Calcium gluconate in a digitalised heart with hyperkalemia! OK...or..NOT OK???

Today's morning report was about a young guy who was admitted with rhabdomyolysis, renal failure and hyperkalemia(K- 12mEq/dl) with sine wave pattern on his EKG. All this was due to a electrocution injury.So ...going through the management of hyperkalemia, someone pitched in the problem of giving Calcium gluconate in patients on Digoxin. Well....we had a couple of explanations for the interaction.So lets review the problem with these two drugs together.
First.....the mechanism of action of Digoxin- Digoxin inhibits the Na⁺/K⁺-ATPase(exchanges 2 K for 3Na) in the cardiac myocyte by competing with potassium,and causes intracellular sodium concentration to increase. This then leads to an accumulation of intracellular calcium by blocking the Na⁺-Ca⁺⁺ exchange system. In the heart, increased intracellular calcium causes more calcium to be released by the sarcoplasmic reticulum, thereby making more calcium available to bind to troponin-C, which increases contractility (inotropy).


Second.....the mechanism of action of Calcium gluconate- a litlte more cellular pathology! . Normally the cardiac myocyte has a resting membrane potential(RMP is -90mV) and a threshold potential at which it is excited(TP is-75mV).So a 15mV depolarisation is needed to excite the myocyte. In hyperkalemia, the RMP becomes less negative (-80mV) , but the TP remains at -75mV. This means that ..now..only a 5mV depolarisation is enough to excite the myocyte. This is the cause of hyperexcitability leading to arrhythmia.Calcium gluconate...by increasing Ca transport across the membrane reduces the TP from -75mV to around -65mV ...restoring the 15mV depolarisation needed to excite the myocyte. (the numbers in mV are just an example)  ...... Annals of Emer Med 2011


Sooo...in patients on Digoxin(which causes positive inotropy through calcium)...if more calcium is given....it can lead to more intracellular calcium in mycocyte leading to what has been described as cardiac tetany due to prolonged depolarisation. So ,does hyperkalemia make this process worse?? Well, probably not. ------Since K+ and digoxin compete for Na/KATPase, the binding depends on the concentration of the two. In hyperkalemic state...K+ binds preferentially than digoxin, on Na/K ATPase, and thus resulting in diminished digoxin action. (to better understand...think about hypokalemic states...where digoxin will bind preferentially to the receptor, and hence result in digoxin toxicity!--which is well known)
A slightly different scenario would be...when some one(with no K+ problems) takes too much digoxin...which will also result in digoxin binding preferentially than K+,  to Na/KATP ase resulting in Dig toxicity. In this setting....pt may go hyperkalemia..as more K+ ends up extracellularly (due to not binding with Na/K ATPase), and if this patient gets Ca gluconate..then again..it can causes arrhythmias.


Bottom line is...if Calcium is given(and pt made hypercalcemic) to any pt on Digoxin ..there is a increased possibility for cardiac arrhythmias(PG Med J 1999) ...irrespective of whether they have hyperkalemia or not. 
Whether these pathophysiologies!! are clinically relevant is not clear, as these interactions are based on few case reports only. Have a look at this animal study (J clin Tox 2004) and this retrospective study on pts ..over 18 years from a hospital in Arizona(J Emer Med 2011).Both of them show no clinically relevant interaction of Calcium administration even in Digoxin toxicity.     !!!!!!!

Some key aspects of Surviving sepsis

The key recommendations covering all aspects of sepsis treatment were outlined in the 2008 update on Surviving sepsis campaign. This is a tribute to my 2 month CU rotation which I completed this week.....


Early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C)
Blood cultures before antibiotic therapy (1C);
 Imaging studies performed promptly to confirm potential source of infection (1C); 
Administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D);
 Reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D);
 Source control with attention to the balance of risks and benefits of the chosen method (1C);
 Administration of either crystalloid or colloid fluid resuscitation (1B);
 Fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); Vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C);
 Stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); 
Recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients).
 In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B);
 A low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); 
Application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A);
 To decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C);
 Protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B);
Institution of glycemic control , targeting a blood glucose <150 mg/dL after initial stabilization (2C);
 Equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); 
prophylaxis for deep vein thrombosis (1A); 
Use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D).


Our hospital has a Sepsis alert system whereby anyone getting into ER with tachycardia and fever will be eligible for a STAT call to the ICU resident (which was unfortunately 'I' for the last 2 months!!). http://www.survivingsepsis.org/About_the_Campaign/Documents/Final%2008%20SSC%20Guidelines.pdf