Anaesthesia, 1992, Volume 47, pages 1086-1087
Administration of vancomycin during cardiopulmonary bypass A. Baraka, MB, BCh, DA, DM, MD, FRCAnaes (Hon), Professor and Chairman, S. Taha, M D , Instructor, A. Bijjani, MD, Resident, W. Arab, MD, Clinical Fellow, G. Meshefedjian, MS, Departments of Anesthesiology and Epidemiology and Biostatistics, American University of Beirut, Beirut, Lebanon.
Summary
Vancomycin was given during cardiopulmonary bypass to 12 anaesthetised patients undergoing open heart surgery. Injection of vancomycin 1 g within 60 s via the venous inlet of the oxygenator resulted in a moderate and transient decrease of mean arterial pressure. This minimal reaction may be attributed to dilution of vancomycin by the extracorporeal circuit volume, to the bypassing of the lungs which are a major site of storage of vasoactive substances, or to the maintenance of adequate perfusion flow during cardiopulmonary bypass. The results suggest that the haemodynamic adverse reactions to vancomycin, given as antibiotic prophylaxis, may be decreased by its administration after initiation of cardiopulmonary bypass.
Key words Antibiotics; vancomycin. Anaphylactoid reactions. Cardiopulmonary bypass.
Prophylactic administration of antibiotics in patients undergoing open heart surgery has reduced the incidence of infection. Vancomycin prophylaxis is recommended in patients with known hypersensitivity to the penicillins, and wherever the endemic rate of methicillin-resistant staphylococci is high [ 11. However, serious anaphylactoid reactions, including cardiovascular collapse and severe bronchospasm, may follow the infusion of vancomycin [ 1-51. Although the incidence and severity of vancomycininduced reactions may be decreased by using a slow rate of infusion, a number of reports have described the reaction following slow infusions [6,7]. Vancomycin-induced complications may be potentially life-threatening during the prebypass period in cardiac patients [ I , 2,8]. We have experienced a serious cardiovascular collapse following the administration of vancomycin during the prebypass period in a patient undergoing coronary artery grafting. As a consequence of this we have avoided the administration of vancomycin during the prebypass period and have chosen instead to give it after initiation of cardiopulmonary bypass (CPB). This study was set up to observe the cardiovascular changes associated with this technique. Method
The investigation was carried out on 12 patients, aged 20-70 years, weighing 50-100 kg, who underwent coronary artery bypass grafting or valve replacement during hypothermic CPB. The investigation was approved by the Institution Research Committee, and informed consent was obtained. The patients were premedicated with morphine 0.1 mg.kg-', hyoscine 0.3 mg and promethazine 25 mg given intramuscularly. Anaesthesia was induced with midazolam 0.1 mg.kg-', fentanyl 50 pg.kg-' and a mixture of pancuronium 0.1 mg.kg-' and vecuronium 0.1 mg.kg-'. Following tracheal intubation, ventilation was maintained with 100% oxygen without any inhalational anaesthetic supplementation. Patients were monitored by means of an Accepted 13 February 1992.
electrocardiogram (ECG), a radial artery cannula, and a pulmonary artery catheter. During CPB, a bubble oxygenator (Bentley-10, American Bentley, Irvine, CA, USA) was used which had been primed with 1500 ml of compound sodium lactate solution. The patients were perfused using a roller pump (Sarns 5000, Ann Arbor, MI, USA) at a constant flow of 2.4 I.rnin-'.m-', and the oxygenator was supplied with an equal flow of 100% oxygen. The temperature was gradually reduced to 27-30°C, and the heart was arrested by a cardioplegic solution (K+30mmol.1-' at 4°C) after aortic cross clamping. After about 10-20min of CPB when the mean arterial pressure (MAP) and reservoir volume had stabilised, vancomycin 1 g diluted in 20ml of 5% dextrose solution was injected over 60s into the venous line of the oxygenator. The MAP and reservoir volume were continuously monitored, while the perfusion flow was maintained constant at 2.4 I.min-'.m-*. MAP and reservoir volume values were recorded every minute from the time of injection over a 10 min period. Changes of MAP and reservoir volume were taken to reflect the effect of vancomycin on the systemic vascular resistance and the capacitance vessels, respectively [9]. The paired t-test was used to compare the MAP and reservoir volume values achieved following vancomycin with the control values. A value of p < 0.05 was considered significant. Results
Table 1 shows the mean control MAP value achieved during CPB in the 12 patients and the mean MAP values obtained at every minute from the time of injection of vancomycin over a 10 min period. The MAP significantly decreased from a control level of 76.2 (1 1.3) mmHg to 52.5 (17.1) mmHg 2 min following vancomycin administration. Recovery to control values was achieved after 6 min. Table 2 shows the mean control reservoir volume achieved during CPB in the 12 patients and the mean
1087
Forum Table 1. Mean arterial pressure (MAP) in the 12 patients before and after the administration of vancomycin. Values are expressed as mean (SD). Time; min 0 1 2 3 4 5 6 7 8 9 10
MAP; mmHg 76.25 (11.31) 67.08 (9.16) 52.50 (17.12) 57.08 (1 7.77) 62.50 (17.12) 66.25 (18.23) 69.58 (17.90) 72.92 (18.76) 74.58 ( I 8.88) 73.33 (21.03) 75.83 (20.09)
% change of
MAP*
Significance*
-
-
12.30 31.15 25.14 18.03 13.11 8.75 4.37 2.19 3.83 0.55
< 0.05 < 0.05 < 0.05 < 0.05
Table 2. Mean reservoir volume (RV) in the 12 patients before and after the administration of vancomycin. Values are expressed as mean (SD). Time; min 0 1 2 3 4
< 0.05
5
NS NS NS NS NS
6 7 8 9 I10
Mean RV;
YO change of
I
mean RV*
Significance* (p value)
2.37 (0.96) 2.34 (0.97) 2.22 (1.03) 2.12 (1.04) 2.02 (0.99) 2.01 (1.00) 1.97 (0.97) 1.93 (0.99) 1.90 (0.95) 1.82 (0.97) 1.82 (0.96)
I .27 6.33
NS NS
10.55
14.77 15.19 16.88 18.56 19.83 23.21 23.21
-
< 0.05 < 0.05 < 0.05
< 0.05 < 0.05 < 0.05 < 0.05 < 0.05
0 time, control MAP; NS, not significant. *Reference to zero minute.
0 time, control mean RV; NS, not significant, *Reference to zero minute.
reservoir volume values obtained at every minute following the administration of vancomycin. The reservoir volume gradually decreased within 10 min from a control value of 2.37 (0.96 1) to 1.82 (0.96 I).
dynamic instability and/or ischaemic heart disease, when cardiovascular collapse may be life-threatening and therapeutic options are narrowed [I, 21.
References Discussion
This report demonstrates the safety of administration of vancomycin after initiation of CPB. The injection of a bolus of vancomycin 1 g over 60 s into the venous inlet to the reservoir of the oxygenator resulted only in a moderate and transient decrease of MAP. Vancomycin-induced anaphylactoid reaction [ 1-81 may be attributed to a direct effect on mast cells and basophils that results in their degranulation with subsequent release of various vasoactive mediators; histamine release probably represents the mechanism responsible for hypotension following vancomycin administration in man [lo]. Hypotension is the most frequent and the most serious immediate adverse effect associated with the use of vancomycin and the administration of a single dose of vancomycin as antibiotic prophylaxis has been shown to produce a high incidence of severe hypotension in cardiac surgical patients [8]. The minimal and transient decrease of MAP following the rapid administration of a large bolus of vancomycin during CPB may be attributed to dilution by the extracorporeal circuit volume, as well as to bypassing the pulmonary circulation. Adverse cardiovascular responses to drugs such as protamine and vancomycin may be increased by its passage through the pulmonary vasculature as the lungs are a major site of storage of many vasoactive substances, including histamine [ 1 1, 121. Thus, histamine release by vancomycin may be decreased when the lungs are bypassed. The decreased hypotensive response to vancomycin given during CPB may be also attributed to maintenance of adequate perfusion by the pump, despite the increased venous capacitance as manifested by the decreased reservoir volume. In contrast, during the prebypass period, excessive histamine release does not only decrease systemic vascular resistance but also increases the vascular capacitance and traps large amounts of blood, with a subsequent decrease of the venous return and cardiac output [13]. This will be compounded in the cardiac patient with haemo-
[I] BLOOMB, CHALMERS PC, DANKER RR, KUMARS, SHEIKH F. Cardiovascular collapse and refractory bronchospasm following administration of vancomycin, esmolol, and heparin. Journal of Cardiothoracic Anesthesia 1989; 3 748-51. [2] DMEEH, LAKSH, MILLER J, OVENR. Profound hypotension from rapid vancomycin administration during cardiac operation. Journal of Thoracic and Cardiovascular Surgery 1984; 87: 145-6. [3] MILLERR, TAUSKHC. Anaphylactoid reaction to vancomycin during anesthesia: a case report. Anesthesia and Analgesia 1977; 56: 870-2. [4] SYMONS NLP, HOBBESAFT, LEAVERHK. Anaphylactoid reactions to vancomycin during anaesthesia: two clinical reports. Canadian Anaesthetists’ Society Journal 1985; 3 2 178-81. [5] MAYHEWJF, DEUTSCH S. Cardiac arrest following administration of vancomycin. Canadian Anaesthetists’ Society Journal 1985; 3 2 65-6. [6] PAU AK. KHAKW R. ‘Red-Neck Syndrome’ with slow infusion of vancomycin. New England Journal of Medicine 1985; 313 756-7. [7] DAVISRL, SMITHAL, KOUPJR. The ‘Red Man’s Syndrome’ and slow infusion of vancomycin. Annals of Internal Medicine 1986; 104: 285-6. [8] VALEROR, GOMARC, FITAG, GONZALEZ M, PACHECO M, MULETJ, NALDAMA. Adverse reactions to vancomycin prophylaxis in cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 1991; 5: 574-6. [9] BARAKAA, HAROUN S, BAROODYM, NAWFAL M. SIBAIA. Action of adrenergic agonists on resistance v. capacitance vessels during cardiopulmonary bypass. Journal of Cardiothoracic Anesthesia 1989; 3 193-5. [lo] LEVYJH, KETTLEKAMP N, GOERTZP, HERMENS J, HIRSHMAN CA. Histamine release by vancomycin: a mechanism for hypotension in man. Anesthesiology 1987; 67: 122-5. [I I] GOLDMAN BS, JOISONJ, AUSTENWG. Cardiovascular effects of protamine sulfate. Annals of Thoracic Surgery 1969; 7: 459-71. [I21 CASTHELYPA. GOODMANK, FYMANPN, ABRAMSLM, AAROND. Hemodynamic changes after the administration of protamine. Anesthesia and Analgesia 1986 6 5 78-80. [I31 DALE HH, LAIDLAWPP. Histamine shock. Journal of Physiology 1919; 5 2 355-90.
Administration of vancomycin during cardiopulmonary bypass A. Baraka, MB, BCh, DA, DM, MD, FRCAnaes (Hon), Professor and Chairman, S. Taha, M D , Instructor, A. Bijjani, MD, Resident, W. Arab, MD, Clinical Fellow, G. Meshefedjian, MS, Departments of Anesthesiology and Epidemiology and Biostatistics, American University of Beirut, Beirut, Lebanon.
Summary
Vancomycin was given during cardiopulmonary bypass to 12 anaesthetised patients undergoing open heart surgery. Injection of vancomycin 1 g within 60 s via the venous inlet of the oxygenator resulted in a moderate and transient decrease of mean arterial pressure. This minimal reaction may be attributed to dilution of vancomycin by the extracorporeal circuit volume, to the bypassing of the lungs which are a major site of storage of vasoactive substances, or to the maintenance of adequate perfusion flow during cardiopulmonary bypass. The results suggest that the haemodynamic adverse reactions to vancomycin, given as antibiotic prophylaxis, may be decreased by its administration after initiation of cardiopulmonary bypass.
Key words Antibiotics; vancomycin. Anaphylactoid reactions. Cardiopulmonary bypass.
Prophylactic administration of antibiotics in patients undergoing open heart surgery has reduced the incidence of infection. Vancomycin prophylaxis is recommended in patients with known hypersensitivity to the penicillins, and wherever the endemic rate of methicillin-resistant staphylococci is high [ 11. However, serious anaphylactoid reactions, including cardiovascular collapse and severe bronchospasm, may follow the infusion of vancomycin [ 1-51. Although the incidence and severity of vancomycininduced reactions may be decreased by using a slow rate of infusion, a number of reports have described the reaction following slow infusions [6,7]. Vancomycin-induced complications may be potentially life-threatening during the prebypass period in cardiac patients [ I , 2,8]. We have experienced a serious cardiovascular collapse following the administration of vancomycin during the prebypass period in a patient undergoing coronary artery grafting. As a consequence of this we have avoided the administration of vancomycin during the prebypass period and have chosen instead to give it after initiation of cardiopulmonary bypass (CPB). This study was set up to observe the cardiovascular changes associated with this technique. Method
The investigation was carried out on 12 patients, aged 20-70 years, weighing 50-100 kg, who underwent coronary artery bypass grafting or valve replacement during hypothermic CPB. The investigation was approved by the Institution Research Committee, and informed consent was obtained. The patients were premedicated with morphine 0.1 mg.kg-', hyoscine 0.3 mg and promethazine 25 mg given intramuscularly. Anaesthesia was induced with midazolam 0.1 mg.kg-', fentanyl 50 pg.kg-' and a mixture of pancuronium 0.1 mg.kg-' and vecuronium 0.1 mg.kg-'. Following tracheal intubation, ventilation was maintained with 100% oxygen without any inhalational anaesthetic supplementation. Patients were monitored by means of an Accepted 13 February 1992.
electrocardiogram (ECG), a radial artery cannula, and a pulmonary artery catheter. During CPB, a bubble oxygenator (Bentley-10, American Bentley, Irvine, CA, USA) was used which had been primed with 1500 ml of compound sodium lactate solution. The patients were perfused using a roller pump (Sarns 5000, Ann Arbor, MI, USA) at a constant flow of 2.4 I.rnin-'.m-', and the oxygenator was supplied with an equal flow of 100% oxygen. The temperature was gradually reduced to 27-30°C, and the heart was arrested by a cardioplegic solution (K+30mmol.1-' at 4°C) after aortic cross clamping. After about 10-20min of CPB when the mean arterial pressure (MAP) and reservoir volume had stabilised, vancomycin 1 g diluted in 20ml of 5% dextrose solution was injected over 60s into the venous line of the oxygenator. The MAP and reservoir volume were continuously monitored, while the perfusion flow was maintained constant at 2.4 I.min-'.m-*. MAP and reservoir volume values were recorded every minute from the time of injection over a 10 min period. Changes of MAP and reservoir volume were taken to reflect the effect of vancomycin on the systemic vascular resistance and the capacitance vessels, respectively [9]. The paired t-test was used to compare the MAP and reservoir volume values achieved following vancomycin with the control values. A value of p < 0.05 was considered significant. Results
Table 1 shows the mean control MAP value achieved during CPB in the 12 patients and the mean MAP values obtained at every minute from the time of injection of vancomycin over a 10 min period. The MAP significantly decreased from a control level of 76.2 (1 1.3) mmHg to 52.5 (17.1) mmHg 2 min following vancomycin administration. Recovery to control values was achieved after 6 min. Table 2 shows the mean control reservoir volume achieved during CPB in the 12 patients and the mean
1087
Forum Table 1. Mean arterial pressure (MAP) in the 12 patients before and after the administration of vancomycin. Values are expressed as mean (SD). Time; min 0 1 2 3 4 5 6 7 8 9 10
MAP; mmHg 76.25 (11.31) 67.08 (9.16) 52.50 (17.12) 57.08 (1 7.77) 62.50 (17.12) 66.25 (18.23) 69.58 (17.90) 72.92 (18.76) 74.58 ( I 8.88) 73.33 (21.03) 75.83 (20.09)
% change of
MAP*
Significance*
-
-
12.30 31.15 25.14 18.03 13.11 8.75 4.37 2.19 3.83 0.55
< 0.05 < 0.05 < 0.05 < 0.05
Table 2. Mean reservoir volume (RV) in the 12 patients before and after the administration of vancomycin. Values are expressed as mean (SD). Time; min 0 1 2 3 4
< 0.05
5
NS NS NS NS NS
6 7 8 9 I10
Mean RV;
YO change of
I
mean RV*
Significance* (p value)
2.37 (0.96) 2.34 (0.97) 2.22 (1.03) 2.12 (1.04) 2.02 (0.99) 2.01 (1.00) 1.97 (0.97) 1.93 (0.99) 1.90 (0.95) 1.82 (0.97) 1.82 (0.96)
I .27 6.33
NS NS
10.55
14.77 15.19 16.88 18.56 19.83 23.21 23.21
-
< 0.05 < 0.05 < 0.05
< 0.05 < 0.05 < 0.05 < 0.05 < 0.05
0 time, control MAP; NS, not significant. *Reference to zero minute.
0 time, control mean RV; NS, not significant, *Reference to zero minute.
reservoir volume values obtained at every minute following the administration of vancomycin. The reservoir volume gradually decreased within 10 min from a control value of 2.37 (0.96 1) to 1.82 (0.96 I).
dynamic instability and/or ischaemic heart disease, when cardiovascular collapse may be life-threatening and therapeutic options are narrowed [I, 21.
References Discussion
This report demonstrates the safety of administration of vancomycin after initiation of CPB. The injection of a bolus of vancomycin 1 g over 60 s into the venous inlet to the reservoir of the oxygenator resulted only in a moderate and transient decrease of MAP. Vancomycin-induced anaphylactoid reaction [ 1-81 may be attributed to a direct effect on mast cells and basophils that results in their degranulation with subsequent release of various vasoactive mediators; histamine release probably represents the mechanism responsible for hypotension following vancomycin administration in man [lo]. Hypotension is the most frequent and the most serious immediate adverse effect associated with the use of vancomycin and the administration of a single dose of vancomycin as antibiotic prophylaxis has been shown to produce a high incidence of severe hypotension in cardiac surgical patients [8]. The minimal and transient decrease of MAP following the rapid administration of a large bolus of vancomycin during CPB may be attributed to dilution by the extracorporeal circuit volume, as well as to bypassing the pulmonary circulation. Adverse cardiovascular responses to drugs such as protamine and vancomycin may be increased by its passage through the pulmonary vasculature as the lungs are a major site of storage of many vasoactive substances, including histamine [ 1 1, 121. Thus, histamine release by vancomycin may be decreased when the lungs are bypassed. The decreased hypotensive response to vancomycin given during CPB may be also attributed to maintenance of adequate perfusion by the pump, despite the increased venous capacitance as manifested by the decreased reservoir volume. In contrast, during the prebypass period, excessive histamine release does not only decrease systemic vascular resistance but also increases the vascular capacitance and traps large amounts of blood, with a subsequent decrease of the venous return and cardiac output [13]. This will be compounded in the cardiac patient with haemo-
[I] BLOOMB, CHALMERS PC, DANKER RR, KUMARS, SHEIKH F. Cardiovascular collapse and refractory bronchospasm following administration of vancomycin, esmolol, and heparin. Journal of Cardiothoracic Anesthesia 1989; 3 748-51. [2] DMEEH, LAKSH, MILLER J, OVENR. Profound hypotension from rapid vancomycin administration during cardiac operation. Journal of Thoracic and Cardiovascular Surgery 1984; 87: 145-6. [3] MILLERR, TAUSKHC. Anaphylactoid reaction to vancomycin during anesthesia: a case report. Anesthesia and Analgesia 1977; 56: 870-2. [4] SYMONS NLP, HOBBESAFT, LEAVERHK. Anaphylactoid reactions to vancomycin during anaesthesia: two clinical reports. Canadian Anaesthetists’ Society Journal 1985; 3 2 178-81. [5] MAYHEWJF, DEUTSCH S. Cardiac arrest following administration of vancomycin. Canadian Anaesthetists’ Society Journal 1985; 3 2 65-6. [6] PAU AK. KHAKW R. ‘Red-Neck Syndrome’ with slow infusion of vancomycin. New England Journal of Medicine 1985; 313 756-7. [7] DAVISRL, SMITHAL, KOUPJR. The ‘Red Man’s Syndrome’ and slow infusion of vancomycin. Annals of Internal Medicine 1986; 104: 285-6. [8] VALEROR, GOMARC, FITAG, GONZALEZ M, PACHECO M, MULETJ, NALDAMA. Adverse reactions to vancomycin prophylaxis in cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia 1991; 5: 574-6. [9] BARAKAA, HAROUN S, BAROODYM, NAWFAL M. SIBAIA. Action of adrenergic agonists on resistance v. capacitance vessels during cardiopulmonary bypass. Journal of Cardiothoracic Anesthesia 1989; 3 193-5. [lo] LEVYJH, KETTLEKAMP N, GOERTZP, HERMENS J, HIRSHMAN CA. Histamine release by vancomycin: a mechanism for hypotension in man. Anesthesiology 1987; 67: 122-5. [I I] GOLDMAN BS, JOISONJ, AUSTENWG. Cardiovascular effects of protamine sulfate. Annals of Thoracic Surgery 1969; 7: 459-71. [I21 CASTHELYPA. GOODMANK, FYMANPN, ABRAMSLM, AAROND. Hemodynamic changes after the administration of protamine. Anesthesia and Analgesia 1986 6 5 78-80. [I31 DALE HH, LAIDLAWPP. Histamine shock. Journal of Physiology 1919; 5 2 355-90.
