BRITISH JOURNAL OF ANAESTHESIA
1268 INADVERTENT ADMINISTRATION OF 1 0 0 % OXYGEN DURING ANAESTHESIA
N. J. PAYMASTER
Wirral HYPOTENSION FOLLOWING METOCLOPRAMIDE ADMINISTRATION DURING HYFOTENSIVE ANAESTHESIA FOR INTRACRANIAL ANEURYSM
Sir,—Four patients undergoing surgery for repair of a ruptured intracranial aneurysm developed hypotension following the i.v. administration of metoclopramide (Maxolon) as an anti-emetic. All four patients received the same anaesthetic technique TABLE I. Cardiovascular changes following the i.v. administration of metoclopramide 10 mg Before metoclopramide Type of aneurysm (Injection time) Mid-cer. (TA 40)* (TB 100)f Ant. com. (TA28) (TB 60) Ant. com. (TA 32) (TB 68) Post. com. (TA 32) (TB 84)
AP (mm Hg)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
135 80
98
68
90 60
70
54
110 ~70
83
68
120 75
90
64
CVP (mm Hg) 3.6
Type of aneurysm (Injection time) Mid-cer. (TA40) (TB 100) Ant. com. (TA 28) (TB 60) Ant. com. (TA 32) (TB 68) Post. com. (TA 32) (TB 84)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
CVP (mmHg)
85
68
72
2.4
60 70
56
56
—
50 90
67
75
4
55 100
80
70
8
AP (mm Hg)
ert
60 Changes in readings
Type of aneurysm (Injection time)
AP (mm Hg)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
CVP (mm Hg)
Mid cer. (TA40) (TB 100) Ant. com. (TA 28) (TB 60) Ant. com.
— 50
-30
+4
-1.2
20 -20
-14
+2
—
-16
+7
0
(TB 68) Post. com. (TA 32) (TB 84)
-20 15 -20
-10
+6
0
i r\ 10
13
* Time (s) from injection of drug to start in decrease in arterial pressure. •f Time (s) from injection of drug to return of arterial pressure to pre-injection values. AP = Arterial pressure ; M.a.p. = mean arterial pressure j CVP = central venous pressure. Mid cer. = Mid cerebral; ant. com. = anterior communicating; post, com = posterior communicating.
consisting of thiopentone, pancuronium, phenoperidine and nitrous oxide. An e.c.g., indwelling radial arterial line and central venous line, were used for monitoring. All results were recorded on a Sanborn hot-wire chart recorder. Arterial hypotension was induced, by the use of halothane and sodium nitroprusside, to a mean arterial pressure (m.a.p.) of 50 mm Hg. After the aneurysm was clipped the administration of these drugs was stopped. Shortly before closure of the dura, after the effects of the hypotensive agents had ceased, metoclopramide 10 mg was given. This was followed quickly by a decrease in arterial pressure (one patient showing a decrease of 50 mm Hg in systolic arterial pressure) and an increase in
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on May 11, 2015
Sir,—Modern anaesthetic machines have a device (usually referred to as "the oxygen bypass" or "emergency oxygen") which enables the anaesthetist to administer high flows of 100% oxygen. When a patient is connected to an anaesthetic machine it is possible to overlook the fact that the emergency oxygen device is in the "on" position and is delivering 100% oxygen. This occurrence is most likely if the device operates quietly and uses a "push-pull" switch. The Cape Waine Mark II anaesthetic machine and ventilator has such a mechanism. Accidents have occurred in our operating theatre on two occasions when patients had been transferred from the anaesthetic room to the operating theatre and connected to a machine. On both occasions a junior anaesthetist failed to notice for some time that the emergency oxygen device was "on" and the paralysed patients received higher concentrations of oxygen than intended. The following day, not unexpectedlyj the patients complained of awareness during anaesthesia. Anaesthetists use the emergency oxygen device frequently at the termination of anaesthesia and, occasionally, during anaesthesia. Sometimes, it is left inadvertently in t i e "on" position after use. Incidents similar to those reported here probably occur more often than is generally believed. They could be avoided by a suitable audio-visual device fitted to the anaesthetic machine warning the anaesthetist that the machine is delivering 100% oxygen.
Maximum change after metoclopramide
1269
CORRESPONDENCE
G. R. PARK
Edinburgh REFERENCES
Goodman, L. S., and Gilman, A. (1975). The Pharmacological Basis of Therapeutics. 5th edn, p. 695. Tornetta, F. J. (1969). Clinical studies with the new antiemetic metoclopramide. Anesth. Analg. (Cleve.), 48, 198.
TABLE I. pKa, pH and calculated ratio of unionized : ionized local anaesthetic present in solution at room temperature Anaesthetic
pKa
PH
[B]/[BH+]
Chloroprocaine 3.0%* Bupivacaine 0.75% t Lignocaine 2.0% %
8.7 8.1 7.7
3.5 5.8 6.6
0.005 0.1 0.3
Bupivacaine 0.75% + chloroprocaine 3.0%
8.1 8.7
3.7 3.7
0.01 0.007
Bupivacaine 0.75% + lignocaine 2.0%
8.1 7.7
6.5 6.5
0.2 0.3
* Winthrop Laboratories, New York, U.S.A. t Penwalt Corp., Rochester, U.S.A. % Astra Pharmaceuticals, Worcester, U.S.A. nation may lead to earlier exhaustion of local tissue buffering capacity and a reduction in the effectiveness of the bupivacaine. A bupivacaine-lignocaine mixture may be a more reasonable choice if a local anaesthetic mixture is to be repeated. JAY B. BRODSKY JOHN G. BROCK-UTNE
Stanford, California REFERENCES
MIXING LOCAL ANAESTHETICS
Sir,—Local anaesthetic solutions are frequently mixed to take advantage of the useful properties of each drug (Bromage and Gertel, 1972; Moore et al., 1972; Cunningham and Kaplan, 1974). The pH of these combinations may be important. In solution, local anaesthetics exist in both the uncharged (B) and the positively charged (BH+) forms. The relative proportion of each depends on the pH of solution and the pKa of the specific agent. Since pKa of a drug is constant, the ratio of free base to charged cation will be determined by pH of the solution. The uncharged form of the anaesthetic penetrates the nerve. An increase in pH increases the depth and rapidity of onset of anaesthetics by increasing the unionized moiety and hence penetration of the drug. The free anaesthetic base is usually unstable and poorly soluble in water. Local anaesthetics are prepared commercially as the water-soluble salt of a strong acid. An equal volume of bupivacaine (0.75%) combined with chloroprocaine (3.0%) will produce a strongly acid mixture (pH 3.7). An equal mixture of bupivacaine (0.75%) and lignocaine (2.0%) has a pH of 6.5, and so approximately 20 times more uncharged bupivacaine is available in this solution than when mixed with chloroprocaine (table I). These considerations are probably unimportant when an anaesthetic mixture is used for a single administration, since the buffering capacity of most tissues is sufficient to increase the pH of the anaesthetic solution rapidly to within the physiological range. Tachyphylaxis to local anaesthetics follows repeated administrations to spaces with limited buffering capacities (Cohen et al., 1968), since an acid milieu develops, greater amounts of charged cations accumulate outside and less drug enters the nerve. Continued use of the acid bupivacaine-chloroprocaine combi-
Bromage, P. R., and Gertel, M. (1972). Improved brachial plexus blockade with bupivacaine hydrochloride and carbonated lidocaine. Anesthesiology, 36, 479. Cohen, E. N., Levine, D. A., Colliss, J. E., and Gunther, R. E. (1968). The role of pH in the development of tachyphylaxis to local anesthetic agents. Anesthesiology, 29, 994. Cunningham, N . L., and Kaplan, J. A. (1974). A rapid onset, long-acting regional anesthetic technique. Anesthesiology, 41, 509. Moore, D. C , Bridenbaugh, L. D., Bridenbaugh, P. O., Thompson, G. E., and Tucker, G. T. (1972). Does compounding of local anesthetic agents increase their toxicity in humans? Anesth. Analg. (Cleve.), 51, 579. CURARE AND VENTILATION
Sir,—When referring to my use of tubocurarine to maintain neuromuscular blockade (Ryan, 1964), Drs Somogyi, Shanks and Triggs (1978) stated that I employed this drug in a manner similar to that of Evans and Spencer Gray (1953) who allowed their patients to breathe spontaneously. By 1964 most anaesthetists were using controlled ventilation and this was also my technique. ALBERT R. RYAN
Stevenage REFERENCES
Evans, F. T., and Spencer Gray, P. W. (1953). Continuous intravenous thiopentone (Flaxedil). Anaesthesia, 8, 104. Ryan, A. R. (1964). Tubocurarine administration based upon its disappearance and accumulation curves in anaesthetized man. Br. J. Anaesth., 36, 287. Somogyi, A. A., Shanks, C. A., and Triggs, E. J. (1978). Combined i.v. bolus and infusion of pancuronium bromide. Br. J. Anaesth., 50, 575.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on May 11, 2015
heart rate in all patients. Central venous pressure decreased in one patient and remained unchanged in the other two in whom the measurement was available (table I). Metoclopramide has- been reported previously as having no cardiovascular effects in man (Tornetta, 1969). This small series has shown that, following hypotensive anaesthesia, significant cardiovascular effects may be seen, probably resulting from peripheral vasodilatation. Metoclopramide resembles procaineamide in structure. Procaineamide administration results in both cardiac depression and peripheral vasodilatation (Goodman and Gilman, 1975). The peripheral vasodilatation may be accentuated by the prior administration of smooth muscle relaxants (halothane and sodium nitroprusside) explaining the discrepancy between previous studies in conscious patients and our findings. Further work is in progress to elucidate the exact cause of the hypotension.
1268 INADVERTENT ADMINISTRATION OF 1 0 0 % OXYGEN DURING ANAESTHESIA
N. J. PAYMASTER
Wirral HYPOTENSION FOLLOWING METOCLOPRAMIDE ADMINISTRATION DURING HYFOTENSIVE ANAESTHESIA FOR INTRACRANIAL ANEURYSM
Sir,—Four patients undergoing surgery for repair of a ruptured intracranial aneurysm developed hypotension following the i.v. administration of metoclopramide (Maxolon) as an anti-emetic. All four patients received the same anaesthetic technique TABLE I. Cardiovascular changes following the i.v. administration of metoclopramide 10 mg Before metoclopramide Type of aneurysm (Injection time) Mid-cer. (TA 40)* (TB 100)f Ant. com. (TA28) (TB 60) Ant. com. (TA 32) (TB 68) Post. com. (TA 32) (TB 84)
AP (mm Hg)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
135 80
98
68
90 60
70
54
110 ~70
83
68
120 75
90
64
CVP (mm Hg) 3.6
Type of aneurysm (Injection time) Mid-cer. (TA40) (TB 100) Ant. com. (TA 28) (TB 60) Ant. com. (TA 32) (TB 68) Post. com. (TA 32) (TB 84)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
CVP (mmHg)
85
68
72
2.4
60 70
56
56
—
50 90
67
75
4
55 100
80
70
8
AP (mm Hg)
ert
60 Changes in readings
Type of aneurysm (Injection time)
AP (mm Hg)
M.a.p. (mm Hg)
Heart rate (beat min" 1 )
CVP (mm Hg)
Mid cer. (TA40) (TB 100) Ant. com. (TA 28) (TB 60) Ant. com.
— 50
-30
+4
-1.2
20 -20
-14
+2
—
-16
+7
0
(TB 68) Post. com. (TA 32) (TB 84)
-20 15 -20
-10
+6
0
i r\ 10
13
* Time (s) from injection of drug to start in decrease in arterial pressure. •f Time (s) from injection of drug to return of arterial pressure to pre-injection values. AP = Arterial pressure ; M.a.p. = mean arterial pressure j CVP = central venous pressure. Mid cer. = Mid cerebral; ant. com. = anterior communicating; post, com = posterior communicating.
consisting of thiopentone, pancuronium, phenoperidine and nitrous oxide. An e.c.g., indwelling radial arterial line and central venous line, were used for monitoring. All results were recorded on a Sanborn hot-wire chart recorder. Arterial hypotension was induced, by the use of halothane and sodium nitroprusside, to a mean arterial pressure (m.a.p.) of 50 mm Hg. After the aneurysm was clipped the administration of these drugs was stopped. Shortly before closure of the dura, after the effects of the hypotensive agents had ceased, metoclopramide 10 mg was given. This was followed quickly by a decrease in arterial pressure (one patient showing a decrease of 50 mm Hg in systolic arterial pressure) and an increase in
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on May 11, 2015
Sir,—Modern anaesthetic machines have a device (usually referred to as "the oxygen bypass" or "emergency oxygen") which enables the anaesthetist to administer high flows of 100% oxygen. When a patient is connected to an anaesthetic machine it is possible to overlook the fact that the emergency oxygen device is in the "on" position and is delivering 100% oxygen. This occurrence is most likely if the device operates quietly and uses a "push-pull" switch. The Cape Waine Mark II anaesthetic machine and ventilator has such a mechanism. Accidents have occurred in our operating theatre on two occasions when patients had been transferred from the anaesthetic room to the operating theatre and connected to a machine. On both occasions a junior anaesthetist failed to notice for some time that the emergency oxygen device was "on" and the paralysed patients received higher concentrations of oxygen than intended. The following day, not unexpectedlyj the patients complained of awareness during anaesthesia. Anaesthetists use the emergency oxygen device frequently at the termination of anaesthesia and, occasionally, during anaesthesia. Sometimes, it is left inadvertently in t i e "on" position after use. Incidents similar to those reported here probably occur more often than is generally believed. They could be avoided by a suitable audio-visual device fitted to the anaesthetic machine warning the anaesthetist that the machine is delivering 100% oxygen.
Maximum change after metoclopramide
1269
CORRESPONDENCE
G. R. PARK
Edinburgh REFERENCES
Goodman, L. S., and Gilman, A. (1975). The Pharmacological Basis of Therapeutics. 5th edn, p. 695. Tornetta, F. J. (1969). Clinical studies with the new antiemetic metoclopramide. Anesth. Analg. (Cleve.), 48, 198.
TABLE I. pKa, pH and calculated ratio of unionized : ionized local anaesthetic present in solution at room temperature Anaesthetic
pKa
PH
[B]/[BH+]
Chloroprocaine 3.0%* Bupivacaine 0.75% t Lignocaine 2.0% %
8.7 8.1 7.7
3.5 5.8 6.6
0.005 0.1 0.3
Bupivacaine 0.75% + chloroprocaine 3.0%
8.1 8.7
3.7 3.7
0.01 0.007
Bupivacaine 0.75% + lignocaine 2.0%
8.1 7.7
6.5 6.5
0.2 0.3
* Winthrop Laboratories, New York, U.S.A. t Penwalt Corp., Rochester, U.S.A. % Astra Pharmaceuticals, Worcester, U.S.A. nation may lead to earlier exhaustion of local tissue buffering capacity and a reduction in the effectiveness of the bupivacaine. A bupivacaine-lignocaine mixture may be a more reasonable choice if a local anaesthetic mixture is to be repeated. JAY B. BRODSKY JOHN G. BROCK-UTNE
Stanford, California REFERENCES
MIXING LOCAL ANAESTHETICS
Sir,—Local anaesthetic solutions are frequently mixed to take advantage of the useful properties of each drug (Bromage and Gertel, 1972; Moore et al., 1972; Cunningham and Kaplan, 1974). The pH of these combinations may be important. In solution, local anaesthetics exist in both the uncharged (B) and the positively charged (BH+) forms. The relative proportion of each depends on the pH of solution and the pKa of the specific agent. Since pKa of a drug is constant, the ratio of free base to charged cation will be determined by pH of the solution. The uncharged form of the anaesthetic penetrates the nerve. An increase in pH increases the depth and rapidity of onset of anaesthetics by increasing the unionized moiety and hence penetration of the drug. The free anaesthetic base is usually unstable and poorly soluble in water. Local anaesthetics are prepared commercially as the water-soluble salt of a strong acid. An equal volume of bupivacaine (0.75%) combined with chloroprocaine (3.0%) will produce a strongly acid mixture (pH 3.7). An equal mixture of bupivacaine (0.75%) and lignocaine (2.0%) has a pH of 6.5, and so approximately 20 times more uncharged bupivacaine is available in this solution than when mixed with chloroprocaine (table I). These considerations are probably unimportant when an anaesthetic mixture is used for a single administration, since the buffering capacity of most tissues is sufficient to increase the pH of the anaesthetic solution rapidly to within the physiological range. Tachyphylaxis to local anaesthetics follows repeated administrations to spaces with limited buffering capacities (Cohen et al., 1968), since an acid milieu develops, greater amounts of charged cations accumulate outside and less drug enters the nerve. Continued use of the acid bupivacaine-chloroprocaine combi-
Bromage, P. R., and Gertel, M. (1972). Improved brachial plexus blockade with bupivacaine hydrochloride and carbonated lidocaine. Anesthesiology, 36, 479. Cohen, E. N., Levine, D. A., Colliss, J. E., and Gunther, R. E. (1968). The role of pH in the development of tachyphylaxis to local anesthetic agents. Anesthesiology, 29, 994. Cunningham, N . L., and Kaplan, J. A. (1974). A rapid onset, long-acting regional anesthetic technique. Anesthesiology, 41, 509. Moore, D. C , Bridenbaugh, L. D., Bridenbaugh, P. O., Thompson, G. E., and Tucker, G. T. (1972). Does compounding of local anesthetic agents increase their toxicity in humans? Anesth. Analg. (Cleve.), 51, 579. CURARE AND VENTILATION
Sir,—When referring to my use of tubocurarine to maintain neuromuscular blockade (Ryan, 1964), Drs Somogyi, Shanks and Triggs (1978) stated that I employed this drug in a manner similar to that of Evans and Spencer Gray (1953) who allowed their patients to breathe spontaneously. By 1964 most anaesthetists were using controlled ventilation and this was also my technique. ALBERT R. RYAN
Stevenage REFERENCES
Evans, F. T., and Spencer Gray, P. W. (1953). Continuous intravenous thiopentone (Flaxedil). Anaesthesia, 8, 104. Ryan, A. R. (1964). Tubocurarine administration based upon its disappearance and accumulation curves in anaesthetized man. Br. J. Anaesth., 36, 287. Somogyi, A. A., Shanks, C. A., and Triggs, E. J. (1978). Combined i.v. bolus and infusion of pancuronium bromide. Br. J. Anaesth., 50, 575.
Downloaded from http://bja.oxfordjournals.org/ at Carleton University on May 11, 2015
heart rate in all patients. Central venous pressure decreased in one patient and remained unchanged in the other two in whom the measurement was available (table I). Metoclopramide has- been reported previously as having no cardiovascular effects in man (Tornetta, 1969). This small series has shown that, following hypotensive anaesthesia, significant cardiovascular effects may be seen, probably resulting from peripheral vasodilatation. Metoclopramide resembles procaineamide in structure. Procaineamide administration results in both cardiac depression and peripheral vasodilatation (Goodman and Gilman, 1975). The peripheral vasodilatation may be accentuated by the prior administration of smooth muscle relaxants (halothane and sodium nitroprusside) explaining the discrepancy between previous studies in conscious patients and our findings. Further work is in progress to elucidate the exact cause of the hypotension.
