The patient with Long lie - Rhabdomyolysis

Skeletal muscle injury caused by any mechanism (direct, genetic, biochemical) is termed as rhabdomyolysis. Injured muscle fibers release cellular contents into the circulation leading to myoglobinuria. Besides myoglobin, cellular contents also include enzymes suck as creatine kinase (CK), aldolase, LDH, AST, and potassium. Eventually, the Na+K+ATPase pump and Ca transport takes the hit resulting in increased intracellular calcium and muscle injury. Calcium also activates intracellular enzymes including proteases inducing production of free oxygen radicals. 

Pathophysiology of Rhabdomyolysis

Potential causes of rhabdomyolysis include:

• Alcohol (Prolonged immobilisation and direct alcohol related toxicity, Low K/Mg/PO4 also predispose)
• Recreational Drug use (Cocaine, Amphetamines, Opoids)
• Medications (Statins, TCAs, SSRIs, Lithium, Steroids, MAOi )
• Myopathies(Dermatomyositis, Polymyositis)
• Trauma (Electricity, Crush Injury)
• Seizures
• Prolonged Immobility (Post Falls in Elderly)
• Infection (Bacterial and Viral)
• Strenuous physical activity
• Heat-related illness. 

Inherited metabolic disorders should be suspected with recurrent episodes of rhabdomyolysis

Clinical Presentation

• Acute onset muscle aches
• Muscle stiffness and weakness
• Fever
• Dark coloured urine. 
• Nausea, vomiting and tachycardia 
• Tenderness Muscles 

Examination may be completely normal. Therefore, look for cues in the history and work up based on that.


Diagnosis

Raised CK is a marker of muscle injury. The degree of elevation correlates with the amount of damage but it is unrelated with the morbidity. A rise in CK >5 times than normal is considered as significant. CK levels begin to rise 2 to 12 hours after the onset of injury, and peak within 24 to 72 hours.

Pattern of Myoglobin and CK rise during Rhabdomyolysis

Myoglobin elevation actually occurs before CK elevation but it rapidly cleared from the plasma. It enters urine only when the plasma concentration is significantly elevated. Because myoglobin contains heme, dipstick tests may turn positive as then test cannot differentiate among hemoglobin, myoglobin, and red blood cells. Therefore, suspect myoglobinuria when the urine dipstick test is positive for blood but no red blood cells are present on microscopic examination. 

Myoglobin levels may return to normal within 1 to 6 hours after the onset of muscle necrosis, therefore absence of an elevated serum myoglobin level or of myoglobinuria does not exclude the diagnosis. 

Due to cellular injury, serum electrolyte disturbances are seen commonly (Low Ca, High K/Uric Acid/Phosphorus). Renal Function tests reflect the extent of kidney injury. 


Management

• Treat the underlying cause
• Aggressive Fluid Resuscitation (Normal Saline)
• Target Urine Output is 200-300ml/hr (catheterise to check output in critically ill)
• Treat Hyperkalemia with usual measures
• Avoid Nephrotoxic Medications 
• Renal Replacement therapy
• Consider mannitol, especially if compartment syndrome - Low grade evidence 

As usual - Bicarbonate is recommended by some but without any definite evidence base. 

The idea of urine arlkalinization stems from the fact that myoglobin precipitation is increased in acidic urine. However, in clinical studies - urine alkalinization has not been shown to impact outcomes. 

  

Compartment syndrome and peripheral nerve injury are potential mechanical complications of Rhabdomyolysis. Rarely, thromboplastin release from damaged muscle leads to consumptive coagulopathy and DIC. 

Take Home

• Early recognition and prompt initiation of treatment is the key
• Pick cues from the history as examinations findings can be subtle or absent
• Watch for the complications (DIC, Compartment Syndrome)

References:

1. Parekh R, Care DA, Tainter CR. Rhabdomyolysis: advances in diagnosis and treatment. Emergency medicine practice. 2012 Mar;14(3):1-5.
2. Malinoski DJ, Slater MS, Mullins RJ. Crush injury and rhabdomyolysis. Critical care clinics. 2004 Jan 1;20(1):171-92.
3. Giannoglou GD, Chatzizisis YS, Misirli G. The syndrome of rhabdomyolysis: pathophysiology and diagnosis. European journal of internal medicine. 2007 Mar 31;18(2):90-100.
4. ThomasR:Towardsevidence-basedemergencymedicine: bestBETS from the Manchester Royal Infirmary. Emerg Med J 27: 305, 2010. 
5. Dalakas MC: Toxic and drug-induced myopathies. J Neurol Neurosurg Psychiatry 80: 832, 2009.
6. Clarkson PM, Eichner ER: Exertional rhabdomyolysis: does elevated blood creatine kinase foretell renal failure? Curr Sports Med Rep 5: 57, 2006. [PMID: 16529674]
7. Vanholder R, Sever MS, Ekrem E, et al: Rhabdomyolysis. J Am Soc Nephrol 11: 1553, 2000. 

Posted by:

              

     Lakshay Chanana

     

     Speciality Doctor

     Northwick Park Hospital

     Department of Emergency Medicine

     England

     @EMDidactic

Understanding Diabetic Ketoacidosis

This episode talks about diabetic ketoacidosis.
Some key points on how insulin maintains normoglycemia before we end with a couple of clinical take home points.

Diabetic Ketoacidosis

Want to read more on DKA, then checkout:
http://rebelem.com/diabetic-ketoacidosis-dka-myths/
http://lifeinthefastlane.com/ebm-diabetic-ketoacidosis/
http://www.emdocs.net/myths-dka-management/

Hyperkalemia Revisited

This week lets review a topic, parts of which have been covered in the past.

Hyperkalemia is a life threatening electrolyte imbalance. Prompt recognition and treatment of severe hyperkalemia is crucial to avoid potential cardiac arrhythmias. Hyperkalemia (K+ >5.5 mEq/L) can be the result of:

1.    Transcellular Shift (Acidosis, Rhabdomyolysis, Tumor Lysis, Transfusions, Medications)

2.    Impaired renal excretion of potassium (CRF, Adrenal Insufficiency)

3.    Ex vivo hemolysis (pseudohyperkalemia) – Obtain a repeat sample

If the source of the hyperkalemia is unclear, a spot urine K + can be useful. A high urine K+ (>30 mEq/L) suggests a transcellular shift, and a low urine K+ (<30 mEq/L) indicates impaired renal excretion.

Clinical Features of Hyperkalemia

ECG Abnormalities: Often ECG is used as the first investigation when hyperkalemia is suspected. The classic teaching of sequential ECG changes with progressive hyperkalemia does not always hold true. Threshold for ECG changes can vary widely. ECG can be bang normal with severe HyperK OR the first cardiac manifestation of hyperkalemia may be ventricular fibrillation. So overall, ECG has got a poor sensitivity to diagnose hyperK. Nevertheless, It is important to be aware of the important ECG findings of HyperK:

• Peaked T waves, Prolonged PR, flattening of P waves, widenced QRS, Sine wave, VF
• Bradycardia, BBB, AV Blocks, ST Elevation

Here, I am not saying that you should not use ECG for suspected HyperK. But if the ECG turns out to be normal don't have that false sense of reassurance. On the other hand, if you see hyperkalemic changes of EKG, go ahead with potassium correction. Since the treatment for hyperK is almost harmless, but hyperK itself is lethal, it makes sense to have a low threshold for treating hyperK.

So, ECG changes should not be considered necessary for treating emergent hyperK.

Neuromuscular Effects: Hyperkalemia may result in paraesthesias and weakness progressing to a depressed DTRs, flaccid paralysis.

Management 

Severe hyperkalemia is defined as a serum K+ >6.5 mEq/L, or any serum K+ associated with ECG changes. We have 3 goals here:

1.    Cardiac membrane Stabilisation (Calcium, Hypertonic Saline)

2.    Redistribution of K (Insulin, Beta agonists)

3.    K Elimination (Diuretics, Kayexylate, NaHCO3, HD)

Some medications that can cause HyperK are listed below:

•    Acute Digitalis Toxicity 
•     Succinylcholine 
•     Beta blockers
•     ACE/ARBC
•     K Sparing diuretics
•     NSAIDS
•     Heparin
•     Cotrimoxazole

Is Calcium safe for those on digoxin?
Though  the traditional teaching was "Calcium must be used cautiously in patients receiving digoxin because hypercalcemia aggravates digitalis cardiotoxicity. It appears that Ca is safe in those with hyperK on digoxin.

Which one is preferred, Ca gluconate or Ca Chloride?

Use what you are more familiar with 

Ca Gluconate: less likely to cause necrosis

Ca Chloride: needs central venous access, contains 3 times more calcium than gluconate

Hypertonic Saline: Restrict use to HypoNa with HyperK

Insulin and Dextrose: Always watch for hypoglycaemia and skip the dextrose when treating hyperK with hyperglycaemia. 

Kayexylate: Use this only if you don't have nephrology back up, otherwise stay away from this drug. Read the post on Kayexylate to find out more on this.

What is the appropriate dose of Beta 2 agonists to treat hyperK?

The dose of inhaled β2- agonists needed to produce a significant drop in serum K+ is at least 4 times the therapeutic dose, and this can produce unwanted side effects (e.g., tachycardia). As many as 40% seem to be resistant to the hypokalemic effect of albuterol due to unknown reasons. Therefore, beta 2 agonists should never be used as a single agent for the treatment of hyperkalemia.

Bicarbonate

Sodium bicarbonate seems to have no effect to shift K into cells, even after several hours. It is likely to be effective in combination with a diuretic drug. I tend to use it when they have acidosis in addition to hyperK. Bicarbonate can also  form complexes with calcium antagonising the membrane stabilising effects of Ca.

Key Points:

• Don't be reassured with a normal ECG in hyperkalemia.
• 
Have a low threshold to administer Calcium for hyperK.
• Calcium appears to be safe for treating hyperK patients who are on digoxin.
• When using beta 2 agonists, give 10-20mg news and avoid using beta 2 agnostic alone for treating hyperkalemia.

References:

• Weisberg L. Management of severe hyperkalemia. Crit Care Med 2008; 36:3246–3251.
• Levine, Michael, Heikki Nikkanen, and Daniel J. Pallin. "The effects of intravenous calcium in patients with digoxin toxicity." The Journal of emergency medicine 40.1 (2011): 41-46.
• Alfonzo AVM, Isles C, Geddes C, Deighan C. Potassium disorders—clinical spectrum and emergency management. Resusc 2006; 70:10–25.
• Schaefer TJ, Wolford RW. Disorders of potassium. Emerg Med Clin North Am 2005; 23:723–747, viii–ix.
• Tran HA. Extreme hyperkalemia. South Med J 2005; 98:729–732. 

The story of Kayexalate!

Hyperkalemia is a life-threatening emergency that can cause arrhythmias and cardiovascular collapse. As Emergency Physicians, we must be able to anticipate and treat Hyperkalemia better than anyone else. No surprise, why we have been about the management of Hyperkalemia “n” number of times. Lets look at the evidence behind one of the treatment modalities for Hyperkalemia;  “Kayexylate” aka “K-Bind/SPS”.

Sodium polystyrene sulfonate (SPS, Kayexalate) is a cation-exchange resin that has a higher affinity for potassium than sodium. In the lumen of the colon, it exchanges sodium for secreted potassium. It can cause severe constipation; therefore sorbitol/mannitol is added to it as a cathartic. FDA approved K Bind in 1958. This was based in two studies done with very limited number of patients were published in NEJM, 1961 supported the use of SPS. There were potential flaws with these studies like no control group; patients were fed with sugar (which causes insulin release and decreases potassium) and poor statistical analysis.

1. Scherr et al. 32 patients with hyperkalemia and renal failure, various doses of SPS were given with various dosing schedules and courses of treatment. Reduction of serum K by 0.4 in 66% pts after 24 hours. Not a RCT, no controls, patients in the study were also on: low potassium diets, many received bicarb/insulin/glucose

2. Flinn et al, 10 patients, 5 kayexalate/sorbitol PO, 3 sorbitol, 2 kayexalate/sorbitol enema. All on low potassium diets and diuretics. 5 days QID dosing, steady decrease in potassium.

In addition to the questionable benefit, now there is mounting evidence describing constipation and colonic necrosis with the use of SPS. In 2011, FDA issued a warning with the use of SPS. There is more and more literature coming up against the use of SPS. Evidence Based Medicine has come a long way over last 50 years and we need to review this practice.

So, SPS is a potentially harmful therapy to treat hyperkalemia, it has a slow onset action (if at all) and  doubtful efficacy. It also carries risk of life threatening gastrointestinal complications. There is no convincing evidence that SPS increases fecal potassium losses.

So next time, ask yourself if SPS (K-Bind) is really required !

References:

1.  Sterns RH, Rojas M, Bernstein P, Chennupati S. Ion-exchange resins for the treatment of hyperkalemia: Are they safe and effective? J Am Soc Nephrol 21: 733-5, 2010

2.   Gruy-Kapral C, Emmett M, Santa Ana CA, et al. Effect of single dose resin-cathartic therapy on serum potassium concentration in patients with end-stage renal disease. J Am Soc Nephrol 9: 1924–30, 1998.

3.  Bomback A, Woosley JT, Kshirsagar AV. Colonic necrosis due to sodium polystyrene sulfate (kayexalate). Am J of EM 27: 753.e1-753.e2, 2009.

4.   Welsberg LS. Management of severe hyperkalemia. Crit Care Med 36: 3246-51, 2008.

5.  Rogers BR, LI SC. Acute colonic necrosis associated with sodium polystyrene sulfonate (kayexalate) enemas in a critically ill patient: Case report and review of the literature. J Trauma 51: 395-7, 2001.

6. Systematic review of adverse events caused by kayexalate (The American Journal of Medicine Volume 126, Issue 3 , Pages 264.e9-264.e24, March 2013)

7.  http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/011287s023lbl.pdf

HyperK - Get the ECG

Hello friends

This week we are gonna talk about something which we come across in the ED almost everyday.

We all learned to look for the ECG changes for hyperK and also how the changes correlate with the levels of potassium.

K levels        ECG changes

5.5 - 6.5       Tall tented T waves
6.5 - 7.5       Loss of P waves
7.5 - 8.5       Widening QRS
> 8.5            Sine Wave pattern, Ventricular Arrythmias

Well, Don't waste your time in memorising these changes and the corresponding potassium levels. Patients don't read textbooks and they don't follow this textbook pattern of ECG changes.

A potassium of 8 may not produce any ECG changes and at the same time Ventricular Fibrillation can be the first ECG change in hyperK. So if they have elevated K which concerns you, just go ahead and give them some calcium regardless of ECG changes. And if they have ECG changes with hyperK, be more aggressive with the correction.

HyperK often comes up with strange rhthyms and I learned this pearl from the EKG Guru "Amal Mattu" --> "Any bizarre EKG changes, think hyperKalemia and try some calcium". Lets hear it from the EKG GOD himself.

Reference:
Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008 Dec;36(12):3246-51.