British Journal of Anaesthesia 1991; 66: 496-499
EFFECT OF KETANSERIN ON INTRAOPERATIVE BLOOD LOSS DURING TOTAL HIP ARTHROPLASTY IN ELDERLY PATIENTS UNDER GENERAL ANAESTHESIA R. VAN EE AND J. C. VAN OENE SUMMARY
KEY WORDS Age factors. Blood: loss. Serotonin: ketanserin. Surgery: orthopaedic.
Total hip arthroplasty (THA) is associated frequently with considerable intraoperative bleeding, necessitating the replacement of circulating volume with blood products. Blood loss may be reduced by induced arterial hypotension and by spinal or extradural anaesthesia [1-7]. The beneficial effect on blood loss is caused probably by arterial and venous dilatation with redistribution of blood flow away from the operation site to dependent parts. Both techniques have disadvantages in the elderly, and other methods of reducing blood loss merit investigation.
PATIENTS AND METHODS
The study was approved by the Institutional Ethics Committee. Written informed consent was obtained from all patients. Exclusion criteria were coagulation disturbances, severe hepatic dysfunction, hypokalaemia (serum potassium < 3.5 mmol litre"1) and concomitant use of vasodilators (such as nitroprusside, nitroglycerin, labetalol, droperidol) or NSAID. Initially, we studied 20 patients aged > 60 yr, ASA I and II. Subsequently, three of these were excluded: one patient because of a previously undetected abnormality in the R. VAN EE, M.D., Department of Anaesthesiology, Onze Lieve Vrouwe Gasthuis (OLVG), Eerste Oosterparkstraat 179, 1091 HA Amsterdam, The Netherlands. J. C. VAN OENE, M.D., Department of Clinical Pharmacology, Janssen Pharmaceutica B.V., Tilburg, The Netherlands. Accepted for Publication: November 22, 1990.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
We have studied the effect of ketanserin. a selective serotonin S2-receptor antagonist, on surgical bleeding in a double-blind, placebocontrolled study in elderly patients undergoing total hip arthroplasty. One group of patients (n = 9) received ketanserin 10 mg i.v. followed by an infusion of 0.075 mg kg~' h~1. The second group (n = 8) received placebo. Both groups were comparable with regard to age, height and body weight. Mean intraoperative blood loss was 454 ml with ketanserin and 894 ml with placebo (P = 0.004; Wi/coxon two-sample test). Mean duration of the operation was less with ketanserin (112 min) than with placebo (134 min) (? = 0.004), but rate of blood loss was also less with ketanserin (4.1 vs 6.7 ml min'1; P = 0.03). In the ketanserin group, mean arterial pressures tended to be less than in the placebo group. Reductions in central venous pressure were similar in both groups. There were no complications in relation to the use of ketanserin.
Ketanserin is a selective 5-HTj antagonist that has additional a-blocking effects [8]. It reduces increased arterial pressure with a slight reduction in heart rate [9] and is used currently as an oral antihypertensive drug that is particularly effective in patients older then 60 yr [8,10]. Ketanserin has a vasodilator action on both resistance and capacitance vessels [9,11]. It is likely that, after i.v. ketanserin, there is diversion of blood to skin vessels [12]; it seems to have a haemodynamic effect similar to that induced by regional anaesthesia. The purpose of this pilot study was to evaluate the feasibility of use of ketanserin as an agent which could contribute to decreased blood loss in THA under general anaesthesia with intermittent positive pressure ventilation (IPPV). As postoperative blood loss seems to be influenced less by the anaesthetic technique [3,13], we have investigated only the effect of ketanserin on intraoperative blood loss.
KETANSERIN AND SURGICAL HAEMORRHAGE
of tracheal extubation, which also marked the end of study. At the end of surgery, residual neuromuscular block was antagonized with neostigmine and atropine if necessary. Measurements
Intraoperative blood loss was estimated by weighing swabs and drapes and by collection in suction bottles. Preoperative values of systolic, diastolic and mean arterial pressures (SAP, DAP, MAP) and heart rate (HR) were recorded on the day before surgery. Intraoperative values for SAP, DAP, MAP, CVP, HR, end-tidal partial pressure of carbon dioxide and ECG (lead II) were monitored and recorded continuously. Measurements were started after placing the patient in the lateral position (r = 0) and repeated at 20-min intervals. Before and after the administration of the trial medication, an arterial blood sample was taken for measurement of blood-gas tensions, serum electrolyte and haemoglobin concentrations and PCV. Preoperative and postoperative partial thromboplastin time (PTT), activated partial thromboplastin time (APTT), thrombocyte count and bleeding time (method of [14]) were estimated. Statistical analysis Data are presented as mean (SEM). Statistical significance was assessed using Wilcoxon's matched-pairs signed rank test for within-group comparisons, and Wilcoxon's two-sample test for between-group comparisons. All statistical tests were performed two-sided and differences were deemed significant if P < 0.05. RESULTS
The patient groups did not differ significantly in age, sex, height, weight and ASA classification (table I). There was only one male patient in each group, reflecting the preponderance of female patients presenting for THA [15-17]. Mean intraoperative blood loss was 454 (SEM 66) ml in the ketanserin group and 894 (100) ml in the placebo group (fig. 1) (P = 0.0044). The duration of surgery was significantly shorter in the ketanserin group (112 (4.6) min) than in the placebo group (134 (5.6) min) (P = 0.0044), and rate of intraoperative blood loss was also less in the ketanserin than in the placebo group (4.11 (0.58) ml min"1 vs 6.67 (0.65) ml min"1) (P = 0.030).
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
coagulation screen, one who had accidentally received dextran before induction and a third patient in whom a different operation was performed. Thus 17 patients (15 women) with advanced osteoarthritis were investigated during THA under general anaesthesia. Only patients whose hip complaints had led to admission and subsequent operation were included in the study. Routine preoperative screening included full blood count, electrolytes, chest x-ray and ECG, and revealed no abnormalities. All patients had normal bleeding times, activated coagulation times, prothrombin times and thrombocyte counts. By random selection, patients were assigned to two groups: the ketanserin group received a loading dose of ketanserin 10 mg i.v. in 2 ml solvent, followed by an i.v. infusion of 0.075 mg kg"1 h"1; the placebo group received a bolus dose of solvent 2 ml i.v., followed by an i.v. infusion of solvent. All operations were performed by the same surgeon, with the patients in a lateral position. The acetabular and femoral prostheses were fixed with two-component methylmethacrylate cement. Osteotomy of the greater trochanter was not carried out. Patients were given diazepam 10 mg orally and atropine 0.5 mg s.c, 1 h before surgery. General anaesthesia was induced with thiopentone 4 mg kg"1 and fentanyl 100-200 ug. The trachea was intubated after neuromuscular block had been produced with a small dose of pancuronium, followed by suxamethonium 1 mg kg"1. The patient's lungs were ventilated to normocapnia with a non-rebreathing semi-circle system, using nitrous oxide and oxygen 4 and 2.5 litre min"1, respectively. Anaesthesia was maintained with fentanyl 3-7 ug kg"1 h"1 and enflurane up to 0.8 vol% and pancuronium 10-20 ug kg"1, given as required. A cannula was inserted into a radial artery under local anaesthesia. Two central venous catheters were inserted into the right internal jugular vein. One catheter was used for continuous recording of central venous pressure (CVP) and the other for the administration of ketanserin. All patients received Ringer's lactate solution via an additional peripheral venous cannula. Packed red blood cells were given if intraoperative blood loss exceeded 10% of calculated blood volume. Trial medication was started immediately after the patient was placed in the lateral position, and was discontinued at the time
497
BRITISH JOURNAL OF ANAESTHESIA
498 TABLE I. Patient characteristics (mean (range or SEM))
Sex (M/F) Age (yr) Height (cm) Weight (kg)
120
Ketanserin (n = 9)
Placebo 1/7 75.1 (60-88) 161.6(2.5) 74.7 (2.6)
1/8 70.2 (60-88) 171.2(3.2) 75.4 (4.0)
1600 1400-
| 1000o 800o o 5
OO
OO O
600
Before 0 20 40 60 80 100 120 °PTime (min) FIG. 2. Haemodynamic changes in patients given ketanserin (solid symbols) or placebo (open symbols). Mean arterial pressure (circles), centra] venous pressure (triangles), heart rate (HR) (squares). *P < 0.05; **P < 0.01 between groups.
400200-
Placebo
Ketanserin
FIG. 1. Intraoperative blood loss for each patient given ketanserin or placebo. Horizontal lines represent mean values (significantly different: P < 0.01).
During operation, mean SAP was 108-118 mm Hg in the ketanserin group and 125-140 mm Hg in the placebo group and mean DAP was 59—66 mm Hg and 62-78 mm Hg, respectively, in the two groups. Mean arterial pressure decreased by 10-20% following induction of anaesthesia (fig. 2). During operation, MAP was less in the ketanserin group than in the placebo group, but statistical significance was achieved only at 20 and 60 min after the start of trial medication (fig. 2). Following induction, there was a slight decrease in heart rate, but during operation, heart rate stabilized at 60-75 beat min^1 in both groups (fig. 2). Central venous pressures were less in the placebo group than in the ketanserin group, but statistical significance was achieved only at 80 min (fig. 2). All measurements of coagulation factors, bloodgas tensions and electrolyte concentrations re-
TABLE II. Mean (SEM) template bleeding time at the beginning and end of operation following either placebo or ketanserin,
**P < 0.01 Bleeding time (s)
Start End Difference
Placebo
Ketanserin
265 (28) 371(30) 116(26)
286(34) 324 (31) 39 (36)
**
mained within the normal range. Intraoperative loss was replaced promptly with electrolyte solutions and packed cells and there were no differences in PCV and haemoglobin concentration between the two groups. Template bleeding times were similar in both groups at the start and end of the operation (table II). A statistically significant increase in bleeding time was observed in the placebo group, but not in the ketanserin group; however, absolute values stayed within the normal limits (120-570 s). No complications were observed in relation to the use of ketanserin.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
1200-
KETANSERIN AND SURGICAL HAEMORRHAGE DISCUSSION
REFERENCES 1. Rosberg B, Fredin H, Gustafson C. Anaesthetic technique and surgical blood loss in total hip arthroplasty. Ada Anaesthesiologica Scandinavica 1982; 26: 189-193. 2. Thomson GE, Miller RD, Stevens WC, Murray WR. Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function. Anesthesiology 1978; 48: 91-96. 3. Keith I. Anaesthesia and blood loss in total hip replacement. Anaesthesia 1977; 32: 444-450. 4. Modig J. Beneficial effects on intra-operative and postoperative blood loss in total hip replacement when performed under epidural anaesthesia. Acta Ctnrurgica Scandinavica 1988; (Suppl. 550): 95-103. 5. Davis F, McDermott E, Hickton C, Wells E, Heaton D,
Laurenson V, GUlespie W, Foate J. Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. British Journal of Anaesthesia 1987; 59: 561-571. 6. Cousin MJ, Wright CJ. Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surgery, Gynecology & Obstetrics 1971; 133: 59. 7. Covert CR, Fox GS. Anaesthesia for hip surgery in the elderly. Canadian Journal of Anaesthesia 1989; 36: 311-319. 8. Vanhoutte P, Amery A, BirkenhSger W, Breckenridge A, Buhler F, Distler A, Dormandy J, Doyle A, Frohlich E, Hansson L, Hedner T, Hollenbcrg N, Jensen HE, LundJohansen P, Meyer P, Opie L, Robertson I, Safar M, Schalekamp M, Symoens J, Trap-Jensen J, Zanchetrj A. Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. Hypertension 1988; 11: 111-133. 9. Schalekamp MADH, Woittiez AJJ, Waiting GJ, Van den Meiracker AH, Man in't Veld AJ. Ketanserin: haemodynamic effects and mechanism of action. Journal of Hypertension 1986; 4 (Suppl.J): S7-12. 10. Rosendorff C, Murray GD. Ketanserin versus metoprolol and hydrochlorothiazidc in essential hypertension: only ketanserin's hypotensive effect is age-related. Journal of Hypertension 1986; 4 (Suppl. 6): S109-S111. 11. Van der Starre PJA, Van Heekeren K, Reneman RS. Peripheral vascular effects of ketanserin and nifedipine during cardiopulmonary bypass. Journal of Hypertension 1987; 5 (Suppl. 5): S205-S208. 12. Kunnen JJ, Dahler HP, Doorenspleet JG, Van O n e JC. Effects of intra-arterial ketanserin in Raynaud's phenomenon assessed by """Tc-pertechnetate scintigraphy. European Journal of Clinical Pharmacology 1988; 34: 267-271. 13. Thorbum J, Louden JR, Vallance R. Spinal and general anaesthesia in total hip replacement. British Journal of Anaesthesia 1980; 52: 1117. 14. Mielke C jr, Kaneshiro MM, Maher LA, Weiner JM, Rapaport SI. The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 1969; 34: 204-215. 15. Editorial. The old woman with a broken hip. Lancet 1982; 2: 419-420. 16. Cummings SR, Kelsey JC, Neville MC, O'Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiological Reviews 1985; 7: 278-208. 17. Milton LJ, Wahner HJ, Richelson LS, O'Fallon WM, Riggs BL. Osteoporosis and risk of hip fracture. American Journal of Epidemiology 1986; 124: 254-261. 18. Koide M, Pilone N, Vandam LD, Lowell JD. Anaesthetic experience with total hip replacement. Clinical Orthopaedics 1974; 99: 78-85. 19. Modig J, Karlstrom G. Intra- and post-operative blood lost and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia. European Journal of Anaesthesia 1987; 4:
345-355.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
The present study confirms the hypothesis that ketanserin reduces blood loss during hip arthroplasty under general anaesthesia by virtue of its haemodynamic effects. Ketanserin reduced MAP to a mean intraoperative value of 80 mm Hg, which may be considered safe [4]. Other cardiovascular changes were minor and similar in nature to those accompanying mild induced hypotension. Central venous pressure tended to be greater in the ketanserin group. As spontaneous ventilation in the lateral position may interfere with alveolar ventilation, all patients' lungs were ventilated mechanically. Theoretically, the resulting increase in intrathoracic pressure would lead to an increase in venous pressure with diminished venous return and subsequent increased bleeding from venous oozing [4,18]. This effect may have been offset by peripheral venodilatation induced by ketanserin. Reduction in peripheral venous pressure reduces venous oozing and is a major factor contributing to diminished blood loss [19]. Thus the reduced blood loss in the ketanserin group may be explained by the combination of a moderate reduction in mean arterial pressure and a reduction in peripheral venous pressure in the surgical wound.
499
EFFECT OF KETANSERIN ON INTRAOPERATIVE BLOOD LOSS DURING TOTAL HIP ARTHROPLASTY IN ELDERLY PATIENTS UNDER GENERAL ANAESTHESIA R. VAN EE AND J. C. VAN OENE SUMMARY
KEY WORDS Age factors. Blood: loss. Serotonin: ketanserin. Surgery: orthopaedic.
Total hip arthroplasty (THA) is associated frequently with considerable intraoperative bleeding, necessitating the replacement of circulating volume with blood products. Blood loss may be reduced by induced arterial hypotension and by spinal or extradural anaesthesia [1-7]. The beneficial effect on blood loss is caused probably by arterial and venous dilatation with redistribution of blood flow away from the operation site to dependent parts. Both techniques have disadvantages in the elderly, and other methods of reducing blood loss merit investigation.
PATIENTS AND METHODS
The study was approved by the Institutional Ethics Committee. Written informed consent was obtained from all patients. Exclusion criteria were coagulation disturbances, severe hepatic dysfunction, hypokalaemia (serum potassium < 3.5 mmol litre"1) and concomitant use of vasodilators (such as nitroprusside, nitroglycerin, labetalol, droperidol) or NSAID. Initially, we studied 20 patients aged > 60 yr, ASA I and II. Subsequently, three of these were excluded: one patient because of a previously undetected abnormality in the R. VAN EE, M.D., Department of Anaesthesiology, Onze Lieve Vrouwe Gasthuis (OLVG), Eerste Oosterparkstraat 179, 1091 HA Amsterdam, The Netherlands. J. C. VAN OENE, M.D., Department of Clinical Pharmacology, Janssen Pharmaceutica B.V., Tilburg, The Netherlands. Accepted for Publication: November 22, 1990.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
We have studied the effect of ketanserin. a selective serotonin S2-receptor antagonist, on surgical bleeding in a double-blind, placebocontrolled study in elderly patients undergoing total hip arthroplasty. One group of patients (n = 9) received ketanserin 10 mg i.v. followed by an infusion of 0.075 mg kg~' h~1. The second group (n = 8) received placebo. Both groups were comparable with regard to age, height and body weight. Mean intraoperative blood loss was 454 ml with ketanserin and 894 ml with placebo (P = 0.004; Wi/coxon two-sample test). Mean duration of the operation was less with ketanserin (112 min) than with placebo (134 min) (? = 0.004), but rate of blood loss was also less with ketanserin (4.1 vs 6.7 ml min'1; P = 0.03). In the ketanserin group, mean arterial pressures tended to be less than in the placebo group. Reductions in central venous pressure were similar in both groups. There were no complications in relation to the use of ketanserin.
Ketanserin is a selective 5-HTj antagonist that has additional a-blocking effects [8]. It reduces increased arterial pressure with a slight reduction in heart rate [9] and is used currently as an oral antihypertensive drug that is particularly effective in patients older then 60 yr [8,10]. Ketanserin has a vasodilator action on both resistance and capacitance vessels [9,11]. It is likely that, after i.v. ketanserin, there is diversion of blood to skin vessels [12]; it seems to have a haemodynamic effect similar to that induced by regional anaesthesia. The purpose of this pilot study was to evaluate the feasibility of use of ketanserin as an agent which could contribute to decreased blood loss in THA under general anaesthesia with intermittent positive pressure ventilation (IPPV). As postoperative blood loss seems to be influenced less by the anaesthetic technique [3,13], we have investigated only the effect of ketanserin on intraoperative blood loss.
KETANSERIN AND SURGICAL HAEMORRHAGE
of tracheal extubation, which also marked the end of study. At the end of surgery, residual neuromuscular block was antagonized with neostigmine and atropine if necessary. Measurements
Intraoperative blood loss was estimated by weighing swabs and drapes and by collection in suction bottles. Preoperative values of systolic, diastolic and mean arterial pressures (SAP, DAP, MAP) and heart rate (HR) were recorded on the day before surgery. Intraoperative values for SAP, DAP, MAP, CVP, HR, end-tidal partial pressure of carbon dioxide and ECG (lead II) were monitored and recorded continuously. Measurements were started after placing the patient in the lateral position (r = 0) and repeated at 20-min intervals. Before and after the administration of the trial medication, an arterial blood sample was taken for measurement of blood-gas tensions, serum electrolyte and haemoglobin concentrations and PCV. Preoperative and postoperative partial thromboplastin time (PTT), activated partial thromboplastin time (APTT), thrombocyte count and bleeding time (method of [14]) were estimated. Statistical analysis Data are presented as mean (SEM). Statistical significance was assessed using Wilcoxon's matched-pairs signed rank test for within-group comparisons, and Wilcoxon's two-sample test for between-group comparisons. All statistical tests were performed two-sided and differences were deemed significant if P < 0.05. RESULTS
The patient groups did not differ significantly in age, sex, height, weight and ASA classification (table I). There was only one male patient in each group, reflecting the preponderance of female patients presenting for THA [15-17]. Mean intraoperative blood loss was 454 (SEM 66) ml in the ketanserin group and 894 (100) ml in the placebo group (fig. 1) (P = 0.0044). The duration of surgery was significantly shorter in the ketanserin group (112 (4.6) min) than in the placebo group (134 (5.6) min) (P = 0.0044), and rate of intraoperative blood loss was also less in the ketanserin than in the placebo group (4.11 (0.58) ml min"1 vs 6.67 (0.65) ml min"1) (P = 0.030).
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
coagulation screen, one who had accidentally received dextran before induction and a third patient in whom a different operation was performed. Thus 17 patients (15 women) with advanced osteoarthritis were investigated during THA under general anaesthesia. Only patients whose hip complaints had led to admission and subsequent operation were included in the study. Routine preoperative screening included full blood count, electrolytes, chest x-ray and ECG, and revealed no abnormalities. All patients had normal bleeding times, activated coagulation times, prothrombin times and thrombocyte counts. By random selection, patients were assigned to two groups: the ketanserin group received a loading dose of ketanserin 10 mg i.v. in 2 ml solvent, followed by an i.v. infusion of 0.075 mg kg"1 h"1; the placebo group received a bolus dose of solvent 2 ml i.v., followed by an i.v. infusion of solvent. All operations were performed by the same surgeon, with the patients in a lateral position. The acetabular and femoral prostheses were fixed with two-component methylmethacrylate cement. Osteotomy of the greater trochanter was not carried out. Patients were given diazepam 10 mg orally and atropine 0.5 mg s.c, 1 h before surgery. General anaesthesia was induced with thiopentone 4 mg kg"1 and fentanyl 100-200 ug. The trachea was intubated after neuromuscular block had been produced with a small dose of pancuronium, followed by suxamethonium 1 mg kg"1. The patient's lungs were ventilated to normocapnia with a non-rebreathing semi-circle system, using nitrous oxide and oxygen 4 and 2.5 litre min"1, respectively. Anaesthesia was maintained with fentanyl 3-7 ug kg"1 h"1 and enflurane up to 0.8 vol% and pancuronium 10-20 ug kg"1, given as required. A cannula was inserted into a radial artery under local anaesthesia. Two central venous catheters were inserted into the right internal jugular vein. One catheter was used for continuous recording of central venous pressure (CVP) and the other for the administration of ketanserin. All patients received Ringer's lactate solution via an additional peripheral venous cannula. Packed red blood cells were given if intraoperative blood loss exceeded 10% of calculated blood volume. Trial medication was started immediately after the patient was placed in the lateral position, and was discontinued at the time
497
BRITISH JOURNAL OF ANAESTHESIA
498 TABLE I. Patient characteristics (mean (range or SEM))
Sex (M/F) Age (yr) Height (cm) Weight (kg)
120
Ketanserin (n = 9)
Placebo 1/7 75.1 (60-88) 161.6(2.5) 74.7 (2.6)
1/8 70.2 (60-88) 171.2(3.2) 75.4 (4.0)
1600 1400-
| 1000o 800o o 5
OO
OO O
600
Before 0 20 40 60 80 100 120 °PTime (min) FIG. 2. Haemodynamic changes in patients given ketanserin (solid symbols) or placebo (open symbols). Mean arterial pressure (circles), centra] venous pressure (triangles), heart rate (HR) (squares). *P < 0.05; **P < 0.01 between groups.
400200-
Placebo
Ketanserin
FIG. 1. Intraoperative blood loss for each patient given ketanserin or placebo. Horizontal lines represent mean values (significantly different: P < 0.01).
During operation, mean SAP was 108-118 mm Hg in the ketanserin group and 125-140 mm Hg in the placebo group and mean DAP was 59—66 mm Hg and 62-78 mm Hg, respectively, in the two groups. Mean arterial pressure decreased by 10-20% following induction of anaesthesia (fig. 2). During operation, MAP was less in the ketanserin group than in the placebo group, but statistical significance was achieved only at 20 and 60 min after the start of trial medication (fig. 2). Following induction, there was a slight decrease in heart rate, but during operation, heart rate stabilized at 60-75 beat min^1 in both groups (fig. 2). Central venous pressures were less in the placebo group than in the ketanserin group, but statistical significance was achieved only at 80 min (fig. 2). All measurements of coagulation factors, bloodgas tensions and electrolyte concentrations re-
TABLE II. Mean (SEM) template bleeding time at the beginning and end of operation following either placebo or ketanserin,
**P < 0.01 Bleeding time (s)
Start End Difference
Placebo
Ketanserin
265 (28) 371(30) 116(26)
286(34) 324 (31) 39 (36)
**
mained within the normal range. Intraoperative loss was replaced promptly with electrolyte solutions and packed cells and there were no differences in PCV and haemoglobin concentration between the two groups. Template bleeding times were similar in both groups at the start and end of the operation (table II). A statistically significant increase in bleeding time was observed in the placebo group, but not in the ketanserin group; however, absolute values stayed within the normal limits (120-570 s). No complications were observed in relation to the use of ketanserin.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
1200-
KETANSERIN AND SURGICAL HAEMORRHAGE DISCUSSION
REFERENCES 1. Rosberg B, Fredin H, Gustafson C. Anaesthetic technique and surgical blood loss in total hip arthroplasty. Ada Anaesthesiologica Scandinavica 1982; 26: 189-193. 2. Thomson GE, Miller RD, Stevens WC, Murray WR. Hypotensive anesthesia for total hip arthroplasty: a study of blood loss and organ function. Anesthesiology 1978; 48: 91-96. 3. Keith I. Anaesthesia and blood loss in total hip replacement. Anaesthesia 1977; 32: 444-450. 4. Modig J. Beneficial effects on intra-operative and postoperative blood loss in total hip replacement when performed under epidural anaesthesia. Acta Ctnrurgica Scandinavica 1988; (Suppl. 550): 95-103. 5. Davis F, McDermott E, Hickton C, Wells E, Heaton D,
Laurenson V, GUlespie W, Foate J. Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. British Journal of Anaesthesia 1987; 59: 561-571. 6. Cousin MJ, Wright CJ. Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surgery, Gynecology & Obstetrics 1971; 133: 59. 7. Covert CR, Fox GS. Anaesthesia for hip surgery in the elderly. Canadian Journal of Anaesthesia 1989; 36: 311-319. 8. Vanhoutte P, Amery A, BirkenhSger W, Breckenridge A, Buhler F, Distler A, Dormandy J, Doyle A, Frohlich E, Hansson L, Hedner T, Hollenbcrg N, Jensen HE, LundJohansen P, Meyer P, Opie L, Robertson I, Safar M, Schalekamp M, Symoens J, Trap-Jensen J, Zanchetrj A. Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. Hypertension 1988; 11: 111-133. 9. Schalekamp MADH, Woittiez AJJ, Waiting GJ, Van den Meiracker AH, Man in't Veld AJ. Ketanserin: haemodynamic effects and mechanism of action. Journal of Hypertension 1986; 4 (Suppl.J): S7-12. 10. Rosendorff C, Murray GD. Ketanserin versus metoprolol and hydrochlorothiazidc in essential hypertension: only ketanserin's hypotensive effect is age-related. Journal of Hypertension 1986; 4 (Suppl. 6): S109-S111. 11. Van der Starre PJA, Van Heekeren K, Reneman RS. Peripheral vascular effects of ketanserin and nifedipine during cardiopulmonary bypass. Journal of Hypertension 1987; 5 (Suppl. 5): S205-S208. 12. Kunnen JJ, Dahler HP, Doorenspleet JG, Van O n e JC. Effects of intra-arterial ketanserin in Raynaud's phenomenon assessed by """Tc-pertechnetate scintigraphy. European Journal of Clinical Pharmacology 1988; 34: 267-271. 13. Thorbum J, Louden JR, Vallance R. Spinal and general anaesthesia in total hip replacement. British Journal of Anaesthesia 1980; 52: 1117. 14. Mielke C jr, Kaneshiro MM, Maher LA, Weiner JM, Rapaport SI. The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood 1969; 34: 204-215. 15. Editorial. The old woman with a broken hip. Lancet 1982; 2: 419-420. 16. Cummings SR, Kelsey JC, Neville MC, O'Dowd KJ. Epidemiology of osteoporosis and osteoporotic fractures. Epidemiological Reviews 1985; 7: 278-208. 17. Milton LJ, Wahner HJ, Richelson LS, O'Fallon WM, Riggs BL. Osteoporosis and risk of hip fracture. American Journal of Epidemiology 1986; 124: 254-261. 18. Koide M, Pilone N, Vandam LD, Lowell JD. Anaesthetic experience with total hip replacement. Clinical Orthopaedics 1974; 99: 78-85. 19. Modig J, Karlstrom G. Intra- and post-operative blood lost and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia. European Journal of Anaesthesia 1987; 4:
345-355.
Downloaded from http://bja.oxfordjournals.org/ at UB Giessen on May 20, 2015
The present study confirms the hypothesis that ketanserin reduces blood loss during hip arthroplasty under general anaesthesia by virtue of its haemodynamic effects. Ketanserin reduced MAP to a mean intraoperative value of 80 mm Hg, which may be considered safe [4]. Other cardiovascular changes were minor and similar in nature to those accompanying mild induced hypotension. Central venous pressure tended to be greater in the ketanserin group. As spontaneous ventilation in the lateral position may interfere with alveolar ventilation, all patients' lungs were ventilated mechanically. Theoretically, the resulting increase in intrathoracic pressure would lead to an increase in venous pressure with diminished venous return and subsequent increased bleeding from venous oozing [4,18]. This effect may have been offset by peripheral venodilatation induced by ketanserin. Reduction in peripheral venous pressure reduces venous oozing and is a major factor contributing to diminished blood loss [19]. Thus the reduced blood loss in the ketanserin group may be explained by the combination of a moderate reduction in mean arterial pressure and a reduction in peripheral venous pressure in the surgical wound.
499
