Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia

Ranitidine 150 mg was given to 126 patients requiring elective Caesarean section under general anaesthesia: 43 women had ranitidine alone, 43 had this supplemented by a pre-induction dose of sodium citrate and 40 patients had ranitidine plus sodium bicarbonate. All three sub-groups provided satisfactory gastric pH and volume. Ranitidine 150 mg was given orally every 6 hours to women in labour. Of 221 patients requiring general anaesthesia during labour, 103 women received 30 ml 0.3 M sodium citrate and 118 women, 20 ml of 8.4% sodium bicarbonate 10 minutes before induction of anaesthesia. In the citrate sub-group there was one patient with a gastric pH less than 2.5 (mean pH 6.2, SEM 0.13 range 2.1-8.4). In the bicarbonate sub-group the lowest gastric acidity was 3.8 (mean pH 8.3, SEM 0.11 range 3.8-9.83).     

The effect of preoperative oral administration of ranitidine on pH and volume of gastric juice]

The effect of ranitidine, administrated 2 or 4 hours prior to induction of anesthesia, on volume and pH of gastric juice was investigated in patients undergoing elective surgery. Three-hundred mg of ranitidine was administrated orally in 54 patients 2 hours prior to anesthesia and in 50 patients 4 hours prior to anesthesia. The volume and pH of gastric juice were measured immediately after induction of anesthesia. In more than 90% of patients of both groups, volume of gastric juice was smaller than 25 ml and its pH was more than 2.5. Ranitidine 450 mg was administrated orally in 7 patients, and its plasma concentration was measured 2, 4 and 6 hours after administration. In one patient, volume of gastric juice was larger than 25 ml and its pH was less than 2.5. Ranitidine concentration in this patient was below the effective level 2 hours after administration and it was above the level after 4 hours. We concluded that oral administration of ranitidine 300 mg, 4 hours preoperatively, could be more effective to prevent aspiration pneumonitis than when it is given 2 hours preoperatively.     

A comparison of the effects of omeprazole and ranitidine on gastric secretion in women undergoing elective Caesarean section

This study compares the efficacy of omeprazole and ranitidine at reducing gastric secretion in obstetric patients. Sixty-five women scheduled to undergo elective Caesarean section under general anaesthesia were randomly allocated to receive either omeprazole 40 mg or ranitidine 150 mg orally at 2200 hours the night before and at 0600 hours on the morning of surgery. Intragastric pH and volume were measured immediately after induction of anaesthesia and on completion of surgery. All patients had gastric aspirates less than 25 ml. None of the omeprazole group had an aspirate of pH less than 3.5. Six patients (19%) in the ranitidine group had aspirates of pH less than 3.5, a significant difference from the omeprazole group (p less than 0.05). Of these six, two (6%) had aspirates of pH less than 2.5. Hence this study showed that omeprazole was more effective and consistent than ranitidine at maintaining gastric pH greater than 3.5.     

Comparative trial of the effect of ranitidine and cimetidine on gastric secretion in fasting patients at induction of anaesthesia

A comparative trial of the H2-receptor antagonists, cimetidine and ranitidine, on gastric pH and volume, was conducted in 168 healthy patients coming to elective surgery. The drugs were administered in random fashion either intravenously (ranitidine 50 mg or 100 mg, cimetidine 300 mg or placebo) or orally (ranitidine 150 mg, cimetidine 300 mg or placebo). The patients received the drugs or placebo 45 minutes to five hours before operation. After induction of anaesthesia, a nasogastric tube was passed and the stomach contents were aspirated. The volume and pH were measured. Those patients receiving ranitidine 50 or 100 mg or cimetidine 300 mg intravenously had statistically significantly higher gastric pH compared to those receiving placebo, but up to eight percent of patients has a pH less than 2.5. Oral administration of cimetidine 300 mg or ranitidine 150 mg were also superior when compared to placebo. However, 25 per cent of the patients receiving oral cimetidine had a pH less than 2.5; cimetidine orally was statistically significantly inferior to ranitidine 100 mg given intravenously. We conclude that the intravenous use of either ranitidine or cimetidine is an acceptable method to decrease the acidity of gastric contents before induction of anaesthesia. Orally, ranitidine appears to be a better choice than cimetidine in the doses studied. Both ranitidine and cimetidine need to be given at least 45 minutes before induction of anaesthesia to be effective; therefore the use of these agents to decrease the risk of acid pulmonary aspiration syndrome by no means obviates the need for proper anaesthesia technique during induction of anaesthesia.     

Ranitidine and prevention of pulmonary aspiration syndrome

Thirty-seven patients undergoing elective abdominal surgery (excluding gastric operations) received either ranitidine 300 mg or placebo orally at 10 p.m. in the evening preceding surgery in a double-blind randomised study. The mean time interval between this oral premedication and induction of anaesthesia was 12 h. When compared to placebo, ranitidine decreased significantly (P less than 0.05) the amount of gastric juice, and none of the ranitidine-treated patients had an increased risk of acid pulmonary aspiration (pH below 2.5 and volume over 25 ml), while four patients in the control group had an increased risk (21%). The mean ranitidine blood level was 237 ng/ml at the time of induction of anaesthesia. It is concluded that in elective abdominal surgery ranitidine included in the premedication is likely to decrease the risk for acid pulmonary aspiration.     

Gastric fluid volume and pH in elective surgical patients: triple prophylaxis is not superior to ranitidine alone

The effect of oral ranitidine alone was compared with sequentially administered ranitidine, metoclopramide, and sodium citrate on gastric fluid volume and pH in 196 healthy, elective surgical inpatients, each of whom was randomly assigned to one of four groups. Patients in all groups received oral ranitidine 150 mg 2-3 hr before the scheduled time of surgery. Those in Group 1 also received oral metoclopramide 10 mg one hour before surgery, and sodium citrate 0.3 M 30 ml on call to the operating room; Group 2 received sodium citrate but no metoclopramide; Group 3 received metoclopramide but no sodium citrate; Group 4 received ranitidine alone. Following induction of anaesthesia a #18 Salem sump tube was passed into the stomach and all available gastric fluid was aspirated. Volumes were recorded and pH measured. In all groups mean pH was greater than 5.8, although at least one patient in each group had pH less than 2.5. Mean volumes were significantly greater in patients who received citrate (Groups 1 and 2: 22 and 19 ml) than in those in those who did not (Groups 3 and 4: 10 and 8 ml). One patient in Group 2 and one in Group 3 had pH less than 2.5 with volume greater than 25 ml. Our results do not demonstrate any advantage of double or triple prophylaxis over ranitidine alone. The practical difficulty of correctly administering two or even three medications, each at different but exact preoperative intervals, is emphasized.     

Sodium bicarbonate as a single dose antacid in obstetric anaesthesia

Gastric pH and volumes were measured in 84 women who had general anaesthesia for emergency Caesarean section. Forty-eight received only 20 ml 8.4% sodium bicarbonate immediately before induction of anaesthesia and 36 ranitidine 150 mg 6-hourly during labour in combination with NaHCO3. Gastric pH was less than 2.5 in four women who received only bicarbonate. All aspirates from the ranitidine plus bicarbonate group had a pH greater than 2.5. Mean volumes of gastric content aspirated were 87 (SD 87.4) and 60 (SD 46.3) ml for the bicarbonate alone and bicarbonate plus ranitidine series respectively. These differences were not significant. Twenty millilitres of 8.4% NaHCO3 cannot be recommended as a single dose antacid for emergency Caesarean section. Ranitidine plus bicarbonate is considered a reliable antacid regimen to ensure elevation of gastric pH to safe levels.     

Sodium citrate premedication in elective caesarean section patients

The pH and volume of gastric contents from thirty-three patients undergoing elective caesarean section with thiopentone, nitrous oxide, succinylcholine anaesthesia were examined. Twenty patients received Gelusil® 30 ml by mouth and thirteen patients received 30 ml of a 0.15 molar solution of sodium citrate. Following trachéal intubation, gastric fluid was sampled through an 18 French Salem sump tube placed orally. Mean pH following Gelusil® was 4.54 ± 2.45 (SD) and 2.29 ± 1.77 following sodium citrate. This difference was statistically different (P < 0.05). There was no difference in gastric volume between the two groups. Thirty-five per cent of patients receiving Gelusil® had a pH < 2.5. This low pH was more likely to occur with prolonged intervals between drug administration and sampling. Significantly more patients receiving sodium citrate had a low pH (85 per cent) and this low pH was not related to the duration of interval between administration and sampling. This study demonstrates that 30 ml of 0.15 molar sodium citrate is not a satisfactory alternative to 30 ml of Gelusil® for increasing gastric pH in the parturient when given sixty minutes before operation.     

Intraoperative, direct and continuous measurement of stomach pH following pretreatment with ranitidine or sodium citrate

We carried out continuous direct pH measurements of gastric fluid in 49 female patients pretreated with 300 mg ranitidine by mouth on the evening prior to surgery and 150 mg by mouth before the operation. A further 51 women were pretreated with 30 ml sodium citrate shortly before admission to the operating room. Twenty patients received 30 ml sodium citrate via a separate gastric tube after the first pH measurement; 22 were given no premedication. In 95% of cases, 30 ml sodium citrate was found to increase the pH to over 3.5 within 5 min; a failure rate of 5% can therefore be expected. This can be explained mainly by the failure of sodium citrate to mix thoroughly with the gastric fluid. Pretreatment with ranitidine increased the pH to over 4.0 in every case, and the pH on extubation was still over 4.0 even after delayed pH on extubation was still over 4.0 even after delayed or prolonged operations. We recommend that 30 ml sodium citrate be given shortly before the beginning of emergency obstetric operations. However, we prefer ranitidine for elective operations in patients at risk for aspiration because it increases of the gastric fluid pH to at least 4.0 in every case.     

EFFECTS OF OMEPRAZOLE, RANITIDINE, FAMOTIDINE AND LACEBO ON GASTRIC SECRETION IN PATIENTS NDERGOING ELECTIVE SURGERY

We have compared the effects of omeprazole, ranitidine, famotidineand placebo on gastric secretion in a double-blind study in110 patients undergoing elective surgery. Three hours beforeoperation, the patients received, orally, omeprazole 40 mg,ranitidine 150 mg, famotidine 40 mg or placebo. Gastric volumeand pH were measured immediately after induction of anaesthesia.Omeprazole, ranitidine and famotidine produced a significantincrease in gastric pH and a significant decrease in gastricvolume compared with placebo. When the effects of omeprazoleon gastric volume were compared with those of ranitidine andfamotidine, no significant difference was found, but omeprazolewas significantly less effective in increasing gastric pH. Thenumber of patients having a pH less than 2.5 and a volume greaterthan 0.4 mlkg^–1 were: none in the ranitidine group, one(3%) in the famotidine group, four (15%) in the omeprazole groupand six (23%) in the placebo group. We conclude that omeprazole40 mg given 2–4 h before surgery does not afford adequateprophylaxis for the acid aspiration syndrome.     

Oral ranitidine for prophylaxis against Mendelson's syndrome

The effect of the new H2 receptor antagonist ranitidine on gastric pH was studied using a double-blind technique in 36 patients undergoing elective surgery, 18 of whom were given 150 mg of ranitidine orally the night before and on the morning of surgery. The incidence of gastric residue pH higher than 2.5 (p less than 0.01) was significantly greater in patients given ranitidine than in 18 untreated control patients. The mean volume of gastric aspirate in the treated group as 6.7 ml (range 2 to 20 ml) compared with the control group 15.6 ml (range 2 to 44 ml). The higher potency, longer duration of action, and fewer side effects of ranitidine compared with cimetidine suggest that this drug may have clinical advantages over other H2 receptor antagonists.     

Utility of premedication with different regimens of omeprazole and ranitidine in the prevention of acid broncho-aspiration syndrome]

OBJECTIVE. To study the usefulness of several omeprazole regimens on gastric fluid volume and pH in patients undergoing elective surgery. MATERIAL AND METHODS. We analyzed 105 patients undergoing to elective surgery who received prophylactic treatment for the acid aspiration syndrome. They were randomly allocated into 7 homogeneous groups according to the therapeutic regime. Placebo (group 1), oral omeprazole (20 mg) the night prior to surgery (group 2), oral ranitidine (150 mg) the night before (group 6), two doses (the previous night and before surgery) in the remaining three groups: 20 mg of omeprazole (group 4), 40 mg of omeprazole (group 5) or 150 mg of ranitidine (group 7). In all patients we measured pH and volume of the gastric content after induction of anesthesia and one hour thereafter. RESULTS. There were no statistically significant differences in mean pH values and gastric volume content among groups 1.2,3, and 6 (2.1 (pH) and 27 ml (gastric volume) in group 1, 2.1 and 23 ml in group 2, 2.6 and 19 ml in group 3, and 2.2 and 32 ml in group 6). With repeated doses of 40 mg omeprazol (group 5), mean pH values were comparable to those found with the two doses of ranitidine (4.1 +/- 1.8 vs 4.1 +/- 3.6) although gastric volumes were significantly less (12 +/- 2.6 ml vs 20 +/- 4.8 ml). These two groups showed significantly greater mean pH values and less gastric volumes than the remaining patients. CONCLUSIONS. The incidence of patients with gastric content deemed at risk for acid aspiration (pH less than 2.5 and gastric volume greater than 25 ml) was less after premedication with two oral doses of omeprazole (40 mg) than either two doses of ranitidine (150 mg) or smaller doses of both drugs.     

Effects of single-dose oral ranitidine and sodium citrate on gastric pH during and after general anaesthesia

The effects on gastric pH of the H₂-receptor antagonist ranitidine (R) with 0.3 molar (M) sodium citrate (SC) as an oral effervescent and those of plain SC were studied in 25 patients scheduled for elective surgery. Following induction of general anaesthesia, the gastric contents were evacuated via a nasogastric tube, and a pH electrode was placed in the stomach. Then, eight patients received R 300 mg plus SC dose (Group R300), ten received R 150 mg plus SC dose (Group R150), and seven received 50 ml SC alone (Group SC). The drugs were administered orally in a double-blind fashion, and the gastric pH was recorded continuously over a period of 24 hr. Mean (range) baseline pH values were 1.2 (0.8–1.8), 1.3 (1.0–1.8), and 1.2 (0.9–1.6) in the R300, R150, and SC groups, respectively (P = NS among groups). These values increased to 7.0 (6.2–7.5), 6.9 (6.3–7.3), and 4.9 (1.9–7.3), respectively, at emergence from anaesthesia (P < 0.05 for R300 vs SC and R150 vs SC). Two minutes after administration of R300 and R150, a mean (range) gastric pH of 6.8 (5.8–7.5), and 5.6 (1.2–7.0), respectively, was reached, and remained above 2.5 for 14 hr (P = NS). Plain SC increased the gastric pH within two minutes to a mean of 6.8 (6.7–7.0), and maintained it above 2.5 for six hours (P < 0.05 for R300 vs SC at 8, 10, 12, and 14 hr after induction). We conclude that both the combination of R plus SC, and SC alone are rapidly effective in neutralizing gastric acid when administered orally after induction of anaesthesia. However, the effectiveness of plain SC is shorter-lived, and if maintenance of gastric pH above 2.5 for longer than six hours is needed, the R plus SC combination should be administered.     

Ranitidine as an antacid before elective Caesarean section

In a preliminary study, 20 women in labour received ranitidine 50 mg intravenously. No significant changes were seen in the height, frequency or amplitude of uterine contractions or in fetal heart rate or pattern. No neonatal problems attributable to ranitidine were found. Ranitidine crossed the placenta, the mean fetal-maternal ratio being 0.9. Levels in the infants 12 hours following delivery were all very low. Ranitidine 150 mg orally was given to 80 healthy women undergoing elective Caesarean section at varying times from 75 to 510 minutes pre-operatively. From 2 to 6 hours following ingestion, the pH of gastric contents was greater than 2.5 in all but one patient. The mean volume aspirated (8 ml) was significantly lower than in a control group receiving magnesium trisilicate (mean volume 30 ml). Neonatal assessment included Apgar scoring, neurobehavioural examination, feeding progress, measurement of acidity and culture of gastric aspirates. No significant differences between groups were found. Blood levels indicated that the oral drug is readily absorbed by the parturient and that a smaller proportion is transferred to the fetus, mean fetal-maternal ratio at delivery being 0.38.     

A comparison of the effects of ranitidine and omeprazole on volume and pH of gastric contents in elective surgical patients

BACKGROUND AND OBJECTIVE: In cases of aspiration of gastric contents the risk of pneumonitis is dependent on the pH and volume of the gastric contents. Omeprazole and rantidine each decrease gastric volume and increase gastric pH. We evaluated the efficacy of preoperative administration of omeprazole (60 mg) or ranitidine (150 mg) in the prophylaxis of aspiration pneumonitis. METHODS: Data were obtained from 75 elective female surgical patients randomly allocated to one of three groups, who received either omeprazole 60 mg orally, or ranitidine 150 mg orally, or neither, on the evening prior to, and on the morning of, surgery. Gastric volume and pH was measured using blind aspiration. RESULTS: Both pH < 2.5 and volume > 25 mL were present in none of the patients in either the ranitidine or omeprazole groups, compared to 15 of 25 control patients (P < 0.0001). CONCLUSIONS: Preoperative oral administration of omeprazole (60 mg) or ranitidine (150 mg) reduced residual gastric content volume and increased pH > 2.5, possibly reducing the effects of pulmonary aspiration of gastric contents.     

Pre-operative intramuscular ranitidine and cimetidine

A controlled trial was carried out on 120 healthy patients presenting for elective surgery. The patients were divided randomly into three groups, which received respectively, 50 mg ranitidine, 100 mg ranitidine, or 300 mg cimetidine intramuscularly at least 45 minutes before operation. Following induction of anaesthesia, a nasogastric tube was passed, the stomach contents aspirated and analysed for volume and pH. Thirteen per cent of cimetidine-treated patients had a gastric pH of 2.5 or less, compared to 8% of those given ranitidine 50 mg and 3% of those given ranitidine 100 mg; however, these differences were not statistically significant. No side effects attributable to the administration of either drug were observed. It is concluded that intramuscular administration of ranitidine or cimetidine is an effective method of reducing the number of patients at risk of acid aspiration during anaesthesia. However, neither drug eliminates the risk of acid aspiration in all patients, and thus careful anaesthetic technique to protect the airway remains essential.     

Comparison of the effect of two dose schedules of oral omeprazole with oral ranitidine on gastric aspirate pH and volume in patients undergoing elective surgery

We have compared gastric aspirate pH and volume at induction of anaesthesia in 222 patients who had received either omeprazole or ranitidine before elective operations. Omeprazole was given orally either as 40 mg on the evening before and 40 mg on the morning of surgery or as 80 mg on the morning of surgery. Ranitidine 150 mg was given orally on the evening before surgery and 2 h before anaesthesia. Treatment success was defined as aspirate pH > or = 2.5 and volume < 25 ml at induction of anaesthesia. Treatment was successful in 84% (95% confidence interval (CI) 73-91%) of patients in the omeprazole 40 + 40 mg group, 84% (95% CI 73-91%) in the ranitidine group and 73% (95% CI 61-83%) in the omeprazole 80 mg group. There were no statistically significant differences between the groups. Twelve patients in the omeprazole 80 mg group had gastric pH < 2.5 and four had volume > 25 ml. Only three patients had a gastric pH < 2.5 in the omeprazole 40 + 40 mg group and none had volume > 25 ml, which compared well with the ranitidine group. Omeprazole, given as 40 mg in the evening and 40 mg on the morning of operation, has a potential role for use in patients at risk for aspiration during general anaesthesia.      

Comparison of the effects of oral nizatidine and ranitidine on gastric volume and pH in patients undergoing gynaecological laparoscopy

Ninety patients who presented for elective gynaecological laparoscopy as day cases were allocated at random to three groups and studied on a double blind basis to compare the effects of nizatidine, ranitidine or placebo on gastric secretion. All the patients received the active drugs or placebo orally at least 45 minutes before the induction of anaesthesia. After tracheal intubation gastric fluid was aspirated via an orogastric tube and the volume and pH of the aspirate were measured. Venous blood samples were obtained at the times of gastric sampling to determine the plasma levels of the drugs. The proportion of patients with both pH greater than 2.5 and volume less than 25 ml were 100%, 90%, and 92.9% in the nizatidine, ranitidine and placebo groups respectively. There was no difference in volume between groups. Two patients in the nizatidine group without a measurable aspirate had blood levels less than the therapeutic range. The median pH values in both treated groups were significantly greater than in the placebo group, but there were no differences between the two treated groups. There were 19 (67.8%) patients in the placebo group with pH less than 2.5. This was significantly higher than the 2 (7.4%) and 6 (20%) in the nizatidine and ranitidine groups respectively. When the time interval between drug administration and induction of anaesthesia was divided arbitrarily into 45-90 minutes and greater than 90 minutes, all the patients in the nizatidine and ranitidine groups with pH less than 2.5 were given the drugs in the 45-90 minute interval; this suggests a latent period is required before the gastric pH increases. Nizatidine may be an effective protective agent against acid aspiration syndrome.     

Effect of preanesthetic intramuscular ranitidine on gastric acidity and volume in children

Study Objective: To evaluate the effects of preanesthetic administration of intramuscular (IM) ranitidine on pH and volume of gastric contents in children.

Design: Three randomized treatment groups.

Setting: Central operating rooms at a university hospital.

Patients: Forty children age 1 to 10 years undergoing a variety of elective surgical procedures requiring general anesthesia with endotracheal intubation.

Interventions: IM ranitidine 1 mg/kg (n = 15) or 2 mglkg (n = 15) was administered 2 hours prior to induction of anesthesia. Ten patients without ranitidine served as the control group. An orogastric tube was inserted into each patient.

Measurements and Main Results: Gastric fluid pH and volume were measured every hour in the three groups. Plasma ranitidine concentrations were measured in ten patients of the ranitidine-treated groups. The mean volume of gastric fluid at induction of anesthesia was significantly lower in the ranitidine-treated patients (2.4 ml for ranitidine 1 mg/kg, 3.2 ml for ranitidine 2 mglkg) than in the controls (8.6 ml, p < 0.05). The mean pH values at induction of anesthesia were significantly higher in the ranitidine-treated patients (4.6 for 1 mg/kg, 6.7 for 2 mg/kg) than in the controls (2.1; p < 0.05). Dose-dependent plasma ranitidine concentrations were obtained.

Conclusions: Preanesthetic IM ranitidine 1 to 2 mglkg resulted in a higher pH and lower volume of gastric fluid at the time of induction and in a higher pH during 3 hours of anesthesia. This therapy may be a useful adjunct to premeditation for children who have a greater than normal risk of pulmonary aspiration during anesthesia.     

Cimetidine as a single oral dose for prophylaxis against Mendelson's syndrome.

Cimetidine, a histamine H2-receptor antagonist which inhibits gastric acid secretion, was administered as a single 400 mg oral dose before anaesthesia to forty-six patients undergoing elective gynaecological surgery. The incidence of gastric residue pH above 2.5 was significantly greater (P less than 0.001) in cimetidine treated patients than in thirty-seven control patients. No patient who received cimetidine between 4 and 6 h prior to anaesthesia had a gastric residue pH less than 2.5. These findings suggest that cimetidine may be effective as a prophylaxis against acid pulmonary aspiration (Mendelson's) syndrome.