Fluid management and blood transfusion Flashcards
Describe water distribution in the body by weight
Water is about 60% of weight so for a 70 kg male
Intracellular 65% 28L
Extracellular 35% 14L
— Interstitial 27.5% 11L
— Plasma 7.5% 3L
TBW 100% 42L
In general how is total body water regulated
ECF as ICF follows changes in the ECF
There are no “water pumps” in the body
ECF is controlled by the movement of Na and thus water as Na is responsible for 90% of the body’s osmotic activity
Na intake (diet/IV)
Na EXTRA-Renal loss (Sweating/faeces)
Na renal excretion
What is transcellular fluid
CSF | Synovial fluid | Ocular fluid
Glandular secretions (lungs/GIT)
Bile
Total transcellular fluid is ± 2 % TBW (± 800 ml)
What is the equation for plasma osmolarity
Plasma osmolarity = 2[Na] + 2[K] + glucose + urea
Sodium and potassium are doubled to account for their conjugate anions - glucose and urea don’t have conjugate anions
What is the difference between molarity and osmolarity
Osmolarity refers to the number of osmotically active particles per litre of solution
Molarity refers to the the number of moles of solute per litre of solution i.e. the concentration
NaCl – contributes 2 osmoles
But the molarity can only represent either Na+ or Cl-
How is osmolality different from osmolarity
Osmolality is the number of dissolved osmotically active particles per unit MASS of solution
Osmolarity is the number of osmotically active particles dissolved per unit VOLUME of solution
The problem with osmolarity (vs osmolality) is that the volume of the solvent (water) changes with the addition of solute and with temperature
Osmolality is independent of changes in mass of solute and temperature.
Why do we use 5% dextrose for infusions instead of just infusing water
Water infusion would lead to acute drop in osmolarity of the fluid surrounding the red blood cells. The circulating RBCs would find themselves surrounded by a hypotonic solution, causing them to swell. RBC can only hold a certain amount of water before haemolysis occurs. For this reason 5% dextrose infusion are used
Osmolarity of 5% Dextrose is 278 mOsm/L and plasma osmolarity is normally 285 - 295 mOsm/L
Once the glucose is metabolized, it is as if free water has been infused but without the acute drop in osmolarity.
How does ADH work in the kidneys to increase H2O reabsorption
- Luminal wall CD is impermeable to water
- Basolateral wall CD has aquaporins 3 and 4 and is permeable to water
- ADH binds to V2 receptors in the CDs –> cAMP 2nd messenger –> aquaporin 2 being inserted into the luminal walls of the CD
- Water moves down Conc gradient created by the high osmolarity in the renal medulla.
- High osmolarity in the renal medulla is generated by active reabsorption of Na in the aLOH and DCT, counter current mechanism and urea cycling.
How is ECF volume controlled
- Brain
- Hyperosmolarity (also stress and pain)
- Hypothalamus: osmoreceptors
- Posterior pituitary: ADH release
- Thirst stimulated - Heart
- Baroreceptors in atria (low P) tonic firing with normal P
- Low P –> low firing –> decreased inhibition ADH release–> increase ADH
- RA stretch –> release ANP –> Natriuresis
- Reduced RAP –> less ANP –> Na retention - Kidneys
- Decreased arterial filling pressure sensed by juxtaglomerular apparatus
- Macula densa cells release renin
- RAAS activated
- Angiotensin 2 restores filling P in renal arterioles
- Aldosterone increases Na retention
How does increased SNS tone affect renal perfusion
- Global RBF decreased
2. Redistribution of RBF to inner juxtamedullary nephrons: improved Na and water retention
Classify the “stress response”
Neurohumoral
Neural –> SNS activation
Humoral –> Glucocorticoids / Thyroid H / GH / CAT = anti-insulin hormones
Describe the neurohumoral response
Neuro
Stress –> CNS (brainstem) –> SNS activation with PSNS inhibition
Adrenalin: Predominant beta agonist effects
- -> Increased CO
- -> Vasodilation in Coronary / Skeletal muscle BV
Noradrenalin: Predominant alpha agonist effects
–> VC - skin / kidney / liver / GIT
Although blood is diverted away from the kidney –> blood distribution in the kidney is shifted toward inner juxtamedullary nephrons which have long LOH and are more suited to Sodium and water retention resulting in accentuated sodium and water retention.
What features of the part of the nephron in the renal medulla assist with the generation of the medullary osmolar gradient?
- Differential permeability of descending and ascending limbs of LOH to water (descending) and ions (ascending)
- Countercurrent exchange mechanism
- Hair pin design of the vasa recta
- Urea reabsorption from inner medullary collecting duct.
What is diabetes insipidus vs SIADH
Central Diabetes insipidus (head injury)
- Posterior pituitary fails to secrete ADH
- Polyuria, hypvolaemia, hypernatraemia, dilute urine
Nephrogenic diabetes insipidus (Lithium toxicity)
- Insensitivity to normal levels of ADH
SIADH (Intracranial pathology vs ectopic source Small cell lung Ca)
- Hyponatraemia (headache/nausea/confusion/seizures/coma)
- Fluid overload (sometimes)
- Inappropriately high urine osmolarity
Describe the humoral aspect of the neurohumoral response
Counter-regulatory hormones: Catecholamines Glucocorticoids Growth Hormone Thyroid Hormone
Anti-insulin hormones that reduce insulin release and tissue sensitivity to preserve and increase blood glucose for use by fight or flight organs (heart/skeletal muscle/lungs and brain)
Glycogen break down initially increased
Then Gluconeogenesis accelerated
Other organs (over days become fat adapted)
Summarise the overall fluid and electrolyte outcome consequent to the stress response
- Maximal sodium and water retention RAAS/ADH
- Hypernatraemia (dilutional) - ADH
- Hypokalaemia - RAAS
- Metabolic alkalosis
- Decreased RBF: Renal failure
- Hyperglycaemia
Describe the redistribution of crystalloid solutions after IV administration and state the clinical relevance of this
1 : 3 ratio
1ml stays intravascular while 3 ml moves into ECF
This means that crystalloids are inefficient effective circulating volume expanders as 3 x the volume lost of crystalloid replacement would is required to replace the blood loss.
What is the goal of maintenance fluids
Provide sufficient water and electrolytes for a patient not taking oral fluids
What is the goal of fluid replacement therapy
Fluids should resemble fluid losses which will generally resemble ECF
Why should glucose containing solutions be avoided in resuscitation
They are usually hypotonic with minimal expansion of effective circulating volume.
Furthermore, in scenarios requiring resuscitation, the physiological response increases blood sugar levels regardless of glucose administration.
What is the daily requirement of the following
H2O Na+ K+ Ca2+ Mg2+ PO4
H2O – 30 mL/kg Na+ – 2mmol/kg K+ – 1mmol/kg Ca2+ – 0.1mmol/kg Mg2+ – 0.1mmol/kg PO4 – 0.1mmolkg
Dextrose ± 100 grams/day (Adults) to prevent ketosis
Whats the difference between normal saline, ringers lactate, modified ringers lactate (Plasmalyte L) and Plasmalyte B (Balsol)
NS: Na 154 | Cl 154 | OSM: 308
RL: Na 131 | Cl 110 | OSM: 273 | K 4 | Ca 1.8 | Lac 28
MRL: Na 131 | Cl 110 | OSM: 273 | K 4 | Ca 0 | Lac 28
Pl. B: Na 131 | Cl 98 | OSM: 273 | K 4 | Mg 1.5 | HCO3 27 (Buffered with gluconate and acetate instead of lactate) (Balsol)
Why should maintenance solutions only ever be given slowly and should never be given as resuscitation fluid
They contain up to 26 mmol/L of potassium
Historically, it was thought that low sodium solutions are preferred in the perioperative period in paediatrics. How has this thinking and practice changed
Balanced salt solutions are preferred now.
Stress response leads to a water retentive state (and possibly hyponatraemia) –> Solutions resembling ECF should preferably be used in the first 24 hours postoperatively.
Why are dextrose concentrations of 5% used rather than 10%
5% provides 50 g of dextrose per 1 L bag of maintenance fluid. 2 - 3 bags over a 24 hour period will provide just enough glucose to prevent ketosis and starvation state.
10% solutions are hypertonic
- -> damage veins into which they are infused
- -> Potentially cause hyperglycaemia
Compare the contents of the following solutions D5W General Maintenance Solution Maintelyte Paediatric Maintenance Solution Neonatelyte
D5W: Na 0 | Cl 0 | OSM: 253 | K 0 | Dex 5%
GMS: Na 26 | Cl 52 | OSM: 382 | K 26 | Dex 5%
Maint: Na 35 | Cl 65 | OSM: 683 | K 25 | Mg 2.5 | Dex 10%
PMS: Na 35 | Cl 47 | OSM: 372 | K 12 | Dex 5%
Neo: Na 20 | Cl 15 | OSM: 638 | K 15 | Dex 10% | Lac 20 | Ca 2.5 | Mg 0.5 | PO4 37.5
What is the fundamental difference between D5W and GMS
D5W has no electrolytes and is hypotonic
GMS attempts to cover all daily requirements for water, electrolytes and glucose
What is the fundamental difference between GMS and Maintelyte
GMS is 5% dex
Maintelyte is 10% dex, more sodium and has Mg
What is the fundamental difference between GMS and Paediatric Maintenance Solution
PMS has less potassium and more sodium
What is the fundamental differnce between PMS and neonatalyte
PMS is 5% dex
Neonatalyte is 10% dex, has less sodium and Mg/Ca/Lac/PO4
Replacement fluids should resemble ECF as this is most commonly the type of fluid that is lost.
Outline some situations when a different strategy for fluid replacement should be adopted
- Diabetes insipidus
- water loss > Na loss
- Rx measure Urine and plasma electrolytes and reduce Na: Water ratio of replacement fluid - Intestinal losses
- K loss - supplement K
- HCO3 loss (upper intestinal fistulae) - Gastric losses
- Cl - loss –
- K loss
- Rx: 0.9% NaCl + K replacement
How many liters of intraoperative 0.9% NaCL can cause acidosis due to chloride load?
2L
What are the suggested harmful effects of hyperchloraemic metabolic acidosis
Clinical Significance yet to be determined
- Cl induced VC
- AbN coagulation
- Renal dysfunction
- Delirium
No human data to suggest decreased survival
When is the slight hypotonic property of ringers lactate possibly probelmatic
In patient’s at risk for cerebral oedema - head injury or when the BBB is disrupted.
Why can ringers lactate and blood transfusion not be transfused via the same administration set
The calcium in Ringers lactate (1.8 - 2.5 mmol/L) is sufficient to coagulate stored blood in the giving set.
NS or RL for renal failure with hyperkalaemia and why
Ringers Lactate is preferred
RL - despite containing potassium - the quantities are minimal and have minimal biochemical impact
NS - Causes acidosis and will increase the K significantly
NS / RL /Balsol for DKA
NS (NO: acidosis –> deranged K)
RL (NO: if patients on metformin: impaired lactate metabolism)
Balsol: Yes –> No lactate (acetate and gluconate used as buffers - also contains HCO3)
How much crystalloid on the day of surgery has been shown to be beneficial and what benefits are cited
- 5L/24 hours on the day of surgery
- Improved postop lung function
- Improved exercise capacity
- Reduced stress home response
- less nausea
- less thirst
- less fatigue
What is the problem with excessive crystalloid therapy
- Positive fluid balance in ICU - independent RF for mortality
- In trauma: supranormal haemodynamic resuscitation with large volumes of crystalloid (13.5 L on average)
- -> Abdominal Compartment Syndrome
- -> Multiple Organ Failure
- -> Mortality
Summarise the advantages and disadvantages of colloids
Advantages
1. Better effective circulating volume expansion than crystalloids
Disadvantages
- Do not resuscitate ECF –> diminished renal function
- Allergic risk (all)
- Coagulation interference
Why is human albumin not used
Higher cost
No evidence that it is superior to synthetic colloids
(for the treatment of both hypovolaemia and hypoalbuminaemia)
What are examples and the pros and cons of the gelatins how are they made
Examples: Gelofusine | Haemaccel
Synthesis: gelatin derived from bovine material
Pros
1. Least effect on coagulation
Cons
- Short acting (1 hour) –> quickly excreted by kidneys
- Highest risk of allergy
What are examples and the pros and cons of the dextrans and how are they made
Examples: Macrodex | Rheomacrodex
Synthesis: Sucrose
Pros
- Last longer
- Good rheological properties (good flow)
Cons
- Bind vWF and Factor VIII and impair coagulation the most approximate effect of SC LMWH
- Interfere with cross matching techniques
- Significant allergy risk
What are examples and the pros and cons of the Hydroxyethyl Starches (HES) how are they made
Examples: Voluven | Volulyte
Synthesis: Potatoes or Maize starch
Pros
- Last longer (6 hours)
- Beneficial effect to vascular endothelium
Cons
- Less Impaired coagulation vs dextrans (higher MW the worse –> Medium MW used preferably because of this)
- Renal impairment (without crystalloid adminsitration)
- Avoid in sepsis
Is there clear evidence of survival benefit with use of colloids
None BUT data suggesting that crystalloid overload may be harmful should be kept in mind
What is fluid optimization
The use of beat to beat dynamic measures (SVV and PPV) to guide appropriate fluid therapy
- -> instead of ‘chasing’ urine volume
- -> urine production is deranged in the perioperative period due to the stress response and less accurately aligns with the patient’s fluid status
Also valid options:
- U/S IVC collapsibility
- Straight leg raise test
Describe an ideal colloid
in vivo MW of 70 kDa (small) and suspended in a balanced salt solution.
Which infections is whole blood donations screened for
HIV 1 and 2
Hep B and C
Syphilis
What is the volume per unit of whole blood
550 mL
What is the haematocrit of whole blood
35%
What is the preservative used for whole blood
CPD - A (Citrate, Phosphate, dextrose , adenine)
What is the shelf life for whole blood
35 days at 4 deg C
What are specific indications for whole blood administration
- Massive haemorrhage with possibility of recurrence
- Rx of established hypovolaemic shock
- Blood replacement after burns
How is red cell concentrate made
Removal of plasma from whole blood
–> plasma can then be used to prepare FFP’s and clotting factors
What is red cell concentrate suspended in?
Small volume of nutrient fluid called:
SAGM (Saline, Adenosine, Glucose, Mannitol)
Does RCC contain citrate
Yes, smaller amounts than whole blood
What is the volume of a unit of RCC
300 ml
What is the haematocrit of RCC
60%
What is the shelf life of RCC
42 days at 4 deg C
How much does RCC increase the patient Hb
4 ml/kg raises HB by 1 g/dl (adults)
So 70 kg male:
1 bag RCC - 300 ml –> should raise Hb by 1 g/dl
What does co-administration of furosemide during a blood transfusion require
Evaluation of fluid status
What is the indication for FFP
To replace deficient clotting factors in patients who also need plasma volume support
What are the risks of administering FFPs
Higher risk of TRALI
Many of the same risks as blood transfusion
Is FFP equivalent to plasma in terms of clotting factors
No. It has less, and specifically, it is relatively low in thrombin. FDP and cryoprecipitate contain more thrombin
What is the difference between FFPs and cryoprecipitate and how is it made
Cryoprecipitate is processed FFP made by skimming off the clotting factors it contains (akin to taking the cream from the top of the glass of milk fresh from the cow)
- Provides high concentration of clotting factors at low volume
Compare the volume of FFP to cryoprecipitate
FFP - 300 ml
Cryoprecipitate - 10 - 20 ml
Cryoprecipitate is concentrated coagulation factors, what is the down side
It is expensive
- Lifesaving in DIC and massive blood loss
When are platelets administered and why are there such limited indications
Extremely expensive resource
Indications
- TEG - indicates platelets abnormal plt function
- Known severe thrombocytopaenia
- As part of massive transfusion protocol
How are platelets stored
At room temp (20 - 24 deg C)
With gentle agitation
For max 5 days
How long until POOLED platelets expire
After platelets are pooled they expire after 4 hours
What does group and screen mean
Blood group determined
Specimen is screened for antibodies
BUT blood will still need to be cross matched
Describe the degrees of urgency for ordering blood
- Routine
- Complete cross match done
- Specify time blood required - ASAP
- Complete cross match done
- Ready 30min - 1 hr of specimen arriving at blood bank - STAT
- Incomplete cross match done
- Group specific blood issued within 5 mins
- higher risks of reactions as full screening for antibodies is not done
What is the most common cause for a transfusion reaction?
Clerical error when collecting the blood sample
Describe the actions to be taken prior to transfusion of blood
- Check the form and products independently against patient demographics
- Check that group is compatible and expiry date
What temperature is blood stored at prior to infusion
2 - 10 deg C
What temperature should blood not be warmed above and why
37 deg C –> haemolysis if higher which may provoke a transfusion reaction
Never rewarm
What is the maximum time for a blood transfusion
6 hours
How is the patient monitored for a transfusion reaction
Vitals, LOC, well being and verbal inquiry
Why should stoppered empty blood bags be returned to the blood bank
The pilot tube contains residual blood that is used for investigation of the transfused blood in the event of a patient reaction
Which study suggested a restrictive policy with regard to blood transfusion and how did this study alter the Hb trigger to initiate a blood transfusion
TRICC ( Transfusion in Critical Care)
- Transfusion trigger of 7 g/dl (instead of 9 g/dl)
- Significantly improved survival
What is the trigger and target for blood transfusion and what are the exceptions
Trigger 7 g/dl
Target 9 g/dl
Exceptions: IHD and elderly
Classify and describe complications of blood transfusions
IMMUNE reactions
Haemolytic
- Early (ABO)
- Late (Rhesus)
Non-hemolytic
- Fever
- Urticaria
- Purpura
- TRALI
- Anaphylaxis
- Immune supression
- Graft vs Host disease
NON- IMMUNE reactions
Infectious
- Viral
- Parasitic
- Bacterial
- Prions
Massive Blood Transfusion
- Hypothermia
- Hyperkalaemia
- Hypocalcaemia
- Citrate toxicity
- DIC
- Acid-base disturbance
- Fluid overload
Define a transfusion reaction
Any potentially adverse sign or symptom that occurs after the start of a transfusion of blood or blood product
Summarise the classification of transfusion reactions
IMMUNE
- Hemolytic
- Non-hemolytic
NON-IMMUNE
- Infection
- Massive blood transfusion
Describe the clinical presentation of ABO incompatibility
Symptoms (Sick patient with SNS activation)
- Anxiety and restlessness
- Nausea and vomiting
- Back/flank/precordial pain
- Itching
- Cold and clammy
Signs Any abnormal autonomic finding Hburia/oliguria/anuria Jaundice Coma Death
Describe the management of a patient with suspected ABO incompatibility transfusion reaction
STOP transfusion Call for help Declare situation ABCDE - Vasopressor/inotropes as needed - Antihistamines/Steroids - Fluids (maintain adequate renal perfusion)
Labs
- FBC for Hb / UE for renal failure and K/ Clotting profile for DIC
- Inform blood bank promptly (legal requirement)
- Send all units / post transfusion specimens/ urine sample / reaction form
What should be sent to blood bank post transfusion reaction
- Call them and tell them promptly
- All units transfused
- Post transfusion specimens (clotted and EDTA)
- Urine sample
- Complete untoward reaction form
What is the definition of a Massive Blood Transfusion and what is haemostatic resuscitation
- More than 10 units in an adult
- Replacement of entire blood volume < 24 hours
- Replacement of > 50% blood volume within 3 hours
- Rate of blood loss > 150 ml/min
Haemostatic resuscitation
- Delivering RBCs and blood components in a fixed ratio - 1:1:1
What is the evidence to suggest that blood transfusions suppress immunity
- Kidney transplant patients - longer kidney survival
- Reduced 5 year survival in cancer patients
- Increase incidence of sepsis
What are the consequences of giving massive transfusion
- Risks of giving a single transfusion are multiplied
- infection
- Incompatibility - Multiple physiological consequences of giving a large amount of stored blood
What happens to platelets and clotting factors after massive blood transfusion
Diluted
What happens to pH after massive blood transfusion
Initially lactic acidosis (stored RBC’s)
Later metabolic alkalosis as liver converts citrate to HCO3
Is the P50 for the OHDC shifted for the transfused cells and why
Significantly reduced 2.3 DPG levels and LEFT shifted P50 OHDC
What effect does massive blood transfusion have on body temperature
Hypothermia –> left shifted OHDC and coagulopathy
Discuss potassium after massive blood transfusion
Initial increase (RBCS lose 1 mmol K per day of storage)
Later: When RBC recover –> rapid uptake of K –> hypokalaemia
What is the effect of citrate in the massive blood transfusion.
What is the stored blood concentration of ionized calcium?
Citrate toxicity
- Prevents coagulation of blood by chelating calcium
- Stored blood Ca concentration < 0.1 mmol/L (normal is 1 mmol/L)
Therefore –> massive transfusion may lower calcium
However, citrate is rapidly metabolized, and hence this is rarely a problem unless during a MASSIVE transfusion or with liver dysfunction
Citrate metabolism –> metabolic alkalosis –> shifts P50 OHDC to the left
What is the effect of the mild hemolysis that has taken place in stored blood
Free Hb –> may cause renal impairment
Why are filters used on administration sets
To reduce the possibility of microemboli
Microemboli are cellular-fibrin aggregates
Describe your approach to the initiation of the massive transfusion protocol
- Recognise need and Declare situation to the team
- Advise surgical/anaesthetic consultant and get help if needed
- Ensure large bore, high capacity IV access, Ensure patient warming and other resuscitation fluids as appropriate.
- Tranexamic acid 1g IV over 10 mins
- Take blood for: FBC, CEUG, INR, Cross match
- Call blood bank - request STAT not ASAP:
- 6 U RCC
- 6 U FFP
- 1 unit pooled plts
- 10 U (1000IU) cryoprecipitate - Repeat as needed
- Before transfer to ICU
- FBC, INR & PTT, Fibrinogen levels - Repeat Tranexamic acid 1 g in 200 ml over 8 hours
- Dont forget to document times
What are the targets for a massive blood transfusion
Hb > 8 g/dl
Plts > 75 x 10^9/L
Fibrinogen > 1.0 g/l
INR & PTT < 1.5 x mean
Which filter should be used for platelet transfusion
The specific one provided by the blood bank (standard blood filters will trap platelets)
What is random donor pooled platelets
Platelets from 5 individual donations pooled together to produce one unit of platelet concentrate
How much should platelets increased after a standard adult dose of pooled platelets
20 - 40x 10^9 /L (but lower in splenomegaly/DIC/Sepsis
Should single donor apheresis platelets be ordered for massive transfusions
NO. These are indicated for patients on long term platelet replacement therapy
What coagulation factors does cryoprecipitate contain and how is cryoprecipitate administered
vWF 100IU Factor 8 100 IU Factor 13 Fibrinogen 200mg Administration: standard blood-giving IV admin set Administered in pools of 10 units
How much does 10 Units of cryoprecipitate increase fibrinogen and what is the target for patient plasma fibrinogen
10 units of cryoprecipitate
Contains ± 200mg fibrinogen
Increases plasma fibrinogen 50 - 100 mg/dL
Target fibrinogen > 1 g/dl
How is cryoprecipitate prepared
Repeated thawing of FFP between 1 deg C and 6 deg C and recovering the precipitate
Compared to FFP, what does cryoprecipitate contain
It contains most of 8, 13, fibrinogen, fibronectin and vWF from the FFP
How long can cryoprecipitate be stored for
12 months at -25 deg C or below
How long after thawing should cryoprecipitate be used?
Within 6 hours (maintain at 20 - 24 deg C)
How long does fibrinogen last
3 - 5 days
What are the Pros and Cons of FFP
Pros
- Replaces coagulation factors
- Has 400 mg fibrinogen
- Volume expander (maintains oncotic pressure)
- Acts as a buffer (improves AB status)
Cons
- Increased incidence TRALI
- Increased incidence of Multi-organ failure
Why are concerns over increased incidence of TRALI with FFPs unfounded
Mortality for patients who require massive transfusion 30 - 60%
TRALI occurs 1 in 5000 - 10 000
- Rx - ventilation ± 24 hours
- Mortality 6 - 9 %
What is the cost of a massive transfusion in RSA public sector
30 000 ZAR
What is the name of the study supporting Tranexamic acid in surgical/trauma patients and what did this study find
CRASH 2 study suggested a 15% reduction in overall mortality with administration of tranexamic acid
What is the mechanism of action of Tranexamic acid
Antifibrinolytic
- Binds to plasminogen and prevents activation to plasmin.
