Viva 4

You have been asked to review a 56-years-old female in recovery, who became hypoxic post bronchoscopy. Bronchoscopy was done to investigate a history of 2 weeks increasing shortness of breath, associated with bilateral chest infiltrates on chest X-ray. She is currently intubated and ventilated, with a SpO2 of 88% on FiO2 1.0. 

Her respiratory function tests from one week prior to admission are tabulated below: 

	Pre-Bronchodilator (BD)			Post- BD
Test	Actual	Predicted	% Predicted	Actual	% Change
FVC (L)	1.73	4.37	40	1.79	4
FEV1 (L)	1.57	3.65	43	1.58	0
FEV1/FVC (%)	91	84		88	- 3
RV (L)	1.01	1.98	51
TLC (L)	2.68	6.12	44
RV/TLC (%)	38	30
DLCO* corr	5.13	32.19	16
DLCO/VA	1.00	5.12	19
*DLCO is measured in ml/min/mmHg

List the differential diagnosis of hypoxia post bronchoscopy in this patient, and outline your management.

Diffuse pulmonary infiltrates in this patient could be caused by any damn thing:

Differential Diagnosis for Diffuse Bilateral Pulmonary Infiltrates

Vascular: Pulmonary haemorrhage Cardiogenic pulonary oedema Infectious Bacterial Viral Fungal PJP Neoplastic Lymphangitis Infiltrative neoplasm Idiopathic ARDS Idiopathic pneumonia syndrome

Drug-induced Eosinophilic pneumonitis BOOP Alveolar haemorrhage Methotrexate-induced Autoimmune Goodpastures (haemorrhagic) Rheumatoid pneumonitis TRALI Graft vs host disease in BMT Engraftment syndrome ATRA syndrome Traumatic / postoperative Bilateral atelectasis Pulmonary contusions Chemical pneumonitis

Can you explain the meaning of the variables in this pulmonary function test panel? What conclusion does this panel suggest, regarding the patient's respiratory function?

FEV1 is the forced expired volume over 1 second, and is a measure of maximal air flow. A decreased FEV1 may mean either an obstructive pattern of lung disease, or a diminished expiratory effort (eg. in a patient who has some sort of myopathy or neuropathy).

FVC is the forced vital capacity, from maximal inspiration to maximal expiration. A decreased FVC may reflect poor respiratory effort.

FEV1/FVC ratio is a measure of airway resistance. A FEV1/FVC ratio less than the 5th percentile of predicted suggests obstructive airways disease

PEF is the peak expiratory flow rate. A low PEF suggests obstructive disease.

FRC is the functional residual capacity. A high FRC suggests hyperinflation (eg. in asthma) or large volumes of dead space (eg. emphysema)

RV is the residual volume. As with FRC, a high RV suggests hyperinflation or bullous dead space.

TLC is the total lung capacity. A high TLC may coexist with a very poor FEV1 and FVC in emphysema. A low TLC (below the 5th percentile of predicted) suggests restrictive lung disease, such as pulmonary fibrosis.

DL_CO is the diffusing capacity for carbon monoxide, a measure of the efficiency of the lung as a gas exchange surface.  Normal  spirometry and lung volumes associated with decreased DLCO may suggest anaemia, pulmonary vascular disorders, early interstitial pulmonary fibrosis or early emphysema. It is expressed in ml/min/mmHg, and a value below 40% of predicted suggests a severe diffusion defect. DLCO may also be decreased if there is reduced lung expansion (i.e. a reduced TLC).

KCO (DlCO/VA) is the transfer coefficient for carbon monoxide. It is calculated as the DLCO per unit of alveolar volume. As such, the KCO will not be confused by changes in lung volume, and is a more faithful representation of the gas diffusion efficiency.

What other investigations would inform your management of this patient?

The candidate may suggest a whole series of possible investigations:

• Bloods, which might include a normal panel 
• BNP to discriminate cardiac from noncardiac causes
• Procalcitonin to discriminate bacterial from viral or nonifgective
• Cultures, including urinary antigens and atypical serology
• A "vasculitic screen" might be asked for
• Ultrasound of the lung to look for pulmonary oedema
• A high-resolution CT or a CTPA
• A TTE

The TTE was reported as "severe pulmonary hypertension" and moderate RV systolic dysfunction with moderate TR.
What is the upper limity normal pulmonary arterial pressure?

Pulmonary arterial pressure is 12-16 mmHg in the normal population. Pulmonary hypertension is diagnosed when the pressure exceeds 25mmHg at rest, or 30mmHg with exercise.

What are the possible causes of pulmonary hypertension? How do you classify them?

In brief, there are 5 major groups of disease which fall under the pulmonary hypertension heading:

1. Pulmonary arterial hypertension 
   • associated with connective tissue disease
   • HIV
   • Congential or heriable
   • Drug-related
   • Due to portal hypertension
2. Pulmonary hypertension due to left heart disease
   • ​​LV systolic or diastolic dysfunction
   • Valve disease
   • Congential cardiomyopathies
3. Pulmonary hypertension due to lung disease or hypoxia
   • COPD
   • Idiopathic pulmonary fibrosis
   • ​​OSA/obesity hypoventilation syndrome
   • Chronic exposure to high altitude
4. Pulmonary hypertension due to chronic PE​​
5. Pulmonary hypertension due to "unclear multifactorial mechanisms"​
   • Myeloproliferative diseases
   • Haemolytic anaemias and MAHA
   • Sarcoidosis, pulmonary histiocytosis
   • Tumour obstruction
   • Fibrosing mediastinitis

Pulmonary Arterial Hypertension
Idiopathic PAH	Familial PAH BMPR2 mutations (a member of the transforming growth factor β signaling family)
Drug and toxin induced PAH	Definite association: aminorex, fenfluramine, dexfenfluramine, toxic rapeseed oil Possible association: cocaine, phenylpropanolamine, St Johns Wort, chemotherapy agents, SSRIs
Connective tissue disease	Systemic sclerosis SLE Sjogren syndrome polymyositis rheumatoid arthritis
HIV infection	clinical, hemodynamic, and histologic characteristics similar to those seen in idiopathic PAH
Portopulmonary hypertension	2% to 6% of patients with portal hypertension have PAH Pulmonary vascular resistance (PVR) is usually normal in these cases
Congential heart disease	systemic-to-pulmonary shunts Eisenmenger syndrome
Schistosomiasis	Embolic obstruction of pulmonary arteries by schistosoma eggs local vascular inflammation as a result of impacted schistosoma eggs
Chronic hemolytic anemia	sickle cell disease (SCD) thalassemia hereditary spherocytosis stomatocytosis microangiopathic hemolytic anemia
Left heart disease	LV failure Mitral valve disease
Alveolar hypoxia	Alveolar hypoxia as a result of lung disease Alveolar hypoxia due to impaired control of breathing (eg. OSA)\ Alveolar hypoxia due to residence at high altitude
Thromboembolism	obstruction of pulmonary arterial vessels by thromboemboli, tumors, or foreign bodies
Pulmonary hypertension due to unclear or multifactorial aetiologies	polycythemia vera essential thrombocythemia chronic myeloid leukemia sarcoidosis Langerhans histiocytosis glycogen storage diseases Gaucher disease mediastinal fibrosis

What extrapulmonary diseases might be associated with pulmonary hypertension?

• Rheumatoid arthritis
• Sarcoidosis
• Amyloidosis
• Scleroderma
• CREST syndrome
• polycythemia vera
• essential thrombocythemia
• chronic myeloid leukemia
• Langerhans histiocytosis
• glycogen storage diseases
• Gaucher disease
• mediastinal fibrosis

You suspect that this patient suffers from some sort of connective tissue disease, either CREST syndrome or scleroderma. What are the cardinal features of CREST syndrome?

• Calcinosis
• Raynaud's phenomenon
• Oesophageal dysmotility
• Sclerodactily
• Telangiectasia

And what are the cardinal features of scleroderma?

Cutaneous manifestations

• Skin thickening
• Oedema of the digits
• Sclerodactyly
• Pitting ulceration, particularly at the fingertip
• Calcinosis over joints
• Telangiectasia
• Raynauds phenomenon

Other associated clinical features:

• Sjogren syndrome
• Limited mouth opening
• Signs of pulmonary hypertension (loud P2, etc)
• Cardiac arrhythmias
• Features of heart failure
• Features of Cushing syndrome due to long term steroids
• Renal artery bruitts

Are you aware of any tests which might confirm the diagnosis of scleroderma?

• Anti-centromere antibodies (most associated with pulmonary hypertension)
• Scl-70 
• RNA polymerase III

A diagnosis of scleroderma is confirmed with a positive anti-centromere antibody titer. What other organ or systemic issues would you anticipate in an ICU patient with this disorder?

1. Difficult intubation:
   1. Limited neck extension
   2. Limited mouth opening
2.   Respiratory involvement:
   1. Pulmonary fibrosis
   2. Restrictive lung disease
   3. Pulmonary hypertension
   4. SpO₂ monitoring may be frustrated by poor end-digital perfusion
   5. The rapidly fatal "scleroderma-pulmonary-renal syndrome (SPRS)" may develop, which manifests as a fulminant course of acute normotensive renal failure associated with diffuse alveolar hemorrhage.
3. Cardiovascular involvement of the disease process:
   1. Cardiac problems:
      1. Arrhythmias,
      2. Myocardial fibrosis (thus, restrictive diastolic failure)
      3. Pericardial stricture (also restricts diastolic filling)
   2. Vascular problems
      1. Difficult vascular access: the skin, being very thick, makes it difficult to palpate vessels (veins and arteries both)
      2. Poor distal perfusion of the extremities, leading to gangrene- as one might expect this is not improved by arterial cannulation.
      3. Poor skin perfusion promotes pressure areas
4. Neurological sequelae: 
   1. Corticosteroid-associated psychosis
   2. Cerebral vasculitis
5. Electrolyte disturbances
   1. Hyponatremia and fluid retention due to corticosteroid therapy
   2. Hyperkalemia due to renal failure
6. Renal involvement
   1. Renal failure, renal artery stenosis
   2. Scleroderma "renal crisis"
7. Gastrointestinal and nutritional issues
   1. Oesophagitis
   2. Poor gut motility
   3. Decreased feed tolerance
   4. Risk of aspiration.
   5. Risk of oesophageal perforation
   6. Telangiectasia is present also on mucosal surfaces; there is an increased risk of bleeding from upper GI sites
8. Haematological problems:
   1. Anaemia of chronic disease is coupled with the poor EPO synthesis from damaged kidneys.
   2. Bone marrow function may be suppressed in other ways, particularly if serious immunosuppresants are in use (eg. cyclophosphamide)
9.     Immunosuppressive therapy
   1. Increased infection risk

How would you manage pulmonary arterial hypertension in this patient?

Pulmonary arterial vasodilators:

• Short term:
  • Inhaled nitric oxide
  • Inhaled prostacycline
• Long term:
  • Sildenafil
  • Bosantan
  • Ambrisantant

The candidate should then go on to talk about optimising RV function.
If not, ask them the next question:

How will you manage right heart failure in this patient?

This is straight from the college answer to Question 17 from the second paper of 2009:

Therapy	Advantages	Disadvantages
Volume	Effective, as RV needs a higher filling pressure. A PA catheter may be useful in guiding volume therapy.	Determination of preload is problematic, RA pressure may be high in chronic right heart failure and may not be a predictor of volume response. Functional parameters of volume responsiveness not useful in right heart failure
Inotropes and vasopressors	-May be of benefit in RV infarction where they may increase coronary perfusion pressure - Some suggestion that levosimendan may improve RV afterload in ARDS	No large scale published data on any specific inotrope or pressor in isolated RV failure
Afterload manipulation - Control of hypoxia and hypercapnia and acidosis	reduce PA pressures	Optimal target levels unclear.
Prostaglandins	Reduce pulmonary pressures	May cause systemic hypotension, flushing
NO	Improves VQ matching, improves oxygenation	Met Hb, platelet dysfunction, requires special delivery systems, not shown to improve mortality
Bosentan	Reduce pulmonary pressures	No large scale data
Phosphodiesterase inhibitors - sildefanil	Reduce pulmonary pressures	No large scale data
Pacing to improve A-V synchrony	Improves preload
Mechanical ventilation	May improve oxygenation and CO2 transfer and may reduce pulmonary hypertension	Deleterious effects of IPPV

Disclaimer: the viva stem above may be an original CICM stem, acquired from their publicly available past papers. Or, perhaps it is a slightly altered version of the original CICM stem. Or, it is a completely original viva stem, concocted by the monstrously amoral author of Deranged Physiology for nothing more than his own personal amusement. In either case, because the college do not make the main viva text or marking criteria available, almost everything here has been confabulated. It might sound like a plausible viva and it could be used for the purpose of practice, but all should be aware that it does not represent the "true" canonical CICM viva station.