Impact of Intravenous Fluids and Enteral Nutrition on the Severity of Gastrointestinal Dysfunction: A Systematic Review and Meta-analysis

Asrani, Varsha M.; Brown, Annabelle; Bissett, Ian; Windsor, John A.

doi:10.2478/jccm-2020-0009

Figures & Tables

Impact of intravenous fluid therapy on variables of gut dysfunction

Symptoms of GDF ^§	Intervention^al	Control	Odds Ratio [95% CI]^*	P Trend	I² (%)^#
Nausea	88/ 274	90/278	0.98 (0.67, 1.44)	0.92	0
Vomiting	62/462	94/447	0.51 (0.28, 0.94)	0.03	45
Ileus	66/832	80/828	0.83 (0.52, 1.32)	0.42	23
GI bleed	15/592	10/587	1.48 (0.66, 3.35)	0.34	0
Anastomotic leak	44/833	43/867	1.03 (0.54, 1.96)	0.93	31
Perforation	7/238	6/234	1.05 (0.36, 3.09)	0.92	0
Intestinal obstruction	5/451	11/445	0.53 (0.20, 1.45)	0.22	0

Impact of enteral feeding on variables of gut dysfunction as classified by feeding categories

Symptoms of GDF^§	Intervention Enteral	Control Parenteral	Odds [95% Ratio CI]*	P Trend	I² [%]^#
A. Route of feeding
Vomiting	605/2388	350/2598	2.02 (1.74, 2.35)	<0.01	0
Diarrhoea	190/1508	421/1515	1.75 (0.39, 7.86)	0.46	92
Abdominal distension	123/1386	90/1390	1.51 (0.93, 2.45)	0.10	28
Ileus	52/347	65/347	0.97 (0.34, 2.76)	0.96	58
Anastomotic leak	28/540	54/545	0.54 (0.31, 0.95)	0.03	14
Intestinal ischaemia	33/2493	16/2495	1.87 (0.72, 4.87)	0.20	42
Peritonitis	5/265	18/268	0.31 (0.11, 0.87)	0.03	0

B. Timing of feeding	Early	Delayed
Vomiting	3/56	19/54	0.11 (0.03, 0.41)	<0.01	0
Diarrhoea	27/39	23/40	2.45 (0.26, 22.75)	0.43	69
Abdominal Distension	12/66	21/69	0.51 (0.22, 1.91)	0.12	0

C. Enteral feeding vs Nil-by-mouth (NBM)	Enteral	NBM
Vomiting	21/220	22/219	0.72 (0.18, 2.90)	0.65	0
Abdominal Distension	66/242	48/240	1.40 (0.75, 2.64)	0.29	33
GI bleed	2/133	2/133	0.99 (0.17, 5.86)	0.99	0
Anastomotic leak	12/244	24/236	0.46 (0.22, 0.95)	0.04	0

Quality assessment for studies on the effect of enteral feeding on gut dysfunction (Cochrane quality grading for randomised controlled trials)7

Study Characteristics of 'good' quality studies on the impact of intravenous fluid therapy on gut dysfunction included in the systematic review

Author	Year	Study Population	Study Setting	Study type	Study patients	Admission diagnosis	Experimental	Intravenous fluid	Control	Intravenous fluid
Brandstrup⁹	2003	elective colorectal resection	surgery	RCT	141	postsurgical	69	restricted	72	standard
Holte¹⁰	2007	elective surgery	surgery	RCT	32	elective colorectal surgery	16	restricted	16	liberal
Holte¹¹	2007	post-surgery	surgery	RCT	48	knee arthroplasty	24	restricted	24	liberal
Gonsalez-Fajardo¹²	2009	post-surgery	surgery	RCT	40	vascular surgery transperitoneal aorto-iliac	20	restricted	20	standard
Yates¹³	2013	elective surgery	surgery	RCT	206	elective colorectal surgery	104	starch	98	crystalloid
Ghodraty¹⁴	2017	post-surgery	surgery	RCT	91	abdominal surgery	46	HES	45	ringers lactate
Gómez-Izquierdo¹⁵	2017	post-surgery	surgery	RCT	128	colorectal surgery	4	GDFT	64	control

Study Characteristics of studies on the impact of enteral feeding on gut dysfunction included in the systematic review

Author	Year	Study Population	Study Setting	Study type	Study patients	Admission diagnosis	Experimental	Control	Dindo-Clavien Classification#				Quality Grading*
									I	II	III	IV
Hoover⁵⁵	1980	surgical	surgical	RCT	48	surgical	26 EF	22IVF					Poor
Adams⁵⁶	1986	ICU surgical	ICU	RCT	46	multiple trauma	23 (EN)	23(PN)					Poor
Moore⁵⁷	1986	major abdo trauma	surgical	RCT	59	surgical	29 (EN)	30 (PN)					Poor
Bower⁵⁸	1986	surgical	surgery	RCT	20	GI/pancreato-biliary surgery	10 (EN-JeJ)	10 (PN)					Poor
Hamoui⁵⁹	1989	surgical	surgical	RCT	19	major GI surgery	11EN	8PN					Poor
Von Meyenfeldt⁶⁰	1992	surgical	surgery	RCT	101	GI/colon cancer	50 (EN)	51(PN)					Poor
Montecalvo⁶¹	1992	surgical	surgical	RCT	38	surgical	19 NG	19 NJ					Poor
Dunham⁶²	1994	critically ill	ICU	RCT	37	trauma	12 (EN)+ 15 (PN) + 10(EN+PN)						Poor
Borzotta⁶³	1994	trauma	surgical trauma	RCT	48	trauma	27 (EN)	21(PN)					Poor
Daly⁶⁴	1995	surgical	surgical	RCT	60	surgical	18ENSD; 12SD-IP; 19 ENSD-IP-OP; 11 EN-IP						Poor
Carr⁶⁵	1996	post-surgical	surgery	RCT	28	intestinal resection	14(EEN)	14(CEN)					Poor
Beier-Holgersen⁶⁶	1996	post-surgical	surgery	RCT	60	major abdominal surgery	30(EEN)	30 (placebo)					Poor
Baigrie⁶⁷	1996	post-surgical	surgery	RCT	97	oesophagectomy/gastrectomy	50 (EN)	47(PN)					Poor
VanBerge⁶⁸	1997	post-surgical	surgery	RCT	57	pancreatoduodenectomy	30 (CON)	27(CYC)					Poor
Kalfarentzos⁶⁹	1997	critically ill	ICU	RCT	38	Severe acute pancreatitis	18(EN)	20 (PN)
Heslin⁷⁰	1997	surgical	surgery	RCT	195	upper GI malignancy	97 (EN)	98(IVF)					Poor
Reynolds⁷¹	1997	major upper GI surgery	surgical	RCT	67	surgical	33 (EN)	34(PN)					Poor
Stewart⁷²	1998	elective surgical	surgery	RCT	80	colorectal resections	40 (EOF)	40 (COF)					Poor
Windsor⁷³	1998	surgical	surgical	RCT	34	acute pancreatitis	16 EN	18PN					Poor
Singh⁷⁴	1998	surgical	surgical	RCT	43	surgical	22JEJ	21IVF					Poor
Braga⁷⁵	1998	surgical	surgical	RCT	166	surgical	55 STD-EN; 55 -STD-EN enriched; 56 TPN						Poor
Taylor⁷⁶	1999	critically ill	ICU	RCT	82	head injury	41TRO	41 EN					Fair
Pupelis⁷⁷	2000	critically ill	S-ICU	RCT	60	severe pancreatitis/peritonitis	30 (JEN)	30 (Control)					Poor
Minard⁷⁸	2000	critically ill	ICU	RCT	27	head injury/trauma	12(EEN)	15(DEN)					Poor
Powell⁷⁹	2000	critically ill	ICU	RCT	27	severe acute pancreatitis	13 (EN)	14(NBM)					Poor
Kearns⁸⁰	2000	critically ill	ICU	RCT	44	critically ill	23 G	21 SI					Poor
Bozzetti⁸¹	2001	elective surgery	surgery	RCT	317	GIcancer	159(EN)	158(PN)					Poor
Braga⁸²	2001	surgical	surgery	RCT	257	GIcancer	126(EEN)	131(PN)					Poor
Montejo⁸³	2002	critically ill	ICU	RCT	101	critically ill	50 (JEN)	51(GEN)					Poor
Davies⁸⁴	2002	critically ill	ICU	RCT	73	critically ill	34 (NJ)	39 (NG)					Poor
Bertolini⁸⁵	2003	critically ill	ICU	RCT	39	Sepsis	18(EN)	17 (PN)					Poor
Kompan⁸⁶	2004	critically ill	ICU	RCT	52	multiple trauma	27(EEN)	21(DEN)					Poor
Malhotra⁸⁷	2004	post-surgical	surgery	RCT	164	perforated gut and peritonitis	83 (EN)	81(NBM)					Poor
Kumar⁸⁸	2006	Surgical	surgical	RCT	31	surgical	15 NG	16 NJ					Poor
Nguyen⁸⁹	2007	critically ill	ICU	RCT	31	critically ill	23 (NJ)	28 (NJ)					Poor
Han-Guerts⁹⁰	2007	post-surgical	surgery	RCT	150	oesophagectomy	71 (ND)	79 (JEJ)					Poor
Descahy⁹¹	2008	critically ill	ICU	RCT	100	ICU	50EEN	50CEN					Poor
Tien⁹²	2009	critically ill	ICU	RCT	200	ICU	98TRO	102 EN					Poor
Barlow⁹³	2011	Surgical	surgery	RCT	121	upper GI malignancy	64 (EN)	57(NBM+IVF)					Poor
Altintas⁹⁴	2011	critically ill	ICU	RCT	71	ICU	30 (EN)	41 (PN)					Poor
Rice⁹⁵	2011	Surgical	surgical	RCT	247	surgical	EN 123	124 IVF					Poor
Davies⁹⁶	2013	critically ill	ICU	RCT	181	ICU	91 NJ	89 NG					Poor
Zhu⁹⁷	2013	post-surgical	surgery	RCT	68	pancreaticoduodenectomy	34(JT)	34(NJT)					Poor
Sun⁹⁸	2013	critically ill	S-ICU	RCT	60	severe acute pancreatitis	30(EEN)	30(DEN)					Poor
Kadamani⁹9	2014	critically ill	ICU	RCT#	15	critically ill	15 (CON)	15 (BOL)					Poor
Boelens¹⁰⁰	2014	elective surgical	surgery	RCT	123	rectal surgery	61(EEN)	62(EPN)					Poor
Harvey¹⁰¹	2014	critically ill	ICU	RCT	2388	critically ill	1197(EN)	1191(PN)					Poor
Ma¹⁰²	2015	acute surgical	surgery	RCT	35	acute pancreatitis	17 (NTF)	18(NPO)					Poor
Bing Li¹⁰³	2015	post-surgical	surgery	RCT	400	gastrectomy	200(EEN)	200 (PN)					Poor
Taylor¹⁰⁴	2016	critically ill	ICU	RCT	50	critically ill	25 (NJ)	25(NG + ProK)					Poor
Ozen¹⁰⁵	2016	critically ill	ICU	RCT	51	critically ill	26(no-GRV's)	25(GRV's)					Poor
Van Barneveld¹⁰⁶	2016	elective surgical	surgery	RCT	123	rectal ca malignancy	61 (EEN)	62(EPN)					Good
Malik¹⁰⁷	2016	critically ill	ICU	RCT	60	critically ill	30 (EF)	30 (placebo)					Poor
Fan¹⁰⁸	2016	critically ill	ICU	RCT	80	Severe TBI	40 (EN)	40 (PN)					Poor
Stimac¹⁰⁹	2016	acute pancreatitis	pancreatitis	RCT	214	acute pancreatitis	107 EN	107 IVF					Poor
Hongyin¹¹⁰	2017	acute surgical	surgery	RCT	161	acute pancreatitis	83 (APD)/61 EN)	78(non-APD)/68(EN)					Poor
Reigner¹¹¹	2018	critically ill	ICU	RCT	2410	shock	1202(EN)	1208(PN)					Fair

Study Characteristics of 'fair ' quality studies on the impact of intravenous fluid therapy on gut dysfunction_

Author	Year	Study Population	Study Setting	Study type	Study patients	Admission diagnosis	Experimental	Intravenous fluid	Control	Intravenous fluid
Gan¹⁶	2002	major elective general, urologic, or gynaecologic surgery	surgery	RCT	100	postsurgical	50	GDFT	50	Standard
Moretti^{1 7}	2003	Major elective cardiac surgery	surgery	RCT	90	postsurgical	30 - HetaStarch normal saline; 30 Heta Starch Balanced salt; 30 Lactated Ringers
Nisanevich¹⁸	2005	elective intraabdominal surgery	surgery	RCT	157	postsurgical	77	Restrictive	75	Liberal
Kabon¹⁹	2005	open colonic resection	surgery	RCT	253	ICU surgical	124	Small volume	129	Large Volume
Lopes²⁰	2007	High-risk surgery	surgery	RCT	33	ICU surgical	17	GDFT	16	Control
Vermuelen²¹	2009	elective major abdominal surgical procedures	surgical	RCT	62	surgical	30	Restricted	32	Standard
Mayer²²	2010	major abdominal surgery	surgery	RCT	60	ICU surgical	30	GDFT	30	Standard
SAFE ²³	2011	ICU	ICU	RCT	1218	ICU	603	Colloid	615	Crystalloid
Guidet²⁴	2012	severe sepsis	ICU	RCT	196	ICU	100	Colloid	96	Crystalloid
Perner²⁵	2012	severe sepsis	ICU	RCT	798	ICU	398	Colloid	400	Crystalloid
Reddy²⁶	2016	critically ill	ICU	RCT	69	critically ill	35	plasmalyte	34	saline

Dindo-Clavien Classification

Grade	Grade Definition
Grade I	Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions Allowed therapeutic regimens are: drugs as antiemetics, antipyretics, analgesics, diuretics, electrolytes, and physiotherapy. This grade also includes wound infections opened at the bedside
Grade II	Requiring pharmacological treatment with drugs other than such allowed for grade I complications, Blood transfusions and total parenteral nutrition are also included
Grade III	Requiring surgical, endoscopic or radiological intervention Grade IIIa Intervention not under general anaesthesia Grade IIIb Intervention under general anaesthesia
Grade IV	Life-threatening complication (including CNS complications)* requiring IC/ICU management Grade IVa Single organ dysfunction (including dialysis) Grade IVb Multiorgan dysfunction)

Study Characteristics of 'poor ' quality studies on the impact of intravenous fluid therapy on gut dysfunction_

Author	Year	Study Population	Study Setting	Study type	Study patients	Admission diagnosis	Experimental	Intravenous fluid	Control	Intravenous fluid	Dindo-Clavien Classification*
Prein²⁷	1990	post-surgery	surgery	RCT	18	modified Whipple's	6- ringers' lactate; 6– starch; 6-albumin				I	II	III	IV
Salim²⁸	1991	elective surgery	surgery	RCT	130	Hartmann's procedure +/- cholecystectomy	71	early oral	59	conventional intravenous
Yogendran²⁹	1995	elective surgery	surgical	RCT	200	surgical	100	Low-infusion	100	High infusion
Wilkes³⁰	2001	elective, open surgical	surgical	RCT	47	surgical	23	Balanced	24	Saline
Lobo ³¹	2002	post-surgery	surgery	RCT	20	colorectal surgery	10	restricted	10	liberal
Conway³²	2002	major bowel surgery	surgical	RCT	57	surgical	28	GDFT	39	Standard
Venn³³	2002	hip fracture surgery	surgical	RCT	90	surgical	29CON- VF ; CVP guided FT- 3 1 ; Doppler-guided FT- 30
SAFE³⁴	2004	ICU	ICU	RCT	6997	ICU	3497	Colloid	3500	Crystalloid
Parker³⁵	2004	hip fracture surgery	surgical	RCT	396	surgical	198	Colloid	198	Crystalloid
Noblett³⁶	2005	elective colorectal resection	surgical	RCT	108	surgical	54	GDFT	54	Standard
Wakeling³⁷	2005	large bowel surgery	surgical	RCT	128	surgical	64	GDFT	64	Standard
Mackay³⁸	2006	elective colorectal surgery	surgical	RCT	80	surgical	41	Restricted	39	Standard
En-quiang³⁸	2009	critically ill	S-ICU	RCT	76	severe acute pancreatitis	30	controlled fluid expansion	30	rapid fluid expansion
Senagore⁴⁰	2009	laparoscopic colectomy	surgical	RCT	64	surgical	21 GDFT/LR; 21 GDFT/HS;2 22 standard
Futier⁴¹	2010	major abdominal surgery	surgery	RCT	70	postsurgical	36	Restricted-GDFT	34	Conservative GDFT
Benes⁴²	2010	elective intraabdominal surgery	surgery	RCT	120	ICU surgical	60	GDFT	60	Standard
Pillai⁴³	2011	post-surgery	surgery	RCT	66	radical cystectomy	34	intervention	32	control
Du⁴⁴	2011	critically ill	ICU	RCT	41	severe acute pancreatitis	20	starch	21	ringers' lactate
James⁴⁵	2011	Blunt and penetrating trauma	surgical	RCT	109	surgical	Penetrating trauma- HES 36 ; SAL 31 Blunt trauma- HES20 ; SAL 22
Challand⁴⁶	2012	major elective colorectal surgery	surgical	RCT	179	surgical	90	GDFT	89	Standard
Myberg⁴⁷	2012	ICU	ICU	RCT	7000	ICU	3500	Colloid	3500	Crystalloid
Srinivasa⁴⁸	2012	elective colectomy	surgical	RCT	85	surgical	37	GDFT Restricted	37	Restricted
Zheng⁴⁹	2013	post-surgery	surgery	RCT	60	gastrointestinal surgery	30	GDFT	30	control
Scheeren⁵⁰	2013	High-risk surgery	ICU	RCT	52	ICU	26	GDFT	26	Control
Pestana⁵¹	2014	post-surgery	S-ICU	RCT	142	abdominal surgery	70	GDFT	72	control
Pearse⁵²	2014	Major Gastrointestinal Surgery	surgery	RCT	734	surgical	368	GDFT	366	Standard
Peng⁵³	2014	elective surgery	surgery	RCT	80	orthopaedic surgery	40	GDFT	40	standard
Reisinger⁵⁴	2017	elective colorectal resection for malignancy	surgery	RCT	58	postsurgical	27	GDFT	31	Standard

Quality assessment for studies on the effect of intravenous fluid therapy on gut dysfunction (Cochrane quality grading for randomised controlled trials)7

Search Strategy

# Searches Results
1 Gastrointestinal Diseases/
2 ((gastrointestinal or intestin* or digestive) adj3 (dysfunction* or failure or disorder* or injur* or disease*)).mp.
3 ((abdominal or gut or bowel or intestin) adj3 (perforat or infarct* or obstruct* or failure or ischemi*)).mp.
4 gastroparesis.mp. or Gastroparesis/
5 gastrointestinal motilit*.mp. or exp Gastrointestinal Motility/
6 (dysmotilit* or intestinal motilit*).mp. 5645
7 Intra-Abdominal Hypertension/
8 (abdominal compartment syndrome* or intra abdominal hypertension or intraabdominal hypertension).mp.
9 feed* intolerance.mp.
10 ileus.mp. or Ileus/
11 Intestinal Obstruction/ or Intestinal Pseudo-Obstruction/ or pseudo obstruction.mp. or ogilvie’s syndrome.mp.
12 (mesenteric or peritonitis).mp. 91360
13 or/1-12 282880
14 enteral nutrition/ or parenteral nutrition/
15 Parenteral Nutrition, Total/
16 ((enteral or parenteral) adj3 (feed* or nutrition)).mp.
17 Fluid Therapy/ or intravenous fluid*.mp.
18 (fluid* adj3 therap*).mp.
19 (resuscitation adj3 fluid*).mp.
20 vasoactive.mp.
21 Vasoconstrictor Agents/ or vasoconstrictor.mp. or vasopressor.mp.
22 inotrope*.mp.
23 or/14-22
24 intensive care/ or critical illness/
25 Intensive Care Units/
26 General Surgery/
27 Postoperative Complications/ or Postoperative Care/
28 (intensive care or ICU or critical care or critical* ill*).mp.
29 (surgery or surgical or postoperative).mp.
30 or/24-29
31 randomized controlled trial.pt.
32 controlled clinical trial.pt.
33 randomized.ab.
34 placebo.ab. 35 drug therapy.fs.
36 randomly.ab.
37 trial.ab. 38 groups.ab.
39 or/31-38
40 adult/ or aged/ or “aged, 80 and over”/ or frail elderly/ or middle aged/ or (adult* or middle aged or older or old or aged or
elderly or geriatric* or frail).mp.
41 13 and 23 and 30 and 39 and 40
42 exp animals/ not humans.sh
43 41 not 42

Impact of Intravenous Fluids and Enteral Nutrition on the Severity of Gastrointestinal Dysfunction: A Systematic Review and Meta-analysis

Figures & Tables

Impact of intravenous fluid therapy on variables of gut dysfunction

Impact of enteral feeding on variables of gut dysfunction as classified by feeding categories

Quality assessment for studies on the effect of enteral feeding on gut dysfunction (Cochrane quality grading for randomised controlled trials)7

Study Characteristics of 'good' quality studies on the impact of intravenous fluid therapy on gut dysfunction included in the systematic review

Study Characteristics of studies on the impact of enteral feeding on gut dysfunction included in the systematic review

Study Characteristics of 'fair ' quality studies on the impact of intravenous fluid therapy on gut dysfunction_

Dindo-Clavien Classification

Study Characteristics of 'poor ' quality studies on the impact of intravenous fluid therapy on gut dysfunction_

Quality assessment for studies on the effect of intravenous fluid therapy on gut dysfunction (Cochrane quality grading for randomised controlled trials)7

Search Strategy

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