Anaesthesia, 1992, Volume 47, pages 101-104
A comparison of omeprazole and ranitidine for prophylaxis against aspiration pneumonitis in emergency Caesarean section
G.YbU,A. F. KAN,T.GIN AND T.E. OH
Summary One hundred and sixty-two Chinese women undergoing emergency Caesarean section were allocated at random on admission to the labour ward to receive one of three regimens for orally administered chemoprophylaxis against acid aspiration: ranitidine 150 mg 6 hourly with sodium citrate at induction of anaesthesia, omeprazole 40 mg I2 hourly with sodium citrate. or omeprazole 40 mg 12 hourly alone. Intragastric pH and volume were measured immediately after induction of anaesthesia. Ten patients ( I 7%) in the omeprazole-only group, three ( 6 % ) in the omeprazole and citrate group and one ( 2 % ) in the ranitidine group had an intragastric pH < 2.5 and volume 7 25 ml ( p < 0.05). The use of sodium citrate resulted in higher intragastric pH but larger intragastric volumes ( p < 0.05). The sodium citrate and ranitidine regimen was the most cost-effective among the three.
Key words Anaesthesia; obstetric. Complications; aspiration. Gastrointestinal tract; intragastric pH, volume.
Acid aspiration syndrome is still an important contributor towards anaesthetic-related deaths [I]. An intragastric pH < 2.5 with an intragastric volume > 25 ml was believed to place the patient at high risk of severe lung damage [2] although this has been questioned recently [3]. Numerous regimens have been used for chemoprophylaxis against acid aspiration in patients undergoing emergency Caesarean section [4, 51 but none consistently maintain intragastric pH > 2.5 with volumes < 25 ml. Ranitidine 6 hourly, with sodium citrate before induction of general anaesthesia, maintained gastric pH 7 2.5, but gastric volumes were still considerable [6-8]. Omeprazole is a new drug which inhibits gastric acid production by selectively blocking the proton pump in gastric parietal cells [9]. It was more effective than ranitidine at maintaining pH > 3.5 in women for elective Caesarean section, without the use of sodium citrate, and all volumes were less than 25 ml [lo]. An omeprazole regimen for patients in active labour may minimise the problem of large intragastric volumes. This study compared the effects of omeprazole 40 mg given 12 hourly, and ranitidine 150 mg given 6 hourly, during labour, on gastric pH and volume in patients undergoing emergency Caesarean section.
Methods The protocol was approved by the Research Ethics Committee of the Chinese University Faculty of Medicine and informed consent was obtained from all patients. All patients on admission to the labour ward were assigned at random on a daily basis to receive one of the following regimens: group 1, ranitidine 150 mg orally 6 hourly, 30 ml 0.3M sodium citrate orally 15 min before induction of anaesthesia, group 2, omeprazole 40 mg orally 12 hourly, 30 ml 0.3M sodium citrate orally 15 min before induction of anaesthesia, group 3, omeprazole 40 mg orally 12 hourly, no sodium citrate. All patients were fasted from the time of admission to the labour ward, and the time of last oral intake was noted. Patients who required urgent Caesarean section within 30 min of admission to the labour ward were not studied. For Caesarean section, all women were placed in the left lateral tilt position and monitored with ECG, pulse oximetry and noninvasive arterial pressure (Dinamap 18465X Critikon Inc, Tampa, F1, USA). Following preoxygenation for 3 min anaesthesia was induced with thiopentone 4 mg.kg-' while cricoid pressure was applied. After loss of the eyelash reflex, suxamethonium
G. Yau, MB, BS, FFARCS, Lecturer, A.F. Kan, MB, BCh, FFA(SA), Lecturer, T. Gin, MB ChB, BSc, F F A R Z FFARACS, Senior Lecturer, T.E. Oh, MB, BS, FFARCS, FFARACS, Professor, Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. Accepted 22 June 1991. 0003-2409/92/020101+04 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
101
102
G. Yau et al.
1.5 mg.kg-' was given to facilitate tracheal intubation. Anaesthesia was maintained with nitrous oxide 50% and enflurane I % in oxygen. Atracurium 0.5 mg.kg-' was given and ventilation controlled to maintain the end-tidal carbon dioxide concentration between 4.0 and 4.5 kPa. At delivery, oxytocin 10 units and morphine 0.2mg.kg-' were given. The nitrous oxide was increased to 70%, enflurane was reduced to 0.5%, and eventually discontinued at the start of skin closure. Atropine 1.2 mg and neostigmine 2.5 mg were given to antagonise residual neuromuscular block. Gastric aspiration was performed after induction of anaesthesia using a 16-FG Salem sump tube (Sherwood Medical, St. Louis, M0.63103, USA) which was inserted orally after tracheal intubation. The Salem sump tube was advanced until the third 10 cm marking was at the lips, and correct positioning checked by auscultation of injected air. Aspiration was performed with a 50ml syringe and repeated after the tube was withdrawn and re-advanced first lOcm and then 20cm. Volumes were measured directly from the 50ml syringe which was graduated in 1 ml markings. Measurements of pH were made using a Corning 240 pH meter (Corning, NY, USA) and also using Millipore pH paper. The pH meter was calibrated daily at pH 4 and 7. All pH measurements were made by an investigator who was unaware of which drug the patient had been given. All infants were examined by a neonatologist and Apgar scores at 1 and 5 min, and birth weight, were recorded. Demographic data were compared among groups using analysis of variance. The times from last oral intake to time of aspiration (fasting time), time from start of drug treatment to time of gastric aspiration (treatment time), intragastric pH and intragastric volumes were compared among groups using the Kruskal-Wallis test. The incidence of treatment failures, defined as the number of patients with gastric pH < 2.5 and volume > 25 ml, was compared using Fishers Exact test. Further analysis was performed on subgroups of the data, including those patients who had received pethidine and groups whose treatment times were less than 6 or 12 h. Kendall rank correlation was used to compare fasting times and treatment times with gastric volume and pH. A p < 0.05 was considered significant.
8 r
I
+
0
431 ml pH 4.84
2l I 0
50
100 150 Gostric volume (mll
200
250
Fig. 1. Intragastric pH and volume in patients after 150mg ranitidine and 30 ml sodium citrate.
0
100
50
150
200
250
Gostrtc volume (ml1
Fig. 2. lntragastric pH and volume in patients after 40mg omeprazole and 30 ml sodium citrate.
0 +
::
0
4F.L
0
Results
A total of 162 patients were studied (49 ranitidine and sodium citrate, 53 omeprazole and sodium citrate, 60 omeprazole alone). There were no differences in age, weight, height or parity among the three groups. The fasting time was longer in the ranitidine group compared with the omeprazole and citrate group (Table I , p c 0.05). The duration of treatment was longer in the omeprazole group compared with the ranitidine group (Table I , p < 0.05).
Fig. 3. Intragastric pH and volume in patients after 40 mg omeprazole.
There was one patient in the omeprazole group who had no gastric aspirate and p H could not be estimated. Plots of intragastric pH values against intragastric volumes are shown in Figures I to 3. By the criteria of Roberts and Shirley [2], patients falling into the quadrant with p H less
Table 1. Median (range) fasting times and treatment times. Group Ranitidine+citrate Omeprazole+citrate Omeprazole
Fasting time (h) ( n = 49) ( n = 53) ( n = 60)
11.0 (2.7-31.3) 9.0 (1.0-19.5)* 10.6 (1.5-30.0)
*p < 0.05 compared with ranitidine group.
Treatment time (h)
5.5 ( I .5-15.4) 6.1 (0.5-18.5)
7.0 ( I .&20.0)'
103
Comparison of omeprazole and ranitidine Table 2. Median (range) intragastric pH and volume. meter pH
paper PH
volume (ml)
6.16 (2.1 1-7.50) 5.67 (1.78-6.99)** 4.44 (0.81-7.28).
6.7 (2.0-7.7) 6.1 (2.0-7.4)** 4.8 (2.0-7.7)*
38 ( 6 4 3 1 ) 45 (1-200) 23 (0-200)*
Group Ranitidine +citrate Omeprazole+citrate Omeprazole
*p < 0.01 compared with other groups, **p < 0.01 compared with ranitidine group.
than 2.5 and volume exceeding 25 ml are considered to be at maximum risk. Group I, ranitidine and sodium citrate Patients in this group had a median intragastric volume of 38 ml and pH of 6.16 (Table 2). There was only one patient in the high risk quadrant with a volume of 48 ml and pH of 2.17 (Fig. 1). One patient in this group had a volume of 431 ml with a pH of 4.84. She had eaten some rice soup only 2 h prior to admission. 0
4
Group 2, omeprazole and sodium citrate
8
12
20
16
24
Drug to osplmtlon time ( h l
Patients in this group had a median intragastric volume of 45 ml and pH of 5.67 (Table 2). There were three patients with a pH < 2.5 and volume > 25 ml (Fig. 2).
Fig. 5. Intragastric pH and time after medication (40mg omeprazole and 30 ml sodium citrate). 8-
Group 3, omeprazole only Patients in this group had a median intragastric volume of 23 ml and pH of 4.44 (Table 2). There were 10 patients in the high risk quadrant (Fig. 3). Intragastric pH was not correlated to fasting time or treatment time (Figs 4-6). There was a wide scatter of pH in those patients taking omeprazole alone (Fig. 6) whereas those patients taking ranitidine and sodium citrate had pH above 'at risk' level when the 'drug to aspiration' time exceeded two hours (Fig. 4). The omeprazole-only group had lower pH than the other two groups (Table 2, p < 0.01). Patients who received omeprazole with citrate had more acidic pH than those who received ranitidine (Table 2, p < 0.01) although the difference between groups was only 0.5 pH unit. Patients in the two groups who received sodium citrate had larger intragastric volumes compared with the omeprazole-only group (Table 2, p < 0.01). 8 r
j4I 0
." _ +
0
-0
I,
4-
6
0
-0
0 0
2 -
0
0
4
8
12
16
20
24
Drug t o ospirotion time ( h )
Fig. 6. Intragastric pH and time after medication (40mg omeprazole).
There was no difference among the groups in the number of patients who received pethidine for pain relief during labour (25% overall). There were no differences in gastric pH or volume between those patients that received pethidine and those that did not. There were no differences in neonatal Apgar scores between the groups. Discussion
. 4
6 -
8
12
16
20
24
Drug to ospirotion tome Lh)
Fig. 4. Intragastric pH and time after medication (IS0 mg ranitidine and 30 ml sodium citrate).
In addition to fasting patients in active labour, most obstetric centres in the United Kingdom carry out some form of chemoprophylaxis against acid aspiration syndrome [4]. The combination of H2 receptor blocker and sodium citrate appears to be the yardstick against which other regimens are measured [4]. However, regimens involving the use of sodium citrate have produced mean intragastric volumes from 43 to 70 ml [7, 81. Reducing the volume of sodium citrate from 30ml resulted in lower mean intragastric volumes but intragastric pH was 'not
104
G. Yau et al.
consistently above 2.5 (81. Ranitidine alone, orally or intramuscular, gave lower mean intragastric volumes but failed to maintain intragastric pH > 2.5 and volumes < 25 ml consistently [8, 111. Two doses of omeprazole 40mg were shown to be superior to two doses of ranitidine 150 mg in maintaining intragastric pH above 3.5 in patients undergoing elective Caesarean section and all volumes were less than 25 ml [lo]. The present study, however, showed that the same regimen was not effective during labour. Forty-seven patients in the omeprazole-only group received just one 40mg dose of omeprazole and this may be considered inadequate but even a single 80mg dose has not been shown to be totally effective [12]. Thirteen patients in the omeprazole-only group received a second dose of 40mg omeprazole and three still had an intragastric pH below 2.5. It is likely that omeprazole would be more effective when given more frequently and in higher dosage. However, omeprazole 40 mg is approximately three times more expensive than ranitidine 150 mg so that omeprazole does not become cost-effective, especially when it does not give superior results to ranitidine. These findings support the reservations that some workers have expressed on the value of omeprazole [14]. Omeprazole is also inactivated by gastric acidity [9], and the large intragastric volumes and possible delays in gastric emptying during labour [ 131 may have resulted in significant loss of efficacy. A delay in gastric emptying was reflected by the large intragastric volumes in all three groups. The addition of sodium citrate to either omeprazole or ranitidine gave safer pH values when compared with omeprazole alone. This indicates that sodium citrate was important in maintaining intragastric pH above ‘at risk‘ levels but also contributes to larger intragastric volumes. Is it acceptable for intragastric volume to exceed 25ml in order to maintain intragastric pH consistently above ‘at risk’ levels? Recent work suggests that a much larger intragastric volume is necessary before there is sufficient gastro-oesophageal reflux to cause 25 ml of pulmonary aspirate [15]. The problem of large intragastric volumes in women during active labour is difficult to overcome. This appears to be a particular problem in this part of the world where patients usually eat a meal just before they come into hospital. We would recommend the routine insertion of orogastric tubes following induction of anaesthesia to empty the stomach. There is currently no regimen which consistently maintains pH and volume at acceptable levels
so that the most critical factors in the prevention of acid aspiration syndrome remain good anaesthetic technique and correctly applied cricoid pressure. References [I] Report on Confidential Enquiries into Maternal Deaths in England and Wales 1982-84. London: Her Majesty’s Stationery Office, 1989. [2] ROBERTSRB, SHIRLEYMA. Reducing the risk of acid aspiration during cesarean section. Anesthesia and Analgesia 1974; 53: 859-68. [3] RAIDOODM, ROCKEDA, BROCK-UTNE JG, MARSZALEK A, ENGELBRECHT HE. Critical volume for pulmonary acid aspiration: reappraisal in a primate model. British Journal of Anaesthesia 1990; 65: 248-50. [4] TORDOFFSG, SWEENEYBP. Acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom. Anaesthesia 1990, 45: 77680. RW, CROWHURSTJA. Acid aspiration prophylaxis in [5] BURGESS Australian obstetric hospitals - A Survey. Anaesthesia and Intensive Care 1989; 17: 492-5. RM. Ranitidine and [a] GILLETTGB, WATSONJD, LANGFORD single-dose antacid therapy as prophylaxis against acid aspiration syndrome in obstetric practice. Anaesthesia 1984; 39: 6 3 8 4 . EM, LOUGHRAN PG, MCAULEYDM, WILSONCM, [7] THOMPSON MOOREJ. Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia. Anaesthesia 1984; 3 9 1086-90. BA, COHEN DC, [8] COLMANRD, FRANK M, LOUGHNAN CATTERMOLE R. Use of IM ranitidine for the prophylaxis of aspiration pneumonitis in obstetrics. British Journal of Anaesthesia 1988; 61: 720-9. DM. Omeprazole. A [9] CLISSOLDSP, CAMPOLI-RICHARDS preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in wptic ulcer disease and Zollinger-Ellison syndrome. Drugs -1986;3 2 15-47. rioi EWART MC. YAU G. GIN T. KOTUR CF. OH TE. A comparison of the effects of omeprazole and ranitidine on gastric secretion in women undergoing elective caesarean section. Anaesthesia 1990; 45: 527-30. [I I] MCAULEYDM, MOOREJ, DUNDEE JW, MCCAUGHEY W. Oral ranitidine in labour. Anaesthesia 1984; 39 433-8. [I21 MOOREJ, FLY” RJ, SAMPAIOM, WILSONCM, GILLON KRW. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia 1989; 44: 559-62. G, eds. Clinical physiology in [I31 HYTTEN F, CHAMBERLAIN pregnancy. Oxford: Blackwell, 1980: 147-62. [I41 EVANSJ, ROUTCC, ROCKEDA. Acid aspiration prophylaxis. Anaesthesia 1991; 46: 73. [IS] HARDY JF. Large volume gastro-esophageal reflux: a rationale for risk reduction in the perioperative period. Canadian Journal of Anaesthesia 1988; 3 5 162-73. L
1
A comparison of omeprazole and ranitidine for prophylaxis against aspiration pneumonitis in emergency Caesarean section
G.YbU,A. F. KAN,T.GIN AND T.E. OH
Summary One hundred and sixty-two Chinese women undergoing emergency Caesarean section were allocated at random on admission to the labour ward to receive one of three regimens for orally administered chemoprophylaxis against acid aspiration: ranitidine 150 mg 6 hourly with sodium citrate at induction of anaesthesia, omeprazole 40 mg I2 hourly with sodium citrate. or omeprazole 40 mg 12 hourly alone. Intragastric pH and volume were measured immediately after induction of anaesthesia. Ten patients ( I 7%) in the omeprazole-only group, three ( 6 % ) in the omeprazole and citrate group and one ( 2 % ) in the ranitidine group had an intragastric pH < 2.5 and volume 7 25 ml ( p < 0.05). The use of sodium citrate resulted in higher intragastric pH but larger intragastric volumes ( p < 0.05). The sodium citrate and ranitidine regimen was the most cost-effective among the three.
Key words Anaesthesia; obstetric. Complications; aspiration. Gastrointestinal tract; intragastric pH, volume.
Acid aspiration syndrome is still an important contributor towards anaesthetic-related deaths [I]. An intragastric pH < 2.5 with an intragastric volume > 25 ml was believed to place the patient at high risk of severe lung damage [2] although this has been questioned recently [3]. Numerous regimens have been used for chemoprophylaxis against acid aspiration in patients undergoing emergency Caesarean section [4, 51 but none consistently maintain intragastric pH > 2.5 with volumes < 25 ml. Ranitidine 6 hourly, with sodium citrate before induction of general anaesthesia, maintained gastric pH 7 2.5, but gastric volumes were still considerable [6-8]. Omeprazole is a new drug which inhibits gastric acid production by selectively blocking the proton pump in gastric parietal cells [9]. It was more effective than ranitidine at maintaining pH > 3.5 in women for elective Caesarean section, without the use of sodium citrate, and all volumes were less than 25 ml [lo]. An omeprazole regimen for patients in active labour may minimise the problem of large intragastric volumes. This study compared the effects of omeprazole 40 mg given 12 hourly, and ranitidine 150 mg given 6 hourly, during labour, on gastric pH and volume in patients undergoing emergency Caesarean section.
Methods The protocol was approved by the Research Ethics Committee of the Chinese University Faculty of Medicine and informed consent was obtained from all patients. All patients on admission to the labour ward were assigned at random on a daily basis to receive one of the following regimens: group 1, ranitidine 150 mg orally 6 hourly, 30 ml 0.3M sodium citrate orally 15 min before induction of anaesthesia, group 2, omeprazole 40 mg orally 12 hourly, 30 ml 0.3M sodium citrate orally 15 min before induction of anaesthesia, group 3, omeprazole 40 mg orally 12 hourly, no sodium citrate. All patients were fasted from the time of admission to the labour ward, and the time of last oral intake was noted. Patients who required urgent Caesarean section within 30 min of admission to the labour ward were not studied. For Caesarean section, all women were placed in the left lateral tilt position and monitored with ECG, pulse oximetry and noninvasive arterial pressure (Dinamap 18465X Critikon Inc, Tampa, F1, USA). Following preoxygenation for 3 min anaesthesia was induced with thiopentone 4 mg.kg-' while cricoid pressure was applied. After loss of the eyelash reflex, suxamethonium
G. Yau, MB, BS, FFARCS, Lecturer, A.F. Kan, MB, BCh, FFA(SA), Lecturer, T. Gin, MB ChB, BSc, F F A R Z FFARACS, Senior Lecturer, T.E. Oh, MB, BS, FFARCS, FFARACS, Professor, Department of Anaesthesia and Intensive Care, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. Accepted 22 June 1991. 0003-2409/92/020101+04 $03.00/0
@ 1992 The Association of Anaesthetists of G t Britain and Ireland
101
102
G. Yau et al.
1.5 mg.kg-' was given to facilitate tracheal intubation. Anaesthesia was maintained with nitrous oxide 50% and enflurane I % in oxygen. Atracurium 0.5 mg.kg-' was given and ventilation controlled to maintain the end-tidal carbon dioxide concentration between 4.0 and 4.5 kPa. At delivery, oxytocin 10 units and morphine 0.2mg.kg-' were given. The nitrous oxide was increased to 70%, enflurane was reduced to 0.5%, and eventually discontinued at the start of skin closure. Atropine 1.2 mg and neostigmine 2.5 mg were given to antagonise residual neuromuscular block. Gastric aspiration was performed after induction of anaesthesia using a 16-FG Salem sump tube (Sherwood Medical, St. Louis, M0.63103, USA) which was inserted orally after tracheal intubation. The Salem sump tube was advanced until the third 10 cm marking was at the lips, and correct positioning checked by auscultation of injected air. Aspiration was performed with a 50ml syringe and repeated after the tube was withdrawn and re-advanced first lOcm and then 20cm. Volumes were measured directly from the 50ml syringe which was graduated in 1 ml markings. Measurements of pH were made using a Corning 240 pH meter (Corning, NY, USA) and also using Millipore pH paper. The pH meter was calibrated daily at pH 4 and 7. All pH measurements were made by an investigator who was unaware of which drug the patient had been given. All infants were examined by a neonatologist and Apgar scores at 1 and 5 min, and birth weight, were recorded. Demographic data were compared among groups using analysis of variance. The times from last oral intake to time of aspiration (fasting time), time from start of drug treatment to time of gastric aspiration (treatment time), intragastric pH and intragastric volumes were compared among groups using the Kruskal-Wallis test. The incidence of treatment failures, defined as the number of patients with gastric pH < 2.5 and volume > 25 ml, was compared using Fishers Exact test. Further analysis was performed on subgroups of the data, including those patients who had received pethidine and groups whose treatment times were less than 6 or 12 h. Kendall rank correlation was used to compare fasting times and treatment times with gastric volume and pH. A p < 0.05 was considered significant.
8 r
I
+
0
431 ml pH 4.84
2l I 0
50
100 150 Gostric volume (mll
200
250
Fig. 1. Intragastric pH and volume in patients after 150mg ranitidine and 30 ml sodium citrate.
0
100
50
150
200
250
Gostrtc volume (ml1
Fig. 2. lntragastric pH and volume in patients after 40mg omeprazole and 30 ml sodium citrate.
0 +
::
0
4F.L
0
Results
A total of 162 patients were studied (49 ranitidine and sodium citrate, 53 omeprazole and sodium citrate, 60 omeprazole alone). There were no differences in age, weight, height or parity among the three groups. The fasting time was longer in the ranitidine group compared with the omeprazole and citrate group (Table I , p c 0.05). The duration of treatment was longer in the omeprazole group compared with the ranitidine group (Table I , p < 0.05).
Fig. 3. Intragastric pH and volume in patients after 40 mg omeprazole.
There was one patient in the omeprazole group who had no gastric aspirate and p H could not be estimated. Plots of intragastric pH values against intragastric volumes are shown in Figures I to 3. By the criteria of Roberts and Shirley [2], patients falling into the quadrant with p H less
Table 1. Median (range) fasting times and treatment times. Group Ranitidine+citrate Omeprazole+citrate Omeprazole
Fasting time (h) ( n = 49) ( n = 53) ( n = 60)
11.0 (2.7-31.3) 9.0 (1.0-19.5)* 10.6 (1.5-30.0)
*p < 0.05 compared with ranitidine group.
Treatment time (h)
5.5 ( I .5-15.4) 6.1 (0.5-18.5)
7.0 ( I .&20.0)'
103
Comparison of omeprazole and ranitidine Table 2. Median (range) intragastric pH and volume. meter pH
paper PH
volume (ml)
6.16 (2.1 1-7.50) 5.67 (1.78-6.99)** 4.44 (0.81-7.28).
6.7 (2.0-7.7) 6.1 (2.0-7.4)** 4.8 (2.0-7.7)*
38 ( 6 4 3 1 ) 45 (1-200) 23 (0-200)*
Group Ranitidine +citrate Omeprazole+citrate Omeprazole
*p < 0.01 compared with other groups, **p < 0.01 compared with ranitidine group.
than 2.5 and volume exceeding 25 ml are considered to be at maximum risk. Group I, ranitidine and sodium citrate Patients in this group had a median intragastric volume of 38 ml and pH of 6.16 (Table 2). There was only one patient in the high risk quadrant with a volume of 48 ml and pH of 2.17 (Fig. 1). One patient in this group had a volume of 431 ml with a pH of 4.84. She had eaten some rice soup only 2 h prior to admission. 0
4
Group 2, omeprazole and sodium citrate
8
12
20
16
24
Drug to osplmtlon time ( h l
Patients in this group had a median intragastric volume of 45 ml and pH of 5.67 (Table 2). There were three patients with a pH < 2.5 and volume > 25 ml (Fig. 2).
Fig. 5. Intragastric pH and time after medication (40mg omeprazole and 30 ml sodium citrate). 8-
Group 3, omeprazole only Patients in this group had a median intragastric volume of 23 ml and pH of 4.44 (Table 2). There were 10 patients in the high risk quadrant (Fig. 3). Intragastric pH was not correlated to fasting time or treatment time (Figs 4-6). There was a wide scatter of pH in those patients taking omeprazole alone (Fig. 6) whereas those patients taking ranitidine and sodium citrate had pH above 'at risk' level when the 'drug to aspiration' time exceeded two hours (Fig. 4). The omeprazole-only group had lower pH than the other two groups (Table 2, p < 0.01). Patients who received omeprazole with citrate had more acidic pH than those who received ranitidine (Table 2, p < 0.01) although the difference between groups was only 0.5 pH unit. Patients in the two groups who received sodium citrate had larger intragastric volumes compared with the omeprazole-only group (Table 2, p < 0.01). 8 r
j4I 0
." _ +
0
-0
I,
4-
6
0
-0
0 0
2 -
0
0
4
8
12
16
20
24
Drug t o ospirotion time ( h )
Fig. 6. Intragastric pH and time after medication (40mg omeprazole).
There was no difference among the groups in the number of patients who received pethidine for pain relief during labour (25% overall). There were no differences in gastric pH or volume between those patients that received pethidine and those that did not. There were no differences in neonatal Apgar scores between the groups. Discussion
. 4
6 -
8
12
16
20
24
Drug to ospirotion tome Lh)
Fig. 4. Intragastric pH and time after medication (IS0 mg ranitidine and 30 ml sodium citrate).
In addition to fasting patients in active labour, most obstetric centres in the United Kingdom carry out some form of chemoprophylaxis against acid aspiration syndrome [4]. The combination of H2 receptor blocker and sodium citrate appears to be the yardstick against which other regimens are measured [4]. However, regimens involving the use of sodium citrate have produced mean intragastric volumes from 43 to 70 ml [7, 81. Reducing the volume of sodium citrate from 30ml resulted in lower mean intragastric volumes but intragastric pH was 'not
104
G. Yau et al.
consistently above 2.5 (81. Ranitidine alone, orally or intramuscular, gave lower mean intragastric volumes but failed to maintain intragastric pH > 2.5 and volumes < 25 ml consistently [8, 111. Two doses of omeprazole 40mg were shown to be superior to two doses of ranitidine 150 mg in maintaining intragastric pH above 3.5 in patients undergoing elective Caesarean section and all volumes were less than 25 ml [lo]. The present study, however, showed that the same regimen was not effective during labour. Forty-seven patients in the omeprazole-only group received just one 40mg dose of omeprazole and this may be considered inadequate but even a single 80mg dose has not been shown to be totally effective [12]. Thirteen patients in the omeprazole-only group received a second dose of 40mg omeprazole and three still had an intragastric pH below 2.5. It is likely that omeprazole would be more effective when given more frequently and in higher dosage. However, omeprazole 40 mg is approximately three times more expensive than ranitidine 150 mg so that omeprazole does not become cost-effective, especially when it does not give superior results to ranitidine. These findings support the reservations that some workers have expressed on the value of omeprazole [14]. Omeprazole is also inactivated by gastric acidity [9], and the large intragastric volumes and possible delays in gastric emptying during labour [ 131 may have resulted in significant loss of efficacy. A delay in gastric emptying was reflected by the large intragastric volumes in all three groups. The addition of sodium citrate to either omeprazole or ranitidine gave safer pH values when compared with omeprazole alone. This indicates that sodium citrate was important in maintaining intragastric pH above ‘at risk‘ levels but also contributes to larger intragastric volumes. Is it acceptable for intragastric volume to exceed 25ml in order to maintain intragastric pH consistently above ‘at risk’ levels? Recent work suggests that a much larger intragastric volume is necessary before there is sufficient gastro-oesophageal reflux to cause 25 ml of pulmonary aspirate [15]. The problem of large intragastric volumes in women during active labour is difficult to overcome. This appears to be a particular problem in this part of the world where patients usually eat a meal just before they come into hospital. We would recommend the routine insertion of orogastric tubes following induction of anaesthesia to empty the stomach. There is currently no regimen which consistently maintains pH and volume at acceptable levels
so that the most critical factors in the prevention of acid aspiration syndrome remain good anaesthetic technique and correctly applied cricoid pressure. References [I] Report on Confidential Enquiries into Maternal Deaths in England and Wales 1982-84. London: Her Majesty’s Stationery Office, 1989. [2] ROBERTSRB, SHIRLEYMA. Reducing the risk of acid aspiration during cesarean section. Anesthesia and Analgesia 1974; 53: 859-68. [3] RAIDOODM, ROCKEDA, BROCK-UTNE JG, MARSZALEK A, ENGELBRECHT HE. Critical volume for pulmonary acid aspiration: reappraisal in a primate model. British Journal of Anaesthesia 1990; 65: 248-50. [4] TORDOFFSG, SWEENEYBP. Acid aspiration prophylaxis in 288 obstetric anaesthetic departments in the United Kingdom. Anaesthesia 1990, 45: 77680. RW, CROWHURSTJA. Acid aspiration prophylaxis in [5] BURGESS Australian obstetric hospitals - A Survey. Anaesthesia and Intensive Care 1989; 17: 492-5. RM. Ranitidine and [a] GILLETTGB, WATSONJD, LANGFORD single-dose antacid therapy as prophylaxis against acid aspiration syndrome in obstetric practice. Anaesthesia 1984; 39: 6 3 8 4 . EM, LOUGHRAN PG, MCAULEYDM, WILSONCM, [7] THOMPSON MOOREJ. Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia. Anaesthesia 1984; 3 9 1086-90. BA, COHEN DC, [8] COLMANRD, FRANK M, LOUGHNAN CATTERMOLE R. Use of IM ranitidine for the prophylaxis of aspiration pneumonitis in obstetrics. British Journal of Anaesthesia 1988; 61: 720-9. DM. Omeprazole. A [9] CLISSOLDSP, CAMPOLI-RICHARDS preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in wptic ulcer disease and Zollinger-Ellison syndrome. Drugs -1986;3 2 15-47. rioi EWART MC. YAU G. GIN T. KOTUR CF. OH TE. A comparison of the effects of omeprazole and ranitidine on gastric secretion in women undergoing elective caesarean section. Anaesthesia 1990; 45: 527-30. [I I] MCAULEYDM, MOOREJ, DUNDEE JW, MCCAUGHEY W. Oral ranitidine in labour. Anaesthesia 1984; 39 433-8. [I21 MOOREJ, FLY” RJ, SAMPAIOM, WILSONCM, GILLON KRW. Effect of single-dose omeprazole on intragastric acidity and volume during obstetric anaesthesia. Anaesthesia 1989; 44: 559-62. G, eds. Clinical physiology in [I31 HYTTEN F, CHAMBERLAIN pregnancy. Oxford: Blackwell, 1980: 147-62. [I41 EVANSJ, ROUTCC, ROCKEDA. Acid aspiration prophylaxis. Anaesthesia 1991; 46: 73. [IS] HARDY JF. Large volume gastro-esophageal reflux: a rationale for risk reduction in the perioperative period. Canadian Journal of Anaesthesia 1988; 3 5 162-73. L
1
