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CATECHOLAMINE LEVELS IN SEVERE TETANUS
195 COMMENT
Among 19 pygmy subjects studied, attenuated responses to the
metabolic effects of exogenous H.G.H.
were
observed.
Thus, after intravenous administration of H.G.H., the change in plasma-F.F.A. levels was less than that in control and H.G.H.-deficient subjects. In addition, after 5 days of H.G.H.-therapy, administered intramuscularly, S.U.N. levels, and the plasma-insulin response to glucose and
arginine, were unchanged, whereas they altered dramatically in control subjects. Thus there is end-organ unresponsiveness in the pygmy. The precise nature of this defect remains
to
be determined.
This work was supported in part by U.S. Public Health Service grants AM-11961, GM-10189, and HD-02422, and diabetes training grant 5T1-AM-5136. T. J. M. holds a research and development award of the American Diabetes Association. D. R. is an established investigator of the American Heart Association, supported by the Heart Association of Maryland. The expedition was organised by L. L. C.-S. and supported by grants from the Italian I.B.P. committee of the Consiglio Nazionale delle Ricerche and from the World Health Organisation. Requests for reprints should be addressed to T. J. M. Boston
University School
T.
of Medicine
Boston, Massachusetts
J. MERIMEE
M.D.
Louisville
Departments of Medicine and Pediatrics,
Washington University School of Medicine, St. Louis, Missouri
D. L. RIMOIN McGill, PH.D. Johns Hopkins L. C. CAVALLI-SFORZA
M.D.
Institute of Genetics, of Pavia, Italy
University
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
M.D.
M.D.
Padua
D. RABINOWITZ* W’srand, M.R.C.P., M.R.C.P.E. V. A. MCKUSICK M.D. Johns Hopkins
CATECHOLAMINE LEVELS IN SEVERE TETANUS ALTHOUGH sedation and curarisation control the muscular manifestations of tetanus and prevent death from hypoxia, an appreciable number of patients develop severe cardiovascular disturbances. These are not associated with acid-base or electrolyte abnormalities, nor can they be correlated with changes in blood-gas levels. are, however, often accompanied by hyperpyrexia. These cardiovascular disturbances are characterised by fluctuations in blood-pressure, with periods of severe hypertension and/or profound hypotension, vasoconstriction, pallor, tachycardia, and periodic irregularities. They may occur for only brief periods over a number of days or persist continuously for up to two weeks. Conventional sedation (chlorpromazine, pethidine, diazepam, and barbiturates) does not appear to affect them, but induction of moderate hypothermia (32’C) is helpful. The outcome is often poor, and 2 of our 4 patients who exhibited such symptoms died suddenly after periods of severe hypertension. These 4 were from a series of 65 consecutive tetanus patients treated in the respiratory unit of the Royal Victoria Hospital, Belfast. Glossop1 has suggested that the blood-pressure changes may be the result of tetanus intoxication of the brainstem, in view of the proximity of the vasomotor centre with the 10th dorsal nucleus. Cardiac output studies reported by Prys-Roberts and Greenbaumin severe tetanus revealed a hyperdynamic state compatible with excessive blood-
Average fluctuations in systolic blood-pressure per 24 hours in 2 patients with severe tetanus and 1 curarised patient without tetanus
..................
Arrow shows start and asterisks end of curarisation.
catecholamine release, and Kerr3 found an increased urinary excretion of these amines in patients with labile blood-pressure. Using a semi-automated method for the differential determination of plasma-catecholamines,4blood-levels have been estimated in three consecutive adult patients who showed such hæmodynamic disturbances and who were fully curarised. The degree of instability is indicated in the accompanying figure, which shows the average hour-to-hour fluctuation in systolic pressure in 2 of these, compared with a non-tetanus patient who was also curarised and similarly sedated. In all 3, the periods of hypertension occurring early in the disease were associated with excessively high levels of circulating adrenaline and noradrenaline, a typical finding being shown in the table. BLOOD-CATECHOLAMINE
LEVELS DURING AND AFTER PHASE IN CURARISED PATIENT
HYPERTENSIVE
They
"Present address: Hadassah
Hospital, Jerusalem,
Israel.
In 1
patient hypertension occurring late in the disease was accompanied by rises in either catecholamine. These preliminary results are reported with a view to suggesting that specific adrenergic blockers or other antiadrenaline drugs might play a part in the treatment of such cases. We ourselves have not used these to date, but they certainly will be considered in future.
not
Requests for reprints should be sent to J. W. D., Department of Anaesthetics, Royal Victoria Hospital, Belfast 12. SAMUEL R. KEILTY M.B. Belf., F.F.A. R.C.S. ROBERT C. GRAY M.D. Dubl., F.F.A. R.C.S. JOHN W. DUNDEE Respiratory Unit and M.D. Belf., PH.D. Lpool, , F.P.A. R.C.S. University Department of Anæsthetics, H. MCCULLOUGH Royal Victoria Hospital, Belfast 3. 4.
B.SC.
Belf.
Kerr, J. H. ibid. p. 49. McCullough, H. J. clin. Path. (in the press).
Among 19 pygmy subjects studied, attenuated responses to the
metabolic effects of exogenous H.G.H.
were
observed.
Thus, after intravenous administration of H.G.H., the change in plasma-F.F.A. levels was less than that in control and H.G.H.-deficient subjects. In addition, after 5 days of H.G.H.-therapy, administered intramuscularly, S.U.N. levels, and the plasma-insulin response to glucose and
arginine, were unchanged, whereas they altered dramatically in control subjects. Thus there is end-organ unresponsiveness in the pygmy. The precise nature of this defect remains
to
be determined.
This work was supported in part by U.S. Public Health Service grants AM-11961, GM-10189, and HD-02422, and diabetes training grant 5T1-AM-5136. T. J. M. holds a research and development award of the American Diabetes Association. D. R. is an established investigator of the American Heart Association, supported by the Heart Association of Maryland. The expedition was organised by L. L. C.-S. and supported by grants from the Italian I.B.P. committee of the Consiglio Nazionale delle Ricerche and from the World Health Organisation. Requests for reprints should be addressed to T. J. M. Boston
University School
T.
of Medicine
Boston, Massachusetts
J. MERIMEE
M.D.
Louisville
Departments of Medicine and Pediatrics,
Washington University School of Medicine, St. Louis, Missouri
D. L. RIMOIN McGill, PH.D. Johns Hopkins L. C. CAVALLI-SFORZA
M.D.
Institute of Genetics, of Pavia, Italy
University
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
M.D.
M.D.
Padua
D. RABINOWITZ* W’srand, M.R.C.P., M.R.C.P.E. V. A. MCKUSICK M.D. Johns Hopkins
CATECHOLAMINE LEVELS IN SEVERE TETANUS ALTHOUGH sedation and curarisation control the muscular manifestations of tetanus and prevent death from hypoxia, an appreciable number of patients develop severe cardiovascular disturbances. These are not associated with acid-base or electrolyte abnormalities, nor can they be correlated with changes in blood-gas levels. are, however, often accompanied by hyperpyrexia. These cardiovascular disturbances are characterised by fluctuations in blood-pressure, with periods of severe hypertension and/or profound hypotension, vasoconstriction, pallor, tachycardia, and periodic irregularities. They may occur for only brief periods over a number of days or persist continuously for up to two weeks. Conventional sedation (chlorpromazine, pethidine, diazepam, and barbiturates) does not appear to affect them, but induction of moderate hypothermia (32’C) is helpful. The outcome is often poor, and 2 of our 4 patients who exhibited such symptoms died suddenly after periods of severe hypertension. These 4 were from a series of 65 consecutive tetanus patients treated in the respiratory unit of the Royal Victoria Hospital, Belfast. Glossop1 has suggested that the blood-pressure changes may be the result of tetanus intoxication of the brainstem, in view of the proximity of the vasomotor centre with the 10th dorsal nucleus. Cardiac output studies reported by Prys-Roberts and Greenbaumin severe tetanus revealed a hyperdynamic state compatible with excessive blood-
Average fluctuations in systolic blood-pressure per 24 hours in 2 patients with severe tetanus and 1 curarised patient without tetanus
..................
Arrow shows start and asterisks end of curarisation.
catecholamine release, and Kerr3 found an increased urinary excretion of these amines in patients with labile blood-pressure. Using a semi-automated method for the differential determination of plasma-catecholamines,4blood-levels have been estimated in three consecutive adult patients who showed such hæmodynamic disturbances and who were fully curarised. The degree of instability is indicated in the accompanying figure, which shows the average hour-to-hour fluctuation in systolic pressure in 2 of these, compared with a non-tetanus patient who was also curarised and similarly sedated. In all 3, the periods of hypertension occurring early in the disease were associated with excessively high levels of circulating adrenaline and noradrenaline, a typical finding being shown in the table. BLOOD-CATECHOLAMINE
LEVELS DURING AND AFTER PHASE IN CURARISED PATIENT
HYPERTENSIVE
They
"Present address: Hadassah
Hospital, Jerusalem,
Israel.
In 1
patient hypertension occurring late in the disease was accompanied by rises in either catecholamine. These preliminary results are reported with a view to suggesting that specific adrenergic blockers or other antiadrenaline drugs might play a part in the treatment of such cases. We ourselves have not used these to date, but they certainly will be considered in future.
not
Requests for reprints should be sent to J. W. D., Department of Anaesthetics, Royal Victoria Hospital, Belfast 12. SAMUEL R. KEILTY M.B. Belf., F.F.A. R.C.S. ROBERT C. GRAY M.D. Dubl., F.F.A. R.C.S. JOHN W. DUNDEE Respiratory Unit and M.D. Belf., PH.D. Lpool, , F.P.A. R.C.S. University Department of Anæsthetics, H. MCCULLOUGH Royal Victoria Hospital, Belfast 3. 4.
B.SC.
Belf.
Kerr, J. H. ibid. p. 49. McCullough, H. J. clin. Path. (in the press).