Abstract
Objectives
A retrospective, observational study to evaluate the association between critical potassium values and clinical symptoms, and to define critical potassium limits in hospital inpatients of Chinese Han ethnicity.
Methods
Adult patients (aged ≥18 years) of Chinese Han ethnicity admitted to the Beilun People’s Hospital of Ningbo, Zhejiang University, China, were sequentially enrolled. Inpatient data recorded on admission (or at first time during hospital stay for serum potassium values) between 1 January 2011 and 31 December 2012 were used to calculate the percentage of patients with relevant clinical symptoms, the percentage of critical patients (presence of neurological symptoms and deterioration of at least two physiological systems), and the hospital prevalence of clinical symptoms. Correlations between critical serum potassium values and clinical symptoms were determined.
Results
Out of 3 665 included patients, 1 514 patients with a critical serum potassium value (as determined in the present study) were mainly treated in the intensive care unit or the haematology department (low serum potassium, ≤2.9 mmol/l), and Renal and Hepatitis departments (high serum potassium, ≥6.0 mmol/l). High critical serum potassium values (≥6.0 mmol/l) were significantly correlated with clinical symptoms (such as neurological symptoms, loss of appetite, oliguria and hypotension). Low critical serum potassium values (≤2.9 mmol/l) were significantly correlated with clinical symptoms (such as neurological symptoms, loss of appetite and dyspnoea).
Conclusions
Based on the present findings, the lower and upper critical potassium limits were defined as 2.9 mmol/l and 6.0 mmol/l, respectively.
Introduction
Critical conditions caused by trauma or disease can be life threatening, and may be accompanied by organ dysfunction and abnormal laboratory marker values. 1 Critical values were first defined in 1972, as ‘pathophysiologic states at such variance with normal as to be life-threatening unless something is done promptly and for which some corrective action can be taken’. 2 Appropriate use of critical values improves patient outcome by ensuring that physicians are promptly notified of immediate life-threatening conditions; appropriate use of such values and also prevents the misuse or overuse of resources. 3 The determination, documentation and communication of critical values has, therefore, become a widely recognized patient safety measure.4,5 Moreover, according to the ISO 15189 standards of the Joint Commission International, the College of American Pathologists and the Chinese Hospital Association, patients’ critical values need to be reported to hospital management.4–7
In the majority of clinical laboratories, critical serum potassium values have been established and included in the list of values to be measured.8–10 Changes in the critical lower and/or upper limits of serum potassium may lead to an increase in the number of callbacks without concomitant improvement in patient care; alternatively they may lead to failure in bringing potentially harmful situations to the notice of clinicians.10,11 The mean low and high critical potassium limits widely used by trauma and medical centres are 2.8 and 6.2 mmol/l, respectively, in adults. If outliers are eliminated, these values can help physicians improve the quality and efficiency of acute patient care and reduce unnecessary notifications.11,12
The accepted critical value limits for serum potassium at the clinical laboratory of Beilun People’s Hospital of Ningbo, Zhejiang University, Ningbo, China are 3.0 mmol/l (lower) and 6.0 mmol/l (upper) for adult patients. These standard limits have been in use for 10 years, with no change in the electrode testing method during that time. It has been suggested, however, that laboratories should periodically review and revise their critical value limits, using appropriate clinical input, to ensure that urgent physician notification and patient evaluation and treatment are not hindered by unnecessary laboratory tests. 13 Critical limits are designed to meet the clinical needs of each department, and if the clinicians are not satisfied with the critical limits in place, laboratories should re-evaluate their limits. 13 Moreover, for laboratories dealing with diverse ethnic populations (such as those in China), it is important to establish critical values for each population to ensure that the limits reflect the needs of both clinicians and patients. In addition, an investigation into the critical values of over 200 hospital laboratories found that the occurrence rate of critical values was associated with the type of hospital (e.g. specialist hospital, tertiary or teaching hospital) and the requirements of priority determination (such as point-of-care tests and conventional tests); 14 the study also suggested that more attention must be paid to the critical values determined from point-of-care testing methods as opposed to conventional tests. 14 These data highlight a potential need to review and revise the accepted critical value limits periodically at hospital laboratories (detected by standard electrode methods, with inter- and intra-laboratory variation <5%).
Beilun People’s Hospital of Ningbo is a teaching hospital that receives referrals from local hospitals, resulting in a high number of patients with severe conditions requiring emergency treatment (and consequently a high percentage of patients with critical serum potassium values). In 2010, the incidence rate of critical values at the Beilun People’s Hospital of Ningbo clinical laboratory was 0.96%. 15 The main aim of the present study, therefore, was to evaluate the association between critical serum potassium values and prevalence of clinical symptoms (e.g. neurological symptoms, hypodynamia, abdominal distension, loss of appetite, emesis, nausea, polyuria, chest distress [a subjective feeling of laboured respiration], tachycardia, dyspnoea, poor sleep quality, oliguria, hypotension, and dysphoria). 16 In addition, the study aimed to clarify the validity of serum potassium critical value limits in use at the Beilun People’s Hospital of Ningbo clinical laboratory.
Patients and methods
Study population
The present retrospective observational study included sequentially enrolled adult inpatients (≥18 years) admitted primarily to the haematology, hepatitis, renal, intensive care unit (ICU), respiratory, hepatopancreatobiliary, cardiothoracic surgery, endocrine, urinary surgery, neurology, gastrointestinal, breast, orthopaedic surgery, or oncology departments at Beilun People’s Hospital of Ningbo, Zhejiang University between 1 January 2011 and 31 December 2012. Detailed data for these patients were routinely stored in the Beilun People’s Hospital of Ningbo laboratory database. In the present study, this database was only searched for Chinese Han ethnicity patients who recorded a serum potassium level of either ≤3.2 mmol/l or ≥5.8 mmol/l (i.e., close to the existing lower and upper critical limits for adult patients at Beilun People’s Hospital of Ningbo, which were 3.0 mmol/l and 6.0 mmol/l) on or shortly after hospital admission. The following additional data were extracted: admission number; name; age; sex; diagnosis; clinical symptoms; serum potassium levels; department. Hyperkalaemia was diagnosed if the serum potassium value was >5.5 mmol/l; hypokalaemia was diagnosed if the value was <3.5 mmol/l. 10 Haemolysed specimens were excluded; one value per patient was included; this was the first critical value obtained after hospital admission.
The study was approved by the ethics committee of the Beilun People’s Hospital of Ningbo, China and was performed in accordance with the Helsinki Declaration. Written informed consent was obtained from each patient at hospital admission.
Study design
Clinical data relating to each patient’s medical history report, detailed physical examination, and serum potassium levels were obtained. The detailed physical examination data included clinical symptom information relating to the nervous, digestive, respiratory and urinary systems. Electrocardiograms were routinely recorded in all patients, and results from electrocardiograms recorded when potassium values were ≤3.2 and ≥5.8 mmol/l were collected. Oliguria was defined as 6 consecutive h of urine output <0.5 ml/kg body weight. 17 Polyuria was defined as urine output >40 ml/kg body weight over a 24-h period. 18 The number of patients with relevant clinical symptoms (including neurological symptoms [absent, weakened or slow response to stimuli within or outside the central nervous system, drowsiness, numbness], abdominal distension, loss of appetite, emesis, nausea, polyuria, oliguria, chest distress [presence of a subjective feeling of laboured respiration], tachycardia [heat rate >100 beats per min], dyspnoea, insomnia [insufficient duration and/or quality of sleep], hypodynamia, hypotension [systolic/diastolic blood pressure <90/60 mmHg, respectively], and dysphoria [feeling agitated, stuffy, or distracted]) were determined.
The following criteria were used to determine critical patient status: presence of neurological symptoms (e.g. syncope and coma), and deterioration of at least two physiological systems (e.g. anuria [urinary system] and dyspnoea [respiratory system]. 16 The number of critical patients organized into different serum potassium level groups, and the number of patients with critical serum potassium values in different departments, were determined.
The Chinese hospital association guidelines state that serum potassium critical value limits should not be wide ranging, and critical value ranges should be agreed on by the clinical laboratory and clinical doctors. There are currently no defined criteria for determining critical serum potassium limits. Based on the present findings, then through discussion and consensus between the laboratory and clinical doctors, the lower and upper critical potassium limits were established. 19
Data analyses
The percentage of patients with relevant clinical symptoms (out of all patients included), the percentage of critical patients (out of all patients with any relevant clinical symptoms), and the prevalence of clinical symptoms were calculated. The prevalence rate of clinical symptoms was calculated for different serum potassium levels as n clinical symptoms/n patients in each serum potassium-level group. The percentage of different clinical symptoms according to different serum potassium levels was calculated as prevalence of each clinical symptom/n patients in each serum potassium-level group × 100. Correlations between serum potassium levels and clinical characteristics were determined using Spearman’s rank correlation coefficient. Prevalence rates were compared using χ2-test. A P-value < 0.05 was considered to indicate statistical significance. Statistical analyses were performed using SPSS® version 16.0 (SPSS Inc., Chicago, IL, USA) for Windows®.
Results
A total of 3665 Chinese Han patients (mean ± SD, 38 ± 15.75 years; female/male, 1466/2199) with serum potassium values of ≤3.2 mmol/l or ≥5.8 mmol/l were included in the present study.
Clinical symptoms according to critical serum potassium levels
Clinical parameters according to different serum potassium levels in 3665 patients admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China.
Data presented as n, or n (%).
In the high serum potassium groups (≥5.8 mmol/l), the percentage of patients with clinical symptoms and percentage of critical patients tended to increase with increased serum potassium level (Table 1). For example, the total number of patients decreased by 126, and there was a proportional increase of 16.1% in the percentage of patients with clinical symptoms (χ2-value, 9.358; P = 0.002) and a proportional increase of 9.9% in the percentage of critical patients (χ2-value, 10.358; P = 0.001), in the >6.0–6.1 mmol/l compared with the >5.9–6.0 mmol/l group.
Correlation between critical serum potassium and other parameters
Spearman’s rank correlation coefficients showing the correlation between serum potassium levels and clinical parameters in patients with low serum potassium and patients with high serum potassium, admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China.
NS, no statistically significant correlation between dyspnoea and serum potassium levels in the high serum potassium groups (P ≥ 0.05).
Association between clinical symptoms and critical serum potassium levels
Prevalence of different clinical symptoms in patients with hypokalaemia (serum potassium <3.5 mmol/l) admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China.
Data presented as n (%) prevalence.
P < 0.05, pooled <2.7 mmol/l group compared with serum potassium levels ≥2.7 mmol/l group; bP<0.05, significant decrease in symptoms between all serum potassium groups; cP<0.05, pooled <2.9 mmol/l group compared with pooled ≥2.9 mmol/l group (χ2-test).
Prevalence of clinical symptoms in patients with hyperkalaemia (serum potassium >5.5 mmol/l) admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China.
Data presented as n (%) prevalence.
P < 0.05, decrease in the percentage of symptoms (>7.0 mmol/l serum potassium group compared with pooled ≤7.0 mmol/l serum potassium group; χ2-test); bP < 0.05, decrease in the percentage of clinical symptoms (pooled >6.0 mmol/l serum potassium group compared with pooled ≤6.0 mmol/l serum potassium group; χ2-test).
Definition of critical value limits
The present results (without any predefined clinical cut-off values) were used for discussion between clinicians and clinical laboratory staff, to determine lower and upper critical serum potassium-value limits. Based on the present findings, 2.9 mmol/l was determined to be the lower, and 6.0 mmol/l to be the upper, critical potassium value limit.17,18 These limits were determined not to alter the turnaround time of 6 h for biochemistry analyses in Beilun People’s Hospital of Ningbo clinical laboratory.
Distribution of critical values
A total of 1514 inpatients were found to have critical serum potassium (low/high) values during the study period according to the newly defined limits (2.9 and 6.0 mmol/l). The hospital distribution of patients with critical serum potassium values is shown in Figure 1: patients with critical serum potassium values were mainly distributed in the haematology, renal and hepatitis departments, and in the ICU. The hospital distribution of patients with critical hypo- and hyperkalaemia is shown in Figure 2: patients with hypokalaemia were mainly distributed in the haematology, renal, and hepatitis departments, and ICU; patients with hyperkalaemia were mainly distributed in the renal department and ICU.
Hospital department distribution of patients with critical serum potassium values admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China. ICU, intensive care unit. Hospital department distribution of the percentage of patients with critical hypo- and hyperkalaemia admitted to Beilun People’s Hospital of Ningbo, Zhejiang University, China. ICU, intensive care unit.

Discussion
In this large-scale retrospective study, the association between critical potassium values and the clinical symptoms of inpatients was investigated to establish critical potassium value limits that were pertinent to the Beilun People’s Hospital of Ningbo. Serum potassium levels were found to be significantly correlated with the percentage of patients with clinical symptoms, the percentage of critical patients and the incidence rate of clinical symptoms. In Beilun People’s Hospital of Ningbo, the laboratory technician follows a protocol for reporting any detected critical values, which includes sending a short message and a screen reminder to the physician, to which the physician may respond accordingly. 15 Such a protocol suggests that critical potassium value limits that are based on clinical symptoms would be appropriate for clinical practice. At present, most reports have investigated the importance and clinical application of critical potassium values; to the best of the authors’ knowledge, no study has evaluated the association between critically low or high serum potassium values and clinical symptoms and disease severity, by searching the electronic medical records.10,11,20–24
In the present study, the different clinical symptoms associated with hypo- and hyperkalaemia were assessed, and trends in changes in these parameters and clinical symptoms were further analysed. In the present study, the incidence of relevant clinical symptoms was used to determine the adverse effects of hypo- and hyperkalaemia. This implied that there were a variety of ways to define critical value limits, but analysis of clinical symptoms that closely associate with the patient's condition may be the most objective and effective method. Hypokalaemia is frequently encountered and hyperkalaemia is rare in Beilun People’s Hospital of Ningbo, but both are potentially life-threatening emergencies. 25 Disorders in potassium homeostasis may influence many important physiological mechanisms and cause clinical symptoms.
Although many reports have focused on the pathological mechanisms, diagnosis and management of hypo- and hyperkalaemia, no study has investigated the association between different critical value limits and changes in clinical symptoms.20–23
In the present study, the association between different critical serum potassium value limits and incidence of clinical symptoms was assessed. Based on the current 6-h turnaround time for biochemistry analyses at Beilun People’s Hospital of Ningbo clinical laboratory, the authors suggest that the lower critical value limit should be decreased from 3.0 mmol/l to 2.9 mmol/l, to decrease the number of callbacks and unnecessary notifications, and improve resource utilization; the upper limit should remain at 6.0 mmol/l. The critical limits suggested in the present study differ from those in other published studies. For example, a national survey on the critical limits used by trauma and medical centers in the USA suggested that the mean low and high critical potassium limits for the most frequently listed tests were 2.8 and 6.2 mmol/l, respectively, 11 however these limits were suggested for trauma and medical centres in the USA rather than tertiary hospitals per se in other countries, and the present study only included adult patients of Chinese Han ethnicity. A national survey of children’s hospitals in the USA determined that the mean low and high critical potassium value limits in children were 2.8 and 6.4 mmol/l respectively, although critical potassium values differ between adults and children, and the present study included adult patients (≥18 years of age) only.12,26,27 In addition, the low and high critical potassium value limits defined at Zhongshan Hospital in China were reported to be 2.0 and 6.5 mmol/l. 24 However, unlike the present study (in which the correlation between serum potassium values and clinical symptoms were evaluated), the values defined at Zhongshan Hospital in China were based on the opinion of clinical experts without such evaluation of data. 24
In conclusion, critical serum potassium values were significantly correlated with relevant clinical symptoms in the present study. Critical serum potassium value limits of 2.9 mmol/l (lower) and 6.0 mmol/l (upper), based on clinical symptoms, were found to be appropriate for clinical practice at the Beilun People’s Hospital of Ningbo, China.
Footnotes
Declaration of conflicting interest
The authors declare that there are no conflicts of interest.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
