- Email: [email protected]
NALOXONE IN SEPTIC SHOCK
786 past decade. Local disintegration of pneumococci within the cerebral capillaries may be the cause of a cerebral vascular permeability syndrome, which could explain why advanced cases of this condition often deteriorate despite adequate treatment. Royal Gwent Hospital, Newport, Gwent
E. N. WARDLE
NALOXONE IN SEPTIC SHOCK
SIR,-The purpose of our controlled study of naloxone in septic shock (June 15, p 1363) appears to have been misconstrued by Dr Soulioti (Aug 24, p 452) and others. Reports of the efficacy of naloxone in uncontrolled studies of human septic shock and in a variety of animals given endotoxin 1-3 provided the impetus for a placebo-controlled clinical trial. Evaluation of the effects of naloxone necessitates treatment regimens that differ only in the presence or absence of naloxone. Our study clearly demonstrated that naloxone failed to improve haemodynamic indices and survival compared with the effects of a placebo (suspending media and preservatives present in the commercially available preparation). Although the possible beneficial effects of methylparaben and propylparaben in the treatment of septic shock can be evaluated in future clinical studies, that was not our objective. Considerable fluctuations in blood pressure may occur inexplicably in patients with septic shock. The modest increases in blood pressure observed after both placebo and naloxone were transient and rarely associated with significant clinical improvement. The references Soulioti cites to support the use of parabens relate to measurements of cerebral blood flow in gerbils after carotid occlusion4and to the relaxation of pial cortical arteries in vitro after contraction induced by a variety of agents.5It is tenuous, at best, to extrapolate these observations to a beneficial effect in treating septic shock in man. Division of Infectious Diseases, Boston University School of Medicine, and Maxwell Finland Laboratory for Infectious Diseases, Boston City Hospital, Boston, Massachusetts 02118, USA
1.
WILLIAM R. MCCABE
Wright DJM, Phillips M, Weller MPI. Naloxone in shock. Lancet 1980; ii: 1361. WP, Friedman PA, Johnson MW, Mitch WE. Pressor effect of naloxone
2. Peters
in
septic shock Lancet 1981; i: 529-32. 3. Faden AI, Holaday JW. Experimental endotoxin shock The pathophysiologic function of endorphins and treatment with opiate antagonists. J Infect Dis 1980; 142: 229-38. 4. Crockard HA, Allen K, Avery S, Ross Russel RW. Cerebral protective properties of the commercial vehicle solution of naloxone. Lancet 1983; ii: 1143. 5. Brandt I, Anderson KE, Hindseef B, Ljungsten B, Pickard JD. Are the vascular effects of naloxone attributable to the preservatives of methyl-propylparaben? JCBF 1983; 3: 395-98
Basal metabolic rate (BMR) was measured in a whole body calorimeter for the first hour after the subject was woken up, usinga protocol which seems identical to the one we use with the same calorimeters. This specified one hour period includes the period of arousal from sleep, during which the readings are unstable and metabolic rate may be raised. It is therefore possible that these figures for BMR are higher than those which would have been obtained under the true basal conditions that are assumed in the calculations for the WHO/FAO/UNU and DHSS recommendations. Small changes in BMR can make substantial differences to the "activity ratio" (total energy expenditure/BMR), and some of the apparent discrepancy found by Prentice et al may thus be explained. The BMR of individuals can now be predicted from height, weight, and age.The mean of the fifteen BMR measurements by Prentice et al (1481[SEM 57] kcal in 24 h) is 5% greater than that predicted for their subjects using these equations (1412 [SEM 46] kcal in 24 h). This difference alone would increase the average activity ratio from 138 to 1’47. An overestimate of this size in measurement ofBMR, if current energy intakes were maintained, would appreciably increase the energy available for physical activity-by an extra hour 2 per day of walking. Diabetic Clinic, Aberdeen Royal Infirmary, Aberdeen AB9 1GS
M. E. J. LEAN W. P. T. JAMES
1. Schofield WN. Basal metabolic rate-review and prediction, together with an annotated bibliography of source material. Hum Nutr Clin Nutr 1985; 39C (suppl 1): 1-41. 2. McDonald I. Statistical studies of recorded energy expenditure of man II: Expenditure on walking related to weight, sex, age, speed and gradient. Nutr Abstr Rev 1961; 31: 739-62.
SIR,-The double-isotope method adds a new dimension to our ability to measure total human energy expenditure (TEE). However, both this method and direct and indirect calorimetry are limited
by
their
cost
and
availability.
The metabolic balance
method can be used to estimate TEE from changes in body composition. It is simple, and it also monitors dietary compliance, which is important in the measurement of energy expenditure especially when supervision is not total. Using this method we found that the index TEEmb/BMR (basal metabolic rate, from standard tables2,3) in six sedentary obese women receiving daily liquid formula diets of 655-789 kcal energy content was 1 - 22 [SEMO-03]. (We used days 29-56 of the diet period since, by this time, adaptive changes in metabolic rate, fluid, and nitrogen balance are largely complete.) This value is even lower than that reported by Prentice et al (1-38 [0 . 04]) in predominantly lean women who were in energy balance and following their normal occupations. Both these values for TEE/BMR are lower than current minimum recommended maintenance requirements for light activity.44 We also studied eight obese men on the same low calorie diets and found TEEmb/BMR to be significantly higher in them than in the
ENERGY EXPENDITURE IN HEALTHY WOMEN
SIR,-Dr Prentice and colleagues (June 22, p 1419) present interesting data, in a format which accords with the impending report on energy requirements from FAO, WHO, and the United Nations University, presenting new nutritional recommendations based on the amounts of physical activity considered desirable for physical and social wellbeing. Prentice et al used the double-labelled water method to estimate energy expenditure in free-living individuals. Although this preliminary communication emphasises that the 12 subjects may not be representative of the general population and that the low levels calculated should not be considered as reflecting any need to reduce current recommended energy requirements, the discussion does not seem to recognise the prescriptive nature of the forthcoming new recommendations. The computation of metabolic rate using the zH2180 method in free-living subjects is still being evaluated by several research centres. The effects of fractionation and compartmentation of isotopes and of fluctuations in respiratory quotient as a result of dietary variations are fundamental to the calculations and are not yet completely understood. Prentice and colleagues’ data demonstrate some of the problems in assessing individual energy requirements.
Correlation between creatinine. The
TEEmb/BMR,
TEESMR
calculated from
and
mean
measurements
daily urinary of
electrolyte and
nitrogen balance between days 29-56 of continuous dieting in obese males (8) and females (0), correlated against the mean daily urinary creatinine excretion (mmol/day) during the first ten days of this period. The basal metabolic rate
(BMR) was obtained from the standard tables of Fleisch2
and
Boothb;.
E. N. WARDLE
NALOXONE IN SEPTIC SHOCK
SIR,-The purpose of our controlled study of naloxone in septic shock (June 15, p 1363) appears to have been misconstrued by Dr Soulioti (Aug 24, p 452) and others. Reports of the efficacy of naloxone in uncontrolled studies of human septic shock and in a variety of animals given endotoxin 1-3 provided the impetus for a placebo-controlled clinical trial. Evaluation of the effects of naloxone necessitates treatment regimens that differ only in the presence or absence of naloxone. Our study clearly demonstrated that naloxone failed to improve haemodynamic indices and survival compared with the effects of a placebo (suspending media and preservatives present in the commercially available preparation). Although the possible beneficial effects of methylparaben and propylparaben in the treatment of septic shock can be evaluated in future clinical studies, that was not our objective. Considerable fluctuations in blood pressure may occur inexplicably in patients with septic shock. The modest increases in blood pressure observed after both placebo and naloxone were transient and rarely associated with significant clinical improvement. The references Soulioti cites to support the use of parabens relate to measurements of cerebral blood flow in gerbils after carotid occlusion4and to the relaxation of pial cortical arteries in vitro after contraction induced by a variety of agents.5It is tenuous, at best, to extrapolate these observations to a beneficial effect in treating septic shock in man. Division of Infectious Diseases, Boston University School of Medicine, and Maxwell Finland Laboratory for Infectious Diseases, Boston City Hospital, Boston, Massachusetts 02118, USA
1.
WILLIAM R. MCCABE
Wright DJM, Phillips M, Weller MPI. Naloxone in shock. Lancet 1980; ii: 1361. WP, Friedman PA, Johnson MW, Mitch WE. Pressor effect of naloxone
2. Peters
in
septic shock Lancet 1981; i: 529-32. 3. Faden AI, Holaday JW. Experimental endotoxin shock The pathophysiologic function of endorphins and treatment with opiate antagonists. J Infect Dis 1980; 142: 229-38. 4. Crockard HA, Allen K, Avery S, Ross Russel RW. Cerebral protective properties of the commercial vehicle solution of naloxone. Lancet 1983; ii: 1143. 5. Brandt I, Anderson KE, Hindseef B, Ljungsten B, Pickard JD. Are the vascular effects of naloxone attributable to the preservatives of methyl-propylparaben? JCBF 1983; 3: 395-98
Basal metabolic rate (BMR) was measured in a whole body calorimeter for the first hour after the subject was woken up, usinga protocol which seems identical to the one we use with the same calorimeters. This specified one hour period includes the period of arousal from sleep, during which the readings are unstable and metabolic rate may be raised. It is therefore possible that these figures for BMR are higher than those which would have been obtained under the true basal conditions that are assumed in the calculations for the WHO/FAO/UNU and DHSS recommendations. Small changes in BMR can make substantial differences to the "activity ratio" (total energy expenditure/BMR), and some of the apparent discrepancy found by Prentice et al may thus be explained. The BMR of individuals can now be predicted from height, weight, and age.The mean of the fifteen BMR measurements by Prentice et al (1481[SEM 57] kcal in 24 h) is 5% greater than that predicted for their subjects using these equations (1412 [SEM 46] kcal in 24 h). This difference alone would increase the average activity ratio from 138 to 1’47. An overestimate of this size in measurement ofBMR, if current energy intakes were maintained, would appreciably increase the energy available for physical activity-by an extra hour 2 per day of walking. Diabetic Clinic, Aberdeen Royal Infirmary, Aberdeen AB9 1GS
M. E. J. LEAN W. P. T. JAMES
1. Schofield WN. Basal metabolic rate-review and prediction, together with an annotated bibliography of source material. Hum Nutr Clin Nutr 1985; 39C (suppl 1): 1-41. 2. McDonald I. Statistical studies of recorded energy expenditure of man II: Expenditure on walking related to weight, sex, age, speed and gradient. Nutr Abstr Rev 1961; 31: 739-62.
SIR,-The double-isotope method adds a new dimension to our ability to measure total human energy expenditure (TEE). However, both this method and direct and indirect calorimetry are limited
by
their
cost
and
availability.
The metabolic balance
method can be used to estimate TEE from changes in body composition. It is simple, and it also monitors dietary compliance, which is important in the measurement of energy expenditure especially when supervision is not total. Using this method we found that the index TEEmb/BMR (basal metabolic rate, from standard tables2,3) in six sedentary obese women receiving daily liquid formula diets of 655-789 kcal energy content was 1 - 22 [SEMO-03]. (We used days 29-56 of the diet period since, by this time, adaptive changes in metabolic rate, fluid, and nitrogen balance are largely complete.) This value is even lower than that reported by Prentice et al (1-38 [0 . 04]) in predominantly lean women who were in energy balance and following their normal occupations. Both these values for TEE/BMR are lower than current minimum recommended maintenance requirements for light activity.44 We also studied eight obese men on the same low calorie diets and found TEEmb/BMR to be significantly higher in them than in the
ENERGY EXPENDITURE IN HEALTHY WOMEN
SIR,-Dr Prentice and colleagues (June 22, p 1419) present interesting data, in a format which accords with the impending report on energy requirements from FAO, WHO, and the United Nations University, presenting new nutritional recommendations based on the amounts of physical activity considered desirable for physical and social wellbeing. Prentice et al used the double-labelled water method to estimate energy expenditure in free-living individuals. Although this preliminary communication emphasises that the 12 subjects may not be representative of the general population and that the low levels calculated should not be considered as reflecting any need to reduce current recommended energy requirements, the discussion does not seem to recognise the prescriptive nature of the forthcoming new recommendations. The computation of metabolic rate using the zH2180 method in free-living subjects is still being evaluated by several research centres. The effects of fractionation and compartmentation of isotopes and of fluctuations in respiratory quotient as a result of dietary variations are fundamental to the calculations and are not yet completely understood. Prentice and colleagues’ data demonstrate some of the problems in assessing individual energy requirements.
Correlation between creatinine. The
TEEmb/BMR,
TEESMR
calculated from
and
mean
measurements
daily urinary of
electrolyte and
nitrogen balance between days 29-56 of continuous dieting in obese males (8) and females (0), correlated against the mean daily urinary creatinine excretion (mmol/day) during the first ten days of this period. The basal metabolic rate
(BMR) was obtained from the standard tables of Fleisch2
and
Boothb;.