ABG Analysis Case 2

Answer the questions at the bottom of the page when all data has been reviewed

History & Examination

A stressed-out married couple attend the ED/ER. They have two young sons aged 4 and 3 years. They have no other family in London and, therefore, had to bring the two youngsters with them to ED. The mother, aged 28 years, complains of worsening fatigue over a period of three months. She had been seen by her GP (family practitioner) and started on anti-depressants four weeks earlier. An initial limited response was not sustained.

Examination of all systems, including the neurological system, is completely normal. All initial tests are normal, including FBC, electrolytes, renal function, liver function, thyroid function, inflammatory markers (CRP and ESR), CXR, ECG, toxicology screen and pregnancy test.

The husband is asked to leave the department and take the children home as they (the children) are poorly behaved and disruptive. The patient then tells the admitting medical consultant that she has days were she struggles to move from her bed. Arguments with her husband have been worsening. Indeed, an argument had precipitated this ED attendance after the 4 year old, unsupervised, had destroyed an original fireplace with a chisel while the husband was at work. The admitting consultant is familiar with the horrors of raising badly behaved children and in spite of the normal investigations, he decides to admit her for a few days to give the couple a rest from one another. In the absence of any examination or laboratory findings, he plans to ask his psychiatry colleagues to review her case on the ward.

Inpatient course

On the ward round, three days post admission, no progress has been made. The psychiatrist’s opinion is that there is no psychiatric diagnosis. CT and MRI brain are normal. It is noted that the patient has rarely been out of bed over the three day period in hospital. The possibility of malingering is raised and a plan is made for discharge.

That night the intern is called to see her. Her oxygen saturations have dropped to 80%. The nursing staff have commenced oxygen therapy. Her chest is clear on examination. He carries out an ABG (below) and calls the admitting consultant. CXR carried out on the ward is clear.

MG bloods n

In view of her acute onset of hypoxia in the setting of immobility, the consultant, a well-meaning but limited fellow, feels that pulmonary embolism is likely and, over the phone, asks the intern to start therapeutic subcutaneous heparin, to organise a CTPA and to call ICU to arrange transfer.

The ICU consultant (senior doctor) comes to the ward and reviews the history and data available. He then asks the Intern to cancel the CTPA, he reduces the heparin to a prophylactic dose and transfers the patient to ICU.


Q1. Why has the ICU consultant cancelled the CTPA?

Q2. What would her ABG have looked like on room air at the time of the desaturation?

Q3. Can you offer a possible overall diagnosis?

Q4. On examination, the ICU consultant feels that she has a degree of bilateral ptosis. As the patint is connected to a cardiac monitor on ICU, he carries out a diagnostic test. What is the test?

Q5. What other tests are indicated?

Q6. Outline the management of the condition diagnosed in the answer to Q3.


Q1. Why has the ICU consultant cancelled the CTPA?

CTPA is the test of choice to exclude/confirm a diagnosis of pulmonary embolism. The key here is that the patients ABG does not support the diagnosis of acute pulmonary embolism. She is hypoxic requiring oxygen to elevate her paO2 (see Ans: Q2). However, with an elevated paCO2, this is type II respiratory failure. Furthermore, as we will see, her A-a gradient is normal. While this is not impossible in the setting of PE, it is unusual. Her ABG implies that her hypoxia is due purely to hypoventilation.

MG bloods ans now

Q2. What would her ABG have looked like on room air at the time of the desaturation?

Faced with a patient with a marked reduction in her oxygen saturations, the nursing staff, have, of course, immediately started oxygen therapy. The intern, like all those before him, has not paid attention during classes on ABG interpretation and wonders what the ABG would look like on room air? Is her pO2 appropriate to her level of oxygen therapy? Is her A-a gradient elevated? If we go back to the alveolar gas equation. At the level of alveolar ventilation indicated by her paCO2 she has a pAO2 (alveolar pO2) on 4L O2 per minute (36%)  of

pAO2 = .36(713) – 65/0.8 = 175 mmHg (175/7.5 = 23.4 kPa) (the alveolar gas equation-link).

This gives her an observed A-a gradient (pAO2 – paO2)  of 21 mmHg. She is 28 years old and on this level of oxygen therapy we would expect her to have an A-a gradient of: age/4 + 4 (+ 7.5 for each 10% increase in FiO2) = 22 mmHg. Her A-a gradient is normal.

What would her ABG on room air look like/ We can have an educated guess at this. She has a marked degree of hypoventilation (paCO2 65mmHg). At the level of alveolar ventilation indicated by her paCO2 she would have a pAO2 (alveolar pO2) on room air of

pAO2 = .21(713) – 65/0.8 = 69 mmHg (69/7.5 = 9.2 kPa) (the alveolar gas equation-link)

We know from the ABG carried out on oxygen (above) that her A-a gradient is normal. So assuming it will be normal on room air (there is no reason to suspect that it will not) we predict a gradient of age/4 + 4 = 11 mmHg. So, her paO2 on room air will be about (paO2 = pAO2 – gradient) 58 mmHg, profound hypoxia. Profound hypoxia but due to hypoventilation (normal A-a gradient and elevated paCO2). This is type II respiratory failure. It moves us into an entirely different differential compared to a case of type I respiratory failure. We urgently need to explain why is there a global reduction in the ventilation of her alveoli?

Q3. Can you offer a possible overall diagnosis?

Myathenia gravis (currently with ‘myasthenic crisis’)

Our patient is ‘hypoventilating’ (you must understand the term ‘hypoventilation’).

Hypoventilation: ‘the volume of air entering the alveoli per unit time is insufficient to remove all CO2 produced during metabolism’. Hence, the characteristic finding is a raised paCO2. Hypoventilation is due to a global reduction in the volume of air per unit time entering the alveoli. It represents failure of the chest wall to adequately ‘move’ the lungs during respiration.

What might cause a global failure to shift a sufficient volume of air into the lungs? What are the important causes of hypoventilation?


*Myasthenia gravis is associated with a generalised failure of transmission of impulses from the nervous system to the skeletal muscles. It may affect the muscles of the chest wall leading to hypoventilation. Undiagnosed myasthenia gravis may present with a myasthenic crises. This is a life-threatening medical emergency where failure to move the chest has resulted in alveolar hypoventiation with type II respiratory failure.

The ICU consultant quickly rules out the possibility of sedative administration by checking the drugs given that day. He feels that ingestion of sedative drugs of abuse is unlikely but will ask for a urine toxicology screen to be sent (subsequently negative). She has no history of COPD.

Underlying myasthenia gravis is a strong possibility in our patient, in light of the symptoms she has been experiencing and this episode of hypoventilation. Note also that the bicarbonate is raised on her ABG. In the context of type II respiratory failure, this suggests that, although the situation has worsened on the evening in question, a degree of hypoventilation has been present for some time (at least 48 hours).

Q4. On examination, the ICU consultant feels that she has a degree of bilateral ptosis. As she is connected to a cardiac monitor on ICU, he carries out a diagnostic test. What is the test?

A tensilon test

From the clinical history and the acute deterioration into type II respiratory failure, we suspect our patient has myasthenia gravis. Myasthenia gravis is an autoimmune condition usually caused by the presence of autoantibodies which block the acetylcholine receptor at the neuromuscular junction. The blockage can be overcome by increasing the level of acetylcholine at the junction. This can be achieved by intravenous administration of the acetylcholine esterase inhibitor edrophonium (tensilon). Resolution/improvement in the observed muscle weakness in the minutes following IV tensilon administration is called a ‘positive’ tensilon test and is suggestive of underlying MG. The test must be carried out with cardiac monitoring as tensilon may precipitate dangerous arrhythmias. Our patient had a positive tensilon test that night in ICU with rapid resolution of her ptosis following administration of the drug.

link to youtube video on the tensilon test

Q5. What other tests are indicated?

Myasthenia gravis is often missed in clinical practice. When the diagnosis is suspected, as in this case, the following tests must be carried out

1) anti-acetylcholine receptor antibodies: present in about 85% of cases

2) anti-tyrosine kinase antibodies: present in 40 – 70% of cases negative for (1)

Serology is important in supporting the diagnosis of myasthenia gravis and in determining treatment. Compared to patients positive for anti-acetylcholine receptor antibodies, patients positive for anti-tyrosine kinase antibodies are less responsive to pyridostigmine. Also, thymectomy, in the absence of thymoma, may be effective in anti-acetylcholine receptor antibody positive cases but is not effective in patients who are anti-tyrosine antibody positive.

CT thorax: About 10% of cases of MG are associated with an underlying thymoma. CT thorax is mandatory.

EMG: may show abnormalities or may be normal in cases of MG.

All of these tests may be negative in a case of myasthenia gravis! Hence, each one is useful if positive! Clinical assessment remains of critical importance in diagnosis.

In general, once the possibility of malingering is mentioned it should immediately ring alarm bells in your head. In my experience, as soon as you start to blame the patient for your inability to make a diagnosis you should redouble your efforts. You may well have missed something.

Q6. Outline the management of the condition diagnosed in the answer to Q3.

Myasthenic crisis

This lady is experiencing a myasthenic crisis, acute ventilatory failure due to worsening of myasthenia gravis affecting the muscles of the chest wall. This is a medical emergency and must be managed on ICU. The effects of tensilon are transient and following admission to ICU, our patient was intubated and ventilated. In such a catastrophic deterioration, intravenous immunoglobulins or plasma exchange will be necessary to control/eliminate the offending autoantibody. Our patient responded to plasma exchange.


Chronic myasthenia gravis

In terms of long-term management the patient will require regular treatment with acetycholinesterase inhibitors, eg pyridostigmine.

The majority of patients will also require immunomodulatory therapy: prednisolone.

In about 10% of cases, myasthenia gravis is associated with an underlying thymoma. Thymectomy is a well established treatment for MG and is carried out in patients with proven thymoma and in most patients under 50 years of age with MG even in the absence of thymoma.

Subsequent Course


Two badly behaved children with two other children

The patient’s myasthenic crisis improved in response to immunopheresis. Subsequent CT thorax confirmed the presence of a thymoma and she was positive for anti-acetylcholine receptor antibodies. The patient had an excellent response to thymomectomy.


Myasthenia gravis

Myasthenia gravis is a humoral autoimmune disease characterised by the presence of antibodies which react with and block the acetylcholine receptor at the neuromuscular junction. Hence, muscular power will be reduced and muscle action easily fatigued. Patients with underlying myasthenia gravis may develop an acute crisis with involvement of the muscles of respiration and life-threatening hypoventilation (a myasthenic crisis). Some cases of myasthenia gravis are negative for anti-acetylcholine receptor antibodies and a proportion of these negative cases have circulating autoantibodies against a muscle-specific tyrosine kinase. The serology of myasthenia gravis is very important in determining treatment.


This figure illustrates the pathophysiology of myasthenia gravis. A. Vesicles containing the neurotransmitter acetylcholine (Ach) are present in the terminals of motor nerves at the motor end plate. B. In response to nerve activation, the vesicles fuse with the nerve terminal cell membrane releasing Ach into the surrounding extracellular fluid. Ach binds to the Ach receptor leading to an increased membrane permeability to sodium ions and this triggers muscle contraction. C. In the majority of myasthenia gravis patients an autoantibody is present which competes for binding to the Ach receptor blocking Ach binding but without activating muscle contraction. Ach at the neuromuscular end plate is normally broken down by acetylcholinesterase. We can improve muscle function by administration of inhibitors of acetylcholinesterase. This results in increased level of Ach at the neuromuscular junction. In a minority (approximately 10% of cases), the disease is mediated by autoantibodies against skeletal muscle tyrosine kinase. The kinase is thought to function in mediating appropriate distribution of Ach receptors in the muscle cell membrane.