EVALUATION OF THE COMBINED EFFECTS OF GLYCOPYRROLATE AND NEOSTIGMINE ON THE LOWER OESOPHAGEAL SPHINCTER

The effects on the lower oesophageal sphincter (LOS) of thesimultaneous administration of glycopyrrolate 0.5 mg and neostigmine2.5 mg, when given to antagonize neuromuscular blockade, werestudied in 10 healthy patients undergoing gynaecological surgery.LOS pressure and gastric pressure (GP) were measured for 20min after the administration of the drug combination and barrierpressure (BrP) was calculated (LOS—GP). There was a significantreduction in BrP which lasted, in some patients, for the durationof the study. These results contrast with those of a similarstudy looking at the effects of atropine and neostigmine inwhich the decrease in BrP, although significant, was transient,and in which control values were regained after 5 min.     

The effect of glycopyrrolate (Robinul) on the lower oesophageal sphincter

Regurgitation and inhalation of acid gastric content, with resultant chemical pneumonitis, remains a common cause of death during anaesthesia. The effects of intravenous glycopyrrolate 0.3 mg on the lower oesophageal sphincter tone was studied in normal human subjects. Glycopyrrolate decreased lower oesophageal sphincter pressure by 0.88 kPa (p less than 0.005). This finding is of clinical importance in the pre-operative preparation of patients presenting for emergency surgery. A drug which decreases lower oesophageal sphincter tone would presumably increase the hazard of gastro-oesophageal reflux and pulmonary aspiration of acid gastric content.     

The administration of metoclopramide with atropine A drug interaction effect on the gastro–oesophageal sphincter in man

The effects of intravenous atropine 0-6 mg alone, metoclopramide (Maxolon) 10mg alone and atropine 0-6 mg and metoclopramide 10 mg in combination, on the lower oesophageal sphincter (LOS) were studied in three groups of normal human volunteers. Atropine decreased the LOS pressure by an average of 8 cm H2O (P less than 0-001), whereas metoclopramide increased the LOS pressure by a mean of 29 cmH2O compared to basal values (P less than 0-001). In contrast, no change in sphincter tone was noted following injection of atropine-metaclopramide mixture. These findings are relevant to the pre-operative preparation of patients presenting for emergency anaesthesia, since gasgro-oesophageal reflux and pulmonary aspiration of acid gastric content continues to be a significant cause of morbidity and mortality.     

Effect of ranitidine given before atropine sulphate on lower oesophageal sphincter tone

The effects on lower oesophageal sphincter tone of intravenous ranitidine 150 mg followed by atropine 0.6 mg were studied in six healthy volunteers. Ranitidine increased the mean lower oesophageal sphincter pressure by 21.2 cm H2O (p less than 0.01). Subsequent injection of atropine lowered the lower oesophageal sphincter pressure but not significantly, mean sphincter pressure remaining 14.2 cm H2O above control. Barrier pressure to reflux (lower oesophageal sphincter pressure minus gastric pressure) increased significantly after intravenous ranitidine injection, and although it fell after intravenous atropine it was still above control levels. The results of this study suggest that ranitidine increases lower oesophageal sphincter tone. When it is given prior to atropine injection within 20 minutes before induction of anaesthesia it counteracts the deleterious effect of the latter on sphincter tone and barrier pressure to reflux.     

EVALUATION OF THE COMBINED EFFECTS OF ATROPINE AND NEOSTIGMINE ON THE LOWER OESOPHAGEAL SPHINCTER

The effects, on the lower oesophageal sphincter, of the simultaneousadministration of atropine and neostigmine were studied in 10healthy patients undergoing gynaecological surgery. Atropine1.2 mg and neostigmine 2.5 mg were given to antagonize neuromuscularblockade at the termination of surgery. For the succeeding 15–20min, frequent measurements of lower oesophageal sphincter pressure(LOSP) were made whilst anaesthesia was maintained. It was demonstratedthat this drug combination resulted in a significant decreasein LOSP initially, but that this potentially deleterious effectwas transient in nature.     

The effect of cyclizine hydrochloride on lower oesophageal sphincter pressure in man.

Gastro-oesophageal reflux and pulmonary aspiration of acid gastric content remain significant causes of morbidity and mortality. A drug which increases lower oesophageal sphincter (LOS) tone would reduce this hazard. The effect of LOS function of intravenous cyclizine (25 mg), in half the recommended adult dose, was investigated in 8 volunteers. Cyclizine increased the LOS pressure by an average of 14,4 cm H2O (P less than 0,005). Cyclizine, like metoclopramide, has a desirable functional effect on the LOS. Both drugs are, in addition, potent anti-emetics. On the grounds of these pharmacological properties they are recommended in the preparation of patients for emergency surgery.     

Effects of thoracic epidural analgesia with morphine or bupivacaine on lower oesophageal motility – an experimental study in man

Lower oesophageal peristalsis and lower oesophageal sphincter (LOS) pressure during thoracic epidural analgesia (TEA) were studied in 20 healthy volunteers. After oesophageal manometric baseline recordings, 10 volunteers received 4 mg epidural morphine. The other ten received 0.5% bupivacaine epidurally in sufficient amounts to block the sympathetic innervation of the oesophagus. Thereafter oesophageal manometry was repeated. During epidural morphine oesophageal peristalsis, resting LOS pressure and the contraction of LOS after swallowing did not change, but the relaxation of the LOS in response to swallowing decreased significantly (P less than 0.01). Following TEA with bupivacaine, neither distal oesophageal peristalsis nor LOS pressure changed.     

Prospective study of the effect of laparoscopic Nissen fundoplication on reflux mechanisms.

BACKGROUND: Laparoscopic Nissen fundoplication effectively reduces acid reflux and reflux symptoms. Little is known about the effect on reflux mechanisms, especially on transient lower oesophageal sphincter relaxations (TLOSRs). METHODS: Twenty-seven patients were studied prospectively before and after laparoscopic Nissen fundoplication, by simultaneous recording of pH and lower oesophageal sphincter (LOS) characteristics using sleeve manometry. In all of the 27 patients the operation was judged successful, based on major improvement or resolution of reflux symptoms and acid reflux. Vagus nerve integrity was studied indirectly by the secretion of pancreatic polypeptide (PP) in response to insulin-induced hypoglycaemia. RESULTS: After fundoplication basal LOS pressure increased significantly from mean(s.e.m.) 13(1) to 22(1) mmHg (P < 0.001). Laparoscopic Nissen fundoplication significantly decreased the frequency of TLOSR in the fasting period from mean(s.e.m.) 2.5(0.5) to 0.6(0.2) per h, and in the postprandial period from 4.0(0.4) to 1.3(0.3) per h (P < 0.01). The percentage of TLOSRs associated with reflux also decreased significantly from 24(10) to 0(0) per cent in the fasting period and from 42(6) to 12(6) per cent in the postprandial period, before and after fundoplication respectively (P < 0.01). After operation the PP response was abnormal in three patients, pointing to vagus nerve dysfunction. Postoperative TLOSR frequency and LOS pressure were no different between patients with and without vagus nerve dysfunction. CONCLUSION: Laparoscopic Nissen fundoplication significantly increased fasting and postprandial LOS pressure and significantly decreased the rate of TLOSR. This resulted in a significant reduction in oesophageal acid exposure but postprandial LOS characteristics were preserved.     

The sphinctometer: a new device for measurement of lower oesophageal sphincter function

Current evidence suggests that lower oesophageal sphincter (LOS) competence depends upon both pressure and length. Existing devices can measure length and pressure, but not simultaneously. This methodological problem is a fundamental drawback to understanding LOS function and its role in oesophageal disease. A 'sphinctometer' has been developed, consisting of an oil-filled 3-mm diameter Silastic chamber, 6 cm in length, incorporating a pressure microtransducer designed to provide an integrated pressure reading as a function of length. Its performance has been tested in vitro using human cadaver oesophagus in a specially constructed chamber in which sphincter length and pressure can be varied independently. Comparisons were made with a conventional pull-through technique. Sphinctometer response was linear throughout the LOS pressure range of 0 to 50 mmHg at a fixed LOS length (RS = 0.99; P less than 0.001). Sphinctometer response was also linear at fixed LOS pressure for sphincter lengths from 1 to 6 cm (RS = 0.99; P less than 0.001). This device thus appeared suitable for monitoring function of the human LOS, and has subsequently been successfully incorporated into an ambulatory system for patient use.     

Analysis and surgical treatment of persistent dysphagia after Nissen fundoplication

BACKGROUND: After Nissen fundoplication, troublesome dysphagia develops in 5-10 per cent of patients. The mechanism of dysphagia has not been fully resolved, in spite of a number of studies focusing on oesophageal motility and lower oesophageal sphincter (LOS) dynamics. Tightness and length of the wrap have had considerable attention, without giving a fully satisfactory explanation of the pathophysiological mechanism. METHODS: Eighteen patients with persistent dysphagia after Nissen fundoplication needing reoperation were studied. Eighteen patients, matched for age and sex, without dysphagia after Nissen fundoplication were used as controls. Reoperation consisted of conversion of a 360 degrees into a 270 degrees wrap. Barium swallow, endoscopy, oesophageal manometry and 24-h pH monitoring were performed before and after (re)operation. RESULTS: Peristaltic amplitude, velocity and duration of contraction were not significantly influenced by operation. In 16 of 18 patients with dysphagia, LOS relaxation was incomplete and the residual relaxation pressure was significantly higher than that in the group without dysphagia (P < 0.01). No correlation was found between LOS pressure and peristaltic amplitude, nor between LOS pressure and ramp pressure in the distal oesophagus. After reoperation, basal LOS pressure decreased significantly (P < 0.01) and LOS relaxation was complete in all but three patients; residual relaxation pressure decreased (P < 0.01) and was significantly lower than that after uncomplicated Nissen fundoplication. In the latter group, LOS pressure, residual relaxation pressure and ramp pressure increased significantly after operation (P < 0.01). CONCLUSION: A return to complete LOS relaxation and a decrease in residual relaxation pressure play an important role in resolving dysphagia.     

Atropine methylbromide and glycopyrrolate. A comparative study during reversal of neuromuscular block

Two quaternary anticholinergics, atropine methylbromide (methylatropine bromide, MAB) and glycopyrrolate (ROBINUL) were compared as adjuncts to neostigmine for the reversal of residual nondepolarising neuromuscular block. MAB 0.75 mg in combination with neostigmine 2 mg produced a marked initial rise in heart rate. This was significantly greater than that produced by the administration of glycopyrrolate 0.4 mg with neostigmine. The antisialogogue effects of the two anticholinergics were identical and the central nervous system status of the patients was similar. It is concluded that, with the doses used in this study, glycopyrrolate is a superior alternative to MAB and is the drug of choice if a quaternary ammonium anticholinergic is required.     

Barrier pressure and muscle relaxants

The effects of pancuronium and vecuronium on the lower oesophageal sphincter pressure were studied in 24 healthy patients anaesthetised with 0.5% halothane in nitrous oxide and oxygen. Following pancuronium 0.1 mg/kg intravenously, there was a significant increase in barrier pressure from a control value of 2.0 (SEM 0.14) kPa to 3.0 (SEM 0.27) kPa 1 minute after injection (p less than 0.05). This increase was sustained throughout the 15 minute period of recording and was accompanied by a significant increase in heart rate (p less than 0.001). Following administration of vecuronium 0.1 mg/kg intravenously there was an initial modest, though not significant increase in barrier pressure. This increase was significant (p less than 0.05) at 15 minutes. There were no cardiovascular changes following vecuronium.     

The lower oesophageal sphincter and the anaesthetist

Pulmonary aspiration of gastric contents during induction of, or emergence from, anaesthesia poses hazards for both surgical and obstetric patients requiring urgent operations. Little emphasis has been placed on the importance of the lower oesophageal sphincter in relation to regurgitation and aspiration. This is especially important since anaesthetic drugs have been known to both decrease and increase lower oesophageal sphincter (LOS) tone. Any drug that will decrease tone will increase the incidence of gastric oesophageal reflux while drugs that increase tone may decrease this hazard. This review outlines the problem of acid aspiration in relation to the LOS and the various drugs which may influence LOS pressure.     

The effect of metoclopramide on the lower oesophageal sphincter in late pregnancy

The effects of intravenous metoclopramide (Maxolon) on the lower oesophageal sphincter (LOS) were studied in three groups of patients, one group being normal control and the other two being pregnant females, one without heartburn and the other with. Metoclopramide increases the LOS pressure 20.5, 15.2 and 10.2 cm H2O respectively (p less than 0.005, p less than 0.005 and p less than 0.05). These findings suggest that for patients undergoing elective or emergency obstetrical anaesthesia, intravenous metoclopramide may help reduce the incidence of regurgitation of gastric contents.     

Pethidine, atropine, metoclopramide and the lower oesophageal sphincter

The effects of an intramuscular injection of pethidine (1.5 mg/kg) plus atropine 0.5 mg, or pethidine (1.5 mg/kg) plus atropine 0.5 mg plus metoclopramide 10 mg on the lower oesophageal sphincter pressure have been studied manometrically in human volunteers. The mean barrier pressure in the former group was significantly lower than the baseline for the 75 minutes studied. In the latter group the mean barrier pressure was significantly lower than the baseline value for the first 45 minutes only of the study. The addition of atropine 0.5 mg to pethidine 1.5 mg/kg further lowers the barrier pressure when compared with the depression seen with pethidine alone in a previous study. While the addition of intramuscular metoclopramide to the mixture of pethidine and atropine fails to return the mean barrier pressure to the baseline value, it does raise the mean barrier pressure to a level which is probably above the opening pressure of the lower oesophageal sphincter.     

Erythromycin enhances oesophageal motility in patients with gastro‐oesophageal reflux

Background : Intravenous (i.v.) erythromycin enhances gastric emptying and oesophageal motility in both healthy and disease situations, acting either as a motilin or acetylcholine agonist. The purpose of the present paper was to investigate any possible effect of i.v. erythromycin on oesophageal motility in patients with gastro‐oesophageal reflux (GOR). Methods : In 15 patients with GOR (proven on 24‐h ambulatory oesophageal pH measurement), standard oesophageal manometry was performed after i.v. injection of placebo and 200 mg erythromycin, in a random blind fashion. Results : Erythromycin significantly increased lower oesophageal sphincter (LOS) pressure from 17 ± 5 to 41 ± 10 mmHg (P < 0.001), without affecting the postdeglutition relaxation of LOS. Erythromycin also increased the amplitude (from 79 ± 34 to 97 ± 40 mmHg; P < 0.001), duration (from 3.4 ± 0.6 to 3.8 ± 0.6 s; P = 0.005), velocity (from 3.1 ± 0.8 to 3.5 ± 1.15 cm/s; P = 0.0047) and strength (from 149 ± 84 to 201 ± 103 mmHg·s; P < 0.001) of peristalsis at 5 cm proximal to the LOS. Similarly, the drug increased the amplitude of peristalsis at 10 and 15 cm proximal to the LOS (from 70 ± 39 to 77.4 ± 37 mmHg; P = 0.049 and from 36 ± 20 to 49 ± 36 mmHg; P = 0.004, respectively) and the duration of peristalsis at the same levels (from 3.1 ± 0.6 to 3.3 ± 0.5 s; P = 0.011, and from 2.7 ± 0.6 to 3 ± 0.5 s; P = 0.003, respectively). Conclusion : Intravenously administered erythromycin improves impaired oesophageal motility in patients with GOR. This observation might be of clinical use.     

The effect of hyoscine and atropine on the lower oesophageal sphincter.

The effects of intravenous hyoscine 0-4 mg and atropine 0-6 mg on lower oesophageal sphincter tone were studied in normal human subjects. Hyoscine and atropine both decreased the lower oesophageal sphincter (L.O.S) pressure by approximately 11 cm H2O (p less than 0-01). There was also an increased incidence of reflux as seen by an indwelling pH electrode in the lower oesophagus. These findings are relevant to the preoperative preparation of patients presenting for emergency obstetrical anaesthesia; since gastro-oesophagus reflux and pulmonary aspiration of acid gastric content continues to be a significant cause of morbidity and mortality.     

Evaluation of the combined effects of atropine and domperidone on the lower oesophageal sphincter

The effects of sequential administration of both domperidone followed by atropine, and atropine followed by domperidone were examined on the lower oesophageal sphincter of 10 healthy volunteers. Domperidone, 10 mg, increased lower oesophageal sphincter pressure (LOSP) within 10 min of injection. Atropine, 0.6 mg given at the time of peak effect of domperidone, subsequently decreased LOSP. However, frequent measurement of LOSP during the succeeding 40 min demonstrated that LOSP did not decrease significantly below control levels during this drug sequence. When the drugs were administered in the reverse sequence, atropine, 0.6 mg, decreased LOSP within 5 min of injection and subsequent administration of domperidone, at the time of peak effect of the atropine, resulted in a gradual increase in LOSP. However, control values were not approached until 30 min had elapsed after the administration of the domperidone.     

A STUDY OF FACTORS RESPONSIBLE FOR THE EFFICACY OF FUNDOPLICATION IN THE TREATMENT OF GASTRO-OESOPHAGEAL REFLUX

Forty-one patients were followed up for a median 14 months after Nissen fundoplication. Patients were questioned regarding their symptoms and 83% considered the surgery a complete success. Oesophageal manometry was performed before and after surgery. Median pre-operative lower oesophageal sphincter pressure (LOSP) was 5.5 mmHg; following operation median LOSP was 14 mmHg. The ability of the lower oesophageal sphincter (LOS) to relax with swallow was impaired by fundoplication; the median residual lower oesophageal sphincter pressure (RLOSP) was 0 mmHg prior to surgery and 3.5 mmHg following operation. Fundoplication appears to superimpose a zone of constant pressure on the lower oesophageal sphincter and this may be a further factor responsible for the efficacy of surgery.     

The effect of fundoplication on the motility of the canine lower oesophageal sphincter

BACKGROUND: A canine model was used to define whether Nissen fundoplication inhibits gastro-oesophageal reflux by inhibiting transient lower oesophageal sphincter relaxations (TLOSR) or by creating a pressure barrier at the gastro-oesophageal junction. METHODS: Four surgical models were studied pre-operatively and postoperatively. These were: (i) the surgical mobilization required for fundoplication (sham fundoplication, n = 5); (ii) a standard fundoplication (n = 4); (iii) anterior and posterior myotomy of the lower oesophageal sphincter (LOS; cardiomyotomy, n = 4); and (iv) combined cardiomyotomy and fundoplication (n = 4). Each operative procedure was assessed for its effect on the incidence of TLOSR and gas reflux events, the mean LOS pressure and the LOS pressure profile during swallow events. RESULTS: Sham fundoplication reduced the rate of evoked TLOSR in response to gaseous gastric insufflation from 9.8+/-1.6/h (mean +/- SEM) to 5.4 +/-1.5/h. The mean LOS pressure was reduced from 25.1+/-2.6 to 18.5+/-2.1 mm Hg but nadir LOS pressure during swallowing was not altered. Nissen fundoplication virtually abolished evoked TLOSR from 10.4+/-1.2/h to 0.4+/-0.4/h, increased mean basal LOS pressure from 19.8+/-2.1 to 27.0+/-1.1 mm Hg and increased the nadir pressure on swallowing from 3.4+/-1.0 mm Hg to 14.4+/-1.0 mm Hg. Cardiomyotomy was associated with a near continuous leakage of gas across a chronically hypotensive LOS. Cardiomyotomy reduced the resting LOS pressure from 14.7+/-1.2 mm Hg to 2.3+/-1.0 mm Hg. Cardiomyotomy with fundoplication was associated with no loss of LOS competence. No gas venting episodes occurred either by passive leakage or by TLOSR. Cardiomyotomy with fundoplication was associated with a fall in mean LOS pressure from 14.3+/-1.5 mm Hg to 7.1+/-1.8 mm Hg but no LOS relaxation occurred during swallowing. CONCLUSION: Nissen fundoplication is highly effective in preventing reflux across a normal or chronically hypotensive LOS. Fundoplication results in a constant, measurable pressure barrier at the lower end of the oesophagus that is not due to a change in intrinsic LOS tone. Following fundoplication TLOSR are prevented by the constant low-pressure barrier.