Paramedic management of out-of-hospital cardiac arrest secondary to hyperkalaemia

Case study

In this case study the author attended a 42-year-old male patient who complained of shortness of breath and fatigue. The patient's medical history was of intravenous drug use, myocardial infarction, CKD and, most significantly, recent non-attendance of two renal dialysis appointments. Initial observations found the patient to have absent radial pulses, a respiratory rate of 18, heart rate of 45, Sp02 unreadable and a Glasgow coma score of 15. The patient suddenly became unresponsive and apnoeac. His cardiac rhythm was found to be asystole and intermediate life support was started with help from the patient's next of kin. Further Critical Care Paramedic (CCP) assistance was requested. The patient was managed with standard advanced life support (ALS) protocols and, because of his recent medical history, was given 10ml calcium chloride 10% and 50ml sodium bicarbonate 8.4% in an attempt to treat suspected hyperkalaemia. Return of spontaneous circulation (ROSC) was achieved on scene after approximately 40 minutes of cardiac arrest with the patient's electrocardiogram (ECG) displaying wide QRS complexes with large peaked T-waves. The patient was conveyed to the nearest Emergency Department where, on arrival, he was found to have a serum potassium level of 9.9 mmol/L. The patient was admitted and later survived to hospital discharge with good neurological outcome.

Potassium

When discussing hyperkalaemia, it is important to first understand its pathophysiology. Potassium is an abundant cation found predominantly within the intracellular fluid (Giebisch, 1998). A significant potassium concentration gradient exists across the cell membrane which is largely responsible for the resting electrical potential and thus excitability of nerve and muscle cells, not least the myocardium (Gennari, 2002). Regulation of serum potassium level is achieved by two systems; the sodium/potassium pump and acid-base balance control intracellular levels whilst the kidneys are responsible for extracellular levels. The kidneys excrete about 95% of the daily potassium load with the remainder leaving through the gastrointestinal tract (Lawrence and Weisburg, 2008). The body maintains extracellular potassium levels carefully between 3.5 and 5.0 mmol L (Truhlár et al, 2015) with small changes to this range having significant effects on the concentration gradient and thus the cells excitability (Lawrence and Weisburg, 2008). This has the potential to lead to life-threatening consequences (Vandan Hoek et al, 2010).

Hyperkalaemia

Hyperkalaemia is when extracellular potassium concentration is above normal levels (Acker et al, 1998). It is most often a result of acute or chronic renal impairment exacerbated by a reduced glomerular filtration rate, metabolic acidosis or high dietary potassium intake (Palmer, 2014). Hyperkalaemia has recently been re-classified as being a serum potassium concentration level > 5.5 mmol with severe hyperkalaemia being deemed as > 6.5 mmol L (Truhlár et al, 2015). This update was facilitated by the European Resuscitation Council, an organisation that develops high-quality, evidence-based guidelines on resuscitation and thus can be regarded as a reliable revision.

A direct correlation between rising serum potassium levels and worsening kidney function has been found (Hsieh et al, 2011). Patients with CKD often benefit from being managed with renin-angiotensin-aldosterone system (RAAS) inhibitors which further increases the risk of hyperkalaemia because most reduce aldosterone levels (responsible for the excretion of potassium in the kidneys) (Bass, 2012). Noize et al (2011) found, in an observational retrospective study with 168 participants, 60% of hyperkalaemic patients were taking at least one drug known to raise serum potassium. It is important to note however, that this study excluded patients with end-stage renal disease (ESRD) requiring haemodialysis so cannot be generalised to all patients suffering from hyperkalaemia. Patients can also suffer with hyperkalaemia in the absence of CKD from several causes including acidosis, damage to tissues from trauma, non-steroidal anti-inflammatory drug use, familial hyperkalaemic periodic paralysis, hyperglycaemia or tumour lysis syndrome (Gennari, 2002).

Hyperkalaemia decreases the resting membrane potential of myocardial cells, which in turn increases their conductivity and excitability. These cells are much more likely to spontaneously depolarise and so block cardiac conduction resulting in cardiac arrhythmias or cardiac standstill (Mattu et al, 2000). Elevated serum potassium concentrations are usually asymptomatic and present with a normal ECG (Szerlip 1986). Severe hyperkalaemia can however, manifest with ECG changes such as peaked T waves, prolonged PR interval, loss of P waves, broadening of QRS complexes, eventual merger of the QRS complex with the T wave and deterioration into cardiac arrest arrhythmias (Ahmed, 2001). These ECG changes do not follow a progressive, dose-dependent pattern, but have been found to develop rapidly even in small increases in serum potassium above 6.5 mmol L (Acker et al, 1998). Shockable rhythms in cardiac arrest secondary to hyperkalaemia are associated with a better outcome when compared to non-shockable rhythms (Davis et al, 2008; Meaney et al, 2010). In addition to cardiac abnormalities, hyperkalaemia can present with generalised fatigue, nausea, vomiting, intestinal colic, diarrhoea, nausea, abdominal pain, paraesthesia, weakness and even paralysis (Mushiyakh et al, 2012; You et al, 2014).

Management

According to the Joint Royal Colleges Ambulance Liaison Committee (JRCALC) (2013a), hyperkalaemia is unlikely to be apparent or reversible in the pre-hospital environment as blood gas analysers are currently unavailable to United Kingdom (UK) ambulance services (Strange, 2010). Contrary to this however, it may be possible to identify the signs, symptoms and medical history of severe hyperkalaemia as discussed earlier (Nyirenda, 2009). Therefore, there is the potential for paramedics to identify some, albeit obvious, cases where hyperkalaemia is the reversible cause of cardiac arrest in the pre-hospital environment. Elliot et al (2010), Mahoney et al (2005) and Nyirenda et al (2009) support this further by suggesting that if hyperkalaemia is suspected then it should be treated before serum potassium levels are known. Unfortunately, there is only limited evidence for the treatment of hyperkalaemia with wide variations depending on locality and even clinician (Acker et al, 1998). Two Cochrane Database systematic reviews have concluded that controversy remains over effective pharmaceutical interventions as there have been few randomised controlled trials (RCTs) with studies having small sample sizes, variable statistical analysis and have largely only included patients with end stage CKD (Batterink et al, 2015; Mahoney et al, 2005). These finding can be considered reliable as systematic reviews are regarded as being the highest form of evidence because they combine samples from a number of different pieces of research to achieve a conclusion (Melnyk and Fineout-Overholt, 2011).

The five key treatment strategies for hyperkalaemia (UKRA, 2014).

Despite there only being limited data, an algorithm has been developed around the core principle of 5 separate stages of treatment for hyperkalaemia: cardiac protection, shifting potassium into the cells, removing potassium from the body, monitoring serum potassium and blood glucose and finally prevention of recurrence (United Kingdom Renal Association (UKRA), 2014). These stages facilitate the movement of potassium into the intracellular space and also encourage the excretion of potassium from the body (Kovesdy, 2014). There is also, unsurprisingly, very little evidence available with regards to managing cardiac arrest secondary to hyperkalaemia with treatment based on the methods used for patient's not experiencing cardiac arrest (Vanden Hoek et al, 2010). Despite this, standard practice has been developed and involves the use of calcium chloride, dextrose-insulin infusion and sodium bicarbonate (UKRA, 2014). These treatments and the limited evidence under-pinning their use will be discussed, whilst taking into account their pre-hospital availability.

Calcium chloride 10%

The European Resuscitation Council recommends that patients suffering cardiac arrest secondary to hyperkalaemia are initially managed with the administration of 10 ml calcium chloride 10% to protect the cardiac membrane (Truhlár et al, 2015), despite its actions having no effect on the movement of potassium (Greenberg 1998). Calcium chloride 10% is available in the pre-hospital environment in the UK and is carried by CCP's. Guidelines on its use vary depending on locality and in this instance guidance from South Western Ambulance Service Trust (SWAST) (2014) was followed. Calcium chloride works by blocking the effects of hyperkalaemia on the myocardium which reduces the excitability of the cardiac membrane (Davey and Caldicott, 2002). This allows time for other interventions that reduce serum potassium levels to be administered. It is well-established that calcium chloride has therapeutic benefit but there is little evidence of RCTs proving its efficacy. As current evidence is largely limited to anecdotal and case reports, Batterink et al (2015) have excluded this therapy from their systematic review evaluating the benefit and harm of pharmacological treatments used in the management of hyperkalaemia in adults. Furthermore, a more recent study by Wang et al (2016), conducted as a result of the lack of evidence regarding the treatment of severe hyperkalaemia during cardiac arrest, found that the use of sodium bicarbonate and calcium chloride may be an effective treatment. Uncertainty remains however as their results were limited by the fact that this was an observational study with a small sample size and partially unreliable methodology.

As calcium chloride has a short duration of action of approximately 30-60 minutes (UKRA 2014) and paramedics can only administer a single dose of 10 ml calcium chloride 10% (SWAST, 2014), this has to be taken into consideration by the pre-hospital clinician when making decisions regarding the patient's management. A further important issue is that in the absence of hyperkalaemia, calcium chloride has a potentially harmful effect on a patient in cardiac arrest. It can cause coronary artery spasm and cerebral ischaemia (UKRA, 2014). Therefore, if the medical history and clinical picture of a patient does not fit that of hyperkalaemia then it may be pertinent to seek further senior advice or withhold calcium chloride treatment all together. If however, cardiac arrest as a result of hyperkalaemia is strongly suspected then the pre-hospital clinician must consider its administration in their management plan.

Sodium bicarbonate 8.4%

Following the use of calcium chloride, other pharmaceutical interventions are also required as it importantly does not lower serum potassium levels. Sodium bicarbonate is often used in hospital in the management of patients with hyperkalaemia (Mahoney, 2005). IV sodium bicarbonate theoretically decreases the serum hydrogen ion concentration, thus encouraging a shift of potassium ions into the intracellular space in exchange for hydrogen (Williams 1985). There is again however, no evidence that this intervention lowers serum potassium inferring that it does not cause potassium to shift across the cell membrane (Batterink et al, 2015). The limited existing evidence demonstrates that sodium bicarbonate monotherapy is unsuccessful at acutely lowering potassium levels. Most of the evidence available comes from studies that are regarded as unreliable as they are dated and use limited sample sizes that include only stable chronic haemodialysis patients (Allon and Shanklin, 1996; Blumberg et al, 1988; Mahoney et al, 2005). Furthermore, the research available consists mainly of retrospective, observational studies; the limited external validity of the methodologies employed constitutes a significant limitation in current understanding and highlights the need for high quality future research.

In addition, there is little evidence to suggest that sodium bicarbonate improves any other pharmaceutical interventions ability to lower serum potassium levels. Allon and Shanklin (1996) found that when sodium bicarbonate was added to insulin and dextrose, or nebulised salbutamol treatment regimens it failed to improve on their effects. Ngugi et al (1997) later found however that a combination of insulin and dextrose, IV salbutamol and intravenous sodium bicarbonate was more effective at lowering serum potassium levels than any two combinations of these treatments. This was however another historical study conducted on a sample size of 70 using merely observational methods and no randomisation. It is conceivable that the limited population involved in the study impedes the research from achieving generalizability.

Studies with similar limitations also found that there is no evidence that sodium bicarbonate is more effective at lowering serum potassium levels as metabolic acidosis increases and that there is no correlation between changes in potassium levels and acid base balance of the blood (Blumberg et al, 1992; Gutierrez, 1991). The homogeneity of the conclusions of the studies discussed implies improved overall confidence in their findings.

Despite the lack of evidence, its use is regarded as being justifiable in cardiac arrest secondary to hyperkalaemia as it reduces metabolic acidosis which is known to exacerbate the effects of hyperkalaemia (UKRA, 2014). Sodium bicarbonate is carried by CCP's so together with calcium chloride is available in the pre-hospital environment depending again on local trust guidance. Therefore, if it is available it should be considered as part of the clinician's proposed patient management. In this case study SWAST (2013) guidance was adhered to.

Salbutamol

Salbutamol has been found by a recent systematic review to significantly reduce serum potassium when administered by nebulisation (Batterink et al, 2015). Salbutamol is a beta-2 adrenoceptor that activates the sodium/potassium pump to shift potassium into the intracellular space. No difference in efficacy has been demonstrated between administrations of beta-2 agonists via a nebulised or IV route (Liou et al, 1994; McClure et al, 1994). The use of the nebulised route is however easier to administer, familiar to UK ambulance crews and results in fewer side effects (Elliot et al, 2010; Strange, 2010). Salbutamol has been shown to increase the efficacy of insulin-glucose therapy (Maxwell et al, 2013) with older studies finding that the combination of the two therapies are more successful at reducing serum potassium levels than any other single treatment (Allon and Copkney, 1990; Lens et al, 1989). Despite small sample sizes, analysis demonstrated the results to be statistically significant using probability values. However, as the confidence interval is not stated the studies generalisability cannot be critiqued. When compared to other potassium shifting agent's salbutamol had a similar efficacy to insulin-dextrose and was also shown to be more successful than sodium bicarbonate at lowering serum potassium (Batterink et al, 2015).

Salbutamol should not be administered as a monotherapy as it may be unsuccessful at lowering serum potassium levels (Weisburg et al, 2008). Two small, non-randomised studies, investigating salbutamol's efficacy have found that, for an unknown reason, up to 40% of an ESRD sample did not respond to salbutamol even when they were not being managed with beta-blocker therapy (Allon and Copkney, 1990; Allon and Dunlay, 1989). These reported findings are significant when considered with another study that found a small transient paradoxical increase in serum potassium levels in 59% of patients shortly after salbutamol administration (Mandleburg et al, 1999). The study found that after 3 minutes the slight rise in potassium level was no more and levels began to fall. This issue has not been documented in other trials and requires further investigation as a rise in serum potassium level together with the risk of some patients having no response to salbutamol means that current recommendations using salbutamol monotherapy could worsen hyperkalaemia (UKRA, 2014). Despite the rigorous methodology of the study as a randomized, double-blind, placebo-controlled trial, a sample size of only 17 was achieved. This limitation may indicate a low external validity and therefore the results must be appreciated within this context.

Salbutamol is not indicated in hyperkalaemic cardiac arrest by the European Resuscitation Council (Truhlár et al, 2015) or UKRA (2014). It is however indicated in moderate (6.0–6.4 mmol L) and severe hyperkalaemia. If ROSC is achieved and hyperkalaemia is still suspected because of medical history, patient response to treatment or ECG changes then its use should be considered. Together with cardiac protection of calcium chloride and the theoretical abilities of sodium bicarbonate to shift potassium, salbutamol 10-20mg could be administered as part of a balanced drug regime. Despite not being indicated for use in hyperkalaemia by guidance produced by the JRCALC (2013b), salbutamol therapy, as part of multi-pharmacological treatment plan, has some of the most compelling evidence to advocate its use.

Other therapies

Although insulin-glucose therapy is not available in the pre-hospital environment, it is important to acknowledge its contribution to the management of the patient as it is currently regarded as being the most effective treatment in shifting potassium (Mahoney, 2005). Paramedics also need to be aware that renal dialysis is ultimately the only intervention that will remove potassium from the body. Depending on clinical situation there must be consideration for potentially moving a patient to a location where both can be accessed. Discussion of these interventions however, is not within the scope of this piece.

Conclusion

Cardiac arrest as a result of hyperkalaemia is ubiquitous in the pre-hospital environment. Paramedics could confidently and reliably identify clear cases through patient signs and symptoms, a detailed medical history and potentially a pre-cardiac arrest ECG. Despite the lack of current good-quality evidence for pharmacological interventions, systematic reviews available have led to the development of clear guidelines. Several stages of care recommended in hospital can also be accomplished in the pre-hospital environment. The use of calcium chloride is recommended to protect the cardiac membrane whilst sodium bicarbonate is also indicated for its ability to reduce metabolic acidosis and theoretically shift potassium to the intracellular space. Both medications are carried by CCP's. It is important to remember that there may be a risk to the patient when using calcium chloride in the absence of hyperkalaemia, so administration should take place with confident diagnosis. Salbutamol therapy has the strongest evidence base of any intervention available out of hospital. It should be considered after the use of the aforementioned medications if the patient achieves ROSC. Regardless of clinical situation, an early decision must be made by clinicians on scene as to whether the patient would benefit from being moved to hospital to reach vital interventions such as insulin/dextrose therapy and dialysis. Regardless of situation, early recognition and effective treatment of this condition is vital to positive patient outcome.

Key Points