Cimetidine — antacid combination as premedication for elective Caesarean section

The effect of premedication with an oral antacid (magnesium trisilicate), oral cimetidine or a combination of both was studied in 80 patients undergoing elective Caesarean section. Twenty patients served as untreated controls. Seventy per cent of the patients were in the high risk range for acid aspiration Pneumonitis (pH < 2.5 plus gastric coment volume > 25 ml). Antacid therapy was effective in raising pH but the gastric volume remained high in 50 per cent of the patients. Cimetidine was effective in decreasing gastric volume and raising pH but the pH was still <2.5 in two patients. None of the patients given the cimetidine-antacid combination were in the high risk range for acid aspiration Pneumonitis. The combination of an oral dose of Cimetidine 400 mg, three to four hours before the operation followed by 20 ml of magnesium trisilicate one hour preoperatively proved to be the most efficacious regimen for prophylaxsis against Mendelson’s syndrome in elective Caesarean section. Recent reports have suggested that non-particulate antacids (e.g., sodium citrate) may be preferable to particulate antacids such as magnesium trisilicate.     

The role of H2 receptor antagonist premedication in pregnant day care patients

In a randomised study of 132 pregnant outpatients, the effect on gastric volume and pH of oral premedication with a single dose of an H2 antagonist was investigated. Either cimetidine 400 mg (n = 33), or ranitidine 150 mg (n = 33), were given 90 to 120 minutes before scheduled surgery. Mean pH was significantly higher in cimetidine (5.0) and ranitidine (5.2) groups, and mean volume was significantly lower in cimetidine (13.2 ml) and ranitidine (11.1 ml) groups compared with 66 untreated patients (pH 1.6, volume 22.1 ml). A gastric pH less than or equal to 2.5 was found in 97 per cent of unpremedicated patients and 35 per cent of these patients also had a gastric volume greater than or equal to 25 ml. Eighty-three per cent of patients received their premedication within 75-200 minutes of surgery. Patients premedicated within that range had a significantly lower incidence of either a gastric pH less than or equal to 2.5 or a volume greater than or equal to 25 ml (p less than 0.01). Both cimetidine and ranitidine significantly reduced the number of patients with these risk factors. Four patients, however, in the cimetidine group had both a pH less than or equal to 2.5 and a volume greater than or equal to 25 ml. Pharmacological manipulation of the gastric environment does not prevent aspiration and clearly cannot be substituted for careful airway management and vigilance on the part of the anaesthetist. However, premedication of pregnant outpatients with a single, oral dose of an H2 antagonist is a simple, inexpensive, safe and effective way of reducing the risk of a severe aspiration pneumonitis.     

Use of cimetidine as an oral antacid in obstetric anesthesia

The H2-receptor antagonist, cimetidine, was used instead of magnesium trisilicate BPC as routine antacid therapy before both elective and emergency obstetric anesthesia. Two trials of its efficacy in increasing intragastric pH and decreasing the volume of gastric contents in parturients are reported. In the first trial, 400 mg of cimetidine given orally to patients being delivered by elective cesarean section effectively decreased gastric acidity, providing induction of anesthesia occurred 90-150 min after its administration. Of 62 patients requiring emergency anesthesia during active labor and who had been treated with 200 mg of cimetidine orally at 2-h intervals, 80% had gastric contents with a pH higher than 2.5. Failure to decrease gastric acidity to this level was mainly due to anesthesia being required within 60 min of the loading dose, but it also was considered that inaccurate timing of repeat doses and possibly delay in uptake due to gastric stasis by narcotic analgesia played a part. In trial 2 the same cimetidine regimen plus a 15-ml oral dose of 0.3 M sodium citrate given 10 min before induction of anesthesia was studied. All 72 women delivered by elective cesarean section had a low volume of gastric contents with pH greater than 2.5. Only 4% of 135 patients requiring emergency anesthesia had gastric aspirates the pH of which was less than 2.5. The volume (97 +/- 8.4 ml) of gastric contents removed from the latter patients were considered to still pose a hazard at induction of general anesthesia. No maternal or infant side effects related to cimetidine therapy were noted.     

Cimetidine premedication in elective caesarean section

A single intramuscular injection of Cimetidine was compared to oral antacid premedication in 17 patients undergoing elective Caesarean section. Seven patients in the Cimetidine group and four in the antacid group had gastric volumes in excess of 50 ml after induction of anaesthesia, while two patients in each group had gastric pH less than 2.5 after induction. Cimetidine was as effective as antacid in raising gastric pH but neither was completely reliable. This study reconfirms the high gastric volumes in pregnant patients with the need for preventative measures against aspiration during the induction of anaesthesia.     

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.     

Acid aspiration prophylaxis in Australian obstetric hospitals--a survey

During 1987 a confidential survey of all hospitals in Australia providing obstetric services was undertaken to determine the antacid medications used routinely as prophylaxis against acid aspiration pneumonitis. Of the 567 hospitals surveyed, 379 (67%) responded. Of these, 243 hospitals provide an obstetric service which includes caesarean section, and 67% of these perform less than 500 deliveries per annum. Aspiration prophylaxis during labour was used in 22.4% of responding hospitals. Prior to elective caesarean section, 11.5% used no prophylaxis, and 39.4% used particulate antacids such as magnesium trisilicate mixture (33.3%) or Mylanta (6.1%). Sodium citrate mixture was the most popular therapy (37%). Results were similar in the emergency caesarean section group. The use of cimetidine or ranitidine was uncommon in all groups. Results of this survey suggest marked differences in attitudes towards acid aspiration prophylaxis between Australian and British obstetric anaesthetic practices.     

Pre-operative neutralization of gastric acidity.

The incidence of Mendelson's syndrome in the four major Auckland hospitals is reviewed. The frequency of this condition was reduced following the pre-operative administration of magnesium trisilicate mixture in two hospitals. A trial was conducted in a third hospital and this showed that a 52 per cent incidence of highly acid gastric juice (pH less than 2.5) in patients prepared for elective surgery was reduced by administration of magnesium trisilicate mixture at the time of premedication. When the magnesium trisilicate mixture was given within the 30 minutes prior to induction of anaesthesia, the number of patients with highly acid gastric content fell to one per cent.     

The effects of intravenous cimetidine and metoclopramide on gastric pH and volume in outpatients

STUDY OBJECTIVE: To evaluate and compare the preinduction effects of intravenously (IV) administered cimetidine alone and combined with metoclopramide on gastric contents and postoperative nausea and vomiting in outpatients undergoing elective surgery. DESIGN: Patients were allocated randomly to 4 groups with 20 patients in each group. SETTING: Ambulatory surgery at a university-affiliated city hospital. PATIENTS: Eighty patients undergoing elective gynecologic or orthopedic procedures were studied. INTERVENTIONS: Outpatients in Group 1 and inpatients in Group 2 served as controls. Outpatients in Group 3 received 300 mg of cimetidine, and outpatients in Group 4 received 300 mg of cimetidine and 10 mg of metoclopramide. All drugs were administered IV as an infusion over a 15-minute period, 30 to 45 minutes prior to induction of anesthesia. MEASUREMENTS AND MAIN RESULTS: After induction of general anesthesia and endotracheal intubation, stomach contents were retrieved and volume and pH measured. Group 1 outpatients had a large residual gastric volume of 29.2 +/- 15.9 ml, with a very low pH of 2.32 +/- 1.23 and 15% frequency of postoperative vomiting. These patients are at high risk of developing significant pneumonitis in the event of the aspiration of gastric contents. The combination of cimetidine and metoclopramide in Group 4 provided the optimal, or safest, condition--i.e., high gastric pH [6.15 +/- 0.71 (p less than 0.005)] and low gastric volume [11.6 +/- 7.37 ml (p less than 0.001)], with no postoperative vomiting. CONCLUSIONS: The combination of cimetidine and metoclopramide given to ambulatory patients during the preinductive phase may prevent severe pulmonary consequences should aspiration occur and is more effective in this regard than cimetidine alone.     

Effects of pre-anaesthetic glycopyrrolate and cimetidine on gastric fluid acidity and volume in children

The effects of pre-anaesthetic glycopyrrolate and cimetidine on gastric fluid pH and volume were studied in 96 paediatric patients from ages 6 months to 12 years undergoing elective surgery. They were randomly allocated into six groups with 16 patients in each group. Patients in group I received neither glycopyrrolate nor cimetidine and served as controls. Group II patients received glycopyrrolate, 5 micrograms kg-1 intramuscularly in a.m. Patients in group III received cimetidine 5 mg kg-1 orally in a.m. Group IV patients received cimetidine 5 5 mg kg-1 orally in a.m. and glycopyrrolate 5 micrograms kg-1 in a.m. Patients in group V received cimetidine 5 mg kg-1 orally h.s. and a.m. Group VI patients received cimetidine as in group V and also received glycopyrrolate as in group II. Patients with gastric pH 2.5 or less and volume of gastric contents 0.4 ml kg-1 or greater were defined to be at risk of pulmonary damage if aspiration should occur. The patients in the control group had a mean gastric pH of 1.91 +/- 0.074 and mean gastric volumes of 0.52 +/- 0.06 ml kg-1. Ninety-four per cent of patients in this group had gastric pH less than or equal to 2.5 and 69% of patients had gastric volumes greater than or equal to 0.4 ml kg-1. Glycopyrrolate (group II) reduced patients with pH less than or equal to 2.5 to 50% and volumes greater than or equal to 0.4 ml kg-1 to 44%. Cimetidine markedly reduced both gastric acidity (gastric pH less than or equal to 2.5 in 0-13% of patients in groups III-VI) and gastric volume (greater than or equal to 0.4 ml kg-1 in 19-38% of patients in groups III-VI). Only a maximum of 13% of the patients presented with combination of both risk factors in groups III-VI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of aspiration pneumonia in obstetrical anesthesia with the effervescent combination of cimetidine and sodium citrate

The effect of an oral effervescent formulation combining 200 mg cimetidine and 1.8 g sodium citrate on gastric pH and volume were studied in patients undergoing caesarean section. Seventy-four patients undergoing elective (group 1) or emergency caesarean section (group 2) were included. Before entering the operating theater (5 to 60 min before intubation), they were given the tablet dissolved in 15 ml of water. Induction and maintenance of anaesthesia were carried out with conventional techniques. The patient's gastric content was aspirated just after endotracheal intubation, and before extubation. its pH and volume were measured at both times. Mean pH was similar in the two groups after intubation (6.07 +/- 1.13 in group 1; 5.52 +/- 1.14 in group 2) and before extubation (6.32 +/- 1.08 vs. 5.85 +/- 1.02 respectively). Gastric pH was therefore greater than 2.5 in all 74 patients at both times. Mean volumes of gastric content after intubation were greater in group 2 (32.7 +/- 23.9 ml vs. 21.6 +/- 15.8 ml; p less than 0.02). However, just before extubation, these were similar (15.0 +/- 15.4 ml in group 1, 20.1 +/- 14.9 ml in group 2). The percentage of patients in the 2 groups with gastric volumes greater than 25 ml at the time of intubation were not significantly different (29.7% vs. 45.9% respectively). No patient was at risk of developing pneumonitis in case of aspiration (gastric content pH less than 2.5 and volume greater than 25 ml), either during endotracheal intubation or extubation.(ABSTRACT TRUNCATED AT 250 WORDS)     

COMPARISON OF THE PROPHYLACTIC USE OF MAGNESIUM TRISILICATE MIXTURE B.P.C., SODIUM CITRATE MIXTURE OR CIMETIDINE IN OBSTETRICS

The effects of magnesium trisilicate mixture B.P.C., sodiumcitrate mixture or cimetidine on gastric pH and aspirated gastricvolumes were compared in 78 obstetric patients during elective(a), or emergency (b) surgery. Magnesium trisilicate mixtureB.P.C. was associated with the most alkaline values of gastricpH (mean (a) 7.9, (b) 7.3; range 2.9–9.1). Sodium citrate0.3 mol litre^–1 mixture resulted in the narrowest rangeof pH values of gastric contents (mean (a) 5.4, (b) 5.9; range3.9–7.7). The ranges of aspirated gastric volumes werewide with both antacid regimens (magnesium trisilicate 12–172ml, sodium citrate9–290ml). Cimetidine increased gastricpH to greater than 2.5 in 82% of patients (mean (a) 6.2, (b)5.0; range 1.6–7.3), and was associated with significantlysmaller volumes of aspirated gastric contents (range 0.5–44ml). When gastric pH and volume were considered together, thegroups of patients who received cimetidine were found to beclosest to the defined "safe limits", of pH 2.5 and volume 25 ml.     

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.     

Antacid anticholinergic regimens in patients undergoing elective caesarean section

The pH and volume of gastric contents were examined in 60 patients undergoing elective Caesarean Section under thiopentone, nitrous oxide-oxygen, succinylcholine anaesthesia. All patients received Gelusil 30 ml per os preoperatively, while 20 were given atropine 7 microgram X kg-1 and another 20 glycopyrrolate 4 microgram X kg-1 intramuscularly along with Gelusil. Following tracheal intubation, gastric fluid was sampled through an orally placed 18 French Salem Sump tube. After Gelusil alone, the mean gastric fluid pH was 4.54 +/- 2.45 (SD) while it was significantly higher following the combined use of antacid and atropine (6.78 +/- 1.20) or antacid and glycopyrrolate (6.42 +/- 1.72), (P less than 0.01). Differences in gastric fluid volume between the groups were insignificant. All three regimens produced a gastric pH greater than 2.5 when given less than 75 minutes before sampling. When the premedication to sampling interval exceeded 75 minutes the addition of atropine or glycopyrrolate decreased the incidence of gastric pH less than 2.5 from 47 per cent in patients given Gelusil alone to 6 per cent and 14 per cent, respectively. In comparison to Gelusil alone, this difference was significant with atropine (P less than 0.05) but not with glycopyrrolate. Atropine and glycopyrrolate respectively produced 6 per cent and 7 per cent incidences of pH lower than 2.5 combined with gastric volume greater than 25 ml, which were significantly lower than was observed with Gelusil alone (P less than 0.05). This study demonstrates that the addition of atropine or glycopyrrolate to Gelusil premedication provides additional protection against the consequences of aspiration, especially when the premedication to anaesthetic induction period is prolonged.     

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.     

The effect of oral administration of roxatidine acetate hydrochloride 3 hours prior to the operation on pH and volume of gastric juice]

The effect of roxatidine acetate hydrochloride, administered 3 hours prior to induction of anesthesia, on pH and volume of gastric juice was investigated in preoperative patients. In fifty patients, who were scheduled to undergo elective surgery, 150 mg of roxatidine acetate hydrochloride was administered orally 3 hours before the induction of anesthesia. The volume and pH of gastric juice were measured immediately after the induction of anesthesia. In 46 patients out of fifty, pH of gastric juice was more than 2.5, and its volume was below 25 ml. In another 4 patients, pH of gastric juice was more than 2.5, or its volume below 25 ml. We conclude that, oral administration of 150 mg roxatidine 3 hours preoperatively could be effective for the prevention of an aspiration pneumonitis.     

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.     

A comparative evaluation of cimetidine and sodium citrate to decrease gastric acidity: Effectiveness at the time of induction of anaesthesia

Patients coming for elective surgery were randomly assigned to one of three treatment groups: control, cimetidine 300 mg orally two hours pre-operatively, or sodium citrate 0.3 M solution 30 ml orally, given as the patient was leaving the ward for the operating room. Each group consisted of 15 patients. This study reconfirms the average 26 per cent risk of significant aspiration in patients, coming for elective surgery, who have not received an agent intended to decrease gastric acidity or to decrease volume of gastric content. Sodium citrate is effective most of the time (87 per cent) in decreasing gastric acidity but is associated with a large mean volume (40.8 ml) of aspirate. From the results of this study cimetidine appears to be the preferable agent to use because it is completely effective in decreasing gastric acidity but does not increase the mean volume (17.0 ml) of the aspirate. Cimetidine appears to be an excellent agent to use as a preventative measure against aspiration during the induction of anaesthesia. Sodium citrate is a reasonable alternative if there is a contraindication to the use of cimetidine. However, these agents should be regarded only as adjuncts in the prevention of aspiration of gastric contents at the time of induction of anaesthesia.     

Reduction of the Risk of Acid Pulmonary Aspiration in Anaesthetized Patients after Cimetidine Prernedication

Forty-two patients undergoing elective general surgery received either placebo, cimetidine 300 mg, or cimetidine 600 mg orally 1.5–2 h before anaesthesia in a double-blind, randomized study. Another 13 subjects received no oral premedication and served as a control group. When compared to placebo or control patients, both doses of cimetidine significantly (P< 0.01) decreased the acidity and volume of gastric contents. None of the subjects given cimetidine were in the risk range of acid pulmonary aspiration (pH under 2.5 plus volume over 25 ml), whereas 46% of the control patients and 40% of the patients given placebo (P<0.005 vs cimetidine in both groups) were in the risk range.     

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.     

Occurrence of gastroesophageal reflux on induction of anaesthesia does not correlate with the volume of gastric contents

In an attempt to explain the discrepancy between the high number of patients said to be at risk of aspiration pneumonitis and the low reported incidence of this anaesthetic complication, 100 ASA physical status I-II elective surgical patients were studied. The volume of fluid present in the stomach at the time of induction of anaesthesia was correlated with gastroesophageal reflux (GER) detected by visual inspection of the pharynx and by continuous measurement of upper oesophageal pH. Mean gastric volume was 30 +/- 28 ml (range 0-210 ml). Gastric fluid volume greater than or equal to 0.4 ml.kg-1 at pH less than or equal to 2.5 was present in 46 patients. No GER was detected during induction of anaesthesia in our sample of 100 patients. Furthermore, patient age, duration of preoperative fasting, body mass index, cigarette smoking, alcohol consumption, preoperative anxiety, and a history of preoperative GER were not correlated with significant modifications of gastric volume or pH. We conclude that the low incidence of aspiration pneumonitis in elective surgical patients may be explained in part by the very low risk of GER, despite gastric fluid volumes of more than 0.4 ml.kg-1 in a high proportion of this patient population.