Fatal Hyperkalemia Research Articles

Destructive disasters, trauma, crush syndrome, and beyond.

Orthopedic injuries, especially fractures of long bones as well as multiple fractures and comminuted fractures, are very common after destructive disasters (e.g., earthquakes, wars, and hurricanes). Another frequent problem is traumatic rhabdomyolysis, which may result in crush syndrome, the second most frequent cause of death after direct traumatic impact following earthquakes. To improve outcomes, interventions should be initiated even before extrication of the victims, which include maintenance of airway patency and spine stabilization, stopping traumatic bleeding by any means, and initiating fluid resuscitation. On-site amputations have been extensively debated to liberate the victims if the release of trapped limbs is impossible. Early after the rescue, a primary survey and triage are performed, a fluid resuscitation policy is planned, complications are treated, the wounds are decontaminated, and the victim is transported to specialized hospitals. A triage and primary survey are also performed at admission to the hospitals, which are followed by a secondary survey, physical, laboratory, and imaging examinations. Washing and cleaning of the soft-tissue injuries and debridement in open, necrotic wounds are vital. Applications of fasciotomies and amputations are controversial since they are associated with both benefits and serious complications; therefore, clear indications should be defined. Crush syndrome has been described as the presence of systemic manifestations following traumatic rhabdomyolysis, the most important component of which is acute kidney injury that may contribute to fatal hyperkalemia. The overall mortality rate is around 20% in crushed patients, which underlines the importance of prevention. Treatment includes maintaining of fluid electrolyte and acid-base balance, application of dialysis, and also prevention and treatment of complications. The principles and practices in disaster medicine may differ from those applied in routine practice; therefore, organizing repeated training courses may be helpful to provide the most effective healthcare and to save as many lives as possible after mass disasters.

Renal Function, Potassium Homeostasis, and Vasopressin Regulation During Acute Hypotensive Stress in a Pig Model of Hemorrhagic Shock

Vasopressin (VP) can regulate potassium excretion in conditions of low urine flow. In severe hemorrhagic shock, the use of pharmacologic doses of VP has advantages over other pressor agents as it can increase urine output. We hypothesized that the physiological response to the rapid rise in plasma potassium (pK+) within minutes of the onset of hemorrhage would involve increased VP synthesis and VP‐mediated maintenance of renal potassium excretion in the face of severely decreased urine flow. In this study we examined the effect of the VP response on renal potassium handling during acute shock stress.Anesthetized, mechanically ventilated Yorkshire cross pigs (body weight 8.8±0.2 kg, n=44) were instrumented with vascular catheters and cardiac Swan Ganz catheter for hemodynamic assessments, and a bladder catheter for continuous urine collection. After baseline measurements, pigs were divided into control (n=14) or hemorrhage (n=30) groups. Hemorrhagic shock was induced by arterial blood withdrawal over 30 minutes (3 ml/kg/min for 7 minutes followed by a rate of 1 ml/kg/min until a goal oxygen debt of over 60 ml/kg was achieved with total shed volume of about 30 ml/kg and decrease in blood pressure by 50%). Blood samples for electrolytes and VP measurements were obtained at 10 minute intervals up to 60 minutes after the start of hemorrhage. Hemodynamics were assessed before resuscitation and up to 4 hours after hemorrhage. Six of the 30 hemorrhaged animals did not survive the acute blood loss beyond the first hour of hemorrhage, so we compared the results of survivors (n=24) to that of non‐survivors (n=6) to determine if altered renal fluid and electrolyte handling may have contributed to non‐survival.Non‐survivors had a higher (p<0.05) pK+ (7.0±0.7 mEq/L) at the end of hemorrhage than survivors (5.4±0.2 mEq/L) vs no change from baseline in controls (4.5±0.1 mEq/L). There was no change in plasma VP in controls whereas hemorrhage increased VP in survivors and non‐survivors (126±14 to 275±41 and 80±18 to 476±211 pg/ml, p<0.05, respectively). Thus, a deficit in VP synthesis and release was not responsible for the fatal hyperkalemia in non‐survivors. Indeed, in hemorrhaged animals VP mRNA, V1aR and V1bR expression in the hypothalamus and pituitary were increased compared to controls. Controls exhibited no change in renal fluid and electrolyte handling. Hemorrhage decreased urine flow (21.0±2.4 to 8.9±1.9 and 20.8±5.8 to 4.0±1.6 ul/min/kg, in survivors and non‐survivors, respectively) along with a decrease in glomerular filtration (p<0.05). Osmotic clearance decreased and was accompanied by increased free water clearance in hemorrhage. Fractional excretion of potassium remained constant. A significantly higher fractional excretion of water distinguished non‐survivors from survivors. A difference in the renal tubular handling of fluid may hinder effective potassium excretion after acute hypotensive stress, and hence results in exacerbated hyperkalemia in non‐survivors despite adequate VP circulating levels.Support or Funding InformationThe views expressed are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.

Recognition and Treatment of Potentially Fatal Hyperkalemia in the Emergency Department

Acute hyperkalemia can be challenging to recognize clinically since its presentation may be vague. Hyperkalemia can be catastrophic in its outcome, leading to sudden death from cardiac arrhythmias if not recognized and treated emergently. This fact emphasizes the critical need to have a vigilant eye for these cases, provide emergent care, and have timely intervention in order to save patients at risk. We are presenting three cases with hyperkalemia with different outcomes. J Med Cases. 2015;6(4):159-162 doi: http://dx.doi.org/10.14740/jmc2078w

Recognition and Treatment of Potentially Fatal Hyperkalemia in the Emergency Department

Acute hyperkalemia can be challenging to recognize clinically since its presentation may be vague. Hyperkalemia can be catastrophic in its outcome, leading to sudden death from cardiac arrhythmias if not recognized and treated emergently. This fact emphasizes the critical need to have a vigilant eye for these cases, provide emergent care, and have timely intervention in order to save patients at risk. We are presenting three cases with hyperkalemia with different outcomes. J Med Cases. 2015;6(4):159-162 doi: http://dx.doi.org/10.14740/jmc2078w

Refractory hyperkalemia related to heparin abuse

Hyperkalemia is a potentially life-threatening condition, which may occur in many clinical settings. Heparin-induced hyperkalemia is less well-recognized than other side effects of heparin therapy. Even lesser known is heparin abuse amongst drug addicts. We report a case of fatal hyperkalemia related to long-term heparin abuse, which was refractory to anti-hyperkalemia therapy including hemodialysis. The objective is to alert the clinicians to possible abuse of heparin in drug addicts, which can be a cause for refractory hyperkalemia. We also briefly review the available literature on heparin-induced hyperkalemia.

Comparison of Hyperkalemic Risk in Hospitalized Patients Treated with Different Angiotensin Receptor Blockers

Clinical use of angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]) is associated with hyperkalemia as an adverse drug reaction. Although it has significant clinical implications, the incidence and relative risks of hyperkalemia with various ARBs have not yet been fully evaluated. The purpose of this study was to determine the risk of hyperkalemic events in hospitalized patients treated with different ARBs and to compare the risk among them. We constructed a retrospective cohort composed of hospitalized adult patients who took ARBs in a single tertiary teaching hospital between April 2004 and March 2010. We estimated the incidence of hyperkalemia (serum potassium level >5.5 mEq/L) with various ARBs, and then compared the risk between them using a multivariate Cox proportional hazard model based on age, sex, Charlson co-morbidity score, baseline serum potassium, underlying diseases, and concomitant drugs. We identified 6992 evaluable intervals from 5449 patients treated with one of the seven ARBs during hospitalization over the 71-month study period with 2521.6 patient-months. We found 381 hyperkalemic events (5.4%) during the study period and an overall event rate of 15.1/100 patient-months. Moderate to fatal hyperkalemia was relatively rare (>6.0 mEq/L, 2.1% [moderate]; >6.5 mEq/L, 0.9% [severe]; >7.0 mEq/L, 0.3% [fatal]). After adjustment for covariates, telmisartan showed a lower risk of hyperkalemia (hazard ratio 0.67; 95% confidence interval 0.51, 0.89) compared with all other ARBs. The risk of hyperkalemic events in hospitalized patients treated with different ARBs was defined. Telmisartan showed a relatively lower hyperkalemic risk profile in hospitalized patients compared with other ARBs.

Successful Use of Succinylcholine for Cesarean Delivery in a Patient with Postpolio Syndrome

We thank Drs. Connelly and Abbot for their interesting comments on our case report.1They give us the opportunity to clarify the choice our anesthetic strategy in the current case.Drs. Connelly and Abbot mention a number of cases reported in the 1970s in which life-threatening hyperkalemia induced by succinylcholine was observed in patients with denervation pathology. As emphasized in our letter, the use of succinylcholine in patients with postpoliomyelitis syndrome remains controversial because of the risk of fatal hyperkalemia observed in patients with pathology close to postpoliomyelitis syndrome. The molecular mechanism of succinylcholine-induced hyperkalemia has been nicely described by Martyn and Richtsfeld2and results primarily from motor endplate receptor up-regulation. This explains why the expected dangerous increase in serum potassium occurs over a very brief period of time, and why normal preoperative potassium levels have limited value in predicting the magnitude of potassium increase. In our case, preoperative blood potassium was 3.4 mm. Although we did not obtain a postoperative potassium determination, we did not observe any significant electrocardiographic modification, such as T-wave changes indicative of hyperkalemia, in the current case after succinylcholine injection.Drs. Connelly and Abbott also discuss the choice of general versus regional anesthesia in our case. We agree that regional anesthesia has been successfully used in some cases of patients with postpoliomyelitis syndrome. However, we did not consider it as a first-choice strategy because the risk of exacerbating the motor deficit of the limbs due to a toxic action of local anesthetics on the motoneurons could not be excluded. Moreover, there was a lack of symptoms suggesting a diagnosis of postpolio-related central disorder. We disagree with Drs. Connelly and Abbott that the use of a nondepolarizing muscle relaxant for rapid sequence intubation always represents an effective and safe alternative to succinylcholine. None of the nondepolarizing muscle relaxants available to date have the same rapidity of onset and reversal of action as that exhibited by succinylcholine. This particular kinetic profile makes this agent preferable to any other nondepolarizing muscle relaxants to decrease the risk of inhalation of the gastric contents, as was particularly important here for cesarean delivery. We agree that careful titration (dose reduction) and monitoring of succinylcholine effects are necessary, which was performed in our case.Finally, we did not state, as mentioned by Drs. Connelly and Abbot, that succinylcholine should be used in patients with postpoliomyelitis syndrome. From this case, we concluded that the anesthetic strategy must be chosen after an extensive risk–benefit discussion, and that succinylcholine may represent a possible alternative in such patients, pending careful titration and monitoring of its effects.*Beaujon University Hospital, Assistance Publique des Hôpitaux de Paris, Clichy, France. anne.wernet@bjn.aphp.fr

Flavopiridol in the treatment of chronic lymphocytic leukemia

The synthetic flavone flavopiridol induces apoptosis of chronic lymphocytic leukemia cells in vitro; however, initial studies administering flavopiridol by a 24- to 72-h continuous intravenous infusion demonstrated no clinical activity. This review focuses on a novel dosing regimen that has achieved significant clinical activity in relapsed, poor-risk chronic lymphocytic leukemia. Binding to human plasma proteins reduces free flavopiridol concentration and makes continuous intravenous infusion dosing ineffective. Pharmacokinetic modeling indicated that administering flavopiridol by a 30-min intravenous bolus followed by a 4-h continuous intravenous infusion would achieve serum concentrations necessary to induce in-vivo apoptosis. Our institution conducted a phase I study in relapsed chronic lymphocytic leukemia. Dose-limiting toxicity was acute tumor lysis syndrome resulting in fatal hyperkalemia. Careful monitoring and aggressive intervention for hyperkalemia, including hemodialysis if necessary, allowed flavopiridol to be given safely. Nineteen of 42 patients responded (45%), including five of 12 patients (42%) with del(17p13) and 13 of 18 patients (72%) with del(11q22). Flavopiridol, when administered by a 30-min intravenous bolus followed by a 4-h continuous intravenous infusion, is active in high-risk, refractory chronic lymphocytic leukemia. Careful monitoring and aggressive intervention for tumor lysis syndrome and hyperkalemia is necessary for safe drug administration. Further studies to optimize the dose and schedule of administration, and to study this drug in other hematologic malignancies, are ongoing.

Successful Use of Succinylcholine for Cesarean Delivery in a Patient with Postpolio Syndrome

Successful Use of Succinylcholine for Cesarean Delivery in a Patient with Postpolio Syndrome

Serum potassium in the crush syndrome victims of the Marmara disaster.

Hyperkalemia is a major cause of mortality in the patients who suffer from crush syndrome in the aftermath of major earthquakes. The aim of this study is to investigate the frequency and effects of hyperkalemia in the 639 victims of catastrophic Marmara earthquake that struck northwestern Turkey, in August 1999. Within the first week of disaster, questionnaires were sent to 35 reference hospitals that treated the victims. Information on serum potassium which was provided in 595 out of 639 questionnaires was submitted to analysis. In the patients who were admitted within the first 3 days of the disaster (n = 401) serum potassium was 5.4 +/- 1.3 mEq/l, which was higher than in those admitted thereafter (n = 171) (4.5 +/- 1.1 mEq/l) (p = 0.02). Considering the whole series, males (p = 0.01), patients needing dialysis support (p < 0.001) and non-survivors (p = 0.001) were characterized by higher serum potassium at admission. Seventy patients' serum potassium was above 7 mEq/l, while 22 patients were hypokalemic (< 3.5 mEq/l). Admission potassium correlated with many clinical and laboratory variables indicating the severity of the trauma, and a logistic regression model with clinical and laboratory parameters upon admission, revealed potassium as the most significant predictor of dialysis needs in the victims admitted within the first 3 days (p = 0.008, OR = 3.33). Among the victims who were admitted to hospitals 1 week after the disaster, 8 had serum potassium levels above 6.5 mEq/l; among 4 of them were complicated by hyperkalemia even higher than 7.5 mEq/l. These findings undeline the importance of hyperkalemia during clinical course. The most important and fatal medical complication in crush syndrome patients is hyperkalemia. Risk of fatal hyperkalemia continues even after hospitalization. Empirical therapy at the scene is indicated especially in male victims with severe soft tissue traumas. Early detection and treatment of hyperkalemia may improve the final outcome of renal disaster victims.

Fatal hyperkalemia related to combined therapy with a COX-2 inhibitor, ACE inhibitor and potassium rich diet

We describe the case of a 77-year old mildly hypertensive woman with no underlying renal disease who was admitted to the Emergency Department (ED) in a comatose state with fever. The patient had been on low dose enalapril and a potassium rich diet. Five days before admission, rofecoxib, a new selective COX-2 inhibitor nonsteroidal anti-inflammatory drug (NSAID), was added for leg pain. She was found to have severe hyperkalemia and died 90 min after her arrival. We cannot absolutely determine whether the COX-2 inhibitor was the dominant contributor to the development of hyperkalemia or the combination itself, with an intercurrent infection and some degree of dehydration. Physicians should be aware of this possible complication and only prescribe NSAIDs, including the new COX-2 drugs, to the elderly under close monitoring of kidney function and electrolyte tests.

#194 Fatal hyperkalemia during surgery for Burkittʼs lymphoma (BL)

#194 Fatal hyperkalemia during surgery for Burkittʼs lymphoma (BL)

Rocuronium for Pediatric RSI

The potential for fatal hyperkalemia in children with undiagnosed neuromuscular disorders has led to the recommendation that succinylcholine (SCh) not

Hyperkalemia after Dantrolene and Verapamil-Dantrolene Administration in Dogs

The concurrent administration of dantrolene and verapamil has the theoretical advantage of being more efficacious than dantrolene alone in the treatment of malignant hyperthermia. However, the combination has been reported to cause fatal hyperkalemia in pigs. The present study evaluated the serum concentrations of cations, serum osmolarity, and cardiovascular responses in 20 mongrel dogs after dantrolene with and without the concurrent administration of verapamil. The dogs were randomly classified into four groups of five dogs each: group 1 received neither dantrolene nor verapamil; group 2 received three successive intravenous doses of dantrolene (1, 3, and 6 mg/kg) at 30-minute intervals; group 3 received verapamil 0.1 mg/kg IV bolus, followed by a continuous infusion of 5 micrograms.kg-1.hr-1; and group 4 received verapamil as in group 3, followed by dantrolene as in group 2. Measurements were made at 15-minute intervals for 2 1/2 hours. Progressive and similar statistically significant increases in mean serum potassium occurred after 105 minutes in dogs given dantrolene (group 2, mean peak serum potassium levels 5.4 +/- 0.5 mmol/L) and after 90 minutes in dogs given verapamil-dantrolene (group 4, 5.2 +/- 1.6 mmol/L). A statistically significant decrease in serum sodium levels was also found in groups 2 and 4. One dog in group 4 developed intermittent second-degree heart block after the final dose of dantrolene. Serum calcium levels (ionized and total) tended to decrease in groups 2 and 4. There were no statistically significant differences in osmolarities, cardiac outputs, or mean arterial blood pressures among groups. In summary, significant elevations of serum potassium were observed in this dog model given dantrolene with and without verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed fatal hyperkalemia in a patient with acute fluoride intoxication

A 19-year-old man presented with acute fluoride poisoning. Initially his serum electrolytes were normal, but two hours later he developed ECG evidence of hyperkalemia followed by refractory ventricular fibrillation, suggesting that hyperkalemia may be important in the cardiotoxicity of acute fluoride intoxication. Treatment of fluoride-induced hyperkalemia consists of removal of fluoride from the body by dialysis, binding fluoride with aluminum or calcium, or enhancing fluoride excretion by inducing a metabolic alkalosis. Direct treatment of the hyperkalemia with glucose, insulin, and bicarbonate is ineffective. Quinidine may be an effective therapy for the hyperkalemia and ventricular irritability, but is as yet untested in human beings.

Near Fatal Hyperkalemia from a Dangerous Treatment for Colic

Life-threatening hyperkalemia is usually the result of renal or adrenal disorders although on some occasions it is an iatrogenic mishap. An alternate etiology of hyperkalemia is an unusual dietary regimen followed by the patient which may or may not be known to his physician. The present case occurred when the parents of a newborn infant followed the advice given for treatment of colic in the popular nutrition book, Let's Have Healthy Children.1 CASE REPORT This 27-day-old boy weighed 4.36 kg at birth, born to a healthy white gravida 2, para 0, abortus 1 by cesarean section for face presentation.

Hyperkalemic Cardiac Arrhythmia Secondary to Spironolactone

Although multiple adverse reactions can occur during the use of spironolactone, the most serious complication is related to its potassium-sparing effect which may induce dangerous and even fatal hyperkalemia. One patient is presented who developed severe hyperkalemia after spironolactone resulting in ventricular standstill and survival following treatment with sodium bicarbonate.

Clinical investigation of the dynamics of peritoneal dialysis

1. 1. Twelve patients with end-stage renal failure were used as subjects in a study evaluating the efficacy, dynamics, and complications of intermittent peritoneal dialysis. 2. 2. The massive loss of all fractions of serum proteins and the inability to clear sufficient quantity of the metabolic wastes on weekly therapy were thought to be contributing factors in the relative inefficiency of this treatment. 3. 3. Peritoneal dialysis was found to be a useful method of preventing potentially fatal hyperkalemia in patients immediately after bilateral nephrectomy. 4. 4. Complications of peritoneal dialysis are discussed.

Recognition and treatment of adrenal crises in the newborn infant

Summary<ul><li>1.Four cases of adrenogenital syndrome, salt-losing type, are presented. They demonstrate the clinical picture of adrenal crisis in the neonatal infant.</li><li>2.The early diagnosis and treatment are of utmost importance for the survival of these infants. All females with the adrenogenital syndrome and males suspected of having adrenogenital syndrome should be observed in the hospital for the first two weeks of life in order to determine the presence or absence of electrolyte imbalance.</li><li>3.Typically, the initial crisis occurs on the seventh day of life. The crisis is characterized by a lethargic infant with a gray pallor, vomiting, weight loss, hypotension, hyperkalemia, hyponatremia, hypochloremia, and dehydration. The excretions of pregnanetriol and 17-ketosteroids in the urine are elevated.</li><li>4.In each patient, the clinical impression is much more important than the confirmatory laboratory results in making a presumptive diagnosis and initiating prompt lifesaving treatment.</li><li>5.Treatment early in life for infants with adrenal crisis includes supplementary salt administration, DOCA given intramuscularly, and cortisone given intramuscularly. Following the initial control of the patient, he should be referred for long-term care to a physician familiar with this particular problem.</li><li>6.The patients reported here took from 40 to 50 days to become stabilized on the medications after initial control.</li><li>7.Hypertension occurred with each patient who was given DOCA, but the hypertension was not severe and did not lead to any complications. When the DOCA was reduced, the hypertension disappeared.</li><li>8.Premature withdrawal of DOCA from two patients was followed by adrenal crisis and death. Therefore, it is advisable to continue the administration of DOCA in spite of apparent electrolyte control and clinical stabilization with salt and cortisone. The maintenance of a normal weight and serum sodium level does not preclude the occurrence of a fatal hyperkalemia in these patients.</li></ul>