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LABETALOL AND PHAEOCHROMOCYTOMA
Br. J. Anaesth. (1984), 56,1179
CORRESPONDENCE LABETALOL AND PHAEOCHROMOCYTOMA
Ross, E. J., Prichard, B. N. C , Kaufman, L., Robertson, A. I. G., and Harries, B. J. (1967). Preoperative and operative management of patients with phaeochromocytoma. Br. Med. 7,1,191.
ANAPHYLACTOID REACTION TO DIAZEMULS
Sir,—Reports of adverse reactions to the induction agent diazepam are few. However, recently, we experienced an anaphylactoid reaction to Diazemuls—a preparation of diazepam dissolved in soyabean oil and emulsified in water. A 20-year-old healthy female patient with no history of allergy or of previous exposure to diazepam was scheduled for gastroscopy. She was premedicated with Diazemuls 10 mg and atropine 0.5 mg. Diazemuls was given in incremental doses(5mgi.v.)toa total of 20 mg. Ten minutes later her face, neck and thorax became flushed and urticaria developed over the same area a few minutes later. There was no coughing, wheezing, tachycardia or change in arterial pressure. The gastroscopy was stopped, and the patient treated with an antihistamine (antazolirte 50 mg) and a corticosteroid (hydrocortisone 100 mg), supplemented with oxygen. The urticaria disappeared, but the patient experienced moderate swelling of the nasal mucous membranes. Laryngotcopy showed no oedema in the larynx. Fifteen minutes later the flushing faded. Gastroscopy was performed on the following day under gemeial anaesthesia using thiopentone, pethidine and nitrous oxide. There were no complications. Analysis of blood samples taken 1, 6 and 23"h after the reaction showed that there was no «ignifv-ant change in the concentrations of C3, C4, C3 act, free C3d of Cl esterase inhibitor and total haemolytic complement. No Cl p immunacomplexes were detected. The Hiniml picture was one of a "histaminoid" cutaneous phenomenon with no activation of the complement pathways (classical or alternate). As the patient had not previously been exposed to the agent the adverse reaction must be considered to be the result of a chemical release of histamine with no antibody or complement involvement (Watkins, 1979). F. BROGGER NIELSEN
Aalborg REFERENCE
Watkins J. (1979). Anaphylactoid reactions to i.v. substances. Br.J. Anaath., 51, 51.
M. NAVARATNARAJAH D. C. WHITE
London
BLOOD VISCOSITY AND BLOOD FILM MORPHOLOGY DURING PROLONGED SEDATION WITH ALTHESIN
REFERENCES
Britain, R. T., and Levy, G. P. (1976). A review of the animal pharmacology of labetalol, a combined a- and (J-adrenoceptorblockmg drug. Br. J. Pharmacol., (Suppl.) 3,681. Rosei, E. A., Brown, J. J., Lever, A. F., Robertson, A. S., Robertson, J. I. S., and Trust P. M. (1976). Treatment of phaeochromocytoma and of clonidine withdrawal hypertension with labetalol. Br. J. Clm. Pharmacol. (Suppl.) 3, 809.
Sir,—Gramstad and Stovner (1979) observed a decrease in plasma viscosity following induction doses of Althesin and other Cremophor EL-containing anaesthetic agents. Orr and colleagues (1982) also observed a marginal decrease at some shear rates. More recently Knell, Turner and Chalmers (1983) suggested that, during prolonged infusions of Althesin, this decrease in viscosity made it impossible to spread blood on a slide for
Downloaded from http://bja.oxfordjournals.org/ at University of Arizona on June 2, 2015
Sir,—Labetalol was introduced to the medical management of phaeochromocytomainl976(Roseietal., 1976). Since then three cases have been reported in which the administration of labetalol caused a paradoxical increase in arterial pressure which could not be controlled by giving more of the drug. Labetalol is 16 times more potent as a blocker at cardiac beta-one receptors than at vascular alpha receptors (Britain and Levy, 1976). It has been clearly demonstrated that in the presence of incomplete alpha blockade, administration of potent beta-blockers can increase rather than reduce the hypertension, particularly in adrenaline secreting tumours (Ross et al., 1967). The explanation for this is that circulating adrenaline reduces peripheral vascular resistance by dilating the peripheral vessels as a result of its action on the beta-two receptors and the administration of a non-selective beta blocker can antagonize this effect and, thus, increase the peripheral vascular resistance and, hence, the arterial pressure. Furthermore, patients with phaeochromocytoma frequently have a reduced blood volume, together with an increased peripheral resistance. These are factors which could significantly increase mortality and morbidity during anaesthesia and surgery. Preoperative selective alpha-blockade with agents such as phenozybenzamine, along with haematocrit measurements to assess the degree of re-expansion of the peripheral circulation, have been advocated to counteract these problems. Recently, we were involved in the treatment of « patient with phaeochromocytoma whose hypertension was controlled with oral labetalol 100 mg t.d.s. and who clearly demonstrated the clinical problems described above. During invasive radiological investigations, she experienced sustained hypertension which could not be controlled by further doses of labetalol i.v. and required hydrallazine i. v. for successful treatment. While she was receiving oral labetalol, her packed cell volume was 35.5% with a haemoglobin of 11.8 g dl~'. Five days before surgery the dose of oral labetalol was reduced to 50 mg t.d.s., and oral phenoxybenzamine 10-20 mg 6-hourly was instituted. This reduced the packed cell volume to 30.5% and the haemoglobin to 10 g dl~', indicating a «ignifimnt increase in circulationg volume and reduction in peripheral resistance. The future conduct of her anaesthetic and surgery was uneventful. Thus, the use of a mixed alpha- and beta-antagonist with a fixed alpha/beta blocking ratio, such as labetalol can result in sustained hypertension because of its predominant beta antagonistic activity, occurring in conjunction with an inadequate degree of alpha-blockade during preoperative preparation.
CORRESPONDENCE LABETALOL AND PHAEOCHROMOCYTOMA
Ross, E. J., Prichard, B. N. C , Kaufman, L., Robertson, A. I. G., and Harries, B. J. (1967). Preoperative and operative management of patients with phaeochromocytoma. Br. Med. 7,1,191.
ANAPHYLACTOID REACTION TO DIAZEMULS
Sir,—Reports of adverse reactions to the induction agent diazepam are few. However, recently, we experienced an anaphylactoid reaction to Diazemuls—a preparation of diazepam dissolved in soyabean oil and emulsified in water. A 20-year-old healthy female patient with no history of allergy or of previous exposure to diazepam was scheduled for gastroscopy. She was premedicated with Diazemuls 10 mg and atropine 0.5 mg. Diazemuls was given in incremental doses(5mgi.v.)toa total of 20 mg. Ten minutes later her face, neck and thorax became flushed and urticaria developed over the same area a few minutes later. There was no coughing, wheezing, tachycardia or change in arterial pressure. The gastroscopy was stopped, and the patient treated with an antihistamine (antazolirte 50 mg) and a corticosteroid (hydrocortisone 100 mg), supplemented with oxygen. The urticaria disappeared, but the patient experienced moderate swelling of the nasal mucous membranes. Laryngotcopy showed no oedema in the larynx. Fifteen minutes later the flushing faded. Gastroscopy was performed on the following day under gemeial anaesthesia using thiopentone, pethidine and nitrous oxide. There were no complications. Analysis of blood samples taken 1, 6 and 23"h after the reaction showed that there was no «ignifv-ant change in the concentrations of C3, C4, C3 act, free C3d of Cl esterase inhibitor and total haemolytic complement. No Cl p immunacomplexes were detected. The Hiniml picture was one of a "histaminoid" cutaneous phenomenon with no activation of the complement pathways (classical or alternate). As the patient had not previously been exposed to the agent the adverse reaction must be considered to be the result of a chemical release of histamine with no antibody or complement involvement (Watkins, 1979). F. BROGGER NIELSEN
Aalborg REFERENCE
Watkins J. (1979). Anaphylactoid reactions to i.v. substances. Br.J. Anaath., 51, 51.
M. NAVARATNARAJAH D. C. WHITE
London
BLOOD VISCOSITY AND BLOOD FILM MORPHOLOGY DURING PROLONGED SEDATION WITH ALTHESIN
REFERENCES
Britain, R. T., and Levy, G. P. (1976). A review of the animal pharmacology of labetalol, a combined a- and (J-adrenoceptorblockmg drug. Br. J. Pharmacol., (Suppl.) 3,681. Rosei, E. A., Brown, J. J., Lever, A. F., Robertson, A. S., Robertson, J. I. S., and Trust P. M. (1976). Treatment of phaeochromocytoma and of clonidine withdrawal hypertension with labetalol. Br. J. Clm. Pharmacol. (Suppl.) 3, 809.
Sir,—Gramstad and Stovner (1979) observed a decrease in plasma viscosity following induction doses of Althesin and other Cremophor EL-containing anaesthetic agents. Orr and colleagues (1982) also observed a marginal decrease at some shear rates. More recently Knell, Turner and Chalmers (1983) suggested that, during prolonged infusions of Althesin, this decrease in viscosity made it impossible to spread blood on a slide for
Downloaded from http://bja.oxfordjournals.org/ at University of Arizona on June 2, 2015
Sir,—Labetalol was introduced to the medical management of phaeochromocytomainl976(Roseietal., 1976). Since then three cases have been reported in which the administration of labetalol caused a paradoxical increase in arterial pressure which could not be controlled by giving more of the drug. Labetalol is 16 times more potent as a blocker at cardiac beta-one receptors than at vascular alpha receptors (Britain and Levy, 1976). It has been clearly demonstrated that in the presence of incomplete alpha blockade, administration of potent beta-blockers can increase rather than reduce the hypertension, particularly in adrenaline secreting tumours (Ross et al., 1967). The explanation for this is that circulating adrenaline reduces peripheral vascular resistance by dilating the peripheral vessels as a result of its action on the beta-two receptors and the administration of a non-selective beta blocker can antagonize this effect and, thus, increase the peripheral vascular resistance and, hence, the arterial pressure. Furthermore, patients with phaeochromocytoma frequently have a reduced blood volume, together with an increased peripheral resistance. These are factors which could significantly increase mortality and morbidity during anaesthesia and surgery. Preoperative selective alpha-blockade with agents such as phenozybenzamine, along with haematocrit measurements to assess the degree of re-expansion of the peripheral circulation, have been advocated to counteract these problems. Recently, we were involved in the treatment of « patient with phaeochromocytoma whose hypertension was controlled with oral labetalol 100 mg t.d.s. and who clearly demonstrated the clinical problems described above. During invasive radiological investigations, she experienced sustained hypertension which could not be controlled by further doses of labetalol i.v. and required hydrallazine i. v. for successful treatment. While she was receiving oral labetalol, her packed cell volume was 35.5% with a haemoglobin of 11.8 g dl~'. Five days before surgery the dose of oral labetalol was reduced to 50 mg t.d.s., and oral phenoxybenzamine 10-20 mg 6-hourly was instituted. This reduced the packed cell volume to 30.5% and the haemoglobin to 10 g dl~', indicating a «ignifimnt increase in circulationg volume and reduction in peripheral resistance. The future conduct of her anaesthetic and surgery was uneventful. Thus, the use of a mixed alpha- and beta-antagonist with a fixed alpha/beta blocking ratio, such as labetalol can result in sustained hypertension because of its predominant beta antagonistic activity, occurring in conjunction with an inadequate degree of alpha-blockade during preoperative preparation.