated cells include: leukemia, lymphoma, hematopoietic stem cell transplants, and DiGeorge syndrome.
What is the most common infectious complication of RBC transfusion? How can this risk be reduced?
Cytomegalovirus is the most common infection complication of transfusion.
Leukoreduction greatly reduces this risk, so immunocompromised patients should receive leukoreduced blood.
List the 4 most common infectious complications of RBC transfusion from most to least common.
The risk of infection following transfusion ordered from most to least common:
- CMV (1-3% of all transfusions)
- Hepatitis B (1 in 366,500)
- Hepatitis C (1 in 1,657,000)
- HIV (1 in 1,860,000)
Why is bacterial contamination more common with platelets than with RBC’s or FFP?
Platelets are stored at room temperature, which explains why bacterial contamination is more common with platelets that with PRBCs or FFP.
Bacterial contamination can progress to sepsis.
what are the signs and symptoms of an acute hemolytic transfusion reaction?
Observed under anesthesia:
* Hemoglobinuria (usually the presenting sign)
* HoTN
* Bleeding
Masked by anesthesia:
* Fever
* Chills
* Chest pain
* Dyspnea
* Nausea
* Flushing
Discuss the complications of an acute hemolytic reaction.
A hemolytic reaction is perhaps the most devastating complication that results from transfusion. Complement is activated in the recipient’s blood, and plasma antibodies attack the antigens present on the donor blood cell membranes. ABO incompatibility is the most lethal. Renal failure, DIC, and HoTN are the most catastrophic complications of intravascular hemolysis.
Renal failure- Acute tubular Necrosis
* Free Hgb in the form of acid hematin precipitates inside the renal tubules. This causes a mechanical obstruction
DIC:
* Erythrocyin is released from RBC, and it activates the intrinsic clotting cascade. This leads to uncontrolled fibrin formation and consumes the body’s supply of platelets and factors 1, 2, 5, and 7
Hemodynamic instability:
* Free Hgb activates the kallikrein system. The final product of this pathway is bradykinin - a potent vasodilator
What is the treatment plan for an acute hemolytic reaction?
- Stop the infusion
- Maintain urine output > 75-100 mL/hr with:
* IV fluids
* Mannitol 12.5-25 g
* furosemide 20-40 mg if IVF and mannitol fail to provide adequate response - alkalinize the urine with sodium bicarbonate
- Send urine and plasma hgb samples to the blood bank
- Check platelets, PT, and fibrinogen
- Send unused blood to the blood bank to double-check cross match
- support hemodynamics with IVF and pressors as needed
Discuss the pathophysiology of transfusion-related acute lung injury.
TRALI is caused by human leukocyte antigens (HLA) and neutrophil antibodies present in the donor plasma.
Donor antibodies -> neutrophil activation in the lungs -> endothelial injury -> capillary leak -> pulmonary edema -> impaired gas exchange -> hypoxemia -> acidosis -> death
FFP and platelets contain the highest concentration of these antibodies.
How does the source of blood products affect the risk of TRALI?
Where the blood producst come from also affects the risk of TRALI. These donor groups impart the highest risk:
- Mulitparous women (highest risk)
- hx of blood transfusion
- hx of organ transplant
What are the diagnostic criteria for TRALI?
Onset <6hours following transfusion
Bilateral infiltrates on frontal CXR
PaO2/FiO2 < 300mmHG or SpO2 < 90% on RA
Normal pulmonary artery occlusion pressure (no left atrial HTN or volume overload)
What physiologic disturbances result from massive transfusion?
Massive transfusion is associated with:
* Alkalosis from citrate metabolism to bicarbonate in the liver
* Hypothermia from transfusion of cold blood
* Hyperglycemia from dextrose additive to stored blood
* hypocalcemia from binding of calcium by citrate
* hyperkalemia from the administration of older blood
What is the lethal triad of trauma?
- Acidosis
- Hypothermia
- Coagulopathy
the problem begins with hemorrhage and hypoperfusion, and this ultimately impacts coagulation and acid-base balance.
What is salvaged blood syndrome?
Cell saver blood does not return platelets and coagulation factors to the patient.
If a large volume of salvaged blood is returned to the patient, you should consider the possibility of dilutional coagulopathy. This is also known as “salvaged blood syndrome”
How is cell saver blood different from PRBCs?
Cell saver blood contains higher concentrations of 2,3 DPG and ATP, so CaO2 is greater, and the cells are better able to maintain their biconcave shape (less sludging in the microcirculation)
List the contraindications and controversial uses for intraoperative blood salvage.
Contraindications:
* Sickle cell dx
* Thalassemia (low Hgb)
* Topical drugs in a sterile field such as betadine, chlorhexidine, and topical antibiotics
* infected surgical site
* Oncologic procedures
Controversial uses:
* C-section due to the theoretical risk of anaphylactoid syndrome of pregnancy (amniotic fluid embolism)
Intraoperative blood salvage is considered safe for transplant surgeries
