Infectious Complications of Ranitidine compared with Sucralfate

 

When compared with sucralfate the use of ranitidine for gastric prophylaxis in the severely injured patient is associated with an increased incidence of pneumonia and other infective complications but has an insignificant affect on mortality. Level of Evidence 1-

 

Citation/s:
Incidence of Infectious Complications Associated With the Use Of Histamine2-Receptor Antagonists in Critically Ill Trauma Patients. O' Keefe GE et al. Annals of Surgery. 1998. 227, (1): 120-125
Lead author's name and fax: Dr Grant E. O'Keefe. Department of Surgery, University of Alberta, Walter MacKenzie Health Services Center, 8440-112 Street, Edmonton, Alberta, Canada, T6G 2B7

 

Three-part Clinical Question: Does the use of the histamine2 (H2) blocker ranitidine, for gastric prophylaxis, lead to an increase in the occurrence of infective complications in the severely ill when compared to sucralfate.

Search Terms: RCT, Gastrointestinal haemorrhage, ranitidine, sucralfate

 

The Study: Double-blinded randomized controlled trial with intention-to-treat.

The Study Patients: Severely injured patients managed in intensive care (average injury severity score (ISS) 28.7). 62% severe head injury, 59% severe chest injury, 29% severe abdominal injury. Average age 34.3. Equal distribution between the two study groups. All patients were intubated and had gastric drainage tubes in situ. Prophylactic antibiotics were only used for open fractures and GI injuries (for 24hrs post-op) Pneumonia data collected prospectively - Pneumonia defined as WCC>12,000/ml, a new or changing infiltrate on CXR, temperature >38.5 or 15 colonies of a single pathogen by semiqunatative culture of the intracutaneous segment of an iv catheter and a temperature of >38.5 or 100,000/ml. For individual patients, each positive catheter culture was counted as a separate complication, as were repeat positive cultures after an appropriate course of antibiotics for bacteraemia. Repeat episodes of pneumonia were defined by the presence of new pathogens on sputum culture.

Control group (N = 47; 47 analyzed): Sulcralfate patients (47). These patients received sucralfate 1g every 6 hours as a slurry via gastric tube.

Experimental group (N = 49; 49 analyzed): Ranitidine patients (49). These patients received a loading dose of ranitidine of 0.5mg/kg followed by a continuous infusion of 0.25mg/kg/hr.

The Evidence:

Outcome	Time to Outcome	CER	EER	RRR	ARR	NNT
Mortality	ICU stay	0.128	0.224	-75%	-0.096	-10
	95% Confidence Intervals:			-193% to 43%	-0.247 to 0.055	NNT = 18 to INF; NNH = 4 to INF
Pneumonia	ICU stay	0.298	0.531	-78%	-0.233	-4
	95% Confidence Intervals:			-142% to -14%	-0.424 to -0.042	-24 to -2
Bacteraemia	ICU stay	0.4	1.12	-180%	-0.720	-1
	95% Confidence Intervals:			-204% to -156%	-0.815 to -0.625	-2 to -1

 

Non-Event Outcomes	Time to outcome/s	Control group	Experimental group	P-value
Total infections	ICU stay	50	128	0.0014
Primary infections (excluding +ve blood cultures within 48hrs of a +ve culture from an other site with same pathogen)	ICU stay	46	114	0.0042
Non-catheter related infections (excluding all positive semiquantitive catheter cultures)	ICU stay	44	102	0.0046

Comments:
1) Is this study relevant to our patients?
Trauma patients only which is not representative of most patient groups
2)Any concerns about the methodology?
Unclear whether the caring teams were blinded to study drugs.
Time of follow-up in unclear - I have presumed it is during ICU stay.
The indication for blood culture and other microbiological investigation is not stated. Each positive culture qualified as a separate event. This could result in a higher rate of infection in the patients which had more investigations performed. An attempt to reduce this has been made by calculating the number of primary infections (by excluding positive blood cultures obtained within 48hrs of a positive culture from another site with the same pathogen)

Additional information
Reduced ICU (p=0.02) and hospital (p=0.16) stay in the sucralfate group

Appraised by: Dr Chris Cairns, Spr, ICU, Royal Infirmary of Edinburgh; Tuesday, March 12, 2002
Email: Chris.Cairns@btinternet.com
Kill or Update By: March 2005

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