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.     

Ranitidine and single-dose antacid therapy as prophylaxis against acid aspiration syndrome in obstetric practice

The efficacy of the non-particulate antacid 0.3 M sodium citrate in single and multiple dose regimes was investigated in 156 obstetric patients, both emergency and elective, who required operative delivery under general anaesthesia. Failure of either of these regimes to elevate the intragastric pH consistently to an acceptable level (greater than 3) led to investigation of a regime combining the histamine H2-receptor antagonist, ranitidine, and a single pre-anaesthetic dose of 0.3 M sodium citrate in a further 170 patients. Satisfactory pH values (greater than 3) were achieved in all patients studied. The results from the first 99 cases were analysed statistically by comparison with the multiple dose sodium citrate regime and showed a very significant improvement in the ranitidine group for intragastric pH and volume. No untoward side-effects were discovered in either mother or baby and the 6-hourly administration of ranitidine, which was easily complied with, had no effect on the progress of labour or operative delivery rate.     

Combination treatment with ranitidine and sodium bicarbonate prior to obstetric anaesthesia

The gastric pH and volume were measured in 175 patients undergoing elective, and 313 undergoing emergency, obstetric procedures. Ranitidine 150 mg was administered orally every 6 hours in labour and at least 2 hours before elective Caesarean section. Patients received 20 ml of 8.4% sodium bicarbonate orally immediately prior to induction of anaesthesia. The combination of ranitidine and sodium bicarbonate produced marked alkalinisation of gastric contents (mean pH 8.9). The administration of sodium bicarbonate pre-operatively in patients who received ranitidine less than 2 hours before operation led to satisfactory elevation of gastric pH. Only four patients had a gastric pH less than 2.5, one patient refused any medication, two received only ranitidine and one patient had a long interval from administration of bicarbonate to aspiration of gastric contents. Gastric volumes were high in labouring patients (mean 84 ml) despite administration of ranitidine. The effectiveness of sodium bicarbonate as a single dose antacid therapy prior to obstetric anaesthesia requires further study.     

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).     

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 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.     

Acid aspiration prophylaxis in morbidly obese patients: famotidine vs. ranitidine

Famotidine and ranitidine were compared as agents for the prevention of acid aspiration syndrome in 32 morbidly obese patients undergoing vertical banded gastroplasty. Single-dose oral famotidine or double-dose oral ranitidine were administered on a random basis before surgery. Gastric contents were aspirated through a gastric tube, manually aided by the surgeon with the abdomen open. Mean (SD) gastric volumes were 13.8 ml (6.7) and 12.1 ml (13.0) for the famotidine and ranitidine groups, respectively. Mean (SD) gastric pH values were 6.2 (1.5) and 6.8 (1.5), respectively. There were no significant differences between the groups and no patient was considered 'at risk' (pH less than 2.5 and gastric volume greater than 25 ml). We conclude that single-dose oral famotidine and double-dose oral ranitidine are equally effective for preventing acid aspiration syndrome in morbidly obese patients.     

The effect of magnesium trisilicate mixture, metoclopramide and ranitidine on gastric pH, volume and serum gastrin

Eighty women (40 for elective Caesarean section and 40 for elective gynaecological surgery) were randomly assigned to one of five treatment groups and received pre-operatively either no medication; magnesium trisilicate mixture (BP) 30 ml; metoclopramide 10 mg intramuscularly; ranitidine 150 mg orally on the night prior to, and the morning of, surgery; or metoclopramide 10 mg intramuscularly in combination with oral ranitidine 150 mg (the latter again given on the night prior, and the morning, of surgery). The effect of these medications on intragastric pH, volume and serum gastrin-17 was measured. No patient receiving ranitidine had a pH of less than 4. Magnesium trisilicate mixture resulted in the largest intragastric pH change although one woman in this group had a pH of 1.7. The largest intragastric volumes were seen in the patients who had received magnesium trisilicate mixture, whilst the patients who had received metoclopramide in combination with ranitidine had the smallest intragastric volumes. Magnesium trisilicate mixture and metoclopramide resulted in no change in serum gastrin levels. However, in the subjects who had received ranitidine on the night prior to surgery, the fasting serum gastrin was significantly higher (p less than 0.01) than the values in the remaining subjects, the mean (SEM) values being 60.3 (6.3) pg/ml in those not receiving ranitidine and 111.3 (19.5) pg/ml in those who had been given ranitidine.     

Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia

Various antacid or antisecretory agents are used to reduce the risk to patients of aspiration of gastric contents during general anaesthesia and a trial of the gastric proton pump inhibitor, omeprazole, is reported here. Twenty women admitted for elective Caesarean section under general anaesthesia received a single 80-mg oral omeprazole dose at 2000 hours on the evening before surgery. Intragastric pH and volume were measured immediately after induction of anaesthesia and on completion of surgery. Eighty-five percent of pH measurements at induction and extubation and 80% and 95% of volume measurements at induction and extubation respectively met the defined success criteria (pH greater than or equal to 2.5, volume less than 25 ml). Omeprazole treatment was well tolerated by the women and Apgar scores and subsequent progress of the babies were acceptable. These results indicate that gastric acidity and volume were acceptable in the majority of women after omeprazole treatment, but the interval from drug administration to induction of anaesthesia may have been too long in some cases and resulted in unacceptably low pHs.     

Premedication with cimetidine and metoclopramide

A randomised, double-blind, placebo-controlled parallel study was conducted in adult females to evaluate the efficacy and safety of a combination of cimetidine 300 mg orally and metoclopramide 10 or 20 mg intravenously in reducing pre-operative residual gastric volume and raising gastric pH. The effect of preoperative metoclopramide on postoperative nausea and vomiting was also investigated. Oral cimetidine was given approximately 2-2.5 hours before, and intravenous metoclopramide either 15 or 30 minutes prior to induction of anaesthesia. The study showed that placebo-treated patients undergoing outpatient operations have an increased risk of acid aspiration because of high residual gastric volume and low pH and increased risk of serious pulmonary injury should acid aspiration occur. Metoclopramide 10 or 20 mg intravenously prior to induction of anaesthesia was effective in reducing the residual gastric volume significantly, but not in raising pH. The combination of cimetidine and metoclopramide, as well as cimetidine alone, reduced the risk factors of acid aspiration by raising gastric pH and reducing residual volume. No anti-emetic effect of metoclopramide was observed. Higher doses of metoclopramide (20 mg) produced significant side effects (flushing, dizziness, extrapyramidal side effects), but were only marginally more effective than 10 mg doses in reducing residual gastric volume.     

The effect of H2 antagonists on duration of action of suxamethonium in the parturient

Fifteen patients who underwent elective Caesarean section were given sodium citrate, either alone or combined with oral cimetidine or ranitidine, as antacid premedication. No significant differences in time to 25 or 50% recovery of the first twitch of a train-of-four after administration of suxamethonium were found between any of the groups. It is concluded that H2-antagonists do not significantly affect the duration of action of suxamethonium in parturients, in contrast to the findings of a study in nonpregnant patients.     

Comparison of the effects of famotidine and ranitidine on gastric secretion in patients undergoing elective surgery

A randomised double-blind comparison of oral famotidine and ranitidine given 2 hours before induction, on gastric secretion (volume and pH) was carried out on 93 patients undergoing elective surgery. Gastric contents were aspirated immediately after tracheal intubation. Famotidine significantly reduced the gastric volume, compared with the other groups, including ranitidine. Both famotidine and ranitidine significantly elevated gastric pH towards neutral, compared with the other groups. There was no significant difference between ranitidine and famotidine in respect of the pH. The patients premedicated with famotidine and ranitidine were well protected against Mendelson's syndrome, whereas 38% of patients from the other groups remained at risk.     

The use of antacids as a prophylaxis against Mendelson''s syndrome in the United Kingdom. A survey

Maternal mortality from aspiration of gastric contents still remains unacceptably high, despite various recommended prophylactic measures. In order to establish which forms of antacid prophylaxis are currently being used, a questionnaire was sent to anaesthetists working in obstetric units in the United Kingdom. Despite its limitations, magnesium trisilicate remains the most popular antacid during labour and before Caesarean section.     

H2 antagonists and bupivacaine clearance

The effect of the H2 receptor antagonists cimetidine and ranitidine on bupivacaine clearance was assessed in women scheduled to undergo elective Caesarean section under epidural anaesthesia. Thirty-six women were randomly allocated to receive either no medication, cimetidine 400 mg or ranitidine 150 mg on the night prior to and on the morning of surgery. No significant difference was found between the peak bupivacaine levels: the mean (SD) values were 0.74 (0.17) microgram/ml, 0.81 (0.38) microgram/ml and 0.70 (0.24) microgram/ml in the control, cimetidine and ranitidine groups, respectively. Similarly, the H2 receptor antagonists did not alter the plasma bupivacaine against time curves, half-life or bupivacaine clearance in the three groups studied.