Br.J. Anaesth. (1979), 51, 469
CORRESPONDENCE ADVERSE REACTIONS TO I.V. AGENTS
that the plasma is separated and stored at —20 to — 25 °C until ready for despatch. Further 5-ml samples of EDTA blood should be taken at 3, 6 and 24 h after the reaction and another 5 ml taken, if possible, 3 days after the event. The last sample provides a convenient baseline for the patient. It would also help the investigation if further samples of blood (in EDTA tubes) are taken within 10 min of reaction, and again at 20 min, 1 h and 24 h after the reaction, and sent to the local Haematology laboratory for both white cell (total and differential) and platelet counts and for haemoglobin measurements. These simple haematological procedures will often provide useful information regarding the mechanism of the adverse response when less sensitive protein assay methods are equivocal (Watkins, Ward and Appleyard, 1977). Full records of the incident, including batch numbers of all agents administered, should be kept and details of the previous administration of these substances and relevant history, such as allergies, should be noted. The first series of samples (taken over 24 h) should be despatched as a single batch as soon as possible by first class mail to Dr Watkins. Packing the samples in "dry ice" is not necessary. Receipt of the blood samples will be acknowledged and results of the blood assays will be communicated as soon as they are available. J. WATKINS J. A. THORNTON
Sheffield R. S. J. CLARKE
Belfast REFERENCES
Watkins, J. (1979). Anaphylactoid reactions to i.v. substances. Br.J. Anaesth., 51, 51. Thornton, J. A., and Clarke, R. S. J. (1976). Adverse reaction to intravenous anaesthetics. Br. J. Anaesth., 48, 1118. Ward, A. M., and Appleyard, T. N. (1977). Changes in peripheral blood leucocytes following i.v. anaesthesia and surgery. Br.J. Anaesth., 49, 953. SURVIVAL FOLLOWING 1 0 0 0 MG OF AMETHOCAINE
Sir,—A male (aged 63 yr) in good general condition was undergoing bronchoscopy under topical anaesthesia for suspected carcinoma of the bronchus. Premedication comprised pethidine 50 mg and atropine 0.5 mg administered i.m. 30 min before the procedure. The surgeon applied 20 ml of amethocaine 5% to the patient's mouth, pharynx and larynx within a 3-min period. Immediately after the insertion of the rigid bronchoscope, the patient became unconscious arid developed convulsions. The anaesthetic team was summoned and the patient's trachea was intubated and the lungs ventilated with 100% oxygen. Diazepam 10 mg, mephentermine 15 mg and hydrocortisone 1.5 g were given i.v. and in 1.5 min the convulsions stopped, but 3 min later they recommenced. A second dose of diazepam 10 mg decreased the frequency and intensity of convulsions but they did not cease.
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 20, 2015
Sir,—We have previously invited all anaesthetists who see an anaphylactoid type of adverse response in a patient following administration of an i.v. hypnotic to contact us and to take blood samples following a simple protocol (Watkins, Thornton and Clarke, 1976). The response to date (almost 100 cases) has been very good and we express again our appreciation to those anaesthetists who have made the effort to forward the necessary samples. The clinical features of the adverse (anaphylactoid) response, which may include cutaneous (urticaria and flushing), pulmonary (bronchospasm) and cardiovascular (hypotension) manifestations are predominantly a result of the release of histamine and are not diagnostic of an anaphylactic (Type I, IgE-mediated) reaction. We are now aware of several mechanisms by which this may occur in vivo without involving IgE antibodies. Indeed, relatively few adverse reactions to any i.v. compound involve antibodies in a classical manner and we therefore view the claims made for skin-testing with a great deal of scepticism, since they must of necessity pre-judge the mechanism of the reaction. Although imperfect, examination of changes in plasma factors such as complement, the immunoglobulins in general, and IgE specifically, does not pre-judge the mechanism of the reaction. As a result of these investigations we are now reaching an understanding of the various mechanisms of the anaphylactoid response and, perhaps more important, of the factors predisposing to such response (Watkins, 1979). Not all reactions involve the induction agent itself. Anaphylactoid reactions may be induced by the neuromuscular blocking drugs or the premedication or even synergistic combinations of these. We have recently encountered a case, reported to the Committee on Safety in Medicines as a possible response to Althesin, which involved a plasma expander, Haemaccel, which is not mentioned in the adverse response report. Anaphylactoid reactions to plasma substitutes probably occur even more frequently than those to i.v. induction agents. Their clinical manifestations resemble those associated with the i.v. induction agents although urticaria and gastrointestinal disturbances appear more frequently. We extend an invitation to all anaesthetists who see an anaphylactoid response in a patient following administration of any i.v. agent (hypnotic, muscle relaxant or plasma substitute) to take blood samples, as closely as possible following the protocol described below and to contact: Dr J. Watkins, Protein Reference Unit, Department of Immunology, Hallamshire Hospital Medical School, Sheffield S10 2RX. Venous blood (5 ml) should be collected into an EDTA tube as soon as possible after the reaction begins. Heparinized tubes are a less satisfactory substitute but can be used in an emergency: the chemical EDTA effectively stabilizes plasma complement proteins. In view of the deterioration of complement components in blood samples it is recommended
CORRESPONDENCE ADVERSE REACTIONS TO I.V. AGENTS
that the plasma is separated and stored at —20 to — 25 °C until ready for despatch. Further 5-ml samples of EDTA blood should be taken at 3, 6 and 24 h after the reaction and another 5 ml taken, if possible, 3 days after the event. The last sample provides a convenient baseline for the patient. It would also help the investigation if further samples of blood (in EDTA tubes) are taken within 10 min of reaction, and again at 20 min, 1 h and 24 h after the reaction, and sent to the local Haematology laboratory for both white cell (total and differential) and platelet counts and for haemoglobin measurements. These simple haematological procedures will often provide useful information regarding the mechanism of the adverse response when less sensitive protein assay methods are equivocal (Watkins, Ward and Appleyard, 1977). Full records of the incident, including batch numbers of all agents administered, should be kept and details of the previous administration of these substances and relevant history, such as allergies, should be noted. The first series of samples (taken over 24 h) should be despatched as a single batch as soon as possible by first class mail to Dr Watkins. Packing the samples in "dry ice" is not necessary. Receipt of the blood samples will be acknowledged and results of the blood assays will be communicated as soon as they are available. J. WATKINS J. A. THORNTON
Sheffield R. S. J. CLARKE
Belfast REFERENCES
Watkins, J. (1979). Anaphylactoid reactions to i.v. substances. Br.J. Anaesth., 51, 51. Thornton, J. A., and Clarke, R. S. J. (1976). Adverse reaction to intravenous anaesthetics. Br. J. Anaesth., 48, 1118. Ward, A. M., and Appleyard, T. N. (1977). Changes in peripheral blood leucocytes following i.v. anaesthesia and surgery. Br.J. Anaesth., 49, 953. SURVIVAL FOLLOWING 1 0 0 0 MG OF AMETHOCAINE
Sir,—A male (aged 63 yr) in good general condition was undergoing bronchoscopy under topical anaesthesia for suspected carcinoma of the bronchus. Premedication comprised pethidine 50 mg and atropine 0.5 mg administered i.m. 30 min before the procedure. The surgeon applied 20 ml of amethocaine 5% to the patient's mouth, pharynx and larynx within a 3-min period. Immediately after the insertion of the rigid bronchoscope, the patient became unconscious arid developed convulsions. The anaesthetic team was summoned and the patient's trachea was intubated and the lungs ventilated with 100% oxygen. Diazepam 10 mg, mephentermine 15 mg and hydrocortisone 1.5 g were given i.v. and in 1.5 min the convulsions stopped, but 3 min later they recommenced. A second dose of diazepam 10 mg decreased the frequency and intensity of convulsions but they did not cease.
Downloaded from http://bja.oxfordjournals.org/ at Harvard University on July 20, 2015
Sir,—We have previously invited all anaesthetists who see an anaphylactoid type of adverse response in a patient following administration of an i.v. hypnotic to contact us and to take blood samples following a simple protocol (Watkins, Thornton and Clarke, 1976). The response to date (almost 100 cases) has been very good and we express again our appreciation to those anaesthetists who have made the effort to forward the necessary samples. The clinical features of the adverse (anaphylactoid) response, which may include cutaneous (urticaria and flushing), pulmonary (bronchospasm) and cardiovascular (hypotension) manifestations are predominantly a result of the release of histamine and are not diagnostic of an anaphylactic (Type I, IgE-mediated) reaction. We are now aware of several mechanisms by which this may occur in vivo without involving IgE antibodies. Indeed, relatively few adverse reactions to any i.v. compound involve antibodies in a classical manner and we therefore view the claims made for skin-testing with a great deal of scepticism, since they must of necessity pre-judge the mechanism of the reaction. Although imperfect, examination of changes in plasma factors such as complement, the immunoglobulins in general, and IgE specifically, does not pre-judge the mechanism of the reaction. As a result of these investigations we are now reaching an understanding of the various mechanisms of the anaphylactoid response and, perhaps more important, of the factors predisposing to such response (Watkins, 1979). Not all reactions involve the induction agent itself. Anaphylactoid reactions may be induced by the neuromuscular blocking drugs or the premedication or even synergistic combinations of these. We have recently encountered a case, reported to the Committee on Safety in Medicines as a possible response to Althesin, which involved a plasma expander, Haemaccel, which is not mentioned in the adverse response report. Anaphylactoid reactions to plasma substitutes probably occur even more frequently than those to i.v. induction agents. Their clinical manifestations resemble those associated with the i.v. induction agents although urticaria and gastrointestinal disturbances appear more frequently. We extend an invitation to all anaesthetists who see an anaphylactoid response in a patient following administration of any i.v. agent (hypnotic, muscle relaxant or plasma substitute) to take blood samples, as closely as possible following the protocol described below and to contact: Dr J. Watkins, Protein Reference Unit, Department of Immunology, Hallamshire Hospital Medical School, Sheffield S10 2RX. Venous blood (5 ml) should be collected into an EDTA tube as soon as possible after the reaction begins. Heparinized tubes are a less satisfactory substitute but can be used in an emergency: the chemical EDTA effectively stabilizes plasma complement proteins. In view of the deterioration of complement components in blood samples it is recommended
