Severe Sepsis of Unknown Cause

Sangram Patil1, Indrani Banerjee2
1. Specialist registrar in Anaesthetics, Morriston Hospital Swansea, SA6 6PU, UK.
2. SHO in Anaesthetics, Ysbyty Gwynedd, Bangor LL57 2PH, UK.

Case summary

37 yr female presented with initial complaints of feeling unwell, poor appetite and abdominal pain. She was referred to a medical unit by her psychiatrist a week before and was diagnosed to have gastritis after upper GI endoscopy. While on ward her BP was recorded to be 75/ 50 mmHg at one point. She was discharged from hospital after couple of days of medical therapy for gastritis.

This time she rapidly developed acute renal failure due to dehydration/sepsis. Due to falling consciousness levels and respiratory failure she was admitted on the ITU. Her clinical picture was not clear. To rule out encephalitis/ meningitis lumbar puncture was performed on admission to ITU. She was intubated and ventilated for deteriorating general condition and sepsis. LiDCO monitoring was initiated.

She met criteria for severe sepsis-
High temperature 40oC
Heart rate 177/ min
Hypotension Systolic BP 45 mm Hg
Hypoxemia SaO2 85 %
Acute oliguria

Her investigations showed-
CXR Clear
CT scan head Normal
Lumbar puncture Unremarkable
Gynaecology referral Normal

‘Sepsis Care Bundle’ was initiated which included-
Early diagnosis and treatment
Hydrocortisone
Glycaemic control
Activated Protein C
Limit ventilation pressures

There is an ongoing research in our hospital which includes serum sampling for cortisol levels taken prior to commencing hydrocortisone administration for every patient with sepsis. This patient was now appearing to be a case of Addison’s disease (cortisol level < 28nmol/L) with MODS and sepsis. She was started on infusion of hydrocortisone 10 mg/ hr. Haemofiltration was instituted to correct acidosis and renal failure. Activated protein C was administered as she fulfilled criterions for it.
CT scan of chest, abdomen and pelvis was normal. Rheumatological screening for organ-specific & systemic auto antibodies screen was negative.

She responded to initial aggressive measures and showed slow clinical improvement, complicated by ARDS, tracheostomy and prolonged ventilatory wean. Cortisol levels during recovery were 741 nmol/ L and depot synacthen test showed no response (proven Addison’s disease now). Hydrocortisone was replaced gradually by 30 mg/ d oral prednisolone. Fludrocortisone was added daily 100 mcg orally and patient was discharged home after few days of ward stay.

Four weeks post discharge she was seen in out patient clinic by endocrinologist, where she complained of lethargy and tiredness. She was put on hydrocortisone 25 mg OD, fludrocortisone 100 mcg OD. Her cortisol/ ACTH day profile showed flat response.

She is now under care of endocrinologist being treated for Addison’s disease.


Discussion

Addison’s disease:

“General languor and debility, remarkable feebleness of the heart’s actions, irritability of the stomach, and a peculiar change in the colour of the skin” – Addison. Primary Addison’s disease is relatively rare. There needs to be 90% functional destruction of adrenals before symptoms of this condition.
Lab findings of Addison’s disease are:
Low urinary cortisol
Low basal cortisol and aldosterone, subnormal response to ACTH
↑ Ca++, ↑ K+, ↓ Na+, ↓ Cl-, ↓ HCO3-.

Short synacthen test:

Indications:
Diagnosis of primary adrenal insufficiency
Assessment of ACTH reserve

Contraindications:
This test is unreliable within 6 weeks of pituitary surgery.
If not urgent female patients should avoid oral HRT or oral contraceptives for 6 weeks. In patients with allergic disorders e.g. asthma.

Procedure:
Patient needs to be non-fasting. If on hydrocortisone, omit previous evening and next morning doses. Take blood at 0900hr for cortisol estimation. Give intramuscular tetracosactide 250µg. Take blood samples at 30 and 60 minutes post synacthen for cortisol estimation.


Interpretation guidelines:
Serum cortisol should rise to >550mmol/L at 30 minutes.
Failure indicates adrenal insufficiency, whether primary or secondary.

NB Unreliable test within 6 weeks of pituitary surgery


Conclusion

Opinion on the value of the short synacthen test is equivocal.1-3
Our patient had cortisol levels done which led to detection of Addison’s disease early in her presentation. Should every patient admitted to ITU with severe sepsis have baseline cortisol estimation? Current evidence is conflicting. More research is needed in this field to provide definitive guidelines.


References

Loisa P Uusaro A Ruokonen E. A single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock. Anaesthesia & Analgesia. 101(6):1792-8, 2005 Dec.
Ligtenberg JJ, Zijlstra JG. The relative adrenal insufficiency syndrome revisited: which patients will benefit from low-dose steroids? Current Opinion in Critical Care. 10(6):456-60. 2004 Dec
Bourne RS, Webber SJ, Hutchinson SP. Adrenal axis testing and corticosteroid replacement therapy in septic shock patients – local and national perspectives. Anaesthesia. 58: 571-596. 2003