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PhilSPEN Online Journal of Parenteral and Enteral Nutrition

(Article 34 | POJ_0028.html) Issue January 2017 - June 2017: 154-162)

Original Clinical Investigation

Refeeding Syndrome: frequency of hypophosphatemia and other electrolyte abnormalities - experience from a private tertiary care hospital in the Philippines

Abstract | Introduction | Methodology | Results | Discussion | Conclusion | References | PDF (138 KB) |Back to Articles Page

Submitted: April 30, 2016 | Posted: February 8, 2017

AUTHORS:

Naheeda Mustofa MD, Reynaldo Sinamban MD, Jesus Fernando Inciong MD, Eliza Mei Francisco MD, Olive Quizon MD, Marianna Ramona Sioson MD, Divina Cristy Redondo-Samin MD, Donabelle Navarrete RND and
Luisito Llido MD

INSTITUTIONS WHERE RESEARCH WAS CONDUCTED:

Clinical Nutrition Service, St. Luke’s Medical Center, E. Rodriguez Avenue, Quezon City, Philippines, 1102

ABSTRACT | Back

Background: Refeeding syndrome is often overlooked when feeding is resumed in “high risk” critically ill patients resulting to increased morbidity, mortality and poor clinical outcomes.

Objective: To report on the prevalence, profile and outcomes of refeeding syndrome in a tertiary care hospital in the Philippines

Methodology: Retrospective study; data of all patients referred to the Clinical Nutrition Service and diagnosed to have refeeding syndrome were collected, analyzed and reviewed. These are the data: a) Clinical data: Age, Height and weight (=BMI), Nutritional status and risk assessment; b) Nutritional data: Total calories calculated and delivered, Total protein calculated and delivered; c) Laboratory data: Serum electrolytes (phosphate, potassium, sodium, and magnesium), serum albumin, and glucose; d) Follow up and outcome data (Arrhythmia incidence, Mechanical ventilation, Hospital days and Status on discharge).

Results: Total number of referrals made to the Clinical Nutrition Service = 341. Total patients diagnosed to have refeeding syndrome = 30 for a refeeding syndrome rate of 9%. 17/30 (57%) had cancer; 14/30 (47%) had BMI <18.5; 30/30 (100%) had SGA “C”, 27/30 (90%) had sub-optimal/starvation intake, and 27/30 (90%) had hypophosphatemia, 19/30 (63%) had hypomagnesemia; 7/30 (23%) developed arrhythmias; 19/30 (63%) were given parenteral nutrition and 16/30 (53%) enteral nutrition; 10/30 (33%) had ventilator support with 6/30 (20%) admitted in the ICU; mortality rate was 5/30 (17%).

Conclusion: The prevalence of Refeeding Syndrome is 9%, hypophosphatemia incidence was 90% and mortality rate is 17%.

KEYWORDS: refeeding, hypophosphatemia, nutrition, critical care

 

INTRODUCTION | Back

Refeeding syndrome has been a clinical dilemma in the management of critically ill patients, especially those with nutrient intake below 25% of their daily requirements. (1,2) It was first identified during World War II among prisoners who experienced cardiac dysfunction upon resumption of feeding after prolonged starvation (3). This syndrome is explained as a condition where patients with prolonged starvation and sub-optimal intake suddenly develop serum electrolyte abnormalities especially hypophosphatemia, vitamin deficiency like thiamine, glucose and fluid derangements after initiating feeding with high calorie and protein content. This results to sudden changes in the external and internal environments of the cell brought about by glucose and amino acid transports in response to the feeding process. The major complications that arose were cardiac arrhythmia, respiratory failure and sudden death. The role of insulin in contributing to this abnormal state is also raised. (4-8)

In 2011 the European Society for Clinical Nutrition and Metabolism (ESPEN) published guidelines for the management of refeeding syndrome which include a three (3) day gradual increment in feeding to avoid the development of this condition. (9,10) Here patients were categorized to be at risk for refeeding based on unintentional weight loss, low nutrient intake, increased losses and decreased nutrient absorption. A list of complications brought about by refeeding hypophosphatemia and an array of multi-organ involvement were also identified which include hematological, musculoskeletal, and renal complications aside from the above mentioned cardiac and pulmonary complications (10).

Despite these developments the value of a thorough nutrient intake history and risk assessment has not gained momentum in the initial evaluation of the critical care patient. Assumptions that any patient can be fed in ‘full’ according to the computed total caloric requirements (TCR) once feeding can be initiated still prevail in our current practice. Refeeding hypophosphatemia typically occurs within the first 2-3 days of nutrition delivery or commencement of intravenous dextrose alone (1,11), but despite these observations there is still a tendency to overlook the determination of serum phosphorus in routine blood electrolyte examinations and correlate the level of hypophosphatemia with corresponding changes in sodium, potassium, and magnesium. (12)

The objectives of this report are: a) To determine the incidence of refeeding syndrome among patients referred to the clinical nutrition service in this institution during the first 24 to 72 hours of initiation of feeding between the months of January 2013 to September 2014 and b) To delineate the patient profile, nutritional and clinical data, electrolyte abnormalities and outcome of patients identified to have refeeding syndrome.

METHODOLOGY | Back

This is a descriptive, retrospective study conducted at St. Luke's Medical Center-Quezon City from January 2013 to September 2014. All patients with the diagnosis of “refeeding risk” were included in the study. The patient records were archived in the Clinical Nutrition Service database of this institution. This study used the validated St. Luke’s Medical Center’s Nutrition Risk and Assessment Forms to determine the severity of nutrition risk of the referred patients. (13) These are the inclusion criteria which classified patients as “Refeeding Risk” which were based on the NICE guidelines of 2006. (14) (Table 1):

Table 1: Inclusion criteria for patients classified to have Refeeding Syndrome

1

Referred to the Clinical Nutrition Service physicians,

2

Assessed to have severe nutrition risk with a Subjective Global Assessment (SGA) of “C:

3

Serum phosphate levels of low to normal (2.8 mg/dl and below) during the first 72-hour of initiation of nutrition management

4

Hospital stay of at least 72 hours to establish presence or absence of refeeding when nutrition was initiated,

5

Pediatric and adult patients

These were the data collected: a) Clinical data: Age, Height and weight (=BMI), Nutritional status and risk assessment; b) Nutritional data: Total calories calculated and delivered, Total protein calculated and delivered; c) Laboratory data: Serum electrolytes (phosphate, potassium, sodium, and magnesium), serum albumin, and glucose; and d) Follow up and outcome data (Arrhythmia incidence, Mechanical ventilation, Hospital days and Status on discharge). Analysis of data were focused on the following: a) calorie intake, b) electrolyte changes, c) patients with at least two serum phosphorus levels and d) pattern of glucose and albumin levels. Statistical analysis was done using the NCSS software (15) on the following: mean, standard deviation and percentages. Significance was set at p < 0.05.

RESULTS | Back

Incidence of Refeeding Syndrome:
A total of 341 referrals were made to the Clinical Nutrition Service during this study period (January 2013 to September 2014). A total of 30 patients were referred to the Clinical Nutrition Service with the diagnosis of “refeeding syndrome” for a refeeding syndrome prevalence of 30/341 or 9%.

Patient Profile:
Majority of the patients are females (63.3%) with over 57% patients aged 60 years old and above. There was one pediatric patient included in this study, aged 10 years old, admitted for severe dehydration due to acute gastroenteritis with associated global developmental delay and starvation. All patients were assessed to be with severe malnutrition (SGA “C”) with 47% having a BMI of less than 18.5 and 63%weight loss of > 10%. All also had a nutrition risk score of >3. (Table 2)


Table 2: Nutritional Status Profile (n=30)

Variable

Number

Percent

BMI < 18.5

14

47%

Nutritional Assessment Risk Score > 3

30

100%

No weight loss

1

3%

Percent Weight Loss

 

 

     < 10% weight loss

10

33%

     > 10% weight loss

19

63%

SGA “C”

30

100%

More than half of the patients had cancer (57%) and the organ system mostly involved was the gastrointestinal tract, be it oncologic or not (40%). (Table 3) One third of the patients had cancer of the gastrointestinal tract (27%). These patients are the ones with feeding and weight loss issues. (15)


Table 3: Disease Profile (n=30)

Cancer

N

Percent

Non-Cancer

N

Percent

GI cancer

8

27%

Gastrointestinal

4

13%

Urologic

3

10%

Neuro

4

13%

Female Reproductive System

3

10%

Pulmonary

2

7%

Breast

2

7%

Renal

1

3%

Others

1

3%

Ortho

1

3%

 

 

 

Trauma

1

3%

Total

17

17/30 or 57%

Total

13

13/30 or 43%

Refeeding Profile according to the ESPEN and NICE criteria (Table 4):
Based on the criteria established by ESPEN and NICE, severe malnutrition (SGA “C”) with suboptimal intake were the most common findings in these patients (100% to 97%). This was followed by age and history of weight loss (63%) then receiving parenteral nutrition as the main feeding regimen (60%). High glucose delivery was the last frequent criteria noted (47%)


Table 4: Risk Factors for “Refeeding Syndrome” according to the ESPEN and NICE guidelines

number

percent

1 Nutrition Assessment (High Risk) with SGA “C”

30

100%

2 Intake - suboptimal to starvation

29

97%

3 Age

19

63%

4 Severe weight loss

19

63%

5 Parenteral nutrition

18

60%

6 Underweight BMI

14

47%

7 High calorie (glucose) delivery

14

47%

Electrolyte Profile: (Table 5)

The main electrolyte noted to be low in all the refeeding cases was hypophosphatemia (27/30 or 90%) and it is the only low electrolyte in one third of all cases with hypophosphatemia (28%). Hypophosphatemia was detected on the first test/exam in 67% of cases and on the second and third exam in 40% of cases. The other concomitant electrolyte abnormalities were low magnesium (57%), low sodium (20%) and low potassium (13%).


Table 5: Electrolyte Data

Electrolyte Status

N=30

Percent

Total Hypophosphatemia

27

90%

  • Hypophosphatemia alone detected on the first exam

20

67%

  • Hypophosphatemia alone detected on the second exam

7

17%

  • Hypophosphatemia alone persisting up to third exam

8

28%

Hypophosphatemia with low magnesium

17

57%

Hypophosphatemia with low sodium

6

20%

Hypophosphatemia with low potassium

4

13%

Low sodium alone

2

7%

Low magnesium alone

2

7%

Low sodium, low potassium

1

3%

Hypophosphatemia and calorie intake: Hypophosphatemia whether mild to severe, was noted to be more frequent in low calorie intake (20 kcal/kg/day, 23%) and most frequent with high calorie intake (30-40 kcal/kg/day, 47%). (Table 6)

Table 6: Level of Hypophosphatemia - based on calorie goals delivered

 

Initial Caloric Goals Delivered

Mild
(2.3-2.7mg/dl)

Moderate
(1.5-2.2mg/dl)

Severe
(<1.5mg/dl)

Frequency

20 kcal (n=4)

0

5

2

7 (23%)

25 kcal (n=6)

1

1

1

3 (10%)

26-29 kcal (n=5)

1

2

2

5 (17%)

30-40 kcal (n=7)

6

4

4

14 (47%)

Total (n=30)

8 (27%)

12 (40%)

10 (33%)

30

Hypophosphatemia and the type of feeding. Hypophosphatemia was most commonly seen in patients with parenteral nutrition (either total or in combination) (19/30 or 63%). (Table 7)


TABLE 7: Type of feeding among patients identified with hypophosphatemia (n=30)

Type of Feeding

Percentage Distribution

Oral Feeding

2 (7%)

Oral + Tube Feeding

4 (13%)

Oral + Parenteral Nutrition

8 (27%)

Tube Feeding

5 (17%)

Parenteral Nutrition + Tube Feeding

7 (23%)

Total Parenteral Nutrition

4 (13%)

Outcome of patients with hypophosphatemia: (Table 8)
Mortality rate was 5/30 or 17%. 10/30 or 33% had ventilator support while 6/30 or 20% admitted in the ICU. 7/30 or 23% of patients developed arrhythmias.


TABLE 8: Outcomes of patients with hypophosphatemia

Outcome Variable

N=30 (%)

Length-of-Hospital Stay

 

  • 1-7 days

11 (37%)

  • 8-15 days          

12 (40%)

  • 16-25 days    

5 (17%)

  • 26-35 days       

4 (13%)

Ventilator Support

10 (33%)

ICU Admission   

6 (20%)

Mortality 

5 (17%)

Discharged Improved 

23(83%)

Discharged Unimproved

2 (7%)

Arrhythmias

7 (23%)

Two of the fatalities were elderly, 85 years old and 91 years old, respectively. The 85 y/o male patient was started on total parenteral nutrition due to suboptimal intake, though had less than 10% weight loss, but had baseline serum phosphorus of 1.2mg/dl after 24 hours of TPN initiation which was then subsequently adjusted to half the dose with concomitant intravenous phosphate replacement. The patient then was transferred to the ICU due to new onset cardiac arrhythmias and concomitant upper GI bleeding with evidence of esophageal erosions upon endoscopy. Despite resuscitative efforts, however, patient went into cardiac arrest but serum phosphorus increased up to 2.2mg/dl on correction, serum magnesium was normal but had mild hypokalemia at 3.2mg/dl. The 91 year old stroke patient was bedridden, had a femoral fracture and was without proper nutrition support at home, with a BMI of 13.5, had >10% weight loss, case was referred to our service 15 days after admission and upon review of events, was initially admitted at the wards and transferred to the ICU. Serum phosphorus on admission was already low at 0.9mg/dl but had no intravenous phosphate replacement. Patient was only managed by the nutrition specialist for 3 days and was not referred back thereafter. This patient had concomitant co-morbidities and eventually succumbed to sepsis due to severe pneumonia with concomitant effusion.

DISCUSSION: | Back

Prevalence of Refeeding Syndrome and profile of patients:
The total number of patients diagnosed to have “Refeeding Syndrome” was 30 out of the 341 patients referred to the Clinical Nutrition Service for a Refeeding Rate of 9%. This is below the reported incidence range of 19% to 28%. (10) The clinical features noted to fit the NICE/ESPEN criteria (13) are: High risk or SGA “C” (100%), sub-optimal intake (97%), age (63%), severe weight loss (63%), parenteral nutrition (63%), underweight by BMI (47%) and high glucose delivery (47%). 57% (17/30) of the severely malnourished patients who had significant recent poor intake and developed refeeding syndrome were cancer patients (Table 4). This is higher than the reported 25% incidence in cancer patients. (16) These patients developed recent weight loss due to oncologic treatments and radiation therapy or other factors like neurologic, partial bowel obstruction, and abnormalities leading to severe underfeeding for several weeks prior to admission as previously reported in a local study on cancer patients. (17) The high calorie delivery (47%) was mainly through parenteral nutrition (63%) (Tables 6 and 7).

Hypophosphatemia:
The main electrolyte noted to be low in all the refeeding cases was hypophosphatemia (27/30) or 90% and it is the only low electrolyte in one third of all cases with “Refeeding Syndrome” (20/30 or 67%). This is higher than the reported 34% in critical care patients (18) Hypophosphatemia with low magnesium is present in 17/30 or 57%. A total of 8 patients (27%) had mild hypophosphatemia, 12 patients (40%) had moderate hypophosphatemia and 10 patients (33%) had severe hypophosphatemia during the first 24-72 hours of nutrition commencement. This is similar to the reported incidence of 50% of refeeding syndrome when artificial feeding was started. (19) The most number of patients with hypophosphatemia were identified to be among those started on a 30-40 calorie per body weight goal followed by those given a 20 calorie per body weight nutrient intake.  

Concomitant electrolyte abnormalities:
All 30 patients with mild to severe hypophosphatemia identified were each assessed for other concomitant electrolyte abnormalities and a total of 20 patients (66.7%) had hypokalemia, while 26% had hypomagnesemia. There were three (3) patients with BMI less than 14 and 2 of whom developed severe hypophosphatemia. This is of concern since deaths were reported in these group of patients (20,21) Hypercalcemia was also included in this study since elevated calcium levels may induce hypophosphatemia and 3 of the patients with hypercalcemia (1.5-2.2) were diagnosed to have bone metastasis from cancer. These electrolyte derangements were all seen as consequences of the feeding regimen to these patients. (21,22)

Type of Feeding
Since clinical nutrition encompasses varying needs for mixed nutrition managements such as combined enteral and parenteral nutrition, it is essential to observe the pattern of feeding which might increase the risk for refeeding syndrome. In most studies, parenteral nutrition brings about the highest risk of refeeding since it is “usually started at the goal rate”. (23) Table 9 presents the frequency of each type of feeding among the 30 patients identified with hypophosphatemia. A total of 19 patients (63%) received either total parenteral nutrition or supplemental parenteral nutrition while 16 (53.3%) patients received enteral feeding whether combined oral and enteral feeding, parenteral and enteral feeding, or pure enteral tube feeding. There were only 2 patients identified to have hypophosphatemia who were on pure oral intake. It has been observed that in some malnourished patients being given total parenteral nutrition even at half the dose, overfeeding can still ensue. (18-19,20-22) It is better to deliver parenteral nutrition and tube feedings slowly than to aggressively deliver computed standard caloric requirements to avoid ‘abrupt hypophosphatemia’. (10,21,23)

Clinical Course and Outcome:
These are the features of patients clinically assessed to have ”refeeding syndrome”: a) Given calories at 30 kcal/kg/day or above = 14/30 (47%), b) Arrhythmia = 2/14 (=both had hypophosphatemia and one had hypokalemia, and one with hyponatremia (no mortality, hospital stay = one had 7 days; the other had 13 days), c) Mechanical ventilation = 3/14 (all had hypophosphatemia, one with hypokalemia, one with hyponatremia; one died, hospital stay = 7 days). Patients had an average hospital stay of 8-15 days, with 10 (33.3%) of patients placed on ventilatory support during admission. Majority of the patients (83.3%) were discharged improved but there were 5 cases of mortality. A total of 7 cases had arrhythmias, though 6 of which already had chronic cardiac dysrhythmia on admission. Deaths resulting to overzealous parenteral nutrition are not new and this is why identifying patients at risk, whether moderate or high, for refeeding syndrome must be closely monitored and a review of the guidelines in treatment, thiamine supplementation, electrolyte correction including hypophosphatemia, and fluid shifts should be done. (21-23) In this study, a direct correlation cannot be established as to whether the death was directly caused by refeeding hypophosphatemia.

Mortality:
There were 5/30 mortalities for a mortality rate of 17%. This is a bit higher to the reported mortality rate of 15% in patients with refeeding syndrome. (19) All had hypophosphatemia with two (2) having hypophosphatemia for 2 tests and one (1) having hypophosphatemia for 3 tests. None had hypokalemia, hyponatremia and hypomagnesemia. Two (2) had arrhythmia and three (3) had ventilator support. The duration of stay was: two (2) had 7 days while the other two (2) had 28-30 days.

Recommendations:
The St. Luke's Medical Center's current nutrition assessment forms can be enhanced to indicate patients at high risk for refeeding. This research aims to provide information that such condition occurs and that medical personnel especially physicians should be made aware of the existence of hypophosphatemia and other related electrolyte disorders that can be worsened with aggressive nutrition interventions. 90% of our refeeding syndrome cases presented with hypophosphatemia which makes this laboratory test together with serum magnesium a requirement whenever the clinical criteria of “refeeding” is met. (Table 1)


CONCLUSION: | Back

The prevalence of Refeeding Syndrome is 9% in this institution in the Philippines with 90% of the patients having hypophosphatemia. The mortality rate is 17%.

 

REFERENCES: | Back

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Abstract | Introduction | Methodology | Results | Discussion | References | Back to Articles Page