> Patients with conditions that make them chronically hypercapneic are at risk of CO₂ retention when they require oxygen therapy.

> The principle of controlled oxygen therapy is to initially give oxygen at low concentrations / flow rates in such patients and slowly up-titrate to allow SpO₂ goals to be reached.

> Postulated mechanisms of CO₂ retention / rising PaCO₂:

o   Decreased hypoxic respiratory drive

o   Worsening of V/Q mismatch (hypoxia-induced vasoconstriction is lost in poorly-ventilated lung areas)

o   Haldane effect (more oxygen binding to Hb reduces Hb’s affinity to CO₂, pushing CO₂ into solution)

> Examples of patients who may benefit from controlled oxygen therapy:

o   Chronic type 2 respiratory failure:

o  COPD

o  Brain stem lesions that result in deranged respiratory regulation 

o  Chronic neuromuscular disorders, e.g. myasthenia gravis

o  Chest wall disorders, e.g. severe kyphoscoliosis

o  Severe obesity

> Aim for an oxygen saturation of 88-92%

> Start at FiO₂ of ~ 24% (or ~1L on nasal cannula)

> Monitor with ABG (for rising PaCO₂ or falling pH):

o   If there is a decrease in PaCO₂: can further increase the FiO₂

o   Titrate upwards at intervals of ~15 minutes; maintain when saturation goal is reached

o   If PaCO₂ continues to increase and patient becomes more acidotic: should consider non-invasive ventilation; if patient GCS drops – may need to consider intubation and mechanical ventilation.

Caveats:

> If patient has severe hypoxemia: may have to start at high FiO₂ despite risk of hypercapnia

> If you see a patient with COPD on high flow oxygen but worsening hypoxia with decreased respiratory drive, temporarily stop the supplemental oxygen to see if saturations improve

 

 

Serum urate target: <6 mg/dL (<360 micromol/L)

 

Indications: 

Any patient with established gouty arthritis AND: 

- tophus or tophi (clinical examination or radiological)

- 2 or more gout attacks per year 

- CKD stage 2 or worse

- past urolithiasis 

 (1) First line (xanthine oxidase inhibitors): 

- Allopurinol (no more than 100mg/day, or renal adjusted lower dose) 

- Febuxostat (bear in mind lack of published safety data in CKD stage 4 or worse)

 

Alternative first-line therapy (in the setting of contraindication/intolerance)

- Probenecid: uricosuric agent (contraindicated in hx of urolithiasis and not recommended if CrCl <50ml/min)

 

(2) Second line therapy (if serum urate target not achieved)
 - combination of 1 xanthineoxidaseinhibitor and 1 uricosuricagent 

(3) Third line therapy (if serum urate target still not achieved)
 - Pegloticase: for patients with severe gout disease burden and refractoriness to, or intolerance of, appropriately dosed first and second line options

Guidelines recommend regular monitoring of urate levels (every 2 – 5 weeks) followed by every 6 months once serum urate target reached. 

- reported mortality 20-25% 

- highest risk in the first few months of therapy 

- ranges from SJS/TEN to systemic disease with features such as eosinophilia, vasculitis, rash, end-organ damage 

- pharmacogenetics: higher risk in patients with positive HLA B*5801 

- patientpopulations: higher risk in Koreans with Stage 3 or worse CKD and Han Chinese/Thai descent 

 
 

PHARMACOLOGIC ANTI-INFLAMMATORY GOUT FLARE PROPHYLAXIS
(to reduce the high acute gout flare frequencies in early ULT)

1. First-line: Colchicine OR low dose NSAIDs (with PPI cover) 

 

2. If unable to tolerate/contraindicated, second-line: low dose oral Pred <10mg/day 

   - risk-benefit ratio must be re-evaluated in view of side effects of prolonged steroids  

 

 

General principles 

1. Pharmacologic therapy should be preferentially initiated within 24 hours of onset 

2. Ongoing prophylactic urate-lowering therapy should be continued during acute gout attack 

 

Choice of pharmacologic therapy depends on (i) severity of pain and (ii) number of joints involved. Combination therapy was recommended as either NSAID + colchicine OR steroids + colchicine. Adequate response is defined as either 20% improvement in pain score within 24 hours or 50% improvement in pain score 24 hours after initiating pharmacologic therapy. 

 

 

 

 

 

 

 

 

 

Guidelines did not rank one therapeutic option over another, but these are guiding principles when choosing pharmacologic treatment for acute gout flare: 

 

1. Oral steroids 
- avoid in patients with concomitant infection, prior steroid intolerance, brittle DM, post-operative (poor wound healing)

 

2. NSAIDS 
- appropriate in younger patients (<60yo) without renal/CVM/GI disease
 
 

3. Colchicine (appropriate if started within 36 hours of symptom onset) 
- disrupts cytoskeletal functions by inhibiting β-tubulin polymerization into microtubules

- also prevents activation and migration of neutrophils associated with gout symptoms
 - avoid in patients with severe renal or hepatic impairment, remember to renal adjust 

- recommended to start with loading dose of 1g, then 500mg BD/TDS as tolerated until attack resolves  

- bear in mind drug interactions with CYP 450 inhibitors eg. clarithromycin, erythromycin, cyclosporine