EP.FRI.362 Improving Prescribing and Minimising Delay in Administration of Potassium Replacement Therapies: Surgical Audit on Management of Hypokalaemia in Emergency Surgical Unit at a District General Hospital in UK

Aims Surgical patients are prone to hypokalaemia due to gastrointestinal losses1. Hypokalaemia prolongs ileus2 and thus prompt management is essential. No current guideline on hypokalaemia focuses on surgical patients. We aimed to identify the prevalence of hypokalaemia in emergency surgical patients as well as measure timeliness and appropriateness of replacement. Methods We retrospectively reviewed adult emergency surgical admissions exceeding 48 hours between 05/05/2020 and 15/07/2020. A sub-group analysis assessed the timing of intravenous replacement and duration taken to normalise potassium (3.5 mmol/L). We used another NHS trust’s guideline3 as standard for appropriate potassium replacement. Results Of 110 surgical admissions, 26 cases were hypokalaemic. Of these, 15 had initially normal potassium level. Three cases were likely iatrogenic secondary to inappropriate fluid prescribing. Mean potassium in the hypokalaemic group was 3.2 mmol/L (80.8% mild vs. 19.2% moderate). Mean length of stay was 11.3 days for hypokalaemia versus 6.54 days in normokalaemic cases. Mean duration of hypokalaemia was 2.13±1.45 days. Potassium replacement was prescribed correctly in only 50% of cases (23% not prescribed; 25% insufficient; 2% incorrect) and of these correct prescriptions, 46% were not actually administered. When intravenous replacement was given, there was a mean 3.55-hour delay between lab result and administration. Conclusion The majority of hypokalaemic cases developed during admission. Only 27% of these patients had correct potassium replacement in terms of both prescription and administration. Consequently, we have created a local guideline for hypokalaemia in surgical patients to standardise both prevention and management.

Narrative review of neuraxial potassium chloride administration errors: clinical features, human factors, and prevention measures

BackgroundAdministration of the wrong drug via the epidural or intrathecal route can cause devastating consequences. Because of the commonality of potassium replacement therapy coupled to its potential neurotoxic profile, we suspected that injuries related to this drug error would be present in the literature.ObjectivesWe aimed to identify clinical characteristics associated with the inadvertent administration of potassium chloride (KCl) during neuraxial anesthesia. Our secondary objective was to identify human factors that may have been associated.Evidence reviewPublished reports of neuraxial administration of KCl in humans were searched using Medline and Google Scholar. Error reports in any language were included.Findings25 case reports/series reported administration of KCl via epidural (25 patients) or intrathecal routes (three patients). There were six cases during interventional pain procedures, five cases in operating rooms and 17 in wards or intensive care units. Neuraxial KCl caused paraplegia in 22 patients. Mechanical ventilation was instituted in 11 of 28 patients. Three patients died. Epidural (eight patients) and spinal (two patients) lavage were performed to minimize consequences. A correctly prepared KCl infusion was connected to the epidural catheter for nine patients on wards (32%; 95% upper confidence limit: 48%) due to epidural–intravenous line confusion. Among the other 19 errors, KCl was confused with normal saline for 13 patients or local anesthetic in three patients. A wide range of concentrations and doses of KCl were administered. Variable use of intravenous steroid (13 patients) and epidural saline (eight patients) was found among patients who received epidural KCl. Human factors identified included incorrect visual perception, inadequate monitoring of infusions and substandard practice related to neuraxial anesthesia or analgesia.ConclusionsKCl administration via epidural or intrathecal route has been reported to cause catastrophic consequences.

Caffeine-induced hypokalemia: a case report

Background With an increase in the global popularity of coffee, caffeine is one of the most consumed ingredients of modern times. However, the consumption of massive amounts of caffeine can lead to severe hypokalemia. Case presentation A 29-year-old man without a specific past medical history was admitted to our hospital with recurrent episodes of sudden and severe lower-extremity weakness. Laboratory tests revealed low serum potassium concentration (2.6–2.9 mmol/L) and low urine osmolality (100–130 mOsm/kgH2O) in three such prior episodes. Urinary potassium/urinary creatinine ratio was 12 and 16 mmol/gCr, respectively. The patient was not under medication with laxatives, diuretics, or herbal remedies. Through an in-depth interview, we found that the patient consumed large amounts of caffeine-containing beverages daily, which included > 15 cups of coffee, soda, and various kinds of tea. After the cessation of coffee intake and concomitant intravenous potassium replacement, the symptoms rapidly resolved, and the serum potassium level normalized. Conclusions An increased intracellular shift of potassium and increased loss of potassium in urine due to the diuretic action have been suggested to be the causes of caffeine-induced hypokalemia. In cases of recurring hypokalemia of unknown cause, high caffeine intake should be considered.

Hypokalemic Periodic Paralysis Precipitated by Thyrotoxicosis and Renal Tubular Acidosis

Background. Hypokalemic periodic paralysis is a rare neuromuscular disorder characterized by transient episodes of flaccid paralysis due to a defect in muscle ion channels. Most cases are hereditary, but it can be acquired. We present a case of acquired hypokalemic periodic paralysis associated with hyperthyroidism and renal tubular acidosis. Clinical Case. A 38-year-old female with a history of Graves’ disease presented to the emergency department with generalized weakness and associated nausea, vomiting, and weight loss. Examination was significant for diffuse weakness in all extremities. Labs showed hypokalemia, hyperthyroidism, and nonanion gap metabolic acidosis with a positive urine anion gap. She was treated for hypokalemic periodic paralysis and renal tubular acidosis. Potassium replacement, propranolol, methimazole, and sodium bicarbonate were initiated. Her potassium gradually corrected with resolution of her symptoms. Further investigation revealed a history of dry eyes, dry mouth, and recurrent dental carries. She had positive ANA, SS-A, and SS-B antibodies. She was diagnosed with Sjögren’s syndrome, which may have been associated with her Graves’ disease and thus contributed to both her RTA and hyperthyroidism. Conclusion. Early recognition and treatment of thyrotoxic periodic paralysis are important to prevent cardiac complications. Management includes potassium replacement with careful monitoring to prevent rebound hyperkalemia. The definitive treatment is to achieve euthyroid status.

Hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism: an uncommon cause of acute muscle paralysis

Hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism is an uncommon clinical phenomenon characterised by lower limb paralysis secondary to hypokalaemia in the background of subclinical hyperthyroidism. In this article, we report a patient who presented with progressive lower limb muscle weakness secondary to hypokalaemia that was refractory to potassium replacement therapy. He has no diarrhoea, no reduced appetite and was not taking any medication that can cause potassium wasting. Although he was clinically euthyroid, his thyroid function test revealed subclinical hyperthyroidism. His 24-hour urine potassium level was normal, which makes a rapid transcellular shift of potassium secondary to subclinical hyperthyroidism as the possible cause. He was successfully treated with potassium supplements, non-selective beta-blockers and anti-thyroid medication. This case report aimed to share an uncommon case of hypokalaemic periodic paralysis secondary to subclinical hyperthyroidism, which to our knowledge, only a few has been reported in the literature.

Thyrotoxic Periodic Paralysis: A Rare Presentation of Graves’ Disease

Background: Thyrotoxic periodic paralysis (TPP) is a rare but serious thyroid emergency characterized by hypokalemia, acute onset flaccid paralysis & thyrotoxicosis. Typically, seen in an Asian male with untreated hyperthyroidism symptoms, who awakens at night or in the early morning with flaccid ascending paralysis. This is precipitated by exercise, alcohol or carbohydrate rich meal. TPP is widely reported & studied in Asian population. Its prevalence is about 2 % in Asian hyperthyroid patients. However, incidence is 0.1-0.2% in non-Asian hyperthyroid patients. Clinical Case: 33-year-old Caucasian male with celiac disease and no thyroid disease sought emergency care for complaints of sudden onset severe weakness in all extremities. He reported 20-pound unintentional weight loss, intermittent palpitations and low-grade fever. He noticed leg cramps with numbness and unable to move his extremities. At initial evaluation, he had acute flaccid paralysis and tachycardia. Initial laboratory studies showed potassium at 1.9 mmol/l, Magnesium at 1.8, suppressed TSH <0.005 uIU/ml with elevations in free T4 at 2.43 ng/dl and total T3 at 1.9 ng/ml. CT and MRI head were normal. Patient’s aldosterone level was normal. The patient’s paralysis and hypokalemia resolved after potassium replacement. Thyroid stimulating immunoglobulin was elevated and increased vascularity suggestive of Grave’s disease noted on thyroid Ultrasound. Methimazole and propranolol were initiated. His neurological workup was negative. After resolution of paralysis and hypokalemia he was discharged home. Since our patient presented with severe hypokalemia, flaccid paralysis and hyperthyroidism, that resolved promptly with potassium replacement, hence likely diagnosis of thyrotoxic periodic paralysis. Discussion: Thyrotoxic periodic paralysis is potentially reversible and mostly seen with Graves’ disease among Asian population. Early diagnosis & treatment prevents life threatening complications. Differential diagnosis of TPP includes familial periodic paralysis, Guillain-Barre Syndrome & acute intermittent porphyria. Diagnosis is based on family history, characteristic presentation, hyperthyroidism with low serum potassium level. Possible mechanism is increased sodium-potassium ATPase activity in the skeletal muscle membrane leading to intracellular shift of potassium causing hypokalemia and muscle inexcitability. Treatment includes potassium replacement, nonselective beta-blocker and definitive treatment of hyperthyroidism, to prevent further episodes.

Thyrotoxic Periodic Paralysis

Thyrotoxic Periodic Paralysis (TPP) is an emergency associated with flaccid paralysis in which the paralysis is reversible with prompt potassium replacement and the attacks are terminated when hyperthyroidism is cured. Timely diagnosis and treatment are therefore prudent. While managing patients with flaccid paralysis, physicians should be aware of TPP as potential etiology and investigate history to identify the triggering factors and provide timely and cautious treatment with replacement of potassium, further addressing permanent approaches to treating thyrotoxicosis to prevent future recurrences of TPP. We report a clinical scenario of a patient who experienced TPP.22-year-old male, laying down at home at around 1:45pm developed sudden onset bilateral lower extremity weakness and was unable to stand up. His weakness was associated with thigh pain with exertion. He was eventually able to walk a few steps, but then fell onto his knees. He reported having a carbohydrate rich lunch at noon. Notably, patient underwent surgery under general anesthesia for a deviated nasal septum the day before. His neurological examination was remarkable for giveaway proximal lower extremity weakness involving only select muscle groups. Examination and CT/CTA of head and neck findings was not consistent with acute stroke. Myopathy secondary to electrolyte imbalance, drug/toxin, infection, or inflammatory disorders, myelopathy and myasthenia gravis were considered in the differential. Labs revealed suppressed TSH <0.01uIU/mL, elevated FT4 of 6ng/dL and low serum potassium of 2.6mmol/L. CT scan of the neck revealed enlarged thyroid gland and thymic enlargement. Patient was given intravenous bolus of potassium chloride 20 mEq and serum potassium normalized in 4 hours to 3.8mmol/L. His lower extremity weakness resolved within 3hours of potassium replacement. The next day his serum potassium was 5.2mmol/L. His thyroid stimulating immunoglobulin index was elevated at 1.4 (normal <1.3). He was started on propranolol, methimazole and advised to return to the endocrinology clinic to discuss permanent treatment options for hyperthyroidism to prevent TPP. Reviewing his prior medical history, he was diagnosed with Graves’ disease 5 months prior to the emergency room evaluation and was started on methimazole. He took methimazole for 2 months and did not return to follow up until the occurrence of TPP. He did not experience symptoms of hyperthyroidism in the interim. Discussion: TPP is a rare disorder with a prevalence of 0.1-0.2% in North America. TPP commonly affects Asian and Latin Americans males. The episodes of TPP are influenced by genetic, environmental, and ethnic factors. Common environmental triggers include carbohydrate rich meals, rest after intense physical exertion, fever, infection, trauma, emotional stress, and smoking. Thymic hyperplasia has also been reported to be associated with hypokalemic periodic paralysis. Clinical Presentation: The motor weakness tends to affect proximal lower extremities as noted in our patient’s presentation and is usually associated with hyporeflexia and is painless. Cardiac arrhythmias due to hypokalemia are rare, though ventricular fibrillation have been reported, and respiratory failure requiring mechanical ventilation is a possibility. Pathophysiology: TPP has been thought to be a channelopathy associated with increased Na+–K+ ATPase activity and loss of function mutation of the Kir 2.6 potassium efflux channel resulting in intracellular pooling of potassium and transient hypokalemia. The attacks are stimulated by thyroid hormone excess and/or hyperadrenergic activity and hyperinsulinemia, most commonly due to carbohydrate load or intravenous fluids containing dextrose. Treatment should include:1.Potassium supplementation to reverse paralysis and prevent life threatening cardiac arrhythmias. Care must be taken to not over replace potassium, as it could result in hyperkalemia when potassium channels revert to functioning normally.2.Propranolol, a non-selective betablocker works by blocking the thyroid hormone mediated adrenergic overstimulation of the Na-K ATPase channel, there by limiting the intracellular pooling of potassium.3.Definitive treatment of thyrotoxicosis should be offered. Studies comparing various modalities of treatment of thyrotoxicosis in the setting of TPP indicate permanent treatment with either radioactive iodine or thyroidectomy are often successful in preventing recurrence of TPP, as relapse events are higher in treatment with antithyroid drugs. Caution should be taken to prevent surge of thyroid hormone release following radioactive iodine treatment, as this can trigger TPP. Higher doses of radioactive iodine might be required to render hypothyroidism and prevent TPP recurrences. There is one case report of hypokalemic periodic paralysis associated with thymic hyperplasia that was treated with thymectomy. Our patient had multiple triggers leading to periodic paralysis, including a prior untreated Graves’ disease due to non-adherence to treatment during COVID-19 pandemic, general anesthesia for nasal septal surgery the day before presenting with TPP, having a carbohydrate rich meal one hour before the episode, and thymic enlargement on neck CT scan. He responded well to potassium replacement, and propranolol. He was started on methimazole and offered permanent treatment options to address hyperthyroidism. References: 1.K Shizume1, Y Shishiba, K Kuma, S Noguchi, J Tajiri, K Ito, J Y Noh. Comparison of the incidence of association of periodic paralysis and hyperthyroidism in Japan in 1957 and 1991. Endocrinol Jpn1992 Jun;39(3):315-8, doi: 10.1507/endocrj1954.39.315 2. R C Griggs, J Resnick, W K Engel. Intravenous treatment of hypokalemic periodic paralysis. Arch Neurol 1983 Sep;40(9):539-40.3. Maciel, R., Lindsey, S. & Dias da Silva, M. Novel etiopathophysiological aspects of thyrotoxic periodic paralysis. Nat Rev Endocrinol7, 657–667 (2011). https://doi.org/10.1038/nrendo.2011.58 4. Chang RY, Lang BH, Chan AC, Wong KP. Evaluating the efficacy of primary treatment for graves’ disease complicated by thyrotoxic periodic paralysis. Int J Endocrinol. 2014; 2014:949068 doi:10.1155/2014/949068 5.Yang R, Jurkat-Rott K, Cao J, et al. Hypokalemic Periodic Paralysis Induced by Thymic Hyperplasia and Relieved by Thymectomy. JAMA Neurol. 2013;70(11):1436–1439. doi:10.1001/jamaneurol.2013.3918

Safety of a Nurse-Driven Standardized Potassium Replacement Protocol in Critically Ill Patients With Renal Insufficiency

Background In critically ill patients, maintaining appropriate serum potassium concentrations requires careful supplementation to correct hypokalemia but avoid hyperkalemia. At the study institution, an institution-based, nurse-driven standardized electrolyte replacement protocol is used in critically ill patients with a serum creatinine concentration of 2 mg/dL or less. If the serum creatinine concentration is greater than 2 mg/dL, electrolyte replacement requires a physician order. Objective To determine if standardized potassium supplementation is safe in critically ill patients with renal insufficiency not requiring renal replacement therapy. Methods This study was an institutional review board–approved, single-center, retrospective evaluation of critically ill patients receiving intravenous potassium replacement per protocol. Patients were grouped according to serum creatinine concentration (≤ 2 mg/dL or > 2 mg/dL) at the time of replacement. The primary outcome was the incidence of hyperkalemia (potassium concentration ≥ 5 mEq/L) following potassium replacement. Secondary outcomes were the incidence of hyperkalemia, change in serum potassium concentration, and need for hyperkalemia treatment. Outcomes were analyzed using χ2 and t tests. Results Of 814 patients screened, 145 were included (99 with serum creatinine ≤ 2 mg/dL and 46 with serum creatinine > 2 mg/dL). The incidence of hyperkalemia was not different between groups (P = .57). Five patients experienced hyperkalemia; none received hyperkalemia treatment. Change in serum potassium was similar for patients in the 2 groups (P = .33). Conclusions A standardized, nurse-driven electrolyte replacement protocol can be used safely in critically ill patients with renal insufficiency not requiring renal replacement therapy.

Potassium Concentration in Initial Fluid Therapy and In-Hospital Mortality of Patients with Diabetic Ketoacidosis

Context Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality. Objective We aimed to determine the association between infused potassium concentration and in-hospital mortality. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia. Results We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further. Conclusion Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality.