Thursday, April 24, 2014

Renal tubular acidosis

Today we discussed a case of acidosis. A young patient presenting with a significant metabolic acidosis of mixed origin (both anion gap and non-anion gap). This was determined by carefully examining the patient electrolytes and blood gas results, identifying the primary acid-base abnormality and calculating what is called the delta-delta.

This refers to the difference between the calculated and expected anion gap and the difference in the bicarbonate from normal serum values. When the bicarbonate value is lower than what would be expected from the anion gap difference (a 1:1 change with respect to AG and bicarbonate) and additional non-anion gap acidosis is identified. When the bicarbonate is higher than expected, a concomitant metabolic alkalosis is diagnosed.

Anion gap acidosis is a commonly encountered scenario, and there are widespread mnemonics to help you consider the differential diagnosis (ex. MUDPILES). Non-anion gap metabolic acidosis seem to be less commonly discussed, but are worth reviewing. The differential diagnosis includes:

Resuscitation with hyperchloremic solution (NS)/hyperalimentation
Medications: acetazolimide
Renal tubular acidosis
Anatomic fistulas: uretoenteric fistuls and pancreaticoduodeneal fistulas

The patient today was known to have chronic metabolic acidosis, raising a RTA as a likely cause. These can be divided anatomically into four categories:

a) proximal RTA (type 2) - here there is an abnormality resulting in the reabsorption of bicarbonate. Patient tend to have mild to moderate acidosis with a relative ability to excrete acid in the form of NH4Cl-, and acidify the urine.

Proximal RTA can be thought of as primary and secondary. There are congenital syndromes associated with this, some of which have associated visual and cognitive deficits. One must look for evidence of the Fanconi's syndrome, where in addition to inability reabsorb bicarbonate, glucose, phosphate and potassium are lost in the urine. When present, paraproteinemia (multiple myeloma), should be considered, given the light chains can block re-absorption of electrolytes in the tubules. Drugs and other metabolic and congenital diseases may also present with this and should be considered (See attached article for details). Other things to watch for include bone disease and renal stones with increased loss of electrolytes in the urine.

b)distal RTA (type 1) - results from the inability to excrete protons at the level of the distal tubules. This results in severe acidosis and inability to acidify the urine. Again, this can be a result of congenital disease (often associated with sensorineural hearing loss because of shared gene expression in the cochlea and the kidney) and acquired. A detailed history for connective tissue and autoimmune disease should be performed, with rheumatoid arthritis and Sjogrens syndrome as common entities identified.

c) Mixed proximal/distal (type 3) - these patients have features of both distal and proximal RTA. Rare mutations in the carbonic anhydrase gene have been attributed to mixed RTA. Other clinical features include osteopetrosis, cerebral calcification and mental retardation.

d) Hyperkalemia RTA (type 4) - is due to impaired ammoniagenesis. Most common causes include hyporeninemic states as a result of primary renal disease (diabetic nephropathy) or medications that cause hypoaldosternonism (spironolactone). Congenital syndromes do exist causing pseudohypoaldosteronism however these are uncommon.

For additional details regarding the diagnosis, investigations and treatment of RTA please see the below review article which provides a good overview.

RTA review

Friday, April 11, 2014

Therapeutic hypothermia

Today we discussed a complicated case of multifocal sepsis in a patient with hypoxic ischemic injury following cardiac arrest. This provides an opportunity to discuss neurologic recovery following cardiac arrest, the role for cooling as part of post-resuscitation care and examining for coma/brain death.

Cardiopulmonary resuscitation has been around since the 1950's, but its practices weren't widely promoted until the 1970's when the promotion of CPR began in the public sector as well. Since then, it has involved from chest compressions and breathing support, to add defibrillation and consideration of advanced life support techniques. In 2012, a Cochrane review looked at several studies from the previous decades at the benefit of post cardiac arrest therapeutic hypothermia, finding it to be beneficial in terms if patient in hospital neurologic recovery and overall survival. This advantages were seen without any adverse effects. This supported the current guideline recommendations, which include therapeutic hypothermia after cardiac arrest.

Although this is not as relevant for residents rotating through internal medicine, many will at some point complete ICU, CCU, cardiology and emergency medicine rotations, where this practice is important. The basics of therapeutic hypothermia should be known, and include the following:

1. Indications
2. Implementation
3. Rewarming
4. Contraindications

Patients with cardiac arrest that do not have a purposeful movement and are not following commands after return of spontaneous circulation should be considered for therapeutic cooling. There are few contraindications. The things to recognize are the risks of coagulopathy in the bleeding patient and electrolytes shifts (particularly potassium) that can occur with cooling and rewarming. Cooling can be accomplished by many methods, including external cooling blankets, ice packs, cold IV fluids (4 degrees) or internal catheter devices. Which to choose depends on the expertise of the centre and comfort of the physician. Cold IV fluids can rapidly degrees core temperature and run the risk of pushing the patient into pulmonary edema, which should be considered if this method is chosen. Targets for therapeutic cooling are somewhat controversial. A target of 33 degrees is likely reasonable in the first 24 hours, with gradual rewarming until 48 hours is reached. Whether or not cooling should be performed for over 48 hours is unclear. A recent paper in the NEJM, found no difference in outcomes when targeting a core temperature 33 vs 36 degrees. See below for a link to the original article.

After the patient is normothermic, an assessment of neurologic status is needed to try and predict neurologic recovery. Predicting neurologic prognosis after cardiac arrest has the most literature, as compared to neurologic injury from other causes. Several systematic reviews have been performed, and found that the useful predictors include:

Absent pupillary response/absent corneal response at 72h
Absent extensor motor response at 72h

One of the original articles is linke below from Neurology.

Predicting neurologic outcome after cardiac arrest
NEJM cooling after cardiac arrest