1 Introduction

Total Knee Arthroplasty (TKA) is commonly performed for age related and destructive arthropathies of the knee joint. Due to improvements in the longevity of prostheses and the aging of the population there has been an exponential increase in the number of procedures performed which is anticipated to continue.^1,2

In 2020, surgery is commonly completed under regional anesthesia with patients ambulating on the day of the procedure.^3,4 In some institutions ‘day-stay’ arthroplasty is offered with rehabilitation being completed in the patient's home.⁵ This desire for rapid discharge means that complications are poorly tolerated and may lead to the unplanned use of hospital resources. Perioperative care pathways have been standardised under the umbrella term ‘Enhanced Recovery After Surgery’ (ERAS).^6,7 It is the goal of an ERAS program to produce a satisfied patient who can leave the hospital more rapidly. This produces gains in productivity which reduces the costs associated with care.

On the background of an ERAS pathway it has been shown that even solitary episodes of pain, muscle weakness or vomiting may contribute to extended hospital stays after hip or knee arthroplasty.^8,9 Patients may be exposed to numerous interventions which can interact with treatments for chronic disease states. These therapies can produce changes in the blood electrolyte balance. In large series of hospitalised patients upwards of 30% of patients may develop hyponatremia during their hospital stay which can impact morbidity and mortality in both univariate and multivariate models.^10,11

Dyscrasias of sodium produce neurological symptoms which can range from headache and nausea to disorientation and confusion and in more severe cases a decreased level of consciousness or neurological deficits.¹⁰ Despite the impact that symptomatic hyponatremia could have on patient recovery, little has been written on the topic in patients undergoing orthopaedic arthroplasty.^12,13 The aim of this retrospective review is to define the incidence and implications of hyponatremia in patients who have undergoing elective, unilateral primary TKA at two hospitals in Auckland, New Zealand.

2 Materials and Methods

Following approval from the University of Auckland Human Participants Ethics Committee (UAHPEC Number 020309) and the Counties-Manukau Health Research Office (Number 475) patients who underwent elective, unilateral primary TKA between the 1st January and the 31^st December 2014 through Counties-Manukau Health in Auckland, New Zealand were identified. This period was selected due to the existence of a database containing demographic and procedural information, inpatient and outpatient medication use, and patient centred outcome data. In January 2018, manual review of patient records took place to extract data on fluid balance, medications administered and laboratory results. This information was linked with the database using the semi-anonymous National Health Index (NHI) identifier. Missing data was treated as unknown and excluded from comparative analyses.

3 Results

4 Discussion

In this series of patients undergoing elective unilateral TKA, 36.4% developed post-operative hyponatremia. These patients were more likely to be older, on diuretic medications and have lower baseline sodium values when compared with the reference group. Hyponatremia was associated with a reduction in post-operative day two QOR scores and significantly more complications. On multivariate modelling, predictors of greater reductions in sodium values were patient age, the total intravenous and oral fluid administered between day one and three post-operatively, diuretic use and a lower baseline sodium value.

Hyponatremia occurred most frequently between the first and second post-operative days with most cases being mild to moderate in severity. Despite demonstrating a reduction in QOR scores, there was no difference in the time to mobilise and the difference in hospital length of stay, while statistically significant may not meet thresholds for clinical or financial relevance. Differences in length of stay become more profound when those with moderate (sodium level 125–130 mmol/L) or severe (sodium level <125 mmol/L) hyponatremia were considered. These results are indicative of a condition which develops frequently and resolves before serious consequences develop that could lead to more significant changes in hospital length of stay or morbidity.

Sodium levels are commonly measured as a part of ‘routine’ chemistry panels.¹⁵ In our series, those with hyponatremia were exposed to a greater number of sodium measurements, indicating caregivers were following the parameter. Following stressful procedures hyponatremia is a frequent occurrence. In patients who have experienced brain trauma, hyponatremia is especially common with an incidence that can exceed 50%.¹⁶ Others have observed that serum sodium levels are often more than 5 mmol/L lower in hospitalised patients when compared with healthy outpatients.¹⁷ The rate of hyponatremia in hospitalised populations sits between 30 and 45%, while the incidence of severe hyponatremia likely sits at between 3.0% and 6.2%.^11,12,18,19 These values are comparable those reported in our study where 3.8% developed severe hyponatremia.

The cause of hyponatremia is often occult – relevant to patients undergoing arthroplasty is the stress response and anesthetic technique. Surgery leads to elevations in circulating catecholamine levels which releases stress hormones such as vasopressin, cortisol, growth hormone and insulin.²⁰ Opiate or regional analgesia may reduce circulating levels of vasopressin however neuraxial anesthesia may lead to increases through the activation of baroreceptors.²¹ Although not alone in its role in regulating water balance, vasopressin leads to water retention with increases in the intracellular and extracellular fluid volume and minimal changes in the sodium content of these fluids. Elevations in vasopressin release can persist for three to five days following surgery depending on the magnitude of the stress response.²⁰ Patients undergoing surgery can be exposed to additional precipitants of vasopressin release including drugs or mechanical ventilation.¹⁰ Other causes of hyponatremia pertinent to the perioperative period include diuretic use, steroid hormone deficiency and cirrhosis, heart failure or the nephrotic syndrome.²² These causes can be exacerbated by diuretic mediations or by using fluids which are sodium deplete.¹³

As evidenced through this study, perioperative hyponatremia is self-terminating with an incidence that peaks within the first two post-operative days. Clinical sequalae can occur when the sodium falls to below 125 mmol/L or with the rapid development of hyponatremia. Symptoms include nausea and malaise which can progress to vomiting, restlessness and disorientation. When hyponatremia develops rapidly, seizures, permanent brain damage and death may eventuate if the condition is not treated with caution.²³ In multiple populations including the elderly, critical care patients, stroke and liver disease, hyponatremia serves as a prognostic marker for adverse events including serious morbidity and mortality.^24–26

There is evidence to suggest that patients who experience complications in the setting of an ERAS pathway experience reductions in both patient centric outcomes when compared with those who do not experience a complication.⁷ While this statement is obvious when applied to conditions such as pulmonary embolism, there is also data to suggest that even more minor complications such as pain, weakness or vomiting can lead to prolongation of length of stay.^8,9 From this study we have shown that moderate to severe hyponatremia can add almost five hours to the hospital length of stay in a setting where rehabilitation and recovery is completed as an inpatient. These results could have greater implications in settings where more aggressive discharge criteria or outpatient arthroplasty are performed which may unmask the negative effects of hyponatremia.

This study represents a significant advancement in our understanding of effects of hyponatremia in patients undergoing TKA. We have assessed the impact of hyponatremia on both patient and systems centric outcome measures. The strengths of our study include the presence of a comprehensive database which the analysis was able to be conducted. This was possible due linkages through the unique NHI number which improved the data quality available for analysis. We have also reported Quality of Recovery scores, the time to assisted mobilisation and ICD-10 complication codes which are patient centric measures of recovery. Weaknesses include the retrospective, single centre design and the fact data collection only encompassed twelve months which limited the total sample size. To further generalise the results data collection could be expanded to encompass total hip and revision arthroplasty procedures, however there are inherent differences in the physiological impact between primary and revision arthroplasty which may have implications in the magnitude of the stress response and the rate of hyponatremia. The use of ICD-10 complication codes may lead to an underestimation of some complication categories. This is in part mitigated by our use of the Quality of Recovery scores which are sensitive to changes the patient experience meaning any inadequacy in coding is only of minor importance.

5 Conclusion

Hyponatremia is a common finding following TKA. This leads to an increase in the hospital length of stay and a reduction in the Quality of Recovery score on the second post-operative day. Those who were older, exposed to greater amounts of oral or intravenous fluid and who were on pre-operative diuretic drugs experienced greater decreases in sodium in the post-operative period.

These results should inform practitioners as to the incidence and predictors of hyponatremia and may have implications in centres where aggressive hospital discharge or ‘same-day’ arthroplasty is performed. Future research should be directed at targeting reductions in the surgical stress response, altering exposure to medications known to influence sodium and rationalisation of fluid use to determine if further gains can be obtained following TKA.