Abnormalities of serum potassium concentration in dialysis-associated hyperglycemia and their correction with insulin: review of published reports

The main difference between dialysis-associated hyperglycemia (DH) and diabetic ketoacidosis (DKA) or nonketotic hyperglycemia (NKH) occurring in patients with preserved renal function is the absence of osmotic diuresis in DH, which eliminates the need for large fluid and solute (including potassium) replacement. We analyzed published reports of serum potassium (K⁺) abnormalities and their treatment in DH. Hyperkalemia was often present at presentation of DH with higher frequency and severity than in hyperglycemic syndromes in patients with preserved renal function. The frequency and severity of hyperkalemia were higher in DH episodes with DKA than those with NKH in both hemodialysis and peritoneal dialysis. For DKA, the frequency and severity of hyperkalemia were similar in hemodialysis and peritoneal dialysis. For NKH, hyperkalemia was more severe and frequent in hemodialysis than in peritoneal dialysis. Insulin infusion corrected the hyperkalemia of DH in most cases. Additional measures for the management of hyperkalemia or modest potassium infusions for hypokalemia were needed in a few DH episodes. The predictors of the decrease in serum K⁺ during treatment of DH with insulin included the starting serum K⁺ level, the decreases in serum values of glucose concentration and tonicity, and the increase in serum total carbon dioxide level. DH represents a risk factor for hyperkalemia. Insulin infusion is the only treatment for hyperkalemia usually required.     

Dialysis-associated hyperglycemia: manifestations and treatment

Purpose

Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH.

Methods

Review of published reports on DAH. Synthesis of guidelines based on these reports.

Results

The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid–base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures.

Conclusions

In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.

     

Effect of hyperglycemia on serum sodium concentration and tonicity in outpatients on chronic dialysis

When serum glucose concentration is nearly normal, serum sodium concentration and tonicity are usually normal in ambulatory outpatient diabetics on chronic hemodialysis or peritoneal dialysis. In hyperglycemia, patients on hemodialysis do not undergo osmotic diuresis and are able to nearly normalize their serum tonicity by increasing the intake of water. Patients on peritoneal dialysis differ from hemodialysis patients because of continued loss of water in the peritoneal dialysate and achieve only partial correction of tonicity by water consumption. The model currently used to predict changes in serum sodium concentration and in tonicity from hyperglycemia assumes no changes in external balance of body water or solute during development of hyperglycemia and, therefore, is not applicable in ambulatory dialysis patients with intact thirst mechanism, because of water retention. In ambulatory patients on chronic dialysis, clinical manifestations of hyperglycemia include thirst, water intake, and weight gain. Neurologic manifestations due to hypertonicity are usually absent.     

Hyperosmolar nature of diabetic coma.

Stupor in patients with nonketotic hyperglycemia has been ascribed to hyperosmolarity, but the cause of depressed consciousness in patients with ketoacidosis has been puzzling. In this study, blood pH, serum glucose and sodium concentrations, and serum osmolality were measured in eighty-five consecutive episodes of diabetic ketoacidosis and forty-seven of nonketotic hyperglycemia. In the acidotic patients, as in those with nonketotic hyperglycemia, stupor closely paralleled hyperosmolarity and not the severity of acidemia. Indeed, the mean elevations of serum osmolarity were almost the same in the ketotic and in the nonketotic patients who were deeply obtunded. It seems likely that depression of consciousness in patients with severely uncontrolled diabetes mellitus, if not due to a nonmetabolic disorder, such as acute stroke, is attributable to hyperosmolarity, whether or not ketoacidosis is present.     

Principles of quantitative water and electrolyte replacement of losses from osmotic diuresis

Osmotic diuresis results from urine loss of large amounts of solutes distributed either in total body water or in the extracellular compartment. Replacement solutions should reflect the volume and monovalent cation (sodium and potassium) content of the fluid lost. Whereas the volume of the solutions used to replace losses that occurred prior to the diagnosis of osmotic diuresis is guided by the clinical picture, the composition of these solutions is predicated on serum sodium concentration and urinary sodium and potassium concentrations at presentation. Water loss is relatively greater than the loss of sodium plus potassium leading to hypernatremia which is seen routinely when the solute responsible for osmotic diuresis (e.g., urea) is distributed in body water. Solutes distributed in the extracellular compartment (e.g., glucose or mannitol) cause, in addition to osmotic diuresis, fluid transfer from the intracellular into the extracellular compartment with concomitant dilution of serum sodium. Serum sodium concentration corrected to euglycemia should be substituted for actual serum sodium concentration when calculating the composition of the replacement solutions in hyperglycemic patients. While the patient is monitored during treatment, the calculation of the volume and composition of the replacement solutions for losses of water, sodium and potassium from ongoing osmotic diuresis should be based directly on measurements of urine volume and urine sodium and potassium concentrations and not by means of any predictive formulas. Monitoring of clinical status, serum sodium, potassium, glucose, other relevant laboratory values, urine volume, and urine sodium and potassium concentrations during treatment of severe osmotic diuresis is of critical importance.     

Plasma vasopressin in uncontrolled diabetes mellitus.

Concentrations of the antidiuretic hormone, arginine vasopressin, were measured in 28 patients with severe hyperglycemia to determine if abnormalities in hormonal regulation of water excretion could contribute to the extreme dehydration of uncontrolled diabetes mellitus. Vasopressin levels were markedly elevated in both nonketotic and ketotic patients, indicating that vasopressin deficiency plays no role in the polyuria that accompanies hyperglycemia. Instead, the observed increases in vasopressin represent an ineffective effort to conserve water in the face of an overwhelming solute diuresis caused by the glucosuria. The reasons for such marked elevations in plasma vasopressin in these diabetic patients are multifactorial. Both groups of diabetic patients had evidence of hypovolemia, which was sufficient in magnitude to stimulate vasopressin release. Furthermore, nausea provided an independent stimulus to vasopressin secretion in many patients. Osmotic stimulation might have resulted from the large fraction of unidentified plasma solutes, but this factor alone was not sufficient to explain the markedly increased concentrations of vasopressin. Whether such elevations in vasopressin could have metabolic and/or hemodynamic effects in uncrontrolled diabetes remains to be established.     

Osmotic diuresis-induced hypernatremia: better explained by solute-free water clearance or electrolyte-free water clearance?

Hypernatremia may result from inadequate water intake, excessive water loss or a combination of the two. Osmotic diuresis leads to losses of both solute and water. The relationship between solute and water losses determines the resulting changes in serum osmolality and sodium concentration. Total solute loss is routinely higher than loss of water in osmotic diuresis. Theoretically, then, decreases in serum osmolality (and serum sodium concentration) should follow. In clinical situations of osmotic diuresis, however, reduction in osmolality can take place, but not reduction in serum sodium concentration. It is of note that serum sodium concentration changes are related to urinary losses of sodium and potassium but not to the loss of total solute. In osmotic diuresis, the combined loss of sodium and potassium per liter of urine is lower than the concurrent serum sodium level. Consequently, hypernatremia can ensue. A patient who presented with osmotic diuresis and hypernatremia is described here. In this patient, we have shown that electrolyte-free water clearance is a better index of the effect of osmotic diuresis on serum sodium concentration than the classic solute-free water clearance.     

Lethal hyperkalemia associated with severe hyperglycemia in diabetic patients with renal failure

Two patients with diabetic nephropathy on maintenance hemodialysis developed extreme hyperkalemia (7.9 and 9.3 mmol/L, respectively) in association with severe episodes of hyperglycemia (1,152 and 1,185 mg/dL, respectively). The increase in serum potassium was out of proportion to the degree of metabolic acidosis that both patients had, and no exogenous source of hyperkalemia could be identified. Despite treatment efforts both patients died shortly after arrival as a consequence of cardiac arrest. It is proposed that the hyperosmolality of extracellular fluid produced by severe hyperglycemia drives potassium passively out of the cells, therefore favoring the rapid development of hyperkalemia. Insulin deficiency could also play a role. This situation is particularly dangerous in individuals with impaired renal function. Adequate blood glucose control in diabetic patients on dialysis is important to avoid life-threatening hyperkalemia.     

Temporal profile of serum potassium concentration in nondiabetic and diabetic outpatients on chronic dialysis

We analyzed routine serum potassium concentration measurements and conditions temporally associated with abnormalities in potassium concentration in outpatients on chronic hemodialysis (136 nondiabetics, 36 diabetics) and continuous ambulatory peritoneal dialysis (16 nondiabetics, 10 diabetics). The following potassium concentration frequencies were found: prehemodialysis, nondiabetics: normal 51.3%, severe hyperkalemia (greater than 6.0 mmol/l) 10%, severe hypokalemia (less than 3.0 mmol/l) 0.3%; diabetics: normal 57.8%, severe hyperkalemia 8.7%, severe hypokalemia 0.5%. Peritoneal dialysis, nondiabetics: normal 73.7%, severe hyperkalemia 0.6%, severe hypokalemia 4.9%; diabetics: normal 72.5%, severe hyperkalemia 0.9%, severe hypokalemia 2.9%. Normokalemia and severe hypokalemia were significantly (chi 2 test) more frequent in peritoneal dialysis than in prehemodialysis, whereas severe hyperkalemia was more frequent in prehemodialysis serum samples. No difference was found between nondiabetics and diabetics for either form of dialysis. 50% of prehemodialysis episodes of hyperkalemia were diet-induced. Hyperkalemic drugs and anuria were not associated with a higher risk of prehemodialysis hyperkalemia, but each one of 3 abnormalities, very high BUN (greater than 40 mmol/l), metabolic acidosis (TCO2 less than 15 mmol/l) and, in diabetics, severe hyperglycemia (serum glucose greater than 30 mmol/l), was associated with a statistically higher risk of hyperkalemia.     

Hypernatremia in neurosurgical pathology

Hypernatraemia is defined as an increase in extracellular sodium concentration, associated with plasma hyperosmolality and cellular dehydration. It can result from excessive water loss, from an increase in the total sodium content or from both mechanisms. As far as neurosurgical pathology is concerned, hypernatraemia due to excessive water loss may be observed in patients who do not sense thirst or are unable to ingest water. Urinary water loss is seen in diabetes insipidus and osmotic diuresis. Extrarenal water losses from pulmonary origin may be observed in intubated or tracheotomized patients. Hypernatraemia with sodium and water retention may be encountered in patients suffering from Cushing diseases or syndromes, or more frequently in those who are given excessive amounts of sodium (hypertonic saline, sodium salts). Clinical manifestations of hypernatraemia consist of neurologic symptoms related to cellular dehydration; their severity is correlated with the rapidity of the onset of the electrolytic disorder. Depending on the pathophysiological mechanism, treatment of hypernatraemia involves stopping sodium intake, restoring normovolaemia and administering hypotonic fluids. Treatment of diabetes insipidus relies on the administration of the antidiuretic hormone and of drugs that increase its secretion rate or its responsiveness in the kidneys.     

Pheochromocytoma presenting with rhabdomyolysis and acute renal failure: a case report

Rhabdomyolysis ranges from an asymptomatic illness with elevated creatine kinase levels to a life-threatening condition associated with extreme elevations in creatine kinase, electrolyte imbalances, acute renal failure, and disseminated intravascular coagulation. The most common causes are crush injury, overexertion, alcohol abuse, certain medicines, and toxic substances. A number of electrolyte abnormalities and endocrinopathies, including hypothyroidism, thyrotoxicosis, diabetic ketoacidosis, nonketotic hyperosmolar state, and hyperaldosteronism, cause rhabdomyolysis. Rhabdomyolysis and acute renal failure are unusual manifestations of pheochromocytoma. There are a few case reports with pheochromocytoma presenting rhabdomyolysis and acute renal failure. Herein, we report a case with pheochromocytoma crisis presenting with rhabdomyolysis and acute renal failure.     

COVID-19 vaccination and diabetic ketoacidosis

An efficient coronavirus disease 2019 (COVID-19) vaccine is urgently required to fight the pandemic due to its high transmission rate and quick dissemination. There have been numerous reports on the side effects of the COVID-19 immu-nization, with a focus on its negative effects. Clinical endocrinology is extremely interested in the endocrine issue that arises after receiving the COVID-19 vaccine. As was already mentioned, after receiving the COVID-19 vaccine, many clinical problems could occur. Additionally, there are some compelling reports on diabetes. After receiving the COVID-19 vaccine, a patient experienced hyperosmolar hyperglycemia state, a case of newly-onset type 2 diabetes. There has also been information on a potential connection between the COVID-19 vaccine and diabetic ketoacidosis. Common symptoms include thirst, polydipsia, polyuria, palpitations, a lack of appetite, and weariness. In extremely rare clinical circumstances, a COVID-19 vaccine recipient may develop diabetes complications such as hyperglycemia and ketoacidosis. In these circumstances, routine clinical care has a successful track record. It is advised to give vaccine recipients who are vulnerable to problems, such as those with type 1 diabetes as an underlying illness, extra attention.     

Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises

Acute and chronic hyperglycemia are proinflammatory states, but the status of proinflammatory cytokines and markers of oxidative stress and cardiovascular risks is not known in hyperglycemic crises of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH). We studied 20 lean and 28 obese patients with DKA, 10 patients with NKH, and 12 lean and 12 obese nondiabetic control subjects. We measured 1) proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL1-beta, and IL-8), 2) markers of cardiovascular risk (C-reactive protein [CRP], homocysteine, and plasminogen activator inhibitor-1 [PAI-1]), 3) products of reactive oxygen species (ROS; thiobarbituric acid [TBA]-reacting material, and dichlorofluorescein [DCF]), and 4) cortisol, growth hormone (GH), and free fatty acids (FFAs) on admission (before insulin therapy) and after insulin therapy and resolution of hyperglycemia and/or ketoacidosis. Results were compared with lean and obese control subjects. Circulating levels of cytokines, TBA, DCF, PAI-1, FFAs, cortisol, and GH on admission were significantly increased two- to fourfold in patients with hyperglycemic crises compared with control subjects, and they returned to normal levels after insulin treatment and resolution of hyperglycemic crises. Changes in CRP and homocysteine in response to insulin therapy did not reach control levels after resolution of hyperglycemia. We conclude that DKA and NKH are associated with elevation of proinflammatory cytokines, ROS, and cardiovascular risk factors in the absence of obvious infection or cardiovascular pathology. Return of these values to normal levels with insulin therapy demonstrates a robust anti-inflammatory effect of insulin.     

Renin-angiotensin system in phlorhizin compared with alloxan diabetes in the rat.

In alloxan-treated diabetic rats, plasma renin activity (PRA) is decreased. One possible mechanism that may explain the decreased PRA is an increased delivery of sodium to the macula densa produced by the glucose osmotic diuresis, resulting in decreased renin release. To evaluate this possible mechanism, rats with phlorhizin diabetes, which produces a glucose osmotic diuresis without hyperglycemia, were studied and compared with rats with alloxan-induced diabetes. Whereas phlorhizin-treated rats had low blood glucose and alloxan-treated rats had elevated glucose, the glucose osmotic diuresis was similar in the two groups. PRA and plasma renin concentration (PRC) were significantly increased in the phlorhizin group. In the alloxan group, PRA was decreased and angiotensin II sensitivity increased, both significantly. Plasma renin substrate (PRS) remained adequate in each group. These results suggest that the decreased PRA in alloxan-induced diabetes is due neither to factors associated with the glucose osmotic diuresis including changes in renal tubular sodium not to decreased PRS.     

Profound hyperkalemia without electrocardiographic manifestations

Although the electrocardiogram (ECG) is not considered a reliable indicator of mild to moderate hyperkalemia, profound elevations of serum potassium concentration generally produce classic ECG manifestations. We report two cases of severe hyperkalemia (greater than 9.0 mEq/L) in which the ECGs did not reveal the expected manifestations of hyperkalemia. Thus, even with profound serum potassium elevations, the ECG cannot reliably be used to exclude the presence of hyperkalemia or to monitor therapy designed to lower the serum potassium concentration.     

Hemodialysis for the Treatment of Severe Accidental Hypothermia

Severe hypothermia is defined as a core body temperature <28°C and is associated with in‐hospital mortality rates of 50% or higher. Delays in rewarming and slower rates of rewarming are the most important prognostic factors associated with increased mortality. Arrhythmias are the most common cause of mortality in patients with severe accidental hypothermia. Electrolyte abnormalities such as hyperkalemia and hypocalcemia that may worsen when patients are rewarmed contribute to the risk of arrhythmias. Cardiopulmonary bypass (CBP) is considered the treatment of choice for active internal rewarming of patients with severe hypothermia, but it is not always available and is time consuming to initiate. We describe a case where hemodialysis (HD) was used to treat accidental hypothermia in a patient with an initial temperature of 23.5°C. Average rewarming rates of 1.5°C/hour were achieved. The advantages of HD when compared with CBP are that it is (1) more widely and readily available, (2) less invasive, (3) less expensive, and (4) can correct associated acidosis and electrolyte abnormalities commonly seen in patients with severe hypothermia.     

Hyperglycemia-induced hemichoreoathetosis: the presenting manifestation of a vascular malformation of the lenticular nucleus

A 72-year-old diabetic woman developed paroxysmal hemichoreoathetosis during an episode of nonketotic hyperglycemia. The movement disorder abated as the blood glucose normalized. A computed tomographic scan revealed a vascular malformation involving the lenticular nucleus on the side contralateral to the dyskinesia. Hyperglycemia has rarely been reported to cause episodic dyskinesias, but there have been no prior reports of patients with striatal vascular abnormalities in whom hyperglycemia seemingly caused a transient movement disorder.     

Acute postoperative metabolic complications of diabetes

Because of several factors, including a change in the hormonal behavior, the postoperative period is at high risk for the diabetic patient to present a metabolic complication. On the other hand, a diabetic metabolic disorder may be secondary and reveal a severe underlying complication (sepsis...). Ketoacidosis is the consequence of an absolute or relative lack of insulin and occurs mainly in insulin dependent diabetic patients. Its incidence should be very low during the postoperative period since insulin protocols are systematically used. The main clinical and biological signs are a polypnea, signs of dehydration, an hyperglycemia associated with a high anion gap metabolic acidosis and the presence of ketoacids in the urine. Its treatment is mainly based on an active rehydration and an insulin and potassium supply. Sodium bicarbonate should not be used systematically any more, even during severe acidosis. Hyperosmolar non ketotic states affects insulin nondependent and older diabetic patients for the most part and occurs under similar conditions than ketoacidosis, revealing most of the time a severe underlying complication. Clinical and biological manifestations include a severe dehydration, alterations in consciousness and a major hyperglycemia associated to a moderate or mild metabolic acidosis. Its main treatment is an active rehydration and insulin plus potassium in a second time. Hypoglycemia is usually the consequence of a mistake in the diabetes care and in the insulin management. Every sickness or consciousness disorder occurring in a diabetic patient treated with insulin should lead to perform a blood glucose measurement. In case of severe manifestations, glucose should be administered in emergency, orally if the patient is conscious or intravenously if he is not. Lactic acidosis occurring during the postoperative period in a diabetic patient is usually non specific of diabetic disease and reflects the existence of an underlying complication (sepsis, hemorrhage, hypoxia,...), as it would in an non diabetic patient. Lactic acidosis due to a treatment with metformin is now very rare and occurs almost only in patients having a contraindication to the use of metformin.     

Hyperkalemia-induced ECG abnormalities in patients with reduced renal function

Hyperkalemia is a potentially lethal condition to be aware of in the presence of ECG abnormalities especially in patients with reduced renal function. However, ECG abnormalities are not always dependent on the degree ofhyperkalemia but may be aggravated by the rapidity of the development of hyperkalemia and by associated electrolyte disorders. We describe 3 patients with renal failure and different ECG changes induced by hyperkalemia. More severe changes were observed when hyperkalemia developed rapidly, but not in presence of electrolyte disorders. Even minor ECG abnormalities must alarm physicians in patients with renal failure since severe hyperkalemia is not always associated with critical ECG changes.     

Renin-Angiotensin System Blockade Is Not Associated with Hyperkalemia in Chronic Hemodialysis Patients

Background.?Serious hyperkalemia was reported in 10% of chronic hemodialysis (HD) patients that could lead to arrhythmia and death. Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) are well accepted for cardio-protective benefits. The relationship between renin-angiotensin system blockade (RASB) and hyperkalemia in chronic HD patients remains controversial. The aim of this study was to find the relationship between RASB and hyperkalemia in these patients.?Methods.?Pre-dialysis serum potassium, clinical factors, and drugs were evaluated in 200 chronic HD patients in one HD center. Hyperkalemia was defined as serum K ≥ 5.3 meq/L. Finally, multivariate analysis with logistic regression was used to evaluate the risk of hyperkalemia by RASB and other factors. Results.?In 200 patients, the mean K was 4.93 ± 0.79 meq/L, and 70 (35%) patients had hyperkalemia. Fifty-eight (29%) patients were prescribed with RASB. Seven variables—non-DM, longer HD duration, lower dialysate calcium, lower serum glucose, higher serum iPTH, not using RASB, and not using furosemide—were more frequent in hyperkalemia group. In logistic regression analysis, RASB was associated with decreased odds for hyperkalemia (OR 0.262, p = 0.001 in model A; OR 0.205, p = 0.001 in model B). In addition, furosemide was associated with decreased odds for hyperkalemia (OR 0.068, p = 0.022 in model B).?Conclusions.?RASB is not associated with hyperkalemia in chronic HD patients.