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DOI: 10.4172/2155-6148.1000819
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ISSN: 2155-6148
Research Article Open Access
The Effectiveness of Standard Single Dose Omeprazole vs. High Dose
Continuous Infusion in High-risk Critically Ill Patients
Ezzeldin Ibrahim* and Hala Koptan
Department of Anaesthesia and Intensive Care, Menoufia University, Shebeen-Elkoom, Egypt
*Corresponding author: Ezzeldin Ibrahim, Department of Anaesthesia and Intensive Care, Menoufia University, Shebeen-Elkoom, Egypt, Tel: +20 1006303178; E-mail:
[email protected]Received date: April 06, 2018; Accepted date: April 23, 2018; Published date: April 27, 2018
Copyright: ©2018 Ibrahim E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Objectives: The present study was carried out to investigate the beneficial effects of high dose omeprazole
versus standard low dose as a prophylaxis against upper GIT bleeding in high risk critically ill patients.
Methods: A hundred and ten high risk critically ill patients were divided into two groups, fifty-five patients each.
Group A received intravenous (IV) omeprazole 40 mg bolus dose once daily followed by normal saline infusion.
Group B received IV bolus of 80 mg omeprazole followed by 8 mg/h infusion. The treatment was for the whole
period of ICU stay. Early morning gastric pH, residual gastric volume, signs of significant upper GIT bleeding, ICU
stay Hb, number of ICU days without ventilator, ICU stay hemoglobin (Hb), number of red cell units transfused in
ICU, ICU stay, and numbers of ICU survivors were recorded.
Results: Gastric pH was higher in group B compared to group A (p<0.05). The number of patients developed
significant upper GIT bleeding were significantly higher in group A. Group A had lower ICU Hb levels and used
significant higher number of RBC units. ICU stay was significantly higher in group A compared to group B (p=0.02).
There were no statistical differences regarding the number of ICU days without ventilator and ICU survivors between
both groups (P<0.05).
Conclusions: High dose PPI continuous infusion can reduce the incidence of upper GIT bleeding in high risk
critically ill patients. High dose PPI can reduce ICU stay with no effect on ICU survivor rate.
Keywords: Proton pump inhibitor; Gastric pH; Upper PPIs are more potent than other medications due to its mechanism
gastrointestinal bleeding; Critically ill patients of action. PPIs do not show acid anti-secretory tolerance [10]. PPIs can
inhibit the parietal cells with an intravenous bolus dose. Continuous
Abbreviations: GIT: Gastrointestinal Tract; IV: Intravenous; ICU: infusion can provide a steady plasma level of the drug to inactivate
Intensive Care Unit; Hb: Haemoglobin; PPI: Proton Pump Inhibitor proton pump stimulation by histamine, food, or gastrin [6].
The present study was carried out to compare the benefits of daily
Introduction standard single shot of intravenous (IV) omeprazole versus continuous
IV infusion in upper GIT bleeders high-risk critically ill patients.
Stress may result in upper gastrointestinal (GIT) mucosal damage
and bleeding [1-3]. The pathophysiology behind gastric mucosal
damage is not completely understood. Inadequate perfusion, Methods
disruption in mucosal blood flow, increase in gastric acidity, and The local ethics committee at El-Menoufia university hospital
inadequate cellular oxygenation can lead to stress ulcers [3]. The approved this prospective randomized study. Informed written assent
incidence of gastric bleeding can be reduced by early enteral feeding was taken from the first of kin for all patients included in the study.
and with the prophylaxis use of antacids [4,5]. The study was performed on critically ill patients admitted to our
It is has been reported that up to 25% of the critically ill patients can intensive care unit (ICU) and met the inclusion criteria. The study is
develop significant GIT bleeding with haemodyanmic instability at one registered on Clinicaltrial.gov number under number NCT03388463.
stage during ICU stay [3]. Mortality rate is higher in critically ill A hundred critically ill patients of both genders, aged between 21
patients with significant gastrointestinal bleeding (48.5%) compared to and 70 years old with high-risk for stress ulcer were included in the
9.1% in non-bleeders [6]. study. Mechanically ventilated patients were identified as high-risk
Prophylaxis against upper GIT bleeding has been recommended by patients. Patients with nasogastric tube inserted as part of their
many guidelines and the surviving sepsis campaign in the critical care medical care were included in the study. Exclusion criteria included:
setting [7]. Sucralfate, histamine-type 2 receptor antagonists, and ICU patients admitted because of upper GIT re-bleeding, patients who
proton pump inhibitors (PPIs) have been recommended as prophylaxis were not scheduled for early enteral nutrition during the first 24 h of
against stress ulcer and bleeding [8,9]. ICU admission, patients with bleeding disorders, renal replacement
J Anesth Clin Res, an open access journal Volume 9 • Issue 4 • 1000819
ISSN:2155-6148
Citation: Ibrahim E, Koptan H (2018) The Effectiveness of Standard Single Dose Omeprazole vs. High Dose Continuous Infusion in High-risk
Critically Ill Patients. J Anesth Clin Res 9: 819. doi:10.4172/2155-6148.1000819
Page 2 of 5
therapy, history of gastric ulcer, gastric surgery, and the use of gastric End point
antacids before ICU admission.
The study end point was to study the effect of two different methods
Patients who met the inclusion criteria were randomized into two of omeprazole on gastric pH and its effect on the number of cases with
groups using computerized software to fifty patients in each group. clinically significant GIT bleeding. Our secondary end points were to
Group A received a daily IV single standard bolus dose of omeprazole study ICU hemoglobin level, red cell units transfused, ICU stay and
intravenously and group B received a daily high dose continuous IV ICU survival rate.
infusion of omeprazole. All patients received omeprazole during the
first hour of ICU admission and for the whole duration of ICU stay. Power analysis
Sample size was calculated using Graph pad Instant statistics
Study Design
version 3 depending on previous observations [13]. Previous studies
The study was a randomized double-blind study. Independent showed that the use of proton pump inhibitors compared to no
pharmacists prepared the omeprazole bolus and infusion syringes. prophylaxis reduced the GIT bleeding. By choosing 5% significance
Patients were randomized using a computerized computer program. level and power of 90%, the calculated sample size was 45. In the
Patients, ICU nurses, investigators, and ICU physicians were blinded present study we recruited 50 patients in each group to have reliable
to the study medications. results.
Omeprazole regimens Statistical analysis
Group A received omeprazole 40 mg bolus once a day followed by It was performed using SPSS base 17.0 package (SPSS Inc, Chicago,
continuous saline infusion (50 ml 0.9% normal saline). Group B IL, USA). Dichotomous variables are reported as percentage and
received 80 mg bolus as a loading dose followed by continuous compared using the chi- square test or exact fisher test (when the
infusion of 8 mg/h (200 mg omeprazole diluted in 0.9% normal saline expected count was <5). Quantitative variables were reported as mean
to form a total of 50 ml). Both groups received the continuous ± SD and analyzed by student t-test where P- values less than 0.05 were
infusions at a rate of 2 ml/h [6,11,12]. considered significant.
All patients were on our unit’s eternal nutrition protocol. The enteral
nutrition protocol started within six hours of patients meeting the Results
enrollment criteria. The feeding was given at a constant rate of 50 to
150 ml/hr and rest the bowel for 8 h during night through nasogastric
tube. Gastric aspirate was taken before starting the enteral feeding to
measure the baseline admission gastric pH. Aspiration of gastric fluid
was done every morning to measure the amount of overnight residual
gastric volume.
For measuring gastric pH, 5 mL of early morning gastric fluid from
the gastric fundus was aspirated. The position of the nasogastric tube
was confirmed by chest and upper abdomen X-ray according to our
unit’s protocol. Gastric fluid was transported as rapid as possible to the
laboratory. Gastric juice was centrifuged (3,000 rpm, 5 min), and
supernatant was collected; then, pH was measured using a glass
electrode. Gastric pH was measured twice daily until ICU discharge.
Gastric fluid was aspirated and measured after the overnight eight
hours rest from enteral feeding to measure the residual gastric volume.
All patients were followed up for clinically significant GIT bleeding.
Clinically significant GIT bleeding was defined if a patient had an
episode of overt sign of bleeding accompanied by reduction in mean
arterial blood pressure ≥ 20 mmHg in the absence of another clinical
cause, reduction in hemoglobin ≥ 20 g/L without another obvious
source of bleeding, or the need for endoscopic or surgical intervention
to stop GIT bleeding. Overt signs of bleeding were diagnosed if the
patient had fresh blood from the nasogastric tube, haematemisis,
melena or haematochezia. Figure 1: Flow chart for the studied patients.
Patients’ demographic data were collected. Signs of clinically
significant GIT bleeding, the number of patients required endoscopic
A total number of 476 patients were admitted to our ICU during a
intervention, feed intolerance (residual gastric volume more than 250
nine months period, 133 were ventilated and did not match the
mL), baseline admission Hb, daily Hb level, number of red cell units
inclusion criteria, and 243 did not require mechanical ventilation. A
transfused, ICU stay, number of ICU days without ventilator, and ICU
hundred patients followed the inclusion criteria and included in the
outcome were recorded.
analysis. Figure 1 shows a flow chart for patients included in the study.
Patients were divided into two equal groups fifty patients each. Group
J Anesth Clin Res, an open access journal Volume 9 • Issue 4 • 1000819
ISSN:2155-6148
Citation: Ibrahim E, Koptan H (2018) The Effectiveness of Standard Single Dose Omeprazole vs. High Dose Continuous Infusion in High-risk
Critically Ill Patients. J Anesth Clin Res 9: 819. doi:10.4172/2155-6148.1000819
Page 3 of 5
A received a daily bolus omeprazole dose and group B received (P>0.05). The length of ICU stay was longer in group A compared to
omeprazole continuous infusion. There was no significance difference group B (P=0.02). There was no statistical difference between the
regarding patients’ demographic data (P>0.05) (Table 1). number of ICU survivors in both groups (P=0.24). Table 2 shows ICU
stay characteristics for both groups.
Variables Group A Group B P value (T-test
(N=50) (N=50) or chi-square
test χ2)
Age (years) 58.40 ± 5.43 57.65 ± 6.15 0.47
Weight (kg) 73.45 ± 6.93 74.39 ± 5.27 0.2
Height (cm) 170.45 ± 3.37 171.87 ± 2.45 0.39
BMI 26.90 ± 2.46 26.83 ± 2.87 0.29
Gender (male/female) 27/23 26/24 0.28
Admission APACHE II 17.57 ± 2.73 17.84 ± 2.96 0.49
score
Admission SOFA score 5.45 ± 1.7 5.85 ± 1.2 0.41
Figure 3: Mean daily residual gastric volume (ml) in ICU.
Table 1: Patient’s demographic data. *Statistical significance (values
presented as mean ± SD).
ICU admission gastric pH (mean ± SD) was 4.68 ± 0.18 and 4.66 ± Discussion
0.14 for group A and B respectively with no statistical difference
(P=0.38). Gastric PH was significantly lower in group A compared to It is not uncommon for critically ill patients to develop upper GIT
group B during the whole period of ICU stay. The daily gastric pH after bleeding at one stage of ICU stay. Increased gastric acidity is one of the
starting omeprazole treatment is shown in Figure 2. There was no risk factors for gastrointestinal bleeding due ulcers [1]. Few protocols
statistical difference regarding residual gastric fluid volume between have been established to reduce the incidence of upper GIT bleeding.
both groups at any day during ICU stay (P>0.05) Figure 3. In the present study we compared the effect of low dose omeprazole
versus high dose in mechanically ventilated patients. We found that
patients on high dose omeprazole had higher gastric pH, lower
incidence of critical significant GIT bleeding, higher ICU stay Hb,
lower number of RBCs transfusion and shorter ICU stay.
Variables Group A (50) Group B (50) p value
Clinical significant bleeding 13/55 (23.6%) 6/55 (10.9%) 0.02*
N (%)
Nasogastric Fresh blood. 1/13 (7.7%) 0/6 (0%) 0.04*
Hematemesis 3/13 (23.1%) 1/6 (16.7%) 0.02*
Melena 8/13 (61.5%) 5/6 (83.3%) 0.01*
Haematochezia 1/13 (7.7%) 0/6 (0%) 0.04*
GIT endoscopy needed. 10/13 (77%) 3/6 (50%) 0.03*
ICU admission Hb (mean ± 11.5 ± 1.8 11.6 ± 1.6 0.65
SD) g/dl
Figure 2: Mean gastric pH during ICU stay.
ICU stay Hb (mean ± SD) 7.5 ± 0.67 8.8 ± 0.89 0.04*
g/dl
The number of cases developed clinically significant GIT bleeding
was higher in group A compared to group B (P<0.05). Different ICU red cell units transfused 6 ± 1.5 3 ± 1.2 0.03*
presentations of GIT bleeding and the number of cases are shown in Number of ICU days without 6 ± 1.7 5 ± 1.3 0.25
Table 2. The number of patients required endoscopy for upper GIT ventilator.
homeostasis was statistically higher in group A compared to group B
(P<0.05). The mean ICU admission Hb level was comparable between ICU stay (day) 12 ± 2.3 8 ± 1.5 0.02*
both groups (P=0.65). The mean ICU stay Hb level was significantly ICU mortality rate N (%) 11/55 (20%) 10/55 (18.2%) 0.58
lower in group A compared to group B (P<0.05). Group A received
more RBCs units during ICU stay than group B (P<0.05). The number
of ICU days without ventilator was comparable between both groups Table 2: ICU stay characteristics. *Statistical significance.
J Anesth Clin Res, an open access journal Volume 9 • Issue 4 • 1000819
ISSN:2155-6148
Citation: Ibrahim E, Koptan H (2018) The Effectiveness of Standard Single Dose Omeprazole vs. High Dose Continuous Infusion in High-risk
Critically Ill Patients. J Anesth Clin Res 9: 819. doi:10.4172/2155-6148.1000819
Page 4 of 5
Most of the studies have investigated the effect of different PPIs authors found that high dose omeprazole reduced the incidence of re-
regimens as an adjuvant treatment for endoscopy in treating of upper bleeding with reduction in the number of red cell units transfused. In
GIT bleeding [14]. Very few studies have investigated the role of the present study we found that high dose omeprazole decreased the
different antacids regimens in the prophylaxis of GIT bleeding. number of red cell units in patients with high risk of GIT bleeding.
From both studies we assume that prophylaxis and treatment of upper
Pang et al. reviewed some studies to investigate the use of PPIs in
GIT bleeding with high dose omeprazole may have a massive impact
different medical scenarios [5]. The authors mentioned that PPIs are
on blood use in patients with risk GIT bleeding. None of the previous
widely used in medical practice. The review did not reach a conclusion
studies recorded the differences in Hb levels between groups, however,
about the clinical relevance of keeping the gastric pH more than 6 in
in our study we showed that ICU Hb level was higher in patients
preventing upper GIT bleeding. In our study we measured gastric pH
received high dose omeprazole.
aiming to explore the clinical relevance of keeping the pH above 6. We
found that higher gastric pH had a good clinical impact on decreasing In contrast to our study Sachar et al. and Wang et al. did two
the incidence of upper GIT bleeding. different systematic reviews and meta-analysis on intermittent versus
continuous PPIs treatment patients with high risk of GIT bleeding
Few studies have investigated the effect of different doses and
[9,11]. The authors found that continuous infusion has no advantage
medications on treatment but not the prophylaxis of upper GIT
over the standard routine bolus dose. The difference between our
bleeding. Labenz et al. did a study to compare the effect of high dose
results and the reviews may be due to the difference in the aim of our
ranitidine and omeprazole on gastric pH in patients with gastric ulcer
study. The reviews primary aim was to investigate re-bleeding up to 30
[3]. The authors found that high dose omeprazole increased gastric pH
days in patients with diagnosed upper GIT ulcer. In the present study
with better patients’ outcome. Our study agrees with Labenz et al.
we did not study the re-bleeding cases because our primary aim was to
regarding the effect of high dose omeprazole on gastric pH. Platelets
compare the prophylactic effect of different regimens of omeprazole
aggregation and better haemostasis occurs in high pH rather than low
but not a therapeutic effect.
pH and bleeding. The gastric pH we achieved by treatment in our high
dose omeprazole group was sufficient to reduce the incidence of gastric Some authors studies the adverse effects from PPI. Osteoporosis,
mucosa dysfunction. renal affection, pneumonia, iron and vitamins deficiency, and
thrombocytopenia were reported in long-term use of PPI [20]. In the
Somberg et al. did a multicenter randomized trial to compare the
present study we did not collect data regarding PPI side effects because
use of intermittent PPI versus continues cemitedine infusion in
we studied patients for short period of time and most of the
prophylaxis against upper GIT bleeding [15]. The advantage of our
complications arise from long-term therapy.
study over Somberg et al. is that we compared two different regimens
of the same drug and one of these regimens is a common standard In conclusion, gastric acid suppression is required in high-risk
practice in most ICUs. Somberg et al. found that intermittent IV PPI is critically ill patients. Prophylactic high dose continuous omeprazole
effective in controlling the gastric pH and protected patients against infusion is more effective than low standard dose to increase gastric
GIT bleeding [15]. In the present study we found that continuous PPI pH and guard against upper GIT bleeding in high-risk patients in the
infusion had a superior effect than intermittent regimen. critical care sitting. This regimen of treatment is more beneficial for
patients with less bleeding, better ICU stay Hb, less red cell
In our literature review we could not find studies to show the effect
transfusion, and shorter time in ICU.
of PPIs or gastric pH on the residual gastric volume in adults. However,
Schmidt et al. studied the effect of gastric pH and its effect on gastric
residual volume in children [16]. The authors found that alteration of References
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J Anesth Clin Res, an open access journal Volume 9 • Issue 4 • 1000819
ISSN:2155-6148
Citation: Ibrahim E, Koptan H (2018) The Effectiveness of Standard Single Dose Omeprazole vs. High Dose Continuous Infusion in High-risk
Critically Ill Patients. J Anesth Clin Res 9: 819. doi:10.4172/2155-6148.1000819
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ISSN:2155-6148
