1

Fluid, Electrolyte and Acid Base Physiology

Sue Ranasinghe, MD

CONTENT OUTLINE:
Body fluids
Osmolality/ Viscosity/ Oncotic pressure- major determinants
Hyponatremia/ Hypernatremia
Electrolyte imbalance due to vomiting
Body fluid electrolytes
Hyperkalemia/Hypokalemia
Hypocalcemia
Hypomagnesemia/ Hypermagnesemia
Glucose physiology
Diabetes mellitus -anesthetic considerations
Routine intaoperative fluid
Fluid Replacement Solutions- crystalloids/ colloids
Fluid Management in Special Situations
Pediatric Fluid Management
Fluid Management in Patients Undergoing Liposuction
Acid- Base Balance Disturbances

Key words 2006-2014

Fluid and Electrolytes

Intravascular: extravascular volume ratio
Hyperkalemia: drug causing/ Rx
Hyperkalemia: angiotensin receptor
Hypokalemia: ECG effects
Drugs causing hyperkalemia and treatment
Hyponatremia: causes, Hyponatrmia: evaluation 2014
Severe hyponatremia: treatment
Hyperosmolar coma
Hypocalcemia: ECG effects
Magnesium: complications
ECG in hypermagnesemia
Hypermagnesemia: Rx
Ascites formation and Starling equation
Vomiting: electrolyte imbalance
Chronic diarrhea: electrolyte imbalance
Maximum ABL calculation
Fluid resus: crystalloid vs colloid
Crystalloid resus: coagulopathy
Metabolic acidosis and normal saline
 2

Hetastarch: platelet function

Hypoglycemis: Glucagon (2012)

Enteral nutrition vs TPN: complications (2012)
TPN discontinuation: hypoglycemia (2012)
TPN: Phosphorous deficiency (2012)
Hyperchloremic metabolic acidosis (2012)
Organ donor treatment of DI (2012)

Acid Base
Acid-base management
ABGs: Resp acidosis/met alka
Compensated resp acidosis: ABG
Respiratory alkalosis: renal compensation
Met alk: Resp compensation
Bicarb administration: CO2 effect
pH buffering:Bicarbonate
Acidosis: anion gap differential diagnosis
ABG: Salicylate toxicity (2012)
Bicarb admin: CO2 effect (2012)
Hypocarbia: electrolyte effects- 2014

Endocrine/ Metabolic Keywords 2014:

Addison’s disease: Blood Chemistry

Carcinoid syndrome symptoms
Corticosteroid deficiency in ICU
Corticosteroids: effects on lab values
Diabetes: Autonomic neuropathy
Hyponatremia and CNS pathology
Metformin: periop management
NMB and hyperparathyroidism
Periop insulin: Effects
Pheochromocytoma: treatment of hypertension
Thyroid surgery and hypocalcemia

Body Fluids
Total body water approximates 60% of the body weight in an average adult. It is divided
into intracellular (40%) and extracellular (20%) compartments. Extracellular fluid is
further divided into plasma (5%) and interstitial fluid (15%). The blood volume (60-
65ml/kg) is distributed as 15% in the arteries and 85% in the venous system.
 3

At birth, low birth weight and full term infants have a greater % of TBW compared to
older children and adults (70-75% vs 50-60%). This increase is mainly from expansion of
ECF.

Osmolality/ Viscosity/ Oncotic Pressure- Major Determinants

OSMOLALITY/ TONICITY
Total osmolal concentration of plasma = 290 mOsmol /L.
This is the concentration of osmotically active particles expressed in osmols.
 4

Osmolality / Osmolarity
Osmolarity = number of Osmoles /L of solution (plasma) – affected by temperature.
Osmolality = number of Osmoles / kg of solvent.

Tonicity = osmolality of a solution relative to plasma.

0.9% saline = isotonic = same osmolality as plasma.

Total osmolal concentration of plasma = 290 mOsmol /L

All but 20 mOsmol/ L is due to sodium ion + accompanying chloride and bicabonate
ions.
Contribution to osmalility from protein is less than 2 mOsmo/L .
Major nonelectrolytes of plasma that contribute to osmolality
= glucose +urea (5 mOsmol/L each)
But can become larger contributors in hyperglycemia or uremia
Hyperosmolality may lead to coma (Hyperosmolar nonketotic coma)

One can approximate plasma osmolality by:

In mOsmol /L = 2 x Na (mEq/L) + 0.055 x glucose (mg/dl) + 0.36 x BUN (mg/dl)

Hyperosmolar nonketotic coma:

Ketoacidosis is not a feature because enough insulin is available to prevent ketone body
formation. Instead, hyperglycemic diuresis causes dehydration and hyperosmolality.
Sever hyperglycemia may lead to factitious hyponatremia.
Each 100 mg/dl increase in plasma glucose lowers plasma sodium by 1.6 mEq/L.
(This is dilutional hyponatremia- High osmotic gradient cause water to move from ICF to
ECF).

Which hormones regulate serum osmolality?

Water and sodium reabsorption in the kidney are influenced by hormonal factors : ADH,
atrial natriuretic peptide (ANP) and aldosterone. Sodium concentration is the primary
determinant of plasma osmolality. Plasma hypertonicity stimulates ADH release, which
enhances water reabsorption in the collecting ducts. ANP, which is released in response
to atrial stretch, has vasodilatory effects and increases excretion of sodium and water.
Aldosterone causes sodium reabsorption in the distal renal tubules.

Hyponatremia (serum Na < 135)

Dysnatrmia is typically associated with disturbed ECF volume.

When looking for the cause of hyponatremia, serum osmolality must be checked.
Next intravascular volume status must be evaluated.

Hyponatremia may occur with low, normal or high osmolality.

 5

(1) True hyponatremia- only when serum osmolality is decreased as well.

(2) Pseudo hyponatremia with normal or decreased osmolality

E.g., Hyperlipidemia, multiple myeloma- Sodium is low because large proportion of
plasma is occupied by lipid or protein and small proportion by water (clue normal
osmolality). Measuring serum sodium (not plasma sodium) avoids the problem.

(3) Hyponatremia with high osmolality- Seen in hyperglycemia, after administration of

mannitol (dilutional).
i.e., addition of osmotically active solutes which are unable to cross cell membranes
easily, such as:
glucose
mannitol
glycine
This causes water to move from ICF to ECF and decrease serum sodium levels.
But total body sodium or total body water is unchanged.

Once these last 2 causes of hyponatremia have been excluded, the approach to
diagnosis of hyponatremia is:

1st evaluate ECF volume from the clinical presentation.

2nd Urinary sodium concentration from spot urinary sample.

Most common cause of hyponatremia is excess of total body water, not reduced total
body sodium.

Hyponatremia with low, high or normal volume.

Hypovolemic hyponatremia:
1. Hemorrhage
2. Burns
3. Peritonitis

Hypervolemic hyponatremia:
1. CHF
2. Nephrotic syndrome
3. Cirrhosis
4. TURP syndrome

Euvolemic hyponatremia:
1. SIADH
2. Pseudohyponatremia

TURP syndrome is a case of true hypotonic hyponatremia (serum sodium < 125mmol/L)
 6

Describe the EKG changes associated with hyponatremia.

At sodium levels below 115mEq/L, one can see QRS widening and ST elevation.

The dose of sodium required to correct a deficit:

In a 70 kg man Na deficit (mmol) = TBW x (Desired(130) – Actual Serum Na (120))

= 60/100 x 70 x 10 = 420

Expected Change in plasma Na+ from 1 L of selected infusate

= Na+ of the infusate – Patient’s Na+
TBW +1
 7

Signs and symptoms of hyponatremia

Depending on the level:

In an awake patient: Nausea/vomiting, visual disturbances, depressed consciousness,
agitation, coma, seizures, muscle cramps, weakness, or myoclonus.
Cerebral edema at < 123 m Eq/L
Cardiac symptoms at < 100 m Eq/L
Hyponatremia with hypervolemia may present with pulmonary edema, hypertension, and
heart failure.

Hyponatremia associated with hypovolemia requires correction of prevailing sodium

deficit with saline.

Dilutional hyponatremia treated with:

• Water restriction and furosemide to limit expansion of ECF.
• Hypertonic saline (3% NACL with 513 mEq Na/L) only when neurological symptoms
are present.
• Optimal rate of correction: 0.6-1 mmol/L/h until sodium level reaches 125 mmol/L.
Relatively small increase (3 to 7 mEq/L ) reverse cerebral edema and stop seizures.

Rate of correction > 12 mEq/ L/Day can cause osmotic demyelination.

Usually ½ the deficit is corrected over first 8 h and the rest over 1-3 days.
• Once the serum sodium concentration of 125 to 130 mEq/L is reached, rate of
correction should be slowed (Serum sodium monitored every 1-2 hours during rapid
correction).

Hypernatremia
Major causes of hypernatremia
Excessive water loss – Sweating
Inadequate water intake- coma
Excessive sodium intake
Lack of ADH- nephrogenic or pituitary diabetes insipidus (DI)
 8

If the urine out put continues to be > 100 ml/h, with hypernatremia, the patient should be
evaluated for DI. The diagnosis of DI is likely if urine osmolality is < 300 mOsm/L and
serum sodium > 150 mEq/L. In central DI, desmopressin acetate (DDAVP) may be
administered.
Lack of thirst in an alert and awake patient with hypernatremia indicates a defect in the
osmoreceptors or cortical thirst center. With an intact thirst mechanisms, even a slight
increase in serum sodium (3-4 mmol/L) above baseline cause intense thirst.
Hypernatremia causes lethargy, mental status change, coma and convulsions. Acute
changes cause osmotic shift of water from the cells, shrinkage of brain with tearing of
meninges and intracranial hemorrhage.
Hypernatremia increases MAC of inhalational agents (enhanced sodium conductance?).

Electrolyte imbalance due to vomiting

Persistent vomiting results in:
• Loss of hydrogen ions from the stomach
• Loss of sodium and chloride ions from the extracellular fluid.
• Kidneys excrete potassium in exchange for hydrogen ions in an effort to maintain
normal arterial pH.

Result is dehydration with hypokalemic, hypochloremic metabolic alkalosis.

VISCOSITY

Factors affecting whole blood viscosity (V):

1. Hematocrit- increase from 40% to 60% = doubling V; 40% to 20% =1/2 V
2. Temperature- has an inverse relationship
3. Plasma proteins- especially fibrinogen and alpha- 2 globulin
4. Red blood cell aggregation increases V
5. Shear rate, when decreased V increases
6. Red blood cell deformability- In hereditary spherocytosis viscosity increases

Viscosity (V) = Shear stress/ Shear rate

In Newtonian fluids, such as Plasma and saline, shear rates increase in a linear
fashion with increasing shear stress. Thus viscosity remains unaltered.
Blood = Non-Newtonian fluid (suspension of cells in plasma)
 9

In blood viscosity increases sharply at low flow rates (for example in post capillary
venules) and remains constant at high and moderate rates (arteries and arterioles) due
to axial streaming and red blood cell deformation.

T
Physiological effects of hemodilution:
The most dramatic decrease in viscosity occurs in post capillary venules when hematocrit
decreases by 15% from normal (40-45% to 25-30%).
 10

Acute normovolemic hemodilution (ANH)

The term acute normovolemic hemodilution (ANH) refers to the removal of blood from a
surgical patient immediately before or just after induction of anesthesia, and replacement
with asanguinous fluid. The removed blood is stored in a CPD bag at room temperature
up to 6 hours to preserve platelet function and later reinfused. ANH is employed to
reduce the need for allogenic blood and to avoid potential transfusion associated
complications. An additional potential advantage of ANH is improvement in tissue
perfusion as a result of decreased viscosity.
The presence of malignancy or wound infection may contraindicate blood recovery
during surgery (cell saver), but not ANH.

Normovolemic hemodilution associated with:

1. Increase in venous return, right atrial pressure, and cardiac output.
2. Decrease in peripheral resistance

Maintenance of oxygen delivery requires this increase in cardiac out put (by increased
stroke volume). Therefore, moderate hemodilution does not impair, but rather improves
tissue blood flow/ tissue oxygenation.

Relationship between systemic transport of oxygen (STO2) and hematocrit (%).

The oxygen delivery is maximum in the hematocrit range of 35% to 45%.

COLLOID OSMOTIC PRESSURE

Colloid Osmotic pressure and Starling forces

The difference in the colloid osmotic pressure (plasma oncotic pressure 20+ mmHg more
than interstitial fluid) helps maintain the intravascular volume.
 11

Edema = excess fluid in the interstitial space (transudate/ exudate)

Increased edema from:
Increased capillary P
Increased permeability
Decreased protein (COP <11 mmHg)
Obstruction to lymph
Ascites is excess fluid in the peritoneal cavity that accumulate due to increased
capillary hydrostatic pressure, increased permeability, decreased intravascular protein
(colloid pressure < 11 mmHg), or due to obstruction to lymph flow. Example:
cirrhosis, malignancy or cardiac failure.

Hemorrhage
Decreased blood volume
 12

↓
Arterioles constrict
↓
Venous pressure falls
↓
Decreased capillary pressure
↓
Fluid moves into capillaries

After moderate h’age:

Circulating blood volume is restored in 12-72 hrs.
Preformed albumin moves into circulation from extra vascular stores.
Hematocrit may not fall for several hours.
Peak reticulocyte count increase occurs in 10 days.
Red blood cells restored in about 4-8 weeks.

Body Fluid Electrolytes

Electrolyte requirement of an adult:
Sodium = 1-2 mEq / kg/day
Chlorides and potassium = 1-1.5 mEq /kg/day

ECF Sodium = 135-145mEq/L.

In ICF, there is only 10 mEq/ L of sodium due to active sodium extrusion.
Sodium is the major determinant of ECF volume since water follows sodium and
diffuses passively across membranes.
Variation in serum sodium leads to changes in osmolality of both ECF and ICF as
stated before. Sodium and its major anions chloride and bicarbonate constitute >90%
of total solutes of ECF.
 13

Preoperative serum sodium levels:

For elective surgery lower limit is 131 mEq/L and all patients undergoing surgery should
have serum sodium concentrations of less than 150 mEq/L before anesthesia.

Body Potassium
Dyskalemia may be accompanied by impaired function of excitable tissues.

Total body K = 50 mEq /kg (or 3500 m Eq in a 70 kg)

98% of the total body K is in ICF; < 1 mEq/Kg ECF (Only 70 mEq) is in ECF.
This huge concentration gradient is maintained by Sodium/potassium activated
ATPase pump.
Fall in 1 mEq of potassium = 200 mEq deficit.
About 10% of the total body K is bound; remaining 90% is exchangeable.

Preop hypokalemia or hyperkalemia:

Major danger in anesthetizing patients who have disorders in potassium balance is

abnormal cardiac function, both electrical disturbance and poor cardiac contractility.

Hyperkalemia:
1. Lowers resting membrane potential of excitable cardiac cells.
2. Decreases upstroke velocity.
3. Decreases duration of the myocardial action potential (potentiated by low serum levels
of calcium and sodium).
T waves are peaked and narrow at > 7 to 9 mEq/L.
>7 mEq/L, atrial conduction disturbances are seen; SVT, PVCs, ventricular tachycardia,
ventricular fibrillation, or sinus arrest may occur.
 14

Causes of hyperkalemia:
1. Acute oliguric renal failure, chronic renal failure (GFR < 15 ml/min).
2. Exogenous K loads: Banked blood
3. Hypoventilation can be dangerous during anesthesia. Each 0.1 change in pH may cause
0.4- to 1.5-mEq/L change in serum potassium levels in the opposite direction.
For example, if pH decreases from 7.4 to 7.3, serum potassium levels could increase from
5.5 to 6.5 mEq/L (respiratory or metabolic acidosis).
Organic acidosis (lactic acidosis, ketoacidosis) has a little effect on potassium level
(unlike mineral acids).
Hyperkalemia is enhanced by concurrent hyponatremia, hypocalcemia and acidosis

.
Hypokalemia - Fall in 1 mEq of K = 200 mEq deficit

Causes:
Drug induced (loss or transcellular shift)
Non drug induced (loss or transcellular shift)

Major worrisome manifestations of hypokalemia:

Pertain to circulatory system, both cardiac and peripheral components.
In addition, chronic hypokalemia causes muscle weakness, hypoperistalsis, and
nephropathy.
 15

Cardiovascular manifestations of hypokalemia:

• autonomic neuropathy, orthostatic hypotension
There is decreased sympathetic reserve.
• impaired myocardial contractility
• electrical conduction abnormalities:
sinus tachycardia
atrial and ventricular arrhythmias such as ventricular fibrillation.
•ECG shows widening of the QRS complex, ST-segment abnormalities, progressive
diminution of the T-wave amplitude, and progressive increase in the U-wave amplitude.
(U waves are not specific for hypokalemia, but sensitive indicators of the condition).
U waves are seen invariably when serum potassium level is < 2.3 mEq/L .

Other manifestations:
In addition, chronic hypokalemia may cause muscle weakness, hypoperistalsis, and
nephropathy (prolonged hypokalemia causes chronic renal interstitial damage).

Preop Hypo/ Hyperkalemia, what to do?

None of the studies have shown increased morbidity or mortality under anesthesia with a
potassium level of more than 2.6 mEq/L.
Although all patients undergoing elective surgery should have normal serum potassium
levels, delaying surgery is not recommended if the serum potassium level is above 2.8
mEq/L or below 5.9 mEq/L, if the cause of the potassium imbalance is known, and if the
patient is in otherwise optimal condition.
This range of safe potassium levels has changed over the years as more data have become
available on the safety of preoperative hypokalemia and the dangers of replacing
potassium in a hospital environment. Potassium-depleted myocardium is unusually
sensitive to digoxin , calcium, and most important, potassium.
Rapid potassium infusion can cause arrhythmias similar to hypokalemia itself.
Maximum recommended rate of infusion of potassium is 0.5 0.7 mEq/Kg/hr (20-40
mEq/Hr). The concentration of the solution should be no higher than 40-60 mEq/L to
avoid pain during infusion. (in glucose free solution). Safety is enhanced with continuous
ECG monitoring during the infusion.
It is important to prevent further worsening of hypokalemia from anxiety and stress.
Therefore use premedication with clonidine or benzodiazepine.

Particular care if: concurrent acidemia, type IV renal tubular acidosis, diabetes mellitus,
receiving NSAID, ACE inhibitors, beta-blockers because there is delay in movement of
extracellular K into cells in this situations.
 16

Treatment of hyperkalemia:

1. 10% Dextrose acts within 30 min and lasts 4-6 hrs.

(10% Dextrose 500 cc + 10 units regular insulin over 30-60 mins).
2. Calcium gluconate reduce effect of increased potassium on myocardial membrane
(membrane stabilization) and has an immediate onset of action and lasts 30-60 mins.
Even though it is reported to be irritating to veins, 10% calcium chloride provides 3 times
calcium than equal volume of 10% calcium gluconate.
3. IV sodium bicarbonate produces transcellular shift and membrane antagonism
4. Resin- orally or rectally causes a colonic exchange of calcium or sodium for
potassium. Effects are seen in 6 mins rectally or in 120 mins orally.

Hypomagnesemia aggravates effects of hypokalemia.

If hypokalemic and acidotic (diabetic ketoacidosis), potassium administration should
precede correction of acidosis to avoid precipitous drop in potassium.

Relationships between electrolyte status and anesthetic requirements (dog study):

Hyponatremia and hypo-osmolality decreased MAC
Hypernatremia increased MAC
Hyperkalemia did not affect the anesthetic requirement.

Body PHOSPHATE
Body contains 700-800G of phosphate. 85% is found in bone.
 17

It is a major intracellular anion and has an important role in intracellular respiration

and metabolism (ADP,ATP).
Normal serum = 3.0-4.5 mg/dl

Hypophosphatemia in: Starvation

Malabsorption
Vomiting
Increased urinary loss

Causes:
Neuromuscular – weakness
Hyporeflexia
Respiratory failure
Seizures
Cardio vascular – CHF
Hematologic- Hemolysis
Platelet dysfunction
Decreased 2,3 DPG
Refeeding syndrome: This is due to carbohydrate induced hypophosphatemia because
insulin increases cellular uptake of phosphate. TPN is the most associated with
hypophosphatemia
Hyperventilation can also leads to reduced phosphate.
Patients on mechanical ventilation for weeks can develop hypophosphatemia

BODY CALCIUM

Hypocalcemia

In the OR, common causes:

 18

• Acute hyperventilation
• Citrated blood given at > 1.5 ml/kg/min
In the hospitalized patients:
• Due to low albumin (critically ill, sepsis, burns, ARF). The ionized calcium level is
normal. These patients require improvement in overall nutrition.
Correction factor: Add 1mg/dl of calcium for every 1 g/dl of albumin levels that is less
than 4g/dl.

Major signs and symptoms: Tetany, laryngospasm, hypotension, dysrhythmias (ECG

prolong QT, heart block, prolongation of ST segment)
Hypocalcemia causes symptoms when serum ionized calcium < 0.7 mM
Carefully consider whether mild, asymptomatic ionized hypocalcemia requires therapy,
especially if there is ischemic and septic state.
There is evidence that calcium therapy may increase cellular damage.

Hyperkalemia and hypomagnesemia potentiate cardiac and neuronal irritability due to

hypocalcemia, and hypokalemia protects.

Hypercalcemia  shortened QT interval (Shortened ST segment)

Medical therapy for severe hypercalcemia.

Maximize renal calcium excretion with normal saline infusion containing 20-30 mEq/L
K+ and furosemide to promote a diuresis of 200-300 cc/hr. Careful monitoring of
potassium and magnesium are required. Additional therapy options include pamidronate,
calcitonin, steroids, mithramycin or dialysis.

MAGNESIUM PHYSIOLOGY
Magnesium is eliminated entirely by the kidney (i.e., related to the glomerular filtration
rate). In the kidney, magnesium is a renal vasodilator and a diuretic.

Advantages and uses:

1. Effective in treating arrhythmias – ventricular arrhythmias, torsades de pointes,
digitalis associated arrhythmias, adrenergically mediated arrhythmias, and partial
protection against bupivacaine induced arrhythmias.
2. Effective bronchodilator- used successfully in severe acute asthma. No effect shown in
chronic asthma.
3. In Obstetrics- used as a tocolytic agent and in prevention of seizures in preeclampsia.
The therapeutic level in preeclampsia is 5 to 7 mg/dL. At levels over 15-20 mg/dL
respiratory depression occurs due to neuromuscular blockade (no effect on central
respiratory drive).

Hypomagnesemia
Risks:
1. Increased risk of perioperative arrhythmias
 19

2. Respiratory muscle weakness

3. CNS irritability manifested as seizures, hyperreflexia (Chvostek sign)

Magnesium deficiency is also known to be accompanied by thrombotic tendencies,

increased platelet aggregatability, and increased coronary artery responsiveness to
contractile stimuli (coronary vasospasm?). These factors are important in the initiation
of acute myocardial infarction. (ref medscape). However, no clear evidence of benefit in
the setting of acute MI (Miller 7th ed)

Treatment: IV magnesium sulphate 1-2g IV over 15 minutes followed by 1g/hr infusion.

Hypermagnesemia (> 2.5 mEq/L)

Symptoms and ECG changes depend on the serum levels.
See below.

Effects of Magnesium:
1. Magnesium is a central nervous system depressant. Although it crosses the blood brain
barrier poorly, the level in the CSF is controlled by an active transport mechanism.
2. Magnesium interferes with the release of acetylcholine at the neuromuscular junction
and potentiates the muscle relaxants, both depolarizers and nondepolarizers. Magnesium
can cause severe muscle weakness in patients with myasthenia gravis or Eaton-Lambert
syndrome.
3. Magnesium potentiates the local anesthetic activity.
4. Magnesium is a direct vasodilator. The vascular tone is decreased also by sympathetic
blockade and inhibition of catecholamine release.

Elimination of magnesium:
1. Fluid loading and diuresis.
2. Temporary reversal with calcium therapy
3. Definitive therapy involves dialysis
 20

GLUCOSE PHYSIOLOGY
Glucose is an important fuel source. It is the sole fuel for most of the brain. The
movement of glucose into cells is facilitated by insulin. This process also requires
potassium and phosphate.
Adults can use glucose only at a rate of 3 to 5 mg/kg/min at rest, even with supramaximal
insulin levels (approx. 240ml/hr of 5% dextrose infusion).

Diabetes Mellitus (DM)

Diagnosis of Diabetes- ADA definition

Fasting (8h) plasma glucose > 126 mg/dl (7 mmol/L)
Symptoms: polyuria, polydipsia, unexplained weight loss
Random blood glucose > 200 (11mmol/L)

Normal fasting < 100 (5.6)

ADA defines fasting 100-125 (5.6-6.9) as impaired
 21

Sulfonylureas: First generation: tolbutamide, chlorpropamide or Second generation:

Glyburide, glipizide- increase release of endgenous insulin and enhance insulin receptor
function.
Biguanides: Decrease hepatic glucose output and increase insulin action. Associated with
lactic acidosis avoid in hepatic or renal impairment.
Metformin: Lactic acidosis is the most serious side effect. This is caused by binding to
mitochondrial membranes and reducing intracellular concentration of ATP hence
anaerobic glucose metabolism and accumulation of lactate.
Other side effects include anorexia, nausea and diarrhea.

Metformin should be discontinued 24 hr preoperatively, and 48 hr after the use of

IV radio contrast dye, until normal renal functions are confirmed. (Metformin
should not be used with serum creatinine > 1.4 mg/dL, or stated better when eGFR
is < 60 ml/min). This is due to fear of lactic acidosis. Key word 2012: Metformin:
contrast dye

Anesthetic considerations of DM
Atherosclerosis, neuropathy, nephropathy, retinopathy- are long term complications of
DM.
HTN, CAD, diastolic dysfunction, CHF, PVD, CVA
Leading cause of RF
DKA fluid deficit > 5L

1. Diabetes affects oxygen transport: Glucose covalently binds to hemoglobin and affects
allosteric interactions between beta chains.
2. Autonomic dysfunction (lack of appropriate vasoconstriction):
a. Increased risk for intraoperative hypothermia
b. Affects the ability to regulate blood pressure (orthostatic hypotension)
c. Increased hypotension with IV propofol, thiopental (etomidate is a better agent)
d. Changes in heart rate with atropine and beta blockers are blunted.
ECG shows loss of R to R variability.
3. Increased risk of coronary artery disease (age adjusted risk = 2x male; 3x female).
Silent ischemias are more likely in diabetic patients. Therefore, preoperatively, question
about exercise tolerance, presence of shortness of breath with exertion.
4. Gastrointestinal tract: Due to damage to the ganglion cells there is delayed gastric
emptying (consider full stomach).
5. Difficult airway: Glycosylation of the atlanto-occipital joint may lead to limited neck
mobility (stiff-neck syndrome).

Hemoglobin A1C levels is the most accurate way to assess glucose control over the
previous 2 months. Normal 4-6%; recommend <7- 8.5% depending on the age.

Perioperative Management:
1. Discontinue long acting insulin or oral hypoglycemic agents 1-2 days preoperatively.
2. Administer short acting insulin every 4-6 hr SC, the dose adjusted to the glucose level.
 22

3. Metformin should be discontinued 24 hr preoperatively, and 48 hr after the use of IV

radio contrast dye, until normal renal functions are confirmed. (Metformin should not be
used with serum creatinine > 1.4 mg/dL, or stated better when eGFR is < 60 ml/min).
This is due to fear of lactic acidosis.
4. Oral intake stopped 12hr before surgery (metoclorpramide, H2 blockers help).
5. On the day of surgery, start a dextrose infusion (2 mg/kg/hr). Check blood glucose
level. Regular insulin infusion of 0.5-2 U/hr started on patients who are taking insulin.
Blood glucose monitored hourly.
However, for short procedures, insulin is simply held the morning of surgery.

Why worry about hyperglycemia?

Acute consequences:
impaired wound healing (impaired blood flow to the wound, impaired fibroblast activity,
vit C uptake by cells), dehydration
impaired immune system response
proteolysis.

Os diuresis: loss of NA, K, Mg, Phophate.

In general, acidosis should not be treated with buffers (ketoacidosis corrected as insulin
and glucose improve; lactic acidosis from poor perfusion responds to IV fluids).
If pH close to 7.15 (HCO3 < 10 mEq/L) hypotension fails to respond to IV fluids.
NaHCO3 may be required.

Diabetic Autonomic neuropathy (DAN)

Can affect any part of the ANS. Autonomic disturbances can be clinical or subclinical.
Subclinical DAN can occur within a year or 2 after diagnosis, while clinical DAN does
not develop for many years and depends on the duration of DM and degree of control.
Cardiovascular DAN:
Resting tachycardia
Loss of heart rate variability during deep breathing
HR that fails to respond to exercise
Limited exercise tolerance from impaired ANS responses
Systolic and diastolic dysfunction of the heart with reduced EF
Dysrhythmias  sudden death
Asymptomatic CAD
Sever orthostatic hypotension (>30mmHg with standing) in severe form
Respiratory: Impaired ventilatory response to hypoxia and hypercube
GI: Impair gastric secretion and gastric motility

Preop Glucose level?

GLUCONTROL trial randomized Adult patients form 21 participating medical-surgical
ICUs to group 1 (target BG 7.8-10.0 mmol/L) or to group 2 (target BG 4.4-6.1 mmol/L).
The rate of hypoglycaemia was higher in the group 2 (8.7%) than in group 1 (2.7%, p <
0.0001). ICU mortality was similar in the two groups (15.3 vs. 17.2%).
 23

Intensive Care Med. 2009 Oct;35(10):1738-48

NICE-SUGAR compared glycemic control in critically ill patients. Large international

study, 6104 patients, randomized to achieve 81-108 or 180 mg/dl.
Conclusion: Intensive glucose control increased mortality among adults in the
ICU(Hypoglycemias- 6.8 vs 0.5%)
N Eng J Med 2009;360:1283-1297
Response to insulin varies from patient to patient and within a patient overtime.
L & D <100
Perioperative avoid > 180

Key word (2012) Hypoglycemia: glucagon

Glucagon is a hormone produced by the pancreas that, along with insulin controls the
level of glucose in the blood. Glucagon has the opposite effect of insulin, that is, it
increases the glucose level in blood. Glucagon, the drug, is a synthetic version of human
glucagon and is manufactured by genetic engineering using the bacteria Escherichia coli.
Glucagon is used to increase the blood glucose level in severe hypoglycemia. Other
glucose-elevating drugs are glucose itself and diazoxide (Proglycem).
Glucagon raises blood glucose levels by:
1. preventing the liver from storing glucose
2. increasing glucose formation in the liver from dietary proteins and fats
3. increasing the release of glucose from the liver into blood.

Glucagon transiently paralyzes the muscles of the intestines and occasionally is used
during testing that requires the intestines to be flaccid, for example, endoscopic
retrograde cholangiopancreatography and barium enema.
(MedicineNet.com)

Fluid management
Routine maintenance fluids:
70 Kg post operative patient requires: 110 ml H2O and 110 kcal per hour
(4-2-1 rule close approximation).
However, the 4-2-1 rule has been challenged recently. The amount of free fluid
administered should be reduced because of the post operative hyponatremia secondary to
ADH secretion.

Routine intaoperative fluid:

Rate of fluid
= CVE (compensatory volume expansion) + deficit+ Maintenance + loss+ third space
 24

CVE:
CVE compensates for the venodilatation and cardiac depression caused by anesthesia.
CVE with 5-7 ml/kg balanced salt solution should be administered before or
simultaneously with onset of anesthesia.
However, this effect subsides rapidly postoperatively, and patients with cardiac and renal
impairment may develop acute hypervolemia.

Deficit:
= maintenance fluid x hours since last intake + unreplaced preoperative external and third
space losses.
For normal patients, the rate of fluid infusion should be 3 to 4 times the maintenance rate
until the calculated deficit has been corrected.

Maintenance:
This meets ongoing basal needs for water and electrolytes (4-2-1).
Surgical (some anesthesia) stress reduces insulin and its effects. Therefore, glucose
containing fluids should not be administered.

Losses:
External losses (e.g., blood and ascites)

(A) Blood loss: 3 ml of crystalloid, or 1 ml of colloid for each 1 ml of blood loss,

or 1 ml of PRBC for each 2 ml of blood loss.
Fully soaked sponge (4x4) –holds 10 ml
Soaked lap - holds 100-150 ml
It is more accurate to weigh especially for pediatric patients.

To calculate necessary volume of PRBC (V):

Determined preoperatively: From Hct + Estimated blood volume (EBV)
V=EBV ({Hct initial – Hct final}/Hct average)
The calculation assumes euvolemia is maintained.

(B) Ascites and pleural effusion:

Electrolyte = ECF; protein = 30-100% of plasma. Balanced salt solution is appropriate,
but colloid should be added if COP is lower (< 17 mmHg).

(C) Evaporation from exposed viscera: entirely water.

This amount is directly proportional to the temperature and exposed surface area, and
inversely to humidity.

(D) Redistribution (third space losses): not available to vascular space.

Colloid enters injured tissue more rapidly than normal tissues, but slower than electrolyte
solutions. Therefore, less edema is likely with colloids.
 25

Composition = ECF electrolytes + small amount of protein. Use balanced salt solution to
replace.
Volume redistributed correlates roughly with degree of manipulation (i.e., hysterectomy
2 ml/kg/hr; major bowel resection 4-6 ml/kg/hr).

Fluid Replacement Solutions

Composition of crystalloids

Half life of crystalloid solution = 20-30 minutes. Electrolyte solutions are isotonic
(replacement –type solution for losses involving both water and electrolytes).

Normal saline produces dilutional hyperchloremic acidosis (chloride = 154), because

bicarbonate level decreases (excreted by kidney) as chloride increases. This leads to
progressive renal vasoconstriction and fall in GFR. Normal saline is preferred when brain
injury or hyponatremia occurs.

Hypertonic Salt Solutions:

They are not commonly used. The sodium concentration of the solutions ranges from 250
to 1200 mEq/L. There is controversy regarding the use of these solutions in hemorrhagic
shock. The advantage is satisfactory resuscitation can be achieved with less total volume.
For example, 250 ml of 7.5% saline is comparable to resuscitation with 2 to 3 ml of 0.9%
saline. They can be useful in mass casualties because of ease of storage, low cost and the
ability to expand plasma volume rapidly with less volume.

Lactated Ringer: Most physiologic when large volumes are needed.

5% Dextrose (D5W): Used as maintenance fluid for patients on sodium restriction,

 26

or to replace losses primarily due to water loss (DI), or to prevent hypoglycemia and
ketosis due to fasting (i.e., children)
D5W is initially isotonic but when glucose is metabolized becomes free water.

Distribution of crystalloid/colloid solutions after transfusion

When the blood loss is replaced with crystalloids, 3 to 4 times the volume lost should be
administered because crystalloid is distributed in ECF in a ratio of 1:4 in the
intravascular: extravascular compartments. Only about 20% remain in the circulation.

Distribution of infused fluids

Expected plasma volume (PV) increment = volume infused x normal PV
distribution volume
Volume infused = expected PV increment x distribution volume/ normal PV
If D5W is used, require 28 L to increase PV by 2 L; 2 x 42 / 3 = 28L
Using LR, 2 x 14 / 3 = 9.1 L
If 5% Alb  remain in PV and attract additional interstitial fluid (1x3/3)=1L
25% Alb, expand PV by approx 400ml for each 100 ml infused
These analysis are simplistic, body has highly regulated systems to maintain different
fluid compartments kinetic models of IV fluid therapy

Colloids:
Half life 3-6 hrs
If prepared in normal saline (Cl 145-154meq/L) they can cause hyperchloremic metabolic
acidosis (i.e., non-anionic gap acidosis)
 27

Colloids are derived from plasma proteins or synthetic glucose polymer.

1. Plasma protein: 5% albumin, 25% albumin, plasma protein fraction (PPF ).

They are heated to 60oC for at least 10 hrs in order to reduce the risk of hepatitis and
other viral infections. The PPF contain alpha and beta globulins in addition to Alb and
may cause hypotension (allergic nature). 5% Alb or PPF has colloid osmotic pressure of
20 mmHg. 25% alb (salt-poor) contains albumin at five times the concentration and has
the potential to cause 5 x expansion of volume provided. It is acceptable when plasma
volume is low but blood pressure is acceptable and ECF volume is expanded (albumin
may deplete the extracellular fluid space of water).

2. Synthetic glucose polymer (Gelatins, Hetastarch, Dextran)

Gelatin (Haemaccel) may cause histamine mediated allergic reactions (not available in
the USA)
Dextran 70,40:
6% dextran 70 is given for the same indications as 5% albumin. Dextran 70 exerts a
higher colloid osmotic pressure than the blood.
Dextran 40 is rarely used as a plasma expander. It is used in vascular surgery to prevent
thrombosis. It improves blood flow through microcirculation by decreased viscosity.
About 70% of dextran is excreted in urine within 24h; larger molecules through gut or
metabolized by endogenous dextranases in reticularendothelial cells.

Side effects:
1. Can be antigenic – May cause mild and sever anaphylactoid and anaphylactic
reactions. (incidence 1: 3300). These are mediated by dextran-reactive antibodies that are
IgG immunoglobulins. Rarely cause noncardiogenic pulmonary edema, thought to be due
to direct toxic effect on the pulmonary capillaries.
Promit (Dextran 1) prior to dextran administration is used to prevent the reactions. Promit
acts as a hapten and binds any circulating dextran antibody.
2. Antiplatelet effect can cause increased bleeding time.
3. Use of >20ml/kg interferes with crossmatching of blood due to rouleaux formation.
4. Higher molecular weight (dextran 70) can be associated with renal failure.
5. Causes reduction in F VIIIc, vWF, and F VIII activity.

Hydroxyethyl Starch (hetastarch): in normal saline, pH 5.5, osmolality 310 mOsm/L.

This is a synthetic molecule resembling glycogen, and is available as a 6% solution with
average M. Wt 450,000.
The small molecules are eliminated by kidney and large molecules must be first broken
down by amylase.
Hetastarch is non antigenic and anaphylactoid reactions are rare
It is highly effective as a plasma expander; less expensive than albumin; last longer than
albumin.
If > 20ml/kg/24 hrs is administered it causes a dilutional effect like other plasma
expanders. It reduces F VIII:C and vWF levels by 50% -80% with prolonged PTT when
 28

more than one liter is administered (produces acquired type I vW syndrome with poor
platelet adhesion). Hetastarch can also interfere with clot formation by direct movement
into the fibrin clot of hetastarch molecules (impair fibrin polymerization).
It interferes with blood typing only if blood sample contains > 30% starch.
Hextend: Hextend contains physiologic concentrations of electrolytes and smaller
molecular mass with shorter half life. It might not affect coagulation as hetastarch.

Pentastarch 10% - Pentastarch is medium M Wt. and has a shorter half-life (few days);
about 90% eliminated within 24 hrs and undetectable after 96 hr.
Anticoagulant effects are similar to hetastarch. Pentastarch has a good initial volume
expanding capacity of 1.5 x infused volume. In critically ill its effect are similar to
albumin.
PentaLyte (pentastarch-LR) = Hextend

Renal Effects of colloids: Use of large amount of colloids is not recommended with
preexisting renal dysfunction. Hypertonic solutions (10% HES 200, 20% Alb, 10%
dextran 40) have the potential to induce renal failure. The low M wt fraction accumulates
within the tubules, form casts and cause obstruction.
This problems does not appear to occur with 5% Alb.

Incidence of anaphylaxis or anaphylactoid events: (life threatening or severe)

These are more frequent with gelatins.
Incidence:
Gelatins < 0.35%
Dextrans < 0.28% (with advent of dextran 1 hapten, risk now < 0.0015%).
Albumin < 0.1%
Hetastarch < 0.06%.
In comparison, the rate of severe reactions to penicillin is < 0.05%.

The Safety of Hydroxyethyl Starch (HES)—Products Now in Doubt (APSF-

Spring/Summer 2013)

The purpose of this short commentary is to draw attention to some recent safety
concerns for HES products. While worries about the possibility of impaired blood
 29

clotting have been a concern for some time (vide infra), more recent studies suggest
that HES products are also associated with acute renal injury as well as other adverse
events, including an increase in mortality. The pathophysiology may be related to the
fact that HES products, while undoubtedly effective at increasing plasma volume, do
not stay localized to the circulation but end up instead as deposits in renal, hepatic,
splenic, endothelial, and other tissues.4 In addition, as discussed later, HES molecules
may interact with the endothelial glycocalyx in an unfavorable manner.

Although it has been known for some time that HES products can affect coagulation
via adverse effects on both von Willebrand factor and platelet aggregation,12 it is now
also known that HES 130/.4 administration results in a weaker, smaller clot.13 These
facts may explain the increased transfusion rate in HES 130/.4 treated individuals
with blunt trauma compared to those treated with normal saline.14

Finally, we would like to comment on the importance of the endothelial glycocalyx in

understanding the effects of fluid administration. The endothelial glycocalyx covers
the endothelial cells present in the lumen of normal blood vessels, playing a central
role in its barrier properties. In conjunction with bound fluid and plasma proteins the
glycocalyx forms an “endothelial surface layer,” typically 500 to 1000 nm thick. The
bound proteins provide the endothelial surface layer with its own colloid osmotic
force, with the consequence that Starling's classic model (of semi-permeable
capillaries subject to hydrostatic and oncotic pressure differences) is now considered
to be an oversimplification.15,16

The glycocalyx harbors a wide variety of anticoagulant proteins like antithrombin,

components of the protein C system, and tissue factor pathway inhibitors.17 The
glycocalyx also plays a vital role in nitric oxide release in endothelial cells as well as
modulating the immune response by preventing the adhesion of leucocytes and
platelets to the endothelial cells.17,18 Damage of the glycocalyx can lead to protein
extravasation and tissue edema as well as impair the processes mentioned above.
Continuing research on the properties of the glycocalyx and endothelial surface layer
is expected to yield a better understanding of the biology of vascular permeability,
inflammatory processes, blood pressure regulation, and blood coagulation, as well as
clinical conditions like ARDS, sepsis and ischemia/reperfusion injury.
HES colloids have negative charges on the surface of their molecules which render
them unattracted to the glycocalyx, which also has negative surface charges.17 As a
result they are unable to contribute to the integrity of the endothelium surface layer in
a manner like albumin, whose distribution of positive and negative surface charges is
more favorable to maintaining the integrity of the endothelial surface layer.19

Are colloids more effective plasma expanders than crystalloids?

Achievement of Hemodynamic Goals: It seems hemodynamic changes by colloids are
immediate effects that do not last long and do not lead to improved clinical outcomes in
comparison with crystalloids.
 30

SAFE trial compared alb to crystalloid in ICU patients 7000 patient, VISEP study > 500
with sepsis,
Wills study in children > 120
- All show safe to resuscitate only with crystalloid..
Edema formation: Extravascular lung water and pulmonary edema no diffrence.
Aggressive over resuscitation is bad with both. Positive fluid balance may be a strong
prognostic risk factor for death.
Albumin may be harmful in some situations such as traumatic brain injury (higher 28-day
mortality in SAFE study)
All synthetic colloids carry inherent risk of anaphylactic reactions, coagulopathy, and
renal impairment- mechanism not fully understood ?osmotic nephrosis.
Third generation HES: 130/0.4 safer?
May be because of different pharmacokinetic properties. But not enough studies to prove
yet.
A & A Hartog CS, Brauer M, Reinhart K. The efficacy and safety of colloid resuscitation
in critically ill 2011;112:56-64.

N Eng J Med 2007; 357: 874-84.

Pediatric Fluid Management:

Infants and young children may have clear liquid (3 ml/kg) 2 hours before their
operation. Breast feeding 4 h before; Bottle feedings (milk) until 6-8 hrs before surgery.
(High metabolic rate and water turnover in infants can cause significant hypoglycemia
and dehydration from prolong starvation)

In infants to replace the third space loss:

During Intra abdominal surgery = 6-10 ml/kg/hr
Intra thoracic = 4-7
Superficial surgery/neurosurgery = 1-2

Fluid Management in Patients Undergoing Liposuction

This type of procedure is usually performed using minimal sedation. The intravascular
volume change depends on the type of liposuction performed.
 31

Tumescent technique:
This technique is used to remove small volumes (<3000ml) of fat. Subcutaneous (SC)
infiltration of large volumes of dilute lidocaine with epinephrine is used to make the
tissue firm and to facilitate removal of adipose tissue. Because of the smaller volume of
tissues removed there is less damage to the SC tissue and fluid shifts are minimal.
Semitumescent liposuction:
This involves removal of large volume of fat. Therefore requires larger volumes of
lidocaine/ epinephrine and more sedation. The patient may require general anesthesia
(>3000 ml fat removal) and may have complications from fluid shifts. The epinephrine in
the solution limits the amount of fluid absorbed systemically. However, if the fluid is not
removed before the effect of epinephrine wears off, the patient may absorb large amount
of fluid leading to pulmonary edema. The large amount of lidocaine infused also has the
potential to cause toxicity. The addition of vasoconstrictor and the removal of most of
infused fluids are thought to limit toxicity. Usually, the patients receive 70-80 mg/kg of
lidocaine and maximum safe dose of lidocaine during tumescent technique is still
controversial.
According to the American Academy of Dermatology guidelines the maximum dose of
lidocaine is 55 mg/kg. The patients should be evaluated to exclude any use of
medications that inhibit the major pathways by which lidocaine is metabolized. These
include cimetidine, beta blockers, phenytoin and procainamide.
It has been shown that peak plasma lidocaine concentration occurs 12-14 h after
beginning the infiltration. Clinical local anesthesia is apparent for up to 18 h, obviating
the need for postoperative analgesia. Epinephrine assures complete vasoconstriction and
there is virtually no blood loss with liposuction
The large volume of normal saline infiltrated into fat as part of the tumescent technique is
more than sufficient to compensate for insensible fluid losses as well as fluid lost by
liposuction.
Gordley KP and Basu CB. ,Optimal Use of Local Anesthetics and Tumescence. Semin Plast Surg.
2006;20:219-224

Are colloids more effective plasma expanders than crystalloids?

Achievement of Hemodynamic Goals: It seems hemodynamic changes by colloids are
immediate effects that do not last long and do not lead to improved clinical outcomes in
comparison with crystalloids.
SAFE trial compared Albumin to crystalloid in ICU patients (7000 patients), VISEP
study > 500 patients with sepsis,
Wills study in children > 120 patients
- All show it is safe to resuscitate only with crystalloid..
Edema formation: Extravascular lung water and pulmonary edema no difference between
crystalloid vs colloids.
Aggressive over resuscitation is bad with both. Positive fluid balance may be a strong
prognostic risk factor for death.
Albumin may be harmful in some situations such as traumatic brain injury (higher 28-day
mortality in SAFE study)
All synthetic colloids carry inherent risk of anaphylactic reactions, coagulopathy, and
renal impairment- mechanism not fully understood ?osmotic nephrosis.
 32

Third generation HES: 130/0.4 safer?

May be safer because of different pharmacokinetic properties. But not enough studies to
prove yet.
A & A Hartog CS, Brauer M, Reinhart K. The efficacy and safety of colloid resuscitation
in critically ill 2011;112:56-64.

Source of Energy for brain during Starvation:

Timeline of starvation
0 hours: Glucose still used as primary fuel.

0 – 6 hours: (Glycogenolysis) Glycogen is broken down to produce glucose for the body.
Because of the blood- brain –barrier, getting nutrients to the human brain is especially
dependent on molecules that can pass this barrier. About 25% of total body glucose
consumption occurs in the brain.

6 – 72 hours: Glycogen stores are used up (usually lasts 24h) and the body breaks down
fatty acids. Ketone bodies are produced to help feed the brain. After 2 or 3 days of
fasting, the liver begins to synthesize ketone bodies from precursors obtained from fatty
acid breakdown. The brain uses these ketone bodies as fuel, thus cutting its requirement
for glucose. After fasting for 3 days, the brain gets 30% of its energy from ketone bodies.
After 40 days, this goes up to 75%

After several days of fasting, all cells in the body begin to break down protein. This
releases amino acids into the bloodstream, which can be converted into glucose by the
liver. Since much of our muscle mass is protein, this phenomenon is responsible for the
wasting away of muscle mass seen in starvation..

The body's rate of protein loss is greatest during the first 72 hours. After several days of
starvation the body adapts and starts to conserve protein

Hormone stress response

According to the stressful event, the body's way to respond to stress is by sympathetic
nervous system activation which results in the fight-or-flight response.
Reactions to stress are associated with enhanced secretion of a number of hormones
including glucocorticoids, catecholamines, growth hormone and prolactin, the effect of
which is to increase mobilization of energy sources and adapt the individual to its new
circumstance.
Insulin may decrease during stress. This along with increase in its antagonistic hormones
can contribute to stress-induced hyperglycemia.
 33

Thyroid function is usually down-regulated during stressful conditions. T3 and T4 levels

decrease with stress. Stress inhibits the thyroid-stimulating hormone (TSH) secretion.
Indian J Endocrinol Metab. 2011 Jan-Mar; 15(1): 18–22.

Basal caloric requirement =

Calories per gram of:

Water = 0kJ (0 Cal)
Protein = 17kJ (4 Cal)
Dietary fibre = 13kJ (3 Cal)
Fat = 37kJ (9 Cal)
Alcohol = 29kJ (7 Cal)
Carbohydrates = 16kJ (4 Cal)

An adult require: Na = 1-2 mEq / kg/day; Cl and K = 1-1.5 mEq

/kg/day
Key words (2012):
1. Postoperative SIRS/ Sepsis Dx
2. Acute septic shock
(see attached ASA article on sepsis)

Key words 2012 on TPN:

1. Enteral nutrition vs TPN, complications
2. TPN: discontinuation: hypoglycemia
3. TPN: Phosporous deficiency

How long should you wait before starting TPN in the critically-ill patient?

At least eight days, according to the Early Parenteral Nutrition Completing Enteral
Nutrition in Adult Critically Ill Patients Study (EPaNIC 2011), a prospective,
 34

randomized, controlled, parallel-group, multicenter investigator-initiated trial in 4640

patients which showed by waiting 8 days to start TPN (as opposed to 48 hours) shortened
ICU stay and lowered infection rates. This study compares early (European guideline)
versus late (American/Canadian guideline) initiation of parenteral nutrition when enteral
nutrition fails to reach a caloric target.

T/F: A recognized complication of TPN is hypophosphatemia?

True. Hypophosphatemia (defined as phosphate <2.5mg/dL) is reported in 17-28% of

critically ill patients. It can result from increased renal excretion of phosphate, decreased
absorption by the GI tract, or most commonly, an increase in intracellular movement of
phosphate. Glucose loading, as occurs with administration of TPN, results in
intracellular glucose movement. As TPN is instituted, glucose transport and oxidative
phosphorylation acutely increase, resulting in increased demand for intracellular
phosphate to support the formation of ATP. Hypophosphatemia and can lead to impaired
myocardial contractility and cardiovascular collapse, as well as respiratory failure,
rhabdomyolysis, seizures, delirium, and death.

Why do some patients on TPN have an increased minute ventilation?

The respiratory quotient (RQ) of a nutritional substance is defined as RQ = CO2

eliminated / O2 consumed. The RQ of glucose is 1.0, whereas the RQ of proteins are 0.8-
0.9, and the RQ of fats are ~ 0.7. Overfeeding patients or providing too much
carbohydrate causes an increase in carbon dioxide production. The patient compensates
by increasing their respiratory rate in order to breathe off the excess CO2.

What are the potential complications of TPN?

Catheter sepsis can occur as a primary or secondary infection. Metabolic complications

arise from too much or too little energy source and electrolyte abnormalities. These
include hyperglycemia, nonketotic hyperosmolar coma, hypoglycemia, prerenal
azotemia, hypercarbia, hypertriglyceridemia, fatty acid deficiency, metabolic acidosis,
hypophosphatemia, hypo/hypermagnesium, hypo/hyperkalemia, hypo/hypercalcemia and
alteration in liver function tests.

How should a patient on TPN scheduled for surgery be managed perioperatively?

The patient should be changed from TPN to 10% dextrose at the same rate to maintain
glucose homeostasis. This prevents rebound hypoglycemia.
Serial accuchecks for serum glucose should be performed every hour to avoid
hypo/hyperglycemia.

During prolonged surgery, what laboratory tests should be monitored when a

patient is receiving total parenteral nutrition (TPN)?

Plasma glucose, potassium and pH.

 35

Enteral feeds should be used whenever possible. It will help to conserve

lean body mass in patients with multiple orthopedic injuries requiring
several surgeries during hospital stay.

Acid- Base Balance Disturbances

Simple evaluation:
1. pH
< 7.35  acidosis; 7.35 – 7.5  normal; > 7.5  alkalosis

2. PCO2 (respiratory component)

< 35 mmHg (respiratory alkalosis or compensation for metabolic acidosis, if so BD > -5).
35- 45 mmHg  normal
> 45 mmHg respiratory acidosis (acute if pH is < 7.35; chronic if pH normal/ BE > +5)

3. Metabolic component
BD > -5  metabolic acidosis
BE –5 to +5  normal range
BE > +5  alkalosis

Possible Options
pH < 7.35 / CO2 < 35 / BD > -5
acute metabolic acidosis + compensation
pH < 7.35 / pCO2 > 45 / BDE normal range
 acute respiratory acidosis
pH 7.35-7.5 / pCO2 > 45 / BE > + 5
 prolonged respiratory acidosis
pH > 7.5 / pCO2 > 45 / BE > +5
 metabolic alkalosis
pH > 7.5 / pCO2 < 35 / BDE –5 to + 5
 acute respiratory alkalosis
If the acid base picture does not conform to any of these options  mixed pattern

Compensatory mechanisms for respiratory acidosis.

In respiratory disorders, pH and PaCO2 are inversely related.

pH decreases 0.08 for each 10 mm Hg increase in PCO2.

Acutely:
 36

1. Augmented ventilatory drive occurs via feedback to the brain and the medullary
respiratory control center, mediated by central and carotid body chemoreceptors.

2. Metabolic buffering through decreased hepatic HCO3 uptake and shift of HCO3 from
red blood cells to plasma, carbonate release from bone, decreased urea and lactic acid
production (which utilizes HCO3).
Acutely HCO3 increases 1 mmol/l for each 10 mm Hg of CO2 greater than 40.

Long-term increase in PaCO2 induces renal compensation with decreased chloride and
phosphate reabsorption, increased HCO3 reabsorption and increased H+ secretion.
Chronically, HCO3 increases 5 mmol/l for each 10 mm Hg of PaCO2 greater than 40.

Met alk: Resp compensation

Two common causes of metabolic alkalosis:
1. Loss of gastric fluid (vomiting and nasogastric suctioning)
2. Loss of acidic urine secondary to diuretic therapy (thiazides, furosemide and
ethacrynic acid).
Acute respiratory compensatory response:
Reflex alveolar hypoventilation.
PaCO2 increases 0.4-0.9 mm Hg per mEq increase in bicarbonate. Eventually, the
kidneys will tend to excrete more bicarbonate (chronic compensatory response) or
increase reabsorption of hydrogen ions.
.

Respiratory alkalosis: renal compensation

E.g., ascent to altitude
Kidney compensate with time for the loss of CO2 by:
excreting bicarbonate ions in association with Na and K ions.

Hyperventlation  tetany
Due to greater affinity of plasma proteins for Ca ions in alkaline environment compared
with acidic solution.

All acid base abnormalities can be explained in terms of SID (strong ion difference),
ATOT, or PCO2. ATOT represent the total concentration of weak ions that influence acid-
base balance. The important molecules in this group are albumin and phosphate.
Respiratory acid base abnormalities occur when there is increase or decrease in CO2.
Metabolic acid-base abnormalities are caused by alterations in the SID or ATOT or both.
Metabolic alkalosis is caused by increased SID or decreased ATOT .
Metabolic acidosis caused by decreased SID or increased ATOT.

Strong ions and Strong ion difference (SID)

 37

In human SID is always positive.

 SID  Acidosis (increase anions or cations loss)
 SID  alkalosis

This could be a change in the total or relative concentration of strong ions.

(A) More anions relative to cations causes decrease in SID or acidosis; net increase in
anions occurs in hyperchloremia, lactacidemia, renal acidosis or ketoacidosis.
Alternatively, cations may be lost, as in severe diarrhea or renal tubular acidosis.
Metabolic alkalosis is caused by increased SID such as sodium gain or chloride loss.

(B) Increase in the volume of distribution of the same quantity of ions. This may occur in
dilutional acidosis such as by infusing 5% dextrose 2L, or by ingestion of osmotically
active molecules that expand extracellular water (ethanol, methanol, poisoning with these
agents cause metabolic acidosis).
Contraction as if 2 L of free water is removed (profuse sweating or dehydration),
opposite effect would occur. The relative ratio of cations to anions increases and system
becomes more alkaline (contraction alkalosis).

In the presence of a low serum sodium <135 mEq/L), dilutional acidosis should be sought
(alcohol poisoning).There is an osmolar gap (measured and calculated serum osmolality
> 12 mOsm) showing the presence of unmeasured osmoles.

Most severe form of acidosis is caused by net gain of “unmeasured” (i.e., electrolytes not
measured on serum chemistry analysis) anions. This causes decreased SID.
These situations are caused by
1. Lactic acidosis such as in hypoxia and hypovolemia (treated with volume
expansion).
 38

2. Uncontrolled diabetes and ketoacidosis (treated with volume resuscitation and

insulin).
3. Severe renal failure, Sulphates and phosphates (“fixed renal acids”) are not
excreted (treated with dialysis).
All these additional anions decrease SID and cause acidosis.
The total weak acid pool (principally serum albumin and phosphates) are also important
causes of acid base disturbances. Hyperphophatemia is associated with acidosis of renal
failure. Hypoalbuminemia is associated with metabolic alkalosis.

When investigating a patient with metabolic acidosis anion gap and base deficit are
simple useful tools.

Anion Gap
Anion Gap: (Na) – (Cl + HCO3) = 9-13 mEq/L

If the gap is normal, acidosis is likely caused by hyperchloremia

Excessive administration of Cl
Excessive loss of Na  diarrhea, illeostomy
Renal tubular acidosis

If gap is wide (>16) there are unmeasured” anions (UMA) present.

(A) Check serum lactate, if > 2, probable cause is lactic acidosis.
If the high lactate is explained by circulatory insufficiency, it is termed type A lactic
acidosis.
When there is no hypoxia or circulatory insufficiency, it is referred to type B lactic
acidosis and is caused by some drugs (biguanides, fructose, nitroprusside, ethylene
glycol, aspirin, liver disease) or associated with inborn error of metabolism.

(B) Look at the creatinine and urine output; if renal failure is present acidosis is caused
by renal acids
 39

(C) Assess blood glucose and urinary ketone level, if elevated diagnose diabetic
ketoacidosis.
(If the patient is ketotic (unmeasured anion), but normoglycemic, the condition is likely
due to alcohol (check blood alcohol) or starvation ketosis. Check for high MCV, gamma
GT on liver panel)

(D) If all of the above tests are negative think of intoxication. Send toxicology tests for
salicylates and serum osmolality. Look for unmeasured source of osmoles
(osmolalility = 2 (Na ) + Glucose/18 + BUN / 2.8)
If the gap between measured and calculated serum osmolality is > 12 think of alcohol
(especially ethylene glycol, methanol).

4 steps in evaluation of Acid-Base status:

1. Evaluate pH-
2. Evaluate PaCO2 -
3. BE?
4. Evaluate compensation

At 3 am , you are presented with a 80 yr old, 60 kg man who has been found
unconscious on the floor at home. He is brought to the OR for emergency
laparotomy, with a presumed diagnosis of ruptured appendix. His vitals: BP 90/60,
HR 120, RR 26, SpO2 96%.
Preop ABG: pH 7.20, PaCO2 25, PaO2 75, HCO3= 8.

1. Evaluate pH- Acidemic

2. Evaluate PaCO2 - resp alkalosis
3. BE?
4. Evaluate compensation
 40

pH –bicarbonate diagram
Acid–base map. Plotting plasma HCO3 (from the serum chemistry panel) against the
PCO2 and H+ (from the arterial blood gas) will fall in the shaded areas in a simple acid–
base disorder. Should a mixed disorder exist, the values may fall in the nonshaded areas.

To find BE , we titrate back to pH of 7.4 by varying only PaCO2.

pH to 7.4= 0.2;
HCO decreases by 0.2 x 10= 2; So, new HCO3 = 6;
BE = 6-24 = -18

To Evaluate compensation:

PaCO2 = 8 x 1.5 + 8 = 20 mm Hg. Patient’s actual PCO2 is 25 (near max)

(See below Table 1)

 41

In respiratory alkalosis that occurs in compensation for metabolic acidosis, reduction in

PCO2 from baselines is equal to the amount of base deficit. For example, if the base
deficit is 10, PCO2 should be 30 mmHg (if baseline was 40 mmHg). If the PCO2
is higher, that indicates a problem with respiration (i.e., inadequate breathing due to
pain).

If both PaCO2 and bicarbonate change in the same direction (both increased or
decreased), there is a primary acid-base disorder with a compensatory secondary disorder
that brings the ratio of HCO3 / CO2 tension back to 20:1.
If HCO3 and PaCO2 change in opposite directions, there is a mixed acid-base disorder.

Regulation of acid base changes:

There are various intracellular and extracellular weak acid buffering systems to prevent
rapid changes in acid base systems.
Carbon dioxide, the major source of acid, is excreted by the lung.
Kidneys participate in excretion of hydrogen-ion promoting anions. Major effect of
kidney is related to handling of sodium and chloride ions. In metabolic acidosis, chloride
is preferentially excreted by the kidney, and in metabolic alkalosis, chloride is retained,
while sodium and potassium are excreted. (For example, in renal tubular acidosis, kidney
is unable to excrete chloride in proportion to sodium. There is hyperchloremic metabolic
acidosis with inappropriately low chloride levels in the urine).
Volatile acid is principally buffered by hemoglobin (deoxyhemoglobin in the venous
system).

A 45-year-old man is admitted after MVA. He is bleeding. Pulse is thready, 120bpm. BP

90/50. RR 36, Temp 35oC.
Na 144, K 4, Cl 110, total CO2 8, urea 10, Cr 2, Alb 4, Lactate 16, pH 7.28, pCO2 24,
HCO3 8, BE –16, AG 26.
pH 7.28, pCO2 24, HCO3 8, BE –16
acidosis caused by measured or unmeasured anions ?
Check serum lactate level. (Lactate = 16)
 42

If > 2, lactic acidosis is the probable cause

Above patient was brought to the OR after aggressive volume resuscitation.

12 hrs later (postoperative) he is back in the ICU ventilated.
Na 148, k 3, Cl 120, total CO2 22, urea 10, Cr 2, Alb 2, lactate 5, pH 7.33, pCO2 35,
HCO3 18, BE –11.
Before: Na 144, K 4, Cl 110, total CO2 8, urea 10, Cr 2, Alb 4, Lactate 16, pH 7.28,
pCO2 24, HCO3 8, BE –16, AG 26
Is the patient still under resuscitated?
What IV fluid was used?
Patient was resuscitated with normal saline!

Neurosurgical patients are vulnerable to a variety of acid base disturbances

Mannitol causes expansion of ECF leading to dilutional acidosis initially; later diuresis
may cause contraction alkalosis. Diabetes insipidus, which frequently occurs in head
injury, can cause contraction alkalosis. Neurosurgical patients are usually treated with
normal saline or frequently with hypertonic saline which may cause hyperchloremic
acidosis.

Adverse Consequences of Severe Acidosis

Nervous System
Obtundation
Coma
Cardiovascular System
Impaired myocardial contractility
Decreased cardiac output
Decreased arterial blood pressure
Sensitization to re-entrant cardiac dysrhythmias
Decreased threshold for ventricular fibrillation
Decreased responsiveness to catecholamines
Ventilation
Hyperventilation
Dyspnea
Fatigue of respiratory muscles
Metabolism
Hyperkalemia
Insulin resistance
Inhibition of anaerobic glycolysis

Adverse Consequences of Alkalosis

Nervous System
Decreased cerebral blood flow
Seizures
Lethargy
Delirium
 43

Tetany
Cardiovascular System
Arteriolar vasoconstriction
Decreased coronary blood flow
Decreased threshold for angina pectoris
Predisposition to refractory dysrhythmias
Ventilation
Hypoventilation
Hypercarbia
Arterial hypoxemia (shift oxygen dissociation curve to left)
Metabolism
Hypokalemia
Hypocalcemia
Hypomagnesemia
Hypophosphatemia
Stimulation of anaerobic glycolysis

A 55-year-old man, an alcoholic, who was disoriented and complaining of recurrent

vomiting and hematemesis, is scheduled for an emergency laparotomy. ABGs and
electrolytes:
pH 7.45, PaCO2 34 mmHg, HCO3 23 mmHg
Na 135, K 4, Cl 85, CO2 24 mEq/L
Acute hypocarbia to 34, pH 7.45 and HCO3 23
Anion Gap?
Alcoholic ketoacidosis (inadequate fluid/carbohydrate intake)
Triple Acid base disturbance: (not simple mild respiratory alkalosis)
Primary metabolic alkalosis
Primary metabolic acidosis
Primary respiratory alkalosis
Failure to calculate anion gap may lead to incorrect interpretation of ABG
 44

Mechanism solving acid base problems. BDEG- base deficit excess gap

Key word: 2012

Bicarb administration: CO2 effect

In general, the severity of these effects of bicarbonate are related to the amount of
bicarbonate used. These undesirable effects include:
hypernatraemia
hyperosmolality
volume overload
rebound or ‘overshoot’ alkalosis
hypokalaemia
impaired oxygen unloading due to left shift of the oxyhaemoglobin dissociation curve
acceleration of lactate production by removal of acidotic inhibition of glycolysis
CSF acidosis
Hypercapnia (If the patient is on mechanical ventilation increased ET CO2)

Key word 2012: ABG salicylate toxicity (Pearls Board review)

 What does the ABG reveal in cases of salicylate toxicity?

Aspirin initially stimulates the respiratory center, resulting in hyperventilation and a

resultant respiratory alkalosis. Later, it interferes with the Kreb’s cycle, resulting in
increased lactate production and the development of a wide anion gap metabolic acidosis.
 45

Thus, patients tend to present with a mixed respiratory alkalosis / metabolic acidosis with
a wide anion gap. If toxicity results in hypoventilation, a pure acidosis may be seen.

 What is the therapy for salicylate toxicity?

Activated charcoal is the primary therapy, as early administration can reduce aspirin
absorption by up to 80%. Fluid replacement is mandatory, and should be accompanied
by alkalinization of the urine. Alkalinizing the urine from a pH of 5 to 8 increases renal
clearance from 1.3 to 100 ml/min. Alkalinization is easily accomplished by
administering a sodium bicarbonate bolus of 1-2 mEq/kg, followed by a slower infusion
rate. Hypokalemia must also be corrected.

 What are the signs and symptoms of acetaminophen toxicity?

Acetaminophen toxicity is divided into 4 phases, depending upon the time of the
ingestion. During Phase 1, occurring 0-24 hours after ingestion, the patient is either
asymptomatic, or complains of generalized symptoms such as nausea, vomiting,
anorexia, and malaise. A subclinical rise in liver transaminase enzyme levels occurs
approximately 12 hours after initial ingestion. During Phase 2, which occurs 18-72 hours
after ingestion, the patient continues to display GI symptoms and will begin to complain
of right upper quadrant pain. Labs will reveal a further increase in transaminase levels.
Phase 3, at 72-96 hours, is the period of centrilobular hepatic necrosis. The patient will
have worsening RUQ abdominal pain, jaundice, coagulopathy, renal failure, hepatic
encephalopathy, and may ultimately succumb. Phase 4, from 96 hours to 3 weeks, is
marked by a gradual resolution of symptoms and organ failure for patients that survive
Phase 3.

References:
1. Barash PH, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Clinical
Anesthesia 6th ed. Philadelphia. Lippincott Williams & Wilkins, 2009:644-695.
2. Miller RD. Miller’s Anesthesia 7th ed. Philadelphia: Churchill Livingstone, 2014.
3. Longnecker DE. Anesthesiology. McGraw-Hill, 2008:767-820.
4. Arterial Blood-Gas Analysis- ASA 2014
5. Perioperative Glycemic Management: A practical guide- ASA 2014
6. Sepsis: Current Concepts and Perioperative Management ASA 2014
7. Current Controversies in Perioperative Fluid Management- ASA 2014
8. Perioperative Fluid Management- ASA 2014
9. Magnesium and cardiovascular disease. Anesthesiology 1998;89:222-40.