Sign up to receive ATOTW weekly - email worldanaesthesia@mac.

com

ACID BASE DISORDERS IN CRITICAL CARE –

PART 1
ANAESTHESIA TUTORIAL OF THE WEEK 66
30TH AUGUST 2007

Dr Alex Grice
Consultant Anaesthetist, Royal Devon and Exeter, UK
[email protected]

Disorders in acid-base balance are commonly found in patients admitted to intensive

care. Clinicians responsible for these patients need a clear understanding of acid-base
pathophysiology in order to provide effective treatment for these disorders. These
tutorials are designed to supplement the tutorial in the Basic Sciences section of
ATOTW and will concentrate on aspects of metabolic acidosis pertinent to critical
care. In part 1 we shall cover the assessment of metabolic acidosis, including
determining cause and assessing severity. In part 2 we shall cover specific types of
metabolic acidosis commonly encountered in critical illness.

Clinical Scenarios
Case 1.
A known diabetic patient presented with severe diabetic ketoacidosis. He was drowsy,
exhibited classical Kussmaul respiration and proceeded to have a respiratory arrest
whilst being admitted to ICU. After immediate intubation the trainee ventilated the
patient with the ventilator’s default settings (rate 12, tidal volume 500ml, PEEP
5cmH2O FiO2 50%) and attempted to secure arterial and central venous access.
Shortly after intubation the patient became asystolic and could not be resuscitated.

Why did this patient have a respiratory arrest?

Why did he deteriorate after intubation?

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 1 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Case 2
A young woman was admitted to the surgical ward with a history of severe vomiting
and increasing right iliac fossa abdominal pain. On examination she was found to
have a rigid abdomen, with visible subdiaphragmatic gas on CXR. She was
cardiovascularly unstable and her admission bloods showed Hb 17.4, WCC 24.6,
Plateletsts 79, Na+ 125, K+ 4.3, Cl- 93, urea 20.4 creatine 310 (mcmol/l) and blood
gas analysis showed:
• pH 7.1
• pCO2 5.2 kPa
• pO2 29.3 kPa
• HCO3- 14.3

Interpret these results. What is the likely cause of her acidosis?

How do you interpret her chloride level?
Is her compensation adequate/maximal?

Case 3.
An elderly lady was admitted from a care home with a week long history of severe
diarrhoea. She was dehydrated and hypotensive. Admission bloods revealed Na + 134,
K+ 2.5, Cl- 122, urea 15.4, creatine 280, and blood gas analysis revealed:
• pH 7.21
• pCO2 2.9 kPa
• pO2 19.5 kPa
• HCO3- 6.4
Describe the acid base disorder present. What is the likely aetiology?
Is her compensation adequate?

Introduction
Metabolic acidosis is a common component of critical illness. Evaluation of this
component can aid diagnosis, assess severity (and likely outcome) and allow the
clinician to determine whether current treatments are proving effective.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 2 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Definitions
Metabolic acidosis exists when there is an excess level of fixed or exogenous acids in
the blood. Fixed acids include hydrochloric acid from arginine, lysine and histidine
metabolism, sulphuric acid from methionine and cystine metabolism, phosphoric acid,
ketoacids and lactic acid. This is always accompanied by a drop in plasma bicarbonate
concentration (relative to the bicarbonate concentration present prior to the onset of
the acidosis). This drop in bicarbonate can either be caused by bicarbonate loss or by
the presence of an acid.

It should be noted that the body can accommodate significant alteration in acid burden
through buffering (bicarbonate being the primary buffer in blood) and the presence of
a metabolic acidosis does not always imply the presence of acidaemia (a low blood
pH). Please refer to the basic science acid/base tutorial for further details on buffering
in blood. Blood pH will only fall appreciably when the buffering capacity of the blood
becomes overwhelmed.

A drop in bicarbonate concentration is the hallmark of metabolic acidosis.

Evaluation
When evaluating a critically ill patient with a metabolic acidosis it is necessary to
determine the type of acidosis in order to identify the cause of the acidosis. To
classify metabolic acidosis it is useful to calculate the anion gap, delta ratio and, if
present, the size of the osmolar gap. These concepts are explained below.

The role of the anion gap

Anions are negatively charged ions (like bicarbonate) and are attracted to anodes.
Cations are the opposite; they are positively charged ions and they are therefore
attracted to a cathode. The anion gap is defined as the concentration difference
between the major (measured) cations and anions within the plasma and is normally
12 to 18 mmol/l. [2] Anionic proteins, phosphate, sulphate and low levels of organic
acids, which are not measured, account for the difference (i.e. the ‘gap’). When
examining the cause of a metabolic acidosis it is useful to calculate the anion gap.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 3 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Anion gap = [Na+ + K+] - [HCO3- + Cl-] = 15 (±3) mmol/l

A normal anion gap implies primary bicarbonate loss:

• Plasma bicarbonate is low (the hallmark of acidosis) and chloride

concentration is raised.
• This bicarbonate loss may be:
Gastrointestinal (diarrhoea, fistula)
Renal (renal tubular acidosis, drug effect).
• Also occurs with rapid intravenous infusion of normal saline (excess chloride)
or infusions of parenteral nutrition rich in cationic amino acids (e.g. arginine).

An increased anion gap implies that fixed acids are being retained or an abnormal
organic acid is present. Plasma bicarbonate is low and chloride concentration is
normal.

Fixed acids may be retained in:

1. uraemia
2. ketoacidosis (diabetic, alcoholic)
3. lactic acidosis.

If fixed acids are normal, exogenous acids should be considered:

1. salicylate poisoning
2. methanol poisoning
3. ethylene glycol poisoning

The role of the Delta Ratio

The delta ratio is defined as:

Delta ratio = [Rise in anion gap]

[Drop in bicarbonate]

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 4 of 10

 Sign up to receive ATOTW weekly - email [email protected]

In an increased anion gap acidosis every molecule of fixed acid that dissociates in
blood will create one hydrogen ion and one acid anion. The H+ will bind one molecule
of bicarbonate (buffering), resulting in a drop in bicarbonate of one for each rise in the
anion gap of one. The delta ratio for an increased anion gap acidosis will
consequently approach one.

If the delta ratio is very low (less than 0.4) then it supports the diagnosis of a normal
anion gap acidosis. If the delta ratio is high (greater than 2) then it suggests that the
bicarbonate was high prior to the onset of the acidosis (as seen in compensated
respiratory acidosis). A ratio between 0.4 and 2.0 suggests a mixed picture.

Limitations of the Anion Gap and Delta Ratio

Whilst the anion gap is useful in evaluating metabolic acidosis it is not sensitive. The
normal range is quoted as 12 to 18 mmol/l which means it is possible for a patient
with a normal anion gap of 12 to acquire a severe lactic acidosis (plasma lactate
greater than 5 mmol/l) without leaving the normal range. The anion gap is also
affected by plasma albumin (an important unmeasured anion) and low albumin levels
can significantly offset an anticipated rise in anion gap.

Similarly the theory behind the delta ratio is also flawed. Bicarbonate only accounts
for 60% of the buffering capacity of blood and this affects the assumption that one
molecule of H+ will bind one molecule of bicarbonate. However when the delta ratio
is very high or low it can still prove useful.

Role of the Osmolar Gap

The osmolar gap represents the difference between a sample’s measured osmolality
and its calculated osmolarity. It is a useful calculation to perform if alcohol poisoning
is suspected as we will discuss in Part B of this tutorial.

Osmolality is measured in the laboratory with an osmometer that either assesses the
depression of a sample’s freezing point or the depression of its vapour pressure. It is
preferable to use the former as any volatile alcohols in the sample will evaporate as
the sample is heated and the results from this method will be inaccurate.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 5 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Osmolarity can be calculated using various formulae. One such formula is:

Calculated Osmolarity = 2 [Na+] + urea + glucose

Osmolality and osmolarity differ according to whether the number of osmotically

active particles is dissolved in a kilogram or a litre of solvent respectively. The
calculated osmolarity utilises the plasma concentration of sodium, glucose and urea.
Even though sodium and chloride represent the most important determinants of
osmolarity in plasma, chloride concentration is not commonly available. The formula
is simplified by taking into account the incomplete dissociation of sodium chloride in
plasma. The contribution from sodium and chloride is therefore calculated from the
sodium concentration alone by multiplying sodium concentration by the dissociation
constant for sodium chloride (1.86) and dividing this by the proportion of water in
serum (0.93). Whilst this formulae is quick and easy its accuracy has been questioned
and several centres now prefer to use

Calculated Osmolarity = 1.86 [Na+] + urea + glucose + 9

The measured and calculated values should lie within 10 of each other (the difference
being created by the inaccuracy of the calculation and the inaccuracy of the
osmometer) and if the gap is larger it suggests the presence of unmeasured
osmotically active species.

It is important to realise that the osmolar gap has significant limitations as well. When
considering alcohol poisoning the osmolar gap is only present as an early feature and
returns towards normal as the alcohol is metabolised and the associated metabolic
acidosis develops. Similarly the osmolar gap is not sensitive as the large molecular
weight of ethylene glycol accounts for a fatal ingestion, only causing a small rise in
osmolar gap.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 6 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Compensation for Metabolic Acidosis

When treating critically ill patients with metabolic acidosis it is important to consider
the adequacy of their ventilatory response when deciding on treatment priorities.
Buffering provides the main means of accommodating a metabolic acidosis. As
buffering capacity is exceeded, acidaemia develops. Once this rise in hydrogen ion
concentration has reached the CSF it is detected by chemoreceptors and compensation
occurs by reducing CO2 levels through hyperventilation (first described by
Kussmaul). Detection of low pH in CSF, rather than blood, explains the delay in this
compensation and why rapid onset acidosis (seen with convulsions for example) tends
not to stimulate respiration in spite of a low blood pH.

Even though respiratory compensation occurs relatively quickly, it can take up to

twelve hours to reach maximal capacity. This maximal capacity can be calculated

pCO2 (maximal response, in kPa) = 0.2 [HCO3-] + 1

If the patient’s pCO2 lies within 0.5 kPa of this calculated value, then the respiratory
response is appropriate. If the pCO2 is higher then either the compensation is in a
very early stage or the patient has a superimposed respiratory acidosis. If this is the
case then earlier intervention with respiratory support is indicated.

When providing respiratory support in patients with a metabolic acidosis it is

important to remember that respiratory compensation causes an increased minute
volume. If you instigate controlled ventilation with a normal minute volume then the
pCO2 level will rise rapidly towards normal, the acidaemia will worsen, and the
patient will become acutely unstable. Young fit patients with severe diabetic
ketoacidosis can generate huge minute volumes (20-30 l/min) and drop their pCO2 to
below 2 kPa. If you ventilate them with a minute volume of 5 l/min then their acidosis
will deteriorate profoundly.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 7 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Pitfalls in Assessing Metabolic Acidosis

It is impossible to interpret arterial gases accurately without considering the history
and presentation first. Consider the following arterial gas:

• pH 7.1
• pCO2 10.5 kPa
• pO2 29.3 kPa
• HCO3- 24.3

The interpretation of this result will vary according to the clinical presentation:
• If the gas sample was taken from a young unconscious patient, admitted through
the emergency room, with pinpoint pupils then you would interpret the gas as
showing primary respiratory acidosis from opiate overdose.

• If the gas was taken from an elderly man with severe COAD presenting with
sepsis then the gas interpretation will be different.

o Full compensation for a chronic respiratory acidosis should raise the

bicarbonate by 3 x (pCO2 – 5.3). If the pCO2 level is chronically raised then
you would expect the bicarbonate to be 36 mmol/l.
o This bicarbonate is significantly lower and this suggests a metabolic
acidosis superimposed on the background of a compensated respiratory
acidosis.

This serves to highlight the importance of basing gas interpretation on clinical details.
Other pitfalls arise from failing to recognise the limitations of the anion gap, delta
ratio and osmolar gap, as discussed earlier in the tutorial.

Summary
Metabolic acidosis is commonly encountered in intensive care and correct
management requires confirmation that an acidosis is present, determination of its
nature and then determination of the probable cause. Identification of the root cause
will then allow specific treatment with improved efficacy.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 8 of 10

 Sign up to receive ATOTW weekly - email [email protected]

Case Examples

Case 1.
In this case the patient presented with a metabolic acidosis caused by loss of diabetic
control, relative insulin deficiency and consequently ketoacidosis. (This will be
covered in more detail in part B of the tutorial). Kussmaul respiration implies
respiratory compensation through hyperventilation. The rise in minute volume can be
substantial and maintaining this compensation is very strenuous. As time passes
patients tire, the minute volume decreases and the acidosis worsens rapidly. Young
patients in particular can maintain full respiratory compensation almost to the point of
respiratory arrest, as in this example. Elderly patients tend to tire more slowly and this
allows timely recognition and support.

When taking over a patient’s ventilation, in the setting of a metabolic acidosis, it is

vital that the minute volume used is raised appropriately. If standard ventilation
settings are applies, as in this case example, the drop in alveolar ventilation post-
induction will remove the respiratory compensation and the acidosis will deteriorate
dramatically. This is likely to be the cause of this patient’s cardiovascular collapse.

Case 2.
The clinical presentation is of an acute abdomen in a previously fit patient. The raised
haemoglobin, urea and creatinine suggest that the patient is dehydrated and this raises
the possibility of an associated lactic acidosis due to inadequate tissue perfusion. The
arterial gasses confirm that acidaemia is present (low pH) and the low bicarbonate
implies that the acidosis is metabolic.

The anion gap is raised at 35 and this strongly suggests the presence of an increased
anion gap acidosis. The delta ratio is calculated then this is raised at 3.5 and this
suggests a pre-existing metabolic alkalosis. While it is impossible to be absolutely
sure this would seem to fit clinically. The vomiting that occurred in the days leading
up to admission may have caused a metabolic alkalosis (loss of hydrogen ions and
chloride) that was confounded by a superimposed lactic acidosis on admission. This
would also explain why a severe increased anion gap acidosis only dropped the pH to
7.1 in this example, when you would expect the pH to be lower.

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 9 of 10

 Sign up to receive ATOTW weekly - email [email protected]

In terms of her respiratory compensation, it is possible to calculate the expected pCO 2

from the bicarbonate level and this would suggest that maximal compensation should
drop the pCO2 to 3.8 kPa. The fact that her pCO2 is higher should serve as a warning
of imminent fatigue and ventilation should be supported as quickly as possible in
order to prevent cardiorespiratory collapse.

Case 3
This lady presented with a low pH on arterial gases and low bicarbonate – this implies
that a metabolic acidosis is present. The extent of the dehydration raises the
possibility of a lactic acidosis however this would create an increased anion gap. The
anion gap in this instance is low (8.5) and the delta ratio is 0.5. This strongly supports
the presence of a normal anion gap acidosis secondary to bicarbonate loss from the
gut.

With a bicarbonate of 6.4 you would expect the patient to drop her pCO 2 to 2.28 and
in this instance her respiratory compensation is appropriate.

References
1. Cohen RD, Woods HF. Disturbances of acid-base homeostasis. In : Weatherall
DJ, Ledingham JGG, Warrell DA, eds. Oxford Textbook of Medicine. Oxford:
Oxford University Press, 1987; 9.174
2. Hoffman RS, Smilkstein MJ, Howland MA, Goldfrank LR. Osmol gaps
revisited. Normal values and limitations. Journal of Toxicology – Clinical
Toxicology. 1993; 31(1): 81-93.
3. Salem MM, Mujais SK. Gaps in the anion gap. Archives of Internal Medicine.
1992;152: 1625-1629.
4. Brandis K. Acid-base physiology. From
http://www.anaesthesiamcq.com/AcidBaseBook/ABindex.php
5. Stewart PA. How to understand acid-base. A quantitative acid-base
primer for biology and medicine. From http://www.acidbase.org/

ATOTW 66 Acid base balance in critical care – part 1 30/08/2007 Page 10 of 10