- Email: [email protected]
Prognostic value of portal haemodynamics
SAPping maternal health In an editorial last year,’ we highlighted the havoc wreaked by the World Bank’s structural adjustment programme (SAP) on the health and welfare of people in sub-Saharan Africa. Maternal health, we pointed out, had been particularly hard hit by macroeconomist-driven policies designed to restructure the financial outlook of ailing govenments. The long-term aim was to encourage economic growth by increasing production and reducing public spending and imports, but even at SAP’s inception in the early 1980s, the devastating short-term health effects were readily pre-
dictable. Within a very few years these effects became painfully obvious. Last week (a week in which a macroeconomic theorist was awarded the Nobel prize for economics), Prof Kelsey Harrison from the University of Port Harcourt, Nigeria, gave the William Meredith Fletcher Shaw lecture at the Royal College of Obstetricians and Gynaecologists in London and described in vivid detail the unremitting nature of that pain. In terms of gross national product (GNP) per caput, countries fall into four categories: rich, middle-income, poor, and poorest. The gulf between the rich and the poorest was eight-fold in 1950 and is now nearly 30-fold. There were 24 countries in the poorest category in 1950 versus 47 today, of which 29 are in sub-Saharan Africa. And this is real poverty, with 62% of the sub-Saharan African population earning less than$6 per week. Viewed from Harrison’s perspective of the consequences on maternal health, the Italian GNP per caput of over$2000 translates into a lifetime risk of dying during pregnancy and childbirth of 1 in 17 360, whereas the respective figures for Mali, West Africa, are$310 and 1 in 7. A 66-fold difference in GNP manifests as a nearly 2500-fold difference in maternal death. Unbooked emergencies comprise the main high-risk group for maternal mortality, this term referring to pregnant women who through neglect, ignorance, poverty, and especially illiteracy do not receive antenatal care and present for the first time when pre-existing disease worsens or when obstetric complications become life-threatening. These emergencies, including puerperal sepsis and obstructed labour, feature hardly at all in rich countries yet account for over 80% of hospital maternal deaths in developing ones. As a result, scarce resources are concentrated on attempts to salvage moribund women, and little remains to care for the rest. Not surprisingly, the babies of unbooked emergencies do very badly. Can economic policies be held responsible for causing so much misery? Not entirely, but they must shoulder a large part of the blame. As Harrison noted, SAP is prejudiced against social welfare and has thereby helped to precipitate a catastrophe in which virtually all economic, social, educational, and public health gains made in the 1960s and 1970s have been wiped out. SAP may work in countries that already have a good administrative infrastructure and high levels of literacy but not where these basic elements are lacking. Expert predictions are that, if such policies continue, it will take another 30 years to attain the living standards of 25 years ago.
spending on public education-an SAP conditionality-condemn many children, especially girls, to continuing illiteracy, and women already account Meanwhile,
cuts
in
for two-thirds of the 1 billion illiterates in the world,
1046
mostly in Asia and Africa. Health resources-from dressings and needles to ambulance parts and vaccines-dwindle, and user fees drive people to self-treatment or quackery. The cost of an uncomplicated caesarean section in Port Harcourt is$274, or 9 months’ average salary. Those who need the operation for obstetric reasons and cannot afford to pay die. Amidst this despair, privatisationanother SAP conditionality-has made a very few people very rich indeed.
Yet it is possible to achieve respectable perinatal statistics, for example, in poor countries. Harrison used the state of Kerala in India to make this point. Whereas the gross domestic product per caput is$200 for Kerala and $225 for India as a whole, average births per woman are 1-9 and 4, respectively, and the infant mortality rates are 17 per 1000 livebirths for Kerala vs 83 per 1000 for India. The key to Kerala’s success is its commitment to progressive social policies, basic professional health care, and female education. 87% of women are literate in Kerala but only 24% in India. As the Nigerian saying puts it: "If you think education is expensive, try illiteracy". Harrison is a powerful advocate of mass education to raise the status of women in society and thereby reduce maternal mortality and bring about socioeconmic change. His view is that, without an improvement in the general level of education, even the writing off of sub-Saharan Africa’s debt would not be enough. For now, who would argue with the obituary captions in Nigerian newspapers, displayed especially in cases of maternal death: "The wicked have done their worst"? And who, even among SAP-minded economists, could in good conscience contemplate Harrison’s rejoinder-"But have the good done their best?"-and say yes?
Imogen
Evans
The Lancet, London, UK 1
Editorial. Structural
adjustment too painful? Lancet 1994; 344:
1377-78.
Prognostic value of portal haemodynamics See page 1056 Portal hypertension is the main precipitant of both variceal bleeding and ascites formation in patients with cirrhosis. The availability of hepatic venous occlusion techniques for the measurement of portal pressure (hepatic venous pressure gradient)’ has spawned numerous attempts to correlate the degree of portal hypertension with the presence of such complications. The first observation to be verified was a threshold portal pressure of 12 mm Hg, below which variceal bleeding did not occur.A linear relation between portal pressure and first variceal haemorrhage has been reported by some researchers3.4 but not others.5 There is some evidence that determination of portal pressure during an episode of active variceal bleeding may predict the risk of early rebleeding.’ Measurement of varix pressure has been proposed as a better way to predict variceal rupture. Despite the technical difficulties of this approach (via direct puncture or endoscopic pressure gauge), there is enough evidence to suggest that varix pressure is consistently lower than portal pressure;’ this difference almost certainly reflects the resistance created within collateral vessels that lie between the portal vein and the
varices. Consequently, the higher this the lower the varix pressure will be in relation resistance to portal pressure, and this may in turn have an important influence on the risk of variceal bleeding. This notion is supported by studies confirming a significant relation between varix pressure and the risk of first haemorrhage.7,8 Although varix pressure measurement has cast light on the process of varix rupture, existing techniques do not lend themselves to widespread use. Introduction of pharmacological agents to reduce portal hypertension (and hence variceal bleeding) has provided a further stimulus to portal haemodynamic measurements. (3-adrenoceptor blocking agents were the first drugs shown to reduce the risk of initial and recurrent episodes of variceal bleeding.9 Monitoring the response of portal pressure to therapy has again provided support for the concept of a 12 mm Hg variceal bleeding threshold. However, only a few patients attain such a reduction, with as many as 30% showing no fall in portal pressure. Several studies have failed to show a correlation between the extent of pressure reduction and the risk of
bleeding varices and portohepatic gradient. Gastroenterology 1975; 69:
oesophageal
bleeding."," In this issue, Feu
and colleagues report another attempt establish such a correlation. These researchers followed 69 cirrhotic patients with previous variceal bleeding in whom propranolol had been prescribed to prevent recurrence. The threshold portal pressure of 12 mm Hg was documented once again, but this cut-off applied to only 12% of patients treated. However, for the first time it to
to show that those patients with a reduction of 20% or more (representing 36% of pressure the population studied) had a significantly lower risk of
proved possible
rebleeding. These important results require some qualification. The population studied consisted almost entirely of good-risk Pugh Grade A and B patients, so the potential for liver function to be identified as a risk factor for rebleeding was diminished. Moreover, the response of portal pressure to propranolol was assessed only after 3 months and therefore did not provide any prognostic data for the period when the patient was most at risk of rebleeding. Studies in which the response of portal pressure was assessed at an earlier time point (1 month) failed to show a relation to the risk of recurrent haernorrhage.11,12 Has the time come when portal pressure measurements graduate into routine clinical use? This step could only be justified if such measurements influenced management and represented the least invasive means by which this I
could be achieved. Whilst there is evidence that the level of portal pressure might predict the risk of bleeding (and perhaps survival), the quality of such data has offered little management gain. The findings of Feu and colleagues raise the possibility of objective portal haemodynamic guidelines to direct therapy. Nevertheless, most patients with chronic liver disease are managed by general gastroenterologists and it is highly unlikely that the available data will change their considerable reluctance to undertake portal pressure measurements. David
Westaby
Gastrointestinal Unit, Chelsea and Westminster Hospital, London, UK
1 Myers JD, Taylor WJ. An estimation of portal venous pressure by occlusive catheterisation of an hepatic venule. J Clin Invest 1951; 30: 662-63.
2 Viallet A, Marleau D, Huet M, et al. Haemodynamic evaluation of patients with intrahepatic portal hypertension: relationship between
3 4
5
6
1297-300. Gludd C, Henriksen JH, Nielson G, et al. Prognostic indicators in alcoholic cirrhotic men. Hepatology 1988; 8: 222-27. Merkel C, Bolognese M, Bellon S, et al. Prognostic usefulness of hepatic vein catheterisation in patients with cirrhosis and esophageal varices. Gastroenterology 1992; 102: 973-79. Lebrec D, de Fleury P, Rueff B, et al. Portal hypertension, size of esophageal varices and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology 1980; 79: 1139-44. Vinel JP, Cassigneul J, Levade M, et al. Assessment of short-term prognosis after variceal bleeding in patients with alcoholic cirrhosis by early measurement of portohepatic gradient. Hepatology 1986; 6: 116-17.
7
Rigau J, Bosch J, Bordas JM, et al. Endoscopic measurement of
variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterology 1989; 96: 873-79. 8 Staritz M, Meyer zum Buschenfelde H. The endoscopic of intravascular pressure and flow in oesophageal varices. J Hepatol 1988; 7: 126-31. 9 Lebrec D, Poynard T, Hillon P, Benhamou J-P. Propranolol for prevention of gastrointestinal bleeding in patients with cirrhosis: a controlled study. N Engl J Med 1981; 305: 1371-74. 10 Groszmann RJ, Bosch J, Grace N, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1990; 99: 1401-07. 11 Poynard T, Lebrec D, Sayegh R, et al. Propranolol for the prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding. Hepatology
1987; 7: 447-51. 12
Westaby D, Polson RJ, Gimson AES, Hayes PC, Hayllar K, Williams R. A controlled trial of oral propranolol compared with injection scleropathy for the long-term management of variceal bleeding. Hepatology 1990; 11: 353-59.
Understanding "informed
consent"
See page 1060 "Informed consent was obtained" is a routine phrase found in the methods section of clinical research papers. Gallo and colleagues’ fascinating study, comparing classical informed consent and randomised consent procedures, shows just how difficult the clinical research concept is for the public to grasp. Most of the surrogate patients who took part when attending a scientific exhibition were young (83% less than 40), educated, and healthy. A poster display clarified the basic principles of clinical research, with information about randomisation and informed consent, yet failure to understand the issues was very common. The consent these people gave may have been "informed" but the information was certainly not properly comprehended. These were interested, young volunteers, uninfluenced by the pressures of family, a clinical setting, or a diagnosed illness. Contrast them with the average patient with cancer or other illness who is invited to participate in a randomised trial. The promotion of any commodity, be it research or a refrigerator, depends on communication of the perception of the need for and value of the commodity to its potential beneficiaries. And that perception has to be conveyed clearly to the recipient. Few prospective purchasers of a refrigerator study the technical specifications in detail but the provision of such datasheets inspires confidence. They will seek out the advantages to themselves and be eager to obtain the best from their purchase. The manufacturer will not proceed beyond the prototype until market surveys have been done. Best-selling refrigerators combine high-quality technical specification with a design process in which the future consumer has been involved. Should not the principles be the same for trials-with
1047
dictable. Within a very few years these effects became painfully obvious. Last week (a week in which a macroeconomic theorist was awarded the Nobel prize for economics), Prof Kelsey Harrison from the University of Port Harcourt, Nigeria, gave the William Meredith Fletcher Shaw lecture at the Royal College of Obstetricians and Gynaecologists in London and described in vivid detail the unremitting nature of that pain. In terms of gross national product (GNP) per caput, countries fall into four categories: rich, middle-income, poor, and poorest. The gulf between the rich and the poorest was eight-fold in 1950 and is now nearly 30-fold. There were 24 countries in the poorest category in 1950 versus 47 today, of which 29 are in sub-Saharan Africa. And this is real poverty, with 62% of the sub-Saharan African population earning less than$6 per week. Viewed from Harrison’s perspective of the consequences on maternal health, the Italian GNP per caput of over$2000 translates into a lifetime risk of dying during pregnancy and childbirth of 1 in 17 360, whereas the respective figures for Mali, West Africa, are$310 and 1 in 7. A 66-fold difference in GNP manifests as a nearly 2500-fold difference in maternal death. Unbooked emergencies comprise the main high-risk group for maternal mortality, this term referring to pregnant women who through neglect, ignorance, poverty, and especially illiteracy do not receive antenatal care and present for the first time when pre-existing disease worsens or when obstetric complications become life-threatening. These emergencies, including puerperal sepsis and obstructed labour, feature hardly at all in rich countries yet account for over 80% of hospital maternal deaths in developing ones. As a result, scarce resources are concentrated on attempts to salvage moribund women, and little remains to care for the rest. Not surprisingly, the babies of unbooked emergencies do very badly. Can economic policies be held responsible for causing so much misery? Not entirely, but they must shoulder a large part of the blame. As Harrison noted, SAP is prejudiced against social welfare and has thereby helped to precipitate a catastrophe in which virtually all economic, social, educational, and public health gains made in the 1960s and 1970s have been wiped out. SAP may work in countries that already have a good administrative infrastructure and high levels of literacy but not where these basic elements are lacking. Expert predictions are that, if such policies continue, it will take another 30 years to attain the living standards of 25 years ago.
spending on public education-an SAP conditionality-condemn many children, especially girls, to continuing illiteracy, and women already account Meanwhile,
cuts
in
for two-thirds of the 1 billion illiterates in the world,
1046
mostly in Asia and Africa. Health resources-from dressings and needles to ambulance parts and vaccines-dwindle, and user fees drive people to self-treatment or quackery. The cost of an uncomplicated caesarean section in Port Harcourt is$274, or 9 months’ average salary. Those who need the operation for obstetric reasons and cannot afford to pay die. Amidst this despair, privatisationanother SAP conditionality-has made a very few people very rich indeed.
Yet it is possible to achieve respectable perinatal statistics, for example, in poor countries. Harrison used the state of Kerala in India to make this point. Whereas the gross domestic product per caput is$200 for Kerala and $225 for India as a whole, average births per woman are 1-9 and 4, respectively, and the infant mortality rates are 17 per 1000 livebirths for Kerala vs 83 per 1000 for India. The key to Kerala’s success is its commitment to progressive social policies, basic professional health care, and female education. 87% of women are literate in Kerala but only 24% in India. As the Nigerian saying puts it: "If you think education is expensive, try illiteracy". Harrison is a powerful advocate of mass education to raise the status of women in society and thereby reduce maternal mortality and bring about socioeconmic change. His view is that, without an improvement in the general level of education, even the writing off of sub-Saharan Africa’s debt would not be enough. For now, who would argue with the obituary captions in Nigerian newspapers, displayed especially in cases of maternal death: "The wicked have done their worst"? And who, even among SAP-minded economists, could in good conscience contemplate Harrison’s rejoinder-"But have the good done their best?"-and say yes?
Imogen
Evans
The Lancet, London, UK 1
Editorial. Structural
adjustment too painful? Lancet 1994; 344:
1377-78.
Prognostic value of portal haemodynamics See page 1056 Portal hypertension is the main precipitant of both variceal bleeding and ascites formation in patients with cirrhosis. The availability of hepatic venous occlusion techniques for the measurement of portal pressure (hepatic venous pressure gradient)’ has spawned numerous attempts to correlate the degree of portal hypertension with the presence of such complications. The first observation to be verified was a threshold portal pressure of 12 mm Hg, below which variceal bleeding did not occur.A linear relation between portal pressure and first variceal haemorrhage has been reported by some researchers3.4 but not others.5 There is some evidence that determination of portal pressure during an episode of active variceal bleeding may predict the risk of early rebleeding.’ Measurement of varix pressure has been proposed as a better way to predict variceal rupture. Despite the technical difficulties of this approach (via direct puncture or endoscopic pressure gauge), there is enough evidence to suggest that varix pressure is consistently lower than portal pressure;’ this difference almost certainly reflects the resistance created within collateral vessels that lie between the portal vein and the
varices. Consequently, the higher this the lower the varix pressure will be in relation resistance to portal pressure, and this may in turn have an important influence on the risk of variceal bleeding. This notion is supported by studies confirming a significant relation between varix pressure and the risk of first haemorrhage.7,8 Although varix pressure measurement has cast light on the process of varix rupture, existing techniques do not lend themselves to widespread use. Introduction of pharmacological agents to reduce portal hypertension (and hence variceal bleeding) has provided a further stimulus to portal haemodynamic measurements. (3-adrenoceptor blocking agents were the first drugs shown to reduce the risk of initial and recurrent episodes of variceal bleeding.9 Monitoring the response of portal pressure to therapy has again provided support for the concept of a 12 mm Hg variceal bleeding threshold. However, only a few patients attain such a reduction, with as many as 30% showing no fall in portal pressure. Several studies have failed to show a correlation between the extent of pressure reduction and the risk of
bleeding varices and portohepatic gradient. Gastroenterology 1975; 69:
oesophageal
bleeding."," In this issue, Feu
and colleagues report another attempt establish such a correlation. These researchers followed 69 cirrhotic patients with previous variceal bleeding in whom propranolol had been prescribed to prevent recurrence. The threshold portal pressure of 12 mm Hg was documented once again, but this cut-off applied to only 12% of patients treated. However, for the first time it to
to show that those patients with a reduction of 20% or more (representing 36% of pressure the population studied) had a significantly lower risk of
proved possible
rebleeding. These important results require some qualification. The population studied consisted almost entirely of good-risk Pugh Grade A and B patients, so the potential for liver function to be identified as a risk factor for rebleeding was diminished. Moreover, the response of portal pressure to propranolol was assessed only after 3 months and therefore did not provide any prognostic data for the period when the patient was most at risk of rebleeding. Studies in which the response of portal pressure was assessed at an earlier time point (1 month) failed to show a relation to the risk of recurrent haernorrhage.11,12 Has the time come when portal pressure measurements graduate into routine clinical use? This step could only be justified if such measurements influenced management and represented the least invasive means by which this I
could be achieved. Whilst there is evidence that the level of portal pressure might predict the risk of bleeding (and perhaps survival), the quality of such data has offered little management gain. The findings of Feu and colleagues raise the possibility of objective portal haemodynamic guidelines to direct therapy. Nevertheless, most patients with chronic liver disease are managed by general gastroenterologists and it is highly unlikely that the available data will change their considerable reluctance to undertake portal pressure measurements. David
Westaby
Gastrointestinal Unit, Chelsea and Westminster Hospital, London, UK
1 Myers JD, Taylor WJ. An estimation of portal venous pressure by occlusive catheterisation of an hepatic venule. J Clin Invest 1951; 30: 662-63.
2 Viallet A, Marleau D, Huet M, et al. Haemodynamic evaluation of patients with intrahepatic portal hypertension: relationship between
3 4
5
6
1297-300. Gludd C, Henriksen JH, Nielson G, et al. Prognostic indicators in alcoholic cirrhotic men. Hepatology 1988; 8: 222-27. Merkel C, Bolognese M, Bellon S, et al. Prognostic usefulness of hepatic vein catheterisation in patients with cirrhosis and esophageal varices. Gastroenterology 1992; 102: 973-79. Lebrec D, de Fleury P, Rueff B, et al. Portal hypertension, size of esophageal varices and risk of gastrointestinal bleeding in alcoholic cirrhosis. Gastroenterology 1980; 79: 1139-44. Vinel JP, Cassigneul J, Levade M, et al. Assessment of short-term prognosis after variceal bleeding in patients with alcoholic cirrhosis by early measurement of portohepatic gradient. Hepatology 1986; 6: 116-17.
7
Rigau J, Bosch J, Bordas JM, et al. Endoscopic measurement of
variceal pressure in cirrhosis: correlation with portal pressure and variceal hemorrhage. Gastroenterology 1989; 96: 873-79. 8 Staritz M, Meyer zum Buschenfelde H. The endoscopic of intravascular pressure and flow in oesophageal varices. J Hepatol 1988; 7: 126-31. 9 Lebrec D, Poynard T, Hillon P, Benhamou J-P. Propranolol for prevention of gastrointestinal bleeding in patients with cirrhosis: a controlled study. N Engl J Med 1981; 305: 1371-74. 10 Groszmann RJ, Bosch J, Grace N, et al. Hemodynamic events in a prospective randomized trial of propranolol versus placebo in the prevention of a first variceal hemorrhage. Gastroenterology 1990; 99: 1401-07. 11 Poynard T, Lebrec D, Sayegh R, et al. Propranolol for the prevention of recurrent gastrointestinal bleeding in patients with cirrhosis: a prospective study of factors associated with rebleeding. Hepatology
1987; 7: 447-51. 12
Westaby D, Polson RJ, Gimson AES, Hayes PC, Hayllar K, Williams R. A controlled trial of oral propranolol compared with injection scleropathy for the long-term management of variceal bleeding. Hepatology 1990; 11: 353-59.
Understanding "informed
consent"
See page 1060 "Informed consent was obtained" is a routine phrase found in the methods section of clinical research papers. Gallo and colleagues’ fascinating study, comparing classical informed consent and randomised consent procedures, shows just how difficult the clinical research concept is for the public to grasp. Most of the surrogate patients who took part when attending a scientific exhibition were young (83% less than 40), educated, and healthy. A poster display clarified the basic principles of clinical research, with information about randomisation and informed consent, yet failure to understand the issues was very common. The consent these people gave may have been "informed" but the information was certainly not properly comprehended. These were interested, young volunteers, uninfluenced by the pressures of family, a clinical setting, or a diagnosed illness. Contrast them with the average patient with cancer or other illness who is invited to participate in a randomised trial. The promotion of any commodity, be it research or a refrigerator, depends on communication of the perception of the need for and value of the commodity to its potential beneficiaries. And that perception has to be conveyed clearly to the recipient. Few prospective purchasers of a refrigerator study the technical specifications in detail but the provision of such datasheets inspires confidence. They will seek out the advantages to themselves and be eager to obtain the best from their purchase. The manufacturer will not proceed beyond the prototype until market surveys have been done. Best-selling refrigerators combine high-quality technical specification with a design process in which the future consumer has been involved. Should not the principles be the same for trials-with
1047