Staten Island Corner

And here I was thinking bicarb was helpful….

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For those of you not in conference last Wednesday, there was a brief review of Rhabdo that listed bicarb as a potential treatment.  Feeling like the junior that I was (but of course am no longer), I was hesitant to speak and, instead, waited anxiously for an official senior or an attending to comment.  But no one did…  So I started looking up bicarb and wanted to share some of what I discovered.  It’s kind of long, but hey, so is residency and you all elected to commit yourself to that.

Let’s start with giving bicarb in CPR.  Though we have been giving bicarb since the 1950s, there is scant evidence for it’s effectiveness.  In fact, studies have shown the following:

  1. Bicarb actually decreases intracellular pH, while increasing the pH arterially. Theory is that the bicarb is broken down into H+, CO2, and H2O and the H+ goes intracellularly.
  2. In animal studies, giving bicarb lowers cardiac perfusion pressure and decreases ROSC after cardiac arrest.
  3. In animal studies 12 of 14 studies reviewed concluded that giving bicarb during CPR worsened myocardial performance with the remaining 2 showing no difference.
  4. Only 1 RCT for bicarb in CPR in adults was done, which showed no improvement in ROSC or mortality.
  5. Out of 19 retrospective reviews, 11 showed no benefit and 8 suggested a worse outcome when Bicarb is given during CPR.

Biochemical explanation (this is the cool part)

Bicarb breaks down into CO2, which can increase the CO2 level in the blood.  If the patient has poor CO2 elimination (aka not breathing), this can lead to increased CO2 levels, especially in cells, leading to worsening intracellular acidosis

Conclusion:  Bicarb during CPR not as helpful as we would think, and may even be harmful!!!!!

This data is so believed, even national guidelines have picked it up.Neonatal resus guidelines (2000) states that “there is insufficient data to recommend routine use of bicarb in the resus of newborns…[it] may be detrimental to myocardial or cerebral function.  The 2005 AHA guidelines no longer recommend bicarb during CPR either.

 

What about in Hyperkalemia you ask?  Well I’ll tell you.

Traditionally bicarb was one of the mainstays of drugs used to push potassium intracellularly, thus decreasing plasma potassium concentration.  According to a paper from 1977 involving 14 patients, it seems to work.    Since then though, some data has showed less than stellar results.

  1. In 12 HD pt’s with hyperkalemia, bicarb therapy + IVF showed no statistically significant change in K until 4 hours (a decrease average of 0.7), and levels returns to baseline by 7 hours (though pH and bicarb levels both increased)
  2. Nondiabetic HD patients received a variety of treatments with potassium measured q15 minutes over 1 hour.  Both bicarb and NS failed to show a significant decrease in plasma potassium  Though pt’s receiving bicarb did see an increase in pH and bicarb level

Conclusion:  Though no studies show harm, the administration of bicarb in hyperkalemia does not seem to acutely decrease potassium levels.  In a patient with a  dangerous arrhythmia due to hyperkalemia, calcium starts working in 1-3 minutes to stabilize the myocardium, while the K is pushed into cells by albuterol “immediately”, and  insulin in 10 minutes.  So at the very least, get the calcium, albuterol, and insulin in first.

 

Next review:  Bicarb in DKA with acidosis

Currently, the ADA says bicarb “may be considered” in patients with pH < 6.9 in DKA.   What about 7.0?  7.1?

            Well, in a retrospective review in Annals of Pharmacotherapy.  Patients with acidosis from DKA who received bicarb (pH<7 with DKA), had no difference in time to pH>7.2, or time to discharge vs standard tx (IVF/Insulin).  Those receiving bicarb did receive more fluid/insulin (significantly significant, but the actual numbers were not different by much).

Another retrospective study of 39 patients with DKA and pH 6.9-7.1 showed no difference in pH, PaCO2, glucose concentration, potassium level, time to normalization of pH, time to clearance of urinary ketone with and without bicarb.

There were no papers that I could find that evaluated patients with pH < 6.9.

Conclusion:  Bicarb unhelpful for pH>6.9 in DKA patients.   Unclear if pH <6.9

Lastly:  Rhabdo

Alkanizing the urine leads to: decreased myoglobin precipitation, less tubule injury from decreased redox cycling of myoglobin and lipid peroxidation, less vasoconstriction due to myoglobin (all in animal studies).

Problematically, bicarb has not shown to be as helpful in actual human studies (though trials are very limited).

1.      A retrospective study showed no difference in mortality between saline vs saline- bicarb-mannitol.  CK was lower in the saline group at baseline. And the study didn’t include saline vs saline +bicarb.  And CK levels were low at start.  And no one actually developed ARF

2.      bicarb-mannitol-saline vs saline only showed no difference in outcomes.

3.      Review of 27 articles found no RCT comparing IVF with IVF + bicarb. 8 of the articles found delay to IVF increased risk of ARF.  “No evidence supported a preferred fluid type or that sodium bicarb with or without mannitol was superior to fluid therapy alone”.  Rec: UOP 300ml/hr, bicarb only to correct systemic acidosis, and mannitol only if uop< 300ml/hr despite adequate fluid administration.

4.      Lastly, our excellent EBM on the topic recommends bicarb if Urine pH <6.5 with CK level > 5000 as class III evidence (may be acceptable, possibly useful, considered optional or alternative treatments).  One concern with bicarb is that is that it can lower calcium levels, which may already be low as rhabdo can initially lead to hypocalcemia (BUT DON”T CORRECT IT, as the calcium deposits eventually break down and the pt can develop hypercalcemia).

 

How does all this effect my clinical practice?

  1. I don’t think I’ll be giving bicarb during codes anymore.
  2. I’m not convinced that giving bicarb helps in hyperkalemia
  3. As long as pH >6.9, no bicarb needed in DKA
  4. Bicarb in rhabdo is controversial.  The patient mostly needs fluids, fluids, fluids.

Just so you don’t think bicarb is completely useless, a brief literature search dose reveal that it is still recommended in: TCA overdose, salicylate toxicity, phenobarb, chlorpropamide and chlorophenoxy herbicide poisoning, cocaine overdose, organophosphate poisoning (per Cochrane review 2005, 2 RCT’s, both small.  One no difference, one “slight benefit”.), and lastly, life-threatening acidoses from methanol and ethylene glycol (enhances formate elimination…but it seems like that’s a good time for HD).

What do y’all think?

 

Resources.

1.     Judy L. Aschner, MD,  Ronald L. Poland, MD  Sodium Bicarbonate: Basically Useless Therapy, Journal of Pediatrics

http://pediatrics.aappublications.org/content/122/4/831.full

 

2.  Contributors and Reviewers for the Neonatal Resuscitation Guidelines , International Guidelines for Neonatal Resuscitation: An Excerpt From the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science

http://pediatrics.aappublications.org/content/106/3/e29.full

 

3.  Viallon A, Zeni F, Lafond P, Venet C, Tardy B, Page Y, Bertrand JC.  Does bicarbonate therapy improve the management of severe diabetic ketoacidosis?  Crit Care Med. 1999 Dec; 27 (12: 2690-3)

 

4.  Duhon B, Attridge RL, Franco-Martinez AC, Maxwell PR, Hughes DW.  Intravenous Sodium Bicarbonate Therapy in Severely Acidotic Diabetic Ketoacidosis (July/August). Annals of Pharmacology. 2013 Jun 4

5.  Scharman EJ, Troutman WG.  Prevention of kidney injury following rhabdomyolysis: a systematic review.  Ann Pharmacology. 2013 Jan;47(1):90-105. doi: 10.1345/aph.1R215. Epub 2013 Jan 16.

6.  Bosch X, Poch E, Grau JM., Rhabdomyolysis and acute kidney injury.  N Engl J Med. 2009 Jul 2;361(1):62-72. doi: 10.1056/NEJMra0801327.

7.  Paul M Wax, GoldFranks Toxicology Emergencies  Antidotes in depth: Sodium Bicarbonate   http://www.accessemergencymedicine.com.newproxy.downstate.edu/content.aspx?aid=6535633

8.  Cooper DJ, Walley KR, Wiggs BR, Russell JA. Bicarbonate does not improve hemodynamics in critically ill patients who have lactic acidosis. A prospective, controlled clinical study. Ann Intern Med. 1990 Apr 1;112(7):492-8.

9.  Fraley DS, Adler S. Correction of hyperkalemia by bicarbonate despite constant blood pH.   Kidney Int. 1977 Nov;12(5):354-60.

10. Blumberg A, Weidmann P, Ferrari P. Effect of prolonged bicarbonate  administration on plasma potassium in terminal renal failure. Kidney

11.  Allon M, Shanklin N. Effect of bicarbonate administration on plasma potassium in dialysis patients: interactions with insulin and albuterol.  Am J Kidney Dis. 1996 Oct;28(4):508-14.

 

 

 

The views expressed on this blog are the author's own and do not reflect the views of their employer. Please read our full disclaimer here. Any references to clinical cases refer to patients treated at a virtual hospital, Janus General Hospital.
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andygrock

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6 comments for “And here I was thinking bicarb was helpful….”

  1. Ian deSouza
    July 1, 2013 at 1:05 pm

    Nice. Bicarbonate is useless in cardiac arrest and has been removed from simplified algorithms. It may have some use in “special situations” as you have elegantly put forth. Here are some references which Sinert once gave me supporting its use in dialysis patients with hyperkalemia…

    Combined effect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in end-stage renal disease patients.

    Kim HJ.
    Source

    Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.
    Abstract

    This study was performed to evaluate the efficacy of various treatment modalities for hyperkalemia in 8 end-stage renal disease (ESRD) patients. Simultaneous administration of sodium bicarbonate and insulin with glucose was compared with infusion of either bicarbonate alone or insulin and glucose. Plasma potassium was measured at the baseline and after 60 min of infusion with each regimen. Infusion of 8.4% solution of sodium bicarbonate at 2 mEq/min for 60 min induced a significant rise in blood bicarbonate from 21.7 +/- 2.1 to 26.3 +/- 1.7 mEq/l (p < 0.01), but failed to lower plasma potassium (6.4 +/- 0.1 vs. 6.3 +/- 0.2 mEq/l, before and after). Intravenous infusion of insulin and glucose (5 mU/kg/min for 60 min) significantly lowered plasma potassium from 6.3 +/- 0.1 to 5.7 +/- 0.1 mEq/l (p < 0.01). The combined infusion of bicarbonate and insulin with glucose showed the greatest decline in plasma potassium, from 6.2 +/- 0.2 to 5.2 +/- 0.1 mEq/l (p < 0.01). With the combined regimen, the increases in plasma bicarbonate (22.3 +/- 1.7 to 25.8 +/- 1.9 mEq/l, p < 0.05) and blood pH (7.36 +/- 0.02 to 7.42 +/- 0.02, p < 0.01) were significant, but somewhat less than those with bicarbonate administration alone. Plasma insulin levels before treatment were similar in all treatment regimens, and increased markedly following the infusion of insulin with glucose, either with or without sodium bicarbonate (9 +/- 1.5 vs. 10 +/- 10 microU/ml before insulin, and 196 +/- 18.0 vs. 201 +/- 26.4 microU/ml after insulin). Plasma epinephrine, norepinephrine, osmolality and plasma aldosterone before and after treatment did not show any significant differences among the 3 different regimens. In conclusion, the ineffectiveness of sodium bicarbonate alone and its synergistic effect with insulin and glucose in acute therapy of hyperkalemia in ESRD patients suggest that mild metabolic acidosis, which is common in patients on maintenance hemodialysis, may contribute to tissue insensitivity to the action of insulin on transcellular potassium shift.
    PMID:
    8852501
    [PubMed – indexed for MEDLINE]

    J Korean Med Sci. 1997 Apr;12(2):111-6.
    Acute therapy for hyperkalemia with the combined regimen of bicarbonate and beta(2)-adrenergic agonist (salbutamol) in chronic renal failure patients.

    Kim HJ.
    Source

    Department of Internal Medicine, Hanyang University Kuri Hospital, Korea.
    Abstract

    This study was aimed to evaluate the efficacy of combination therapy of bicarbonate and salbutamol for hyperkalemia in 9 hemodialysis patients. Simultaneous administration of 8.4% sodium bicarbonate (i.v., 2 mEq/kg) for 1/2 hour and salbutamol (15 mg) in nebulized form for 10 min was compared with treatment modality of either bicarbonate or salbutamol alone. Infusion of sodium bicarbonate induced a significant rise in plasma bicarbonate from 17.3 +/- 3.2 to 22.1 +/- 2.4 mEq/L (p < 0.01), but was ineffective in lowering plasma potassium (-0.13 +/- 0.06 mEq/L). As expected, salbutamol significantly lowered plasma potassium (-0.57 +/0 0.03 mEq/L, p < 0.02 vs. basal value) in all except 2 patients. The combined regimen of bicarbonate and salbutamol to a total 9 patients including 2 patients without hypokalemic effect to salbutamol alone revealed a substantially greater fall in plasma potassium (-0.96 +/- 0.08 mEq/L, p = 0.000 vs. either drug alone) accompanied with significant increase in plasma bicarbonate and blood pH. Treatment with salbutamol or the combined regimen produced slight increases in heart rate but not in blood pressure. It is concluded that the combined regimen of bicarbonate and beta(2)-adrenergic agonist (salbutamol) could be recommended as an efficient alternative for severe hyperkalemia in uremic patients, and is suggested that the enhanced transcellular hypokalemic effects of salbutamol in this combined regimen with bicarbonate would be related to the activation of Na-K pump with acute correction of underlying metabolic acidosis.
    PMID:
    9170015
    [PubMed – indexed for MEDLINE]

    PMCID:
    PMC3054237

  2. mritchie
    July 2, 2013 at 6:02 am

    Great post on sodium bicarbonate!

    I would agree with everything you put in there. When a patient is admitted to the floors with an elevated CK we only use isotonic fluids and not bicarb. We definitely do not use sodium bicarbonate in DKA and as Dr. deSouza said above it has been taken out of ACLS.

    I would add one additional use for it. if you mix lidocaine with a little sodium bicarbonate you can decrease the pain and burning associated with injection.

  3. Ian deSouza
    July 2, 2013 at 11:57 am

    Well, Ritchie, if we’re going to go there…. I’ll add one more. I hear it’s pretty effective for stain removal as well.

  4. jfreedman
    July 2, 2013 at 3:34 pm

    and for stinky feet….RCT pending

  5. jkhadpe
    July 3, 2013 at 5:19 pm

    Thanks Grock, solid review of bicarb and good references! Also wanted to point out a more practical use than for smelly feet which is as an alternative to 3% hypertonic saline which can be difficult to find when you have a seizing hyponatremic patient.

    Wanted to say that a good supplement to this discussion are two podcasts done earlier this year on EmCrit.org, check out the links below:

    http://emcrit.org/podcasts/enough-with-the-bicarb-already/

    http://emcrit.org/podcasts/chloride-free-sodium/

  6. andygrock
    July 5, 2013 at 12:14 am

    Thanks for all the comments. Also, I had a discussion with Dr. EBM himself Dr Sinert about Bicarb. I copied and pasted an email from him below and will email the links to the articles that he sent me.

    Per Dr. Sinert
    I agree with no Bicarb in DKA and CPR, but still use in Rhabdo and hyperkalemia in acidotic states.
    1) Rhabdo and Bicarb. See the NEJM article (attached) makes some good theoretical but not clinical based arguments and since bicarb. won’t hurt I still give it.
    2) Hyperkalemia – Kim et al showed synergistic effects of bicarb + Beta-agonists and Bicarb + Insulin, but not bicarb alone. Probably better cell surface binding of B-agonists and insulin with pH > 7.2. (don’t have the original Kim article – but here are some good reviews.

    04 Rhabdomyolysis and Acute Kidney Injury.pdf
    1453K View Download
    Controversial issues in the treatment of hyperkalaemia Kamel.pdf
    76K View Download
    Effect of Bicarbonate Administration on Plasma Potassium in Dialysis Patients- Interactions With Insulin and Albuterol.pdf
    648K View Download
    Emergency interventions for hyperkalaemia (Review).pdf
    771K View Download

    Enjoy

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