692
expressed in relation to total deliveries in the population ; the success-rate of these women’s operations should be given, along with the previous fetal-salvage rate of the same patients. The current and previous success-rate could then be calculated and a ratio of these two fetal salvage rates might then be compared with a similar ratio calculated from the experience of multiparous normal parturients of similar parity. From these two ratios, a minimum-benefit rate might be obtained. Though these groups might not include similar populations, the effects of variations would be diminished by careful parity matching. Cervical suturing has some complications. It may stimulate myometrial activity when the stitch is inserted, thus doing more harm than good; this is less likely with prophylactic suturing than if the operation is delayed until the cervix has shown signs of opening. There is an increased incidence of sepsis, particularly if suturing is done after membrane rupture while endotoxic shock has been reported. Dystocia of the cervix in labour after the stitch has been removed may necessitate caesarean section, and permanent cervical stenosis can ensue.17 Those who deliver vaginally after suture removal may have cervical lacerations. All these complications are preventable and treatable. They should be weighed against the patient’s desire to have a mature, live baby. A newer technique is now being employed in Europe to prevent premature dilatation of the cervix. The Mayer ring pessary encircles the cervix and can be applied in outpatients. No anaesthetic is required and the procedure is quick and simple. Some say that the pessary can still be used at 3 cm dilation of the cervix and that it is less likely than suturing to damage the cervix. IS The appliance has been used prophylactically in Czechoslovakia with a concomitant reduction in mortality from prematurity. Perhaps this too deserves examination if any assessment of the management of cervical incompetence is contemplated, but only by comparing like with like will the supporters of cervical therapy convince those sceptics who maintain, with W. B. YEATS, that "Our stitching and unstitching has been naught."
The
Leaking Oesophagus
LEAKAGE from the oesophagus may be caused by spontaneous rupture, instrumentation with the cesophagoscope, external trauma, foreign body, or anastomotic leak after a resection. Whatever the cause, the result is the same-a suppurative mediastinitis with a high mortality. In a Bristol series from TRIGGIANI and BELSEyl all the patients 17. Robboy, M. S. Obstet. Gynec. 1973, 41, 108. 18. Bayer, H. Zbl. Gynäk. 1977, 99, 547. 1. Triggiani, E., Belsey, R. Thorax, 1977, 32, 241.
with spontaneous rupture had surgical emphysema in the. neck, but this sign is often missed, myocardial infarction being diagnosed in error. According to ABBOTT and co-workers,2 emphysema is rarely detectable less than twenty-four hours from the time of rupture. In the very early stage of leakage of air, before subcutaneous emphysema has developed, there is an absence of the normal click when the thyroid cartilage is moved from side to side, due to air between the fascial planes. The emphysema can be seen on straight X-ray, which will also reveal the accompanying pneumothorax. To confirm the existence and site of rupture an oesophagogram is performed, but opinions differ about the best medium. Probably an aqueous bronchographic contrast medium is best, though expensive. Perforation of the oesophagus during oesophagoscopy or oesophageal dilatation is a well-known hazard when the rigid oesophagoscope is used. In the series from Bristol there were only 12 perforations in 5900 oesophagoscopies (0 2% ), but the incidence is probably higher in less experienced hands. Fibreoptic oesophagogastroscopes and Eder Puestow dilators are safer, particularly in the elderly patient with spondylitis, but they must still be used with care. All users of oesophagoscopes, of whatever kind, should keep an accurate record of complications: only in this way can improvements be secured in design and technique. Immediate diagnosis and treatment are essential. The rapid onset of pain in the chest, tachycardia, surgical emphysema in the neck, pneumothorax, and dyspnoea make it clear that something is seriously wrong. The oesophagoscope is withdrawn and the site of rupture confirmed by oesophagography. The common sites for perforation during oesophagoscopy are the cervical region and the lower end, where the leak may be intra-abdominal. (Perforation can also complicate vagotomy and hiatus-hernia repair.3) The cervical oesophagus is the only place where conservative treatment is likely to be successful. Otherwise, if surgery is performed within a short time of injury, direct suture and drainage is effective-in the absence of distal obstruction.4When the perforation has occurred during dilatation of achalasia the repair can be combined with Heller’s procedure.s SHEPHERD et al. treated twelve children for 13 perforations (5 of which occurred during oesophagoscopy and dilatation of a lye stricture); on conventional management all survived. Far more common than spontaneous rupture or 2.
Abbott, O. A., Mansour, K. A., Logan, W. D., Hatcher, C. R., Symbas, P. N.J. thorac. cardiovasc. Surg. 1970, 59, 67. 3. McBurney, R. P. Ann. Surg. 1969, 169, 851. 4. Keen, G.J. thorac. cardiovasc. Surg. 1968, 56, 603. 5. McKinnon, W. M. P., Ochsner, J. L. Am.J. Surg. 1974, 127, 115. 6. McKeown, K. C. Ann. R. Coll. Surg. Engl. 1972, 51, 213. 7. Ong, G. B. ibid. 1975, 56, 3. 8. Shepherd, R. L., Faffensperger, J. G., Goldstein, R. J. thorac. cardiovasc Surg. 1977, 74, 261.
693
is anastomotic leak after the problem of oesophageal This is cesophagectomy. in and forty patients treated by pleural surgery drainage, antibiotics, and feeding jejunostomy or gastrostomy, the mortality was 50%. Attempts to resuture the defect or resect and reanastomose nearly always fail because the tissues are oedematous and devitalised and there is a fulminating surrounding mediastinitis. The only treatment that offers any real hope is exteriorisation of the remaining oesophagus, closure of the stomach, cer-
instrumental
trauma
vical
oesophagostomy,
then,
at a
and
feeding gastrostomy; later date, a staged reconstruction is performed with left colon. Some surgeons might argue that such a drastic procedure is unjustified when the original operation was for carcinoma, with its poor prognosis. However, if the initial operation was right, treatment of the complications is usually justified unless evidence of metastases makes life expectancy very short. How can anastomotic breakdown best be prevented ? An oesophageal anastomosis--of all anastomoses-must be right the first time. Success is largely a matter of experience but what does this mean in terms of actual technique? TRIGGIANI and BELSEyl say that an intrathoracic oesophagogastric anastomosis is notoriously the most dangerous form of anastomosis, whereas McKEOWN’ abandoned oesophagojejunostomy in favour of oesophagogastrostomy (in the neck), suggesting that a squamous and a high columnar epithelium may not easily unite. ONG8 uses colon, jejunum, and stomach as required. Probably the care with which the sutures are placed to produce accurate mucosal apposition is the most important factor; too many sutures can be as dangerous as too few. There will always be discussion about the best type of suture material and whether to use one layer or two, but the principles are clear: a cervical anastomosis is safer than an intrathoracic anastomosis; any intrathoracic oesophageal leak requires urgent, and often extensive, surgery.
DRUGSANDTHE ELDERLY account for only 12% of the for about one-third of expendipopulation, they ture on prescription drugs.’ In 1956 Lasagna summarised knowledge of how drug effects are modified by ageing and concluded that "what is obviously required is a good deal more work and a good deal less talk".2 Some of the newer work was reviewed at a valuable symposium held by the Department of Pharmacology and Therapeutics in Dundee. Ageing is accompanied by
ALTHOUGH the
elderly
account
1 Crooks, J., Shepherd, A. M. M., Stevenson, I. H. HlthBull. 1975, 33, 222. 2. Lasagna, L. Proc. Ass. Res. nerv. ment. Dis. 1956, 35, 83. 3. Crooks, J., Stevenson, I. H. (editors) Drugs and the Elderly (in the press).
deterioration in physiological function, impaired homoeostasis, and various progressive diseases. Old people differ from the young both in their response to drugs and in the way their bodies handle drugs.4 Two or more factors may operate simultaneously. Although the intestinal absorption of nutrients may be impaired in old age, drugs are absorbed by passive diffusion and this is unlikely to be affected except indirectly through alteration of gastrointestinal motility. However, plasma albumin and protein binding may be reduced and, although body mass is usually smaller, the ratio of fat to lean tissue is generally higher. This increases the apparent volume in which lipid-soluble drugs are distributed, which in turn reduces their plasma concentration and rate of elimination. More important influences on the rate of elimination are renal excretion and hepatic metabolism. Creatinine clearance in young adults with normal renal function varies between 80 and 120 ml/min. Even though the serum-creatinine may remain misleadingly constant, clearance falls progressively, especially after the age of 60. The age-dependent decrease in the rate of elimination of drugs that are predominantly excreted by the kidney-such as digoxin, gentamicin and other aminoglycoside antibiotics, lithium, and phenobarbitone-means that doses must be reduced to avoid cumulation and toxicity. Nomograms have been devised for some drugs with narrow therapeutic ratios. Decreased capacity for renal tubular secretion may lead to increased plasma concentrations of acidic drugs such as penicillin and salicylates. All these changes are likely to be exaggerated in the presence of dehydration, heart-failure, or renal disease. The ability of the aged liver to metabolise drugs may also be reduced, with prolongation of the elimination half-life, and accumulation on repeated dosage. Within this general trend, however, there seems to be considerable variation between different drugs and, for particular drugs, far greater variability between elderly iridividuals than occurs in the young-e.g., with tricyclic antidepressants. In addition, the response to enzyme inducers is blunted in old people, and this may result in higher plasma levels. Few systematic studies have been done and, to emphasise the difficulty of extrapolation and prediction, it was reported that ageing led to a two to three fold prolongation in the elimination half-life of diazepam and chlordiazepoxide but not of the closely related oxazepam and lorazepam. The elimination of nitrazepam, widely used as a hypnotic, is apparently not prolonged in the old. Nevertheless, a single dose of 10 mg caused significantly greater psychomotor impairment the next day in elderly than in young subjects. This was attributed to increased receptor responsiveness (sensitivity is an ambiguous term in the context). Barbiturates are the classic example of this effect. The increased effect of warfarin in the elderly seemed to be multifactorial in origin. Therefore, on pharmacological grounds alone, there are good reasons for special care in prescribing for old but the situation is made much worse because two, three, and sometimes five or more drugs are often prescribed simultaneously. Adverse reactions are commons
people,
4. Crooks, J., O’Malley, K., Stevenson, I. H. Clin. Pharmacokinet, 280. 5.Hall,M.R.P.Adv.Drug React.Bull.1972,no. 35,p. 108.
1976, 1,
expressed in relation to total deliveries in the population ; the success-rate of these women’s operations should be given, along with the previous fetal-salvage rate of the same patients. The current and previous success-rate could then be calculated and a ratio of these two fetal salvage rates might then be compared with a similar ratio calculated from the experience of multiparous normal parturients of similar parity. From these two ratios, a minimum-benefit rate might be obtained. Though these groups might not include similar populations, the effects of variations would be diminished by careful parity matching. Cervical suturing has some complications. It may stimulate myometrial activity when the stitch is inserted, thus doing more harm than good; this is less likely with prophylactic suturing than if the operation is delayed until the cervix has shown signs of opening. There is an increased incidence of sepsis, particularly if suturing is done after membrane rupture while endotoxic shock has been reported. Dystocia of the cervix in labour after the stitch has been removed may necessitate caesarean section, and permanent cervical stenosis can ensue.17 Those who deliver vaginally after suture removal may have cervical lacerations. All these complications are preventable and treatable. They should be weighed against the patient’s desire to have a mature, live baby. A newer technique is now being employed in Europe to prevent premature dilatation of the cervix. The Mayer ring pessary encircles the cervix and can be applied in outpatients. No anaesthetic is required and the procedure is quick and simple. Some say that the pessary can still be used at 3 cm dilation of the cervix and that it is less likely than suturing to damage the cervix. IS The appliance has been used prophylactically in Czechoslovakia with a concomitant reduction in mortality from prematurity. Perhaps this too deserves examination if any assessment of the management of cervical incompetence is contemplated, but only by comparing like with like will the supporters of cervical therapy convince those sceptics who maintain, with W. B. YEATS, that "Our stitching and unstitching has been naught."
The
Leaking Oesophagus
LEAKAGE from the oesophagus may be caused by spontaneous rupture, instrumentation with the cesophagoscope, external trauma, foreign body, or anastomotic leak after a resection. Whatever the cause, the result is the same-a suppurative mediastinitis with a high mortality. In a Bristol series from TRIGGIANI and BELSEyl all the patients 17. Robboy, M. S. Obstet. Gynec. 1973, 41, 108. 18. Bayer, H. Zbl. Gynäk. 1977, 99, 547. 1. Triggiani, E., Belsey, R. Thorax, 1977, 32, 241.
with spontaneous rupture had surgical emphysema in the. neck, but this sign is often missed, myocardial infarction being diagnosed in error. According to ABBOTT and co-workers,2 emphysema is rarely detectable less than twenty-four hours from the time of rupture. In the very early stage of leakage of air, before subcutaneous emphysema has developed, there is an absence of the normal click when the thyroid cartilage is moved from side to side, due to air between the fascial planes. The emphysema can be seen on straight X-ray, which will also reveal the accompanying pneumothorax. To confirm the existence and site of rupture an oesophagogram is performed, but opinions differ about the best medium. Probably an aqueous bronchographic contrast medium is best, though expensive. Perforation of the oesophagus during oesophagoscopy or oesophageal dilatation is a well-known hazard when the rigid oesophagoscope is used. In the series from Bristol there were only 12 perforations in 5900 oesophagoscopies (0 2% ), but the incidence is probably higher in less experienced hands. Fibreoptic oesophagogastroscopes and Eder Puestow dilators are safer, particularly in the elderly patient with spondylitis, but they must still be used with care. All users of oesophagoscopes, of whatever kind, should keep an accurate record of complications: only in this way can improvements be secured in design and technique. Immediate diagnosis and treatment are essential. The rapid onset of pain in the chest, tachycardia, surgical emphysema in the neck, pneumothorax, and dyspnoea make it clear that something is seriously wrong. The oesophagoscope is withdrawn and the site of rupture confirmed by oesophagography. The common sites for perforation during oesophagoscopy are the cervical region and the lower end, where the leak may be intra-abdominal. (Perforation can also complicate vagotomy and hiatus-hernia repair.3) The cervical oesophagus is the only place where conservative treatment is likely to be successful. Otherwise, if surgery is performed within a short time of injury, direct suture and drainage is effective-in the absence of distal obstruction.4When the perforation has occurred during dilatation of achalasia the repair can be combined with Heller’s procedure.s SHEPHERD et al. treated twelve children for 13 perforations (5 of which occurred during oesophagoscopy and dilatation of a lye stricture); on conventional management all survived. Far more common than spontaneous rupture or 2.
Abbott, O. A., Mansour, K. A., Logan, W. D., Hatcher, C. R., Symbas, P. N.J. thorac. cardiovasc. Surg. 1970, 59, 67. 3. McBurney, R. P. Ann. Surg. 1969, 169, 851. 4. Keen, G.J. thorac. cardiovasc. Surg. 1968, 56, 603. 5. McKinnon, W. M. P., Ochsner, J. L. Am.J. Surg. 1974, 127, 115. 6. McKeown, K. C. Ann. R. Coll. Surg. Engl. 1972, 51, 213. 7. Ong, G. B. ibid. 1975, 56, 3. 8. Shepherd, R. L., Faffensperger, J. G., Goldstein, R. J. thorac. cardiovasc Surg. 1977, 74, 261.
693
is anastomotic leak after the problem of oesophageal This is cesophagectomy. in and forty patients treated by pleural surgery drainage, antibiotics, and feeding jejunostomy or gastrostomy, the mortality was 50%. Attempts to resuture the defect or resect and reanastomose nearly always fail because the tissues are oedematous and devitalised and there is a fulminating surrounding mediastinitis. The only treatment that offers any real hope is exteriorisation of the remaining oesophagus, closure of the stomach, cer-
instrumental
trauma
vical
oesophagostomy,
then,
at a
and
feeding gastrostomy; later date, a staged reconstruction is performed with left colon. Some surgeons might argue that such a drastic procedure is unjustified when the original operation was for carcinoma, with its poor prognosis. However, if the initial operation was right, treatment of the complications is usually justified unless evidence of metastases makes life expectancy very short. How can anastomotic breakdown best be prevented ? An oesophageal anastomosis--of all anastomoses-must be right the first time. Success is largely a matter of experience but what does this mean in terms of actual technique? TRIGGIANI and BELSEyl say that an intrathoracic oesophagogastric anastomosis is notoriously the most dangerous form of anastomosis, whereas McKEOWN’ abandoned oesophagojejunostomy in favour of oesophagogastrostomy (in the neck), suggesting that a squamous and a high columnar epithelium may not easily unite. ONG8 uses colon, jejunum, and stomach as required. Probably the care with which the sutures are placed to produce accurate mucosal apposition is the most important factor; too many sutures can be as dangerous as too few. There will always be discussion about the best type of suture material and whether to use one layer or two, but the principles are clear: a cervical anastomosis is safer than an intrathoracic anastomosis; any intrathoracic oesophageal leak requires urgent, and often extensive, surgery.
DRUGSANDTHE ELDERLY account for only 12% of the for about one-third of expendipopulation, they ture on prescription drugs.’ In 1956 Lasagna summarised knowledge of how drug effects are modified by ageing and concluded that "what is obviously required is a good deal more work and a good deal less talk".2 Some of the newer work was reviewed at a valuable symposium held by the Department of Pharmacology and Therapeutics in Dundee. Ageing is accompanied by
ALTHOUGH the
elderly
account
1 Crooks, J., Shepherd, A. M. M., Stevenson, I. H. HlthBull. 1975, 33, 222. 2. Lasagna, L. Proc. Ass. Res. nerv. ment. Dis. 1956, 35, 83. 3. Crooks, J., Stevenson, I. H. (editors) Drugs and the Elderly (in the press).
deterioration in physiological function, impaired homoeostasis, and various progressive diseases. Old people differ from the young both in their response to drugs and in the way their bodies handle drugs.4 Two or more factors may operate simultaneously. Although the intestinal absorption of nutrients may be impaired in old age, drugs are absorbed by passive diffusion and this is unlikely to be affected except indirectly through alteration of gastrointestinal motility. However, plasma albumin and protein binding may be reduced and, although body mass is usually smaller, the ratio of fat to lean tissue is generally higher. This increases the apparent volume in which lipid-soluble drugs are distributed, which in turn reduces their plasma concentration and rate of elimination. More important influences on the rate of elimination are renal excretion and hepatic metabolism. Creatinine clearance in young adults with normal renal function varies between 80 and 120 ml/min. Even though the serum-creatinine may remain misleadingly constant, clearance falls progressively, especially after the age of 60. The age-dependent decrease in the rate of elimination of drugs that are predominantly excreted by the kidney-such as digoxin, gentamicin and other aminoglycoside antibiotics, lithium, and phenobarbitone-means that doses must be reduced to avoid cumulation and toxicity. Nomograms have been devised for some drugs with narrow therapeutic ratios. Decreased capacity for renal tubular secretion may lead to increased plasma concentrations of acidic drugs such as penicillin and salicylates. All these changes are likely to be exaggerated in the presence of dehydration, heart-failure, or renal disease. The ability of the aged liver to metabolise drugs may also be reduced, with prolongation of the elimination half-life, and accumulation on repeated dosage. Within this general trend, however, there seems to be considerable variation between different drugs and, for particular drugs, far greater variability between elderly iridividuals than occurs in the young-e.g., with tricyclic antidepressants. In addition, the response to enzyme inducers is blunted in old people, and this may result in higher plasma levels. Few systematic studies have been done and, to emphasise the difficulty of extrapolation and prediction, it was reported that ageing led to a two to three fold prolongation in the elimination half-life of diazepam and chlordiazepoxide but not of the closely related oxazepam and lorazepam. The elimination of nitrazepam, widely used as a hypnotic, is apparently not prolonged in the old. Nevertheless, a single dose of 10 mg caused significantly greater psychomotor impairment the next day in elderly than in young subjects. This was attributed to increased receptor responsiveness (sensitivity is an ambiguous term in the context). Barbiturates are the classic example of this effect. The increased effect of warfarin in the elderly seemed to be multifactorial in origin. Therefore, on pharmacological grounds alone, there are good reasons for special care in prescribing for old but the situation is made much worse because two, three, and sometimes five or more drugs are often prescribed simultaneously. Adverse reactions are commons
people,
4. Crooks, J., O’Malley, K., Stevenson, I. H. Clin. Pharmacokinet, 280. 5.Hall,M.R.P.Adv.Drug React.Bull.1972,no. 35,p. 108.
1976, 1,
