No change in plasma potassium concentration during 10 minutes of apnoea: An observational study on potential organ donors

Acute acidosis can increase the plasma potassium concentration. However, data on the effects of acute respiratory acidosis on plasma potassium concentration are conflicting. This study aimed to determine whether acute respiratory acidosis induces an immediate increase in plasma potassium concentration.


| INTRODUC TI ON
Potassium (K) is crucial for normal cellular function, and changes in K concentration [K] may cause organ failure and even death. Critically ill patients often require drugs and interventions that affect the electrolyte and acid-base homeostasis. Any intervention with a potential effect on [K] must be evaluated and monitored carefully. However, the relationship between [K] and changes in partial pressure of carbon dioxide (PaCO 2 ) is not fully understood. Transcellular concentration gradients of the primary extracellular cation sodium [Na] and the primary intracellular cation K play a decisive role in the cell membrane potential. The homeostatic mechanisms regulating their respective concentrations are complex (Figures 1 and 2). Acute respiratory acidosis is common and is often interpreted as a direct cause of increased plasma [K]. However, the representation of this phenomenon in the literature is limited and contradictory. Several studies have shown an increase in plasma [K] during acute respiratory acidosis, 1,2 as opposed to others who have revealed no immediate changes. 3,4 These contradictory findings on the influence of acute acidosis on plasma [K] prompted executing this observational cohort study.
The aim of this study was to determine whether acute respiratory acidosis induces changes in plasma [K] during a standard apnoea test in potential organ donors.

| ME THODS
This was an observational cohort study on all potential organ donors undergoing apnoea testing prior to final radiological examination. All cases were registered in an internal quality registry at Oslo University Of the 316 brain-dead donors, complete data were available for only 124 donors, whilst for the remaining 192 donors, data necessary for the analyses were missing, and in some cases, the apnoea test had not been performed according to the recommended procedure. In addition, donors with a blood glucose concentration exceeding 10 mmol L −1 were excluded (n = 16) since large variations of insulin and blood glucose concentrations could affect the [K]. Of the 108 donors, 34 were administered insulin for blood glucose regulation and 70 were administered vasopressors.
Data were collected from either paper or electronic patient journal, and all routine blood-gas analyses were performed before and immediately following the apnoea test.
In accordance with the Norwegian law, cerebral arteriography or computed tomography angiography must confirm the cessation of brain circulation before permitting any organ donation. As per the organ donor criteria, all brain function tests must reveal an irreversible loss of brain function. Consequently, in all potential organ donors, a standard neurologic examination was performed, and the absence of any response to either of these tests was confirmed. Any potential depressing effect of drugs, alcohol, neuromuscular blocking agents, endocrine substances or hypothermia on the central nervous system must be excluded whilst evaluating a potential donor. In this particular study, no neurologic response was observed in any potential donor during the clinical testing, and ceased brain circulation was confirmed by the radiological examination.
There are diverse protocols around the world on the determination of brain death. 5 In Norway, the standard clinical examination includes coma, noxious stimulation to the face and limbs, the pupillary reflex, the corneal reflex, the oculocephalic reflex, the gag reflex, the cough reflex and finally the apnoea test, as defined in the Norwegian national standard operating procedure. 6 Reduced or abolished brainstem function is associated with vasodilation, and treatment with vasopressors is frequently required.
Based on the departmental procedures, the apnoea test is not performed until the potential organ donor reaches a stable circulatory phase, if necessary, by administration of vasopressors.
In our hospital, all potential donors were treated with 100% oxygen for 15 minutes whilst being normoventilated. Blood sample for bloodgas analyses was collected in a plastic syringe containing 80 units of electrolyte-balanced heparin (Radiometer, Åkandevej 21) from a catheter placed in the radial artery. The ventilator was then disconnected, and a catheter with a continuous flow of 6 L min −1 of oxygen was inserted in the endotracheal tube. Ten minutes later, another blood sample was collected, and the donor was reconnected to the ventilator.
The intensive care units had two different blood-gas analysers: ABL 800 (Radiometer, Åkandevej 21) and COBAS b22 (Roche Diagnostics, Industriestrasse 7). The pre-apnoea and post-apnoea blood samples from individual potential donors were analysed using the same instrument, and the arterial pH, PaCO 2 and partial pressure of oxygen (PaO 2 ) and HCO 3 − , base excess, Na, K and glucose concentrations were recorded.

| Statistical analyses
The arterial pH, PaCO 2 and plasma [K] before and immediately following the apnoea test are presented as mean, standard deviation (SD)

Editorial Comment
This study demonstrates that plasma potassium does not appear to change rapidly with rapid significant variation in PaCO 2 and that short-term respiratory acidosis does not appear to cause large changes in potassium homeostasis.
These findings may be interesting in the context of shortterm management of respiratory failure with high serum potassium levels at the same time.
A relationship was evident between a decrease in pH and an increase in PaCO 2 , with an R 2 of 0.755 (adjusted R 2 , 0.754; P < .01). First, the anaesthetic protocols were not standardised for the infused load of 5% glucose, disregarding that variable insulin production would affect the plasma [K]. Second, the use of opioids was not standardised; moreover, stress-related release of catecholamines during surgery is reportedly reduced by opioids. 7,8 K is an intracellular ion that accounts for nearly 98% of the total body K. The transmembrane [K] gradient is critical for the life-giving membrane potential. An extensive number of endocrine and renal mechanisms are involved in K homeostasis, and insulin has a significant effect on the transcellular movement of K. 9 Insulin stimulates the exchange of Na + and H + , causing cellular Na influx ( Figure 1A). Na is then extruded by Na/K-ATPase in exchange for K. In addition, catecholamine-mediated β-receptor stimulation induces K influx by increasing the Na/K-ATPase activity ( Figure 1B Our study showed unchanged plasma [K] during acute respiratory acidosis, but the methodology differs from that of the two studies in some important aspects. The observation time in our study was only 10 minutes as opposed to 15 and 20 minutes of the other studies. The short observation period was decided based on the protocol for organ preservation. The fact that the potential donors included in our study acted as their own controls represents strength, reducing the variance and increasing the statistical power. This is the first observational study on K homeostasis in braindead potential organ donors. An obvious strength of our model is the elimination of the central nervous system activity. Normal, or at least some, central nervous system reflexes may influence the transcellular P-K shift. In particular, the lack of brain stem regulation of the ventilatory response is a major advantage. In fact, the only variable in our model with a potential impact on the P-K change was the induction of acute respiratory acidosis during apnoea. increased by 0.18 mmol L −1 . The observation period was longer than in our study, and there were several factors which could possibly explain the increasing [K]; the respiratory acidosis could influence the hormonal mechanisms or K feedback mechanisms. Acute acidosis could increase the K reabsorption from the renal distal tubuli. 16 We found a strong correlation between the decrease in pH and increase in CO 2 (R 2 , 0.755). This suggests the acute acidosis to be F I G U R E 2 The exchange of K/H + may occur due to Na/H + exchanger and Na/K-ATPase (A), Na-HCO 3 cotransporter and Na/K-ATPase (B), or Cl-HCO 3 exchanger and K-Cl cotransporter (C). Hyperchloremic acidosis may inhibit the Na/H + exchanger and the Na-HCO 3 co-transporter but may activate the Cl/HCO

| CON CLUS IONS
Acute respiratory acidosis does not lead to rapid changes in plasma [K] during apnoea testing in potential organ donors.

ACK N OWLED G EM ENTS
We would like to thank Editage (www.edita ge.com) for English language editing and graphical designer Monica Akslen Widing for designing of the Figures 1 and 2. This work was supported financially by the Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.

CO N FLI C T O F I NTE R E S T
The authors have no conflicts of interest.