Josh Batterink1, Tara A Cessford2, Robert Ai Taylor1. 1. Providence Health Care, Pharmacy, 1081 Burrard Street, Vancouver, BC, Canada, V6Z 1Y6. 2. University of British Columbia, Internal Medicine, Providence Health Care, St Paul's Hospital, 1081 Burrard Street, Vancouver, BC, Canada, V6Z 1Y6.
Abstract
BACKGROUND: Hyperkalaemia is a potentially life-threatening electrolyte disturbance which may lead to cardiac arrhythmias and death. Renal replacement therapy is known to be effective in treating hyperkalaemia, but safe and effective pharmacological interventions are needed to prevent dialysis or avoid the complications of hyperkalaemia until dialysis is performed. OBJECTIVES: This review looked at the benefits and harms of pharmacological treatments used in the acute management of hyperkalaemia in adults. This review evaluated the therapies that reduce serum potassium as well as those that prevent complications of hyperkalaemia. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 18 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at any pharmacological intervention for the acute management of hyperkalaemia in adults were included in this review. Non-standard study designs such as cross-over studies were also included. Eligible studies enrolled adults (aged 18 years and over) with hyperkalaemia, defined as serum potassium concentration ≥ 4.9 mmol/L, to receive pharmacological therapy to reduce serum potassium or to prevent arrhythmias. Patients with artificially induced hyperkalaemia were excluded from this review. DATA COLLECTION AND ANALYSIS: All three authors screened titles and abstracts, and data extraction and risk of bias assessment was performed independently by at least two authors. Studies reported in non-English language journals were translated before assessment. Authors were contacted when information about results or study methodology was missing from the original publication. Although we planned to group all studies of a particular pharmacological therapy regardless of administration route or dose for analysis, we were unable to conduct meta-analyses because of the small numbers of studies evaluating any given treatment. For continuous data we reported mean difference (MD) and 95% confidence intervals (CI). MAIN RESULTS: We included seven studies (241 participants) in this review. Meta-analysis of these seven included studies was not possible due to heterogeneity of the treatments and because many of the studies did not provide sufficient statistical information with their results. Allocation and blinding methodology was poorly described in most studies. No study evaluated the efficacy of pharmacological interventions for preventing clinically relevant outcomes such as mortality and cardiac arrhythmias; however there is evidence that several commonly used therapies effectively reduce serum potassium levels. Salbutamol administered via either nebulizer or metered-dose inhaler (MDI) significantly reduced serum potassium compared with placebo. The peak effect of 10 mg nebulised salbutamol was seen at 120 minutes (MD -1.29 mmol/L, 95% CI -1.64 to -0.94) and at 90 minutes for 20 mg nebulised salbutamol (1 study: MD -1.18 mmol/L, 95% CI -1.54 to -0.82). One study reported 1.2 mg salbutamol via MDI 1.2 mg produced a significant decrease in serum potassium beginning at 10 minutes (MD -0.20 mmol/L, P < 0.05) and a maximal decrease at 60 minutes (MD -0.34 mmol/L, P < 0.0001). Intravenous (IV) and nebulised salbutamol produced comparable effects (2 studies). When compared to other interventions, salbutamol had similar effect to insulin-dextrose (2 studies) but was more effective than bicarbonate at 60 minutes (MD -0.46 mmol/L, 95% CI -0.82 to -0.10; 1 study). Insulin-dextrose was more effective than IV bicarbonate (1 study) and aminophylline (1 study). Insulin-dextrose, bicarbonate and aminophylline were not studied in any placebo-controlled studies. None of the included studies evaluated the effect of IV calcium or potassium binding resins in the treatment of hyperkalaemia. AUTHORS' CONCLUSIONS: Evidence for the acute pharmacological management of hyperkalaemia is limited, with no clinical studies demonstrating a reduction in adverse patient outcomes. Of the studied agents, salbutamol via any route and IV insulin-dextrose appear to be most effective at reducing serum potassium. There is limited evidence to support the use of other interventions, such as IV sodium bicarbonate or aminophylline. The effectiveness of potassium binding resins and IV calcium salts has not been tested in RCTs and requires further study before firm recommendations for clinical practice can be made.
BACKGROUND: Hyperkalaemia is a potentially life-threatening electrolyte disturbance which may lead to cardiac arrhythmias and death. Renal replacement therapy is known to be effective in treating hyperkalaemia, but safe and effective pharmacological interventions are needed to prevent dialysis or avoid the complications of hyperkalaemia until dialysis is performed. OBJECTIVES: This review looked at the benefits and harms of pharmacological treatments used in the acute management of hyperkalaemia in adults. This review evaluated the therapies that reduce serum potassium as well as those that prevent complications of hyperkalaemia. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 18 August 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at any pharmacological intervention for the acute management of hyperkalaemia in adults were included in this review. Non-standard study designs such as cross-over studies were also included. Eligible studies enrolled adults (aged 18 years and over) with hyperkalaemia, defined as serum potassium concentration ≥ 4.9 mmol/L, to receive pharmacological therapy to reduce serum potassium or to prevent arrhythmias. Patients with artificially induced hyperkalaemia were excluded from this review. DATA COLLECTION AND ANALYSIS: All three authors screened titles and abstracts, and data extraction and risk of bias assessment was performed independently by at least two authors. Studies reported in non-English language journals were translated before assessment. Authors were contacted when information about results or study methodology was missing from the original publication. Although we planned to group all studies of a particular pharmacological therapy regardless of administration route or dose for analysis, we were unable to conduct meta-analyses because of the small numbers of studies evaluating any given treatment. For continuous data we reported mean difference (MD) and 95% confidence intervals (CI). MAIN RESULTS: We included seven studies (241 participants) in this review. Meta-analysis of these seven included studies was not possible due to heterogeneity of the treatments and because many of the studies did not provide sufficient statistical information with their results. Allocation and blinding methodology was poorly described in most studies. No study evaluated the efficacy of pharmacological interventions for preventing clinically relevant outcomes such as mortality and cardiac arrhythmias; however there is evidence that several commonly used therapies effectively reduce serum potassium levels. Salbutamol administered via either nebulizer or metered-dose inhaler (MDI) significantly reduced serum potassium compared with placebo. The peak effect of 10 mg nebulised salbutamol was seen at 120 minutes (MD -1.29 mmol/L, 95% CI -1.64 to -0.94) and at 90 minutes for 20 mg nebulised salbutamol (1 study: MD -1.18 mmol/L, 95% CI -1.54 to -0.82). One study reported 1.2 mg salbutamol via MDI 1.2 mg produced a significant decrease in serum potassium beginning at 10 minutes (MD -0.20 mmol/L, P < 0.05) and a maximal decrease at 60 minutes (MD -0.34 mmol/L, P < 0.0001). Intravenous (IV) and nebulised salbutamol produced comparable effects (2 studies). When compared to other interventions, salbutamol had similar effect to insulin-dextrose (2 studies) but was more effective than bicarbonate at 60 minutes (MD -0.46 mmol/L, 95% CI -0.82 to -0.10; 1 study). Insulin-dextrose was more effective than IV bicarbonate (1 study) and aminophylline (1 study). Insulin-dextrose, bicarbonate and aminophylline were not studied in any placebo-controlled studies. None of the included studies evaluated the effect of IV calcium or potassium binding resins in the treatment of hyperkalaemia. AUTHORS' CONCLUSIONS: Evidence for the acute pharmacological management of hyperkalaemia is limited, with no clinical studies demonstrating a reduction in adverse patient outcomes. Of the studied agents, salbutamol via any route and IV insulin-dextrose appear to be most effective at reducing serum potassium. There is limited evidence to support the use of other interventions, such as IV sodium bicarbonate or aminophylline. The effectiveness of potassium binding resins and IV calcium salts has not been tested in RCTs and requires further study before firm recommendations for clinical practice can be made.
Authors: Matthew R Weir; George L Bakris; David A Bushinsky; Martha R Mayo; Dahlia Garza; Yuri Stasiv; Janet Wittes; Heidi Christ-Schmidt; Lance Berman; Bertram Pitt Journal: N Engl J Med Date: 2014-11-21 Impact factor: 91.245
Authors: Bertram Pitt; George L Bakris; David A Bushinsky; Dahlia Garza; Martha R Mayo; Yuri Stasiv; Heidi Christ-Schmidt; Lance Berman; Matthew R Weir Journal: Eur J Heart Fail Date: 2015-10-12 Impact factor: 15.534