- Email: [email protected]
High-frequency ventilation
706
1. Editorial. Which heart valve prosthesis? Lancet 1985; ii: 756-58. 2. Treasure T. Which heart valves should we use? Lancet 1990; 336: 1115-117. 3. Gersh BJ, Fisher LD, Schaff HV, et al. Issues concerning the clinical evaluation of new prosthetic valves. J Thorac Cardiovasc Surg 1986; 91: 460-66. 4. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve-year comparison of a Björk-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991; 324: 573-79. 5. Collins JJ. The evolution of artificial heart valves. N Engl J Med 1991; 324: 624-26. 6. Bloomfield P, Kitchin AH, Wheatley DJ, Walbaum PR, Lutz W, Miller HC. A prospective evaluation of the Björk-Shiley, Hancock and Carpentier-Edwards heart valve prostheses. Circulation 1986; 73: 1213-22. 7. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Ten year results of a randomised trial of the Bjork-Shiley, Hancock and CarpentierEdwards heart valve prostheses. Br Heart J 1989; 61: 452 (abstr).
Nuclear medicine and the
hepatobiliary tract Imaging of the hepatobiliary tract with ultrasound and computed tomography (CT) provides doctors with anatomical and morphological information and is popular in hospital practice. By contrast, imaging with radionuclides, which can additionally yield physiological information, tends to be under used. Hepatobiliary scintigraphy (HBS) is often regarded as yet another imaging modality with which to confront and confuse a perplexed clinician. HBS is of greatest use in the recognition of biliary obstruction. Both ultrasound and CT are well suited to the diagnosis of bile duct dilatation and therefore the level of obstruction. Ultrasound scans are cheap, widely available, sensitive, and reliable for detecting stones in the gallbladder. CT will detect the presence, level, and cause of obstruction. Neither system delineates the pathophysiology associated with the flow of bile. HBS is the only imaging technique that reliably shows cystic duct obstruction, which occurs in most patients with acute cholecystitis; visualisation of the gallbladder within an hour virtually excludes this condition. After liver or biliary tract surgery, HBS may be used to monitor the flow of bile and display postoperative biliary reflux, leaks, and the patency of a biliary-enteric anastomosis. It can also be used to evaluate post-cholecystectomy syndromes and afferent loop disorders after gastrectomy. Other indications for HBS include abdominal trauma and the differential diagnosis of neonatal jaundice, in which biliary atresia may be excluded by observing the passage of bile into the gut. For HBS a technetium-99- (99Tc-)-labelled derivative of iminodiacetic acid (IDA) is injected intravenously after a 4-6-hour fast. This tracer is a dimer of high molecular weight and lipid solubility and is taken up by the hepatocytes; it is then preferentially excreted by the biliary tract, because the kidneys are unable to remove substances from the body if their molecular weight exceeds 300 daltons. Sequential images of the liver, intrahepatic ducts, common bileduct, gallbladder, and small intestine are usually seen and monitored with a gamma camera/
computer system within an hour of injection of a radiolabelled tracer. Repeated imaging up to 4 hours, and again at 24 hours, may help to determine biliary
patency. Several 99Tcm-IDA complexes have been used to define hepatobiliary function.1 Of these, 99Tc-EHIDA and 99TcmDISIDA are the preferred tracers because their high extraction rate and fast hepatic transit permit more sensitive imaging. However, in jaundiced patients some 9’YfcmDISIDA is excreted via the kidneys and excretion correlates directly with serum bilirubin concentrations.z Consequently, the biliary excretion rate is reduced, making the differentiation between hepatocellular disease and biliary obstruction or leakage less certain. 99T cm- I OD IDA,3with its lower urinary excretion and higher biliary excretion than other 99Tcm-IDA derivatives, has been advocated for assessment of the biliary tree after liver transplantation,4 but this radionuclide likewise is of only limited use when the serum bilirubin rises to more than 200 unol/1. The general availability of radionuclide imaging facilities in hospitals, the low cost, and the low radiation dose should encourage clinicians to consider HBS as a practical clinicophysiological test that is readily applicable for general use, especially in the early stages of biliary obstruction. 1. Williams
AG, Mettler FA, Christie JH. Hepatobiliary and pancreatic imaging. In: Mettler FA, ed. Radionuclide imaging of the GI tract. London: Churchill-Livingstone, 1986: 183-216. 2. Klingensmith WC, Fritzberg AR, Spitzer VM, Kuni CC, Shanahan WM. Clinical comparison of diisopropyl-IDA-Tc99m and diethylIDA-Tc99m for evaluation of the hepatobiliary system. Radiology 1981; 140: 791-95. R, Kotzerke J, Hundeshagen H, Bocker K, Ringe B
3. Schwarzrock
99Tcm-diethyl-ioda-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with 99mTc-disopropyl-HIDA (DISIDA) in jaundiced patients. Eur J Nuclear Med 1986, 12: 346-50. 4. Anselmi M, Lancberg S, Deakin M, et al. Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning. Br J Surg 1990; 77: 1233-37.
High-frequency ventilation High-frequency ventilation has been with us now for over twenty years1 and in clinical use for over ten.2,3 Sykes4 referred to it as "a physiological curiosity looking for a clinical application". The term is generally applied when respiratory frequency is more than four times greater than normal-ie, 60-1800 breaths/min (1-30 Hz).5 Tidal volume diminishes as frequency increases,6and dead space increases relative to tidal volume, so high minute volumes are used. Broadly there are three techniques: (a) high-frequency positive-pressure ventilation (1-1-7 Hz) with an endotracheal tube; (b) high-frequency jet ventilation (1-5 Hz) by which pulses of gas are passed through a small bore cannula from a high pressure (1-4 bar) source which may entrain additional gas depending on volume, pressure, compliance, &C;7 and (c) highfrequency oscillation at 3-30 Hz with a sine-wave pump. At lower frequencies (1 -6 Hz) tidal volume still
707
be large and gas exchange probably takes place by conventional mechanisms.’ As frequency increases other processes come into play: convective turbulent and laminar dispersion, recirculation of gas among units with different time constants, and gas mixing caused by the contractile motion of the heart have all been invoked.S The putative advantages of high-frequency ventilation are a diminution in the wide swings in airway pressure seen with conventional mechanical ventilation and a decrease in mean airway pressure. Apart from the advantage of cardiovascular stability there is evidence that reduction in pressure variations may reduce ventilator-induced lung injury,although this has not been confirmed.9 Maintenance of gas exchange in the presence of low airway pressures has an obvious advantage in the management of some forms of bronchopulmonary fistula, and highfrequency jet ventilation can be valuable during surgery of the trachea and bronchpl,12 because conventional gas-tight endotracheal tubes increase the technical difficulties.13 High-frequency jet ventilation has been shown to have potential advantages in cardiac tamponade,14 and is also useful for maintaining a motionless operative field-eg, during lithotripsyl5 or laser surgery in the upper abdomen. Why has the technique not enjoyed greater popularity, especially in intensive care units? No controlled study has shown that it has any advantage over conventional mechanical ventilation and there are several potential drawbacks. A high pressure gas source in the airway can cause considerable damage if it gets in the wrong place, and there are obvious difficulties if the exhaust route for these high minute volumes gets blocked.lb°1’ Satisfactory humidification is also difficult to achieve with high minute volumes, and it may be hard to monitor airway pressures and lung volumes.18 There is no doubt that much of the effectiveness of high-frequency ventilation in maintaining arterial oxygenation is due to the increases in lung volume and functional residual capacity by a "continuous positive end-expiratory pressure" effect; 18 for this reason it has been advised that use of the technique should be restricted to patients with "stiff lungs".7 If the pressure is too high cardiovascular function will be impaired.19 Tracheal pressure reflects alveolar pressure6 and indirectly alveolar volume18 and functional residual capacity (FRC), but to monitor tracheal pressure adequately and therefore get some indication of FRC necessitates another catheter in the trachea, which is cumbersome. Techniques have been introduced to monitor tends
to
pressure through the injectorO and to measure expired
volume, from which tidal volume can be calculated.21 It is still difficult to judge which patients will benefit from high-frequency ventilation and what frequencies should be used. Froese and Bryanshave suggested that the technique could maintain arterial oxygen by keeping open airways and alveoli that were open at
the peak inflation pressure of conventional mechanical ventilation but then closed as the lung deflated. They suggested that airway and alveoli could be opened by applying some high-pressure inflation manoeuvre and then kept open at modest airway pressures by means of high-frequency ventilation. They also argued that the most efficient way of using high frequency ventilation is to ventilate the lung at its resonant frequency. Lin and colleagues22 have suggested that the thorax and abdomen behave as "coupled masses and compliances", and that the relation between these two, each with its own resonant frequency, will be important determinants of gas exchange. The problem is that, in a diseased lung with areas of atelectasis and alveolar flooding, resonant frequency differs from one area to another and as the condition improves.5 Routine determination of resonant frequencies is not yet a practical proposition. High-frequency ventilation has at least found something of a specialist niche in upper airway surgery, and it is reassuring to know that there is an alternative to conventional mechanical ventilation for patients who remain obstinately hypoxic no matter what the ventilator or PEEP setting. Jonzon A, Oberg PA, Sedin G, Sjostrand U. High frequency positivepressure ventilation by endotracheal insufflation. Acta Anaesthesiol Scand 1971; 43 (suppl): 1-38. 2. Carlon GC, Cole R, Klain M, McCormack PM. High frequency positive pressure ventilation in management of a patient with bronchopleural fistula. Anesthesiology 1980; 52: 160-62. 3. Carlon GC, Kahn RC, Howland WA, Ray C, Turnbull AD. Clinical experience with high frequency jet ventilation. Crit Care Med 1981; 9: 1.
1-6. 4. Sykes MK. High frequency ventilation. Br J Anaesth 1989; 62: 475-774. 5. Froese AB, Bryan AC. High frequency ventilation. Am Rev Respir Dis 1987; 135: 1363-74. 6. Frantz ID, Close RH. Elevated lung volume and alveolar pressure during jet ventilation of rabbits. Am Rev Respir Dis 1985; 131: 134-38. 7. Rouby JJ, Simonneau G, Benhamou D, Sartene R, Sardnal F, Dereiaz H, Duroux P, Viars P. Factors influencing pulmonary volumes and CO2
elimination during high frequency jet ventilation. Anesthesiology 1985; 63: 473-82. 8. Hamilton PP, Onayemi A, Smyth JA, Gillan JE, Cutz E, Froese AB, Bryan AC. Comparison of conventional and high frequency ventilation: oxygenation and lung pathology. J Appl Physiol: Respir Environ Exercise Physiol 1983; 55: 131-38. 9. Niblett DJ, Sandhar BK, Dunnill MS, Sykes MK. Comparisons of the effects of high frequency oscillation and controlled mechanical ventilation on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Br J Anaesth 1989; 62: 628-36. 10. Bishop MJ, Benson MS, Sato P, Pierson DJ. Comparison of high frequency jet ventilation with conventional mechanical ventilation for bronchopleural fistula. Anesth Analg 1987; 66: 833-38. 11. McKinney M, Coppel DL, Gibbons JR, Cosgrove J. A new technique for sleeve resection and major bronchial resection using twin catheters and high frequency ventilation. Anaesthesia 1988; 43: 25-26. 12. Schur MS, Maccioli GA, Azakhan RG, Wood RE. High frequency jet ventilation in the management of tracheal stenosis. Anesthesiology 1988; 69: 952-55. 13. Barclay RS, McSwan N, Welsh TM. Tracheal reconstruction without the use of grafts. Thorax 1957; 12: 177-80. 14. Goto K, Goto H, Benson KT, Unruh GK, Arakawa K. Efficacy of high-frequency jet ventilation in cardiac tamponade. Anesth Analg 1990; 70: 375-81. 15. Zeitlin GL, Roth RA. Effect of three anesthetic techniques on the success of extracorporeal shock wave lithotripsy in nephrolithaisis.
Anesthesiology 1988; 68: 272-76. 16. Vivori E. Anaesthesia for laryngoscopy. Br J Anaesth 1980; 52: 638. 17. Craft TM, Chambers PH, Ward ME, Goat V. Two cases of barotrauma associated with transtracheal jet ventilation. Br J Anaesth 1990; 64: 524-27.
708
Rouby JJ, Fusciardi J, Bourgain JL, Viars P. High frequency jet ventilation in postoperative respiratory failure: determinants of oxygenation. Anesthesiol 1983; 59: 281-87. 19. Chakrabarti MK, Sykes MK. Cardiorespiratory effects of highfrequency intermittent positive pressure ventilation in the dog. Br J
18.
Anaesth 1980; 52: 475-82. 20.
Bourgain JL, Desruennes E, Cossett MF, Mamelle G, Belaiche S, Truffa-Bachi J. Measurement of end expiratory pressure during transtracheal high frequency jet ventilation for laryngoscopy. Br J
Anaesth 1990; 65: 373-4326. 21. Young JD, Sykes MK. A method for measuring tidal volume during high frequency ventilation. Br J Anaesth 1988; 61: 601-05. 22. Lin ES, Jones MJ, Mottram SD, Smith BE, Smith G. Relationship between resonance and gas exchange during high frequency jet ventilation. Br J Anaesth 1990; 64: 453-59.
Tumour necrosis factor and malaria How is it that tissues
not
invaded
by
the
damaged during malaria? plasmodium parasite Earlier notions that the parasites competed for nutrients or released a toxin that had a direct effect on the host have been discarded, and it now seems that damage is caused by proteins released by the host in response to infection. Tumour necrosis factor alpha (TNF-a) has been the focus of special attention in this context. This cytokine is released by are
monocytes/macrophages
and T
lymphocytes
in
inflammation and infection. Increased response concentrations of TNF-oc have been found in various infectious diseases,l including malaria,in which it is probably released in response to schizont ruptures3 TNF-a is an essential part of the host’s immune response because it modulates the effects of macrophages, neutrophils, lymphocytes, and endothelial cells and thereby mediates destruction of invading organisms. However, excessive amounts of TNF-a seem to be harmful. Injection of mice with recombinant TNF-a to
produces
the
same
changes
as
are
seen
in
terminal Plasmodium vinckei malaria, including hypoglycaemia.4 The effects of TNF-a treatment of tumours in man resemble the features of malaria—eg,
vomiting, fever, rigor, headache, myalgia, hypotension, thrombocytopenia, and neurological changes.s Since TNF-a was detected in the serum of patients with malaria,2interest has tended to focus on the relation of this cytokine to severe and cerebral disease. Kwiatkowski and colleagues reported significantly higher plasma concentrations in Gambian children with P falciparum malaria than in those with other illnesses.6They also found that plasma concentrations of TNF-a were much greater in cerebral malaria than in uncomplicated malaria-twice as high in those with cerebral malaria who survived and ten times as high in fatal cases. Previously, the same group had found that nausea,
raised concentrations were associated with acute P falciparum infection but did not correlate with disease severity or outcome.3Grau and colleagues,’ in a study of Malawian children with severe falciparum increased TNF-a malaria, reported that concentrations were associated with fatal outcome,
cerebral malaria, and hypoglycaemia; the association between high concentrations and complicated malaria was also found in European adults.8 The relation between raised TNF-a concentrations and severe malaria has been confirmed in children in Zaire,l but there was no particular association with cerebral malaria. That increased concentrations of circulating TNF-a are related to the illness of malaria is now beyond doubt; but does this association represent cause and effect? TNF-a might lead to cerebral involvement in malaria by increasing expression of parasite receptors on the endothelium of cerebral blood vessels, or by inducing hypoglycaemia, lactic acidosis, and other metabolic changes.So how can one explain the low concentrations of circulating TNF-a in some comatose patients and the high concentrations in some healthy individuals?9 Although TNF -cx has a short half-life in human serum (about 20 min), the effects persist; thus, the circulating concentration should correlate more closelv with time since schizogony than with the patient’s illness.3 High concentrations in a patient without severe malaria can be explained-provided they occur late rather than early during the disease-in terms of acquired tolerance to TNF-cx.5 TNF-a is only one of a family of cytokines with overlapping functions. Concentrations of lymphotoxin (TNF-&bgr;),lO interleukin-lcx,6 and interleukin-68 are all increased in malaria and correlate with disease severity. These cytokines may induce another family of mediators-eg, platelet-activated factor, prostaglandin E2-that actually cause the tissue damaged5 Treatment of malaria with neutralising antibody to TNF-a now seems a distinct possibility, but antibodies directed against other cytokines will probably be required as well.
Shaffer N, Grau GE, Hedberg K, et al. Tumor necrosis factor and severe malaria. J Infect Dis 1991; 163: 96-101. 2. Scuderi P, Lam KS, Ryan KJ, et al. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet 1986; i: 1364-65. 3. Kwiatkowski D, Cannon JG, Manogue KR, Cerami A, Dinarello CA. Tumour necrosis factor production in falciparum malaria and its association with schizont rupture. Clin Exp Immunol 1989; 77: 361-66. 4. Clark IA, Cowden WB, Butcher GA, Hunt NH. Possible roles of tumor necrosis factor in the pathology of malaria. Am J Pathol 1987; 129: 1.
192-99. 5. Clark IA, Chaudhri G, Cowden WB. Roles of tumour necrosis factor in the illness and pathology of malaria. Trans R Soc Trop Med Hyg 1989; 83: 436-40.
6. Kwiatkowski D, Hill AVS, Sambou I, et al. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990; 336: 1201-04. 7. Grau GE, Taylor TE, Molyneux ME, et al. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989; 320: 1586-91. 8. Kern P, Hemmer CJ, Van Damme J, Gruss HJ, Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med 1989; 87: 139-43.
9.
Phillips RE, Solomon T. Cerebral malaria in children. Lancet 1990; 336: 1355-60.
10. Clark IA, Rockett KA, Cowden WB. Role of TNF in cerebral malana Lancet 1991; 337: 302-03.
1. Editorial. Which heart valve prosthesis? Lancet 1985; ii: 756-58. 2. Treasure T. Which heart valves should we use? Lancet 1990; 336: 1115-117. 3. Gersh BJ, Fisher LD, Schaff HV, et al. Issues concerning the clinical evaluation of new prosthetic valves. J Thorac Cardiovasc Surg 1986; 91: 460-66. 4. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Twelve-year comparison of a Björk-Shiley mechanical heart valve with porcine bioprostheses. N Engl J Med 1991; 324: 573-79. 5. Collins JJ. The evolution of artificial heart valves. N Engl J Med 1991; 324: 624-26. 6. Bloomfield P, Kitchin AH, Wheatley DJ, Walbaum PR, Lutz W, Miller HC. A prospective evaluation of the Björk-Shiley, Hancock and Carpentier-Edwards heart valve prostheses. Circulation 1986; 73: 1213-22. 7. Bloomfield P, Wheatley DJ, Prescott RJ, Miller HC. Ten year results of a randomised trial of the Bjork-Shiley, Hancock and CarpentierEdwards heart valve prostheses. Br Heart J 1989; 61: 452 (abstr).
Nuclear medicine and the
hepatobiliary tract Imaging of the hepatobiliary tract with ultrasound and computed tomography (CT) provides doctors with anatomical and morphological information and is popular in hospital practice. By contrast, imaging with radionuclides, which can additionally yield physiological information, tends to be under used. Hepatobiliary scintigraphy (HBS) is often regarded as yet another imaging modality with which to confront and confuse a perplexed clinician. HBS is of greatest use in the recognition of biliary obstruction. Both ultrasound and CT are well suited to the diagnosis of bile duct dilatation and therefore the level of obstruction. Ultrasound scans are cheap, widely available, sensitive, and reliable for detecting stones in the gallbladder. CT will detect the presence, level, and cause of obstruction. Neither system delineates the pathophysiology associated with the flow of bile. HBS is the only imaging technique that reliably shows cystic duct obstruction, which occurs in most patients with acute cholecystitis; visualisation of the gallbladder within an hour virtually excludes this condition. After liver or biliary tract surgery, HBS may be used to monitor the flow of bile and display postoperative biliary reflux, leaks, and the patency of a biliary-enteric anastomosis. It can also be used to evaluate post-cholecystectomy syndromes and afferent loop disorders after gastrectomy. Other indications for HBS include abdominal trauma and the differential diagnosis of neonatal jaundice, in which biliary atresia may be excluded by observing the passage of bile into the gut. For HBS a technetium-99- (99Tc-)-labelled derivative of iminodiacetic acid (IDA) is injected intravenously after a 4-6-hour fast. This tracer is a dimer of high molecular weight and lipid solubility and is taken up by the hepatocytes; it is then preferentially excreted by the biliary tract, because the kidneys are unable to remove substances from the body if their molecular weight exceeds 300 daltons. Sequential images of the liver, intrahepatic ducts, common bileduct, gallbladder, and small intestine are usually seen and monitored with a gamma camera/
computer system within an hour of injection of a radiolabelled tracer. Repeated imaging up to 4 hours, and again at 24 hours, may help to determine biliary
patency. Several 99Tcm-IDA complexes have been used to define hepatobiliary function.1 Of these, 99Tc-EHIDA and 99TcmDISIDA are the preferred tracers because their high extraction rate and fast hepatic transit permit more sensitive imaging. However, in jaundiced patients some 9’YfcmDISIDA is excreted via the kidneys and excretion correlates directly with serum bilirubin concentrations.z Consequently, the biliary excretion rate is reduced, making the differentiation between hepatocellular disease and biliary obstruction or leakage less certain. 99T cm- I OD IDA,3with its lower urinary excretion and higher biliary excretion than other 99Tcm-IDA derivatives, has been advocated for assessment of the biliary tree after liver transplantation,4 but this radionuclide likewise is of only limited use when the serum bilirubin rises to more than 200 unol/1. The general availability of radionuclide imaging facilities in hospitals, the low cost, and the low radiation dose should encourage clinicians to consider HBS as a practical clinicophysiological test that is readily applicable for general use, especially in the early stages of biliary obstruction. 1. Williams
AG, Mettler FA, Christie JH. Hepatobiliary and pancreatic imaging. In: Mettler FA, ed. Radionuclide imaging of the GI tract. London: Churchill-Livingstone, 1986: 183-216. 2. Klingensmith WC, Fritzberg AR, Spitzer VM, Kuni CC, Shanahan WM. Clinical comparison of diisopropyl-IDA-Tc99m and diethylIDA-Tc99m for evaluation of the hepatobiliary system. Radiology 1981; 140: 791-95. R, Kotzerke J, Hundeshagen H, Bocker K, Ringe B
3. Schwarzrock
99Tcm-diethyl-ioda-HIDA (JODIDA): a new hepatobiliary agent in clinical comparison with 99mTc-disopropyl-HIDA (DISIDA) in jaundiced patients. Eur J Nuclear Med 1986, 12: 346-50. 4. Anselmi M, Lancberg S, Deakin M, et al. Assessment of the biliary tract after liver transplantation: T tube cholangiography or IODIDA scanning. Br J Surg 1990; 77: 1233-37.
High-frequency ventilation High-frequency ventilation has been with us now for over twenty years1 and in clinical use for over ten.2,3 Sykes4 referred to it as "a physiological curiosity looking for a clinical application". The term is generally applied when respiratory frequency is more than four times greater than normal-ie, 60-1800 breaths/min (1-30 Hz).5 Tidal volume diminishes as frequency increases,6and dead space increases relative to tidal volume, so high minute volumes are used. Broadly there are three techniques: (a) high-frequency positive-pressure ventilation (1-1-7 Hz) with an endotracheal tube; (b) high-frequency jet ventilation (1-5 Hz) by which pulses of gas are passed through a small bore cannula from a high pressure (1-4 bar) source which may entrain additional gas depending on volume, pressure, compliance, &C;7 and (c) highfrequency oscillation at 3-30 Hz with a sine-wave pump. At lower frequencies (1 -6 Hz) tidal volume still
707
be large and gas exchange probably takes place by conventional mechanisms.’ As frequency increases other processes come into play: convective turbulent and laminar dispersion, recirculation of gas among units with different time constants, and gas mixing caused by the contractile motion of the heart have all been invoked.S The putative advantages of high-frequency ventilation are a diminution in the wide swings in airway pressure seen with conventional mechanical ventilation and a decrease in mean airway pressure. Apart from the advantage of cardiovascular stability there is evidence that reduction in pressure variations may reduce ventilator-induced lung injury,although this has not been confirmed.9 Maintenance of gas exchange in the presence of low airway pressures has an obvious advantage in the management of some forms of bronchopulmonary fistula, and highfrequency jet ventilation can be valuable during surgery of the trachea and bronchpl,12 because conventional gas-tight endotracheal tubes increase the technical difficulties.13 High-frequency jet ventilation has been shown to have potential advantages in cardiac tamponade,14 and is also useful for maintaining a motionless operative field-eg, during lithotripsyl5 or laser surgery in the upper abdomen. Why has the technique not enjoyed greater popularity, especially in intensive care units? No controlled study has shown that it has any advantage over conventional mechanical ventilation and there are several potential drawbacks. A high pressure gas source in the airway can cause considerable damage if it gets in the wrong place, and there are obvious difficulties if the exhaust route for these high minute volumes gets blocked.lb°1’ Satisfactory humidification is also difficult to achieve with high minute volumes, and it may be hard to monitor airway pressures and lung volumes.18 There is no doubt that much of the effectiveness of high-frequency ventilation in maintaining arterial oxygenation is due to the increases in lung volume and functional residual capacity by a "continuous positive end-expiratory pressure" effect; 18 for this reason it has been advised that use of the technique should be restricted to patients with "stiff lungs".7 If the pressure is too high cardiovascular function will be impaired.19 Tracheal pressure reflects alveolar pressure6 and indirectly alveolar volume18 and functional residual capacity (FRC), but to monitor tracheal pressure adequately and therefore get some indication of FRC necessitates another catheter in the trachea, which is cumbersome. Techniques have been introduced to monitor tends
to
pressure through the injectorO and to measure expired
volume, from which tidal volume can be calculated.21 It is still difficult to judge which patients will benefit from high-frequency ventilation and what frequencies should be used. Froese and Bryanshave suggested that the technique could maintain arterial oxygen by keeping open airways and alveoli that were open at
the peak inflation pressure of conventional mechanical ventilation but then closed as the lung deflated. They suggested that airway and alveoli could be opened by applying some high-pressure inflation manoeuvre and then kept open at modest airway pressures by means of high-frequency ventilation. They also argued that the most efficient way of using high frequency ventilation is to ventilate the lung at its resonant frequency. Lin and colleagues22 have suggested that the thorax and abdomen behave as "coupled masses and compliances", and that the relation between these two, each with its own resonant frequency, will be important determinants of gas exchange. The problem is that, in a diseased lung with areas of atelectasis and alveolar flooding, resonant frequency differs from one area to another and as the condition improves.5 Routine determination of resonant frequencies is not yet a practical proposition. High-frequency ventilation has at least found something of a specialist niche in upper airway surgery, and it is reassuring to know that there is an alternative to conventional mechanical ventilation for patients who remain obstinately hypoxic no matter what the ventilator or PEEP setting. Jonzon A, Oberg PA, Sedin G, Sjostrand U. High frequency positivepressure ventilation by endotracheal insufflation. Acta Anaesthesiol Scand 1971; 43 (suppl): 1-38. 2. Carlon GC, Cole R, Klain M, McCormack PM. High frequency positive pressure ventilation in management of a patient with bronchopleural fistula. Anesthesiology 1980; 52: 160-62. 3. Carlon GC, Kahn RC, Howland WA, Ray C, Turnbull AD. Clinical experience with high frequency jet ventilation. Crit Care Med 1981; 9: 1.
1-6. 4. Sykes MK. High frequency ventilation. Br J Anaesth 1989; 62: 475-774. 5. Froese AB, Bryan AC. High frequency ventilation. Am Rev Respir Dis 1987; 135: 1363-74. 6. Frantz ID, Close RH. Elevated lung volume and alveolar pressure during jet ventilation of rabbits. Am Rev Respir Dis 1985; 131: 134-38. 7. Rouby JJ, Simonneau G, Benhamou D, Sartene R, Sardnal F, Dereiaz H, Duroux P, Viars P. Factors influencing pulmonary volumes and CO2
elimination during high frequency jet ventilation. Anesthesiology 1985; 63: 473-82. 8. Hamilton PP, Onayemi A, Smyth JA, Gillan JE, Cutz E, Froese AB, Bryan AC. Comparison of conventional and high frequency ventilation: oxygenation and lung pathology. J Appl Physiol: Respir Environ Exercise Physiol 1983; 55: 131-38. 9. Niblett DJ, Sandhar BK, Dunnill MS, Sykes MK. Comparisons of the effects of high frequency oscillation and controlled mechanical ventilation on hyaline membrane formation in a rabbit model of the neonatal respiratory distress syndrome. Br J Anaesth 1989; 62: 628-36. 10. Bishop MJ, Benson MS, Sato P, Pierson DJ. Comparison of high frequency jet ventilation with conventional mechanical ventilation for bronchopleural fistula. Anesth Analg 1987; 66: 833-38. 11. McKinney M, Coppel DL, Gibbons JR, Cosgrove J. A new technique for sleeve resection and major bronchial resection using twin catheters and high frequency ventilation. Anaesthesia 1988; 43: 25-26. 12. Schur MS, Maccioli GA, Azakhan RG, Wood RE. High frequency jet ventilation in the management of tracheal stenosis. Anesthesiology 1988; 69: 952-55. 13. Barclay RS, McSwan N, Welsh TM. Tracheal reconstruction without the use of grafts. Thorax 1957; 12: 177-80. 14. Goto K, Goto H, Benson KT, Unruh GK, Arakawa K. Efficacy of high-frequency jet ventilation in cardiac tamponade. Anesth Analg 1990; 70: 375-81. 15. Zeitlin GL, Roth RA. Effect of three anesthetic techniques on the success of extracorporeal shock wave lithotripsy in nephrolithaisis.
Anesthesiology 1988; 68: 272-76. 16. Vivori E. Anaesthesia for laryngoscopy. Br J Anaesth 1980; 52: 638. 17. Craft TM, Chambers PH, Ward ME, Goat V. Two cases of barotrauma associated with transtracheal jet ventilation. Br J Anaesth 1990; 64: 524-27.
708
Rouby JJ, Fusciardi J, Bourgain JL, Viars P. High frequency jet ventilation in postoperative respiratory failure: determinants of oxygenation. Anesthesiol 1983; 59: 281-87. 19. Chakrabarti MK, Sykes MK. Cardiorespiratory effects of highfrequency intermittent positive pressure ventilation in the dog. Br J
18.
Anaesth 1980; 52: 475-82. 20.
Bourgain JL, Desruennes E, Cossett MF, Mamelle G, Belaiche S, Truffa-Bachi J. Measurement of end expiratory pressure during transtracheal high frequency jet ventilation for laryngoscopy. Br J
Anaesth 1990; 65: 373-4326. 21. Young JD, Sykes MK. A method for measuring tidal volume during high frequency ventilation. Br J Anaesth 1988; 61: 601-05. 22. Lin ES, Jones MJ, Mottram SD, Smith BE, Smith G. Relationship between resonance and gas exchange during high frequency jet ventilation. Br J Anaesth 1990; 64: 453-59.
Tumour necrosis factor and malaria How is it that tissues
not
invaded
by
the
damaged during malaria? plasmodium parasite Earlier notions that the parasites competed for nutrients or released a toxin that had a direct effect on the host have been discarded, and it now seems that damage is caused by proteins released by the host in response to infection. Tumour necrosis factor alpha (TNF-a) has been the focus of special attention in this context. This cytokine is released by are
monocytes/macrophages
and T
lymphocytes
in
inflammation and infection. Increased response concentrations of TNF-oc have been found in various infectious diseases,l including malaria,in which it is probably released in response to schizont ruptures3 TNF-a is an essential part of the host’s immune response because it modulates the effects of macrophages, neutrophils, lymphocytes, and endothelial cells and thereby mediates destruction of invading organisms. However, excessive amounts of TNF-a seem to be harmful. Injection of mice with recombinant TNF-a to
produces
the
same
changes
as
are
seen
in
terminal Plasmodium vinckei malaria, including hypoglycaemia.4 The effects of TNF-a treatment of tumours in man resemble the features of malaria—eg,
vomiting, fever, rigor, headache, myalgia, hypotension, thrombocytopenia, and neurological changes.s Since TNF-a was detected in the serum of patients with malaria,2interest has tended to focus on the relation of this cytokine to severe and cerebral disease. Kwiatkowski and colleagues reported significantly higher plasma concentrations in Gambian children with P falciparum malaria than in those with other illnesses.6They also found that plasma concentrations of TNF-a were much greater in cerebral malaria than in uncomplicated malaria-twice as high in those with cerebral malaria who survived and ten times as high in fatal cases. Previously, the same group had found that nausea,
raised concentrations were associated with acute P falciparum infection but did not correlate with disease severity or outcome.3Grau and colleagues,’ in a study of Malawian children with severe falciparum increased TNF-a malaria, reported that concentrations were associated with fatal outcome,
cerebral malaria, and hypoglycaemia; the association between high concentrations and complicated malaria was also found in European adults.8 The relation between raised TNF-a concentrations and severe malaria has been confirmed in children in Zaire,l but there was no particular association with cerebral malaria. That increased concentrations of circulating TNF-a are related to the illness of malaria is now beyond doubt; but does this association represent cause and effect? TNF-a might lead to cerebral involvement in malaria by increasing expression of parasite receptors on the endothelium of cerebral blood vessels, or by inducing hypoglycaemia, lactic acidosis, and other metabolic changes.So how can one explain the low concentrations of circulating TNF-a in some comatose patients and the high concentrations in some healthy individuals?9 Although TNF -cx has a short half-life in human serum (about 20 min), the effects persist; thus, the circulating concentration should correlate more closelv with time since schizogony than with the patient’s illness.3 High concentrations in a patient without severe malaria can be explained-provided they occur late rather than early during the disease-in terms of acquired tolerance to TNF-cx.5 TNF-a is only one of a family of cytokines with overlapping functions. Concentrations of lymphotoxin (TNF-&bgr;),lO interleukin-lcx,6 and interleukin-68 are all increased in malaria and correlate with disease severity. These cytokines may induce another family of mediators-eg, platelet-activated factor, prostaglandin E2-that actually cause the tissue damaged5 Treatment of malaria with neutralising antibody to TNF-a now seems a distinct possibility, but antibodies directed against other cytokines will probably be required as well.
Shaffer N, Grau GE, Hedberg K, et al. Tumor necrosis factor and severe malaria. J Infect Dis 1991; 163: 96-101. 2. Scuderi P, Lam KS, Ryan KJ, et al. Raised serum levels of tumour necrosis factor in parasitic infections. Lancet 1986; i: 1364-65. 3. Kwiatkowski D, Cannon JG, Manogue KR, Cerami A, Dinarello CA. Tumour necrosis factor production in falciparum malaria and its association with schizont rupture. Clin Exp Immunol 1989; 77: 361-66. 4. Clark IA, Cowden WB, Butcher GA, Hunt NH. Possible roles of tumor necrosis factor in the pathology of malaria. Am J Pathol 1987; 129: 1.
192-99. 5. Clark IA, Chaudhri G, Cowden WB. Roles of tumour necrosis factor in the illness and pathology of malaria. Trans R Soc Trop Med Hyg 1989; 83: 436-40.
6. Kwiatkowski D, Hill AVS, Sambou I, et al. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet 1990; 336: 1201-04. 7. Grau GE, Taylor TE, Molyneux ME, et al. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med 1989; 320: 1586-91. 8. Kern P, Hemmer CJ, Van Damme J, Gruss HJ, Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med 1989; 87: 139-43.
9.
Phillips RE, Solomon T. Cerebral malaria in children. Lancet 1990; 336: 1355-60.
10. Clark IA, Rockett KA, Cowden WB. Role of TNF in cerebral malana Lancet 1991; 337: 302-03.