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THE PHARMACOKINETICS OF INCREMANTAL DOSES OF PANCURONIUM
PROCEEDINGS OF THE ANAESTHETIC RESEARCH SOCIETY EVALUATION OF ELECTRICAL IMPEDANCE PLETHYSMOGRAPHY FOR THE NON-INVASIVE MEASUREMENT OF BLOOD FLOW HELENA M. ARENSON AND SURYA MOHAPATRA Research Department of Anaesthetics, Royal College of Surgeons of England, London
In the lithotomy position, the Lloyd Davies support produced a larger decrease in limb blood flow than the stirrup support. The measured haemodynamic variables, cardiac output, stroke volume, calf blood flow and the mean impedance (20) agreed well with the corresponding changes in the arterial pressure and heart rate. The potential use of electrical impedance measurements to obtain data such as stroke volume, cardiac output and also the peak value of the first derivative dZ/dr makes the technique useful. ZQ is another function of the peripheral circulation which may be monitored also by impedance measurements. For limb blood flow it is a valuable index of the circulatory blood volume. Although empirical, our results indicate that impedance methods may provide a good assessment of the state of the circulation. REFERENCE
Hill, D. W., and Hope, C. E. (1973). Digest, 10th Internal. Conf, Med. Biol. Eng., Dresden, p. 245. THE PHARMACOKINETICS OF INCREMENTAL DOSES OF PANCURONIUM K. MCLEOD, D. W. RYAN, M. J. WATSON AND C. J. HULL Departments of Anaesthesia and Clinical Biochemistry, University of Newcastle
A previous study has investigated the pharmacokinetics of pancuronium following a single i.v. dose, in patients with normal and impaired renal function (McLeod, Watson and Rawlings, 1976). This study suggested that redistribution determines the duration of action of pancuronium following a single dose, but that the duration of action following repeated doses would depend also upon the rate of excretion.
fa i
r =0.8773 I.FLOW=O.45to(S.G.FLOW)+O.537
U
2
2
4
STRAIN GAUGE FLOW
fa (ML
8
10
100 ML-MIN")
FIG. 1. A comparison of measurements of calf blood flow obtained by the strain gauge and impedance techniques.
Downloaded from http://bja.oxfordjournals.org/ at University of Michigan on June 18, 2015
In this study, impedance measurements of calf blood flow (c.b.f.) and cardiac output (()) were performed in 20 conscious healthy volunteers and 20 anaesthetized patients with no evidence of cardiovascular disease. Additional observations of venous occlusion plethysmography were made in 12 of the subjects using a mercury-in-rubber strain gauge. In the comparative study of the strain gauge (S.G.) and impedance techniques, the slopes of the electrical impedance plethysmogram agreed with those obtained by the conventional Whitney's plethysmogram. From 119 pairs of data points (fig. 1) the regression equation was: Flow (impedance) = 0.456 (Flow S.G.)+ 0.537 and r = 0.877. Similar results were reported previously by Hill and Hope (1973), who compared the impedance technique with volume displacement and strain gauge methods. The experiment was performed in the horizontal and reclining positions by tilting the subjects on a surgical table in order to analyse the effect of position and to promote changes in blood flow. The sequence of changes was from supine to Trendelenburg 10-20 ° to reverse Trendelenburg 10-20 ° to horizontal. Each position was maintained for a period of 5 min to allow for circulatory adaptation. Subsequently, the lithotomy position was maintained for 20 min, and cardiac output and limb blood flow were recorded twice at 10-min intervals. Ultimately, the subjects were returned to the supine position for the final measurements.
185
BRITISH JOURNAL OF ANAESTHESIA
186 Six patients, undergoing prolonged IPPV, were given single doses of pancuronium, followed some hours later by a series of incremental doses. Plasma pancuronium concentrations were determined at frequent intervals. In each instance an electrical analog model was used to construct a two-compartment open model for that patient which could be programmed to predict the effect of the ensuing increments (Hull and McLeod, 1976). Model predictions were then compared with the actual plasma concentrations. A good agreement showed that the model is likely to be valid, and as predicted, cumulation of pancuronium occurs after repeated doses.
former was a reasonable indicator of the development of lactic acidosis, probably resulting from tissue hypoxia. (7) SNP 1.5 mg/kg body weight is a safe maximum dose for an infusion of short duration. REFERENCES
Smith, R. P., and Kruszyna, H. (1974). J. Pharmacol. Exp. Ther., 191, 557. Vesey, C. J., Cole, P., and Simpson, P. (1976a). Br. J. Anaesth., 48, 268. (1976b). Br.J. Anaesth., 48, 651.
REFERENCES
ASSESSMENT OF LONG-TERM RECOVERY FROM SHORT DURATION ANAESTHESIA, USING THE CEREBRAL FUNCTION MONITOR M. DUBOIS, T. M. SAVEGE AND D. F. SCOTT
THE METABOLISM AND TOXICITY OF SODIUM NITROPRUSSIDE
Anaesthetics Unit and EEG Department, The London Hospital
P. SIMPSON, L. ADAMS, P. COLE AND C. VESEY
Results from previous studies (Dubois and Geddes, 1974) have shown that patients who received single doses of thiopentone were impaired markedly on psychomotor tasks at 2 h after administration. The e.e.g. has been used also to assess the prolonged effects of anaesthetic drugs on the c.n.s. (Doenicke, Kugler and Laub, 1967), revealing that full recovery is delayed even longer. In the present study a variety of psychomotor tests were employed and the e.e.g. recorded. In addition to conventional electroencephalograph techniques, the Cerebral Function Monitor (CFM) was employed. This purpose-built device produces a readily interpretable tracing and has proved of value in a variety of acute clinical situations, for example, cardiopulmonary bypass (Schwartz et al., 1973). The aim of the present investigation was to determine the place of the CFM in the assessment of long-term recovery from short duration anaesthesia. Eighteen female patients undergoing minor gynaecological surgery received an induction dose of methohexitone 2-3 mg/kg followed by one increment of £ induction dose). On two occasions before the anaesthetic was given and seven times during the following 24 h, various tests were administered in a standard manner to minimize extraneous environmental factors. Clinical state was assessed, the CFM recorded and the response to six different psychomotor tests—"Maddox Wing", visual reaction timer, three tests of balance and "Memory Drum"—were determined. All the psychomotor tasks yielded numerical data. Quantitative data were collected from the CFM using a digital chart reader and the paper tape obtained was subjected to statistical analysis. Six of the patients had conventional multi-channel e.e.g.'s recorded together with the CFM in order to compare the two types of tracing. The e.e.g.'s were rated visually, using a technique which gave numerical values for both the amount and duration of drowsiness and sleep. Our results indicated that while clinical signs and performance tests returned to pre-anaesthetic levels 2 h following the injection of the anaesthetic drug, CFM tracings were still significantly different from those before injection (P < 0.05) at 8 h. In the six patients in whom the conventional e.e.g. was recorded, quantitative analysis
Department of Anaesthetics, St Bartholomew's Hospital, London Sodium nitroprusside (SNP) breaks down in whole blood to yield free cyanide (HCN). The presence of sulphydryl groups is probably necessary for this reaction both in plasma (Vesey, Cole and Simpson, 1976a) and in red cells. The decomposition of SNP may occur in the erythrocytes and necessitates the free transfer of the intact nitroprusside molecule across the red cell membrane (Smith and Kruszyna, 1974). Two groups of anaesthetized dogs received either bolus doses of potassium cyanide 1.09 mg/kg body weight or bolus doses of SNP 1 mg/kg body weight. The increase and decrease of plasma and red cell cyanide concentrations in these two groups were compared in order to assess the rate of breakdown of SNP and the detoxication of HCN. A third group of anaesthetized dogs received SNP 1.5 mg/kg body weight at a steady rate for 1 h, in order to simulate the effects in patients receiving our maximum recommended dose (Vesey, Cole and Simpson, 1976b). Measurements of arterial base deficit and plasma lactate and pyruvate concentrations were made also to test the reliability of acid-base status measurements as an index of the development of tissue hypoxia. Our results may be summarized as follows: (1) The increase in plasma cyanide concentrations occurs before the increase in RBC cyanide concentration. (2) Ultimately, red cell cyanide concentrations reach 50-100 times those in the plasma. (3) In the bolus-dosed animals KCN produced plasma HCN values 10 times those produced by SNP, whereas RBC concentrations were similar. (4) Peak thiocyanate concentrations of 40-60 nmol/litre were attained 2 h following injection or infusion. (5) In the bolus SNP and infused SNP groups of dogs the calculated mean percentage of cyanide in the nitroprusside converted to thiocyanate was 63 and 64.5%, whereas the value for the bolus KCN dogs was 82%. (6) The correlation between arterial base deficit and lactate concentrations during SNP infusion showed that the
Downloaded from http://bja.oxfordjournals.org/ at University of Michigan on June 18, 2015
Hull, C. J., and McLeod, K. (1976) Br.J. Anaesth., 48, 677. McLeod, K., Watson, M. J., and Rawlins, M. D. (1976). Br. J. Anaesth., 48, 341.
In the lithotomy position, the Lloyd Davies support produced a larger decrease in limb blood flow than the stirrup support. The measured haemodynamic variables, cardiac output, stroke volume, calf blood flow and the mean impedance (20) agreed well with the corresponding changes in the arterial pressure and heart rate. The potential use of electrical impedance measurements to obtain data such as stroke volume, cardiac output and also the peak value of the first derivative dZ/dr makes the technique useful. ZQ is another function of the peripheral circulation which may be monitored also by impedance measurements. For limb blood flow it is a valuable index of the circulatory blood volume. Although empirical, our results indicate that impedance methods may provide a good assessment of the state of the circulation. REFERENCE
Hill, D. W., and Hope, C. E. (1973). Digest, 10th Internal. Conf, Med. Biol. Eng., Dresden, p. 245. THE PHARMACOKINETICS OF INCREMENTAL DOSES OF PANCURONIUM K. MCLEOD, D. W. RYAN, M. J. WATSON AND C. J. HULL Departments of Anaesthesia and Clinical Biochemistry, University of Newcastle
A previous study has investigated the pharmacokinetics of pancuronium following a single i.v. dose, in patients with normal and impaired renal function (McLeod, Watson and Rawlings, 1976). This study suggested that redistribution determines the duration of action of pancuronium following a single dose, but that the duration of action following repeated doses would depend also upon the rate of excretion.
fa i
r =0.8773 I.FLOW=O.45to(S.G.FLOW)+O.537
U
2
2
4
STRAIN GAUGE FLOW
fa (ML
8
10
100 ML-MIN")
FIG. 1. A comparison of measurements of calf blood flow obtained by the strain gauge and impedance techniques.
Downloaded from http://bja.oxfordjournals.org/ at University of Michigan on June 18, 2015
In this study, impedance measurements of calf blood flow (c.b.f.) and cardiac output (()) were performed in 20 conscious healthy volunteers and 20 anaesthetized patients with no evidence of cardiovascular disease. Additional observations of venous occlusion plethysmography were made in 12 of the subjects using a mercury-in-rubber strain gauge. In the comparative study of the strain gauge (S.G.) and impedance techniques, the slopes of the electrical impedance plethysmogram agreed with those obtained by the conventional Whitney's plethysmogram. From 119 pairs of data points (fig. 1) the regression equation was: Flow (impedance) = 0.456 (Flow S.G.)+ 0.537 and r = 0.877. Similar results were reported previously by Hill and Hope (1973), who compared the impedance technique with volume displacement and strain gauge methods. The experiment was performed in the horizontal and reclining positions by tilting the subjects on a surgical table in order to analyse the effect of position and to promote changes in blood flow. The sequence of changes was from supine to Trendelenburg 10-20 ° to reverse Trendelenburg 10-20 ° to horizontal. Each position was maintained for a period of 5 min to allow for circulatory adaptation. Subsequently, the lithotomy position was maintained for 20 min, and cardiac output and limb blood flow were recorded twice at 10-min intervals. Ultimately, the subjects were returned to the supine position for the final measurements.
185
BRITISH JOURNAL OF ANAESTHESIA
186 Six patients, undergoing prolonged IPPV, were given single doses of pancuronium, followed some hours later by a series of incremental doses. Plasma pancuronium concentrations were determined at frequent intervals. In each instance an electrical analog model was used to construct a two-compartment open model for that patient which could be programmed to predict the effect of the ensuing increments (Hull and McLeod, 1976). Model predictions were then compared with the actual plasma concentrations. A good agreement showed that the model is likely to be valid, and as predicted, cumulation of pancuronium occurs after repeated doses.
former was a reasonable indicator of the development of lactic acidosis, probably resulting from tissue hypoxia. (7) SNP 1.5 mg/kg body weight is a safe maximum dose for an infusion of short duration. REFERENCES
Smith, R. P., and Kruszyna, H. (1974). J. Pharmacol. Exp. Ther., 191, 557. Vesey, C. J., Cole, P., and Simpson, P. (1976a). Br. J. Anaesth., 48, 268. (1976b). Br.J. Anaesth., 48, 651.
REFERENCES
ASSESSMENT OF LONG-TERM RECOVERY FROM SHORT DURATION ANAESTHESIA, USING THE CEREBRAL FUNCTION MONITOR M. DUBOIS, T. M. SAVEGE AND D. F. SCOTT
THE METABOLISM AND TOXICITY OF SODIUM NITROPRUSSIDE
Anaesthetics Unit and EEG Department, The London Hospital
P. SIMPSON, L. ADAMS, P. COLE AND C. VESEY
Results from previous studies (Dubois and Geddes, 1974) have shown that patients who received single doses of thiopentone were impaired markedly on psychomotor tasks at 2 h after administration. The e.e.g. has been used also to assess the prolonged effects of anaesthetic drugs on the c.n.s. (Doenicke, Kugler and Laub, 1967), revealing that full recovery is delayed even longer. In the present study a variety of psychomotor tests were employed and the e.e.g. recorded. In addition to conventional electroencephalograph techniques, the Cerebral Function Monitor (CFM) was employed. This purpose-built device produces a readily interpretable tracing and has proved of value in a variety of acute clinical situations, for example, cardiopulmonary bypass (Schwartz et al., 1973). The aim of the present investigation was to determine the place of the CFM in the assessment of long-term recovery from short duration anaesthesia. Eighteen female patients undergoing minor gynaecological surgery received an induction dose of methohexitone 2-3 mg/kg followed by one increment of £ induction dose). On two occasions before the anaesthetic was given and seven times during the following 24 h, various tests were administered in a standard manner to minimize extraneous environmental factors. Clinical state was assessed, the CFM recorded and the response to six different psychomotor tests—"Maddox Wing", visual reaction timer, three tests of balance and "Memory Drum"—were determined. All the psychomotor tasks yielded numerical data. Quantitative data were collected from the CFM using a digital chart reader and the paper tape obtained was subjected to statistical analysis. Six of the patients had conventional multi-channel e.e.g.'s recorded together with the CFM in order to compare the two types of tracing. The e.e.g.'s were rated visually, using a technique which gave numerical values for both the amount and duration of drowsiness and sleep. Our results indicated that while clinical signs and performance tests returned to pre-anaesthetic levels 2 h following the injection of the anaesthetic drug, CFM tracings were still significantly different from those before injection (P < 0.05) at 8 h. In the six patients in whom the conventional e.e.g. was recorded, quantitative analysis
Department of Anaesthetics, St Bartholomew's Hospital, London Sodium nitroprusside (SNP) breaks down in whole blood to yield free cyanide (HCN). The presence of sulphydryl groups is probably necessary for this reaction both in plasma (Vesey, Cole and Simpson, 1976a) and in red cells. The decomposition of SNP may occur in the erythrocytes and necessitates the free transfer of the intact nitroprusside molecule across the red cell membrane (Smith and Kruszyna, 1974). Two groups of anaesthetized dogs received either bolus doses of potassium cyanide 1.09 mg/kg body weight or bolus doses of SNP 1 mg/kg body weight. The increase and decrease of plasma and red cell cyanide concentrations in these two groups were compared in order to assess the rate of breakdown of SNP and the detoxication of HCN. A third group of anaesthetized dogs received SNP 1.5 mg/kg body weight at a steady rate for 1 h, in order to simulate the effects in patients receiving our maximum recommended dose (Vesey, Cole and Simpson, 1976b). Measurements of arterial base deficit and plasma lactate and pyruvate concentrations were made also to test the reliability of acid-base status measurements as an index of the development of tissue hypoxia. Our results may be summarized as follows: (1) The increase in plasma cyanide concentrations occurs before the increase in RBC cyanide concentration. (2) Ultimately, red cell cyanide concentrations reach 50-100 times those in the plasma. (3) In the bolus-dosed animals KCN produced plasma HCN values 10 times those produced by SNP, whereas RBC concentrations were similar. (4) Peak thiocyanate concentrations of 40-60 nmol/litre were attained 2 h following injection or infusion. (5) In the bolus SNP and infused SNP groups of dogs the calculated mean percentage of cyanide in the nitroprusside converted to thiocyanate was 63 and 64.5%, whereas the value for the bolus KCN dogs was 82%. (6) The correlation between arterial base deficit and lactate concentrations during SNP infusion showed that the
Downloaded from http://bja.oxfordjournals.org/ at University of Michigan on June 18, 2015
Hull, C. J., and McLeod, K. (1976) Br.J. Anaesth., 48, 677. McLeod, K., Watson, M. J., and Rawlins, M. D. (1976). Br. J. Anaesth., 48, 341.