Hypophosphatemia in the emergency department therapeutics

doi:10.1053/ajem.2000.7347

The American Journal of Emergency Medicine

Volume 18, Issue 4, July 2000, Pages 457-461

https://doi.org/10.1053/ajem.2000.7347 Get rights and content

Abstract

Although hypophosphatemia is relatively uncommon, it may be seen in anywhere from 20% to 80% of patients who present to the ED with alcoholic emergencies, diabetic ketoacidosis (DKA), and sepsis. Severe hypophosphatemia, as defined by a serum level below 1.0 mg/dL, may cause acute respiratory failure, myocardial depression, or seizures. Because hypophosphatemia is not as often treated by ED physicians, becoming familiar with a single intravenous phosphate solution and specific guidelines for phosphate repletion are essential. One mL of the most commonly available phosphate solution (K₂PO₄) contains 4.4 meq of potassium and 3 mmol (93 mgs) of phosphate. Administering K₂PO₄ at a rate of 1 mL per hour is almost always a very safe and appropriate treatment for hypophosphatemia. This article provides guidelines for phosphate therapy in hypophosphatemic ED patients including those in DKA, those presenting with alcohol-related complaints including alcoholic ketoacidosis and patients with acute excerbation of asthma and chronic obstructive pulmonary disease. (Am J Emerg Med 2000;18:457-461. Copyright © 2000 by W.B. Saunders Company)

Section snippets

Phosphorus in biological systems

Phosphorus is a necessary component for many biological functions. Although phosphorus acts at the molecular level, it directly affects entire organ systems. It is a component of cellular membranes, nucleic acids, and nucleoproteins.¹ Phosphorus is involved in the glycolytic pathway, acts as a urinary buffer, and is a key component of numerous enzymatic functions including the phosphorylated enzymatic intermediaries 2,3-DPG and ATP.1, 2, 3, 4, 5 Deficiencies of this ion may result in

Phosphorus regulation

Normal adult dietary phosphorus intake is approximately 1,000 mg per day of which about 80% is absorbed by the jejunum.1, 9 Total body stores of phosphorus are about 500 to 800 grams.¹ Most of total body phosphorous is stored in bone, skeletal muscle, and soft tissues in the form of phospholipids, phosphosugars, and phosphoproteins.3, 13 Phosphate excretion is approximately 90% renal and 10% gastrointestinal. Phosphate serum levels may be altered via hormonal regulation by both vitamin D

Causes of hypophosphatemia

Hypophosphatemia is defined as a serum phosphate level below 2.5 mg/dL in adults and below 4.0 mg/dL in children.³ The list of disease states that may cause hypophosphatemia is quite diverse. Table 1 outlines the most common causes of hypophosphatemia in patients who present to the ED.

. The Most Common Causes of Hypophosphatemia in the Emergency Department

Decreased intake or decreased absorptive states	Chronic alcoholism
	Parenteral nutrition
	AIDS
	Chemotherapy
	Vomiting
	Malabsorption syndromes
	Secretory

Diagnosing hypophosphatemia

The incidence of hypophosphatemia ranges from 1% to 5% in the general medication population to 20% to 40% in patients who present to the ED with alcoholism, diabetic ketoacidosis, and up to 80% of patients with sepsis.14, 15, 16, 17 Although hypophosphatemia is relatively common, it often goes undiagnosed because affected patients often present with nonspecific symptoms such as a fatigue and general irritability. Hypophosphatemia may present in dramatic and life-threatening ways including acute

General guidelines for phosphate repletion

It is imperative to recognize several important concepts when considering administering phosphate. Firstly, phosphate is largely an intracellular ion.³ Therefore, serum phosphate values which measure extracellular phosphate may be an unreliable reflection of total body phosphate stores.19, 20, 21 Secondly, the effect that any given dose of phosphate will have on serum levels is unpredictable.²² Thus, serum levels must be monitored during phosphate administration to guide the amount, rate, and

Intravenous phosphate replacement

Intravenous phosphate repletion is indicated for any hypophosphatemic patient who is symptomatic, or who has severe hypophosphatemia as defined by a serum phosphorus level less than 1 mg/dL.9, 19 We recommend becoming familiar with one single intravenous phosphate preparation and learning how to dose it in both milliliters and millimoles to avoid errors during repletion. Selecting a phosphate solution with a potassium salt base is generally appropriate because most of the conditions associated

Selected conditions associated with hypophosphatemia and specific recommendations on phosphate repletion

The guidelines for phosphate repletion for the following conditions are the same as those already discussed in the section “General Guidelines for Phosphate Repletion” except where specifically noted.

Diabetic ketoacidosis

DKA is one of the most common, potentially life-threatening, diseases seen in the ED that is associated with hypophosphatemia. Although hyperphosphatemia is typical on presentation with DKA, up to 90% of patients will become acutely hypophosphatemic within 6 to 12 hours of beginning therapy.34, 35, 36 Of these, 15% of patients will have serum phosphorus levels below 1.5 mg/dL.14, 37 The hypophosphatemia resulting from the treatment of DKA appears to be attributable to transcellular shifts from

Chronic alcoholism

The incidence of hypophosphatemia in hospitalized chronic alcohol abusers has been reported to be as high as 50%.2, 52 The hypophosphatemia of alcoholism is multifactorial, and appears to be predominantly caused by defects in renal tubular function in conjunction with chronic antacid ingestion, poor nutrition, vomiting, diarrhea, hypomagnesemia, and intravenous glucose administration.1, 53, 54, 55

Alcoholic ketoacidosis (AKA)

AKA is a relatively common syndrome usually seen in chronic alcoholics after a period of binge

Respiratory disorders including asthma and COPD

Hypophosphatemia may exacerbate preexisting respiratory disease or cause acute respiratory failure.58, 59, 60, 61, 62 Low serum phosphate levels have been correlated well with diminished diaphragmatic contractility, impaired tissue oxygenation, and decreased 2,3 DPG levels, all of which are reversible with phosphate supplementation.1, 10, 11 In addition to hypophosphatemia causing respiratory compromise, there are numerous pulmonary diseases associated with hypophosphatemia.

Any prolonged

Conclusions

The phosphate ion plays a critical role in a diverse group of biological processes. Depletion of this ion has wide-reaching adverse effects that may involve every major organ system. Hypophosphatemia is a condition associated with many disease processes seen commonly in the ED. Missed or delayed diagnosis of hypophosphatemia can cause the underlying medical conditions to become resistant to standard medical therapy as well as result in increased morbidity. We have presented strategies aimed at

References (64)

MP Peppers et al.
Endocrine crises: Hypophosphatemia and hyperphosphatemia
Crit Care Clin
(1991)
C Janson et al.
Hypophosphatemia
Ann Emerg Med
(1983)
PE Bollaert et al.
Hemodynamic and metabolic effects of rapid correction of hypophosphatemia in patients with septic shock
Chest
(1995)
V Barak et al.
Prevalence of hypophosphatemia in sepsis and infection: the Role of cytokines
Am J Med
(1998)
JP Knochel
Neuromuscular manifestations of electrolyte disorders
Am J Med
(1982)
SF Hodgson et al.
Acquired hypophosphatemia
Endo Met Clin NAmer
(1993)
R Kebler et al.
Dynamic changes in serum phosphorus levels in diabetic ketoacidosis
Am J Med
(1985)
HE Martin et al.
The fluid and electrolyte therapy of severe diabetic acidosis and ketosis. A study on twenty-nine episodes (26 patients)
Am J Med
(1958)
W Berger et al.
Ketoacidosis and non-ketotic hyper osmolar coma
Baillieres Clin Endocrino Metab
(1992)
MS Riley et al.
Effects of insulin infusion on plasma phosphate in diabetic patients
Metabolism
(1979)

RJ Winter et al.

Diabetic ketoacidosis. Induction of hypocalcemia and hypomagnesemia by phosphate therapy

Am J Med

(1979)

KG Alberti et al.

2-3 Diphosphoglycerate and tissue oxygenation in uncontrolled diabetes mellitus

Lancet

(1972)

P Angeli et al.

Hypophosphatemia and renal tubular dysfunction in alcoholics. Are they related to liver function impairment?

Gastroenterology

(1991)

H Spencer et al.

Effect of small doses of aluminum-containing antacids on calcium and phosphorus metabolism

Am J Clin Nutr

(1982)

KD Wrenn et al.

The syndrome of alcoholic ketoacidosis

Amer J Med

(1991)

E Fiaccadori et al.

Hypophosphatemia in the course of chronic obstructive pulmonary disease

Chest

(1990)

MF Rubin et al.

Hypophosphatemia: Pathophysiological and practical aspects of its therapy

Semin Nephrol

(1990)

JP Knochel

The pathophysiology and clinical characteristics of severe hypophosphatemia

Arch Intern Med

(1977)

HS Jacob et al.

Acute hemolytic anemia with rigid red cells in hypophosphatemia

N Engl J Med

(1971)

MA Lichtman et al.

Erythrocyte adenosine triphosphate depletion during hypophosphatemia in a uremic subject

N Engl J Med

(1969)

LR O'Connor et al.

Effect of hypophospha-temia on myocardial performance in man

N Engl J Med

(1977)

MA Lichtman et al.

Reduced red cell glycolysis, 2,3-diphosphoglycerate and adenosine triphosphate con-centration, and increased hemoglobin-oxygen affinity caused by hypophosphatemia

Ann Intern Med

(1971)

JP Knochel et al.

Hypophosphatemia and rhabdomyolysis

J Clin Invest

(1978)

S Rapaport et al.

The effect of voluntary overbreathing on the electrolyte equilibrium of arterial blood in man

J Biol Chem

(1946)

M Aubier et al.

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure

N Engl J Med

(1985)

RA Kreisberg

Phosphorus deficiency and hypophosphatemia

Hosp Pract

(1977)

MA Camp et al.

Severe hypophosphatemia in hospitalized patients

Miner Electrolyte Metab

(1990)

FR Gilbert et al.

Admission inorganic phosphorus correlated with discharge diagnosis and other metabolic profile components

Ala J Med Sci

(1970)

RS Rybach et al.

Clinical relationships between serum phosphorus and other blood chemistry values in alcoholics

Arch Intern Med

(1980)

C Berkelhammer et al.

A clinical approach to common electrolyte problems: 3. Hypophosphatemia

Can Med Assoc J

(1984)

RD Lentz et al.

The treatment of severe hypophosphatemia

Ann Intern Med

(1978)

JP Knochel

Skelatal muscle in hypophosphatemia and phosphorus deficiency

Adv Exp Med Biol

(1978)

Cited by (62)

Hyperosmolar Hyperglycemic State
2023, Emergency Medicine Clinics of North America
How do I diagnose and manage acute endocrine emergencies in the ICU?
2019, Evidence-Based Practice of Critical Care
Endocrine emergencies are frequently encountered in the intensive care unit. This chapter will focus on several common disorders including diabetic ketoacidosis, hyperosmolar hyperglycemia, thyroid storm, myxedema coma, and vasopressin deficiency. Adrenal insufficiency is addressed elsewhere in this volume. Understanding the pathophysiology of these different states will enable the intensivist to make a rapid diagnosis, initiate appropriate therapy, and avoid major pitfalls.
The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management
2016, Metabolism: Clinical and Experimental
Citation Excerpt :
To replace phosphate stores and to avoid hyperchloremia, intravenous potassium repletion can be administered in a ratio of two-thirds potassium chloride and one-third potassium phosphate. The maximal rate of phosphate replacement generally regarded as safe to treat severe hypophosphatemia is 4.5 mmol/h (1.5 ml/h of K2PO4) [129]. The most frequent complications of DKA are hypoglycemia and hypokalemia, which result from overzealous treatment with insulin.
The prognosis of diabetic ketoacidosis has undergone incredibly remarkable evolution since the discovery of insulin nearly a century ago. The incidence and economic burden of diabetic ketoacidosis have continued to rise but its mortality has decreased to less than 1% in good centers. Improved outcome is attributable to a better understanding of the pathophysiology of the disease and widespread application of treatment guidelines. In this review, we present the changes that have occurred over the years, highlighting the evidence behind the recommendations that have improved outcome. We begin with a discussion of the precipitants and pathogenesis of DKA as a prelude to understanding the rationale for the recommendations. A brief review of ketosis-prone type 2 diabetes, an update relating to the diagnosis of DKA and a future perspective are also provided.
Hypophosphatemia in critically ill patients
2013, Journal of Critical Care
Citation Excerpt :
Hypoalbuminemia and poor nutritional state may also increase the risk of hypophosphatemia [36], a finding supported by our observations. Although most patients with hypophosphatemia are asymptomatic, life-threatening complications of hypophosphatemia including altered mental status, hypotension, arrhythmia, or respiratory distress, have been described [3,7,22,24,37]. Thus, it is generally recommended to correct hypophosphatemia in all critically ill hypophosphatemic patients [3,6,7,22,23,27].
The aim of this study was to assess the association of phosphate concentration with key clinical outcomes in a heterogeneous cohort of critically ill patients.
This was a retrospective observational study at a general intensive care unit (ICU) of an Australian university teaching hospital enrolling 2730 adult critically ill patients.
We studied 10 504 phosphate measurements with a mean value of 1.17 mmol/L (measurements every 28.8 hours on average). Hyperphosphatemia (inorganic phosphate [iP] concentration > 1.4 mmol/L) occurred in 45% and hypophosphatemia (iP ≤ 0.6 mmol/L) in 20%. Among patients without any episodes of hyperphosphatemia, patients with at least 1 episode of hypophosphatemia had a higher ICU mortality than those without hypophosphatemia (P = .004). In addition, ICU nonsurvivors had lower minimum phosphate concentrations than did survivors (P = .009). Similar results were seen for hospital mortality. However, on multivariable logistic regression analysis, hypophosphatemia was not independently associated with ICU mortality (adjusted odds ratio, 0.86 [95% confidence interval, 0.66-1.10]; P = .24) and hospital mortality (odds ratio, 0.89 [0.73-1.07]; P = .21). Even when different cutoff points were used for hypophosphatemia (iP ≤ 0.5, 0.4, 0.3, or 0.2 mmol/L), hypophosphatemia was not an independent risk factor for ICU and hospital morality. In addition, timing of onset and duration of hypophosphatemia were not independent risk factor for ICU and hospital mortality.
Hypophosphatemia behaves like a general marker of illness severity and not as an independent predictor of ICU or in-hospital mortality in critically ill patients.
Hypophosphatemia and its clinical implications in critically ill children: A retrospective study
2012, Journal of Critical Care
Citation Excerpt :
Several factors warrant more attention in clinical practice for their potential to predispose patients toward hypophosphatemia. The prevalence of hypophosphatemia in critically ill adult patients with sepsis has been reported as high as 80% [2,15,16]. Barak et al [2] found associations between hypophosphatemia and early sepsis and between hypophosphatemia and elevated blood cytokine levels.
The aims of this study were to determine the prevalence of hypophosphatemia and to discuss the clinical implications of hypophosphatemia in critically ill children.
A retrospective review of the medical records of children admitted to the pediatric intensive care unit from December 2006 to December 2007 was conducted.
In 60.2% (n = 71) of the patients, any serum phosphorous level at admission and at the third day or seventh day after admission to pediatric intensive care unit was in hypophosphatemic range. Sepsis was present in 22.9% (n = 27) of the children studied and was associated with hypophosphatemia (P = .02). Hypophosphatemia was also associated with use of furosemide (P = .04), use of steroid (P = .04), use of β₂ agonist (P = .026), and use of an H₂ blocker (P = .004). There was a significant association between hypophosphatemia and the rate to attain target caloric requirements by enteral route (P = .007). The median time to attain target caloric requirements by enteral route was 2.9 ± 1.9 (0.2-10) days in the normophosphatemic group and 4.4 ± 2.8 (0.3-12) days in the hypophosphatemic group. In the multiple regression model, solely the rate to attain the target caloric requirements by enteral route demonstrated independent association with hypophosphatemia (P = .006; β = .27; 95% confidence interval, 0.02-0.09). Significant association was found between hypophosphatemia and the duration of mechanical ventilation and between hypophosphatemia and pediatric intensive care unit length of stay (P = .02 and P = .001, respectively).
Critically ill pediatric patients are prone to hypophosphatemia, especially if they cannot be fed early by enteral route. Hypophosphatemia is associated with an increased duration of mechanical ventilation and increased length of stay in the pediatric intensive care unit, suggesting that active repletion might improve these parameters.
Early phosphatemia changes in acute cardiac care patients
2012, Cor et Vasa
Citation Excerpt :
In critically ill patients, hypophosphatemia might be associated with higher mortality but the evidence as to whether correction of hypophosphatemia improves the outcome is poor. There is a general agreement to reserve intravenous correction of hypophosphatemia for patients with associated symptoms or phosphate levels <0.32 mmol/l [2,20]. Zazzo et al. [21] found a positive effect of hypophosphatemia correction on cardiac output in surgical intensive care patients.
The significance of inorganic serum phosphate levels (Pi) in patients with acute coronary syndromes (ACS) in the reperfusion era is unknown, as well as its relation to biomarkers of myocardial necrosis. Our aim was to assess admission Pi and its dynamics in patients admitted to the intensive cardiac care unit (ICCU), with emphasis on patients with ST segment elevation myocardial infarction (STEMI).
We studied 192 patients admitted to the ICCU during a 4-month period. The first group included 92 patients with STEMI (STEMI group) treated by primary percutaneous coronary intervention (PCI). The second group consisted of 100 patients without ACS (non-ACS group). Normophosphatemia was defined as Pi 0.7–1.6 mmol/l. Phosphatemia was measured at admission and then 6 h and 12 h later as well as troponin I.
Admission phosphatemia was lower in the STEMI group as compared to the non-ACS group (Pi 0.95 mmol/l vs. 1.18 mmol/l, p<0.001). Admission hypophosphatemia (Pi<0.7 mmol/l) was more often present in the STEMI group than in the non-ACS group (21% vs. 4%, p=0.001). In all hypophosphatemic STEMI patients, serum Pi normalized itself within 6 h without substitution. Admission hyperphosphatemia (Pi>1.6 mmol/l) was more frequent in non-ACS group (6.5% STEMI pts. vs. 13% non-ACS pts.). In the STEMI group, admission phosphatemia did not correlate with peak troponin I.
We conclude that patients with STEMI treated by primary PCI have lower Pi and more frequent transient hypophosphatemia at admission than acute cardiac care patients without acute coronary syndrome.

View all citing articles on Scopus

^☆: Address reprint requests to Corey M. Slovis, MD, Emergency Medicine, Vanderbilt University Medical Center, 703 Oxford House, Nashville, TN 37232-4700. E-mail: Corey.Slovis@mcmail,vanderbilt.edu

^☆☆: Returned August 17, 1998.

^★: Am J Emerg Med 2000;18:457-461.

^★★: 0735-6757/00/1804-0021$10.00/0

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TherapeuticsHypophosphatemia in the emergency department therapeutics☆,☆☆,★,★★

Abstract

Section snippets

Phosphorus in biological systems

Phosphorus regulation

Causes of hypophosphatemia

Diagnosing hypophosphatemia

General guidelines for phosphate repletion

Intravenous phosphate replacement

Selected conditions associated with hypophosphatemia and specific recommendations on phosphate repletion

Diabetic ketoacidosis

Chronic alcoholism

Alcoholic ketoacidosis (AKA)

Respiratory disorders including asthma and COPD

Conclusions

Crit Care Clin

Ann Emerg Med

Chest

Am J Med

Am J Med

Endo Met Clin NAmer

Am J Med

Am J Med

Baillieres Clin Endocrino Metab

Metabolism

Am J Med

Lancet

Gastroenterology

Am J Clin Nutr

Amer J Med

Chest

Hypophosphatemia: Pathophysiological and practical aspects of its therapy

Semin Nephrol

The pathophysiology and clinical characteristics of severe hypophosphatemia

Arch Intern Med

Acute hemolytic anemia with rigid red cells in hypophosphatemia

N Engl J Med

Erythrocyte adenosine triphosphate depletion during hypophosphatemia in a uremic subject

N Engl J Med

Effect of hypophospha-temia on myocardial performance in man

N Engl J Med

Reduced red cell glycolysis, 2,3-diphosphoglycerate and adenosine triphosphate con-centration, and increased hemoglobin-oxygen affinity caused by hypophosphatemia

Ann Intern Med

Hypophosphatemia and rhabdomyolysis

J Clin Invest

The effect of voluntary overbreathing on the electrolyte equilibrium of arterial blood in man

J Biol Chem

Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure

N Engl J Med

Phosphorus deficiency and hypophosphatemia

Hosp Pract

Severe hypophosphatemia in hospitalized patients

Miner Electrolyte Metab

Admission inorganic phosphorus correlated with discharge diagnosis and other metabolic profile components

Ala J Med Sci

Clinical relationships between serum phosphorus and other blood chemistry values in alcoholics

Arch Intern Med

A clinical approach to common electrolyte problems: 3. Hypophosphatemia

Can Med Assoc J

The treatment of severe hypophosphatemia

Ann Intern Med

Skelatal muscle in hypophosphatemia and phosphorus deficiency

Adv Exp Med Biol

Therapeutics
Hypophosphatemia in the emergency department therapeutics☆,☆☆,★,★★