Chen 2015ᵃ

Type of study:

RCT

Setting and country:

210 stroke patients, who were hospitalized for more than 96 hours in the Department of Neurology of the First Affiliated Hospital of Sun Yat-sen University from January 2010 to December 2012

Funding and conflicts of interest:

None

Inclusion criteria:

1) definite indication for EN; 2) age ≥18 years old; and 3) planned ICU length of stay >5 days

Exclusion criteria:

1) immuno-compromised; 2) hepatic failure; or 3) gastrointestinal issues postoperatively

N total at baseline:

Intervention: 84

Control: 126

Important prognostic factors²:

Sex N (%):

I: 44 (55.0) M

C: 71 (56.3) M

APACHE II score mean±SD:

I: 18.7±4.1

C: 19.1±3.4

Mechanical ventilation N (%)

I: 51 (63.8)

C: 92 (73.0)

Groups comparable at baseline? Yes

No GRV measurement.

The infusion was performed by a feeding pump at a constant rate from 7:00 am to 3:00 am next morning. The infusion rate was determined based on the total volume of EN.

The volume of EN was increased gradually every day according to energy requirements as follows: Day 1: 33% of the target volume, Day 2: 66% of the target volume, and Day 3: 100% of the target volume.

GRV was measured on all nasogastric tubes and recorded every 4 hours. The GRV was assessed at 7 am, 11 am, 3 pm, 7 pm, 11 pm, and 3 am next day. The EN infusion rate was adjusted based on the gastric residual volume. The original rate of infusion was maintained if the residue was ≤200 mL. Rate was increased if the residue was ≤100 mL. The rate was lowered and motility agents were added if the residue was ≥200 mL.

Length of follow-up:

72 hours

Loss-to-follow-up:

Intervention: 0

Control: 4

Reasons: complications (gastrointestinal bleeding (n=2)), extubation before 72h (n=2) 

Incomplete outcome data:

Excluded four participants allocated to the control group

and who failed to continue EN for more than 72 hours

Regurgitation, N (%)

I: 15 (18.8)

C: 8 (6.3)

P=0.006

Aspiration, N (%)

I: 14 (17.5)

C: 10 (7.9)

P=0.037

Author’s conclusions

The risk of reflux and aspiration was not increased in stroke patients when EN infusion volume was increased from 500 to 1500 mL with carefully monitoring of the GRV.

During EN therapy for patients with stroke, using feeding pump with a continuous infusion for 20 hours and adjusting infusion rate based on GRV could reduce the incidence of respiratory complications

Ozen 2016

Type of study

RCT

Setting and country:

Adult medical ICU of 2 university

hospitals in Ankara, Turkey, between March 2014 and April 2015.

Funding and conflicts of interest:

none

Inclusion criteria:

Patients who were planned to receive >5 days of invasive

MV treatment, >18 years, patients where EF treatment would be started with a NG tube, and patients whose relative provided written consent were included in the study

Exclusion criteria:

Paralytic ileus, acute pancreatitis, pregnancy, inflammatory bowel disease, short bowel syndrome, Crohn disease, gastrointestinal bleeding, esophageal and fundic varices, morbid obesity, or gastrostomy/jejunostomy; those receiving thoracic or abdominal radiotherapy.

N total at baseline:

Intervention: 27

Control: 34

Important prognostic factors²:

Age mean±SD

I: 68.08 ± 18.04

C: 64.92 ± 14.95

Sex N (%):

I: 17 (65.4) M

C: 15 (40.0) M

APACHE II score:

I: 25.29 ± 7.43

C: 23.58 ± 6.97

Gastric residual volume was not measured in this group. EF was stopped and the physician informed if the patient developed vomiting, regurgitation, diarrhea, or abdominal distention, and another appropriate feeding method was started. (TPN)

The GRV was measured by the nurses with the syringe method every 8 hours at 8:00 AM, 4:00 PM, and midnight. EF was stopped for 1 hour before the measurement, and the amount aspirated was returned to the patient at the end of the measurement.

Length of follow-up:

5 days

Loss-to-follow-up:

Intervention: 1

Reasons: Exitus (n = 1)

Control: 9

Reasons: GRV amount > 250 mL twice (n = 1); Going to TPN due to continuous vomiting during the four hours in the first day of the study (n = 1); Exitus (n = 3); Going to TPN due to cholestasis development (n = 1); Going to TPN due to ileus development (n = 1); Extubation (n = 1);

Postoperative hemodynamic instability (n = 1)

Incomplete outcome data:

In GRV monitoring group, 9 participants were lost to follow-up and excluded

after randomization and thus not included in the overall analysis.

Vomiting N (%)

I: 1 (3.8)

C: 0

P=0.322

Feeding intolerance N (%)

I: 1 (3.8)

C: 2 (8)

P=0.529

Mortality at the end of follow-up N (%)

I: 15 (57.7)

C: 20 (80.0)

P=0.157

Time in ICU, days mean±SD

I: 27.35 ± 24.01

C: 32.96 ± 21.81

P=0.154

Cumulative calorie deficit (kcal)

Day 1:

I: 162.3 ± 260.5

C: 301.6 ± 267.7

Day 2:

I: 33.8 ± 146.3

C: 52.8 ± 139.0

Day 3:

I: 12.3 ± 45.2

C: 86.0 ± 163.1

Day 4:

I: 8.2 ± 14.7

C: 162.6 ± 210.6

Day 5:

I: 5.7 ± 32.5

C: 71.2 ± 150.9

P<0.001

Author’s conclusions:

The discrepancies in GRV measurement make it unreliable for monitoring feeding intolerance and

gastroesophageal

reflux. The use of GRV measurements may therefore be discontinued as part of the standard care protocol in medical

ICUs.

Reiginier 2013

Type of study

RCT

Setting and country:

Multicenter ICU in France. Of the 9 ICUs, 3 were medical and 6 were medical-

surgical; 3 were in university hospitals and 6 in general university affiliated

hospitals.

The trial lasted from May 2010 to March 2011.

Funding and conflicts of interest:

none

Inclusion criteria:

adults (aged ≥18 years) admitted to the

study ICUs between May 2010 and March 2011, expected to require more

than 48 hours of invasive mechanical ventilation, and started on enteral nutrition via a nasogastric tube within 36h after intubation

Exclusion criteria:

abdominal surgery

within the past month; history of esophageal, duodenal, pancreatic, or gastric surgery; bleeding from the esophagus,

stomach, or bowel; contraindications

to prokinetic agents; enteral nutrition via

a jejunostomy or gastrostomy; pregnancy;

treatment-limitation decisions; and current inclusion in a trial of VAP

prevention, enteral nutrition tolerance,

or both.

N total at baseline:

Intervention: 230

Control: 222

Important prognostic factors²:

Age mean±SD

I: 61±15

C: 62±14

Sex N

I: 159

C: 156

SAPS II score:

I: 49 ±17

C: 51±16

The intervention consisted in not monitoring

residual gastric volume. In the intervention group, intolerance to enteral nutrition was diagnosed when vomiting occurred.

Enteral nutrition was initiated within 36 hours after intubation and delivered according to the same protocol in both

groups

In the control group, the diagnosis of intolerance to enteral nutrition relied on

the presence of vomiting, of residual gastric

volume greater than 250 mL, or both. Residual gastric volume was measured every 6 hours by aspiration through the

nasogastric tube using a 50-mL syringe. Aspirates smaller than 250 mL were returned to the patient.

Length of follow-up:

90 days

Loss-to-follow-up:

Intervention: 41

Reasons: Excluded per-protocol (n=19), did not meet inclusion criteria (n=7), mechanical ventilation for <48h (n=9), medical reasons (n=3), withdrew consent (n=3) 

Control: 14

Reasons: Excluded per-protocol (n=7), did not meet inclusion criteria (n=5), mechanical ventilation for <48h (n=2) 

Incomplete outcome data:

All analyses were conducted in both a modified ITT population and a per-protocol population. The modified ITT population comprised all randomized participants except those who withdrew consent

Vomiting, N (%)

I: 90 (39.6)

C: 60 (27.0)

Intolerance to EN, N (%)

I: 90 (39.6)

C: 141 (63.5)

ICU length of stay, median (IQR)

I: 10 (6-17)

C: 10 (7-17)

MD (90% CI): -1 (-2 to 0)

Hospital length of stay, median (IQR)

I: 17 (9-31)

C: 19 (10-32)

MD (90% CI): -1 (-3 to 1)

Mortality up to 28 days, N (%)

I: 63 (27.8)

C: 61 (27.5)

Cumulative calorie deficit from day 0 to 7, median (IQR)

I: 319 (93-1012)

C: 509 (185-1252)

MD (90% CI): -111 (-198 to -36)

Author’s conclusions:

Not monitoring gastric volume was not inferior to routine residual gastric volume monitoring in terms of development of VAP among adults requiring mechanical ventilation and receiving early enteral nutrition.

Note:

Similar results were obtained in the per-protocol analysis

Prest 2021

Type of study:

Prospective cohort

Setting and country:

One surgical trauma ICU in the USA

Funding and conflicts of interest:

Grant provided by Nestlé Health Science. First and second author received speaking honoraria from Nestlé.

Inclusion criteria:

adults over 18 years of age who received enteral nutrition for>48 hours

and who had an ICU LOS of at least 72 hours.

Exclusion criteria:

Death within 72 hours

N total at baseline:

I: 145

C: 156

Important prognostic factors²

Age mean±SD

I: 48.3±18.5

C: 46.3±17.3

Sex N (%)

I: 105 (72.4) M

C: 116 (74.4) M

Triggered GRV: Not checking gastric residuals until a secondary sign of intolerance is present. These include nausea, abdominal distention, abdominal pain, or cramping. Feeds are not

reduced or held until residuals are >500 ml. If emesis is present, feeds are automatically held for 4 hours before checking residual amounts, and feeds restart for residuals

of <500 ml

Routine GRV: check residuals every 4 hours; if the residual amount was twice the rate of enteral nutrition, then the nurse was to hold the feeds and contact the rounding team.

At this point, the rounding team was at liberty to either continue to hold or resume enteral nutrition.

Length of follow-up:

Until ICU discharge

Loss-to-follow-up:

“25 were excluded because they were missing injury severity information”

Incomplete outcome data:

6 patients under the routine GRV protocol and 19 patients under the triggered GRV protocol were excluded due to missing ISS scores.

ICU length of stay, median (IQR)

I: 12 (9-16)

C: 13 (9—20)

P=0.057

Pneumonia, N (%)

I: 31 (21.4)

C: 61 (39.1)

P=0.001

Mortality (>72h), N (%)

I: 20 (13.8)
C: 11 (7.1)
P=0.055

Author’s conclusions:

The elimination of GRV assessments results in the delivery of an equivalent amount of protein and calories when compared with routine monitoring of GRVs.

The data suggest that this is a safe practice.

Study reference

(first author, publication year)

Was the allocation sequence adequately generated? ^a

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?^b

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?^c

Were patients blinded?

Were healthcare providers blinded?

Were data collectors blinded?

Were outcome assessors blinded?

Were data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?^d

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?^e

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?^f

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure^g

LOW

Some concerns

HIGH

Chen 2015

Probably yes;

Reason: method of randomization is not reported, however authors of a Cochrane review requested additional information affirming that randomization was performed using a random number table

Probably no;

Reason: method of allocation and concealment are not reported

Definitely no;

Reason: Blinding of patients, health care providers and data collectors could not be performed. Blinding of data analysts is not reported.

Probably yes;

Reason: Loss to follow-up was infrequent in the intervention group. In the control group, 4 patients were excluded later on.

Probably yes;

Reason: no study protocol available, but the published study included all

planned/expected outcomes

Definitely yes;

Reason: No other problems noted

Some concerns

(all outcomes except mortality)

Lack of details on concealment of allocation, lack of blinding, frequent loss to follow-up.

Ozen 2016

Definitely yes;

Reason: Computer-generated randomization

Probably no;

Reason: method of concealment is not reported

Definitely no;

Reason: Blinding of patients, health care providers and data collectors could not be performed. Data analysts were unblinded as well.

Probably no;

Reason: Nine patients were lost to follow-up in the GRV monitoring group.

Probably yes;

Reason: no study protocol available, but the published study included all

planned/expected outcomes

Definitely yes;

Reason: No other problems noted

Some concerns

(all outcomes except mortality)

Lack of details on concealment of allocation, lack of blinding, frequent loss to follow-up.

Reignier 2013

Definitely yes;

Reason: Randomization by an external computer-generated,

interactive, web-response system

Definitely yes;

Reason: Allocation using an external computer-generated,

interactive, web-response system

Probably no;

Blinding of patients and health care providers could not be performed. Outcome assessors were blinded.

Probably yes;

Reason: Data were analysed according to the intention-to-treat principle

Definitely yes;

Reason: This study was registered in ClinicalTrials.gov (identifier: NCT01137487). Published reports included all expected outcomes.

Definitely yes;

Reason: No other problems noted

Some concerns

(all outcomes except mortality)

Lack of blinding

Study reference

(first author, year of publication)

Bias due to a non-representative or ill-defined sample of patients?¹

(unlikely/likely/unclear)

Bias due to insufficiently long, or   incomplete follow-up, or differences in follow-up between treatment groups?²

(unlikely/likely/unclear)

Bias due to ill-defined or inadequately measured outcome ?³

(unlikely/likely/unclear)

Bias due to inadequate adjustment for all  important prognostic factors?⁴

(unlikely/likely/unclear)

Prest, 2021

Unlikely

Note: patients whose residuals were checked according to the new protocol were matched to patients who were treated according to the preceding protocol

Unclear

Note: The length of follow-up is not reported and may differ between groups

Unlikely

Note: Outcomes are well-defined and measured adequately

Unlikely

Note: results were adjusted for prognostic factors