Corticosteroids are a class of drugs that are used in conditions with chronic inflammatory reactions. Chronic inflammatory processes are characterised by increased transcription of proinflammatory genes like NF Kappa beta and activator protein 1 which get activated by acetylation with core histone proteins.
Corticosteroids inhibit this process by reversing the acetylation of these genes. Since their discovery, Corticosteroids have been used liberally in asthma, irritable bowel disease and autoimmune disorders. Advancements in drug development have made them safe and tolerable with relatively fewer side effects on long term use.
Corticosteroids and Bacterial Infections
- Septic shock is one of the most dreaded events in an intensive care unit setting. Mostly caused by gram-positive bacteria, it is a severe immune response that also raises the basal metabolic rate of the body in terms of degradation of proteins, cellular respiration, metabolic acidosis and the resulting compensatory respiratory alkalosis. The mechanism involved includes the release of exotoxins from gram-positive bacteria that disrupt the cell membranes and cause haemolysis.
Gram-negative bacteria are also involved and they attach to macrophages, monocytes and neutrophils via the CD14 receptor and lipopolysaccharide component. This, in turn, results in the activation of NF Kappa beta that aids in the transcription of pro-inflammatory genes. This massive inflammatory response is countered by a group of anti-inflammatory substances including Interleukin-4, Cortisol, and Interleukin-1.
The cascade of events is called CARS (Compensatory Anti-inflammatory Response Syndrome) and the suppression of immunity from this event is believed to cause super-infection by other pathogenic organisms, further adding insult to the injury. Corticosteroids like low dose Hydrocortisone are often added in the treatment regimen for these patients, particularly in refractory hypotension that is unresponsive to fluid therapy and vasopressors. The recommended dose is 50mg IV every 6 hours. Once haemodynamic stability has been achieved, hydrocortisone should be tapered off over the next couple of days.
- Bacterial meningitis, as the name suggests is an inflammation of the meningeal coverings, particularly of the arachnoid and pia mater. E. coli is the most common causative organism for this, however, other bacteria like Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae can also cause significant morbidity and mortality.
- Emerging antibiotic resistance is a challenge commonly encountered in the treatment. This makes the infection life-threatening. Initial symptoms are often non-specific and include nausea, projectile vomiting, photophobia, stiff neck and fever. These symptoms can worsen with altered sensorium, neurological deficits and even hearing loss. The key to diagnosis lies in the presence of bacteria in the cerebrospinal fluid collected by the procedure of Lumbar puncture. This is where Corticosteroids come into play.
- Data from randomised controlled trials show that administration of oral or intravenous Corticosteroids reduces the severity of bacterial meningitis induced hearing loss and neurological sequalae in children. This is particularly true in the case of Streptococcus pneumoniae. Corticosteroids also play a role by reducing brain oedema and intracranial hypertension. The first steroid dose should be administered 10-20 minutes prior to antibiotic therapy or at least concomitantly.
- Recommended dosage includes 0.15mg/kg of Dexamethasone every six hours for 2-4 days for community-acquired meningitis infection in children. In adults, the dose is 10mg every 6 hours. Discontinuation is advised if Haemophilus influenzae can be ruled out as the causative pathogen in children.
- Acute otitis media is a severe bacterial infection of the middle ear, commonly affecting the paediatric age group. Bulging eardrum, red and tensed, perforation and fluid accumulation in the middle ear canal is commonly observed. The shorter Eustachian tube in children allows easy access to the bacteria to enter the middle ear. Bottle feeding and tooth infection in infants are some risk factors for this.
- Streptococcus pneumoniae and Haemophilus influenzae account for more than 85% of these cases of otitis media, the rest are often viral in origin. Young children with middle ear infections may particularly appear irritable or fussy due to discomfort in the ear, often this is preceded by an upper respiratory tract infection. Transient hearing loss is often associated with it. Hydrocortisone or Dexamethasone infused in alcohol or glacial acetic acid is often administered with a dropper into the ears of young children.
Side effects of using Corticosteroids
Although Corticosteroids have proven to be beneficial in terms of reducing the duration of hospital stay, the severity of inflammatory response and some mortality benefits; they are associated with a multitude of adverse effects that require careful monitoring. Wrong dose, duration and abrupt withdrawal from high dose Corticosteroids have been associated with fatal outcomes. Since they suppress the immune response, they can pose a risk to the development of super-infection with other bacterial or viral entities.
Apart from infections, bone loss is a well-documented effect seen in patients on long term steroid therapy. This occurs due to a steroid-induced reduction in the number of osteoclasts and osteocytes. Osteonecrosis of the hip and knee is particularly common in Prednisolone users.