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Three Part Question

In [adult patients (18+) presenting to the A&E department with hyperkalaemia] is [salbutamol] better at [reducing potassium levels and side effects than insulin]

Clinical Scenario

A man presents to your department with hyperkalaemia, and you are about to begin the standard insulin and glucose therapy, when you recall someone mentioning the use of salbutamol for hyperkalaemia. You quickly treat the gentleman before going to find out.

Search Strategy

Search Medline 1950- July 2007, Embase 1980 – July 2007, ACP Journal Club 1991 to May/June 2007, Cochrane Central Register of Controlled Trials 3rd Quarter 2007, Cochrane Database of Systematic Reviews 2nd Quarter 2007, Database of Abstracts of Reviews of Effects 2nd Quarter 2007 using the OVID interface.
[({exp Adrenergic beta-Agonists/ OR albuterol.mp. OR exp Albuterol/ OR salbutamol.mp OR ventolin.mp} AND {hyperkalemia.mp. OR exp Hyperkalemia/ OR Hyperkalaemia.mp OR Hyperpotass$.mp} AND {exp Insulin/ OR insulin.mp}) LIMIT TO English and humans]

Search Outcome

150 papers were found of which 3 were relevant.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Lens XM et al. 1989 Spain	Group A, 24 patients, received salbutamol 0.5 mg i.v. diluted in 100 ml of 5% dextrose in water administered over a 15-min period Group B, 10 patients, were treated with glucose 40 g in water (100 ml) in 15 min plus 10 units of regular insulin as an i.v. bolus. Group C, 10 patients, received both salbutamol 0.5 mg diluted in 100 ml of water with glucose 40 g i.v. over a 15-min period, plus 10 units of regular insulin as an i.v.bolus	PRCT	Group A – salbutamol	Maximal change in K+ level: -1.4±0.14 mEq/1, maximal effect reached at 30mins	Small number of patients in each group. 18 year old paper.
			Group B – glucose and insulin	Maximal change in K+ level: -1.1±0 mEq/1, maximal effect reached at 60mins
			Group C – combined regimen	Maximal change in K+ level: -1.5±0.2 mEq/1, maximal effect reached at 60mins
Mushtaq et al. 2006 Pakistan	Group A received 0.5 mg salbutamol diluted in 100 ml 5% water Group B received glucose 25 gm diluted in 100 ml of water plus 10 units of regular insulin Group C received both salbutamol 0.5 mg diluted in 100 ml of water with 25 grams of glucose plus 10 units of regular insulin	Clinical trial	Group A - salbutamol	Maximum decrease in K+: -0.9 ± 0.3mmol/L	Very small number of patients. No statistical analysis. Presumably not statistically significant.
			Group B - insulin	Maximum decrease in K+: -0.8 ± 0.2mmol/L
			Group C – combined regimen	Maximum decrease in K+: -1.1 ± 0.1mmol/L
Allon M et al. 1990 USA	10 patients (aged 34 to 72) on maintenance haemodialysis (3-4 hours of dialysis, 3x /week) with pre-dialysis potassium > 5 mmol/L on three separate occassions in 1 month	Clinical trial	Group A – Insulin	Maximal change in K+ conc: 0.65±(0.09)mmol/L	Very small patient number. Poor study design. 4 out of 10 patients had very little response to albuterol, but very little discussion is made of why, and these patients are included in the statistical analysis.
			Group B – Albuterol	Maximal change in K+ conc: 0.66±(0.12)mmol/L
			Group C – Combined regimen	Maximal change in K+ conc: 1.21±(0.19)mmol/L

Comment(s)

Salbutamol has been proposed as an alternative therapy for hyperkalaemia. It has a number of theoretical advantages: easy to administer, trivial side effects, cheap, and it eliminates the risk of disturbing a patient's glucose balance. These studies compared the effects of insulin and salbutamol. All studies found that salbutamol had a lowering effect on potassium levels, and none reported any major side effects. Allon M et al's paper is included to highlight a finding of several papers: a large proportion of patients do not respond to salbutamol therapy. This is to be expected in patients on beta blockers, and Allon et al make no mention of this. However it is an aspect that requires a greater depth of research. Although the evidence to support salbutamol is not perfect, it is effective in a lot of patients, easy to prepare and give rapidly, and its side effects are well documented. It can also be used in combination with insulin for an additive effect.

Clinical Bottom Line

Salbutamol should be considered in a certain group of patients: Those with a dangerously high potassium, where therapy is needed as quickly as possible, as it is easier to administer than glucose and insulin. Those who have had an inadequate response to insulin alone. Those with a contra indication to insulin and glucose therapy. In those with a very high potassium level, it can be given at the same time as insulin and glucose. However very regular repeat potassium levels must be checked to ensure salbutamol is having an effect, and to prevent combination therapy causing hypokalaemia.

References

1. Lens XM et al. Treatment of Hyperkalaemia in Renal Failure: Salbutamol v. Insulin Nephrol Dial Transplant 4(3); 228-32
2. Mushtaq et al. Treatment of hyperkalemia with salbutamol and insulin Pak J Med Sci 22(2); 176 - 179
3. Allon M et al. Albuterol and insulin for treatment of hyperkalemia in hemodialysis patients Kidney Int 38(5); 869-72