Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia

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1 Anaesthesia, 1984, Volume 39, pages Combined treatment with ranitidine and saline antacids prior to obstetric anaesthesia E M THOMPSON, P G LOUGHRAN, D M McAULEY, C M WILSON AND J MOORE Summary Ranitidine I50 mg was given to 126patients 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 03 M sodium citrate and 118 women, 20 ml of 84% sodium bicarbonate 10 minutes before induction of anaesthesia In the citrate sub-group there was one patient with a gastric ph less than 25 (mean ph 62, SEM 013 range 21-84) In the bicarbonate sub-group the lowest gastric acidity was 38 (mean ph 83, SEM 011 range ) Key words Gastrointestinal tract; stomach, ph Histamine; H,-receptor antagonist, ranitidine Antacid; sodium citrate, sodium bicarbonate Ranitidine 150 mg given orally at 6-hourly intervals effectively controls gastric hyperacidity in the majority of women during childbirth' There are two main reasons for failure to achieve a safe intragastric ph with this treatment In those patients requiring anaesthesia within 2 hours of the initial dose the time interval between treatment and induction is too short to allow for emptying of existing gastric acid and achievement of an effective therapeutic plasma level of ranitidine During labour the absorption of ranitidine is slowed by the concurrent admin- istration of narcotic analgesics because of their slowing effect on gastro-intestinal motility' As the aim of any antacid treatment is to reduce gastric acidity to safe levels in all parturients such deficiencies have to be resolved This might be achieved by giving an immediate pre-anaesthetic treatment with a saline antacid They have been shown to be less likely to provoke a severe pulmonary reaction than emulsion antacids should lung soiling occurz This report deals with the use of oral ranitidine to inhibit gastric acid secretion in all parturients and its supplementa- EM Thompson, MB, FFARCS, Senior Tutor/Senior Registrar, PG Loughran,* MB, FFARCS, Senior Tutor/Senior Registrar, DM McAuley, MB, FFARCS Consultant CM Wilson, MB, FFARCS, Senior Tutor/Senior Registrar, J Moore,MD, PhD, FFARCS, Consultant, Department of Anaesthetics, The Queen's University of Belfast, Northern Ireland Present appointment: Consultant Anaesthetist, Daisy Hill Hospital, Newry /84/ The Association of Anaesthetists of Gt Britain and Ireland 1086

2 Treatment with ranitidine and saline antacids 1087 tion by an oral dose of either 03 M sodium citrate or 84% sodium bicarbonate immediately before general anaesthesia Methods All patients entering the delivery suite were included and were either in active labour or to be delivered by elective Caesarean section Those in active labour received ranitidine 150 mg by mouth and this was repeated at 6-hourly intervals until completion of the third stage If vomiting occurred within 30 minutes of receiving ranitidine it was repeated In the elective series a similar dose was given at least 2 hours before induction of general anaesthesia All women, except 43 in the elective Caesarean group and 12 in active labour, requiring to be anaesthetised were given either 30 ml or 03 M sodium citrate or 20 ml 84% sodium bicarbonate 10 minutes prior to induction All were anaesthetised using a technique involving pre-oxygenation, application of cricoid pressure, rapid intravenous induction and muscle relaxation followed by tracheal intubation Gastric contents were obtained immediately after the establishment of safe anaesthesia as in previous ~tudies~ A lightly lubricated No 18 Salem sump tube was introduced into the stomach via a 75 mm uncuffed orotracheal tube placed in the oesophagus until only the last 10 cm remained visible Aspirates were obtained during its slow withdrawal Their volume was noted and the ph determined using a Corning 1 I3 ph meter and microelectrode With samples of less than 10 ml the ph was measured using universal indicator paper Volumes of gastric contents are expressed as mean (SEM) and their range is given All treatments were noted on a special record sheet which also included details of labour, use of narcotic analgesics, maternal and fetal cardiovascular variables, progress in labour and the occurrence of vomiting Side effects, subjective or objective, that might be related to the antacid treatment together with mode of delivery, conduct of third stage and blood loss were also noted The condition of the infant, as assessed by the Apgar score at 2 and 5 minutes together with any problems with its resuscitation were recorded Results Of the I26 women delivered by elective Caesarean section, 43 were treated with ranitidine alone, while 43 and 40 received ranitidine plus sodium citrate or sodium bicarbonate respectively The scatter of the ph of the gastric aspirations following induction is shown in Fig I Gastric I a 5 4L Fig 1 ph of gastric contents from women undergoing elective Caesarean section who were given 150 mg ranitidine alone (m) or ranitidine supplemented with either 20 ml 84% sodium bicarbonate (0) or 30 ml 03 M sodium citrate (0) orally acidity was satisfactorily reduced in all patients irrespective of the type of antacid treatment given, including 14 who were anaesthetised within the latent 2-hour interval The mean ph and gastric volumes from these sub-groups are seen in Table I Gastric acidity was significantly less in patients treated with ranitidine and sodium Table 1 Mean (SEM) with range, of gastric volume and ph in patients undergoing elective Caesarean section who received ranitidine alone or supplemented bv sodium citrate or sodium bicarbonate Rani tidine Mean (SEM, range) supplemented by PH Vol (ml) Nil (n = 43) 66 (015) 77 (126) Sodium citrate (n = 43) (31-82) 70 (016) (05-40) (05-90) Sodium bicarbonate (53-87) 282 (312) 895 (0073) 261 (229) (n = 40) (71-97)' (3&56)* *Significantly greater than control group (ranitidine alone)

3 ~~ ~~ 1088 EM Thompson et al bicarbonate than in those given sodium citrate plus ranitidine or ranitidine alone The volume of the total gastric aspirate was significantly less when saline antacids were not given but the mean volumes were small in all three sub-groups Two hundred and forty two women required a general anaesthetic during active labour All, except nine, received ranitidine I50 mg orally at 6-hourly intervals; 103 were given an immediate pre-anaesthetic dose of sodium citrate, I18 sodium bicarbonate and 12 had ranitidine alone The distribution of the ph of gastric aspirates from the citrate and bicarbonate series is shown in Figs 2 and 3 respectively In the citrate group one reading of 212 was recorded whereas the lowest value in the bicarbonate group was 38 Fig 2 ph of gastric contents from women who required general anaesthesia in labour who were given 150 mg ranitidine 6-hourly plus a dose of 30 ml 03 M sodium citrate orally 10 minutes pre-induction r Table 2 Mean (SEM), with range, of gastric ph and volume in patients requiring general anaesthesia in labour who received ranitidine supplemented with sodium citrate or sodium bicarbonate Ranitidine Mean (SEM, range) supplemented by PH Vol (ml) Sodium citrate (n = 103) 62 (013) 702 (1053) (21-84) (05-872) Sodium bicarbonate 82 (01 1) 844 (951) (n = 1181 (38-983)* ( *Significant The mean gastric ph and volume of the aspirates for the two series are shown in Table 2 and intragastric acidity is significantly less with bicarbonate treatment 1:; 9r A wide range of gastric volumes occurred with 8 ** either treatment but the mean values were not 9 7 *;,$ n ; *, significantly different However in 74 of the ; * patients the volume of gastric aspirate was less a i * * *! than the arbitrary safe value of 25 ml4 z5 : Fifty four out of 242 patients in active labour required a general anaesthetic within the 2-hour latent period Of these, 27 received sodium citrate 2 and 19 sodium bicarbonate as a pre-induction antacid The ph and volumes of the gastric aspirates are shown in Fig 4 and Table 3 While the ph of gastric aspirates was above 25 in all of the bicarbonate treated patients, one aspirate in the citrate series had a ph of 212, as discussed above Despite the short duration of labour quite large values were occasionally aspirated During active labour 12 patients received ranitidine alone, the on duty anaesthetist 2 : I I I I I I I I ~ Fig 3 ph ofgastriccontents from women who required general anaesthesia in labour who were given 150 mg ranitidine 6-hourly plus a dose of 20 ml 840/, sodium bicarbonate orally 10 minutes pre-induction 0, no bicarbonate; 0, same patient; A no third tablet; 63, no second tablet 9t 45 a- * I - 0 lb $0,b 410,b,b 70 lo :o la0 I:, ; : 1 Time (min) Fig 4 ph of gastric contents from women anaesthetised within 2 hours of receiving the first dose of ranitidine 150 mg only (m) or ranitidine supplemented with either of the saline antacids (0)

4 Treatment with ranitidine and saline antacids 1089 Table 3 Mean (SEM), with range, of gastric ph and volume in patients requiring general anaesthesia within two hours of receiving the first 150 mg dose of ranitidine alone or ranitidine supplemented with sodium citrate or sodium bicarbonate Ranitidine Mean, (SEM range) supplemented by Time (min) ph Volume (ml) Sodium citrate (n = 27) 72 (62) 58 (032) 458 (725) (1CL120) ( ) (2-125) Sodium bicarbonate 69 (98) 73 (038) 735 (194) (n = 19) (10-120) (38-97)' (8-360) Nil (n = 8) 888 (146) 49 (09) 458 (138) (5-120) (17-87) (05-100) *Significant neglecting to give the pre-induction saline antacid Of this group, eight patients sampled during the 2-hour latent period are shown in Fig 4 The mean gastric ph was 49 (Table 3), three out of eight readings being less than 25 Of the remaining four women, three required general anaesthesia between 5 and 6 hours after the administration of ranitidine The ph of their gastric contents was 81,245 and 596 The fourth patient required anaesthesia for exploration of the uterus 12 hours after ranitidine treatment Her gastric contents had a ph of 64 By contrast nine women who received no ranitidine, despite its having been ordered, but had their preinduction dose of sodium bicarbonate, had gastric ph values varying from 745 to 925 No maternal or infant effects which could be attributed to the ranitidine or saline antacids were recorded Patients did however find the bicarbonate unpalatable compared to the aniseed flavoured citrate Discussion Ranitidine, because of its longer duration, is a more acceptable antacid than cimetidine for use in labour Its use, however, presents similar problems to those encountered with the latter drug, ie delayed onset and slowed uptake if narcotic analgesics are used In patients delivered by elective Caesarean section, ranitidine alone given orally at least two hours before induction provides reliable safe intragastric conditionss This study confirms this finding and indicates that saline antacids reduce further the intragastric acidity but at the expense of a slight increase in stomach content However, the addition of a saline antacid has the advantage that the labour ward antacid regime is similar for all patients requiring general anaesthesia In women requiring anaesthesia during active labour, less than 1% had an intragastric ph below the critical value if the ranitidine plus saline antacid regime was adhered to: 46 were anaesthetised within 2 hours of the initial ranitidine treatment and the addition of either of the two saline antacids reduced their gastric acidity to safe levels However the inadequacy of ranitidine alone in the first 2 hours is again evident in that three out of eight mothers had dangerous levels of gastric acidity Roberts and Shirle~,~ using data obtained from animal experiments, arbitrarily defined the patient at risk as having at least 25 ml of gastric contents of ph below 25 Gastric volumes in excess of this value were present in all treatment groups in both the elective and active labour series As stomach emptying is slowed during active labour by such factors as narcotic analgesics and stress, further addition to gastric contents by the repetitive use of emulsion antacids would seem inappropriate Ranitidine, by decreasing acid output, helps to decrease their build up and will also minimise any possible rebound acidity associated with antacid treatment, thereby contributing to safe induction and emergence from general anaesthesia The findings make it difficult to decide which saline antacid is better Sodium citrate has been recommended as a single-dose antacid treatment6 These workers considered that a 15-mI dose was effective especially in the emergency situation However, their technique was questionable as samples were taken via the same tube by which the citrate was instilled Further investigation of this antacid by Holdsworth et a1l showed

5 1090 EM Thompson et al that it mixed more readily with gastric contents than emulsion antacids However, Hester and Heath,* using a 15-ml dose prior to anaesthesia for elective surgery, reported a failure rate of 37 per cent, while Fo~lkes,~ giving twice this amount, had two out of IS patients with an intragastric ph below 25 Sodium bicarbonate has not found favour in obstetric anaesthesia, yet it has been shown by Lim et all0 to be an effective antacid These workers treated 55 emergency obstetric patients with an immediate pre-anaesthetic dose of 20 ml of an 84% solution and found that the lowest intragastric ph was 684 and that its duration was sufficient to cover the emergence period However a pilot study undertaken by the authors, using gynaecological patients of reproductive age, indicated that sodium bicarbonate had a brief neutralising action not exceeding 30 minutes Rebound acidity was demonstrated in our pilot study by a group of 12 patients given sodium bicarbonate one hour pre-operatively The gastric ph was less than 25 in I1 patients, a higher percentage than the control group (56 per cent) given no alkali, confirming the in vitro study by Lahiri et a16 Carbon dioxide release from the reaction of sodium bicarbonate and hydrochloric acid might theoretically increase the risk of regurgitation during induction The dose used here would evolve approximately 509 ml of gas in a complete reaction with hydrochloric acid In comparison, the sodium bicarbonate in 30 ml of mist magnesium trisilicate BP can release approximately 454 ml, while the magnesium carbonate present can potentially contribute a further 314 ml gas On the other hand sodium citrate does not involve the evolution of carbon dioxide if mixed with acid The combined use of ranitidine and a saline antacid immediately before induction allows each treatment to complement the other and ensure safe intragastric conditions for general anaesthesia In the present study sodium bicarbonate was most effective in the elective group and despite occasional failures to adhere strictly to the ranitidine therapy in the active labour series adequate reduction in intragastric acidity was recorded There is universal agreement that gastric hyperacidity in the parturient requiring general anaesthesia should be treated It is our opinion that in elective situations this can be done by a single oral 150 mg dose of ranitidine given at least 2 hours before induction For those women in active labour a similar dose given at 6-hourly intervals should be supplemented with a preoperative dose of a saline antacid either 30 ml sodium citrate or 20 ml 84% sodium bicarbonate Our choice would be the latter because of its rapid onset and greater effectiveness Acknowledgments Our thanks go to the staff of the labour and maternity wards of Belfast City Hospital; Daisy Hill Hospital, Newry; Ulster Hospital, Dundonald and Craigavon Area Hospital References I MCAULEY DM, MOORE J DUNUEE JW, Mc- CAUGHEY W Oral ranitidine in labour Anaesthesia 1984; 39 43S8 2 GIBBS CP, SCHWARTZ DJ, WYNNE JW, HOOD C1, KUCK EJ Antacid pulmonary aspiration in the dog Anesthesiology 1919; 51: JOHNSTON JR, MCCAUGHEY W, MOORE J, DUNDEE JW Cimetidine as an oral antacid before elective Caesarean section Anaesthesia 1982; 37: ROBERTS RB SHIRLEY MA Reducing the risk of acid aspiration during Cesarean section Anesrhesia and Analgesia 1974; 53: MCAULEY DM, MOORE J, MCCAUGHEY W, DONNELLY BD, DUNUEE JW Ranitidine as an antacid before elective Caesarean section Anaesthesia 1983; LAHIRI SK, THOMAS TA, HODGSON RMH Singledose antacid therapy for the prevention of Mendelson's syndrome British Journul of Anaesthesia 1973; HOLDSWORTH JD, JOHNSON K, MASCALL G ROULSTON RG, TOMLINSON PA Mixing of antacids with stomach contents Another approach to the prevention of acid aspiration (Mendelson's) syndrome Anaesthesia 1980; 35: 64-SO 8 HESTER JB, HEATH ML Pulmonary acid aspiration syndrome: should prophylaxis be routine? Brirish Journal of Anaesthesia 1911; FOULKES E, JENKINS LC A comparative evaluation of cimetidine and sodium citrate to decrease gastric acidity: effectiveness at the time of induction of anaesthesia Canadian Anaesthetists' Society Journal 1981; u1: LIM HS, TAN PL Sodium bicarbonate USP as an oral antacid for emergency Caesarean section patients Survey of Anesrhesiology 198 I; 25 A339