Anaesthesia, 1990, Volume 45, pages 436-438
Omeprazole for prophylaxis of acid aspiration in elective surgery
L. NG WINGTIN, D. GLOMAUD, F. HARDY
AND
S. PHIL
Summary The aim of the study was to determine whether a single oral dose of omeprazole 40 mg is effective in increasing the p H of gastric residue above 2.5 at the time of anaesthetic induction in adult patients scheduled for elective gynaecological surgery. The patients were allocated to receive either chlorazepate dipotassium 25 mg alone or omeprazole 40 mg and chlorazepate dipotassium 25 mg on the night before surgery. Gastric volume and p H were measured after induction of anaesthesia. Patients who received omeprazole had a higher mean p H than control patients ( p < 0.001). The p H was less than 3.5 in 50% of patients in the control group, but in only 4.5% of rhose who received omeprazole ( p < 0.01). Mean ( S E M ) volume of gastricfluid was 15.2 (2.7) ml in the control group and 9.2 (1.8) ml in the omeprazole group, but the results were not statistically signijicant. A single dose of 40 mg omeprazole significantly decreased the number of patients at risk of aspiration pneumonitis.
Key words Gastrointestinal tract; gastric pH, gastric volume. Pharmacology; omeprazole.
The danger of pulmonary aspiration is always of concern Numerous studies have shown almost total inhibition of to anaesthetists. Between 30 and 50% of patients scheduled gastric secretion and acidity with no detectable side effects in normal individuals and patients with duodenal ulcers for elective surgery after a fasting period of more than 8 after treatment with ~ m e p r a z o l e . ~ ~ J ~ hours have a gastric volume greater than 25 m11-3and an even greater percentage (6482%) have a gastric pH less The aim of the study was to determine whether a single than 2.5.'-' Several attempts have been made to eliminate oral dose of omeprazole 40 mg is effective in increasing the pH of gastric residue above 2.5 at the time of induction of the risk of pulmonary aspiration by altering the pH of anaesthesia. gastric contents towards neutral. Antacids and H,-receptor antagonists are employed with variable success. Cimetidine was investigated widely as a premedicant to increase the pH Methods and decrease the volume of gastric content^.^-^ However, Forty-four adult patients (ASA 1 or 2) scheduled for some patients have a gastric pH of 2.5 or less after cimetidine and are potentially at risk of gastric a ~ p i r a t i o n . ~ ~ . ~elective gynaecological surgery were studied. Informed verbal consent was obtained from each patient, and the Ranitidine, a more potent H,-receptor antagonist, seems to study was approved by the hospital's ethics committee. No be more effective than cimetidine in increasing gastric pH"* patient had gastrointestinal disease or was taking drugs but 8% of patients still have a pH less than 2.5 and 17% known to influence gastric acidity or volume. Obese less than 3.5.9 Omeprazole, a substituted benzimidazole, patients were not included in the study (body weight 20% decreases gastric secretion by inhibiting the action of the above the ideal weight was defined as obesity). Age, weight proton pump H+-K+ ATP-ase, which exchanges luminal and fasting interval were recorded. All the patients had potassium for cellular hydrogen ions.'O Omeprazole is more fasted for a minimum of 8 hours before induction of potent than H,-receptor antagonists because it acts on the anaesthesia. Patients were allocated randomly to one of final step in the stimulatory process for acid secretion." L. Ng Wingtin, MB, Head of Department, F. Hardy, MB, S. Phil, MB, Department of Anaesthesia I, H6pital Delafontaine, 93205 Saint Denis, France. D. Glomaud, MB, Department of Anaesthesia, H6pital HBtel-Dieu, I place Parvis Notre Dame, 75004 Paris, France. Accepted 18 December 1989. 0003-2409/90/060436 + 03 !$03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland
436
Pre-anaesthetic omeprazole for acid aspiration prophylaxis
431
Table 1. Patients’ characteristics. Data are presented as mean (SEM).
Number of patients
Age (years)
Weight (kg)
Fasting interval (hours)
22 22
36.8 (2.4) 36.4 (2.7)
60.3 (1.4) 60.9 (1.8)
10.7 (0.2) 10.5 (0.5)
Group 1 (control) Group 2 (omeprazole)
Table 2. Gastric pH and volume.
pH mean (SEM) and range Group I (control)
% patients with gastric pH (3.5
Volume (ml) mean (SEM) and range
50
15.2 (2.7) &50 9.2 (1.8) 0-50
3.1 (0.5) 1.1-7.5 5.9 (0.4) 2.4-7.8
Group 2 (omeprazole)
4.5
p 25 ml. Results were considered statistically significant if the p value was less than 0.05.
Results The two groups were comparable in respect of age, weight and fasting interval (Table I). There were no differences between groups in the incidences of smoking, heartburn or dyspepsia. Gastric contents could not be obtained from three patients in group 1 and five patients in group 2. Consequently, the pH data are not available for these eight patients. The volume and pH of gastric fluid are shown in Table 2. Mean pH was higher in patients treated with omeprazole than in the control group (p < 0.001). Fifty percent of patients in the control group had a pH of less than 3.5 compared with 4.5% in the omeprazole group (p < 0.01). Mean (SEM) gastric volume was 15.2 (2.7) ml in the control group and 9.2 ( I .8) ml in the omeprazole group but the difference was not statistically significant. Twenty-three percent of patients in the control group had a gastric volume in excess of 25 ml compared with 9% in the treated group. Figure 1 is a scattergram of volume and pH values in the two groups. Most of the values from the omeprazole
. .
-
I
-E W
E 3 -
8
201
; .: ..
-,
I
2
1,:...
,
,
5
6
*..
0 .
3
4
.;..... .I
7
8
PH
Fig. 1. Scattergram of volume versus pH in the control
groups (m).
( 0 ) and
the omeprazole
438
L. N g Wingtin et al.
group fell in the safest area, i.e. low volume with high pH. Most of the values from the control group fell in the low pH area.
Discussion Mendelson14 and TeabeautI5 have demonstrated the importance of pH in the aetiology of aspiration. A gastric p H below 2.5 and a volume of 25 ml or greater are considered critical factors for the development of pulmonary damage in adults.I6 According to this definition, 17 to 64% of elective adult patients who have been fasting are said to be at risk.24 However, a higher percentage of patients coming for elective surgery are at risk if Crawford’s suggestion of a limit of pH of 3.5 i6 accepted.” Omeprazole reduced significantly the number of patients at risk if aspiration should occur. Only one patient (4.5%) had a p H < 3.5 (pH = 2.4). One possible explanation for the failure of omeprazole to increase the pH‘of the gastric contents to more than 3.5 in that patient is inadequate dosage. It is known that single oral administration of omeprazole 20-80 mg gives a dosedependent inhibition of acid secretion of about 30 to 100% for 24-48 hours. A single dose of 40 mg reduces pentagastrin-stimulated acid output by 65%. The inhibition of gastric secretion is total (goo/,) with a single dose of 80 mg. I 2 - l H Omeprazole did not reduce significantly the residual gastric volume. Sampling through a Salem sump tube may underestimate the total volume,’9but there is a good correlation between volume aspirated and volume determined by indicator dilution.20 In conclusion, omeprazole was effective in reducing gastric acidity in adult patients scheduled for elective gynaecological surgery. A single oral dose of 40 mg decreased significantly the number of patients at risk of serious pulmonary damage. Further study of the effect on gastric pH and volume is indicated with a dose of 60 to 80 mg.
References I . CWMBS DW, HWPER D, COLTON T. Acid-aspiration prophylaxis by use of preoperative oral administration of cimetidine. Anesthesiology 1979; 51: 352-6. 2. MANCHIKANTI L, MARRERO TC, ROUSHJR. Preanesthetic cimetidine and metoclopramide for acid aspiration prophylaxis in elective surgery. Anesthesiology 1984; 61: 48-54. 3. SUTHEKLAND AD, MALTBY JR, SALEJP, REIDCRG. The effect
of pre-operative oral fluid and ranitidine on gastric fluid volume and pH. Canadian Journal of Anaesthesia 1987; 34: 117-21. 4. STOELTINGRK. Gastric fluid pH in patients receiving cimetidine. Anesthesia and Analgesia 1978; 57: 675-7. 5. MANCHIKANTI L, KRAUSJW, EDDSSP. Cimetidine and related drugs in anesthesia. Anesthesia and Analgesia 1982; 61: 595-608. 6. MORISON DH, DUNNGL, FARGAS-BABJAK AM, MOUDGIL GC, SMEDSTAD K, Woo J. A double-blind comparison of cimetidine and ranitidine as prophylaxis against gastric aspiration syndrome. Anesthesia and Analgesia 1982; 61: 988-92. 7. MCCARTHY DM. Ranitidine or cimetidine? Annals of Internal Medicine 1983; 9 9 551-3. 8. FRANCIS RN, KWIT RSH. Oral ranitidine for prophylaxis against Mendelson’s syndrome. Anesthesia and Analgesia 1982; 61: 13G2. 9. DURRANT JM, STRUNIN L. Comparative trial of the effect of ranitidine and cimetidine on gastric secretion in fasting patients at induction of anaesthesia. Canadian Anaesthetists’ Society Journal 1982; 2 9 44651. 10. FELLINUS E, BERGLINDH T, SACHSG, OLBEL, ELANDER B, SJOSTRAND SE, WALLMARK B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+-K+)ATPase. Nature 1981; 290: 159-61. 11. WALLMARK B, JARESTEMBM, LARSSONH, RYBERGB, BRANDSTROM A, FELLENIUS E. Differentiation among inhibitory actions of omeprazole, cimetidine, and SCN on gastric acid secretion. American Journal of Physiology 1983; 245 (Suppl. 1): G 6 6 G 7 1 . C , EKENVED G, HAGLUND U, OLBEL. 12. LINDT, CEDERBERG Effect of omeprazole-a gastric proton pump inhibitor-on pentagastrin stimulated acid secretion in man. Gut 1983; 2 4 270-6. 13. PRICHARD PJ, YEOMANS ND, MIHALY GW, JONESDB, BUCKLE PJ, SMALLWWD RA. LOUISWJ. Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage. Gastroenterology 1985; 88: 64-9. 14. MENDELSON CL. Aspiration of stomach contents into lungs during obstetric anesthesia. American Journal of Obstetrics and Gynecology 1946; 5 3 191-205. 15. TEABEAUT JR. Aspiration of gastric contents. An experimental study. American Journal of Pathology 1952; 2 8 51-62. 16. ROBERTSRB, SHIRLEYMA. Reducing the risk of acid aspiration during cesarean section. Anesthesia and Analgesia 1974; 53: 859-68. 17. CRAWFORDS. Cimetidine in elective Caesarian section. Anaesthesia 1981; 36:641-2. 18. MULLERP, DAMMANN HG, SEITZ H, SIMONB. Effect of repeated, once daily. oral omeprazole on gastric secretion. Lancet 1983; 1: 66. 19. ADELHOJB, PETRINGOU, HAGELSTEN JO. Inaccuracy of peranesthetic gastric intubation for emptying liquid stomach contents. Acta Anaesthesiologica Scandinavica 1986; 3 0 41-3. 20. HARDYJF, PLOURDE G, LEBRUN M, COTEC, DUBES, LEPAGE Y. Determining gastric contents during general anaesthesia: evaluation of two methods. Canadian Journal of Anaesthesia 1987; 3 4 474-7.
Omeprazole for prophylaxis of acid aspiration in elective surgery
L. NG WINGTIN, D. GLOMAUD, F. HARDY
AND
S. PHIL
Summary The aim of the study was to determine whether a single oral dose of omeprazole 40 mg is effective in increasing the p H of gastric residue above 2.5 at the time of anaesthetic induction in adult patients scheduled for elective gynaecological surgery. The patients were allocated to receive either chlorazepate dipotassium 25 mg alone or omeprazole 40 mg and chlorazepate dipotassium 25 mg on the night before surgery. Gastric volume and p H were measured after induction of anaesthesia. Patients who received omeprazole had a higher mean p H than control patients ( p < 0.001). The p H was less than 3.5 in 50% of patients in the control group, but in only 4.5% of rhose who received omeprazole ( p < 0.01). Mean ( S E M ) volume of gastricfluid was 15.2 (2.7) ml in the control group and 9.2 (1.8) ml in the omeprazole group, but the results were not statistically signijicant. A single dose of 40 mg omeprazole significantly decreased the number of patients at risk of aspiration pneumonitis.
Key words Gastrointestinal tract; gastric pH, gastric volume. Pharmacology; omeprazole.
The danger of pulmonary aspiration is always of concern Numerous studies have shown almost total inhibition of to anaesthetists. Between 30 and 50% of patients scheduled gastric secretion and acidity with no detectable side effects in normal individuals and patients with duodenal ulcers for elective surgery after a fasting period of more than 8 after treatment with ~ m e p r a z o l e . ~ ~ J ~ hours have a gastric volume greater than 25 m11-3and an even greater percentage (6482%) have a gastric pH less The aim of the study was to determine whether a single than 2.5.'-' Several attempts have been made to eliminate oral dose of omeprazole 40 mg is effective in increasing the pH of gastric residue above 2.5 at the time of induction of the risk of pulmonary aspiration by altering the pH of anaesthesia. gastric contents towards neutral. Antacids and H,-receptor antagonists are employed with variable success. Cimetidine was investigated widely as a premedicant to increase the pH Methods and decrease the volume of gastric content^.^-^ However, Forty-four adult patients (ASA 1 or 2) scheduled for some patients have a gastric pH of 2.5 or less after cimetidine and are potentially at risk of gastric a ~ p i r a t i o n . ~ ~ . ~elective gynaecological surgery were studied. Informed verbal consent was obtained from each patient, and the Ranitidine, a more potent H,-receptor antagonist, seems to study was approved by the hospital's ethics committee. No be more effective than cimetidine in increasing gastric pH"* patient had gastrointestinal disease or was taking drugs but 8% of patients still have a pH less than 2.5 and 17% known to influence gastric acidity or volume. Obese less than 3.5.9 Omeprazole, a substituted benzimidazole, patients were not included in the study (body weight 20% decreases gastric secretion by inhibiting the action of the above the ideal weight was defined as obesity). Age, weight proton pump H+-K+ ATP-ase, which exchanges luminal and fasting interval were recorded. All the patients had potassium for cellular hydrogen ions.'O Omeprazole is more fasted for a minimum of 8 hours before induction of potent than H,-receptor antagonists because it acts on the anaesthesia. Patients were allocated randomly to one of final step in the stimulatory process for acid secretion." L. Ng Wingtin, MB, Head of Department, F. Hardy, MB, S. Phil, MB, Department of Anaesthesia I, H6pital Delafontaine, 93205 Saint Denis, France. D. Glomaud, MB, Department of Anaesthesia, H6pital HBtel-Dieu, I place Parvis Notre Dame, 75004 Paris, France. Accepted 18 December 1989. 0003-2409/90/060436 + 03 !$03.00/0
@ 1990 The Association of Anaesthetists of Gt Britain and Ireland
436
Pre-anaesthetic omeprazole for acid aspiration prophylaxis
431
Table 1. Patients’ characteristics. Data are presented as mean (SEM).
Number of patients
Age (years)
Weight (kg)
Fasting interval (hours)
22 22
36.8 (2.4) 36.4 (2.7)
60.3 (1.4) 60.9 (1.8)
10.7 (0.2) 10.5 (0.5)
Group 1 (control) Group 2 (omeprazole)
Table 2. Gastric pH and volume.
pH mean (SEM) and range Group I (control)
% patients with gastric pH (3.5
Volume (ml) mean (SEM) and range
50
15.2 (2.7) &50 9.2 (1.8) 0-50
3.1 (0.5) 1.1-7.5 5.9 (0.4) 2.4-7.8
Group 2 (omeprazole)
4.5
p 25 ml. Results were considered statistically significant if the p value was less than 0.05.
Results The two groups were comparable in respect of age, weight and fasting interval (Table I). There were no differences between groups in the incidences of smoking, heartburn or dyspepsia. Gastric contents could not be obtained from three patients in group 1 and five patients in group 2. Consequently, the pH data are not available for these eight patients. The volume and pH of gastric fluid are shown in Table 2. Mean pH was higher in patients treated with omeprazole than in the control group (p < 0.001). Fifty percent of patients in the control group had a pH of less than 3.5 compared with 4.5% in the omeprazole group (p < 0.01). Mean (SEM) gastric volume was 15.2 (2.7) ml in the control group and 9.2 ( I .8) ml in the omeprazole group but the difference was not statistically significant. Twenty-three percent of patients in the control group had a gastric volume in excess of 25 ml compared with 9% in the treated group. Figure 1 is a scattergram of volume and pH values in the two groups. Most of the values from the omeprazole
. .
-
I
-E W
E 3 -
8
201
; .: ..
-,
I
2
1,:...
,
,
5
6
*..
0 .
3
4
.;..... .I
7
8
PH
Fig. 1. Scattergram of volume versus pH in the control
groups (m).
( 0 ) and
the omeprazole
438
L. N g Wingtin et al.
group fell in the safest area, i.e. low volume with high pH. Most of the values from the control group fell in the low pH area.
Discussion Mendelson14 and TeabeautI5 have demonstrated the importance of pH in the aetiology of aspiration. A gastric p H below 2.5 and a volume of 25 ml or greater are considered critical factors for the development of pulmonary damage in adults.I6 According to this definition, 17 to 64% of elective adult patients who have been fasting are said to be at risk.24 However, a higher percentage of patients coming for elective surgery are at risk if Crawford’s suggestion of a limit of pH of 3.5 i6 accepted.” Omeprazole reduced significantly the number of patients at risk if aspiration should occur. Only one patient (4.5%) had a p H < 3.5 (pH = 2.4). One possible explanation for the failure of omeprazole to increase the pH‘of the gastric contents to more than 3.5 in that patient is inadequate dosage. It is known that single oral administration of omeprazole 20-80 mg gives a dosedependent inhibition of acid secretion of about 30 to 100% for 24-48 hours. A single dose of 40 mg reduces pentagastrin-stimulated acid output by 65%. The inhibition of gastric secretion is total (goo/,) with a single dose of 80 mg. I 2 - l H Omeprazole did not reduce significantly the residual gastric volume. Sampling through a Salem sump tube may underestimate the total volume,’9but there is a good correlation between volume aspirated and volume determined by indicator dilution.20 In conclusion, omeprazole was effective in reducing gastric acidity in adult patients scheduled for elective gynaecological surgery. A single oral dose of 40 mg decreased significantly the number of patients at risk of serious pulmonary damage. Further study of the effect on gastric pH and volume is indicated with a dose of 60 to 80 mg.
References I . CWMBS DW, HWPER D, COLTON T. Acid-aspiration prophylaxis by use of preoperative oral administration of cimetidine. Anesthesiology 1979; 51: 352-6. 2. MANCHIKANTI L, MARRERO TC, ROUSHJR. Preanesthetic cimetidine and metoclopramide for acid aspiration prophylaxis in elective surgery. Anesthesiology 1984; 61: 48-54. 3. SUTHEKLAND AD, MALTBY JR, SALEJP, REIDCRG. The effect
of pre-operative oral fluid and ranitidine on gastric fluid volume and pH. Canadian Journal of Anaesthesia 1987; 34: 117-21. 4. STOELTINGRK. Gastric fluid pH in patients receiving cimetidine. Anesthesia and Analgesia 1978; 57: 675-7. 5. MANCHIKANTI L, KRAUSJW, EDDSSP. Cimetidine and related drugs in anesthesia. Anesthesia and Analgesia 1982; 61: 595-608. 6. MORISON DH, DUNNGL, FARGAS-BABJAK AM, MOUDGIL GC, SMEDSTAD K, Woo J. A double-blind comparison of cimetidine and ranitidine as prophylaxis against gastric aspiration syndrome. Anesthesia and Analgesia 1982; 61: 988-92. 7. MCCARTHY DM. Ranitidine or cimetidine? Annals of Internal Medicine 1983; 9 9 551-3. 8. FRANCIS RN, KWIT RSH. Oral ranitidine for prophylaxis against Mendelson’s syndrome. Anesthesia and Analgesia 1982; 61: 13G2. 9. DURRANT JM, STRUNIN L. Comparative trial of the effect of ranitidine and cimetidine on gastric secretion in fasting patients at induction of anaesthesia. Canadian Anaesthetists’ Society Journal 1982; 2 9 44651. 10. FELLINUS E, BERGLINDH T, SACHSG, OLBEL, ELANDER B, SJOSTRAND SE, WALLMARK B. Substituted benzimidazoles inhibit gastric acid secretion by blocking (H+-K+)ATPase. Nature 1981; 290: 159-61. 11. WALLMARK B, JARESTEMBM, LARSSONH, RYBERGB, BRANDSTROM A, FELLENIUS E. Differentiation among inhibitory actions of omeprazole, cimetidine, and SCN on gastric acid secretion. American Journal of Physiology 1983; 245 (Suppl. 1): G 6 6 G 7 1 . C , EKENVED G, HAGLUND U, OLBEL. 12. LINDT, CEDERBERG Effect of omeprazole-a gastric proton pump inhibitor-on pentagastrin stimulated acid secretion in man. Gut 1983; 2 4 270-6. 13. PRICHARD PJ, YEOMANS ND, MIHALY GW, JONESDB, BUCKLE PJ, SMALLWWD RA. LOUISWJ. Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics after morning or evening dosage. Gastroenterology 1985; 88: 64-9. 14. MENDELSON CL. Aspiration of stomach contents into lungs during obstetric anesthesia. American Journal of Obstetrics and Gynecology 1946; 5 3 191-205. 15. TEABEAUT JR. Aspiration of gastric contents. An experimental study. American Journal of Pathology 1952; 2 8 51-62. 16. ROBERTSRB, SHIRLEYMA. Reducing the risk of acid aspiration during cesarean section. Anesthesia and Analgesia 1974; 53: 859-68. 17. CRAWFORDS. Cimetidine in elective Caesarian section. Anaesthesia 1981; 36:641-2. 18. MULLERP, DAMMANN HG, SEITZ H, SIMONB. Effect of repeated, once daily. oral omeprazole on gastric secretion. Lancet 1983; 1: 66. 19. ADELHOJB, PETRINGOU, HAGELSTEN JO. Inaccuracy of peranesthetic gastric intubation for emptying liquid stomach contents. Acta Anaesthesiologica Scandinavica 1986; 3 0 41-3. 20. HARDYJF, PLOURDE G, LEBRUN M, COTEC, DUBES, LEPAGE Y. Determining gastric contents during general anaesthesia: evaluation of two methods. Canadian Journal of Anaesthesia 1987; 3 4 474-7.
