112
Asthma after ovarian
hyperstimulation syndrome
SIR,-Ovarian hyperstimulation syndrome (OHSS) is the most complication of ovulation induction. Ascites, pleural effusion, and haemoconcentration due to capillary leak, renal failure, hypovolaemic shock, adult respiratory distress syndrome, serious
and thromboembolic complications are the most severe effects of ovarian overstimulation.1 We describe a patient in whom bronchial asthma developed during severe OHSS. A 36-year-old woman had had primary infertility for 14 years. Repeated insemination procedures did not result in pregnancy and in-vitro fertilisation was tried. Buserelin, a synthetic LHRH analogue, was given as a nasal aerosol thrice daily, and human menopausal gonadotropin in a daily dose of 150 U intramuscularly. After ovulation induction follicle aspiration was done and 3 days later two embryos were transferred. 9 days later the patient was admitted because of OHSS. She had nausea, vomiting, abdominal pain, and malaise. She had haemoconcentration and raised plasma creatinine. Ultrasonographic examination of the abdomen revealed enlarged ovaries (10-15 cm in diameter) with multiple follicles and ascites. Hormone treatment was stopped and naproxen 500 mg thrice daily was given for 3 days. 4 days later she complained of wheezing and chest tightness. She had no history of asthma or wheezing, and frequent use of calcium acetylsalicylate because of migraine had not caused respiratory symptoms. Chest radiography showed some pleural effusion and congested pulmonary vessels. Intravenous frusemide 20 mg was given with inhaled salbutamol four times daily. After discharge wheezing and tightness of the chest remained. Lung function tests showed restriction without obstruction, and a histamine challenge test was positive with a PD20 histamine of 5-4 mg/ml (normal over 8 mg/ml). RAST-test was negative for a panel of environmental allergens. Six months later an inhaled corticosteroid was necessary because of worsening symptoms. Persistent bronchial asthma during OHSS developed in this patient, which as far as we are aware has not been reported previously. Although she was treated with naproxen, which can precipitate asthmatic attacks in susceptible subjects,2 this did not seem to be the precipitating factor for asthma. She often used calcium acetylsalicylate, which is also a cyclo-oxygenase inhibitor, without pulmonary symptoms. The exact mechanism of OHSS is not yet clear, but several mediators such as histamine and prostaglandins seem to be involved,3 which also have an important role in asthma.4 OHSS seems to be the most likely precipitant of asthma in this patient. Departments of Pulmonary Diseases, and Obstetrics and Gynaecology, University Hospital Nijmegen, 6500 HB Nijmegen, Netherlands
C. A. R. GROOT J.-W. LAMMERS J. M. G. HOLLANDERS
1. Borenstein R,
Elhalah U, Lunenfeld B, Schwartz Zs. Severe ovanan hyperstimulation syndrome: a reevaluated therapeutic approach. Fertil Steril 1989, 51: 791-95. 2. Lewis RV. Severe asthma after naproxen. Lancet 1987; i: 1270. 3. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome. an update review. Obstet Gynecol Surv 1989; 44: 430-40. 4. Barnes PJ, Chung KF,
Page CP. Inflammatory mediators in asthma Pharmacol Rev
1988; 40: 49-84.
Angiotensin-converting-enzyme inhibitors and anaphylactoid reactions to high-flux membrane dialysis SIR,-We observed similar anaphylactoid reactions (AR) to those reported by Dr Verresen and colleagues (Dec 1, p 1360) in 10 of 13 patients receiving angiotensin-converting-enzyme (ACE) inhibitors while on dialysis with the AN69 high-flux (HF) membrane. Although Verresen et al suggest that these reactions are related to the HF characteristics of AN69, we believe that they occur mainly within the AN69 membrane. Indeed, AR disappeared (0 of 15 sessions) or became rare (3 of 26 sessions) in 2 of our patients when they were switched to polysulfone, another type of HF membrane. Tielemans et aP hypothesised that AR resulted from the negative charge of the surface of AN69, unlike polysulfone, which
would thus allow bradykinin formation through activation of the Hageman factor. Verresen et al proposed a pathogenic role for dialysate bacterial products adsorbed on the HF membranes, based on two observations: firstly, in 2 patients, a new dialyser, whose blood and dialysate compartments were previously rinsed with sterile saline, failed to elicit AR if blood was allowed to circulate initially for 5 min without dialysate flow, and, secondly, the lack of reactions in 3 patients treated by haemofiltration with the AN69 membrane. We believe that presence of dialysate is probably not a prerequisite for development of AR. We made detailed observations in a single patient over a 4-month period. AR was seen within 5 min of isolated ultrafiltration with a new AN69 dialyser in 5 of 11sessions, a proportion similar to that with new AN69 dialysers in the presence of dialysate (3 of 6 sessions), and with hypochlorite treated dialysers with (6 of 11) and without (9 of 13) dialysate. These observations suggest that the interaction of blood and membrane releases a vasoactive substance in the absence of dialysate. Interestingly, no AR was seen when dialysers were reused after treatment with formaldehyde (0 of 7 sessions), a sterilising compound which, unlike hypochlorite, leaves intact the protein coating of the membrane.2 A preventive effect of protein coating is also suggested by the absence of AR (0 of 8) when dialysis was preceded by an initial 2 min circulation of blood and priming fluid at low flow rate (60 ml/min) followed by a 4 min closed-circuit recirculation without dialysate. These data also suggest that the substance released within the dialyser during the 2 min blood priming disappears during the 4 min recirculation. Thus, it has a short biological half-life (spontaneous or through removal by the
membrane). Department of Nephrology, Cliniques Universitaires St Luc, University of Louvain Medical School, 1200 Brussels, Belgium
M. JADOUL J. STRUYVEN A. STRAGIER C. VAN YPERSELE DE STRIHOU
C, Madhoun P, Lenaers M, Schandene L, Goldman M, Vanherweghem JL Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int 1990, 38: 982-84. 2. Chenoweth DE, Cheung AK, Ward DM, Henderson LW Anaphylatoxin formation during hemodialysis comparison of new and re-used dialyzers Kidney Int 1983, 1. Tielemans
24: 770-74
SIR,-Dr Verresen and colleagues describe anaphylactoid reactions to high-flux membrane dialysis in 9 of 14 patients treated with ACE inhibitors. Patients not receiving ACE inhibitors did not have such reactions. Verresen and colleagues’ patients were treated with a polyacrylonitrile ("AN69", Hospal) dialyser and an acetatecontaining dialysis solution. In 1988, standard treatment in our unit was changed to high-flux polysulfone hollow fibre ("HemoflowF", Fresenius) membranes and bicarbonate dialysis solution. Dialysers are not re-used, and the "Bioprime" rinse method (Hospal) (described by Verresen and colleagues) is not applied. ACE inhibitors have been prescribed to 13 of our 83 patients on the standard haemodialysis programme (captopril 5, perindopril 5, enalapril 3). None of our patients on polysulfone membrane dialysis have had anaphylactoid reactions. Verresen and colleagues suggest that ACE inhibitors might facilitate anaphylactoid reactions in response to bacterial products of the dialysate which transfer across high-flux dialysis membranes. Our protocols for water processing and control of minimal transmembrane pressure may differ from those of Verresen and colleagues, resulting in differences in bacterial product load and back flush rate. Furthermore, polysulfone high-flux membranes are relatively impermeable to endotoxins and other bacterial
products. 1,2 A case history suports the theory outlined above. One of our patients was treated initially with an AN69 dialyser. Two years later, shortly after starting ACE inhibitor therapy, she had repeated anaphylactoid reactions within minutes of haemodialysis being started. Subsequent dialysis was done with a Hemoflow-F60 dialyser; anaphylactoid reactions did not recur. Our observations, and those of Verresen and colleagues, suggest that anaphylactoid reactions to high-flux membranes in combination with ACE inhibitors are dependent on the type of
Asthma after ovarian
hyperstimulation syndrome
SIR,-Ovarian hyperstimulation syndrome (OHSS) is the most complication of ovulation induction. Ascites, pleural effusion, and haemoconcentration due to capillary leak, renal failure, hypovolaemic shock, adult respiratory distress syndrome, serious
and thromboembolic complications are the most severe effects of ovarian overstimulation.1 We describe a patient in whom bronchial asthma developed during severe OHSS. A 36-year-old woman had had primary infertility for 14 years. Repeated insemination procedures did not result in pregnancy and in-vitro fertilisation was tried. Buserelin, a synthetic LHRH analogue, was given as a nasal aerosol thrice daily, and human menopausal gonadotropin in a daily dose of 150 U intramuscularly. After ovulation induction follicle aspiration was done and 3 days later two embryos were transferred. 9 days later the patient was admitted because of OHSS. She had nausea, vomiting, abdominal pain, and malaise. She had haemoconcentration and raised plasma creatinine. Ultrasonographic examination of the abdomen revealed enlarged ovaries (10-15 cm in diameter) with multiple follicles and ascites. Hormone treatment was stopped and naproxen 500 mg thrice daily was given for 3 days. 4 days later she complained of wheezing and chest tightness. She had no history of asthma or wheezing, and frequent use of calcium acetylsalicylate because of migraine had not caused respiratory symptoms. Chest radiography showed some pleural effusion and congested pulmonary vessels. Intravenous frusemide 20 mg was given with inhaled salbutamol four times daily. After discharge wheezing and tightness of the chest remained. Lung function tests showed restriction without obstruction, and a histamine challenge test was positive with a PD20 histamine of 5-4 mg/ml (normal over 8 mg/ml). RAST-test was negative for a panel of environmental allergens. Six months later an inhaled corticosteroid was necessary because of worsening symptoms. Persistent bronchial asthma during OHSS developed in this patient, which as far as we are aware has not been reported previously. Although she was treated with naproxen, which can precipitate asthmatic attacks in susceptible subjects,2 this did not seem to be the precipitating factor for asthma. She often used calcium acetylsalicylate, which is also a cyclo-oxygenase inhibitor, without pulmonary symptoms. The exact mechanism of OHSS is not yet clear, but several mediators such as histamine and prostaglandins seem to be involved,3 which also have an important role in asthma.4 OHSS seems to be the most likely precipitant of asthma in this patient. Departments of Pulmonary Diseases, and Obstetrics and Gynaecology, University Hospital Nijmegen, 6500 HB Nijmegen, Netherlands
C. A. R. GROOT J.-W. LAMMERS J. M. G. HOLLANDERS
1. Borenstein R,
Elhalah U, Lunenfeld B, Schwartz Zs. Severe ovanan hyperstimulation syndrome: a reevaluated therapeutic approach. Fertil Steril 1989, 51: 791-95. 2. Lewis RV. Severe asthma after naproxen. Lancet 1987; i: 1270. 3. Golan A, Ron-el R, Herman A, Soffer Y, Weinraub Z, Caspi E. Ovarian hyperstimulation syndrome. an update review. Obstet Gynecol Surv 1989; 44: 430-40. 4. Barnes PJ, Chung KF,
Page CP. Inflammatory mediators in asthma Pharmacol Rev
1988; 40: 49-84.
Angiotensin-converting-enzyme inhibitors and anaphylactoid reactions to high-flux membrane dialysis SIR,-We observed similar anaphylactoid reactions (AR) to those reported by Dr Verresen and colleagues (Dec 1, p 1360) in 10 of 13 patients receiving angiotensin-converting-enzyme (ACE) inhibitors while on dialysis with the AN69 high-flux (HF) membrane. Although Verresen et al suggest that these reactions are related to the HF characteristics of AN69, we believe that they occur mainly within the AN69 membrane. Indeed, AR disappeared (0 of 15 sessions) or became rare (3 of 26 sessions) in 2 of our patients when they were switched to polysulfone, another type of HF membrane. Tielemans et aP hypothesised that AR resulted from the negative charge of the surface of AN69, unlike polysulfone, which
would thus allow bradykinin formation through activation of the Hageman factor. Verresen et al proposed a pathogenic role for dialysate bacterial products adsorbed on the HF membranes, based on two observations: firstly, in 2 patients, a new dialyser, whose blood and dialysate compartments were previously rinsed with sterile saline, failed to elicit AR if blood was allowed to circulate initially for 5 min without dialysate flow, and, secondly, the lack of reactions in 3 patients treated by haemofiltration with the AN69 membrane. We believe that presence of dialysate is probably not a prerequisite for development of AR. We made detailed observations in a single patient over a 4-month period. AR was seen within 5 min of isolated ultrafiltration with a new AN69 dialyser in 5 of 11sessions, a proportion similar to that with new AN69 dialysers in the presence of dialysate (3 of 6 sessions), and with hypochlorite treated dialysers with (6 of 11) and without (9 of 13) dialysate. These observations suggest that the interaction of blood and membrane releases a vasoactive substance in the absence of dialysate. Interestingly, no AR was seen when dialysers were reused after treatment with formaldehyde (0 of 7 sessions), a sterilising compound which, unlike hypochlorite, leaves intact the protein coating of the membrane.2 A preventive effect of protein coating is also suggested by the absence of AR (0 of 8) when dialysis was preceded by an initial 2 min circulation of blood and priming fluid at low flow rate (60 ml/min) followed by a 4 min closed-circuit recirculation without dialysate. These data also suggest that the substance released within the dialyser during the 2 min blood priming disappears during the 4 min recirculation. Thus, it has a short biological half-life (spontaneous or through removal by the
membrane). Department of Nephrology, Cliniques Universitaires St Luc, University of Louvain Medical School, 1200 Brussels, Belgium
M. JADOUL J. STRUYVEN A. STRAGIER C. VAN YPERSELE DE STRIHOU
C, Madhoun P, Lenaers M, Schandene L, Goldman M, Vanherweghem JL Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors. Kidney Int 1990, 38: 982-84. 2. Chenoweth DE, Cheung AK, Ward DM, Henderson LW Anaphylatoxin formation during hemodialysis comparison of new and re-used dialyzers Kidney Int 1983, 1. Tielemans
24: 770-74
SIR,-Dr Verresen and colleagues describe anaphylactoid reactions to high-flux membrane dialysis in 9 of 14 patients treated with ACE inhibitors. Patients not receiving ACE inhibitors did not have such reactions. Verresen and colleagues’ patients were treated with a polyacrylonitrile ("AN69", Hospal) dialyser and an acetatecontaining dialysis solution. In 1988, standard treatment in our unit was changed to high-flux polysulfone hollow fibre ("HemoflowF", Fresenius) membranes and bicarbonate dialysis solution. Dialysers are not re-used, and the "Bioprime" rinse method (Hospal) (described by Verresen and colleagues) is not applied. ACE inhibitors have been prescribed to 13 of our 83 patients on the standard haemodialysis programme (captopril 5, perindopril 5, enalapril 3). None of our patients on polysulfone membrane dialysis have had anaphylactoid reactions. Verresen and colleagues suggest that ACE inhibitors might facilitate anaphylactoid reactions in response to bacterial products of the dialysate which transfer across high-flux dialysis membranes. Our protocols for water processing and control of minimal transmembrane pressure may differ from those of Verresen and colleagues, resulting in differences in bacterial product load and back flush rate. Furthermore, polysulfone high-flux membranes are relatively impermeable to endotoxins and other bacterial
products. 1,2 A case history suports the theory outlined above. One of our patients was treated initially with an AN69 dialyser. Two years later, shortly after starting ACE inhibitor therapy, she had repeated anaphylactoid reactions within minutes of haemodialysis being started. Subsequent dialysis was done with a Hemoflow-F60 dialyser; anaphylactoid reactions did not recur. Our observations, and those of Verresen and colleagues, suggest that anaphylactoid reactions to high-flux membranes in combination with ACE inhibitors are dependent on the type of
